Notes

A macrophage strike concluding in microthromboses characterizes COVID 19 pneumonia.
The empirical evidence is weak for carer group interventions in the management of BPSD. Practice reasons for this are discussed. Future studies designed to measure BPSD as a primary outcome would be a welcome addition to the literature.
The empirical evidence is weak for carer group interventions in the management of BPSD. Practice reasons for this are discussed. Future studies designed to measure BPSD as a primary outcome would be a welcome addition to the literature.The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered in November 2021, the omicron variant is more transmissible and is able to evade the immune system better than other previously identified SARS-CoV-2 variants, leading to a spike in cases. Great efforts have been made to discover inhibitors against SARS-CoV-2. Main protease (Mpro) inhibitors are considered promising anti-SARS-CoV-2 agents. The U.S. 4-HNE cell line FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir is the first orally bioavailable inhibitor of SARS-CoV-2 Mpro. There is an urgent need to monitor the mutations and solve the problem of resistance, especially omicron Mpro, which contains one mutation - P132H. In the present study, 132,57 phytochemicals from 80 medicinal plants grown in Saudi Arabia were docked into the active site of Mpro omicron variant. Free binding energies were also calculated. This led to the discovery of five phytochemicals that showed better docking scores than the bound ligand nirmatrelvir. In addition, these molecules exhibited favorable free binding energies. The stability of compounds 1-5 with the protein was studied using molecular dynamics (MD) simulations. These compounds showed acceptable ADMET properties. The results were compared with the wild type. These candidates could be envisioned as new hits against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.Purpose This article aims to gather and review the available knowledge on several implications of smoking and environmental tobacco smoke (ETS) exposure in ocular disorders and provides pathomechanistic insights where applicable.Materials and Methods PubMed and Scopus databases were searched for relevant studies on the association of smoking and ETS exposure with various ocular disorders. Studies with different evidence levels, e.g., in-vivo, case-control, cohort, and meta-analysis, were included.Results Smoking is an established, modifiable risk factor in several ocular diseases, including cataract, age-related macular degeneration, and Graves' ophthalmopathy; smokers are subject to more severe disease courses and less favorable treatment outcomes. Uveitis is twice as likely in smokers; smoking may also delay its resolution. Smoking and ETS exposure are major risk factors for diseases of other organs, with associated ocular complications as well, such as diabetes mellitus. ETS exposure is also associated with ocular surface pathologies, including dry eye syndrome. In children, early-life ETS exposure and maternal smoking during pregnancy are strongly associated with refractive errors and strabismus. Currently, available data on potential risks attributable to ETS exposure regarding ocular diseases are scarce and, in some instances, controversial.Conclusion In addition to smoking, ETS exposure is also a significant public health concern with possible links to several ocular diseases. However, the level of education of at-risk populations in this regard does not match the strength of the evidence.Vinorelbine, a vinca alkaloid, is an antimitotic drug that inhibits polymerisation process of tubulins to microtubules, and is widely used in cancer chemotherapy. Due to the importance of the structure-activity relationship, in this work the conformational preferences of the vinorelbine molecule were surched by PM3 method. The obtained lowest energy conformer was then optimized at DFT/B3LYP/6-31G(d,p) level of theory and the structural characteristics were determined. Frontier orbital (HOMO, LUMO) and molecular electrostatic potential (MEP) analyses were performed for the optimized structure. The experimental FT-IR, Raman and UV-VIS spectral data of vinorelbine along with the theoretical DFT/B3LYP/6-31G(d,p) calculations were investigated in detail. The vibrational wavenumbers were assigned based on the calculated potential energy distribution (PED) of the vibrational modes. To shed light into the anticancer property of vinorelbine as microtubule destabilizer, the most favourable binding mode and the interaction details between vinorelbine and tubulin were revealed by molecular docking studies of vinorelbine into the α,β-tubulin (PDB IDs 4O2B; 1SA0; 7CNN) and binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MMGBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) methods MM/PB(GB)SA. The calculated vinorelbine-7CNN binding free energy, using by MM/PB(GB)SA approach, was found to be the best (-50.39 kcal/mol), and followed by vinorelbine-4O2B (-28.5 kcal/mol) and vinorelbine-1SA0 (-17.59 kcal/mol) systems. Moreover, the interaction of vinorelbine with the cytochrome P450 enzymes (CYP), which are known to help in the metabolism of many drugs in the body, was investigated by docking studies against CYP2D6 and CYP3A4 targets.Communicated by Ramaswamy H. Sarma.Drug distribution relies heavily on polymers, which also offer a variety of benefits like controlled release, targeted release, prolonged release, etc. Due to their low toxicity and great safety, biodegradable polymers are highly preferred. The exopolysaccharide known as pullulan is generated from a fungus known as Aureobasidium pullulan. It has many different qualities, including biodegradability, appropriate adhesion, antioxidant, film-forming capacity, blood compatibility, mucosal adhesion, etc. However, its application in the pharmaceutical industry is restricted by its insolubility in organic solvents, mechanical characteristics, and lack of macromolecule-carrying ability groups. This review provides an overview of the modifications made to pullulan, including periodate oxidation, etherification, esterification, sulfation, urethane derivatization, PEG incorporation, and cationization, to enhance its solubility in organic solvents, mechanical properties, pH sensitivity, drug delivery, anticoagulant, and antimicrobial properties. Pullulan has nine active hydroxyl groups in its structure that react chemically that can be used for physicochemical modification to produce pullulan derivatives. A key area of pullulan research has been pullulan modification, which has demonstrated enhanced solubility, pH-sensitive targeting, broadened horizons for delivery systems, anticoagulation, and antibacterial properties.The biologically relevant structures of proteins and nucleic acids and their complexes are dynamic. They include a combination of regions ranging from rigid structural segments to structural switches to regions that are almost always disordered, which interact with each other in various ways. Comparing conformational changes and variation in contacts between different conformational states is essential to understand the biological functions of proteins, nucleic acids, and their complexes. Here, we describe a new computational tool, 1D2DSimScore, for comparing contacts and contact interfaces in all kinds of macromolecules and macromolecular complexes, including proteins, nucleic acids, and other molecules. 1D2DSimScore can be used to compare structural features of macromolecular models between alternative structures obtained in a particular experiment or to score various predictions against a defined "ideal" reference structure. Comparisons at the level of contacts are particularly useful for flexible molecules, for which comparisons in 3D that require rigid-body superpositions are difficult, and in biological systems where the formation of specific inter-residue contacts is more relevant for the biological function than the maintenance of a specific global 3D structure. Similarity/dissimilarity scores calculated by 1D2DSimScore can be used to complement scores describing 3D structural similarity measures calculated by the existing tools.
Promoting help-seeking is a key suicide prevention strategy. Yet, research on help-seeking patterns by high-risk individuals is limited. This study examined help-seeking among United States military Service members admitted for psychiatric inpatient care.

Participants were active duty Service members (N=111) psychiatrically hospitalized for a suicide-related event. Data were collected as part of a larger randomized controlled trial. Reported types and perceived helpfulness of resources sought 30 days before hospitalization were examined. Hierarchical binary logistic regressions were used to examine associations among types of helping resources, mental health treatment stigma, and perceived social support.

Approximately 90% of participants sought help prior to hospitalization, most frequently from behavioral health providers and friends. Accessed resources were generally considered helpful. Adjusting for covariates, mental health treatment stigma was not associated with seeking help from any resource type. Higher perceived social support was associated with greater likelihood of help-seeking from a friend (OR=1.08, p=0.013 [95% CI=1.02, 1.14]). Marital status, education level, and organizational barriers were associated with specific types of resources, and/or not seeking help.

Help-seeking is a complex human behavior. Promoting help-seeking among vulnerable subgroups requires further understanding of multiple interconnected factors.
Help-seeking is a complex human behavior. Promoting help-seeking among vulnerable subgroups requires further understanding of multiple interconnected factors.Growth hormone receptor (GHR) gene is considered to be an important candidate gene in growth traits. Therefore, the purpose of this study was to detect whether there were potential indel variations in the GHR gene that were related to the growth traits of the Shaanbei white cashmere goats (SBWC). In this study, genomic DNA from 931 healthy SBWC individuals were used to verify the relationship between the indel of the GHR gene and growth traits. Two indel variants, P49-bp indel in intron 1 and P1410-bp indel in 3'-UTR, were confirmed. Association analyses demonstrated that these two indel polymorphism loci were associated with the chest circumference and chest width of SBWC. Additionally, for the P49-bp and P1410-bp indel loci, the ID and II genotypes were dominant genotypes, respectively. Moreover, the genotypic distributions of these two indel loci in SBWC were significantly different from those in three other Chinese indigenous goat breeds (HNBG, GZDG and IMWC) (p  less then  0.05). Taken together, two indel loci (P49-bp indel and P1410-bp indel) both significantly affected the growth traits of goats. This illustrated that these two indel loci might be the potential DNA marker for use in improving the selection and breeding of goats.Colorectal cancer (CRC) is one of the leading malignancies that causes death worldwide. Cancer vaccines and oncolytic immunotherapy bring new hope for patients with advanced CRC. The capability of vaccinia virus (VV) in carrying foreign genes as antigens or immunostimulatory factors has been demonstrated in animal models. VV of Wyeth, Western Reserve, Lister, Tian Tan, and Copenhagen strains have been engineered for the induction of antitumor response in multiple cancers. This paper summarized the preclinical and clinical application and development of VV serving as cancer vaccines and oncolytic vectors in CRC treatment. Additionally, the remaining challenges and future direction are also discussed.
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