Reduced digestion of circulating genomic DNA in systemic sclerosis patients with the DNASE1L3 R206C variant.

OBJECTIVES: Polymorphism in a coding region of deoxyribonuclease I-like III (DNASE1L3), causing amino acid substitution of Arg-206 to Cys (R206C), is a robustly replicated heritable risk factor for SSc and other autoimmune diseases. DNASE1L3 is secreted into the circulation, where it can digest genomic DNA (gDNA) in apoptosis-derived membrane vesicles (AdMVs). We sought to determine the impact of DNASE1L3 R206C on digestion of circulating gDNA in SSc patients and healthy controls (HCs). METHODS: The ability of DNASE1L3 to digest AdMV-associated gDNA was tested in vitro. The effect of R206C substitution on extracellular secretion of DNASE1L3 was determined using a transfected cell line and primary monocyte-derived dendritic cells from SSc patients. Plasma samples from SSc patients and HCs with DNASE1L3 R206C or R206 wild type were compared for their ability to digest AdMV-associated gDNA. The digestion status of endogenous gDNA in plasma samples from 123 SSc patients and 74 HCs was determined by measuring the proportion of relatively long to short gDNA fragments. RESULTS: The unique ability of DNASE1L3 to digest AdMV-associated gDNA was confirmed. Extracellular secretion of DNASE1L3 R206C was impaired. Plasma from individuals with DNASE1L3 R206C had reduced ability to digest AdMV-associated gDNA. The ratio of long: short gDNA fragments was increased in plasma from SSc patients with DNASE1L3 R206C, and this ratio correlated inversely with DNase activity. CONCLUSION: Our results confirm that circulating gDNA is a physiological DNASE1L3 substrate and show that its digestion is reduced in SSc patients with the DNASE1L3 R206C variant.

Artificial Intelligence and Chatbots in Psychiatry.

The utilization of artificial intelligence (AI) in psychiatry has risen over the past several years to meet the growing need for improved access to mental health solutions. Additionally, shortages of mental health providers during the COVID-19 pandemic have continued to exacerbate the burden of mental illness worldwide. AI applications already in existence include those enabled to assist with psychiatric diagnoses, symptom tracking, disease course prediction, and psychoeducation. Modalities of AI mental health care delivery include availability through the internet, smartphone applications, and digital gaming. Here we review emerging AI-based interventions in the form of chat and therapy bots, specifically conversational applications that teach the user emotional coping mechanisms and provide support for people with communication difficulties, computer generated images of faces that form the basis of avatar therapy, and intelligent animal-like robots with new advances in digital psychiatry. We discuss the implications of incorporating AI chatbots into clinical practice and offer perspectives on how these AI-based interventions will further impact the field of psychiatry.

Multimodality lymphatic imaging of postoperative chylothorax in an infant with Noonan syndrome: a case report.

BACKGROUND: Chylothorax is a rare complication of pediatric cardiac operations that occurs more frequently in children with Noonan syndrome, a genetic disorder associated with cardiac defects and lymphatic anomalies. CASE PRESENTATION: We report a case of postoperative chylothorax in a 6-month-old infant with Noonan syndrome where multimodality lymphatic imaging guided management was followed. Drainage patterns of the lymphatic capillaries in the lower and upper extremities were visualized during near-infrared fluorescence lymphatic imaging (NIRFLI). Dynamic magnetic resonance lymphangiography (MRL) further identified the site of leakage in the thoracic duct and subsequently guided surgical intervention. CONCLUSIONS: Application of multimodality imaging allows for greater individualization of treatment and should be considered in patients with complex cases such as those with syndromes associated with a higher incidence of chylothorax. IRB Number: HSC-MS-13-0754, December 10, 2013.