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Decreased work ability (t2) was associated with more cognitive impairment, higher effort coping with the disease, comorbidities, sick leave > 6 months (since diagnosis), and having children (adj R

= .48). Cognitive impairments occurred in approximately every fifth patient at both surveys.

Achieving maximum work ability is a major challenge for AYAs. Our results show the need for multimodal cancer survivorship and rehabilitation programmes with a special focus on improving cognitive and psychosocial functioning.

AYAs with cancer should receive targeted occupational counselling early in the course of the disease.

AYAs with cancer should receive targeted occupational counselling early in the course of the disease.

We aimed to explore the real-world clinical application value and challenges of metagenomic next-generation sequencing (mNGS) for pulmonary infection diagnosis.

We retrospectively reviewed the results of mNGS and conventional tests from 140 hospitalized patients with suspected pulmonary infections from January 2019 to December 2020. The sample types included bronchoalveolar lavage fluid, lung tissue by transbronchial lung biopsy, pleural effusion, blood, and bronchial sputum. Apart from the mNGS reports that our patients received, an extra comprehensive and thorough literature search was conducted.

Significant differences were noticed in the positive detection rates of pathogens between mNGS and conventional diagnostic testing (115/140, 82.14% vs 50/140, 35.71%, P < 0.05). The percentage of mNGS-positive patients was significantly higher than that of conventional testing-positive patients with regard to bacterial detection (P < 0.01), but no significant differences were found with regard to fungaled to be refined.

mNGS is a valuable tool for the detection of pulmonary infections, especially mixed pulmonary infections. The most common combinations we found were bacterial-fungal coinfection and bacterial-bacterial coinfection. Still, there are many challenges in the clinical application of mNGS in the diagnosis of pulmonary infections. There is still a lot of work to be done in interpreting the mNGS reports, because both clinical judgment and literature analysis strategy need to be refined.Pertussis is a highly contagious disease of the respiratory tract caused by Bordetella pertussis. Although the burden of pertussis is highest in children, available data suggests that pertussis in the elderly and those with underlying chronic conditions or illnesses can result in significant morbidity, mortality and costs. We undertook a comprehensive review to assess the association between pertussis and chronic conditions/illnesses. A search was undertaken on 17 June 2019 across EMBASE, Medline and BIOSIS. Citations were limited to those in English, in humans and published since 1 January 1990. There were 1179 papers identified with an additional 70 identified through a review of the reference lists. Of these, 34 met the inclusion criteria. Papers included were categorised in groups, those which reported associations between prior pertussis and subsequent chronic conditions or illnesses; a link between chronic conditions/illnesses and subsequent risk of pertussis; and those which reported on the effect of tirm or disprove these associations, and to characterise the pathophysiological mechanisms behind the potential associations with pertussis.Mesenchymal stem cells (MSCs) are self-renewing, multi-potent heterogeneous stem cells that display strong tissue protective and restorative properties by differentiating into cells of the mesodermal lineages. In addition to multi-lineage differentiation capacity, MSCs play important roles in regulating immune responses, inflammation, and tissue regeneration. MSCs play a role in the outcome of the pathogenesis of several infectious diseases. A unique subset of MSCs accumulates in secondary lymphoid organs during malaria disease progression. These MSCs counteract the capacity of malaria parasites to subvert activating co-stimulatory molecules and to regulate expression of negative co-stimulatory molecules on T lymphocytes. Consequently, MSCs have the capacity to restore the functions of CD34+ haematopoietic cells and CD4+ and CD8+ T cells during malaria infection. These observations suggest that cell-based therapeutics for intervention in malaria may be useful in achieving sterile clearance and preventing disease reactivation. In addition, MSCs provide host protection against malaria by reprogramming erythropoiesis through accelerated formation of colony-forming-units-erythroid (CFU-E) cells in the bone marrow. These findings suggest that MSCs are positive regulators of erythropoiesis, making them attractive targets for treatment of malarial anemia. MSC-based therapies, unlike anti-malarial drugs, display therapeutic effects by targeting a large variety of cellular processes rather than a single pathway. In the present review we focus on these recent research findings and discuss clinical applications of MSC-based therapies for malaria.

Antenatal care (ANC), delivery by skilled birth attendants, and postnatal care (PNC) are critical components of maternal health services for reducing maternal mortality. The study aimed to compare the utilization of maternal health services in the two most recent rounds of Ethiopia Demographic and Health Surveys (EDHS) and identify the factors influencing the utilization of these services using the 2016 EDHS.

Two rounds of EDHS data in 2011 and 2016 were used to estimate the proportion of women who had ANC, delivered by skilled birth attendants, and had a postnatal checkup and other characteristics of the surveyed population. The most recent round of data-the 2016 EDHS-was used to examine the socio-cultural and reproductive health factors associated with the three maternal health services utilization. Chi-square tests and multivariate logistic regression analyses with adjusted Odds Ratios (AOR) were conducted using Stata 15.0.

The use of ANC services and skilled birth attendants increased significantly rural and urban areas, and the need of addressing the social, economic, and physical barriers that prevent women from using these services. Further, programs should be targeted at promoting the use of professional birth and postnatal services in Ethiopia.Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system that typically develops within 4 weeks after infection. In addition to conventional infectious diseases with which we are familiar, emerging infectious diseases, such as Zika virus infection and coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have also been suggested to be associated with GBS. GBS is mainly categorized into a demyelinating subtype known as acute inflammatory demyelinating polyneuropathy (AIDP) and an axonal subtype known as acute motor axonal neuropathy (AMAN). Most patients who develop GBS after Zika virus infection or COVID-19 have AIDP. The concept of molecular mimicry between pathogens and human peripheral nerve components was established through studies of AMAN with anti-ganglioside GM1 antibodies occurring after Campylobacter jejuni infection. Dihydromyricetin Although such mimicry between specific pathogens and myelin or Schwann cell components has not beeas been demonstrated.Herein, we reported a novel series of α-aminophosphonates derivatives (IV)a-m bearing an important pharmacophore coumarylthiazole moiety. All the new compounds have been synthesized via Kabachnik-Fields reaction under ultrasonic irradiation. The products were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. All these compounds (IV)a-m were screened for their in vitro for antimicrobial activity against thirteen Gram-negative bacteria and five Gram-positive bacteria and Candida albicans strains. The results showed that all the synthesized compounds exhibited moderate antibacterial activities against both references and multidrug-resistant and antifungal strains. The compound (IV)e showed the highest activities against all pathogens of the tested microbial strains with MIC of 0.125 μg/mL. The compounds (IV)h, (IV)f, (IV)b, and (IV)d exhibited moderate and promising activities with MIC of 0.125 μg/mL. Structure-activity relationship revealed that inhibitory activity of the synthesized compounds is related to the type of the substituted group on phenyl rings, and these results showed that the electron-donating groups at ortho and para positions have a high relationship increasing antimicrobial activities than the electron-withdrawing groups. These results confirm that coumarylthiazole α-aminophosphonates compounds can be potential antimicrobial drugs candidate.The SARS-CoV-2 helicase Nsp13 is a promising target for developing anti-COVID drugs. In the present study, we have identified potential natural product inhibitors of SARS-CoV-2 Nsp13 targeting the ATP-binding site using molecular docking and molecular dynamics (MD) simulations. MD simulation of the prepared crystal structure of SARS-CoV-2 Nsp13 was performed to generate an ensemble of structures of helicase Nsp13 capturing the conformational diversity of the ATP-binding site. A natural product library of more than 14,000 phytochemicals from Indian medicinal plants was used to perform virtual screening against the ensemble of Nsp13 structures. Subsequently, a two-stage filter, first based on protein-ligand docking binding energy value and second based on protein residues in the ligand-binding site and non-covalent interactions between the protein residues and the ligand in the best-docked pose, was used to identify 368 phytochemicals as potential inhibitors of SARS-CoV-2 helicase Nsp13. MD simulations of the top inhibitors complexed with protein were performed to confirm stable binding, and to compute MM-PBSA based binding energy. From among the 368 potential phytochemical inhibitors, the top identified potential inhibitors of SARS-CoV-2 helicase Nsp13 namely, Picrasidine M, (+)-Epiexcelsin, Isorhoeadine, Euphorbetin and Picrasidine N, can be taken up initially for experimental studies.

We identified a patient with a novel heterozygous variant fibrinogen, γp.C352R (Niigata II; N-II), who had a bleeding episode and failed infertility treatment and was suspected to have hypodysfibrinogenemia based on low and discordant fibrinogen levels (functional assay 0.33g/L, immunological assay 0.91g/L). We analyzed the mechanism of this rare phenotype of a congenital fibrinogen disorder.

Patient plasma fibrinogen was purified and protein characterization and thrombin-catalyzed fibrin polymerization performed. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cells were established and the assembly and secretion of variant fibrinogen analyzed by ELISA and western blotting.

Purified N-II plasma fibrinogen had a small lower molecular weight band below the normal γ-chain and slightly reduced fibrin polymerization. A limited proportion of p.C352R fibrinogen was secreted into the culture medium of established CHO cell lines, but the γ-chain of p.C352R was synthesized and variant fibrinogen was assembled inside the cells.