Influence of a Neonicotinoid Seed Treatment on a Nontarget Herbivore of Soybean (Twospotted Spider Mite) and Diet Switching by a Co-occurring Omnivore (Western Flower Thrips).
Insecticidal neonicotinoid seed treatments are a common agricultural insect pest management strategy; however, effects on nontarget pests and omnivorous arthropods are understudied. We used a series of experiments to evaluate impacts of the neonicotinoid seed treatment thiamethoxam on densities of herbivorous twospotted spider mites (Tetranychus urticae Koch [Acari: Tetranychidae]) and feeding behavior of western flower thrips (Frankliniella occidentalis Pergande [Thysanoptera: Thripidae]), an omnivore that feeds on spider mite eggs but is also a significant plant pest. Spider mite densities were higher on neonicotinoid-treated soybeans, but only when mites were not spatially confined. We then examined how availability of thiamethoxam-treated food items (i.e., eggs from spider mites reared on treated soybeans, soybean leaf discs, or a combination of the two), and previous exposure to thiamethoxam-treated soybean impacted thrips feeding. Regardless of the presence of leaf tissue, thrips consumed fewer spider mite eggs laid by females reared on treated soybeans, suggesting spider mite eggs can serve as poisoned prey. Overall, thrips consumed less treated soybean leaf tissue, and thrips on treated leaf discs had a lower percentage of herbivorous feeding events and consumed more nontreated spider mite eggs, indicating a dietary shift from herbivory to predation. The neonicotinoid status of spider mite eggs and prior exposure of thrips also caused shifts in the number and size of leaf scars, likely as a result of altered foraging behavior and/or movement. Shifts between herbivory and predation have implications for thrips damage, virus transmission, and pest management, especially in systems with mixtures of nontreated and neonicotinoid-treated plants.


Conformational transitions of a weak polyampholyte.
Using grand canonical Monte Carlo simulations of a flexible polyelectrolyte where the charges are in contact with a reservoir of constant chemical potential given by the solution pH, we study the behavior of weak polyelectrolytes in poor and good solvent conditions for polymer backbone. We address the titration behavior and conformational properties of a flexible diblock polyampholyte chain formed of two oppositely charged weak polyelectrolyte blocks, each containing equal number of identical monomers. The change of solution pH induces charge asymmetry in a diblock polyampholyte. For diblock polyampholyte chains in poor solvents, we demonstrate that a discontinuous transition between extended (tadpole) and collapsed (globular) conformational states is attainable by varying the solution pH. The double-minima structure in the probability distribution of the free energy provides direct evidence for the first-order like nature of this transition. At the isoelectric point electrostatically driven coil-globule transition of diblock polyampholytes in good solvents is found to consist of different regimes identified with increasing electrostatic interaction strength. At pH values above or below the isoelectric point diblock chains are found to have polyelectrolyte-like behavior due to repulsion between uncompensated charges along the chain.


Posterior tilting of the tibial component decreases femoral rollback in posterior-substituting knee replacement: a computer simulation study.
Posterior tilting of the tibial component is thought to increase the range of motion in posterior cruciate-retaining total knee replacement, but its effect on implant motion in posterior cruciate-substituting total knee replacement is unknown. This issue has become of interest recently because manufacturers have introduced instrumentation that produces a posteriorly tilted tibial cut for both implant types. The purpose of this study was to investigate how motion of posterior cruciate-substituting total knee replacement is affected when the tibial component is installed with posterior tilt. Sagittal plane implant motions were predicted from prosthesis geometry with use of a computer simulation in which the femoral condyles were assumed to sit in the bottoms of the tibial condylar wells when the knee was in extension. Rollback of the femoral component was produced by a cam-spine mechanism at higher angles of flexion. The simulations revealed that even small degrees of posterior tilt reduced rollback by limiting the interaction between the cam and spine. Tilting the component posteriorly by 5 degrees caused the cam to contact the spine at a knee flexion angle that was 18 degrees higher than with the untilted component. The results suggest that posterior tilting of the tibial component in posterior cruciate-substituting knee replacement may not produce the same beneficial effects that have been reported for the tilting of tibial components in posterior cruciate-retaining knee replacement.


[Acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia].
To analyze the acupoint selection rules of acupuncture for pseudobulbar palsy dysphagia using data mining technology. The literature of acupuncture for pseudobulbar palsy dysphagia published from January 1, 1990 to May 1, 2021 was retrieved from CNKI, SinoMed, Wanfang, VIP, and PubMed databases. Acupuncture prescription database was established. The frequency of acupoint selection was analyzed by Microsoft Excel 2016; Apriori algorithm was used to analyze the association rules and draw the high-frequency acupoint co-occurrence network diagram; SPSS21.0 was used to perform clustering analysis. A total of 87 literature was included, involving 89 acupuncture prescriptions and 71 acupoints. Fengchi (GB 20) was the most frequently-used acupoint; the commonly-selected meridians were gallbladder meridian, conception vessel, governor vessel and stomach meridian; the acupoints located at the neck were the most frequently-used acupoints; the crossing points were commonly selected among the special acupoints. The most commonly-used acupoint combination was Jinjin (EX-HN 12) plus Yuye (EX-HN 13). The modern acupuncture for pseudobulbar palsy dysphagia usually selects local acupoints, especially the neck acupoints such as Fengchi (GB 20) and Lianquan (CV 23). The acupoints in the front and back are concurrently selected with needles towards the disease location.


A latent class analysis of age differences in choosing service providers to treat mental and substance use disorders.
OBJECTIVE This study investigated choice of service provider for treatment of a mental or substance use disorder and its association with consumers' age. METHODS Data were from the Collaborative Psychiatric Epidemiology Surveys. Service users born between 1946 and 1964 were compared with those born in 1945 or earlier (N=4,082). Latent class analysis was used to identify groups of service users according to nine dichotomous items reflecting lifetime visits with different types of professionals. Multinomial logistic regression was used to analyze factors predicting latent class membership, with particular focus on both the direct and moderating effects of age. Analyses controlled for sociodemographic characteristics and disorder-related variables. RESULTS Five classes of service user were identified. Class 1 (10.8%) included individuals who visited six of the nine types of providers (multiple providers visited). Class 2 (21.9%) had low probability of visiting most providers (limited providers visited). Class 3 (24.1%) visited a psychiatrist (primarily psychiatrist). Class 4 (28.1%) visited a family physician or other physician (primarily family physician). Class 5 (15.1%) visited a psychologist (primarily psychologist). A higher proportion of service users born before 1946 were in the primarily family physician class. Although 21% of service users born later also fell into this class, overall they were more evenly distributed across the five classes. CONCLUSIONS Family physicians played a significant role in behavioral health treatment for both age groups. However, findings suggest that younger adults may rely on more complex combinations of service providers that will require greater coordination between the behavioral and general health care systems in the future.


Living through unsuccessful conception attempts: a grounded theory of resilience among women undergoing fertility treatment.
To provide a model of resilience among women undergoing fertility treatments, who experience repeated unsuccessful conception attempts. Assisted reproductive treatment is emotionally and physically challenging. Women undergoing such treatments report experiencing high levels of anxiety and depression. There continues to be a lack of understanding of the process women go through to adapt to the challenges associated with fertility treatment, in order to continue to pursue their goal of pregnancy. The study employed a qualitative Grounded Theory design. Eleven women aged between 24 and 42 years took part in individual semi-structured interviews around their experiences of living through unsuccessful fertility treatment attempts. Three core categories were identified: 'Appraisal'; 'Stepping away from treatment'; and 'Building self up for the next attempt'. Following the failure of treatment, participants appraised their ability to carry on with further treatment attempts. Those who felt they had depleted their resources through the cycle of attempting pregnancy had taken a step back from the treatment cycle to reconnect with themselves and gather sufficient resources to attempt treatment again. During preparation for the next treatment, participants demonstrated their resilience by taking steps to build up their resources, such as nurturing their strength and taking control of their fertility experience. Women undergoing fertility treatment demonstrate their resilience through a variety of actions that enable them to continue to pursue their pregnancy goal. Clinical staff should be mindful of their clients' need to withdraw from the treatment cycle and offer support to enable them to do this.


Gender difference in N170 elicited under oddball task.
Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in response to the target. Clear N170 was elicited in response to target and non-target stimuli in both males and females. However, females showed more negative amplitude of N170 in response to target compared with non-target, while males did not show different N170 responses between target and non-target. The present results suggest that females have a characteristic of allocating attention at an early stage when responding to faces actively (target) compared to viewing faces passively (non-target). This supports previous findings suggesting that task demand is an important factor in gender differences in N170.


High growth per cycle thermal atomic layer deposition of Ni films using an electron-rich precursor.
An efficient process for thermal atomic layer deposition (ALD) of Ni film with high growth per cycle (GPC) value is developed in this study using an electron-rich compound (N,N,N',N'-tetramethylethylenediamine) (bis(2,4-pentanedionato)) nickel(ii) and anhydrous hydrazine as the reactants. The thermal properties and adsorption behavior of selected compounds were studied. Significantly, a high film GPC value of 2.1 Å per cycle for ALD was achieved, and the deposited film exhibited high purity, low resistivity and a smooth surface. We believe that such an efficient method for high GPC thermal ALD of Ni and even other transition metals will benefit ALD technology development.


The 65-kilodalton antigen of Mycobacterium tuberculosis.
The immune response of the host to the antigens of Mycobacterium tuberculosis plays the key role in determining immunity from infection with as well as the pathogenicity of this organism. A 65-kilodalton (kDa) protein has been identified as one of the medically important antigens of M. tuberculosis. The gene encoding this antigen was isolated from a lambda gt11-M. tuberculosis recombinant DNA library using monoclonal antibodies directed against the 65-kDa antigen as the specific probes. The nucleotide sequence of this gene was determined, and a 540-amino-acid sequence was deduced. This sequence was shown to correspond to that of the 65-kDa antigen by constructing a plasmid in which this open reading frame was fused to the lacZ gene. The resulting fusion protein reacted specifically with the anti-65-kDa protein antibodies. A second long open reading frame was found downstream of the 65-kDa antigen gene which could encode a protein of 517 amino acids. This putative protein contained 29 tandemly arranged partial or complete matches to a pentapeptide sequence.


Determination of the expression pattern of the dual promoter of zebrafish fushi tarazu factor-1a following microinjections into zebrafish one cell stage embryos.
The zebrafish fushi tarazu factor-1a (ff1a) is a transcription factor belonging to the NR5A subgroup of nuclear receptors. The NR5A receptors bind DNA as monomers and are considered to be orphans due to their ability to promote transcription of downstream genes without ligands. In zebrafish, four ff1 homologues (Ff1a, Ff1b, Ff1c, and Ff1d) have been identified so far. The gene coding for Ff1a is driven by two separate promoters, and give rise to four splice variants. Ff1a is expressed in the somites and pronephric ducts during somitogenesis and in the brain, liver, and mandibular arch during later embryonic stages. In adults the gene is highly expressed in gonads, liver, and intestine, but can be detected in most tissues. The broad variety of embryonic expression domains indicates several important developmental features. One of the mammalian fushi tarazu factor-1 genes, steroidogenic factor-1 (SF-1), is essential for the development of gonads and adrenals. SF-1 is together with Sox9, WT1, and GATA4 a positive transcriptional regulator of human anti-mullerian hormone (AMH) and thereby linked to the male sex-determining pathway. The zebrafish ff1a dual promoter contains several GATA binding sites and E-boxes, a site for DR4, XFD2, MyoD, Snail, HNF3, S8, and an HMG-box recognition site for Sox9. In a first attempt to dissect the ff1a promoter in vivo we have produced first generation transgenes in order to determine the correlation between the expression of the endogenous ff1a gene and the microinjected ff1a dual promoter coupled to the pEGFP reporter vector. Our results show that the microinjected constructs are expressed in the correct tissues.


Sustained hyperglycemia results in testicular dysfunction and reduced fertility potential in BBWOR diabetic rats.
Rats with short-term diabetes show a greater than 50% reduction of serum testosterone and increased lipid in Leydig cells but normal testicular structure. The purpose of this study was to determine the extent of testicular pathology (morphology index), integrity of the blood-testis barrier, daily sperm production (DSP), number of Leydig cells per testis (LC/T), and total trunk testosterone (TTT) in diabetic rats (BBWORdp) with long-term hyperglycemia (300-350 mg/dl for greater than 180 days) and to evaluate its effects on fertility potential. Results were compared with similarly aged normoglycemic rats (BBWORdr) and normal control Wistar rats. After 6 mo of diabetes, testis weights, DSPs, TTTs, and the morphology index were significantly reduced. The LC/T was not different from BBWORdr rats. The blood-testis barrier appeared intact, although structural abnormalities were noted in Sertoli-Sertoli junction complexes. There was a significant reduction in the number of pregnancies per rat and implantations per pregnancy in matings utilizing the diabetic BBWORdp rat and control Wistar female rats. Results indicate that long-term diabetes with sustained hyperglycemia leads to significant testicular dysfunction associated with decreased fertility potential.


Specialized formations of the endoplasmic reticulum in cultures of murine neuroblastoma cells.
Ultrastructural features of cytodifferentiation in monolayer cultures of mouse neuroblastoma cells (clone neuro-2A) was further characterized by the presence of annulate lamellar arrays with up to 10 lamellae. The lamellae were made up of fused smooth surfaced cisternae forming pores or annuli and were surrounded by a dense filamentous to granular material. Stacks of nonfenestrated, parallel, regularly spaced cisternae, designated as lamellar bodies, also appeared in the cytoplasm in association with the endoplasmic reticulum and the nucleus. Such flattened cisternae were also seen to be formed from transformed endoplasmic reticulum. Furthermore a relatively large number of concentric whorled lamellar bodies were presented as well as dense whorled structures reminiscent of the cytoplasmic laminar bodies. All of these structures are derived from the rough endoplasmic reticulum, the tubules of which are coexistent with those of the latter. In addition there is a topographic relationship of these bodies with mitochondria and with the nucleus. There is a relative persistence of most of these organelles in old or atropic cells which show marked changes including loss of endoplasmic reticulum. The significance of all of these cytoplasmic inclusions is discussed.


Linking interdecadal changes in British river ecosystems to water quality and climate dynamics.
Macroinvertebrate communities in Western European rivers have changed substantially in recent decades. Understanding the causes is challenging because improvements in water quality have coincided with climatic variations over this period. Using data covering >2300 rivers and 21 years (1991-2011) across England and Wales, we analysed family-level distributions and nationwide trends in prevalence (proportion of sampling locations where an organism was present) to diagnose the causes of ecological change. Our aims were to: (i) reveal the taxa driving assemblage-level trends; (ii) identify the main changes in family-level prevalence and distribution patterns; and (iii) test whether changes were accounted for by improving water quality, increasing temperatures or variations in discharge. While previous analyses revealed increasing richness among British river invertebrates, a partial turnover of taxa is now evident. Two distinct components of temporal trend have comprised: (i) overall increases or decreases in taxon prevalence over 21 years, which correlated with pollution sensitivity and discharge; and (ii) short-term variations in prevalence that correlated primarily with temperature and nutrient concentrations. The longer-term changes in prevalence were reflected in expansions or contractions in families' distributions linked to water quality, with little evidence of shifts consistent with increasing temperatures. Although these monitoring data had limitations (e.g., family-level data, few headwaters), they provide no clear evidence of long-term climate effects on invertebrates; the one feature consistent with climate warming - a small northward expansion of the range of many taxa - was accounted for by large improvements in water quality in northern England. Nevertheless, changes linked to discharge and temperature over the shorter-term (<2 years) point to the climatic sensitivity of invertebrate communities. It is therefore likely that any long-term climatic changes since 1990 have been outweighed by the strength and geographical extent of the recovery from poor water quality.


A rapid antimicrobial photodynamic water treatment strategy utilizing a xanthene dye with subsequent removal by Goethite Nanoparticles.
Although widely accepted as a water sterilisation technique, chlorination results in the production of potentially harmful by-products, mainly Trihalomethanes. Furthermore, the chlorination process requires specialised infrastructure, management and high costs. In this research paper a potential alternative sterilisation technique was investigated. This rapid three-step process utilized Goethite Nanoparticles and the photosensitising capabilities of a xanthene dye. Rose Bengal (RB) a compound primarily used as a stain to diagnose damaged tissue in the eye was utilized under visible light excitation to sterilise water containing gram-positive Staphylococcus aureus and Bacillus cereus. Bacterial reductions (cfu/ml) of up to 6log10 are reported at RB concentrations of 0.5 mg/L and 10 mg/L for S. aureus and B. cereus, respectively. Goethite Nanoparticles (GNP's), an iron oxyhydroxide, were synthesised by co-precipitation of iron salts and used to adsorb RB post-sterilisation. Poly-vinyl Alcohol (PVA) functionalised GNP's were synthesised to highlight the adsorbent capabilities of the GNP surface. The adsorption capacity for uncoated GNPs was 476.19 mg/g, this reduced to 170.4 mg/g for PVA-GNP's, highlighting the highly porous nature of the synthesised GNP surface. Adsorption was optimal in slightly acidic conditions (pH5-6). The adsorption parameters best followed Lagergens Pseudo-second order kinetics with correlation coefficients close to unity. At the highest envisaged RB concentration (10 mg/L) approximately 20 mg/L GNP's was required to remove the dye from solution post-treatment. Flame Atomic Absorption analysis of the water post-removal revealed Iron concentrations of 0.058 mg/L. This correlates to removal efficacy of 99.71% with residual iron levels below the EU recommended limit of 0.2 mg/L.


Chromosomal distribution of the human cardiovascular transcriptome.
On the basis of previous observations in chromosomes 21 and 22, we hypothesize that there is a tissue-specific organization of cardiovascular gene transcripts in the human genome. To examine the distribution of heart-derived transcripts, we assigned a nonredundant set of 4628 fetal and 3574 adult known and uncharacterized cardiovascular expressed-sequence tags (cvESTs) to 5-Mb chromosomal 'windows' on the basis of publicly available sequence mapping data. On a whole-genome level (36,617 genes), chromosome 17 (19.2% in fetal, 16.5% in adult) contained the highest proportion of cvESTs, whereas chromosome Y (2.0% in fetal and adult) contained the lowest. In total, 50 of the 639 windows contained a significantly higher proportion of cvESTs (P < 0.003) compared with the genome-wide cvEST gene density, particularly on gene-dense chromosomes (that is, 17, 19, 22) as opposed to gene-rich chromosomes (for example, 1, 2, 11). This report provides insight into a possible role for complex tissue-specific gene regulation in the human genome.


Christian Raetz: scientist and friend extraordinaire.
Chris Raetz passed away on August 16, 2011, still at the height of his productive years. His seminal contributions to biomedical research were in the genetics, biochemistry, and structural biology of phospholipid and lipid A biosynthesis in Escherichia coli and other gram-negative bacteria. He defined the catalytic properties and structures of many of the enzymes responsible for the "Raetz pathway for lipid A biosynthesis." His deep understanding of chemistry, coupled with knowledge of medicine, biochemistry, genetics, and structural biology, formed the underpinnings for his contributions to the lipid field. He displayed an intense passion for science and a broad interest that came from a strong commitment to curiosity-driven research, a commitment he imparted to his mentees and colleagues. What follows is a testament to both Chris's science and humanity from his friends and colleagues.


Estimation of rear-end vehicle crash frequencies in urban road tunnels.
According to The Handbook of Tunnel Fire Safety, over 90% (55 out of 61 cases) of fires in road tunnels are caused by vehicle crashes (especially rear-end crashes). It is thus important to develop a proper methodology that is able to estimate the rear-end vehicle crash frequency in road tunnels. In this paper, we first analyze the time to collision (TTC) data collected from two road tunnels of Singapore and conclude that Inverse Gaussian distribution is the best-fitted distribution to the TTC data. An Inverse Gaussian regression model is hence used to establish the relationship between the TTC and its contributing factors. We then proceed to introduce a new concept of exposure to traffic conflicts as the mean sojourn time in a given time period that vehicles are exposed to dangerous scenarios, namely, the TTC is lower than a predetermined threshold value. We further establish the relationship between the proposed exposure to traffic conflicts and crash count by using negative binomial regression models. Based on the limited data samples used in this study, the negative binomial regression models perform well although a further study using more data is needed.


Aldosterone-induced proteins: characterization using lectin-affinity chromatography.
Aldosterone-stimulated Na+ transport in toad urinary bladder is associated with the synthesis of a specific group of proteins whose induction appears to be related to the natriferic effect of the hormone. These aldosterone-induced proteins (AIPs) occur in two slightly different molecular weight classes (around 70 kDa), each class being composed of several proteins with discrete isoelectric points (range, 5.5-6.0). Because glycosylation is a common cause of such electrophoretic polymorphism and microheterogeneity, we examined whether these proteins are glycoproteins. Tunicamycin (a specific inhibitor of N-linked glycosylation) inhibited aldosterone-stimulated Na+ transport and AIP synthesis without affecting overall protein synthesis. The vast majority of epithelial cell proteins did not bind to the mannose-specific lectin, concanavalin A-sepharose. In contrast, both classes of AIPs bound to concanavalin A-sepharose, but the affinities of the higher and lower molecular weight proteins were markedly different: the former were readily eluted with 0.2 M alpha-methyl-D-mannoside alone, whereas the latter could only be eluted with 0.4 M alpha-methyl-D-mannoside in combination with high concentrations of NaCl (2.5-5.0 M). These studies indicate that 1) glycosylation is important in the natriferic response to aldosterone, 2) the AIPs are N-linked mannose-containing glycoproteins, and 3) the electrophoretic polymorphism of the AIPs is due, at least in part, to differences in glycosylation. Furthermore, concanavalin A-affinity chromatography provides a simple means for the partial purification of these putative "effectors" of the cellular action of aldosterone.


Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI.
Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, P<.001) and at 24 hours (34.5±35.0 and 153.5±75.5, respectively, P<.001). The primary end point was observed in 87.8% (n=65) in the ticagrelor-treated patients compared to 57.6% (n=38) of clopidogrel-treated patients, P<.001. Fibrinolysis-treated STEMI patients who received clopidogrel and aspirin at the time of fibrinolysis and were undergoing early PCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591).


Measuring Social Support among Soldiers with the Experienced Post-Deployment Social Support Scale (EPSSS): A Rasch-Based Construct Validity Study.
Perceived social support following deployment is a known buffer against post-deployment adverse mental health outcomes. Given contextual sensitivity of social support measures, scales that address specific social support needs of soldiers in the first months after home coming should be developed and validated. In a sample of 553 soldiers deployed to Afghanistan at two different time points (2009 and 2013, respectively), we selected items for and tested the construct validity of an 8-item measure of experienced post-deployment social support (experienced post-deployment social support scale; EPSSS). Within the item response theory framework, we used Rasch models (RM) to conduct item analysis with an emphasis on testing for differential item functioning (DIF) across background variables such as previous deployments and cohort. In short, we found that the scale did not fit the Rasch model, but with exclusion of two items, a 6-item version of the scale did fit an extended graphical loglinear Rasch model (GLLRM) with only one instance of DIF, for which the score can be adjusted. We also demonstrated that when applied as a scale, the DIF will not affect the results substantially. Hence, we conclude that the constructed 6-item EPSSS can be validly applied without score correction to assess the level of social support in Danish soldiers after home coming.


Non-specific interference of cobalt with siderophore-dependent iron uptake pathways.
Much data shows that biological metals other than Fe3+ can interfere with Fe3+ acquisition by siderophores in bacteria. Siderophores are small Fe3+ chelators produced by the microorganisms to obtain access to Fe3+. Here, we show that Co2+ is imported into Pseudomonas aeruginosa cells in a complex with the siderophore pyochelin (PCH) by the ferri-PCH outer membrane transporter FptA. Moreover, the presence of Co2+ in the bacterial environment strongly affects the production of PCH. Proteomic and transcriptomic approaches showed that a decrease of PCH production is associated with repression of the expression of the genes involved in PCH biosynthesis. We used various molecular biology approaches to show that this repression is not Fur-(ferric uptake transcriptional regulator) dependent but due to competition of PCH-Co with PCH-Fe for PchR (transcriptional activator), thus inhibiting the formation of PchR-PCH-Fe and consequently the expression of the PCH genes. We observed a similar mechanism of repression of PCH production, but to a lesser extent, by Ni2+, but not for Zn2+, Cu2+, or Mn2+. Here, we show, for the first time at a molecular level, how the presence of a contaminant metal can interfere with Fe3+ acquisition by the siderophores PCH and PVD.


Male-biased effects of gonadotropin-releasing hormone neuron-specific deletion of the phosphoinositide 3-kinase regulatory subunit p85alpha on the reproductive axis.
GnRH neurosecretion is subject to regulation by insulin, IGF-I, leptin, and other neuroendocrine modulators whose effects may be conveyed by activation of phosphoinositide 3-kinase (PI3K)-mediated pathways. It is not known, however, whether any of these regulatory actions are exerted directly, via activation of PI3K in GnRH neurons, or whether they are primarily conveyed via effects on afferent circuitries governing GnRH neurosecretion. To investigate the role of PI3K signaling in GnRH neurons, we used conditional gene targeting to ablate expression of the major PI3K regulatory subunit, p85alpha, in GnRH neurons. Combined in situ hybridization and immunohistochemistry confirmed reduction of p85alpha mRNA expression in GnRH neurons of GnRH-p85alpha knockout (KO) animals. Females of both genotypes exhibited estrous cyclicity and had comparable serum LH, estradiol-17beta, and FSH levels. In male GnRH-p85alphaKO mice, serum LH, testosterone, and sperm counts were significantly reduced compared with wild type. To investigate the role of the other major regulatory subunit, p85beta, on the direct control of GnRH neuronal function, we generated mice with a GnRH-neuron-specific p85alpha deletion on a global betaKO background. No additional reproductive effects in male or female mice were found, suggesting that p85beta does not substitute p85 activity toward PI3K function in GnRH neurons. Our results suggest that p85alpha, and thus PI3K activity, participates in the control of GnRH neuronal activity in male mice. The sex-specific phenotype in these mice raises the possibility that PI3K activation during early development may establish sex differences in GnRH neuronal function.


Yeast tissue phase of Emmonsia pasteuriana inoculated in golden hamster by intratesticular way.
The scope of our study was to present an experimental model reproducing the dimorphic yeast-like population (as for Histoplasma capsulatum, Blastomyces dermatitidis) similar to that observed in the cutaneous biopsy of an Italian woman who had never traveled abroad, being intravenous drug user and HIV positive for 10 years, finally infected with the new dimorphic fungus Emmonsia pasteuriana. Experimental inoculation was unsuccessful by intraperitoneal (i. p.) and intravenous (i. v.) ways in a mouse and in a guinea-pig model inoculated by cutaneous or subcutaneous routes, reason for that we chose the golden hamster, highly sensitive to dimorphic fungi as agents of systemic mycoses as histoplasmosis, blastomycosis, sporotrichosis, penicilliosis marneffei, paracoccidioidomycosis when the inoculation was done by intraperitoneal route. We inoculated young golden hamsters by i. p. and intratesticular ways. Only by this last route we reproduced an orchiepididymitis with necrosis, haemorrhages and a polymorphic yeast-like population similar to the polymorphism observed in the cutaneous biopsy of the patient. The intratesticular affinity of E. pasteuriana provided an interesting model for this infection.


Association of Body Fluid Expansion With Optical Coherence Tomography Measurements in Diabetic Retinopathy and Diabetic Macular Edema.
To evaluate associations of body fluid status with optical coherence tomography measurements in patients with diabetic retinopathy (DR). This prospective, cross-sectional study enrolled a total of 104 eyes from 104 patients with diabetes mellitus for fundus evaluations of DR and optical coherence tomography examinations. DR severity was graded via fundus photography. Systemic body fluid status was recorded via a body composition monitor with output values of total body water, extracellular water (ECW), intracellular water, and overhydration (OH). Relative overhydration (ROH) was defined as OH/ECW. Volume overload was defined as ROH ≥7%. Correlations of central subfield thickness (CST) with body fluid status were analyzed by partial correlation with adjustment for age, sex, and body mass index (BMI). Logistic regression analysis was used to evaluate factors associated with diabetic macular edema (DME). Higher levels of ECW, OH, and ROH were correlated with thick CST in patients with DR (P = 0.006, 0.021, and 0.008, respectively), but not in those without any DR (all P > 0.05), after adjusting for age, sex, and BMI. Patients with DME (n = 31) had higher OH than DR patients without DME (n = 28) or those without any DR (n = 45) (P = 0.002 and P < 0.001, respectively). Multiple regression model showed that volume overload was the independent factor for the presence of DME (odds ratio, 9.532; 95% confidence interval, 2.898-31.348; P < 0.001). While both ECW and OH reflect CST in patients with DR, overhydration had particularly strong associations with DME. This study provides a novel insight into our current understanding regarding the pathogenesis for DME.


Effects of whole-body electromyostimulation on function, muscle mass, strength, social participation, and falls-efficacy in older people: A randomized trial protocol.
Resistance training has a positive impact on functional capacity and muscle mass in the elderly. However, due to physical limitations or a simple aversion against regular exercise, a majority of the elderly do not reach the recommended exercise doses. This led us to evaluate the effect of whole-body electromyostimulation (WB-EMS), a novel, time-efficient, and smooth training technology on physical function, fat-free mass, strength, falls-efficacy, and social participation of the elderly. The present study is a randomized, parallel group clinical trial approved by the Ethics Committee of our Institution. Sixty-six volunteers (age ≥ 60 years) will be recruited from the geriatric outpatient department in a tertiary hospital and primary care units and randomized into two groups: WB-EMS group or active control group (aCG). The WB-EMS or aCG protocol will consist of 16 sessions for 8 consecutive weeks, twice per week. The primary outcomes will be maximal isometric knee extension (IKE), functional lower extremity strength, fat-free mass, gait speed, and risk of falls measured before and after intervention. The secondary outcomes will be social participation and falls-efficacy assessed before and after the intervention and at three and six months of follow-up. Participant's satisfaction with and awareness of electrical stimulation therapy will also be assessed immediately after the 8-week intervention. Patients receiving WB-EMS exercises are believed to have better outcomes than those receiving conventional, more time-consuming resistance exercises. Hence, innovative, time-efficient, joint-friendly, and highly individualized exercise technologies (such as WB-EMS) may be a good choice for the elderly with time constraints, physical limitations, or little enthusiasm, who are exercising less than the recommended amounts for impact on muscle mass, strength, and function.


Cleansing orthodontic brackets with air-powder polishing: effects on frictional force and degree of debris.
Debris buildup on the bracket-wire interface can influence friction. Cleansing brackets with air-powder polishing can affect this process. The aim of this study was to evaluate the frictional force and amount of debris remaining on orthodontic brackets subjected to prophylaxis with air-powder polishing. Frictional force and debris buildup on the surface of 28 premolar brackets were evaluated after orthodontic treatment. In one hemiarch, each bracket was subjected to air-powder polishing (n = 14) for five seconds, while the contralateral hemiarch (n = 14) served as control. Mechanical friction tests were performed and images of the polished bracket surfaces and control surfaces were examined. Wilcoxon test was applied for comparative analysis between hemiarches at p < 0.05. Brackets that had been cleaned with air-powder polishing showed lower friction (median = 1.27 N) when compared to the control surfaces (median = 4.52 N) (p < 0.01). Image analysis showed that the control group exhibited greater debris buildup (median = 2.0) compared with the group that received prophylaxis with air-powder polishing (median = 0.5) (p < 0.05). Cleansing orthodontic brackets with air-powder polishing significantly reduces debris buildup on the bracket surface while decreasing friction levels observed during sliding mechanics.


Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.
Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.


[Comparative results of thyroid ultrasound and laboratory studies in patients exposed to radiation].
The paper presents the data of thyroid ultrasound and laboratory studies in 233 persons exposed to radiation: 63 X-ray physicians, 36 Chernobyl accident liquidators, 31 patients with lymphogranulomatosis, receiving radiotherapy, and 103 individuals (a control group) who were physicians of various specialties whose professional activity is unassociated with radiation factors. Thyroid changes were found in 67.7% of the examinees after gamma teletherapy and in 31% in the control group; among X-rat physicians and Chernobyl accident liquidators, the occurrence of thyroid changes was equal--44.4%. Direct radiation exposure of the thyroid in a dose of above 30 Gy led to the development of postradiation fibrosis (22.5%) and postradiation thyroiditis (32.3%) with thyroid dysfunction that is most commonly presented by hypothyroidism (22.45%). Autoimmune thyroiditis (11.1%) more predominantly with subclinical hypothyroidism, and diffuse thyroid hyperplasia (19.4%) resulted from mixed internal and external radiation. Thyroid changes revealed in X-ray physicians mainly appeared as nodular masses (22.2%) without functional impairments but to be followed up. It is recommended that the annual preventive examination protocol be supplemented by thyroid ultrasound studies in X-ray physicians.


Difference in racket head trajectory and muscle activity between the standard volley and the drop volley in tennis.
Among tennis coaches and players, the standard volley and drop volley are considered basically similar, but muscles need to be relaxed (deactivation) just at the moment of impact when hitting the drop volley. However, this is not evidence-based. The aim of this study was to clarify racket head trajectory and muscle activity during the drop volley and to compare them with those of the standard volley. We hypothesized that 1) the racket head would move less forward for the drop volley than for the standard volley and 2) the wrist and elbow muscles be relaxed for the drop volley at the time of ball impact. Eleven male college students with sufficient tennis experience volunteered to participate in this study. Wireless EMG sensors recorded activation of the four arm muscles. Each subject performed the standard volley or the drop volley with both a forehand and a backhand from a position near the net. Four high speed video cameras (300 Hz) were set up on the court to measure ball speed and racket head trajectory. Returned ball speed of the drop volley was significantly lower than that of the standard volley (p < 0.05). The racket head moved less forward than in the standard volley, supporting the first hypothesis. Muscle activity of the drop volley, just before and after ball impact for both the forehand and backhand, was lower than that of the standard volley. However, the activity was in the form of a gradual increase as impact time approached, rather than a sudden deactivation (relaxation), which did not support the second hypothesis. For the drop volley, lower muscle activity in the forearm enabled a softer grip and thus allowed a "flip" movement of the racket to diminish the speed of the returned ball.


Hyponatraemic states following 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') ingestion.
Life-threatening and fatal hyponatraemic complications following ecstasy use have previously been documented. To define clinical features of hyponatraemia following the ingestion of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Retrospective case series. All enquiries to the London centre of the National Poisons Information Service (NPIS) between December 1993 and March 1996 were screened for cases of MDMA use associated with hyponatraemia (serum sodium <130 mmol/l). History of fluid consumption, presenting features and subsequent clinical course were recorded. Seventeen patients, aged 15-26 years, were identified. Serum sodium levels ranged between 107 mmol/l and 128 mmol/l. In six patients, biochemical results were consistent with inappropriate secretion of antidiuretic hormone (SIADH). Analytical confirmation of MDMA ingestion was obtained in 10 patients. Ten patients were known to have ingested a large amount of non-alcoholic or alcoholic fluid. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed in 11 patients by seizures. Drowsiness, a mute state and disorientation were observed for up to 3 days. Two patients died; 14 made a complete recovery. MDMA can cause life-threatening hyponatraemic encephalopathy when accompanied by excessive fluid ingestion. The mechanism involves inappropriate secretion of antidiuretic hormone.


[Cardiac arrest due to torsades de pointes ventricular tachycardia in a patient with Lyme carditis].
A 45-year-old female presented with third degree atrioventricular block and was diagnosed with Lyme carditis. Despite appropriate antibiotic treatment and continuous ventricular pacing, she suffered sudden cardiac arrest due to torsades de pointes ventricular tachycardia. Although rare, severe and potentially fatal ventricular tachyarrhythmias can occur in patients with Lyme borreliosis.


Restorative treatment thresholds: factors influencing the treatment thresholds and modalities of general dentists in Kuwait.
This study investigated the thresholds at which general dentists in Kuwait would restore approximal and occlusal carious lesions and examined the demographic characteristics of the dentists in relation to their decision making. The study population consisted of a random sample of 185 general dentists practicing in the Ministry of Health of Kuwait. A survey questionnaire was administered. The questionnaire presented different stages and locations of carious lesions; the participants were asked to identify the stage at which a restoration is required under different conditions, the preparation technique, and their choice of restorative material. For approximal carious lesions, 74 (40%) of the participants reported that they would restoratively intervene when the carious lesion reached the outer third of the dentin. A total of 91 (49.2%) reported the use of traditional class II restorations. For occlusal carious lesions, 128 (69.2%) said they would intervene when lesions reached the middle third of the dentin. 146 (78.9%) said they would remove the carious tissue only in their preparation. For both approximal and occlusal lesions, the participants preferred resin composite as the material for restoration. The respondents tended to delay restorative intervention until dentinal penetration of the caries. Resin restorative materials were used in conservatively prepared cavities. Participants chose a conservative approach for occlusal lesions but still believed in a traditional approach when it concerned approximal lesions. Experience, university dental education, and participation in continuous education courses were most significantly related to restorative treatment.


Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry.
The mode of entry of West Nile virus (WNV) into the macrophage-like cell line P388D1 was investigated at the electron microscopical level using synchronized infections. The presence of the antiviral monoclonal antibody F6/16A at a concentration that enhanced viral attachment to P388D1 cells ninefold made no difference to the entry pathway of WNV. In both the absence and presence of F6/16A the initial uptake of single viral particles was mediated by coated pits, and started within 30 s of warming the cells to 37 degrees C. Viral particles later appeared in fully or partially coated vesicles and later in uncoated prelysosomal endocytic vacuoles before degradation in lysosomes. However, aggregates of viral particles (five or more virus particles in cross-section), appeared to be phagocytosed whole by cells in a process which involved aggregates being engulfed by extensions of the plasma membrane. This process exhibited a slower time course than the uptake of single viral particles, becoming prominent 15 to 30 min after warming the cells to 37 degrees C. The involvement of a prelysosomal vacuolar compartment in the entry process was shown by a failure to stain for acid phosphatase. This compartment could be specifically loaded with viral particles when viral internalization occurred at 20 degrees C in the presence of 50 mM-ammonium chloride.


Home-based hand rehabilitation with a robotic glove in hemiplegic patients after stroke: a pilot feasibility study.
To evaluate the feasibility and safety of home rehabilitation of the hand using a robotic glove, and, in addition, its effectiveness, in hemiplegic patients after stroke. In this non-randomized pilot study, 21 hemiplegic stroke patients (Ashworth spasticity index ≤ 3) were prescribed, after in-hospital rehabilitation, a 2-month home-program of intensive hand training using the Gloreha Lite glove that provides computer-controlled passive mobilization of the fingers. Feasibility was measured by: number of patients who completed the home-program, minutes of exercise and number of sessions/patient performed. Safety was assessed by: hand pain with a visual analog scale (VAS), Ashworth spasticity index for finger flexors, opponents of the thumb and wrist flexors, and hand edema (circumference of forearm, wrist and fingers), measured at start (T0) and end (T1) of rehabilitation. Hand motor function (Motricity Index, MI), fine manual dexterity (Nine Hole Peg Test, NHPT) and strength (Grip test) were also measured at T0 and T1. Patients performed, over a mean period 56 (49-63) days, a total of 1699 (1353-2045) min/patient of exercise with Gloreha Lite, 5.1 (4.3-5.8) days/week. Seventeen patients (81%) completed the full program. The mean VAS score of hand pain, Ashworth spasticity index and hand edema did not change significantly at T1 compared to T0. The MI, NHPT and Grip test improved significantly (p = 0.0020, 0.0156 and 0.0024, respectively) compared to baseline. Gloreha Lite is feasible and safe for use in home rehabilitation. The efficacy data show a therapeutic effect which need to be confirmed by a randomized controlled study.


Investigation of rare earth-based magnetic nanocomposites for specific enrichment of exosomes from human plasma.
Exosomes, also known as small extracellular vesicles, are widely present in a variety of body fluids (e.g., blood, urine, and saliva). Exosomes are becoming an alternative promising source of diagnostic markers for disease rich in cargo of metabolites, proteins, and nucleic acids. However, due to the low abundance and structure similarity with protein complex, the efficient isolation of exosomes is one of the most important issues for biomedical applications. With a higher order of f-orbitals in rare earth element, it will have strong adsorption toward the phosphate group on the surface of the phospholipid bilayer of exosomes. In this study, we systematically investigated the ability of various rare earths interacting with phosphate-containing molecules and plasma exosomes. One of the best binding europium was selected and used to synthesize core-shell magnetic nanomaterials (Fe3O4@SiO2@Eu2O3) for the enrichment of exosomes from human plasma. The developed nanomaterials exhibited higher enrichment capacity, less time consumption and more convenient handling compared to commonly used ultracentrifugation method. The nanomaterials were applied to separate exosomes from the plasma of patients with hepatocellular carcinoma and healthy controls for metabolomics study with high-resolution mass spectrometry, where 70 differentially expressed metabolites were identified, involving amino acid and lipid metabolic pathway. We anticipated the rare earth-based materials to be an alternative approach on exosome isolation for disease diagnosis or postoperative clinical monitoring.


An Integrative Review of Grandparents' Experiences in Childhood Cancer.
Background: While it is generally accepted that childhood cancer has a profound impact on the family unit, there has been little focus on the experiences of grandparents who are affected by the diagnosis. Grandparents play an integral role throughout the child's illness trajectory as they are called upon to provide support physically, spiritually, emotionally, and at times financially. This integrative review examines the current research specific to grandparents' experiences of childhood cancer. Method: CINAHL, PubMed, and Web of Science were searched using the key terms "grandparent*" AND "experience*" AND "child*" AND "cancer." Inclusion criteria used for this review were as follows: electronic full text, peer-reviewed, and published in English between 2012 and 2022. Results: Grandparents of children with cancer experience an emotional whirlwind, a double-whammy effect, the giving and receiving of support, a balancing act, and attempt to find meaning throughout the diagnosis. They feel unacknowledged and unsupported by the health care team. Discussion: It is difficult to deny the emotional and familial impact the child's cancer diagnosis has not only on the child and immediate family but also on grandparents. While the reports of grandparents are consistent across studies, there have been lackluster attempts to mitigate the suffering experienced by this group. Pediatric oncology nurses, with their family-centered care approach, are in a unique position to uncover and meet the specific needs of grandparents of children diagnosed with cancer.


Crises and chaotic scattering in hydrodynamic pilot-wave experiments.
Theoretical foundations of chaos have been predominantly laid out for finite-dimensional dynamical systems, such as the three-body problem in classical mechanics and the Lorenz model in dissipative systems. In contrast, many real-world chaotic phenomena, e.g., weather, arise in systems with many (formally infinite) degrees of freedom, which limits direct quantitative analysis of such systems using chaos theory. In the present work, we demonstrate that the hydrodynamic pilot-wave systems offer a bridge between low- and high-dimensional chaotic phenomena by allowing for a systematic study of how the former connects to the latter. Specifically, we present experimental results, which show the formation of low-dimensional chaotic attractors upon destabilization of regular dynamics and a final transition to high-dimensional chaos via the merging of distinct chaotic regions through a crisis bifurcation. Moreover, we show that the post-crisis dynamics of the system can be rationalized as consecutive scatterings from the nonattracting chaotic sets with lifetimes following exponential distributions.


Coronary Plaque Characteristics and Underlying Mechanism of Acute Coronary Syndromes in Different Age Groups of Patients With Diabetes.
High cardiovascular mortality has been reported in young patients with diabetes. However, the underlying pathology in different age groups of patients with diabetes has not been studied. The aim of this study was to investigate the plaque characteristics and underlying pathology of acute coronary syndrome in different age groups of patients with or without diabetes in a large cohort. Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging were included. Culprit plaque was classified as plaque rupture, plaque erosion, or calcified plaque and stratified into 5 age groups. Plaque characteristics including features of vulnerability were examined by optical coherence tomography. Among 1394 patients, 482 (34.6%) had diabetes. Patients with diabetes, compared with patients without diabetes, had a higher prevalence of lipid-rich plaque (71.2% versus 64.8%, P=0.016), macrophage (72.0% versus 62.6%, P<0.001), and cholesterol crystal (27.6% versus 19.7%, P<0.001). Both diabetes and nondiabetes groups showed a decreasing trend in plaque erosion with age (patients with diabetes, P=0.020; patients without diabetes, P<0.001). Patients without diabetes showed an increasing trend with age in plaque rupture (P=0.004) and lipid-rich plaque (P=0.018), whereas patients with diabetes had a high prevalence of these vulnerable features at an early age that remained high across age groups. Patients without diabetes showed an increasing trend with age in plaque rupture and lipid-rich plaque, whereas patients with diabetes had a high prevalence of these vulnerable features at an early age. These results suggest that atherosclerotic vascular changes with increased vulnerability start at a younger age in patients with diabetes. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04523194, NCT03479723. URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041692.


Control of bone remodeling by the peripheral sympathetic nervous system.
The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis.


Spread of Multidrug-Resistant Rhodococcus equi, United States.
Multidrug resistance has been detected in the animal and zoonotic human pathogen Rhodococcus equi after mass macrolide/rifampin antibioprophylaxis in endemically affected equine farms in the United States. Multidrug-resistant (MDR) R. equi emerged upon acquisition of pRERm46, a conjugative plasmid conferring resistance to macrolides, lincosamides, streptogramins, and, as we describe, tetracycline. Phylogenomic analyses indicate that the increasing prevalence of MDR R. equi since it was first documented in 2002 is caused by a clone, R. equi 2287, attributable to coselection of pRErm46 with a chromosomal rpoBS531F mutation driven by macrolide/rifampin therapy. pRErm46 spillover to other R. equi genotypes has given rise to a novel MDR clone, G2016, associated with a distinct rpoBS531Y mutation. Our findings illustrate that overuse of antimicrobial prophylaxis in animals can generate MDR pathogens with zoonotic potential. MDR R. equi and pRErm46-mediated resistance are currently disseminating in the United States and are likely to spread internationally through horse movements.


A randomised controlled trial of phenylephrine and noradrenaline boluses for treatment of postspinal hypotension during elective caesarean section.
Phenylephrine is currently the vasopressor of choice during elective caesarean section, but it can cause reflex bradycardia. Noradrenaline, a potent α-agonist and weak β-agonist, may be associated with a lower incidence of bradycardia. However, comparative information is limited. This double-blind randomised controlled trial compared the effects of 100 μg phenylephrine and 5 μg noradrenaline administered as boluses for the treatment of postspinal hypotension during elective caesarean section in women with an uncomplicated singleton pregnancy. Hypotension was defined as a decrease of ≥ 20% from baseline systolic arterial pressure, or an absolute value < 100 mmHg. Ninety women were included in the study. The primary outcome was the incidence of maternal bradycardia < 60 beats.min-1 . There was no difference in the incidence of bradycardia (37.8% with phenylephrine vs. 22.2% with noradrenaline; p = 0.167), number of hypotensive episodes, number of boluses required to treat the first hypotensive episode or reactive hypertension. The total number of boluses used was higher in the phenylephrine group (p = 0.01). Maternal heart rate at 1 min after vasopressor administration was non-significantly lower using phenylephrine vs. noradrenaline (p = 0.034, considering p < 0.01 as statistically significant). The umbilical artery pH was higher using phenylephrine than with noradrenaline (p = 0.034). In conclusion, both vasopressors reversed postspinal hypotension without a statistically significant difference in maternal bradycardia. However, in view of the lower umbilical artery pH when using noradrenaline, further research is warranted to study its placental transfer and fetal metabolic effects.


Abscisic Acid Modulates Seed Germination via ABA INSENSITIVE5-Mediated PHOSPHATE1.
The phytohormone abscisic acid (ABA) controls many developmental and physiological processes. Here, we report that PHOSPHATE1 (PHO1) participates in ABA-mediated seed germination and early seedling development. The transcription of PHO1 was obviously enhanced during seed germination and early seedling development and repressed by exogenous ABA. The pho1 mutants (pho1-2, pho1-4, and pho1-5) showed ABA-hypersensitive phenotypes, whereas the PHO1-overexpressing lines were ABA-insensitive during seed germination and early seedling development. The expression of PHO1 was repressed in the ABI5-overexpressing line and elevated in the abi5 mutant, and ABI5 can bind to the PHO1 promoter in vitro and in vivo, indicating that ABI5 directly down-regulated PHO1 expression. Disruption of PHO1 abolished the ABA-insensitive germination phenotypes of abi5 mutant, demonstrating that PHO1 was epistatic to ABI5 Together, these data demonstrate that PHO1 is involved in ABA-mediated seed germination and early seedling development and transcriptionally regulated by ABI5.


Escaping the healthcare leadership cul-de-sac.
Purpose This paper aims to propose that healthcare is dominated by a managerialist ideology, powerfully shaped by business schools and embodied in the Masters in Business Administration. It suggests that there may be unconscious collusion between universities, healthcare employers and student leaders and managers. Design/methodology/approach Based on a review of relevant literature, the paper examines critiques of managerialism generally and explores the assumptions behind leadership development. It draws upon work which suggests that leading in healthcare organisations is fundamentally different and proposes that leadership development should be more practice-based. Findings The way forward for higher education institutions is to include work- or practice-based approaches alongside academic approaches. Practical implications The paper suggests that there is a challenge for higher education institutions to adopt and integrate practice-based development methods into their programme designs. Originality/value The paper provides a challenge to the future role of higher education institutions in developing leadership in healthcare.


Modulation of the activity of N-methyl-d-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13).
Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation.


Htra2-beta 1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 (SMN2).
Spinal muscular atrophy (SMA), a common motor neuron disease in humans, results from loss of functional survival motor neuron (SMN1) alleles. A nearly identical copy of the gene, SMN2, fails to provide protection from SMA because of a single translationally silent nucleotide difference in exon 7. This likely disrupts an exonic splicing enhancer and causes exon 7 skipping, leading to abundant production of a shorter isoform, SMN2Delta7. The truncated transcript encodes a less stable protein with reduced self-oligomerization activity that fails to compensate for the loss of SMN1. This report describes the identification of an in vivo regulator of SMN mRNA processing. Htra2-beta1, an SR-like splicing factor and ortholog of Drosophila melanogaster transformer-2, promoted the inclusion of SMN exon 7, which would stimulate full-length SMN2 expression. Htra2-beta1 specifically functioned through and bound an AG-rich exonic splicing enhancer in SMN exon 7. This effect is not species-specific as expression of Htra2-beta1 in human or mouse cells carrying an SMN2 minigene dramatically increased production of full-length SMN2. This demonstrates that SMN2 mRNA processing can be modulated in vivo. Because all SMA patients retain at least one SMN2 copy, these results show that an in vivo modulation of SMN RNA processing could serve as a therapeutic strategy to prevent SMA.


Operando Modeling of Multicomponent Reactive Solutions in Homogeneous Catalysis: from Non-standard Free Energies to Reaction Network Control.
Optimization and execution of chemical reactions are to a large extend based on experience and chemical intuition of a chemist. The chemical intuition is rooted in the phenomenological Le Chatelier's principle that teaches us how to shift equilibrium by manipulating the reaction conditions. To access the underlying thermodynamic parameters and their condition-dependencies from the first principles is a challenge. Here, we present a theoretical approach to model non-standard free energies for a complex catalytic CO2 hydrogenation system under operando conditions and identify the condition spaces where catalyst deactivation can potentially be suppressed. Investigation of the non-standard reaction free energy dependencies allows rationalizing the experimentally observed activity patterns and provides a practical approach to optimization of the reaction paths in complex multicomponent reactive catalytic systems.


Intact cell adhesion to glycan microarrays.
A rapid and reproducible method was developed to detect and quantify carbohydrate-mediated cell adhesion to glycans arrayed on glass slides. Monosaccharides and oligosaccharides were covalently attached to glass slides in 1.7-mm-diameter spots (200 spots/slide) separated by a Teflon gasket. Primary chicken hepatocytes, which constitutively express a C-type lectin that binds to nonreducing terminal N-acetylglucosamine residues, were labeled with a fluorescent dye and incubated in 1.3-microL aliquots on the glycosylated spots. After incubating to allow cell adhesion, nonadherent cells were removed by immersing the slide in phosphate buffered saline, inverting, and centrifuging in a sealed custom acrylic chamber so that cells on the derivatized spots were subjected to a uniform and controlled centrifugal detachment force while avoiding an air-liquid interface. After centrifugation, adherent cells were fixed in place and detected by fluorescent imaging. Chicken hepatocytes bound to nonreducing terminal GlcNAc residues in different linkages and orientations but not to nonreducing terminal galactose or N-acetylgalactosamine residues. Addition of soluble GlcNAc (but not Gal) prior to incubation reduced cell adhesion to background levels. Extension of the method to CD4+ human T-cells on a 45-glycan diversity array revealed specific adhesion to the sialyl Lewis x structure. The described method is a robust approach to quantify selective cell adhesion using a wide variety of glycans and may contribute to the repertoire of tools for the study of glycomics.


Smoking did not modify the effects of anti-TNF treatment on health-related quality of life among Australian ankylosing spondylitis patients.
The aim of this study was to examine the impact of smoking on health-related quality of life (HRQoL) among AS patients who were taking biologic DMARDS. This is a longitudinal cohort study of AS patients with anti-TNF treatment in the Australian Rheumatology Association Database (2003-11). They were assessed using the 36-item Short Form Health Survey (SF-36), Assessment of Quality of Life (AQoL) and HAQ for spondylitis (HAQ-S) on a biannual basis. Linear mixed models were used to assess the impact of smoking on HRQoL outcomes over the first 2 years of treatment. Four hundred and twenty-two patients [73% male, mean age 44.9 years (s.d. 12.7) provided 1189 assessments for the study. Current smokers (n = 79) were slightly younger, more likely to be male, less likely to use or to have previously used prednisolone and had a slightly shorter disease duration than past smokers (n = 138) or non-smokers (n = 205). After adjusting for smoking, gender, age, education, employment, co-morbidities and medication use, including DMARDs, anti-inflammatories and analgesics, all the HRQoL measures improved significantly over the study period and the improvements were not modified by smoking status (all P-values >0.36). Current smokers tended to have a poorer HRQoL on the SF-36 physical score [-1.93 (95% CI -3.94, 0.09), P = 0.06] and the HAQ-S score [0.10 (95% CI -0.01, 0.20), P = 0.07] compared with non-smokers. Among AS patients, active smoking did not diminish or modify the improvements in HRQoL from anti-TNF treatment, even though current smokers compared with non-smokers tended to have poorer scores in some HRQoL measures.


The GPR54 gene as a regulator of puberty.
Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus. We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty. We used complementary genetic approaches in humans and in mice. A consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism) was examined for mutations in a candidate gene, GPR54, which encodes a G protein-coupled receptor. Functional differences between wild-type and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. Responsiveness to exogenous gonadotropin-releasing hormone was assessed in both the humans and the mice. Affected patients in the index pedigree were homozygous for an L148S mutation in GPR54, and an unrelated proband with idiopathic hypogonadotropic hypogonadism was determined to have two separate mutations, R331X and X399R. The in vitro transfection of COS-7 cells with mutant constructs demonstrated a significantly decreased accumulation of inositol phosphate. The patient carrying the compound heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous gonadotropin-releasing hormone and a left-shifted dose-response curve for gonadotropin-releasing hormone as compared with six patients who had idiopathic hypogonadotropic hypogonadism without GPR54 mutations. The Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in male mice and a delay in vaginal opening and an absence of follicular maturation in female mice), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus. Mutations in GPR54, a G protein-coupled receptor gene, cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and mice, suggesting that this receptor is essential for normal gonadotropin-releasing hormone physiology and for puberty.


The Impact of Spatially Correlated Heterogeneity and Adsorption on Modified Salinity Water in Carbonates.
Modified salinity water (MSW) core flooding tests conducted in carbonates often exhibit a delay in the additional oil recovery. It has been suggested that the ionic adsorption process controls this delay. In this study, we examine the adverse effect of the adsorption process on the performance of MSW flooding in various models categorized as layered and heterogeneous reservoirs and a North Sea field sector model. To evaluate the impact of porous media's heterogeneity on the delay caused by the adsorption, we introduce the net present volumetric value based on which the cost of delay is calculated. This evaluation is achieved by comparing the calculated cost of delay for heterogeneous systems and that of their equivalent homogeneous porous media. It is found that, as the level of reservoir heterogeneity increases, the adverse effect of ionic adsorption on the improved oil production decreases. Further, computational results suggest that the connectivity index, which is defined as the effective permeability between injection and production wells divided by the average permeability, is a better alternative to the vorticity index to describe the impact of the delay of additional oil recovery in heterogeneous reservoirs subjected to MSW flooding.


[The problem of the "settlement" of the mentally ill elderly in psychiatric hospitals].
The gerontopsychiatric contingent of long-term stayers (LTS) (the patients who had permanently continued to stay in hospital for more than 5 years) was studied in two mental hospitals of Tver Province. There were 27.6% and 20.2% of LTS cases of overall geriatric contingents in these hospitals which included the patients older than 60 years old. The study covered different demographical, clinical and social aspects of this problem. In both groups it was established that more than half of the patients suffered from chronic schizophrenia (in the state of hallucinatory-delusional psychosis or in schizophrenic defect). The residual organic defect prevailed in the remaining patients. The factor furthering a long-term stay in hospitals was unfavorable social status of patients, namely most of the patients were lonely, more than half of them hadn't got any own habitation.


Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.
In this study we investigated specific biological and clinical features associated with chronic lymphocytic leukemia (CLL) patients carrying stereotyped BCR subset #4 (IGHV4-34) among a prospective cohort of 462 CLL/MBL patients in early stage (Binet A). All subset #4 patients (n = 16) were characterized by the IGHV mutated gene configuration, and absence of unfavorable cytogenetic lesions, NOTCH1 or SF3B1 mutations. Gene and miRNA expression profiling evidenced that the leukemic cells of subset #4 cases showed significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC gene transcripts, as well as the upregulation of miR-497 and miR-29c. The transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, a known validated target of this miRNA. Our data identify biological characteristics associated with subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the tumor cells in CLL.


Effectiveness of aromatherapy with light thai massage for cellular immunity improvement in colorectal cancer patients receiving chemotherapy.
Patients with colorectal cancer are usually treated with chemotherapy, which reduces the number of blood cells, especially white blood cells, and consequently increases the risk of infections. Some research studies have reported that aromatherapy massage affects the immune system and improves immune function by, for example, increasing the numbers of natural killer cells and peripheral blood lymphocytes. However, there has been no report of any study which provided good evidence as to whether aromatherapy with Thai massage could improve the immune system in patients with colorectal cancer. The objectives of this study were to determine whether the use of aromatherapy with light Thai massage in patients with colorectal cancer, who have received chemotherapy, can result in improvement of the cellular immunity and reduce the severity of the common symptoms of side effects. Sixty-six patients with colorectal cancer in Phichit Hospital, Thailand, were enrolled in a single-blind, randomised-controlled trial. The intervention consisted of three massage sessions with ginger and coconut oil over a 1-week period. The control group received standard supportive care only. Assessments were conducted at pre-assessment and at the end of one week of massage or standard care. Changes from pre-assessment to the end of treatment were measured in terms of white blood cells, neutrophils, lymphocytes, CD4 and CD8 cells and the CD4/CD8 ratio and also the severity of self-rated symptom scores. The main finding was that after adjusting for pre-assessment values the mean lymphocyte count at the post-assessment was significantly higher (P=0.04) in the treatment group than in the controls. The size of this difference suggested that aromatherapy with Thai massage could boost lymphocyte numbers by 11%. The secondary outcomes were that at the post assessment the symptom severity scores for fatigue, presenting symptom, pain and stress were significantly lower in the massage group than in the standard care controls. Aromatherapy with light Thai massage can be beneficial for the immune systems of cancer patients who are undergoing chemotherapy by increasing the number of lymphocytes and can help to reduce the severity of common symptoms.


Metabolomic profiles associated with physical activity in White and African American adult men.
Physical activity (PA) is associated with various health benefits, especially in improving chronic health conditions. However, the metabolic changes in host metabolism in response to PA remain unclear, especially in racially/ethnically diverse populations. This study is to assess the metabolic profiles associated with the frequency of PA in White and African American (AA) men. Using the untargeted metabolomics data collected from 698 White and AA participants (mean age: 38.0±8.0, age range: 20-50) from the Louisiana Osteoporosis Study (LOS), we conducted linear regression models to examine metabolites that are associated with PA levels (assessed by self-reported regular exercise frequency levels: 0, 1-2, and ≥3 times per week) in White and AA men, respectively, as well as in the pooled sample. Covariates considered for statistical adjustments included race (only for the pooled sample), age, BMI, waist circumstance, smoking status, and alcohol drinking. Of the 1133 untargeted compounds, we identified 7 metabolites associated with PA levels in the pooled sample after covariate adjustment with a false discovery rate of 0.15. Specifically, compared to participants who did not exercise, those who exercised at a frequency ≥3 times/week showed higher abundances in uracil, orotate, 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) (GPE), threonate, and glycerate, but lower abundances in salicyluric glucuronide and adenine in the pooled sample. However, in Whites, salicyluric glucuronide and orotate were not significant. Adenine, GPE, and threonate were not significant in AAs. In addition, the seven metabolites were not significantly different between participants who exercised ≥3 times/week and 1-2 times/week, nor significantly different between participants with 1-2 times/week and 0/week in the pooled sample and respective White and AA groups. Metabolite responses to PA are dose sensitive and may differ between White and AA populations. The identified metabolites may help advance our knowledge of guiding precision PA interventions. Studies with rigorous study designs are warranted to elucidate the relationship between PA and metabolites.


Getting ahead of the game: in-hospital initiation of HFrEF therapies.
Hospitalizations for heart failure (HF) have become a global problem worldwide. Each episode of HF decompensation may lead to deleterious short- and long- term consequences, but on the other hand is an unique opportunity to adjust the heart failure pharmacotherapy. Thus, in-hospital and an early post-discharge period comprise an optimal timing for initiation and optimization of the comprehensive management of HF. This timeframe affords clinicians an opportunity to up titrate and adjust guideline-directed medical therapies (GDMT) to potentially mitigate poor outcomes associated post-discharge and longer-term. This review will cover this timely concept, present the data of utilization of GDMT in HF populations, discuss recent evidence for in-hospital initiation and up-titration of GDMT with a need for post-discharge follow-up and implementation this into clinical practice in patients with heart failure and reduced ejection fraction.


A phoneme effect in visual word recognition.
In alphabetic writing systems like English or French, many words are composed of more letters than phonemes (e.g. BEACH is composed of five letters and three phonemes, i.e./biJ/). This is due to the presence of higher order graphemes, that is, groups of letters that map into a single phoneme (e.g. EA and CH in BEACH map into the single phonemes /i/ and /J/, respectively). The present study investigated the potential role of these subsyllabic components for the visual recognition of words in a perceptual identification task. In Experiment 1, we manipulated the number of phonemes in monosyllabic, low frequency, five-letter, English words, and found that identification times were longer for words with a small number of phonemes than for words with a large number of phonemes. In Experiment 2, this 'phoneme effect' was replicated in French for low frequency, but not for high frequency, monosyllabic words. These results suggest that subsyllabic components, also referred to as functional orthographic units, play a crucial role as elementary building blocks of visual word recognition.


Residual effects of compost and plowing on phosphorus and sediment in runoff.
Manure application can lead to excessive soil test P levels in surface soil, which can contribute to increased P concentration in runoff. However, manure application often results in reduced runoff and sediment loss. Research was conducted to determine the residual effects of previously applied compost, plowing of soil with excessive soil test P, and application of additional compost after plowing on volume of runoff and loss of sediment and P in runoff. The research was conducted in 2004 and 2005 under natural rainfall events with plots of 11-m length where low-P and high-P compost had been applied during April 1998 to January 2001. During this initial application period, Bray-P1 in the surface 5-cm of depth was increased from 14 to 553 mg kg(-1) for the high-P compost. Inversion plowing in the spring of 2004 greatly decreased P levels in the surface soil and over the following year reduced runoff by 35% and total P losses by 51% compared with the unplowed compost treatments. Sediment loss was increased with plowing compared with the unplowed compost applied treatments but less than with the no-compost treatment. The application of additional compost after plowing increased surface soil P and dissolved reactive P (DRP) in runoff but did not increase particulate P in runoff. Unplowed compost-amended soil continued to reduce sediment loss but exhibited increased DRP loss even 5 yr after the last application. Plowing to invert excessively high-P surface soil was effective in reducing runoff and DRP loss.


Genotype and phenotype predictors of relapse of graves' disease after antithyroid drug withdrawal.
For patients with Graves' disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. FOUR SNPS WERE SIGNIFICANTLY ASSOCIATED WITH DISEASE RELAPSE: rs231775 (OR 1.96, 95% CI 1.18-3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01-62.7), rs11569309 (OR 8.09, 95% CI 1.03-63.7), and rs3765457 (OR 2.60, 95% CI 1.08-6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09-1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05-1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15-2.35), and smoking habit (HR 1.60, 95% CI 1.05-2.42). Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.


Balkan endemic nephropathy and papillary transitional cell tumors of the renal pelvis and ureters.
Papillary transitional cell tumors of the renal pelvis and ureters occur more frequently in the Balkan countries than in other areas in the world. The populations involved are the same as those who are at risk to develop Balkan endemic nephropathy (BEN). Seventy-seven patients were treated in the Urology Clinic for papillary cell tumors of the renal pelvis and ureters (UTT) from 1986 to 1988. Forty-four of the patients were from areas where BEN is endemic. The at-risk population is estimated to be less than 2% of the control population. Eleven of the 77 were on hemodialysis when UTT were detected, and all but one of those were from BEN areas. This finding emphasizes the need for continual monitoring of end-stage renal disease patients for evidence of these tumors. Comparing the frequency of the tumors from our study (1986 to 1988) with that of early studies indicates that the risk of developing the tumors remains very high in the BEN areas. We conclude that the causative agent(s) is still prevalent in the involved areas.


Patterns of care for clinically distinct segments of high cost Medicare beneficiaries.
Efforts to improve the efficiency of care for the Medicare population commonly target high cost beneficiaries. We describe and evaluate a novel management approach, population segmentation, for identifying and managing high cost beneficiaries. A retrospective cross-sectional analysis of 6,919,439 Medicare fee-for-service beneficiaries in 2012. We defined and characterized eight distinct clinical population segments, and assessed heterogeneity in managing practitioners. The eight segments comprised 9.8% of the population and 47.6% of annual Medicare payments. The eight segments included 61% and 69% of the population in the top decile and top 5% of annual Medicare payments. The positive-predictive values within each segment for meeting thresholds of Medicare payments ranged from 72% to 100%, 30% to 83%, and 14% to 56% for the upper quartile, upper decile, and upper 5% of Medicare payments respectively. Sensitivity and positive-predictive values were substantially improved over predictive algorithms based on historical utilization patterns and comorbidities. The mean [95% confidence interval] number of unique practitioners and practices delivering E&M services ranged from 1.82 [1.79-1.84] to 6.94 [6.91-6.98] and 1.48 [1.46-1.50] to 4.98 [4.95-5.00] respectively. The percentage of cognitive services delivered by primary care practitioners ranged from 23.8% to 67.9% across segments, with significant variability among specialty types. Most high cost Medicare beneficiaries can be identified based on a single clinical reason and are managed by different practitioners. Population segmentation holds potential to improve efficiency in the Medicare population by identifying opportunities to improve care for specific populations and managing clinicians, and forecasting and evaluating the impact of specific interventions.


Quantitative evaluation of the recombinant HIV-1 phenotype to protease inhibitors by a single-step strategy.
To develop and optimize a fast and quantitative recombinant strategy for evaluating the HIV-1 phenotype to protease inhibitors (PI). A non-replicative HIV-1 molecular vector (designated pdelta prodelta env) capable of expressing exogenous HIV-1 protease-encoding sequences was developed in this study. The HIV-1 protease sequences were amplified from either viral isolates or plasma samples (both from 21 HIV-1-infected individuals, 19 of whom were failing different anti-HIV-1 combination treatments) and cloned in the pdelta prodelta env backbone. The HIV-1 recombinant phenotype to PI was determined directly after transfection of viral chimeric clones by measuring protease activity and calculating a percentage sensitivity index (SI%; the ratio between the results from each clone and those from a PI-sensitive reference strain). The SI% values obtained from the recombinant clones paralleled the IC50 results of the viral isolates and documented different degrees of resistance and cross-resistance to PI, compatible, with few exceptions, with the respective genotype. Interestingly, an inverse correlation between SI% values and the presence of primary mutations for resistance to PI (P = 0.0038 and P = 0.0414, for indinavir and ritonavir, respectively) and a difference in SI% between samples harbouring an increasing number of mutations (indinavir, P = 0.022; ritonavir, P = 0.0466) were observed. The data substantiate the reliability of the novel strategy for a fast (5 day) quantitative evaluation of HIV-1 phenotype to PI, and indicate that this method may contribute to the understanding of mechanisms of virus resistance to PI.


Prevalence and Overtesting of True Heparin-Induced Thrombocytopenia in a 591-Bed Tertiary Care, Teaching Hospital.
Heparin-induced thrombocytopenia type II (HIT) is a rare but potentially fatal antibody-mediated reaction to all forms of heparin (unfractionated heparin, low-molecular weight heparin, heparin flushes, and heparin-coated catheters), which can lead to HIT with thrombosis. Two tests commonly used to screen for HIT include the enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). This is a retrospective chart review study conducted from January 1, 2013, through December 31, 2014, to estimate the rate of true HIT in critical care patients at Winthrop-University Hospital, located in Mineola, New York. Patients are classified as positive for HIT if both ELISA and SRA immunoassays are positive. We reviewed 507 heparin immunoassays, excluding 64 who had an inappropriate ELISA test sent due to no administration of heparin, enoxaparin, or heparin lock flush at this or previous hospital stays at Winthrop. Of the 443 heparin immunoassays, ELISA results were positive for 66 patients (15.1%), and only 11 (2.5%) patients had true cases of HIT with a 95% confidence interval of 1.3% to 4.4%. The 4T score for those with true HIT (median: 5.0) was statistically higher compared to those without true HIT (median: 2.0; P < .001). Despite guidelines in place, overtesting for HIT is still a prevalent issue.


Castleman's disease: an unusual presentation.
Castleman's disease is a rare lymphoproliferative disorder, with focal or systemic lymph node involvement, which rarely affects the lung parenchyma. We report the case of an asymptomatic immunocompetent male patient who had the rarest histological variant of the disease, a nodular parenchymal presentation. The patient underwent lobectomy, and the postoperative evolution was favorable. In the last 10 years, there have been only five reports of Castleman's disease presenting as a solitary pulmonary nodule. This case underscores the fact that Castleman's disease, albeit rare, should be included in the differential diagnosis of pulmonary nodules.


Analysis of preoperative condition and interstage mortality in Norwood and hybrid procedures for hypoplastic left heart syndrome using the Aristotle scoring system.
The 'hybrid procedure', consisting of surgical banding of the pulmonary arteries with intraoperative stenting of the arterial duct, was developed as primary palliation in hypoplastic left heart syndrome (HLHS), avoiding the risks of cardiopulmonary bypass. In many centres, it is reserved for low birth weight, premature or unstable neonates; however, its role in such high risk cases of HLHS has yet to be defined. The preoperative condition of all patients with HLHS who underwent either the hybrid or the Norwood procedure for HLHS between 2005-2011 was analysed retrospectively, using a modified comprehensive Aristotle score. We then compared operative, interstage and 1 year mortalities between the groups after Aristotle adjustment via Cox proportional hazards analyses. Of 138 patients with HLHS, 27 had hybrid and 111 Norwood procedures. The hybrid group had significantly higher Aristotle scores (mean 4.1 vs 1.8; p<0.001); however, there was no significant difference in mortality at any stage. At 1 year, the overall unadjusted survival among Norwood and hybrid patients was 58.6% and 51.9%, respectively, yielding an Aristotle adjusted hazard ratio for mortality among hybrid patients of 1.09 (95% CI 0.56 to 2.11, p=0.80). Applying a hybrid approach to high risk patients with HLHS produces a comparable early and interstage mortality risk to lower risk patients undergoing the Norwood procedure. Prospective studies are needed to establish whether the hybrid procedure is a viable alternative to the Norwood procedure in all HLHS patients in terms of both mortality and long term morbidity.


Two-dimensional approach to full-reference image quality assessment based on positional structural information.
A method for full-reference visual quality assessment based on the 2-D combination of two diverse metrics is described. The first metric is a measure of structural information loss based on the Fisher information about the position of the structures in the observed images. The second metric acts as a categorical indicator of the type of distortion that images underwent. These two metrics constitute the inner state of a virtual cognitive model, viewed as a system whose output is the automatic visual quality estimate. The use of a 2-D metric fills the intrinsic incompleteness of methods based on a single metric while providing consistent response across different image impairment factors and blind distortion classification capability with a modest computational overhead. The high accuracy and robustness of the method are demonstrated through cross-validation experiments.