Choosing a genome browser for a Model Organism Database: surveying the maize community.
As the B73 maize genome sequencing project neared completion, MaizeGDB began to integrate a graphical genome browser with its existing web interface and database. To ensure that maize researchers would optimally benefit from the potential addition of a genome browser to the existing MaizeGDB resource, personnel at MaizeGDB surveyed researchers' needs. Collected data indicate that existing genome browsers for maize were inadequate and suggest implementation of a browser with quick interface and intuitive tools would meet most researchers' needs. Here, we document the survey's outcomes, review functionalities of available genome browser software platforms and offer our rationale for choosing the GBrowse software suite for MaizeGDB. Because the genome as represented within the MaizeGDB Genome Browser is tied to detailed phenotypic data, molecular marker information, available stocks, etc., the MaizeGDB Genome Browser represents a novel mechanism by which the researchers can leverage maize sequence information toward crop improvement directly. Database URL: http://gbrowse.maizegdb.org/


JC virus in CD34+ and CD19+ cells in patients with multiple sclerosis treated with natalizumab.
Infection with JC virus (JCV) may lead to development of demyelinating progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) who are treated with natalizumab. To determine whether mononuclear cells in circulation from MS patients treated with natalizumab harbor JCV DNA. In this prospective investigation, we enrolled 49 MS patients from the Clinical Center for Multiple Sclerosis at The University of Texas Southwestern Medical Center and 18 healthy volunteers. We drew 120-mL blood samples from 26 MS patients at baseline and at approximately 3-month intervals to 10 months during the course of natalizumab infusions. One blood sample was drawn from 23 MS patients receiving natalizumab for more than 24 months and from 18 healthy volunteers. Natalizumab treatment of MS. The blood samples were separated using flow cytometry into CD34+, CD19+, and CD3+ cell subsets; DNA templates were prepared using quantitative polymerase chain reaction for JCV DNA identification. Plasma samples were tested for anti-JCV antibodies by enzyme-linked immunosorbent assays performed at the Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological and Communicative Diseases and Stroke. Thirteen of the 26 patients (50%) with baseline and follow-up blood samples had detectable viral DNA in at least 1 cell compartment at 1 or more points. Ten of the 23 patients (44%) receiving treatment for more than 24 months and 3 of the 18 healthy volunteers (17%) also had detectable viral DNA in 1 or more cell compartment. Fifteen of the 49 MS patients (31%) were confirmed to harbor JCV in CD34+ cells and 12 of 49 (24%) in CD19+ cells. Only 1 of 18 healthy volunteers were viremic in CD34+ cells and none in CD19+ cells. Nine patients and 1 healthy volunteer were viremic but had seronegative test results for JCV antibodies. JC virus DNA was detectable within cell compartments of natalizumab-treated MS patients after treatment inception and longer. JC virus DNA may harbor in CD34+ cells in bone marrow that mobilize into the peripheral circulation at high concentrations. Latently infected cells initiate differentiation to CD19+ cells that favors growth of JCV. These data link the mechanism of natalizumab treatment with progressive multifocal leukoencephalopathy.


An Economic Evaluation of a Comprehensive School-Based Caries Prevention Program.
Current economic evaluations of school-based caries prevention programs (SCPPs) do not compare multiple types of SCPPs against each other and do not consider teeth beyond permanent first molars. To assess the cost-effectiveness of a comprehensive SCPP relative to an SCPP focused on delivering sealants for permanent first molars only and to a default of no SCPP. Based on a societal perspective, a simulation model was used that compared the health and cost impacts on 1) permanent first molars only and 2) all posterior teeth. To calibrate the model, we used data from CariedAway, a comprehensive SCPP that used glass ionomer to prevent and arrest active decay among children. We then evaluated the incremental cost-effectiveness of implementing 3 alternate school-based approaches (comprehensive, sealant only, and no program) on only first molars and all posterior teeth. Probabilistic, 1-, and 2-way sensitivity analyses are included for robustness. Cost-effectiveness is assessed with a threshold of $54,639 per averted disability-adjusted life year (DALY). We first compared the 3 programs under the assumption of treating only first molars. This assessment indicated that CariedAway was less cost-effective than school-based sealant programs (SSPs): the resulting incremental cost-effectiveness ratio (ICER) for CariedAway versus SSPs was $283,455 per averted DALY. However, when the model was extended to include CariedAway's treatment of all posterior teeth, CariedAway was not only cost-effective but also cost-saving relative to SSPs (ICER, -$943,460.88 per averted DALY; net cost, -$261.45) and no SCPP (ICER, -$400,645.52 per averted DALY; net cost, -$239.77). This study finds that economic evaluations assessing only cost and health impacts on permanent first molars may underestimate the cost-effectiveness of comprehensive SCPPs 1) preventing and arresting decay and 2) treating all teeth. Hence, there is an urgent need for economic evaluations of SCPPs to assess cost and health impacts across teeth beyond only permanent first molars. The results of this study can be used by policy makers to understand how to evaluate economic evaluations of school-based caries prevention programs and what factors to consider when deciding on what types of programs to implement.


Clinical practice: Breastfeeding and the prevention of allergy.
The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fueled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4-6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations.


Immunohistochemical aspects of the fibrogenic pathway in nephrogenic systemic fibrosis.
Nephrogenic systemic fibrosis (NSF) is a rare gadolinium-dependent disorder of the skin and viscera. The aim of this study was to revisit some immunopathologic clues of NSF, including the characterization of glycosaminoglycans, cell tensegrity, and cell proliferation in the dermis. Immunohistochemistry was done using antibodies directed to vimentin, CD34, Factor XIIIa, calprotectin, α-smooth muscle actin, Ulex europaeus agglutinin-1 (UEA-1), and MIB1/Ki67 and to glycosaminoglycans, including CD44 var3, versican, and perlecan. The vimentin+ cell density was markedly increased. The vast majority of them corresponded to CD34+ or Factor XIIIa+ dermal dendrocytes (DD) showing distinct cell tensegrity. CD34+DD were slender, elongated, and usually scattered in the dermis but focally clustered in nodular collections. By contrast, Factor XIIIa+ was plump with squat dendrites showing no evidence for being under mechanical stress. Cells in the vicinity of the microvasculature were rounded and exhibited calprotectin immunoreactivity typical for monocyte/macrophages. The microvasculature highlighted by UEA-1 and α-smooth muscle actin looked unremarkable. The cell proliferation highlighted by the MIB/Ki67 immunoreactivity was unusually high (>20%) in the interstitial stromal cells. Stromal cells enriched in versican were plump, abundant, and seemed interconnected each other by a dense network of dendrites. By contrast, the immunolabeling for perlecan and CD44 var 3 was unremarkable. In conclusion, the cell population involved in NSF seemed phenotypically heterogeneous, and its growth fraction was clearly boosted in the skin. The intracellular load in versican was prominent. The aspect of cell tensegrity did not suggest the influence of mechanical stress putting stromal cells under tension in the dermis.


A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism.
The purpose of this study was to elucidate the molecular basis of ocular albinism type I in a Chinese pedigree. Complete ophthalmologic examinations were performed on 4 patients, 7 carriers and 17 unaffected individuals in this five-generation family. All coding exons of four-point-one (4.1), ezrin, radixin, moesin (FERM) domain-containing 7 (FRMD7) and G protein-coupled receptor 143 (GPR143) genes were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Ocular albinism and nystagmus were found in all patients of this family. Macular hypoplasia was present in the patients including the proband. A novel nonsense hemizygous mutation c.807T>A in the GPR143 gene was identified in four patients and the heterozygous mutation was found in seven asymptomatic individuals. This mutation is a substitution of tyrosine for adenine which leads to a premature stop codon at position 269 (p.Y269X) of GPR143. This is the first report that p.Y269X mutation of GPR143 gene is responsible for the pathogenesis of familial ocular albinism. These results expand the mutation spectrum of GPR143, and demonstrate the clinical characteristics of ocular albinism type I in Chinese population.


The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line.
Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.


Light quality influences indigo precursors production and seed germination in Isatis tinctoria L. and Isatis indigotica Fort.
Isatis tinctoria L. and Isatis indigotica Fort. are biennial herbaceous plants belonging to the family of Cruciferae that are used as a source of natural indigo and show several morphological and genetic differences. Production of indigo (indigotin) precursors, indican (indoxyl beta-D glucoside) and isatan B (indoxyl ketogluconate), together with seed germination ability were compared in Isatis tinctoria and Isatis indigotica grown under six different light conditions (darkness, white, red, far red, blue, yellow light) at 25 degrees C. Light quality influenced both germination and production of indigo precursors in the two Isatis species. Different responsiveness to far red and blue light was observed. Indeed, a detrimental effect on germination by blue and far red light was found in I. tinctoria only. Different amounts of isatan B were produced under red and far red light in the two Isatis species. In I. tinctoria, the level of main indigo precursor isatan B was maximal under red light and minimal under far red light. Whereas in I. indigotica far red light promoted a large accumulation of isatan B. The photon fluence rate dependency for white and yellow light responses showed that the accumulation of indigo precursors was differently influenced in the two Isatis species. In particular, both white and yellow light enhanced above 40 micromol m(-2) s(-1) the production of isatan B in I. indigotica while only white light showed a photon fluence dependency in I. tinctoria. These results suggest a different role played by the labile and stable phytochrome species (phyA and phyB) in the isatan B production in I. tinctoria and I. indigotica. I. indigotica, whose germination percentage was not influenced by light quality, demonstrated higher germination capability compared with I. tinctoria. In fact, I. tinctoria showed high frequency of germination in darkness and under light sources that establish high phytochrome photoequilibrium (red, white and yellow light). Germination in I. tinctoria was negatively affected by far red and blue light. I. indigotica seeds appear to be indifferent to canopy-like light (far red). Our results provide further insights on the distinct behaviour of I. tinctoria and I. indigotica that belong to two different genetic clusters and different original environments.


Twenty-four hour intraocular pressure measurements and home tonometry.
IOP is the only treatable risk factor contributing to glaucoma and most management and treatment of glaucoma is based on IOP. However, current IOP measurements are limited to office hours and control of glaucoma in many patients would benefit from the ability to monitor IOP diurnally so as not to miss abnormal pressures, which occur outside of office hours Consequently, to improve patient care, the ability to enable accurate and minimally disruptive diurnal IOP monitoring would improve caring for these patients. The studies we selected for this review can be divided into three categories: self-/home-tonometry, continuous invasive intraocular pressure measurements, and continuous noninvasive ocular measurements. The desire to obtain better insight in our patients' true diurnal IOP has led to the development of home-tonometers, in addition to extraocular and intraocular continuous pressure measurement devices. All of the devices have respective advantages and disadvantages, but none to date completely fulfills the goal of providing a true diurnal IOP profile.Video abstracthttp://links.lww.com/COOP/A27.


Predictors of HIV-related risk perception and PrEP acceptability among young adult female family planning patients.
HIV pre-exposure prophylaxis (PrEP) presents new opportunities for HIV prevention. While women comprise approximately 20% of new HIV infections in the US, significant questions remain about how to most effectively facilitate PrEP uptake for this population. Family planning clinics are a dominant source of health care for young women and support an estimated 4.5 million women annually. We explore characteristics associated with HIV risk perception and PrEP acceptability among young adult women seeking reproductive health services in a high-prevalence setting. A cross-sectional, clinic-based survey was conducted with women ages 18-35 (n = 146) seeking health care at two family planning clinics in the greater Baltimore, Maryland area, from January to April 2014. An estimated 22% of women reported being worried about HIV risk, and 60% reported they would consider taking a pill daily to prevent HIV. In adjusted models, HIV-related worry was associated with having no college education, being single or dating more than one person, practicing consistent condom use during vaginal sex, and having ever traded sex. PrEP acceptability was significantly associated with being Black (71% vs. 49%, AOR 2.23, CI: 1.89-2.64) and having ever traded sex (83% vs. 58%, AOR 4.94, CI: 2.00-12.22). For women with a history of intimate partner violence (IPV), PrEP acceptability was significantly lower (57% vs. 62%, AOR .71, CI: .59-.85) relative to their non-abused counterparts. Results suggest that family planning clinics may be a natural setting for PrEP discussion and roll-out. They should be considered in the context of integrating HIV prevention with reproductive health services. Women with a trauma history may need additional support for implementing HIV prevention in the form of PrEP.


Surface modification and direct plasma amination of L605 CoCr alloys: on the optimization of the oxide layer for application in cardiovascular implants.
Stents are cardiovascular devices used to treat atherosclerosis, and are deployed into narrowed arteries and implanted by expansion to reopen the biological lumen. Nevertheless, complications after implantation are still observed in 10-14% of the implantations. Therefore, functionalizing these devices with active molecules to improve the interfacial effects with the surrounding tissue strongly impacts their success. A plasma-based procedure to directly graft biomolecules to the surface of cobalt chromium alloys, without any polymeric coating, has been recently reported. Assuring the stability of the coating during plastic deformation generated during the implantation whilst avoiding the corrosion of the surface is crucial. This study explores different surface treatments to be used as a pre-treatment for this novel procedure. The effects of (i) electropolishing, (ii) thermal treatments, and (iii) the plasma immersion ion implantation of oxygen on the chemical composition, roughness, wettability and efficiency during the plasma-amination procedure whilst avoiding cracks after deformation, thus maintaining corrosion resistant behaviour, were investigated by XPS, AFM, ToF-SIMS imaging and depth profile, and WCA. Furthermore, the hemocompatibility of the surface and cell viability assays were also performed. Results showed that all of the treatments created a different surface chemical composition: EP mainly of chromium oxide, PIII with a layer of cobalt oxide and TT with a mixture of oxides, as observed by XPS and ToF-SIMS. Moreover, EP was the process that generated a surface with the highest efficiency to amination and the most corrosion resistance among the treatments, and it appeared as the most suitable pre-treatment for stent functionalization.


Neuronal synchronization and selective color processing in the human brain.
In the present study, subjects selectively attended to the color of checkerboards in a feature-based attention paradigm. Induced gamma band responses (GBRs), the induced alpha band, and the event-related potential (ERP) were analyzed to uncover neuronal dynamics during selective feature processing. Replicating previous ERP findings, the selection negativity (SN) with a latency of about 160 msec was extracted. Furthermore, and similarly to previous EEG studies, a gamma band peak in a time window between 290 and 380 msec was found. This peak had its major energy in the 55- to 70-Hz range and was significantly larger for the attended color. Contrary to previous human induced gamma band studies, a much earlier 40- to 50-Hz peak in a time window between 160 and 220 msec after stimulus onset and, thus, concurrently to the SN was prominent with significantly more energy for attended as opposed to unattended color. The induced alpha band (9.8-11.7 Hz), on the other hand, exhibited a marked suppression for attended color in a time window between 450 and 600 msec after stimulus onset. A comparison of the time course of the 40- to 50-Hz and 55- to 70-Hz induced GBR, the induced alpha band, and the ERP revealed temporal coincidences for changes in the morphology of these brain responses. Despite these similarities in the time domain, the cortical source configuration was found to discriminate between induced GBRs and the SN. Our results suggest that large-scale synchronous high-frequency brain activity as measured in the human GBR play a specific role in attentive processing of stimulus features.


Recent advances in electrocatalysts toward the oxygen reduction reaction: the case of PtNi octahedra.
Designing highly efficient and durable electrocatalysts for the oxygen reduction reaction (ORR), the key step for the operation of polymer electrolyte membrane fuel cells (PEMFCs), is of a pivotal importance for advancing PEMFC technology. Since the most significant progress has been made on Pt3Ni(111) alloy surfaces, nanoscale PtNi alloy octahedra enclosed by (111) facets have emerged as promising electrocatalysts toward the ORR. However, because their practical uses have been hampered by the cost, sluggish reaction kinetics, and poor durability, recent advances have engendered a wide variety of structure-, size-, and composition-controlled bimetallic PtNi octahedra. Herein, we therefore review the important recent developments of PtNi octahedral electrocatalysts point by point to give an overview of the most promising strategies. Specifically, the present review article focuses on the synthetic methods for the PtNi octahedra, the core-shell and multi-metallic strategies for performance improvement, and their structure-, size-, and composition-control-based ORR activity. By considering the results achieved in this field, a prospect for this alloy nanocatalysts system for future sustainable energy applications is also proposed.


The gastric mucus layers: constituents and regulation of accumulation.
The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.


Flagellar membranes are rich in raft-forming phospholipids.
The observation that the membranes of flagella are enriched in sterols and sphingolipids has led to the hypothesis that flagella might be enriched in raft-forming lipids. However, a detailed lipidomic analysis of flagellar membranes is not available. Novel protocols to detach and isolate intact flagella from Trypanosoma brucei procyclic forms in combination with reverse-phase liquid chromatography high-resolution tandem mass spectrometry allowed us to determine the phospholipid composition of flagellar membranes relative to whole cells. Our analyses revealed that phosphatidylethanolamine, phosphatidylserine, ceramide and the sphingolipids inositol phosphorylceramide and sphingomyelin are enriched in flagella relative to whole cells. In contrast, phosphatidylcholine and phosphatidylinositol are strongly depleted in flagella. Within individual glycerophospholipid classes, we observed a preference for ether-type over diacyl-type molecular species in membranes of flagella. Our study provides direct evidence for a preferential presence of raft-forming phospholipids in flagellar membranes of T. brucei.


[A case of interstitial pneumonia induced by intravesical administration of bacillus Calmette-Guerin (BCG)].
A 61-year-old man with superficial bladder cancer, which was detected after he complained of hematuria, was treated three times with intravesical BCG administration. Since liver dysfunction was detected thereafter, he was admitted to our hospital. Three days after admission, he complained of dyspnea on exertion associated with severe hypoxemia, as well as abnormal findings on chest X-ray, i.e. extensive bilateral lung densities. We performed bronchoscopic examination and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens (TBLB). In the BALF, a marked increase in the total cell number, particularly lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the lesions to be numerous non-caseating granulomas. We failed to obtain definite evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these findings, severe interstitial pneumonia probably induced by hypersensitivity against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy followed by oral administration of relatively low dose of steroid ameliorated the abnormal conditions, including chest X-ray film findings and hypoxemia. The population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well. Serious interstitial pneumonia was induced by the intravesical administration of BCG, which resulted in transitional changes in the BALF cell component.


Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis.
Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the CASR gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel CASR gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function. A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patient's sister. The coding region of the CASR gene was sequenced in both probands and their available first-degree relatives. The first patient had a novel heterozygous inactivating CASR mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating CASR mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive. We reported two novel heterozygous mutations of the CASR gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing of CASR gene to aid correct diagnosis and to assist in clinical management.


Urinary Excretion Profile of 11-Nor-9-Carboxy-Δ9-Tetrahydrocannabinol (THCCOOH) Following Smoked and Vaporized Cannabis Administration in Infrequent Cannabis Users.
As cannabis has become more accessible, use of alternative methods for cannabis administration such as vaporizers has become more prevalent. Most prior controlled pharmacokinetic evaluations have examined smoked cannabis in frequent (often daily) cannabis users. This study characterized the urinary excretion profile of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH), the primary analytical outcome for detection of cannabis use, among infrequent cannabis users following controlled administration of both smoked and vaporized cannabis. Healthy adults (N = 17), with a mean of 398 (range 30-1,825) days since last cannabis use, smoked and vaporized cannabis containing 0, 10, and 25 mg of Δ9-tetrahydrocannabinol (THC) across six outpatient sessions. Urinary concentrations of THCCOOH were measured at baseline and for 8 h after cannabis administration. Sensitivity, specificity, and agreement between three immunoassays (IA) for THCCOOH (with cutoffs of 20, 50, and 100 ng/mL) and gas chromatography-mass spectrometry (GC/MS) results (confirmatory concentration of 15 ng/mL) were assessed. THCCOOH concentrations peaked 4-6 h after cannabis administration. Median maximum concentrations (Cmax) for THCCOOH were qualitatively higher after administration of vaporized cannabis compared to equal doses of smoked cannabis. Urine THCCOOH concentrations were substantially lower in this study relative to prior examinations of experienced cannabis users. The highest agreement between IA and GC/MS was observed at the 50 ng/mL IA cutoff while sensitivity and specificity were highest at the 20 and 100 ng/mL IA cutoffs, respectively. Using federal workplace drug-testing criteria (IA cutoff of 50 ng/mL and GC/MS concentration ≥15 ng/mL) urine specimens tested positive in 47% of vaporized sessions and 21% of smoked sessions with active THC doses (N = 68). Urinary concentrations of THCCOOH are dissimilar after administration of smoked and vaporized cannabis, with qualitatively higher concentrations observed after vaporization. Infrequent users of cannabis may excrete relatively low concentrations of THCCOOH following acute inhalation of smoked or vaporized cannabis.


Acculturation, gender, and alcohol use among Mexican American college students.
Prior research with non-college samples of Mexican Americans has demonstrated that gender moderates the association between acculturation and alcohol use. We replicated this finding in a college student sample and attempted to account for the differential impact of acculturation on Mexican American men and women by examining the mediating effects of social context, family conflict and psychological functioning. Participants were 148 Mexican Americans (67% female; M age 23 years) from three state universities in California and Texas who completed self-report surveys. In multivariate analyses controlling for age, maternal education, living situation, and site, linguistic acculturation was associated with increased alcohol use and misuse among women but not men. Two social context variables (social facilitation and family drinking) mediated the association between acculturation and alcohol use (heavy drinking, past year alcohol use, and a composite drinking variable) among women. The findings highlight the importance of social context for understanding alcohol use by Latina college students and indicate directions for future research and intervention development.


Methods for environmental change; an exploratory study.
While the interest of health promotion researchers in change methods directed at the target population has a long tradition, interest in change methods directed at the environment is still developing. In this survey, the focus is on methods for environmental change; especially about how these are composed of methods for individual change ('Bundling') and how within one environmental level, organizations, methods differ when directed at the management ('At') or applied by the management ('From'). The first part of this online survey dealt with examining the 'bundling' of individual level methods to methods at the environmental level. The question asked was to what extent the use of an environmental level method would involve the use of certain individual level methods. In the second part of the survey the question was whether there are differences between applying methods directed 'at' an organization (for instance, by a health promoter) versus 'from' within an organization itself. All of the 20 respondents are experts in the field of health promotion. Methods at the individual level are frequently bundled together as part of a method at a higher ecological level. A number of individual level methods are popular as part of most of the environmental level methods, while others are not chosen very often. Interventions directed at environmental agents often have a strong focus on the motivational part of behavior change.There are different approaches targeting a level or being targeted from a level. The health promoter will use combinations of motivation and facilitation. The manager will use individual level change methods focusing on self-efficacy and skills. Respondents think that any method may be used under the right circumstances, although few endorsed coercive methods. Taxonomies of theoretical change methods for environmental change should include combinations of individual level methods that may be bundled and separate suggestions for methods targeting a level or being targeted from a level. Future research needs to cover more methods to rate and to be rated. Qualitative data may explain some of the surprising outcomes, such as the lack of large differences and the avoidance of coercion. Taxonomies should include the theoretical parameters that limit the effectiveness of the method.


Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution.
To explore the mechanisms and evolution of cell-cycle control, we analyzed the position and conservation of large numbers of phosphorylation sites for the cyclin-dependent kinase Cdk1 in the budding yeast Saccharomyces cerevisiae. We combined specific chemical inhibition of Cdk1 with quantitative mass spectrometry to identify the positions of 547 phosphorylation sites on 308 Cdk1 substrates in vivo. Comparisons of these substrates with orthologs throughout the ascomycete lineage revealed that the position of most phosphorylation sites is not conserved in evolution; instead, clusters of sites shift position in rapidly evolving disordered regions. We propose that the regulation of protein function by phosphorylation often depends on simple nonspecific mechanisms that disrupt or enhance protein-protein interactions. The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits.


Association of the Individual and Context Inequalities on the Breastfeeding: A Study from the Sicily Region.
Despite the advantages of breastfeeding being widely recognized, the economic level can have an influence on breastfeeding rates, with rich women breastfeeding longer than poor in high-income countries. In Italy, socio-economic differences affect breastfeeding start and continuation among most deprived people, such as in Southern Italy. The objective of the study was to evaluate the prevalence of the initiation and continuation of exclusive breastfeeding and its association with the levels of socio-economic deprivation in Sicily. A prospective cohort study with a two-phase survey in three breastfeeding detection times was conducted. Overall, 1,055 mothers were recruited with a mean age of 31 years. Breastfeeding decreased from 86% during hospitalization to 69% at the first month and 42% at the sixth month, yet at the same time, exclusive breastfeeding increased from 34% to 38% during hospitalization to the first month and went down to 20.2% at the sixth month. The adjusted multivariate analysis showed no association with individual inequalities. On the other hand, the context inequalities had a significant association with the risk of not following exclusive breastfeeding in the deprived class (odds ratio (OR): 2.08, confidence interval (CI) 95% 1.01-4.27) and in the very deprived class (OR: 1.83, CI 95% 1.00-3.38) at the six-month survey. These results indicate that the context inequalities begin to emerge from the return home of the mother and the child.


Reduced expression of aquaporin-9 in rat optic nerve head and retina following elevated intraocular pressure.
To investigate the effect of chronically elevated intraocular pressure (IOP) on the expression of water channel aquaporins (AQPs) 1, 4, and 9 in the optic nerve and retina in rats. Three episcleral veins were cauterized to elevate IOP in the left eyes of Sprague-Dawley rats. IOPs were monitored with a rebound tonometer. At 2 and 4 weeks after surgery, eyeballs with the attached optic nerve were enucleated for cryosectioning with immunohistochemistry, or dissected retinas and desheathed optic nerves were subjected to gene expression analyses. IOP was significantly increased after surgery up to 4 weeks (P=0.0008). In the control optic nerve, the unmyelinated portion showed only AQP9 immunoreactivity, whereas the myelinated portion expressed both AQP4 and AQP9 immunoreactivities colabeled for glial fibrillary acidic protein but not for neurofilament. In the control retina, AQP1 was expressed in the outer nuclear layer and photoreceptors, AQP4 was expressed in Müller cell endfeet, and AQP9 was expressed primarily in NeuN-positive cells in the ganglion cell layer (GCL). Elevated IOPs substantially reduced AQP9 expression in the optic nerve head (ONH) and the GCL and decreased the retinal gene expression, but not immunoreactivity, of AQP1. AQP9 was the only water channel expressed in the unmyelinated portion of the ONH and in the GCL whose expression was reduced after IOP elevation. Given that AQP9 presumably acts as a channel for metabolites to pass from astrocytes to neurons, the reduced expression of AQP9 at these specific sites may be implicated in the pathogenesis of glaucomatous optic neuropathy.


Deconstructing a plant macromolecular assembly: chemical architecture, molecular flexibility, and mechanical performance of natural and engineered potato suberins.
Periderms present in plant barks are essential protective barriers to water diffusion, mechanical breakdown, and pathogenic invasion. They consist of densely packed layers of dead cells with cell walls that are embedded with suberin. Understanding the interplay of molecular structure, dynamics, and biomechanics in these cell wall-associated insoluble amorphous polymeric assemblies presents substantial investigative challenges. We report solid-state NMR coordinated with FT-IR and tensile strength measurements for periderms from native and wound-healing potatoes and from potatoes with genetically modified suberins. The analyses include the intact suberin aromatic-aliphatic polymer and cell-wall polysaccharides, previously reported soluble depolymerized transmethylation products, and undegraded residues including suberan. Wound-healing suberized potato cell walls, which are 2 orders of magnitude more permeable to water than native periderms, display a strikingly enhanced hydrophilic-hydrophobic balance, a degradation-resistant aromatic domain, and flexibility suggestive of an altered supramolecular organization in the periderm. Suppression of ferulate ester formation in suberin and associated wax remodels the periderm with more flexible aliphatic chains and abundant aromatic constituents that can resist transesterification, attenuates cooperative hydroxyfatty acid motions, and produces a mechanically compromised and highly water-permeable periderm.


Complete genome sequence of Deinococcus maricopensis type strain (LB-34).
Deinococcus maricopensis (Rainey and da Costa 2005) is a member of the genus Deinococcus, which is comprised of 44 validly named species and is located within the deeply branching bacterial phylum Deinococcus-Thermus. Strain LB-34(T) was isolated from a soil sample from the Sonoran Desert in Arizona. Various species of the genus Deinococcus are characterized by extreme radiation resistance, with D. maricopensis being resistant in excess of 10 kGy. Even though the genomes of three Deinococcus species, D. radiodurans, D. geothermalis and D. deserti, have already been published, no special physiological characteristic is currently known that is unique to this group. It is therefore of special interest to analyze the genomes of additional species of the genus Deinococcus to better understand how these species adapted to gamma- or UV ionizing-radiation. The 3,498,530 bp long genome of D. maricopensis with its 3,301 protein-coding and 66 RNA genes consists of one circular chromosome and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.


Can the reliability of three-dimensional running kinematics be improved using functional joint methodology?
Traditional three-dimensional gait analyses require the skilled palpation of anatomical landmarks to identify joint parameters and produce reliable joint kinematics. Functional methods have been developed to help improve the reliability and validity of identifying joint kinematic parameters. The purpose of this study was to investigate whether a functional method could improve the between-day reliability of joint kinematics during running compared to a traditional manual marker placement method. It was hypothesised that the functional technique would result in greater within- and between-tester reliability. An eight-camera motion analysis system was used to evaluate the reliability of 3D lower extremity kinematics during running for both a functional and a manual marker placement technique. Reliability of the waveform shape, amplitude and offset of the kinematic curves was assessed using the coefficient of multiple correlation, range of motion and root mean square error respectively. The functional joint methodology did not improve the within- and between-tester reliability in terms of kinematic curve shape, amplitude or offset compared to the manual placement technique. When experienced examiners are used to place the anatomical markers together with a lean subject sample, functional methods may not improve the day-to-day reliability of three-dimensional gait kinematics over traditional marker placement techniques.


Laparoscopic vs transvaginal cuff closure after total laparoscopic hysterectomy: a randomized trial by the Italian Society of Gynecologic Endoscopy.
Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devastating complication. Different possible techniques for cuff closure have been proposed to reduce this threatening adverse event. The aim of the present randomized study was to compare laparoscopic and transvaginal suture of the vaginal vault at the end of a total laparoscopic hysterectomy, in terms of incidence of vaginal dehiscence and vaginal cuff complications. Factors associated with vaginal dehiscence were also analyzed. This article presents the results of the interim analysis of the trial. Patients undergoing total laparoscopic hysterectomy for benign indications were randomized at the time of colpotomy to receive vaginal closure through transvaginal vs laparoscopic approach using a 1:1 ratio. Allocation concealment was obtained using a password-protected randomization database. Monopolar energy for colpotomy was set at 60W. Vaginal closure was performed with a single-layer running braided and coated 0-polyglactin suture. In all cases an attempt was performed to include the posterior peritoneum in the suture. Laparoscopic knots were tied intracorporeally. All patients were scheduled for a postoperative follow-up visit 3 months after surgery, to detect possible vaginal cuff complications. Univariate and multivariable analyses were performed to identify independent predictors of vaginal cuff dehiscence after total laparoscopic hysterectomy. After enrollment of 1408 patients, a prespecified interim analysis was conducted. Thirteen (0.9%) women did not undergo the postoperative assessment and were excluded. Baseline characteristics of the 1395 patients included (695 in the transvaginal group and 700 in the laparoscopic group) were similar between groups. Patients in the transvaginal group had a significantly higher incidence of vaginal dehiscence (2.7% vs 1%; odds ratio, 2.78; 95% confidence interval, 1.16-6.63; P = .01) and of any cuff complication (9.8% vs 4.7%; odds ratio, 2.19; 95% confidence interval, 1.43-3.37; P = .0003). Based on these findings, the data monitoring committee recommended that the trial be terminated early. After multivariable analysis, transvaginal closure of the vault was independently associated with a higher incidence of vaginal dehiscence and any vaginal complication; premenopausal status and smoking habit were independently associated with a higher risk of dehiscence. Laparoscopic closure of the vaginal cuff at the end of total laparoscopic hysterectomy is associated with a significant reduction of vaginal dehiscence, any cuff complication, vaginal bleeding, vaginal cuff hematoma, postoperative infection, need for vaginal resuture, and reintervention.


Recent advances in sample preparation techniques to overcome difficulties encountered during quantitative analysis of small molecules from biofluids using LC-MS/MS.
Liquid chromatography-mass spectrometry analysis of small molecules from biofluids requires sensitive and robust assays. Because of the very complex nature of many biological samples, efficient sample preparation protocols to remove unwanted components and to selectively extract the compounds of interest are an essential part of almost every bioanalytical workflow. This review describes the most common problems encountered during sample preparation, ways to optimize established sample preparation techniques and important recent developments to reduce or eliminate major interferents from biofluids.


Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature.
Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF), and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.


HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease.
Peripheral nerve axons require a well-organized axonal microtubule network for efficient transport to ensure the constant crosstalk between soma and synapse. Mutations in more than 80 different genes cause Charcot-Marie-Tooth disease, which is the most common inherited disorder affecting peripheral nerves. This genetic heterogeneity has hampered the development of therapeutics for Charcot-Marie-Tooth disease. The aim of this study was to explore whether histone deacetylase 6 (HDAC6) can serve as a therapeutic target focusing on the mutant glycyl-tRNA synthetase (GlyRS/GARS)-induced peripheral neuropathy. Peripheral nerves and dorsal root ganglia from the C201R mutant Gars mouse model showed reduced acetylated α-tubulin levels. In primary dorsal root ganglion neurons, mutant GlyRS affected neurite length and disrupted normal mitochondrial transport. We demonstrated that GlyRS co-immunoprecipitated with HDAC6 and that this interaction was blocked by tubastatin A, a selective inhibitor of the deacetylating function of HDAC6. Moreover, HDAC6 inhibition restored mitochondrial axonal transport in mutant GlyRS-expressing neurons. Systemic delivery of a specific HDAC6 inhibitor increased α-tubulin acetylation in peripheral nerves and partially restored nerve conduction and motor behaviour in mutant Gars mice. Our study demonstrates that α-tubulin deacetylation and disrupted axonal transport may represent a common pathogenic mechanism underlying Charcot-Marie-Tooth disease and it broadens the therapeutic potential of selective HDAC6 inhibition to other genetic forms of axonal Charcot-Marie-Tooth disease.


Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature.
Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1,220 articles. After application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature.


Downregulation of mitochondrial connexin 43 by high glucose triggers mitochondrial shape change and cytochrome C release in retinal endothelial cells.
To determine connexin 43 (Cx43) localization in mitochondria and investigate the effects of high glucose (HG) on mitochondrial Cx43 (mtCx43) expression and whether altered mtCx43 channel activity is involved in promoting apoptosis in retinal endothelial cells. MtCx43 localization was determined using immunostaining, green fluorescent protein (GFP)-tagged Cx43 followed by confocal imaging, and Western blot analysis using protein isolated from mitochondria of rat retinal endothelial cells (RRECs). To assess HG effects on mtCx43 expression, RRECs were grown in normal (5 mM) or HG (30 mM) medium for 7 days, and mtCx43 protein level assessed by Western blot analysis. To determine if mtCx43 channel inhibition affected mitochondrial morphology, RRECs grown sparsely were left untreated or treated with β-glycerrhetinic acid (β-GA), an inhibitor of connexin channels, and imaged using confocal microscopy. Additionally, mitochondria isolated from RRECs were treated with β-GA, and cytochrome c release assessed by Western blot. Cx43 localization on the mitochondria of RRECs was confirmed with immunofluorescence staining using Cx43 antibody and GFP-tagged Cx43 imaged in live cells. Western blot analysis indicated that Cx43 was located primarily on the inner mitochondrial membrane, and mtCx43 protein level was significantly reduced in RRECs grown in HG condition. Treatment of RRECs with β-GA significantly decreased mtCx43 phosphorylation, induced mitochondrial fragmentation, and isolated mitochondria treated with β-GA showed increased cytochrome c release. HG-induced downregulation of mtCx43 protein resulting in decreased channel activity may promote mitochondrial morphology changes and cytochrome c release, suggesting a novel mechanism for hyperglycemia-induced apoptosis in diabetic retinopathy.


Polycrystalline graphene and other two-dimensional materials.
Graphene, a single atomic layer of graphitic carbon, has attracted intense attention because of its extraordinary properties that make it a suitable material for a wide range of technological applications. Large-area graphene films, which are necessary for industrial applications, are typically polycrystalline - that is, composed of single-crystalline grains of varying orientation joined by grain boundaries. Here, we present a review of the large body of research reported in the past few years on polycrystalline graphene. We discuss its growth and formation, the microscopic structure of grain boundaries and their relations to other types of topological defect such as dislocations. The Review further covers electronic transport, optical and mechanical properties pertaining to the characterizations of grain boundaries, and applications of polycrystalline graphene. We also discuss research, still in its infancy, performed on other two-dimensional materials such as transition metal dichalcogenides, and offer perspectives for future directions of research.


The SARS-COV-2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device.
There is an urgent need to understand the behavior of the novel coronavirus (SARS-COV-2), which is the causative agent of COVID-19, and to develop point-of-care diagnostics. Here, a glyconanoparticle platform is used to discover that N-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, demonstrating its glycan-binding function. Optimization of the particle size and coating enabled detection of the spike glycoprotein in lateral flow and showed selectivity over the SARS-COV-1 spike protein. Using a virus-like particle and a pseudotyped lentivirus model, paper-based lateral flow detection was demonstrated in under 30 min, showing the potential of this system as a low-cost detection platform.


Influence of biased clinician statements on patient report of referred pain.
The purpose of this study was to examine the influence of clinician bias on patients' reports of referred pain. Diagnosis of temporomandibular disorders is dependent on subjective reports of pain and referred pain upon manual muscle palpation. The influence of biased clinician statements in such subjective reports has not been previously investigated. Forty subjects with pain and who met specific inclusion criteria were randomly assigned to 1 of 2 experimental groups. One group was subjected to a standardized biasing statement, while the other group was not. Tender points in the masseter muscle were then stimulated with a pressure algometer to the pressure-pain threshold. Subjects then recorded the presence or absence, location, intensity, and unpleasantness of any referred pain. State-trait anxiety and social desirability were also assessed to explore the possibility that anxiety levels or subjects' desires to please the experimenter influenced results. The biased group reported increased presence (P < 0.01), intensity (P < 0.001), and unpleasantness (P < 0.003) of referred pain as compared to the non-biased group. There were no differences between groups on state-trait anxiety or social desirability (P > 0.05). These data suggest that patient reports of pain referral may be subject to clinician bias, and recommendations to control this bias are offered.


Cell-surface biotinylation of GLUT4 using bis-mannose photolabels.
New cell-impermeant bis-mannose photolabels have been developed with biotinyl groups attached to 4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1, 3-bis(d-mannos-4-yloxy)-2-propylamine (ATB-BMPA) by either a polyethoxy spacer (Bio-ATB-BMPA) or an additional hexanoic acid spacer (Bio-LC-ATB-BMPA). The half-maximal inhibition constants, Ki values, for inhibition of glucose transport activity in insulin-stimulated rat adipocytes were determined to be 359+/-10 and 273+/-28 microM for Bio-ATB-BMPA and Bio-LC-ATB-BMPA, respectively. These values are similar to those previously reported for the non-biotinylated compound ATB-BMPA. Following UV-irradiation-induced cross-linking of the biotinylated photolabels to rat adipocytes, the biotinylated glucose transporter isoform 4 (GLUT4) could be detected by non-radioactive and radioactive methods that utilized the interaction with streptavidin. Biotinylated GLUT4 from 1-2 microg of adipose cell membranes, precipitated onto magnetic streptavidin beads, could be sensitively and quantitatively detected using an electrochemiluminescent assay method. This utilized a ruthenium-tagged anti-GLUT4 antibody that on excitation at an electrode generated an electrochemiluminescent signal in an ORIGEN analyser. Alternatively, surface-biotinylated GLUT4 could be easily, but less sensitively, detected in streptavidin agarose precipitates which were analysed by conventional GLUT4 Western blotting. Data obtained using the non-radioactive methods compared favourably with those using tritiated versions of the biotinylated probes. Insulin treatment of adipocytes increased the levels of signals from surface biotinylated GLUT4 by approximately 10-fold or approximately 20-fold, respectively, when the electrochemiluminescent or the Western blot detection methods were used and these signals were blocked by cytochalasin B.


Antigenic heterogeneity of breast cell lines detected by monoclonal antibodies and its relationship with the cell cycle.
Established cell lines were stained by immunofluorescence with four monoclonal antibodies to study the phenomenon of antigenic heterogeneity and its possible relation to the cell cycle. Five cell lines thought to be of breast origin, MCF-7, ZR-75-1, T47D, MDA-MB-231 and HBL-100, were stained with three monoclonal antibodies (LICR-LON-M8, LICR-LON-M18, LICR-LON-M24) that each stain a distinct subset of normal breast epithelial cells, i.e. demonstrate antigenic heterogeneity in normal breast epithelial cells. Contrasting monoclonal antibodies LICR-LON-FIB75 and LICR-LON-FIB86 to homogeneously expressed antigens were also used. For the antibodies demonstrating heterogeneity distinct positive and negative fractions were not seen by flow cytometry; the intensity of fluorescence varied continuously from background to a hundred times stronger than background. Fluorescent DNA staining showed no obvious relation between antigen expression and the cell cycle. The essentially constant proportion of cells of a given antigenic phenotype in the various phases suggests that these antibodies do not distinguish a phenotype associated with a distinct proliferating population of cells.


Contemporary concepts in hernia prevention: Selected proceedings from the 2017 International Symposium on Prevention of Incisional Hernias.
Incisional hernia is a frequent complication of midline laparotomy and enterostomal creation and is associated with high morbidity, decreased quality of life, and high costs. The International Symposium on Incisional Hernia Prevention was held October 19-20, 2017, at the InterContinental Hotel in San Francisco, CA, hosted by the Department of Surgery, University of California, San Francisco. One hundred and three attendees included general and plastic surgeons from 9 countries, including principal participants for several of the seminal studies in the field. Over the course of the 2-day meeting, there were 38 oral presentations, 3 keynote lectures, and 2 panel discussions. The Symposium was a combination of new information but also a comprehensive review of the existing data so as to assess the current state of the field and to set the stage for future research. Further, the Symposium sought to increase awareness and thus emphasize the importance of preventing the formation of incisional and enterostomal hernias.


A systematic review of Hepatitis C virus treatment uptake among people who inject drugs in the European Region.
Fifteen million adults in the World Health Organization European Region are estimated to have active hepatitis C infection. Intravenous drug use is a major hepatitis C transmission route in this region, and people who inject drugs (PWID) constitute a high-risk and high-prevalence population. A systematic review was conducted to assess levels of hepatitis C treatment uptake among PWID in Europe. Searches in MEDLINE and EMBASE were carried out for articles in any language published between 1 January 2000 and 31 December 2012. Articles were included in the review if they presented original research findings about hepatitis C treatment uptake levels among people who reported injecting drugs currently or formerly, as well as those who reported using drugs currently or formerly (mode of consumption not specified). Treatment uptake data were extracted if uptake was measurable in relation to the number of patients who either: (a) tested HCV antibody-positive; (b) tested positive for HCV-RNA; or (c) tested positive for HCV-RNA and met additional treatment criteria. Twenty-five articles from 12 countries were included in the review. Among groups of drug-using study participants who were hepatitis C antibody-positive, the median treatment uptake level was 17%, and among those who were hepatitis C RNA-positive, the median was 30%. In the 11 studies reporting specifically on treatment uptake among current and former injecting drug users, hepatitis C RNA-positive study populations had a median treatment uptake level of 32%. Only one study reported on treatment uptake for current drug users. This systematic review indicates that hepatitis C treatment uptake is relatively low among drug users in several European countries, and also points to considerable knowledge gaps regarding treatment uptake levels in this population. There was large variability in treatment uptake levels, suggesting that there may be major differences between and within countries in relation to treatment availability, drug-using populations in need of treatment, and the existence of integrated health care services targeting drug users. Stronger national hepatitis C treatment policies are needed, along with efforts to increase knowledge and reduce misconceptions among physicians regarding the feasibility and importance of treating drug users who have hepatitis C.


Retrospective Study of Midazolam Protocol for Prehospital Behavioral Emergencies.
Agitated patients in the prehospital setting pose challenges for both patient care and emergency medical services (EMS) provider safety. Midazolam is frequently used to control agitation in the emergency department setting; however, limited data exist in the prehospital setting. We describe our experience treating patients with midazolam for behavioral emergencies in a large urban EMS system. We hypothesized that using midazolam for acute agitation leads to improved clinical conditions without causing significant clinical deterioration. We performed a retrospective review of EMS patient care reports following implementation of a behavioral emergencies protocol in a large urban EMS system from February 2014-June 2016. For acute agitation, paramedics administered midazolam 1 milligram (mg) intravenous (IV), 5 mg intramuscular (IM), or 5 mg intranasal (IN). Results were analyzed using descriptive statistics, Levene's test for assessing variance among study groups, and t-test to evaluate effectiveness based on route. In total, midazolam was administered 294 times to 257 patients. Median age was 30 (interquartile range 24-42) years, and 66.5% were male. Doses administered were 1 mg (7.1%) and 5 mg (92.9%). Routes were IM (52.0%), IN (40.8%), and IV (7.1%). A second dose was administered to 37 patients. In the majority of administrations, midazolam improved the patient's condition (73.5%) with infrequent adverse events (3.4%). There was no significant difference between the effectiveness of IM and IN midazolam (71.0% vs 75.4%; p = 0.24). A midazolam protocol for prehospital agitation was associated with reduced agitation and a low rate of adverse events.


Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein.
Plant secondary metabolites, such as phenolic acids are commonly associated with benefits for human health. Two of the most abundant phenylpropanoid-derived compounds detected in human faecal samples are phenylacetic acid (PAA) and 4-hydroxylphenylacetic acid (4-hydroxyPAA). Although they have the potential to be derived from diets rich in plant-based foods, evidence suggests that these compounds can be derived from the microbial fermentation of aromatic amino acids (AAAs) in the colon. To identify the bacteria responsible, 26 strains representing 25 of the dominant human colonic species were screened for phenyl metabolite formation. Seven strains produced significant amounts of both PAA and 4-hydroxyPAA. These included five out of seven Bacteroidetes (Bacteroides thetaiotaomicron, Bacteroides eggerthii, Bacteroides ovatus, Bacteroides fragilis, Parabacteroides distasonis), and two out of 17 Firmicutes (Eubacterium hallii and Clostridium bartlettii). These species also produced indole-3-acetic acid (IAA), the corresponding tryptophan metabolite, but C. bartlettii showed 100 times higher IAA production than the other six strains. Four strains were further tested and PAA formation was substantially increased by phenylalanine, 4-hydroxyPAA by tyrosine and IAA by tryptophan. This study demonstrates that certain microbial species have the ability to ferment all three AAAs and that protein fermentation is the likely source of major phenylpropanoid-derived metabolites in the colon.


Synergistic cranberry juice combinations with natural-borne antimicrobials for the eradication of uropathogenic Escherichia coli biofilm within a short time.
Urinary tract infections (UTI), one of the most common diseases in humans, are caused primarily by uropathogenic Escherichia coli (UPEC). Cranberry juice (CB) is a widely known prophylaxis for UTI, but the treatment of CB alone could not effectively eradicate preformed UPEC biofilms. The aim of this study was to develop enforced CB composites within a short time by adding a small quantity of natural borne antimicrobials. UPEC biofilms (initial: 6·0 log CFU per cm2 ), formed on silicone coupons in artificial urine medium, were exposed to CB (4-8%), caprylic acid (CAR; 0·025-0·05%) and thymol (TM; 0·025-0·05%) at 37°C for 1 min. Individual treatment of each compound did not show the significant antibacterial effect on UPEC biofilms (P > 0·05). Otherwise, the survivor counts of biofilms were synergistically reduced with CB containing any of the antimicrobials. For example combined treatment with CB (8%) + CAR (0·05%) + TM (0·05%) resulted in a 6 log reduction in UPEC populations in the biofilm (no detectable bacteria remained) with 4·6 log of synergistic bactericidal effect. The confocal laser scanning microscope images indicated that any composites including TM might result in biofilm detachment from the surface. The present method is cost-effective and more acceptable to consumers as it is based on the synergistic interaction of natural borne antimicrobials. The results of this study could be widely applicable in the functional food, medical and healthcare field. SIGNIFICANCE AND IMPACT OF THE STUDY: Anti-biofilm effect of cranberry juice (CB) has been focused mainly on inhibiting biofilm formation of uropathogenic Escherichia coli (UPEC); however, combined treatment with natural borne antimicrobials derived from coconut oil (caprylic acid) and oregano essential oil (thymol) could synergistically enhance its eradicating activity against biofilms. This study developed novel CB composites showing marked anti-biofilm effects (complete eradication of UPEC biofilms within just 1 min).


A Vegetarian Diet Is a Major Determinant of Gut Microbiota Composition in Early Pregnancy.
The composition of the gut microbiota can be influenced by dietary composition. In pregnancy, the maternal gut microbiome has associations with maternal and infant metabolic status. There is little known regarding the impact of a vegetarian diet in pregnancy on maternal gut microbiota. This study explored the gut microbiota profile in women who were vegetarian or omnivorous in early gestation. Women were selected from participants in the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. Nine women identified as vegetarians were matched to omnivorous women in a 1:2 ratio. Microbiota analyses were performed using 16S rRNA gene amplicon sequencing and analysed using the Quantitative Insights Into Microbial Ecology (QIIME) and Calypso software tools. There was no difference in alpha diversity, but beta diversity was slightly reduced in vegetarians. There were differences seen in the relative abundance of several genera in those on a vegetarian diet, specifically a reduction in Collinsella, Holdemania, and increases in the relative abundances of Roseburia and Lachnospiraceae. In this sub-analysis of gut microbiota from women in early pregnancy, a vegetarian as compared to omnivorous diet, was associated with a different gut microbiome, with features suggesting alterations in fermentation end products from a mixed acid fermentation towards more acetate/butyrate.


Does cheating pay: the role of externally supplied momentum on muscular force in resistance exercise.
Our work investigates the use of "external momentum" in the context of hypertrophy-oriented training. This is momentum supplied to the load (such as a dumbbell) used in an exercise by means of action of muscles not inherently involved in the exercise. We challenge the general consensus that the use of such momentum often described as "cheating" is counterproductive. We focus on the use of external momentum in the shoulder lateral raise and adopt a framework whereby exercise execution is simulated on a computer. This is achieved using a physical model of motion which is combined with anthropomorphic measurements and empirical data of muscular recruitment from previous work. The introduction of moderate momentum (producing initial angular velocities around 57.5° s(-1)) increases the torque of the target muscles even without an increase in the load used. A moderate increase in the load and the use of momentum allows the torque to be increased even further. In contrast, excessive use of momentum results in lower demands on the target muscles, while an excessive increase of the load reduces the total hypertrophy stimulus by virtue of the decreased number of repetitions which can be performed successfully and thus the dramatically shortened time under tension. Our results disprove the conventional belief that the use of external momentum necessarily reduces the overload of the target muscles. A moderate use of external momentum increases both the per-repetition peak torque and the total hypertrophy stimulus in a set.


Social anxiety disorder under scrutiny.
Social anxiety disorder (social phobia) is a chronic disabling condition. As with many psychiatric disorders, the condition is likely to have several causes, including genetic and familial factors, early experiences, and cognitive mechanisms. This review will briefly examine the etiology of social anxiety disorder. The approach required during diagnosis of the condition will also be addressed, in particular, the differentiation between social anxiety disorder and other anxiety disorders with similar presentation. The main focus of this article is to review available treatment options for social anxiety disorder, both psychosocial and pharmacotherapeutic. A number of management strategies have shown promise for the treatment of the condition. The International Consensus Group on Depression and Anxiety recently recommended that a selective serotonin reuptake inhibitor (SSRI) should be considered as first-line pharmacotherapy. To date, however, paroxetine is the only SSRI that is licensed for the treatment of social anxiety disorder.


Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1.
Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the cell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established. We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade.


High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8- and 9-year-olds.
Associations between antenatal maternal anxiety, measured with the State Trait Anxiety Inventory, and disorders in 8- and 9-year-olds were studied prospectively in 71 normal mothers and their 72 firstborns. Clinical scales were completed by the mother, the child, the teacher, and an external observer. Hierarchical multiple regression analyses showed that maternal state anxiety during pregnancy explained 22%, 15%, and 9% of the variance in cross-situational attention deficit hyperactivity disorder symptoms, externalizing problems, and self-report anxiety, respectively, even after controlling for child's gender, parents' educational level, smoking during pregnancy, birth weight, and postnatal maternal anxiety. Anxiety at 12 to 22 weeks postmenstrual age turned out to be a significant independent predictor whereas anxiety at 32 to 40 weeks was not. Results are consistent with a fetal programming hypothesis.


The role of laboratory and field leaching tests in hazard identification for solid materials.
The use of various in vitro toxicity assays for testing environmental solid samples is dependent on the availability of reliable methods for the sampling and pretreatment of the material. This study focuses on the evaluation of leaching behaviour as a first step in the context of the toxicity testing of solid environmental matter. Spent shale, from oil shale retorting, was chosen as a suitable example of deposited solid waste material. For the generation of leachate in the laboratory setting, a standard two-stage batch-leaching test was applied to the samples of technogenic waste. In the field, a new type of lysimeter, which does not disturb the surface, was used for in situ leachate collection. The chemical composition of water extracts was found to be different under field conditions, as compared with the laboratory experiments. Thus, the hazard identification of a solid technogenic waste by in vitro toxicological tests applied to laboratory leachates would not be the best solution. The content of hazardous ingredients could be underestimated if only laboratory tests are used. For risk assessment concerned with solid waste materials, the generation of leachate by using field lysimeters is recommended.


HMG chromosomal proteins in development and disease.
The high mobility group (HMG) proteins are a superfamily of abundant and ubiquitous nuclear proteins that bind to DNA and nucleosomes and induce structural changes in the chromatin fiber. They are important in chromatin dynamics and influence DNA processing in the context of chromatin. Results emerging from studies of human disease, genetically modified mice and cells with altered HMG expression indicate that the expression of the HMG proteins is developmentally regulated and that changes in HMG protein levels alter the cellular phenotype and can lead to developmental abnormalities and disease. Here, we focus on the biological function of HMG proteins and highlight their possible roles in cellular differentiation and in the etiology of various diseases.


Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.


Withdrawal severity after chronic intermittent ethanol in inbred mouse strains.
To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 +/- 0.02 mg/ml and we restricted the range of this value to 1.00-2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 +/- 0.1 mg/ml) and high dose (1.71 +/- 0.02 mg/ml). After the third inhalation exposure, ethanol-exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses.


Central venous catheter-related complications in patients with hematological malignancies: a retrospective analysis of risk factors and prophylactic measures.
We retrospectively analyzed the incidence of thrombotic and infectious complications in relation with the use of central venous catheters (CVCs), in a series of patients with hematological malignancies and low platelet and leucocyte counts. 126 patients with hematological malignancies were analyzed. A total of 207 CVCs were implanted: 137 centrally (CICCs) and 70 peripherally (PICCs). The median duration of the CVCs was 19 days for a total of 4051 catheter-days. Antithrombotic prophylaxis was unfractionated heparin (UFH), 2,500 IU daily by 24 h continuous infusion in 169 CVCs, low molecular weight heparin (LMWH), 3,800 IU daily by single bolus intravenous injection (i.v.) in 21 and warfarin in one. No prophylaxis was given in 16 CVCs. Thrombotic complications developed in 15.5% of the CVCs (7.9 events/1000 catheter days), and the frequency of infectious complications was 10.6% (5.2 events/1000 catheter days). On multivariate analysis thromboses were more frequent and earlier with PICCs than CICCs (p = 0.0001), and in patients on UFH (16.6%) than in LMWH prophylaxis (4.7%), but the last difference was not statistically significant. In conclusions the incidence of thrombotic complications in our series was comparable to that observed in non-thrombocytopenic patients and was significantly higher in those carrying PICC than CICC (p = 0.0001). There were fewer thrombotic events in the patients receiving i.v. LMWH prophylaxis than in those receiving i.v. UFH. The use of anticoagulants was safe and not associated with hemorrhages.


The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of randomized clinical trials.
Recent studies suggest that carboplatin with pegylated liposomal doxorubicin (C+PLD) is as efficacious as carboplatin with paclitaxel (C+P) and possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal doxorubicin (PLD) may also be efficacious and tolerable as monotherapy in recurrent or platinum-resistant disease. We performed a meta-analysis of randomized trials in order to elucidate the role of PLD in ovarian cancer. We searched PubMed, Scopus, and ISI Web of Knowledge for studies comparing C+PLD with C+P and comparing PLD with another monotherapy. Summary hazard ratios (HRs) and relative risks with their corresponding 95% confidence intervals (CIs) were calculated using a fixed-effects model. Three trials were included in the doublet regimen analysis, and five trials were included in the monotherapy regimen analysis. C+PLD provided superior progression-free survival (PFS) (HR, 0.87; 95% CI, 0.78-0.96) and similar overall survival (OS; HR, 0.95; 95% CI, 0.84-1.07) compared with C+P. There was no evidence of improved tolerability: C+PLD had more gastrointestinal toxicity, anemia, thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS (HR, 0.99; 95% CI, 0.89-1.11) and OS (HR, 0.99; 95% CI, 0.88-1.11) to other monotherapies, but it was more tolerable. There was less neutropenia, anemia, thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was increased. C+PLD had better PFS and similar OS compared with C+P and had a very different toxicity profile. Therapy selection could be based on patient risks for side effects. PLD is as efficacious as other monotherapies and is more tolerable.


Non-silent story on synonymous sites in voltage-gated ion channel genes.
Synonymous mutations are usually referred to as "silent", but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel.


Linear infrastructure drives habitat conversion and forest fragmentation associated with Marcellus shale gas development in a forested landscape.
Large, continuous forest provides critical habitat for some species of forest dependent wildlife. The rapid expansion of shale gas development within the northern Appalachians results in direct loss of such habitat at well sites, pipelines, and access roads; however the resulting habitat fragmentation surrounding such areas may be of greater importance. Previous research has suggested that infrastructure supporting gas development is the driver for habitat loss, but knowledge of what specific infrastructure affects habitat is limited by a lack of spatial tracking of infrastructure development in different land uses. We used high-resolution aerial imagery, land cover data, and well point data to quantify shale gas development across four time periods (2010, 2012, 2014, 2016), including: the number of wells permitted, drilled, and producing gas (a measure of pipeline development); land use change; and forest fragmentation on both private and public land. As of April 2016, the majority of shale gas development was located on private land (74% of constructed well pads); however, the number of wells drilled per pad was lower on private compared to public land (3.5 and 5.4, respectively). Loss of core forest was more than double on private than public land (4.3 and 2.0%, respectively), which likely results from better management practices implemented on public land. Pipelines were by far the largest contributor to the fragmentation of core forest due to shale gas development. Forecasting future land use change resulting from gas development suggests that the greatest loss of core forest will occur with pads constructed farthest from pre-existing pipelines (new pipelines must be built to connect pads) and in areas with greater amounts of core forest. To reduce future fragmentation, our results suggest new pads should be placed near pre-existing pipelines and methods to consolidate pipelines with other infrastructure should be used. Without these mitigation practices, we will continue to lose core forest as a result of new pipelines and infrastructure particularly on private land.


An Indoor Monitoring System for Ambient Assisted Living Based on Internet of Things Architecture.
The study of systems and architectures for ambient assisted living (AAL) is undoubtedly a topic of great relevance given the aging of the world population. The AAL technologies are designed to meet the needs of the aging population in order to maintain their independence as long as possible. As people typically spend more than 90% of their time in indoor environments, indoor air quality (iAQ) is perceived as an imperative variable to be controlled for the inhabitants' wellbeing and comfort. Advances in networking, sensors, and embedded devices have made it possible to monitor and provide assistance to people in their homes. The continuous technological advancements make it possible to build smart objects with great capabilities for sensing and connecting several possible advancements in ambient assisted living systems architectures. Indoor environments are characterized by several pollutant sources. Most of the monitoring frameworks instantly accessible are exceptionally costly and only permit the gathering of arbitrary examples. iAQ is an indoor air quality system based on an Internet of Things paradigm that incorporates in its construction Arduino, ESP8266, and XBee technologies for processing and data transmission and micro sensors for data acquisition. It also allows access to data collected through web access and through a mobile application in real time, and this data can be accessed by doctors in order to support medical diagnostics. Five smaller scale sensors of natural parameters (air temperature, moistness, carbon monoxide, carbon dioxide, and glow) were utilized. Different sensors can be included to check for particular contamination. The results reveal that the system can give a viable indoor air quality appraisal in order to anticipate technical interventions for improving indoor air quality. Indeed indoor air quality might be distinctively contrasted with what is normal for a quality living environment.


Meta-analytic evidence for a core problem solving network across multiple representational domains.
Problem solving is a complex skill engaging multi-stepped reasoning processes to find unknown solutions. The breadth of real-world contexts requiring problem solving is mirrored by a similarly broad, yet unfocused neuroimaging literature, and the domain-general or context-specific brain networks associated with problem solving are not well understood. To more fully characterize those brain networks, we performed activation likelihood estimation meta-analysis on 280 neuroimaging problem solving experiments reporting 3166 foci from 1919 individuals across 131 papers. The general map of problem solving revealed broad fronto-cingulo-parietal convergence, regions similarly identified when considering separate mathematical, verbal, and visuospatial problem solving domain-specific analyses. Conjunction analysis revealed a common network supporting problem solving across diverse contexts, and difference maps distinguished functionally-selective sub-networks specific to task type. Our results suggest cooperation between representationally specialized sub-network and whole-brain systems provide a neural basis for problem solving, with the core network contributing general purpose resources to perform cognitive operations and manage problem demand. Further characterization of cross-network dynamics could inform neuroeducational studies on problem solving skill development.


Improving glycemic control in critically ill patients: personalized care to mimic the endocrine pancreas.
There is considerable physiological and clinical evidence of harm and increased risk of death associated with dysglycemia in critical care. However, glycemic control (GC) currently leads to increased hypoglycemia, independently associated with a greater risk of death. Indeed, recent evidence suggests GC is difficult to safely and effectively achieve for all patients. In this review, leading experts in the field discuss this evidence and relevant data in diabetology, including the artificial pancreas, and suggest how safe, effective GC can be achieved in critically ill patients in ways seeking to mimic normal islet cell function. The review is structured around the specific clinical hurdles of: understanding the patient's metabolic state; designing GC to fit clinical practice, safety, efficacy, and workload; and the need for standardized metrics. These aspects are addressed by reviewing relevant recent advances in science and technology. Finally, we provide a set of concise recommendations to advance the safety, quality, consistency, and clinical uptake of GC in critical care. This review thus presents a roadmap toward better, more personalized metabolic care and improved patient outcomes.


Intestinal Dysbiosis Disguised as a Rectal Fistula Treated With Autologous Fecal Microbiota Transplantation.
Fecal microbiota transplantation (FMT) has been efficacious in the treatment of intestinal dysbiosis, derangement of the native intestinal microflora, and the indications for autologous FMT are growing. A 69-year-old Caucasian man with a past medical history of paraplegia secondary to motor vehicle accident and sigmoid-end colostomy presented to his gastroenterologist with the complaint of rectal discharge. A complicated medical course pre-dated his presentation and included multiple decubitus ulcers requiring debridement and several courses of broad-spectrum antibiotics. The rectal discharge was initially presumed to be from a fistula leading to one of his ulcers; however, workup with anoscopy, flexible sigmoidoscopy, and magnetic resonance imaging of the pelvis showed no visible perirectal abscess or connection to the sigmoid colon through a fistula. Intestinal dysbiosis was an alternative theory considered to be the cause of his copious rectal discharge due to his several courses of broad-spectrum antibiotics and prolonged inactivity of his gut. This prompted a trial treatment plan utilizing autologous FMT, with the patient administering enemas containing his own stool to the distal limb of his bowel. As a result of this treatment, the patient's chief complaint completely resolved within days of initiating treatment, although symptoms did eventually return. We would like to propose that further randomized studies should be done to investigate autologous FMT as a treatment for patients suffering from intestinal dysbiosis following sigmoid-end colostomy.


Three-dimensional transcranial microbubble imaging for guiding volumetric ultrasound-mediated blood-brain barrier opening.
Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening recently entered clinical testing for targeted drug delivery to the brain. Sources of variability exist in the current procedures, motivating the development of real-time monitoring and control techniques to improve treatment safety and efficacy. Here we used three-dimensional (3D) transcranial microbubble imaging to calibrate FUS exposure levels for volumetric BBB opening. Methods: Using a sparse hemispherical transmit/receive ultrasound phased array, pulsed ultrasound was focused transcranially into the thalamus of rabbits during microbubble infusion and multi-channel 3D beamforming was performed online with receiver signals captured at the subharmonic frequency. Pressures were increased pulse-by-pulse until subharmonic activity was detected on acoustic imaging (psub), and tissue volumes surrounding the calibration point were exposed at 50-100%psub via rapid electronic beam steering. Results: Spatially-coherent subharmonic microbubble activity was successfully reconstructed transcranially in vivo during calibration sonications. Multi-point exposures induced volumetric regions of elevated BBB permeability assessed via contrast-enhanced magnetic resonance imaging (MRI). At exposure levels ≥75%psub, MRI and histological examination occasionally revealed tissue damage, whereas sonications at 50%psub were performed safely. Substantial intra-grid variability of FUS-induced bioeffects was observed via MRI, prompting future development of multi-point calibration schemes for improved treatment consistency. Receiver array sparsity and sensor configuration had substantial impacts on subharmonic detection sensitivity, and are factors that should be considered when designing next-generation clinical FUS brain therapy systems. Conclusion: Our findings suggest that 3D subharmonic imaging can be used to calibrate exposure levels for safe FUS-induced volumetric BBB opening, and should be explored further as a method for cavitation-mediated treatment guidance.


Charge induced pattern formation on surfaces: segregation in cylindrical micelles of cationic-anionic peptide-amphiphiles.
Micelles, vesicles, and films composed of two species of incompatible heterogeneous molecules exhibit full internal segregation of the component species. This macroscopic segregation can be inhibited by oppositely charging the two different molecular species. The degree of compatibility achieved by the charges leads to either fully homogenous mixtures or to local segregation and the possible formation of regular patterns. We investigate the induction of periodic surface patterns by the presence of opposite charges in flat films and cylindrical micelles. In the strong segregation limit the incompatibility between species can be described by a line tension parameter gamma. The size of the patterns formed is of the order of a characteristic size L approximately (gamma/sigma(2))(1/2), where sigma is the surface charge density. The pattern symmetry on flat surfaces is function only of the fraction of area covered by the components, f: lamellar for 0.34<f<0.66 and hexagonal otherwise. In cationic and anionic mixtures aggregated into cylindrical micelles the symmetry and size of the surface charged domains depends also on the radius R of the cylinder. For large radii the patterns are similar to those in the plane, but for small radii only lamellar patterns are formed. At high salt concentration the surface domain size jumps discontinuously to an infinite value, resulting in macroscopic phase segregation.