The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are a relatively recently discovered class of atypical ganglion cell photoreceptor. These ipRGCs are a morphologically and physiologically heterogeneous population that project widely throughout the brain and mediate a wide array of visual functions ranging from photoentrainment of our circadian rhythms, to driving the pupillary light reflex to improve visual function, to modulating our mood, alertness, learning, sleep/wakefulness, regulation of body temperature, and even our visual perception. The presence of melanopsin as a unique molecular signature of ipRGCs has allowed for the development of a vast array of molecular and genetic tools to study ipRGC circuits. Given the emerging complexity of this system, this review will provide an overview of the genetic tools and methods used to study ipRGCs, how these tools have been used to dissect their role in a variety of visual circuits and behaviors in mice, and identify important directions for future study.The gut microbiota has a crucial effect on regulating the intestinal mucosal immunity and maintaining intestinal homeostasis both in health and in disease state. Many effects are mediated by gut microbiota-derived metabolites and tryptophan, an essential aromatic amino acid, is considered important among many metabolites in the crosstalk between gut microbiota and the host. Kynurenine, serotonin, and indole derivatives are derived from the three major tryptophan metabolism pathways modulated by gut microbiota directly or indirectly. Aryl hydrocarbon receptor (AHR) is a cytoplasmic ligand-activated transcription factor involved in multiple cellular processes. Tryptophan metabolites as ligands can activate AHR signaling in various diseases such as inflammation, oxidative stress injury, cancer, aging-related diseases, cardiovascular diseases (CVD), and chronic kidney diseases (CKD). Accumulated uremic toxins in the body fluids of CKD patients activate AHR and affect disease progression. In this review, we will elucidate the relationship between gut microbiota-derived uremic toxins by tryptophan metabolism and AHR activation in CKD and its complications. This review will provide therapeutic avenues for targeting CKD and concurrently present challenges and opportunities for designing new therapeutic strategies against renal fibrosis.Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF.
This study aimed at developing a quantitative approach to assess abnormalities on MRI of the brachial plexus and the cervical roots in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) and to evaluate interrater reliability and its diagnostic value.
We performed a cross-sectional study in 50 patients with CIDP, 31 with MMN and 42 disease controls. We systematically measured cervical nerve root sizes on MRI bilaterally (C5, C6, C7) in the coronal [diameter (mm)] and sagittal planes [area (mm
)], next to the ganglion (G
) and 1cm distal from the ganglion (G
). We determined their diagnostic value using a multivariate binary logistic model and ROC analysis. In addition, we evaluated intra- and interrater reliability.
Nerve root size was larger in patients with CIDP and MMN compared to controls at all predetermined anatomical sites. We found that nerve root diameters in the coronal plane had optimal reliability (intrarater ICC 0.55-0.87; interrater ICC 0.65-0.90). AUC was 0.78 (95% CI 0.69-0.87) for measurements at G
and 0.81 (95% CI 0.72-0.91) for measurements at G
. Importantly, our quantitative assessment of brachial plexus MRI identified an additional 10% of patients that showed response to treatment, but were missed by nerve conduction (NCS) and nerve ultrasound studies.
Our study showed that a quantitative assessment of brachial plexus MRI is reliable. MRI can serve as an important additional diagnostic tool to identify treatment-responsive patients, complementary to NCS and nerve ultrasound.
Our study showed that a quantitative assessment of brachial plexus MRI is reliable. MRI can serve as an important additional diagnostic tool to identify treatment-responsive patients, complementary to NCS and nerve ultrasound.Following the work of Avenell et al. that has raised concerns about the integrity of the Yamaguchi Osteoporosis Prevention Study (YOPS) conducted by Ishida and Kawai we issue here an adjustment to all meta-analysis estimates that contained this work within our systematic review.Due to a high heterogeneity and dynamic changes in the course of acute respiratory distress syndrome (ARDS), intensive care physicians are faced with extraordinary challenges. While the current definition, pathophysiology and differential diagnoses were previously addressed in this journal, this article focuses on some specific and individualized treatment options. Ventilation treatment with limitation of tidal volumes and pressure amplitudes has been shown to be advantageous with respect to mortality. Selleck BRD-6929 Nevertheless, because of the multifactorial etiology of ARDS in the context of individual circumstances, this strategy needs to be adjusted to each patient's needs. In recent years it has become increasingly evident that prone positioning, early spontaneous breathing and early mobilization improve the course of the disease. Therefore, an individualized treatment should consider these issues and take the characteristics of the patient and the specific disease progression into account.Selleck BRD-6929
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