Alzheimer's disease heterogeneity revealed by neuroanatomical normative modeling.

Introduction: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy.

Methods: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD ( = 86).

Bioprinting Neural Systems to Model Central Nervous System Diseases.

To date, pharmaceutical progresses in central nervous system (CNS) diseases are clearly hampered by the lack of suitable disease models. Indeed, animal models do not faithfully represent human neurodegenerative processes and human in vitro 2D cell culture systems cannot recapitulate the in vivo complexity of neural systems. The search for valuable models of neurodegenerative diseases has recently been revived by the addition of 3D culture that allows to re-create the in vivo microenvironment including the interactions among different neural cell types and the surrounding extracellular matrix (ECM) components.

A Phase I dose-escalation study of two cycles carboplatin-olaparib followed by olaparib monotherapy in patients with advanced cancer.

Preclinical studies have shown synergistic effects when combining PARP1/2 inhibitors and platinum drugs in BRCA1/2 mutated cancer cell models. After a formulation change of olaparib from capsules to tablets, we initiated a dose finding study of olaparib tablets bidaily (BID) continuously with carboplatin to prepare comparative studies in this patient group. Patients were included in a 3 + 3 dose-escalation schedule: olaparib 25 mg BID and carboplatin area under the curve (AUC) 3 mg*min/mL d1/d22, olaparib 25 mg BID and carboplatin AUC 4 mg*min/mL d1/d22, followed by increasing dose-levels of olaparib from 50 mg BID, 75 mg BID, to 100 mg BID with carboplatin at AUC 4 mg*min/mL d1/d22.

Placenta Pathology From Term Born Neonates With Normal or Adverse Outcome.

Background: The incidence of umbilical cord or placental parenchyma abnormalities associated with mortality or morbidity of term infants is lacking.

Methods: Placentas of 55 antepartum stillbirths (APD), 21 intrapartum stillbirths (IPD), 12 neonatal deaths (ND), and 80 admissions to a level 3 neonatal intensive care unit (NS) were studied and compared with 439 placentas from neonates from normal term pregnancies and normal outcome after vaginal delivery (NPVD) and with 105 placentas after an elective caesarian sections (NPEC).

Results: NPVD and NPEC placentas showed no or one abnormality in 70% and placentas from stillbirth showed two or more abnormalities in 80% of cases.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction.

Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease.

Background In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin-stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (FGF23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin-stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on FGF23.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction.

Symptom Intensity of Hospice Patients: A Longitudinal Analysis of Concordance Between Patients' and Nurses' Outcomes.

Context: Nearing death, hospice patients are increasingly unable or unwilling to self-report their symptom intensity and rely on nurses' assessments.

Objectives: We hypothesized that concordance between patients' and nurses' assessments of symptom intensity improves over time.

Method: A prospective longitudinal study was conducted from January 2012 to June 2015 using dyads of patient- and nurse-reported outcome measures, collected in daily hospice practice in the first three weeks after admission.

Flare-Up After Maxillofacial Surgery in a Patient With Fibrodysplasia Ossificans Progressiva: An [F]-NaF PET/CT Study and a Systematic Review.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder leading to progressive heterotopic ossifications (HO) of muscles, tendons, and ligaments, which can be induced by trauma or by surgery. Despite strong medical advice to the contrary, an FOP patient insisted on surgery to alleviate her complete trismus, which caused an unbearable impact on her quality of life (QOL). The entire trismus history of this FOP patient is presented.

Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice.

Objective: Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model.

Design: Male STR/Ort mice received control diet or control diet containing two different dosages of simvastatin or fenofibrate or a combination of both.

Optimization of adeno-associated viral vector-mediated gene delivery to the hypothalamus.

To efficiently deliver genes and short hairpin RNAs to the hypothalamus we aimed to optimize the transduction efficiency of adeno-associated virus (AAV) in the rat hypothalamus. We compared the transduction efficiencies of AAV2 vectors pseudotyped with AAV1, AAV8, and mosaic AAV1/2 and AAV2/8 coats with that of an AAV2 coated vector after injection into the lateral hypothalamus of rats. In addition, we determined the transduction areas and the percentage of neurons infected after injection of various titers and volumes of two AAV1-pseudotyped vectors in the paraventricular hypothalamus (PVN).