Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs

Purpose To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs. Methods A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed. Results Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = −4.38 ± 0.57D, 0.3 % TPMPA = −3.00 ± 0.48D, P < 0.01; 1 % TPMPA = −0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05). Conclusions Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

LacO-LacI interaction in affinity adsorption of plasmid DNA

Current approaches for purifying plasmids from bacterial production systems exploit the physiochemical properties of nucleic acids in non-specific capture systems. In this study, an affinity system for plasmid DNA (pDNA) purification has been developed utilizing the interaction between the lac operon (lacO) sequence contained in the pDNA and a 64mer synthetic peptide representing the DNA-binding domain of the lac repressor protein, LacI. Two plasmids were evaluated, the native pUC19 and pUC19 with dual lacO3/lacOs operators (pUC19lacO3/lacOs), where the lacOs operator is perfectly symmetrical. The DNA-protein affinity interaction was evaluated by surface plasmon resonance using a Biacore system. The affinity capture of DNA in a chromatography system was evaluated using LacI peptide that had been immobilized to Streamline™ adsorbent. The KD-values for double stranded DNA (dsDNA) fragments containing lacO1 and lacO3 and lacOs and lacO3 were 5.7 ± 0.3 × 10 -11 M and 4.1 ± 0.2 × 10-11 M respectively, which compare favorably with literature reports of 5 × 10-10 - 1 × 10-9 M for native laCO1 and 1-1.2 × 10-10 M for lacO1 in a saline buffer. Densitometric analysis of the gel bands from the affinity chromatography run clearly showed a significant preference for capture of the supercoiled fraction from the feed pDNA sample. The results indicate the feasibility of the affinity approach for pDNA capture and purification using native protein-DNA interaction.

Vibrational spectroscopic characterization of the sulphate-carbonate mineral burkeite: Implications for evaporites

Burkeite formation is important in saline evaporites and in pipe scales. Burkeite is an anhydrous sulphate-carbonate with an apparent variable anion ratio. Such a formula with two oxyanions lends itself to vibrational spectroscopy. Two symmetric sulphate stretching modes are observed, indicating at least at the molecular level the nonequivalence of the sulphate ions in the burkeite structure. The strong Raman band at 1065 cm−1 is assigned to the carbonate symmetric stretching vibration. The series of Raman bands at 622, 635, 645, and 704 cm−1 are assigned to the ν4 sulphate bending modes. The observation of multiple bands supports the concept of a reduction in symmetry of the sulphate anion from T d to C 3v or even C 2v.

Environment, political economies and livelihood change

Between the national and household factors, community or “meso-level” changes in political economy and livelihoods in southwestern Bangladesh illustrate that in order to understand the impacts on people and nations of climate change-related environmental changes – changes that are expected to include rising sea level, saline inundation, and increased likelihood and intensity of cyclones in Bangladesh – we need to understand the dynamics of the built and natural environment and the political economies these sustain. Meso-level political economies affect the sources of income and livelihood available in distressed environmental conditions, and therefore influence how well the people in them can adapt to changing environmental conditions. In this study we have seen the underlying political economies whose dynamics, and not slow onset environmental changes or disastrous environmental events, are pushing Bangladeshis to incorporate migration strategies into their livelihood strategies.

Are we getting accurate measurements of Ksat for sodic clay soils?

In this paper we discuss the use of a series of column experiments to improve understanding of the effect irrigation water chemistry (saline solutions) has on measurements of saturated hydraulic conductivity (Ksat) of a sodic clay soil. We highlight in particular the use of extended leaching periods to determine whether the duration of leaching affects the results. In the experiments, mixed cation solutions of two different salinity levels, 50 meq/L and 100 meq/L, were applied under constant head to columns of a repacked sodic clay soil using three replicates for each treatment. The maximum Ksat measured during leaching with the 100 meq/L solution was approximately double the maximum Ksat measured during leaching with the 50 meq/L solution. Measured flow rates were found to increase rapidly after flow commenced then decrease gradually until flow rates became stable. The final, stable flow rate was roughly 80% less than the maximum flow rate measured. Reasons for these changes in saturated hydraulic conductivity are discussed. The key finding from these experiments is that long term leaching, involving significantly more pore volumes than is commonly reported in the literature, is required to obtain a ‘stable’ Ksat. We recommend that further studies be carried out to (1) determine whether similar behaviour in Ksat occurs in a wide range of sodic clay soils and (2) to help build a better understanding of the causes and implications of the observed behaviour in Ksat.

Relationships between major ions in coal seam gas groundwaters: Examples from the Surat and Clarence-Moreton basins

Using a combination of multivariate statistical techniques and the graphical assessment of major ion ratios, the influences on hydrochemical variability of coal seam gas (or coal bed methane) groundwaters from several sites in the Surat and Clarence-Moreton basins in Queensland, Australia, were investigated. Several characteristic relationships between major ions were observed: 1) strong positive linear correlation between the Na/Cl and alkalinity/Cl ratios; 2) an exponentially decaying trend between the Na/Cl and Na/alkalinity ratios; 3) inverse linear relationships between increasing chloride concentrations and decreasing pH for high salinity groundwaters, and; 4) high residual alkalinity for lower salinity waters, and an inverse relationship between decreasing residual alkalinity and increasing chloride concentrations for more saline waters. The interpretation of the hydrochemical data provides invaluable insights into the hydrochemical evolution of coal seam gas (CSG) groundwaters that considers both the source of major ions in coals and the influence of microbial activity. Elevated chloride and sodium concentrations in more saline groundwaters appear to be influenced by organic-bound chlorine held in the coal matrix; a sodium and chloride ion source that has largely been neglected in previous CSG groundwater studies. However, contrastingly high concentrations of bicarbonate in low salinity waters could not be explained, and are possibly associated with a number of different factors such as coal degradation, methanogenic processes, the evolution of high-bicarbonate NaHCO3 water types earlier on in the evolutionary pathway, and variability in gas reservoir characteristics. Using recently published data for CSG groundwaters in different basins, the characteristic major ion relationships identified for new data presented in this study were also observed in other CSG groundwaters from Australia, as well as for those in the Illinois Basin in the USA. This observation suggests that where coal maceral content and the dominant methanogenic pathway are similar, and where organic-bound chlorine is relatively abundant, distinct hydrochemical responses may be observed. Comparisons with published data of other NaHCO3 water types in non-CSG environments suggest that these characteristic major ion relationships described here can: i) serve as an indicator of potential CSG groundwaters in certain coal-bearing aquifers that contain methane; and ii) help in the development of strategic sampling programmes for CSG exploration and to monitor potential impacts of CSG activities on groundwater resources.

A comprehensive ovine model of blood transfusion

Background The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. Results Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline–adenine–glucose–mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge

Summary The neonatal period is characterized by significant plasticity where the immune, endocrine, and nociceptive systems undergo fine-tuning and maturation. Painful experiences during this period can result in long-term alterations in the neurocircuitry underlying nociception, including increased sensitivity to mechanical or thermal stimuli. Less is known about the impact of neonatal exposure to mild inflammatory stimuli, such as lipopolysaccharide (LPS), on subsequent inflammatory pain responses. Here we examine the impact of neonatal LPS exposure on inflammatory pain sensitivity and HPA axis activity during the first three postnatal weeks. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection, blood was collected to assess corticosterone responses. Transverse spinal cord slices were also prepared for whole-cell patch clamp recording from lumbar superficial dorsal horn neurons (SDH). Brains were obtained at PND 22 and the hypothalamus was isolated to measure glucocorticoid (GR) and mineralocorticoid receptor (MR) transcript expression using qRT-PCR. Behavioural analyses indicate that at PND 7, no significant differences were observed between saline- or LPS-challenged rats. At PND 13, LPS-challenged rats exhibited enhanced licking (p < .01), and at PND 22, increased flinching in response to formalin injection (p < .05). LPS-challenged rats also displayed increased plasma corticosterone at PND 7 and PND 22 (p < .001) but not at PND 13 following formalin administration. Furthermore, at PND 22 neonatal LPS exposure induced decreased levels of GR mRNA and increased levels of MR mRNA in the hypothalamus. The intrinsic properties of SDH neurons were similar at PND 7 and PND 13. However, at PND 22, ipsilateral SDH neurons in LPS-challenged rats had a lower input resistance compared to their saline-challenged counterparts (p < .05). These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, corticosterone levels, and dorsal horn neuron properties following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping pain sensitivity later in life. This programming involves both spinal cord neurons and the HPA axis.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children

Background Guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion, however there is debate regarding the need for heparin and evidence to suggest 0.9% sodium chloride (normal saline) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. Objectives To assess the clinical effects (benefits and harms) of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Search Methods The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (Issue 3, 2015). We also searched the reference lists of retrieved trials. Selection criteria Randomised controlled trials that compared the efficacy of normal saline with heparin to prevent occlusion of long term CVCs in infants and children aged up to 18 years of age were included. We excluded temporary CVCs and peripherally inserted central catheters (PICC). Data Collection and Analysis Two review authors independently assessed trial inclusion criteria, trial quality and extracted data. Rate ratios were calculated for two outcome measures - occlusion of the CVC and central line-associated blood stream infection. Other outcome measures included duration of catheter placement, inability to withdraw blood from the catheter, use of urokinase or recombinant tissue plasminogen, incidence of removal or re-insertion of the catheter, or both, and other CVC-related complications such as dislocation of CVCs, other CVC site infections and thrombosis. Main Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin, however, between studies, all used different protocols for the standard and experimental arms with different concentrations of heparin and different frequency of flushes reported. In addition, not all studies reported on all outcomes. The quality of the evidence ranged from low to very low because there was no blinding, heterogeneity and inconsistency between studies was high and the confidence intervals were wide. CVC occlusion was assessed in all three trials (243 participants). We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). The duration of catheter placement was reported to be similar between the two study arms, in one study (203 participants). Authors' Conclusions The review found that there was not enough evidence to determine the effects of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Impacts of sodic soil amelioration on deep drainage

Groundwater tables are rising beneath irrigated fields in some areas of the Lower Burdekin in North Queensland, Australia. The soils where this occurs are predominantly sodic clay soils with low hydraulic conductivities. Many of these soils have been treated by applying gypsum or by increasing the salinity of irrigation water by mixing saline groundwater with fresh river water. While the purpose of these treatments is to increase infiltration into the surface soils and improve productivity of the root zone, it is thought that the treatments may have altered the soil hydraulic properties well below the root zone leading to increased groundwater recharge and rising water tables. In this paper we discuss the use of column experiments and HYDRUS modelling, with major ion reaction and transport and soil water chemistry-dependent hydraulic conductivity, to assess the likely depth, magnitude and timing of the impacts of surface soil amelioration on soil hydraulic properties below the root zone and hence groundwater recharge. In the experiments, columns of sodic clays from the Lower Burdekin were leached for extended periods of time with either gypsum solutions or mixed cation salt solutions and change s in hydraulic conductivity were measured. Leaching with a gypsum solution for an extended time period, until the flow rate stabilised, resulted in an approximately twenty fold increase in the hydraulic conductivity when compared with a low salinity, mixed cation solution. HYDRUS modelling was used to high light the role of those factors which might influence the impacts of soil treatment, particularly at depth, including the large amounts of rain during the relatively short wet season and the presence of thick low permeability clay layers.

GABAB Receptor antagonist CGP46381 inhibits form-deprivation myopia development in guinea pigs

The aim was to investigate the effects of the GABAB receptor antagonist, CGP46381, on form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25). The deprived eyes were treated with daily subconjunctival injections (100 μl) of either 2% CGP46381, 0.2% CGP46381, or saline or received no injection. The fellow eyes were left untreated. Another six animals received no treatment. At the start and end of the treatment period, ocular refractions were measured using retinoscopy and vitreous chamber depth (VCD) and axial length (AL) using A-scan ultrasound. All of the deprived eyes developed relative myopia (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001). The highest dose tested, 2% CGP46381, significantly inhibited myopia development compared to saline (2% CGP46381: -1.08 ± 0.40 D, saline: -4.33 ± 0.67 D, P < 0.01). The majority of these effects were due to less AL (2% CGP46381: 0.03 ± 0.01 mm, saline: 0.13 ± 0.02 mm, P < 0.01) and VCD (2% CGP46381: 0.02 ± 0.01 mm, saline: 0.08 ± 0.01 mm, P < 0.01) elongation. The lower dose tested, 0.2% CGP46381, did not significantly inhibit FDM (P > 0.05). Subconjunctival injections of CGP46381 inhibit FDM development in guinea pigs in a dose-dependent manner.

Amber teething necklaces: Is there any basis to their use in teething infants?

Introduction. Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound said to have analgesic and anti-inflammatory properties), which is then absorbed through the skin. Aims. To investigate whether succinic acid is contained in Baltic amber teething necklaces purchased in Australia, whether it can be released from the beads, and whether it has anti-inflammatory activity. Methods. Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol. Anti-inflammatory activity of succinic acid was compared with ibuprofen, paracetamol and hydrocortisone in vitro using THP-1 human macrophages stimulated with LPS. Secretion of the cytokines IL-1a, IL-1b, IL-8 and TNF-α were determined by ELISA. Results. Each necklace (33 beads in length) contained 19.17 ± 4.89 mg of succinic acid (mean ± se). Over a 6-month period, no succinic acid was detected in PBS. While 0.13 ± 0.09 mg of succinic acid per necklace was released in octanol, this was due to only one replicate of amber beads which had fragmented into shards free-floating in the solvent. Succinic acid had no effect on cytokine secretion unless extremely high concentrations were used and changes were likely to be associated with cell apoptosis and death. Discussion. No evidence for anti-inflammatory activity was found in the cytokines studied. It is possible that succinic acid could exert an effect via some other mechanism, but while the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

Amber teething necklaces – medical marvel or maternal myth?

BACKGROUND: Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound with analgesic and anti-inflammatory properties), which is then absorbed through the skin. AIM: To investigate whether Baltic amber teething necklaces purchased in Australia contained succinic acid, and to quantify succinic acid release from the beads. METHODS: Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol to simulate aqueous or oily skin environments. RESULTS: Each necklace (33 beads in length) contained 19.17±4.89 mg of succinic acid (mean±se). Over a 6-month period, no succinic acid was detected in PBS, while 0.13±0.09 mg of succinic acid per necklace was released in octanol. Only one replicate of amber beads in octanol released succinic acid, and they had fragmented, with shards free-floating in the solvent. DISCUSSION: It is likely succinic acid was only detected because the beads were breaking down in octanol, which does not occur when worn around the neck of a child. Furthermore, the hydrophilic properties of succinic acid would not favour its absorption across hydrophobic layers of the skin and into the bloodstream. CONCLUSION: While the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.

In response: UV–vis light transmittance through tinted contact lenses and the effect of color on values

In the study, we used the Agilent 8453 spectrophotometer (which is equipped with a limiting aperture that restricts the light beam to the central 5 mm of the contact lens), to measure the transmittance of various coloured contact lenses including the one Day Acuvue define manufactured by Johnson and Johnson which the authors represent. We measured the instrument baseline before the transmittance spectra of lenses were tested. The values of lens transmittances were thus the difference between baseline and lens measurement at each time. The transmittance measurements were obtained at 0.5 nm intervals, from 200 to 700 nm after a soak in saline to remove the influence of any surface active agents within the packaging products. The technique used in our study was not very different from how other research studies [2], [3], [4], [5] and [6] have measured the spectra transmittances of contact lenses...

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review

Background Around the world, guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) vary greatly. To prevent occlusion, most institutions recommend the use of heparin when the CVC is not in use. However, there is debate regarding the need for heparin and evidence to suggest normal saline may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased costs. Objectives To assess the clinical effects (benefits and harms) of heparin versus normal saline to prevent occlusion in long-term central venous catheters in infants, children and adolescents. Design A Cochrane systematic review of randomised controlled trials was undertaken. - Data sources: The Cochrane Vascular Group Specialised Register (including MEDLINE, CINAHL, EMBASE and AMED) and the Cochrane Register of Studies were searched. Hand searching of relevant journals and reference lists of retrieved articles was also undertaken. - Review Methods: Data were extracted and appraisal undertaken. We included studies that compared the efficacy of normal saline with heparin to prevent occlusion. We excluded temporary CVCs and peripherally inserted central catheters. Rate ratios per 1000 catheter days were calculated for two outcomes, occlusion of the CVC, and CVC-associated blood stream infection. Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin. However, between studies, all used different protocols with various concentrations of heparin and frequency of flushes. The quality of the evidence ranged from low to very low. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). Conclusions It remains unclear whether heparin is necessary for CVC maintenance. More well-designed studies are required to understand this relatively simple, but clinically important question. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.