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An editorial is presented on Acute Disease Quality Initiative (ADQI) has a more than two-decade legacy. Topics include relates to the current state of practice of diagnosis and management of acute kidney injury and other conditions in critical care nephrology; and have a focus on AKI education in resource-plentiful and resource-challenged areas.

Kinase activating missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenically linked to neurodegenerative Parkinson's disease (PD). Over the past decade, substantial effort has been devoted to the development of potent and selective small molecule inhibitors of LRRK2, as well as their preclinical testing across different Parkinson's disease models. This review outlines the genetic and biochemical evidence that pathogenic missense mutations increase LRRK2 kinase activity, which in turn provides the rationale for the development of small molecule inhibitors as potential PD therapeutics. An overview of progress in the development of LRRK2 inhibitors is provided, which in particular indicates that highly selective and potent compounds capable of clinical utility have been developed. We outline evidence from rodent- and human-induced pluripotent stem cell models that support a pathogenic role for LRRK2 kinase activity, and review the substantial experiments aimed at evaluating the safety of LRRK2 inhibitors. We address challenges still to overcome in the translational therapeutic pipeline, including biomarker development and clinical trial strategies, and finally outline the potential utility of LRRK2 inhibitors for other genetic forms of PD and ultimately sporadic PD. Collective evidence supports the ongoing clinical translation of LRRK2 inhibitors as a therapeutic intervention for PD is greatly needed. [ABSTRACT FROM AUTHOR]

The authors discuss a study that gives some insights into the typical vasculopathy in the context of systemic sclerosis (SSc). Highlights include the role of lysyl oxidases (LOXs) in several crucial physiological functions, the role of LOXs in multiple pathological fibrotic conditions, and the potential origin of serum LOX in SSc.

The article focuses on the clinical aspects of systemic inflammation and arrhythmogenesis, particularly atrial fibrillation. Topics discussed include analysis of mechanisms associated with inflammation, causation of arrhythmias, and its clinical implications; role of anti-inflammatory medications for the treatment of arrhythmias; and association of multiple disease with inflammation'.

The article discusses significance of cognitive, emotional and motivational targets in personalized treatments for traumatic brain injury. It states that apathy, irritability and impulsivity are common but vary depending on the location and severity of the injury, and mentions that TBI has also been shown to alter functional connectivity underlying emotion regulation. It notes that comprehensive assessment of affective domains would be useful for evaluating treatment effects on emotion.

Aims To compare the effects of vildagliptin with those of glimepiride on glycaemic control, fat tolerance and inflammatory markers in people with Type 2 diabetes mellitus receiving metformin treatment. Methods A total of 167 participants were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day, for 6 months. We evaluated the following variables: BMI; glycaemic control; fasting plasma insulin; homeostatic model assessment of insulin resistance index; fasting plasma proinsulin; glucagon; lipid profile; adiponectin; high-sensitivity C-reactive protein; interleukin-6; and tumour necrosis factor-α. A euglycaemic-hyperinsulinaemic clamp procedure and an oral fat load test were also performed. Results Despite a similar decrease in HbA1c levels ( P = 0.009, and P = 0.008, respectively), body weight increased with glimepiride ( P = 0.048 vs baseline) and decreased with vildagliptin ( P = 0.041 vs baseline and vs glimepiride). Fasting plasma insulin and homeostatic model assessment of insulin resistance index were significantly lower with vildagliptin compared with glimepiride ( P = 0.035 and 0.047). M value, an index of insulin sensitivity, increased with vildagliptin, both compared with baseline and with glimepiride ( P = 0.028 and 0.039, respectively). Vildagliptin improved all post-oral fat load peaks of lipid profile compared with glimepiride. Adiponectin levels were higher ( P = 0.035) and high-sensitivity C-reactive protein levels were lower ( P = 0.038) with vildagliptin vs glimepiride. During the oral fat load test, interleukin-6, high-sensitivity C-reactive protein and tumour necrosis factor-α peaks were lower and adiponectin peak was higher in the vildagliptin group than in the glimepiride group. There was a higher dropout rate as a result of hypoglycaemia in the glimepiride group than in the vildagliptin group. Conclusions Vildagliptin was more effective than glimepiride in reducing post-oral fat load peaks of lipid-trafficking adipocytokines and inflammatory markers. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor refers to topics in the issue, including Cardiac resynchronization therapy (CRT) in adult congenital heart disease (ACHD).

The article discusses a study on the immunologic heterogeneity within the overall group of patients classified as having psoriatic arthritis. The authors examined the efficacy of steering the choice of biologic on a per-patient immunologic basis in the strategic arm as compared with a standard-of-care approach. The authors have addressed recent calls for novel trial design. Slight caution is warranted as the strategic arm and standard-of-care arm were different in some key factors.

The authors discuss the article "Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use," by K. G. Heinzerling and colleagues. They argue that the study has no evidence for an effect of bupropion in treating methamphetamine dependence. The authors express disappointment with the results of the study as bupropion may be added to the growing methamphetamine-dependence therapeutics.

The article discusses various reports published within this issue including one on the association of autoantibodies with improved response of people with rheumatoid arthritis patients to abatacept, one on the use of differential methylation in rheumatoid arthritis patients and one on the resistance of diabetes patients to osteoarthritis.