Objective Assessment of Covid-19 Severity Affecting the Vocal and Respiratory System Using a Wearable, Autonomous Sound Collar.

Introduction: Since the outbreak began in January 2020, Covid-19 has affected more than 161 million people worldwide and resulted in about 3.3 million deaths. Despite efforts to detect human infection with the virus as early as possible, the confirmatory test still requires the analysis of sputum or blood with estimated results available within approximately 30 minutes; this may potentially be followed by clinical referral if the patient shows signs of aggravated pneumonia. This work aims to implement a soft collar as a sound device dedicated to the objective evaluation of the pathophysiological state resulting from dysphonia of laryngeal origin or respiratory failure of inflammatory origin, in particular caused by Covid-19. Methods: In this study, we exploit the vibrations of waves generated by the vocal and respiratory system of 30 people. A biocompatible acoustic sensor embedded in a soft collar around the neck collects these waves. The collar is also equipped with thermal sensors and a cross-data analysis module in both the temporal and frequency domains (STFT). The optimal coupling conditions and the electrical and dimensional characteristics of the sensors were defined based on a mathematical approach using a matrix formalism. Results: The characteristics of the signals in the time domain combined with the quantities obtained from the STFT offer multidimensional information and a decision support tool for determining a pathophysiological state representative of the symptoms explored. The device, tested on 30 people, was able to differentiate patients with mild symptoms from those who had developed acute signs of respiratory failure on a severity scale of 1 to 10. Conclusion: With the health constraints imposed by the effects of Covid-19, the heavy organization to be implemented resulting from the flow of diagnostics, tests and clinical management, it was urgent to develop innovative and safe biomedical technologies. This passive listening technique will contribute to the non-invasive assessment and dynamic observation of lesions. Moreover, it merits further examination to provide support for medical operators to improve clinical management. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-021-00712-w.

An autonomous low-power management system for energy harvesting from a miniaturized spherical piezoelectric transducer.

A new spherical vibrational energy harvesting device with an additional low power management circuit for optimizing the power transfer from the mechanical vibrations to a storage capacitor is presented. The device is devoted to underwater wireless sensor network applications due to its broadband vibrational energy harvesting, sensing, and communicating facilities. The sensing node container consists of two acrylic glass (PMMA) half-spherical shells and a Pz26 piezoelectric ring clamped between the shells. The energy harvesting, the management circuit, and communication electronics were fitted within the hollow portion of the sphere. A simulation model of the energy extraction and management system using spice has been developed. This simulation shows the feasibility and efficiency of the low power extraction circuit; a level of the necessary stored voltage was set at 3 V. The numerical model was validated by underwater experimental measurements; a voltage of 3 V was obtained at the terminals of a storage capacitor (47 µF) which was sufficient to supply the communication electronics. Power harvesting performances were measured relative to the transmitter/sensor distance and the incident acoustical field excitation voltage. Finally, 175 µW of harvested power has been measured with an excitation voltage of 8 Vpp at 5 cm distance from the emitter.

Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage.

Acetaminophen (paracetamol) is a well-tolerated analgesic and antipyretic drug when used at therapeutic doses. Overdoses, however, cause oxidative stress, which leads to acute liver failure. Alpha lipoic acid is an antioxidant that has proven effective for ameliorating many pathological conditions caused by oxidative stress. We evaluated the effect of alpha lipoic acid on the histological and histochemical alterations of liver caused by an acute overdose of acetaminophen in rats. Livers of acetaminophen-intoxicated rats were congested and showed centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration. Necrotic hepatocytes lost most of their carbohydrates, lipids and structural proteins. Liver sections from rats pre-treated with lipoic acid showed fewer pathological changes; the hepatocytes appeared moderately vacuolated with moderate staining of carbohydrates and proteins. Nevertheless, alpha lipoic acid at the dose we used did not protect the liver fully from acetaminophen-induced acute toxicity.

Inline high frequency ultrasonic particle sizer.

This paper reports the development of a new method of particle sizing in a liquid. This method uses high frequency focused ultrasounds to detect particles crossing the focal zone of an ultrasonic sensor and to determine their size distribution by processing the reflected echoes. The major advantage of this technique compared to optical sizing methods is its ability to measure the size of particles suspended in an opaque liquid without any dedicated sample preparation. Validations of ultrasonic measurements were achieved on suspensions of polymethyl methacrylate beads in a size range extending from a few micrometer to several hundred micrometer with a temporal resolution of 1 s. The inline detection of aggregate formation was also demonstrated.

Global transmission and reflection coefficients of the ultrasonic component in porous media: a new approach.

The purpose of this paper is to propose a new approach to determining the global ultrasonic transmission and reflection coefficients in a random porous medium. Boundary conditions at the interface of the medium were used to determine local transmission and reflection coefficients. A study of the behavior of different waves inside the medium was carried out to derive a new global formulation that takes interior phenomena into consideration. All the results were obtained independently of the geometrical and physical characteristics of the medium so that the method can be applied to any two-phase porous medium. This study is based on normal incidence ultrasonic wave propagation.

Ultrasonic measurement of bulk and shear moduli variations in porous alumina media.

In this paper we studied some acoustical parameters of a porous medium based on the Biot's theory. The basic idea was to find, using an inversion method, variations in the bulk modulus K(b) and the shear modulus G(b) in the frequency domain. This was achieved by comparing the theoretical and experimental results obtained on a selection of porous alumina samples with different physical characteristics. Then, using the transmission coefficient, a numerical process was applied to a virtual porous alumina medium in order to find K(b) and G(b) values at low frequency under static conditions. Using a frequency range of 50kHz to 600kHz, fast and slow waves were considered and both were included in the transmission coefficient.

Fewer dose changes with once-monthly C.E.R.A. in patients with chronic kidney disease.

BACKGROUND: Frequent dosing and requirements for dose adjustments of erythropoiesis-stimulating agents (ESAs) create significant burdens for healthcare providers and have been associated with hemoglobin (Hb) cycling, hampering maintenance of target Hb levels. We compared the frequency of dose changes in dialysis patients who received methoxy polyethylene glycolepoetin beta; (a continuous erythropoietin receptor activator (C.E.R.A.)) or a shorter-acting ESA. METHODS: Data were analyzed from three Phase III maintenance trials, using almost identical protocols, in dialysis patients treated with C.E.R.A. every 2 weeks (q2w) or every 4 weeks (q4w) or a comparator ESA (epoetin or darbepoetin alpha; at their previous dose/administration interval). Dosage was adjusted to maintain Hb ± 1 g/dl of baseline and 10 - 13.5 g/dl during titration (28 weeks) and evaluation (8 weeks), and 11 - 13 g/dl during follow-up (16 weeks). RESULTS: Data were analyzed from 564 patients treated with C.E.R.A. q2w, 410 with C.E.R.A. q4w and 572 with comparator ESA at their usual dosing interval. Significantly fewer dose changes were needed in patients receiving C.E.R.A. q2w (p < 0.05) or C.E.R.A. q4w (p < 0.001) than in patients treated with comparator ESAs. CONCLUSION: This retrospective analysis suggests that C.E.R.A. q4w maintains Hb levels in dialysis patients and requires fewer dose changes compared with other ESAs.

Postdialysis outcomes associated with consistent anemia treatment in predialysis patients with chronic kidney disease.

AIMS: Anemia and cardiovascular (CV) events are major complications of chronic kidney disease (CKD) during dialysis. We conducted a retrospective observational study in CKD patients with anemia to evaluate the association between predialysis use of erythropoiesis-stimulating agents (ESAs) and postdialysis CV outcomes. METHODS: The study analyzed claims data on incident hemodialysis patients aged > or = 18 years (identified between January 2000 and November 2005). Patients were identified as anemic and ESA-treated prior to dialysis. ESA treatment was categorized into 4 consistency groups (from least to most consistent ESA use). RESULTS: Of 5,848 hemodialysis patients, 52% were identified as anemic prior to onset of dialysis. Predialysis ESA treatment was received by 62% of anemic patients, with only 23% receiving the most consistent treatment. The risk of a CV event was significantly lower for the ESA-treated compared with ESA-untreated patients (relative risk (RR) 0.70, 95% (95% confidence intervals (CI) 0.61 - 0.82)). Compared with ESA-untreated, those who received ESAs had significantly lower risk of acute myocardial infarction (RR 0.65 (95% CI 0.44 - 0.95)) or inpatient mortality (RR 0.52 (95% CI 0.40 - 0.68)). ESA-treated patients in each of the 4 consistency groups had significantly lower risk of CV events compared with ESA-untreated patients, with the greatest benefit seen in patients who received most consistent ESA (RR 0.61 (95% CI 0.48 - 0.76)). CONCLUSIONS: This analysis suggests consistent ESA use to treat anemia of CKD in the predialysis period is associated with improved cardiovascular outcomes in postdialysis patients.

Design of low-frequency ultrasonic sensors for the analysis of the draining stage of cheese production.

This work presents a new ultrasonic system with a transmission mode in the 100-200 kHz frequency range. The system, composed of ultrasonic point sources, is used to monitor the mechanical properties of cheese during the early phases of production. First, our specialized sensor system is presented, and then the results obtained with the system model are compared to the results of actual experiments using the system to monitor the evolution of the medium during draining. The results of a rheological compliance test and shock pulse ultrasonic amplitude measurements agree and correspond quite accurately to the mechanical properties of the evolving physical state of the medium. This method could be used in the future to study the effect on the final cheese quality of the process parameters that interfere with cheese grain consolidation during the draining process.

Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature.

Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known. Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies. Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups. Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease. Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case). Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity. These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis.

Renal cell apoptosis in chronic obstructive uropathy: the roles of caspases.

BACKGROUND: Apoptosis of tubular and interstitial cells is well documented in kidneys with chronic obstructive uropathy (COU) and probably plays an important role in the pathogenesis of this condition. The molecular control of apoptosis in COU remains poorly understood. Apoptosis in general is known to proceed initially along distinct pathways, which later converge into a common arm characterized by orderly activation of caspases. Caspases are cytosolic enzymes that belong to a 12-member family and serve as effector molecules for apoptosis. The role of individual caspases in mediating renal cell apoptosis in kidneys with COU is studied. METHODS: Kidneys were harvested from sham-operated mice and mice with COU created by left ureter ligation at days 4, 7, 15, 20, and 30. The following studies were performed: (1) determination of dried kidney weight; (2) in situ end labeling of fragmented DNA to detect apoptotic tubular and interstitial cells; (3) ribonuclease protection assay with specific anti-sense RNA probes for caspases 1, 2, 3, 6, 7, 8, 9, 11, and 12 to detect the expression of individual caspases; (4) immunostaining for caspases; and (5) assay for caspase 3. To assess the role of caspases in COU-associated renal cell apoptosis, the frequencies of apoptotic tubular and interstitial cells were separately quantitated for each experimental time point, and their patterns of variation were correlated with those of individual caspases. RESULTS: The obstructed kidneys showed progressive tissue loss (60% of control at day 15). Apoptosis of both tubular and interstitial cells was seen in obstructed kidneys. Tubular cell apoptosis peaked at four days after ureter ligation (13-fold of control), remained high between days 4 to 15, and thereafter decreased rapidly. Apoptotic interstitial cells were scanty initially, but gradually increased throughout the entire experiment. Apoptosis was minimal throughout the experiment in control and contralateral kidneys. In control and contralateral kidneys, caspases 2, 3, 6, 7, 8, and 9 mRNAs were expressed at low levels, whereas those for caspases 1, 11, and 12 were not detected. The obstructed kidneys displayed increased expression of all tested caspases. Caspases 1, 11, and 12 mRNAs were detected in obstructed kidneys in a common pattern characterized by a sharp increase at day 4, followed by a decrease until day 20, and a subsequent sharp increase until the end of the study at day 30. A similar pattern was noted for other caspases (2, 3, 6, 7, 8, and 9), which maximally reached twofold to fourfold that of controls. Immunostaining for caspases 1, 2, 3, 6, 7, 8, and 9 showed the same pattern characterized by focal and weak expression in proximal tubules of control or contralateral kidney, contrasting with increased staining in atrophic or dilated tubules of obstructed kidneys. Interstitial cells also displayed staining for several caspases, which paralleled the increasing density of interstitial cells toward the end of the experiment. Caspase-3 assay showed a marked increased activity in obstructed kidneys that reached fourfold and sevenfold of control at days 4 and 30, respectively. The rise and fall of caspase mRNAs between days 4 and 30 paralleled a similar fluctuation in tubular cell apoptosis. The subsequent increase of mRNAs was correlated with a continuous rise of interstitial cell apoptosis. CONCLUSIONS: Urinary obstruction in mice induces apoptosis of both tubular and interstitial cells in the affected kidney in a distinctive pattern that parallels an increased expression of caspases. This correlation suggests that these caspases mediate COU-associated renal cell apoptosis. Among the evaluated caspases, increased renal caspase 3 activity implies its central role in renal cell apoptosis associated with urinary obstruction.

Infectious complications of the hemodialysis access.

Infectious complications of the vascular access are a major source of morbidity and mortality among hemodialysis (HD) patients. Numerous reports implicate the vascular access in up to 48 to 73% of all bacteremias in HD patients. The incidence of vascular access-related infection is highest when central venous dialysis catheters are employed. Native arteriovenous fistulas carry the lowest risk of infection. Unfortunately, prosthetic arteriovenous grafts, which represent the most common type of HD access in the United States, have been repeatedly shown to be a risk factor for bacteremic and nonbacteremic infections. Silent infection in old nonfunctional clotted prosthetic arteriovenous grafts has recently been recognized as a frequent cause of bacteremia and morbidity among HD patients. High proportions of infections related to the vascular access are caused by staphylococcal organisms, which carry high rates of mortality, recurrence, and metastatic complications. Management of vascular access-related infection has two aspects: The first relates to the choice, duration, and mode of administration of antibiotic therapy. Empiric antibiotic therapy, guided by demographic data and severity of illness, should be employed when the causative organisms are unknown. Prolonged administration of specific parenteral antibiotics is crucial in decreasing complications of infection, especially in cases of staphylococcal bacteremia. The second aspect relates to management of the vascular access. Efforts directed toward bacteriological cure should be concurrent with efforts to preserve native venous access sites whenever possible. Efforts to prevent vascular access-related infection should focus on increasing placement of arteriovenous fistulas and minimizing insertion of central venous dialysis catheters. Careful inspection and monitoring of the vascular access is of paramount importance in early detection of vascular access site-related infections. Several new approaches aimed at preventing catheter and prosthetic graft-related infection are being explored.

The human temporary threshold shift after exposure to 60 minutes' noise in an aerobics class.

The potential hazard of noise to hearing is well documented. However, there are some experiences of noise-induced hearing loss (NIHL) that are not so well-known, for example the effects of leisure noise, and in particular, leisure noise experienced during an aerobics class. A preliminary study of the noise level in aerobics classes in the Manchester region was carried out and their mean noise level was found to be 89.6 dB(A) (+/-4.7 dB(A)). Pure tone thresholds in the audible frequency range were obtained from 28 young adult volunteers (mean age 21 years; standard deviation (SD) 2.3 years) and 14 subjects (the 'exposure' group) were then invited to join (but not participate in) an aerobics class (mean noise level 91.8 dB(A) (+/-1.5 dB(A)) for 60 minutes. The noise levels in the aerobics class were monitored throughout the 60 minutes and the subjects did not stray from a small marked area (2 m2). Subjects' hearing thresholds were obtained for a second time, beginning within 2 minutes of the cessation of the noise, and any temporary threshold shifts (TTS) were noted. A second group of 14 subjects (the control group) was invited for a second audiogram after at least 60 minutes, during which time subjects were not exposed to any noise. The data obtained here were analysed and of the 14 subjects in the exposure group all had significant TTS at all frequencies except 1,000 Hz. Subjects in the control group, who had not experienced any noise, showed significantly reduced hearing thresholds (all frequencies; p>0.02), showing evidence of a possible practice effect with audiometric testing.

Reciprocal regulation of LTA(4) hydrolase expression in human monocytes by gamma-interferon and interleukins 4 and 13: potential relevance to leukotriene regulation in glomerular disease.

BACKGROUND/AIMS: Leukotriene A(4) (LTA(4)) hydrolase catalyzes the final step in the synthesis of leukotriene B(4) (LTB(4)). TH-1- and TH-2-derived cytokines may regulate LTB(4) synthesis by monocytes through their actions on the expression of LTA(4) hydrolase. METHODS: Freshly isolated monocytes were incubated with pro- and anti-inflammatory cytokines for 36 h. mRNA expression was determined by Northern blot, protein expression was determined by Western blot and LTB(4) synthesis was determined by ELISA. RESULTS: Interferon-gamma (a TH-2-derived cytokine) increased significantly LTA(4) hydrolase mRNA expression, whereas interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA(4) hydrolase mRNA expression in these cells. The same effects were seen on the expression of immunoreactive LTA(4) hydrolase after incubating the monocytes with either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1 beta did not show any significant effect on LTA(4) hydrolase mRNA expression. When LTB(4) release was measured, both IL-1 beta and interferon-gamma significantly increased LTB(4) production by monocytes, while TH-2 cytokines (IL-4 and IL-13) decreased it. CONCLUSION: The opposing effects of TH-1- and TH-2-derived cytokines on the expression of LTA(4) hydrolase mRNA may regulate LTB(4) synthesis by monocytes during inflammation.

Optimizaition of a low-frequency ultrasonic technique to monitor the change in physical states in viscoelastic media: gelation process

A new low-frequency ultrasonic device (50-100 kHz) in highly sharpened end sensors that behave as point sources were examined. The application of this new ultrasonic technique with two sensors coupled in the near field is to explore the relations between the physical properties measured through the evolution of the wave time of flight and structural changes during gel formation which is related to two factors: the ambient temperature and the mechanical resistance of the medium. The network evolution was interpreted by an approach based on the Flory model. The physical significance of this model was shown through a series of experiments using a low-frequency ultrasonic technique. Response curves demonstrate the different stages during gel formation.

"Pauci-Immune" proliferative and necrotizing glomerulonephritis with thrombotic microangiopathy in patients with systemic lupus erythematosus and lupus-like syndrome.

In the glomerulonephritides of systemic lupus erythematosus (SLE), the number of subendothelial deposits, when present, generally corresponds to the degree of light microscopic glomerular hypercellularity; only very rarely are no or few such deposits present in cases of focal (WHO class III) or diffuse (WHO class IV) proliferative lupus nephritis. We have recently encountered five cases of active diffuse proliferative glomerlonephritis with no subendothelial and few or no mesangial deposits and thrombotic microangiopathy (TMA) in four patients with SLE and one patient with lupus-like syndrome. Three of the five patients were tested for circulating lupus anticoagulants or anticardiolipin antibodies, and two were positive. All five patients tested negatively for antineutrophil cytoplasmic antibodies (ANCA). Three patients responded to steroid and cyclophosphamide treatment, although one of them died of acute bacterial bronchopneumonia. One patient was lost to follow-up. We conclude that "pauci-immune" proliferative lupus nephritis is rare and should be treated as proliferative lupus nephritis with a proportionate number of subendothelial deposits. The negative ANCA suggests that these cases do not represent incidental ANCA-associated pauci-immune necrotizing and crescentic glomerulonephritis in patients with SLE. Of particular interest is that, in patients with SLE, if associated with TMA, an active proliferative necrotizing glomerulonephritis may be present even in the absence of significant glomerular immune complex deposition.

Free-radical-generated F2-isoprostane stimulates cell proliferation and endothelin-1 expression on endothelial cells.

BACKGROUND: Free-radical-generated F2-isoprostane stimulates DNA synthesis and endothelin-1 (ET-1) expression on endothelial cells. 8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a member of the recently discovered family of prostanoids, the F2-isoprostanes, produced in vivo by cyclooxygenase-independent, free-radical-catalyzed lipid peroxidation. The goal of our study is to establish the effect of isoprostane on ET-1 production by endothelial cells, as well to determine the receptors responsible for these effects. METHODS: The proliferative effect of isoprostanes was measured as an increase of viable cell number and [3H]-thymidine uptake. ET-1 gene expression and protein synthesis were determined by Northern blot and radioimmunoassay, respectively. We also determined inositol 1,4,5-trisphosphate synthesis. Thromboxane A2 (TXA2) receptor antagonist SQ29,548 was used to establish the role of TXA2 receptor in isoprostane effect, as well as to determine the type of receptors involved in these effects. RESULTS: Our results show that physiological concentrations of 8-iso-PGF2alpha stimulated cell proliferation, DNA synthesis, and ET-1 mRNA and protein expression in bovine aortic endothelial cells (BAECs). The proliferative effect was partially abolished by treatment with anti-endothelin antibody. 8-Iso-PGF2alpha also increased inositol 1, 4,5-trisphosphate formation in these cells. These effects were partially inhibited by SQ29,548. In competitive binding assays, two binding sites were recognized on BAECs with dissociation constants (Kd) and binding site densities at equilibrium similar to those previously described in smooth muscle cells and likely represent [3H]-8-iso-PGF2alpha binding to its own receptor (high-affinity binding site) and cross-recognition of the TXA2 receptor (low-affinity binding site). CONCLUSION: These studies expand the potential scope of the pathophysiologic significance of F2-isoprostanes, released during oxidant injury, to include alteration of endothelial cell biology.

Novel approaches to treatment of glomerulonephritis.

Our improved understanding of the mechanisms of glomerular injury has allowed the design of novel therapeutic strategies to treat glomerulonephritis. While elimination of the etiologic factors continues to be a difficult task, modulation of the inflammatory response seems more promising at present. Several proinflammatory mediators have been identified as therapeutic targets and their inhibition has ameliorated glomerular injury in experimental animals. The role of anti-inflammatory molecules and the phenomenon of immunotolerance have gained particular attention and may prove to be useful therapeutically. Mediators of tissue repair have been found to contribute to glomerular destruction, and their inhibition was protective in a variety of experiments. In this review we discuss some of these novel approaches which may be targeted against human glomerulonephritis in the near future.