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himeric HA; HBc hepatitis B virus core protein; HA hemagglutinin; HLA human leucocyte antigen; IIV inactivated influenza vaccine; KLH keyhole limpet hemocyanin; LAH long alpha helix; LAIV live attenuated influenza vaccine; M2e extracellular domain of matrix 2 protein; MHC major histocompatibility complex; mRNA messenger ribonucleic acid; NA neuraminidase; NS1 non-structural protein 1; qNIV quadrivalent nanoparticle influenza vaccine; TRM tissue-resident memory T cells; VE vaccine effectiveness; VLP virus-like particles; VSV vesicular stomatitis virus.

To study antibiotic prescriptions among 0- to 4-year-old children before and after implementing a quality project on prudent prescribing of antibiotics in primary healthcare in the capital region of Iceland.

An observational, descriptive, retrospective study using quantitative methodology.

Primary healthcare in the Reykjavik area with a total population of approximately 220,000.

A total of 6420 children 0-4 years of age presenting at the primary healthcare centres in the metropolitan area over three years from 2016 to 2018.

Reduction of antibiotic prescriptions and change in antibiotic profile. Data on antibiotic prescriptions for children 0-4 years of age was obtained from the medical records. Out-of-hours prescriptions were not included in the database.

The number of prescriptions during the study period ranged from 263.6 to 289.6 prescriptions/1000 inhabitants/year. A reduction of 9% in the total number of prescriptions between 2017-2018 was observed. More than half of all prescriptions were fole was observed.

The results show an overall decrease in antibiotic prescribing concurrent with a change in the choice of antibiotics prescribed and in line with the recommendations presented in the prescribing guidelines implemented by the Primary Healthcare of the Capital Area, and consistent with the project's goals.Key pointsA substantial proportion of antibiotic prescribing can be considered inappropriate and the antibiotic prescription rate is highest in Iceland of the Nordic countries.After implementing guidance on the treatment of common infections together with feedback on antibiotic prescribing, a decrease in the total number of prescriptions accompanied by a shift in the antibiotic profile was observed.

Antibody-mediated rejection (AMR) is one of the leading causes of graft loss in kidney transplant recipients but little is known about the associated cost and healthcare burden of AMR.

We developed an algorithm to detect AMR using the 2006-2011 Centers for Medicare & Medicaid Services (CMS) using ICD-10 and billing codes as there is no specific ICD-10 or procedure code for AMR. We then compared healthcare utilization, cost, and risk of graft failure or death in AMR. patients versus matched controls.

The algorithm had a 39.4% true-positive rate (69/175) and a 4.1% false-positive rate (110/2,655). We identified 5,679/101,554 (5.6%) with AMR, who had a nearly 3-fold higher risk of graft failure (hazard ratio [HR], 2.75, 95% confidence interval [CI], 2.50 to 3.03;

 < .0001) and death (HR, 2.59; 95% CI, 2.35 to 2.86;

 < .0001) at 2 years, nearly 5 times the hospitalizations in the 60 d before AMR diagnosis, and increased nephrology and emergency department visits. Mean AMR attributable healthcare costs were 4 times higher than matched controls, at $13,066 more per patient in the 60 d before AMR diagnosis and $35,740 per patient per year higher in the 2 years after AMR diagnosis.

US kidney transplant recipients with AMR have substantially greater healthcare utilization and higher costs and risk of graft loss and mortality.

US kidney transplant recipients with AMR have substantially greater healthcare utilization and higher costs and risk of graft loss and mortality.The appreciation of human microbiome is gaining strong grounds in biomedical research. In addition to gut-brain axis, is the lung-brain axis, which is hypothesised to link pulmonary microbes to neurodegenerative disorders and behavioural changes. There is a need for analysis based on emerging studies to map out the prospects for lung-brain axis. In this review, relevant English literature and researches in the field of 'lung-brain axis' is reported. HDAC inhibitor We recommend all the highlighted prospective studies to be integrated with an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units, while exploring the research gaps and making reference to the already existing human data. The overall microbiome medicine is gaining more ground. Aetiological paths and experimental recommendations as per prospective studies in this review will be an important guideline to develop effective treatments for any ready existing human data.

The objective of this manuscript is to provide a comprehensive and critical overview of the current evidence on the association between Diabetes mellitus (DM) and mood disorders [i.e., Major depressive disorder (MDD) and bipolar disorder (BD)], and therapeutic opportunities.

We searched in MEDLINE (via Ovid) for placebo-controlled clinical trials published in the last 20 years that assessed drug repurposing approaches for the treatment of DM or mood disorders.

We found seven studies that aimed to verify the effects of antidepressants in patients diagnosed with DM, and eight studies that tested the effect of antidiabetic drugs in patients diagnosed with MDD or BD. Most studies published in the last two decades did not report a positive effect of antidepressants on glycemic control in patients with DM. On the other hand, antidiabetic drugs seem to have a positive effect on the treatment of MDD and BD.

While effect of antidepressants on glycemic control in patients with DM is still controversial, the usecontrol, potentially increasing mortality risk.The effect of antidepressants on glycemic control in patients with DM is still controversial. The coexistence of complicated DM and a mood disorders would require a careful, individualised, and comprehensive evaluation.Insulin resistance may increase the risk of depressive symptoms and is associated with worse outcomes in BD.The use antidiabetic drugs may be a promising strategy for patients with MDD or BD. However, prospective trials are needed to prove a potential antidepressant activity of antidiabetic drugs.Identifying isoform-specific inhibitors for closely related kinase family members remains a substantial challenge. The necessity for achieving this specificity is exemplified by the RSK family, downstream effectors of ERK1/2, which have divergent physiological effects. The natural product, SL0101, a flavonoid glycoside, binds specifically to RSK1/2 through a binding pocket generated by an extensive conformational rearrangement within the RSK N-terminal kinase domain (NTKD). In modelling experiments a single amino acid that is divergent in RSK3/4 most likely prevents the required conformational rearrangement necessary for SL0101 binding. Kinetic analysis of RSK2 association with SL0101 and its derivatives identified that regions outside of the NTKD contribute to stable inhibitor binding. An analogue with an n-propyl-carbamate at the 4" position on the rhamnose moiety was identified that forms a highly stable inhibitor complex with RSK2 but not with RSK1. These results identify a SL0101 modification that will aid the identification of RSK2 specific inhibitors.

Mitral annulus calcification (MAC) is a chronic, non-inflammatory, degenerative mechanism of the fibrous base of the mitral valve. While MAC was originally thought to be an age-related degenerative process, there is evidence that other mechanisms, such as atherosclerosis and abnormal calcium phosphorus metabolism, also contribute to the development of MAC.

This paper summarizes, existing perception of clinically valid definition of MAC and the pathophysiological processes that lead to the development of MAC and the diagnostic implications of this disease entity.

Minimal evidence exists on the natural history and progression of MAC. Characterization of MAC progression and identification of predisposing risk factors can help to validate hypotheses. MAC is most commonly asymptomatic and incidental finding. Echocardiography is the primary imaging modality for identification and characterization of MAC and associated mitral valve (MV) disease. For patients with an indication for MV surgery, computed tomography (CT) is a complementary imaging modality for MAC. MAC is generally recognized by its characteristic density, location, and shape on echocardiography and CT, unusual variants are sometimes confused with other lesions.

Minimal evidence exists on the natural history and progression of MAC. Characterization of MAC progression and identification of predisposing risk factors can help to validate hypotheses. MAC is most commonly asymptomatic and incidental finding. Echocardiography is the primary imaging modality for identification and characterization of MAC and associated mitral valve (MV) disease. For patients with an indication for MV surgery, computed tomography (CT) is a complementary imaging modality for MAC. MAC is generally recognized by its characteristic density, location, and shape on echocardiography and CT, unusual variants are sometimes confused with other lesions.To evaluate whether outcomes following allogeneic hematopoietic cell transplantation differ according to disease type, a three-way comparison for patients with de novo acute myeloid leukemia (AML) (n = 3318), AML evolving from myelodysplastic syndromes (MDS) (n = 208), and MDS with excess blasts (MDS-EB) (n = 994) was performed. The 5-year probabilities of overall survival (OS) for de novo AML, AML evolving from MDS, and MDS-EB were 60%, 42%, and 41% (p  less then  0.001), respectively. Multivariate analysis revealed that, compared to de novo AML, AML evolving from MDS was associated with a higher risk of NRM (p = 0.030) and MDS-EB with a higher risk of relapse (p  less then  0.001), both leading to lower OS (p = 0.010 and p  less then  0.001, respectively). These findings demonstrate inter-disease differences in post-transplant outcomes and highlight the needs to reduce NRM for AML evolving from MDS and to reduce relapse for MDS-EB.The stigmatization of Senegalese return migrants as COVID-19 vectors by fellow Senegalese during the early days of the COVID-19 pandemic troubles the self/other distinction that underpins the scholarly focus on epidemics and xenophobia and encourages the broader task of exploring epidemics and phobia. The casting of return migrants as COVID-19 vectors was influenced by longstanding ambivalence toward these migrants that had encouraged some Senegalese to seek to "confine" them to Europe long before the pandemic. Old preoccupations help us understand how Senegalese interpreted and deployed COVID-19 control and prevention measures like "confinement," lockdowns, and border closures.As the largest organ exposed to the outside of mammals, skin has direct photosensitivity. Recent studies have even shown that cutaneous irradiation played a role in local circadian systems. However, whether it can further affect the central clock system is controversial. Here, plasm melatonin rhythm of melatonin-proficient C3H/He mice was assessed, and on this basis, a well-designed segmented lighting method was used to investigate the effects of dorsal skin irradiation on locomotor activity and plasm melatonin content in male C3H/He mice. In brief, mice were separately exposed to cutaneous irradiation, intraocular irradiation or darkness for 60 min at specific moments. The results showed that neither blue nor red cutaneous exposure had obvious effect on central rhythm oscillation while intraocular irradiation could significantly change the central clock of mice, and the effect of blue light was more forceful than red light. It suggests that intraocular nonvisual channels still play a dominant role in rhythmic regulation, which has not been challenged by the discovery of local light entrainment in exposed peripheral tissues.

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