Developing Topics.

Background: About half of the patients suffering from Alzheimer's disease (AD) display sleeping disorders. Disruptions in the central circadian clock (CC), located in the brain, accelerate AD pathogenesis, making the CC a promising target. In preclinical trials, this strategy have shown efficacy but clinical results are inconsistent.

Antiproliferative and Morphological Effects of Fenretinide Lipid Nanosystems in Colon Adenocarcinoma Cells.

Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major limitations to their use include tolerability and acquired resistance. In this study, we evaluated fenretinide, a semisynthetic derivative of all-trans retinoic acid, in an HT-29 cell line.

"I Didn't Have to Worry about It": Patient and Family Experiences with Health System Involvement in Notifying Relatives of Genetic Test Results.

Introduction: In the USA, patients who undergo genetic testing for hereditary cancer risk are responsible for informing relatives about their genetic test results, but many relatives never find out they might be at risk. A health system-mediated relative notification program might help fill this gap, but questions remain about the acceptability of this approach.

Methods: We analyzed qualitative data from a single-arm, nonrandomized, mixed-methods study to understand how patients and families experienced a new health system-mediated relative notification program.

Chalcones induce apoptosis, autophagy and reduce spreading in osteosarcoma 3D models.

Osteosarcoma is the most common primary bone malignancy with a challenging prognosis marked by a high rate of metastasis. The limited success of current treatments may be partially attributed to an incomplete understanding of osteosarcoma pathophysiology and to the absence of reliable in vitro models to select the best molecules for in vivo studies. Among the natural compounds relevant for osteosarcoma treatment, Licochalcone A (Lic-A) and chalcone derivatives are particularly interesting.

Nano-fenretinide demonstrates remarkable activity in acute promyeloid leukemia cells.

Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments.

Small-angle X-ray scattering unveils the internal structure of lipid nanoparticles.

Lipid nanoparticles own a remarkable potential in nanomedicine, only partially disclosed. While the clinical use of liposomes and cationic lipid-nucleic acid complexes is well-established, liquid lipid nanoparticles (nanoemulsions), solid lipid nanoparticles, and nanostructured lipid carriers have even greater possibilities. However, they face obstacles in being used in clinics due to a lack of understanding about the molecular mechanisms controlling their drug loading and release, interactions with the biological environment (such as the protein corona), and shelf-life stability.

Skin Cancer Screening: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Skin cancer is the most common cancer type and is a major cause of morbidity.

Objective: To systematically review the benefits and harms of screening for skin cancer to inform the US Preventive Services Task Force.

Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022.

Feasibility of using an app-based coaching intervention to improve provider communication about HPV vaccination.

Provider communication training is effective for increasing HPV vaccination rates among U.S. adolescents.

Human-Centered Design Study to Inform Traceback Cascade Genetic Testing Programs at Three Integrated Health Systems.

Introduction: A traceback genetic testing program for ovarian cancer has the potential to identify individuals with hereditary breast and ovarian cancer and their relatives. Successful implementation depends on understanding and addressing the experiences, barriers, and preferences of the people served.

Methods: We conducted a remote, human-centered design research study of people with ovarian, fallopian tube, or peritoneal cancer (probands) and people with a family history of ovarian cancer (relatives) at three integrated health systems between May and September 2021.

Naxitamab Activity in Neuroblastoma Cells Is Enhanced by Nanofenretinide and Nanospermidine.

Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential.

Effect of Cocoa Roasting on Chocolate Polyphenols Evolution.

Cocoa and chocolate antioxidants might contribute to human health through, for instance, blood flow improvement or blood pressure and glycemia reduction, as well as cognitive function improvement. Unfortunately, polyphenol content is reduced during cocoa fermentation, drying, roasting and all the other phases involved in the chocolate production. Here, we investigated the evolution of the polyphenol content during all the different steps of chocolate production, with a special emphasis on roasting (3 different roasting cycles with 80, 100, and 130 °C as maximum temperature).

In Silico Identification and In Vitro Evaluation of New ABCG2 Transporter Inhibitors as Potential Anticancer Agents.

Different molecular mechanisms contribute to the development of multidrug resistance in cancer, including increased drug efflux, enhanced cellular repair mechanisms and alterations of drug metabolism or drug targets. ABCG2 is a member of the ATP-binding cassette superfamily transporters that promotes drug efflux, inducing chemotherapeutic resistance in malignant cells. In this context, the development of selective ABCG2 inhibitors might be a suitable strategy to improve chemotherapy efficacy.

Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation.

Background: Genetic testing for pathogenic variants associated with hereditary breast and ovarian cancer risk can improve cancer outcomes through enhanced preventive care in both people with known variants and their biologic relatives. Cascade screening-the process of case-finding in relatives by notifying and inviting them to consider testing-currently relies on the patient to notify their own at-risk relatives. However, many of these relatives never learn they might be at risk.

Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective.

Multicellular tumor spheroids are largely exploited in cancer research since they are more predictive than bi-dimensional cell cultures. Nanomedicine would benefit from the integration of this three-dimensional model in screening protocols. In this brief work, we discuss some of the issues that cancer nanomedicine will need to consider in the switch from bi-dimensional to three-dimensional multicellular tumor spheroid models.

Nanospermidine in Combination with Nanofenretinide Induces Cell Death in Neuroblastoma Cell Lines.

A new strategy to cause cell death in tumors might be the increase of intracellular polyamines at concentrations above their physiological values to trigger the production of oxidation metabolites at levels exceeding cell tolerance. To test this hypothesis, we prepared nanospermidine as a carrier for spermidine penetration into the cells, able to escape the polyamine transport system that strictly regulates intracellular polyamine levels. Nanospermidine was prepared by spermidine encapsulation in nanomicelles and was characterized by size, zeta potential, loading, dimensional stability to dilution, and stability to spermidine leakage.

Natural-like Chalcones with Antitumor Activity on Human MG63 Osteosarcoma Cells.

Osteosarcoma (OS) is a malignant disease characterized by poor prognosis due to a high incidence of metastasis and chemoresistance. Recently, Licochalcone A (Lic-A) has been reported as a promising agent against OS. Starting from chalcones selected from a wide in-house library, a new series was designed and synthetized.

Pragmatic Randomized Study of Targeted Text Message Reminders to Reduce Missed Clinic Visits.

Introduction: Missed clinic appointments ("no-shows") waste health system resources, decrease physician availability, and may worsen patient outcomes. Appointment reminders reduce no-shows, though evidence on the optimal number of reminders is limited and sending multiple reminders for every visit is costly. Risk prediction models can be used to target reminders for visits that are likely to be missed.

Tablet Splitting in Elderly Patients with Dementia: The Case of Quetiapine.

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets.

Transitioning patients from outpatient mental health services to primary care: A rapid literature review.

Background: A lack of access to mental health services is a critical barrier to obtaining evidence-based care. One strategy to improve access is to transition stable patients out of mental health specialty services and into primary care, thus opening availability for new patients and those with acute mental health needs. To support these transitions, organizations might explore a range of new practices and implementation strategies.

Amelogenin-Derived Peptides in Bone Regeneration: A Systematic Review.

Amelogenins are enamel matrix proteins currently used to treat bone defects in periodontal surgery. Recent studies have highlighted the relevance of amelogenin-derived peptides, named LRAP, TRAP, SP, and C11, in bone tissue engineering. Interestingly, these peptides seem to maintain or even improve the biological activity of the full-length protein, which has received attention in the field of bone regeneration.

Erratum: Signature of Energy Losses on the Cosmic Ray Electron Spectrum [Phys. Rev. Lett. 125, 051101 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.

Patient and Family Preferences on Health System-Led Direct Contact for Cascade Screening.

Health benefits to relatives of people at known genetic risk for hereditary cancer syndromes is key to realizing the promise of precision medicine. We conducted a qualitative study to design a patient- and family-centered program for direct contact of relatives to recommend cascade genetic testing. We conducted two rounds of data collection using focus groups followed by individual interviews with patients with HBOC or Lynch syndrome and a separate sample of people with a family history of hereditary cancers.

Barriers to Human Papillomavirus Vaccine Series Completion among Insured Individuals in an Integrated Healthcare Setting.

Introduction: Infection with certain types of human papillomavirus (HPV) can lead to cervical cancer as well as other cancers in both men and women. However, the requirement for multiple doses may limit the vaccine's effectiveness for cancer prevention. We conducted a pilot study to investigate barriers to HPV vaccine series completion among members of an integrated healthcare system with clinical documentation of only 1 dose.