Community pharmacists' perceptions of their challenges in relation to older adults prescribed psychotropic medications: a focus-group study.

Background: The management of psychotropic medication in older adults is a challenge for every healthcare professional, but data concerning community pharmacists are scarce in the literature.

Aim: Our objectives were i) to understand the difficulties encountered by community pharmacists in managing older adults on psychotropic medication, and ii) to identify potential solutions to the difficulties discussed.

Method: A qualitative study by focus group was proposed to all community pharmacists in the vicinity of the university hospital of Angers, France, between May and June 2023.

Pharmacist intervention is associated with fewer serious falls over 3 months among older fallers at a day hospital: A quasi-experimental study.

Objectives: Some drugs increase the risk of falls, including serious falls. The objective of this quasi-experimental study was to determine whether the intervention of a clinical pharmacist among older outpatients receiving a multifactorial fall prevention program at a geriatric day hospital dedicated to older patients with a recent history of falls was effective in preventing serious falls over a 3-month follow-up, compared with usual care.

Study Design: Quasi-experimental study in 296 consecutive older outpatients, including 85 with pharmacist intervention (the intervention group) and 148 without (the control group).

Preventable or potentially inappropriate psychotropics and adverse health outcomes in older adults: systematic review and meta-analysis.

Objective: To systematically review and quantitatively synthetize evidence on the use of PIPs linked to adverse health outcomes in older adults.

Methods: A Medline, Embase® and Opengrey libraries search was conducted from 2004 to February 2021, using the PICO model: older people, psychotropic drugs, inappropriate prescribing, and adverse drug events. Fixed-effects and random-effects meta-analysis were performed from 3 eligible studies using an inverse-variance method.

Identifying older inpatients at high risk of unintentional medication discrepancies: a classification tree analysis.

Unintentional medication discrepancies at admission are differences between the best possible medication history and the prescribed treatment at admission, and are associated with adverse outcomes, particularly in older people. This study aimed to identify the clinical profiles of geriatric inpatients with unintentional medication discrepancies at hospital admission. A classification tree Chi-square Automatic Interaction Detector (CHAID) analysis was conducted to assess those patients' profiles and characteristics that were associated with a higher risk of unintentional medication discrepancies.

[How to optimise the use of psychotropic drugs in the elderly? Focus groups in a geriatric unit].

The elderly person (EP) treated with psychotropics is at risk of iatropathology. The guidelines for the proper use of these treatments are difficult to apply and the difficulties met by hospital teams are little described in the literature. Our objective was to investigate the problem of psychotropic management in EP among the medical and care teams.

[Implementation of pharmaceutical consultations in oncohematology in a teaching hospital: Over one year outcomes].

The development of Oral Cancer Therapies (OAT) raises the question of the therapeutic adherence of patients, put in difficulty by the isolation of the patient in the management of treatment and adverse reactions. Accompanying processes are developing, such as Pharmaceutical Consultations (PC), whose monitoring and education objectives are multiple. The PCs and their implementation are presented here, as well as the first results at 15months.

Hubbing the Cancer Cell.

Oncogenic transformation drives adaptive changes in a growing tumor that affect the cellular organization of cancerous cells, resulting in the loss of specialized cellular functions in the polarized compartmentalization of cells. The resulting altered metabolic and morphological patterns are used clinically as diagnostic markers. This review recapitulates the known functions of actin, microtubules and the γ-tubulin meshwork in orchestrating cell metabolism and functional cellular asymmetry.

Large Predominance of Off-Label Prescriptions of C1-Inhibitor Concentrates and Icatibant in a Real-Life Setting: A Retrospective Clinical Study.

C1-inhibitor (C1INH) concentrates and the selective bradykinin B2 receptor antagonist icatibant are approved only for treating hereditary angioedema with C1INH deficiency. Yet, they are regularly prescribed off label in other types of bradykinin-mediated angioedema including angiotensin-converting enzyme inhibitor (ACEi)-related and undetermined angioedema. We conducted a retrospective chart review of inpatient prescriptions of C1INH concentrates and icatibant between 2016 and 2020 in the University Hospital of Angers.

Impact of the COVID-19 pandemic on drug-related problems and pharmacist interventions in geriatric acute care units.

Objectives: To assess and compare the pharmaceutical analysis on drug management in a geriatric acute care unit prior to and during the COVID-19 pandemic.

Methods: This was a single-centre, retrospective, and comparative cohort study. All Pharmacist Interventions (PIs) carried out in the unit between 27 January 2020 and 30 April 2020 were distinguished according to whether they were conducted prior to or during the first wave of COVID-19.

The γ-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells.

Changes in the location of γ-tubulin ensure cell survival and preserve genome integrity. We investigated whether the nuclear accumulation of γ-tubulin facilitates the transport of proliferating cell nuclear antigen (PCNA) between the cytosolic and the nuclear compartment in mammalian cells. We found that the γ-tubulin meshwork assists in the recruitment of PCNA to chromatin.

Predictors of Short Latency Period Exceeding 48 h after Preterm Premature Rupture of Membranes.

Background: Preterm premature rupture of membranes (PPROM) is a complication responsible for a third of preterm births. Clinical management is initially hospital based, but homecare management is possible if patients are clinically stable 48 h after PPROM. This study set out to determine factors that are predictive of short latency (delivery ≤ 7 days) exceeding 48 h after PPROM, enabling estimation of the prevalence of maternal and neonatal complications and comparison of maternal and fetal outcomes between inpatient and outpatient management.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

Background: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients.

Methods: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2).

Non-Canonical Functions of the Gamma-Tubulin Meshwork in the Regulation of the Nuclear Architecture.

The nuclear architecture describes the organization of the various compartments in the nucleus of eukaryotic cells, where a plethora of processes such as nucleocytoplasmic transport, gene expression, and assembly of ribosomal subunits occur in a dynamic manner. During the different phases of the cell cycle, in post-mitotic cells and after oncogenic transformation, rearrangements of the nuclear architecture take place, and, among other things, these alterations result in reorganization of the chromatin and changes in gene expression. A member of the tubulin family, γtubulin, was first identified as part of a multiprotein complex that allows nucleation of microtubules.

Gemcitabine-induced epithelial-mesenchymal transition-like changes sustain chemoresistance of pancreatic cancer cells of mesenchymal-like phenotype.

Growing body of evidence suggests that epithelial-mesenchymal transition (EMT) is a critical process in tumor progression and chemoresistance in pancreatic cancer (PC). The aim of this study was to analyze the role of EMT-like changes in acquisition of resistance to gemcitabine in pancreatic cells of the mesenchymal or epithelial phenotype. Therefore, chemoresistant BxPC-3, Capan-2, Panc-1, and MiaPaca-2 cells were selected by chronic exposure to increasing concentrations of gemcitabine.

γ-Tubulin⁻γ-Tubulin Interactions as the Basis for the Formation of a Meshwork.

In cytoplasm, protein γ-tubulin joins with various γ-tubulin complex proteins (GCPs) to form a heterotetramer γ-tubulin small complex (γ-TuSC) that can grow into a ring-shaped structure called the γ-tubulin ring complex (γ-TuRC). Both γ-TuSC and γ-TuRC are required for microtubule nucleation. Recent knowledge on γ-tubulin with regard to its cellular functions beyond participation in its creation of microtubules suggests that this protein forms a cellular meshwork.

Laparoscopic cervico-isthmic cerclage: About 25 cases.

Introduction: The purpose of this study is to report on our experience of laparoscopic cervico-isthmic cerclage.

Material And Method: A monocentric retrospective study covering a 13-year period during which 25 cases of laparoscopic cerclage outside of pregnancy were performed, using the technique described by Dubuisson, at the University Hospital of Clermont-Ferrand. Individual patient data included pregnancy outcomes before and after cerclage and the characteristics of surgery.

Toward the Discovery of a Novel Class of YAP⁻TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP⁻TEAD Protein⁻Protein Interface.

Intrinsically disordered protein YAP (yes-associated protein) interacts with TEADs transcriptional factors family (transcriptional enhancer associated domain) creating three interfaces. Interface 3, between the Ω-loop of YAP and a shallow pocket of TEAD was identified as the most important TEAD zone for YAP-TEAD interaction. Using the first X-ray structure of the hYAP-hTEAD1 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD.

Molecular Features of the YAP Inhibitor Verteporfin: Synthesis of Hexasubstituted Dipyrrins as Potential Inhibitors of YAP/TAZ, the Downstream Effectors of the Hippo Pathway.

Porphyrin derivatives, in particular verteporfin (VP), a photosensitizer initially designed for cancer therapy, have been identified as inhibitors of the YAP-TEAD interaction and transcriptional activity. Herein we report the efficient convergent synthesis of the dipyrrin half of protoporphyrin IX dimethyl ester (PPIX-DME), in which the sensitive vinyl group was created at the final stage by a dehydroiodination reaction. Two other dipyrrin derivatives were synthesized, including dipyrrin 19 [(Z)-2-((3,5-dimethyl-4-vinyl-2H-pyrrol-2-ylidene)methyl)-3,5-dimethyl-4-vinyl-1H-pyrrole], containing two vinyl groups.

Regulation of cellular quiescence by YAP/TAZ and Cyclin E1 in colon cancer cells: Implication in chemoresistance and cancer relapse.

Our aim was to decipher the role and clinical relevance of the YAP/TAZ transcriptional coactivators in the regulation of the proliferation/quiescence balance in human colon cancer cells (CCC) and survival after 5FU-based chemotherapy. The prognostic value of YAP/TAZ on tumor relapse and overall survival was assessed in a five-year follow-up study using specimens of liver metastases (n = 70) from colon cancer patients. In 5FU-chemoresistant HT29-5F31 and -chemosensitive HCT116 and RKO CCC, a reversible G0 quiescent state mediated by Cyclin E1 down-regulation was induced by 5FU in 5F31 cells and recapitulated in CCC by either YAP/TAZ or Cyclin E1 siRNAs or the YAP inhibitor Verteporfin.

Non-Photoinduced Biological Properties of Verteporfin.

Background: Verteporfin is a porphyrinic photosensitizer clinically used for the photodynamic treatment of age-related macular degeneration. It has been identified almost simultaneously as a YAP/TEAD and an autophagosome inhibitor. Over the last few years, YAP (TAZ), the downstream effectors of the Hippo pathway, have emerged as promising anticancer targets, as shown by several experimental lines of evidence, showing the overproduction of YAP in several cancers.

Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis.

Purpose: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery.

IL-26 is overexpressed in rheumatoid arthritis and induces proinflammatory cytokine production and Th17 cell generation.

Interleukin-26 (IL-26), a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn's disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by joint synovial inflammation.

The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes.

The nervous system influences immune responses through the release of neural factors such as neuropeptides. Among them, the tachykinin substance P (SP) signals via the neurokinin 1 receptor (NK-1R), which is expressed by various immune cells. We thereby analyzed in this paper whether tachykinins may participate in human CD4(+) Th cell polarization.

Tumor-reactive CD4+ CD8αβ+ CD103+ αβT cells: a prevalent tumor-reactive T-cell subset in metastatic colorectal cancers.

High level of T-cell infiltration in colorectal carcinomas (CRCs) is a good prognostic indicator, but the tumor reactivity of this infiltrate (tumor infiltrating lymphocytes [TIL]) is poorly documented. This study examined the presence, phenotype and functional features of tumor-reactive lymphocytes in human CRC. Freshly dissociated TIL and T cell lines were isolated from CRC samples and from some paired normal colonic mucosa.