The Effect of Testosterone Replacement Therapy on Nonalcoholic Fatty Liver Disease in Older Hypogonadal Men.

CONTEXT: Male hypogonadism is associated with visceral obesity and the metabolic syndrome: factors important for the development of nonalcoholic fatty liver disease (NAFLD). The Testosterone Trials (The T Trials) showed testosterone (T) treatment compared with placebo in older hypogonadal men was associated with decreases in cholesterol and insulin levels suggesting that T treatment may improve NAFLD. OBJECTIVE: Compare effects of T vs placebo treatment on NAFLD scores and liver scans in elderly hypogonadal men. METHODS: Secondary data analyses from 479 older hypogonadal men with total T < 275 ng/dL from The T Trials were performed. Three clinical liver fat scores-lipid accumulation product index, hepatic steatosis index, nonalcoholic fatty liver disease-metabolic syndrome score-and liver computed tomography (CT) Hounsfield units and liver to spleen ratio were evaluated at baseline and 12 months after treatment. RESULTS: There were no statistically significant differences of change in lipid accumulation product index (P = .98), hepatic steatosis index (P = .67), and nonalcoholic fatty liver disease-metabolic syndrome (P = .52) in 246 men treated with T compared with 233 treated with placebo for 12 months. Liver CT showed no statistically significant difference of change in Hounsfield units (P = .24; n = 71 for T, n = 69 for placebo) and liver to spleen ratio (P = .74; n = 55 for T, n = 62 for placebo) between the 2 groups. CONCLUSIONS: Our study did not show improvement of NAFLD in older hypogonadal men after 12 months of T vs placebo treatment, as assessed by 3 clinical scores and liver CT for hepatic steatosis. Future studies with longer treatment duration and additional NAFLD diagnostic modalities as primary outcome are warranted.

Tissue perfusion pressure enables continuous hemodynamic evaluation and risk prediction in the intensive care unit.

Treatment of circulatory shock in critically ill patients requires management of blood pressure using invasive monitoring, but uncertainty remains as to optimal individual blood pressure targets. Critical closing pressure, which refers to the arterial pressure when blood flow stops, can provide a fundamental measure of vascular tone in response to disease and therapy, but it has not previously been possible to measure this parameter routinely in clinical care. Here we describe a method to continuously measure critical closing pressure in the systemic circulation using readily available blood pressure monitors and then show that tissue perfusion pressure (TPP), defined as the difference between mean arterial pressure and critical closing pressure, provides unique information compared to other hemodynamic parameters. Using analyses of 5,988 admissions to a modern cardiac intensive care unit, and externally validated with 864 admissions to another institution, we show that TPP can predict the risk of mortality, length of hospital stay and peak blood lactate levels. These results indicate that TPP may provide an additional target for blood pressure optimization in patients with circulatory shock.

Non-Invasive Evaluation of a Carotid Arterial Pressure Waveform Using Motion-Tolerant Ultrasound Measurements During the Valsalva Maneuver.

This work details the non-invasive evaluation of a carotid arterial blood pressure (ABP) waveform during the Valsalva maneuver. Unfocused and wide acoustic beams are insonated on the carotid artery to achieve motion-tolerant measurements with a simple two-element ultrasound scanner. Arterial flow and distension waveforms are reliably estimated from spectral Doppler and M-mode ultrasound images whose qualities are consistently maintained in different phases of the maneuver despite possible displacements of the artery. A local pulse wave velocity is estimated using a flow-area method, and it is then combined with the distension waveform to produce the ABP waveform. Human subject validation on seven healthy subjects shows that the bias in pulse pressure estimates across subjects is 0.47 ± 13.1 mmHg. The average root mean square deviations of the ultrasonically measured waveform across subjects is 10.1 ± 2.43 mmHg, excluding the strain phase of the Valsalva maneuver, and 17.7 ± 6.30 mmHg in all phases. The mean correlation coefficient between the ultrasonically measured and reference waveform is calculated to be 0.92 ± 0.04 across subjects. Detailed morphological features and their changes across different phases are observed as reported. This uninterrupted central ABP waveform monitoring under hemodynamics changes supports the idea of a novel stress test to evaluate the health and dynamics of the cardiovascular system at a spot check in clinical settings.

Monitoring of Pulse Pressure and Arterial Pressure Waveform Changes during the Valsalva Maneuver by a Portable Ultrasound System.

This work presents non-invasive evaluation of the arterial blood pressure (ABP) waveform during the Valsalva maneuver. Ultrasound scanning is conducted to acquire blood flow and arterial distension signals. Motion-tolerant ultrasound measurement schemes are employed by using two wide rectangular transducers. Pulse pressure (PP) estimated at the common carotid artery is compared to that of a finger waveform measured by a volume clamping device. The changes of PP are correlated between the two measurements. A more depressed dicrotic notch during the Valsalva strain is observed, and beat-to-beat variations of PP and a pulse rate caused by respiration and baroreflex is observed during the control. This validation suggests novel opportunities to investigate the pathophysiology of cardiovascular diseases through the noninvasive ABP waveform monitoring during the stress test.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3D Plane-wave Imaging and Tx 2nd-Order Harmonic Distortion (HD2) Reduction.

We propose a Column-Row-Parallel imaging frontend architecture for integrated and low-power 3D medical ultrasound imaging. The Column-Row-Parallel architecture offers linear-scaling interconnection, acquisition and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data / control interface to a 2D array. A 16×16 CMUT-ASIC Column-Row-Parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3mm in both azimuth and elevation, 8.5mm in depth. At a hypothetically scaled up 64x64 array size, the frame rate can still be kept at 31.2 Hz for a volume of 40mm in both azimuth and elevation, 150mm in depth. An interleaved checker board pattern with in-phase (I) and quadrature (Q) excitations is also demonstrated for reducing CMUT second harmonic distortion (HD2) emission by up to 25 dB at the loss of 3 dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

Motion Tolerant Unfocused Imaging of Physiological Waveforms for Blood Pressure Waveform Estimation Using Ultrasound.

This paper details unfocused imaging using single-element ultrasound transducers for motion tolerant arterial blood pressure (ABP) waveform estimation. The ABP waveform is estimated based on pulse wave velocity and arterial pulsation through Doppler and M-mode ultrasound. This paper discusses approaches to mitigate the effect of increased clutter due to unfocused imaging on blood flow and diameter waveform estimation. An intensity reduction model (IRM) estimator is described to track the change of diameter, which outperforms a complex cross-correlation model (C3M) estimator in low contrast environments. An adaptive clutter filtering approach is also presented, which reduces the increased Doppler angle estimation error due to unfocused imaging. Experimental results in a flow phantom demonstrate that flow velocity and diameter waveforms can be reliably measured with wide lateral offsets of the transducer position. The distension waveform estimated from human carotid M-mode imaging using the IRM estimator shows physiological baseline fluctuations and 0.6-mm pulsatile diameter change on average, which is within the expected physiological range. These results show the feasibility of this low cost and portable ABP waveform estimation device.

A Column-Row-Parallel Ultrasound Imaging Architecture for 3-D Plane-Wave Imaging and Tx Second-Order Harmonic Distortion Reduction.

We propose a column-row-parallel imaging front-end architecture for integrated and low-power 3-D medical ultrasound imaging. The column-row-parallel architecture offers linear-scaling interconnection, acquisition, and programming time with row-by-row or column-by-column operations, while supporting volumetric imaging functionality and fault-tolerance against possible transducer element defects with per-element controls. The combination of column-parallel selection logic, row-parallel selection logic, and per-element selection logic reaches a balance between flexible imaging aperture definition and manageable imaging data/control interface to a 2-D array. A capacitive micromachined ultrasonic transducer (CMUT)-application-specific integrated circuit (ASIC) column-row-parallel prototype is fabricated and assembled with a flip-chip bonding process. It facilitates the 3-D plane-wave coherent compounding algorithm for volumetric imaging with a fast frame rate of 62.5 Hz and 46% improved lateral resolution with 10-angle compounding and a field of view volume of 2.3 mm in both azimuth and elevation, 8.5 mm in depth. At a hypothetically scaled up array size, the frame rate can still be kept at 31.2 Hz for a volume of 40 mm in both azimuth and elevation, 150 mm in depth. An interleaved checkerboard pattern with in-phase ( ) and quadrature ( ) excitations is also demonstrated for reducing CMUT second-harmonic distortion emission by up to 25 dB at the loss of 3-dB fundamental energy reduction. The method reduces nonlinear effects from both transducers and circuits and is a wide band technique that is applicable to arbitrary pulse shapes.

A Wearable Transcranial Doppler Ultrasound Phased Array System.

OBJECTIVE: Practical deficiencies related to conventional transcranial Doppler (TCD) sonography have restricted its use and applicability. This work seeks to mitigate several such constraints through the development of a wearable, electronically steered TCD velocimetry system, which enables noninvasive measurement of cerebral blood flow velocity (CBFV) for monitoring applications with limited operator interaction. MATERIALS AND METHODS: A highly-compact, discrete prototype system was designed and experimentally validated through flow phantom and preliminary human subject testing. The prototype system incorporates a custom two-dimensional transducer array and multi-channel transceiver electronics, thereby facilitating acoustic beamformation via phased array operation. Electronic steering of acoustic energy enables algorithmic system controls to map Doppler power throughout the tissue volume of interest and localize regions of maximal flow. Multi-focal reception permits dynamic vessel position tracking and simultaneous flow velocimetry over the time-course of monitoring. RESULTS: Experimental flow phantom testing yielded high correlation with concurrent flowmeter recordings across the expected range of physiological flow velocities. Doppler power mapping has been validated in both flow phantom and preliminary human subject testing, resulting in average vessel location mapping times <14 s. Dynamic vessel tracking has been realized in both flow phantom and preliminary human subject testing. CONCLUSIONS: A wearable prototype CBFV measurement system capable of autonomous vessel search and tracking has been presented. Although flow phantom and preliminary human validation show promise, further human subject testing is necessary to compare velocimetry data against existing commercial TCD systems. Additional human subject testing must also verify acceptable vessel search and tracking performance under a variety of subject populations and motion dynamics-such as head movement and ambulation.

Integrated microHall magnetometer to measure the magnetic properties of nanoparticles.

Magnetic nanoparticles (MNPs) are widely used in biomedical and clinical applications, including medical imaging, therapeutics, and biological sample processing. Rapid characterization of MNPs, notably their magnetic moments, should facilitate optimization of particle synthesis and accelerate assay development. Here, we report a compact and low-cost magnetometer for fast, on-site MNP characterization. Termed integrated microHall magnetometer (iHM), our device was fabricated using standard semiconductor processes: an array of Hall sensors, transistor switches, and amplifiers were integrated into a single chip, thus improving the detection sensitivity and facilitating chip operation. By applying the iHM, we demonstrate versatile magnetic assays. We measured the magnetic susceptibility and moments of MNPs using small sample amounts (∼10 pL), identified different MNP compositions in mixtures, and detected MNP-labeled single cells.

Noninvasive arterial blood pressure waveform monitoring using two- element ultrasound system.

This work details noninvasive arterial blood pressure (ABP) waveform estimation based on an arterial vessel cross-sectional area measurement combined with an elasticity measurement of the vessel, represented by pulse wave velocity (PWV), using a two-element ultrasound system. The overall ABP waveform estimation is validated in a custom-designed experimental setup mimicking the heart and an arterial vessel segment with two single element transducers, assuming a constant hemodynamic system. The estimation of local PWV using the flow-area method produces unbiased elasticity estimation of the tube in a pressure waveform comparison. The measured PWV using 16 cardiac cycles of data is 8.47 + 0.63 m/s with an associated scaling error of -1.56 + 14.0% in a direct pressure waveform comparison, showing negligible bias error on average. The distension waveform obtained from a complex cross-correlation model estimator (C3M) reliably traces small pressure changes reflected by the diameter change. The excellent agreement of an estimated pressure waveform to the reference pressure waveform suggests the promising potential of a readily available, inexpensive, and portable ABP waveform monitoring device.

trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-α.

Intake of dietary aroma compounds may regulate cellular lipid metabolism. We demonstrated that trans-caryophyllene, a flavor compound in plant foods and teas, activates peroxisome proliferator-activated receptor (PPAR)-α through direct interaction with the ligand-binding domain of PPAR-α. The agonistic activity of trans-caryophyllene was investigated by the luciferase reporter assay, surface plasmon resonance, and time-resolved fluorescence resonance energy transfer assay. Following the stimulation of cells with trans-caryophyllene, intracellular triglyceride concentrations were significantly reduced by 17%, and hepatic fatty acid uptake was significantly increased by 31%. The rate of fatty acid oxidation was also significantly increased. The expressions of PPAR-α and its target genes and proteins in fatty acid uptake and oxidation were significantly up-regulated as well. In HepG2 cells transfected with small interfering RNA of PPAR-α, the effects of trans-caryophyllene on PPAR-α responsive gene expressions, intracellular triglyceride, fatty acid uptake and oxidation were disappeared. These results indicate that the aroma compound, trans-caryophyllene, is PPAR-α agonist thus regulates cellular lipid metabolism in PPAR-α dependent manners.

A case of type B lactic acidosis in acute leukemia.

Type B lactic acidosis is a rare condition in patients with solid tumors or hematological malignancies. Although there have been several theories to explain its mechanism, the exact cause of lactic acidosis remains to be discovered. Lactic acidosis is usually related to increased tumor burden in patients with malignancy. We experienced a case of lactic acidosis in a 39-year-old man who visited an emergency room because of dyspnea, and the cause of lactic acidosis turned out to be recurrent acute leukemia. Chemotherapy relieved the degree of lactic acidosis initially, but as the disease progressed, lactic acidosis became aggravated. Type B lactic acidosis can be a clinical presentation of acute exacerbation of acute leukemia.

Clinical observation of 12 farmers who believe themselves to have suffered from chronic pesticide intoxication.

BACKGROUND/AIM: We assessed twelve cases of suspected chronic pesticide intoxication, with medically unexplained physical symptoms. METHODS: Complete blood cell count (CBC), blood chemistry, routine urinalysis, chest X-ray, ECG, gastrofiberscopy, abdominal ultrasonography, neuroselective sensory nerve conduction threshold, and psychological assessment were performed on 12 farmers who believe themselves to have suffered from chronic pesticide intoxication. RESULTS: No specific abnormalities were observed on CBC, routine urinalysis, chest X-ray, ECG, gastroscopy, abdominal ultrasonography, or peripheral nerve conduction velocity test. They persistently manifested helplessness, depression, and anxiety. The results of both psychological assessment and general physical examination revealed the following clinical features: depression (8 cases), multiple chemical hypersensitivity syndrome (2 cases), alcoholism (1 case), and religious preoccupation (1 case). CONCLUSION: In those living in the western rural area of South Korea, depression is a prominent ongoing presentation in pesticide-exposed farmers, in addition to unexplainable physical symptoms.