Clinical practice during the COVID-19 pandemic: a qualitative study among child and adolescent psychiatrists across the world

Background The COVID-19 pandemic has directly impacted the field of child and adolescent psychiatry, affecting all aspects of the lives of children and their families and increasing their risk of distress and mental health issues, especially among children with preexisting psychiatric disorders. Child and adolescent psychiatrists (CAPs) across the world have had to adapt their practice, due to lockdown and social distancing measures. This study aimed to explore how CAPs experienced their clinical practice in these singular conditions. Methods This exploratory international qualitative study used the Inductive Process to analyse the Structure of lived Experience (IPSE) approach, which is a five-stage inductive process used to explore the lived experience of participants in depth and to analyze their structure of lived experience. This study took place from March through July 2020 through individual in-depth video interviews. The sample size was determined according to the principles of theoretical sufficiency. Results 39 CAPs from 26 countries participated (age range 32–70 years; 23 women). Data analysis produced a structure of lived experience comprising three central axes of experience: (1) lost in space, lost in time, describing CAPs’ experience of disorganization of their clinical practice in the dimensions of lived time and lived space, (2) the body—of CAPs and patients—underlining their disconcerting experience of both sensory aspects and the non-embodied encounter during clinical practice, and (3) unpleasant emotions, with angst and loneliness the two main feelings coloring their clinical practice experience. Conclusions This analysis of the structure of lived experience of CAPs went beyond the sole context of the pandemic and revealed key aspects of what usually organizes CAP clinical practice. It identified two blind spots or conceptual voids within the child and adolescent psychiatry field: first, the intrinsic therapeutic function of a CAP clinical practice and, second, the important diagnostic and therapeutic function of the embodied encounter during CAP consultations. Beyond the context of COVID-19, further research should investigate these aspects to better define what a CAP does in practice and to increase both attractiveness and recruitment in this specialty.

Cargo proteins in extracellular vesicles: potential for novel therapeutics in non-alcoholic steatohepatitis

Background Extracellular vesicles (EVs) are recognized as novel cell-free therapeutics. Non-alcoholic steatohepatitis (NASH) remains a critical health problem. Herein, we show that EVs from pan peroxisome proliferator-activated receptor agonist-primed induced mesenchymal stem cell (pan PPAR-iMSC-EVs) has unique cargo protein signatures, and demonstrate its therapeutic function in NASH. Results A unique protein signatures were identified in pan PPAR-iMSC-EVs against those from non-stimulated iMSC-EVs. NASH mice receiving pan PPAR-iMSC-EVs showed reduced steatotic changes and ameliorated ER stress and mitochondiral oxidative stress induced by inflammation. Moreover, pan PPAR-iMSC-EVs promoted liver regeneration via inhibiting apoptosis and enhancing proliferation. Conclusions We conclude that our strategy for enriching unique cargo proteins in EVs may facilitate the development of novel therapeutic option for NASH. Graphical Abstract

Mesenchymal stromal cell apoptosis is required for their therapeutic function

Multipotent mesenchymal stromal cells (MSCs) ameliorate a wide range of diseases in preclinical models, but the lack of clarity around their mechanisms of action has impeded their clinical utility. The therapeutic effects of MSCs are often attributed to bioactive molecules secreted by viable MSCs. However, we found that MSCs underwent apoptosis in the lung after intravenous administration, even in the absence of host cytotoxic or alloreactive cells. Deletion of the apoptotic effectors BAK and BAX prevented MSC death and attenuated their immunosuppressive effects in disease models used to define MSC potency. Mechanistically, apoptosis of MSCs and their efferocytosis induced changes in metabolic and inflammatory pathways in alveolar macrophages to effect immunosuppression and reduce disease severity. Our data reveal a mode of action whereby the host response to dying MSCs is key to their therapeutic effects; findings that have broad implications for the effective translation of cell-based therapies.

Taste and chemical composition as drives for utilitarian redundancy and equivalence: a case study in local medical systems in Northeastern Brazil

Background We aimed to verify whether the taste and chemical composition influence the selection of plants in each medicinal category, whether within a socio-ecological system or between different socio-ecological systems. To this end, we use the theoretical bases of the Utilitarian Redundancy Model and the Utilitarian Equivalence Model. We studied the local medical systems of four rural communities in northeastern Brazil, used as models to test our assumptions. Methods The data on medicinal plants and local therapeutic function were obtained from semi-structured interviews associated with the free-listing method, allowing to generate indexes of similarity of therapeutic use between the plants cited in each region. During the interviews, each informer was also asked to report the tastes of the plants cited. Subsequently, we classified each plant in each region according to the most cited taste. The data about the chemical composition of each plant were obtained from a systematic review, using Web of Knowledge and Scopus databases. Results Pairs of plants with similar tastes are 1.46 times more likely to have the same therapeutic function within a local medical system (redundancy), but not between medical systems (equivalence). We also find that chemical compounds are not primarily responsible for utilitarian redundancy and equivalence. However, there was a tendency for alkaloids to be doubly present with greater expressiveness in pairs of equivalent plants. Conclusions The results indicate that each social group can create its means of using the organoleptic characteristics as clues to select new species as medicinal. Furthermore, this study corroborates the main prediction of the Utilitarian Equivalence Model, that people in different environments choose plants with traits in common for the same functions.

Controlled Release of Doxorubicin for Targeted Chemo-Photothermal Therapy in Breast Cancer HS578T Cells Using Albumin Modified Hybrid Nanocarriers

Hybrid nanomaterials have attracted research interest owing to their intriguing properties, which may offer new diagnostic options with triggering features, able to realize a new kind of tunable nanotherapeutics. Hybrid silica/melanin nanoparticles (NPs) containing silver seeds (Me-laSil_Ag-HSA NPs) disclosed relevant photoacoustic contrast for molecular imaging. In this study we explored therapeutic function in the same nanoplatform. For this purpose, MelaSil_Ag-HSA were loaded with doxorubicin (DOX) (MelaSil_Ag-HSA@DOX) and tested to assess the efficiency of drug delivery combined with concurrent photothermal treatment. The excellent photothermal properties allowed enhanced cytotoxic activity at significantly lower doses than neat chemotherapeutic treatment. The results revealed that MelaSil_Ag-HSA@DOX is a promising platform for an integrated photothermal (PT) chemotherapy approach, reducing the efficacy concentration of the DOX and, thus, potentially limiting the several adverse side effects of the drug in in vivo treatments.

Dual Emissive Ir(III) Complexes for Photodynamic Therapy and Bioimaging

Photodynamic therapy (PDT) is a cancer treatment still bearing enormous prospects of improvement. Within the toolbox of PDT, developing photosensitizers (PSs) that can specifically reach tumor cells and promote the generation of high concentration of reactive oxygen species (ROS) is a constant research goal. Mitochondria is known as a highly appealing target for PSs, thus being able to assess the biodistribution of the PSs prior to its light activation would be crucial for therapeutic maximization. Bifunctional Ir(III) complexes of the type [Ir(C^N)2(N^N-R)]+, where N^C is either phenylpyridine (ppy) or benzoquinoline (bzq), N^N is 2,2′-dipyridylamine (dpa) and R either anthracene (1 and 3) or acridine (2 and 4), have been developed as novel trackable PSs agents. Activation of the tracking or therapeutic function could be achieved specifically by irradiating the complex with a different light wavelength (405 nm vs. 470 nm respectively). Only complex 4 ([Ir(bzq)2(dpa-acr)]+) clearly showed dual emissive pattern, acridine based emission between 407–450 nm vs. Ir(III) based emission between 521 and 547 nm. The sensitivity of A549 lung cancer cells to 4 evidenced the importance of involving the metal center within the activation process of the PS, reaching values of photosensitivity over 110 times higher than in dark conditions. Moreover, complex 4 promoted apoptotic cell death and possibly the paraptotic pathway, as well as higher ROS generation under irradiation than in dark conditions. Complexes 2–4 accumulated in the mitochondria but species 2 and 4 also localizes in other subcellular organelles.

Gene-circuit therapy on the horizon: synthetic biology tools for engineered therapeutics

Therapeutic genome modification requires precise control over the introduced therapeutic functions. Current approaches of gene and cell therapy fail to deliver such command and rely on semi-quantitative methods with limited influence on timing, contextuality and levels of transgene expression, and hence on therapeutic function. Synthetic biology offers new opportunities for quantitative functionality in designing therapeutic systems and their components. Here, we discuss synthetic biology tools in their therapeutic context, with examples of proof-of-principle and clinical applications of engineered synthetic biomolecules and higher-order functional systems, i.e. gene circuits. We also present the prospects of future development towards advanced gene-circuit therapy.

One-Step Synthesis of Ribonucleases A–Ag Nanocomposites as Fluorescent Nanodrugs for in vivo Delivery

Proteins and enzymes with potential therapeutic function have been widely used in drug delivery. Meanwhile, nanocrystals (NCs) have showed their advantage as in vivo fluorescent indicators. Combining of these two kinds of materials can result in multifunctional composites. Here, a one-step synthesis of protein–NCs nanocomposites with near infrared (NIR) fluorescence and efficient therapeutic function was developed. Ag NCs were formed using ribonucleases A (RNase A) enzyme as a stabilizer. Meanwhile, the RNase A with long chain rapped around Ag NCs and formed RNase A–Ag nanocomposites. The nanocomposites remained both the NIR fluorescence of Ag NCs and antitumor activity of RNase A. The inhibition of the growth of tumor cells by the nanocomposites was confirmed. This study developed an efficient drug delivery system through combination of the protein and nanoparticles, which had potential clinical application in the future.