Generalized Anxiety Disorder (GAD) is a very prevalent disorder in primary care (PC). Most patients with GAD never seek treatment, and those who do seek treatment often drop out before completing ...treatment. Although it is an understudied treatment, Mindfulness-Based Interventions (MBIs) indicate preliminary efficacy for the treatment of GAD symptoms, but many patients with GAD present other associated symptoms (e.g., attention deficits) that complicate the treatment. Virtual Reality DBT
Mindfulness Skills learning has recently been developed to make learning mindfulness easier for patients with emotion dysregulation who have trouble concentrating. Virtual Reality (VR) might serve as a visual guide for practicing mindfulness as it gives patients the illusion of "being there" in the 3D computer generated world. The main goal of this study was to evaluate the effect of two MBIs (a MBI in a group setting alone and the same MBI plus 10 min VR DBT
Mindfulness skills training) to reduce GAD symptoms. A secondary aim was to explore the effect in depression, emotion regulation, mindfulness, and interoceptive awareness. Other exploratory aims regarding the use of VR DBT
Mindfulness skills were also carried out. The sample was composed of 42 patients (roughly half in each group) with GAD attending PC visits. After treatment, both groups of patients showed significant improvements in General Anxiety Disorder measured by the GAD-7 using mixed regression models MBI alone (
= -5.70;
< 0.001;
= -1.36), MBI+VR DBT
Mindfulness skills (
= -4.38;
< 0.001;
= -1.33). Both groups also showed significant improvements in anxiety, depression, difficulties of emotion regulation and several aspects of mindfulness and interoceptive awareness. Patients in the group that received additional 10 min VR DBT Mindfulness Skills training were significantly more adherent to the treatment than those receiving only standard MBI (100% completion rate in MBI + VR vs. 70% completion rate in MBI alone;
= 0.020). Although randomized controlled studies with larger samples are needed, this pilot study shows preliminary effectiveness of MBI to treat GAD, and preliminary evidence that adjunctive VR DBT
Mindfulness Skills may reduce dropouts.
•The expansion of cell-based therapies needs for scalable and robust manufacturing.•Scale up procedures should yield high cell numbers and meet defined specifications.•Monitored single-use ...bioreactors are convenient platforms for hMSC production.•Key culture conditions to support successful expansion of hMSC are revised.•Materials, reagents and regulatory compliance are key to ensure reproducibility.
Production of sufficient numbers of multipotent Mesenchymal Stromal Cells is a great challenge that the industry must address to meet the increasing demand for clinical size product batches. This can be understood as an opportunity to exploit existing bioprocessing technologies already tested successfully in the production of vaccines and biologicals. Herein we analyse the transition from traditional manual cell expansion 2D methodologies to scalable and automated platforms with the capacity to yield billions of cells per batch in a robust, reproducible and cost-effective manner in compliance with current Good Manufacturing Practices. This review gives special relevance to the key features of multiple manufacturing platforms, particularly those using microcarriers to support cell expansion and single-use bioreactors.
Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize ...microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.
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•Polyrotaxane is selected as the supporter material for PEG based leakage-proof phase change materials.•The form-stable PCM performed high thermal conductivity with value of ...2.72 W/(m·K).•The PCM retains excellent heat processability and flexibility.•It showed outstanding performances in thermal management of smart phone and peak shifting and valley filling effect for thermoelectric generator (TEG).
In this work, we tried to overcome the typical limitations of phase change materials (PCMs), namely, leakage and low thermal conductivity. To realize the leakage proof PCM, a polyrotaxane (PLR) was selected as a support material to encapsulate Polyethylene glycol (PEG) 1 k. Subsequently, different contents of Boron Nitride (BN) were blended to enhance the thermal conductivity of PLR/PEG matrix. The PCMs created in this work achieves a high thermal performance with enthalpy values (91.2–123.5 J/g) and high flexibility and shows a great shape stability and no leakage and shape change during its phase transition. Due to the action of BN as a multifunctional filler, the PCMs also experienced an increase of 186.7% to 806.7% in thermal conductivity values, and enhanced flame retardancy (with decrease of 16.6% for pHRR and 25.5% for THR). These improvements solve the main problems of organic PCMs thus making PLR-PEG-BN based materials a good candidate to be used as thermal energy storage material in industrial applications. For the exact application cases, it showed obvious Peak Shaving and Valley Filling for thermoelectric generator and heat regulation for the smart phone.
YMnO3 is a P-type semiconductor with a perovskite-type structure (ABO3). It presents two crystalline systems: rhombohedral and hexagonal, the latter being the most stable and studied. In the ...hexagonal system, Mn3+ ions are coordinated by five oxygen ions forming a trigonal bipyramid, and the Y3+ ions are coordinated by five oxygen ions. This arrangement favors its ferroelectric and ferromagnetic properties, which have been widely studied since 1963. However, applications based on their optical properties have yet to be explored. This work evaluates the photoelectric response and the photocatalytic activity of yttrium manganite in visible spectrum wavelengths. To conduct this, a rod-obelisk-shaped yttrium manganite with a reduced indirect bandgap value of 1.43 eV in its hexagonal phase was synthesized through the precipitation method. The synthesized yttrium manganite was elucidated by solid-state techniques, such as DRX, XPS, and UV-vis. It was non-toxic as shown by the 100% leukocyte viability of mice BALB/c.
Cell therapies based on multipotent mesenchymal stromal cells (MSCs) are traditionally produced using 2D culture systems and platelet lysate‐ or serum‐containing media (SCM). Although cost‐effective ...for single‐dose autologous treatments, this approach is not suitable for larger scale manufacturing (e.g., multiple‐dose autologous or allogeneic therapies with banked MSCs); automated, scalable and Good Manufacturing Practices (GMP)‐compliant platforms are urgently needed. The feasibility of transitioning was evaluated from an established Wharton's jelly MSCs (WJ‐MSCs) 2D production strategy to a new one with stirred‐tank bioreactors (STRs). Experimental conditions included four GMP‐compliant xeno‐ and serum‐free media (XSFM) screened in 2D conditions and two GMP‐grade microcarriers assessed in 0.25 L‐STRs using SCM. From the screening, a XSFM was selected and compared against SCM using the best‐performing microcarrier. It was observed that SCM outperformed the 2D‐selected medium in STRs, reinforcing the importance of 2D‐to‐3D transition studies before translation into clinical production settings. It was also found that attachment efficiency and microcarrier colonization were essential to attain higher fold expansions, and were therefore defined as critical process parameters. Nevertheless, WJ‐MSCs were readily expanded in STRs with both media, preserving critical quality attributes in terms of identity, viability and differentiation potency, and yielding up to 1.47 × 109 cells in a real‐scale 2.4‐L batch.
Graphical and Lay Summary
The development of cost‐effective platforms for mesenchymal stromal cells (MSCs) production is challenging. Herein, the transition was explored from a traditional 2D production strategy to a volumetric (3D) approach utilizing stirred‐tank bioreactors (STRs). To do this, Good Manufacturing Practice (GMP)‐compliant xeno‐ and serum‐free media (XSFM) and two GMP‐grade microcarriers were assessed while developing the 3D bioprocess protocol. Significant cell numbers meeting the MSC minimal criteria definition were obtained, potentially yielding 1.47 × 109 cells in a single real scale batch production.
Head and neck squamous cell carcinoma present a high mortality rate. Melatonin has been shown to have oncostatic effects in different types of cancers. However, inconsistent results have been ...reported for in vivo applications. Consequently, an alternative administration route is needed to improve bioavailability and establish the optimal dosage of melatonin for cancer treatment. On the other hand, the use of patient-derived tumor models has transformed the field of drug research because they reflect the heterogeneity of patient tumor tissues. In the present study, we explore mechanisms for increasing melatonin bioavailability in tumors and investigate its potential as an adjuvant to improve the therapeutic efficacy of cisplatin in the setting of both xenotransplanted cell lines and primary human HNSCC. We analyzed the effect of two different formulations of melatonin administered subcutaneously or intratumorally in Cal-27 and SCC-9 xenografts and in patient-derived xenografts. Melatonin effects on tumor mitochondrial metabolism was also evaluated as well as melatonin actions on tumor cell migration. In contrast to the results obtained with the subcutaneous melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. We demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting mitochondria. Melatonin also reduces migration capacities and metastasis markers. These results illustrate the great clinical potential of intratumoral melatonin treatment and encourage a future clinical trial in cancer patients to establish a proper clinical melatonin treatment.
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•High concentrations of melatonin completely abolish tumor growth.•Melatonin synergized the effects of cisplatin.•Intratumoral melatonin also reduces tumor formation in patient-derived models.•Melatonin induces changes in tumor mitochondrial morphology and distribution.
Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ...ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P. aeruginosa isolates recovered during 1 year (2020) from patients with a documented P. aeruginosa infection. Fifteen isolates showing ceftolozane-tazobactam and ceftazidime-avibactam resistance were evaluated. Clinical conditions, previous positive cultures, and β-lactams received in the previous month were reviewed for each patient. MICs were determined by broth microdilution. Multilocus sequence types (MLSTs) and resistance mechanisms were determined using short- and long-read whole-genome sequencing (WGS). The impact of Pseudomonas
derived cephalosporinases (PDCs) on β-lactam resistance was demonstrated by cloning into an
-deficient PAO1 derivative (PAOΔC) and construction of 3D models. Genetic support of acquired β-lactamases was determined
from high-quality hybrid assemblies. In most cases, the isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Seven isolates from different sequence types (STs) owed their β-lactam resistance to chromosomal mutations and all displayed specific substitutions in PDC: Phe121Leu and Gly222Ser, Pro154Leu, Ala201Thr, Gly214Arg, ΔGly203-Glu219, and Glu219Lys. In the other eight isolates, the ST175 clone was overrepresented (6 isolates) and associated with IMP-28 and IMP-13, whereas two ST1284 isolates produced VIM-2. The cloned PDCs conferred enhanced cephalosporin resistance. The 3D PDC models revealed rearrangements affecting residues involved in cephalosporin hydrolysis. Carbapenemases were chromosomal (VIM-2) or plasmid-borne (IMP-28, IMP-13) and associated with class-1 integrons located in Tn402-like transposition modules. Our findings highlighted that cephalosporin/β-lactamase inhibitors are potential selectors of MDR/XDR P. aeruginosa strains producing PDC variants or metallo-β-lactamases. Judicious use of these agents is encouraged.
The term third-wave cognitive behavioral therapy (CBT) encompasses new forms of CBT that both extend and innovate within CBT. Most third-wave therapies have been subject to randomized controlled ...trials (RCTs) focused on clinical effectiveness; however, the number and quality of economic evaluations in these RCTs has been unknown and may be few. Evidence about efficiency of these therapies may help support decisions on efficient allocation of resources in health policies. The main aim of this study was to systematically review the economic impact of third-wave therapies in the treatment of patients with physical or mental conditions. We conducted a systematic literature search in PubMed, PsycINFO, EMBASE, and CINALH to identify economic evaluations of third-wave therapies. Quality and Risk of Bias (RoB) assessment of economic evaluations was also made using the Drummond 35-item checklist and the Cochrane Collaboration’s tool for assessing risk of bias, respectively. Eleven RCTs were included in this systematic review. Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Dialectical Behavior Therapy (DBT), and extended Behaviour Activation (eBA) showed acceptable cost-effectiveness and cost-utility ratios. No study employed a time horizon of more than 3 years. Quality and RoB assessments highlight some limitations that temper the findings. There is some evidence that MBCT, MBSR, ACT, DBT, and eBA are efficient from a societal or a third-party payer perspective. No economic analysis was found for many third-wave therapies. Therefore, more economic evaluations with high methodological quality are needed.
•First review of economic impact of third-wave cognitive behavioral therapies.•Only 11 RCTs with economic evaluations found in this systematic review.•Five third-wave therapies show promising cost-effectiveness findings.•The quality and risk of bias assessments revealed some methodological limitations.
DyMnO3 is a p-type semiconductor oxide with two crystal systems, orthorhombic and hexagonal. This material highlights its ferroelectric and ferromagnetic properties, which have been the subject of ...numerous studies. Nevertheless, its photocatalytic activity has been less explored. In this work, the photocatalytic activity of DyMnO3 is evaluated through the photodegradation of MG dye. For the synthesis of this oxide, a novel and effective method was used: polymer-decomposition. The synthesized powders contain an orthorhombic phase, with a range of absorbances from 300 to 500 nm and a band gap energy of 2.4 eV. It is also highlighted that, when using this synthesis method, some of the main diffraction lines related to the orthorhombic phase appear at 100 °C. Regarding its photocatalytic activity, it was evaluated under visible light (λ = 405 nm), reaching a photodegradation of approximately 88% in a period of 30 min. Photocurrent tests reveal a charge carrier separation (e−,h+) at a 405 nm wavelength. The main reactive oxygen species (ROS) involved in the photodegradation process were radicals, OH•, and photo-holes (h+). These results stand out because it is the first time that the photodegradation capability of this oxide in the visible spectrum has been evaluated.
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