Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of „neuroinflammaging” has emerged. In this deregulated neuroinflammatory process, a variety of immune cells participate, especially glial cells, proinflammatory cytokines, receptors, and subcellular organelles including mitochondria, which are mainly responsible for maintaining redox balance at the cellular level. Senescence and autophagic processes also play a crucial role in the neuroinflammatory disease associated with aging. Of particular interest, melatonin, cannabinoids, and the receptors of both molecules which are closely related, exert beneficial effects on the neuroinflammatory processes that precede the onset of neurodegenerative pathologies such as Parkinson’s and Alzheimer’s diseases. Some of these neuroprotective effects are fundamentally related to its anti-inflammatory and antioxidative actions at the mitochondrial level due to the strategic functions of this organelle. The aim of this review is to summarize the most recent advances in the study of neuroinflammation and neurodegeneration associated with age and to consider the use of new mitochondrial therapeutic targets related to the endocannabinoid system and the pineal gland.Huntington’s disease is an autosomal dominant neurodegenerative disease that leads to premature death. The disease is caused by a pathological CAG triplet expansion in the huntingtin gene. The disease is most common in Western populations, with onset in middle age and causing progressive motor, cognitive, and psychiatric symptoms. Currently, only symptomatic treatment is provided, but new molecular technologies may allow treatments reducing levels of mutated huntingtin.Alzheimer’s disease is the most common cause of dementia. As many as 250,000 people in Sweden will have a dementia disease in 2050. The »amyloid cascade hypothesis« is a common model which explains how β-amyloid affects the function of the nerve cells. Alzheimer’s disease has a long-lasting course and can present in typical and atypical forms. CSF analyses for »core AD CSF biomarkers« and synaptic proteins have been available for clinical diagnostics. PET scanning can detect either β-amyloid or tau aggregates in the brain of living humans. Current Alzheimer’s disease therapy is based on two classes of cognition-enhancing drugs acetylcholinesterase inhibitor and NMDA-receptor antagonist, which delays cognitive decline in most patients. The latest clinical development of potential therapy for Alzheimer’s is active or passive immunotherapy against brain β-amyloid and tau, where several studies have shown varying but promising treatment effects. Non-pharmacological interventions in patients with AD aim to delay the loss of mental abilities, helping people to be independent in everyday life for as long as possible, and to increase their well-being and quality of life.Parkinson’s disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson’s disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson’s disease.ALS is characterized by the degeneration of upper and lower motor neurons. In about 70% of patients with ALS the disease has an spinal onset, while about 30% of the patients have a bulbar onset.  Cognitive dysfunction and behavioral changes are seen in about 50% of the patients, and 15% develop frontotemporal dementia.  There is no single test that provides the ALS diagnosis. The diagnosis is based on clinical and electrophysiological signs, and the exclusion of other diseases. The only disease modulating treatment approved for ALS in Sweden is Riluzole, sadly only with limited effect. Other treatments are symptomatic and the goal is to help patients achieve the best possible quality of life through multidiciplinary ALS teams.Ataxias constitute a group of heterogeneous diseases with overlapping symptoms. The clinical investigation should primarily seek for treatable conditions such as neurometabolic disorders and autoimmune diseases. Rapid progression is often characteristic for paraneoplastic cerebellar degeneration, autoimmune diseases or multiple system atrophy (MSA). The rapid development of massive parallel DNA sequencing and its increased accessibility have enabled for improved diagnostic resolution of patients. A diagnosis based on the etiology is crucial for prognosis and treatment of ataxias. In hereditary forms, the identification of causative genetic factors is essential for family planning.In the past decade, physiological roles and molecular functions of GPRC5 family receptors, originally identified as retinoic acid-induced gene products, have been uncovered, even though their intrinsic agonists are still a mystery. They are differentially distributed in certain tissues and cells in the body suggesting that cell-type specific regulations and functions are significant. Molecular biological approaches and knockout mouse studies reveal that GPRC5 family proteins have pivotal roles in cancer progression and control of metabolic homeostasis pathways. Remarkably, GPRC5B-mediated tyrosine-phosphorylation signaling cascades play a critical role in development of obesity and insulin resistance through dynamic sphingolipid metabolism. © The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.Site-specific conjugation of double-stranded DNA using antibodies enables the development of unique applications for antibody drug conjugates utilizing recent advances in nucleic acid medicines. Here, we describe a novel method to conjugate a camelid-derived single domain VHH antibody with arbitrarily-sized double-stranded DNA by PCR. Cysteine in anti-human EGFR VHH were replaced by alanine, and an unpaired cysteine was introduced at the carboxyl-terminus. These modifications enabled site-specific labeling with a maleimide-modified DNA oligo via thioether bond formation; the ensuing product-single-stranded DNA conjugated at the C-terminus of VHH-retained its affinity for EGFR. To investigate whether this VHH-single-stranded DNA conjugate might be used as a forward primer, we subjected it to PCR, producing 100-500 bp DNA. We confirmed the amplification of the VHH-double-stranded DNA conjugate by examining its mobility on acrylamide gel; retention of the binding affinity of the conjugate for EGFR was identified by immuno-PCR. © The Author(s) 2020. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.BACKGROUND Compositional data comprise the parts of some whole, for which all parts sum to that whole. They are prevalent in many epidemiological contexts. Although many of the challenges associated with analysing compositional data have been discussed previously, we do so within a formal causal framework by utilizing directed acyclic graphs (DAGs). METHODS We depict compositional data using DAGs and identify two distinct effect estimands in the generic case (i) the total effect, and (ii) the relative effect. We consider each in the context of three specific example scenarios involving compositional data (1) the relationship between the economically active population and area-level gross domestic product; (2) the relationship between fat consumption and body weight; and (3) the relationship between time spent sedentary and body weight. For each, we consider the distinct interpretation of each effect, and the resulting implications for related analyses. RESULTS For scenarios (1) and (2), both the total and relative effects may be identifiable and causally meaningful, depending upon the specific question of interest. For scenario (3), only the relative effect is identifiable. In all scenarios, the relative effect represents a joint effect, and thus requires careful interpretation. CONCLUSIONS DAGs are useful for considering causal effects for compositional data. In all analyses involving compositional data, researchers should explicitly consider and declare which causal effect is sought and how it should be interpreted. Curaxin 137 activator © The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.Runt-related transcription factor-1 (RUNX1), also known as acute myeloid leukaemia 1 protein (AML1), is a member of the core-binding factor family of transcription factors which modulate cell proliferation, differentiation, and survival in multiple systems. It is a master-regulator transcription factor, which has been implicated in diverse signalling pathways and cellular mechanisms during normal development and disease. RUNX1 is best characterized for its indispensable role for definitive haematopoiesis and its involvement in haematological malignancies. However, more recently RUNX1 has been identified as a key regulator of adverse cardiac remodelling following myocardial infarction. This review discusses the role RUNX1 plays in the heart and highlights its therapeutic potential as a target to limit the progression of adverse cardiac remodelling and heart failure. © The Author(s) 2020. link2 Published by Oxford University Press on behalf of the European Society of Cardiology.Importance Social and economic contexts shape children’s short- and long-term health. Efforts to address contextual risk factors are increasingly incorporated into pediatric health care. Objective To compare the effectiveness of 2 social risk-related interventions. Design, Setting, and Participants This randomized clinical trial included English- and/or Spanish-speaking caregiver-child dyads recruited from a pediatric urgent care clinic nested in a large, urban, safety-net hospital. Study recruitment, enrollment, and follow-up were conducted from July 18, 2016, to March 8, 2019. Data analysis was conducted from January 1, 2019, to January 20, 2020. Interventions Following standardized social risk assessment, caregivers were randomly assigned to receive either written information regarding relevant government and community social services resources or comparable written information plus in-person assistance and follow-up focused on service access. Main Outcomes and Measures Caregiver-reported number of social written resources plus in-person assistance, 0.24 [0.07]; both P  less then  .001). Conclusions and Relevance This randomized clinical trial compared 2 approaches to addressing social risks in a pediatric urgent care setting and found no statistically significant differences in the social risk and child and caregiver health effects of providing written resources at the point of care with vs without in-person longitudinal navigation services. Caregivers in both groups reported fewer social risks and improved child and caregiver health 6 months after the intervention. These findings deepen understanding of effective doses of social risk-related interventions. link3 Trial Registration ClinicalTrials.gov Identifier NCT02746393.