[First report of Neisseria polysaccharea in Cuba].
The National Laboratory of Reference of Pathogenic Neisserias of "Pedro Kourí" Tropical Medicine Institute studied 58 strains which had been previously identified as Neisseria meningiditis and isolated from nasopharyngeal carriers from 1985-1998. They were applied the knapp detection scheme plus the glutamiltransferase production test. The latter and the polyscharide production based on 5% sacarose allowed to make a differential diagnosis between N. meningitidis and Neisseria polyccharea. It was possible to identify a N. polysaccharia strain, a species that is reported for the first time in Cuba.


Shape reconstruction of metallic objects from intensity scattered field data only.
We address an inverse scattering problem using only amplitude information of the scattered field. In particular, we are concerned with the reconstruction of the shape of a metallic planar obstacle, located in a known plane (aperture plane), starting from the knowledge of the intensity of the scattered field over two measurement planes in near zone and parallel to the aperture plane, when a single-frequency incident plane wave is exploited. The formulation of the inverse scattering problem is given under the physical optics approximation, and thus the resulting phase retrieval problem is quadratic. This allows us to apply some phase retrieval techniques already developed for antenna diagnostics. Reconstruction results with synthetic data indicate the feasibility of the proposed approach.


Regulation of paracrine cytokine balance controlling collagenase synthesis by corneal cells.
Classic studies have demonstrated that corneal epithelial cell density in culture can alter the balance of stimulatory and inhibitory cytokines controlling the elaboration of collagenolytic activity by co-cultured stromal cells. The current study attempts to bring the understanding of this mechanism to a molecular level. A rabbit primary corneal cell culture model was used. Using molecular probes that bind to and neutralize specific cytokines, a major stimulator for stromal cell collagenase synthesis released by corneal epithelial cells into culture medium was identified as interleukin-1 alpha (IL-1 alpha), and a secondary stimulator was characterized as a heparin-binding cytokine. An inverse relationship between net collagenase stimulatory activity and epithelial cell plating density was demonstrated. In contrast, the release of inhibitory activity for IL-1-stimulated collagenase synthesis was not subject to the cell density effect. Direct measurement of IL-1 alpha protein levels revealed that this cytokine was released much more efficiently on a per cell basis when cells were plated at low density than when they were plated at high density. The effect was not caused by greater cell lysis at low cell density and was mediated only partially by changes at the IL-1 alpha synthesis level. These data provide evidence that epithelial cells release stimulatory cytokines for collagenase expression more efficiently when they have limited contact with their neighbors and that this has important consequences for the overall paracrine cytokine balance controlling collagenase synthesis. Alteration of the paracrine cytokine balance by changes in cell contact may be an important means for regulating epithelial-stromal interactions involved in corneal development and repair.


MAGP1, the extracellular matrix, and metabolism.
Adipose tissue and the extracellular matrix were once considered passive players in regulating physiological processes. Now, both entities are acknowledged for their capacity to engage signal transduction pathways, and for their involvement in maintaining normal tissue homeostasis. We recently published a series of studies that identified a novel mechanism whereby an extracellular matrix molecule, MAGP1 (microfibril associated glycoprotein 1), can regulate energy metabolism in adipose tissue. MAGP1 is a component of extracellular microfibrils and plays a supportive role in maintaining thermoregulation by indirectly regulating expression of the thermogenic uncoupling proteins (UCPs). The focus of this commentary is to draw attention to the role of the extracellular matrix in regulating the bioavailability of signaling molecules, like transforming growth factor β (TGFβ), and exemplify that a better understanding of the extracellular matrix's biological properties could unveil a new source of therapeutic targets for metabolic diseases.


Early ambulation after colorectal oncologic resection with perineal reconstruction is safe and effective.
Post-operative bedrest is common following perineal reconstruction despite little supporting data. We sought to determine the safety of early ambulation following colorectal oncologic resection and flap-based perineal reconstruction. A retrospective cohort study was conducted with two cohorts: standard bedrest (BC) and early ambulation (EAC). Ambulation capacity was objectively assessed. Regression analysis was performed to determine the effects of ambulation timing on 60-day reoperations or readmissions and other surgical outcomes. There were 57 participants. Those in the EAC were significantly more ambulatory on post-operative days one through three (p < 0.0001). There was no significant difference in 60-day reoperations (25% BC versus 9% EAC, p = 0.14) or readmissions (33% BC versus 15% EAC, p = 0.12). Early ambulation significantly reduced minor complication rates (38% BC versus 9% EAC, p = 0.02). Early ambulation following perineal reconstruction is safe and may potentially decrease wound complications. Institution of early ambulation protocols is rapidly becoming the standard of care for many oncological surgery patients. In cases requiring perineal reconstruction with vascularized flaps, however, there is no data to uproot the historical practice of mandatory bedrest. Our study demonstrates that the benefits of early ambulation are attainable in these patients without compromising reconstructive outcomes.


The sociogenesis of insect colonies.
Studies on the social insects (ants, bees, wasps, and termites) have focused increasingly on sociogenesis, the process by which colony members undergo changes in caste, behavior, and physical location incident to colonial development. Caste is determined in individuals largely by environmental cues that trigger a sequence of progressive physiological restrictions. Individual determination, which is socially mediated, yields an age-size frequency distribution of the worker population that enhances survival and reproduction of the colony as a whole, typically at the expense of individuals. This "adaptive demography" varies in a predictable manner according to the species and size of the colony. The demography is richly augmented by behavioral pacemaking on the part of certain castes and programmed changes in the physical position of colony members according to age and size. Much of what has been observed in these three colony-level traits (adaptive demography, pacemaking, and positional effects) can be interpreted as the product of ritualization of dominance and other forms of selfish behavior that is still found in the more primitive insect societies. Some of the processes can also be usefully compared with morphogenesis at the levels of cells and tissues.


A New Caco-2 Cell Model of in Vitro Intestinal Barrier: Application for the Evaluation of Magnesium Salts Absorption.
Experimental data concerning the bioavailability of the different Mg-salts in human organism is inconsistent. Mg-absorption reported by clinical studies largely varies depending on the method used for evaluation. The aim of this study was to evaluate the bioavailability and accessibility of magnesium bound in different Mg-salt compounds, using an in vitro model of intestinal cell barrier. The study included a variety of inorganic (oxide, sulphate, chloride, carbonate) and organic salts (lactate, citrate, pidolate). Caco-2 cells were cultivated in a complete culture medium with different magnesium salts treatments in ascending concentrations. The viability and quantity of cells was analysed by FACS. Mg-absorption was analysed by a direct colorimetric assay, measured by spectrometry. T-test identified a significant decrease in cell count treatment with mg-lactate compared with citrate. Mg-pidolate showed a significantly higher cell viability compared with Mg-citrate, Mg-lactate and Mg-chloride. Even though the difference was not significant, we showed that an increase in Mg2+ salt concentration progressively decreased the cell count and the viability and the effect was universal for all the used Mg-salt treatments. Mg-citrate, chloride, and sulphate showed a significantly lower absorption compared to Mg-carbonate, pidolate and oxide. Our in vitro monolayer model of human intestinal transport showed that viability and quantity of cell decreased with increasing Mg-concentration. We admit that our experiment model may have some limitations in accurately describing an in vivo Mg2+ absorption. Moreover, it is also necessary to assess the relevance of our data in vivo and especially in clinical practice.


Force calculation on walls and embedded particles in multiparticle-collision-dynamics simulations.
Colloidal solutions posses a wide range of time and length scales so that it is unfeasible to keep track of all of them within a single simulation. As a consequence, some form of coarse graining must be applied. In this work we use the multiparticle collision dynamics scheme. We describe a particular implementation of no-slip boundary conditions upon a solid surface, capable of providing correct forces on the solid bypassing the calculation of the velocity profile or the stress tensor in the fluid near the surface. As an application we measure the friction on a spherical particle when it is placed in a bulk fluid and when it is confined in a slit. We show that the implementation of the no-slip boundary conditions leads to an enhanced Enskog friction, which can be understood analytically. Because of the long-range nature of hydrodynamic interactions, the Stokes friction obtained from the simulations is sensitive of the simulation box size. We address this topic for the slit geometry, showing that the dependence on the system size differs very much from what is expected in a three-dimensional system where periodic boundary conditions are used in all directions.


Age of drinking onset as a moderator of the efficacy of parent-based, brief motivational, and combined intervention approaches to reduce drinking and consequences among college students.
The current study tested age of onset as a moderator of intervention efficacy on drinking and consequence outcomes among a high-risk population of college students (i.e., former high school athletes). Students were randomized to one of four conditions: assessment only control, combined parent-based intervention (PBI) and brief motivational intervention (BMI), PBI alone, and BMI alone. Participants (n = 1,275) completed web-administered measures at baseline (summer before starting college) and 10-month follow-up. Overall, the combined intervention demonstrated the strongest and most consistent reductions across all outcomes, particularly with the youngest initiators. Participants who initiated drinking at the youngest ages had significantly lower peak drinking, typical weekly drinking, and reported consequences at follow-up when they received the combined intervention when compared to the control group. The BMI and PBI groups, when examined independently, demonstrated significant effects across outcomes but were inconsistent across the different age groups. Results suggest the combination of a PBI and a peer-delivered BMI is an appropriate and efficacious way to reduce drinking and related consequences among individuals who initiated drinking earlier in adolescence and are at an increased risk of experiencing alcohol problems.


Pattern of sexually transmitted infections in a tertiary care centre at Puducherry.
The prevalence of sexually transmitted infections (STI) varies widely from region to region in our country. To highlight the pattern of STIs and the profile of patients with HIV infection in STD patients as seen at our hospital. A retrospective chart analysis of clients attending STI clinic, JIPMER, Puducherry, from June 2004 to June 2006 was done. A total of 866 clients attended our STI clinic, out of whom 435 (50.2%) had proven STI. STIs were more common in men, with a male (290): female (145) ratio of 2:1. Their age ranged from 1 year to 75 years (mean age = 32.38 years) with the maximum number of patients in the age group of 21-30 years, while children constituted only 2.8%. Herpes genitalis (107 patients, 32.8%) was the most common ulcerative STI, while genital wart was the most common nonulcerative STI (56 patients, 17.1%). Non-gonococcal urethritis (46 patients, 14.1%) was more common than gonococcal urethritis. HIV infection was the most common STI in our study, at an alarmingly high rate of 34.5% (151/435). HIV seropositivity was more common in patients who presented with ulcerative STIs than with nonulcerative STIs. Herpes genitalis was the most common ulcerative STD, while genital wart was the most common nonulcerative STI in our study. The prevalence of HIV among STI clients in India has been on the rise, but has quite alarmingly become the most common STI in our study.


Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fat.
The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPARγ, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot.


Multifocal electroretinographic features of central retinal vein occlusion.
To determine the features of wide-field multifocal electroretinography (WF-mfERG) recorded in patients with central retinal vein occlusion (CRVO) and to compare WF-mfERG responses of the affected and fellow eyes. In addition, WF-mfERG responses were also compared by using standard electroretinography (ERG). WF-mfERG and ERG responses were recorded from both eyes of 56 patients with CRVO. The WF-mfERG responses, obtained using a custom-built system were grouped into central and peripheral rings. The P1 amplitudes, and P1 and N1 implicit times were grouped and averaged within both rings. Nonparametric statistical analysis was used to compare the ERG results from the affected and fellow eyes. The results were also compared with normative data (5% to 95% confidence limits). CRVO markedly affected all the parameters of the WF-mfERG. In the affected eyes, 98% of the central and 91% of the peripheral P1 implicit times fell outside the normal range, as opposed to 35% of the 30-Hz flicker implicit times. The WF-mfERG responses obtained from eyes with CRVO were significantly different (P<0.01) from those derived from the fellow eye. The central and peripheral P1 implicit times were also abnormal in 59.2% and 46.9% of the fellow eyes, respectively. WF-mfERG is more susceptible than the standard ERG to changes in the nonlinear dynamics of the eye due to the multiple frequencies of stimulation used to record WF-mfERG responses. WF-mfERG could be a sensitive indicator of the underlying disease affecting the retina in eyes with CRVO and may have a role in the clinical setting.


Identification of the Hub Genes Associated with the Prognosis of Ovarian Cancer Patients via Integrated Bioinformatics Analysis and Experimental Validation.
This study aimed to identify the hub genes associated with prognosis of patients with ovarian cancer by using integrated bioinformatics analysis and experimental validation. Four microarray datasets (GSE12470, GSE14407, GSE18521 and GSE46169) were analyzed by the GEO2R tool to screen common differentially expressed genes (DEGs). Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, the (KEGG) pathway and Reactome pathway enrichment analysis, protein-protein interaction (PPI) construction, and the identification of hub genes were performed. Furthermore, we performed the survival and expression analysis of the hub genes. In vitro functional assays were performed to assess the effects of hub genes on ovarian cancer cell proliferation, caspase-3/7 activity and invasion. A total of 89 common DEGs were identified among these four datasets. The KEGG and Reactome pathway results showed that the DEGs were mainly associated with cell cycle, mitotic and p53 signaling pathway. A total of 20 hub genes were identified from the PPI network by using sub-module analysis. The survival analysis revealed that high expression of six hub genes (AURKA, BUB1B, CENPF, KIF11, KIF23 and TOP2A) were significantly correlated with shorter overall survival and progression-free survival of patients with ovarian cancer. Furthermore, the expression of the six hub genes were validated by the GEPIA database and Human Protein Atlas, and functional studies revealed that knockdown of KIF11 and KIF23 suppressed the SKOV3 cell proliferation, increased caspase-3/7 activity and attenuated invasive potentials of SKOV3 cells. In addition, knockdown of KIF11 and KIF23 up-regulated E-cadherin mRNA expression but down-regulated N-cadherin and vimentin mRNA expression in SKOV3 cells. Our results showed that six hub genes were up-regulated in ovarian cancer tissues and may predict poor prognosis of patients with ovarian cancer. KIF11 and KIF23 may play oncogenic roles in ovarian cancer cell progression via promoting ovarian cancer cell proliferation and invasion.


A child with suprasellar mass and ascites.
A 7-year-old child having short stature presented with headache and vomiting of 6 months' duration. MRI of the brain showed a sellar and suprasellar mass suggestive of craniopharyngioma with hydrocephalus. He underwent a right ventriculo-peritoneal (V-P) shunting followed by a subtotal resection of the tumour. A year later, he presented with progressive ascites and umbilical hernia. Systemic examination was unremarkable except for massive ascites. Ultrasound abdomen confirmed free-fluid in the peritoneal cavity and the ascitic fluid was transudative. Ventriculo-cysternography revealed a functional and patent V-P shunt. A diagnosis of cerebrospinal fluid ascites (shunt ascites) was made and he underwent ventriculo-atrial shunting. After treatment the patient improved with the gradual disappearance of ascites.


The impact of the minimum wage on health.
This study evaluates the effect of minimum wage on risky health behaviors, healthcare access, and self-reported health. We use data from the 1993-2015 Behavioral Risk Factor Surveillance System, and employ a difference-in-differences strategy that utilizes time variation in new minimum wage laws across U.S. states. Results suggest that the minimum wage increases the probability of being obese and decreases daily fruit and vegetable intake, but also decreases days with functional limitations while having no impact on healthcare access. Subsample analyses reveal that the increase in weight and decrease in fruit and vegetable intake are driven by the older population, married, and whites. The improvement in self-reported health is especially strong among non-whites, females, and married.


Factors associated with intention to breastfeed in Vietnamese mothers: A cross-sectional study.
Breastfeeding has many benefits for mothers, children, and the environment over both the short and longr-term. Prenatal intention to breastfeed is a powerful predictor of short-term breastfeeding outcomes. This study aims to analyze breastfeeding intentions, including the intention to feed infants with breastmilk only and to continue exclusive breastfeeding to 6 months among pregnant mothers in Hanoi, Vietnam. The analysis included 1230 singleton mothers, between 24- and 36-weeks' gestation, who attended antenatal clinics in two hospitals in Hanoi in 2020. The proportion of mothers with an "breastfeeding intention" (i.e., intention to feed an infant with breastmilk only) and "exclusive breastfeeding intention" to 6 months was 59.9% and 41.7%, respectively. Mothers who were 25 years or older (aOR = 1.35, 95%CI:1.00-1.81), had an undergraduate educational degree or higher (aOR = 1.38, 95%CI: 1.08-1.76), had observed another woman breastfeeding (aOR = 1.43, 95%CI: 1.03-2.00), were not living with parents-in-law (aOR = 1.34, CI: 1.05-1.70), and were multiparous (aOR = 1.60, 95%CI: 1.16-2.19) had higher odds of "exclusive breastfeeding intention" to 6 months. Among primiparous women, those who thought their husbands support breastfeeding were more likely to intend to feed an infant with breastmilk only. Among multiparous women, feeding the previous child with breastmilk exclusively before the introduction of complementary foods and not giving solid foods together with water until 6 months, were significant predictors for both breastfeeding intentions. Mothers without exclusive breastfeeding experience should be provided with greater support to promote exclusive breastfeeding intention and outcomes.


Alanine scanning mutants of rat proinsulin I show functional diversity of anti-insulin monoclonal antibodies.
In contrast to autoantibodies that are functionally silenced or deleted, IgG Abs that react with autologous insulin routinely follow hormone administration and arise spontaneously in autoimmune (type I) diabetes mellitus. To understand Ab interactions with autologous insulin, rat proinsulin I and 32 alanine substituted analogues were expressed as fusion proteins and used to examine 16 anti-insulin mAb in ELISA. The results identify several amino acid residues that contribute to binding by a large majority (>75%) of mAb, although no single residue is uniformly required for binding by all mAb. Replacements at charged or polar residues on the insulin surface including A4 (Asp), A5 (Gln), A9 (Ser) A12 (Ser), A17 (Gln), A18 (Asn), B13 (Glu), and B21 (Glu) consistently decreased mAb binding. Single alanine substitutions at positions A16 (Leu), A11 (Cys), B8 (Gly), and B15 (Leu) that are predicted to alter the core structure or chain folding vary widely in their impact on Ab binding. mAb that bind insulin preferentially on solid phase (i.e., ELISA) are highly sensitive to replacement of single residues, and substitutions that alter conformation abolish binding. In contrast, high affinity mAb that bind insulin in solution are relatively insensitive to substitutions at single residues, and they maintain binding to all mutants, including those with disrupted conformation. For such high affinity mAb, replacement of long hydrophobic side chains can augment binding, suggesting mAb interactions with insulin include an induced fit. Thus, the ability of insulin to function as a "molten globule" may contribute to the diversity and autoreactivity of the anti-insulin repertoire.


EmPHasis-10 as a measure of health-related quality of life in pulmonary arterial hypertension: data from PHAR.
While the performance of the emPHasis-10 (e10) score has been evaluated against limited patient characteristics within the United Kingdom, there is an unmet need for exploring the performance of the e10 score among pulmonary arterial hypertension (PAH) patients in the United States. Using the Pulmonary Hypertension Association Registry, we evaluated relationships between the e10 score and demographic, functional, haemodynamic and additional clinical characteristics at baseline and over time. Furthermore, we derived a minimally important difference (MID) estimate for the e10 score. We analysed data from 565 PAH (75% female) adults aged mean±sd 55.6±16.0 years. At baseline, the e10 score had notable correlation with factors expected to impact quality of life in the general population, including age, education level, income, smoking status and body mass index. Clinically important parameters including 6-min walk distance and B-type natriuretic peptide (BNP)/N-terminal proBNP were also significantly associated with e10 score at baseline and over time. We generated a MID estimate for the e10 score of -6.0 points (range -5.0--7.6 points). The e10 score was associated with demographic and clinical patient characteristics, suggesting that health-related quality of life in PAH is influenced by both social factors and indicators of disease severity. Future studies are needed to demonstrate the impact of the e10 score on clinical decision-making and its potential utility for assessing clinically important interventions.


Differential modulation of the molecular dynamics of the type IIa and IIc sodium phosphate cotransporters by parathyroid hormone.
The kidney is a key regulator of phosphate homeostasis. There are two predominant renal sodium phosphate cotransporters, NaPi2a and NaPi2c. Both are regulated by parathyroid hormone (PTH), which decreases the abundance of the NaPi cotransporters in the apical membrane of renal proximal tubule cells. The time course of PTH-induced removal of the two cotransporters from the apical membrane, however, is markedly different for NaPi2a compared with NaPi2c. In animals and in cell culture, PTH treatment results in almost complete removal of NaPi2a from the brush border (BB) within 1 h whereas for NaPi2c this process in not complete until 4 to 8 h after PTH treatment. The reason for this is poorly understood. We have previously shown that the unconventional myosin motor myosin VI is required for PTH-induced removal of NaPi2a from the proximal tubule BB. Here we demonstrate that myosin VI is also necessary for PTH-induced removal of NaPi2c from the apical membrane. In addition, we show that, while at baseline the two cotransporters have similar diffusion coefficients within the membrane, after PTH addition the diffusion coefficient for NaPi2a initially exceeds that for NaPi2c. Thus NaPi2c appears to remain "tethered" in the apical membrane for longer periods of time after PTH treatment, accounting, at least in part, for the difference in response times to PTH of NaPi2a versus NaPi2c.


Left ventricular function in adults with muscular dystrophies: genotype-phenotype correlations.
Left ventricular dysfunction (LVD) is a clinical manifestation of muscular dystrophy (MD) in adults and an important prognostic factor. However, there is a lack of recommendations concerning cardiac followup of these patients. The aim of this work was to evaluate the prevalence of systolic LVD in adults with MD. The patients, referred from a Neuromuscular Diseases Unit, underwent clinical evaluation, ECG and transthoracic echocardiogram. Serum troponin I and NT-proBNP were also evaluated. Systolic LVD was defined by an ejection fraction of <0.45 and/or shortening fraction of <0.25. During a one-year period, we evaluated 24 consecutive patients, 16 men, age 33 +/- 12 years (age at myopathy diagnosis 23 +/- 12 years). They had the following MD: dystrophinopathies--four patients (Duchenne: 1, Becker: 3); Steinert myotonic dystrophy--nine patients; limb-girdle myopathies--six patients; facioscapulohumeral (FSH) myopathies--four patients; and one dysferlinopathy (Miyoshi myopathy). The MD diagnosis, based on clinical and histological criteria, was genetically confirmed in 18 cases (75%). Five patients (20.8%) had thoracic pain, four (16.6%) dyspnea and one a history of syncope. ECG abnormalities were present in 14 cases (58.3%). Stolic LVD or left ventricular remodeling were present in six patients (25%): three with dystrophinopathies, one with limb-girdle myopathy, one with FSH dystrophy and one with myotonic dystrophy. Three patients (12.5%) were diagnosed with heart failure according to the European Society of Cardiology criteria. Three of the five patients with left ventricular dysfunction had elevation of NT-proBNP. One patient with Becker dystrophy had slight elevation of troponin I. In patients with systolic LVD or LV remodeling, the mutations identified were: deletion in intron 1 to exon 49 (one Duchenne MD patient) and deletions in exons 45 to 51 (two Becker MD patients) in the dystrophin gene; deletion of D4Z4 repeats in the DFS locus (4q35) (one patient with FSH MD); and 1300-1500 CTG triplet repeats in the DMPK gene (one patient with myotonic dystrophy). These results, although preliminary, show that a high percentage of patients with genetically determined skeletal myopathies exhibit cardiac myocyte functional impairment, with severe LVD and heart failure, justifying periodic cardiovascular evaluation. In the future, phenotype-genotype correlations could help to determine the best cardiac surveillance in MD patients.


Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways.
A standard therapy used today for prostate cancer is androgen ablation by gonadotropin-releasing hormone analogs (GnRH-a). Although most patients respond to androgen ablation as an initial systemic therapy, nearly all cases will develop androgen resistance, the management of which is still a major challenge. Here, we report that GnRH-a can directly induce apoptosis of the androgen-independent prostate cancer-derived DU145 and PC3 cell lines. Using specific inhibitors, we found that the apoptotic effect of GnRH-a is mediated by c-Jun NH2-terminal kinase (JNK) and inhibited by the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (PKB) pathway. Indeed, in DU145 cells, GnRH-a activates the JNK cascade in a c-Src- and MLK3-dependent manner but does not involve protein kinase C and epidermal growth factor receptor. Concomitantly, GnRH-a reduces the activity of the PI3K-PKB pathway, which results in the dephosphorylation of PKB mainly in the nucleus. The reduction of PKB activity releases PKB-induced inhibition of MLK3 and thus further stimulates JNK activity and accelerates the apoptotic effect of GnRH-a. Interestingly, extracellular signal-regulated kinase is also activated by GnRH-a, and this occurs via a pathway that involves matrix metalloproteinases and epidermal growth factor receptor, but its activation does not affect JNK activation and the GnRH-a-induced apoptosis. Our results support a potential use of GnRH-a for the treatment of advanced prostate cancer and suggest that the outcome of this treatment can be amplified by using PI3K-PKB inhibitors.


[Debriefing of psychically traumatized persons].
Debriefing involves the expert psychological care of victims directly following a calamity. It includes seven items: introduction, facts, thoughts, emotions, symptoms, education, and conclusion. It was thought that early debriefing after a calamity would reduce posttraumatic stress disorder later on, but controlled trials have yielded equivocal results; in some the stress disorder was even more severe in debriefed persons. People with an adequate social network may not need debriefing.


Time-Gated Raman Spectroscopy for Quantitative Determination of Solid-State Forms of Fluorescent Pharmaceuticals.
Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 × (2) × 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.


MRI assessment of cervical spinal cord cross-sectional area in patients with multiple sclerosis.
Spinal cord abnormalities including cervical cord atrophy are common in multiple sclerosis (MS). This study aimed to assess the cervical spinal cord cross-sectional area (CSA) using magnetic resonance imaging (MRI) in MS patients. Sixty participants were enrolled in this study (16 male and 44 female), 30 patients with MS, diagnosed according to the revised McDonald criteria, and 30 apparently healthy individuals as the control group. CSA of the spinal cord was measured on axial T2-weighted images of the cervical MRI studies from C2 to C7 vertebral levels. There was a significant difference between MS patients and the control group in mean CSA at a different level. The mean CSA at C2, in MS cases, was significantly lower than controls (67.7 ± 9.4 mm2 vs. 81.3 ± 4.6 mm2). Similarly, the mean CSA at C7 (64.4 ± 9.9 mm2) and average C2-7 (68 ± 9.1 mm2) of MS cases were significantly lower than the control. There was a strong inverse correlation between mean cervical cord CSA and duration of the disease and disability score. The reduction in cervical cord CSA was more prominent in patients with secondary progressive MS. There was no significant difference regarding age, gender, type of treatment, or the number of cervical cord lesions. The mean CSA was significantly lower in patients with MS than in the control group and was lesser in progressive types. Patients with a longer duration of MS and a high disability score tend to have smaller CSA.


Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue.
Benefit from selective serotonin reuptake inhibitor (SSRI) treatment in major depressive disorder (MDD) usually takes several weeks. Typically, a third of patients achieve remission and roughly half achieve response with acute treatment. This open-label study evaluated the efficacy and safety of modafinil treatment initiated with an SSRI in patients with MDD and fatigue. Twenty-nine patients with DSM-IV MDD, free from antidepressant therapy (> or = 4 weeks), were administered modafinil (titrated to 200 mg/day) and fluoxetine or paroxetine (20 mg/day) for 6 weeks. Assessments included the 21-item Hamilton Rating Scale for Depression (HAM-D), Structured Interview Guide for the HAM-D (SIGH-D), Fatigue Severity Scale (FSS), and Epworth Sleepiness Scale (ESS). The SIGH-D ratings were videotaped and rated by an independent rater masked to the visit schedule. Data were collected from August 2002 through March 2003. Modafinil combined with an SSRI at treatment initiation significantly improved mean total SIGH-D scores within 1 week (-9.3, p <.001), and this improvement was progressive throughout the study (-21.2 at week 6, p <.001). Forty-two percent (11 of 26) and 79% (19 of 24) of patients were responders, and 39% (10 of 26) and 58% (14 of 24) of patients were remitters (HAM-D) by week 2 and week 6, respectively. Adjunct modafinil rapidly and significantly reduced fatigue (FSS score reduction from baseline = 0.7 at week 1, p <.01) and improved wakefulness (ESS score reduction from baseline = 3.6 at week 1, p <.01). The combination caused few adverse events, with nausea and headache being the most common. Modafinil combined with an SSRI at treatment initiation may enhance the onset and degree of symptom benefit in patients with MDD and fatigue. Treatment with adjunct modafinil was generally well tolerated, with most adverse effects being mild or moderate in severity.


Sclerostin Blockade and Zoledronic Acid Improve Bone Mass and Strength in Male Mice With Exogenous Hyperthyroidism.
Hyperthyroidism in mice is associated with low bone mass, high bone turnover, and high concentrations of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either increasing bone formation with sclerostin antibodies (Scl-Ab) or reducing bone turnover with bisphosphonates on bone mass and strength in hyperthyroid mice. Twelve-week-old C57BL/6 male mice were rendered hyperthyroid using l-thyroxine (T4; 1.2 µg/mL added to the drinking water) and treated with 20 mg/kg Scl-Ab twice weekly or 100 µg/kg zoledronic acid (ZOL) once weekly or phosphate-buffered saline for 4 weeks. Hyperthyroid mice displayed a lower trabecular bone volume at the spine (-42%, P < 0.05) and the distal femur (-55%, P < 0.05) compared with euthyroid controls. Scl-Ab and ZOL treatment of hyperthyroid mice increased trabecular bone volume at the spine by threefold and twofold, respectively. Serum bone formation and resorption markers were increased in hyperthyroid mice and suppressed by treatment with ZOL but not Scl-Ab. Trabecular bone stiffness at the lumbar vertebra was 63% lower in hyperthyroid mice (P < 0.05) and was increased fourfold by Sci-Ab (P < 0.001) and threefold by ZOL treatment (P < 0.01). Bone strength based on ultimate load, which was 10% lower in hyperthyroidism, was increased by Scl-Ab by 71% and ZOL by 22% (both P < 0.001). Increased proportion of low mineralized bone seen in hyperthyroid mice was restored by treatment with Scl-Ab and ZOL. Thus, bone-forming and antiresorptive drugs prevent bone loss in hyperthyroid mice via different mechanisms.


Carcinoma of the esophagus: an analysis of results and of treatment techniques.
Results of radiation therapy in 85 patients with squamous cell carcinoma of the esophagus are presented. Whereas the majority of patients with this tumor have been shown to die within the first year, occasional patients may survive longer (21.5 percent in this series); late radiation complications must therefore be maintained at a minimum. A localization technique to evaluate esophageal mobility away from the spinal cord is described.


Studies of Staphylococcus aureus FabI inhibitors: fragment-based approach based on holographic structure-activity relationship analyses.
FabI is a key enzyme in the fatty acid metabolism of Gram-positive bacteria such as Staphylococcus aureus and is an established drug target for known antibiotics such as triclosan. However, due to increasing antibacterial resistance, there is an urgent demand for new drug discovery. Recently, aminopyridine derivatives have been proposed as promising competitive inhibitors of FabI. In the present study, holographic structure-activity relationship (HQSAR) analyses were employed for determining structural contributions of a series containing 105 FabI inhibitors. The final HQSAR model was robust and predictive according to statistical validation (q2 and r2pred equal to 0.696 and 0.854, respectively) and could be further employed to generate fragment contribution maps. Then, final HQSAR model together with FabI active site information can be useful for designing novel bioactive ligands.


The relationship between hospital charges and a modified Parsonnet risk score.
Health care now consumes approximately 14 percent of the U.S. Gross National Product (GNP). The amount of money spent on health care in America per capita and as a percentage of GNP far exceeds that of any other industrialized country. Currently, the financial burden of health care is being shouldered by government and business. The expenditure of billions of dollars of corporate profits on health care progressively undermines the global competitiveness of American business. These economic realities have emerged as the dominant driving force in health care reform. Cost control efforts to date have focused on strategies to limit inpatient hospital expenditures. The DRG prospective payment system is designed to reimburse a fixed sum based on the diagnostic category of the patient. The DRG payment is essentially independent of underlying patient characteristics that can potentially drive up expenditures. The work reported in this article was done to develop a descriptive formula that could be used to predict resource consumption in the care of patients. The financial viability of a hospital depends on its ability to predict expenditures, allocate resources, and choose its service areas correctly. Errors in financial forecasting in the era of prospective payment will result in financial failures of entire institutions.


Participation in a System-Thinking Simulation Experience Changes Adverse Event Reporting.
System failures are contributing factors in the thousands of adverse events occurring in US healthcare institutions yearly. This study explored the premise that exposure to a simulation experience designed to improve system thinking (ST) would impact adverse event reporting patterns. An intervention-control study was used to explore impacts of participation in a simulation designed to improve ST on adverse event reporting. Each summer Bachelor in Nursing Science students along with medical students participate in a week-long simulation-based interprofessional patient safety course. During the 2017 course, Friday Night in the ER, a table-top simulation designed to develop ST was included. As part of the school nursing's simulation program, students are asked to report adverse events observed or committed during simulation encounters into a simulated adverse event reporting system outside the simulation-based interprofessional patient safety course. Adverse event reporting system data were used to examine patterns of adverse event reporting in control and intervention groups studied. Findings demonstrated differences in proportions of reported adverse events. The proportion of reported adverse events by students with the second and terminal semesters of course work combined and the 2016 and 2018 control groups combined demonstrated statistically significant differences, P < 0.001. Additional analysis revealed that the intervention group reported more medication-related events, whereas the control group reported more failure to rescue and airway-related events. Exposure to a simulation designed to develop ST seems to impact adverse event reporting. These findings support the idea that ST may change safety monitoring behaviors.


[Biophysical double-lives, 1939-1946. Or: spaces of boredom. On 'information discourse' and (dis)continuities in the life sciences].
Arguably, few things have shaped the historiography of the mid-twentieth century psy-sciences (and indeed, of the life sciences and science/technology/intellectual life quite generally) more profoundly than the story of cybernetics. This essay aims to undermine this technofuturistic picture of epistemological upheavals, of cyborg regimes of knowing, and of the incipient post-human, by reinserting back into the story the rather dull and unspectacular lives (and occupations) of the great majority of British, 'diverted' biologists during World War II. Instead of Ratio Clubbers or Macy-Conference frequenters, this essay is concerned with a much larger population of would-be biologists and their most pedestrian appropriations of, and exposures to, electronics. What I argue is that the prevalence and systematicity of such exposures in the course of the personnel-hungry radio-war points to a very different--low-key--picture of the war/technology-induced deflections of biological science at mid-century. As an example of how deeply at odds narrations of cybernetic's ascent tend to sit with developments on ground level, special attention will be devoted to the physiologists-turned-radar-scientists Alan Hodgkin and Andrew Huxley, and their war-time, or more properly, spare-time investigations into the biophysics of nerve. The latter--technical, difficult, and utterly unphilosophical--while absent from the cyber-theme-focused historiography, provided the basis for the tremendous impact Hodkgin and Huxley would in fact have on the mainstream, disciplinarily conservative physiological sciences; the larger aim however is to weave these far from peculiar biographical trajectories into a somewhat bigger picture of the intersections between radar electronics and biological science: a picture which does not centre on sensational discourses but on mundane electronic practices; and thus, on the generational experience of those who were known at the time as "ex radar folk with biological leanings".


Promotion and nucleation of carbonate precipitation during microbial iron reduction.
Iron-bearing early diagenetic carbonate cements are common in sedimentary rocks, where they are thought to be associated with microbial iron reduction. However, little is yet known about how local environments around actively iron-reducing cells affect carbonate mineral precipitation rates and compositions. Precipitation experiments with the iron-reducing bacterium Shewanella oneidensis MR-1 were conducted to examine the potential role of cells in promoting precipitation and to explore the possible range of precipitate compositions generated in varying fluid compositions. Actively iron-reducing cells induced increased carbonate mineral saturation and nucleated precipitation on their poles. However, precipitation only occurred when calcium was present in solution, suggesting that cell surfaces lowered local ferrous iron concentrations by adsorption or intracellular iron oxide precipitation even as they locally raised pH. Resultant precipitates were a range of thermodynamically unstable calcium-rich siderites that would likely act as precursors to siderite, calcite, or even dolomite in nature. By modifying local pH, providing nucleation sites, and altering metal ion concentrations around cell surfaces, iron-reducing micro-organisms could produce a wide range of carbonate cements in natural sediments.


Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer.
We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.


Altered gene expression in murine placentas in an infection-induced intrauterine growth restriction model: a microarray analysis.
The biological mechanisms leading to incomplete intrauterine growth are not completely elucidated and few studies have investigated infection-mediated growth restriction. In this investigation we report the alterations induced by maternal infectious challenge in placental gene expression patterns using a murine model. Pregnant dams were challenged at day E7.5 with the oral human pathogen Campylobacter rectus to elicit fetal growth restriction. At embryonic day E16.5 placentas were collected to compare placental gene expression patterns from normal fetuses of unchallenged dams and growth restricted fetuses from infected dams. Differential gene expression patterns were determined using Agilent Oligo array (G4121A) with a false discovery rate of P<0.05 and pathway analyses were performed. Seventy-four genes were differentially expressed during infection-mediated growth restriction with 9 genes significantly up-regulated, indicating that the effects of maternal infection on gene expression were predominantly suppressive. Pathway analyses indicated that 46 of the 65 genes that were significantly down-regulated were associated with placental/fetal development, and 26 of those were imprinted genes. Among the 9 genes that were up-regulated, 4 are involved in oxygen supply to the fetus and the development of the vascular system. Microarray analysis demonstrated that in the pregnant mouse model, maternal infection that induced growth restriction was associated with down-regulated placental expression of critical growth and developmental related genes, including many imprinted genes. These findings may have significant implications for our understanding of the mechanisms underlying infection-associated human fetal growth restriction and the role of differential placental expression of imprinted genes in fetal growth.


Tissue expander breast reconstruction using prehydrated human acellular dermis.
Human acellular dermal matrices help facilitate immediate tissue expander-implant breast reconstruction by providing support to the inferolateral pole, improving control of implant position, and enhancing early volume expansion. Although several freeze-dried human acellular dermal products have demonstrated reasonable safety and efficacy in immediate tissue expander-implant breast reconstruction, no dedicated studies have evaluated clinical outcomes of prehydrated human acellular dermal matrix (PHADM) in breast reconstruction. The outcomes of 121 consecutive tissue expander reconstructions performed by the senior author using PHADM were evaluated. Mean intraoperative tissue expander fill volume was 256.6 ± 133 mL, 60% of final expander volume. Patients required an average of 3.2 additional expansions prior to tissue expander-to-implant exchange. Mean follow-up period after reconstruction was 44 ± 26.5 weeks. Complications occurred in 20 (16.5%) breasts, including 9 (7.4%) soft-tissue infections, 8 (6.6%) partial mastectomy flap necroses, and 2 (1.7%) seromas. Eleven (9.1%) breasts ultimately required explantation. Patients receiving radiation demonstrated a strong trend toward greater complications (30.8% vs. 13.7%, P = 0.0749). The outcomes and complication rates of PHADM tissue expander breast reconstruction are comparable to those reported with freeze-dried human acellular dermis.


Prognostic value of somatostatin receptor-2 positivitiy in gastroenteropancreatic neuroendocrine tumors in reference to known prognostic factors.
Identification of the predictive factors for the prognosis of gastroenteropancreatic neuroendocrine tumors is important but rather challenging due to the rarity of the condition. This study aimed to examine the association between somatostatin receptor-2 positivity and known prognostic factors for gastroenteropancreatic neuroendocrine tumor to identify the value of somatostatin receptor-2 positivity itself as a predictive factor for prognosis. Records of 41 gastroenteropancreatic neuroendocrine tumor patients (24 females, 17 males) were retrospectively reviewed. The relations between somatostatin receptor-2 positivity and known prognostic factors including tumor stage, Ki-67 positivity, vascular or perineural invasion, lymph node metastasis, presence of necrosis, and soft tissue extension were analyzed. Sixty percent of the patients had histologically confirmed somatostatin receptor-2 positivity with 45% exhibiting focal and 15% showing diffuse staining characteristic. No significant relation was found between somatostatin receptor-2 positivity and any of the known prognostic factors for gastroenteropancreatic neuroendocrine tumor: versus stage, p=0.67; vs. lymph node metastasis, p=0.51; vs. vascular invasion, p=0.11; vs. extension to surrounding soft tissue, p=0.54; vs. necrosis, p=0.23; vs. lymphatic invasion, p=0.25; and vs. perineural invasion, p=0.42. Somatostatin receptor-2 positivity, either focal or diffuse, does not seem to predict prognosis in gastroenteropancreatic neuroendocrine tumors. However, growing evidence supports the benefits of somatostatin analogues as adjunctive treatment in this group of patients.


Differences in Conformational Sampling and Intrinsic Electric Fields Drive Ion Binding in Telomeric and TERRA G-Quadruplexes.
The formation of G-quadruplexes (GQs) occurs in guanine-rich sequences of DNA and RNA, producing highly stable and structurally diverse noncanonical nucleic acid structures. GQs play crucial roles in regulating transcription, translation, and replication and maintaining the genome, among others; thus, changes to their structures can lead to diseases such as cancer. Previous studies using polarizable molecular dynamics simulations have shown differences in ion binding properties between telomeric and telomeric repeat-containing RNA GQs despite architectural similarities. Here, we used volume-based metadynamics and repulsive potential simulations in conjunction with polarizable force fields to quantify the impact of ion binding on the GQ dynamics and ion binding free energies. Furthermore, we describe how GQs exert electric fields on their surroundings to link dynamics with variations in the electronic structure. Our findings provide new insights into the energetic, physical, and conformational properties of GQs and expose subtle but important differences between DNA and RNA GQs with the same fold.


Predicting saturated fat consumption: exploring the role of subjective well-being.
Consumption of saturated fat (SF) is associated with obesity, cardiovascular disease and cancer; which are among the leading causes of death in Australia and worldwide. A causal relationship between subjective well-being and positive health outcomes has been established, although few studies have specifically focused on health-enhancing or health-risk behaviours. The aim of this research was to develop an improved understanding of the processes underlying SF consumption by exploring the relationship between subjective well-being and SF consumption, within the Theory of Planned Behaviour framework. Questionnaires related to the TPB variables, subjective well-being and SF intake were administered online to 96 participants. Perceived behavioural control (PBC) was found to be a significant predictor of intention to limit SF intake. Intention and PBC accounted for 25% of variance in behaviour; with PBC the only significant predictor of SF consumption. While subjective well-being variables were not significant unique predictors of SF consumption, these variables contributed an additional 2% to the prediction of behaviour, and this model was significant. The addition of subjective well-being to the TPB is novel and the results partially support the potential of subjective well-being in improving the prediction of this health-risk behaviour. Future research will need to replicate and extend these preliminary findings before such a framework may be translated into an intervention targeting SF consumption.


Regulation of growth and metabolism by imprinted genes.
A small sub-set of mammalian genes are subject to regulation by genomic imprinting such that only one parental allele is active in at least some sites of expression. Imprinted genes have diverse functions, notably including the regulation of growth. Much attention has been devoted to the insulin-like growth factor signalling pathway that has a major influence on fetal size and contains two components encoded by the oppositely imprinted genes, Igf2 (a growth promoting factor expressed from the paternal allele) and Igf2r (a growth inhibitory factor expressed from the maternal allele). These genes fit the parent-offspring conflict hypothesis for the evolution of genomic imprinting. Accumulated evidence indicates that at least one other fetal growth pathway exists that has also fallen under the influence of imprinting. It is clear that not all components of growth regulatory pathways are encoded by imprinted genes and instead it may be that within a pathway the influence of a single gene by each of the parental genomes may be sufficient for parent-offspring conflict to be enacted. A number of imprinted genes have been found to influence energy homeostasis and some, including Igf2 and Grb10, may coordinate growth with glucose-regulated metabolism. Since perturbation of fetal growth can be correlated with metabolic disorders in adulthood these imprinted genes are considered as candidates for involvement in this phenomenon of fetal programming.


Computational modelling of the speed-accuracy tradeoff: No evidence for an association with depression symptomatology.
Successful decision making often requires finding the right balance between the speed and accuracy of responding: Emphasising speed can lead to error-prone performance, yet emphasising accuracy leads to a slowing of performance. Such speed-accuracy tradeoffs (SATs) therefore require establishing appropriate response settings to optimise performance in response to changing environmental demands. Such strategic adaptation of response settings relies on the striatum component of the basal ganglia, an area implicated in depression. The current study explored the association between depression symptomatology and SAT performance. Two experiments presented participants with an SAT paradigm embedded within a simple decision-making task, together with measures of depression symptomatology. Experiment 1 (N = 349) was correlational, whereas Experiment 2 was a two-phase experiment where participants (N = 501) were first pre-screened on depression symptomatology and extreme-low and extreme-high responders (total N = 91) were invited to Phase 2. Behavioural data were modelled with a drift diffusion model. Behavioural data and associated diffusion modelling showed large and robust SAT effects. Emphasising accuracy led to an increase in boundary separation, an increase in drift rate, and an increase in non-decision time. However, the magnitude of the changes of these parameters with SAT instructions was not associated with measures of depression symptomatology. The results suggest that the strategic adaptation of response settings in response to environmental changes in speed-accuracy instructions does not appear to be associated with depression symptomatology.


Radiomics and Artificial Intelligence Analysis with Textural Metrics Extracted by Contrast-Enhanced Mammography in the Breast Lesions Classification.
The aim of the study was to estimate the diagnostic accuracy of textural features extracted by dual-energy contrast-enhanced mammography (CEM) images, by carrying out univariate and multivariate statistical analyses including artificial intelligence approaches. In total, 80 patients with known breast lesion were enrolled in this prospective study according to regulations issued by the local Institutional Review Board. All patients underwent dual-energy CEM examination in both craniocaudally (CC) and double acquisition of mediolateral oblique (MLO) projections (early and late). The reference standard was pathology from a surgical specimen for malignant lesions and pathology from a surgical specimen or fine needle aspiration cytology, core or Tru-Cut needle biopsy, and vacuum assisted breast biopsy for benign lesions. In total, 104 samples of 80 patients were analyzed. Furthermore, 48 textural parameters were extracted by manually segmenting regions of interest. Univariate and multivariate approaches were performed: non-parametric Wilcoxon-Mann-Whitney test; receiver operating characteristic (ROC), linear classifier (LDA), decision tree (DT), k-nearest neighbors (KNN), artificial neural network (NNET), and support vector machine (SVM) were utilized. A balancing approach and feature selection methods were used. The univariate analysis showed low accuracy and area under the curve (AUC) for all considered features. Instead, in the multivariate textural analysis, the best performance considering the CC view (accuracy (ACC) = 0.75; AUC = 0.82) was reached with a DT trained with leave-one-out cross-variation (LOOCV) and balanced data (with adaptive synthetic (ADASYN) function) and a subset of three robust textural features (MAD, VARIANCE, and LRLGE). The best performance (ACC = 0.77; AUC = 0.83) considering the early-MLO view was reached with a NNET trained with LOOCV and balanced data (with ADASYN function) and a subset of ten robust features (MEAN, MAD, RANGE, IQR, VARIANCE, CORRELATION, RLV, COARSNESS, BUSYNESS, and STRENGTH). The best performance (ACC = 0.73; AUC = 0.82) considering the late-MLO view was reached with a NNET trained with LOOCV and balanced data (with ADASYN function) and a subset of eleven robust features (MODE, MEDIAN, RANGE, RLN, LRLGE, RLV, LZLGE, GLV_GLSZM, ZSV, COARSNESS, and BUSYNESS). Multivariate analyses using pattern recognition approaches, considering 144 textural features extracted from all three mammographic projections (CC, early MLO, and late MLO), optimized by adaptive synthetic sampling and feature selection operations obtained the best results (ACC = 0.87; AUC = 0.90) and showed the best performance in the discrimination of benign and malignant lesions.


[The association between post anoxic encephalopathy and startle epilepsy].
The startle is a variant of primitive physiological reflex, present in developed animals. It could be defined as a sudden defensive reaction triggered by an adequate sensorial stimulus, most effective if auditory, consisting under a clinical basis on the sudden and sequential contraction of some muscular groups, in first place affecting the facial territory (orbicularis oculi bilaterally), followed by the rest of the cranial nerves, the axial musculature and finally the limbs, predominantly proximal and flexor regions of superior extremities. The pathological startle is that which is precipitated by inadequate stimulus and excessive in response to it (under a low level of intensity or duration). It appears on account of different causes and mechanisms, among them a peculiar form of reflex epilepsy, the startle epilepsy. This form of epilepsy commonly present on infant postanoxic encephalopathy, shares its clinical features with other causes of pathologic startle, even though it presents a very characteristic electroencephalographic semiology. We present the case of a child with a startle epilepsy clinically presented as a form of subintrant status epilepticus under the context of a postanoxic encephalopathy secondary to drowsiness. With an adequate treatment it was possible to eliminate the epileptic phenomena, thus notoriously improving his quality of life (vigil and asleep). We review the characteristics and classifications of a variant of reflex epilepsy, the startle epilepsy.


[Toxoplasma serology in HIV infected patients and suspected cerebral toxoplasmosis at the Central Hospital of Bobo-Dioulasso (Burkina Faso)].
A study was conducted in the Internal Medicine unit of Bobo-Dioulasso Hospital. Of the 1828 HIV positive patients admitted in medical wards, 268 presented neurological symptoms. 25.4% had positive Toxoplasma gondii serology. Encephalitis was associated with 12.5% of this latter group and intracranial hypertension with focal neurological defects affected a further 47.5% of them. Presumptive treatment of toxoplasmosis led to significant clinical improvement in 60% of cases. Toxoplasma gondii serology should be part of the standard check-up for every HIV-infected patient, and toxoplasmosis chemoprophylaxis should be given to those with positive toxoplasma serology. Presumptive therapy of toxoplasmosis should be started for all HIV positive patients with focal neurological manifestations in the absence of a cerebral scanner.


Laparoscopic intraoperative ultrasonography.
Ultrasonography has been an integral part of gynecology and general surgery in recent years. New technology has allowed this modality to be extended to include intraoperative assessment through a laparoscopic approach. This allows more accurate imaging with higher resolution than previously attainable. Combining the ultrasonic and visual images on the monitor screen simultaneously (picture in a picture) allows a further dimension of information which can modify surgical direction. The equipment used by the author is described and clinical experience discussed. Further clinical applications are considered and the prac- ticality of the methodology assessed.


Molecular Characterization Identifies Upstream Presence of IS Aba1 to OXA Carbapenemase Genes in Carbapenem-Resistant Acinetobacter baumannii.
Background Evaluating the expression pattern of oxacillinases (OXA) carbapenemases is essential to understand the prevalence and spread of carbapenem resistance Acinetobacter baumannii . Objectives The aim of the study is to evaluate the presence of OXA carbapenemase genes and IS Aba1 upstream to these genes in carbapenem-resistant A. baumannii clinical isolates. Materials and Methods A. baumannii isolated from clinical samples were phenotypically identified and antibiotics sensitivity was performed. Multiplex polymerase chain reaction (PCR) was used to detect OXA51-like gene, OXA carbapenemases genes (OXA-23-like, OXA-24-like, and OXA-58-like), and IS Aba1 in carbapenem-resistant isolates. Results Out of 55 Acinetobacter isolates, 54 were confirmed as A. baumannii by PCR. Bla OXA-23 -like gene was observed in 51 isolates of A. baumannii and none of the isolates showed the presence of bla OXA-24 -like and bla OXA-58 -like genes. Presence of IS Aba1 upstream to OXA-23-like gene, OXA-51-like gene, and both OXA-51-like/OXA-23-like genes was observed in 51, 7, and 4 A. baumannii isolates, respectively. Conclusion The genetic pattern of carbapenem-resistant A. baumannii isolated in this study was unique, which should be factored for clinical protocols to manage infections caused by emerging resistant strains of A. baumannii .


The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis.
The iron storage protein ferritin has been continuously studied for over 70years and its function as the primary iron storage protein in cells is well established. Although the intracellular functions of ferritin are for the most part well-characterized, the significance of serum (extracellular) ferritin in human biology is poorly understood. Recently, several lines of evidence have demonstrated that ferritin is a multi-functional protein with possible roles in proliferation, angiogenesis, immunosuppression, and iron delivery. In the context of cancer, ferritin is detected at higher levels in the sera of many cancer patients, and the higher levels correlate with aggressive disease and poor clinical outcome. Furthermore, ferritin is highly expressed in tumor-associated macrophages which have been recently recognized as having critical roles in tumor progression and therapy resistance. These characteristics suggest ferritin could be an attractive target for cancer therapy because its down-regulation could disrupt the supportive tumor microenvironment, kill cancer cells, and increase sensitivity to chemotherapy. In this review, we provide an overview of the current knowledge on the function and regulation of ferritin. Moreover, we examine the literature on ferritin's contributions to tumor progression and therapy resistance, in addition to its therapeutic potential.


Dual action of the active oxygen species during plant stress responses.
Adaptation to environmental changes is crucial for plant growth and survival. However, the molecular and biochemical mechanisms of adaptation are still poorly understood and the signaling pathways involved remain elusive. Active oxygen species (AOS) have been proposed as a central component of plant adaptation to both biotic and abiotic stresses. Under such conditions, AOS may play two very different roles: exacerbating damage or signaling the activation of defense responses. Such a dual function was first described in pathogenesis but has also recently been demonstrated during several abiotic stress responses. To allow for these different roles, cellular levels of AOS must be tightly controlled. The numerous AOS sources and a complex system of oxidant scavengers provide the flexibility necessary for these functions. This review discusses the dual action of AOS during plant stress responses.


Fall impacts from standing show equivalence between experts in stage combat landing strategy and naïve participants after training.
Slips, trips, and falls are the second leading cause of non-fatal injuries in workplace in the United States. A stage combat landing strategy is used in the theatre arts to reduce the risk of fall-induced injury, and may be a viable approach among some working populations. The goal of this study was to compare fall impact characteristics between experts in stage combat landing strategy and naïve participants after four training sessions of stage combat landing strategy training. Forward and backward falls from standing were induced by releasing participants from static leans. Participants fell onto a foam mat, and impact force was measured using force platforms under the mat. A statistical equivalence test was used to determine if impact characteristics between groups were similar. Results indicated equivalence between groups in peak impact force during backward but not forward falls. Equivalence between groups in impact time suggested a mechanism by which equivalence in peak impact force as achieve. Four training sessions was sufficient for naïve participants to exhibit fall impact characteristics similar to experts in an anecdotally-effective landing strategy, and support further study. To our knowledge, this was the first study to investigate training for a landing strategy involving stepping after losses of balance from standing.


Mineral water intake reduces blood pressure among subjects with low urinary magnesium and calcium levels.
Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure. A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks. Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks. The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium.


Ontogeny and social dominance: a developmental view of human power patterns.
Developmental science has long evolutionary roots and has historically focused on individual differences. Accordingly, developmental models can inform conversations about phylogeny and personality. The present paper evokes life history theory to describe a theoretical model of competitive behavior that applies to both children and adults (resource control theory: RCT). The model suggests that prosocial and coercive behavior, though different in manifest form, serve similar evolutionary functions. Accordingly, RCT presents a view on social dominance that gives primacy to function over form that contrasts sharply from traditional views. This reformulation gives rise to novel questions (both developmental and non-developmental) and challenges long accepted views on prosociality (e.g., that it is altruistic) and aggression (e.g., that it is maladaptive). Similarly, RCT gives rise to a minority perspective that aligns aggression with social competence.


The current state of cancer family history collection tools in primary care: a systematic review.
Systematic collection of family history is a prerequisite for identifying genetic risk. This study reviewed tools applicable to the primary care assessment of family history of breast, colorectal, ovarian, and prostate cancer. MEDLINE, EMBASE, CINAHL, and Cochrane Central were searched for publications. All primary study designs were included. Characteristics of the studies, the family history collection tools, and the setting were evaluated. Of 40 eligible studies, 18 relevant family history tools were identified, with 11 developed for use in primary care. Most collected information on more than one cancer and on affected relatives used self-administered questionnaires and paper-based formats. Eleven tools had been evaluated relative to current practice, demonstrating 46-78% improvement in data recording over family history recording in patient charts and 75-100% agreement with structured genetic interviews. Few tools have been developed specifically for primary care settings. The few that have been evaluated performed well. The very limited evidence, which depends in part on extrapolation from studies in settings other than primary care, suggests that systematic tools may add significant family health information compared with current primary care practice. The effect of their use on health outcomes has not been evaluated.


Non-frozen preservation of mammalian tissue using green tea polyphenolic compounds.
The number of tissue or organ transplants has increased substantially in recent years with the advances in surgical methods and the development of immunosuppressive agents. Ideally, tissues should be transplanted immediately from the donor to the recipient. However, this is not always possible, and the problem of tissue preservation is very important for ensuring a successful transplantation. Therefore, it is essential to develop storage solutions that can maintain the viability and function of the tissues or organs for longer periods. Recent improvements in tissue and organ harvesting techniques and cryopreservation have made it possible to store various kinds of allografts and subsequently use these grafts as alternatives for supply-limited autografts. Moreover, tissue engineering techniques and regenerative medicine have been explored as a potential method to restore natural tissue and repair lesions. Nevertheless, no optimal method for the cryopreservation of mammalian tissues or organs as well as tissue engineered products has been established. Also, current methods can result in a substantial loss of function and lead to damage and destruction of the cells and tissues. Green tea polyphenolic compounds (GTPC) are well known as a functional food with various bioactivities, such as anti-oxidative, anti-carcinogenic, anti-mutagenic, anti-inflammatory, anti-microbial and anti-viral activities. However, less attention has been paid to the effects of GTPC on the non-frozen preservation of mammalian cells and blood vessels. Furthermore, the mechanism of this preservation effect of GTPC is not clearly understood. This review was written on the basis of the hypothesis that the non-frozen preservation of mammalian cells or tissues might be involved in cell cycle control through the cytostatic activity of GTPC.


Membrane phospholipid synthesis in Escherichia coli. Cloning of a structural gene (plsB) of the sn-glycerol-3-phosphate acyl/transferase.
Si+ hybrid ColE1 plasmids of the Clarke-Carbon collection (Clarke, C., and Carbon, J. (1976) Cell 9, 91-99) which eliminate the sn-glycerol 3-phosphate growth requirement of a mutant of Escherichia coli with a Km defect in sn-glycerol-3-phosphate acyltransferase (plsB) were identified. Marked overproduction of a plasmid-encoded sn-glycerol-3-phosphate acyltransferase with a wild type Km in a host plsB- background indicates that the hybrid plasmids carry a structural gene for this enzyme. In addition, all of these plasmids suppress the phenotype of a mutation in a second locus involved in phospholipid biosynthesis, dgk (diglyceride kinase), and one of them also bears the dnaB structural gene. Diglyceride kinase activity is also overproduced in these strains. The linkage of plsB, dgk and dnaB loci was confirmed by transduction analysis which demonstrated the clockwise gene order malB, dnaB, dgk, plsB, and uvrA near Minute 91 on the E. coli linkage map. This is in contrast to the previously reported co-transduction of plsB with dctA near Minute 78 (Cronan, J. E., Jr., and Bell, R. M. (1974) J. Bacteriol., 120, 227-233). Recloning of restriction endonuclease fragments and in vitro mutagenesis have localized the dgk, and plsB loci to a 2.2-megadalton DNA segment, and have demonstrated that diglyceride kinase and sn-glycerol-3-phosphate acyltransferase activities reside in separate polypeptides. Availability of these clones and mutationally altered derivatives has allowed the identification of a single polypeptide (Mr = 83,000) corresponding to the sn-glycerol-3-phosphate acyltransferase and purification of this membrane-bound enzyme to near homogeneity (Larson, T. J., Lightner, V. A., Green, P. R., Modrich, P., and Bell, R. M. (1980) J. Biol. Chem. 255, 9421-9426). The size of the plsB polypeptide indicates that a major fraction of the DNA segment to which this gene has been localized is involved in coding for the sn-glycerol-3-phosphate acyltransferase.


Metabolomics of medicinal plants: the importance of multivariate analysis of analytical chemistry data.
Metabolomics, the comprehensive and global analysis of diverse metabolites produced in cells and organisms, has greatly expanded metabolite fingerprinting and profiling as well as the selection and identification of marker metabolites. The methodology typically employs multivariate analysis to statistically process the massive amount of analytical chemistry data resulting from high-throughput and simultaneous metabolite analysis. Although the technology of plant metabolomics has mainly developed with other post-genomics in systems biology and functional genomics, it is independently applied to the evaluation of the qualities of medicinal plants, based on the diversity of metabolite fingerprints resulting from multivariate analysis of non-targeted or widely targeted metabolite analysis. One advantage of applying metabolomics is that medicinal plants are evaluated based not only on the limited number of metabolites that are pharmacologically important chemicals, but also on the fingerprints of minor metabolites and bioactive chemicals. In particular, score plot and loading plot analyses e.g. principal component analysis (PCA), partial-least-squares discriminant analysis (PLS-DA), and discrimination map analysis such as batch-learning self-organizing map (BL-SOM) analysis, are often employed for the reduction of a metabolite fingerprint and the classification of analyzed samples. Based on recent studies, we now understand that metabolomics can be an effective approach for comprehensive evaluation of the qualities of medicinal plants. In this review, we describe practical cases in which metabolomic study was performed on medicinal plants, and discuss the utility of metabolomics for this research field, with focus on multivariate analysis.


A Universal Electrode Approach for Automated Electrochemical Molecular Analyses.
Transforming microfluidics-based biosensing systems from laboratory research into clinical reality remains an elusive goal despite decades of intensive research. A fundamental obstacle for the development of fully automated microfluidic diagnostic systems is the lack of an effective strategy for combining pumping, sample preparation, and detection modules into an integrated biosensing platform. Herein, we report a universal electrode approach, which incorporates DC electrolytic pumping, AC electrokinetic sample preparation, and self-assembled monolayer based electrochemical sensing on a single microfluidic platform, to automate complicated molecular analysis procedures that will enable biosensing applications in non-traditional healthcare settings. Using the universal electrode approach, major microfluidic operations required in molecular analyses, such as pumping, mixing, washing, and sensing can be performed in a single platform. We demonstrate the universal electrode platform for detecting bacterial 16S rRNA, a phylogenetic marker, toward rapid diagnostics of urinary tract infection. Since only electronic interfaces are required to operate the platform, the universal electrode approach represents an effective system integration strategy to realize the potential of microfluidics in molecular diagnostics at the point of care.


ADP-ribosylation factor 6 and a functional PIX/p95-APP1 complex are required for Rac1B-mediated neurite outgrowth.
The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1-derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis.


Regional health care systems: implications for health care reform.
Not only should there be payment reform, but health care delivery should be redesigned to achieve the triple goals of access to services, quality improvement, and cost control. The authors review the forces that have formed multihospital and health care systems in the past, and the seven stages that health care systems traverse toward competency. They briefly discuss the implications of those realities for reform implementation. One premise is that the natural evolution of such health care systems toward competency will take a longer time than most nonproviders expect.


Transcriptomics technologies.
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. Here, mRNA serves as a transient intermediary molecule in the information network, whilst noncoding RNAs perform additional diverse functions. A transcriptome captures a snapshot in time of the total transcripts present in a cell. The first attempts to study the whole transcriptome began in the early 1990s, and technological advances since the late 1990s have made transcriptomics a widespread discipline. Transcriptomics has been defined by repeated technological innovations that transform the field. There are two key contemporary techniques in the field: microarrays, which quantify a set of predetermined sequences, and RNA sequencing (RNA-Seq), which uses high-throughput sequencing to capture all sequences. Measuring the expression of an organism's genes in different tissues, conditions, or time points gives information on how genes are regulated and reveals details of an organism's biology. It can also help to infer the functions of previously unannotated genes. Transcriptomic analysis has enabled the study of how gene expression changes in different organisms and has been instrumental in the understanding of human disease. An analysis of gene expression in its entirety allows detection of broad coordinated trends which cannot be discerned by more targeted assays.


Insight into the role of niche concept in deciphering the ecological drivers of MPs-associated bacterial communities in mangrove forest.
Myriad inherent and variable environmental features are controlling the assembly and succession of bacterial communities colonizing on mangrove microplastics (MPs). However, the mechanisms governing mangrove MPs-associated bacterial responses to environmental changes still remain unknown. Here, we assessed the dissimilarities of MPs-associated bacterial composition, diversity and functionality as well as quantified the niche variations of each taxon on plastispheres along river-mangrove-ocean and mangrove landward-to-seaward gradients in the Beibu Gulf, China, respectively. The bacterial richness and diversity as well as the niche breadth on mangrove sedimentary MPs dramatically decreased from landward to seaward regions. Characterizing the niche variations linked the difference of ecological drivers of MPs-associated bacterial populations and functions between river-mangrove-ocean (microplastic properties) and mangrove landward-to-seaward plastispheres (sediment physicochemical properties) to the trade-offs between selective stress exerted by inherent plastic substrates and microbial competitive stress imposed by environmental conditions. Notably, Rhodococcus erythropolis was predicted to be the generalist species and closely associated to biogeochemical cycles of mangrove plastispheres. Our work provides a reliable pathway for tackling the hidden mechanisms of environmental factors driving MPs-associated microbe from perspectives of niches and highlights the spatial dynamic variations of mangrove MPs-associated bacteria.


Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation.
Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of β-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes. Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler "clinically feasible" model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively). Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.


Transcription factors in light and circadian clock signaling networks revealed by genomewide mapping of direct targets for neurospora white collar complex.
Light signaling pathways and circadian clocks are inextricably linked and have profound effects on behavior in most organisms. Here, we used chromatin immunoprecipitation (ChIP) sequencing to uncover direct targets of the Neurospora crassa circadian regulator White Collar Complex (WCC). The WCC is a blue-light receptor and the key transcription factor of the circadian oscillator. It controls a transcriptional network that regulates ∼20% of all genes, generating daily rhythms and responses to light. We found that in response to light, WCC binds to hundreds of genomic regions, including the promoters of previously identified clock- and light-regulated genes. We show that WCC directly controls the expression of 24 transcription factor genes, including the clock-controlled adv-1 gene, which controls a circadian output pathway required for daily rhythms in development. Our findings provide links between the key circadian activator and effectors in downstream regulatory pathways.


Thromboxane synthetase inhibition in acute focal cerebral ischemia in cats.
The purpose of this investigation was to study the effects of a selective thromboxane A2 (TXA2) synthetase inhibitor (TSI) upon the evolution of cerebral infarction in the cat. Adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion for 4 hours followed by a 2-hour period of reperfusion before sacrifice. Ten cats received 3 mg/kg TSI intravenously immediately before, and 10 cats received 3 mg/kg TSI intravenously immediately after MCA occlusion. Ten cats were used as controls receiving no treatment. The bleeding time was determined at baseline and at the end of each experiment. Electroencephalographic (EEG) recordings were obtained before and after MCA clipping and MCA release, and at hourly intervals thereafter. Regional cerebral blood flow (rCBF) was measured using the xenon-133 (133Xe) clearance technique before and after MCA occlusion, after MCA reopening, and before terminating each experiment. Thirty minutes before each cat was sacrificed, Evans blue dye and sodium fluorescein were given intravenously. The animals were then perfused with colloidal carbon and the brains removed and evaluated for midline shift. Evans blue dye and sodium fluorescein extravasation, carbon staining, and infarct size. The bleeding time, arterial blood pressure, rCBF changes, brain swelling, and vital dye extravasation were not statistically different between the three treatment groups. The EEG changes, carbon staining, and infarct size differences between the three groups also failed to reach statistical significance, but there was a suggestion that these parameters were adversely affected in the cats pretreated with TSI. Ten additional cats undergoing MCA occlusion and reperfusion were used for pharmacological studies. Five of them received 3 mg/kg TSI intravenously immediately after MCA occlusion, and serial drug and thromboxane B2 (TXB2) levels (a stable metabolite of TXA2) were determined. Another five cats were not treated and serial TXB2 levels were obtained. Production of TXA2 was inhibited by 95% in cats receiving TSI. In conclusion, thromboxane synthetase inhibition failed to modify favorably the evolution of cerebral infarction. When TSI was given before MCA occlusion, cerebral infarction tended to be more extensive.


IgM polymerization inhibits the Golgi-mediated processing of the mu-chain carboxy-terminal glycans.
Secreted glycoproteins generally contain oligosaccharides of the complex type. However, several molecules have been described in which individual glycans are processed differently from one another. Folding, assembly and oligomerization could affect the maturation of certain glycans by hindering them to the Golgi processing machinery. We have tested this possibility by analysing a panel of engineered murine mu chains secreted as mu2L2 monomers or as polymers, and having or not the carboxy-terminal glycan (Asn563). In secreted IgM polymers, Asn563 bears high-mannose oligosaccharides, typical of endoplasmic reticulum resident proteins, while complex sugars are found at the other four sites (Brenckle and Kornfeld, 1980 Arch. Biochem. Biophys. 243, 605-618). Polymeric and monomeric IgM contain mu chains whose glycans are processed differently. We show here that this is mainly due to the differential processing at the Asn563 glycan, which undergoes Golgi-mediated processing when IgM are secreted in the monomeric form. These results indicate that the oligomerization-dependent accessibility to the sugar modifying enzymes can be one of the key features that dictate the extent of oligosaccharide processing in multimeric glycoproteins. The presence of high mannose glycans at Asn563 implies that IgM polymerization takes place before encountering mannosidase II, likely in a pre-Golgi compartment.


Variable rainfall intensity and tillage effects on runoff, sediment, and carbon losses from a loamy sand under simulated rainfall.
The low-carbon, intensively cropped Coastal Plain soils of Georgia are susceptible to runoff, soil loss, and drought. Reduced tillage systems offer the best management tool for sustained row crop production. Understanding runoff, sediment, and chemical losses from conventional and reduced tillage systems is expected to improve if the effect of a variable rainfall intensity storm was quantified. Our objective was to quantify and compare effects of a constant (Ic) intensity pattern and a more realistic, observed, variable (Iv) rainfall intensity pattern on runoff (R), sediment (E), and carbon losses (C) from a Tifton loamy sand cropped to conventional-till (CT) and strip-till (ST) cotton (Gossypium hirsutum L.). Four treatments were evaluated: CT-Ic, CT-Iv, ST-Ic, and ST-Iv, each replicated three times. Field plots (n=12), each 2 by 3 m, were established on each treatment. Each 6-m2 field plot received simulated rainfall at a constant (57 mm h(-1)) or variable rainfall intensity pattern for 70 min (12-run ave.=1402 mL; CV=3%). The Iv pattern represented the most frequent occurring intensity pattern for spring storms in the region. Compared with CT, ST decreased R by 2.5-fold, E by 3.5-fold, and C by 7-fold. Maximum runoff values for Iv events were 1.6-fold higher than those for Ic events and occurred 38 min earlier. Values for Etot and Ctot for Iv events were 19-36% and 1.5-fold higher than corresponding values for Ic events. Values for Emax and Cmax for Iv events were 3-fold and 4-fold higher than corresponding values for Ic events. Carbon enrichment ratios (CER) were <or=1.0 for ST plots and >or=1.0 for CT plots (except for first 20 min). Maximum CER for CT-Ic, CT-Iv, ST-Ic, and ST-Iv were 2.0, 2.2, 1.0, and 1.2, respectively. Transport of sediment, carbon, and agrichemicals would be better understood if variable rainfall intensity patterns derived from natural rainfall were used in rainfall simulations to evaluate their fate and transport from CT and ST systems.


Cytochrome P-450 monooxygenase system. Localization in smooth muscle of rabbit aorta.
Cytochrome P-450 monooxygenase isozymes and NADPH-cytochrome P-450 reductase were detected in the microsomal fraction of rabbit aorta by immunoblotting and by enzymatic activity. The monomeric molecular weights of aortal proteins that cross-reacted with antibodies to cytochrome P-450 forms 2 or 6 and reductase were identical to those of the proteins purified from the liver. The induction of form 6 immunoreactive protein and O-deethylation of 7-ethoxyresorufin (a reaction catalyzed by form 6) was observed in aorta following treatment of rabbits with 2,3,7,8-tetrachlorodibenzo-p-dioxin or beta-naphthoflavone. The amount of reductase protein (equivalent to 22.4 +/- 3.2 activity units/mg of protein) correlated with the cytochrome c reductase activity (18.3 +/- 1.8 units/mg) and was the same for both treated and untreated rabbits. Consistent with immunoblot data, the amount of form 2 was insufficient for detection of activity (N-demethylation of benzphetamine). Significantly, removal of the endothelium, which was confirmed by light microscopy and by scanning electron microscopy, reduced by only 8 to 32% the specific enzymatic activity or content of immunoreactive proteins; only traces of protein or activity were recovered in the endothelial fraction. In studies of the vasculature, the potential of this metabolic pathway for the activation or detoxication of mutagens, carcinogens, toxins, or drugs and metabolism of endogenous substrates warrants consideration, especially in regard to the mutational events reported to be involved in the formation of atherosclerotic plaques.