Common cold symptoms may be mitigated by products in caplet, nasal spray, and oral solution formulations, although variations exist in the bioavailability of the active ingredients contained within ...these products. Rapid gastric emptying (GE) of these active ingredients is important for reducing the delay between drug absorption and onset of cold symptom relief. Hot drink cold remedies are associated with greater comfort and may enhance the bioavailability of active ingredients. The objective of this study was to characterize the gastrointestinal transit of powder (reconstituted in hot water) and caplet formulations of commercially available multisymptom cold medications.
This was an open-label, single-dose, parallel-group study. Healthy male adults under fasted conditions were randomized 1:1 to receive a single dose of radiolabeled Theraflu Daytime Severe Cold and Cough powder for oral solution or radiolabeled Theraflu ExpressMax Daytime Severe Cold and Cough caplet. External gamma scintigraphy was utilized to monitor GE and intestinal transit of two radiolabeled drug formulations.
A total of 28 participants completed the study. The mean ± SE GE onset times were 1.1 ± 0.3 min and 8.5 ± 1.8 min for powder and caplet formulations, respectively. The mean ± SE GE completion times were 121 ± 13 min and 65 ± 13 min, respectively. Despite the similar mean times to GE25%, the powder had later mean GE50% (23 ± 3.0 vs 16 ± 3.2 min, respectively) and GE90% (85 ± 12 vs 36 ± 9 min, respectively) than caplets. Caplets had a shorter overall GE half-life, lower total gastric exposure, and faster transit time through the small intestine versus the powder formulation. No serious safety events were observed.
The results of this study in healthy male adults suggest that the Theraflu powder formulation had a more rapid GE onset but longer time to GE completion than the caplet formulation.
ClinicalTrials.gov NCT03415243.
Although iron (Fe) is one of the most abundant elements in the earth's crust, its low solubility in soils restricts Fe uptake by plants. Most plant species acquire Fe by acidifying the rhizosphere ...and reducing ferric to ferrous Fe prior to membrane transport. However, it is unclear how these plants access Fe in the rhizosphere and cope with high soil pH. In a mutant screening, we identified 2-oxoglutarate-dependent dioxygenäse Feruloyl-CoA 6'-Hydroxylasel (F6'H1) to be essential for tolerance of Arabidopsis (Arabidopsis thaliana) to high pH-induced Fe deficiency. Under Fe deficiency, F6'H1 is required for the biosynthesis of fluorescent coumarins that are released into the rhizosphere, some of which possess Fe(III)-mobilizing capacity and prevent f6'h1 mutant plants from Fe deficiency-induced chlorosis. Scopoletin was the most prominent coumarin found in Fe-deficient root exudates but failed to mobilize Fe(III), while esculetin, i.e. 6,7-dihydroxycoumarin, occurred in lower amounts but was effective in Fe(III) mobilization. Our results indicate that Fe-deficient Arabidopsis plants release Fe(III)-chelating coumarins as part of the strategy I-type Fe acquisition machinery.
A coiled-up thermoelectric micro power generator is presented using metal films sputtered on a thin polyimide foil. The principle of coiling-up yields higher voltages at a smaller generator area. ...Design optimizations were made for maximum long-term power output using the human body as heat source. It is shown that for low-power electronics like a wrist-watch even simple materials are sufficient and allow lowest-cost production, e.g. screen printing. Thermoelectrical screen-printing pastes were developed and results of first screen printed thermocouples are given.
Patients with cancer represent a unique patient population with increased susceptibility to kidney disease. Drug-induced acute kidney injury (AKI) in patients with cancer is a common problem. ...Cisplatin is a highly effective treatment used in many solid-organ cancers and causes AKI in 30% of patients, increasing the risk of chronic kidney disease development. Most preclinical cisplatin toxicity studies have been completed in mice without cancer. We believe that the physiology of patients with cancer is not adequately represented in preclinical models, and the objective of this study was to determine how lung cancer will alter the nephrotoxicity of cisplatin. A genetically engineered mouse model and a syngeneic xenograft model of lung cancer were used. Mice were divided into the following four groups:
) noncancer/vehicle,
) noncancer/cisplatin,
) cancer/vehicle, and
) cancer/cisplatin. Mice were administered cisplatin via intraperitoneal injection once a week for 4 wk. Animals were euthanized 72 h following their final cisplatin injection. Mice with lung cancer had increased renal toxicity, injury, and fibrosis following repeated low doses of cisplatin. In addition, lung cancer alone induced kidney injury and fibrosis in the kidney before cisplatin treatment. In conclusion, this is the first study that we are aware of that assesses the impact of cancer on the kidney in conjunction with the nephrotoxicity of cisplatin. We believe that cancer is providing the first hit to the kidney and the subsequent damage from repeated doses of cisplatin becomes unsurmountable, leading to AKI and progression to chronic kidney disease.
Patients with cancer have impaired kidney function and increased susceptibility to nephrotoxic agents. Cisplatin is a commonly used chemotherapeutic with nephrotoxicity as the dose-limiting side effect. Cisplatin nephrotoxicity is almost exclusively studied in mice without cancer. Our current preclinical models do not adequately represent the complexity of patients with cancer. This study demonstrates increased renal toxicity, injury, and fibrosis in mice with lung cancer, which is exacerbated with cisplatin treatment. These results highlight the necessity of using preclinical models that more accurately capture the altered physiology of patients with cancer treated with cisplatin.
Parallel tempering, or replica exchange, is a popular method for simulating complex systems. The idea is to run parallel simulations at different temperatures, and at a given swap rate exchange ...configurations between the parallel simulations. From the perspective of large deviations it is optimal to let the swap rate tend to infinity and it is possible to construct a corresponding simulation scheme, known as infinite swapping. In this paper we propose a novel use of large deviations for empirical measures for a more detailed analysis of the infinite swapping limit in the setting of continuous time jump Markov processes. Using the large deviations rate function and associated stochastic control problems we consider a diagnostic based on temperature assignments, which can be easily computed during a simulation. We show that the convergence of this diagnostic to its a priori known limit is a necessary condition for the convergence of infinite swapping. The rate function is also used to investigate the impact of asymmetries in the underlying potential landscape, and where in the state space poor sampling is most likely to occur.
Almond canker diseases are destructive and can reduce the yield as well as the lifespan of almond orchards. These diseases may affect the trunk and branches of both young and mature trees and can ...result in tree death soon after orchard establishment in severe cases. Between 2015 and 2018, 70 almond orchards were visited throughout the Central Valley of California upon requests from farm advisors for canker disease diagnosis. Two major canker diseases were identified, including Botryosphaeriaceae cankers and Ceratocystis canker. In addition, five less prevalent canker diseases were identified, including Cytospora, Eutypa, Diaporthe, Collophorina, and Pallidophorina canker. Seventy-four fungal isolates were selected for multilocus phylogenetic analyses of internal transcribed spacer region ITS1-5.8S-ITS2 and part of the translation elongation factor 1-α, β-tubulin, and glyceraldehyde 3-phosphate dehydrogenase gene sequences; 27 species were identified, including 12 Botryosphaeriaceae species,
, five
species,
, four
species, two
species,
, and
. The most frequently isolated species were
,
, and
. Pathogenicity experiments on almond cultivar Nonpareil revealed that
,
, and
were the most virulent. Botryosphaeriaceae cankers were predominantly found in young orchards and symptoms were most prevalent on the trunks of trees. Ceratocystis canker was most commonly found in mature orchards and associated with symptoms found on trunks or large scaffold branches. This study provides a thorough examination of the diversity and pathogenicity of fungal pathogens associated with branch and trunk cankers of almond in California.
Background In the current study, we aimed to develop an algorithm based on biomarkers obtained through non- or minimally invasive procedures to identify healthy elderly subjects who have an increased ...risk of abnormal cerebrospinal fluid (CSF) amyloid beta42 (Abeta) levels consistent with the presence of Alzheimer's disease (AD) pathology. The use of the algorithm may help to identify subjects with preclinical AD who are eligible for potential participation in trials with disease modifying compounds being developed for AD. Due to this pre-selection, fewer lumbar punctures will be needed, decreasing overall burden for study subjects and costs. Methods Healthy elderly subjects (n = 200; age 65-70 (N = 100) and age > 70 (N = 100)) with an MMSE > 24 were recruited. An automated central nervous system test battery was used for cognitive profiling. CSF Abeta1-42 concentrations, plasma Abeta1-40, Abeta1-42, neurofilament light, and total Tau concentrations were measured. Abeta1-42/1-40 ratio was calculated for plasma. The neuroinflammation biomarker YKL-40 and APOE epsilon4 status were determined in plasma. Different mathematical models were evaluated on their sensitivity, specificity, and positive predictive value. A logistic regression algorithm described the data best. Data were analyzed using a 5-fold cross validation logistic regression classifier. Results Two hundred healthy elderly subjects were enrolled in this study. Data of 154 subjects were used for the per protocol analysis. The average age of the 154 subjects was 72.1 (65-86) years. Twenty-four (27.3%) were Abeta positive for AD (age 65-83). The results of the logistic regression classifier showed that predictive features for Abeta positivity/negativity in CSF consist of sex, 7 CNS tests, and 1 plasma-based assay. The model achieved a sensitivity of 70.82% (+ or - 4.35) and a specificity of 89.25% (+ or - 4.35) with respect to identifying abnormal CSF in healthy elderly subjects. The receiver operating characteristic curve showed an AUC of 65% (+ or - 0.10). Conclusion This algorithm would allow for a 70% reduction of lumbar punctures needed to identify subjects with abnormal CSF Abeta levels consistent with AD. The use of this algorithm can be expected to lower overall subject burden and costs of identifying subjects with preclinical AD and therefore of total study costs. Trial registration ISRCTN.org identifier: ISRCTN79036545 (retrospectively registered). Keywords: Alzheimer, Preclinical AD, Clinical trial, Algorithm, CSF Abeta
Interest in electronic hand hygiene monitoring systems (EHHMSs) is now widespread throughout the infection control community. We tested 2 types of EHHMS for accuracy. The type B EHHMS captured more ...HH events with superior accuracy. Hospitals considering an EHHMS should assess the technology's ability to accurately capture HH performance in the clinical workflow.
PDF
