The Commerce and Crossover of Resources: Resource Conservation in the Service of Resilience

Conservation of resources (COR) theory was originally introduced as a framework for understanding and predicting the consequences of major and traumatic stress, but following the work of Hobfoll and Shirom (1993), COR theory has been adopted to understanding and predicting work‐related stress and both the stress and resilience that occur within work settings and work culture. COR theory underscores the critical role of resource possession, lack, loss and gain and depicts personal, social and material resources co‐travelling in resource caravans, rather than piecemeal. We briefly review the principles of COR theory and integrate it in the crossover model, which provides a key mechanism for multi‐person exchange of emotions, experiences and resources. Understanding the impact of resource reservoirs, resource passageways and crossover provides a framework for research and intervention promoting resilience to employees as well as to organizations. It emphasizes that the creation and maintenance of resource caravan passageways promote resource gain climates through resource crossover processes. Copyright © 2014 John Wiley & Sons, Ltd.     

Impact of dosing regimen of custirsen,an antisense oligonucleotide,on safety,tolerability and cardiac repolarization in healthy subjects

Aims

Custirsen (OGX-011/TV-1011), a second-generation antisense oligonucleotide (ASO) that reduces clusterin production, is under investigation with chemotherapy in patients with solid tumours. Custirsen is associated with constitutional symptoms (CS) that may interfere with clinical pharmacology investigations, such as QT interval studies. Experience with other ASOs suggests NSAID premedication may ameliorate CS, but we observed suboptimal outcomes in healthy subjects given custirsen and NSAIDs. We sought to establish a custirsen regimen for future clinical pharmacology studies in healthy subjects.

Methods

Subjects received custirsen (640 mg intravenously over 120 min) with dexamethasone premedication or increasing doses (320, 480, 640 mg over 6 days) of custirsen with dexamethasone premedication, then one full custirsen dose without premedication on day 8. Incidence/severity of adverse events (AEs) and extensive electrocardiogram readings were evaluated. Pharmacokinetic parameters were estimated.

Results

AEs included CS, elevated transaminases and prolonged activated partial thromboplastin time (aPTT) that were predominantly grade 1/2. Administration of increasing custirsen doses and dexamethasone premedication reduced the incidence of CS associated with full dose custirsen. Transaminase elevation showed a dose-dependent effect (0% at days 2, 4, 27% at day 6) with the highest custirsen doses. Increasing doses of custirsen may have mitigated the severity but not incidence of aPTT prolongation. Neither regimen was associated with cardiac repolarization changes in QT values or concentration–effect analyses. The custirsen pharmacokinetic profile was consistent with previous experience.

Conclusion

Escalation of custirsen dose combined with dexamethasone premedication reduced CS associated with full dose custirsen and should be considered in future clinical pharmacology studies of custirsen.     

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.     

Endoscopic dacryocystorhinostomy among the old and oldest-old populations - A case control study

ObjectiveDespite increased risks of nasolacrimal duct obstruction (NLDO) with age, and the continuous growth of the old population proportion, data on endoscopic dacryocystorhinostomy (eDCR) among the old is lacking. This study aims to evaluate long-term eDCR efficacy and safety in the old and oldest-old population.MethodsA retrospective case-control study of patients aged 80 ≤ (oldest-old) and 65–79 (old) compared with younger controls who underwent eDCR, between 2002 and 2017. Pre-, intra- and postoperative factors were collected using an integrated hospital-community system. Success rates were analyzed and measured at the first visit following surgery (immediate success), and after five years. Demographics, comorbidities, complications rates, and outcomes were compared between the groups.ResultsThe study groups included 52 oldest-old patients (mean age 83.4 ± 3.6), 127 old patients (72.3 ± 4.14) and 142 control patients (57.8 ± 18.0). The immediate and success rates were 94.2%, 93.7% and 90.8% and five-year success rates were 80.0%, 76.6% and 80% among oldest-old, old and controls, respectively. No significant differences in success rates were found, even despite higher comorbidity rates among the study's group (96 and 92.8% vs. 63.2%, among oldest-old, old and controls respectively, p <0.001). Intra- and postoperative complications rates were low in all groups.ConclusionsAmong older population, including oldest-old and old, eDCR safety and long-term outcomes are comparable with younger patients, suggesting that eDCR should be offered to NLDO patients, regardless of age.     

Determination of transmembrane topology of an inward-rectifying potassium channel from Arabidopsis thaliana based on functional expression in Escherichia coli

We report here that the inward-rectifying potassium channels KAT1 and AKT2 were functionally expressed in K⁺ uptake-deficient Escherichia coli. Immunological assays showed that KAT1 was translocated into the cell membrane of E. coli. Functional assays suggested that KAT1 was inserted topologically correctly into the cell membrane. In control experiments, the inactive point mutation in KAT1, T256R, did not complement for K⁺ uptake in E. coli. The inward-rectifying K⁺ channels of plants share a common hydrophobic domain comprising at least six membrane-spanning segments (S1–S6). The finding that a K⁺ channel can be expressed in bacteria was further exploited to determine the KAT1 membrane topology by a gene fusion approach using the bacterial reporter enzymes, alkaline phosphatase, which is active only in the periplasm, and β-galactosidase. The enzyme activity from the alkaline phosphatase and β-galactosidase fusion plasmid showed that the widely predicted S1, S2, S5, and S6 segments were inserted into the membrane. Although the S3 segment in the alkaline phosphatase fusion protein could not function as an export signal, the replacement of a negatively charged residue inside S3 with a neutral amino acid resulted in an increase in alkaline phosphatase activity, which indicates that the alkaline phosphatase was translocated into the periplasm. For membrane translocation of S3, the neutralization of a negatively charged residue in S3 may be required presumably because of pairing with a positively charged residue of S4. These results revealed that KAT1 has the common six transmembrane-spanning membrane topology that has been predicted for the Shaker superfamily of voltage-dependent K⁺ channels. Furthermore, the functional complementation of a bacterial K⁺ uptake mutant in this study is shown to be an alternative expression system for plant K⁺ channel proteins and a potent tool for their topological analysis.     

Global water resources affected by human interventions and climate change

Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future.Terrestrial water fluxes are affected by both climate and direct human interventions, e.g., dam operations and water withdrawals. Climate change is expected to alter the water cycle and will subsequently impact water availability and demand. Several hydrologic modeling studies have focused on climate change impacts on discharge in large river basins or global terrestrial areas under naturalized conditions using a single hydrologic model forced with multiple climate projections (1, 2). Recently, hydrological projections from eight global hydrological models (GHMs) were compared (3). In many areas, there was a large spread in projected runoff changes within the climate–hydrology modeling chain. However, at high latitudes there was a clear increase in runoff, whereas some midlatitude regions showed a robust signal of reduced runoff. The study also concluded that the choice of GHM adds to the uncertainty for hydrological change caused by the choice of atmosphere–ocean general circulation models (hereafter called GCMs) (3). Expected runoff increases in the north and decreases in parts of the middle latitudes have been found also when analyzing runoff from 23 GCMs (4).These studies focused on the naturalized hydrological cycle, i.e., the effects of direct human interventions were not taken into account. However, in many river basins humans substantially alter the hydrological cycle by constructing dams and through water withdrawals. Reservoir operations alter the timing of discharge, although mean annual discharge does not necessarily change much. A study with the water balance model (WBM) showed that the impact of human disturbances, i.e., dams and water consumption, in some river basins is equal to or greater than the impact of expected climate changes on annual runoff over the next 40 y (5). Also, rising water demands are found to outweigh global warming in defining the state of global water systems in the near future (6). Water for irrigation is the largest water use sector, currently accounting for about 70% of global water withdrawals and nearly 90% of consumptive water use (7). A recent synthesis of simulations from seven GHMs found that irrigation water consumption currently amounts to 1,250 km³⋅y⁻¹ (±25%) and that considerable differences among models appear in the spatiotemporal patterns of water consumption (8).Direct comparisons of the climate impact and human intervention modeling studies can be difficult given that the setups are not identical, i.e., the input forcing data and climate models vary. Also, because of the uncertainty of model-specific results, a multimodel approach is preferable in impact modeling studies (3, 9). This approach is similar to assessments performed within the climate community. Here, multimodel results on current and future water availability and consumption at the global scale from the Water Model Intercomparison Project (WaterMIP) within the European Union Water and Global Change (EU WATCH) project (9, 10), and Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) (11) are presented. (Information on how to get access to WaterMIP and ISI-MIP simulation results can be found at www.eu-watch.org and www.isi-mip.org, respectively.) Results from these two projects are synthesized to obtain a large ensemble of impact model results. The integration of results from the different projects is achieved by extracting impacts for time periods of global mean temperature (GMT) increases of 2 and 3 K from the simulations, largely following the method of Tang and Lettenmaier (4). The advantage of this approach is that it allows presenting results in a way that is in line with temperature targets used in climate mitigation discussions.Other studies have focused on future water scarcity using results from WaterMIP and ISI-MIP, but have analyzed changes of naturalized runoff only (3, 12). We here aim to fill this knowledge gap by comparing the different impacts from climate change and direct human impacts and analyzing their interplay. The models included take into account water withdrawals and consumption in different sectors; for more information, see Models and Data and Supporting Information, SI Models and Data. The objectives of this study are to (i) assess the relative contribution of anthropogenic impacts and climate change to river basin scale water fluxes, and (ii) identify areas where climate change can be expected to cause substantial changes in water consumption and water scarcity, focusing on water for irrigation. The effects of future changes in irrigated areas or irrigation practices are not taken into account, and only dams that currently exist are included in the analyses. In this paper, simulations considering man-made reservoirs, water withdrawals, and water consumption are referred to as human impact simulations, whereas the simulations without these disturbances are referred to as naturalized simulations. The results are mainly presented in a way intended to give an overview of impacts at larger spatial scales (river basin and country levels). However, some finer-scale results are included to reveal effects that can be concealed at coarse spatial scales.     

Therapeutic effect of secretin in patients with jaundice; Double-blind placebo-controlled multicentric trial

Secretin, a gastrointestinal hormone, has been shown to have a potent choleretic effect. Having already obtained some beneficial effects with secretin in patients with intrahepatic cholestasis, we sought to confirm its effects in a double-blind placebo-controlled study in patients with mild jaundice after acute or during chronic hepatitis, where total bilirubin level was in excess of 4.0 mg/dl for 3 days or more. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and familiar hyperbilirubinemia were excluded from the study. Ninety-three patients were included in this analysis, but the final evaluation covered 69 of them. No statisticaly significant differences were found in the reduction of serum bilirubin levels between secretin and placebo groups. As a number of patients with liver cirrhosis had been included, the subjects were subdivided into one group with cholestasis in hepatitis and one with liver cirrhosis. In the subgroup of cirrhotic patients who received secretin, serum levels of AST were significantly increased compared with the placebo group. However, since the choleretic effect of secretin is unique, further studies seem to be warranted.     

Prosthetic valve endocarditis caused by Gemella sanguinis: a consequence of persistent dental infection

Late prosthetic valve endocarditis is usually caused by streptococci, staphylococci, gram-negative bacilli and candida. The authors report the first case of prosthetic valve endocarditis caused by Gemella sanguinis. The patient's risk factors for the development of Gemella endocarditis were the persistent severe dental caries and the presence of prosthetic valves. The patient required surgical replacement of the infected valve but had a good outcome with preservation of cardiac and valvular function. Evaluation and treatment of the persistent dental infection before initial valvular surgery may have prevented secondary infection of the prosthetic valve.