The prevalence of melanonychia is approximately 1%, and it is a common symptom encountered in daily practise. However, it may also be the first symptom of melanoma of the nail apparatus. Evaluation ...of adult melanonychia with clinical information and clinical images is sometimes difficult for clinicians. Dermoscopic observation provides important information based on the algorithm method. Melanonychia in children requires a different approach, because dermoscopic features observed in adult nail apparatus melanoma are generally observed in benign pediatric cases.
•During the COVID-19 pandemic, infectious disease epidemiology has changed worldwide.•In Japan, 75% of infectious diseases decreased in incidence.•In contrast, 17% of those increased, particularly ...vector-borne diseases.•Respiratory syncytial virus infection and hand-foot-and-mouth disease showed unique epidemiological changes.•These changes can occur even in countries applying mitigation policies.
To elucidate the impact of the COVID-19 pandemic on the epidemiology of other infectious diseases.
We investigated the epidemiology of 36 communicable diseases during 2015-2021 in Japan and compared the number of cases in each disease between the prepandemic (2015-2019) and intrapandemic (2020-2021) periods. Relationships between the incidence of the infectious diseases and the COVID-19 pandemic were also investigated.
Of 36 communicable diseases, the number of cases in the 27 diseases (75%) mainly caused by pathogens transmitted by droplet or contact was lower intrapandemic than prepandemic, and the cases of 21 diseases (58%) continued to decrease intrapandemic. The number of cases of six diseases (17%) was higher intrapandemic than prepandemic, and the cases of two diseases (5.6%), Japanese spotted fever and syphilis, continued to increase intrapandemic. Time trend analyses revealed a positive correlation between case numbers of communicable diseases and the COVID-19 pandemic, whereas the case numbers of hand-foot-and-mouth disease and respiratory syncytial virus infection rebounded in 2021 after decreasing in 2020.
The COVID-19 pandemic has greatly impacted the epidemiology of communicable diseases, suggesting that countermeasures against COVID-19 and lifestyle changes might be involved in these epidemiological changes.
Display omitted
Abstract Chaperone-mediated autophagy (CMA) contributes to selective degradation of individual soluble proteins in lysosomes. Unique to this type of autophagy is the fact that proteins reach the ...lysosomal lumen for degradation by directly crossing the lysosomal membrane, in contrast with the vesicle-mediated delivery characteristic of the other types of autophagy. These two characteristics – selective targeting and direct translocation of substrates – determine the contribution of CMA to different physiological functions and the type of pathological conditions associated with CMA dysfunction. In this review, we briefly revise recent findings on the molecular mechanisms behind CMA function, and describe the physiological relevance of the selective lysosomal degradation through this pathway. We also comment on the cellular consequences of CMA malfunction and on the connections already established between CMA dysfunction and different human disorders, with special emphasis on neurodegenerative diseases. This article is part of a Special Issue entitled “Autophagy and protein degradation in neurological diseases.”
Pemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the ...dermal‐epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients. PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis of PDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models of PD have been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis of PDs. We summarize spontaneously arising PD in animals and the induction of PD by transfer of (auto)antibodies, transfer of (auto)‐antigen‐specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects of PD pathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding of PD pathogenesis and to develop novel treatments for patients suffering from these life‐threatening and difficult‐to‐treat autoimmune diseases.
The incidence of neutropenia and the association between neutropenia and severity of respiratory symptoms among infants with respiratory syncytial virus (RSV) infections remain to be elucidated. This ...single-center, retrospective study included immunocompetent infants (<10 months old) with laboratory-confirmed RSV infection admitted to our center between January 2012 and December 2019. Incidence of neutropenia (<1.0 × 10
/L) within 10 days of onset and risk factors associated with subsequent neutropenia were evaluated. Among the 292 infants with RSV infection, including 232 (79%) with mild infection, neutropenia was observed in 31 (11%), with severe neutropenia (<0.5 × 10
/L) in 3 (1.0%). No neutropenic infants developed serious infection or hematological disorder. Infants without neutropenia showed age <3 months at onset in 34%, C-reactive protein level <1.0 mg/L in 27%, and nasopharyngeal microbiota composition with any of
,
, or
in 63%. In comparison, infants with neutropenia showed age <3 months at onset in 74% (relative risk RR 2.15; 95% confidence interval CI 1.65-2.81), C-reactive protein level <1.0 mg/L in 55% (RR 2.02; 95% CI 1.38-2.94), and microbiota including
,
, or
in 15% (RR 0.24; 95% CI 0.10-0.61). Multiple logistic regression analyses showed that younger age at onset and absence of that nasopharyngeal microbiota profile were associated with development of neutropenia. In conclusion, age and airway microbiota are considered as risk factors for the development of transient neutropenia among infants with RSV infection. However, the neutropenia seems not to develop serious infection or hematological disorder.
Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Alterations in macroautophagy, the main process responsible for bulk ...autophagic degradation, have been proposed to contribute to pathogenesis in Huntington's disease (HD), a genetic neurodegenerative disorder caused by an expanded polyglutamine tract in the huntingtin protein. However, the precise mechanism behind macroautophagy malfunction in HD is poorly understood. In this work, using cellular and mouse models of HD and cells from humans with HD, we have identified a primary defect in the ability of autophagic vacuoles to recognize cytosolic cargo in HD cells. Autophagic vacuoles form at normal or even enhanced rates in HD cells and are adequately eliminated by lysosomes, but they fail to efficiently trap cytosolic cargo in their lumen. We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells.
Autophagy contributes to the removal of prone-to-aggregate proteins, but in several instances these pathogenic proteins have been shown to interfere with autophagic activity. In the case of ...Huntington's disease (HD), a congenital neurodegenerative disorder resulting from mutation in the huntingtin protein, we have previously described that the mutant protein interferes with the ability of autophagic vacuoles to recognize cytosolic cargo. Growing evidence supports the existence of cross talk among autophagic pathways, suggesting the possibility of functional compensation when one of them is compromised. In this study, we have identified a compensatory upregulation of chaperone-mediated autophagy (CMA) in different cellular and mouse models of HD. Components of CMA, namely the lysosome-associated membrane protein type 2A (LAMP-2A) and lysosomal-hsc70, are markedly increased in HD models. The increase in LAMP-2A is achieved through both an increase in the stability of this protein at the lysosomal membrane and transcriptional upregulation of this splice variant of the lamp-2 gene. We propose that CMA activity increases in response to macroautophagic dysfunction in the early stages of HD, but that the efficiency of this compensatory mechanism may decrease with age and so contribute to cellular failure and the onset of pathological manifestations.
PDF
