Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic ...review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED
) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED
of morphine alone. In addition, the ED
for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED
of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.
The current lack of pharmacological treatments for cannabis use disorder (CUD) warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols ...(27 mg/ml Δ9-tetrahydrocannabinol (THC)/ 25 mg/ml cannabidiol (CBD), Sativex®) can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.
Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.
Medication was well tolerated and no serious adverse events (SAEs) were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS). There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS). Cannabis use was reduced in the nabiximols (70.5%) and placebo groups (42.6%). Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores.
Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.
We use high quality climate data from ground meteorological stations in the Iberian Peninsula (IP) and robust drought indices to confirm that drought severity has increased in the past five decades, ...as a consequence of greater atmospheric evaporative demand resulting from temperature rise. Increased drought severity is independent of the model used to quantify the reference evapotranspiration. We have also focused on drought impacts to drought-sensitive systems, such as river discharge, by analyzing streamflow data for 287 rivers in the IP, and found that hydrological drought frequency and severity have also increased in the past five decades in natural, regulated and highly regulated basins. Recent positive trend in the atmospheric water demand has had a direct influence on the temporal evolution of streamflows, clearly identified during the warm season, in which higher evapotranspiration rates are recorded. This pattern of increase in evaporative demand and greater drought severity is probably applicable to other semiarid regions of the world, including other Mediterranean areas, the Sahel, southern Australia and South Africa, and can be expected to increasingly compromise water supplies and cause political, social and economic tensions among regions in the near future.
We describe herein the state of the art following the last 8 years of research into aromatic polyamides, wholly aromatic polyamides or aramids. These polymers belong to the family of high performance ...materials because of their exceptional thermal and mechanical behavior. Commercially, they have been transformed into fibers mainly for production of advanced composites, paper, and cut and fire protective garments. Huge research efforts have been carried out to take advantage of the mentioned characteristics in advanced fields related to transport applications, optically active materials, electroactive materials, smart materials, or materials with even better mechanical and thermal behavior.
Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients ...retrieved from lung cancer registries is scarce. This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or greater than or equal to 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8-10.2 months), with an estimated rate of 70.3% (95% CI 67.2-73.4%), 38.9% (95% CI 35.4-42.4%), and 14.8% (95% CI 11.8-17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1-2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.
Land surface temperature (LST) is estimated from thermal infrared data provided by the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard Meteosat Second Generation (MSG), using a ...generalized split-window (GSW) algorithm. The uncertainty of the LST retrievals is highly dependent on the input accuracy and retrieval conditions, particularly the sensor view angle and the atmospheric water vapor content. This paper presents a quantification of the uncertainty of LST estimations, taking into account error statistics of the GSW under a globally representative collection of atmospheric profiles, and a careful characterization of the uncertainty of input data, particularly the surface emissivity and forecasts of the total water vapor content. Such analysis is the basis for LST uncertainty estimation, also distributed to users, in the form of error bars, along with the LST retrievals. Moreover, the spatial coverage of SEVIRI LST is essentially determined by the LST expected uncertainty, instead of being restricted to view zenith angles below a given threshold (e.g., 60°). Within the MSG disk, the atmosphere is often dry for clear-sky conditions where angles are large (e.g., Northern and Eastern Europe and Saudi Arabia). By considering several factors that contribute to LST inaccuracies, it is possible to increase the spatial coverage to regions such as those mentioned earlier. Retrieved values are also compared with in situ observations collected in Namibia, covering a seasonal cycle. The two data sets are in good agreement with root-mean-square differences ranging between 1°C and 2°C, which is well below the average error estimated for the satellite retrievals.
In recent years, sensory polymers have evolved significantly, emerging as versatile and cost-effective materials valued for their flexibility and lightweight nature. These polymers have transformed ...into sophisticated, active systems capable of precise detection and interaction, driving innovation across various domains, including smart materials, biomedical diagnostics, environmental monitoring, and industrial safety. Their unique responsiveness to specific stimuli has sparked considerable interest and exploration in numerous applications. However, along with these advancements, notable challenges need to be addressed. Issues such as wearable technology integration, biocompatibility, selectivity and sensitivity enhancement, stability and reliability improvement, signal processing optimization, IoT integration, and data analysis pose significant hurdles. When considered collectively, these challenges present formidable barriers to the commercial viability of sensory polymer-based technologies. Addressing these challenges requires a multifaceted approach encompassing technological innovation, regulatory compliance, market analysis, and commercialization strategies. Successfully navigating these complexities is essential for unlocking the full potential of sensory polymers and ensuring their widespread adoption and impact across industries, while also providing guidance to the scientific community to focus their research on the challenges of polymeric sensors and to understand the future prospects where research efforts need to be directed.
Low‐density porous aramid films using inexpensive and widely available polymers as porosity promoters, that is, polyvinyl alcohol (PVA), poly(2‐ethyl‐2‐oxazoline) (PEOx), and cellulose polyacetate ...(CA) were fabricated. Porous poly (m‐phenylene isophthalamide) films were obtained by the standard casting procedure using mixtures of the aramid with either PVA, PEOx, or CA, followed by the removal of the porosity promoter polymers by immersing them in water or acetone. As a result, films with up to a 65% density reduction with pore sizes ranging from 0.02 to 10 μm and up to 30% increment in Young's modulus were obtained. In addition, the morphology of the films was homogeneous and was controlled by the proportion and nature of the porosity promoter polymer. The density reduction of materials plays a significant role in energy crises and the need for fuel reduction. This study revealed that it is possible to prepare low‐density porous aramid films inexpensively without impairing their outstanding performance by using PVA in the casting procedure as a porosity promoter polymer.
Preparation of porous m‐aramids using different porosoty promoter polymers
Aramids, renowned for their high-performance attributes, find applications in critical fields such as protective equipment, aerospace components, and industrial filters. However, challenges arise in ...scenarios in which frequent washing is impractical, leading to bacterial proliferation, especially in textiles. This study outlines a straightforward and scalable method for preparing aramid-coated textiles and films endowed with inherent bactericidal activity, achieved by reacting parent aramids with vanillin. The functionalization of the aramids with bactericide moieties not only preserved the high-performance characteristics of commercial aramids but also improved their crucial mechanical properties. Tensile tests revealed an increase in Young’s modulus, up to 50% compared to commercial m-aramid, accompanied by thermal performance comparable to commercial m-aramids. The evaluation of these coated textiles as bactericidal materials demonstrated robust effectiveness with A parameters (antibacterial activity) of 4.31 for S. aureus and 3.44 for K. pneumoniae. Reusability tests (washing the textiles in harsh conditions) underscored that the bactericide-coated textiles maintain their performance over at least 5 cycles. Regarding practical applications, tests performed with reconstructed human epidermis affirmed the nonirritating nature of these materials to the skin. The distinctive qualities of these metal-free intrinsic bactericidal aramids position them as ideal candidates for scenarios demanding a synergy of high performance and bactericidal properties. Applications such as first responders’ textiles or filters stand to benefit significantly from these advanced materials.
Olive tree-derived products have been associated with numerous benefits for health. The aim of the present study was to characterize an olive leaf extract enriched in oleuropein (OLE) concerning ...phenolic content and profile as well as antioxidant capacity. Short-term and long-term toxicity, including oxidative stress, was in vivo evaluated in the experimental model Caenorhabditis elegans. Moreover, the potential therapeutic effect of the extract against Aβ induced- and tau protein induced-toxicity was also evaluated in C. elegans. OLE treatment did not exert toxicity. On the contrary, the extract was able to ameliorate oxidative stress and proteotoxicity related to Aβ and tau aggregation. The potential molecular mechanisms present behind the observed results explored by RNAi technology revealed that DAF-16/FOXO and SKN-1/NRF2, elements of the insulin insulin-like signalling pathway, as well as HSP-16.2 overexpression were involved.
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●OLE is a source of phenolics that exert a strong antioxidant effect in vitro.●Short- and long-term toxicity, including oxidative stress, is prevented by OLE.●OLE prevented Aβ peptide and tau protein induced toxicity in C. elegans.●DAF-16/FOXO, SKN-1/NRF2 and HSP16.2 are involved in OLE anti-AD effects.●OLE could be an interesting formulation for the development of nutraceutics.
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