Dynamic Stability of Volatile Organic Compounds in Respiratory Air in Schizophrenic Patients and Its Potential Predicting Efficacy of TAAR Agonists.
Volatile organic compounds (VOCs) in the breathing air were found to be altered in schizophrenia patients compared to healthy participants. The aim of this study was to confirm these findings and to examine for the first time whether these VOCs are stable or change in concentration during the early treatment course. Moreover, it was investigated whether there is a correlation of the VOCs with the existing psychopathology of schizophrenia patients, i.e., whether the concentration of masses detected in the breath gas changes when the psychopathology of the participants changes. The breath of a total of 22 patients with schizophrenia disorder was examined regarding the concentration of VOCs using proton transfer reaction mass spectrometry. The measurements were carried out at baseline and after two weeks at three different time points, the first time immediately after waking up in the morning, after 30 min, and then after 60 min. Furthermore, 22 healthy participants were investigated once as a control group. Using bootstrap mixed model analyses, significant concentration differences were found between schizophrenia patients and healthy control participants (m/z 19, 33, 42, 59, 60, 69, 74, 89, and 93). Moreover, concentration differences were detected between the sexes for masses m/z 42, 45, 57, 69, and 91. Mass m/z 67 and 95 showed significant temporal changes with decreasing concentration during awakening. Significant temporal change over two weeks of treatment could not be detected for any mass. Masses m/z 61, 71, 73, and 79 showed a significant relationship to the respective olanzapine equivalents. The length of hospital stay showed no significant relationship to the masses studied. Breath gas analysis is an easy-to-use method to detect differences in VOCs in the breath of schizophrenia patients with high temporal stability. m/z 60 corresponding to trimethylamine might be of potential interest because of its natural affinity to TAAR receptors, currently a novel therapeutic target under investigation. Overall, breath signatures seemed to stable over time in patients with schizophrenia. In the future, the development of a biomarker could potentially have an impact on the early detection of the disease, treatment, and, thus, patient outcome.


Thyroid cancer--surgical decision making.
Although there are arguments for different approaches, we have presented a format based upon the current literature and our clinical experiences for the management for thyroid nodules and cancers. The limited value of suppressive therapy in solitary nodules is stressed. Lobectomy with isthmectomy is the initial surgical procedure for dominant nodules. Total thyroidectomy for proven thyroid cancers is performed when possible. Regional lymph nodes in the central or visceral compartment are removed therapeutically by a modified technique in order to prevent significant functional loss and deformity. In the postoperative period, radioactive iodine therapy can be extremely beneficial. Postoperative thyroid suppressive therapy is useful in patients with thyroid cancer although a third or more of these tumors will eventually escape from beneficial effects. Clinical experiences of recurrent or metastatic thyroid cancer regressions following suppression therapy are difficult to document.


Evolution of paedomorphosis in plethodontid salamanders: ecological correlates and re-evolution of metamorphosis.
Life-history modes can profoundly impact the biology of a species, and a classic example is the dichotomy between metamorphic (biphasic) and paedomorphic (permanently aquatic) life-history strategies in salamanders. However, despite centuries of research on this system, several basic questions about the evolution of paedomorphosis in salamanders have not been addressed. Here, we use a nearly comprehensive, time-calibrated phylogeny of spelerpine plethodontids to reconstruct the evolution of paedomorphosis and to test if paedomorphosis is (1) reversible; (2) associated with living in caves; (3) associated with relatively dry climatic conditions on the surface; and (4) correlated with limited range size and geographic dispersal. We find that paedomorphosis arose multiple times in spelerpines. We also find evidence for re-evolution of metamorphosis after several million years of paedomorphosis in a lineage of Eurycea from the Edwards Plateau region of Texas. We also show for the first time using phylogenetic comparative methods that paedomorphosis is highly correlated with cave-dwelling, arid surface environments, and small geographic range sizes, providing insights into both the causes and consequences of this major life history transition.


Dose-dependent transitions in mechanisms of toxicity: case studies.
Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003.


A study of emergency unit waiting time.
Administrators at Mercy Hospital in Springfield, Massachusetts, studied the effects of daily patient number and arrival rate on waiting time in the Emergency Unit. These two factors were found to have a smaller impact on waiting times than might be expected. Several issues relating to staffing and to patients' illnesses were addressed to reduce visit lengths (ie, inadequate number of admitting registrars, inefficient use of staff, insufficient locations for the rapid treatment of patients requiring suturing, and large numbers of ancillary services requested on a stat basis). Subsequent studies showed that changes instituted as a result of the initial study had reduced overall emergency waiting time by 12%, even though average daily census had increased by 17%.


Permanent Paraplegia as a Complication of Injection of Contrast Media at L2-L3 Vertebral Level.
The lumbar intrathecal (subarachnoid) space is accessed for both therapeutic and diagnostic purposes. Occasionally, the needle may unintentionally enter the intrathecal space during lumbar interlaminar epidural steroid injections (LESIs)-one of the most commonly performed medical procedures in the United States. Ordinarily, this merely constitutes a minor complication or even a desired placement (in the case of some diagnostic procedures). However, some patients have a rare condition wherein the spinal cord terminates below the L2 vertebral level (tethered cord). In such cases, injections administered at the lumbar level may potentially result in spinal cord damage and irreversible paraplegia if the physician performing the intervention does not recognize the intramedullary position of the needle. The aim of this study is to describe and analyze an unintentional L2-L3 injection of contrast medium into a tethered spinal cord. Many physicians may consider lumbar injections "safe" because the spinal cord usually terminates at or above the L2 vertebral level. However, complacency stemming from this false impression of safety contributes to nonadherence to practice guidelines, which may lead to catastrophic neurological complications. Presented here is the first published occurrence of paraplegia that resulted from contrast medium injection into the spinal cord during a myelography study performed below the L2 vertebral level. Disregard of the procedural guidelines by the physicians performing an elective diagnostic intervention may cause devastating neurological complications. The described casualty occurred because of failure to review previous imaging studies, injection of the contrast medium despite unsuccessful attempts to aspirate cerebrospinal fluid, and an unwillingness to terminate the procedure immediately when the patient reported an unusual sensation in both of his lower extremities. Consequently, we suggest that not only for cervical and thoracic but also for lumbar interlaminar ESIs, previous imaging studies should be reviewed before the injection.


A double blind randomised placebo controlled trial of hexopal in primary Raynaud's disease.
The peripheral vasospastic symptoms associated with Raynaud's disease continue to be an unsolved clinical problem. Hexopal (Hexanicotinate inositol) has shown promise in uncontrolled studies and its use in patients with Raynaud's disease may reduce such vasospasm. This study examines the effects of 4 g/day of Hexopal or placebo, during cold weather, in 23 patients with primary Raynaud's disease. The Hexopal group felt subjectively better and had demonstrably shorter and fewer attacks of vasospasm during the trial period. Serum biochemistry and rheology was not significantly different between the two groups. Although the mechanism of action remains unclear Hexopal is safe and is effective in reducing the vasospasm of primary Raynaud's disease during the winter months.


Serological responses to the B subunit of Shiga-like toxin 1 and its peptide fragments indicate that the B subunit is a vaccine candidate to counter action of the toxin.
The B subunit of Shiga toxin and Shiga-like toxin (SLT-1) and its fragments are potentially immunogenic and may generate protective humoral responses against the action of these toxins. We have analyzed the antibody response of rabbits immunized with pure B subunit of SLT-1 or synthetic fragments of the subunit. The immune response to the native B subunit was found to be largely directed at conformational epitopes. More importantly, rabbits immunized with the B subunit were protected from a lethal challenge with SLT-1, indicating that the B subunit represents an excellent vaccine candidate to counter the effects of Shiga toxin and SLT-1 in humans. Polyclonal antibodies against a synthetic peptide corresponding to residues 28 to 40 of the B subunit neutralized the cytotoxicity of SLT-1 towards Vero cells. This region is thus exposed in the native state of the B subunit. The sequence specificity of other antipeptide antisera also provides clues to the state of folding and assembly of the B subunit. Antisera to synthetic peptides representing the N- and C-terminal regions of the SLT-1 B subunit did not cross-react with native B subunit but strongly recognized denatured forms of the protein. Finally, the monoclonal antibody 13C4 was shown to bind to a discontinuous epitope expressed only on the native form of the protein. These immunological reagents can be used to probe the conformational state of the B subunit and the holotoxin as it relates to their functional properties.


Hydroxylation of p-coumaric acid by horseradish peroxidase. The role of superoxide and hydroxyl radicals.
1. In the presence of dihydroxyfumarate, horseradish peroxidase catalyses the conversion of p-coumaric acid into caffeic acid at pH 6. This hydroxylation is completely inhibited by superoxide dismutase. 2. Dihydroxyfumarate cannot be replaced by ascorbate H2O2, NADH, cysteine or sulphite. Peroxidase can be replaced by high (10 mM) concentrations of FeSO4, but this reaction is almost unaffected by superoxide dismutase. 3. Hydroxylation by the peroxidase/dihydroxyfumarate system is completely inhibited by low concentrations of Mn2+ or Cu2+. It is proposed that this is due to the ability of these metal ions to react with the superoxide radical O2--. 4. Hydroxylation is partially inhibited by mannitol, Tris or ethanol and completely inhibited by formate. This seems to be due to the ability of these reagents to react with the hydroxyl radical -OH. 5. It is concluded that O2-- is generated during the oxidation of dihydroxyfumarate by peroxidase and reacts with H2O2 to produce hydroxyl radicals, which then convert p-coumaric acid into caffeic acid.


Effectiveness of 50% nitrous oxide/50% oxygen during laceration repair in children.
To determine the effect of an inhaled 50% nitrous oxide/50% oxygen mixture on measures of observed anxiety in children during laceration repair. A prospective, randomized, placebo-controlled, double-blind comparison of an inhaled 50% nitrous oxide/50% oxygen mixture (treatment group) with 100% oxygen (control group) during repair of lacerations was performed. The study population was a convenience sample of children aged 2-7 years in an urban pediatric ED. The primary outcome variable was the change in scores before and during laceration repair with a 10-point modified Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) assessment. The secondary outcome variable was a 4-point anxiety scale measured before and during the procedure. Thirty patients were entered into the study. Seventeen children inhaled the 50% nitrous oxide/oxygen mixture and 13 inhaled 100% oxygen during laceration repair. There was no statistically significant difference in initial CHEOPS and anxiety scores between the 2 groups (p = 0.687 and 0.809, respectively). The median CHEOPS scores in the treatment group decreased by 5 points, while those of the control patients increased by 3 (p < 0.001). The median anxiety scores in the treatment population decreased by 1 point, with an increase of 1 for the control patients (p < 0.001). Administration of a 50% nitrous oxide/50% oxygen mixture to children during their laceration repair resulted in a significant decrease in measures of anxiety when compared with inhalation of 100% oxygen.


Role of Intracellular and Extracellular MicroRNA-92a in Colorectal Cancer.
Colorectal cancer is one of the leading causes of cancer-related death worldwide. Previous studies have shown that miR-92a has an oncogenic function in several cancers and that its up-regulation is correlated with malignant clinicopathologic behaviors of colorectal cancer. It also has been suggested that circulating miR-92a in patients' plasma can be a potential biomarker for colorectal cancer. However, the precise roles of intracellular and extracellular miR-92a are not yet understood. In this study, we examined the expression levels of miR-92a in colorectal tumors (38 cancer specimens and 56 adenoma specimens) and paired adjacent nontumorous tissues. Increased expression of miR-92a was frequently observed in the cancers compared with that in the adenomas and was correlated with advanced clinical stages, tumor depth, and size. We also demonstrated that the levels of miR-92a within microvesicles (MVs) in the plasma of mice bearing colon cancer xenografts were significantly increased compared with those in control mice. One of the roles of intracellular and extracellular miR-92a was shown to be down-regulation of Dickkopf-3 (Dkk-3), a presumed tumor suppressor gene. Within the colon cancer cells, suppression of Dkk-3 by miR-92a contributed to the cell proliferation. Extracellular miR-92a packed within MVs secreted by colon cancer cells was delivered into endothelial cells and contributed to the proliferation and motility of these cells through down-regulation of the same target gene, Dkk-3. These data suggest that intracellular and extracellular miR-92a had important roles in tumor growth and the tumor microenvironment in colorectal cancer.


No association between myeloperoxidase gene rs2333227 G>A polymorphism and Alzheimer's disease risk: a meta-analysis and trial sequential analysis.
Evidence suggests that there is a close association between myeloperoxidase (MPO) gene rs2333227 G>A polymorphism with Alzheimer's disease (AD) susceptibility. We conducted a meta-analysis to explore the precise association between MPO rs2333227 G>A polymorphism and AD susceptibility. Online databases were searched and the relevant information was collected. Crudeodds ratios with 95% confidence intervals were calculated. Trial sequential analysis (TSA), heterogeneity analyses, accumulative analyses, sensitivity analyses, and publication biasestests were performed. Overall, nine publications (ten independent case-controls) were included in this meta-analysis, involving 3260 participants. Pooled results revealed no significant association between MPO rs2333227 G>A polymorphism and AD susceptibility was observed. TSA showed that the present meta-analysis remained inconclusive due to insufficient evidence. In summary, the current meta-analysis indicated that the MPO rs2333227 G>A polymorphism may not be acausalfactor in the development of AD.


Estimating technical efficiency and allocative distortions of water companies: evidence from the English and Welsh water and sewerage industry.
Regulated water industries need to improve their technical efficiency and allocate their resources efficiently. This is the case of the water industry in England and Wales which was privatized in 1989, and the method of price cap regulation was implemented. This study uses an input distance function system approach to estimate the technical efficiency and distortions in the choice of input mixes for the English and Welsh water and sewerage companies (WaSCs) over the years 1991-2016. The results indicated that an average WaSC was 75.3% technically efficient which means that inputs could be reduced by 24.7% keeping the level of output constant. On average, the input mix was considered to be allocated inefficiently as there was an over-utilization of capital and other inputs relative to employment. Moreover, the low degree of substitutability among inputs implied that reducing allocative inefficiency could be costly. The findings of our study is of interest to policy makers who want to implement effective policies to improve efficiency in the water industry.


Characterization of columnar absorptive epithelial cells isolated from rat jejunum.
The origin and yield of cells isolated from rat jejunum have been assessed; 80-90% of the mature columnar absorptive cells but none of the Paneth, endocrine or regenerating crypt cells were recovered by the methods described. The structural integrity of the isolated cells was tested by phase contrast-, Nomarski interference- and fluorescence light-microscopy; and also by transmission electron microscopy; the isolated cells appeared structurally intact by all microscopic criteria applied. The isolated cells were judged to be functionally intact because they satisfied a number of tests designed to answer three logically related questions, namely: was the cell-surface membrane intact; were the cells able to accumulate selected solutes against a concentration gradient from the exterior medium; and were the cells able to perform biochemical functions which depended upon the integrated activities of several subcellular structures? The isolated cells did retain and accumulate selected solutes, respired at a steady rate on endogenous substrates, showed enhanced respiration on exogenous glucose and glutamine, maintained favourable intracellular proportions of adenine nucleotides (ATP:ADP:AMP), and synthesized cell protein from extracellular amino acids in proportion to the time of incubation. The isolated cells accounted for 80% of the lactic acid produced by intact rat jejunum under similar conditions of incubation.


Solitary hamartomatous polyp of the duodenum in the absence of familial polyposis.
A large hamartomatous polyp of the Peutz-Jegher type was discovered in the distal duodenum by endoscopy in a patient with occult gastrointestinal bleeding. There were no other polyps in the gastrointestinal tract and the patient lacked any stigmata associated with the familial polyposis syndromes. This is the second well-documented case of an isolated hamartomatous polyp of the Peutz-Jegher type in the small intestine occurring in the absence of familial polyposis.


Architecture, composition, and contractile properties of rat soleus muscle grafts.
Skeletal muscle grafts have a deficit in tension development compared with control muscles, even after accounting for reduced mass and total muscle cross-sectional area. Our purpose was to determine relationships among the architecture, tissue composition, and contractile properties of rat soleus muscle grafts. Data were compared with control soleus muscles obtained from littermates. Female Wistar rats were anesthetized with pentobarbital sodium for grafting of soleus muscles with nerve implant and for dissection of muscles 56 days after grafting. Compared with control values, the maximum specific tension (N/cm2) of grafts was 76%, the interstitial (inulin) space was 135%, and the connective tissue protein concentration was 177%. For grafts, total muscle length and fiber length were 91 and 123% of control values, respectively. The extrapolated shortening velocity at zero load (fiber lengths/s) for grafts was not different from the control value. The deficit in specific tension of grafts is explained by a greater concentration of noncontractile tissue components. Changes in muscle architecture and composition following grafting had little affect on contraction dynamics.


Characterization of a locus encoding four paralogous outer membrane lipoproteins of Brachyspira hyodysenteriae.
The identification of Brachyspira hyodysenteriae outer membrane proteins (OMPs) that may stimulate immunity to swine dysentery is important for vaccine development. We report here the analysis of a novel locus, blpGFEA, encoding four tandem paralogous proteins of approximately 30 kDa from B. hyodysenteriae. The four proteins share 31-39% sequence identity with lipoproteins from several species of bacterial pathogens, but the locus possesses a unique genetic organization. Using antisera raised to recombinant versions of each of these proteins, only BlpA and BlpE were found to be immunologically cross-reactive with the other proteins encoded by the locus. Northern hybridization indicated that only blpA was expressed under in vitro growth conditions. In addition, convalescent swine serum recognized recombinant BlpA in immunoblotting experiments, demonstrating that it is also expressed during infection. Analysis of the translated sequences of each of the genes revealed atypical spirochetal signal peptidase II recognition sites, and BlpA was shown to be a lipoprotein by incorporation of tritiated palmitic acid. Native BlpA was completely extracted by Triton X-114 (TX-114) and partitioned exclusively into the detergent phase during extraction of whole B. hyodysenteriae cells, implicating it as a component of the brachyspiral outer membrane. Consistent with the transcriptional and immunological data, analysis of the brachyspiral outer membrane proteome also revealed expression of only BlpA. Notably, inactivation of blpA homologs in Haemophilus influenzae and Salmonella enteritidis resulted in attenuation of virulence.


Heat-aggregated noninfectious influenza virus induces a more balanced CD8(+)-T-lymphocyte immunodominance hierarchy than infectious virus.
CD8(+)-T-cell (T(CD8+)) responses to infectious viruses are characterized by an immunodominance hierarchy in which the majority of T(CD8+) respond to one or a few immunodominant determinants, with a minority of T(CD8+) responding to a number of subdominant determinants. It is now well established that exogenous antigens are capable of inducing T(CD8+) to such immunodominant determinants, but the diversity of the response and the nature of the immunodominance hierarchy have not been examined. We addressed this issue by characterizing T(CD8+) responses to influenza virus preparations rendered inert by incubation for 10 min at 100 degrees C, as first reported by Speidel et al. (Eur. J. Immunol. 27:2391-2399, 1997). Extending these findings, we show that the primary T(CD8+) response to boiled virus can be sufficiently robust to be detected ex vivo by intracellular cytokine staining and that the response encompasses many of the peptides recognized by T(CD8+) induced by infectious virus. Importantly, the immunodominance hierarchy elicited was leveled, and we were unable to detect T(CD8+) that were specific for boiled virus. We used peritoneal exudate cells as antigen-presenting cells in vitro, and a number of observations indicated that boiled virus is processed via a phagocytic route that is likely to be endosomal in nature. These findings suggest that the repertoires of immunogenic peptides generated by endosomes and cytosolic processes overlap to a surprising degree. Furthermore, they demonstrate that the form of antigen administered can influence immunodominance hierarchies and that exogenous-antigen vaccines can induce broad and balanced T(CD8+) responses.


Systemic coagulation and fibrinolysis in patients with or at risk for the adult respiratory distress syndrome.
The authors sought to evaluate the pathogenetic and prognostic role of a procoagulant and hypofibrinolytic state in the adult respiratory distress syndrome (ARDS). Twenty-two consecutive patients admitted to the intensive care unit (ICU) for respiratory monitoring (n = 2) or mechanical ventilation (n = 20) were studied, of whom 13 had ARDS and 9 were at risk for the syndrome. Plasma levels of thrombin-antithrombin III complexes (TAT), the plasmin-alpha2-antiplasmin complexes (PAP), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were measured within 48 h after admission, together with respiratory variables allowing computation of the lung injury score (LIS), and pulmonary microvascular permeability [67Gallium-transferrin pulmonary leak index (PLI)], as measures of pulmonary dysfunction. Blood was also sampled 6-hourly until 2 days after admission. The LIS and PLI were higher in ARDS than at risk patients, in the presence of similar systemic morbidity and mortality. TAT complexes were elevated in a minority of patients of both groups, whereas the PAP, tPA and PAI levels were elevated above normal in the majority of ARDS and at risk patients, but groups did not differ. Neither circulating coagulation nor fibrinolysis variables correlated to either LIS or PLI. Furthermore, the course of haemostatic variables did not relate to outcome. These data indicate that systemic activation of coagulation and impaired fibrinolysis do not play a major role in ARDS development and outcome in patients with acute lung injury.


A unique nucleosome arrangement, maintained actively by chromatin remodelers facilitates transcription of yeast tRNA genes.
RNA polymerase (pol) III transcribes a unique class of genes with intra-genic promoters and high transcriptional activity. The major contributors to the pol III transcriptome, tRNAs genes are found scattered on all chromosomes of yeast. A prototype tDNA of <150 bp length, is generally considered nucleosome-free while some pol III-transcribed genes have been shown to have nucleosome-positioning properties. Using high resolution ChIP-chip and ChIP-seq methods, we found several unique features associated with nucleosome profiles on all tRNA genes of budding yeast, not seen on nucleosome-dense counterparts in fission yeast and resting human CD4+ T cells. The nucleosome-free region (NFR) on all but three yeast tDNAs is found bordered by an upstream (US) nucleosome strongly positioned at -140 bp position and a downstream (DS) nucleosome at variable positions with respect to the gene terminator. Perturbation in this nucleosomal arrangement interferes with the tRNA production. Three different chromatin remodelers generate and maintain the NFR by targeting different gene regions. Isw1 localizes to the gene body and makes it nucleosome-depleted, Isw2 maintains periodicity in the upstream nucleosomal array, while RSC targets the downstream nucleosome. Direct communication of pol III with RSC serves as a stress-sensory mechanism for these genes. In its absence, the downstream nucleosome moves towards the gene terminator. Levels of tRNAs from different families are found to vary considerably as different pol III levels are seen even on isogenes within a family. Pol III levels show negative correlation with the nucleosome occupancies on different genes. Budding yeast tRNA genes maintain an open chromatin structure, which is not due to sequence-directed nucleosome positioning or high transcription activity of genes. Unlike 5' NFR on pol II-transcribed genes, the tDNA NFR, which facilitates tDNA transcription, results from action of chromatin remodeler Isw1, aided by Isw2 and RSC. The RSC-regulated nucleosome dynamics at the 3' gene-end serves as a novel regulatory mechanism for pol III transcription in vivo, probably by controlling terminator-dependent facilitated recycling of pol III. Salient features of yeast tDNA chromatin structure reported in this study can explain the basis of the novel non-transcriptional roles ascribed to tDNAs.


Application of powdered activated carbon (PAC) for membrane fouling control in a pilot-scale MBR system.
Membrane fouling is considered to be the most serious drawback in wastewater treatment when using membrane bioreactors (MBRs), leading to membrane permeability decrease and efficiency deterioration. This work aims to develop an integrated methodology for membrane fouling control, using powdered activated carbon (PAC), which will enhance the adsorption of soluble microbial products (SMP) and improve membrane filterability, by altering the mixed liquor's characteristics. Reversible fouling was assessed in terms of sludge filterability measurements, according to the standard time-to-filter (TTF) method, while irreversible fouling was assessed in terms of SMP removal. Results showed that the addition of PAC at the concentration of 3 g/L in the mixed liquor reduced SMP concentration and enhanced substantially the sludge filterability. Furthermore, the TTFPAC/TTFno PAC ratios were lower, than the corresponding SMPPAC./SMPno PAC ratios, indicating that the batch-mode, short-term addition of PAC promotes the reversible, rather than the irreversible fouling mitigation.


A Bayesian dose-finding design incorporating toxicity data from multiple treatment cycles.
Phase I oncology trials are designed to identify a safe dose with an acceptable toxicity profile. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle, although patients continue to receive treatment for multiple cycles. In addition, the toxicity data from multiple types and grades are typically summarized into a single binary outcome of dose-limiting toxicity. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades. In this work, we propose to account for longitudinal repeated measures of total toxicity profile over multiple treatment cycles, accounting for cumulative toxicity during dosing-finding. A linear mixed model was utilized in the Bayesian framework, with addition of Bayesian risk functions for decision-making in dose assignment. The performance of this design is evaluated using simulation studies and compared with the previously proposed quasi-likelihood continual reassessment method (QLCRM) design. Twelve clinical scenarios incorporating four different locations of maximum tolerated dose and three different time trends (decreasing, increasing, and no effect) were investigated. The proposed repeated measures design was comparable with the QLCRM when only cycle 1 data were utilized in dose-finding; however, it demonstrated an improvement over the QLCRM when data from multiple cycles were used across all scenarios. Copyright © 2016 John Wiley & Sons, Ltd.


Koi herpesvirus (KHV) and KHV disease (KHVD) - a recently updated overview.
Over the last years, there has been an enormous increase in the knowledge on koi herpesvirus (KHV), koi herpesvirus disease (KHVD), pathogenesis and virus variants. Different KHV lineages have clearly been identified, possible genomic changes during replication in different cell cultures at different temperatures but also in several hosts have been identified, a persistent stage of infection has been specified and it has been shown that infection with KHV is not host specific at all, but KHVD is. Additionally, it has been shown that it is possible to combat KHVD by immunization with inactivated and attenuated live vaccines using different delivery systems but also to benefit from alternative treatments with e.g. exopolysaccharids obtained from Arthrospira platensis.


Analysis of the effects of inhaled diesel exhaust on the alveolar intravascular and interstitial cellular components of rodent lungs.
Transmission electron microscopy (TEM) was used to determine the effect of diesel engine exhaust (DEE) on the intravascular and interstitial cellular population of the lungs of exposed rats and guinea pigs. Animals with matched controls were subjected to environments of either 250, 750, 1500 or 6000 micrograms/m3 for either 2 weeks, 6 weeks, 10 weeks or 18 months. These animals were sacrificed immediately following the exposure periods and their lungs perfused with fixative. Following dissection, random stratified biopsies from the lungs of these animals were made. Ultrathin sections from the alveolar lung were prepared and conventionally processed for TEM and randomly photographed to compose a micrograph database. These micrographs were analyzed by point counting using a Zeiss MOP 3 Digital Image Analyzer. The results indicated no significant intravascular cellular response but a significant increase in the mononuclear population in the interstitium.


Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency.
The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell-associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals. Serial VOR exposures separated by 72 hours most often resulted in an increase in cell-associated HIV RNA within circulating resting CD4+ T cells. VOR was well tolerated by all participants. However, despite serial reversal of latency over 1 month of VOR dosing, we did not observe a measurable decrease (>0.3 log10) in the frequency of latent infection within resting CD4+ T cells. These findings outline parameters for the experimental use of VOR to clear latent infection. Latency reversal can be achieved by VOR safely and repeatedly, but effective depletion of persistent HIV infection will require additional advances. In addition to improvements in latency reversal, these advances may include the sustained induction of potent antiviral immune responses capable of recognizing and clearing the rare cells in which HIV latency has been reversed. Clinicaltrials.gov NCT01319383. NIH grants U01 AI095052, AI50410, and P30 CA016086 and National Center for Advancing Translational Sciences grant KL2 TR001109.


Non-invasive Evaluation of Right Ventricular Function with Real-Time 3-D Echocardiography.
The aim of this study was to evaluate the accuracy and feasibility of real-time 3-D echocardiography (3-DE) in assessing right ventricular (RV) systolic function. A latex balloon was inserted into the right ventricle of 20 freshly harvested pig hearts which were then passively driven by a pulsatile pump apparatus. The RV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and RV ejection fraction (RVEF), derived from 3-DE, as well as the RVEF obtained from 2-D echocardiography (2-DE) were quantified at different stroke volumes (30-70 mL) and compared with sonomicrometry data. In all comparisons, 3-D GLS, GCS, GAS, 2-D RVEF and 3-D RVEF exhibited strong correlations with sonomicrometry data (r = 0.89, 0.79, 0.74, 0.80, and 0.93, respectively; all p values < 0.001). Bland-Altman analyses revealed slight overestimations of echo-derived GLS, GCS, 2-DE RVEF and 3-DE RVEF compared with sonomicrometry values (bias = 1.55, 2.72, 3.59 and 2.21, respectively). Furthermore, there is better agreement among GLS, 3-D RVEF and the sonomicrometry values than between GCS and 2-D RVEF. Real-time 3-DE is more feasible and accurate for assessing RV function than 2-DE. GLS is a potential alternative parameter for quantifying RV systolic function.


Delineation of the motor disorder of Lesch-Nyhan disease.
Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.


Application of multiplex ARMS and SSCP/HD analysis in molecular diagnosis of cystic fibrosis in Indian patients.
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The most severe, DeltaF508, mutation accounts for nearly 70% of CF cases worldwide. Besides DeltaF508, there are other point mutations, namely G542X, G551D, R553X, N1303K, and 621+1(G-->T), which are common among Caucasians. Additionally, a polyT polymorphism in intron 8 is also involved in the pathogenesis of CF. However, neither the prevalence nor the types of mutations causing CF in India are known. In this study, we aimed at estimating the frequency of the above common mutations and polymorphism in clinically suspected CF cases. We also carried out partial analysis of the CFTR gene, limited to exons 10 and 11, to identify other variations in these exons. The multiplex amplification refractory mutation system (ARMS) test was applied for rapid simultaneous analysis of six most common CF mutations, in 100 normal and 39 elevated sweat chloride cases. The scanning of exons 10 and 11 was carried out by single-stranded conformation polymorphism/heteroduplex (SSCP/HD) analysis, followed by DNA sequencing in 50 normal and 37 elevated sweat chloride cases. A single ARMS-polymerase chain reaction assay was used to distinguish the 5T, 7T, and 9T alleles in 100 normal and 33 elevated sweat chloride cases. The multiplex ARMS analysis identified the DeltaF508 mutation at an allele frequency of 24% in Indian CF cases. However, the other predominant CF mutations were found to be absent. The 7T polyT variant was observed to be the most common allele, followed by the 9T, and 5T, which was the lowest. The DeltaF508 mutation was observed in all instances with the 9T variant. The SSCP/HD and DNA sequencing additionally revealed a known polymorphism (M470V, exon 10) and a known mutation [1525-1(G-->A), intron 9]. The 1525-1(G-->A) mutation, observed in a single 4-year-old male, is predicted to code for a class II defective CFTR protein. The findings of this study suggest a difference in relative frequencies and spectrum of CFTR mutations in Indian CF cases. A larger screening study of the entire CFTR gene in clinically well defined CF cases is required to delineate common mutations in the CFTR gene and enable molecular diagnosis of CF in India.


Simultaneous direct measurement of the electrocaloric and dielectric dynamics of ferroelectrics with microsecond temporal resolution.
A contactless technique for direct time-resolved measurements of the full dynamics of the adiabatic temperature change in electrocaloric materials is introduced. The infrared radiation emitted by the electrocaloric sample is sensitively detected with μs time resolution and mK temperature resolution. We present time-resolved measurements of the electrocaloric effect up to kHz frequencies of the driving electric field and down to small field strengths. The simultaneous recording of transients for applied electric field and induced polarization gives a comprehensive view of the correlation of electrocaloric and ferroelectric properties. The technique can further be applied to the continuous measurement of fatigue for >106 electric field cycles.


Molecular Characterization and Expression Analysis of Ribosomal Protein S6 Gene in the Cashmere Goat (Capra hircus).
Ribosomal protein (rp) S6 is the substrate of ribosomal protein S6K (S6 kinase) and is involved in protein synthesis by mTOR/S6K/S6 signaling pathway. Some S6 cDNA have been cloned in mammals in recent years but has not been identified in the goat. To facilitate such studies, we cloned the cDNA encoding Cashmere goat (Capra hircus) S6 (GenBank accession GU131122) and then detected mRNA expression in seven tissues by real time PCR and protein expression in testis tissue by immunohistochemisty. Sequence analysis indicated that the obtained goat S6 was a 808 bp product, including a 3' untranslated region of 58 bp and an open reading frame of 750 bp which predicted a protein of 249 amino acids. The predicted amino acid sequence was highly homologous to cattle, human, mouse and rat S6. Expression analysis indicated S6 mRNA was expressed extensively in detected tissues and S6 protein was expressed in testis tissue.


Inflammatory and oxidative stress‑associated factors in chronic intermittent hypoxia in Chinese patients, rats, lymphocytes and endotheliocytes.
In order to investigate the association between inflammatory and oxidative stress (OS)‑associated factors in chronic intermittent hypoxia (CIH), 238 CIH patients and 156 healthy volunteers were included. CIH rat and lymphocytes were used as experimental models. Interleukin (IL)‑6, tumor necrosis factor‑α (TNF‑α), C‑reactive protein (CRP), nitric oxide (NO) and nitric oxide synthase (NOS) were analyzed. Patients with CIH were older, with hypertension, increased heart rate (HR) and body mass index (BMI), and there were more males than females. Those with a history of smoking or type 2 diabetes (T2DM) history exhibited an increased risk of CIH. Serum IL‑6, TNF‑α and CRP in patients with CIH were increased, while NO and NOS were decreased. Hakka patients exhibited increased BMI measurements and NO expression, and decreased systolic arterial pressure, IL‑6 and TNF‑α compared with non‑Hakka patients. Rats with CIH exhibited hypertension and stable weight, less activity and decreased appetite, increased HR and serum IL‑6, TNF‑α and CRP, and decreased NO and NOS. IL‑6, TNF‑α, CRP, NO and induced‑NOS (iNOS) were increased in the lymphocytes of CIH rats compared with healthy ones. In rat endotheliocytes induced by CIH, IL‑6, TNF‑α, CRP and iNOS increased, while NO and endothelial‑NOS (eNOS) decreased. In the supernatant of co‑cultured lymphocytes and endotheliocytes, IL‑6, TNF‑α and CRP increased, although NO and NOS decreased. In conclusion, age, male gender, BMI, smoking and T2DM history, serum IL‑6, TNF‑α and CRP were positively correlated with CIH combined with hypertension, while NO and NOS were negatively correlated with CIH. Serum NO was predominantly synthesized and released by eNOS. Hakka patients exhibited decreased inflammation and OS with CIH. Increasing IL‑6, TNF‑α and CRP, and decreasing NO and NOS are biomarkers of CIH, which could be targets in diagnosis, treatment and prevention of CIH.


[Welcoming learners, a DEPHI on the DMU!]
The reception of learner-caregivers is a challenge for the care sectors in the context of clinical training, moreover in view of the current situation in connection with the health of our hospitals. Remember that internship periods represent 50 % of apprenticeship time in training institutes. So how does a Medical-University Department of Hematology and Immunology try to implement a policy of welcoming and supporting trainees, taking into account their level of training and promoting interest and emulation for future professionals health?


[Optimized analgesic sedation techniques for ESWL].
Analgo-sedation for ESWL treatment has been associated with a variety of problems. Minimal invasiveness of this technique should combine with haemodynamic stability as well as with adequate oxygenation. Patient acceptance has to be considered as another important aspect. Our study demonstrates the effectiveness of an analgosedative regimen with regard to these aspects. 50 ASA I-III patients scheduled for ESWL treatment were randomly allocated to receive either no premedication (n = 25) or chlorazepam as oral premedication (n = 25). The analgosedative technique was identical in both groups, consisting of atropine 0.25 mg, droperidol 5 mg (2.5 mg, if body weight less than 60 kg), and alfentanil 10 micrograms/kg intravenously. If necessary, repeated boluses of alfentanil 5 micrograms/kg were administered up to a maximum of 2 mg. Heart rates, arterial blood pressures, and peripheral oxygen saturation were measured during treatment. Post-treatment, patients were interviewed to assess the quality of analgesia. The results showed that our analgo-sedative regimen is suitable for ASA I-III patients. Stable heamodynamic conditions and adequate oxygenation were achieved in all patients. Patient acceptance was good. Patients with anxiolytic premedication benefited in terms of reduction in blood pressure and heart rate. The study also showed that anaesthesiologists may underestimate the pain intensity experienced and assessed by the patient.


Unhealthy complacency: The vulnerability of US hospitals to direct terrorist attacks.
Since the attacks of September 11, 2001, terrorists have demonstrated both the intent and capability to execute direct attacks on US public hospitals. Nonetheless, hospital administrators have basically ignored this threat, as they do not view hospitals as likely targets. Unfortunately, it may take a catastrophic event before policymakers appreciate this threat enough to take appropriate actions. However, analyzing and managing these threats is just another part of risk management, as the cost of doing so up front to protect against such loss is no different than other risk management assessments. While the threat may never be completely eradicated, failing to implement reasonable security measures to specifically address the threat of direct terrorist attacks leaves hospitals vulnerable to severe loss.


Endogenous Serotonin 5-HT2A and 5-HT2C Receptors Associate in the Medial Prefrontal Cortex.
The 5-HT2A receptor (5-HT2AR) and 5-HT2CR are localized to the same neurons within the medial prefrontal cortex (mPFC), which regulates executive function, decision-making, and reward-guided learning and memory processes. The 5-HT2AR and 5-HT2CR coimmunoprecipitate in the mPFC of male Sprague-Dawley rats, while in vitro studies demonstrate the presence of a physical interaction between the 5-HT2AR and 5-HT2CR. The purpose of this study was to identify mPFC subregions in which the 5-HT2AR and 5-HT2CR physically interact ex vivo in the male Sprague-Dawley rat. We established the expression patterns of 5-HT2AR and 5-HT2CR in layers I-VI of the anterior cingulate cortex (ACC), prelimbic (PL), and infralimbic (IL) subregions using double-label fluorescence immunohistochemistry in male rats. We then employed the proximity ligation assay (PLA) to test the hypothesis that the 5-HT2AR and 5-HT2CR form a close, physical association within these mPFC subregions. Our results demonstrate subregion- and layer-specific expression of the 5-HT2AR and 5-HT2CR proteins using immunofluorescence and single recognition PLA, and a spatially close (within 40 nm) interaction between the 5-HT2AR and 5-HT2CR that occurs along a dorsal-ventral gradient in the rat mPFC.


A syndemic examination of injecting drug use, incarceration and multiple drug-related harms in French opioid users.
People who inject drugs (PWID) face multiple health problems, including infectious diseases and drug overdoses. Applying syndemic and risk environment frameworks, this paper aims to examine the co-occurrence and clustering of drug-related harms and their association with incarceration experience with or without in-prison drug injection. The authors used data from a cross-sectional survey conducted in 2015 among 557 active opioid injectors. Self-reported data were collected through face-to-face or online questionnaires. They distinguished three harm categories, namely, viral infections, bacterial infections and overdoses, and built an index variable by summing the number of harm categories experienced, yielding a score from 0 to 3. Association between incarceration experience and co-occurrence of harms was modelled using a multinomial logistic regression. Of the 557 participants, 30% reported lifetime experience of drug-related viral infection, 46% bacterial infection and 22% drug overdose. Multinomial logistic models showed that those who injected drugs during incarceration were more likely to report two (aOR = 2.35, 95% CI: 1.03-5.36) and three (aOR = 9.72, 95% CI: 3.23-29.22) harm categories than those who had never been incarcerated. They were also more likely to report three harm categories than formerly incarcerated respondents who did not inject drugs in prison (aOR = 5.14, 95% CI: 1.71-15.48). This study provides insights of the syndemic nature of drug-related harms and highlights that drug injection during incarceration is associated with co-occurring harms. Public health interventions and policy changes are needed to limit the deleterious impact of prison on PWID.


A study on possibility of Rosa canina seed use as feed ıngredient in diets of Morkaraman male lambs.
This experiment was carried out to evaluate the ground Rosa canina seed at various levels (0%, 5%, and 15%) in barley-soybean-based concentrates offered to Morkaraman male lambs at approximately 8 months of age, on fattening performance, carcass, and meat quality characteristics. The lambs were divided into three treatment groups including R1 (concentrate without R. canina seed; n = 12), R2 (concentrate with 5% R. canina seed; n = 12), and R3 (concentrate with 15% R. canina seed; n = 12) at the beginning of fattening period. The soybean meal was used as main protein source in treatment groups. All of the groups were fed a diet consisting of concentrate offered ad libitum and 300 g of grass hay per lamb per day during 60-day fattening period. The effect of diet on daily weight gain was found statistically significant. The control group had higher daily weight gain than R3 groups with 15% of ground R. canina seed. The hot carcass and cold carcass weights and dressing percentage values were affected by diets, and R3 group fed concentrate with 15% R. canina seed had higher carcass weights and dressing percentages than R1 and R2 groups. Differences among the groups in terms of leg, rib, and hindshank weights were found highly significant. While R1 and R2 groups were not significantly different, R3 group was significantly higher to R1 and R2 groups in leg, rib, and hindshank weights. In addition, meat color parameters and pH values were not affected by diets in present study.


Osteocalcin and its forms across the lifespan in adult men.
Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.


Targeted Alpha Therapy in mCRPC (Metastatic Castration-Resistant Prostate Cancer) Patients: Predictive Dosimetry and Toxicity Modeling of 225Ac-PSMA (Prostate-Specific Membrane Antigen).
Radioligand therapy is a type of internal radiotherapy combining a short-range radioisotope labeled to a carrier with a high affinity for a specific receptor expressed on tumor cells. Targeted alpha therapy (TAT) combines a high-linear energy transfer (LET) emitter (225Ac) with a prostate-specific membrane antigen (PSMA) carrier, specifically binding tumor cells in patients with metastatic castration-resistant prostate cancer. Although the antitumor activity of 225Ac-PSMA is well-documented, this treatment is nowadays only used as salvage therapy because the high incidence of xerostomia limits the therapeutic window. Thus, methods to reduce salivary toxicity and models able to describe xerostomia incidence are needed. We recently studied the efficacy of salivary gland protectors administered in combination with 177Lu-PSMA therapy. Starting from these data, we performed a predictive dosimetric evaluation of 225Ac-PSMA to assess the impact of salivary gland protectors in TAT. 225Ac-PSMA predictive dosimetry was performed in 13 patients treated with 177Lu-PSMA. Sequential whole-body planar images were acquired 0.5-1, 16-24, 36-48, and 120 h post-injection. 177Lu time-activity curves were corrected for 225Ac physical decay and assumed in equilibrium for all daughters. The OLINDA/EXM spherical model was used for dose estimation of the parotid and submandibular glands. The dose for each daughter was calculated and summed for the total dose estimation. The biologically effective dose formalism was extended to high-LET emitters. For the total biologically effective dose formalism extended to high-LET emitters, including the contribution of all daughter isotopes, the brachytherapy formalism for a mixture of radionuclides was implemented. Equivalent doses in 2 Gy/fraction (EQD2) were then calculated and compared with the normal tissue complication probability model derived from external beam radiotherapy for grade ≥2 xerostomia induction. Median predictive doses were 0.86 BdRBE5/MBq for parotid glands and 1.05 BdRBE5/MBq for submandibular glands, with a 53% reduction compared with previously published data. The results show that the radiobiological model implemented is conservative, as it overestimates the complication rate with respect to the clinical data. Our data shows the possibility of reducing salivary gland uptake in TAT with the coadministration of organ protectors, but these results should be confirmed for TAT with 225Ac-PSMA by carrying out prospective trials with defined toxicity endpoints and dosimetry procedures.


Photoautotrophic production of D-lactic acid in an engineered cyanobacterium.
The world faces the challenge to develop sustainable technologies to replace thousands of products that have been generated from fossil fuels. Microbial cell factories serve as promising alternatives for the production of diverse commodity chemicals and biofuels from renewable resources. For example, polylactic acid (PLA) with its biodegradable properties is a sustainable, environmentally friendly alternative to polyethylene. At present, PLA microbial production is mainly dependent on food crops such as corn and sugarcane. Moreover, optically pure isomers of lactic acid are required for the production of PLA, where D-lactic acid controls the thermochemical and physical properties of PLA. Henceforth, production of D-lactic acid through a more sustainable source (CO2) is desirable. We have performed metabolic engineering on Synechocystis sp. PCC 6803 for the phototrophic synthesis of optically pure D-lactic acid from CO2. Synthesis of optically pure D-lactic acid was achieved by utilizing a recently discovered enzyme (i.e., a mutated glycerol dehydrogenase, GlyDH*). Significant improvements in D-lactic acid synthesis were achieved through codon optimization and by balancing the cofactor (NADH) availability through the heterologous expression of a soluble transhydrogenase. We have also discovered that addition of acetate to the cultures improved lactic acid production. More interestingly, (13)C-pathway analysis revealed that acetate was not used for the synthesis of lactic acid, but was mainly used for synthesis of certain biomass building blocks (such as leucine and glutamate). Finally, the optimal strain was able to accumulate 1.14 g/L (photoautotrophic condition) and 2.17 g/L (phototrophic condition with acetate) of D-lactate in 24 days. We have demonstrated the photoautotrophic production of D-lactic acid by engineering a cyanobacterium Synechocystis 6803. The engineered strain shows an excellent D-lactic acid productivity from CO2. In the late growth phase, the lactate production rate by the engineered strain reached a maximum of ~0.19 g D-lactate/L/day (in the presence of acetate). This study serves as a good complement to the recent metabolic engineering work done on Synechocystis 6803 for L-lactate production. Thereby, our study may facilitate future developments in the use of cyanobacterial cell factories for the commercial production of high quality PLA.


Increased utilization of healthcare services in children with craniosynostosis.
Craniosynostosis is characterized by the premature fusion of at least one cranial suture. Although evidence suggests that patients with both syndromic and nonsyndromic craniosynostosis may benefit from developmental, behavioral, and mental health support, data on utilization of healthcare services are lacking. In this study the authors compared utilization of mental health care, rehabilitation therapies, and other specialty medical services among children with craniosynostosis, children with plagiocephaly, and healthy controls. The Optum Clinformatics Data Mart database was queried to identify 1340 patients with craniosynostosis, of whom 200 had syndromic craniosynostosis. Long-term utilization of mental health care, rehabilitation therapies, and other medical services up to the age of 6 years was calculated. Rates of utilization were compared to healthy controls (n = 1577) and children with plagiocephaly (n = 1249). Patients with syndromic and nonsyndromic craniosynostosis used mental health care, occupational therapy, speech-language pathology, and other medical services at similar rates (p = 0.1198, p > 0.9999, p = 0.1097, and p = 0.8119, respectively). Mental health services were used more frequently by patients with craniosynostosis (11.0% in patients with syndromic craniosynostosis and 7.5% in those with nonsyndromic craniosynostosis) compared to patients in the plagiocephaly (5.0%, p = 0.0020) and healthy control (2.9%, p < 0.0001) cohorts. Rehabilitation therapies were more frequently used by patients with syndromic craniosynostosis and plagiocephaly (16.0% and 14.1%, respectively), which was significantly higher than use by healthy controls (p < 0.0001). Other medical subspecialty services (developmental pediatrics, ophthalmology, optometry, and audiology) were used by 37.0% of patients with craniosynostosis, compared with 20.9% (p < 0.0001) and 15.1% (p < 0.0001) of patients with plagiocephaly and healthy controls, respectively. Among patients with craniosynostosis, utilization did not differ by race or household income, but it was not uniform by age. Whereas ophthalmology utilization did not differ by age (p = 0.1003), mental health care was most commonly used among older children (p = 0.0107). In this study, the authors demonstrate that rates of utilization of mental health care, rehabilitation therapies, and other medical subspecialty services are similar between patients with syndromic and those with nonsyndromic craniosynostosis, but higher than in healthy controls. Although surgical correction may be considered an isolated event, providers and parents need to monitor all children with craniosynostosis-syndromic and nonsyndromic-for developmental and mental health support longitudinally. Future work should explore risk factors driving utilization, including suture involvement, repair type, and comorbidities.


Enzyme-free detection of hydrogen peroxide from cerium oxide nanoparticles immobilized on poly(4-vinylpyridine) self-assembled monolayers.
A simple enzyme-free spectrophotometric detection of hydrogen peroxide is demonstrated based on its colorimetric reaction with oxygen deficient cerium oxide nanoparticles (CNPs). This colorimetric sensitivity of CNPs towards H2O2 increases significantly with decreasing crystallite size due to an increase in the surface area as well as the concentration of Ce3+ on the surface. The origin of this colorimetric reaction was studied using DFT that suggests the adsorption of peroxide and oxygen molecules on ceria nanoparticles creates new states in the electronic structure leading to transitions absorbing in the visible region of the electromagnetic spectrum. For detection, a single layer of nanoparticles was immobilized on transparent microscopic glass slides using self-assembled monolayers (SAMs) of poly(4-vinylpyridine) (PVP). Cluster-free and uniform immobilization of nanoparticles was confirmed from atomic force microscopy (AFM) and helium ion microscopy (HIM). UV-Visible absorption measurements showed a concentration dependent increase in absorbance from immobilized CNPs that were exposed to increasing concentrations (10-400 μM) of hydrogen peroxide. The immobilized CNPs can be baked at 80 °C after initial use to regenerate the sensor for reuse. The development of a direct, reusable, enzyme-free and dye-free peroxide sensing technology is possible and can be immediately applied in various areas, including biomedicine and national security.


Keloid formation after syndactyly reconstruction: associated conditions, prevalence, and preliminary report of a treatment method.
The purpose of this study is 3-fold: to review our cases of keloid formation after syndactyly release, to report a clinical association between primary enlargement of the digits and risk of keloid formation, and to report treatment using low-dose, short-term methotrexate as an adjunct to revision surgery. A retrospective review of patients identified with keloid formation after syndactyly reconstruction showed associated enlargement of the involved digits. A search of medical records for cases in which both syndactyly and digital enlargement occurred was carried out. Charts and images, where available, were reviewed for information about age, gender, involved site, associated conditions, and treatment. Eight cases of keloids occurred in 1004 surgical procedures in 681 patients carried out during the 20-year period reviewed. Seven patients were white and 1 was Hispanic. Seven of the 8 had associated primary digital enlargement. Two patients who had enlarged syndactylized digits did not develop keloids after surgery. There was no family history in any case. Standard treatment (pressure, topical or intralesional corticosteroids, and re-excision) was unsuccessful in resolving the keloids. Two children treated with adjunctive methotrexate had successful treatment of their keloids and near-normal healing. Length of follow-up time after the last treatment ranged from 6 months to 11 years (average, 5.5 years). Primary digital enlargement is highly predictive of risk of keloid formation after syndactyly reconstruction. Very-low-dose, short-term methotrexate was successful as an adjunct to surgical treatment in 2 cases.


[Lung damage due to mechanical ventilation].
Mechanical ventilation in both children and adults is still associated with development of lung injury, both short term and long term. In particular, ventilation with high tidal volumes and low positive end-expiratory pressures (PEEP) contributes significantly to development of lung injury. Suggested preventive measures consist of limiting peak inflation pressures, preventing high tidal volumes, and applying high PEEP to prevent alveolar collapse. Recent studies have demonstrated that mechanical ventilation, via stretch of lung tissue, results in an inflammatory reaction in the lungs. This is known as biotrauma. The degree of inflammation depends on the ventilator settings and mode of ventilation. This inflammatory reaction may not be limited to the lungs but, via inflammatory mediators, may cause multiple organ dysfunction as well. Future research needs to be concentrated on how to modify this ventilator induced inflammatory reaction in order to prevent lung injury as well as systemic injury.


Natural history of schizophrenia subtypes. I. Longitudinal study of paranoid, hebephrenic, and undifferentiated schizophrenia.
To explore the validity of different approaches for subtyping schizophrenia, the conditions of 187 schizophrenic patients from the Chestnut Lodge follow-up study were rediagnosed with the use of classic subtype criteria. Independently collected data allowed construction of a longitudinal profile of the natural history of illness for patients who met operational criteria for paranoid (n = 78), hebephrenic (n = 26), and undifferentiated (n = 83) schizophrenia. Paranoid schizophrenia had an older age at onset, often developed rapidly in individuals with good premorbid functioning, tended to be intermittent during the first 5 years of illness, and was most associated with good outcome or recovery. Hebephrenia had an earlier age at onset, often developed insidiously, and was associated with a greater family history of psychopathology, poor premorbid functioning, and, frequently, a continuous illness with a poor long-term prognosis. While also early and insidious in onset, unlike hebephrenia, undifferentiated schizophrenia was poorly distinguished from the patients' premorbid state, associated with an early history of behavioral difficulties, and often resulted in a continuous but stable disability. We discuss implications for nosology. Although distinctive patterns were discernible, the considerable heterogeneity within subtypes calls for continued efforts to develop and explore alternate classification schemes.


Aorto-left ventricular communication after closure. Late postoperative problems.
The long-term follow-up of six patients operated on for aorto-left ventricular communication has been reviewed in detail. All had residual aortic regurgitation after the initial repair of the defect. It was severe in four and required repeated reoperation in three with ultimate aortic valve replacement. The failure of early repair to solve the haemodynamic problem has provoked a reconsideration of the basic anatomy, of the surgical approach, and of the postoperative physiology of this anomaly. The so called "tunnel" is not a tunnel with length but should be considered as a localised breach at the insertion of the right coronary cusp. The localised aortic root dilatation at the site is a weakness that remains after closure of the tunnel leaving a poorly supported aortic valve and a weak root. Thus, the initial repair of the aorto-left ventricular communication must not only close the communication but reinforce, strengthen, and support the right aortic sinus in order to maintain cusp competence.


Basic protein-specific T-cell lines that induce experimental autoimmune encephalomyelitis in SJL/J mice: comparison with Lewis rat lines.
Myelin basic protein (BP)-specific T-cell lines were selected from SJL/J mice using techniques to select similar lines from Lewis rats. SJL/J BP-specific T-cell lines were composed of T cells with the helper/inducer phenotype (Lyt 1.2+, 2.2- and L3T4+) and proliferated in response to both the 1-37 and the 89-169 fragments of guinea pig BP. BP-specific T-cell lines transferred delayed-type hypersensitivity (DTH) responses to BP that persisted for over 60 days. Most recipient animals (32/41) developed acute experimental autoimmune encephalomyelitis (EAE), and most survivors (19/24) developed chronic relapsing EAE. Spinal cords of animals during both the acute and the chronic phases of illness contained plaques of demyelination and infiltrates of lymphocytes and macrophages. These findings differed from those of Lewis rat BP-specific lines which respond to a different region of BP, transfer DTH responses that last less than 12 days, and induce acute EAE in which demyelination does not occur.


Separation of spring viraemia of carp virus from large-volume samples using immunomagnetic beads.
A method for separation of spring viraemia of carp virus (SVCV) from large-volume samples using immunomagnetic beads (IMBs) coated with a polyclonal antibody against SVCV was developed. The optimum amount of IMBs was 2 mg in 100 mL. After IMB treatment, the detection limit of SVCV in reverse transcription quantitative PCR (RT-qPCR) was 103 times the 50% tissue culture infectious dose per mL in 100-mL samples. The concentration of viral RNA extracted from SVCV that had been separated using IMBs was 5.18 × 103-fold higher than that of the unseparated SVCV. When fish samples were tested, the concordance rates of the IMBs/RT-qPCR and RT-qPCR were 100% and 67.5%, respectively.


Estimating the peer effect on youth overweight and inactivity using an intervention study.
Understanding peer effect is potentially important for finding ways to combat the obesity epidemic. Nevertheless, it is not clear whether a peer effect exists because of the composition of the peer group, because the group members have similar, unobserved individual characteristics, or because of an endogenous effect. This issue is addressed here by using a unique longitudinal data set of 573 schoolchildren attending state schools in the Municipality of Aalborg, Denmark, during 2008-2010. To identify the spillover effect of a targeted intervention on peers, we use a difference-in-differences approach. A targeted health intervention reduced body mass index (BMI) among overweight, inactive individuals and, more interestingly, that BMI among the nontreated peers was reduced by 1.04%. The analysis suggests that individually targeted health intervention has a health benefit beyond the treated individual, which needs to be included when evaluating targeted policies aiming to combat childhood overweight and inactivity.


Biosynthetic code for divergolide assembly in a bacterial mangrove endophyte.
Divergolides are structurally diverse ansamycins produced by a bacterial endophyte (Streptomyces sp.) of the mangrove tree Bruguiera gymnorrhiza. By genomic analyses a gene locus coding for the divergolide pathway was detected. The div gene cluster encodes genes for the biosynthesis of 3-amino-5-hydroxybenzoate and the rare extender units ethylmalonyl-CoA and isobutylmalonyl-CoA, polyketide assembly by a modular type I polyketide synthase (PKS), and enzymes involved in tailoring reactions, such as a Baeyer-Villiger oxygenase. A detailed PKS domain analysis confirmed the stereochemical integrity of the divergolides and provided valuable new insights into the formation of the diverse aromatic chromophores. The bioinformatic analyses and the isolation and full structural elucidation of four new divergolide congeners led to a revised biosynthetic model that illustrates the formation of four different types of ansamycin chromophores from a single polyketide precursor.


Polarization caging in diffusion-controlled electron transfer reactions in solution.
In some bimolecular diffusion-controlled electron transfer (ET) reactions such as ion recombination (IR), both solvent polarization relaxation and the mutual diffusion of the reacting ion pair may determine the rate and even the yield of the reaction. However, a full treatment with these two reaction coordinates is a challenging task and has been left mostly unsolved. In this work, we address this problem by developing a dynamic theory by combining the ideas from ET reaction literature and barrierless chemical reactions. Two-dimensional coupled Smoluchowski equations are employed to compute the time evolution of joint probability distribution for the reactant (P((1))(X,R,t)) and the product (P((2))(X,R,t)), where X, as is usual in ET reactions, describes the solvent polarization coordinate and R is the distance between the reacting ion pair. The reaction is described by a reaction line (sink) which is a function of X and R obtained by imposing a condition of equal energy on the initial and final states of a reacting ion pair. The resulting two-dimensional coupled equations of motion have been solved numerically using an alternate direction implicit (ADI) scheme (Peaceman and Rachford, J. Soc. Ind. Appl. Math. 1955, 3, 28). The results reveal interesting interplay between polarization relaxation and translational dynamics. The following new results have been obtained. (i) For solvents with slow longitudinal polarization relaxation, the escape probability decreases drastically as the polarization relaxation time increases. We attribute this to caging by polarization of the surrounding solvent. As expected, for the solvents having fast polarization relaxation, the escape probability is independent of the polarization relaxation time. (ii) In the slow relaxation limit, there is a significant dependence of escape probability and average rate on the initial solvent polarization, again displaying the effects of polarization caging. Escape probability increases, and the average rate decreases on increasing the initial polarization. Again, in the fast polarization relaxation limit, there is no effect of initial polarization on the escape probability and the average rate of IR. (iii) For normal and barrierless regions the dependence of escape probability and the rate of IR on initial polarization is stronger than in the inverted region. (iv) Because of the involvement of dynamics along R coordinate, the asymmetrical parabolic (that is, non-Marcus) energy gap dependence of the rate is observed.


Effect and mechanism of Salicornia bigelovii Torr. plant salt on blood pressure in SD rats.
In this paper, the effect and mechanism of Salicornia bigelovii Torr. plant salt (SPS) on blood pressure in Sprague Dawley (SD) rats were investigated. The results showed that the edible salt induced hypertension, but the SPS did not. Organ indices and Hematoxylin-Eosin (HE) staining analysis indicated that SPS had a protective effect on the kidney and liver. In comparison with the edible salt-treated group, nitric oxide (NO) content, angiotensin-II (Ang-II) and endothelin-1 (ET-1) levels in the serum of the SPS-treated group had no obvious changes, but serum creatinine concentration significantly decreased. Moreover, superoxide dismutase (SOD) and Na(+)-K(+)-ATPase activity increased while malondialdehyde (MDA) content decreased in the SPS-treated group. In conclusion, a long-term high salt intake could lead to hypertension. SPS, as a salt substitute, could increase the body's antioxidant ability to protect the kidney and liver from the damage caused by a high salt intake and effectively avoid the occurrence of hypertension.


A highly efficient sorbitol dehydrogenase from Gluconobacter oxydans G624 and improvement of its stability through immobilization.
A sorbitol dehydrogenase (GoSLDH) from Gluconobacter oxydans G624 (G. oxydans G624) was expressed in Escherichia coli BL21(DE3)-CodonPlus RIL. The complete 1455-bp codon-optimized gene was amplified, expressed, and thoroughly characterized for the first time. GoSLDH exhibited Km and kcat values of 38.9 mM and 3820 s(-1) toward L-sorbitol, respectively. The enzyme exhibited high preference for NADP(+) (vs. only 2.5% relative activity with NAD(+)). GoSLDH sequencing, structure analyses, and biochemical studies, suggested that it belongs to the NADP(+)-dependent polyol-specific long-chain sorbitol dehydrogenase family. GoSLDH is the first fully characterized SLDH to date, and it is distinguished from other L-sorbose-producing enzymes by its high activity and substrate specificity. Isothermal titration calorimetry showed that the protein binds more strongly to D-sorbitol than other L-sorbose-producing enzymes, and substrate docking analysis confirmed a higher turnover rate. The high oxidation potential of GoSLDH for D-sorbitol was confirmed by cyclovoltametric analysis. Further, stability of GoSLDH significantly improved (up to 13.6-fold) after cross-linking of immobilized enzyme on silica nanoparticles and retained 62.8% residual activity after 10 cycles of reuse. Therefore, immobilized GoSLDH may be useful for L-sorbose production from D-sorbitol.


Photoreceptor transplantation in inherited and environmentally induced retinal degeneration: anatomy, immunohistochemistry and function.
In conclusion, we have shown that photoreceptors can be transplanted to retina in which the host's photoreceptors are lost by environmental (constant light) or inherited deficits. Furthermore transplanted photoreceptor cells maintain basic characteristics of normal photoreceptor cells by producing opsin and maintaining an intercellular organization and apposition to the host retina that is similar to that seen in the normal outer nuclear layer. To accomplish this we have devised a method to isolate the intact photoreceptor layer. This is significant because it will be necessary to maintain tight matrix organization if coherent vision is to be restored to the retina compromised by the loss of photoreceptors. We have further developed a surgical approach which minimizes trauma to the eye and allows controlled positioning of sheets of transplanted photoreceptors to their homotopic location within the eye. In addition these methods for transplantation and isolation of photoreceptors could be utilized to prepare and transplant other retinal layers so that selected populations of retinal cells can be used in other neurobiological investigations. Photoreceptors can be transplanted when developing or when mature. Not only can mature rat photoreceptors can be transplanted, but we have shown that mature photoreceptors from human donors can be transplanted as well. This is significantly different from neurons which must be immature in order to be transplanted. At present the reason for this difference is not known but has obvious importance for retinal and neural transplantation research in general. Finally, we have shown that transplanted photoreceptors activate the host's dystrophic retina in a light dependent manner that closely resembles the activation pattern seen in normal retina. This finding taken together with our results showing that human photoreceptors can be transplanted presents the possibility that some forms of human blindness might eventually be ameliorated by photoreceptor transplantation. The authors are grateful to A. I. Cohen, and N. W. Daw for helpful discussions; to C. Barnstable for gifts of antibody; and to J. Lett for excellent technical assistance. This work was supported by grants from NIH, National Retinitis Pigmentosa Foundation, the Monsanto Company; and an Alfred P. Sloan Fellowship to MSS.


Testosterone and sexual risk among transmen: a mixed methods exploratory study.
Little research has explored the link between the behavioural effects of testosterone use among transmen and HIV risk. We conducted a mixed methods study to explore testosterone use among transmen and the behavioural effects on HIV risk. A sample of 122 transmen from San Francisco participated in a cross-sectional quantitative survey and 14 transmen participated in 2 focus group discussions. Most participants (81.9%) were currently taking hormones. Participants attributed testosterone use to new sexual behaviours among 69% of transmen, changes in sexual attraction (49%), and increased frequency of sexual activity (72%). Among current testosterone users, 3.3% had cisgender men as partners before starting testosterone, whereas after starting testosterone, 25.4% did. Similarly, 4.1% had a transgender woman as a sexual partner before starting testosterone and 13.9% after starting testosterone. Findings suggest that testosterone's side effects were associated with transmen's desires for sex with cisgender men who have sex with men. The reported increase in attraction to and sex with partners from populations with a high HIV prevalence may have important implications for HIV risk among transmen, especially as the availability of transgender health services may draw transmen to a context in which HIV prevalence is high.


Multicomponent gauge cell method.
The gauge cell Monte Carlo method [Neimark and Vishnyakov, J. Chem. Phys. 122, 234108 (2005)] for calculations of chemical potential in dense and strongly inhomogeneous fluids is extended to multicomponent systems. The system of interest is simulated in a sample cell that is placed in chemical contact with several gauge cells of limited capacity, one gauge cell per component. Thus, each component can be exchanged between the sample cell and the respective gauge cell. The sample and gauge cells are immersed into the thermal bath of a given temperature. The size of the gauge cell controls the level of concentration fluctuations for the respective component in the sample cell. The chemical potentials are rigorously calculated from the equilibrium distribution of particles between the system and the gauges, and the results do not depend on the gauge size. For large systems, the chemical potentials can be accurately estimated from the average densities in the gauge cells. The proposed method was tested against the literature data on the vapor-liquid equilibrium in a binary mixture of subcritical and supercritical fluids and against the grand canonical and Widom insertion Monte Carlo methods for a binary mixture confined to a very narrow spherical pore. The method is specifically suitable for simulations of metastable and labile states in multicomponent confined fluids.


[Current status of the female condom in Africa].
The female condom was developed in the 1980s. It is a contraceptive device used by women that protects against both pregnancy and sexually-transmitted diseases (STDs) including HIV infection. Two studies have investigated the contraceptive effectiveness of the female condom, and it was found to be as effective as other barrier methods. It has been shown to be effective against STD and HIV transmission in vitro but there is only limited evidence of its efficacy in vivo. No serious local side effects or allergies have been reported and the female condom can be used with any type of lubricant, spermicidal cream or foam. The female condom is the only device other than the male condom that has been shown to prevent HIV transmission. The female condom has been marketed in 13 countries since the summer of 1996. Most of these countries are industrialized and the selling price in these countries is too high for developing countries. Sub-Saharan Africa has very high prevalence rates for HIV infection, at least 30% of the general population in Eastern and Central regions. The epidemic is also spreading fast in some parts of the Western region. In Ivory Coast for example, 12 to 15% of pregnant women are infected. African women are subordinate to men in many aspects of their lives, politically, educationally, socially and sexually. This sexual inequality makes them highly vulnerable to STDs, including HIV, and unwanted pregnancies. This paper reviews 10 of the 15 studies carried out in sub-Saharan African countries between 1990 and 1996 and compiled by the World Health Organization. Recruitment methods, education of subjects, methodology and assessment of acceptability differed between studies. Despite these limitations, most studies concluded that the women who participated in the trials generally found the female condom acceptable. Acceptability was established quicker among prostitutes than among other women and men found the female condom less acceptable than did women. However, the sample size is too small to draw any firm conclusions. Commercial sex workers in the studies reviewed were very interested in this new method because it gave them an additional method of safer protection during sex. However, they were occasionally faced with difficult negotiations with some clients, refusal to use the female condom and sexual violence. Reuse of the device was reported in four studies, but the term reuse is seldom defined. In cases where it was defined, the frequency of reuse, with washing of the device, accounted for no more than 1% of the total number of uses. The acceptability of the female condom among women other than prostitutes faces two obstacles, the reaction of the woman's regular partner and attitudes to the device itself (appearance, difficulties or uneasiness concerning its use). However, some women liked it because it provided dual protection against pregnancy and STDs and sexual pleasure. The moderate level of acceptability to male partners may be overestimated because women whose partners disliked the device would be more likely to discontinue its use. The studies of acceptability reviewed here show that use of the female condom in Africa is realistic and that it provides women with more independent protection. Initial negative perceptions of the device are often replaced with a more positive reaction after several uses. The experience gained with use reduces the technical problems. We need to overcome the stereotypes, simplifications and strong opinions that threaten to damage the acceptance of this new method and efforts to encourage women to adopt it. However, we still require further clinical data on the effectiveness of the female condom at preventing pregnancy and HIV transmission. Availability of the female condom is improving in Africa. Pilot marketing studies were launched in 1996 in Guinea, Zambia, South Africa, followed by Uganda and Tanzania. There are local initiatives in Ivory Coast and Zimbabwe. (ABSTRACT TRUNC


Genetic parameters for test day milk yields of first lactation Holstein cows by random regression models.
Covariance components for test day milk yield using 263 390 first lactation records of 32 448 Holstein cows were estimated using random regression animal models by restricted maximum likelihood. Three functions were used to adjust the lactation curve: the five-parameter logarithmic Ali and Schaeffer function (AS), the three-parameter exponential Wilmink function in its standard form (W) and in a modified form (W*), by reducing the range of covariate, and the combination of Legendre polynomial and W (LEG+W). Heterogeneous residual variance (RV) for different classes (4 and 29) of days in milk was considered in adjusting the functions. Estimates of RV were quite similar, rating from 4.15 to 5.29 kg2. Heritability estimates for AS (0.29 to 0.42), LEG+W (0.28 to 0.42) and W* (0.33 to 0.40) were similar, but heritability estimates used W (0.25 to 0.65) were highest than those estimated by the other functions, particularly at the end of lactation. Genetic correlations between milk yield on consecutive test days were close to unity, but decreased as the interval between test days increased. The AS function with homogeneous RV model had the best fit among those evaluated.


Entrenching Inequity, Eroding Democracy: State Preemption of Local Housing Policy.
Housing is a fundamental right and a vital determinant of health. Health equity is not possible without widespread access to safe, affordable, high-quality housing. Local housing policy is a central conduit for advancing such ends. However, preemption of local law is a powerful institutional mechanism that state legislatures sometimes deploy to inhibit or nullify municipal efforts to address housing-based inequities. Local housing policies often have high stakes, are ideologically laden, and are politically salient. This makes them a clear target for preemptive action. Political science research to date has focused on broadly explaining the causes of preemption, with scant emphasis on its consequences and minimal attention to the implications for racial and economic equity. This article highlights the political repercussions of state preemption. Drawing on in-depth qualitative interviews, the article examines how local tenant organizations that work to build power within racially and economically marginalized communities perceive and respond to state preemption. The findings demonstrate how both the reality and the threat of state preemption prompt tenant organizations to adjust (and often minimize) their policy goals and to adapt their political strategies in ways that strain their capacity. By burdening local organizations that are crucial power resources in marginalized communities, state preemption of local housing policy risks entrenching inequity and eroding democracy.


Genomic Stability of Composite SCCmec ACME and COMER-Like Genetic Elements in Staphylococcus epidermidis Correlates With Rate of Excision.
The epidemiological success of methicillin-resistant Staphylococcus aureus USA300 has been associated with the presence of two mobile elements, the arginine catabolic mobile element (ACME) and the copper and mercury resistance (COMER) element. These two mobile elements are associated with resistance to copper, which has been related to host fitness and survival within macrophages. Several studies found that ACME is more prevalent, and exhibits greater diversity, in Staphylococcus epidermidis while COMER has not been identified in S. epidermidis or any other staphylococcal species. We aimed in this study to evaluate the presence and diversity of ACME and COMER-like elements in our S. epidermidis clinical isolates. The genomes of 58 S. epidermidis clinical isolates, collected between 2009 and 2018 in a Scottish hospital, were sequenced. A core-genome phylogenetic tree and genome based MLST typing showed that more than half of the isolates belong to the clinically predominant sequence type2 (ST2) and these isolates have been found to split into two lineages within the phylogenetic tree. Analysis showed the presence of SCCmec in the majority of isolates. Comparative analysis identified a cluster of ACME-positive isolates with most of them belonging to ST48. ACME showed high variation even between isolates of the same ACME type and ST. COMER-like elements have been identified in one of the two major hospital adapted drug resistant ST2 lineages; and showed high stability. This difference in stability at the genomic level correlates well with the up to one hundred times higher excision frequency found for the SCCmec elements in ACME-containing isolates compared to COMER-like element containing isolates. ACME/COMER-like element positive isolates did not show a significant phenotype of decreased copper susceptibility, while resistance to mercury was over-represented in COMER-like element positive isolates. To the best of our knowledge, this is the first molecular characterization of COMER-like elements in S. epidermidis isolates. The presence of the COMER-like elements is the most prominent accessory genome feature of these successful lineages suggesting that this chromosomal island contributes to the success and wide clinical distribution of ST2 S. epidermidis.


[Various biochemical and biophysical properties of a subpopulation of rat thymocytes isolated in a Ficoll gradient].
Subpopulations of rat thymocytes were obtained by cell precipitation in a single-stage transient phycoll gradient (isorapid precipitation). The fraction obtained were characterized in terms of the size, intensity of UV fluorescence, protein content and nucleoid mobility. The radius of thymocytes and UV fluorescence intensity monotonously increased during the transfer from the upper to lower fractions. The cells of medium-size fractions were characterized by the minimum content of cytoproteins and maximum mobility of nucleoid. In order to evaluate the density of thymocytes in the fractions, use was made of an additional cell precipitation in the phycoll-paque stage rho = 1.077. Incubation of thymocytes in medium 199 with a 10% rat serum led to the increased cell density in all the fractions, particularly in medium-size ones. Gamma-irradiation of thymocytes in a dose of 5 Gy appreciably accelerated the process under consideration. It is assumed that the medium-size fractions are enriched with thymocytes in G1 S phase, while lower fractions in G2 phase of the mitotic cycle. At the same time the fractions obtained appear to contain the subpopulations of thymocytes undergoing different stages of differentiation.


Reduced Mitochondrial Respiration in Hybrid Asexual Lizards.
AbstractThe scarcity of asexual reproduction in vertebrates alludes to an inherent cost. Several groups of asexual vertebrates exhibit lower endurance capacity (a trait predominantly sourced by mitochondrial respiration) compared with congeneric sexual species. Here we measure endurance capacity in five species of Aspidoscelis lizards and examine mitochondrial respiration between sexual and asexual species using mitochondrial respirometry. Our results show reduced endurance capacity, reduced mitochondrial respiration, and reduced phenotypic variability in asexual species compared with parental sexual species, along with a positive relationship between endurance capacity and mitochondrial respiration. Results of lower endurance capacity and lower mitochondrial respiration in asexual Aspidoscelis are consistent with hypotheses involving mitonuclear incompatibility.


[Bacteremia in 2 hospitals in Rosario, Argentina].
Bacteremia is associated with high morbidity and mortality. Nosocomial bacteremia is associated with an attributable mortality of 35%. In order to characterize the etiological agent of bacteremia cases during two time periods, 6605 patients were studied as follows: 1) from 1980 to 1982 (n = 2401) and 2) from 1988 to 2000 (n = 4204). A total of 596 cases of bacteremia were detected. The most frequent agents were Staphylococcus aureus, negative coagulase (CNS) Staphylococcus, Klebsiella pneumoniae and Escherichia coli. In the second period, an increase in the frequency of bacteremia caused by gram positive bacteria, particularly gram-positive cocci, was noted. Conversely, gram negative bacteria diminished significantly in the second period, specially enterobacterial species. Methicillin-resistant S. aureus and CNS were significantly more frequently isolated in the second period. Infrequent agents of endocarditis, such as Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, and Corynebacterium urealyticum, were isolated.


Anion-exchange extraction of cephapirin, cefotaxime, and cefoxitin from serum for liquid chromatography.
An anion-exchange column technique for extraction of antibiotics from serum proteins has been developed for use in the assay of cephapirin, cefotaxime, and cefoxitin by high-pressure liquid chromatography. Anion-exchange extraction of cephapirin from serum samples by this technique was compared with protein precipitation methods, using 6% trichloroacetic acid or absolute ethanol. Column extraction gave improved quantitative drug recovery and reduced background serum interferences in the resultant chromatograms when evaluated against protein precipitation. Comparisons of this method with microbiological assay gave statistically equivalent results. Twelve patient samples were assayed for cephapirin, and no interferences were encountered from the 22 systemic agents these subjects were receiving. The anion-exchange technique for antibiotic extraction provides a rapid, precise, and quantitative antibiotic assay when used with liquid chromatography.