Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting ...enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice.
Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested.
ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment.
Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.
This study investigated changes in the kinematics of elderly people who experienced at least one fall 6 months prior to data collection. The authors hypothesized that, in order to decrease ...variability of walking, people with a history of falls would show different kinematic adaptations of their walking patterns compared with elderly people with no history of falls.
Twenty-one elderly people who had fallen within the previous 6 months ("fallers"; mean age=72.1 years, SD=4.9) and 27 elderly people with no history of falls ("nonfallers"; mean age=73.8 years, SD=6.4) walked at their preferred stride frequency (STF) as treadmill speed was gradually increased (from 0.18 m/s to 1.52 m/s) and then decreased in steps of 0.2 m/s. Gait parameter measurements were recorded, and statistical analysis was applied using walking speed and STF as independent variables.
Fifty-seven percent of the fallers were unable to walk at the fastest speed, whereas all nonfallers walked comfortably at all walking speeds. Although the fallers showed significantly greater STF, smaller stride lengths, smaller center-of-mass lateral sway, and smaller ankle plantar flexion and hip extension during push-off, they showed increased variability of kinematic measures in their coordination of walking compared with the nonfallers.
Although the fallers' adaptations were expected to reduce variability in the coordination of walking, they showed less stable gait patterns (ie, greater variability) compared with the nonfallers. Increased variability of walking patterns may be an important gait risk factor in elderly people with a history of falls.
Background. Studies indicate that the strategy for postural control may be affected by psychological factors, and that young adults respond to perceived threat to stability by increasing their ankle ...stiffness. The objective of this study was to compare the postural control strategy adopted by young and old adults when faced with postural threat induced by manipulating surface height. Methods. Sixty elderly (mean age 77.5 ± 4.4 years) and 20 young volunteers (mean age 21.5 ± 3.7 years) participated in the study. Movement of the center of pressure (COP) was recorded for 60 seconds with a portable force-plate, as participants stood with eyes open and closed, both at ground level and 85 cm above ground level. Analysis of variance and Tukey–Kramer tests were conducted to determine the effects of age, postural threat, and vision on mean power frequency (MPF), on amplitude variability both in the anterior–posterior (AP) and medio-lateral (ML) directions, and on mean COP sway velocity, with the significance level set at p =.05. Results. Postural threat did not affect COP measures for the young adults, whereas it induced greater changes in MPF in the AP and ML directions in the elderly participants. A similar trend was observed in the elderly group for amplitude variability in the ML direction and for mean COP sway velocity. Conclusions. In comparison with young adults, elderly adults tend to have an exaggerated postural response to conditions that are perceived as threatening to stability. This response involves primarily increases in MPF, with limited compensatory decreases in amplitude variability observed only in the ML direction.
This study was aimed at exploring the transferability of short range of motion (RoM) isokinetic conditioning on quadriceps performance inside and outside the trained range.
Fifty-five women were ...randomly assigned to one of four groups: G1 (N = 14) and G2 (N = 14) trained concentrically at 30 and 90degrees x s(-1), respectively, whereas G3 (N = 13) and G4 (N = 14) trained similarly but using the eccentric mode. All four groups trained within 30-60degrees of knee flexion. The training paradigm consisted of 4 sets of 10 maximal repetitions, 3x wk(-1) for a total period of 6 wk. Before the training period and 2 d after its termination, the isokinetic work output (Wisk) was assessed within three angular RoM: 85-60degrees (R1), 60-30degrees (R2), and 30-5degrees (R3). Isometric peak extension moment (PM) and rate of force development (RFD) were evaluated at 10degrees, 45degrees and 80degrees.
Significant increases were observed in the isometric output (at all three angles), Wisk (in R1 and R2), and the RFD (45degrees). The PM increased significantly more in G3 and G4 compared with G1 and G2, evidencing specificity of contraction mode.
These findings point out to the potential benefits of short RoM conditioning, particularly in those cases where, during specific phases of rehabilitation, a wider RoM may be contraindicative.
This study was aimed at exploring the carryover effect of short range of motion (RoM) isokinetic conditioning on vastus medialis (VM) motor unit recruitment (MUR) across the full RoM. Fifty-five ...women were randomly assigned to one of four groups: G1 (
n
=
14) and G2 (
n
=
14) trained concentrically at 30 and 90°/s, respectively whereas G3 (
n
=
13) and G4 (
n
=
14) trained similarly but using the eccentric mode. All 4 groups trained within 30–60° of knee flexion. The training protocol consisted of 4 sets of 10 maximal repetitions, 3 times a week for 6 weeks. sEMG was recorded from the VM for analysis of mean frequency of the EMG power spectrum prior to the training period and 2 days after its termination. The EMG assessments took place during dynamic contractions within 3 angular RoM’s: 85–60° (R1), 60–30° (R2) and 30–5° (R3). In addition MUR was evaluated during isometric contractions at 10°, 45° and 80°. Significant increases were observed in the MUR at R1, R2, and R3 during dynamic contractions as well as in all 3 angles during isometric contractions. These findings applied equally regardless of the mode of contraction and motion speed during training. The fact that MUR increased significantly within untrained RoM’s may point out to the potential benefits of short RoM conditioning, particularly in those cases where, during specific phases of rehabilitation, a wider RoM may be contraindicative.
The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on ...the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device‐related, and patient–device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non‐LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non‐LVAD specialized physician — ambulance clinicians, emergency ward physicians, general cardiologists, and internists — to comply with the medical needs of this fast‐growing population of LVAD supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner.
G-quadruplexes are non-B-DNA structures that form in the genome facilitated by Hoogsteen bonds between guanines in single or multiple strands of DNA. The functions of G-quadruplexes are linked to ...various molecular and disease phenotypes, and thus researchers are interested in measuring G-quadruplex formation genome-wide. Experimentally measuring G-quadruplexes is a long and laborious process. Computational prediction of G-quadruplex propensity from a given DNA sequence is thus a long-standing challenge. Unfortunately, despite the availability of high-throughput datasets measuring G-quadruplex propensity in the form of mismatch scores, extant methods to predict G-quadruplex formation either rely on small datasets or are based on domain-knowledge rules. We developed G4mismatch, a novel algorithm to accurately and efficiently predict G-quadruplex propensity for any genomic sequence. G4mismatch is based on a convolutional neural network trained on almost 400 millions human genomic loci measured in a single G4-seq experiment. When tested on sequences from a held-out chromosome, G4mismatch, the first method to predict mismatch scores genome-wide, achieved a Pearson correlation of over 0.8. When benchmarked on independent datasets derived from various animal species, G4mismatch trained on human data predicted G-quadruplex propensity genome-wide with high accuracy (Pearson correlations greater than 0.7). Moreover, when tested in detecting G-quadruplexes genome-wide using the predicted mismatch scores, G4mismatch achieved superior performance compared to extant methods. Last, we demonstrate the ability to deduce the mechanism behind G-quadruplex formation by unique visualization of the principles learned by the model.
Purpose
Information regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction ...has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome.
Methods
Between 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)—36 (worst) was assigned to each patient. LUS findings were compared with clinical data.
Results
The median baseline total LUS score was 15, IQR 7–20. Baseline LUS score was 0–18 in 80 (67%) patients, and 19–36 in 40 (33%) patients. The majority had patchy pleural thickening (
n
= 100; 83%), or patchy subpleural consolidations (
n
= 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (
p
= 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0–18. Unadjusted hazard ratio of death for LUS score was 1.08 per point 1.02–1.16,
p
= 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point 1.05–1.2,
p
= 0.0008.
Conclusion
Hospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients’ management strategies, as well as resource allocation in case of surge capacity.
PDF
