Association between serum uric acid and perioperative and late cardiovascular outcome in patients with suspected or definite coronary artery disease undergoing elective vascular surgery

The role of uric acid as an independent marker of cardiovascular risk is unclear. Therefore, our aim was to assess the independent contribution of preoperative serum uric acid levels to the risk of 30-day and late mortality and major adverse cardiac event (MACE) in patients scheduled for open vascular surgery. In total, 936 patients (76% male, age 68 +/- 11 years) were enrolled. Hyperuricemia was defined as serum uric acid >0.42 mmol/l for men and >0.36 mmol/l for women, as defined by large epidemiological studies. Outcome measures were 30-day and late mortality and MACE (cardiac death or myocardial infarction). Multivariable logistic and Cox regression analysis were used, adjusting for age, gender, and all cardiac risk factors. Data are presented as odds ratios or hazard ratios, with 95% confidence intervals. Hyperuricemia was present in 299 patients (32%). The presence of hyperuricemia was associated with heart failure, chronic kidney disease, and the use of diuretics. Perioperatively, 46 patients (5%) died and 61 patients (7%) experienced a MACE. Mean follow-up was 3.7 years (range: 0 to 17 years). During follow-up, 282 patients (30%) died and 170 patients (18%) experienced a MACE. After adjustment for all clinical risk factors, the presence of hyperuricemia was not significantly associated with an increased risk of 30-day mortality or MACE, odds ratios of 1.5 (0.8 to 2.8) and 1.7 (0.9 to 3.0), respectively. However, the presence of hyperuricemia was associated with an increased risk of late mortality and MACE, with hazard ratios of 1.4 (1.1 to 1.7) and 1.7 (1.3 to 2.3), respectively. In conclusion, the presence of preoperative hyperuricemia in vascular patients is a significant predictor of late mortality and MACE.     

A role for interstitial matrix in tissue tension of alveolar wall

Single alveolar walls subjected to length-tension studies in saline and Bicine (0.2 M) undergo a progressive decay in tissue tension (TTD). We have examined the effect of different solutions on this TTD and looked for corresponding changes in the ultrastructure. Lung parenchyma was dissected to single alveolar walls (30 X 30 X 150 microns) in phosphate-buffered saline (0.15 M). Transferred to a length-tension bath, the tissue was immersed in Bicine, saline, fortified Hank's solution, 0.25% Alcian blue in saline, or a sodium dodecyl sulfate solution, for variable periods. Cycled through a given extension with peak force measured over time, these same tissues were fixed in buffered glutaraldehyde/tannic acid and processed for electron microscopy. Single alveolar walls immersed in saline or Bicine showed a progressive TTD. Vacuoles or spaces appeared in the interstitium which with cellular disorganization progressed with the TTD. Seen within 0.3 h, the changes were well advanced at 0.6 h. In sodium dodecyl sulfate (70 mM), however, there was no TTD and structurally there was no interstitium, with only basement membranes and fibrous proteins remaining. In fortified Hank's solution or 0.25% Alcian blue the interstitial matrix, cell morphology and tissue tension were well preserved for 1 h. This study suggest that leaching of the interstitial matrix occurs in saline or Bicine, and an intact matrix is essential for the preservation of tissue tension.     

17β-Estradiol and estrogen receptor α protect right ventricular function in pulmonary hypertension via BMPR2 and apelin

Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α–null or ER-β–null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex.     

Interference with Ca2+ release activated Ca2+ (CRAC) channel function delays T‐cell arrest in vivo

Entry of lymphocytes into secondary lymphoid organs (SLOs) involves intravascular arrest and intracellular calcium ion ([Ca²⁺]_i) elevation. TCR activation triggers increased [Ca²⁺]_i and can arrest T‐cell motility in vitro. However, the requirement for [Ca²⁺]_i elevation in arresting T cells in vivo has not been tested. Here, we have manipulated the Ca²⁺ release‐activated Ca²⁺ (CRAC) channel pathway required for [Ca²⁺]_i elevation in T cells through genetic deletion of stromal interaction molecule (STIM) 1 or by expression of a dominant‐negative ORAI1 channel subunit (ORAI1‐DN). Interestingly, the absence of CRAC did not interfere with homing of naïve CD4⁺ T cells to SLOs and only moderately reduced crawling speeds in vivo. T cells expressing ORAI1‐DN lacked TCR activation induced [Ca²⁺]_i elevation, yet arrested motility similar to control T cells in vitro. In contrast, antigen‐specific ORAI1‐DN T cells had a twofold delayed onset of arrest following injection of OVA peptide in vivo. CRAC channel function is not required for homing to SLOs, but enhances spatiotemporal coordination of TCR signaling and motility arrest.     

A phonetic radical account of the phonology-to-Orthography consistency effect on writing Chinese characters: Evidence from a Chinese Dysgraphic patient

ABSTRACT

This study investigated the sublexical route in writing Chinese characters. Using a writing-to-dictation task, we compared neurotypical participants’ performance on writing a set of 40 characters with homophones sharing different phonetic radicals and another set of 40 characters with homophones sharing the same phonetic radicals. The first set of stimuli was regarded as both syllable-to-character and syllable-to-radical inconsistent, while the second set of stimuli was considered syllable-to-radical consistent but syllable-to-character inconsistent. The results of the error analysis showed that the control participants demonstrated a greater tendency to make errors with preserved phonetic radicals in the second set of stimuli. Furthermore, we conducted the same task with a Chinese brain-injured patient, WCY, who had mild dyslexia and severe dysgraphia associated with mild impairment to the lexical semantic route as shown by the patient’s character writing. The results showed that WCY demonstrated similar error patterns as those of the control participants and a shorter writing time in the second set of stimuli. Altogether, the observations were taken as evidence that supported our claim that a syllable-to-phonetic radical route governs the sublexical route in Chinese character writing.