Treatment of acromioclavicular dislocation of the shoulder in adults - press review

Introduction:  Acromioclavicular joint dislocation is one of the most common shoulder injuries treated in a sport‐active population. In this article we reviewed the epidemiology, symptoms, and various surgical techniques for the treatment of acromioclavicular dislocation. Material and methods: The work was based on medical articles collected in PubMed, websites and medical books. The research was conducted by looking at keywords such as: "acromioclaviculal dislocation", "treatment of acromioclaviculal dislocation ". Results: There are many methods of treating acromioclaviculal dislocation, ranging from conservative treatment to surgical treatment. Conclusions: Treating acute and chronic ACJ injuries is still a challenging task.The myriad of existing techniques is indicative for the uncertainty regarding this topic and a gold standard has not yet been determined. However, when diagnosed correctly and treated accordingly, results are overall satisfactory

The portion size effect and overconsumption – towards downsizing solutions for children and adolescents

Portion sizes of foods offered to consumers have increased at the same time as overweight and obesity levels have risen. It has been suggested that large portions of high energy density (HED) foods increase total energy intake and that this is not compensated for in the short- to medium-term, potentially promoting weight gain. In the laboratory setting, offering large portions of HED foods increases overall energy intake in both children and adults. This phenomenon is known as the portion size effect (PSE), and it is robust, reliable and enduring. The possible impact of the PSE is that large portions served over time may facilitate overeating and could contribute to overweight and obesity. Explanations for the PSE vary from simple heuristics, such as the tendency to clear the plate, to more complex biobehavioural processes, including individual differences in susceptibility to external food cues through eating traits. Consumers may eat in accordance with available consumption norms or eat opportunistically when large portions are made available. An obvious solution to the PSE is to ‘downsize’ HED meal items and snacks, but whether this strategy is acceptable or feasible is not clear. In adults, the effects of downsizing are mixed and for children and adolescents, as yet unclear. The contention is that for those who are still learning about social norms and appropriate portions, there remains the potential to counter the PSE through downsizing strategies

Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals

Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions

G protein-coupled receptor-mediated calcium signaling in astrocytes

Astrocytes express a large variety of G~protein-coupled receptors (GPCRs) which mediate the transduction of extracellular signals into intracellular calcium responses. This transduction is provided by a complex network of biochemical reactions which mobilizes a wealth of possible calcium-mobilizing second messenger molecules. Inositol 1,4,5-trisphosphate is probably the best known of these molecules whose enzymes for its production and degradation are nonetheless calcium-dependent. We present a biophysical modeling approach based on the assumption of Michaelis-Menten enzyme kinetics, to effectively describe GPCR-mediated astrocytic calcium signals. Our model is then used to study different mechanisms at play in stimulus encoding by shape and frequency of calcium oscillations in astrocytes.Comment: 35 pages, 6 figures, 1 table, 3 appendices (book chapter

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions