Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.
Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury.


Structural studies of the [tris(imidazolyl)phosphine]metal nitrate complexes [[PimPrl,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg): comparison of nitrate-binding modes in synthetic analogues of carbonic anhydrase.
X-ray diffraction studies on a series of cationic divalent metal nitrate complexes supported by the tris(1-isopropyl-4-tert-butylimidazolyl)phosphine ligand, [[PimPri,But]M(NO3)]+ (M = Co, Cu, Zn, Cd, Hg), demonstrate that the nitrate ligand coordination mode is strongly dependent upon the metal. With the exception of that for the HgII derivative, the nitrate ligand coordination modes correlate with the activities of metal-substituted carbonic anhydrases, such that the only MII-carbonic anhydrases which exhibit significant activity, i.e., the Zn and Co species, are those for which the [[PimPri,But]M(NO3)]+ complexes possess strongly asymmetric nitrate ligands. This trend supports the notion that access to a unidentate, rather than a bidentate, bicarbonate intermediate may be a critical requirement for significant carbonic anhydrase activity. Interestingly, the nitrate coordination modes in the series of group 12 complexes, [[PimPri,But]M(NO3)]+ (M = Zn, Cd, Hg), do not exhibit a monotonic periodic trend: the bidenticity is greater for the cadmium complex than for either the zinc or mercury complexes. Since HgII-carbonic anhydrase is inactive, the correlation between nitrate coordination mode and enzyme activity is anomalous for the mercury complex. Therefore, it is suggested that the inactivity of HgII-carbonic anhydrase may be consequence of the reduced tendency of the mercury center in HgII-carbonic anhydrase to bind water.


Neural bases for individual differences in the subjective experience of short durations (less than 2 seconds).
The current research was designed to establish whether individual differences in timing performance predict neural activation in the areas that subserve the perception of short durations ranging between 400 and 1600 milliseconds. Seventeen participants completed both a temporal bisection task and a control task, in a mixed fMRI design. In keeping with previous research, there was increased activation in a network of regions typically active during time perception including the right supplementary motor area (SMA) and right pre-SMA and basal ganglia (including the putamen and right pallidum). Furthermore, correlations between neural activity in the right inferior frontal gyrus and SMA and timing performance corroborate the results of a recent meta-analysis and are further evidence that the SMA forms part of a neural clock that is responsible for the accumulation of temporal information. Specifically, subjective lengthening of the perceived duration were associated with increased activation in both the right SMA (and right pre-SMA) and right inferior frontal gyrus.


A genome-wide screen for normally methylated human CpG islands that can identify novel imprinted genes.
DNA methylation is a covalent modification of the nucleotide cytosine that is stably inherited at the dinucleotide CpG by somatic cells, and 70% of CpG dinucleotides in the genome are methylated. The exception to this pattern of methylation are CpG islands, CpG-rich sequences that are protected from methylation, and generally are thought to be methylated only on the inactive X-chromosome and in tumors, as well as differentially methylated regions (DMRs) in the vicinity of imprinted genes. To identify chromosomal regions that might harbor imprinted genes, we devised a strategy for isolating a library of normally methylated CpG islands. Most of the methylated CpG islands represented high copy number dispersed repeats. However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content >50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp) >0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues. We term these sequences gDMRs, for germline differentially methylated regions. At least two gDMRs mapped near imprinted genes, HYMA1 and a novel homolog of Elongin A and Elongin A2, which we term Elongin A3. Surprisingly, 18 of the methylated CpG islands were methylated in germline tissues of both parental origins, representing a previously uncharacterized class of normally methylated CpG islands in the genome, and which we term similarly methylated regions (SMRs). These SMRs, in contrast to the gDMRs, were significantly associated with telomeric band locations (P =.0008), suggesting a potential role for SMRs in chromosome organization. At least 10 of the methylated CpG islands were on average 85% conserved between mouse and human. These sequences will provide a valuable resource in the search for novel imprinted genes, for defining the molecular substrates of the normal methylome, and for identifying novel targets for mammalian chromatin formation.


Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries.
Increased cardiovascular risk after mercury exposure has been described, but the underlying mechanisms are not well explored. We analyzed the effects of chronic exposure to low mercury concentrations on endothelium-dependent responses in aorta and mesenteric resistance arteries (MRA). Wistar rats were treated with mercury chloride (1st dose 4.6 microg/kg, subsequent dose 0.07 microg.kg(-1).day(-1) im, 30 days) or vehicle. Blood levels at the end of treatment were 7.97 +/- 0.59 ng/ml. Mercury treatment: 1) did not affect systolic blood pressure; 2) increased phenylephrine-induced vasoconstriction; 3) reduced acetylcholine-induced vasodilatation; and 4) reduced in aorta and abolished in MRA the increased phenylephrine responses induced by either endothelium removal or the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 100 microM). Superoxide dismutase (SOD, 150 U/ml) and the NADPH oxidase inhibitor apocynin (0.3 mM) decreased the phenylephrine-induced contraction in aorta more in mercury-treated rats than controls. In MRA, SOD did not affect phenylephrine responses; however, when coincubated with l-NAME, the l-NAME effect on phenylephrine response was restored in mercury-treated rats. Both apocynin and SOD restored the impaired acetylcholine-induced vasodilatation in vessels from treated rats. Endothelial NOS expression did not change in aorta but was increased in MRA from mercury-treated rats. Vascular O2(-) production, plasmatic malondialdehyde levels, and total antioxidant status increased with the mercury treatment. In conclusion, chronic exposure to low concentrations of mercury promotes endothelial dysfunction as a result of the decreased NO bioavailability induced by increases in oxidative stress. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.


Hospitalizations for people with type 1 and type 2 diabetes compared with the nondiabetic population of Tayside, Scotland: a retrospective cohort study of resource use.
To compare the hospitalizations of people with type 1 and type 2 diabetes with those of the nondiabetic population of Tayside, Scotland. This was a retrospective cohort study set in Tayside, Scotland. Study subjects were eligible for inclusion if they lived in Tayside from 1 January 1995 to 31 December 1995. The primary end point was hospitalization. Comparisons between people with and without diabetes were assessed using logistic regression modeling. The fixed population for the year 1995 included 366,849 people registered with a Tayside general practitioner; 7,735 (2.1%) of these had diabetes. Approximately 25% of all study subjects with diabetes had at least one hospital admission, compared with 12% of the nondiabetic population. The length of stay was highest for patients with type 2 diabetes (median of 7 days). People with diabetes accounted for 8.2% of the total bed days and had approximately double the risk of admission. Type 2 diabetic patients had increased risks of myocardial infarction and stroke; both type 1 and type 2 diabetic patients were at increased risk for an endocrine/metabolic admission or renal failure. The risk of ophthalmic admissions, especially for cataract, was much higher in patients with type 1 diabetes compared with the nondiabetic population. Type 2 diabetes was associated with more frequent and longer admissions compared with the nondiabetic population. This was due to a higher risk of neurological, cardiovascular, renal, and ophthalmic hospitalizations compared with people without diabetes.


Hypotension is uncommon in patients presenting to the emergency department with non-traumatic cardiac tamponade.
Cardiac tamponade is a life-threatening disease in which hypotension is believed to be a common finding. Prior inpatient studies have described normotensive or hypertensive cases of tamponade; however, because the data were not collected from the Emergency Department (ED), the hemodynamic spectrum may differ from those presenting to the ED. We hypothesized that hypotension is uncommon in patients presenting to the ED with non-traumatic tamponade. A retrospective chart review was conducted between January 2002 and December 2007 of patients presenting to our ED who were subsequently diagnosed with cardiac tamponade. A total of 34 patients were identified with a diagnosis of tamponade. The mean blood pressure on ED arrival was 131/79mm Hg. Upon initial presentation to the ED, 35% (n=12) of patients were hypertensive, 50% (n=17) were normotensive, and 15% (n=5) were hypotensive. Of the 5 patients who were hypotensive on ED arrival, only 2 (6% of all patients) remained hypotensive upon admission to the hospital and before a pericardiocentesis. An average of 995mL of fluid was removed from the pericardium. The chief complaint for the majority of patients in tamponade was shortness of breath (70%); 59% were tachycardic in the ED, and 72% had cardiomegaly on chest X-ray study. Hypotension is uncommon in patients presenting to the ED with non-traumatic cardiac tamponade. The majority of patients are normotensive or even hypertensive. Thus, the emergency physician should not exclude the diagnosis of tamponade even in light of normotension or hypertension.


Nanoparticle- and liposome-carried drugs: new strategies for active targeting and drug delivery across blood-brain barrier.
The blood-brain barrier (BBB), the unusual microvascular endothelial interface between the central nervous system (CNS) and the circulatory system, is a major hindrance to drug delivery in the brain parenchyma. Besides the absence of fenestrations and the abundance of tight junctions, ATP-binding cassette (ABC) transporters critically reduce drug entry within the CNS, as they carry many drugs back into the bloodstream. Nanoparticle- and liposome-carried drugs, because of their increased cellular uptake and reduced efflux through ABC transporters, have been developed in recent times to circumvent the low drug permeability of the BBB. This review discusses the role of ABC transporters in controlling drug penetration into the brain parenchyma, the rationale for using nanoparticle- and liposome-based strategies to increase drug delivery across the BBB and new therapeutic strategies for using nanoparticle- and liposome-carried drugs in different conditions, ranging from CNS tumors and neurodegenerative diseases to viral infections and epilepsy.


Increased global transcription activity as a mechanism of replication stress in cancer.
Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.


Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.
Colorectal cancers (CRCs) diagnosed within a few years after an index colonoscopy can arise from missed lesions or the development of a new tumor. We investigated the proportion, characteristics, and factors that predict interval CRCs that develop within 6-60 months of colonoscopy. We performed a population-based cohort study of Utah residents who underwent colonoscopy examinations from 1995 through 2009 at Intermountain Healthcare or the University of Utah Health System, which provide care to more than 85% of state residents. Colonoscopy results were linked with cancer histories from the Utah Population Database to identify patients who underwent colonoscopy 6-60 months before a diagnosis of CRC (interval cancer). Logistic regression was performed to identify risk factors associated with interval cancers. Of 126,851 patients who underwent colonoscopies, 2659 were diagnosed with CRC; 6% of these CRCs (159 of 2659) developed within 6 to 60 months of a colonoscopy. Sex and age were not associated with interval CRCs. A higher percentage of patients with interval CRC were found to have adenomas at their index colonoscopy (57.2%), compared with patients found to have CRC detected at colonoscopy (36%) or patients who did not develop cancer (26%) (P < .001). Interval CRCs tended to be earlier-stage tumors than those detected at index colonoscopy, and to be proximally located (odds ratio, 2.24; P < .001). Patients with interval CRC were more likely to have a family history of CRC (odds ratio, 2.27; P = .008) and had a lower risk of death than patients found to have CRC at their index colonoscopy (hazard ratio, 0.63; P < .001). In a population-based study in Utah, 6% of all patients with CRC had interval cancers (cancer that developed within 6 to 60 months of a colonoscopy). Interval CRCs were associated with the proximal colon, earlier-stage cancer, lower risk of death, higher rate of adenoma, and family history of CRC. These findings indicate that interval colorectal tumors may arise as the result of distinct biologic features and/or suboptimal management of polyps at colonoscopy.


An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer's disease.
Protein aggregation is the hallmark of neurodegeneration, but the molecular mechanisms underlying late-onset Alzheimer's disease (AD) are unclear. Here we integrated transcriptomic, proteomic and epigenomic analyses of postmortem human brains to identify molecular pathways involved in AD. RNA sequencing analysis revealed upregulation of transcription- and chromatin-related genes, including the histone acetyltransferases for H3K27ac and H3K9ac. An unbiased proteomic screening singled out H3K27ac and H3K9ac as the main enrichments specific to AD. In turn, epigenomic profiling revealed gains in the histone H3 modifications H3K27ac and H3K9ac linked to transcription, chromatin and disease pathways in AD. Increasing genome-wide H3K27ac and H3K9ac in a fly model of AD exacerbated amyloid-β42-driven neurodegeneration. Together, these findings suggest that AD involves a reconfiguration of the epigenome, wherein H3K27ac and H3K9ac affect disease pathways by dysregulating transcription- and chromatin-gene feedback loops. The identification of this process highlights potential epigenetic strategies for early-stage disease treatment.


Anthraquinone as a redox label for DNA: synthesis, enzymatic incorporation, and electrochemistry of anthraquinone-modified nucleosides, nucleotides, and DNA.
Modified 2'-deoxynucleosides and deoxynucleoside triphosphates (dNTPs) bearing anthraquinone (AQ) attached through an acetylene or propargylcarbamoyl linker at the 5-position of pyrimidine (C) or at the 7-position of 7-deazaadenine were prepared by Sonogashira cross-coupling of halogenated dNTPs with 2-ethynylanthraquinone or 2-(2-propynylcarbamoyl)anthraquinone. Polymerase incorporations of the AQ-labeled dNTPs into DNA by primer extension with KOD XL polymerase have been successfully developed. The electrochemical properties of the AQ-labeled nucleosides, nucleotides, and DNA were studied by cyclic and square-wave voltammetry, which show a distinct reversible couple of peaks around -0.4 V that make the AQ a suitable redox label for DNA.


Significance of microRNA targeted estrogen receptor in male fertility.
Estrogen receptor-alpha (ERα) mediates estrogen action in regulation of different levels of the hypothalamic-pituitary-testis axis. It has a key role in spermatogenesis. Estrogen receptor alpha knock-out (ER koα) male mice were infertile and severe impairment in spermatogenesis and seminiferous tubules was observed. Recently, it has been reported that microRNA (miRNA) mir-100 and let-7b were predicted to target ERα gene. MiRNA are small, endogenous, single stranded RNA molecules that regulate gene expression and have been implicated in various disease states. It has been proved that some miRNAs expression is tissue- and disease-specific, giving potential for identifying miRNAs as a diagnostic tool. In this study, the change in the expression levels of mir-100, let-7b and ERα expression levels were evaluated in oligospermic infertile patients (n=43) compared to control fertile subjects (n=43). After washing and separating sperms, total RNA was isolated and then cDNA was synthesized. The expression levels of mir-100 and let-7b and ERα were evaluated by real time PCR. Mir-100, let-7b levels were significantly higher than those in control group (P=0.008 and P=0.009, respectively). We have found that, ERα level was significantly decreased in comparison with normal group (P< 0.0001). Changes in mir-100, let-7b and ERα expression levels in oligospermic patients may be associated with the susceptibility and progression of infertility. The results of this study indicate that miRNA can have a key role in spermatogenesis and might have a diagnostic and prognostic value in men infertility.


Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury.
MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denuded vessel area. Genetic deletion of miR-92a in Tie2-expressing cells, representing mainly endothelial cells, enhanced re-endothelialization, whereas no phenotype was observed in mice lacking miR-92a expression in haematopoietic cells. The enhanced endothelial recovery was associated with reduced accumulation of leucocytes and inhibition of neointimal formation 21 days after injury and led to the de-repression of the miR-92a targets integrin α5 and sirtuin1. Our data indicate that inhibition of endothelial miR-92a attenuates neointimal lesion formation by accelerating re-endothelialization and thus represents a putative novel mechanism to enhance the functional recovery following vascular injury.


Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells.
Promoting ectopic development of pancreatic beta cells from other cell types is one of the strategies being pursued for the treatment of diabetes. To achieve this, a detailed outline of the molecular lineage that operates in pancreatic progenitor cells to generate beta cells over other endocrine cell types is necessary. Here, we demonstrate that early transient expression of the endocrine progenitor bHLH protein Neurogenin 3 (Ngn3) favors the promotion of pancreatic beta and delta cell fates over an alpha cell fate, while later transient expression promotes ectopic development of all three endocrine cell fates. We found that short-term activation of Ngn3 in Xenopus laevis endoderm just after gastrulation was sufficient to promote both early and ectopic development of beta and delta cells. By examining gene expression changes 4 h after Ngn3 activation we identified several new downstream targets of Ngn3. We show that several of these are required for the promotion of ectopic beta cells by Ngn3 as well as for normal beta cell development. These results provide new detail regarding the Ngn3 transcriptional network operating in endocrine progenitor cells to specify a beta cell phenotype and should help define new approaches to promote ectopic development of beta cells for diabetes therapy.


Metabolism of Doubly para-Substituted Hydroxychlorobiphenyls by Bacterial Biphenyl Dioxygenases.
In this work, we examined the profile of metabolites produced from the doubly para-substituted biphenyl analogs 4,4'-dihydroxybiphenyl, 4-hydroxy-4'-chlorobiphenyl, 3-hydroxy-4,4'-dichlorobiphenyl, and 3,3'-dihydroxy-4,4'-chlorobiphenyl by biphenyl-induced Pandoraea pnomenusa B356 and by its biphenyl dioxygenase (BPDO). 4-Hydroxy-4'-chlorobiphenyl was hydroxylated principally through a 2,3-dioxygenation of the hydroxylated ring to generate 2,3-dihydro-2,3,4-trihydroxy-4'-chlorobiphenyl and 3,4-dihydroxy-4'-chlorobiphenyl after the removal of water. The former was further oxidized by the biphenyl dioxygenase to produce ultimately 3,4,5-trihydroxy-4'-chlorobiphenyl, a dead-end metabolite. 3-Hydroxy-4,4'-dichlorobiphenyl was oxygenated on both rings. Hydroxylation of the nonhydroxylated ring generated 2,3,3'-trihydroxy-4'-chlorobiphenyl with concomitant dechlorination, and 2,3,3'-trihydroxy-4'-chlorobiphenyl was ultimately metabolized to 2-hydroxy-4-chlorobenzoate, but hydroxylation of the hydroxylated ring generated dead-end metabolites. 3,3'-Dihydroxy-4,4'-dichlorobiphenyl was principally metabolized through a 2,3-dioxygenation to generate 2,3-dihydro-2,3,3'-trihydroxy-4,4'-dichlorobiphenyl, which was ultimately converted to 3-hydroxy-4-chlorobenzoate. Similar metabolites were produced when the biphenyl dioxygenase of Burkholderia xenovorans LB400 was used to catalyze the reactions, except that for the three substrates used, the BPDO of LB400 was less efficient than that of B356, and unlike that of B356, it was unable to further oxidize the initial reaction products. Together the data show that BPDO oxidation of doubly para-substituted hydroxychlorobiphenyls may generate nonnegligible amounts of dead-end metabolites. Therefore, biphenyl dioxygenase could produce metabolites other than those expected, corresponding to dihydrodihydroxy metabolites from initial doubly para-substituted substrates. This finding shows that a clear picture of the fate of polychlorinated biphenyls in contaminated sites will require more insights into the bacterial metabolism of hydroxychlorobiphenyls and the chemistry of the dihydrodihydroxylated metabolites derived from them.


An Empirical Investigation of Domain Generalization with Empirical Risk Minimizers.
Recent work demonstrates that deep neural networks trained using Empirical Risk Minimization (ERM) can generalize under distribution shift, outperforming specialized training algorithms for domain generalization. The goal of this paper is to further understand this phenomenon. In particular, we study the extent to which the seminal domain adaptation theory of Ben-David et al. (2007) explains the performance of ERMs. Perhaps surprisingly, we find that this theory does not provide a tight explanation of the out-of-domain generalization observed across a large number of ERM models trained on three popular domain generalization datasets. This motivates us to investigate other possible measures-that, however, lack theory-which could explain generalization in this setting. Our investigation reveals that measures relating to the Fisher information, predictive entropy, and maximum mean discrepancy are good predictors of the out-of-distribution generalization of ERM models. We hope that our work helps galvanize the community towards building a better understanding of when deep networks trained with ERM generalize out-of-distribution.


A step toward polytwistane: synthesis and characterization of C2-symmetric tritwistane.
Twistane is a classic hydrocarbon with fascinating stereochemical properties. Herein we describe a series of oligomers of twistane that converges on a chiral nanorod, which we term polytwistane. A member of this series, C2-symmetric tritwistane, has been synthesized for the first time.


The effects of weight loss strategies on gastric emptying and appetite control.
The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g. sleeve gastrectomy and Roux-en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying, which we hypothesize will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g. diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.


Massively parallel amplicon sequencing reveals isotype-specific variability of antimicrobial peptide transcripts in Mytilus galloprovincialis.
Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP) precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio-induced diversity of AMP transcripts in mussel hemocytes from three European regions. Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France), Vigo (Spain) and Venice (Italy). To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore) and wild (lagoon) Venice mussels, both injected with 10(7) Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC) minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related to geographical origin or Vibrio injection emerged. Whether or not the contact with potential pathogens can increase the amount of AMP transcript variants in mussels requires additional study.


Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis.
Objectives The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). Methods Twenty cats from 3.3-82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. Results Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1-7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1-7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3-4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5-14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16-18 weeks of age. Conclusions and relevance GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.


Reflex vascular responses in the finger to contralateral thermal stimuli during the normal menstrual cycle: a hormonal basis to Raynaud's phenomenon?
1. Raynaud's phenomenon is a condition which primarily affects women and it must be assumed that hormonal influences are responsible. 2. To further investigate this assumption the effect of cyclic sex hormone fluctuations on the digital vascular reactivity of ten normal young women was studied by the diagnostic techniques of thermal entrainment of finger blood flow and Doppler ultrasound mapping of the digital arteries. 3. In the immediate pre-ovulatory period the results obtained were comparable with those found in patients with established Raynaud's phenomenon, suggesting that oestrogen has an important modulating effect in vivo on reflex peripheral vasomotor responses to thermal stimuli. 4. 'Primary' Raynaud's phenomenon may represent an exaggerated response to oestrogen.


A difference in inward rectification and polyamine block and permeation between the Kir2.1 and Kir3.1/Kir3.4 K+ channels.
Inward rectification is caused by voltage-dependent block of the channel pore by intracellular Mg2+ and polyamines such as spermine. In the present study, we compared inward rectification in the Kir3.1/Kir3.4 channel, which underlies the cardiac current I(K,ACh), and the Kir2.1 channel, which underlies the cardiac current I(K,1). Sustained outward current at potentials positive to the K+ reversal potential was observed through Kir3.1/Kir3.4, but not Kir2.1, demonstrating that Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1. We show that Kir3.1/Kir3.4 is more sensitive to extracellular spermine block than Kir2.1, and that intracellular and extracellular polyamines can permeate Kir3.1/Kir3.4, but not Kir2.1, to a limited extent. We describe a simple kinetic model in which polyamines act as permeant blockers of Kir3.1/Kir3.4, but as relatively impermeant blockers of Kir2.1. The model shows the difference in sensitivity to extracellular spermine block, as well as the difference in the extent of inward rectification between the two channels. This suggests that Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1 because of the difference in the balance of polyamine block and permeation of the two channels.


Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment.
Adult house flies, Musca domestica L., are mechanical vectors of more than 100 devastating diseases that have severe consequences for human and animal health. House fly larvae play a vital role as decomposers of animal wastes, and thus live in intimate association with many animal pathogens. We have sequenced and analyzed the genome of the house fly using DNA from female flies. The sequenced genome is 691 Mb. Compared with Drosophila melanogaster, the genome contains a rich resource of shared and novel protein coding genes, a significantly higher amount of repetitive elements, and substantial increases in copy number and diversity of both the recognition and effector components of the immune system, consistent with life in a pathogen-rich environment. There are 146 P450 genes, plus 11 pseudogenes, in M. domestica, representing a significant increase relative to D. melanogaster and suggesting the presence of enhanced detoxification in house flies. Relative to D. melanogaster, M. domestica has also evolved an expanded repertoire of chemoreceptors and odorant binding proteins, many associated with gustation. This represents the first genome sequence of an insect that lives in intimate association with abundant animal pathogens. The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, and for exploring the basic biology of this important pest. The genome of this species will also serve as a close out-group to Drosophila in comparative genomic studies.


Effect of Non-invasive Vagus Nerve Stimulation on Resting-State Electroencephalography and Laser-Evoked Potentials in Migraine Patients: Mechanistic Insights.
A recent multicenter trial provided Class I evidence that for patients with an episodic migraine, non-invasive vagus nerve stimulation (nVNS) significantly increases the probability of having mild pain or being pain-free 2 h post-stimulation. Here we aimed to investigate the potential effect of nVNS in the modulation of spontaneous and pain related bioelectrical activity in a subgroup of migraine patients enrolled in the PRESTO trial by using resting-state electroencephalography and trigeminal laser-evoked potentials (LEPs). LEPs were recorded for 27 migraine patients who received active or sham nVNS over the cervical vagus nerve. We measured power values for frequencies between 1-100 Hz in a resting-state condition and the latency and amplitude of N1, N2, and P2 components of LEPs in a basal condition during and after active or sham vagus nerve stimulation (T0, T1, T2). The P2 evoked by the right and the left trigeminal branch was smaller during active nVNS. The sham device also attenuated the P2 amplitude evoked by the left trigeminal branch at T1 and T2, but this attenuation did not reach significance. No changes were observed for N1 amplitude, N1, N2, P2 latency, or pain rating. nVNS induced an increase of EEG power in both slow and fast rhythms, but this effect was not significant as compared to the sham device. These findings suggest that nVNS acts on the cortical areas that are responsible for trigeminal pain control and pave the ground for future studies aimed at confirming the possible correlations with clinical outcomes, including the effect on symptoms that are directly correlated with trigeminal pain processing and modulation.


Quantitative changes in testicular structure and function in rat exposed to mobile phone radiation.
The possible effects of the electromagnetic fields (EMF) generated by mobile phones on reproductive functions have been discussed in recent years. The aim of this study was to evaluate the effects of EMF emitted from mobile phones on the rat testis morphology and histopathology using stereological techniques. We also investigated cortisol, testosterone, FSH and LH levels. A total of thirty-two (n = 32) male Wistar albino rats were used in this study. Animals were randomly divided into four groups as control (C, n = 8), sham (Sh, n = 8), mobile phone speech (Sp, n = 8) and mobile phone standby (ST by). Morphometric measurements were made with the help of a computer-assisted stereological analysis system. The testis weight and volume were significantly lower in the EMF exposed groups. The mean volume fraction of interstitial tissue was higher, but the volume fraction of tubular tissue was lower in the EMF-exposed groups. The mean tubular and germinal tissue volume, seminiferous tubule diameter and germinal epithelium height were also lower in EMF exposed groups. The cortisol levels in the EMF-exposed groups were significantly higher. In conclusion, the EMF created by mobile phones caused morphologic and histological changes by the affecting germinal epithelium tissue negatively.


Short-term evaluation of autologous transplantation of bone marrow-derived mesenchymal stem cells in patients with cirrhosis: Egyptian study.
Stem cell-based therapy has received attention as a possible alternative to organ transplantation. The aim of this study was to assess the safety and efficacy of autologous transplantation of bone marrow (BM)-derived stromal cells in post-HCV liver cirrhosis patients. 10 × 10(6) of isolated human bone marrow (HBM)-stromal cells in 10 mL normal saline were injected in the spleen of 20 patients with end-stage liver cirrhosis guided by the ultrasonography, and then patients were followed up on monthly basis for six months. A statistically significant decrease was detected in the total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) (p-value<0.01), prothrombin time (PT), and international normalized ratio (INR) levels (p-value<0.05), while a statistically significant increase in the albumin and PC (p-value<0.05) after follow-up. This study suggested the safety, feasibility, and efficacy of the intrasplenic injection of autologous BM stromal cells in improving liver function in Egyptian patients with cirrhosis.


Health in middle-aged and elderly women: A conceptual framework for healthy menopause.
Middle-aged and elderly women constitute a large and growing proportion of the population. The peri and postmenopausal period constitutes a challenging transition time for women's health, and menopausal health is a crucial aspect in healthy and successful aging. Currently, no framework for the concept of healthy menopause exists, despite its recognized importance. Therefore, we aimed to: (i) characterize healthy menopause; (ii) identify aspects that contribute to it; and (iii) explore potential approaches to measure it. We propose healthy menopause as a dynamic state, following the permanent loss of ovarian function, which is characterized by self-perceived satisfactory physical, psychological and social functioning, incorporating disease and disability, allowing the attainment of a woman's desired ability to adapt and capacity to self-manage. The concept of healthy menopause applies to all women from the moment they enter the menopausal transition, up until they reach early and late postmenopause and includes women with spontaneous, iatrogenic, and premature menopause. This conceptualization can be considered as a further step in the maintenance and improvement of health in menopausal women from different perspectives, foremost the woman's own perspective, followed by the clinical, public health, and societal perspectives, and can be seen as a further step in delineating lines for future research. Furthermore, it could facilitate the improvement of adequate preventive and treatment strategies, guide scientific efforts, and aid education and communication to health care practitioners and the general public, allowing women the achievement of their potential and the fulfillment of their fundamental role in society.


Differentiation of molecular genotypes and virulence phenotypes of Puccinia triticina from common wheat in North America.
Wheat leaf rust caused by Puccinia triticina is widely distributed in the wheat growing regions of the United States and Canada, and is subject to selection for virulence phenotype by leaf rust resistance genes in wheat cultivars. The objective of this study was to determine the number of genetically differentiated groups of P. triticina that are currently present in North America. In total, 148 isolates of P. triticina from the 1980s to 2005 were collected from wheat-growing regions of the United States and Canada and tested for virulence on 20 lines of wheat with single genes for leaf rust resistance and for molecular genotype with 23 simple sequence repeat (SSR) markers. In total, 91 virulence phenotypes and 65 SSR genotypes were found. After removal of isolates with identical virulence and SSR genotypes, 125 isolates were included for further analysis. Bayesian cluster analysis indicated five different groups of isolates based on SSR genotypes that also differed for virulence to leaf rust resistance genes Lr2a, Lr2c, Lr3bg, Lr17, and Lr28. Isolates avirulent to Lr14a and Lr20 that have increased since 2003 had SSR genotypes identical or similar to older isolates in one of the five groups, indicating that these isolates were derived by mutation from the previously existing population of P. triticina. The representative collection of P. triticina isolates had characteristics consistent with an asexual dikaryotic population of genetically differentiated groups of SSR genotypes with high levels of heterozygosity and disequilibrium within which stepwise mutation at avirulence or virulence loci regularly occurs.


Structure-Based Virtual Screening and Biological Evaluation of a Calpain Inhibitor for Prevention of Selenite-Induced Cataractogenesis in an in Vitro System.
Calpains belong to the family of calcium-dependent, structurally related intracellular cysteine proteases that exhibit significant functions in evolution of different types of cataracts in human as well as animal models. Application of calpain inhibitors generated through a virtual screening workflow may provide new avenues for the prevention of cataractogenesis. Hence, in the current study, compounds were first screened for potent calpain inhibitory activity by employing a structure-based approach, and the screening results were then validated through biological experiments in rat lenses. A hit compound, HTS08688, was obtained by structure-based virtual screening. A micromolar concentration of HTS08688 was found to prevent in vitro cataractogenesis in isolated Wistar rat lenses, while maintaining the antioxidant and calcium concentrations at near normal levels. Inhibition of superoxide anion generation, as observed through cytochemical localization studies, and maintenance of structural integrity, as demonstrated by histological analysis of lenticular tissue, also suggested that HTS08688 can ameliorate the cataractous condition induced by selenite in an in vitro rodent model. A cell proliferation assay was performed; the IC 50 value of the screened calpain inhibitor, HTS08688, against human lenticular epithelial cells-b3 was found to be 177 μM/mL. This combined theoretical and experimental approach has demonstrated a potent lead compound, HTS08688, that exhibits putative anticataractogenic activity by virtue of its potential to inhibit calpain.


Racial disparities in patients with head and neck squamous cell carcinoma.
Black patients are reported to have a higher incidence of advanced disease and increased mortality from head and neck squamous cell carcinoma (HNSCC) but constitute the minority of patients in large-scale studies investigating the effect of race on outcome. This study sought to determine if racial disparities exist between black and white patients with HNSCC treated at a single large institution in the South with a high proportion of black patients. The authors conducted a nonrandomized retrospective cohort analysis. The tumor registry was used to identify patients diagnosed with HNSCC from 1985 to 2002. The medical records of non-Hispanic white and black adult patients were retrospectively reviewed. Median household income, percentage of population below poverty level, and education level based on census tract and block information were obtained from U.S. Census 2000 data. Standard statistical analysis, including Kaplan-Meier survival curve analysis and Cox proportional hazards models, was used to analyze the effects of covariables on survival. A total of 1,128 patients met study criteria (478 black, 650 white). Compared with white patients, black patients were significantly younger (mean age, 53.9 vs. 56.4 years, P<.0001), male (81.2% vs. 72.3%, P=.0005), more commonly abused alcohol (88.0% vs. 74.3%, P<.0001), and were significantly less likely to have insurance (8.6% vs. 21.7%, P<.0001). There was no difference in the incidence of tobacco use (91.7%), advanced comorbidity (35.9%), or primary tumor site. Black patients had a significantly greater incidence of stage IV disease (65.7% vs. 46.6%, P<.0001) and nonoperative treatment (48.7% vs. 30.8%, P<.0001), which was performed for inoperable disease in 57.1% of black compared with 31.0% of white patients (P<.0001). Black patients resided in census block groups with significantly lower mean education level, median income, and a higher percentage of population below poverty compared with white patients. The 5-year disease-specific survival differed significantly between black (29.3%) and white (54.7%) patients (P<.0001). Cox proportional hazards models revealed that alcohol abuse, advanced TNM stage, high tumor grade, nodal disease, extracapsular spread, advanced comorbidity, and regional or distant metastatic disease were associated with poorer survival for all patients. An interaction with race was found for insurance status, nonoperative treatment, and extracapsular spread. Stepwise variable selection adjusting for patient, tumor, and treatment characteristics showed a significant effect only for race by payor status on disease-specific survival (P=.0228). Insurance status, treatment, and extracapsular spread differentially affected the survival of black patients compared with white patients. Only insurance status had a significant effect on survival in black patients after controlling for other variables. These data suggest that racial differences in HNSCC outcomes are primarily related to differences in access to health care.


Vitreous Wiping, a new technique for removal of vitreous cortex remnants during vitrectomy.
Unremoved vitreoschisis-induced vitreous cortex remnants (VCR) are associated with macular pathology. When present on the retinal periphery, they may play a role in proliferative vitreoretinopathy and retinal detachment after vitrectomy. Existing instruments for their removal involve substantial risk of iatrogenic retinal damage. Purpose of this study was to evaluate the use of a new technique, Vitreous Wiping, for removal of VCR during vitrectomy. Proof-of-concept case series of six eyes (six patients) treated with vitrectomy for various pathologies (macula-on and macula-off retinal detachment, macular hole, macular pucker and vitreous floaters). Vitreous cortex remnants on the surface of the retina were visualized with triamcinolone and removed by Vitreous Wiping with a rectangular piece of polyvinyl alcohol (PVA) held with intra-ocular forceps. Visual acuity and clinical course were assessed during a follow-up of 6 months. All eyes underwent postoperative macular optical coherence tomography. Eyes without preoperative macular pathology, underwent retinal sensitivity testing and eyes without paracentral pathology underwent visual field analysis. Vitreous cortex remnants could be removed completely in all eyes. There were no intra- or postoperative complications. We observed that PVA is soft like a sponge and vitreous sticks to it, making Vitreous Wiping easier and safer, compared to alternative instruments. Visual acuity improved in all eyes. Microperimetry and visual field analysis revealed no abnormalities related to Vitreous Wiping. Vitreoschisis-induced VCR can be removed effectively and safely from the retinal surface by Vitreous Wiping. Larger studies are needed to confirm this promising finding and its potential impact.


Hearing immaturity found by ABR and its clinical impact on otoneurological evaluation.
Auditory Brainstem Response (ABR) is the most reliable and most frequently used procedure to evaluate audiological conditions in early infancy. However, several reports have demonstrated that developmental change in the central nervous system may affect the results of ABR in audiological evaluations. We examined statistically the reliability of ABR for the diagnosis of profound deafness in early childhood according to our experience over the past 12 years of follow-up in our facility. Subjects included 371 children among 1,041 children who were admitted to Kanariya-Gakuen (institute for pre-school deaf children) from April 1985 to March 1997. These children were examined with ABR to determine their hearing levels. In five cases with an abnormal hearing threshold determined by ABR and other audiological tests, repeated examinations carried out during a 5- to 6-month follow-up period revealed that they had normal hearing. Three of these children had been diagnosed previously with mental retardation and the remaining two were infants < 5 months old. The specificity and sensitivity of ABR were calculated as 97.3% and 100%, respectively. The predictive value of a positive result was 94.7%. There remains the possibility of a false negative for such cases, although the rate seems to be very low (< 0.2%).


Natural microbe-mediated refractoriness to Plasmodium infection in Anopheles gambiae.
Malaria parasite transmission depends on the successful transition of Plasmodium through discrete developmental stages in the lumen of the mosquito midgut. Like the human intestinal tract, the mosquito midgut contains a diverse microbial flora, which may compromise the ability of Plasmodium to establish infection. We have identified an Enterobacter bacterium isolated from wild mosquito populations in Zambia that renders the mosquito resistant to infection with the human malaria parasite Plasmodium falciparum by interfering with parasite development before invasion of the midgut epithelium. Phenotypic analyses showed that the anti-Plasmodium mechanism requires small populations of replicating bacteria and is mediated through a mosquito-independent interaction with the malaria parasite. We show that this anti-Plasmodium effect is largely caused by bacterial generation of reactive oxygen species.


Comparison of glomerular filtration rate measured by plasma sample technique, Cockroft Gault method and Gates' method in voluntary kidney donors and renal transplant recipients.
There are numerous methods for calculation of glomerular filtration rate (GFR), which is a crucial measurement to identify patients with renal disease. The aim of this study is to compare four different methods of GFR calculation. Clinical setup, prospective study. Data was collected from routine renal scans done for voluntary kidney donors (VKD) or renal transplant recipients 6 months after transplantation. Following technetium-99m diethylene triamine penta acetic acid injection, venous blood samples were collected from contralateral arm at 120, 180, and 240 min through an indwelling venous cannula and direct collection by syringe. A total volume of 1 ml of plasma from each sample and standards were counted in an automatic gamma counter for 1 min. Blood samples taken at 120 min and 240 min were used for double plasma sample method (DPSM) and a sample taken at 180 min for single plasma sample method (SPSM). Russell's formulae for SPSM and DPSM were used for GFR estimation. Gates' method GFR was calculated by vendor provided software. Correlation analysis was performed using Pearson's correlation test. SPSM correlated well with DPSM. GFR value in healthy potential kidney donors has a significant role in the selection of donors. The mean GFR ± (standard deviation) in VKD using SPSM, DPSM, camera depth method and Cockroft Gault method was 134.6 (25.9), 137.5 (42.4), 98.6 (15.9), 83.5 (21.1) respectively. Gates' GFR calculation did not correlate well with plasma sampling method. Calculation of GFR plays a vital role in the management of renal patients, hence it was noted that Gates GFR may not be a reliable method of calculation. SPSM was more reliable. DPSM is reliable but cumbersome. It is difficult to accurately calculate GFR without a gold standard.


Molecular evidence of late preconditioning after sevoflurane inhalation in healthy volunteers.
Late preconditioning by volatile anesthetics evolves in response to transcriptional changes. We hypothesized that sevoflurane inhalation would modify the transcriptome in human blood and modulate the expression of adhesion molecules in white blood cells consistent with the occurrence of a late preconditioning phase. Five healthy male subjects inhaled sevoflurane at an end-tidal concentration of 0.5%-1.0% for 60 min. Venous blood samples were collected at baseline, after 15 and 60 min of inhalation, and 6, 24, 48, and 72 h thereafter and immediately processed for flow cytometry and mRNA extraction and hybridization to Affymetrix U133 Plus 2.0 microarrays. Data were analyzed using Significance Analysis of Microarray and Gene Set Enrichment Analysis and confirmed by real-time reverse transcription polymerase chain reaction. L-selectin (CD62L) and beta2-integrin (CD11b) expression was determined on granulocytes and monocytes using flow cytometry. Sevoflurane inhalation rapidly and markedly altered gene expression in white blood cells. Key transcripts potentially involved in late preconditioning or organ protection including paraoxonase, 12-lipoxygenase, heat shock protein 40, chemokine ligand 5, and phosphodiesterase 5A were regulated in response to sevoflurane. Sevoflurane further decreased transcripts involved in peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) signaling and fatty acid oxidation. Reduced L-selectin (CD62L) expression on granulocytes accompanied with increased resistance to inflammatory activation was present at 24 to 48 h after sevoflurane exposure. Sevoflurane at subanesthetic concentrations modifies blood transcriptome and decreases the expression of the proinflammatory L-selectin (CD62L), consistent with a "second window of protection" in humans.


A Comparison of Hyporheic Transport at a Cross-Vane Structure and Natural Riffle.
While restoring hyporheic flowpaths has been cited as a benefit to stream restoration structures, little documentation exists confirming that constructed restoration structures induce comparable hyporheic exchange to natural stream features. This study compares a stream restoration structure (cross-vane) to a natural feature (riffle) concurrently in the same stream reach using time-lapsed electrical resistivity (ER) tomography. Using this hydrogeophysical approach, we were able to quantify hyporheic extent and transport beneath the cross-vane structure and the riffle. We interpret from the geophysical data that the cross-vane and the natural riffle induced spatially and temporally unique hyporheic extent and transport, and the cross-vane created both spatially larger and temporally longer hyporheic flowpaths than the natural riffle. Tracer from the 4.67-h injection was detected along flowpaths for 4.6 h at the cross-vane and 4.2 h at the riffle. The spatial extent of the hyporheic zone at the cross-vane was 12% larger than that at the riffle. We compare ER results of this study to vertical fluxes calculated from temperature profiles and conclude significant differences in the interpretation of hyporheic transport from these different field techniques. Results of this study demonstrate a high degree of heterogeneity in transport metrics at both the cross-vane and the riffle and differences between the hyporheic flowpath networks at the two different features. Our results suggest that restoration structures may be capable of creating sufficient exchange flux and timescales of transport to achieve the same ecological functions as natural features, but engineering of the physical and biogeochemical environment may be necessary to realize these benefits.


Student selection to a rural veterinary school. 2: predictors of student performance and attrition.
To evaluate the extent to which current selection processes at Charles Sturt University, New South Wales, Australia, predict performance within and attrition from the veterinary degree program. Retrospective evaluation of application details and student performance data. Database records of 424 students entering the veterinary program were retrieved from university records, including all students graduating (n = 356) or leaving the program without completing (n = 68) between 2005 and 2016. Demographic data were related to results of selection processes and achievement within the degree using univariable and multivariable general linear and logistic regression analyses. The grade point average achieved over the 6 years of the degree was influenced by academic achievement prior to entry, gender (females performed ≈ 2% better than males) and interview scores. Preceptor evaluation of final-year clinical performance was associated with interview scores, gender (males performed ≈ 4% better than females) and residential address at the time of application. Attrition for personal reasons was more common for female students and students who had completed a prior degree, and students who experienced academic or personal attrition had lower written application scores. Factors that have been previously linked to poor academic outcomes, including rural or low socioeconomic background, were not associated with adverse student outcomes. Selection processes did not systematically disadvantage students admitted to the degree program. Gender differences in personal attrition and academic and clinical performance warrant further evaluation. Factors in addition to academic aptitude predicted student success.


Effects of ferumoxides-protamine sulfate labeling on immunomodulatory characteristics of macrophage-like THP-1 cells.
Superparamagnetic Iron Oxide (SPIO) complexed with cationic transfection agent is used to label various mammalian cells. Labeled cells can then be utilized as an in vivo magnetic resonance imaging (MRI) probes. However, certain number of in vivo administered labeled cells may be cleared from tissues by the host's macrophages. For successful translation to routine clinical application of SPIO labeling method it is important that this mode of in vivo clearance of iron does not elicit any diverse immunological effects. The purpose of this study was to demonstrate that SPIO agent ferumoxides-protamine sulfate (FePro) incorporation into macrophages does not alter immunological properties of these cells with regard to differentiation, chemotaxis, and ability to respond to the activation stimuli and to modulate T cell response. We used THP-1 cell line as a model for studying macrophage cell type. THP-1 cells were magnetically labeled with FePro, differentiated with 100 nM of phorbol ester, 12-Myristate-13-acetate (TPA) and stimulated with 100 ng/ml of LPS. The results showed 1) FePro labeling had no effect on the changes in morphology and expression of cell surface proteins associated with TPA induced differentiation; 2) FePro labeled cells responded to LPS with slightly higher levels of NFkappaB pathway activation, as shown by immunobloting; TNF-alpha secretion and cell surface expression levels of CD54 and CD83 activation markers, under these conditions, were still comparable to the levels observed in non-labeled cells; 3) FePro labeling exhibited differential, chemokine dependent, effect on THP-1 chemotaxis with a decrease in cell directional migration to MCP-1; 4) FePro labeling did not affect the ability of THP-1 cells to down-regulate T cell expression of CD4 and CD8 and to induce T cell proliferation. Our study demonstrated that intracellular incorporation of FePro complexes does not alter overall immunological properties of THP-1 cells. The described experiments provide the model for studying the effects of in vivo clearance of iron particles via incorporation into the host's macrophages that may follow after in vivo application of any type of magnetically labeled mammalian cells. To better mimic the complex in vivo scenario, this model may be further exploited by introducing additional cellular and biological, immunologically relevant, components.


Labor Analgesia Consumption and Time to Neuraxial Catheter Placement in Women with a History of Surgical Correction for Scoliosis: A Case-Matched Study.
Neuraxial analgesic techniques are the most effective form of labor analgesia. Small studies (9-21 patients), conducted 10 to 20 years ago, demonstrated successful neuraxial labor analgesia in only 50% to 66% of patients with surgical correction for scoliosis. Newer surgical techniques for scoliosis correction make the epidural space more accessible, but postsurgical changes may still alter the efficacy of neuraxial labor analgesia. The purpose of this prospective case-matched study was to compare hourly bupivacaine consumption and time to placement of neuraxial technique in laboring women with spinal instrumentation compared with women without previous back surgery. All women with previous spinal instrumentation surgery for scoliosis correction who requested neuraxial labor analgesia at Prentice Women's Hospital during the study period were approached. Control subjects were matched for anesthesiologist level of experience. The primary outcomes were bupivacaine consumption per hour of labor analgesia and time to placement of the neuraxial technique. Secondary outcomes included supplemental analgesia requirements and neuraxial analgesia failures and complications. Data from 41 women with surgical correction for scoliosis and 41 control subjects requesting neuraxial labor analgesia were analyzed. Obstetric and demographic characteristics of study participants were not different between groups. Median (interquartile range) hourly bupivacaine consumption was 15.2 mg/h (12.5-18.7) in the spinal instrumentation group and 14.2 mg/h (11.8-16.0) in the control group; the difference in medians was 1 mg/h (95% confidence interval [CI], -1.3 to 3.0; P = 0.38). The total bupivacaine consumption, number of manual reboluses, and number of subjects requiring greater bupivacaine concentrations did not differ between groups. Neuraxial analgesia failure occurred in 5 (12%) of women in the spinal instrumentation group but in none of the control patients (difference [95% CI], 12% [-0.3% to 25%]; P = 0.06). The mean time required to complete the neuraxial technique was 41% (95% CI, 7%-108%; P = 0.01) longer in the spinal instrumentation group than in the control group. The spinal instrumentation group also required a greater number of needle redirections, attempted interspaces, and need to switch to a more experienced provider than matched controls. The findings of this investigation suggest that previous surgery for scoliosis repair does not affect neuraxial labor analgesia consumption, but performance of the neuraxial technique is more difficult. Our findings suggest that neuraxial labor analgesia should be offered to parturients with previous surgery for scoliosis repair although informed consent should include a discussion of the possibility of technical difficulties and surgical anesthesia failure.


Added sugars in the diet are positively associated with diastolic blood pressure and triglycerides in children.
Hypertension and dyslipidemia have traditionally been associated with dietary sodium and fat intakes, respectively; however, they have recently been associated with the consumption of added sugars in adults and older adolescents, but there is no clear indication of how early in the life span this association manifests. This study explored the cross-sectional association between added sugar (sugars not naturally occurring in foods) consumption in children, blood pressure (BP), and fasting blood lipids [triglycerides and total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol]. BP, blood lipids, and dietary intakes were obtained in a multiethnic pediatric sample aged 7-12 y of 122 European American (EA), 106 African American (AA), 84 Hispanic American (HA), and 8 mixed-race children participating in the Admixture Mapping of Ethnic and Racial Insulin Complex Outcomes (AMERICO) study-a cross-sectional study conducted in the Birmingham, AL, metro area investigating the effects of racial-ethnic differences on metabolic and health outcomes. Multiple regression analyses were performed to evaluate the relations of added sugars and sodium intakes with BP and of added sugars and dietary fat intakes with blood lipids. Models were controlled for sex, race-ethnicity, socioeconomic status, Tanner pubertal status, percentage body fat, physical activity, and total energy intake. Added sugars were positively associated with diastolic BP (P = 0.0462, β = 0.0206) and serum triglycerides (P = 0.0206, β = 0.1090). Sodium was not significantly associated with either measure of BP nor was dietary fat with blood lipids. HA children had higher triglycerides but lower added sugar consumption than did either the AA or EA children. The AA participants had higher BP and HDL but lower triglycerides than did either the EA or HA children. These data suggest that increased consumption of added sugars may be associated with adverse cardiovascular health factors in children, specifically elevated diastolic BP and triglycerides. Identification of dietary factors influencing cardiovascular health during childhood could serve as a tool to reduce cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT00726778.


Human dorsomedial parieto-motor circuit specifies grasp during the planning of goal-directed hand actions.
According to one influential view, two specialized parieto-frontal circuits control prehension: a dorsomedial stream for hand transport during reaching and a dorsolateral stream for preshaping the fingers during grasping. However, recent evidence argues that an area within the dorsomedial stream-macaque area V6A and, its putative human homolog, superior parietal occipital cortex (SPOC) - encodes both hand transport and grip formation. We tested whether planning varied hand actions modulates functional connectivity between left SPOC and ipsilateral primary motor cortex (M1) using a dual-site, paired-pulse transcranial magnetic stimulation paradigm with two coils (dsTMS). Participants performed three different hand actions to a target object comprising a small cylinder atop a larger cylinder. These actions were: reaching-to-grasp the top (GT) using a precision grip, reaching-to-grasp the bottom (GB) using a whole-hand grip, or reaching-to-touch (Touch) the side of the target object without forming a grip. Motor-evoked potentials (MEPs) from TMS to M1, with or without preceding TMS to SPOC, were recorded from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) hand muscles in two experiments that varied timing parameters (the stimulus onset asynchrony, SOA, between the 'GO' cue and stimulation and interpulse interval, IPI, between SPOC and M1 stimulation). We found that preparatory response amplitudes in the SPOC-M1 circuit of different hand muscles were selectively modulated early in the motor plan for different types of grasps. First, based on SPOC-M1 interactions, across two experiments, the role of the ADM was facilitated during a whole-hand grasp of a large object (GB) relative to other conditions under certain timing parameters (SOA = 150 msec; IPI = 6 msec). Second, the role of the FDI was facilitated during hand action planning compared to rest. These findings suggest that the human dorsomedial parieto-motor stream plays a causal role in planning grip formation for object-directed actions.


Market Intelligence and Incentive-Based Trait Ranking for Plant Breeding: A Sweetpotato Pilot in Uganda.
Crop breeding programs must accelerate crop improvement, spur widespread adoption of new varieties and increase variety turnover they are to meet the diverse needs of their clients. More comprehensive quantitative approaches are needed to better inform breeding programs about the preferred traits among farmers and other actors. However, the ability of current breeding programs to meet the demands of their clients is limited by the lack of insights about value chain actor preference for individual or packages of traits. Ranking traits based on monetary incentives, rather than subjective values, represents a more comprehensive, consistent, and quantitative approach to inform breeding programs. We conducted a large pilot in Uganda to assess the implementation of a novel approach to trait ranking, using a uniquely large sample of diverse sweetpotato value chain actors. We found meaningful differences in trait ranking and heterogeneity among different actors using this approach. We also show our approach's effectiveness at uncovering unmet demand for root quality traits and at characterizing the substantial trait demand heterogeneity among value chain players. Implementing this approach more broadly for sweetpotato and other crops would increase the effectiveness of breeding programs to improve food security in developing countries.


Supporting general practice to make timely decisions for better health care: a population health approach.
Primary Health Networks (PHNs) are tasked to enhance the efficiency and effectiveness of general practice. Gold Coast Primary Health Network (GCPHN) has been collecting de-identified aggregated clinical data from general practices and reporting back on areas for improvement on data coding and some clinical metrics, such as blood pressure not being recorded. However, aggregated data cannot be used to intervene at the individual patient level, and because of the collection-to-reporting time-lag, the data cannot help facilitate immediate action in the general practice. GCPHN developed a practice-based population health management approach based on mapping data from general practices to international coding classification systems, and applying evidenced-based algorithms and tools. General practices are provided with a health profile of their entire patient population, from the healthiest to the most complex comorbid patients. The information is conveyed as alerts and reports on areas including medication quality and safety, possible gaps in care and high-risk patients. The information is received based on the practice's preferences; this can be at the time of data entry, the following day or as specified. Strong clinical governance has ensured GCPHN's approach and methodologies are evidenced-based and appropriate. The consistent application of clinical governance within general practices is also needed to ensure the approach is sustainable and improves clinical outcomes.


Analysis of the hydrogenotrophic microbiota of wild and captive black howler monkeys (Alouatta pigra) in palenque national park, Mexico.
Intestinal methanogenesis is one of the major pathways for consumption of hydrogen produced by bacterial fermentation and is considered to affect the efficiency of host energy harvest; however, little information is available regarding the hydrogenotrophic pathways of nonhuman primates in the wild, in general, and of howler monkeys, in particular. Microbial fermentation of plant structural carbohydrates is an important feature in wild howlers owing to the high fiber and low available energy content of leaves, which make up the primary component of their diet. In contrast, captive howlers may consume greater quantities of fruits and vegetables that are higher in water, lower in fiber, and, along with commercial monkey chow commonly added to captive monkey diets, more readily digestible than the natural diet. In this study, we analyzed the composition of methanogens and sulfate-reducing bacteria (SRB) from fecal samples of black howler monkeys (Alouatta pigra) in the wild and in captivity. The hydrogenotrophic microbiota of three groups of monkeys was evaluated by PCR-denaturing gradient gel electrophoresis (DGGE) fingerprinting, small clone library construction, and quantitative real-time PCR. Abundance of methanogens was lower than SRB in all howler monkey groups studied. DGGE banding patterns were highly similar within each wild and captive group but distinct among groups. Desulfovibrionales-enriched DGGE showed reduced microbial diversity in the captive animals compared with their wild counterparts. Taken together, the data demonstrate that environmental or dietary changes of the host imposed by captivity likely influence the composition of intestinal hydrogenotrophs in black howler monkeys.


A toolkit for e-health partnerships in low-income nations.
Collecting, managing, and communicating information is a critical part of delivering high-quality, efficient health care. Low-income countries often lack the information technology that is taking root in developed countries to manage health data and work toward evidence-based practice and culture. Partnerships between academic and government institutions in high- and low-income countries can help establish health informatics programs. These programs, in turn, can capture and manage data that are useful to all parties. Several partnerships among academic institutions and public and private organizations, in areas such as sub-Saharan Africa, Haiti, and Peru, are leading the way.


The change in capacity and service delivery at public and private hospitals in Turkey: a closer look at regional differences.
Substantial regional health inequalities have been shown to exist in Turkey for major health indicators. Turkish data on hospitals deserves a closer examination with a special emphasis on the regional differences in the context of the rapid privatization of the secondary or tertiary level health services.This study aims to evaluate the change in capacity and service delivery at public and private hospitals in Turkey between 2001-2006 and to determine the regional differences. Data for this retrospective study was provided from Statistical Almanacs of Inpatient Services (2001-2006). Hospitals in each of the 81 provinces were grouped into two categories: public and private. Provinces were grouped into six regions according to a development index composed by the State Planning Organisation. The number of facilities, hospital beds, outpatient admissions, inpatient admissions (per 100 000), number of deliveries and surgical operations (per 10 000) were calculated for public and private hospitals in each province and region. Regional comparisons were based on calculation of ratios for Region 1(R1) to Region 6(R6). Public facilities had a fundamental role in service delivery. However, private sector grew rapidly in Turkey between 2001-2006 in capacity and service delivery. In public sector, there were 2.3 fold increase in the number of beds in R1 to R6 in 2001. This ratio was 69.9 fold for private sector. The substantial regional inequalities in public and private sector decreased for the private sector enormously while a little decrease was observed for the public sector. In 2001 in R1, big surgical operations were performed six times more than R6 at the public sector whereas the difference was 117.7 fold for the same operations in the same regions for the private sector. These ratios decreased to 3.6 for the public sector and 13.9 for the private sector in 2006. The private health sector has grown enormously between 2001-2006 in Turkey including the less developed regions of the country. Given the fact that majority of people living in these underdeveloped regions are uninsured, the expansion of the private sector may not contribute in reducing the inequalities in access to health care. In fact, it may widen the existing gap for access to health between high and low income earners in these underdeveloped regions.


Endovascular grafts for noninfected aortoiliac anastomotic aneurysms.
This report describes our experience with endovascular repair of aortic and iliac anastomotic aneurysms. Between June 1994 and March 1996, 12 noninfected aortic or iliac anastomotic aneurysms in 10 patients who had serious comorbid medical conditions that precluded or made difficult standard operative repair were treated using endovascular grafts. No patient in this study had a history of fever, leukocytosis, or computed tomographic evidence of a periprosthetic fluid collection that was suggestive of infection of the original graft. Endovascular grafts composed of polytetrafluoroethylene and balloon-expandable stents were introduced through a femoral arteriotomy and were placed using over-the-wire techniques under C-arm fluoroscopic guidance. Endovascular grafts were successfully inserted in all patients with aortic or iliac anastomotic aneurysms. There were no procedure-related deaths, and complications included one postprocedure wound hematoma and one perioperative myocardial infarction. Graft patency has been maintained for a mean of 16.1 months, with no computed tomographic evidence of aneurysmal enlargement or perigraft leakage. Endovascular grafts appear to be a safe and effective technique for excluding some noninfected aortoiliac anastomotic aneurysms in high-risk patients and may become a treatment option in all patients who have clinically significant lesions.


The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.
Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.


Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status.
The incidence of hepatocellular carcinoma (HCC) seems to be rising in the United States (US), and considerable variability in the incidence and etiology of HCC has been noted among different racial and ethnic groups in this country. The aim of this study was to evaluate the influence of racial and ethnic status in the viral etiology of HCC in the US. Retrospective surveys were conducted at liver transplantation centers in the US. Respondents were asked to review the charts of all patients with HCC seen at their institution for the 2-yr period between July, 1997, and June, 1999, and provide information about the racial and ethnic distribution of cases and their serological status with regard to hepatitis B and C markers. Complete information was available on 691 patients who formed the basis of this study, comprising 59% whites, 14% blacks, 16% Asians, and 11% other racial groups. Of the patients, 107 patients (15.4%) were positive for hepatitis B surface antigen (HBsAg), 322 had antibodies to hepatitis C virus (anti-HCV) (46.5%), 33 (4.7%) had both HBsAg and anti-HCV), and 229 (33.1%) had neither marker present. Clear differences were seen among racial groups. Anti-HCV positivity was the most frequent risk factor in both blacks and whites, whereas HBsAg positivity was the most frequent etiological factor in Asians with HCC. HCV infection seems to be the major risk factor for HCC in the US, particularly among individuals of white and black ethnicity, whereas hepatitis B remains the main risk factor among patients of Asian ethnicity. These preliminary findings indicate the need for a more detailed study of ethnic variability in the pathogenesis of HCC.


Three-dimensional plasmon rulers.
Plasmon rulers can be used to determine nanoscale distances within chemical or biological species. They are based on the spectral shift of the scattering spectrum when two plasmonic nanoparticles approach one another. However, the one-dimensionality of current plasmon rulers hampers the comprehensive understanding of many intriguing processes in soft matter, which take place in three dimensions. We demonstrated a three-dimensional plasmon ruler that is based on coupled plasmonic oligomers in combination with high-resolution plasmon spectroscopy. This enables retrieval of the complete spatial configuration of complex macromolecular and biological processes as well as their dynamic evolution.


Cell type-specific filamin complex regulation by a novel class of HECT ubiquitin ligase is required for normal cell motility and patterning.
Differential cell motility, which plays a key role in many developmental processes, is perhaps most evident in examples of pattern formation in which the different cell types arise intermingled before sorting out into discrete tissues. This is thought to require heterogeneities in responsiveness to differentiation-inducing signals that result in the activation of cell type-specific genes and 'salt and pepper' patterning. How differential gene expression results in cell sorting is poorly defined. Here we describe a novel gene (hfnA) that provides the first mechanistic link between cell signalling, differential gene expression and cell type-specific sorting in Dictyostelium. HfnA defines a novel group of evolutionarily conserved HECT ubiquitin ligases with an N-terminal filamin domain (HFNs). HfnA expression is induced by the stalk differentiation-inducing factor DIF-1 and is restricted to a subset of prestalk cells (pstO). hfnA(-) pstO cells differentiate but their sorting out is delayed. Genetic interactions suggest that this is due to misregulation of filamin complex activity. Overexpression of filamin complex members phenocopies the hfnA(-) pstO cell sorting defect, whereas disruption of filamin complex function in a wild-type background results in pstO cells sorting more strongly. Filamin disruption in an hfnA(-) background rescues pstO cell localisation. hfnA(-) cells exhibit altered slug phototaxis phenotypes consistent with filamin complex hyperactivity. We propose that HfnA regulates filamin complex activity and cell type-specific motility through the breakdown of filamin complexes. These findings provide a novel mechanism for filamin regulation and demonstrate that filamin is a crucial mechanistic link between responses to differentiation signals and cell movement in patterning based on 'salt and pepper' differentiation and sorting out.


Endophilin promotes a late step in endocytosis at glial invaginations in Drosophila photoreceptor terminals.
Retrieval of synaptic vesicles from the membrane of neurons is crucial to maintain normal rates of neurotransmitter release. Photoreceptor terminals of the fly's eye release neurotransmitter in a tonic manner. They therefore rely heavily on vesicle regeneration. Null mutations in endophilin (endo) block clathrin-mediated endocytosis at the Drosophila neuromuscular junction, where previous analysis of hypomorphic mutations has suggested a function for Endophilin (Endo) before vesicle fission, during membrane bending. Here, at fly photoreceptor synapses, we show that Endo is localized to synaptic vesicles at sites of endocytosis that are glial invaginations called capitate projections, and that when the photoreceptor synapses lack Endo they are impaired in their ability to release neurotransmitter. Detailed ultrastructural analysis of endo null mutant photoreceptor synapses fails to reveal a defect at early stages of vesicle reformation but, instead, reveals an accumulation of clusters of electron-dense, apparently nonfunctional, late endocytotic vesicles. Using dynamin;endo double-mutant photoreceptors, we provide further evidence that ultimately the function of Endophilin is required late in endocytosis, allowing vesicles to progress through the synaptic vesicle cycle.


Providing safe and effective pleural medicine services in the UK: an aspirational statement from UK pleural physicians.
Physicians face considerable challenges in ensuring safe and effective care for patients admitted to hospital with pleural disease. While subspecialty development has driven up standards of care, this has been tempered by the resulting loss of procedural experience in general medical teams tasked with managing acute pleural disease. This review aims to define a framework though which a minimum standard of care might be implemented. This review has been written by pleural clinicians from across the UK representing all types of secondary care hospital. Its content has been formed on the basis of literature review, national guidelines, National Health Service England policy and consensus opinion following a round table discussion. Recommendations have been provided in the broad themes of procedural training, out-of-hours management and pleural service specification. Procedural competences have been defined into descriptive categories: emergency, basic, intermediate and advanced. Provision of emergency level operators at all times in all trusts is the cornerstone of out-of-hours recommendations, alongside readily available escalation pathways. A proposal for minimum standards to ensure the safe delivery of pleural medicine have been described with the aim of driving local conversations and providing a framework for service development, review and risk assessment.


HSP22, a new member of the small heat shock protein superfamily, interacts with mimic of phosphorylated HSP27 ((3D)HSP27).
Most of the members of the superfamily of mammalian small heat shock or stress proteins are abundant in muscles where they play a role in muscle function and maintenance of muscle integrity. One member of this protein superfamily, human HSP27, is rapidly phosphorylated on three serine residues (Ser(15), Ser(78), and Ser(82)) during cellular response to a number of extracellular factors. To understand better the role of HSP27, we performed a yeast two-hybrid screen of a human heart cDNA library for HSP27-interacting proteins. By using the triple aspartate mutant, a mimic of phosphorylated HSP27, as "bait" construct, a protein with a molecular mass of 21.6 kDa was identified as an HSP27-binding protein. Sequence analysis revealed that this new protein shares an overall sequence identity of 33% with human HSP27. This protein also contains the alpha-crystallin domain in its C-terminal half, a hallmark of the superfamily of small stress proteins. Thus, the new protein itself is a member of this protein superfamily, and consequently we designated it HSP22. According to the two-hybrid data, HSP22 interacts preferentially with the triple aspartate form of HSP27 as compared with wild-type HSP27. HSP22 is expressed predominantly in muscles. In vitro, HSP22 is phosphorylated by protein kinase C (at residues Ser(14) and Thr(63)) and by p44 mitogen-activated protein kinase (at residues Ser(27) and Thr(87)) but not by MAPKAPK-2.


Body condition scoring system for greater one-horned rhino (Rhinoceros unicornis): Development and application.
Preventing obesity in zoo animals is increasingly recognized as an important husbandry objective. To achieve this goal, body condition scoring (BCS) systems are available for an ever-increasing number of species. Here, we present a BCS for the greater one-horned rhinoceros (Rhinoceros unicornis) based on an evaluation (on a scale from 1 to 5) of seven different body regions, and report resulting scores for 62 animals from 27 facilities, based on digital photographs. In animals above 4 years of age, this BCS correlated with the body mass:shoulder height ratio. Although differences between the sexes for individual regions were noted (with consistently higher scores in males for the neck and shoulder and in parous females for the abdomen), the average BCS of all regions did not differ significantly between males (4.3 ± 0.4) and females (4.1 ± 0.5). Linking the BCS to results of a questionnaire survey and studbook information, there were no differences in BCS between animals with and without foot problems or between parous and non-parous females. In a very limited sample of 11 females, those eight that had been diagnosed with leiomyoma in a previous study had a higher BCS (range 3.9-4.9) than the three that had been diagnosed as leiomyoma-free (range 3.5-3.7). The BCS was correlated to the amount of food offered as estimated from the questionnaire. Adjusting the amounts and the nutritional quality of the diet components is an evident measure to maintain animals at a target BCS (suggested as 3-3.5). Zoo Biol. 35:432-443, 2016. © Wiley Periodicals, Inc.


100 Most Influential Publications in Scoliosis Surgery.
Bibliometric analysis. To apply the established technique of citation analysis to identify the 100 most influential articles in scoliosis surgery research published between 1900 and 2015. Previous studies have applied the technique of citation analysis to other areas of study. This is the first article to apply this technique to the field of scoliosis surgery. A two-step search of the Thomson Reuters Web of Science was conducted to identify all articles relevant to the field of scoliosis surgery. The top 100 articles with the most citations were identified based on analysis of titles and abstracts. Further statistical analysis was conducted to determine whether measures of author reputation and overall publication influence affected the rate at which publications were recognized and incorporated by other researchers in the field. Total citations for the final 100 publications included in the list ranged from 82 to 509. The period for publication ranged from 1954 to 2010. Most studies were published in the journal Spine (n = 63). The most frequently published topics of study were surgical techniques (n = 35) and outcomes (n = 35). Measures of author reputation (number of total studies in the top 100, number of first-author studies in the top 100) were found to have no effect on the rate at which studies were adopted by other researchers (number of years until first citation, and number of years until maximum citations). The number of citations/year a publication received was found to be negatively correlated with the rate at which it was adopted by other researchers, indicating that more influential manuscripts attained more rapid recognition by the scientific community at large. In assembling this publication, we have strived to identify and recognize the 100 most influential articles in scoliosis surgery research from 1900 to 2015. N/A.


Improvements in Cycling Time Trial Performance Are Not Sustained Following the Acute Provision of Challenging and Deceptive Feedback.
The provision of performance-related feedback during exercise is acknowledged as an influential external cue used to inform pacing decisions. The provision of this feedback in a challenging or deceptive context allows research to explore how feedback can be used to improve performance and influence perceptual responses. However, the effects of deception on both acute and residual responses have yet to be explored, despite potential application for performance enhancement. Therefore, this study investigated the effects of challenging and deceptive feedback on perceptual responses and performance in self-paced cycling time trials (TT) and explored whether changes in performance are sustained in a subsequent TT following the disclosure of the deception. Seventeen trained male cyclists were assigned to either an accurate or deceptive feedback group and performed four 16.1 km cycling TTs; (1 and 2) ride-alone baseline TTs where a fastest baseline (FBL) performance was identified, (3) a TT against a virtual avatar representing 102% of their FBL performance (PACER), and (4) a subsequent ride-alone TT (SUB). The deception group, however, were initially informed that the avatar accurately represented their FBL, but prior to SUB were correctly informed of the nature of the avatar. Affect, self-efficacy and RPE were measured every quartile. Both groups performed PACER faster than FBL and SUB (p < 0.05) and experienced lower affect (p = 0.016), lower self-efficacy (p = 0.011), and higher RPE (p < 0.001) in PACER than FBL. No significant differences were found between FBL and SUB for any variable. The presence of the pacer rather than the manipulation of performance beliefs acutely facilitates TT performance and perceptual responses. Revealing that athletes' performance beliefs were falsely negative due to deceptive feedback provision has no effect on subsequent perceptions or performance. A single experiential exposure may not be sufficient to produce meaningful changes in the performance beliefs of trained individuals beyond the acute setting.