Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia.

Cells sense and respond to changes in oxygen concentration through gene regulatory processes that are fundamental to survival. Surprisingly, little is known about how anemia affects hypoxia signaling. Because nitric oxide synthases (NOSs) figure prominently in the cellular responses to acute hypoxia, we defined the effects of NOS deficiency in acute anemia. In contrast to endothelial NOS or inducible NOS deficiency, neuronal NOS (nNOS)(-/-) mice demonstrated increased mortality during anemia. Unlike wild-type (WT) animals, anemia did not increase cardiac output (CO) or reduce systemic vascular resistance (SVR) in nNOS(-/-) mice. At the cellular level, anemia increased expression of HIF-1α protein and HIF-responsive mRNA levels (EPO, VEGF, GLUT1, PDK1) in the brain of WT, but not nNOS(-/-) mice, despite comparable reductions in tissue PO(2). Paradoxically, nNOS(-/-) mice survived longer during hypoxia, retained the ability to regulate CO and SVR, and increased brain HIF-α protein levels and HIF-responsive mRNA transcripts. Real-time imaging of transgenic animals expressing a reporter HIF-α(ODD)-luciferase chimeric protein confirmed that nNOS was essential for anemia-mediated increases in HIF-α protein stability in vivo. S-nitrosylation effects the functional interaction between HIF and pVHL. We found that anemia led to nNOS-dependent S-nitrosylation of pVHL in vivo and, of interest, led to decreased expression of GSNO reductase. These findings identify nNOS effects on the HIF/pVHL signaling pathway as critically important in the physiological responses to anemia in vivo and provide essential mechanistic insight into the differences between anemia and hypoxia.

Anesthetic Considerations for Cardiac Tamponade after Internal Jugular Central Line Placement during Trauma Resuscitation: A Case Report.

Numerous complications are associated with central venous catheters. Among them, cardiac tamponade is a rare but well-documented catastrophic complication. A 22-year-old healthy male presented with Code 1 trauma resulting from gunshot wounds in the abdomen. Upon examination, he was found to have a large pericardial fluid collection, a large right supraclavicular hematoma, and significant amount of bilateral pleural effusions secondary to extraluminal placement of the right internal jugular central line during resuscitation. After repairing the internal jugular injury and draining the pericardial fluid, the patient was transferred from the intensive care unit to the regular hospital floor. However, 15 days later, imaging revealed re-accumulation of a large pericardial effusion, which was eventually treated with a pericardial window operation. This case report explores potential complications that could arise from central line placement and the anesthetic considerations in a patient with cardiac tamponade from extraluminal central line placement.

Using wearables to screen motor performance deterioration because of cancer and chemotherapy-induced peripheral neuropathy (CIPN) in adults - Toward an early diagnosis of CIPN.

OBJECTIVE: An essential component for optimizing quality of life in adults with cancer is determining the degree to which therapy may negatively impact motor-performance, so that patients can maintain their quality of life and independence. This study examined whether instrumented gait and balance could determine the magnitude of deterioration in motor-performance from chemotherapy-induced peripheral neuropathy (CIPN). METHODS: We recruited 84 adults with cancer (age = 71.1 ±â€¯9.7 years old, BMI = 26.8 ±â€¯6.2 kg/m2, gender = 56%female) and 57 age-matched non-cancer patients (age = 69.5 ±â€¯9.8 years old, BMI = 27.1 ±â€¯6.0 kg/m2, gender = 79%female). Based on clinical screening, the group with cancer was classified into two groups: participants with CIPN (CIPN+) and without CIPN (CIPN-). Gait and balance were quantified using validated wearables. The Vibration Perception Threshold (VPT) test was used to stratify the CIPN+ group into mild (Mild-CIPN) and severe (Severe-CIPN) subgroups. RESULTS: All gait and balance parameters were deteriorated in the group with cancer compared to non-cancer group with the largest effects observed for stride-time (11%, Cohen's effect size d = 1.00, p < 0.001) and eyes-closed ankle sway (94%, d = 0.49, p = 0.001). The same trend was observed when the Severe-CIPN subgroup was compared to the Mild-CIPN. VPT correlates significantly with motor deterioration, with the largest correlation found in stride-time (Rho = 0.37, p = 0.007). Severe-CIPN subjects were significantly older and overall had more deterioration in the majority of motor-performance parameters after adjusting for age (p < 0.050). CONCLUSION: These results confirmed the negative impact of CIPN on motor-performance with the largest effects on ankle stability and stride-time. VPT is a predictor of motor deterioration and may be used to determine the severity of CIPN symptom.