Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume.

In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.

Presynaptic to postsynaptic relationships of the neuromuscular junction are held constant across age and muscle fiber type.

The neuromuscular junction (NMJ) displays considerable morphological plasticity as a result of differences in activity level, as well as aging. This is true of both presynaptic and postsynaptic components of the NMJ. Yet, despite these variations in NMJ structure, proper presynaptic to postsynaptic coupling must be maintained in order for effective cell-to-cell communication to occur. Here, we examined the NMJs of muscles with different activity profiles (soleus and EDL), on both slow- and fast-twitch fibers in those muscles, and among young adult and aged animals. We used immunofluorescent techniques to stain nerve terminal branching, presynaptic vesicles, postsynaptic receptors, as well as fast/slow myosin heavy chain. Confocal microscopy was used to capture images of NMJs for later quantitative analysis. Data were subjected to a two-way ANOVA (main effects for myofiber type and age), and in the event of a significant (p < 0.05) F ratio, a post hoc analysis was performed to identify pairwise differences. Results showed that the NMJs of different myofiber types routinely displayed differences in presynaptic and postsynaptic morphology (although the effect on NMJ size was reversed in the soleus and the EDL), but presynaptic to postsynaptic relationships were tightly maintained. Moreover, the ratio of presynaptic vesicles relative to nerve terminal branch length also was similar despite differences in muscles, their fiber type, and age. Thus, in the face of considerable overall structural differences of the NMJ, presynaptic to postsynaptic coupling remains constant, as does the relationship between presynaptic vesicles and the nerve terminal branches that support them.