Lower negative bounds on the static electric susceptibility of nonequilibrium cubic crystals

We use a classical, microscopic model of pointlike dipolarizable entities (a model that is standard in the case of positive polarizability) and investigate its behavior for simple cubic (sc), body-centered cubic (bcc), and face-centered cubic (fcc) crystals with one entity per primitive cell when the static polarizability of the entities is negative and the mutual electrostatic interaction between the entities is taken into account. We find that the static electric susceptibility is bounded below due to an instability towards self-polarization but negative values are possible in each case. The usual Clausius-Mossotti relation between the static polarizability and the static electric susceptibility remains valid in the case of negative parameters but is truncated at the lower bound; the value of the bound depends on the crystal structure and is always unrelated to the asymptote of the Clausius-Mossotti curve. The lower bounds of the static electric susceptibility are found to be -0.906 for sc and -1.00 for bcc and fcc. These results confirm that, although the magnitude of the static electric susceptibility does not diverge in the negative case (as it can in the positive case), the magnitudes attainable in the negative case for condensed media may, nevertheless, be many orders of magnitude greater than those predicted previously for inverted vapors and gases. This is a promising result in relation to the development of potential new technologies that exploit the phenomenon

Validation of the optical Aktiia bracelet in different body positions for the persistent monitoring of blood pressure.

The diagnosis of hypertension and the adjustment of antihypertensive drugs are evolving from isolated measurements performed at the physician offices to the full phenotyping of patients in real-life conditions. Indeed, the strongest predictor of cardiovascular risk comes from night measurements. The aim of this study was to demonstrate that a wearable device (the Aktiia Bracelet) can accurately estimate BP in the most common body positions of daily life and thus become a candidate solution for the BP phenotyping of patients. We recruited 91 patients with BP ranging from low to hypertensive levels and compared BP values from the Aktiia Bracelet against auscultatory reference values for 4 weeks according to an extended ISO 81060-2 protocol. After initializing on day one, the observed means and standard deviations of differences for systolic BP were of 0.46 ± 7.75 mmHg in the sitting position, - 2.44 ± 10.15 mmHg in the lying, - 3.02 ± 6.10 mmHg in the sitting with the device on the lap, and - 0.62 ± 12.51 mmHg in the standing position. Differences for diastolic BP readings were respectively of 0.39 ± 6.86 mmHg, - 1.93 ± 7.65 mmHg, - 4.22 ± 6.56 mmHg and - 4.85 ± 9.11 mmHg. This study demonstrates that a wearable device can accurately estimate BP in the most common body positions compared to auscultation, although precision varies across positions. While wearable persistent BP monitors have the potential to facilitate the identification of individual BP phenotypes at scale, their prognostic value for cardiovascular events and its association with target organ damage will need cross-sectional and longitudinal studies. Deploying this technology at a community level may be also useful to drive public health interventions against the epidemy of hypertension

Validation of the optical Aktiia bracelet in different body positions for the persistent monitoring of blood pressure.

The diagnosis of hypertension and the adjustment of antihypertensive drugs are evolving from isolated measurements performed at the physician offices to the full phenotyping of patients in real-life conditions. Indeed, the strongest predictor of cardiovascular risk comes from night measurements. The aim of this study was to demonstrate that a wearable device (the Aktiia Bracelet) can accurately estimate BP in the most common body positions of daily life and thus become a candidate solution for the BP phenotyping of patients. We recruited 91 patients with BP ranging from low to hypertensive levels and compared BP values from the Aktiia Bracelet against auscultatory reference values for 4 weeks according to an extended ISO 81060-2 protocol. After initializing on day one, the observed means and standard deviations of differences for systolic BP were of 0.46 ± 7.75 mmHg in the sitting position, - 2.44 ± 10.15 mmHg in the lying, - 3.02 ± 6.10 mmHg in the sitting with the device on the lap, and - 0.62 ± 12.51 mmHg in the standing position. Differences for diastolic BP readings were respectively of 0.39 ± 6.86 mmHg, - 1.93 ± 7.65 mmHg, - 4.22 ± 6.56 mmHg and - 4.85 ± 9.11 mmHg. This study demonstrates that a wearable device can accurately estimate BP in the most common body positions compared to auscultation, although precision varies across positions. While wearable persistent BP monitors have the potential to facilitate the identification of individual BP phenotypes at scale, their prognostic value for cardiovascular events and its association with target organ damage will need cross-sectional and longitudinal studies. Deploying this technology at a community level may be also useful to drive public health interventions against the epidemy of hypertension

Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo-Controlled Trial.

Background The sodium/glucose cotransporter 2 inhibitor empagliflozin has cardiorenal protective properties through mechanisms beyond glucose control. In this study we assessed whether empagliflozin modifies renal oxygenation as a possible mechanism of renal protection, and determined the metabolic, renal, and hemodynamic effects of empagliflozin in nondiabetic subjects. Methods and Results In this double-blind, randomized, placebo-controlled study, 45 healthy volunteers underwent blood and urine sampling, renal ultrasound, and blood-oxygenation-level-dependent magnetic resonance imaging before and 180 minutes after administration of 10 mg empagliflozin (n=30) or placebo (n=15). These examinations were repeated after 1 month of daily intake. Cortical and medullary renal oxygenation were not affected by the acute or chronic administration of empagliflozin, as determined by 148 renal blood-oxygenation-level-dependent magnetic resonance imaging examinations. Empagliflozin increased glucosuria (24-hour glucosuria at 1 month: +50.1±16.3 g). The acute decrease in proximal sodium reabsorption, as determined by endogenous fractional excretion of lithium (-34.6% versus placebo), was compensated at 1 month by a rise in plasma renin activity (+28.6%) and aldosterone (+55.7%). The 24-hour systolic and diastolic ambulatory blood pressures decreased significantly after 1 month of empagliflozin administration (-5.1 and -2.0 mm Hg, respectively). Serum uric acid levels decreased (-28.4%), hemoglobin increased (+1.7%), and erythropoietin remained the same. Conclusions Empagliflozin has a rapid and significant effect on tubular function, with sustained glucosuria and transient natriuresis in nondiabetic normotensive subjects. These effects favor blood pressure reduction. No acute or sustained changes were found in renal cortical or medullary tissue oxygenation. It remains to be determined whether this is the case in nondiabetic or diabetic patients with congestive heart failure or kidney disease. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03093103

Purification, Cloning, and Expression of a Novel Salivary Anticomplement Protein from the Tick, Ixodes scapularis

The alternative pathway of complement is an important defense against pathogens and in tick rejection reactions. The tick Ixodes scapularis is able to feed repeatedly on its natural host and has a salivary anticomplement activity that presumably facilitates feeding. In this study, we purified and then obtained the amino-terminal sequence of the I. scapularissalivary anticomplement (Isac). We found a full-length clone coding for Isac by random screening of a salivary gland cDNA library. Expressing Isac cDNA in COS cells reproduced the activity found in tick saliva, namely, inhibition of rabbit erythrocyte lysis by human serum in the presence of Mg2+ and EGTA, inhibition of C3b binding to agarose in the presence of Mg2+ and EGTA, and acceleration of factor Bb uncoupling from the C3 convertase generated by the alternative pathway. Recombinant Isac had no effect on the recalcification time of human platelet-poor plasma or in the classical complement pathway, indicating that it is a specific inhibitor similar to the regulators of complement activation of the alternative pathway such as factor H. Isac, however, has no similarity to any protein in the GenBankTM data base, indicating that it is a novel and relatively small (18.5 kDa) anticomplement molecule

Smartphone based blood pressure measurement: accuracy of the OptiBP mobile application according to the AAMI/ESH/ISO universal validation protocol.

The aim of this study was to assess the accuracy of the OptiBP mobile application based on an optical signal recorded by placing the patient's fingertip on a smartphone's camera to estimate blood pressure (BP). Measurements were carried out in a general population according to existing standards of the Association for the Advancement of Medical Instrumentation (AAMI), the European Society of Hypertension (ESH) and the International Organization for Standardization (ISO). Participants were recruited during a scheduled appointment at the hypertension clinic of Lausanne University Hospital in Switzerland. Age, gender and BP distribution were collected to fulfill AAMI/ESH/ISO universal standards. Both auscultatory BP references and OptiBP were measured and compared using the opposite arm simultaneous method as described in the 81060-2:2018 ISO norm. A total of 353 paired recordings from 91 subjects were analyzed. For validation criterion 1, the mean ± SD between OptiBP and reference BP recordings was respectively 0.5 ± 7.7 mmHg and 0.4 ± 4.6 mmHg for SBP and DBP. For validation criterion 2, the SD of the averaged BP differences between OptiBP and reference BP per subject was 6.3 mmHg and 3.5 mmHg for SBP and DBP. OptiBP acceptance rate was 85%. The smartphone embedded OptiBP cuffless mobile application fulfills the validation requirements of AAMI/ESH/ISO universal standards in a general population for the measurement of SBP and DBP

Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants A case report

Rationale: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. Patient concerns: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. Diagnosis: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. Interventions: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. Outcomes: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. Lessons: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI

The structure of the Shiga toxin 2a A-subunit dictates the interactions of the toxin with blood components

Hemolytic uremic syndrome (eHUS) is a severe complication of human infections with Shiga toxins (Stxs)-producing Escherichia coli. A key step in the pathogenesis of eHUS is the interaction of Stxs with blood components before the targeting of renal endothelial cells. Here, we show that a single proteolytic cleavage in the Stx2a A-subunit, resulting into two fragments (A1 and A2) linked by a disulfide bridge (cleaved Stx2a), dictates different binding abilities. Uncleaved Stx2a was confirmed to bind to human neutrophils and to trigger leukocyte/platelet aggregate formation, whereas cleaved Stx2a was ineffective. Conversely, binding of complement factor H was confirmed for cleaved Stx2a and not for uncleaved Stx2a. It is worth noting that uncleaved and cleaved Stx2a showed no differences in cytotoxicity for Vero cells or Raji cells, structural conformation, and contaminating endotoxin. These results have been obtained by comparing two Stx2a batches, purified in different laboratories by using different protocols, termed Stx2a(cl; cleaved toxin, Innsbruck) and Stx2a(uncl; uncleaved toxin, Bologna). Stx2a(uncl) behaved as Stx2a(cl) after mild trypsin treatment. In this light, previous controversial results obtained with purified Stx2a has to be critically re-evaluated; furthermore, characterisation of the structure of circulating Stx2a is mandatory to understand eHUS-pathogenesis and to develop therapeutic approaches