The association of chronic liver disorders with exacerbation of symptoms and complications related to COVID‐19: A systematic review and meta‐analysis of cohort studies

IntroductionThe aim of this review was to combine the results of published cohort studies to determine the exact association between chronic liver disorders, and the severe form of COVID‐19, and its associated complications.MethodsThis meta‐analysis employed a keyword search (COVID‐19 and chronic liver disorders) using PubMed (Medline), Scopus, Web of Sciences, and Embase (Elsevier). All articles related from January 2019 to May 2022 were reviewed. The STATA software was used for analysis.ResultsThe risk of death in COVID‐19 patients with chronic liver disorders was higher than in ones without the chronic liver disease (RR: 1.52; CI 95%: 1.46–1.57; I ²: 86.14%). Also, the risk of acute respiratory distress syndrome (ARDS) and hospitalization in COVID‐19 patients with chronic liver disorders was higher than in ones without the chronic liver disease ([RR: 1.65; CI 95%: 1.09–2.50; I ²: 0.00%] and [RR: 1.39; CI 95%: 1.23–1.58; I ²: 0.20%]). Also, the meta‐analysis showed cough, headache, myalgia, nausea, diarrhea, and fatigue were 1.37 (CI 95%: 1.20–1.55), 1.23 (CI 95%: 1.09–1.38), 1.25 (CI 95%: 1.04–1.50), 1.19 (CI 95%: 1.02–1.40), 1.89 (CI 95%: 1.30–2.75), 1.49 (CI 95%: 1.07–2.09), and 1.14 (CI 95%: 0.98–1.33), respectively, whereas the risk of all these symptoms was higher in COVID‐19 patients with chronic liver diseases than ones without chronic liver disorders.ConclusionThe mortality and complications due to COVID‐19 were significantly different between patients with the chronic liver disease and the general population.     

Nuclear magnetic resonance diffraction with subangstrom precision

We have combined ultrasensitive force-based spin detection with high-fidelity spin control to achieve NMR diffraction (NMRd) measurement of ~2 million 31P spins in a (50 nm)3 volume of an indium-phosphide (InP) nanowire. NMRd is a technique originally proposed for studying the structure of periodic arrangements of spins, with complete access to the spectroscopic capabilities of NMR. We describe two experiments that realize NMRd detection with subangstrom precision. In the first experiment, we encode a nanometer-scale spatial modulation of the z-axis magnetization of 31P spins and detect the period and position of the modulation with a precision of <0.8 Å. In the second experiment, we demonstrate an interferometric technique, utilizing NMRd, to detect an angstrom-scale displacement of the InP sample with a precision of 0.07 Å. The diffraction-based techniques developed in this work extend the Fourier-encoding capabilities of NMR to the angstrom scale and demonstrate the potential of NMRd as a tool for probing the structure and dynamics of nanocrystalline materials.

Scattering techniques that employ coherent sources, such as X-rays, neutrons, and electrons, are universal tools in many branches of natural science for exploring the structure of matter. In crystalline materials, these approaches provide a direct and efficient means of characterizing the periodicity of charge and magnetic order. MRI, like other scattering approaches, is a reciprocal space technique, in which the measured signal is proportional to the Fourier transform of the spin density. This similarity between MRI and scattering was recognized very early in the development of MRI and led Mansfield and Grannell in 1973 to propose NMR “diffraction” (NMRd) as a method for determining the lattice structure of crystalline solids (1–3), taking advantage of the chemical specificity of NMR.The main challenge to achieving atomic-scale NMRd lies in the difficulty of generating a sufficiently large wavenumber k, capable of encoding a relative phase difference as large as 2π between adjacent spins on a lattice, separated by angstrom-scale distances. For example, the largest encoding wavenumbers achieved in clinical high-resolution MRI scanners are of order k/(2π)~104 m−1, more than a factor of 10⁵ smaller than what is needed to measure typical atomic spacings in condensed-matter systems (4). Consequently, while MRI has become a transformative technique in medical science, earning Sir Peter Mansfield and Paul Lauterbur the Nobel Prize in Physiology and Medicine, the original vision of NMRd as a method for exploring material structure has not yet been realized.The realization of atomic-scale NMRd would be a powerful tool for characterizing periodic nuclear spin structures, combining the spectroscopic capabilities of NMR with spatial encoding at condensed matter’s fundamental length scale. NMRd is a phase-sensitive technique that permits real-space reconstruction of the spin density, without the loss of phase information common to scattering techniques, such as X-rays, that measure the scattered-field intensity (5). Being nondestructive and particularly sensitive to hydrogen, NMRd could be of great importance in the study of ordered biological systems, such as protein nanocrystals that are of great interest in structural biology (6, 7). Furthermore, the combination of scattering with NMR’s rich repertoire of spectroscopic tools opens additional avenues for spatially resolved studies of nuclear-spin Hamiltonians (e.g., chemical shifts or spin–spin interactions), which are currently achieved only through increasingly complex and indirect methods (8). Finally, NMRd could be used to study quantum many-body dynamics on the atomic scale. NMR scattering experiments have previously been used in the direct measurement of spin diffusion in CaF₂ on the micrometer scale (9). Experiments on many-body dynamics have also been conducted in engineered quantum simulators, such as ultracold atoms (10–12), trapped ions (13–15), superconducting circuits (16–18), and quantum dots (19). However, these measurements have thus far been limited to small-scale quantum systems that are at most hundreds of qubits. Angstrom-scale NMRd measurements would permit studying the dynamics of complex large-scale spin networks in condensed-matter systems on length scales as short as the lattice spacing.Over the past two decades the principal technologies needed to encode nuclear spin states with wavenumbers of order 1 Å−1 have been developed in the context of force-detected nanoMRI (20–26). In this work, we report two experiments that utilize key advances in nanoMRI technology—namely the ability to generate large time-dependent magnetic-field gradients and the ability to detect and coherently control nanoscale ensembles of nuclear spins (27–31)—to generate encoding wavenumbers as large as k/(2π)~0.48 Å−1.Our first experiment demonstrates the use of spatial spin-state modulation that encodes position information the way it was envisioned in the initial NMRd proposal. Phase-sensitive NMRd detection enables us to determine the position and period of a “diffraction grating” with a precision of <0.8 Å. The diffraction grating itself is a z-axis 31P spin magnetization modulation, the mean period of which is 4.5 nm in our (50 nm)3 detection volume. Our second experiment utilizes spatially modulated spin phase in an alternative way—as a label for the physical displacement of the spins. Our interferometric technique detects an angstrom-scale displacement of the indium-phosphide (InP) sample with a precision of 0.07 Å.     

Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature

Hepatobiliary scintigraphy is an important diagnostic modality for work-up of neonatal cholestasis. Therefore, our objective was to evaluate the literature regarding the accuracy of hepatobiliary scintigraphy in differentiating biliary atresia from non-biliary atresia causes of cholestasis (collectively called neonatal hepatitis). Our search included Medline, SCOPUS and Google Scholar. Only studies using Tc-99 m-labeled immunodiacetic acid (IDA) derivatives were included. Overall, 81 studies were included in the meta-analysis. Pooled sensitivity and specificity were 98.7% (range 98.1–99.2%) and 70.4% (range 68.5–72.2%), respectively. Factors that increased specificity included the use of radiotracers with high hepatic extraction, administration of hepatic-inducing drugs (such as phenobarbital), use of a calculated dose/kg and administration of a booster dose in cases of non-excretion of the tracer in the bowel. SPECT imaging and duodenal fluid sampling also had high specificity; however, they need further validation because of the low number of studies. Semiquantitative imaging methods do not seem to have any incremental value. We conclude that hepatobiliary scintigraphy using IDA derivatives can be very useful for diagnostic work-up of neonatal cholestasis. To improve the specificity, several measures can be followed regarding type and dose of the radiotracer and imaging protocols. Non-imaging methods seem to be promising and warrant further validation.     

Involvement of dopamine D2-like receptors in the antiepileptogenic effects of deep brain stimulation during kindling in rats

Aims

Deep brain electrical stimulation (DBS), as a potential therapy for drug resistive epileptic patients, has inhibitory action on epileptogenesis. In the present investigation, the role of dopamine D₂-like receptors in the antiepileptogenic action of DBS was studied.

Methods

Seizures were induced in adult rats by stimulating the perforant path in a semi-rapid kindling method. Five minutes after the last kindling stimulation, daily DBS was applied to the perforant path at the pattern of low frequency stimulation (LFS; 1 Hz; pulse duration: 0.1 ms; intensity: 50–150 μA; 4 trains of 200 pulses at 5 min intervals). Sulpiride (10 μg/1 μl, i.c.v.), a selective dopamine D₂-like receptor antagonist, was administered prior to the daily LFS application.

Results

Kindling stimulations increased cumulative daily behavioral seizure stages, daily afterdischarge duration (dADD), and population spike amplitude (PS) in dentate gyrus following perforant path stimulation, while applying LFS decreased the kindled seizures' parameters. In addition, kindling potentiated the early (at 10–50 ms inter-pulse interval) and late (at 150–1000 ms inter-pulse interval) paired-pulse inhibition and decreased the paired-pulse facilitation (at 70–100 ms inter-pulse interval). These effects were also inhibited by applying LFS. All inhibitory effects of LFS on kindling procedure were prevented by sulpiride administration.

Conclusion

These data may suggest that LFS exerts its preventive effect on kindling development, at least partly, through the receptors on which sulpiride acts which are mainly dopamine D₂-like (including D₂, D₃, and D₄) receptors.     

The effects of Gymnema Sylvestre supplementation on lipid profile,glycemic control,blood pressure,and anthropometric indices in adults: A systematic review and meta-analysis

There is a growing interest in the considerable health benefits of Gymnema Sylvestre (GS) supplementation, as some studies have reported that it may improve cardiometabolic risk factors. However, the widespread impact of GS supplementation on the parameters mentioned above is not fully resolved. Consequently, this study aimed to examine the effects of GS supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults. Eligible randomized controlled trials (RCT), published up to November 2021, were identified through PubMed, Scopus, and ISI Web of Science databases. Six studies were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI). All studies were conducted in adults that used a GC supplement (>1 week) and assessed our selected cardiovascular risk factors. Outcomes revealed that GS supplementation significantly decreased triglyceride (p < .001), total cholesterol (p < .001), low-density lipoprotein (p < .001), fasting blood sugar (p < .001), and diastolic blood pressure (p = .003). Some limitations, including notable heterogeneity, low quality of studies, and lack of diversity among research participants, should be considered when interpreting our results. Our outcomes suggest that GS supplementation may improve cardiovascular risk factors. Future large-high-quality RCTs with longer duration and various populations are needed to firmly establish the clinical efficacy of the plant.     

MiR-34 by targeting p53 induces apoptosis and DNA damage in paclitaxel-resistant human oral squamous carcinoma cells

MicroRNA-34 (miR-34) is one the most important tumor suppressor miRNAs involving in the various aspects of oral cancer. The present study aimed to evaluate the effects of miR-34 restoration in OECM-1 oral cancer resistant to paclitaxel (OECM-1/PTX) and its underlying mechanisms through p53-mediated DNA damage and apoptosis. OECM-1 and OECM-1/PTX were transfected with miR-34 mimic and inhibitor. Cellular proliferation and apoptosis were evaluated through MTT assay and flow cytometry, respectively. The mRNA and protein expression levels of p53, p-glycoprotein (P-gp), ATM, ATR, CHK1, and CHK2 were assessed through qRT-PCR and western blotting. Rhodamin123 uptake assay was used to measure the P-gp activities. P53 expression was also suppressed by sing a siRNA transfection of cells. The expression levels of miR-34 were downregulated in OECM-1/PTX. Restoration of miR-34 led to increase in cytotoxic effects of paclitaxel in cells. In addition, the expression levels and activities of P-gp were reduced following miR-34 transfection. miR-34 transfection upregulated the p53, ATM, ATR, CHK1, and CHK2 expression levels in OECM-1/PTX cells. Furthermore, cells transfected with miR-34 showed higher levels of apoptosis. miR-34 restoration reverses paclitaxel resistance in OECM-1 oral cancer. The chemosensitive effects of miR-34 is mediated through increasing DNA damage and apoptosis in a p53 depended manner.