Prevalence of and Barriers to Dual-Contraceptive Methods Use among Married Men and Women Living with HIV in India

Objective. To describe the prevalence and correlates of dual-contraceptive methods use (condoms and an effective pregnancy prevention method) and barriers to their use among married persons living with HIV (PLHIV) in India. Methods. We conducted a quantitative survey (93 men, 97 women), 25 in-depth interviews, seven focus groups, and five key informant interviews. Results. Prevalence of dual- contraceptive method use increased from 5% before HIV diagnosis to 23% after diagnosis (P < 0.001). Condoms were the most common contraceptive method, with prevalence increasing from 13% before diagnosis to 92% after diagnosis (P < 0.001). Barriers to using noncondom contraceptives were lack of discussion about noncondom contraceptives by health care providers, lack of acceptability of noncondom contraceptives among PLHIV, and lack of involvement of husbands in family planning counseling. Conclusion. There is a need for interventions, including training of health care providers, to increase dual-contraceptive methods use among married PLHIV

Direct replacement of oral sodium benzoate with glycerol phenylbutyrate in children with urea cycle disorders

Long-term management of urea cycle disorders (UCDs) often involves unlicensed oral sodium benzoate (NaBz) which has a high volume and unpleasant taste. A more palatable treatment is licenced and available (glycerol phenylbutyrate [GPB], Ravicti) but guidance on how to transition patients from NaBz is lacking. A retrospective analysis of clinical and biochemical data was performed for eight children who transitioned from treatment with a single ammonia scavenger, NaBz, to GPB at a single metabolic centre; UCDs included arginosuccinic aciduria (ASA) (n = 5), citrullinaemia type 1 (n = 2) and carbamoyl phosphate synthetase I deficiency (CPS1) (n = 1). Patients transitioned either by gradual transition over 1–2 weeks (n = 3) or direct replacement of NaBz with GPB (n = 5). Median initial dose of GPB was 8.5 mL/m2/day based on published product information; doses were revisited subsequently in clinic and titrated individually (range 4.5–11 mL/m2/day). Pre-transition and post-transition mean ammonia levels were 37 μmol/L (SD 28 μmol/L) and 29 μmol/L (SD 22 μmol/L), respectively (p = 0.09), and mean glutamine levels were 664 μmol/L (SD 225 μmol/L) and 598 μmol/L (SD 185 μmol/L), respectively (p = 0.24). There were no reductions in levels of branched chain amino acids. No related adverse drug reactions were reported. Patients preferred GPB because of its lower volume and greater palatability. Direct replacement of NaBz with GPB maintained metabolic control and was simple for the health service and patients to manage. A more cautious approach with additional monitoring would be warranted in brittle patients and patients whose ammonia levels are difficult to control

Atomic Hole Doping of Graphene

Graphene is an excellent candidate for the next generation of electronic materials due to the strict two-dimensionality of its electronic structure as well as the extremely high carrier mobility. A prerequisite for the development of graphene based electronics is the reliable control of the type and density of the charge carriers by external (gate) and internal (doping) means. While gating has been successfully demonstrated for graphene flakes and epitaxial graphene on silicon carbide, the development of reliable chemical doping methods turns out to be a real challenge. In particular hole doping is an unsolved issue. So far it has only been achieved with reactive molecular adsorbates, which are largely incompatible with any device technology. Here we show by angle-resolved photoemission spectroscopy that atomic doping of an epitaxial graphene layer on a silicon carbide substrate with bismuth, antimony or gold presents effective means of p-type doping. Not only is the atomic doping the method of choice for the internal control of the carrier density. In combination with the intrinsic n-type character of epitaxial graphene on SiC, the charge carriers can be tuned from electrons to holes, without affecting the conical band structure

MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

Background: Propionic acidaemia (PA) results from deficiency of Propionyl CoA carboxylase, the commonest form presenting in the neonatal period. Despite best current management, PA is associated with severe neurological sequelae, in particular movement disorders resulting from basal ganglia infarction, although the pathogenesis remains poorly understood. The role of liver transplantation remains controversial but may confer some neuro-protection. The present study utilises quantitative magnetic resonance spectroscopy (MRS) to investigate brain metabolite alterations in propionic acidaemia during metabolic stability and acute encephalopathic episodes.Methods: Quantitative MRS was used to evaluate brain metabolites in eight children with neonatal onset propionic acidaemia, with six elective studies acquired during metabolic stability and five studies during acute encephalopathic episodes. MRS studies were acquired concurrently with clinically indicated MR imaging studies at 1.5 Tesla. LCModel software was used to provide metabolite quantification. Comparison was made with a dataset of MRS metabolite concentrations from a cohort of children with normal appearing MR imaging.Results: MRI findings confirm the vulnerability of basal ganglia to infarction during acute encephalopathy. We identified statistically significant decreases in basal ganglia glutamate+glutamine and N-Acetylaspartate, and increase in lactate, during encephalopathic episodes. In white matter lactate was significantly elevated but other metabolites not significantly altered. Metabolite data from two children who had received liver transplantation were not significantly different from the comparator group.Conclusions: The metabolite alterations seen in propionic acidaemia in the basal ganglia during acute encephalopathy reflect loss of viable neurons, and a switch to anaerobic respiration. The decrease in glutamine + glutamate supports the hypothesis that they are consumed to replenish a compromised Krebs cycle and that this is a marker of compromised aerobic respiration within brain tissue. Thus there is a need for improved brain protective strategies during acute metabolic decompensations. MRS provides a non-invasive tool for which could be employed to evaluate novel treatments aimed at restoring basal ganglia homeostasis. The results from the liver transplantation sub-group supports the hypothesis that liver transplantation provides systemic metabolic stability by providing a hepatic pool of functional propionyl CoA carboxylase, thus preventing further acute decompensations which are associated with the risk of brain infarction

Transient excited singlet state absorption in Rhodamine 6G

Transient excited singlet state absorption (ESSA) has been studied in Rhodamine 6G in ethanol using a nitrogen laser and nitrogen laser-pumped dye laser. Broad absorption with several submaxima and possible shoulders, which represent the vibrational structure, has been observed in Rhodamine 6G in the region, 4175-4640 &#197; . The position of the lowest vibrational level of the first excited singlet state S 1 has been determined from the crossing point of the long and short wavelength spectral wings of absorption and fluorescence respectively. The energy level scheme of the molecule has been obtained with the help of the absorption and fluorescence spectra recorded. The observed structure in ESSA has been tentatively interpreted to be due to transitions from the different vibrational levels of S 1 to one or more vibrational levels of the upper singlet electronic state S4

Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

Water-Gated Charge Doping of Graphene Induced by Mica Substrates

We report on the existence of water-gated charge doping of graphene deposited on atomically flat mica substrates. Molecular films of water in units of ~0.4 nm-thick bilayers were found to be present in regions of the interface of graphene/mica hetero-stacks prepared by micromechanical exfoliation of kish graphite. The spectral variation of the G and 2D bands, as visualized by Raman mapping, shows that mica substrates induce strong p-type doping in graphene, with hole densities of $(9 \pm 2) \times 1012 cm${-2}$. The ultrathin water films, however, effectively block interfacial charge transfer, rendering graphene significantly less hole-doped. Scanning Kelvin probe microscopy independently confirmed a water-gated modulation of the Fermi level by 0.35 eV, in agreement with the optically determined hole density. The manipulation of the electronic properties of graphene demonstrated in this study should serve as a useful tool in realizing future graphene applications.Comment: 15 pages, 4 figures; Nano Letters, accepted (2012

Seasonal variation in the incidence of preeclampsia and eclampsia in tropical climatic conditions

<p>Abstract</p> <p>Background</p> <p>Observational studies have demonstrated various correlations between hypertensive disorders of pregnancy and different weather parameters. We aim to study if a correlation exists between the incidence of eclampsia and pre-eclampsia and various weather parameters in the tropical coastal city of Mumbai which has the distinction of having relatively uniform meteorological variables all throughout the year, except for the monsoon season.</p> <p>Methods</p> <p>We retrospectively analysed data from a large maternity centre in Mumbai, India over a period of 36 months from March 1993 to February 1996, recording the incidence of preeclampsia and eclampsia. Meteorological data was acquired from the regional meteorological centre recording the monthly average temperature, humidity, barometric pressure and rainfall during the study period. Study period was then divided into two climate conditions: monsoon season (June to August) and dry season September to May. The incidence of preeclampsia and eclampsia and the meteorological differences between the two seasons were compared.</p> <p>Results</p> <p>Over a 36-month period, a total of 29562 deliveries were recorded, of which 1238 patients developed preeclampsia (4.18%) and 34 developed eclampsia (0.11%). The incidence of preeclampsia did not differ between the monsoon and the dry season (4.3% vs. 4.15%, p = 0.5). The incidence of eclampsia was significantly higher in the monsoon (0.2% vs. 0.08%, p = 0.01). The monsoon was significantly cooler (median maximum temperature 30.7°C vs. 32.3°C, p = 0.01), more humid (median relative humidity 85% vs. 70%, p = 0.0008), and received higher rainfall (median 504.9 mm vs. 0.3 mm, p = 0.0002) than the rest of the year. The median barometric pressure (1005 mb) during the monsoon season was significantly lower than the rest of the year (1012 mb, p < 0.0001).</p> <p>Conclusion</p> <p>In the tropical climate of Mumbai, the incidence of eclampsia is significantly higher in monsoon, when the weather is cooler and humid with a lower barometric pressure than the rest of the year. This effect is not seen with preeclampsia. This strengthens the association of low temperature and high humidity with triggering of eclampsia.</p