Nevin Manimala

J Am Geriatr Soc. 2022 May 10. doi: 10.1111/jgs.17810. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related morbidities and frailty are associated with impaired blood pressure (BP) and heart rate (HR) recovery after standing. Here we investigate how multimorbidity affects cerebral and peripheral hemodynamics during standing in a large sample of older patients.

METHODS: Patients were recruited from a national Falls and Syncope Unit. They underwent an active stand test (5-10 min lying +3 min standing) with monitoring of continuous BP, HR, total peripheral resistance (TPR), stroke volume (SV), and a near-infrared spectroscopy (NIRS) derived cerebral tissue saturation index (TSI). A multimorbidity count was derived from a 26-item list of conditions. Features derived from the signals included: nadir, overshoot, value at 30 s, steady-state and recovery rate. Robust linear regression was used to assess the association between multimorbidity, TSI and peripheral hemodynamics while correcting for covariates. A p-value <0.05 was considered statistically significant.

RESULTS: Multimorbidity was associated with poorer recovery of TSI at 30 s after standing (β: -0.15, CI:[-0.25-0.06], p = 0.009) independent of all peripheral hemodynamics. Impaired diastolic BP (DBP) recovery at 30s (β:-1.34, CI:[-2.29-0.40], p = 0.032), DBP steady-state (β:-1.18, CI:[-2.04-0.32], p = 0.032), TPR overshoot-to-nadir difference (β:-0.041, CI:[-0.070-0.013], p = 0.045), and SV at 30s (β:1.30, CI:[0.45 2.15], p = 0.027) were also associated with increasing multimorbidity. After sex stratification, only females demonstrated impaired TSI with multimorbidity at overshoot (β: -0.19, CI: [-0.32 -0.07], p = 0.009), 30 s (β: -0.22 [-0.35-0.10], p = 0.005) and steady-state (β: -0.20, CI:[-0.35-0.04], p = 0.023), independent of peripheral hemodynamics.

CONCLUSIONS: Transient cerebral oxygenation and peripheral hemodynamic responses are impaired with multimorbidity (frailty) in older patients, particularly in females. This study demonstrates the feasibility of using NIRS in this clinical context and may inform the development of clinical management strategies targeting both cerebral oxygenation and blood pressure impairments in patients with faints and falls.

PMID:35535653 | DOI:10.1111/jgs.17810

Soft Matter. 2022 May 10. doi: 10.1039/d2sm00258b. Online ahead of print.

ABSTRACT

Biofilm formation is the most successful survival strategy for bacterial communities. In the biofilm lifestyle, bacteria embed themselves in a self-secreted matrix of extracellular polymeric substances (EPS), which acts as a shield against mechanical and chemical insults. When ambient flow is present, this viscoelastic scaffold can take a streamlined shape, forming biofilm filaments suspended in flow, called streamers. Streamers significantly disrupt the fluid flow by causing rapid clogging and affect transport in aquatic environments. Despite their relevance, the structural and rheological characterization of biofilm streamers is still at an early stage. In this work, we present a microfluidic platform that allows the reproducible growth of biofilm streamers in controlled physico-chemical conditions and the characterization of their biochemical composition, morphology, and rheology in situ. We employed isolated micropillars as nucleation sites for the growth of single biofilm streamers under the continuous flow of a diluted bacterial suspension. By combining fluorescent staining of the EPS components and epifluorescence microscopy, we were able to characterize the biochemical composition and morphology of the streamers. Additionally, we optimized a protocol to perform hydrodynamic stress tests in situ, by inducing controlled variations of the fluid shear stress exerted on the streamers by the flow. Thus, the reproducibility of the formation process and the testing protocol make it possible to perform several consistent experimental replicates that provide statistically significant information. By allowing the systematic investigation of the role of biochemical composition on the structure and rheology of streamers, this platform will advance our understanding of biofilm formation.

PMID:35535650 | DOI:10.1039/d2sm00258b

Soft Matter. 2022 May 10. doi: 10.1039/d1sm01765a. Online ahead of print.

ABSTRACT

Two different tensions can be defined for a fluid membrane: the internal tension, γ, conjugated to the real membrane area in the Hamiltonian, and the frame tension, τ, conjugated to the projected (or frame) area. According to the standard statistical description of a membrane, the fluctuation spectrum is governed by γ. However, using rotational invariance arguments, several studies argued that the fluctuation spectrum must be governed by the frame tension τ instead. These studies disagree on the origin of the result obtained with the standard description yet: either a miscounting of configurations, quantified with the integration measure, or the use of a quadratic approximation of the Helfrich Hamiltonian. Analyzing the simplest case of a one-dimensional membrane, for which the arc length offers a natural parametrization, we give a new proof that the fluctuations are driven by τ, and show that the origin of the issue with the standard description is a miscounting of membrane configurations. The origin itself of this miscounting depends on the thermodynamic ensemble in which calculations are made.

PMID:35535647 | DOI:10.1039/d1sm01765a

Dermatol Ther. 2022 May 10:e15573. doi: 10.1111/dth.15573. Online ahead of print.

ABSTRACT

BACKGROUND: During the SARS-COV-2 pandemic, using face masks became mandatory in many countries. Although evidence suggests that masks can exacerbate several inflammatory skin diseases, few studies focus on their real impact on eczema localized to the face in atopic dermatitis (AD) patients.

OBJECTIVE: The aim of this study is to evaluate facial eczema prevalence during pandemic and its psychological impact in AD patients pre-assessed for systemic treatment and/or in therapy with dupilumab.

METHODS: This study includes 71 patients affected by moderate-severe AD, treated with dupilumab at SCDU of Dermatology in Novara, Italy. We calculated the number of subjects with facial involvement in pre- and post-pandemic periods and the related localization trend. We evaluated, in the two groups, clinical and psychological indicators recorded at each visit and the score modifications during the observational period.

RESULTS: No statistically significant differences were observed in facial eczema prevalence, between pre- and post-pandemic periods (p = 0.7618) and in facial eczema remission among the two groups (p = 0.1903). In post-pandemic period, psychological scores were significantly lower (DLQI and HADS respectively with p <0.0001 and p = 0.0025) and the reduction in EASI score during observational period was significantly greater (p = 0.0001).

CONCLUSIONS: Our analysis revealed a potential protective effect of masks on face eczema, suggesting that they could enhance dupilumab efficacy. Face masks, covering sensitive areas, can positively contribute to mental distress in patients with facial eczema, and being associated with a lower allergic diseases incidence may sustain dupilumab in reducing AD severity. This article is protected by copyright. All rights reserved.

PMID:35535633 | DOI:10.1111/dth.15573

J Am Heart Assoc. 2022 May 10:e023010. doi: 10.1161/JAHA.121.023010. Online ahead of print.

ABSTRACT

Background Experiments measuring the contractile properties of human myocardium are important for translational research but complicated by the logistical difficulties of acquiring specimens. Accordingly, many groups perform contractile assays using samples that are acquired from patients at one institution and shipped to another institution for experiments. This necessitates freezing the samples and performing subsequent assays using chemically permeabilized preparations. It is unknown how prior freezing affects the contractile function of these preparations. Methods and Results To examine the effects of freezing we measured the contractile function of never-frozen and previously frozen myocardial samples. Samples of left ventricular tissue were obtained from 7 patients who were having a ventricular assist device implanted. Half of each sample was chemically permeabilized and used immediately for contractile assays. The other half of the sample was snap frozen in liquid nitrogen and maintained at -180 °C for at least 6 months before being thawed and tested in a second series of experiments. Maximum isometric force measured in pCa 4.5 solution, passive force measured in pCa 9.0 solution, and Hill coefficients were not influenced by prior freezing (P=0.07, P=0.14, and P=0.27 respectively). pCa₅₀ in never-frozen samples (6.11±0.04) was statistically greater (P<0.001) than that measured after prior freezing (5.99±0.04) but the magnitude of the effect was only ≈0.1 pCa units. Conclusions We conclude that prior freezing has minimal impact on the contractile properties that can be measured using chemically permeabilized human myocardium.

PMID:35535623 | DOI:10.1161/JAHA.121.023010

Hum Brain Mapp. 2022 May 10. doi: 10.1002/hbm.25898. Online ahead of print.

ABSTRACT

In recent neuroimaging studies, threshold-free cluster enhancement (TFCE) gained popularity as a sophisticated thresholding method for statistical inference. It was shown to feature higher sensitivity than the frequently used approach of controlling the cluster-level family-wise error (cFWE) and it does not require setting a cluster-forming threshold at voxel level. Here, we examined the applicability of TFCE to a widely used method for coordinate-based neuroimaging meta-analysis, Activation Likelihood Estimation (ALE), by means of large-scale simulations. We created over 200,000 artificial meta-analysis datasets by independently varying the total number of experiments included and the amount of spatial convergence across experiments. Next, we applied ALE to all datasets and compared the performance of TFCE to both voxel-level and cluster-level FWE correction approaches. All three multiple-comparison correction methods yielded valid results, with only about 5% of the significant clusters being based on spurious convergence, which corresponds to the nominal level the methods were controlling for. On average, TFCE’s sensitivity was comparable to that of cFWE correction, but it was slightly worse for a subset of parameter combinations, even after TFCE parameter optimization. cFWE yielded the largest significant clusters, closely followed by TFCE, while voxel-level FWE correction yielded substantially smaller clusters, showcasing its high spatial specificity. Given that TFCE does not outperform the standard cFWE correction but is computationally much more expensive, we conclude that employing TFCE for ALE cannot be recommended to the general user.

PMID:35535616 | DOI:10.1002/hbm.25898

Circulation. 2022 May 10. doi: 10.1161/CIRCULATIONAHA.122.059235. Online ahead of print.

ABSTRACT

BACKGROUND: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection (LoD) of 5 ng/L to exclude acute myocardial infarction. Per the United States (US) Food and Drug Administration (FDA), hs-cTnT can only report to the limit of quantitation (LoQ) of 6 ng/L, a threshold for which there is limited data. Our goal was to determine whether a single hs-cTnT below the LoQ of 6 ng/L is a safe strategy to identify patients at low-risk for acute myocardial injury and infarction.

METHODS: The efficacy (proportion identified as low-risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least one hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99^th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic electrocardiogram with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling-out acute myocardial infarction and safety (myocardial infarction or death at 30-days) were evaluated.

RESULTS: A total of 85,610 patients were evaluated in the CV Data Mart Biomarker cohort, amongst which 24,646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% vs. 20%, p<0.0001). Among 11,962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI 98.6, 99.0) and sensitivity of 99.6% (95% CI 99.5, 99.6). In the adjudicated cohort, a nonischemic electrocardiogram with hs-cTnT<6 ng/L identified 33% of patients (610 of 1849) as low-risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for 30-day myocardial infarction or death.

CONCLUSIONS: A single hs-cTnT below the LoQ of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

PMID:35535607 | DOI:10.1161/CIRCULATIONAHA.122.059235

Popul Stud (Camb). 2022 May 10:1-19. doi: 10.1080/00324728.2022.2057576. Online ahead of print.

ABSTRACT

The study of the mortality differences between groups has traditionally focused on metrics that describe average levels of mortality, for example life expectancy and standardized mortality rates. Additional insights can be gained by using statistical distance metrics to examine differences in lifespan distributions between groups. Here, we use a distance metric, the non-overlap index, to capture the sociological concept of stratification, which emphasizes the emergence of unique, hierarchically layered social strata. We show an application using Finnish registration data that cover the entire population over the period from 1996 to 2017. The results indicate that lifespan stratification and life-expectancy differences between income groups both increased substantially from 1996 to 2008; subsequently, life-expectancy differences declined, whereas stratification stagnated for men and increased for women. We conclude that the non-overlap index uncovers a unique domain of inequalities in mortality and helps to capture important between-group differences that conventional approaches miss.

PMID:35535591 | DOI:10.1080/00324728.2022.2057576

Phys Chem Chem Phys. 2022 May 10. doi: 10.1039/d2cp00490a. Online ahead of print.

ABSTRACT

We report measurements of the statistical vibrational autodetachment (VAD, also called thermionic emission) and radiative cooling rates of isolated para-benzoquinone (pBQ, C₆H₄O₂) radical anions using the cryogenic electrostatic ion storage ring facility DESIREE. The results are interpreted using master equation simulations with rate coefficients calculated using statistical detailed balance theory. The VAD rate is determined by measuring the time-dependent yield of neutral pBQ due to spontaneous electron emission from a highly-excited ensemble of anions formed in an electron-attachment ion source. Competition with radiative cooling quenches the VAD rate after a critical time of τ_c = 11.00(5) ms. Master equation simulations which reproduce the VAD yield provide an estimate of the initial effective vibrational temperature of the ions of 1100(20) K, and provide insight into the anion formation scenario. A second measurement of the radiative cooling rate of pBQ^– stored for up to 0.5 s was achieved using time-dependent photodetachment action spectroscopy across the ²A_u ← ²B_2g and ²B_2u ← ²B_2g transitions. The rate at which hot-band contributions fade from the action spectrum is quantified by non-negative matrix factorisation. This is found to be commensurate with the average vibrational energy extracted from the simulations, with 1/e lifetimes of 0.16(3) s and 0.1602(7) s, respectively. Implications for astrochemistry are discussed.

PMID:35535575 | DOI:10.1039/d2cp00490a

Future Oncol. 2022 May 10. doi: 10.2217/fon-2022-0093. Online ahead of print.

ABSTRACT

Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further clinical development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with gastric/gastroesophageal junction cancer. Accumulating evidence indicates that ICIs combined with FLOT chemotherapy improve clinical outcomes in patients with advanced or metastatic cancer. We describe the rationale for and the design of MATTERHORN, a randomized, double-blind, placebo-controlled, phase III study investigating the efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy followed by adjuvant durvalumab monotherapy in patients with resectable gastric/gastroesophageal junction cancer. The planned sample size is 900 patients, the primary end point is event-free survival, and safety and tolerability will be evaluated. Clinical trial registration: NCT04592913 (ClinicalTrials.gov).

PMID:35535555 | DOI:10.2217/fon-2022-0093