Analysis of complete genomes suggests that many prokaryotes do not rely on hairpin formation in transcription termination.
Free energy values of mRNA tertiary structures around stop codons were systematically calculated to surmise the hairpin-forming potential for all genes in each of the 16 complete prokaryote genomes. Instead of trying to detect each individual hairpin, we averaged the free energy values around the stop codons over the entire genome to predict how extensively the organism relies on hairpin formation in the process of transcription termination. The free energy values of Escherichia coli K-12 shows a sharp drop, as expected, at 30 bp downstream of the stop codon, presumably due to hairpin-forming sequences. Similar drops are observed for Haemophilus influenzae Rd, Bacillus subtilis and Chlamydia trachomatis, suggesting that these organisms also form hairpins at their transcription termination sites. On the other hand, 12 other prokaryotes- Mycoplasma genitalium, Mycoplasma pneumoniae, Synechocystis PCC6803, Helicobacter pylori, Borrelia burgdorferi, Methanococcus jannaschii, Archaeoglobus fulgidus, Methanobacterium thermoautotrophicum, Aquifex aeolicus, Pyrococcus horikoshii, Mycobacterium tuberculosis and Treponema pallidum -show no apparent decrease in free energy value at the corresponding regions. This result suggests that these prokaryotes, or at least some of them, may never form hairpins at their transcription termination sites.


Patterns of growth and body condition in sea otters from the Aleutian archipelago before and after the recent population decline.
1. Growth models for body mass and length were fitted to data collected from 1842 sea otters Enhydra lutris shot or live-captured throughout south-west Alaska between 1967 and 2004. Growth curves were constructed for each of two main year groups: 1967-71 when the population was at or near carrying capacity and 1992-97 when the population was in steep decline. Analyses of data collected from animals caught during 2004, when the population density was very low, were precluded by a small sample size and consequently only examined incidentally to the main growth curves. 2. Growth curves demonstrated a significant increase in body mass and body length at age in the 1990s. Asymptotic values of body mass were 12-18% higher in the 1990s than in the 1960s/70s, and asymptotic values for body length were 10-11% higher between the same periods. Data collected in 2004 suggest a continued increase in body size, with nearly all data points for mass and length falling significantly above the 1990s growth curves. 3. In addition to larger asymptotic values for mass and length, the rate of growth towards asymptotic values was more rapid in the 1990s than in the 1960s/70s: sea otters reached 95% of asymptotic body mass and body length 1-2 years earlier in the 1990s. 4. Body condition (as measured by the log mass/log length ratio) was significantly greater in males than in females. There was also an increasing trend from the 1960s/70s through 2004 despite much year-to-year variation. 5. Population age structures differed significantly between the 1960s/70s and the 1990s with the latter distribution skewed toward younger age classes (indicating an altered lx function) suggesting almost complete relaxation of age-dependent mortality patterns (i.e. those typical of food-limited populations). 6. This study spanned a period of time over which the population status of sea otters in the Aleutian archipelago declined precipitously from levels at or near equilibrium densities at some islands in the 1960s/70s to < 5% of estimated carrying capacity by the late 1990s. The results of this study indicate an improved overall health of sea otters over the period of decline and suggest that limited nutritional resources were not the cause of the observed reduced population abundance. Our findings are consistent with the hypothesis that the decline was caused by increased killer whale predation.


Hydrogen radicals, nitrogen radicals, and the production of O3 in the upper troposphere
The concentrations of the hydrogen radicals OH and HO2 in the middle and upper troposphere were measured simultaneously with those of NO, O3, CO, H2O, CH4, non-methane hydrocarbons, and with the ultraviolet and visible radiation field. The data allow a direct examination of the processes that produce O3 in this region of the atmosphere. Comparison of the measured concentrations of OH and HO2 with calculations based on their production from water vapor, ozone, and methane demonstrate that these sources are insufficient to explain the observed radical concentrations in the upper troposphere. The photolysis of carbonyl and peroxide compounds transported to this region from the lower troposphere may provide the source of HOx required to sustain the measured abundances of these radical species. The mechanism by which NO affects the production of O3 is also illustrated by the measurements. In the upper tropospheric air masses sampled, the production rate for ozone (determined from the measured concentrations of HO2 and NO) is calculated to be about 1 part per billion by volume each day. This production rate is faster than previously thought and implies that anthropogenic activities that add NO to the upper troposphere, such as biomass burning and aviation, will lead to production of more O3 than expected.


Inhibiting Solid Tumor Growth In Vivo by Non-Tumor-Penetrating Nanomedicine.
Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor-penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual-functional, nontumor-penetrating NM is demonstrated. The intended NM contains 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular-disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual-functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.


Subthreshold sodium current underlies essential functional specializations at primary auditory afferents.
Primary auditory afferents are generally perceived as passive, timing-preserving lines of communication. Contrasting this view, identifiable auditory afferents to the goldfish Mauthner cell undergo potentiation of their mixed--electrical and chemical--synapses in response to high-frequency bursts of activity. This property likely represents a mechanism of input sensitization because they provide the Mauthner cell with essential information for the initiation of an escape response. Consistent with this synaptic specialization, we show here that these afferents exhibit an intrinsic ability to respond with bursts of 200-600 Hz and this property critically relies on the activation of a persistent sodium current, which is counterbalanced by the delayed activation of an A-type potassium current. Furthermore, the interaction between these conductances with the membrane passive properties supports the presence of electrical resonance, whose frequency preference is consistent with both the effective range of hearing in goldfish and the firing frequencies required for synaptic facilitation, an obligatory requisite for the induction of activity-dependent changes. Thus our data show that the presence of a persistent sodium current is functionally essential and allows these afferents to translate behaviorally relevant auditory signals into patterns of activity that match the requirements of their fast and highly modifiable synapses. The functional specializations of these neurons suggest that auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized.


Avarol-induced DNA strand breakage in vitro and in Friend erythroleukemia cells.
The hydroquinone-containing cytostatic compound avarol inhibits predominantly growth of those cell lines which have a low level of superoxide dismutase. The substrate of this enzyme, the superoxide anion, was found to be formed during the in vitro oxidation reaction of avarol to its semiquinone radical in the presence of oxygen. Under the same incubation conditions plasmid DNA (pBR322) was converted from the fully supercoiled circular form mainly to the nicked circular form, indicating that the compound causes primarily single-strand breaks. Using Friend erythroleukemia cells (FLC) it was found that avarol induces a dose-dependent DNA damage; the maximum number of DNA strand breaks was observed at 5 h after addition of the compound to the cells. Removal of avarol resulted in a rapid DNA rejoining with biphasic repair kinetics [first half-time, 8 min (90% of the breaks) and a second half-time, 40 min (10% of the breaks)]. When the degree of avarol-induced DNA damage in FLC was compared with the drug-caused inhibition of cell growth a close correlation was established. Avarol displayed no effect on dimethyl sulfoxide-induced erythrodifferentiation of FLC as determined by the benzidine reaction and by dot blot hybridization experiments. From incubation studies of FLC with [3H]avarol no hint was obtained for the formation of an adduct between DNA and the compound. The subcellular distribution of [3H]avarol was studied in liver cells after i.v. application of the compound. The predominant amount of the compound was present in the cytosolic fraction; little avarol was associated with plasma membranes, nuclei, and mitochondria. Using (a) oxidative phosphorylation and (b) oxygen uptake as parameters for mitochondria function, no effect of the compound on the activity of this organelle was determined. These results suggest that avarol forms superoxide anions (and in consequence possibly also hydroxyl radicals) especially in those cells which have low levels of superoxide dismutase. Moreover, evidence is provided that the active oxygen species cause DNA damage resulting in the observed cytotoxic effect.


Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform.
With read lengths of currently up to 2 × 300 bp, high throughput and low sequencing costs Illumina's MiSeq is becoming one of the most utilized sequencing platforms worldwide. The platform is manageable and affordable even for smaller labs. This enables quick turnaround on a broad range of applications such as targeted gene sequencing, metagenomics, small genome sequencing and clinical molecular diagnostics. However, Illumina error profiles are still poorly understood and programs are therefore not designed for the idiosyncrasies of Illumina data. A better knowledge of the error patterns is essential for sequence analysis and vital if we are to draw valid conclusions. Studying true genetic variation in a population sample is fundamental for understanding diseases, evolution and origin. We conducted a large study on the error patterns for the MiSeq based on 16S rRNA amplicon sequencing data. We tested state-of-the-art library preparation methods for amplicon sequencing and showed that the library preparation method and the choice of primers are the most significant sources of bias and cause distinct error patterns. Furthermore we tested the efficiency of various error correction strategies and identified quality trimming (Sickle) combined with error correction (BayesHammer) followed by read overlapping (PANDAseq) as the most successful approach, reducing substitution error rates on average by 93%.


Herpetic ulcer of the eyelids in an immunocompromised patient.
A 24-year-old black female (HIV-positive) was referred to our clinic with a 4-week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised.


An integrated logic circuit assembled on a single carbon nanotube.
Single-walled carbon nanotubes (SWCNTs) have been shown to exhibit excellent electrical properties, such as ballistic transport over several hundred nanometers at room temperature. Field-effect transistors (FETs) made from individual tubes show dc performance specifications rivaling those of state-of-the-art silicon devices. An important next step is the fabrication of integrated circuits on SWCNTs to study the high-frequency ac capabilities of SWCNTs. We built a five-stage ring oscillator that comprises, in total, 12 FETs side by side along the length of an individual carbon nanotube. A complementary metal-oxide semiconductor-type architecture was achieved by adjusting the gate work functions of the individual p-type and n-type FETs used.


Modeling of peptides containing D-amino acids: implications on cyclization.
Cyclic peptides are therapeutically attractive due to their high bioavailability, potential selectivity, and scaffold novelty. Furthermore, the presence of D-residues induces conformational preferences not followed by peptides consisting of naturally abundant L-residues. Therefore, comprehending how amino acids induce turns in peptides, subsequently facilitating cyclization, is significant in peptide design. Here, we performed 20-ns explicit-solvent molecular dynamics simulations for three diastereomeric peptides with stereochemistries: LLLLL, LLLDL, and LDLDL. Experimentally LLLLL and LDLDL readily cyclize, whereas LLLDL cyclizes in low yield. Simulations at 310 K produced conformations with inter-terminal hydrogen bonds that correlated qualitatively with the experimental cyclization trend. Energies obtained for representative structures from quantum chemical (B3LYP/PCM/cc-pVTZ//HF/6-31G*) calculations predicted pseudo-cyclic and extended conformations as the most stable for LLLLL and LLLDL, respectively, in agreement with the experimental data. In contrast, the most stable conformer predicted for peptide LDLDL was not a pseudo-cyclic structure. Moreover, D-residues preferred the experimentally less populated alpha(L) rotamers even when simulations were performed at a higher temperature and with strategically selected starting conformations. Energies calculated with molecular mechanics were consistent only with peptide LLLLL. Thus, the conformational preferences obtained for the all L: -amino acid peptide were in agreement with the experimental observations. Moreover, refinement of the force field is expected to provide far-reaching conformational sampling of peptides containing D-residues to further develop force field-based conformational-searching methods.


A new developing class of gene delivery: messenger RNA-based therapeutics.
Gene therapy has long been held as having the potential to become a front line treatment for various genetic disorders. However, the direct delivery of nucleic acids to correct a genetic disorder has numerous limitations owing to the inability of naked nucleic acids (DNA and RNA) to traverse the cell membrane. Recently, messenger RNA (mRNA) based delivery has become a more attractive alternative to DNA due to the relatively easier transfection process, higher efficiency and safety profile. As with all gene therapies, the central challenge that remains is the efficient delivery of nucleic acids intracellularly. This review presents the recent progress in mRNA delivery, focusing on comparing the advantages and limitations of non-viral based delivery vectors.


Audiovisual Integration Varies With Target and Environment Richness in Immersive Virtual Reality.
We are continually bombarded by information arriving to each of our senses; however, the brain seems to effortlessly integrate this separate information into a unified percept. Although multisensory integration has been researched extensively using simple computer tasks and stimuli, much less is known about how multisensory integration functions in real-world contexts. Additionally, several recent studies have demonstrated that multisensory integration varies tremendously across naturalistic stimuli. Virtual reality can be used to study multisensory integration in realistic settings because it combines realism with precise control over the environment and stimulus presentation. In the current study, we investigated whether multisensory integration as measured by the redundant signals effects (RSE) is observable in naturalistic environments using virtual reality and whether it differs as a function of target and/or environment cue-richness. Participants detected auditory, visual, and audiovisual targets which varied in cue-richness within three distinct virtual worlds that also varied in cue-richness. We demonstrated integrative effects in each environment-by-target pairing and further showed a modest effect on multisensory integration as a function of target cue-richness but only in the cue-rich environment. Our study is the first to definitively show that minimal and more naturalistic tasks elicit comparable redundant signals effects. Our results also suggest that multisensory integration may function differently depending on the features of the environment. The results of this study have important implications in the design of virtual multisensory environments that are currently being used for training, educational, and entertainment purposes.


Worldwide distribution of major clones of Listeria monocytogenes.
Listeria monocytogenes is worldwide a pathogen, but the geographic distribution of clones remains largely unknown. Genotyping of 300 isolates from the 5 continents and diverse sources showed the existence of few prevalent and globally distributed clones, some of which include previously described epidemic clones. Cosmopolitan distribution indicates the need for genotyping standardization.


Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in the clinical outcomes and HRQoL improvements that exceed minimally important thresholds.
The primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity. The objective of this study was to explore the association between clinical endpoints used to gauge RA treatment efficacy and patient-reported outcomes of health-related quality of life, fatigue, and physical function in RA patients treated with secukinumab in a phase 2 randomized controlled trial (RCT). Adult RA patients (n = 237) with incomplete responses to methotrexate were randomized equally to receive monthly s.c. injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. Clinical endpoints used in this study included the ACR response criteria and its components and simplified disease activity score. Patient-reported outcomes (PRO) included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 [SF-36] Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Patients were categorized into mutually exclusive groups according to the magnitude and direction of change from baseline to week 16 in each clinical endpoint. Definitions of minimal important differences [MID] in each clinical endpoint were used to categorize patients, as well as thresholds beyond MID. Mean changes from baseline to week 16 were computed for each PRO and analyses of variance to test the differences in PRO changes observed across groups of patients that differed in each clinical endpoint. Analyses were limited to patients randomized to secukinumab treatment. All dose groups were combined (n = 187). Mean changes from baseline in each PRO differed significantly across groups of patients in the expected direction. With few exceptions, there was considerable agreement between clinical endpoints and PROs concerning the magnitude of change defined as clinically meaningful. More importantly, results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in HRQoL, fatigue, and physical function. Results of this study show considerable agreement between minimal thresholds of improvement established for PROs and clinical outcome measures used in RA treatment studies and provide thresholds to be considered in gauging the importance of a treatment effect that goes beyond what is considered as minimally important for PRO measures.


Predictors of Short-Term Outcomes after Syncope: A Systematic Review and Meta-Analysis.
We performed a systematic review and meta-analysis to identify predictors of serious clinical outcomes after an acute-care evaluation for syncope. We identified studies that assessed for predictors of short-term (≤30 days) serious clinical events after an emergency department (ED) visit for syncope. We performed a MEDLINE search (January 1, 1990 - July 1, 2017) and reviewed reference lists of retrieved articles. The primary outcome was the occurrence of a serious clinical event (composite of mortality, arrhythmia, ischemic or structural heart disease, major bleed, or neurovascular event) within 30 days. We estimated the sensitivity, specificity, and likelihood ratio of findings for the primary outcome. We created summary estimates of association on a variable-by-variable basis using a Bayesian random-effects model. We reviewed 2,773 unique articles; 17 met inclusion criteria. The clinical findings most predictive of a short-term, serious event were the following: 1) An elevated blood urea nitrogen level (positive likelihood ratio [LR+]: 2.86, 95% confidence interval [CI] [1.15, 5.42]); 2); history of congestive heart failure (LR+: 2.65, 95%CI [1.69, 3.91]); 3) initial low blood pressure in the ED (LR+: 2.62, 95%CI [1.12, 4.9]); 4) history of arrhythmia (LR+: 2.32, 95%CI [1.31, 3.62]); and 5) an abnormal troponin value (LR+: 2.49, 95%CI [1.36, 4.1]). Younger age was associated with lower risk (LR-: 0.44, 95%CI [0.25, 0.68]). An abnormal electrocardiogram was mildly predictive of increased risk (LR+ 1.79, 95%CI [1.14, 2.63]). We identified specific risk factors that may aid clinical judgment and that should be considered in the development of future risk-prediction tools for serious clinical events after an ED visit for syncope.


When a local Hamiltonian must be frustration-free.
A broad range of quantum optimization problems can be phrased as the question of whether a specific system has a ground state at zero energy, i.e., whether its Hamiltonian is frustration-free. Frustration-free Hamiltonians, in turn, play a central role for constructing and understanding new phases of matter in quantum many-body physics. Unfortunately, determining whether this is the case is known to be a complexity-theoretically intractable problem. This makes it highly desirable to search for efficient heuristics and algorithms to, at least, partially answer this question. Here we prove a general criterion-a sufficient condition-under which a local Hamiltonian is guaranteed to be frustration-free by lifting Shearer's theorem from classical probability theory to the quantum world. Remarkably, evaluating this condition proceeds via a fully classical analysis of a hardcore lattice gas at negative fugacity on the Hamiltonian's interaction graph, which, as a statistical mechanics problem, is of interest in its own right. We concretely apply this criterion to local Hamiltonians on various regular lattices, while bringing to bear the tools of spin glass physics that permit us to obtain new bounds on the satisfiable to unsatisfiable transition in random quantum satisfiability. We are then led to natural conjectures for when such bounds will be tight, as well as to a novel notion of universality for these computer science problems. Besides providing concrete algorithms leading to detailed and quantitative insights, this work underscores the power of marrying classical statistical mechanics with quantum computation and complexity theory.


mtDNA control-region sequence variation suggests multiple independent origins of an "Asian-specific" 9-bp deletion in sub-Saharan Africans.
The intergenic COII/tRNA(Lys) 9-bp deletion in human mtDNA, which is found at varying frequencies in Asia, Southeast Asia, Polynesia, and the New World, was also found in 81 of 919 sub-Saharan Africans. Using mtDNA control-region sequence data from a subset of 41 individuals with the deletion, we identified 22 unique mtDNA types associated with the deletion in Africa. A comparison of the unique mtDNA types from sub-Saharan Africans and Asians with the 9-bp deletion revealed that sub-Saharan Africans and Asians have sequence profiles that differ in the locations and frequencies of variant sites. Both phylogenetic and mismatch-distribution analysis suggest that 9-bp deletion arose independently in sub-Saharan Africa and Asia and that the deletion has arisen more than once in Africa. Within Africa, the deletion was not found among Khoisan peoples and was rare to absent in western and southwestern African populations, but it did occur in Pygmy and Negroid populations from central Africa and in Malawi and southern African Bantu-speakers. The distribution of the 9-bp deletion in Africa suggests that the deletion could have arisen in central Africa and was then introduced to southern Africa via the recent "Bantu expansion."


Monoamines and ovarian hormone-linked sexual and emotional changes: A review.
Emotional upsets related to changes in ovarian hormones are highly prevalent and are responsible for psychiatric morbidity and mortality. Significant increases in acute psychiatric hospitalizations, suicidal activity, and other psychopathology occur during the premenstruum and during menstruation. This paper reviews evidence indicating that menstrual cycle psychopathology may be mediated by the effects of estrogen, progesterone, and possibly the renin-angiotensin-aldosterone system on the brain monoamines, norepinephrine, dopamine, and serotonin. During the menstrual cycle, psychopathology often begins with the onset of luteal estrogen-progesterone-angiotensin-aldosterone secretion and intensifies as these hormone levels later fall, prior to and during menstruation. Aldosterone is reported elevated in cases of premenstrual tension syndrome. There are numerous reports of affective upsets occurring with the use of estrogen-progestin oral contraceptives and following their withdrawal. Contraceptives stimulate the renin-angiotensin-aldosterone system and are reported useful in alleviating premenstrual-menstrual emotional upsets and postpartum depressive episodes. Affective lability, prevalent at parturition, occurs when estrogen, progesterone, and aldosterone levels are first high and later falling. Exogenous estrogen and progesterone profoundly affect mating activity in castrated rhesus monkeys, and cyclic fluctuations in sexual activity in humans may occur during the menstrual cycle. Much information links manic and depressive reactions with alterations in brain monoamines. Lithium, monoamine oxidase inhibitors, and tricylic antidepressants, specifically used to treat affective disorders, are reported useful in treating ovarian hormone-linked upsets. Similarities exist between changes in animal behavior caused by drugs altering affective states and the effects of ovarian hormones. Like certain antidepressants, estrogen induces hyperactivity in rats. Like reserpine, progesterone exhibits sedative and soporific effects. Sexual behavior in female rats is reported linked to changes in brain monoamines. Agents increasing brain monoamine levels and availability decrease mating responses, and monoamine depletors, such as reserpine may be substituted for progesterone in activating mating behavior. Serotonin and dopamine appear to be important in the regulation of ovulation. Brain norepinephrine varies with the phases of the rat estrus cycle. Castration increases brain norepinephrine and decreases brain dopamine. Exogenous estrogen decreases rat brain norepinephrine content. The monoamine-destroying enzymes, monoamine oxidase, and catechol O-methyl transferase are affected by ovarian steroids and show fluctuating levels during the reproductive cycle. The effects of reserpine, monoamine oxidase inhibitors, tricyclic antidepressants, and lithium on monoamines in neurophysiological preparations have been used as evidence supporting theories linking monoamine changes with human affective disorders. Estrogen, progesterone, and angiotensin also exhibit effects on in vitromonoamine systems. Like the tricyclic antidepressants, uptake of norepinephrine and dopamine by nerve endings is inhibited in the presence of estrogen, progesterone, and angiotensin. As with reserpine, the flow of these monoamines from nerve endings is increased by progesterone. Estrogen slows the flow of norepinephrine from nerve endings and decreases the electrically induced release of serotonin and norepinephrine from brain slices. The above information provides clues that ovarian hormone-linked psychopathology, like affective disorders in general, may be related to alterations in brain monoamines.


Gefitinib reverses breast cancer resistance protein-mediated drug resistance.
Breast cancer resistance protein (BCRP) is an ATP binding cassette transporter that confers resistance to a series of anticancer agents such as 7-ethyl-10-hydroxycamptothecin (SN-38), topotecan, and mitoxantrone. In this study, we evaluated the possible interaction of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, with BCRP. BCRP-transduced human epidermoid carcinoma A431 (A431/BCRP) cells acquired cellular resistance to gefitinib, suggesting that BCRP could be one of the determinants of gefitinib sensitivity in a certain sort of cells. Next, the effect of gefitinib on BCRP-mediated drug resistance was examined. Gefitinib reversed SN-38 resistance in BCRP-transduced human myelogenous leukemia K562 (K562/BCRP) or BCRP-transduced murine lymphocytic leukemia P388 (P388/BCRP) cells but not in these parental cells. In addition, gefitinib sensitized human colon cancer HT-29 cells, which endogenously express BCRP, to SN-38. Gefitinib increased intracellular accumulation of topotecan in K562/BCRP cells and suppressed ATP-dependent transport of estrone 3-sulfate, a substrate of BCRP, in membrane vesicles from K562/BCRP cells. These results suggest that gefitinib may overcome BCRP-mediated drug resistance by inhibiting the pump function of BCRP. Furthermore, P388/BCRP-transplanted mice treated with combination of irinotecan and gefitinib survived significantly longer than those treated with irinotecan alone or gefitinib alone. In conclusion, gefitinib is shown to interact with BCRP. BCRP expression in a certain sort of cells is supposed to be one of the determinants of gefitinib sensitivity. Gefitinib inhibits the transporter function of BCRP and reverses BCRP-mediated drug resistance both in vitro and in vivo.


Comigration of tyrosine hydroxylase- and gonadotropin-releasing hormone-immunoreactive neurons in the nasal area of human embryos.
Tyrosine hydroxylase (TH) immunoreactive (IR) central catecholaminergic neurons have been observed in human CNS from 4.5 gestational weeks (g.w.) on [Verney, C., Zecevic, N. and Puelles, L. Eur. J. Neurosci., Suppl. 8 (1995) 7044; Zecevic, N. and Verney, C., J. Comp, Neurol., 351 (1995) 509-535]. We describe here a discrete TH-IR cell population localized in the rostral nasal region during embryonic development. Tyrosine hydroxylase-IR cells spread from the olfactory placode towards the basal and medial telencephalon. They follow the same migration path as the gonadotropin-releasing hormone (GnRH)-IR hypothalamic neurons. Tyrosine hydroxylase-IR neurons are first detected at 4.5 g.w., while GnRH-IR cells are visualized later at 5.5 g.w. Double immunocytochemical labeling reveals the presence of three neuronal populations comigrating along the developing vomeronasal-nervus terminalis complex. These populations express either one or both TH and GnRH phenotypes depending on their position in the migration route. At 6 g.w., most of the neurons express TH immunoreactivity as they leave the vomeronasal organ whereas most of the GnRH-IR neurons are detected closer to the CNS and in the CNS itself. These results emphasize the early phenotypic heterogeneity of the different migrating neuronal populations generated in the olfactory placode in humans. At later stages, very few TH-IR neurons are detected in the anterior forebrain suggesting a transient expression of TH immunoreactivity within these neuronal populations.


The Effect of the COVID-19 Pandemic on Functioning of Neurosurgery Clinics and the Anxiety Levels of Neurosurgeons in Turkey.
To reveal the impacts of the novel coronavirus 2019 (COVID-19) pandemic on the functioning of neurosurgery clinics and to determine the anxiety levels and attitudes of Turkish neurosurgeons towards their profession during the pandemic. The Beck anxiety inventory and a clinical activities scale were utilized as data collection tools and distributed to neurosurgeons in Turkey as an online survey. Descriptive statistical methods, significance tests and correlation and regression analyses were employed to analyze the data. The data analysis was carried out in a 95% confidence interval. Of the 240 neurosurgeons who participated in the study, 63.8% had encountered cases of COVID-19 and 53.8% had handled patients diagnosed with COVID-19. The study results showed that the pandemic did not cause anxiety in 62.9% of the respondents, but it caused mild anxiety in 13.8% and moderate anxiety in 12.12%. The findings also revealed a low linear correlation between the anxiety values and occupational anxiety of the neurosurgeons and low inverse correlation between anxiety values and the protection factor in the pandemic period. The COVID-19 pandemic has caused serious disruptions in the routine functioning of neurosurgery clinics and changes in the attitudes of neurosurgeons. Healthcare organizations should take the necessary precautions and measures to resolve the anxiety problems of healthcare professionals, such as providing professional support, and ensure that they can work in a safer environment.


Substance deposition assessment in obstructed pulmonary system through numerical characterization of airflow and inhaled particles attributes.
Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches. In this context, computational fluid dynamics (CFD) simulations accompanied by fluid particle tracing (FPT) analysis of the inhaled ambient particles are deemed critical for lung function assessment. Also they enable the understanding of particle depositions on the airways of patients, since these accumulations may affect or lead to inflammations. In this direction, the current study conducts an initial investigation for the better comprehension of particle deposition within the lungs. More specifically, accurate models of the airways obstructions that relate to pulmonary disease are developed and a thorough assessment of the airflow behavior together with identification of the effects of inhaled particle properties, such as size and density, is conducted. Our approach presents a first step towards an effective personalization of pulmonary treatment in regards to the geometric characteristics of the lungs and the in depth understanding of airflows within the airways. A geometry processing technique involving contraction algorithms is established and used to employ the different respiratory arrangements associated with lung related diseases that exhibit airways obstructions. Apart from the normal lung case, two categories of obstructed cases are examined, i.e. models with obstructions in both lungs and models with narrowings in the right lung only. Precise assumptions regarding airflow and deposition fraction (DF) over various sections of the lungs are drawn by simulating these distinct incidents through the finite volume method (FVM) and particularly the CFD and FPT algorithms. Moreover, a detailed parametric analysis clarifies the effects of the particles size and density in terms of regional deposition upon several parts of the pulmonary system. In this manner, the deposition pattern of various substances can be assessed. For the specific case of the unobstructed lung model most particles are detected on the right lung (48.56% of total, when the air flowrate is 12.6 L/min), a fact that is also true when obstructions arise symmetrically in both lungs (51.45% of total, when the air flowrate is 6.06 L/min and obstructions occur after the second generation). In contrast, when narrowings are developed on the right lung only, most particles are pushed on the left section (68.22% of total, when the air flowrate is 11.2 L/min) indicating that inhaled medication is generally deposited away from the areas of inflammation. This observation is useful when designing medical treatment of lung diseases. Furthermore, particles with diameters from 1 μm to 10 μm are shown to be mainly deposited on the lower airways, whereas particles with diameters of 20 μm and 30 μm are mostly accumulated in the upper airways. As a result, the current analysis indicates increased DF levels in the upper airways when the particle diameter is enlarged. Additionally, when the particles density increases from 1000 Kg/m3 to 2000 Kg/m3, the DF is enhanced on every generation and for all cases investigated herein. The results obtained by our simulations provide an accurate and quantitative estimation of all important parameters involved in lung modeling. The treatment of respiratory diseases with inhaled medical substances can be advanced by the clinical use of accurate CFD and FPT simulations and specifically by evaluating the deposition of inhaled particles in a regional oriented perspective in regards to different particle sizes and particle densities. Since a drug with specific characteristics (i.e. particle size and density) exhibits maximum deposition on particular lung areas, the current study provides initial indications to a qualified physician for proper selection of medication.


Gambling among adolescents with and without hearing loss.
This exploratory study investigates the prevalence of gambling, preferred types of gambling, and problem gambling in Swedish young people aged 15-18 years with and without hearing loss. A cross-sectional health survey was conducted in Örebro County, Sweden in 2014. A standardized questionnaire was distributed to 4888 students, and 4329 filled it. There were 318 (8 %) students with hearing loss. The response rate was 82 %. The 2-item Lie/Bet questionnaire (Johnson et al. in Psychol Rep 80:83-88, 1997) was used for measuring problem gambling. More students with hearing loss had gambled during their lifetime (35 %) and in the past year (25 %) than their hearing counterparts (lifetime: 24 %; past-year: 19 %). More students with hearing loss compared to normal hearing students were identified as problem gamblers (7.7 % compared to 4.3 %). More research is needed on gambling among people with hearing loss as well as other disabilities.


Using germline variants to estimate glioma and subtype risks.
Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes. Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray. Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85. These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.


Comparison of prediction models for use of medical resources at urban auto-racing events.
INTRODUCTION Predicting the number of patient encounters and transports during mass gatherings can be challenging. The nature of these events necessitates that proper resources are available to meet the needs that arise. Several prediction models to assist event planners in forecasting medical utilization have been proposed in the literature. The objective of this study was to determine the accuracy of the Arbon and Hartman models in predicting the number of patient encounters and transportations from the Baltimore Grand Prix (BGP), held in 2011 and 2012. It was hypothesized that the Arbon method, which utilizes regression model-derived equations to estimate, would be more accurate than the Hartman model, which categorizes events into only three discreet severity types. This retrospective analysis of the BGP utilized data collected from an electronic patient tracker system. The actual number of patients evaluated and transported at the BGP was tabulated and compared to the numbers predicted by the two studied models. Several environmental features including weather, crowd attendance, and presence of alcohol were used in the Arbon and Hartman models. Approximately 130,000 spectators attended the first event, and approximately 131,000 attended the second. The number of patient encounters per day ranged from 19 to 57 in 2011, and the number of transports from the scene ranged from two to nine. In 2012, the number of patients ranged from 19 to 44 per day, and the number of transports to emergency departments ranged from four to nine. With the exception of one day in 2011, the Arbon model over predicted the number of encounters. For both events, the Hartman model over predicted the number of patient encounters. In regard to hospital transports, the Arbon model under predicted the actual numbers whereas the Hartman model both over predicted and under predicted the number of transports from both events, varying by day. These findings call attention to the need for the development of a versatile and accurate model that can more accurately predict the number of patient encounters and transports associated with mass-gathering events so that medical needs can be anticipated and sufficient resources can be provided.


The effect of exercise interventions on resting metabolic rate: A systematic review and meta-analysis.
The systematic review and meta-analysis evaluated the effect of aerobic, resistance and combined exercise on RMR (kCal·day-1) and performed a methodological assessment of indirect calorimetry protocols within the included studies. Subgroup analyses included energy/diet restriction and body composition changes. Randomized control trials (RCTs), quasi - RCTs and cohort trials featuring a physical activity intervention of any form and duration excluding single exercise bouts were included. Participant exclusions included medical conditions impacting upon RMR, the elderly (≥65 years of age) or pregnant, lactating or post-menopausal women. The review was registered in the International Prospective Register of Systematic Reviews (CRD 42,017,058,503). 1669 articles were identified; 22 were included in the qualitative analysis and 18 were meta-analysed. Exercise interventions (aerobic and resistance exercise combined) did not increase resting metabolic rate (mean difference (MD): 74.6 kCal·day-1[95% CI: -13.01, 161.33], P = 0.10). While there was no effect of aerobic exercise on RMR (MD: 81.65 kCal·day-1[95% CI: -57.81, 221.10], P = 0.25), resistance exercise increased RMR compared to controls (MD: 96.17 kCal·day-1[95% CI: 45.17, 147.16], P = 0.0002). This systematic review effectively synthesises the effect of exercise interventions on RMR in comparison to controls; despite heterogenous methodologies and high risk of bias within included studies.


Benefit of dietary integrators for treating functional dyspepsia: a prospective pilot study.
Because of the multifactorial pathogenesis of functional dyspepsia, strategies alternative to antacid therapy are being sought for treating the disorder. This prospective study evaluated the benefit of treatment with a dietary integrator composed of sodium alginate, sodium bicarbonate, bromelin and essential oils. The study population included 53 consecutive patients (22 males, 31 females; mean age, 54+/-2.5 years) with functional dyspepsia and negative for Helicobacter pylori infection. The patients were categorized into four subgroups according to predominant symptom: ulcer-like dyspepsia, motility-like dyspepsia, reflux-like dyspepsia, and nonspecific dyspepsia. All received TUBES gastro (0.80 g oral tablets bid) for a minimum of 3 months (range, 3-11). Treatment efficacy was measured by means of a Visual Analogue Scale (VAS). Two patients were lost to follow-up; of the remaining 51 patients who completed the study, 35 (68%) showed an improvement in VAS score. The difference in scores between the initial and the final visit was -1.9+/-2.1 cm (range, -6 to +3), or 23.8+/-40.8% (range, -150% to 100%) compared to the scores at the baseline visit (P=0.0001). The study results indicate that in the short term TUBES gastro can significantly improve dyspeptic symptoms in dyspeptic patients negative for H. pylori infection through the synergistic action of its components: alginate buffers gastric acid; bicarbonate helps to eliminate gas and rebalance pH; essential oils regulate motility; and bromelin stimulates enzymatic activity.


Validity of the Japanese version of the Munich ChronoType Questionnaire.
To assess circadian preference with a score, the Morningness-Eveningness Questionnaire (MEQ) has been used for more than 3 decades now. More recently, the Munich ChronoType Questionnaire (MCTQ) was developed: it asks for sleep-wake behavior on work and free days and uses the midpoint of sleep on free days (MSF), corrected for sleep debt accumulated during the work week as an indicator of chronotype (MSFsc). In this study, we developed a Japanese version of the MCTQ by using a translation/back-translation approach including an examination of its semantic validity. In a subsequent questionnaire survey, 450 adult men and women completed the Japanese versions of the MCTQ and MEQ. Results showed that MEQ scores were significantly negatively correlated with mid-sleep parameters assessed by the MCTQ, on both, work and free days, as well as with the chronotype measure MSFsc (r = -0.580 to -0.652, all p < 0.001). As in the original German version, the strongest correlation was observed between MEQ score and MSF. A physiological validation study using dim light melatonin onset as a circadian phase marker (N = 37) showed a high correlation between chronotype as assessed with the MSFsc (r = 0.542, p < 0.001), and less so for MEQ score (r = -0.402, p = 0.055). These results demonstrate the validity of the Japanese MCTQ and provide further support of the adequacy of the MCTQ as a chronotype measure.


The promotion of condom use in non-regular sexual partnerships in urban Mozambique.
This study uses data from a representative sample of sexually active adults in urban Mozambique to examine the effectiveness of the JeitO condom social marketing (CSM) project in increasing condom use among men and women at risk of contracting HIV. More specifically, this study tests the hypothesis that exposure to programme interventions (communications and access) increases condom use with non-regular partners. Exposure to the CSM programme is high, and multivariate analyses show that exposure to CSM advertising and communications and knowledge of a condom source are associated with higher reports of condom use with non-regular partners. Analyses of regional differences in condom use show that knowledge and use of condoms with non-regular partners are higher than the national average in all four provinces where the CSM project has been operating for longer (18 months vs. 6 months). Multivariate analyses show that the above-average level of condom use in the capital, Maputo, can be attributed to the higher socioeconomic status of this population, but the above-average level of condom use among men and women in Sofala and Manica provinces is due, in part, to their high level of exposure to the CSM programme. These findings indicate that the JeitO CSM project's behaviour-change communications and condom distribution are effective in encouraging safer sex practices among persons engaged in sex with non-regular partners.


Genetic Variants in Metabolic Signaling Pathways and Their Interaction with Lifestyle Factors on Breast Cancer Risk: A Random Survival Forest Analysis.
Genetic variants in the insulin-like growth factor-I (IGF-I)/insulin resistance axis may interact with lifestyle factors, influencing postmenopausal breast cancer risk, but these interrelated pathways are not fully understood. In this study, we examined 54 single-nucleotide polymorphisms (SNP) in genes related to IGF-I/insulin phenotypes and signaling pathways and lifestyle factors in relation to postmenopausal breast cancer, using data from 6,567 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies. We used a machine-learning method, two-stage random survival forest analysis. We identified three genetic variants (AKT1 rs2494740, AKT1 rs2494744, and AKT1 rs2498789) and two lifestyle factors [body mass index (BMI) and dietary alcohol intake] as the top five most influential predictors for breast cancer risk. The combination of the three SNPs, BMI, and alcohol consumption (≥1 g/day) significantly increased the risk of breast cancer in a gene and lifestyle dose-dependent manner. Our findings provide insight into gene-lifestyle interactions and will enable researchers to focus on individuals with risk genotypes to promote intervention strategies. These data also suggest potential genetic targets in future intervention/clinical trials for cancer prevention in order to reduce the risk for breast cancer in postmenopausal women. Cancer Prev Res; 11(1); 44-51. ©2017 AACR.


Hygiene self-care of older adults in West Virginia: effects of gender.
This study investigated whether oral hygiene self-care behavior differs between genders in older adults in Appalachia, a geographic area with significant oral health concerns. Identify ing the practices of older adults may provide valuable information for designing interventions and improving overall oral health outcomes. As part of a larger, on-going study on cognition and oral health in later life in Appalachia, a sample of dentate, older adults without dementia aged 70 and above (n=245, 86 men and 159 women) received an oral assessment by either a dentist or dental hygienist. Psychometricians assessed cognition using a standardized battery of neuropsychological tests. They also administered the General Oral Health Assessment Index and conducted structured interviews concerning diet, oral hygiene practices, oral health, social support, income and years of education Results: Over 80% of women (n=128) and 52.3% of men (n=45) reported brushing their teeth twice daily. Multivariate logistic regression analysis was conducted, controlling for socioeconomic status, social support (i.e., frequency of contacting friends and relatives), general oral health assessment items, number of decayed, missing and filled surfaces, plaque index and having regular dental visits. The results showed that women reported more frequent tooth brushing than their male counterparts (OR=4.04, 95% CI:1.93,8.42). Older women in West Virginia had significantly better oral hygiene practices than older men, particularly regarding tooth brushing. Interventions are needed to improve older men's dental hygiene behaviors to improve overall oral health outcomes.


Now you see it, now you don't: controlling for contingencies and stimulus repetitions eliminates the Gratton effect.
The Gratton (or sequential congruency) effect is the finding that conflict effects (e.g., Stroop and Eriksen flanker effects) are larger following congruent trials relative to incongruent trials. The standard account given for this is that a cognitive control mechanism detects conflict when it occurs and adapts to this conflict on the following trial. Others, however, have questioned the conflict adaptation account and suggested that sequential biases might account for the Gratton effect. In two experiments, contingency biases were removed from the task and stimulus repetitions were deleted to control for stimulus bindings. This eliminated the Gratton effect in the response times in both experiments, supporting a non-conflict explanation of the Gratton effect. A Gratton effect did persist in the errors of Experiment 1; however, this effect was not produced by the type of errors (word reading errors) that a conflict adaptation account should predict. Instead, tentative support was found for a congruency switch cost hypothesis. In all, the conflict adaptation account failed to account for any of the reported data. Implications for future work on cognitive control are discussed.


Computed tomography of masses of the brachial plexus and contributing nerve roots in dogs.
A retrospective analysis of masses of the brachial plexus and contributing nerve roots in dogs seen at the University of Minnesota over a 17-year period was conducted. The goal of the study was to characterize their computed tomographic (CT) appearance and determine the minimum mass size confidently detectable. Twenty-four cases with a recorded diagnosis of brachial plexus or caudal cervical nerve root mass were found, wherein both the medical records and CT images were available for evaluation. These masses were characterized based on the presence or absence of contrast enhancement, margin character, size, extent of local invasion, and presence of vertebral canal or spinal cord involvement. Within the limits of this study, and the available histopathology, there appeared to be no clinically exploitable relationship between the tomographic appearance and the histologic interpretation. Twenty masses were noted to contrast enhance, typically with rim enhancement and a hypodense center. Only two dogs had a palpable axillary mass on physical examination. As measured, based on the largest dimension within a single slice, detectable masses ranged from 1.0 to 6.5 cm.


[Tuberculosis: steady dynamics between past and present to imagine the future].
Progress in understanding the biological processes that allow Mycobacterium tuberculosis to be a successful parasite have accelerated in the last twenty years. This progress has been stimulated by the return of tuberculosis (TB) as an important disease in industrialized countries, by its increase in emergent nations in the tail of population increases and poverty and by the spread of multiple drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis as a result of treatment failures. Progress on M. tuberculosis biology has also been fueled by advances in microbiology and molecular biology, including molecular genetics, genomics, proteomics and in vitro and in vivo models of infection. The study of latency or dormancy, a phenomenon central to understanding the persistence of M. tuberculosis and the development of TB in individuals, its spread in human populations and the emergence of antibiotic-resistant/tolerant organisms, has been preferred targets for investigators in this area. In this manner, factors that trigger M. tuberculosis latency (e. g, hypoxia, nutrient starvation, NO exposure) have been characterized and the metabolic shifts to host lipid utilization, tolerance to antimicrobials and resistance to host immune mechanisms involved in latency have been determined. Similarly, genetic changes and the resulting antimicrobial mechanisms mediating the MDR and XDR states have been characterized and potential new vaccines that avoid reactivation from latency and infection are being developed. Despite this progress, and given the fact that effective anti tuberculosis therapy was developed and first introduced clinically at the end of the 1940s, there are now more cases of latent and active TB worldwide than ever before. This reinforces the concept of TB as a bacterial disease with strong social and economical! determinants which are presently stimulating increased transmission in many human groups, undermining diagnostics, treatment and prevention. It suggests that in a scenario of global economical crisis the struggle against TB will be weakened, unless efforts are included to alleviate poverty, decrease economic inequality, improve public health and allow democracy and political organization.


Pathologic characteristics of pediatric intracranial pilocytic astrocytomas and their impact on outcome in 3 countries: a multi-institutional study.
Pilocytic astrocytoma (PA) is one of the most common glial neoplasms in the pediatric population, and its gross total resection can be curative. Treatment of partially resected or recurrent tumors is challenging, and the factors associated with increased recurrence risk are not well defined. Identification of favorable and unfavorable factors can lead to a better understanding and management of patients with PA. We studied the pathologic characteristics of 116 intracranial PAs from 4 institutions representing 3 distinct geographic regions to identify factors that may be associated with biological behavior. The study included 65 boys and 51 girls with a median age of 6 years. Median follow-up for all patients was 101 months, during which time 38 patients had recurrence. Progression-free and overall survivals were better in patients who underwent gross total resection. We were not able to identify any differences in pathologic and molecular markers among the 4 institutions from 3 different countries. However, progression-free survival varied significantly among institutions. Sox-2 was the most prevalent stem cell marker in PA, and many tumors showed synaptophysin positivity. BRAF immunostaining was not useful in determining BRAF duplication. BRAF duplication was more typical of posterior fossa tumors. There was a strong correlation between BRAF duplication and pERK immunostaining, suggesting that the RAF/MEK/ERK pathway is active in these tumors. This finding has significant implications given its role in oncogen-induced senescence and possible influence on treatment decisions of subtotally resected tumors.


Down's syndrome: an atheroma-free model?
Postmortem examination of five institutionalised patients with Down's syndrome (DS) aged 40-66 years showed a complete absence of atheroma, while a similar number of mental defectives with DS were found to have mild or severe atheroma. Previous investigation of risk factors for atheroma in 70 patients with DS and 70 age-and sex-matched mental defectives living in the same institution showed significantly lower systolic and diastolic blood pressures in the DS group, with the exception of systolic pressure in men under 40. Fasting serum cholesterol and triglyceride concentrations were similar in the two groups, but triglyceride concentrations were significantly lower than in normal people without a history of vascular disease. These unexplained observations may be relevant in further studies of the pathogenesis of atheroma.


The effect of visual salience on memory-based choices.
Deciding whether a stimulus is the "same" or "different" from a previous presented one involves integrating among the incoming sensory information, working memory, and perceptual decision making. Visual selective attention plays a crucial role in selecting the relevant information that informs a subsequent course of action. Previous studies have mainly investigated the role of visual attention during the encoding phase of working memory tasks. In this study, we investigate whether manipulation of bottom-up attention by changing stimulus visual salience impacts on later stages of memory-based decisions. In two experiments, we asked subjects to identify whether a stimulus had either the same or a different feature to that of a memorized sample. We manipulated visual salience of the test stimuli by varying a task-irrelevant feature contrast. Subjects chose a visually salient item more often when they looked for matching features and less often so when they looked for a nonmatch. This pattern of results indicates that salient items are more likely to be identified as a match. We interpret the findings in terms of capacity limitations at a comparison stage where a visually salient item is more likely to exhaust resources leading it to be prematurely parsed as a match.


Improving MR image quality in the presence of motion by using rephasing gradients.
Numerous techniques exist for suppressing ghosting artifacts due to respiratory motion on MR images. Although such methods can remove coherent ghosting artifacts, motion during gradient pulses also leads to poor image quality. This is due to phase variations at the echo caused by changes in velocity from one phase-encoding view to the next. The effect becomes severe for long sampling times and long TE values and can lead to low estimates of T2. We discuss general, robust modifications of the standard gradient or spin-echo sequences by using rephasing gradients that force the phase of constant-velocity moving spins to be zero at the echo. These sequences lead to a significant reduction in motion artifacts and hence improvement in image quality. They can be applied to multislice, multiecho, water/fat, and gating schemes as well. Since motion problems are universal, it would appear that these modified sequences should come into common usage for MR imaging.


Latex allergy in clinical practice.
A continuous exposure or contact to latex products may sensitize the human body by causing mild to fatal reactions. Despite the availability of the literature, medical personnel are still unaware of the implications of the use of latex materials. The increased awareness to prevent the transmission of infectious blood borne pathogens has lead to increased usage of medical gloves among health care workers. This increased usage of medical gloves, along with improved methods in diagnosing latex allergy, has been the reason for the rise in the number of reported cases. This has lead to recognition of latex allergy as a serious medical concern. Patients in high-risk groups must be assessed carefully, so that appropriate protocols can be used to protect them from contact with latex.


Effective iron chelation practice for patients with β-thalassemia major.
Chronic blood transfusion is the only treatment for severe anemia in patients with β-thalassemia major. However, red blood cell transfusions lead to iron overload and subsequent organ damage because of the toxic effects of iron. The heart is particularly vulnerable to iron toxicity, and heart failure is the leading cause of death among these patients. Iron chelation therapy prevents or reverses iron loading, thereby reducing the risk of complications from excess iron. Serum ferritin and liver iron concentration often are used to gauge the risk of organ iron overload, but these measurements may not correlate well with cardiac iron load. Magnetic resonance imaging (MRI) is a noninvasive diagnostic tool that can provide a more direct measure of iron concentration in both the heart and liver. Cardiac iron determined by MRI is expressed as a function of T2*, in which higher values represent lower concentrations. Changes in T2* are used to assess the effectiveness of iron chelation and to adjust therapy. Early treatment and compliance are keys to successful therapy. Nursing strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. The efficacy and safety of iron chelators, as well as nursing best practices, are reviewed.


Social shaping of food intervention initiatives at worksites: canteen takeaway schemes at two Danish hospitals.
The aim of this article is to analyse the social shaping of worksite food interventions at two Danish worksites. The overall aims are to contribute first, to the theoretical frameworks for the planning and analysis of food and health interventions at worksites and second, to a foodscape approach to worksite food interventions. The article is based on a case study of the design of a canteen takeaway (CTA) scheme for employees at two Danish hospitals. This was carried out as part of a project to investigate the shaping and impact of schemes that offer employees meals to buy, to take home or to eat at the worksite during irregular working hours. Data collection was carried out through semi-structured interviews with stakeholders within the two change processes. Two focus group interviews were also carried out at one hospital and results from a user survey carried out by other researchers at the other hospital were included. Theoretically, the study was based on the social constitution approach to change processes at worksites and a co-evolution approach to problem-solution complexes as part of change processes. Both interventions were initiated because of the need to improve the food supply for the evening shift and the work-life balance. The shaping of the schemes at the two hospitals became rather different change processes due to the local organizational processes shaped by previously developed norms and values. At one hospital the change process challenged norms and values about food culture and challenged ideas in the canteen kitchen about working hours. At the other hospital, the change was more of a learning process that aimed at finding the best way to offer a CTA scheme. Worksite health promotion practitioners should be aware that the intervention itself is an object of negotiation between different stakeholders at a worksite based on existing norms and values. The social contextual model and the setting approach to worksite health interventions lack reflections about how such norms and values might influence the shaping of the intervention. It is recommended that future planning and analyses of worksite health promotion interventions apply a combination of the social constitution approach to worksites and an integrated food supply and demand perspective based on analyses of the co-evolution of problem-solution complexes.


Time-critical social mobilization.
The World Wide Web is commonly seen as a platform that can harness the collective abilities of large numbers of people to accomplish tasks with unprecedented speed, accuracy, and scale. To explore the Web's ability for social mobilization, the Defense Advanced Research Projects Agency (DARPA) held the DARPA Network Challenge, in which competing teams were asked to locate 10 red weather balloons placed at locations around the continental United States. Using a recursive incentive mechanism that both spread information about the task and incentivized individuals to act, our team was able to find all 10 balloons in less than 9 hours, thus winning the Challenge. We analyzed the theoretical and practical properties of this mechanism and compared it with other approaches.


Directed neuronal differentiation of human embryonic stem cells.
We have developed a culture system for the efficient and directed differentiation of human embryonic stem cells (HESCs) to neural precursors and neurons.HESC were maintained by manual passaging and were differentiated to a morphologically distinct OCT-4+/SSEA-4- monolayer cell type prior to the derivation of embryoid bodies. Embryoid bodies were grown in suspension in serum free conditions, in the presence of 50% conditioned medium from the human hepatocarcinoma cell line HepG2 (MedII). A neural precursor population was observed within HESC derived serum free embryoid bodies cultured in MedII conditioned medium, around 7-10 days after derivation. The neural precursors were organized into rosettes comprised of a central cavity surrounded by ring of cells, 4 to 8 cells in width. The central cells within rosettes were proliferating, as indicated by the presence of condensed mitotic chromosomes and by phosphoHistone H3 immunostaining. When plated and maintained in adherent culture, the rosettes of neural precursors were surrounded by large interwoven networks of neurites. Immunostaining demonstrated the expression of nestin in rosettes and associated non-neuronal cell types, and a radial expression of Map-2 in rosettes. Differentiated neurons expressed the markers Map-2 and Neurofilament H, and a subpopulation of the neurons expressed tyrosine hydroxylase, a marker for dopaminergic neurons. This novel directed differentiation approach led to the efficient derivation of neuronal cultures from HESCs, including the differentiation of tyrosine hydroxylase expressing neurons. HESC were morphologically differentiated to a monolayer OCT-4+ cell type, which was used to derive embryoid bodies directly into serum free conditions. Exposure to the MedII conditioned medium enhanced the derivation of neural precursors, the first example of the effect of this conditioned medium on HESC.


Recent developments in sensing methods for eutrophying nutrients with a focus on automation for environmental applications.
The demand for autonomous sensors for unattended, continuous nutrient monitoring in water is rapidly growing with the increasing need for more frequent and widespread environmental pollution monitoring. Legislative bodies, local authorities and industries all require frequent water quality monitoring, however, this is time and labour intensive, and an expensive undertaking. Autonomous sensors allow for frequent, unattended data collection. While this solves the time and labour intensive aspects of water monitoring, sensors can be very expensive. Development of low-cost sensors is essential to realise the concept of Internet of Things (IoT). However there is much work yet to be done in this field. This article reviews current literature on the research and development efforts towards deployable autonomous sensors for phosphorus (in the form of phosphate) and nitrogen (in the form of nitrate), with a focus on analytical performance and cost considerations. Additionally, some recent sensing approaches that could be automated in the future are included, along with an overview of approaches to monitoring both nutrients. These approaches are compared with standard laboratory methods and also with commercially available sensors for both phosphate and nitrate. Application of nutrient sensors in agriculture is discussed as an example of how sensor networks can provide improvements in decision making.


Spontaneous expulsion of an intravesical bullet.
Gunshot wounds of the pelvis are not uncommon. Penetrating injuries of the bladder are usually documented by means of a cystogram. The patient reported here was shot with a small caliber bullet. No extravasation was demonstrated. The authors caution that not all penetrating injuries to the bladder will demonstrate extravasation on a properly performed cystogram.


Can metal ion complexes be used as polarizing agents for solution DNP? A theoretical discussion.
Dynamic nuclear polarization (DNP) can be used to dramatically increase the NMR signal intensities in solutions and solids. DNP is usually performed using nitroxide radicals as polarizing agents, characterized by sharp EPR lines, fast rotation, fast diffusion, and favorable distribution of the unpaired electron. These features make the nitroxide radicals ideally suited for solution DNP. Here, we report some theoretical considerations on the different behavior of some inorganic compounds with respect to nitroxide radicals. The relaxation profiles of slow relaxing paramagnetic metal aqua ions [copper(II), manganese(II), gadolinium(III) and oxovanadium(IV)] and complexes have been re-analyzed according to the standard theory for dipolar and contact relaxation, in order to estimate the coupling factor responsible for the maximum DNP enhancement that can be achieved in solution and its dependence on field, temperature and relative importance of outer-sphere versus inner-sphere relaxation.


Field-induced quantum soliton lattice in a frustrated two-leg spin-1/2 ladder.
Based on high-field (31)P nuclear magnetic resonance experiments and accompanying numerical calculations, it is argued that in the frustrated S=1/2 ladder compound BiCu(2)PO(6) a field-induced soliton lattice develops above a critical field of μ(0)H(c1)=20.96(7) T. Solitons result from the fractionalization of the S=1, bosonlike triplet excitations, which in other quantum antiferromagnets are commonly known to experience Bose-Einstein condensation or to crystallize in a superstructure. Unlike in spin-Peierls systems, these field-induced quantum domain walls do not arise from a state with broken translational symmetry and are triggered exclusively by magnetic frustration. Our model predicts yet another second-order phase transition at H(c2)>H(c1), driven by soliton-soliton interactions, most likely corresponding to the one observed in recent magnetocaloric and other bulk measurements.


NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination.
Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form synapses with glutamatergic neurons throughout the CNS. Although glutamate influences the proliferation and maturation of these progenitors in vitro, the role of NMDAR signaling in oligodendrogenesis and myelination in vivo is not known. Here, we investigated the consequences of genetically deleting the obligatory NMDAR subunit NR1 from OPCs and their oligodendrocyte progeny in the CNS of developing and mature mice. NMDAR-deficient OPCs proliferated normally, achieved appropriate densities in gray and white matter, and differentiated to form major white matter tracts without delay. OPCs also retained their characteristic physiological and morphological properties in the absence of NMDAR signaling and were able to form synapses with glutamatergic axons. However, expression of calcium-permeable AMPA receptors (AMPARs) was enhanced in NMDAR-deficient OPCs. These results suggest that NMDAR signaling is not used to control OPC development but to regulate AMPAR-dependent signaling with surrounding axons, pointing to additional functions for these ubiquitous glial cells.


Cattle MHC: evolution in action?
Because major histocompatibility complex (MHC) genes play a major role in the development of acquired immune responses, it is essential to obtain comparative information on their organisation, expression and possible functional dichotomies in different species. In human, three classical, polymorphic class I genes (HLA-A, B- and -C) and four expressed A/B class II gene pairs (HLA-DM, -DP, -DQ and -DR) are each present on all haplotypes. With the exception of the HLA-DRB loci, it has been assumed that a similar rigid organisational situation exists in other mammalian species. However, extensive analysis of the bovine MHC (BoLA) at both the genomic and transcriptional levels has revealed a degree of genetic fluidity not described in other species. None of the four (or more) classical class I genes identified is consistently expressed, and haplotypes differ from one another in both the number and composition of expressed class I genes. Similarly, in the class II region, the number of DQ genes varies between haplotypes in both number and composition. These variations in both class I and II (which appear to reflect differences at the genomic level) are likely to play an important role in cattle immune responses. The observed phenotypic differences in cattle demonstrate very clearly the dynamic nature of the MHC region. This review addresses the functional impact of such variation in different breeds and populations, and its significance in terms of MHC evolution.


Thrombosis in Cerebral Aneurysms and the Computational Modeling Thereof: A Review.
Thrombosis is a condition closely related to cerebral aneurysms and controlled thrombosis is the main purpose of endovascular embolization treatment. The mechanisms governing thrombus initiation and evolution in cerebral aneurysms have not been fully elucidated and this presents challenges for interventional planning. Significant effort has been directed towards developing computational methods aimed at streamlining the interventional planning process for unruptured cerebral aneurysm treatment. Included in these methods are computational models of thrombus development following endovascular device placement. The main challenge with developing computational models for thrombosis in disease cases is that there exists a wide body of literature that addresses various aspects of the clotting process, but it may not be obvious what information is of direct consequence for what modeling purpose (e.g., for understanding the effect of endovascular therapies). The aim of this review is to present the information so it will be of benefit to the community attempting to model cerebral aneurysm thrombosis for interventional planning purposes, in a simplified yet appropriate manner. The paper begins by explaining current understanding of physiological coagulation and highlights the documented distinctions between the physiological process and cerebral aneurysm thrombosis. Clinical observations of thrombosis following endovascular device placement are then presented. This is followed by a section detailing the demands placed on computational models developed for interventional planning. Finally, existing computational models of thrombosis are presented. This last section begins with description and discussion of physiological computational clotting models, as they are of immense value in understanding how to construct a general computational model of clotting. This is then followed by a review of computational models of clotting in cerebral aneurysms, specifically. Even though some progress has been made towards computational predictions of thrombosis following device placement in cerebral aneurysms, many gaps still remain. Answering the key questions will require the combined efforts of the clinical, experimental and computational communities.


Evaluation of active dried yeast in the diets of feedlot steers-I: Effects on feeding performance traits, the composition of growth, and carcass characteristics1.
The use of active dried yeast (ADY) in the diets of feedlot steers may improve feed efficiency, growth performance, and reduce days on feed. Strategic timing of ADY inclusion in the diet may increase feed conversion or aid in the dietary transition from growing to finishing diets. One hundred twenty steers, blocked by weight, were fed four diets for 164 d: grower (70 d), first transition diet (7 d), second transition diet for (7 d), and finisher (80 d) in a GrowSafe System. Four treatment sequences of ADY inclusion were evaluated in a Balaam's design where steers were fed a control diet before and after the grower phase (CC), control before and ADY after the grower phase (CY), ADY before and control after the grower phase (YC), and ADY before and after the grower phase (YY). A random coefficients model was used to evaluate the following variables of interest: feeding performance and growth traits, including biometric measurements and carcass ultrasound measurements, and carcass characteristics. Treatment was a fixed effect and block was a random effect. Treatment did not affect feeding performance or behavior (P ≥ 0.14). The rate of change of biometric measurements were not different (P ≥ 0.16) across treatment groups except for rib girth circumference, which was greater for the YY and CY groups intermediate for the CC group and least for the YC group (0.828 and 0.809 vs. 0.751 vs. 0.666 cm/d, respectively; P < 0.01). Faster growth rates of rib girth circumference resulted in larger final measurements for steers that were finished on ADY (P < 0.01). Ultrasound measurements (backfat, LM area, intra-muscular fat, and rump fat) were not different across treatments (P ≥ 0.15). However, there was a tendency for the YC group to have a slower rate of back fat deposition than other treatment groups (P = 0.09). Steers' final shrunk BWs did not differ (P = 0.61), but shrink percentage was greater for CC than for YY groups (3.7% vs. 2.7%, respectively; P = 0.05). Carcass characteristics were not different across treatments (P ≥ 0.20). Crude fat, CP, ash and moisture analyses of the 9th to 11th rib section were not different across treatments, and there was no difference in adjusted final shrunk BW (P ≥ 0.45). Feeding the ADY strain used in this study to growing and finishing feedlot steers increased rib girth circumference development rate and reduced shrink loss without affecting feeding behavior, feeding performance, or carcass characteristics.


Safety and immunogenicity of an 8 year interval heterologous prime-boost influenza A/H7N7-H7N9 vaccination.
Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of "boosting" with IIV1 A/H7N9 in subjects "primed" 8 years previously with IIV1 A/H7N7. We administered 1 booster dose containing 45 mcg of IIV1 A/H7N9 hemagglutinin to 17 recipients of 2 prior doses of IIV1 A/H7N7, and to 10 influenza A/H7-naïve subjects. We tested their post-boosting sera for antibodies (Ab) against homologous influenza A/H7N9 using a hemagglutination inhibition assay; and compared their Ab titers to those in stored sera from recipients of AS03-adjuvanted IIV1 A/H7N9 against 9 strains of influenza A/H7N9 viruses. The percentage of subjects with Ab titers ≥40 on Days 9 and 29 post boosting, respectively, was 65% and 41% in primed subjects and 10% and 0% in unprimed subjects. The Ab titers in recipients of AS03-adjuvanted IIV1 A/H7N9 were higher than those in the prime-boost group against a panel of influenza A/H7N9 viruses, except for 2 highly pathogenic strains. Priming with IIV1 A/H7 results in serological responses following a delayed boost with 1 dose of unadjuvanted IIV1 A/H7N9, despite lack of antibody response after the prime. Optimizing prime-boost approaches would benefit pandemic preparedness. ClinicalTrials.gov identifier: NCT02586792.


Test-Retest Reliability of EQ-5D-5L Valuation Techniques: The Composite Time Trade-Off and Discrete Choice Experiments.
To explore the test-retest reliability of the composite time trade-off (C-TTO) and discrete choice experiment (DCE) used in the Indonesian five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) valuation study. A representative sample aged 17 years and older was recruited from the Indonesian general population by stratified quota sampling with respect to residence, sex, and age. Trained interviewers conducted computer-assisted face-to-face interviews using the EuroQol valuation technology. Each respondent valued 10 health states using C-TTO and 7 pairs of health states in a DCE exercise. The retest interview was conducted after 2 weeks by the same interviewer. The Wilcoxon matched-pairs signed-rank test, intraclass correlation coefficient, and multilevel regression were applied in comparing the C-TTO test and retest data. For DCE, the analysis of proportions was used. A total of 226 respondents with characteristics similar to the Indonesian population completed the retest interview. For C-TTO, 82 (95.3%) of 86 health states had no significant mean value differences between test and retest. The mean value of the second test was statistically significantly higher than that of the first test by 0.042. For DCE, 72.5% of responses were identical. DCE retest showed a different pattern concerning the relative importance of the dimensions, whereas the C-TTO remained the same. C-TTO is stable over time, whereas in DCE the relative values of the dimensions shift. The results support the use of the C-TTO, in particular the Indonesian EQ-5D-5L value set, and suggest a critical examination of the reliability of DCE results over time.


A comparison of salivary calprotectin levels in subjects with and without oral candidiasis.
The purpose of this study was to compare salivary calprotectin levels in subjects with oral candidiasis to the levels in healthy age- and sex-matched control subjects and to investigate the relationship of salivary calprotectin to intensity of oral candidal carriage and infection and to predisposing factors for candidiasis. Using enzyme-linked immunosorbent assay, we measured calprotectin in unstimulated whole saliva collected from 22 subjects with oral candidiasis and in saliva collected from 22 control subjects. Calprotectin levels in the 2 groups were compared by using the Wilcoxon signed rank test. The relationships between calprotectin levels and Candida counts were assessed by using the Spearman rank correlation test. The nonparametric 1-way analysis of variance test was used to study the relationship between calprotectin levels and presence of non-albicans Candida and individual predisposing factors for candidiasis. The Kruskal-Wallis test was used to evaluate the relationship between calprotectin and predisposing factors in subjects grouped by total number of predisposing factors identified. No relationship was found between calprotectin and individual or total number of predisposing factors. Higher calprotectin levels were found in subjects with candidiasis, and calprotectin concentration positively correlated with intensity of candidal infection. These findings suggest that calprotectin production, or release, or both, may be increased in subjects with candidiasis.


Active transport of Ca2+ by an artificial photosynthetic membrane.
Transport of calcium ions across membranes and against a thermodynamic gradient is essential to many biological processes, including muscle contraction, the citric acid cycle, glycogen metabolism, release of neurotransmitters, vision, biological signal transduction and immune response. Synthetic systems that transport metal ions across lipid or liquid membranes are well known, and in some cases light has been used to facilitate transport. Typically, a carrier molecule located in a symmetric membrane binds the ion from aqueous solution on one side and releases it on the other. The thermodynamic driving force is provided by an ion concentration difference between the two aqueous solutions, coupling to such a gradient in an auxiliary species, or photomodulation of the carrier by an asymmetric photon flux. Here we report a different approach, in which active transport is driven not by concentration gradients, but by light-induced electron transfer in a photoactive molecule that is asymmetrically disposed across a lipid bilayer. The system comprises a synthetic, light-driven transmembrane Ca2+ pump based on a redox-sensitive, lipophilic Ca2+-binding shuttle molecule whose function is powered by an intramembrane artificial photosynthetic reaction centre. The resulting structure transports calcium ions across the bilayer of a liposome to develop both a calcium ion concentration gradient and a membrane potential, expanding Mitchell's concept of a redox loop mechanism for protons to include divalent cations. Although the quantum yield is relatively low (approximately 1 per cent), the Ca2+ electrochemical potential developed is significant.


Assessment of Antioxidant Properties in Fruits of Myrica esculenta: A Popular Wild Edible Species in Indian Himalayan Region.
Crude extract of Myrica esculenta fruits, a wild edible species of Indian Himalayan Region, was evaluated for phenolic compounds and antioxidant properties. Results revealed significant variation in total phenolic and flavonoid contents across populations. Among populations, total phenolic content varied between 1.78 and 2.51 mg gallic acid equivalent/g fresh weight (fw) of fruits and total flavonoids ranged between 1.31 and 1.59 mg quercetin equivalent/g fw. Antioxidant activity determined by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging, 1,1-diphenyl-2-picrylhydrazyl radical scavenging and ferric reducing antioxidant power (FRAP) exhibited considerable antioxidant potential and showed significant positive correlation with total phenolic and total flavonoids content. High performance liquid chromatography analysis revealed significant variation (P < .01) in phenolic compounds (i.e., gallic acid, catechin, hydroxybenzioc acid and ρ-coumaric acid) across populations. This study provides evidences to establish that consumption of M. esculenta fruits while providing relished taste would also help in reduction of free radicals. Therefore, this wild edible species deserves promotion in the region through horticulture and forestry interventions.


Dietary Interventions and Type 2 Diabetes in Youth: a Fresh Look at the Evidence.
The incidence of type 2 diabetes among children and adolescents has sharply increased, highly influenced by prevalence of obesity in youth. Here, we provide an overview of the pathogenesis of diabetes, and summarize recent dietary interventions investigating effects of diet on metabolic risk factors in overweight and obese youth. Seven dietary interventions were identified randomly assigning participants to weekly or bi-weekly dietary counseling sessions over 12-24-week period, with mixed results. Four interventions showed significant reductions in fasting insulin and insulin resistance levels relative to baseline concentrations ranging from 26 to 50%. Recent evidence is mixed, with four studies showing improvements to insulin concentrations and insulin resistance in obese children and adolescents associated with energy restriction and/or change to carbohydrate consumption. Further work is needed to investigate long-term effects of dietary factors including carbohydrate quality and energy restriction on metabolic health and diabetes prevention early in life.


Fabrication of Low-Cost Flexible Superhydrophobic Antibacterial Surface with Dual-Scale Roughness.
In this work, we report a large-area fabrication of a flexible superhydrophobic bactericidal surface decorated with copper hydroxide nanowires. This involves a simple two-step method which involves growth followed by transfer of the nanowires onto the polydimethylsiloxane (PDMS) surface by mechanical peeling. Additional roughness in PDMS is obtained through incomplete wetting of the nanoscale gaps which leads to dual-scale roughness and superhydrophobicity with a contact angle of 169° and hysteresis of less than 2°. The simplicity of the process makes it low-cost and easily scalable. The process allows fabrication of nonplanar 3D surfaces. The surface shows blood repellence and antibacterial activity against Escherichia coli with more than 5 log reductions in bacterial colony. The surface also shows hemocompatible behavior, making it suitable for healthcare applications. The fabricated surface is found to be extremely robust against stretching, twisting, sandpaper abrasion, solid weight impact, and tape peel test. The surface is found to withstand human weight multiple times without losing its hydrophobicity, making it suitable for several practical scenarios in healthcare and household applications.


Modeling culture profiles of the heterocystous N2-fixing cyanobacterium Anabaena flos-aquae.
Heterocyst differentiation is a unique feature of nitrogen-fixing cyanobacteria, potentially important for photobiological hydrogen production. Despite the significant advances in genetic investigation on heterocyst differentiation, there were no quantitative culture-level models that describe the effects of cellular activities and cultivation conditions on the heterocyst differentiation. Such a model was developed in this study, incorporating photosynthetic growth of vegetative cells, heterocyst differentiation, self-shading effect on light penetration, and nitrogen fixation. The model parameters were determined by fitting experimental results from the growth of the heterocystous cyanobacterium Anabaena flos-aquae CCAP 1403/13f in media without and with different nitrate concentrations and under continuous illumination of white light at different light intensities (2, 5, 10, 17, 20 and 50 microE m-2 s-1). The model describes the experimental profiles well and gives reasonable predictions even for the transition of growth from that on external N source to that via nitrogen fixation, responding to the change in external N concentrations. The significance and implications of the best-fit values of the model parameters are discussed.


A Novel Web Application for Rapidly Searching the Diagnostic Case Archive.
Academic pathologists must have the ability to search their institution's archive of diagnostic case data. This ability is foundational for research, education, and other academic activities. However, the built-in search functions of commercial laboratory information systems are not always optimized for this activity, leading to delays between an initial search request, and eventual results delivery. To solve this problem, a novel web-based search platform was developed, named Pathtools, which allows our staff and trainees to directly and rapidly search our diagnostic case archive. Pathtools was built with open-source components and features a web-based user-interface. Pathtools uses an SQL database which was populated with anatomic pathology case data going back to 1980, and contains 4.2 million cases (as of July 31, 2020). Pathtools has two major modes of operation, "Preview Mode" and "Research Mode." Since deployment in February of 2019, Pathtools carried out 33,817 searches in Preview Mode, averaging 0.72 s (standard deviation = 1.7) between search submission, and on-screen display of search results. In Research Mode, Pathtools has also been used to produce data sets for research activity, providing the data used in many abstracts and manuscripts our investigators submitted recently. Interestingly, 75% of search activity is from trainees during their preview time. In a survey of residents and fellows, 83% used Pathtools during the majority of their preview sessions, demonstrating an important role for this resource in trainee education. In conclusion, a web-based search tool can rapidly and securely provide search capability directly to end-users, which has augmented trainee education and research activity in our department.


Fluorescent in situ hybridization evaluation of human Y-bearing spermatozoa separated by albumin density gradients.
Fluorescent in situ hybridization of decondensed sperm nuclei was employed to evaluate the effectiveness of the Ericsson albumin gradient enrichment technique of Y-bearing sperm. Mature human spermatozoa were separated from donor- and randomly selected patient semen using three different albumin density layers. Sperm nuclei, in the albumin layer with highest density, were decondensed and the percentage Y-bearing sperm was determined by fluorescent in situ hybridization. A slight, although statistically significant, increase in percentage Y-bearing sperm was observed. Although statistically significant, the clinical relevance of the small increase in Y-bearing sperm remains uncertain. A randomized controlled clinical study should help to clarify the above laboratory results.


Reduced corneal nerve fibre length in prediabetes and type 2 diabetes: The Maastricht Study.
In individuals with diabetes, injury to the corneal nerve fibres predisposes to delayed corneal epithelial healing, reduced corneal sensitivity and corneal erosion. We investigated to what extent a reduction in corneal nerve fibre length (CNFL) is present in individuals with prediabetes or type 2 diabetes (DM2) compared with individuals with normal glucose metabolism (NGM). Using composite images acquired by corneal confocal microscopy, we assessed total CNFL per mm2 in the subbasal nerve plexus of the cornea in 134 participants (mean age 59 ± 8 years, 49% men, 87 NGM, 20 prediabetes, 27 DM2). Multivariable linear regression was used to assess the association between CNFL and glucose metabolism status, adjusted for age and sex. In individuals with type 2 diabetes, the mean CNFL was significantly reduced [β = -1.86 mm/mm2 (95% CI -3.64 to -0.08), p = 0.04], as compared with individuals with normal glucose metabolism after adjustment for age and sex. Part of the reduction was present in individuals with prediabetes [β = -0.96 mm/mm2 (95% CI -2.91 to 0.99), p = 0.34], with a linear trend of corneal nerve fibre reduction with severity of glucose metabolism status (p trend = 0.04). A significant reduction in CNFL was found in individuals with DM2 compared with individuals with NGM. A trend of reduction in CNFL was observed between individuals with NGM and prediabetes. The reduction in corneal nerve fibre length could contribute to a delayed corneal healing and an increased risk for corneal complications after surgery.