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There is mounting evidence which suggests the involvement of gut microbiota dysbiosis in the pathogenesis of various cardiovascular diseases (CVD) and associated risk states such as hypertension, type 2 diabetes, obesity and dyslipidaemia, atherosclerosis, heart failure and atrial fibrillation. The current review comprehensively summarizes the various pathogenetic mechanisms of dysbiosis in these conditions and discusses the key therapeutic implications. Further deeper understanding of the pathogenetic links between CVD and gut microbiota dysbiosis can aid in the development of novel microbiota-based targets for the management of CVDs.The pathophysiology of acute coronary syndromes was thought to be coronary thrombosis over a plaque rupture. Autopsy studies revealed that not all cases were due to plaque rupture, even denuded endothelium or calcific nodule can beget a thrombus. Introduction of OCT made, in vivo recognition of lesion morphology clear. Plaque ruptures are most common and need primary angioplasty. Recent studies established plaque erosion is responsible for ACS in one third of the cases and majority of them present as Non ST elevation myocardial infarction and commonly found in young patients without major risk factors. Evidence from recent studies suggested that stenting can be deferred and they can be managed conservatively with good long term outcomes. More randomized trials are needed comparing plaque rupture and plaque erosion as regards conservative versus invasive management. If these studies substantiate the concept of conservative management, it will lead to a paradigm shift in their management.Tools to identify monoclonal Ig deposits within tissue specimens include immunofluorescence (IF) staining on frozen tissue for Ig heavy chains and light chains, pronase IF to unmask monoclonal Ig deposits not seen by IF staining on frozen tissue, and IF staining for IgG subclasses (IgG1-IgG4). In this issue of Kidney International, a novel diagnostic tool is introduced IF staining for conformational epitopes at the junction of the Ig heavy chains and light chains. This technique has the potential to significantly enhance our ability to evaluate apparent monoclonal forms of renal disease.Apolipoprotein L1 (APOL1) high-risk genotypes strongly associate with HIV-associated nephropathy, and antiretroviral therapy reduces the incidence of HIV-associated nephropathy and progression to end-stage kidney disease. Wudil et al. report cross-sectional APOL1 associations with proteinuria and estimated glomerular filtration rate in a northern Nigerian sample with HIV infection on antiretroviral therapy. Multiple ethnic groups with different APOL1 risk variant frequencies were included. Overall, APOL1 was associated with proteinuric chronic kidney disease; however, relationships with underlying causes of nephropathy and progression rates require further study.When affected by coronavirus disease 2019 (COVID-19), most children have milder disease than what is experienced by adults. However, a subset of these children develops a multisystem inflammatory syndrome that can lead to shock and multiorgan failure. In the current issue, Basalely et al. characterize acute kidney injury in pediatric patients with acute COVID-19 and multisystem inflammatory syndrome. Despite the associated morbidity, this cohort provides evidence of kidney recovery in most affected children.Hanudel et al. investigated the effects of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) on iron metabolism in a chronic kidney disease (CKD) mouse model and showed that vadadustat, an HIF-PHI, exerted beneficial effects on anemia and iron disorders independently of erythroferrone. Vadadustat also inhibited the progression of CKD and the CKD-associated increase of plasma fibroblast growth factor 23 in CKD mice. This study provides new insights into the action of HIF-PIHs in CKD.
Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).
We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.
On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.
Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.
This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.
This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.Increasing testing for viral hepatitis and HIV is central to meeting World Health Organization and Australian targets to eliminate blood-borne viruses as public health priorities by 2030. In this paper we draw on findings and recommendations from a Victorian consultation with 40 health and community practitioners engaged with blood-borne virus testing. The consultation focused on identifying what constitutes best practice in pre- and post-testing discussion in the current era of highly effective treatments for HIV and hepatitis C. Overall, the consultation found that the pre- and post-test discussion remains an important feature of testing, but, given that stigma continues to impact the lives of people affected by these viruses, sensitivity to this issue needs to inform how these discussions take place. We describe how primary healthcare settings can support the goal of upscaling HIV and hepatitis C testing in a way that delivers safe and stigma-free testing encounters. We offer the notion of 'stigma-sensitive practice' as a term to describe this approach to pre- and post-test discussions.Older people who live in the community and need assistance with daily activities are a unique group of patients to treat in the primary care (PC) setting. This study aimed to understand access-related PC needs and experiences of community-living people over 65 years of age receiving home-based assistance through the Home and Community Care (HACC) program in Melbourne, Australia. This descriptive qualitative study used thematic analysis of in-depth interviews with HACC program clients and assessment officers. Access-related needs and experiences were examined using the patient-centred access to care framework. Client (n=11) and assessment officer (n=4) interviews showed that community-living older people receiving home-based assistance from social services are able to find a GP according to their preferences; however, some challenges in access to comprehensive care exist. These challenges relate to regularity of PC attendance, out-of-pocket fees for specialist care and maintaining an enduring patient-GP relationship. GPs can play an important role in improving PC access for vulnerable older people. In particular, GPs can contribute to improving PC attendance and facilitating more affordable access to specialist care by improving systems to recall patients more regularly and developing explicit systems for linking vulnerable patients to affordable specialist services.Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this minireview, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma. [BMB Reports 2021; 54(7) 344-355].Proper targeting of the βPAK-interacting exchange factor (βPIX)/G protein-coupled receptor kinase-interacting target protein (GIT) complex into distinct cellular compartments is essential for its diverse functions including neurite extension and synaptogenesis. However, the mechanism for translocation of this complex is still unknown. In the present study, we reported that the conventional kinesin, called kinesin-1, can transport the βPIX/GIT complex. Additionally, βPIX bind to KIF5A, a neuronal isoform of kinesin-1 heavy chain, but not KIF1 and KIF3. Mapping analysis revealed that the tail of KIF5s and LZ domain of βPIX were the respective binding domains. Silencing KIF5A or the expression of a variety of mutant forms of KIF5A inhibited βPIX targeting the neurite tips in PC12 cells. Furthermore, truncated mutants of βPIX without LZ domain did not interact with KIF5A, and were unable to target the neurite tips in PC12 cells. These results defined kinesin-1 as a motor protein of βPIX, and may provide new insights into βPIX/GIT complex-dependent neuronal pathophysiology. [BMB Reports 2021; 54(7) 380-385].Cell-based therapy is a promising approach in the field of regenerative medicine. As cells are formed into spheroids, their survival, functions, and engraftment in the transplanted site are significantly improved compared to single cell transplantation. To improve the therapeutic effect of cell spheroids even further, various biomaterials (e.g., nano- or microparticles, fibers, and hydrogels) have been developed for spheroid engineering. These biomaterials not only can control the overall spheroid formation (e.g., size, shape, aggregation speed, and degree of compaction), but also can regulate cell-to-cell and cell-to-matrix interactions in spheroids. Therefore, cell spheroids in synergy with biomaterials have recently emerged for cell-based regenerative therapy. Biomaterials-assisted spheroid engineering has been extensively studied for regeneration of bone or/and cartilage defects, critical limb ischemia, and myocardial infarction. Furthermore, it has been expanded to pancreas islets and hair follicle transplantation. This paper comprehensively reviews biomaterials-assisted spheroid engineering for regenerative therapy. [BMB Reports 2021; 54(7) 356-367].Owing to rapid advancements in NGS (next generation sequencing), genomic alteration is now considered an essential predictive biomarkers that impact the treatment decision in many cases of cancer. Among the various predictive biomarkers, tumor mutation burden (TMB) was identified by NGS and was considered to be useful in predicting a clinical response in cancer cases treated by immunotherapy. In this study, we directly compared the lab-developed-test (LDT) results by target sequencing panel, K-MASTER panel v3.0 and whole-exome sequencing (WES) to evaluate the concordance of TMB. As an initial step, the reference materials (n = 3) with known TMB status were used as an exploratory test. To validate and evaluate TMB, we used one hundred samples that were acquired from surgically resected tissues of non-small cell lung cancer (NSCLC) patients. The TMB of each sample was tested by using both LDT and WES methods, which extracted the DNA from samples at the same time. check details In addition, we evaluated the impact of capture region, which might lead to different values of TMB; the evaluation of capture region was based on the size of NGS and target sequencing panels.
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