Pulmonary Rehabilitation in COVID-19 patients: A scoping review of current practice and its application during the pandemic.

The novel coronavirus-2019 (COVID-19) pandemic primarily affects the respiratory system. Elderly individuals with comorbidity are severely affected. Survivors weaned from mechanical ventilation are at a higher risk of developing post-intensive care syndrome (PICS). This scoping review, based on 40 recent publications, highlights pulmonary rehabilitation (PR) in COVID-19. There is a paucity of high-quality research on this topic. However, rehabilitation societies including the Turkish Society of Physical Medicine and Rehabilitation have issued PR recommendations in COVID-19 pneumonia with productive cough can benefit from diaphragmatic breathing, pursed-lip breathing, and resistance-breathing training. Besides, those in mechanical ventilation and post-PICS COVID-19 cases, oxygen therapy, early mobilization, airway clearance, aerobic exercise, gradual-graded limb muscle resistance exercise, nutritional and psychological interventions should be consideration. During PR, careful evaluation of vital signs and exercise-induced symptoms is also required. When in-person PR is not possible, telerehabilitation should be explored. However, the long-term effects of PR in COVID-19 need further evaluation. [Abstract copyright: Copyright © 2020, Turkish Society of Physical Medicine and Rehabilitation.

Phonons in fcc Strontium

A more realistic model, requiring a few parameters to explain the interactions among distant neighbours and valid to various crystallographic structures, is developed to study the phonon dispersion in fcc metals the model free from usual fitting procedure, is employed to obtain phonon dispersion in fcc stiontium, which has attracted scant attention so far .The computed results showing good agreement with the recent experimental findings lend reliability and credibility to the theory

Critical Role of the Secondary Binding Pocket in Modulating the Enzymatic Activity of DUSP5 toward Phosphorylated ERKs

DUSP5 is an inducible nuclear dual-specificity phosphatase that specifically interacts with and deactivates extracellular signal-regulated kinases ERK1 and ERK2, which are responsible for cell proliferation, differentiation, and survival. The phosphatase domain (PD) of DUSP5 has unique structural features absent from other nuclear DUSPs, such as the presence of a secondary anion-binding site in the proximity of the reaction center and a glutamic acid E264 positioned next to the catalytic cysteine C263, as well as a remote intramolecular disulfide linkage. The overall 400 ns molecular dynamics simulations indicate that the secondary binding site of DUSP5 PD acts as an allosteric regulator of the phosphatase activity of DUSP5. Our studies have identified E264 as a critical constituent of the dual binding pocket, which regulates the catalytic activity of DUSP5 by forming a salt bridge with arginine R269. Molecular dynamics studies showed that initial occupation of the secondary binding pocket leads to the breakage of the salt bridge, which then allows the occupation of the active site. Indeed, biochemical analysis using the pERK assay on mutant E264Q demonstrated that mutation of glutamic acid E264 leads to an increase in the DUSP5 catalytic activity. The role of the secondary binding site in assembling the DUSP5–pERK pre-reactive complex was further demonstrated by molecular dynamics simulations that showed that the remote C197–C219 disulfide linkage controls the structure of the secondary binding pocket based on its redox state (i.e., disulfide/dithiol) and, in turn, the enzymatic activity of DUSP5

Pharmaceutical Process Validation: A Mini Review

Pharmaceutical Process Validation emphasizes on process design elements and maintaining process control during commercialization and communicate that process validation is an ongoing program and align process validation activities with product lifecycle. According to GMP validation studies are essential part of GMP these are required to be done as per predefined protocols, the minimum that should be validated include process, testing and cleaning as a result such control procedure stablish to monitor the output and validation of manufacturing processes that may be responsible for variability of drug product. The validation study provide the accuracy, sensitivity, specificity and reproducibility of the test methods employed by the firms, shall be established and documented. Thus the validation is an essential part of the quality assurance

Charge Delocalization in Self-Assembled Mixed-Valence Aromatic Cation Radicals

The spontaneous assembly of aromatic cation radicals (D+•) with their neutral counterpart (D) affords dimer cation radicals (D2+•). The intermolecular dimeric cation radicals are readily characterized by the appearance of an intervalence charge-resonance transition in the NIR region of their electronic spectra and by ESR spectroscopy. The X-ray crystal structure analysis and DFT calculations of a representative dimer cation radical (i.e., the octamethylbiphenylene dimer cation radical) have established that a hole (or single positive charge) is completely delocalized over both aromatic moieties. The energetics and the geometrical considerations for the formation of dimer cation radicals is deliberated with the aid of a series of cyclophane-like bichromophoric donors with drastically varied interplanar angles between the cofacially arranged aryl moieties. X-ray crystallography of a number of mixed-valence cation radicals derived from monochromophoric benzenoid donors established that they generally assemble in 1D stacks in the solid state. However, the use of polychromophoric intervalence cation radicals, where a single charge is effectively delocalized among all of the chromophores, can lead to higher-order assemblies with potential applications in long-range charge transport. As a proof of concept, we show that a single charge in the cation radical of a triptycene derivative is evenly distributed on all three benzenoid rings and this triptycene cation radical forms a 2D electronically coupled assembly, as established by X-ray crystallography

Resonant Excitation of White Dwarf Oscillations in Compact Object Binaries: 1. The No Back Reaction Approximation

We consider the evolution of white dwarfs with compact object companions (specifically black holes with masses up to 10^6 solar masses, neutron stars, and other white dwarfs). We suppose that the orbits are initially quite elliptical and then shrink and circularise under the action of gravitational radiation. During this evolution, the white dwarfs will pass through resonances when harmonics of the orbital frequency match the stellar oscillation eigenfrequencies. As a star passes through these resonances, the associated modes will be excited and can be driven to amplitudes that are so large that there is a back reaction on the orbit which, in turn, limits the growth of the modes. A formalism is presented for describing this dynamical interaction for a non-rotating star in the linear approximation when the orbit can be treated as non-relativistic. A semi-analytical expression is found for computing the resonant energy transfer as a function of stellar and orbital parameters for the regime where back reaction may be neglected. This is used to calculate the results of passage through a sequence of resonances for several hypothetical systems. It is found that the amplitude of the l=m=2 f-mode can be driven into the non-linear regime for appropriate initial conditions. We also discuss where the no back reaction approximation is expected to fail, and the qualitative effects of back reaction.Comment: 14 pages, 4 figures. Figure 3 corrected. Accepted for publication in MNRA

Effects of Carbohydrates on in vitro axillary shoot initiation and multiplication of Bambusa pallida Munro.

The purpose of the current study was to optimize the carbohydrate sources and sucrose concentrations for mass clonal propagation of B. pallida. Sucrose in MS liquid medium consisting additives (ascorbic acid, 50mg/l + citric acid, 25 mg/l + cysteine, 25 mg/l) was found to be the best carbohydrate source for shoot induction and shoot multiplication.  NAA 0.25mg/l in combination with TDZ 0.25mg/l in the medium exhibited high frequency shoot induction and NAA 0.25mg/l with BAP 1.0mg/l helped for further multiplication of quality shoots.  IBA pulse treated shoots were rooted in the MS half strength agar gelled medium fortified with sucrose (2%) and glucose (1%). Rooted plantlets were well established in the green house with more than 95% survivability within four weeks period.&nbsp

Dynamical evolution and leading order gravitational wave emission of Riemann-S binaries

An approximate strategy for studying the evolution of binary systems of extended objects is introduced. The stars are assumed to be polytropic ellipsoids. The surfaces of constant density maintain their ellipsoidal shape during the time evolution. The equations of hydrodynamics then reduce to a system of ordinary differential equations for the internal velocities, the principal axes of the stars and the orbital parameters. The equations of motion are given within Lagrangian and Hamiltonian formalism. The special case when both stars are axially symmetric fluid configurations is considered. Leading order gravitational radiation reaction is incorporated, where the quasi-static approximation is applied to the internal degrees of freedom of the stars. The influence of the stellar parameters, in particular the influence of the polytropic index $n$, on the leading order gravitational waveforms is studied.Comment: 31 pages, 7 figures, typos correcte

Serendipitous Discovery of Light-Induced \u3cem\u3e(In Situ)\u3c/em\u3e Formation of An Azo-Bridged Dimeric Sulfonated Naphthol as a Potent PTP1B Inhibito

Background Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Results Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. Conclusion We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds