Mediation Response Unit Shows Potential as an Alternative 911 Response

In May 2022, the City of Dayton, Ohio formally launched a new pilot program that sends trained mediators to respond to low emergency 911 calls to de-escalate non-violent conflicts and mediate disputes among community members. This new initiative, called the Mediation Response Unit (MRU), is the first of its kind in the nation as it sends mediation teams to respond to calls without a co-response by police. The idea for the MRU came about through discussions among a Community Engagement Working Group that was formed in 2020 to implement police reforms in the City. The MRU states that its goals are “to work on improving community police relations, provide alternatives to police response in our community . . . and allow officers more time to take higher emergent calls. ”Some examples of the types of calls the Unit responds to are noise complaints, neighbor disputes, loitering, and other low-level disturbances. The services are performed over the phone, or in-person when necessary, and provide the parties with resource connections as well as follow-up case management. During its first months of operation, the MRU has shown promising early success and positive community reception. As of August 2022, the MRU has logged over 400 calls for service and plans to continue its growth. In an interview with The Mediate.com Podcast, Mediation Response Coordinator, Raven Cruz Loaiza, expressed hope that other cities across the country would be able to adopt this model of alternative response in the near future. This post was originally published on the Cardozo Journal of Conflict Resolution website on February 23, 2023. The original post can be accessed via the Archived Link button above

Genotype and Phenotype in 12 additional individuals with SATB2-Associated Syndrome

SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible

Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017

Comprehensive analysis of rare variants of 101 autism-linked genes in a Hungarian cohort of autism spectrum disorder patients

BackgroundAutism spectrum disorder (ASD) is genetically and phenotypically heterogeneous. Former genetic studies suggested that both common and rare genetic variants play a role in the etiology. In this study, we aimed to analyze rare variants detected by next generation sequencing (NGS) in an autism cohort from Hungary.MethodsWe investigated the yield of NGS panel sequencing of an unselected ASD cohort (N = 174 ) for the detection of ASD associated syndromes. Besides, we analyzed rare variants in a common disease-rare variant framework and performed rare variant burden analysis and gene enrichment analysis in phenotype based clusters.ResultsWe have diagnosed 13 molecularly proven syndromic autism cases. Strongest indicators of syndromic autism were intellectual disability, epilepsy or other neurological plus symptoms. Rare variant analysis on a cohort level confirmed the association of five genes with autism (AUTS2, NHS, NSD1, SLC9A9, and VPS13). We found no correlation between rare variant burden and number of minor malformation or autism severity. We identified four phenotypic clusters, but no specific gene was enriched in a given cluster.ConclusionOur study indicates that NGS panel gene sequencing can be useful, where the clinical picture suggests a clinically defined syndromic autism. In this group, targeted panel sequencing may provide reasonable diagnostic yield. Unselected NGS panel screening in the clinic remains controversial, because of uncertain utility, and difficulties of the variant interpretation. However, the detected rare variants may still significantly influence autism risk and subphenotypes in a polygenic model, but to detect the effects of these variants larger cohorts are needed

Long noncoding RNA and its contribution to autism spectrum disorders

Recent studies have indicated that long noncoding RNAs (lncRNAs) play important roles in multiple processes, such as epigenetic regulation, gene expression regulation, development, nutrition‐related and other diseases, toxic response, and response to drugs. Although the functional roles and mechanisms of several lncRNAs have been discovered, a better understanding of the vast majority of lncRNAs remains elusive. To understand the functional roles and mechanisms of lncRNAs is critical because these transcripts represent the majority of the transcriptional output of the mammalian genome. Recent studies have also suggested that lncRNAs are more abundant in the human brain and are involved in neurodevelopment and neurodevelopmental disorders, including autism spectrum disorders (ASDs). In this study, we review several known functions of lncRNAs and the potential contribution of lncRNAs to ASDs and to other genetic syndromes that have a similar clinical presentation to ASDs, such as fragile X syndrome and Rett syndrome.This work was supported by Guangdong Natural Science Foundation (Grant No: 2015A030313455) and National Science Foundation of China (Grant No 81302445).Published versio

Regulation of vascular tone, molecular mechanisms

The goal of this survey was to review briefly the molecular mechanisms that regulate vascular smooth muscle function. Components of the machinery involved in the contraction and relaxation of vascular smooth muscle include the following.Contractile proteins. The force generated by vascular smooth muscle is the result of thin (actin) and thick (myosin) filaments being pulled by one another so that the cell tends to shorten. The processes by which this intereaction is regulated are a matter of some debate. However, most observations indicate that the process that initiates contraction is a calcium-dependent phosphorylation of the myosin light chain.Cellular sites for the regulation of myoplasmic calcium concentration. The final event that initiates the contractile process is an increase in the intracellular concentration of ionized calcium. Cellular sites that may contribute to the raising and lowering of ionized calcium include the following: (A) cell membrane, (B) sarcoplasmic reticulum, and (C) mitochondria.Membrane electrical events. The electrical state of the cell membrane influences contractile responses of vascular smooth muscle. Over the physiologic range, an elevation in the membrane potential has a reciprocal influence on muscle excitability. The membrane potential is the sum of the diffusion potentials and the electrogenic pump.Excitation-contraction coupling. The excitatory events of the cell membrane (changes in membrane potential and the generation of action potentials) are coupled to the interaction of the contractile proteins by an increase in myoplasmic ionized calcium.Cyclic nucleotides and calcium. Cyclic AMP and cyclic GMP may link contraction and relaxation to the release and uptake of activator calcium by subcellular organelles. These nucleotides also influence the level of phosphorylation of the myosin light chain.Energy metabolism and hypoxia. The chemical energy source for cellular processes in vascular smooth muscle is ATP. Vascular tone, or maintenance of a contractile force, in this muscle is a relatively efficient process that may reflect a special noncycling link between myosin and actin. Current evidence suggests that hypoxic conditions influence vascular tone by altering the activity of the electrogenic sodium pump.This listing of statements is by no means the final word in molecular mechanisms that govern vascular tone. Indeed, vascular smooth muscle remains to be a constant source of surprises for the interested investigator.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24206/1/0000465.pd