Delayed Onset of COVID-19 in an Immunosuppressed Patient.

We report on a case of delayed presentation of COVID-19 in a postpartum immunosuppressed patient with the confounding variable of cytomegalovirus viremia. This case highlights the importance of maintaining high suspicion for COVID-19 disease even with delayed onset of symptoms, as this diagnosis as important treatment and public health implications.

Heartfulness meditation improves sleep in chronic insomnia.

Background: Chronic insomnia is characterized by disturbed sleep that occurs despite adequate opportunity and circumstances to sleep. Many patients with chronic insomnia have comorbid mental illnesses or medical illnesses that contribute and precipitate insomnia. Hallmark of chronic insomnia treatment includes non-pharmacological measures such as Cognitive Behavioral Therapy for Insomnia (CBT-I). Pharmacologic treatment (sedative or hypnotic agents) has been disappointing because of poor efficacy and numerous undesirable side effects. Other new therapies including meditation have been proven to be effective. Objective: This study investigates the effectiveness of Heartfulness meditation coupled with sleep hygiene to treat chronic insomnia. Methods: In this prospective pre-post design cohort study, 32 adult patients with chronic primary insomnia engaged in Heartfulness meditation along with appropriate sleep hygiene for eight weeks. Insomnia Severity Index (ISI) scores, usage of sedative or hypnotic agents were measured at baseline and at the end of the eight-week period. Results: There was a significant decrease in the mean ISI scores from 20.9 to 10.4 (p < 0.001) after eight weeks of Heartfulness meditation. Twenty four of 32 patients were initially on sedative or hypnotic medications. At week eight, 21 of 24 patients (87.5%) were off these medications or the dosage was reduced (p < 0.001). Conclusion: This study demonstrated statistical improvements in the measures of ISI in patients undergoing a Heartfulness meditation program. Heartfulness meditation may facilitate the taper and eventual cessation of sedative hypnotics in patients suffering from chronic insomnia.

Transverse oriented electric field re-entrant resonator (TERR) with automatic tuning and coupling control for EPR spectroscopy and imaging of the beating heart.

Sample motion, particularly that of a beating heart, induces baseline noise and spectral distortion on an EPR spectrum. In order to quench motional noise and restore the EPR signal amplitude and line-width, an L-band transverse oriented electric field re-entrant resonator (TERR) was designed and constructed with provisions for automatic tuning control (ATC) and automatic coupling control (ACC) suited for studies of isolated beating rat hearts. Two sets of electronic circuits providing DC biased voltage to two varactor diodes were implemented to electronically adjust coupling and tuning. The resonator has a rectangular cross-sectional sample arm of 25 mm diameter with a Q value of 1100 without sample. Once inserted with lossy aqueous samples of 0.45% NaCl, Q value drops to 400 with a volume of 0.5 ml and 150 with 5 ml. The ATC/ACC functions were tested with a moving phantom and isolated beating rat hearts with the improvement of signal to noise ratio (S/N, peak amplitude of signal over peak amplitude of baseline noise) of 6.7-, and 4 to 6-fold, respectively. With these improvements, EPR imaging could be performed on an isolated beating rat heart. Thus, this TERR resonator with ATC/ACC enables application of EPR spectroscopy and imaging for the measurement and imaging of radical metabolism, redox state, and oxygenation in the isolated beating rat heart.

Leptin modulates the negative inotropic effect of interleukin-1beta in cardiac myocytes.

Interleukin-1beta (IL-1beta) is a potent negative inotrope implicated in the functional abnormalities of heart failure. Because the adipokine, leptin, protects against some of the cardiovascular effects of endotoxin, we hypothesized that leptin may modulate the cardiosuppressive effects of IL-1beta in isolated cardiomyocytes. Ventricular cardiac myocytes isolated from adult male Sprague Dawley rats were analyzed simultaneously for electrically stimulated contractility and calcium transients following 30 min exposure to IL-1beta (10 ng/ml) with or without 60 min pretreatment with leptin (25 ng/ml). IL-1beta decreased cell shortening, depressed maximal velocities of shortening and relengthening, and prolonged the time to 90% relaxation. The change in fura2-AM fluorescence ratio amplitude (Delta[Ca(2+)]) was significantly depressed and the time to return to baseline [Ca(2+)] was prolonged. The negative inotropic effects of IL-1beta were blocked by the neutral sphingomyelinase inhibitor Manumycin A (5 microM) or the ceramidase inhibitor N-oleoyl ethanolamine (1 microM). Prior exposure of myocytes to leptin blocked IL-1beta-induced cardiosuppression in conjunction with a blunting of IL-1beta stimulated ceramide accumulation. These data suggest that leptin may modulate IL-1beta signaling through the sphingolipid signaling pathway in cardiomyocytes.

Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4.

Coronary vasodilation is impaired in the postischemic heart with a loss of endothelial nitric oxide synthase (eNOS) activity, but the mechanisms underlying ischemia-induced eNOS dysfunction are not understood. For nitric oxide (NO) synthesis, eNOS requires the redox-sensitive cofactor tetrahydrobiopterin (BH(4)); however, the role of BH(4) in ischemia-induced endothelial dysfunction remains unknown. Therefore, isolated rat hearts were subjected to varying durations of ischemia, and the alterations in NOS-dependent vasodilation were measured and correlated with assays of eNOS activity and cardiac BH(4) concentrations. Ischemia time-dependently decreased cardiac BH(4) content with 85, 95, or 97% irreversible degradation after 30, 45, or 60 min of ischemia, respectively. Paralleling the decreases in BH(4), reductions of eNOS activity were seen of 58, 86, or 92%, and NOS-derived superoxide production was greatly increased. Addition of 10 microM BH(4) enhanced eNOS activity in nonischemic hearts and partially restored activity after ischemia. It also suppressed NOS-derived superoxide production. Impaired coronary flow during postischemic reperfusion was improved by BH(4) infusion. Thus, BH(4) depletion contributes to postischemic eNOS dysfunction, and BH(4) treatment is effective in partial restoration of endothelium-dependent coronary flow. Supplementation of BH(4) may therefore be an important therapeutic approach to reverse endothelial dysfunction in postischemic tissues.

Phase I and phase II of short-term mechanical restitution in perfused rat left ventricles.

We examined the contributions of the Ca(2+) channels of the sarcolemma and of the sarcoplasmic reticulum to electromechanical restitution. Extrasystoles (F(1)) were interpolated 40-600 ms following a steady-state beat (F(0)) in perfused rat ventricles paced at 2 or 3 Hz. Plots of F(1)/F(0) versus the extrasystolic interval consisted of phase I, which occurred before relaxation of the steady-state beat, and phase II, which occurred later. Phase I exhibited a period of enhanced left ventricular pressure development that coincided with action potential prolongation. Phase I was eliminated by -BAY K 8644 (100 nM) and FPL 64176 (150 nM), augmented by 3 microM thapsigargin plus 200 nM ryanodine and unaffected by KN-93 and KB-R7943. Phase II was accelerated by the Ca(2+) channel agonists and by isoproterenol but was eliminated by thapsigargin plus ryanodine. The results suggest that phase I of electromechanical restitution is caused by a transient L-type Ca(2+) current facilitation, whereas phase II represents the recovery of the ability of the sarcoplasmic reticulum to release Ca(2+).

Mechanical alternans and restitution in failing SHHF rat left ventricles.

We examined mechanical alternans and electromechanical restitution in normal and failing rat hearts. Alternans occurred at 5 Hz in failing versus 9 Hz in control hearts and was reversed by 300 nM isoproterenol, 6 mM extracellular Ca(2+), 300 nM -BAY K 8644, or 50 nM ryanodine. Restitution curves comprised phase I, which was completed before relaxation of the steady-state beat, and phase II, which occurred later. Phase I action potential area and developed pressure ratios were significantly reduced in the failing versus control hearts. Phase II was a monoexponential increase in relative developed pressure as the extrasystolic interval was increased. The plateau of phase II was significantly elevated in failing hearts. Thapsigargin (3 microM) plus ryanodine (200 nM) potentiated phase I to a significantly greater extent in control versus failing hearts and abolished phase II in both groups. The results suggest that both regulation of Ca(2+) influx across the sarcolemma and Ca(2+) release by the sarcoplasmic reticulum may contribute to altered excitation-contraction coupling in the failing spontaneously hypertensive heart failure prone rat heart.