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To identify patterns of medication adherence during the pandemic and factors associated with these patterns among Medicaid-enrolled individuals with schizophrenia who had highly adherent medication use prior to the COVID-19 pandemic. We used Medicaid claims from Philadelphia to identify individuals with schizophrenia ≥ 18 years of age, their demographic characteristics, and health service use. We used group trajectory models to identify adherence trends, and ANOVA to examine associations between adherence groups and demographic characteristics and service use. The sample included 1,622 individuals. A 4-group trajectory model best fit our data. Seventy percent of individuals averaged about 92% adherence throughout the study period; 10% experienced a pronounced decline when the pandemic started (pandemic non-adherers); 11% experienced a sharp decline mid-pandemic (late non-adherers); and 9% experienced a sharp decline at the beginning of the pandemic and returned to higher adherence after a year (disrupted adherers). Adherers were least likely to be diagnosed with a substance use disorder, and had more telehealth visits, mental health outpatient visits, and fewer emergency department visits on average. Late non-adherers were more likely than adherers to have substance use disorders and physical health conditions. Pandemic non-adherers had more co-occurring psychiatric disorders than adherers and had the lowest use of case management. Three in ten previously adherent individuals with schizophrenia became less adherent to antipsychotic medications, either at the onset or later in the pandemic. Our findings point to telehealth and case management as critical strategies for treatment engagement, especially during public health crises, and well as the need to address co-occurring conditions., (© 2024. The Author(s).)

Background: The Collaborative Care Model (CoCM) increases access to mental health treatment and improves outcomes among patients with mild to moderate psychopathology; however, it is unclear how effective CoCM is for patients with elevated suicide risk., Methods: We examined data from the Penn Integrated Care program, a CoCM program including an intake and referral management center plus traditional CoCM services implemented in primary care clinics within a large, diverse academic medical system. In this community setting, we examined: (1) characteristics of patients with and without suicidal ideation who initiated CoCM, (2) changes in suicidal ideation (Patient Health Questionnaire-9 [PHQ-9] item 9), depression (PHQ-9 total scores), and anxiety (Generalized Anxiety Disorder Scale-7 scores) from the first to last CoCM visit overall and across demographic subgroups, and (3) the relationship between amount of CoCM services provided and degree of symptom reduction., Results: From 2018 to 2022, 3,487 patients were referred to CoCM, initiated treatment for at least 15 days, and had completed symptom measures at the first and last visit. Patients were 74% female, 45% Black/African American, and 45% White. The percentage of patients reporting suicidal ideation declined 11%-7% from the first to last visit. Suicidal ideation severity typically improved, and very rarely worsened, during CoCM. Depression and anxiety declined significantly among patients with and without suicidal ideation and across demographic subgroups; however, the magnitude of these declines differed across race, ethnicity, and age. Patients with suicidal ideation at the start of CoCM had higher depression scores than patients without suicidal ideation at the start and end of treatment. Longer CoCM episodes were associated with greater reductions in depression severity., Conclusions: Suicidal ideation, depression, and anxiety declined following CoCM among individuals with suicidal ideation in a community setting. Findings are consistent with emerging evidence from clinical trials suggesting CoCM's potential for increasing access to mental healthcare and improving outcomes among patients at risk for suicide., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Atomic force microscopy (AFM) has become indispensable for studying biological and medical samples. More than two decades of experiments have revealed that cancer cells are softer than healthy cells (for measured cells cultured on stiff substrates). The softness or, more precisely, the larger deformability of cancer cells, primarily independent of cancer types, could be used as a sensitive marker of pathological changes. The wide application of biomechanics in clinics would require designing instruments with specific calibration, data collection, and analysis procedures. For these reasons, such development is, at present, still very limited, hampering the clinical exploitation of mechanical measurements. Here, we propose a standardized operational protocol (SOP), developed within the EU ITN network Phys2BioMed, which allows the detection of the biomechanical properties of living cancer cells regardless of the nanoindentation instruments used (AFMs and other indenters) and the laboratory involved in the research. We standardized the cell cultures, AFM calibration, measurements, and data analysis. This effort resulted in a step-by-step SOP for cell cultures, instrument calibration, measurements, and data analysis, leading to the concordance of the results (Young's modulus) measured among the six EU laboratories involved. Our results highlight the importance of the SOP in obtaining a reproducible mechanical characterization of cancer cells and paving the way toward exploiting biomechanics for diagnostic purposes in clinics.

Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the extracellular matrix (ECM) are important in cancer development; studying their changes is crucial to understand CRC-PM development. We studied the elastic properties of ECMs derived from human samples of normal and neoplastic PM by atomic force microscopy (AFM); results were correlated with patient clinical data and expression of ECM components related to metastatic spread. We show that PM progression is accompanied by stiffening of the ECM, increased cancer associated fibroblasts (CAF) activity and increased deposition and crosslinking in neoplastic matrices; on the other hand, softer regions are also found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells. We have found correlations between the mechanical properties (relative stiffening between normal and neoplastic ECM) of the ECM and patients' clinical data, like age, sex, presence of protein activating mutations in BRAF and KRAS genes and tumour grade. Our findings suggest that the mechanical phenotyping of PM-ECM has the potential to predict tumour development., (© 2023. The Author(s).)

Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments., (© The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Biosensors are aimed at detecting tiny physical and chemical stimuli in biological systems. Physical forces are ubiquitous, being implied in all cellular processes, including cell adhesion, migration, and differentiation. Given the strong interplay between cells and their microenvironment, the extracellular matrix (ECM) and the structural and mechanical properties of the ECM play an important role in the transmission of external stimuli to single cells within the tissue. Vice versa, cells themselves also use self-generated forces to probe the biophysical properties of the ECM. ECM mechanics influence cell fate, regulate tissue development, and show peculiar features in health and disease conditions of living organisms. Force sensing in biological systems is therefore crucial to dissecting and understanding complex biological processes, such as mechanotransduction. Atomic Force Microscopy (AFM), which can both sense and apply forces at the nanoscale, with sub-nanonewton sensitivity, represents an enabling technology and a crucial experimental tool in biophysics and mechanobiology. In this work, we report on the application of AFM to the study of biomechanical fingerprints of different components of biological systems, such as the ECM, the whole cell, and cellular components, such as the nucleus, lamellipodia and the glycocalyx. We show that physical observables such as the (spatially resolved) Young's Modulus (YM) of elasticity of ECMs or cells, and the effective thickness and stiffness of the glycocalyx, can be quantitatively characterized by AFM. Their modification can be correlated to changes in the microenvironment, physio-pathological conditions, or gene regulation.

Doxorubicin (DOX) therapy is limited by both cancer cells resistance and cardiotoxicity. DOX biotransformation to doxorubicinol (DOXol) by reductases enzymes (mainly by CBR1; carbonyl reductase 1) is a key process responsible for DOX adverse effects development. Thus, inhibition of CBR1 can increase the therapeutic effect of DOX. In the present study, we used a group of new synthetized cinnamic acid (CA) derivatives to improve the effectiveness and safety profile of DOX therapy against cancer cells in vitro. The possible mechanism of CBR1 inhibition was simulated by molecular modelling studies. The kinetics of DOX reduction in the presence of active CA derivatives were measured in cytosols. The chemosensitising activity of CA derivatives including proapoptotic, anti-invasiveness activity were investigated in A549 lung cancer cell line. In our research 7 from 16 tested CA derivatives binded to the active site of CBR1 enzyme and improved DOX stability by inhibition of DOXol formation. Co-treatment of A549 cells with active CA derivatives and DOX induced cells apoptosis by activation of caspase cascade. At the same time we observed decrease of invasive properties (cell migration and transmigration assays) and the rearangments of F-actin cytoskeleton in CA derivatves + DOX treated cells. Meanwhile, control, human lung fibroblasts stay realtivelly unvulnerable and viable. New synthetized CA derivatives may inhibit the activity of CBR1 leading to the stabilization of DOX therapeutic levels in cancer cells and to protect the myocardium against DOXol cytotoxic effect. Favourable physicochemical properties supported by a safety profile and multidirectional chemosensitising activity render CA derivatives a promising group for the development of agent useful in combined therapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Three groups of eggs, intact, cumulus-free and zona-free, were inseminated in vitro with spermatozoa from C57BL/Kw male mice and incubated for 1-2 h. In fixed, toluidine blue-stained preparations, spermatozoa surrounding the eggs or attached to them remained colourless, while sperm heads that had penetrated the vitellus were deeply stained. Those in the early stage with still condensed chromatin were used to evaluate the head shapes. In zona-free and in cumulus-free eggs, only severely misshapen sperm heads appeared at a lower frequency than in the samples used for insemination. The proportion of abnormal sperm heads of all classes was significantly lower in intact than in cumulus-free eggs and most severely abnormal forms were not found in intact eggs. The results suggest that abnormal spermatozoa are able to participate in fertilization, although their chances of penetrating the ova in vitro are greatly reduced in the presence of egg investments, especially of the cumulus.