The contribution of the supplementary motor area to explicit and implicit timing: A high-definition transcranial Random Noise Stimulation (HD-tRNS) study.

It is becoming increasingly accepted that timing tasks, and underlying temporal processes, can be partitioned on the basis of whether they require an explicit or implicit temporal judgement. Most neuroimaging studies of timing associated explicit timing tasks with activation of the supplementary motor area (SMA). However, transcranial magnetic stimulation (TMS) studies perturbing SMA functioning across explicit timing tasks have generally reported null effects, thus failing to causally link SMA to explicit timing. The present study probed the involvement of SMA in both explicit and implicit timing tasks within a single experiment and using High-Definition transcranial Random Noise Stimulation (HD-tRNS), a previously less used technique in studies of the SMA. Participants performed two tasks that comprised the same stimulus presentation but differed in the received task instructions, which might or might not require explicit temporal judgments. Results showed a significant HD-tRNS-induced shift of perceived durations (i.e., overestimation) in the explicit timing task, whereas there was no modulation of implicit timing by HD-tRNS. Overall, these results provide initial non-invasive brain stimulation evidence on the contribution of the SMA to explicit and implicit timing tasks.

Unmet dental and orthodontic need of children with special healthcare needs in West Virginia.

INTRODUCTION: Of children aged 0-17 years in the USA, an estimated 11 203 616 (15.1%; 95% CI: 14.8, 15.3) are Children with Special Health Care Needs (CSHCN). The state of West Virginia, the heart of Appalachia, has a land mass which is 97.65% rural with previously identified high overall dental need and oral health disparities. It is home to an estimated 70 609 CSHCN, or 18.5% (95% CI: 17.0, 19.9) of the state's children in 2009-2010. The purpose of this study was to determine the parent/guardian's perceived unmet dental care need of CSHCN in West Virginia. METHODS: Data from the National Survey of Children with Special Health Care Needs was used to determine prevalence. A telephone survey of 59 941 parents/guardians of CSHCN (1149 from West Virginia) for the dental interview was conducted in 2009-2010. RESULTS: Nationwide, 26.7% (25.9, 27.5) of parents/guardians reported their CSHCN had dental care or orthodontia needs other than preventive care. In West Virginia, the perceived dental care or orthodontia needs other than preventive dental care need was 26.5% (22.2, 30.0). Unmet national dental care need other than preventive dental care was 5.4% (5.0, 5.9) and in West Virginia 5.0% (2.4, 7.5). CONCLUSIONS: CSHCN have significant unmet dental needs. Parents/guardians in West Virginia reported similar unmet need compared with national reporting. Policies to address the health care of CSHCN should include dental needs. The clinical implications are that CSHCN have a variety of needs, including orthodontia. The benefits of orthodontic referrals should be considered in treatment planning options for CSHCN.

Breastfeeding prevalence and distribution in the USA and Appalachia by rural and urban setting.

INTRODUCTION: Breastfeeding provides health benefits to infants and mothers, yet many women decide against breastfeeding. This study examined differences in the prevalence of breastfeeding among national, urban, rural, and Appalachian regions of the USA. METHODS: Secondary data analysis of the US 2007 National Survey of Children's Health (n=27 388) data were completed for prevalence, insurance coverage, and medical home (a source of comprehensive primary care) determinations according to rural or urban location. RESULTS: The weighted US and Appalachian prevalences of breastfeeding were 0.755 (CI 0.743-0.767) and 0.683 (CI 0.672-0.694). National and Appalachian urban prevalences were 0.770 (CI 0.757-0.784) and 0.715 (CI 0.702-0.728). Rural areas had a significantly lower prevalence of breastfeeding of 0.687 (CI 0.661-0.713). Appalachia was significantly lower than the national rural level at 0.576 (CI 0.554-0.598). Women with Medicaid/State Children's Health Insurance Program (SCHIP) had an odds ratio of 1.79 of not breastfeeding compared with privately insured women. Nationally, 26.6% (CI 24.5-28.7) of children of women who did not breastfeed did not have a medical home. CONCLUSIONS: Anticipatory guidance about breastfeeding with culturally sensitive awareness programs and interventions directed at rural populations, especially in high risk geographic areas such as Appalachia, may be needed. Healthcare professionals have a unique opportunity to provide anticipatory guidance to pregnant women by discussing the benefits of breastfeeding during visits. High school health educational programs should address the benefits of breastfeeding with rural females.

Time series analysis of water use and indirect reuse within a HUC-4 basin (Wabash) over a nine year period.

Anthropogenic water use and reuse represent major components of the water cycle. In the context of climate change, water reuse and recycling are considered necessary components for an integrated water management approach. Unplanned, or de facto, indirect water reuse occurs in most of the U.S. river systems, however, there is little real-time documentation of it. Despite the fact that there are national and state agencies that systematically collect data on water withdrawals and wastewater discharges, their databases are organized and managed in a way that makes it challenging to use them for water resource management analysis. The ability to combine reported water data to perform large scale analysis about water use and reuse is severely limited. In this paper, we apply a simple but effective methodology to complete a time series watershed-scale analysis of water use and unplanned indirect reuse for the Wabash River Watershed. Results document the occurrence of indirect water reuse, ranging from 3% to 134%, in a water-rich area of the U.S. The time series analysis shows that reported data effectively describe the water use trends through nine years, from 2009 to 2017, clearly reflecting both anthropogenic and natural events in the watershed, such as the retirement of thermoelectric power plants, and the occurrence of an extreme drought in 2012. We demonstrate the feasibility and significance of using available water datasets to perform large scale water use analysis, describe limitations encountered in the process, and highlight areas for improvement in water data management.

Abnormal thyroid function in older men with or at risk for HIV infection.

OBJECTIVES: The aim of the study was to evaluate the prevalence of and factors associated with abnormal thyroid function in older men with or at risk for HIV infection. METHODS: A cross-sectional analysis of 636 men > or =49 years old was carried out using data obtained from interviews, from measurements of body mass index (BMI), HIV-1 serology and viral load, CD4 cell count, hepatitis C virus (HCV) assays, thyroid-stimulating hormone (TSH) and free thyroid hormone levels. RESULTS: Participants were 54% black, 57% overweight/obese, 57% HIV seropositive, and 72% HCV seropositive; 38% reported recent cocaine or heroin use. Decreased TSH was found in 56 men (8.8%) and raised TSH in 23 men (3.6%). Only three men had abnormal free thyroxine levels. CONCLUSIONS: Abnormal TSH levels were noted in 12.4% of older men with or at risk for HIV infection, but nearly all reflected subclinical hyperthyroidism or subclinical hypothyroidism.

Follow-up schedules after treatment for malignant melanoma.

BACKGROUND: Existing follow-up guidelines after treatment for melanoma are based largely on dated literature and historical precedent. This study aimed to calculate recurrence rates and establish prognostic factors for recurrence to help redesign a follow-up schedule. METHODS: Data were retrieved from the Sydney Melanoma Unit database for all patients with a single primary melanoma and American Joint Committee on Cancer (AJCC) stage I-II disease, who had received their first treatment between 1959 and 2002. Recurrence rates, timing and survival were recorded by substage, and predictive factors were analysed. RESULTS: Recurrence occurred in 18.9 per cent (895 of 4748) of patients overall, 5.2 per cent (95 of 1822) of those with stage IA disease, 18.4 per cent (264 of 1436) with IB, 28.7 per cent (215 of 750) with IIA, 40.6 per cent (213 of 524) with IIB and 44.3 per cent (86 of 194) with IIC disease. Overall, the median disease-free survival time was 2.6 years, but there were marked differences between AJCC subgroups. Primary tumour thickness, ulceration and tumour mitotic rate were important predictors of recurrence. CONCLUSION: A new follow-up schedule was proposed: stage I annually, stage IIA 6-monthly for 2 years and then annually, stage IIB-IIC 4-monthly for 2 years, 6-monthly in the third year and annually thereafter.

Ion-channel-forming colicins.

Several features of ion-channel-forming colicins have been illuminated by recent revelations: its four-domain structure, the mechanism and thermodynamics of binding to the gating loop of outer membrane porins, the mechanism of translocation, competition for the transperiplasmic excursion facilitated by the Tol or Ton transperiplasmic proteins, and the formation of a waisted, funnel-shaped transmembrane channel of well-characterized shape.

Bacterial export takes its Tol.

The recent crystal structure of TolC elegantly indicates its function and provides insight into its mechanism for export of a wide range of molecules across the periplasmic space and outer membrane of Gram-negative bacteria. The structure is compared to those of other proteins that are embedded in bacterial outer membranes or that traverse the periplasmic space.

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Structure of fully hydrated bilayer dispersions.

A systemic formalism is developed that shows how the results for absolute specific volumes of multilamellar lipid dispersions may be combined with results from diffraction studies to obtain quantitative characterizations of the average structure of fully hydrated lipid bilayers. Quantities obtained are the area per molecule, the thickness and volumes of the bilayer, the water layer, the hydrocarbon chain layer and the headgroup layer, and where appropriate, the tilt angle of the hydrocarbon chains. In the case of the C phase of DPPC this formalism leads to the detection of inconsistencies between three data. Results for the G phases of DPPC and DLPE are in reasonable agreement with, though more comprehensive than, previous work that used fewer data and equations. Various diffraction data for the F phase of DPPC are in disagreement and it is shown how this disagreement affects results for the bilayer structure. A recent method of McIntosh and Simon for obtaining fluid phase structure utilizing gel phase structure is slightly modified to obtain results for the F phase of DLPE. Methods of obtaining the average methylene and methyl volumes in the fluid phases are critically examined.

New phases of DPPC/water mixtures.

Hydration of DPPC at low temperatures yielded two new phases, a non-lamellar C1 phase and a lamellar C2 phase, as well as the normal gel phase, depending upon the initial physical state of the dry lipid. From the results of wide-angle diffraction and calorimetry the C2 phase appears very similar to the normal C phase, but the D spacing is considerably larger, suggesting that the C2 phase is a C phase with untilted chains.

Dilatometric studies of isobranched phosphatidylcholines.

Absolute apparent specific volumes have been obtained for phosphatidylcholine lipids with saturated, isobranched hydrocarbon chains with ni = 15 to 20 carbons, with an emphasis upon phase transition behavior, both equilibrium and kinetic. The temperature of the chain-melting transition extrapolates with increasing chain length to the melting temperature of polyethylene with a small odd/even alternation. There are also odd/even alternations in the volume of transition and in the hysteresis of the chain-melting transition, but with the odd and even reversed when compared with the larger odd/even alternation in the lower solid-solid transition that occurs in the longer chain ni lipids. A phenomenological picture is given for the coalescence of the two transitions for shorter ni lipids and this picture is used to sharpen the discussion of the kinetic mechanism of melting. A temperature-reversal experiment shows that the melting from the lowest temperature crystal or C phase to the fluid F phase does not proceed via the metastable gel G phase for 16i. The dilatometric results are combined with recent X-ray structural results for the C and G phases of 17i and 20i to deduce various structural information, including the hydration numbers and the volume of the headgroup, VH = 341 A3, which agrees very well with VH for straight-chain phosphatidylcholines. For the chain-melted F phase the assumption that the methylene volumes of the different ni lipids should be the same at the same temperature is used to obtain the volumes of the methylene and the methyl groups.

Specific volumes of lipids in fully hydrated bilayer dispersions.

The neutral buoyancy method of obtaining absolute specific volumes of lipid in multilamellar dispersions is critically investigated. Control experiments show that there is no preferential partitioning of 2H2O vs. H2O into the liposomes, and several thermodynamic properties of the samples, such as the enthalpy change and the volume change of the main transition, are changed very little with deuteration of the solvent. The assumption that the molecular volume of the solvent in the interlamellar space is essentially the same as in bulk solution is discussed; and it is shown to introduce rather small corrections. Previous procedures have been modified to avoid possible kinetic limitations in phases with low water permeability. It is concluded that the molecular volume of lipid in bilayers can be obtained to an accuracy better than 0.002 nm3 (2A3) which is less than 0.2% of typical molecular volumes of lipids.

Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens.

Alpha1 -adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A -adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L -adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [(3) H]tamsulosin binding experiments to identify the α1 -adrenoceptor subtype population present in the human vas deferens. The α1A -adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D -adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A - and α1D -adrenoceptor selective) had a high affinity (pKd = 9.9). [(3) H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [(3) H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively). These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1 -adrenoceptors which have the pharmacological properties of the putative α1L -adrenoceptor, the same functional receptor previously identified in the human prostate.

Outer membrane protein A of E. coli folds into detergent micelles, but not in the presence of monomeric detergent.

Outer membrane protein A (OmpA) of Escherichia coli is a beta-barrel membrane protein that unfolds in 8 M urea to a random coil. OmpA refolds upon urea dilution in the presence of certain detergents or lipids. To examine the minimal requirements for secondary and tertiary structure formation in beta-barrel membrane proteins, folding of OmpA was studied as a function of the hydrophobic chain length, the chemical structure of the polar headgroup, and the concentration of a large array of amphiphiles. OmpA folded in the presence of detergents only above a critical minimal chain length of the apolar chain as determined by circular dichroism spectroscopy and a SDS-PAGE assay that measures tertiary structure formation. Details of the chemical structure of the polar headgroup were unimportant for folding. The minimal chain length required for folding correlated with the critical micelle concentration in each detergent series. Therefore, OmpA requires preformed detergent micelles for folding and does not adsorb monomeric detergent to its perimeter after folding. Formation of secondary and tertiary structure is thermodynamically coupled and strictly dependent on the interaction with aggregated amphiphiles.

Mesoscopic surfactant organization and membrane protein crystallization.

The paucity of detailed X-ray crystallographic structures of integral membrane proteins arises from substantive technical obstacles in the overexpression of multimilligram quantities of protein, and in the crystallization of purified protein-detergent complexes (PDCs). With rare exception, crystal contacts within the lattice are mediated by protein-protein interaction, and the detergent surrounding the protein behaves as a disordered solvent. The addition and use of surfactants that display mesoscopic self-assembly behavior in membrane protein crystallization experiments presents a novel alternative strategy. Well-ordered crystals of the water channel human aquaporin-1 (hAQP1) that diffract to 4 A resolution have been obtained with this approach.

Species differences in the handling of lysosomotropic metals and Triton WR 1339 by rat and Chinese hamster liver.

The study was undertaken in order to understand the reasons for the distinct differences in the elimination rate of lanthanides and transuranium elements from the liver of different mammalian species. The binding of monomeric 239Pu in livers of rats and Chinese hamsters was analyzed by density gradient centrifugation and electrophoresis. It was concluded that this nuclide is initially bound to lysosomes in liver of rats and Chinese hamsters. The influence of Triton WR 1339 (TWR) on the density of lysosomal marker enzymes from rat and Chinese hamster liver at day 4 was very similar for both animal species but the TWR induced shift persisted in Chinese hamsters up to day 60 whereas in rat liver the lysosomal density increased again with time. Electron microscopic inspection confirmed the similarity of the initial reaction of hepatocyte lysosomes. However, after 60 to 70 days typical TWR induced "tritosomes" were absent from rat hepatocytes but could be found regularly in hepatocytes from Chinese hamsters. The elimination rate of 3H-activity from liver injection of 3H-TWR was lower in Chinese hamsters than in rats. It was concluded that the differences in elimination rate of lanthanides and transuranium elements from liver of various mammalian species and the differences observed after TWR injection might reflect differences in the composition or function of the lysosomal system in the livers of different mammalian species. With respect to the transport of certain heavy metals the rat liver is not a reliable model for human liver.

Expression, purification, and initial structural characterization of YadQ, a bacterial homolog of mammalian ClC chloride channel proteins.

YadQ of Escherichia coli is a homolog of the mammalian chloride channels of the ClC family. The yadQ gene was cloned as a fusion protein with a hexahistidine tag and tobacco etch virus protease site for the removal of the tag. The protein was expressed in the membrane of E. coli and extracted with decylmaltoside. Purification was achieved by metal affinity chromatography followed by cation exchange. Circular dichroism revealed a high alpha-helical content. Size exclusion chromatography suggests that YadQ forms dimers. The similarity in primary, secondary, and quaternary structure and the ability to recombinantly express YadQ in the cell membrane make the protein a good candidate for the structural study of ClC chloride channels.

Control of placental 3 beta-hydroxy-delta 5-steroid dehydrogenase: partial characterization of an endogenous inhibitor and an endogenous activator.

Two substances which affect the activity and kinetic characteristics of 3 beta-hydroxy-delta 5-steroid dehydrogenase (delta 5-3 beta-HSD) have been recovered from homogenates of term human placenta by extraction with organic solvents after ethanol precipitation of protein. One of these substances, an inhibitor of the enzyme, is a non-polar unstable substance, which dialyzes through a cellulose nitrate membrane and which appears to be present in the tissue both in the free state and bound to either the enzyme or the microsomal membrane. It was not possible to produce a delta 5-3 beta-HSD preparation free of the inhibitor. The other substance is an activator, polar and stable with a molecular weight of less then 500, which increases both the apparent Km and the apparent V max of delta 5-3 beta-HSD. It is postulated that both substances play a part in control of placental progesterone synthesis.