Cortical Gyrification,Psychotic-Like Experiences,and Cognitive Performance in Nonclinical Subjects

BackgroundPsychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects. MethodsWe analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition. ResultsPositive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations. ConclusionOur results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation.     

The multiple facets of drug resistance: one history,different approaches

Some cancers like melanoma and pancreatic and ovarian cancers, for example, commonly display resistance to chemotherapy, and this is the major obstacle to a better prognosis of patients. Frequently, literature presents studies in monolayer cell cultures, 3D cell cultures or in vivo studies, but rarely the same work compares results of drug resistance in different models. Several of these works are presented in this review and show that usually cells in 3D culture are more resistant to drugs than monolayer cultured cells due to different mechanisms. Searching for new strategies to sensitize different tumors to chemotherapy, many methods have been studied to understand the mechanisms whereby cancer cells acquire drug resistance. These methods have been strongly advanced along the years and therapies using different drugs have been increasingly proposed to induce cell death in resistant cells of different cancers. Recently, cancer stem cells (CSCs) have been extensively studied because they would be the only cells capable of sustaining tumorigenesis. It is believed that the resistance of CSCs to currently used chemotherapeutics is a major contributing factor in cancer recurrence and later metastasis development. This review aims to appraise the experimental progress in the study of acquired drug resistance of cancer cells in different models as well as to understand the role of CSCs as the major contributing factor in cancer recurrence and metastasis development, describing how CSCs can be identified and isolated.     

Designing a Primary Care–Based Deprescribing Intervention for Patients with Dementia and Multiple Chronic Conditions: a Qualitative Study

BackgroundPatients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events.ObjectivesTo elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing.DesignQualitative approach based on semi-structured interviews with patients, caregivers, and physicians.ParticipantsPatients aged ≥ 65 years with claims-based diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations.ApproachWe used constant comparison to identify and compare themes between patients, caregivers, and physicians.Key ResultsWe conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers’ expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations.ConclusionsCulturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06063-y) contains supplementary material, which is available to authorized users.KEY WORDS: deprescribing, patient-physician communication, dementia