Assessment of a standalone photoplethysmography (PPG) algorithm for detection of atrial fibrillation on wristband-derived data.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world. Using photoplethysmography (PPG) and software algorithms, AF can be detected with high accuracy using smartphone camera-derived data. However, reports of diagnostic accuracy of standalone algorithms using wristband-derived PPG data are sparse, while this provides a means to perform long-term AF screening and monitoring. This study evaluated the diagnostic accuracy of a well-known standalone algorithm using wristband-derived PPG data. MATERIALS AND METHODS: Subjects recruited from a community senior care organization were instructed to wear the Wavelet PPG wristband on one arm and the Alivecor KardiaBand one-lead-ECG wristband on the other. Three consecutive measurements (duration per measurement: 60 s for PPG and 30 s for one-lead ECG) were performed with both devices, simultaneously. The PPG data were analyzed by the Fibricheck standalone algorithm and the ECG data by the Kardia algorithm. The results were compared to a reference standard (interpretation of the one-lead ECG by two independent cardiologists). RESULTS: A total of 180 PPGs and one-lead ECGs were recorded in 60 subjects, with a mean age of 70±17. AF was identified in 6 (10%) of the users, two users (3%) were not classifiable by the PPG algorithm and 1 user (2%) was not classifiable by the one-lead ECG algorithm. The diagnostic performance (sensitivity/specificity/positive predictive value/negative predictive value/accuracy) on user level was 100/96/75/100/97% for the PPG wristband and 100/98/86/100/98% for the one-lead ECG wristband. CONCLUSIONS: In a small real-world cohort of elderly people, the standalone Fibricheck AF algorithm can accurately detect AF using Wavelet wristband-derived PPG data. Results are comparable to the Alivecor Kardia one-lead ECG device, with an acceptable unclassifiable/bad quality rate. This opens the door for long-term AF screening and monitoring.

Nebivolol: a review of its clinical and pharmacological characteristics.

Nebivolol is a cardioselective lipophilic beta-blocker devoid of intrinsic sympathomimetic and membrane-stabilizing actions. The pharmacological profile differs from that of conventional cardioselective beta3-blockers in that it displays nitric oxide- (NO) mediated vasodilator activity. The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta3-blockade and an action that tends to maintain cardiac output, presumably connected with its afterload reducing vasodilator effect. Recent studies suggest that nebivolol may also restore endothelial dysfunction. Long-term follow-up studies indicate that the compound is efficacious and safe both in patients with mild hypertension and those with stable angina. An interesting effect of chronic nebivolol therapy in elderly patients with mild hypertension is the reversal of a depressor effect into a pressor effect on standing. This action indicates that nebivolol has advantages over other antihypertensive drugs and that it may protect elderly hypertensive patients from orthostatic complaints. The observation that nebivolol improves exercise capacity in non-claudicant hypertensives is also of clinical interest. Nebivolol resembles serotonin reuptake inhibitors in that it is metabolized by CYP450 2D6 and, therefore, concomitant treatment with serotonin uptake inhibitors may lead to overdosing. Nebivolol compared to placebo does not significantly reduce the mortality risk in elderly subjects. The effects of biological age and comorbidities may be responsible for this finding. In conclusion, clinical studies suggest that nebivolol is effective and safe in patients with hypertension, angina pectoris and heart failure. The beneficial effects on endothelial function, autonomic control and exercise capacity are of considerable clinical interest.

The effect of cysteine modification and proteinases on the major antigens (D, C, c, E and e) of the Rh blood group system.

We have confirmed and extended previous observations showing that the (Rh) D antigen of erythrocyte membranes is destroyed by various reagents that modify cysteine (Cys) residues (Res.) and by trypsin as well as chymotrypsin, using thirty examples of monoclonal or polyclonal anti-D in heamglutination inhibition assays. We have also shown that most C, c, E, e and BS58 epitopes are inactivated or weakened by most Cys reagents and by these proteinases, using monoclonal and polyclonal antibodies. Inactivation by 5,5-dithiobis-(2-nitrobenzoic acid) was always fully reversible after subsequent dithioerythritol treatment. The essential Cys Res. appear to be buried in the membrane in view of the inability of some reagents to inactivate (iodoacetamide, iodoacetic acid) or reactivate (reduced glutathione) the antigens. Data obtained with N-ethylmaleimide indicate that inactivation of the C and c antigens is, at least in part, attributable to (a) Cys Res. that is (are) different from that (those) involved in the E and e antigens. Data obtained with the Cys reagents and the proteinases suggest that more than one peptide loop of the Rh proteins is involved in the major Rh antigens.

Sialic acid removal modulates the myocardial and vascular activity of calcium channel ligands.

Selective removal of sialic acid from isolated guinea pig left atrial strips and rabbit thoracic aortic ring segments was performed by neuraminidase prepared from Clostridium perfringens and was controlled electron microscopically. Preincubation of these organs (2 units/mL; 2 hr) resulted in enzyme mediated hydrolysis of total tissue sialic acid; 55.2% for atria and 60.9% for aorta. Contractile force of atria and arterial diameter of thoracic aorta were measured isometrically and isotonically by means of a force displacement transducer. Pretreatment of both organs with neuraminidase (2 units/mL; 2 hr) in a carbogen saturated organ bath caused a moderate left-hand shift of the cumulative concentration response curves for the dihydropyridine type calcium antagonist nisoldipine, the phenylalkylamine derivative gallopamil and the benzothiazepine diltiazem. EC50 values were significantly lower (P less than 0.05), particularly in the atrial muscle, when compared to untreated preparations. There was no effect of neuraminidase on the negative inotropic and vasodilator potency of the calcium channel modulator fendiline. Conversely, neuraminidase induced a right-hand shift in the concentration response curves shown by the pure calcium agonist (-)-S-Bay K 8644 leading to significantly higher EC50 values in both organs. Similarly, the contractile potency of calcium chloride (atria) and potassium chloride (aorta) was attenuated upon neuraminidase treatment. From the results obtained it is concluded that sialic acid removal may modulate the action of calcium channel ligands through an inhibitory effect on transmembrane calcium fluxes and/or by decreasing the external calcium availability. Whether the present results suggest a functional role for sialic acid in the regulation of calcium channels warrants further investigation.

Characterization of the Ss sialoglycoprotein and its antigens in Rhnull erythrocytes.

The Ss sialoglycoprotein (glycophorin B) and its antigens in Rhnull erythrocytes, which lack the Rhesus blood group antigens, due to apparently silent (amorphic type) or independent suppressor (regulator type) genes, were investigated. The quantity of the molecule in amorphic and in regulator type red cell membranes was found to be decreased by about 60%-70%, as judged from sodium-dodecylsulfate polyacrylamide gel electrophoresis. The Ss glycoprotein content in the erythrocytes from heterozygotes (regulator type) was diminished to an extent of about 30%. Confirming and extending previous studies, the S, s, Ux, Uz and 'N' antigens were slightly weakened in Rhnull erythrocytes. The U and Duclos receptors were only slightly or not depressed in amorphic Rhnull cells, but almost absent from or not detectable in those of the regulator type. This demonstrates that an additional alteration, apart from the decreased Ss glycoprotein content of the membranes, accounts for the weakness of these receptors in regulator type cells. We propose the hypothesis that (a) protein(s) encoded by the Rhesus locus form(s) a complex with the Ss glycoprotein. Thus, it (they) might facilitate the incorporation of the Ss glycoprotein into the membrane and also contribute to the complete expression of the U and Duclos antigens in normal cells.

Blocking action of intracellularly injected neuraminidase on central synapses in vivo.

The effect of neuraminidase on synaptic transmission was studied at cholinergic and noncholinergic contacts in the buccal and cerebral ganglion of Ap]lysia. The amplitudes of monosynaptic unitary postsynaptic potentials generated by intracellular stimulation of identified presynaptic neurones were measured as indication for the efficacy of synaptic transmission. Neuraminidase was either intrasomatically injected into a presynaptic neurone, or the whole ganglion was incubated with the enzyme. Intrasomatic injection of the enzyme resulted in complete failure of synaptic transmission. This effect occurred independently of the transmitter used. The synaptic failure was presynaptic in origin. The biophysical characteristics of an injected neurone, particularly the amplitude and propagation of its action potential, did not appear to be affected by neuraminidase. Synaptic transmission and biophysical membrane properties were unaffected by extracellular neuraminidase. We conclude that the synaptic blockade is due to the enzyme's action inside the presynaptic nerve ending. It seems most likely that neuraminidase cleaves sialic-acid-containing-compounds associated with the nerve terminal surface membrane, probably thus causing failure of transmitter release.

[Clinical significant of sialic acid concentrations in the serum of melanoma patients]. / Klinische Bedeutung der Sialinsäurekonzentration im Serum von Melanompatienten.

Sialyltransferase activities and sialic acid concentrations were measured in sera form patients with malignant melanoma (n = 49), healthy control persons (n = 20), and patients with non-malignant skin disorders (n = 30). Both parameters were found to be higher in malignant melanoma patients than in healthy control persons, but they were not significantly higher in primary melanoma patients than in patients with benign skin orders, unless widespread dissemination of metastases had occurred. The highest values were found in patients with liver and lung metastases. In early stages of the disease, shedding from tumor cells seems not to be the major source of elevated serum levels of sialyltransferase and sialic acid, respectively. There is no general correlation between sialyltransferase activities and sialic acid concentrations. However, a correlation was found between serum concentrations of sialic acid and orosomucoid in patients with melanomas stage III, indicating that humoral defense mechanisms contribute to the higher values in advanced stages of the disease.

Structure of the Ss blood group antigens, II: a methionine/threonine polymorphism within the N-terminal sequence of the Ss glycoprotein.

The N-terminal amino acid sequence (residues 1--35) of the Ss sialoglycoprotein (or glycophorin B) from human erythrocyte membranes of defined Ss blood group activity was determined by manual sequencing methods, using N-terminal tryptic or chymotryptic glycopeptides and various secondary peptides. The proposed structure differs considerably from that suggested on the basis of work with glucopeptides of unknown Ss blood group activity (Furthmayr, Nature 271, 519--523, 1978). Only one difference between glycopeptides from Ss and ss erythrocytes was found, i.e. a methionine/threonine polymorphism at position 29. On the basis of previous work (Dahr et al., Hoppe-Seyler's Z. Physiol. Chem. 361, 145--152, 1980), it is concluded that this amino acid heterogeneity represents the Ss polymorphism rather than the UX or UZ polymorphisms, which are in strong genetic linkage disequilibrium with the Ss antigens. A part of the sequence (residues 9--30) of the major (MN) red cell membrane sialoglycoprotein (glycophorin A) was re-investigated and revised at positions 11 and 17. As judged from the present data, the first 26 residues of the Ss and the blood group N-specific MN glycoprotein are identical. The sequence 27--35 of the Ss glycoprotein shows a homology with the residues 56--64 and 59--67 of the MN glycoprotein. Data on the partial N-terminal sequence of glycopeptides from a third erythrocyte membrane sialoglycoprotein (component D or glycophorin C) indicate that its structure is different from those of the two other glycoproteins.

Structure of the Ss blood group antigens. I. Isolation of Ss-active glycopeptides and differentiation of the antigens by modification of methionine.

The Ss blood group antigen determinants were found to be associated with the N-terminal tryptic and chymotryptic glycopeptides (residues 1--35 or 1--32) of the Ss sialoglycoprotein from human erythrocyte membranes. The N-terminal portion (residues 1--26) of these peptides is largely identical with that of the MN sialoglycoprotein. Therefore, and since the Ss activity of tryptic glycopeptides was higher than that of chymotryptic fragments, it is concluded that the structural difference between the S and s antigens is located on the C-terminal part (residues 27--32) of these peptides. Chemical modification of sialoglycoproteins by various methods suggests that Glu residue(s) (positions 29 or 28, 31) and possibly alpha-GalNAc-Thr (residue 25) are recognized by anti-S and -s. Carboxymethylation, performic acid, hydrogen peroxide and cyanogen bromide treatment destroy the S antigen, but have no effect on the s receptor. This suggests that the S antigen is determined by a methionyl-residue.

Sialyltransferase levels and sialic acid concentrations in sera of patients with malignant melanomas.

Serum levels of sialyltransferase and sialic acid were measured in patients with malignant melanomas (n = 49), healthy control persons (n = 20), and patients with non-malignant skin disorders (n = 30). Both parameters were found to be higher in malignant melanoma patients than in healthy control persons, but they were not significantly higher in melanoma patients than in patients with benign skin disorders, unless widespread dissemination of metastases had occurred. The highest values were measured in patients with liver and lung metastases. No general correlation was found between sialyltransferase activities and sialic acid concentrations. Sialic acid concentrations seem to be a better index for tumor spreading than sialyltransferase activities. In early stages of the disease, shedding from tumor cells is not the major source of elevated serum levels of sialyltransferase and sialic acid, respectively.