A large-scale transcontinental river system crossed West Antarctica during the Eocene.

Extensive ice coverage largely prevents investigations of Antarctica's unglaciated past. Knowledge about environmental and tectonic development before large-scale glaciation, however, is important for understanding the transition into the modern icehouse world. We report geochronological and sedimentological data from a drill core from the Amundsen Sea shelf, providing insights into tectonic and topographic conditions during the Eocene (~44 to 34 million years ago), shortly before major ice sheet buildup. Our findings reveal the Eocene as a transition period from >40 million years of relative tectonic quiescence toward reactivation of the West Antarctic Rift System, coinciding with incipient volcanism, rise of the Transantarctic Mountains, and renewed sedimentation under temperate climate conditions. The recovered sediments were deposited in a coastal-estuarine swamp environment at the outlet of a >1500-km-long transcontinental river system, draining from the rising Transantarctic Mountains into the Amundsen Sea. Much of West Antarctica hence lied above sea level, but low topographic relief combined with low elevation inhibited widespread ice sheet formation.

Successful hyperbaric oxygen treatment of a patient with a HeartMate III left ventricular assist device.

A 53-year-old woman with a HeartMate III left ventricular assist device (LVAD) was successfully treated under hyperbaric conditions for haemorrhagic cystitis. The HeartMate III LVAD inserted in this patient had not previously been tested or certified for use under hyperbaric conditions. To our knowledge this is the first report of the HeartMate III LVAD being used to support a patient undergoing hyperbaric treatment. The overview detailed here of the safety and technical aspects of managing this patient for hyperbaric treatment was possible due to the collaboration of a multi-disciplinary team. We believe that our experience has demonstrated a pathway to safe hyperbaric treatment of patients dependent upon a HeartMate III LVAD.

A rapid change in magma plumbing taps porphyry copper deposit-forming magmas.

Porphyry-type deposits are a vital source of green technology metals such as copper and molybdenum. They typically form in subduction-related settings from large, long-lived magmatic systems. The most widely accepted model for their formation requires that mantle-derived magmas undergo an increase in volatiles and ore-forming constituents in mid- to lower crustal reservoirs over millions of years, however, this is mostly based on observations from shallow, sporadically exposed parts of porphyry systems. To examine this paradigm, we have evaluated the timeframe and geochemical signatures of magmatism in a ~ 8 km palaeodepth cross-section through plutonic and volcanic rocks of the classic Yerington magmatic system, Nevada. We show that the magmas in the upper parts of the system (< 8 km) underwent a major and rapid change in chemistry over a period of < 200 kyrs that is coincident with the initiation of ore formation. We attribute this change to a shift from extraction of quartz monzodiorite and quartz monzonite magmas evolving in mid-crustal reservoirs, and that had relatively poor ore-forming potential, to extraction of volatile-rich granitic magmas from greater (~ 30 km) depths. As the granites crystallised, late stage melts were intruded through the carapace as aplite dykes which contain traceable expressions of the porphyry deposit-forming fluids. The rapid nature of the shift in ore-forming potential narrows the temporal-geochemical footprint of magmas associated with porphyry mineralisation and provides new constraints for exploration models.

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Severe carbon monoxide poisonings in scuba divers: Asia-Pacific cases and causation.

Aim: Reports of fatal incidents in recreational scuba divers from carbon monoxide (CO) poisoning are rare. This study aimed to identify scuba fatalities in the Asia-Pacific region caused by breathing-gas contamination to better understand the likely sources of contamination and reduce such preventable deaths. Methods: A hand search of Project Stickybeak reports, subsequent Australian fatality series reports, and of published New Zealand diving fatality reports and associated data was conducted, as well as key word searches of the National Coronial Information System for scuba fatalities in Australia and New Zealand. Cases identified were matched with the Australasian Diving Safety Foundation diving fatality database. Available reports were examined. Results: Four scuba deaths resulting from CO poisoning were identified from 645 scuba fatalities, including one report from each of Australia, New Zealand, Singapore, and the Maldives. A near-fatal incident was also identified in Indonesia. Two of the fatal incidents and the near-fatal incident involved internal combustion engine exhaust gases from the compressor system or elsewhere entering the air intake. Two deaths likely resulted from combustion within compressor systems. Conclusions: Scuba fatalities from CO poisoning are uncommon, albeit likely under-reported. Sources of CO include exhaust gases entering the compressor and CO production by pyrolysis or gasification within the compressor or its filter system. Preventive measures include proper installation (including positioning of the air intake relative to combustion exhaust), appropriate maintenance, fitting of pressure-maintaining valves and avoidance of overheating. Formal training of compressor operators, improved diver education, mandatory requirements for installation compliance assessments, safety inspections, and the use of carbon monoxide alarms are recommended.

Simultaneous and extensive removal of the East Asian lithospheric root.

Much evidence points to a dramatic thinning of East Asian lithosphere during the Mesozoic, but with little precision on when, or over what time scale. Using geochemical constraints, we examine an extensive compilation of dated volcanic samples from Russia, Mongolia and North China to determine when the lithosphere thinned and how long that process took. Geochemical results suggest that magmatism before 107 Ma derived from metasomatised subcontinental lithospheric mantle (SCLM), whereas after 107 Ma, melt predominantly derived from an asthenospheric source. The switch to an asthenospheric magma source at ~107 Ma occurred in both Mongolia and North China (>1600 km apart), whereas in eastern Russia the switch occurred a little later (~85 Ma). Such a dramatic change to an asthenospheric contribution appears to have taken, from beginning to end, just ~30 Myrs, suggesting this is the duration for lithospheric mantle weakening and removal. Subsequent volcanism, through the Cenozoic in Mongolia and North China does not appear to include any contribution from the removed SCLM, despite melts predominantly deriving from the asthenosphere.

The early transcriptome response of cassava (Manihot esculenta Crantz) to mealybug (Phenacoccus manihoti) feeding.

The mealybug, Phenacoccus manihoti, is a leading pest of cassava (Manihot esculenta Crantz), damaging this crop globally. Although the biological control of this mealybug using natural predators has been established, resistance breeding remains an important means of control. Understanding plant responses to insect herbivory, by determining and identifying differentially expressed genes (DEGs), is a vital step towards the understanding of molecular mechanisms of defence responses in plants and the development of resistant cultivars by gene editing. Morphological and molecular analysis confirmed the mealybug identity as Phenacoccus manihoti (Matile-Ferrero). The transcriptome response of the green mite resistant cassava genotype AR23.1 was compared to P40/1 with no known resistance at 24 and 72 hours of mealybug infestation compared to non-infested mock. A total of 301 and 206 genes were differentially expressed at 24 and 72 of mealybug infestation for AR23.1 and P40/1 genotypes respectively, using a log2 fold change and P-value ≤ 0.05. Gene ontology functional classification revealed an enrichment of genes in the secondary metabolic process category in AR23.1 in comparison with P40/1, while genes in the regulation of molecular function, cellular component biogenesis and electron carrier categories were more significantly enriched in P40/1 than in AR23.1. Biological pathway analysis, based on KEGG, revealed a significant enrichment of plant-pathogen interaction and plant hormonal signal transduction pathways for a cohort of up-regulated and down-regulated DEGs in both genotypes. Defence-related genes such as 2-oxogluterate, gibberellin oxidase and terpene synthase proteins were only induced in genotype AR23.1 and not in P40/1, and subsequently validated by RT-qPCR. The study revealed a difference in response to mealybug infestation in the two genotypes studied, with AR23.1 showing a higher number of differentially expressed transcripts post mealybug infestation at 24 and 72 hours. Candidate defence-related genes that were overexpressed in the AR23.1 genotype post mealybug infestation will be useful in future functional studies towards the control of mealybugs.

Cerebral arterial gas embolism from attempted mechanical thrombectomy: recovery following hyperbaric oxygen therapy.

Cerebral arterial gas embolism is a recognised complication of endovascular intervention with an estimated incidence of 0.08%. Its diagnosis is predominantly clinical, supported by neuroimaging. The treatment relies on alleviating mechanical obstruction and reversing the proinflammatory processes that contribute to tissue ischaemia. Hyperbaric oxygen therapy is an effective treatment and has multiple mechanisms to reverse the pathological processes involved in cerebral arterial gas embolism. Symptomatic cerebral arterial gas embolism is a rare complication of endovascular intervention for acute ischaemic stroke. Although there are no previous descriptions of its successful treatment with hyperbaric oxygen therapy following mechanical thrombectomy, this is likely to become more common as mechanical thrombectomy is increasingly used worldwide to treat acute ischaemic stroke.

A pleural vacuum relief device for pleural drain unit use in the hyperbaric environment.

INTRODUCTION: When a standard water-seal pleural drain unit (PDU) is used under hyperbaric conditions there are scenarios where excessive negative intrapleural pressure (IPP) and/or fluid reflux can be induced, risking significant morbidity. We developed and tested a pleural vacuum relief (PVR) device which automatically manages these risks, whilst allowing more rapid hyperbaric pressure change rates. METHODS: The custom-made PVR device consists of a one-way pressure relief valve connected in line with a sterile micro filter selected for its specific flow capacity. The PVR device is designed for connection to the patient side sampling port of a PDU system, allowing inflow of ambient air whenever negative pressure is present, creating a small, controlled air leak which prevents excessive negative pressure. The hyperbaric performance of a Pleur-Evac A-6000 intercostal drain was assessed with and without this added device by measuring simulated IPP with an electronic pressure monitor connected at the patient end of the PDU. IPP readings were taken at 10, 15, 20 and 30 cmH2O of suction (set on the drain unit) at compression rates of 10, 30, 60, 80, 90 and 180 kPa·min⁻¹ to a pressure of 280 kPa. RESULTS: At any compression rate of > 10 kPa·min⁻¹, the negative IPP generated by the Pleur-Evac A-6000 alone was excessive and resulted in back flow through the PDU water seal. By adding the PVR device, the generated negative IPP remains within a clinically acceptable range, allowing compression rates of at least 30 kPa·min⁻¹ with suction settings up to -20 cmH2O during all phases of hyperbaric treatment. CONCLUSIONS: The PDU PVR device we have developed works well, minimising attendant workload and automatically avoiding the excessive negative IPPs that can otherwise occur. This device should only be used with suction.

How effectively are your patients taking their medicines? A critical review of the Strathclyde Compliance Risk Assessment Tool in relation to the 'MMAS' and 'MARS'.

RATIONALE, AIMS AND OBJECTIVES: A useful assessment tool that can support health care professionals in anticipating elderly patients' care needs regarding additional support in managing their own medicines is essential, but currently lacking. Thus, the aim of the study was to assess whether the 13-item Strathclyde Compliance Risk Assessment Tool (SCRAT) is an appropriate instrument for identifying community-dwelling elderly people who may be at risk of medication non-adherence. METHOD: An 8-week survey was performed from October to November 2009. Patients were ≥65 years old, receiving ≥3 medications and were either using multi-compartment compliance aids or receiving social care support, or both. The data were collected in 45 face-to-face structured interviews using the 13-item SCRAT, 5-item Medication Adherence Rating Scale (MARS) and 8-item Modified Morisky Adherence Scale (MMAS) in sheltered housing complexes in Glasgow, Scotland. Interviews were analysed quantitatively using SPSS version 21 software. RESULTS: The SCRAT instrument showed substantial inter-rater reliability (Cohen's kappa of 0.730 for the 13-item scale). There was a significant strong negative correlation between the 13-item SCRAT total risk score and 8-item MMAS (r = -0.654; P = 0.0036), and the 13-item SCRAT total risk score and 5-item MARS (r = -0.481; P = 0.0084). The SCRAT instrument showed satisfactory internal consistency (Cronbach's alpha of 0.853 for the 13-item scale). The area under the receiver operator characteristic curve (AUC ± standard error; 95% confidence interval) showed that the SCRAT had good discriminatory capacity and was able to distinguish between adherent and non-adherent participants on the MARS (0.729 ± 0.17; 0.39, 1.00). The best cut-off (sensitivity, specificity) was <3 (75%, 45%). In the sub-analyses, there was a significant difference in total risk score (3 vs. 2, P = 0.011) between users and non-users of multi-compartment compliance aids. CONCLUSION: The study shows that the 13-item SCRAT has the potential to be used in identifying elderly participants who may have problems managing their own medicines and it may help to determine the level and type of assistance that patients require to manage their medicines.

Hyperbaric Oxygen in Lower Limb Trauma (HOLLT); protocol for a randomised controlled trial.

INTRODUCTION: Open fractures with significant soft tissue injury are associated with high rates of complications, such as non-union, infection, chronic pain and disability. Complications often require further inpatient care, and in many cases, multiple operations and prolonged rehabilitation. Use of hyperbaric oxygen therapy as an adjunct to standard orthopaedic trauma care has the potential to reduce the complications of musculoskeletal injury and thus improve outcomes. Two previous randomised trials have suggested some positive effect, but neither functional measures nor long-term outcomes were reported. METHODS AND ANALYSIS: An international, multicentre, randomised, open-label, clinical trial. Patients with trauma with an acute open fracture of the tibia with severe soft tissue injury (Gustilo grade 3) and high risk of injury-related complications were recruited from participating major trauma hospitals with hyperbaric facilities. Patients were enrolled with the expectation of commencing 12 sessions of hyperbaric oxygen therapy within 48 h of injury. The primary outcome measure is the incidence of acute complications of the open fracture wound at 14 days. Other short-term outcome measures include amputation, need for fasciotomy, time until wound closure, breakdown of closed wounds, time until definitive orthopaedic fixation, number of operative procedures, intensive care stay and hospital stay. Long-term follow-up will continue for 2 years postinjury. ETHICS AND DISSEMINATION: Ethics approval was given by The Alfred Health Human Ethics Committee (206/04) and the Monash University Human Research Ethics Committee (CF07/4208). Approval was also obtained from the institutional research ethics committee at each participating site. This study will make a significant contribution to the trauma literature and should answer the question of whether hyperbaric oxygen therapy can significantly improve outcomes in severe lower limb trauma. Collective study results will be published in international journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT00264511; Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12607000559415.

Hyperbaric intensive care technology and equipment.

In an emergency, life support can be provided during recompression or hyperbaric oxygen therapy using very basic equipment, provided the equipment is hyperbaric-compatible and the clinicians have appropriate experience. For hyperbaric critical care to be provided safely on a routine basis, however, a great deal of preparation and specific equipment is needed, and relatively few facilities have optimal capabilities at present. The type, size and location of the chamber are very influential factors. Although monoplace chamber critical care is possible, it involves special adaptations and inherent limitations that make it inappropriate for all but specifically experienced teams. A large, purpose-designed chamber co-located with an intensive care unit is ideal. Keeping the critically ill patient on their normal bed significantly improves quality of care where this is possible. The latest hyperbaric ventilators have resolved many of the issues normally associated with hyperbaric ventilation, but at significant cost. Multi-parameter monitoring is relatively simple with advanced portable monitors, or preferably installed units that are of the same type as used elsewhere in the hospital. Whilst end-tidal CO2 readings are changed by pressure and require interpretation, most other parameters display normally. All normal infusions can be continued, with several examples of syringe drivers and infusion pumps shown to function essentially normally at pressure. Techniques exist for continuous suction drainage and most other aspects of standard critical care. At present, the most complex life support technologies such as haemofiltration, cardiac assist devices and extra-corporeal membrane oxygenation remain incompatible with the hyperbaric environment.

Adjunctive hyperbaric oxygen for necrotizing fasciitis.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) involves the therapeutic administration of 100% oxygen in a pressure chamber at pressures above one atmosphere absolute. This therapy has been used as an adjunct to surgery and antibiotics in the treatment of patients with necrotizing fasciitis with the aim of reducing morbidity and mortality. OBJECTIVES: To review the evidence concerning the use of HBOT as an adjunctive treatment for patients with necrotizing fasciitis (NF). Specifically, we wish to address the following questions.1. Does administration of HBOT reduce mortality or morbidity associated with NF?2. What adverse effects are associated with use of HBOT in the treatment of individuals with NF? SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE Ovid (1966 to September 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ovid (1982 to September 2014); EMBASE Ovid (1980 to September 2014); and the Database of Randomised Controlled Trials in Hyperbaric Medicine (DORCTHIM, M Bennett) (from inception to September 2014). In addition, we performed a systematic search of specific hyperbaric literature sources. This included handsearching of relevant hyperbaric textbooks; hyperbaric journals (Hyperbaric Medicine Review, South Pacific Underwater Medicine Society Journal, European Journal of Underwater and Hyperbaric Medicine, Aviation Space and Environmental Medicine Journal); and conference proceedings of the major hyperbaric societies (Undersea and Hyperbaric Medical Society, South Pacific Underwater Medicine Society, European Underwater and Baromedical Society, International Congress of Hyperbaric Medicine). SELECTION CRITERIA: We included all randomized and pseudo-randomized trials (trials in which an attempt at randomization has been made but the method was inappropriate, for example, alternate allocation) that compared the effects of HBOT with the effects of no HBOT (no treatment or sham) in the treatment of children and adults with necrotizing fasciitis. DATA COLLECTION AND ANALYSIS: We planned independent data collection by two review authors using standardized forms. MAIN RESULTS: We found no trials that met the inclusion criteria. AUTHORS' CONCLUSIONS: This systematic review failed to locate relevant clinical evidence to support or refute the effectiveness of HBOT in the management of necrotizing fasciitis. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of individuals with necrotizing fasciitis.

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation.

BACKGROUND: Approaches to increase organ availability for orthotopic liver transplantation (OLT) often result in the procurement of marginal livers that are more susceptible to ischaemia, preservation and reperfusion injury (IPRI). METHODS: The effects of post-OLT hyperbaric oxygen (HBO) therapy on IPRI in a syngeneic rat OLT model were examined at various time-points. The effects of IPRI and HBO on hepatocyte necrosis, apoptosis, proliferation, and sinusoidal morphology and ultrastructure were assessed. RESULTS: Post-OLT HBO therapy significantly reduced the severity of IPRI; both apoptosis [at 12 h: 6.4 ± 0.4% in controls vs. 1.6 ± 0.7% in the HBO treatment group (p < 0.001); at 48 h: 2.4 ± 0.2% in controls vs. 0.4 ± 0.1% in the HBO treatment group (p < 0.001)] and necrosis [at 12 h: 18.7 ± 1.8% in controls vs. 2.4 ± 0.4% in the HBO treatment group (p < 0.001); at 48 h: 8.5 ± 1.3% in controls vs. 3.4 ± 0.9% in the HBO treatment group (P= 0.019)] were decreased. Serum alanine transaminase was reduced [at 12 h: 1068 ± 920 IU/l in controls vs. 370 ± 63 IU/l in the HBO treatment group (P= 0.030); at 48 h: 573 ± 261 IU/l in controls vs. 160 ± 10 IU/l in the HBO treatment group (P= 0.029)]. Treatment with HBO also promoted liver regeneration [proliferation at 12 h: 4.5 ± 0.1% in controls vs. 1.0 ± 0.3% in the HBO treatment group (p < 0.001); at 48 h: 8.6 ± 0.7% in controls vs. 2.9 ± 0.2% in the HBO treatment group (p < 0.01)] and improved sinusoidal diameter and microvascular density index. CONCLUSIONS: Hyperbaric oxygen therapy has persistent positive effects post-OLT that may potentially transfer into clinical practice.

Pilot evaluation of the psychometric properties of a self-medication Risk Assessment Tool among elderly patients in a community setting.

BACKGROUND: Although community pharmacists in the United Kingdom are expected to assess elderly patients' needs for additional support in managing their medicines, there is limited data on potentially useful assessment tools. We sought to evaluate a 13-item assessment instrument among community dwelling elderly patients, 65 years and above. The instrument is composed of a cognitive risk sub-scale of 6 items and a physical risk sub-scale of 7 items. FINDINGS: The instrument was administered to elderly patients in a survey performed in a community to the west of Glasgow, Scotland. The survey recruited 37 participants, 31 from 4 community pharmacies and 6 patients whose medication management tasks were managed by the West Glasgow Community Health and Care Partnership (managed patients). Community pharmacists independently rated 29 of the 37 participants' comprehension of, and dexterity in handling their medicines. We assessed scale reliability, convergent validity and criterion validity. In sub-analyses, we assessed differences in scores between the managed patients and those recruited from the community pharmacies, and between multi-compartment compliance aid users and non-users. The instrument showed satisfactory internal consistency (Cronbach's alpha of 0.792 for 13-item scale). There was significant strong negative correlation between the cognitive risk sub-scores and community pharmacists' assessment of comprehension (ρ = -0.546, p = 0.0038); and physical risk sub-scores and community pharmacists' assessment of dexterity (ρ = -0.491, p = 0.0093). The Area Under the Receiver Operator Characteristic Curve (AUC ± SE; 95%CI) showed that the instrument had good discriminatory capacity (0.86 ± 0.07; 0.68, 0.96). The best cut-off (sensitivity, specificity) was ≥4 (65%, 100%). In the sub-analyses, managed patients had significantly higher cognitive risk sub-scores (6.5 versus 4.0, p = 0.0461) compared to non-managed patients. There was a significant difference in total risk score (4 versus 2, p = 0.0135) and cognitive risk sub-score (4 versus 1.5, p = 0.0029) between users and non-users of multi-compartment compliance aids. CONCLUSIONS: This instrument shows potential for use in identifying elderly patients who may have problems managing their own medicines in the community setting. However, more robust validity and reliability assessments are needed prior to introduction of the tool into routine practice.

Changes in oxygenation in mechanically ventilated critically ill patients following hyperbaric treatment.

BACKGROUND: Some ventilated intensive care unit (ICU) patients may experience reduced oxygenation following hyperbaric oxygen treatment (HBOT). METHODS: In a prospective, single-centre, observational study, we documented changes in oxygenation and the need for associated changes in ventilator settings in 25 consecutive, mechanically ventilated ICU patients immediately post-treatment and 1, 2, 3 and 6 hours following 61 HBOT sessions. The primary outcome measure of oxygenation was the ratio of arterial partial pressure of oxygen (P(a)O2) against the level of inspired oxygen (F(i)O2), P(a)O2/F(i)O2. RESULTS: Following HBOT, the P(a)O2/F(i)O2 ratio decreased by 27% on return to ICU (P < 0.001, 95% confidence intervals (CI) 20.6 to 34.2); 22% at 1 hour post-HBOT (P < 0.001, 95% CI 15.1 to 28.6); and 8% at 2 hours post (P = 0.03, 95% CI 0.8 to 14.4). The ratio showed no significant differences from pre-HBOT at 3 and 6 hours post-HBOT. P(a)O2/F(i)O2 ratio changes necessitated adjustments to ventilation parameters upon return to ICU following 30 of 61 HBOT sessions in 17 out of the 25 patients. The most common ventilation parameter altered was F(i)O2 (n = 20), increased by a mean of +0.17 (95% CI 0.11 to 0.23) above baseline for two hours following HBOT. CONCLUSIONS: Following HBOT, oxygenation is reduced in a majority of mechanically ventilated ICU patients and requires temporary alterations to mechanical ventilation settings. Further study to identify predictive characteristics and to determine causation for those at risk of needing ventilation alterations is required.

Functional characterization of bestrophin-1 missense mutations associated with autosomal recessive bestrophinopathy.

PURPOSE: Autosomal recessive bestrophinopathy (ARB) is a retinal dystrophy affecting macular and retinal pigmented epithelium function resulting from homozygous or compound heterozygous mutations in BEST1. In this study we characterize the functional implications of missense bestrophin-1 mutations that cause ARB by investigating their effect on bestrophin-1's chloride conductance, cellular localization, and stability. METHODS: The chloride conductance of wild-type bestropin-1 and a series of ARB mutants were determined by whole-cell patch-clamping of transiently transfected HEK cells. The effect of ARB mutations on the cellular localization of bestrophin-1 was determined by confocal immunofluorescence on transiently transfected MDCK II cells that had been polarized on Transwell filters. Protein stability of wild-type and ARB mutant forms of bestrophin-l was determined by the addition of proteasomal or lysosomal inhibitors to transiently transfected MDCK II cells. Lysates were then analyzed by Western blot analysis. RESULTS: All ARB mutants investigated produced significantly smaller chloride currents compared to wild-type bestrophin-1. Additionally, co-transfection of compound heterozygous mutants abolished chloride conductance in contrast to co-transfections of a single mutant with wild-type bestrophin-l, reflecting the recessive nature of the condition. In control experiments, expression of two dominant vitelliform macular dystrophy mutants was shown to inhibit wild-type currents. Cellular localization of ARB mutants demonstrated that the majority did not traffic correctly to the plasma membrane and that five of these seven mutants were rapidly degraded by the proteasome. Two ARB-associated mutants (p.D312N and p.V317M) that were not trafficked correctly nor targeted to the proteasome had a distinctive appearance, possibly indicative of aggresome or aggresome-like inclusion bodies. CONCLUSIONS: Differences in cellular processing mechanisms for different ARB associated mutants lead to the same disease phenotype. The existence of distinct pathogenic disease mechanisms has important ramifications for potential gene replacement therapies since we show that missense mutations associated with an autosomal recessive disease have a pathogenic influence beyond simple loss of function.

Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa.

Bestrophin-1 is preferentially expressed at the basolateral membrane of the retinal pigmented epithelium (RPE) of the retina. Mutations in the BEST1 gene cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant vitreochoroidopathy, and autosomal-recessive bestrophinopathy. Here, we describe four missense mutations in bestrophin-1, three that we believe are previously unreported, in patients diagnosed with autosomal-dominant and -recessive forms of retinitis pigmentosa (RP). The physiological function of bestrophin-1 remains poorly understood although its heterologous expression induces a Cl--specific current. We tested the effect of RP-causing variants on Cl- channel activity and cellular localization of bestrophin-1. Two (p.L140V and p.I205T) produced significantly decreased chloride-selective whole-cell currents in comparison to those of wild-type protein. In a model system of a polarized epithelium, two of three mutations (p.L140V and p.D228N) caused mislocalization of bestrophin-1 from the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are increasingly recognized as an important cause of inherited retinal dystrophy.

A survey of scale insects (Sternorryncha: Coccoidea) occurring on table grapes in South Africa.

Increasing international trade and tourism have led to an increase in the introduction of exotic pests that pose a considerable economic threat to the agro-ecosystems of importing countries. Scale insects (Sternorryncha: Coccoidea) may be contaminants of export consignments from the South African deciduous fruit industry to the European Union, Israel, United Kingdom and the United States, for example. Infestations of immature scale insects found on South African fruit destined for export have resulted in increasing rates of rejection of such consignments. To identify the risk posed by scale insect species listed as phytosanitary pests on table grapes to the abovementioned importing countries, a field survey was undertaken in 2004-2005 in vineyards throughout all grape-producing regions in South Africa. Coccoidea species found during the current field survey were Planococcus ficus (Signoret), Pseudococcus longispinus (Targioni Tozzetti), Coccus hesperidum L. and Nipaecoccus viridis (Newstead). With the exception of Pl. ficus, which has only been collected from Vitis vinifera (Vitaceae) and Ficus carica (Moraceae) in South Africa, these species are polyphagous and have a wide host range. None of the scale insect species found to occur in vineyards in South Africa pose a phytosanitary risk to countries where fruit are exported except for Ferrisia malvastra (McDaniel) and N. viridis that have not been recorded in the USA. All scale insects previously found in vineyards in South Africa are listed and their phytosanitary status discussed. The results of the survey show that the risk of exporting scale insect pests of phytosanitary importance on table grapes from South Africa is limited.

NBCe2 exhibits a 3 HCO3(-):1 Na+ stoichiometry in mouse choroid plexus epithelial cells.

The transport stoichiometry of the electrogenic sodium-bicarbonate cotransporter (SLC4A5 or NBCe2) in mouse choroid plexus was examined. Whole-cell recording methods measured the currents carried by the NBCe2, using experimental solutions determined to minimise the contributions of the other ion conductances present. Increases in outward current were observed when 21.2 mM HCO3(-) was added to the bath solution in the presence of Na(+), but not N-methyl-D-glucamine. This HCO3(-)-induced current was completely abolished by 500 microM 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid. The reversal potential for the HCO3(-)-induced current was -95.1+/-7.1 mV (n=11), a value which corresponds to a NBCe2 transport stoichiometry of 3 HCO3(-) with 1 Na(+). The NBCe2, with this stoichiometry, will mediate the efflux of HCO3(-) and Na(+) from the cell into the cerebrospinal fluid at the apical membrane of the choroid plexus.