Nevin Manimala

Minerva Med. 2021 Nov 11. doi: 10.23736/S0026-4806.21.07894-0. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac involvement significantly contributes to coronavirus disease 2019 (COVID-19)mortality.12-lead electrocardiogram (ECG) represents a fast, cheap, and easy to perform exam with the adjunctive advantage of the remote reporting possibility. In this study, we sought to investigate if electrocardiographic parameters are able to identify patients, deemed at low-risk at admission,who will face in-hospital unfavourable course.

METHODS: From March 1, 2020 through March 30, 2021, 384 consecutive patients with confirmed low-risk COVID-19 were hospitalized at the AziendaOspedalieroUniversitariaPoliclinico di Bari (Italy). Criteria for low-risk were: admission to the division of Pneumology or Infectious Diseases, no need for immediate (within 24 hours from admission) transfer to Intensive Care Unit or for respiratory support with invasive mechanical ventilation (IMV) or for circulation support (either mechanical or pharmacological). Admission ECGs were reviewed and interpreted by two expert cardiologists. The primary outcomes were in-hospital death and the composite outcome of in-hospitaldeath and IMV.

RESULTS: In low-risk COVID-19 patients, atrial fibrillation (AF), poor R wave progression (PRWP), tachycardia, and right bundle branch block (RBBB) resulted as statistically significant and independent predictors of in-hospital all-cause mortality; AF, PRWP, Tachycardia, RBBB, and corrected QT interval showed to be statistically significant and independent risk factors for the occurrence of the composite endpoint of death and IMV.

CONCLUSIONS: Our study demonstrated for the first time that RBBB and PRWP, assessed upon admission with ECG, are associated with unfavourable clinical course in a baseline low-risk population hospitalized for COVID-19.

PMID:34761885 | DOI:10.23736/S0026-4806.21.07894-0

Minerva Med. 2021 Nov 11. doi: 10.23736/S0026-4806.21.07665-5. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the present study was to investigate the possible correlation between various inflammation-nutritional scores to histological determined Non-Alcoholic Steatohepatitis (NASH) and other liver injury suggestive for Non-Alcoholic Fatty Liver Disease (NAFLD) in a bariatric population.

METHODS: We evaluated consecutively and retrospectively all the patients referred to the department of bariatric surgery in Trieste, Italy. Inflammation-nutritional scores were calculated starting from pre-operative hematologic data. Liver biopsy was performed at the time of bariatric surgery (sleeve gastrectomy or gastric bypass) and pathological assessment was performed using Kleiner-Brunt staging system (NAS score).

RESULTS: Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/ mGPS) and Prognostic Index (PI) were associated to the diagnosis of NASH (p= 0,024 and p=0,03 respectively). The presence of perisinusoidal and/or periportal fibrosis was correlated to Prognostic Nutritional Index (PNI) and Platelet-to-Lymphocyte ratio (PLR) values (p=0,02 and p=0,009 respectively).

CONCLUSIONS: GPS/mGPS and PI are statistically associated to the histological diagnosis of NASH. Further studies on large series are needed to better understand the relationship between these serum markers and liver injury in obese patients.

PMID:34761883 | DOI:10.23736/S0026-4806.21.07665-5

Aust N Z J Public Health. 2021 Nov 11. doi: 10.1111/1753-6405.13159. Online ahead of print.

ABSTRACT

OBJECTIVE: This study assessed the effectiveness of a school-based intervention in reducing adolescents’ sugar-sweetened beverage (SSB) consumption and percentage of energy from SSBs. Secondary outcomes were SSB consumption within school, average daily energy intake, and body mass index z-scores.

METHODS: Six secondary schools located in New South Wales, Australia were recruited to participate in a six-month pilot randomised controlled trial (1:1). The intervention included components targeting the school nutrition environment, curricula and community. Outcomes were collected via online surveys, observations, anthropometric measurements and project records. Between-group differences were assessed via linear mixed models.

RESULTS: At the six-month intervention endpoint (n=862) there were no statistically significant differences between students in intervention or control schools for mean daily intake of SSBs (8.55mL; CI -26.77, 43.87; p=0.63), percentage daily energy from SSBs (0.12% kJ; CI -0.55, 0.80; p=0.72), or for secondary outcomes. Acceptability of the school-based strategies were high, however intervention fidelity varied across schools.

CONCLUSION: While acceptable, improving fidelity of implementation and increasing the duration or intensity of the intervention may be required to reduce SSB intake. Implications for public health: Engaging parents and education stakeholders in the development phase to co-design interventions may prove beneficial in improving intervention fidelity and enhance behavioural outcomes.

PMID:34761854 | DOI:10.1111/1753-6405.13159

Alzheimers Dement. 2021 Nov 11. doi: 10.1002/alz.12411. Online ahead of print.

ABSTRACT

INTRODUCTION: We examined the temporal sequence of the core features in probable dementia with Lewy bodies (DLB).

METHODS: In 488 patients with probable DLB, the onset of each core feature and time to diagnosis was determined for men and women, and a pathologic subgroup (n = 209).

RESULTS: REM sleep behavior disorder (RBD) developed before the other core features in men and women. Men were more likely to have RBD and were diagnosed with probable DLB earlier than women. Visual hallucinations developed after the other core features in men, but in women, they appeared earlier and concurrently with fluctuations and parkinsonism. Women were older and more cognitively impaired at first visit, were less likely to have RBD, more likely to be diagnosed with probable DLB later than men, and more likely to have neocortical tangles.

DISCUSSION: An earlier latency to probable DLB was associated with men, RBD, and Lewy body disease without neocortical tangles.

PMID:34761850 | DOI:10.1002/alz.12411

Am J Bot. 2021 Nov 11. doi: 10.1002/ajb2.1803. Online ahead of print.

ABSTRACT

PREMISE OF THE STUDY: Relict species provide valuable insights into the origin and formation of extant vegetation. Here, we aimed to elucidate the genetic structure and diversity of a riparian relic Acer miyabei in Japan; this species used to have a wide distribution but now occurs in three isolated regions. The most northern regional group is located at low elevation on Hokkaido Island, whereas the southern group is at high elevation in a mountainous landscape. This contrastive distribution enables us to examine the effects of climate oscillations on genetic diversity in relation to topographic variation.

METHODS: We collected 604 individuals of A. miyabei from 43 sites. Their genetic structure and diversity were analyzed using 12 microsatellite markers and cpDNA sequences.

KEY RESULTS: According to STRUCTURE analyses, ∆K statistic was lowest at K = 2; the clustering essentially separated many of the individuals in the most northern regional group from the others. In contrast, the two southern groups were not clearly differentiated from each other, despite their geographic discontinuity. The proportion of private alleles was high in populations from mountain terrain in the southern group although the number of extant populations is limited.

CONCLUSIONS: Genetic clustering of A. miyabei is not perfectly congruent with the current patterns of geographic distribution. We infer that disjunction of the two southern groups occurred more recently than that between these groups and the northern group. Mountainous landscape in the most southern region likely provided multiple refugia and contributed to the retention of distinctive genetic variation. This article is protected by copyright. All rights reserved.

PMID:34761814 | DOI:10.1002/ajb2.1803

J Physiol. 2021 Nov 11. doi: 10.1113/JP282228. Online ahead of print.

ABSTRACT

KEY POINTS: Spatiotemporal contractility analysis of human induced pluripotent stem cell derived cardiomyocyte (hiPSC-CM) monolayers seeded on conventional, rigid surfaces (glass or plastic) revealed the presence of multiphasic contraction patterns across the monolayer with a high variability, despite action potentials recorded in the same areas being identical. These multiphasic patterns are not present in single cells, in detached monolayers or in monolayers seeded on soft substrates such as a hydrogel, where only ‘twitch’-like transients are observed. HiPSC-CM monolayers that display a high percentage of regions with multiphasic contraction have significantly increased contractile duration and a decreased lusotropic drug response. There is no indication that the multiphasic contraction patterns are associated with significant activation of the stress-activated NPPA or NPPB signalling pathways. A computational model of cell clusters supports the biological findings that the rigid surface and the differential cell-substrate adhesion underly multiphasic contractile behaviour of hiPSC-CMs.

ABSTRACT: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in monolayers interact mechanically via cell-cell and cell-substrate adhesion. Spatiotemporal features of contraction were analysed in hiPSC-CM monolayers 1) attached to glass or plastic (Young’s modulus (E) >1 GPa), 2) detached (substrate-free) and 3) attached to a flexible collagen hydrogel (E = 22 kPa). The effects of isoprenaline on contraction were compared between rigid and flexible substrates. To clarify underlying mechanisms, further gene expression and computational studies were performed. HiPSC-CM monolayers exhibited multi-phasic contractile profiles on rigid surfaces in contrast to hydrogels, substrate-free cultures or single cells where only simple twitch-like time-courses were observed. Isoprenaline did not change the contraction profile on either surface, but its lusitropic and chronotropic effects were greater in hydrogel compared to glass. There was no significant difference between stiff and flexible substrates in regard to expression of the stress activated genes NPPA and NPPB. A computational model of cell clusters demonstrated similar complex contractile interactions on stiff substrates as a consequence of cell-to-cell functional heterogeneity. Rigid biomaterial surfaces give rise to unphysiological, multi-phasic contractions in hiPSC-CM monolayers. Flexible substrates are necessary for normal twitch-like contractility kinetics and interpretation of inotropic interventions. This article is protected by copyright. All rights reserved.

PMID:34761809 | DOI:10.1113/JP282228

Chem Commun (Camb). 2021 Nov 11. doi: 10.1039/d1cc03756k. Online ahead of print.

ABSTRACT

Fluorescence lifetime imaging (FLIM) was used to study the behaviour of a BODIPY dye in a giant unilamellar vesicle (GUV) in the presence of an electric field. The modulation of the electric field resulted in distinctive fluorescence lifetime changes in line with environment alterations within the membrane mimic.

PMID:34761753 | DOI:10.1039/d1cc03756k

Curr Med Res Opin. 2021 Nov 11:1-15. doi: 10.1080/03007995.2021.2003671. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to characterize the risk of people living with HIV (PLHIV) in the UK progressing to pre-specified HIV-associated comorbidities, compared with matched, HIV-negative controls.

METHODS: Primary and secondary care records from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) were used to identify PLHIV, and a matched cohort from the HIV-negative population. Kaplan Meier curves and cox proportional hazard models were used to evaluate the risk of developing comorbidities including central nervous system (CNS) disorders, end-stage renal disease, osteoporosis, diabetes, cardiovascular disease (CVD), hypertension, stroke, and cancer.

RESULTS: 2,945 PLHIV were matched to a cohort of 5,890 HIV-negative controls. PLHIV demonstrated an increased hazard ratio (HR) for time to development of incident sleep disorders, depression, osteoporosis, stroke, cancer and renal disease when compared with their matched HIV-negative control. The HRs for anxiety, hypertension, diabetes, and CVD were not significantly increased.

CONCLUSIONS: PLHIV in the UK were at a higher risk of developing a number of comorbid conditions, highlighting the need for regular attendance of health reviews such as the annual health reviews recommended by the British HIV Associations (BHIVA) quality standard for care, which are currently not uniformly conducted.

PMID:34761727 | DOI:10.1080/03007995.2021.2003671

Ann Med. 2021 Dec;53(1):2034-2040. doi: 10.1080/07853890.2021.1999490.

ABSTRACT

BACKGROUND: The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality.

METHODS AND PATIENTS: Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality.

RESULTS: A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p<.0001; p<.0001; p=.0007, respectively). The AUC for overall mortality was similar for BSI, FACED score, and DSP (0.80 versus 0.85, p=.491; 0.85 versus 0.83, p=.831).

CONCLUSION: DSP had comparable predictive power for mortality as the well-validated BSI and FACED scores and is relatively easy to use in clinical practice.KEY MESSAGEDistance-saturation product (DSP) comprised with the product of distance walked, and lowest oxygen saturation during the 6-min walk test, which is common used in clinical practice.DSP demonstrated strong and comparable predictive power of mortality as the well-validated BSI and FACED scores in non-CF bronchiectasis patients.

PMID:34761709 | DOI:10.1080/07853890.2021.1999490

Acc Chem Res. 2021 Nov 11. doi: 10.1021/acs.accounts.1c00575. Online ahead of print.

ABSTRACT

ConspectusHomogeneous metal-mediated organometallic reactions represent a very large and diverse reaction class. Density functional theory calculations are now routinely carried out and reported for analyzing organometallic mechanisms and reaction pathways. While density functional theory calculations are extremely powerful to understand the energy and structure of organometallic reactions, there are several assumptions in their use and interpretation to define reaction mechanisms and to analyze reaction selectivity. Almost always it is assumed that potential energy structures calculated with density functional theory adequately describe mechanisms and selectivity within the framework of statistical theories, for example, transition state theory and RRKM theory. However, these static structures and corresponding energy landscapes do not provide atomic motion information during reactions that could reveal nonstatistical intermediates without complete intramolecular vibrational redistribution and nonintrinsic reaction coordinate (non-IRC) pathways. While nonstatistical intermediates and non-IRC reaction pathways are now relatively well established for organic reactions, these dynamic effects have heretofore been highly underexplored in organometallic reactions. Through a series of quasiclassical density functional theory direct dynamics trajectory studies, my group has recently demonstrated that dynamic effects occur in a variety of fundamental organometallic reactions, especially bond activation reactions. For example, in the C-H activation reaction between methane and [Cp*(PMe₃)Ir^III(CH₃)]⁺, while the density functional theory energy landscape showed a two-step oxidative cleavage and reductive coupling mechanism, trajectories revealed a mixture of this two-step mechanism and a dynamic one-step mechanism that skipped the [Cp*(PMe₃)Ir^V(H)(CH₃)₂]⁺ intermediate. This study also showed that despite a methane σ-complex being located on the density functional theory surface before oxidative cleavage and after reductive coupling, this intermediate is always skipped and should not be considered an intermediate during reactive trajectories. For non-IRC reaction pathways, quasiclassical direct dynamics trajectories showed that for the isomerization of [Tp(NO)(PMe₃)W(η²-benzene)] to [Tp(NO)(PMe₃)W(H)(Ph)], there are many dynamic reaction pathway connections due to a relatively flat energy landscape and π coordination is not necessary for C-H bond activation through oxidative cleavage. Trajectories also showed that dynamic effects are important in selectivity for ethylene C-H activation versus π coordination in reaction with Cp(PMe₃)₂Re, and trajectories provide a more quantitative model of selectivity than transition state theory. Quasiclassical trajectories examining Au-catalyzed monoallylic diol cyclizations showed dynamic coupling of several reaction steps that include alkoxylation π bond addition, proton shuttling, and water elimination reaction steps. Overall, these studies highlight the need to use direct dynamics trajectory simulations to consider atomic motion during reactions to understand organometallic reaction mechanisms and selectivity.

PMID:34761673 | DOI:10.1021/acs.accounts.1c00575