Fatty acid composition of hepatic and cardiac tissue from chickens dying of sudden death syndrome.
Gas chromatographic analysis of tissue lipids from broiler chickens dying from sudden death syndrome (SDS) were carried out to determine if anomalies in fatty acid composition could be linked to the disease. Crude extracts of lipids from hearts and livers of chickens dying from SDS and their matched controls (matched for pen number, sex and time of death) were fractionated by thin layer chromatography and the phospholipid, triacylglycerol (TG) and nonesterified aliphatic carboxylic acid [C14-C22] (FA) fractions were transmethylated and analysed by capillary gas chromatography. A number of significant (P less than .05) differences in fatty acid composition were found to exist between males dying of SDS and their controls, the most notable being elevated levels of arachidonic acid in the hepatic TG and cardiac FA fractions of SDS males. Few significant differences were found between SDS females and their controls. There was a trend toward increased desaturation of cardiac and hepatic tissue lipids of male SDS chickens, although this was significant only for the hepatic TG fraction. The results did not support the hypothesis that a lack of arachidonic acid as a precursor of prostaglandin synthesis was a causative factor in the disease.


Cutaneous Fungal Infections.
Mycology is a subject many practitioners seem to want to avoid. It always seems to be easier to treat empirically or send a culture off to the lab. If you trust the lab. Doing your own mycology tests takes time and interest while trying to remember all the mycology you learned for the boards and promptly forgot. If you want to get beyond the stage of remembering that you once knew some mycology, and do it as painlessly as possible, Dr Elewski's book is exactly the tool you need.This is not an all-inclusive resource. It is more a survey of mycology, appropriate for dermatologists rather than microbiologists. It is replete with summary tables, such as which dermatophytes result in hair fluorescence under Wood's light or mycetoma agents listed by grain color. Colony morphology and tissue morphology of organisms are easy to find. In addition to photographs, some in color.


In vitro analysis of antioxidant activities of Oxalis corniculata Linn. fractions in various solvents.
As part of our search for natural antioxidants, this work presents an evaluation of antioxidant activities of methanolic extract of Oxalis corniculata and its sub-fractions in hexane, chloroform, ethyl acetate, n-butanol and water. The total phenolic contents in terms of µg of gallic acid equivalents per mg of dried mass were approximately 21.0, 28.2, 34.5, 162.0, 70.0, and 49.2 in methanolic, hexane, chloroform, ethyl acetate, n-butanolic and aqueous fractions respectively, while the flavonoid contents in these solvents were 362.4, 214.1, 317.1, 177.1, 98.8 and 53.5 respectively in terms of µg of rutin per mg of dried mass. In DPPH assay, the ethyl acetate fraction showed the highest free radical scavenging activity, 24.0% with 1 mg/mL concentration. The second strongest fraction was chloroform (21.5%). The EC50 and TEC50 values of the methanolic extract were 3.63 mg/mL and 23 min respectively. The FRAP values in terms of µg of ascorbic acid equivalents per mg of dried mass for these solvents were 288.0, 1705.3, 437.1, 72.0, 28.0, and 44.0 respectively while total antioxidant activity measured by phosphomolybdate assay in terms of µg of ascorbic acid equivalents per mg of dried mass were 50.0, 117.0, 78.6, 57.8, 3.4 and 8.3 respectively. All the samples showed remarkable ability to inhibit lipid peroxidation exhibiting much better and sustainable peroxidation inhibitory activity than the standard butylated hydroxyanisole.


Incidence of microsatellite instability in synchronous tumors of the ovary and endometrium.
Families with hereditary nonpolyposis colorectal cancer (HNPCC) have an increased lifetime risk of endometrial (40%) and ovarian (10%) carcinomas. Endometrial and ovarian carcinomas from members of these families frequently display a mutator phenotype as manifest by high levels of microsatellite instability (MSI-H). Microsatellite instability (MSI) occurs in 17-32% of sporadic endometrial carcinomas and 3-17% of sporadic ovarian carcinomas. We hypothesized that there might be a higher rate of MSI in tumors from women with synchronous primary carcinomas of the ovary and endometrium. We identified 52 cases of synchronous tumors of the ovary and endometrium from the databases of four gynecological oncology units. Archival material and clinical data were available on 45 of these patients. We examined DNA extracted from ovarian and endometrial tumor tissue for MSI using DNA extracted from normal tissue of that patient as a germ-line DNA control. MSI was assessed using a panel of five standard microsatellite markers: D2S123, D5S346, D17S250, BAT25, and BAT26. MSI-H was defined by more than two markers being positive. Low-level MSI (MSI-L) was defined as one or two markers positive and microsatellite stable (MSS) was defined as no markers positive. The 45 patients had a median age at diagnosis of 53 years. Of a total of 134 samples analyzed, only three samples (3.3%) were MSI-H. No patient had high levels of MSI in both ovarian and endometrial tumors. One ovarian carcinoma had five of five markers positive with the corresponding endometrial carcinoma being MSI-L. Two endometrial carcinomas were MSI-H, and the corresponding ovarian carcinomas were MSI-L and MSS, respectively. Seven ovarian tumors and seven endometrial tumors were MSI-L. The majority of patients had early-stage ovarian carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage I, 44.4%; stage II, 26.7%; and stage III, 26.6%]. Eighty-two % of the endometrial primaries were FIGO stage I. Progression-free survival was significantly better for patients with synchronous primaries than those presenting with ovarian carcinoma alone [adjusted hazards ratio, 1.94; P = 0.023; 95% confidence interval, 1.096-3.44]. Synchronous primary carcinomas of the ovary and endometrium are unlikely to be part of the HNPCC syndrome unless the family history is in keeping with the modified Amsterdam criteria.


Ab initio/GIAO-CCSD(T) study of structures, energies, and 13C NMR chemical shifts of C4H7(+) and C5H9(+) ions: relative stability and dynamic aspects of the cyclopropylcarbinyl vs bicyclobutonium ions.
The structures and energies of the carbocations C 4H 7 (+) and C 5H 9 (+) were calculated using the ab initio method. The (13)C NMR chemical shifts of the carbocations were calculated using the GIAO-CCSD(T) method. The pisigma-delocalized bisected cyclopropylcarbinyl cation, 1 and nonclassical bicyclobutonium ion, 2 were found to be the minima for C 4H 7 (+) at the MP2/cc-pVTZ level. At the MP4(SDTQ)/cc-pVTZ//MP2/cc-pVTZ + ZPE level the structure 2 is 0.4 kcal/mol more stable than the structure 1. The (13)C NMR chemical shifts of 1 and 2 were calculated by the GIAO-CCSD(T) method. Based on relative energies and (13)C NMR chemical shift calculations, an equilibrium involving the 1 and 2 in superacid solutions is most likely responsible for the experimentally observed (13)C NMR chemical shifts, with the latter as the predominant equilibrating species. The alpha-methylcyclopropylcarbinyl cation, 4, and nonclassical bicyclobutonium ion, 5, were found to be the minima for C 5H 9 (+) at the MP2/cc-pVTZ level. At the MP4(SDTQ)/cc-pVTZ//MP2/cc-pVTZ + ZPE level ion 5 is 5.9 kcal/mol more stable than the structure 4. The calculated (13)C NMR chemical shifts of 5 agree rather well with the experimental values of C 5H 9 (+).


Elucidating the Nuclear Quantum Dynamics of Intramolecular Double Hydrogen Transfer in Porphycene.
We address the double hydrogen transfer (DHT) dynamics of the porphycene molecule, a complex paradigmatic system in which the making and breaking of H-bonds in a highly anharmonic potential energy surface require a quantum mechanical treatment not only of the electrons but also of the nuclei. We combine density functional theory calculations, employing hybrid functionals and van der Waals corrections, with recently proposed and optimized path-integral ring-polymer methods for the approximation of quantum vibrational spectra and reaction rates. Our full-dimensional ring-polymer instanton simulations show that below 100 K the concerted DHT tunneling pathway dominates but between 100 and 300 K there is a competition between concerted and stepwise pathways when nuclear quantum effects are included. We obtain ground-state reaction rates of 2.19 × 1011 s-1 at 150 K and 0.63 × 1011 s-1 at 100 K, in good agreement with experiment. We also reproduce the puzzling N-H stretching band of porphycene with very good accuracy from thermostated ring-polymer molecular dynamics simulations. The position and line shape of this peak, centered at around 2600 cm-1 and spanning 750 cm-1, stem from a combination of very strong H-bonds, the coupling to low-frequency modes, and the access to cis-like isomeric conformations, which cannot be appropriately captured with classical-nuclei dynamics. These results verify the appropriateness of our general theoretical approach and provide a framework for a deeper physical understanding of hydrogen transfer dynamics in complex systems.


Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.
Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F(4,14) = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR > 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad.


An interdisciplinary framework for derivation of occupational exposure limits.
Protecting the health and safety of workers in industrial operations is a top priority. One of the resources used in industry to ensure worker safety is the occupational exposure limit (OEL). OELs are derived from the assessment and interpretation of empirical data from animal and/or human studies. There are various guidelines for the derivation and implementation of OELs globally, with a range of stakeholders (including regulatory bodies, governmental agencies, expert groups and others). The purpose of this manuscript is to supplement existing guidance with learnings from a multidisciplinary team approach within an industry setting. The framework we present is similar in construct to other risk assessment frameworks and includes: (1) problem formulation, (2) literature review, (3) weight of evidence considerations, (4) point of departure selection/derivation, (5) application of assessment factors, and the final step, (6) derivation of the OEL. Within each step are descriptions and examples to consider when incorporating data from various disciplines such as toxicology, epidemiology, and exposure science. This manuscript describes a technical framework by which available data relevant for occupational exposures is compiled, analyzed, and utilized to inform safety threshold derivation applicable to OELs.


Cross-validation of a new procedure for early screening of smoking cessation medications in humans.
Brief procedures for evaluating medication efficacy may reveal which candidate drugs warrant further testing in clinical trials and which do not. We previously carried out a study of smoking abstinence, involving the nicotine patch, and established the sensitivity of our procedure. In this study, we sought to cross-validate our earlier work by comparing short-term smoking abstinence due to varenicline (relative to placebo) in smokers with high intrinsic quit interest (n = 57) and those with low intrinsic quit interest (n = 67). All the subjects were randomly assigned to either abstinence reinforcement ($12/day) or no reinforcement. In a crossover design, all the subjects participated in two 3-week phases: ad libitum smoking (week 1), dose run-up of varenicline (1.0 mg b.i.d.) or placebo (week 2), and quit attempt on medication verified daily by carbon monoxide <5 ppm (week 3). As with the nicotine patch in the previous study, varenicline (relative to placebo) increased abstinence more effectively in those with high intrinsic quit interest than in those with low quit interest but did not affect abstinence due to reinforcement. These data confirm the feasibility of a brief, sensitive test of the efficacy of cessation medications in smokers with high quit interest.


Sporadic diffuse leucoencephalopathy with axonal spheroids: report of a profuse and rapid cortical-spinal degeneration.
Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement.


Precision and accuracy in smFRET based structural studies-A benchmark study of the Fast-Nano-Positioning System.
Modern hybrid structural analysis methods have opened new possibilities to analyze and resolve flexible protein complexes where conventional crystallographic methods have reached their limits. Here, the Fast-Nano-Positioning System (Fast-NPS), a Bayesian parameter estimation-based analysis method and software, is an interesting method since it allows for the localization of unknown fluorescent dye molecules attached to macromolecular complexes based on single-molecule Förster resonance energy transfer (smFRET) measurements. However, the precision, accuracy, and reliability of structural models derived from results based on such complex calculation schemes are oftentimes difficult to evaluate. Therefore, we present two proof-of-principle benchmark studies where we use smFRET data to localize supposedly unknown positions on a DNA as well as on a protein-nucleic acid complex. Since we use complexes where structural information is available, we can compare Fast-NPS localization to the existing structural data. In particular, we compare different dye models and discuss how both accuracy and precision can be optimized.


Social influences on eating: implications for nutritional interventions.
We review recent research on the effect of social context on food intake and food choice and assess the implications for nutritional interventions. We focus on studies of modelling of eating behaviour and the impact of perceived eating norms on the amounts and types of food that individuals eat. We suggest that social context influences eating via multiple mechanisms, including identity signalling and self-presentation concerns. However, building on existing theoretical models, we propose that social factors may be particularly influential on nutrition because following the behaviour of others is adaptive and social norms inform individuals about behaviours that are likely to be optimal ('if everyone else is doing it, I probably should be'). Guided by understanding of the potential underlying mechanisms, we discuss how social norms might be used to promote healthier nutrition.


Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions.
Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)] are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin (CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently reported that male CORT deficient mice (cort-/-) are insulin-resistant and present a clear dysregulation in the stomach ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at pancreas level in cort-/- mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort-/- mice compared with controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin and GHS-R was observed in obese cort+/+ but not in cort-/- mice. Interestingly, insulin expression and release was elevated in obese cort+/+, while these changes were not observed in obese cort-/- mice. Altogether, our results indicate that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort -/- under normal and/or obesity conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data demonstrate, for the first time, that endogenous CORT is essential for the obesity-induced changes in insulin expression/secretion observed in mice, suggesting that CORT is a key regulatory component of the pancreatic function.


Evolution of Microdroplet Morphology Confined on Asymmetric Micropillar Structures.
The design of topological features to control the spreading of liquid has been widely investigated. Micropillar structures, for example, can retain stable droplets on the tip by inhibiting the contact line from advancing over a sharp solid edge. The pinning behavior of droplets on noncircular pillars, however, has received little attention. In this study, we analyze the retention of microdroplets with high and low surface tensions on axisymmetric and asymmetric porous micropillar structures. Circular, square, and triangular structures fabricated on silicon substrates are used to characterize the dynamic behavior of droplets before and after bursting. The critical pinning conditions are based on the visualization and pressure measurements of droplets. A theoretical model is developed based on a free energy analysis for predicting the change in pressure as the working fluid advances on the micropillar. For high surface tension liquids (e.g., water), the maximum pressure occurs when the contact line is pinned along the edge of the inner pore. For low surface tension liquids (e.g., Isopropanol and Novec 7500), the maximum pressure occurs when the contact line is pinned along the outer edge of the structure. The theoretical and experimental results demonstrate how a droplet pinned atop a triangular micropillar exhibits the smallest critical volume at the bursting moment. When using IPA solution (γ = 23 mN/m) and Novec 7500 (γ = 16 mN/m) as the working fluids, a change in the micropillar shape from circle to triangle, respectively, yields a 83% and 76% reduction in the critical burst volume. Meanwhile, the bursting pressure increases from 172 to 300 Pa and from 127 to 216 Pa for IPA and Novec 7500, respectively. These findings provide new insights to the rational design of surface micro/nanoengineered structures for tuning the surface wetting characteristics in scientific and engineering applications.


Experimental infection of Ixodes scapularis larvae (Acari: Ixodidae) by immersion in low passage cultures of Borrelia burgdorferi.
We describe a procedure for the introduction of Borrelia burgdorferi, the spirochetal agent of Lyme disease, into larvae of the tick vector Ixodes scapularis. Internalized spirochetes were observed in larvae examined after 15 or 45 min immersion at 32 degrees C in liquid culture suspensions of low passage B. burgdorferi strain B31. Larval ticks immersed in low passage strain B31 were able to feed to repletion on white-footed mice. Midguts of larvae contained many spirochetes 1 wk postengorgement, while larvae incubated with high passage strain B31 were free of detectable spirochetes at the same interval. Larvae incubated with low passage strain B31 were competent to transmit the pathogen to mice, as shown by serology, reisolation of B. burgdorferi from mice, and xenodiagnosis. Ticks maintained the infection transstadially to the nymphal stage and transmitted the infection to naive mice, replicating an essential aspect of natural infection. This method requires no special equipment and allows artificial infection of large numbers of ticks at the larval stage. It will facilitate studies of the contribution of specific B. burgdorferi genetic loci to tick colonization.


Retinoid acid-induced effects on atrial and pacemaker cell differentiation and expression of cardiac ion channels.
Whereas retinoid acid (RA) signaling has been implicated in embryonic heart development, its significance in differentiation of specific cardiac subtypes remains largely unknown. In the present study, we took advantage of lineage-specific expression of atrial natriuretic peptide (ANP) in embryonic stem (ES) cells to study RA-induced effects on differentiation of atrial- and pacemaker-like phenotypes. Embryoid bodies (EB) were exposed to 10(-5), 10(-7), and 10(-9) M RA at early (days 1-5 [d1-5]) and late (d6-10) developmental stages, and RA effects on expression of lineage-specific cardiac markers and ion channels were examined. Our initial experiments revealed a detrimental effect of 10(-5) M RA on EB development by inducing marked apoptosis. Morphologic and expression analysis demonstrated that 10(-7) M RA applied at d1-5 was most effective to induce the atrial sublineage. RA did not affect differentiation of pacemaker-like cells, independent of RA concentration and application time. Conversely, RA exposure at an early developmental stage inhibited ventricular-specific MLC-2v gene expression. Late-stage RA administration exhibited no significant alterations in cardiomyogenic differentiation. Terminally differentiated cardiomyocytes exposed to RA at d1-5 or d6-10 displayed unchanged I(Ca,L) and I(to) channel expression compared with untreated cells. However, patch clamp studies revealed a significant increase of I(Ca,L) and I(to) current densities associated with increased levels of the underlying channel subunits in 6-7-day-old cardiomyocytes upon early RA exposure. In contrast, I(f) current density and HCN4 expression remained largely unaffected by RA. Our results imply that RA induces differentiation of ANP-expressing EBs toward an atrial phenotype in a time- and concentration-dependent manner and accelerates expression of I(Ca,L) and I(to) ion channels without affecting differentiation of pacemaker cells.


Annelids as models of germ cell and gonad regeneration.
Germ cells (reproductive cells and their progenitors) give rise to the next generation in sexually reproducing organisms. The loss or removal of germ cells often leads to sterility in established research organisms such as the fruit fly, nematodes, frog, and mouse. The failure to regenerate germ cells in these organisms reinforced the dogma of germline-soma barrier in which germ cells are set-aside during embryogenesis and cannot be replaced by somatic cells. However, in stark contrast, many animals including segmented worms (annelids), hydrozoans, planaria, sea stars, sea urchins, and tunicates can regenerate germ cells. Here I review germ cell and gonad regeneration in annelids, a rich history of research that dates back to the early 20th century in this highly regenerative group. Examples include annelids from across the annelid phylogeny, across developmental stages, and reproductive strategies. Adult annelids regenerate germ cells as a part of regeneration, grafting, and asexual reproduction. Annelids can also recover germ cells after ablation of germ cell progenitors in the embryos. I present a framework to investigate cellular sources of germ cell regeneration in annelids, and discuss the literature that supports different possibilities within this framework, where germ-soma separation may or may not be preserved. With contemporary genetic-lineage tracing and bioinformatics tools, and several genetically enabled annelid models, we are at the brink of answering the big questions that puzzled many for over more than a century.


Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo.
Adeno-associated virus (AAV) vectors are ideal for performing gene repair due to their ability to target multiple different genomic loci, low immunogenicity, capability to achieve targeted and stable expression through integration, and low mutagenic and oncogenic potential. However, many handicaps to gene repair therapy remain. Most notable is the low frequency of correction in vivo. To date, this frequency is too low to be of therapeutic value for any disease. To address this, a point-mutation-based mouse model of the metabolic disease hereditary tyrosinemia type I was used to test whether targeted AAV integration by homologous recombination could achieve high-level stable gene repair in vivo. Both neonatal and adult mice were treated with AAV serotypes 2 and 8 carrying a wild-type genomic sequence for repairing the mutated Fah (fumarylacetoacetate hydrolase) gene. Hepatic gene repair was quantified by immunohistochemistry and supported with reverse transcription polymerase chain reaction and serology for functional correction parameters. Successful gene repair was observed with both serotypes but was more efficient with AAV8. Correction frequencies of up to 10(-3) were achieved and highly reproducible within typical dose ranges. In this model, repaired hepatocytes have a selective growth advantage and are thus able to proliferate to efficiently repopulate mutant livers and cure the underlying metabolic disease. AAV-mediated gene repair is feasible in vivo and can functionally correct an appropriate selection-based metabolic liver disease in both adults and neonates.


Cellular action of vasopressin in medullary tubules of mice with hereditary nephrogenic diabetes insipidus.
Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI. Adenylate cyclase activity stimulated by VP or by NaF was only slightly lower (-24%) in MCT from NDI mice, compared with controls. In MAL of NDI mice, basal, VP-sensitive, and NaF-sensitive adenylate cyclase was markedly (> -60%) lower compared with MAL of controls. The specific activity of cAMP-PDIE was markedly higher in MCT of NDI mice compared with controls, but was not different between MAL of control and NDI mice. Under present in vitro conditions, incubation of intact MCT from control mice with VP caused a striking increase in cAMP levels (>10), but VP failed to elicit a change in cAMP levels in MCT from NDI mice. When the cAMP-PDIE inhibitor 1-methyl-3-isobutyl xanthine (MIX) was added to the above incubation, VP caused a significant increase in cAMP levels in MCT from both NDI mice and control mice. Under all tested conditions, cAMP levels in MCT of NDI mice were lower than corresponding values in control MCT. Under the present experimental setting, VP and other stimulating factors (MIX, cholera toxin) did not change cAMP levels in MAL from either control mice or from NDI mice. The results of the present in vitro experiments suggest that the functional unresponsiveness of NDI mice to VP is perhaps mainly the result of the inability of collecting tubules to increase intracellular cAMP levels in response to VP. In turn, this inability to increase cAMP in response to VP is at least partly the result of abnormally high activity of cAMP-PDIE, a somewhat lower activity of VP-sensitive adenylate cyclase in MCT of NDI mice, and perhaps to a deficiency of some other as yet unidentified factors. The possible contribution of low VP-sensitive adenylate cyclase activity in MAL of NDI mice to the renal resistance to VP remains to be defined.


Fusarium species causing invasive fungal pneumonia in an immunocompetent patient: a case report.
Fusarium is a large genus of filamentous fungi that are rarely associated with disease in humans. In the clinical setting, Fusarium species are often difficult to distinguish from other fungal organisms, particularly Aspergillus species. Invasive fungal pneumonia caused by Fusarium species has rarely been reported, especially in immunocompetent patients. In this study, we reported a case of invasive Fusarium pneumonia in a previously healthy 68-year-old woman. The disease was initially misdiagnosed as invasive Aspergillus pneumonia because of the similarity in radiologic and histopathologic findings between these conditions. After Fusarium was identified via microbiological analysis, the antifungal agent was changed, and the patient recovered fully.


Detection of post-translational sulfation of alpha-5 beta-1 integrin and its role in integrin-fibronectin binding.
Fibronectins are glycoproteins of the extracellular matrix composed of two 220-kDa polypeptide chains named A and B bound by two disulfide bridges. Both chains when digested with proteolytic enzymes give rise to six different domains named I to VI that are involved in the ligand properties of this molecule. Fibronectins bind fibrin, collagen, glycosaminoglycan residues and several integrins. In this study, using metabolic radiolabeling of alpha 5 beta 1 integrin with sodium sulfate, an immunoprecipitation reaction, inhibition of sulfate incorporation and a fibronectin-binding assay, we were able to detect this integrin as a sulfated molecule and this sulfation appears to regulate the integrin-fibronectin binding.


Low-content quantification in powders using Raman spectroscopy: a facile chemometric approach to sub 0.1% limits of detection.
A robust and accurate analytical methodology for low-content (<0.1%) quantification in the solid-state using Raman spectroscopy, subsampling, and chemometrics was demonstrated using a piracetam-proline model. The method involved a 5-step process: collection of a relatively large number of spectra (8410) from each sample by Raman mapping, meticulous data pretreatment to remove spectral artifacts, use of a 0-100% concentration range partial least-squares (PLS) regression model to estimate concentration at each pixel, use of a more accurate, reduced concentration range PLS model to calculate analyte concentration at each pixel, and finally statistical analysis of all 8000+ concentration predictions to produce an accurate overall sample concentration. The relative prediction accuracy was ∼2.4% for a 0.05-1.0% concentration range, and the limit of detection was comparable to high performance liquid chromatography (0.03% versus 0.041%). For data pretreatment, we developed a unique cosmic ray removal method and used an automated baseline correction method, neither of which required subjective user intervention and thus were fully automatable. The method is applicable to systems which cannot be easily analyzed chromatographically, such as hydrate, polymorph, or solvate contamination.


The crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonohydroxamic acid.
Phosphoglucose isomerase (EC ) catalyzes the second step in glycolysis, the reversible isomerization of D-glucose 6-phosphate to D-fructose 6-phosphate. The reaction mechanism involves acid-base catalysis with proton transfer and proceeds through a cis-enediol(ate) intermediate. 5-Phospho-D-arabinonohydroxamic acid (5PAH) is a synthetic small molecule that resembles the reaction intermediate, differing only in that it has a nitrogen atom in place of C1. Hence, 5PAH is the best inhibitor of the isomerization reaction reported to date with a K(i) of 2 x 10(-7) M. Here we report the crystal structure of rabbit phosphoglucose isomerase complexed with 5PAH at 1.9 A resolution. The interaction of 5PAH with amino acid residues in the enzyme active site supports a model of the catalytic mechanism in which Glu-357 transfers a proton between C1 and C2 and Arg-272 helps stabilize the intermediate. It also suggests a mechanism for proton transfer between O1 and O2.


Detection of differentially expressed genes involved in osteoarthritis pathology.
Osteoarthritis (OA) is the most common chronic disorder of joints; however, the key genes and transcription factors (TFs) associated with OA are still unclear. Through bioinformatics tools, the study aimed to understand the mechanism of genes associated with the development of OA. Four gene expression profiling datasets were used to identify differentially expressed genes (DEGs) between OA and healthy control samples by a meta-analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed with Multifaceted Analysis Tool for Human Transcriptome (MATHT). Subsequently, a protein-protein interaction (PPI) network was constructed for these DEGs. Significant network modules were identified using ReactomeFIViz, and the pathway of each module was enriched using MATHT. In addition, TFs in the DEGs were identified. In total, 690 DEGs were identified between OA and healthy control samples, including 449 upregulated and 241 downregulated DEGs. Additionally, 622 nodes and 2752 interactions constituted the PPI network, including 401 upregulated and 221 downregulated DEGs. Among them, FOS, TWIST1, POU2F1, SMARCA4, and CREBBP were also identified as TFs. RT-PCR results showed that the expression levels of Fos, Twist1, Pou2f1, Smarca4, and Crebbp decreased in mice with OA. In addition, FOS, TWIST1, SMARCA4, and CREBBP were involved in the positive regulation of transcription from the RNA polymerase II promoter. TWIST1, POU2F1, SMARCA4, and CREBBP may play an important role in OA pathology.


Peripheral and central mechanisms of orofacial pain and their clinical correlates.
This paper reviews recent research that has provided important insights into the peripheral processes by which noxious stimuli activate or modulate nociceptive afferent inputs into the brainstem, that has identified the critical neural elements and pathways in the brainstem and higher levels of the trigeminal (V) somatosensory system that receive and transmit nociceptive inputs from orofacial tissues, and that has clarified some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. The paper also outlines some of the clinical correlates of these research advances.


Calcium phosphate-based nanosystems for advanced targeted nanomedicine.
Synthetic calcium phosphates (CaPs) are the most widely accepted bioceramics for the repair and reconstruction of bone tissue defects. The recent advancements in materials science have prompted a rapid progress in the preparation of CaPs with nanometric dimensions, tailored surface characteristics, and colloidal stability opening new perspectives in their use for applications not strictly related to bone. In particular, the employment of CaPs nanoparticles as carriers of therapeutic and imaging agents has recently raised great interest in nanomedicine. CaPs nanoparticles, as well as other kinds of nanoparticles, can be engineered to specifically target the site of the disease (cells or organs), thus minimizing their dispersion in the body and undesired organism-nanoparticles interactions. The most promising and efficient approach to improve their specificity is the 'active targeting', where nanoparticles are conjugated with a targeting moiety able to recognize and bind with high efficacy and selectivity to receptors that are highly expressed only in the therapeutic site. The aim of this review is to give an overview on advanced targeted nanomedicine with a focus on the most recent reports on CaP nanoparticles-based systems, specifically designed for the active targeting. The distinctive characteristics of CaP nanoparticles with respect to the other kinds of nanomaterials used in nanomedicine are also discussed.


"The Red Dress or the Blue?": How Do Staff Perceive That They Support Decision Making for People With Dementia Living in Residential Aged Care Facilities?
Respect for a person's right to make choices and participate in decision making is generally seen as central to quality of life and well-being. When a person moves into a residential aged care facility (RACF), however, decision making becomes more complicated, particularly if the person has a diagnosis of dementia. Little is known about how staff in RACFs perceive that they support decision making for people with dementia within their everyday practice, and this article seeks to address this knowledge gap. The article reports on the findings of a qualitative study conducted in the states of Victoria and Queensland, Australia with 80 direct care staff members. Findings revealed that the participants utilized a number of strategies in their intention to support decision making for people with dementia, and had an overall perception that "a little effort goes a long way."


Stage-dependent restoration of sensory dorsal columns following spinal cord transection in anuran tadpoles.
In frogs sensory axons from the lumbar dorsal roots ascend in the dorsal column of the spinal cord to terminate in the medulla and cerebellum. The response of these axons to complete transection of the thoracic spinal cord has been analysed in Rana temporaria tadpoles at different stages of development. The presence and position of dorsal column axons were assessed by using the anterograde transport of horseradish peroxidase or by electrophysiological methods. Before developmental stage VIII, dorsal column axons can grow across the transection and reach their normal areas of termination in the brainstem. Axons that do cross the transection follow their normal pathways. From stage VIII onwards this capacity for growth is largely lost. These results are discussed in terms of the relation between neurogenesis, axon growth and axonal regeneration.


Impact of complications on patient satisfaction in breast reconstruction.
The development of a complication after surgery can be difficult for both patient and surgeon. With a growing body of literature evaluating patient satisfaction after breast reconstruction, few studies directly focus on the impact of surgical complications on satisfaction. This study analyzed the effect of complications on general and aesthetic satisfaction after breast reconstruction. All women at an academic institution undergoing breast reconstruction between 1999 and 2006 were identified. Patient demographics and history of complications were collected. A questionnaire adapted from the Michigan Breast Reconstruction Outcomes Survey was administered examining general and aesthetic satisfaction. Patients with complications were compared with patients with no complications. Overall, 716 women underwent 932 reconstructions; 233 patients had a complication. Patient demographics and response rate were similar between the two groups (overall response rate 75.4 percent). Development of a complication correlated with increased odds of aesthetic dissatisfaction (odds ratio = 1.61, p = 0.047). Other predictors of dissatisfaction were older age, reconstruction with an implant, and a longer time interval between reconstruction and survey, while autologous reconstruction was a predictor of satisfaction. Among patients with a complication, implant reconstruction and mastectomy for prophylaxis were significant predictors of dissatisfaction. Aesthetic satisfaction after breast reconstruction is lower in patients developing a complication, older patients, and those receiving an implant reconstruction. Furthermore, patients with a prophylactic mastectomy are more likely than those with a therapeutic mastectomy to be dissatisfied when complications arise. These relationships are important, as measures to improve quality and decrease complications can directly improve patient satisfaction.


Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.
A database has been created to collect information on families carrying a germ-line mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes [Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL)]. Data from the published literature have been included. The database is available online at http://www.iarc.fr/p53, as part of the IARC TP53 Database. The analysis of the 265 families/individuals that have been included thus far has revealed several new findings. In classical LFS families with a germ-line TP53 mutation (83 families), the mean age of onset of breast cancer was significantly lower than in LFS families (16 families) without a TP53 mutation (34.6 versus 42.5 years; P = 0.0035). In individuals with a TP53 mutation, a correlation between the genotype and phenotype was found. Brain tumors were associated with missense TP53 mutations located in the DNA-binding loop that contact the minor groove of DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense mutations located in the loops opposing the protein-DNA contact surface (P = 0.003). Finally, mutations likely to result in a null phenotype (absence of the protein or loss of function) were associated with earlier onset brain tumors (P = 0.004). These observations have clinical implications for genetic testing and tumor surveillance in LFS/LFL families.


Exosomes Derived From Epigallocatechin Gallate-Treated Cardiomyocytes Attenuated Acute Myocardial Infarction by Modulating MicroRNA-30a.
Ischemia-derived exosomes can restrict excessive autophagy by transferring microRNA-30a (miR30a) to cells. Reports have confirmed that epigallocatechin gallate (EGCG) alleviates acute myocardial infarction (AMI) by regulating autophagy; however, research evaluating the communication with cardiomyocytes and exosomes is lacking. This study aimed to explore whether exosomes derived from EGCG-treated cardiomyocytes mitigated AMI by adjusting miR30a to inactivate apoptosis and autophagy. Exosomes were extracted from cardiomyocytes, cultured either in control or AMI condition, with or without EGCG pretreatment. The exosome characteristics were analyzed by nanoparticle tracking analyses and transmission electron microscopy. The change in miR30a in cells and exosomes was demonstrated by qRT-PCR. H9c2 or stable miR30a knockdown (miR30aKD) cell lines were incubated with exosomes derived from EGCG-treated cardiomyocytes in vitro or in vivo. The effect of EGCG and exosomes on I/R-induced cardiomyocyte apoptosis and autophagy was assessed. EGCG improved the activity of cardiomyocytes, and increased average diameter, concentration, miR30a mRNA level, and specific protein expression in AMI-derived exosomes produced by cardiomyocytes. Moreover, the coincubation of AMI cells with EGCG or exosomes derived from EGCG-treated cardiomyocytes attenuated cardiomyocyte apoptosis and autophagy. The findings showed that EGCG upregulates miR30a, which was efficiently transferred via exosomes between cardiomyocytes, thereby contributing to the suppression of apoptosis and autophagy. By focusing on the cardiomyocyte microenvironment, we identified a new target of EGCG alleviating AMI by regulating apoptosis and autophagy.


The timing of discharge from the intensive care unit and subsequent mortality. A prospective, multicenter study.
Previous studies suggested an association between after-hours intensive care unit (ICU) discharge and increased hospital mortality. Their retrospective design and lack of correction for patient factors present at the time of discharge make this association problematic. To determine factors independently associated with mortality after ICU discharge. This was a prospective, multicenter, binational observational study involving 40 ICUs in Australia and New Zealand. Participants were consecutive adult patients discharged alive from the ICU between September 2009 and February 2010. We studied 10,211 patients discharged alive from the ICU. Median age was 63 years (interquartile range, 49-74), 6,224 (61%) were male, 5,707 (56%) required mechanical ventilation, and their median Acute Physiology and Chronic Health Evaluation III risk of death was 9% (interquartile range, 3-25%). A total of 8,539 (83.6%) patients were discharged in-hours (06:00-18:00) and 1,672 (16.4%) after-hours (18:00-06:00). Of these, 408 (4.8%) and 124 (7.4%), respectively, subsequently died in hospital (P < 0.001). After risk adjustment for markers of illness severity at time of ICU discharge including limitations of medical therapy (LOMT) orders, the time of discharge was no longer a significant predictor of mortality. The presence of a LOMT order was the strongest predictor of death (odds ratio, 35.4; 95% confidence interval, 27.5-45.6). In this large, prospective, multicenter, binational observational study, we found that patient status at ICU discharge, particularly the presence of LOMT orders, was the chief predictor of hospital survival. In contrast to previous studies, the timing of discharge did not have an independent association with mortality.


A Quantile-Based g-Computation Approach to Addressing the Effects of Exposure Mixtures.
Exposure mixtures frequently occur in data across many domains, particularly in the fields of environmental and nutritional epidemiology. Various strategies have arisen to answer questions about exposure mixtures, including methods such as weighted quantile sum (WQS) regression that estimate a joint effect of the mixture components. We demonstrate a new approach to estimating the joint effects of a mixture: quantile g-computation. This approach combines the inferential simplicity of WQS regression with the flexibility of g-computation, a method of causal effect estimation. We use simulations to examine whether quantile g-computation and WQS regression can accurately and precisely estimate the effects of mixtures in a variety of common scenarios. We examine the bias, confidence interval (CI) coverage, and bias-variance tradeoff of quantile g-computation and WQS regression and how these quantities are impacted by the presence of noncausal exposures, exposure correlation, unmeasured confounding, and nonlinearity of exposure effects. Quantile g-computation, unlike WQS regression, allows inference on mixture effects that is unbiased with appropriate CI coverage at sample sizes typically encountered in epidemiologic studies and when the assumptions of WQS regression are not met. Further, WQS regression can magnify bias from unmeasured confounding that might occur if important components of the mixture are omitted from the analysis. Unlike inferential approaches that examine the effects of individual exposures while holding other exposures constant, methods like quantile g-computation that can estimate the effect of a mixture are essential for understanding the effects of potential public health actions that act on exposure sources. Our approach may serve to help bridge gaps between epidemiologic analysis and interventions such as regulations on industrial emissions or mining processes, dietary changes, or consumer behavioral changes that act on multiple exposures simultaneously. https://doi.org/10.1289/EHP5838.


Adherence to antiretroviral therapy in patients enrolled in a comprehensive care program in Cambodia: a 24-month follow-up assessment.
The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence. Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence. A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence. At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.


Cross-talk of Brassinosteroid signaling in controlling growth and stress responses.
Plants are faced with a barrage of stresses in their environment and must constantly balance their growth and survival. As such, plants have evolved complex control systems that perceive and respond to external and internal stimuli in order to optimize these responses, many of which are mediated by signaling molecules such as phytohormones. One such class of molecules called Brassinosteroids (BRs) are an important group of plant steroid hormones involved in numerous aspects of plant life including growth, development and response to various stresses. The molecular determinants of the BR signaling pathway have been extensively defined, starting with the membrane-localized receptor BRI1 and co-receptor BAK1 and ultimately culminating in the activation of BES1/BZR1 family transcription factors, which direct a transcriptional network controlling the expression of thousands of genes enabling BRs to influence growth and stress programs. Here, we highlight recent progress in understanding the relationship between the BR pathway and plant stress responses and provide an integrated view of the mechanisms mediating cross-talk between BR and stress signaling.


18-kDa Translocator Protein Ligands Protect H9C2 Cardiomyocytes from Cigarette Smoke-induced Cell Death: In Vitro Study.
Cigarette smoke (CS) can induce cellular damage via alterations in 18 kDa translocator protein (TSPO)-related functions, leading to cardiovascular diseases. The current study focused on the possible protective effect of TSPO ligands against CS-induced damage to cardiac cells. H9C2 Cardiomyocyte cell line of rat origin was pre-treated with TSPO ligands. Cell death, TSPO binding, and TSPO protein expression levels were assessed following 30-min CS exposure with/without TSPO ligands. CS exposure of H9C2 cells significantly incensed cell death (by 26%, p<0.001). Pre-treatment with TSPO ligands at two concentrations prevented cell death. Neither CS nor ligands affected TSPO protein expression in H9C2 cells. CS led to increased cell death and reduced TSPO binding. Reduced TSPO binding may have a role in CS-induced cell death, and TSPO ligand MGV-1 can prevent suppression of TSPO binding and corresponding cell death. These results may be relevant to treatment of cardiovascular diseases associated with CS.


An acoustofluidic sputum liquefier.
We demonstrate the first microfluidic-based on-chip liquefaction device for human sputum samples. Our device is based on an acoustofluidic micromixer using oscillating sharp edges. This acoustofluidic sputum liquefier can effectively and uniformly liquefy sputum samples at a throughput of 30 μL min(-1). Cell viability and integrity are maintained during the sputum liquefaction process. Our acoustofluidic sputum liquefier can be conveniently integrated with other microfluidic units to enable automated on-chip sputum processing and analysis.


Evaluation of corrosion behaviour and some mechanical properties of silver-rich, gamma 2 free amalgam.
Corrosion behaviour, creep resistance, compressive and tensile strength and hardness of a newly developed silver-rich commercial amalgam were investigated in order to evaluate its performance, as compared with three high copper amalgams, namely; admixed, unicompositional and Pd-enriched. The results have shown that Ag-rich amalgam was superior in corrosion behaviour, compressive and tensile strength. Creep values were comparable to those of Pd-enriched amalgam, whereas hardness measurements of the latter were significantly higher. The results were analysed on a compositional and microstructural bases.


Quantitative imaging: systematic review of perfusion/flow phantoms.
We aimed at reviewing design and realisation of perfusion/flow phantoms for validating quantitative perfusion imaging (PI) applications to encourage best practices. A systematic search was performed on the Scopus database for "perfusion", "flow", and "phantom", limited to articles written in English published between January 1999 and December 2018. Information on phantom design, used PI and phantom applications was extracted. Of 463 retrieved articles, 397 were rejected after abstract screening and 32 after full-text reading. The 37 accepted articles resulted to address PI simulation in brain (n = 11), myocardial (n = 8), liver (n = 2), tumour (n = 1), finger (n = 1), and non-specific tissue (n = 14), with diverse modalities: ultrasound (n = 11), computed tomography (n = 11), magnetic resonance imaging (n = 17), and positron emission tomography (n = 2). Three phantom designs were described: basic (n = 6), aligned capillary (n = 22), and tissue-filled (n = 12). Microvasculature and tissue perfusion were combined in one compartment (n = 23) or in two separated compartments (n = 17). With the only exception of one study, inter-compartmental fluid exchange could not be controlled. Nine studies compared phantom results with human or animal perfusion data. Only one commercially available perfusion phantom was identified. We provided insights into contemporary phantom approaches to PI, which can be used for ground truth evaluation of quantitative PI applications. Investigators are recommended to verify and validate whether assumptions underlying PI phantom modelling are justified for their intended phantom application.


Facile fabrication of a three-dimensional gold nanowire array for high-performance electrochemical sensing.
Great challenges remain in the template-assisted fabrication of metal nanowire arrays on substrates, because enormous effort is required to address the adhesion issues between substrates and adopted templates, e.g. anodic aluminum oxide (AAO). Therefore, novel and promising templates are highly desired for the construction of proposed structures. Here, vertical 1,5-diaminoanthraquinone (DAAQ) nanowires were prepared in situ on substrates by a facile method, and these were proven to be a reliable and alternative template for the preparation of a metal nanowire array. As an example, with the wet chemical reduction of HAuCl4, a three-dimensional gold nanowire array (3D GNA) was successfully obtained with a DAAQ template. The proposed 3D GNA has an extremely large roughness factor of ca. 15, as well as high stability and a favorable surface structure for the diffusion of analytes, making it a suitable candidate for the construction of high-performance electrochemical biosensors. As a result, an ultrasensitive aptasensor was constructed for the detection of thrombin, with a general sensing scheme. The fabricated aptasensor displays an impressively ultralow detection limit of 3 fM (S/N = 3) with a wide linear response from 10 fM to 1 nM, as well as excellent selectivity, good reproducibility and acceptable stability. Further, the biosensor exhibits potential for application in the analysis of real serum samples. The developed DAAQ nanowires are envisaged to become a general template for the fabrication of more nanowire arrays and the as-synthesized 3D GNA could open up a wide range of possibilities for potential applications in biological sensing.


Knock-down of superoxide dismutase 1 sensitizes cisplatin-resistant human ovarian cancer cells.
Overexpression of superoxide dismutase 1 (SOD1) has been shown to be one of the factors involved in causing cisplatin resistance in ovarian cancer. Reduction of SOD1 expression is expected to restore, at least partially, cisplatin sensitivity in ovarian cancer chemotherapy. Here, we explored the potential of RNAi as a therapy for reversal of cisplatin resistance. SOD1-specific small-interfering RNA (siRNA) was synthesized and transfected into cisplatin-resistant cell line A2780/CP prior to treatment with 15 muM cisplatin. Cell survival was assessed by clonogenic assay. An enhanced cisplatin sensitivity was observed in the A2780/CP cells treated with SOD1-specific siRNA, compared to non-siRNA-treated or scrambled-siRNA-treated control cells. Specifically targeting SOD1 could lead to sensitization of cisplatin-resistant ovarian cancer cells, and SOD1 may be used as a potential target for chemosensitizers.


Serum Calcium and Risk of Sudden Cardiac Arrest in the General Population.
To evaluate the potential role of low serum Ca levels in the occurrence of sudden cardiac arrest (SCA) in the community. We compared 267 SCA cases [177 (66%) men] and 445 controls [314 (71%) men] from a large population-based study (catchment population ∼1 million individuals) in the US Northwest from February 1, 2002, through December 31, 2015. Patients were included if their age was 18 years or older with available creatinine clearance (CrCl) and serum electrolyte levels for analyses to enable adjustment for renal function. For cases, creatinine clearance and electrolyte levels were required to be measured within 90 days of the SCA event. Cases of SCA had higher proportions of blacks [31 (12%) vs 14 (3%); P<.001], diabetes mellitus [122 (46%) vs 126 (28%); P<.001], and chronic kidney disease [102 (38%) vs 73 (16%); P<.001] than did controls. In multivariable logistic regression analysis, a 1-unit decrease in Ca levels was associated with a 1.6-fold increase in odds of SCA (odds ratio, 1.63; 95% CI, 1.06-2.51). Blood Ca levels lower than 8.95 mg/dL (to convert to mmol/L, multiply by 0.025) were associated with a 2.3-fold increase in odds of SCA as compared with levels higher than 9.55 mg/dL (odds ratio, 2.33; 95% CI, 1.17-4.61). Cases of SCA had significantly prolonged corrected QT intervals on the 12-lead electrocardiogram than did controls (465±37 ms vs 425±33 ms; P<.001). Lower serum Ca levels were independently associated with an increased risk of SCA in the community.


Perioperative Assessment and Management for Sleep Apnea in the Ambulatory Surgical Patient.
The overwhelming majority of surgical procedures performed in the United States are done on an outpatient basis. Patients with complicated medical problems are routinely scheduled for ambulatory procedures that have become progressively more complex. Appropriate patient selection is paramount to ensuring optimal perioperative outcomes, and the patient with known or suspected OSA presents unique challenges to the anesthesia care team regarding airway management, pain control, and postoperative monitoring requirements. Currently, a relative paucity of high-quality evidence exists on which to base guidelines or recommendations for the anesthetic care of these patients. It is generally agreed that early identification of those at risk for OSA allows for planning and implementation of strategies to help to reduce the risk of adverse perioperative events. Although various national societies have published consensus statements aimed at guiding the perioperative management of the patient at risk for OSA, more studies are needed to define the optimal approach to the perioperative care of this population.


Metabolic Syndrome Alters the Cargo of Mitochondria-Related microRNAs in Swine Mesenchymal Stem Cell-Derived Extracellular Vesicles, Impairing Their Capacity to Repair the Stenotic Kidney.
Coexisting metabolic syndrome (MetS) and renal artery stenosis (RAS) are linked to poor renal outcomes. Mesenchymal stem/stromal cell- (MSC-) derived extracellular vesicles (EVs) from lean animals show superior ability to repair the experimental MetS+RAS kidney compared to EVs from MetS pig MSCs. We hypothesized that MetS leads to selective packaging in porcine EVs of microRNAs capable of targeting mitochondrial genes, interfering with their capacity to repair the MetS+RAS kidney. Five groups of pigs (n = 7 each) were studied after 16 weeks of diet-induced MetS and RAS (MetS+RAS) and MetS+RAS 4 weeks after a single intrarenal delivery of EVs harvested from allogeneic adipose tissue-derived MSCs isolated from Lean or MetS pigs, and Lean or MetS sham controls. Single-kidney blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multidetector CT, whereas EV microRNA cargo, renal tubular mitochondrial structure and bioenergetics, and renal injury pathways were assessed ex vivo. microRNA sequencing revealed 19 dysregulated microRNAs capable of targeting several mitochondrial genes in MetS-EVs versus Lean-EVs. Lean- and MetS-EVs were detected in the stenotic kidney 4 weeks after administration. However, only MetS-EVs failed to improve renal mitochondrial density, structure, and function or attenuate oxidative stress, tubular injury, and fibrosis. Furthermore, Lean-EVs but not MetS-EVs restored RBF and GFR in MetS+RAS. MetS alters the cargo of mitochondria-related microRNAs in swine MSC-derived EVs, which might impair their capacity to repair the poststenotic kidney in MetS+RAS. These observations may contribute to develop approaches to improve the efficacy of MSC-EVs for patients with MetS.


Diagnosis of canine brucellosis: comparison between serological and microbiological tests and a PCR based on primers to 16S-23S rDNA interspacer.
A pair of primers directed to 16S-23S rDNA interspacer (ITS) was designed directed to Brucella genetic sequences in order to develop a polymerase chain reaction (PCR) putatively capable of amplifying DNA from any Brucella species. Nucleic acid extracts from whole-blood from naive dogs were spiked with decreasing amounts of Brucella canis RM6/66 DNA and the resulting solutions were tested by PCR. In addition, the ability of PCR to amplify Brucella spp. genetic sequences from naturally infected dogs was evaluated using 210 whole-blood samples of dogs from 19 kennels. The whole-blood samples collected were subjected to blood culture and PCR. Serodiagnosis was performed using the rapid slide agglutination test with and without 2-mercaptoethanol. The DNA from whole blood was extracted using proteinase-K, sodium dodecyl sulphate and cetyl trimethyl ammonium bromide followed by phenol-chloroform purification. The PCR was capable of detecting as little as 3.8 fg of Brucella DNA mixed with 450 ng of host DNA. Theoretically, 3.8 fg of Brucella DNA represents the total genomic mass of fewer than two bacterial cells. The PCR diagnostic sensitivity and specificity were 100%. From the results observed in the present study, we conclude that PCR could be used as confirmatory test for diagnosis of B. canis infection.


Unravelling the confusion caused by GASB, FASB accounting rules.
Separate GASB and FASB accounting and financial reporting rules for governmental healthcare providers are producing confusion. Among other problems, they reduce the usefulness of aggregated data about the healthcare industry. This article addresses the inconsistencies of the various reporting standards and identified problems they can cause.


'The word that comes to mind is polymath': medical students' perceptions of rural postgraduate careers.
Physician shortages in rural and remote areas challenge accessibility and delivery of care to rural and remote communities, including within Scotland. Medical education is a reform priority to establish a sustainable medical workforce. Although there is evidence to support aspects of medical education that enhance the likelihood of practising rurally, the mechanism by which these educational initiatives work is not clearly understood. This study aimed to examine medical students' perceptions of rural and remote practice, how these perceptions motivate their interest to practise rurally, and what aspects of education are thought to influence these perceptions. This cross-sectional study utilised semistructured interviews with 10 University of St Andrews medical students enrolled in undergraduate or graduate-entry medical education programs. Feldman and Ng's theoretical framework was deductively applied. Interviews informed additional subthemes, which were integrated into the original framework. The final framework helped examine medical students' perceptions of rural medicine and mechanisms that shape these perceptions. Structural (countrywide) themes included geographical barriers affecting patients and physicians. Organisational themes included perceptions of inequitable allocation of resources between urban and rural areas, as well as limited staff and support in rural practices. Occupational themes included the perception of rural clinical generalists. Personal life themes included the perception of community in rural areas. Mechanisms shaping medical students' perceptions most profoundly were their experiences (educational, personal experience or working). Medical students' perceptions align with other professionals' reasons for staying in a particular job. Perceptions regarding rural careers included challenges due to geographical proximity to patients, resource allocation in rural areas, and the potential to subspecialise as a general rural practitioner. Identified mechanisms, which shape perceptions, can be addressed and strengthened by educators, policy-makers and governments to optimise medical education that promotes rural recruitment and retention.


Separation of nearly identical repeats in shotgun assemblies using defined nucleotide positions, DNPs.
An increasingly important problem in genome sequencing is the failure of the commonly used shotgun assembly programs to correctly assemble repetitive sequences. The assembly of non-repetitive regions or regions containing repeats considerably shorter than the average read length is in practice easy to solve, while longer repeats have been a difficult problem. We here present a statistical method to separate arbitrarily long, almost identical repeats, which makes it possible to correctly assemble complex repetitive sequence regions. The differences between repeat units may be as low as 1% and the sequencing error may be up to ten times higher. The method is based on the realization that a comparison of only a part of all overlapping sequences at a time in a data set does not generate enough information for a conclusive analysis. Our method uses optimal multi-alignments consisting of all the overlaps of each read. This makes it possible to determine defined nucleotide positions, DNPs, which constitute the differences between the repeat units. Differences between repeats are distinguished from sequencing errors using statistical methods, where the probabilities of obtaining certain combinations of candidate DNPs are calculated using the information from the multi-alignments. The use of DNPs and combinations of DNPs will allow for optimal and rapid assemblies of repeated regions. This method can solve repeats that differ in only two positions in a read length, which is the theoretical limit for repeat separation. We predict that this method will be highly useful in shotgun sequencing in the future.


Immunochemical characterization of a new platelet specific monoclonal antibody and its use to demonstrate the cytoskeletal association of the platelet glycoprotein IIb-IIIa complex.
We describe the production and characterization of a monoclonal antibody specific for platelets. This antibody reacts strongly with human and primate platelets, but does not recognise human monocytes, polymorphonuclear leucocytes, lymphocytes, erythrocytes, leukaemic nor fibroblast cell lines, nor rodent platelets. Immunoprecipitation studies using radiolabelled platelet membrane proteins showed that the monoclonal antibody binds to the platelet membrane glycoprotein IIb-IIIa complex. Affinity chromatography using immobilized monoclonal antibody allows purification of the antigen, but also co-purifies the cytoskeletal proteins actin and myosin. Our results demonstrate immunochemically that although the GP IIb-IIIa complex is an external structure, it is connected through the cell membrane to the microfilament system.


Identification of RNA helicases in human immunodeficiency virus 1 (HIV-1) replication - a targeted small interfering RNA library screen using pseudotyped and WT HIV-1.
Central to the development of new treatments for human immunodeficiency virus 1 (HIV-1) is a more thorough understanding of the viral life cycle and the cellular cofactors upon which this depends. Targeting cellular proteins and their interaction with HIV-1 has the potential to reduce the problem of emerging viral resistance to drugs as mutational escape is more difficult. We performed a short interfering RNA (siRNA) library screen targeting 59 cellular RNA helicases, assessing the effect on both viral capsid protein production and infectious virion formation. Five RNA helicases were identified which, when knocked down, reproducibly decreased infectious particle production: DDX5, DDX10, DDX17, DDX28 and DDX52. Two of these proteins (DDX5 and DDX17) have known roles in HIV-1 replication. A further helicase (DDX10) was a positive hit from a previous genome-wide siRNA screen; however, DDX28 and DDX52 have not previously been implicated as essential cofactors for HIV-1.


Clinical safety of 1500 mg oral naltrexone overdose.
This case represents a clinical overdose of the largest known dose of oral naltrexone, equivalent to the taking of a whole bottle of the oral naltrexone preparation. The patient's intention was to control craving for alcohol and opiates. The patient quickly settled with expectant management. As such it demonstrates that earlier concerns that have been voiced in this area, particularly relating to naltrexone-related hepatotoxicity and depression, may have been overstated, at least in the experience of this patient. This patient's course was marked only by gastric irritation, of which she had some history. As such the present profile provides case report evidence consistent with more robust views of the patient safety of naltrexone itself, and opposing more cautious views. Her polydrug craving was suppressed for a period of 2 weeks, which raises the important question of the mechanism of action of naltrexone's generalised suppression of refractory hedonic consumptive addictive behaviours.


Biomineralization by particle attachment in early animals.
Crystallization by particle attachment (CPA) of amorphous precursors has been demonstrated in modern biomineralized skeletons across a broad phylogenetic range of animals. Precisely the same precursors, hydrated (ACC-H2O) and anhydrous calcium carbonate (ACC), have been observed spectromicroscopically in echinoderms, mollusks, and cnidarians, phyla drawn from the 3 major clades of eumetazoans. Scanning electron microscopy (SEM) here also shows evidence of CPA in tunicate chordates. This is surprising, as species in these clades have no common ancestor that formed a mineralized skeleton and appear to have evolved carbonate biomineralization independently millions of years after their late Neoproterozoic divergence. Here we correlate the occurrence of CPA from ACC precursor particles with nanoparticulate fabric and then use the latter to investigate the antiquity of the former. SEM images of early biominerals from Ediacaran and Cambrian shelly fossils show that these early calcifiers used attachment of ACC particles to form their biominerals. The convergent evolution of biomineral CPA may have been dictated by the same thermodynamics and kinetics as we observe today.


Microdiscectomy or tubular discectomy: Is any of them a better option for management of lumbar disc prolapse.
Various types of minimally invasive techniques have been developed for the treatment of lumbar disc herniation. The original laminectomy was refined into microdiscectomy (MD). MD is the gold standard in management of lumbar disc herniation and is used as a yardstick for comparison with newer procedures such as tubular discectomy. So far, no studies have been reported in Indian population comparing tubular discectomy and microdiscectomy. The aim of this study was to compare immediate postoperative and 1-year outcome of patients undergoing tubular discectomy with those undergoing MD and to evaluate the learning curve as well as complication rates of tubular discectomy. Forty-six patients of MD and 102 (48 early and 54 late) patients of tubular discectomy (TD) were operated at Indian Spinal Injuries Centre, which is a tertiary level center between July 2009 and January 2012. They were studied for the following data: Baseline characteristics, visual analog scale (VAS) for leg pain and back pain, Oswestry Disability Index (ODI) scores, length of hospital stay, time taken to return to work, duration of surgery, intra- and post-operative complications, and reoperation rates. The VAS score for leg pain, back pain, and ODI scores showed improvement in both groups during the 1(st) year after surgery. Time taken to return to work and mean hospital stay was shorter in case of TD as compared to MD group. The mean duration of surgery was 34 min shorter for conventional MD. The incidence of dural tear was 6.5% in MD group and 10.4% in early TD and decreased to 7.4% in late TD group. This study revealed that rate of recovery is significantly faster for TD as compared to conventional MD. In contrast, we encountered fewer complications in MD approach as compared to TD which although were not statistically significant and which also decreased as we gained experience.


[Ultrasonic diagnosis of tricuspid valve insufficiency].
Twenty-nine patients were investigated in order to assess diagnostic possibilities of ultrasonic investigation with regard to tricuspid incompetence. Three highly specific and fairly sensitive criteria of trans-tricuspid regurgitation were identified in addition to a series of indirect echographic signs of tricuspid incompetence. Ultrasonic investigations of the heart, such as one- and two-dimensional and, particularly, contrast echocardiography, are fairly reliable instruments of the preoperative diagnosis of tricuspid incompetence.


[On the proposed mechanism of action of antidepressants (author's transl)].
Classical antidepressants (MAOI, uptake inhibitors) increase monoamine levels in the synaptic cleft. However other presynaptic mechanisms of action have been proposed: increase in release (amineptin), blockade of presynaptic alpha-adrenoceptors (mianserin). A postsynaptic approach is also possible: stimulation of beta-receptor (salbutamol), blockade of muscarinic receptor (quinupramine). Moreover the side effects have been correlated to a blockade of postsynaptic receptors: alpha 1 for aorthostatic hypotension, H1 for sedation and muscarinic for anticholinergic effects. However these effects do not explain the delay for the clinical efficiency of antidepressants. A desensitization of presynaptic receptors or a decrease in beta-postsynaptic receptors have been advanced. In fact a possible pharmacokinetic explanation for the delay of clinical efficiency, i.e. the necessary delay to reach brain steady state level, is possible. Finally the presence of imipramine binding sites might be a new approach of the mechanism of action of antidepressants.


Max Brödel's contributions to otolaryngology-head and neck surgery.
Max Brödel arrived in the United States in 1894 to work as a medical illustrator at the Johns Hopkins Hospital. He brought with him an extensive background in medical sciences and illustration. This allowed him to develop an advanced style and technique that would greatly influence the profession of medical illustration. Much of Brödel's work concerned the head and neck region and is of particular interest to otolaryngologists. This article reviews the historical aspects of Brödel's career and highlights his contributions to Otolaryngology-Head and Neck Surgery.


Detection of IgE-reactive proteins in hydrolysed dog foods.
Commercial hydrolysed diets are used for the diagnosis of food allergy in dogs. The cleaved parent proteins are presumed to be too small to elicit an allergic response by reacting with allergen-specific immunoglobin E (IgE). To evaluate three commercial hydrolysed dog diets for proteins. Sera were collected from dogs with suspected food allergy. Two batches of each hydrolysed diet were examined by electrophoresis and visualized by Coomassie blue, silver nitrate staining and IgE immunoblotting. From two to five proteins, ranging from 21 to 67 kDa, were detected in all three diets evaluated. Circulating IgE antibodies targeting these proteins were detected by immunoblotting of dog sera. Six different carbohydrate proteins were identified by mass spectrometry; maize/potato granule-bound starch synthase-1, soybean glycinin, soybean β-conglycinin α chain, potato aspartic protease inhibitor, rice glutelin type B1 and soybean sucrose-binding protein. Four of these proteins have been described as allergens in humans. Some commercial hydrolysed diets contain carbohydrate proteins. Some dogs have circulating IgE antibodies targeting these proteins. The clinical significance of these findings is unknown.


[Preferred secondary attachment site of prophage phi80 on Escherichia coli K-12 chromosome].
The integration frequency of phage att80 immlambdac1857 into the chromosome of a mutant strain H47 Escherichia coli K-12 deleted for the normal prophage insertion site is found to be about 20-fold decreased as compared with its integration into the wild type strain. The most of the resulting lysogens contain the prophage at the secondary attachment site of the mutant bacterial chromosome which is preferentially utilized for prophage insertion. This attachment site (att80-II) is located close to his-genes on the chromosome of H47 strain. Prophage curing procedure of such abnormal lysogens results in the appearance of rare auxotrophic heat-resistant survivors with the His- phenotype. In some cases the prophage insertion can induce an inversion of a neighbouring genetic region. Such lysogens contain the purC gene near prophage located at the att80-II site, and after curing they segregate the heat-resistant His- and Pur- colonies.


Anomalous kinetics in diffusion limited reactions linked to non-Gaussian concentration probability distribution function.
We investigate anomalous reaction kinetics related to segregation in the one-dimensional reaction-diffusion system A + B → C. It is well known that spatial fluctuations in the species concentrations cause a breakdown of the mean-field behavior at low concentration values. The scaling of the average concentration with time changes from the mean-field t(-1) to the anomalous t(-1/4) behavior. Using a stochastic modeling approach, the reaction-diffusion system can be fully characterized by the multi-point probability distribution function (PDF) of the species concentrations. Its evolution is governed by a Fokker-Planck equation with moving boundaries, which are determined by the positivity of the species concentrations. The concentration PDF is in general non-Gaussian. As long as the concentration fluctuations are small compared to the mean, the PDF can be approximated by a Gaussian distribution. This behavior breaks down in the fluctuation dominated regime, for which anomalous reaction kinetics are observed. We show that the transition from mean field to anomalous reaction kinetics is intimately linked to the evolution of the concentration PDF from a Gaussian to non-Gaussian shape. This establishes a direct relationship between anomalous reaction kinetics, incomplete mixing and the non-Gaussian nature of the concentration PDF.


Methodological issues in evaluating workplace interventions to reduce work-related musculoskeletal disorders through mechanical exposure reduction.
Researchers of work-related musculoskeletal disorders are increasingly asked about the evidentiary base for mechanical exposure reductions. Mixed messages can arise from the different disciplinary cultures of evidence, and these mixed messages make different sets of findings incommensurate. Interventions also operate at different levels within workplaces and result in different intensities of mechanical exposure reduction. Heterogeneity in reporting intervention processes and in measuring relevant outcomes makes the synthesis of research reports difficult. As a means of synthesizing the current understanding of measures, this paper describes a set of intervention and observation nodes for which relevant workplace indicators prior to, during, and after mechanical exposure reduction can provide useful information. On the basis of this path of impacts from exposure reduction, an approach to the evaluation of multilevel ergonomic interventions is described that can assist fellow researchers in producing evidence relevant to the challenges faced by workplace parties and policy makers.


Postauricular Island Flap in Reconstruction of Auricula Tumor Defects.
The most common malignant tumor in humans is skin cancers. Skin cancers are most commonly seen in the head and neck region due to direct exposure to sunlight. Most frequently seen skin cancer in the auricula are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study is to evaluate the results of postauricular island flap after resection of tumors in the auricula.Twelve patients aged 58 to 84 years were included in the study. Eight patients had BCC, 3 had SCC, and 1 had basosquamous carcinoma (BSC). The tumor was located at the cavum concha in 7 cases, antihelix in 3 cases, triangular fossa in 1 case and scapha in 1 case. Surgical procedure was performed under local anesthesia in 7 patients and under general anesthesia in 5 patients. Postauricular island flap was used in all cases. There were no early complications. Three patients had non-apparent narrowing of the auriculomastoid angle. The patients were followed for an average of 2.6 years between 1 and 9 years. Only one patient with basosquamous carcinoma of the cavum concha had recurrence at 19 months.We believe that the postauricular island flap may be a good alternative for the reconstruction of the defect after resection of tumors in the auricle due to its proximity to the surgical site, color matching, adequate thickness, good vascularization, aesthetic acceptance by the patient and completion of the procedure in one session.


Cavernous hemangiomas of the orbit: value of CT, angiography, and phlebography.
Neuroradiologic studies performed in 18 cases of surgically verified intraorbital cavernous hemangioma are reported. Skull films usually showed enlargement of the orbit and evidence of soft-tissue mass. Phlebography rarely demonstrated filling of the cavernous hemangioma or enlarged draining veins. On angiography, in addition to displacement of vessels, pooling of contrast medium in the cavities of the hemangioma was observed in more than half the cases. Computed tomography (CT) demonstrated a rounded, hyperdense, enhancing lesion usually in the superior segment of the intraconal space. Although CT may be sufficient for planning the surgical approach, in most cases a combination of CT and angiography will give better, more specific preoperative diagnosis.


Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.
The pleiotropic activities of interferons (IFNs) are mediated primarily through the transcriptional regulation of many downstream effector genes. The mRNA profiles from IFN-alpha, -beta, or -gamma treatments of the human fibrosarcoma cell line, HT1080, were determined by using oligonucleotide arrays with probe sets corresponding to more than 6,800 human genes. Among these were transcripts for known IFN-stimulated genes (ISGs), the expression of which were consistent with previous studies in which the particular ISG was characterized as responsive to either Type I (alpha, beta) or Type II (gamma) IFNs, or both. Importantly, many novel IFN-stimulated genes were identified that were diverse in their known biological functions. For instance, several novel ISGs were identified that are implicated in apoptosis (including RAP46/Bag-1, phospholipid scramblase, and hypoxia inducible factor-1alpha). Furthermore, several IFN-repressed genes also were identified. These results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale. In particular, these findings provide insights into the basic mechanisms of IFN actions and ultimately may contribute to better therapeutic uses for IFNs.


High-resolution three-dimensional T2-weighted sequence for neuronavigation: a new setup and clinical trial.
Conventional imaging for neuronavigation is performed using high-resolution computerized tomography (CT) scanning or a T1-weighted isovoxel magnetic resonance (MR) sequence. The extension of some lesions, however, is depicted much better on T2-weighted MR images. A possible fusion process used to match low-resolution T2-weighted MR image set with a referenced CT or T1-weighted data set leads to poor resolution in the three-dimensional (3D) reconstruction and decreases accuracy, which is unacceptable for neuronavigation. The object of this work was to develop a 3D T2-weighted isovoxel sequence (3D turbo-spin echo [TSE]) for image-guided neuronavigation of the whole brain and to evaluate its clinical application. The authors performed a phantom study and a clinical trial on a newly developed T2-weighted isovoxel sequence, 3D TSE, for image-guided neuronavigation using a common 1.5-tesla MR imager (Siemens Sonata whole-body imager). The accuracy study and intraoperative image guidance were performed with the aid of the pointer-based Medtronic Stealth Station Treon. The 3D TSE data set was easily applied to the navigational setup and demonstrated a high registration accuracy during the experimental trial and during an initial prospective clinical trial in 25 patients. The sequence displayed common disposable skin fiducial markers and provided convincing delineation of lesions that appear hyperintense on T2-weighted images such as low-grade gliomas and cavernomas in its clinical application. Three-dimensional TSE imaging broadens the spectrum of navigational and intraoperative data sets, especially for lesions that appear hyperintense on T2-weighted images. The accuracy of its registration is very reliable and it enables high-resolution reconstruction in any orientation, maintaining the advantages of image-guided surgery.


Dissociations between slant-contrast and reversed slant-contrast.
A vertical test probe is misperceived as slanted in the opposite direction to an inducer when disparity specifies the inducer slant while monocular cues specify a frontoparallel surface (slant-contrast). In reversed cue conditions with vertical axis slant the test probe is misperceived as slanted in the same direction as the inducer (reversed slant-contrast). We found reliable slant-contrast and reversed slant-contrast with inducers having horizontal-axis slant. The reversed slant-contrast was not influenced when the inducer and probe were separated in the frontal plane or in disparity depth whereas slant contrast was degraded, especially in the latter condition. Slant contrast was most pronounced when the inducer was slanted like a ceiling compared to like a ground. No such difference was found for the reversed slant-contrast. When the cue conflict was minimized slant-contrast was reduced, but only with inducers having ground-like slant. Implications for an existing model explaining the slant effects are discussed.


Are We There Yet? Immersive Virtual Reality to Improve Cognitive Function in Dementia and Mild Cognitive Impairment.
Cognitive training therapies may delay cognitive deterioration in dementia. There is potential to enhance delivery through immersive virtual reality (IVR), as removing potential distractors for cognitively impaired individuals can enhance their experience, resulting in increased engagement. Evidence in this field is emerging and not yet synthesized. We aimed to summarize research investigating the use of IVR in dementia to evaluate the current extent of use, acceptability, feasibility, and potential effectiveness. We also aimed to identify gaps in current research and to create a set of recommendations in utilizing this therapy. A systematic literature review was conducted. Our review was registered with PROSPERO, registration number: CRD42019122295. We undertook searches of five databases, article references, and citations. Key authors in the field of health care VR were also contacted to identify additional papers. Articles were assessed for inclusion by two researchers independently. Data were extracted using standardized forms. Our search identified a total of 2,824 citations, following screening for duplicates and application of inclusion and exclusion criteria, five studies were included for analysis. Included studies were heterogeneous, with small sample sizes and mixed outcomes. We were unable to reach definitive conclusions over the use, acceptability, and effectiveness of IVR for dementia and mild cognitive impairment. Future studies should focus on ensuring their interventions are truly immersive, developing more robust controls and account for the rapid rate of obsolescence in digital technologies.


Brain and other central nervous system tumor statistics, 2021.
Brain and other central nervous system (CNS) tumors are among the most fatal cancers and account for substantial morbidity and mortality in the United States. Population-based data from the Central Brain Tumor Registry of the United States (a combined data set of the National Program of Cancer Registries [NPCR] and Surveillance, Epidemiology, and End Results [SEER] registries), NPCR, National Vital Statistics System and SEER program were analyzed to assess the contemporary burden of malignant and nonmalignant brain and other CNS tumors (hereafter brain) by histology, anatomic site, age, sex, and race/ethnicity. Malignant brain tumor incidence rates declined by 0.8% annually from 2008 to 2017 for all ages combined but increased 0.5% to 0.7% per year among children and adolescents. Malignant brain tumor incidence is highest in males and non-Hispanic White individuals, whereas the rates for nonmalignant tumors are highest in females and non-Hispanic Black individuals. Five-year relative survival for all malignant brain tumors combined increased between 1975 to 1977 and 2009 to 2015 from 23% to 36%, with larger gains among younger age groups. Less improvement among older age groups largely reflects a higher burden of glioblastoma, for which there have been few major advances in prevention, early detection, and treatment the past 4 decades. Specifically, 5-year glioblastoma survival only increased from 4% to 7% during the same time period. In addition, important survival disparities by race/ethnicity remain for childhood tumors, with the largest Black-White disparities for diffuse astrocytomas (75% vs 86% for patients diagnosed during 2009-2015) and embryonal tumors (59% vs 67%). Increased resources for the collection and reporting of timely consistent data are critical for advancing research to elucidate the causes of sex, age, and racial/ethnic differences in brain tumor occurrence, especially for rarer subtypes and among understudied populations.


Soil microbial composition and carbon mineralization are associated with vegetation type and temperature regime in mesocosms of a semiarid ecosystem.
Transition from historic grasslands to woody plants in semiarid regions has led to questions about impacts on soil functioning, where microorganisms play a primary role. Understanding the relationship between microbes, plant diversity and soil functioning is relevant to assess such impacts. We evaluate the effect that plant type change in semiarid ecosystems has for microbial diversity and composition, and how this is related to carbon mineralization (CMIN) as a proxy for soil functioning. We followed a mesocosm experiment during 2 years within the Biosphere 2 facility in Oracle, AZ, USA. Two temperature regimes were established with two types of plants (grass or mesquite). Soil samples were analyzed for physicochemical and functional parameters, as well as microbial community composition using 16S rRNA amplicon metagenomics (Illumina MiSeq). Our results show the combined role of plant type and temperature regime in CMIN, where CMIN in grass has lower values at elevated temperatures compared with the opposite trend in mesquite. We also found a strong correlation of microbial composition with plant type but not with temperature regime. Overall, we provide evidence of the major effect of plant type in the specific composition of microbial communities as a potential result of the shrub encroachment.


Increasing tolerance to ozone by elevating foliar ascorbic acid confers greater protection against ozone than increasing avoidance.
Ascorbic acid (Asc) is the most abundant antioxidant in plants and serves as a major contributor to the cell redox state. Exposure to environmental ozone can cause significant damage to plants by imposing conditions of oxidative stress. We examined whether increasing the level of Asc through enhanced Asc recycling would limit the deleterious effects of environmental oxidative stress. Plants overexpressing dehydroascorbate reductase (DHAR), which results in an increase in the endogenous level of Asc, were exposed to acute or chronic levels of ozone. DHAR-overexpressing plants had a lower oxidative load, a lower level of oxidative-related enzyme activities, a higher level of chlorophyll, and a higher level of photosynthetic activity 24 h following an acute exposure (2 h) to 200 ppb ozone than control plants, despite exhibiting a larger stomatal area. Reducing the size of the Asc pool size through suppression of DHAR expression had the opposite effect. Following a chronic exposure (30 d) to 100 ppb ozone, plants with a larger Asc pool size maintained a larger stomatal area and a higher oxidative load, but retained a higher level of photosynthetic activity than control plants, whereas plants suppressed for DHAR had a substantially reduced stomatal area, but also a substantially lower level of photosynthetic activity. Together, these data indicate that, despite a reduced ability to respond to ozone through stomatal closure, increasing the level of Asc through enhanced Asc recycling provided greater protection against oxidative damage than reducing stomatal area.