The Immunology of SARS-CoV-2 Infection and Vaccines in Solid Organ Transplant Recipients

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.     

等位基因特异性引物延伸法在婴儿型和幼儿型神经元蜡样质脂褐质沉积病产前诊断中的应用

Theinfantile (INCL ,NCL1,OMIM :2 5 6 730 )andlate infantile (LINCL ,NCL2 ,OMIM :2 0 4 5 0 0 )neuronalceroid lipofuscinosis (NCLs)areamongthemostcommonchildhoodlysosomallipid proteindisor ders.Theyarecharacterizedbyrapidlyincreasingseverityofseizures ;dete…     

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes

neurogenetics - Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP...     

The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the fibrosis of skin, heart, lung, and kidney as well. Excessive activation of fibroblasts is associated with higher expression of Notch1 and/or Notch3 genes. The constitutive expression of NOTCH genes was described in epithelial cells: epidermal keratinocytes, hair follicle cells and sebaceous glands. The NOTCH signalling pathway may be involved in the development of fibrosis, myofibroblast formation and the process of epithelial-mesenchymal transition. Activation of the NOTCH pathway leads to morphological, phenotypic and functional changes in epithelial cells. Furthermore, inhibition of Notch signalling prevent the development of fibrosis in different models, among them, bleomycin-induced fibrosis and in the Task-1 mause model. Molecular mechanisms, including the role of NOTCH signaling pathway, associated with fibrosis in SSc have not been completely recognized.     

Training in intraoperative neuromonitoring of recurrent laryngeal nerves reduces the risk of their injury during thyroid surgery

IntroductionEven though incidence of recurrent laryngeal nerve palsy (RLNP) is low, it affects importantly the quality of life of patients and remains one of main medicolegal litigation problems in surgery. Intraoperative neuromonitoring (IONM) has become widely accepted tool helping in recurrent laryngeal nerve identification, however no clear association of IONM with RLNP rate has been demonstrated. The aim of our study was to assess whether training in IONM influences rates of RNLP after thyroid surgery as an independent factor.Material and methodsWe analysed retrospectively 1235 patients who underwent thyroidectomy at the 1st Department of General and Endocrine Surgery, Medical University of Bialystok. Possible risk factors for RLNP were evaluated: application or not of IONM, the extent of surgery or thyroid pathology in correlation with surgeons’ experience in IONM (trained or untrained).ResultsThere were 2351 nerves at risk (NAR) and 39 RNLP were diagnosed after thyroid surgery (1.66%). Surgeons trained in IONM performed 52.2% of all operations (1200 NAR) with 7 RLNP (0.58%), whereas not-trained had 32 RLNP for 1151 NAR (2.8%; p < 0.001). After 182 thyroidectomies (357 NAR) guided by IONM (14.7%) 3 RLNP were observed (0.84%) vs. 36 palsies per 1994 NAR without IONM (1.81%; p = 0.189). The highest danger of RLNP was reported after reoperations and the lowest after subtotal thyroidectomies. We found no association between thyroid pathology and RLNP rate.ConclusionsAccording to our study training in IONM decreases chances of RLNP especially during total or near total thyroidectomy.     

β1 Integrin is essential for fascin-mediated breast cancer stem cell function and disease progression

Breast cancer remains the second cause of tumor-related mortality in women worldwide mainly due to chemoresistance and metastasis. The chemoresistance and metastasis are attributed to a rare subpopulation with enriched stem-like characteristics, thus called Cancer Stem Cells (CSCs). We have previously reported aberrant expression of the actin-bundling protein (fascin) in breast cancer cells, which enhances their chemoresistance, metastasis and enriches CSC population. The intracellular mechanisms that link fascin with its downstream effectors are not fully elucidated. Here, loss and gain of function approaches in two different breast cancer models were used to understand how fascin promotes disease progression. Importantly, findings were aligned with expression data from actual breast cancer patients. Expression profiling of a large breast cancer dataset (TCGA, 530 patients) showed statistically significant correlation between fascin expression and a key adherence molecule, β1 integrin (ITGB1). In vitro manipulation of fascin expression in breast cancer cells exhibited its direct effect on ITGB1 expression. Fascin-mediated regulation of ITGB1 was critical for several breast cancer cell functions including adhesion to different extracellular matrix, self-renewability and chemoresistance. Importantly, there was a significant relationship between fascin and ITGB1 co-expression and short disease-free as well as overall survival in chemo-treated breast cancer patients. This novel role of fascin effect on ITGB1 expression and its outcome on cell self-renewability and chemoresistance strongly encourages for dual targeting of fascin-ITGB1 axis as a therapeutic approach to halt breast cancer progression and eradicate it from the root.     

Post-blink tear film dynamics in healthy and dry eyes during spontaneous blinking

Purpose

The aim was to investigate the dynamics of post-blink tear film leveling in natural blinking conditions (NBC) for healthy subjects and those diagnosed with dry eye syndrome (DES) and to relate this phase to the tear film surface quality (TFSQ) before the following blink.

The role of gender in the active attitude toward treatment and health among older patients in primary health care—self-assessed health status and sociodemographic factors as moderators

Background

Active attitude toward treatment and health (ATH) leads to improved cooperation and better health outcomes in patients. Supporting it in the population of older adults is a growing need in primary care. Recognising the role of gender, health and other sociodemographic factors can help to distinguish patients who need the most assistance in activation from general practitioners (GPs). The objective of the study was to investigate gender differences in ATH as well as the moderating role of self-assessed health (SAH) and selected sociodemographic factors (age, education, financial status, marital status).

Methods

A cross-sectional, multicentre study among 4936 primary care older patients (aged 50+) was conducted. The PRACTA-Attitude toward Treatment and Health questionnaire (PRACTA-ATH) was used to measure the cognitive, emotional (positive and negative affect), and motivational dimensions of ATH. Patients were approached before and after their visits in the primary health-care facilities randomly selected in Central Poland.

Results

Generalised linear models (GENLIN) revealed the main effects of gender, SAH, and sociodemographic characteristics, such as financial status, marital status and education. Interaction effects of gender and age (Wald’s χ²?=?24.767, p?<?0.001 for ATH Global), as well as gender and SAH (Wald’s χ²?=?16.712, p?<?0.002 for ATH Global) on ATH were found. The most assistance in regard to ATH was required by men aged 50–74 and men declaring good self-assessed health. Generally, women declared a more active attitude than men, showing more knowledge (M?=?5.40, SD?=?0.07 and M?=?5.21, SD?=?0.07, for women and men, respectively, p?=?0.046), positive emotion (M?=?5.55, SD?=?0.06 and M?=?5.33, SD =0.06, for women and men, respectively, p?=?0.015) and motivation to be involved in their health issues (M?=?5.71, SD?=?0.07 and M?=?5.39, SD?=?0.07, for women and men, respectively, p?=?0.001). The level of negative emotions related to health was not significantly different between genders (p?=?0.971).

Conclusions

The need to create health promoting programmes taking account of particular gender differences in older adults emerges. In regard to clinical practice, building a sense of efficacy and individual responsibility for health, providing information about the means of health promotion and prevention, and recognising health-related cognitions, is recommended especially for men who feel well and are less advanced in age (50–74).

     

HBK-14 and HBK-15 with antidepressant-like and/or memory-enhancing properties increase serotonin levels in the hippocampus after chronic treatment in mice

Metabolic Brain Disease - 5-HT1A and 5-HT7 receptor ligands might have antidepressant-like properties and improve cognitive function. We previously reported significant antidepressant- and...