Denis Depes, Ari Mennander, Paavo Immonen, Artturi Mäkinen, Heini Huhtala, Timo Paavonen, Ivana Kholová
{"title":"The autonomic nerves around the vein of Marshall: a postmortem study with clinical implications","authors":"Denis Depes, Ari Mennander, Paavo Immonen, Artturi Mäkinen, Heini Huhtala, Timo Paavonen, Ivana Kholová","doi":"10.1111/apm.13400","DOIUrl":"10.1111/apm.13400","url":null,"abstract":"<p>This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"430-443"},"PeriodicalIF":2.8,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lailema Ahmady, Manisha Gothwal, Muhammed Mushthaque Mukkoli, Vinay Kumar Bari
{"title":"Antifungal drug resistance in Candida: a special emphasis on amphotericin B","authors":"Lailema Ahmady, Manisha Gothwal, Muhammed Mushthaque Mukkoli, Vinay Kumar Bari","doi":"10.1111/apm.13389","DOIUrl":"10.1111/apm.13389","url":null,"abstract":"<p>Invasive fungal infections in humans caused by several <i>Candida</i> species, increased considerably in immunocompromised or critically ill patients, resulting in substantial morbidity and mortality. <i>Candida albicans</i> is the most prevalent species, although the frequency of these organisms varies greatly according to geographic region. Infections with <i>C. albicans</i> and non-albicans <i>Candida</i> species have become more common, especially in the past 20 years, as a result of aging, immunosuppressive medication use, endocrine disorders, malnourishment, extended use of medical equipment, and an increase in immunogenic diseases. Despite <i>C. albicans</i> being the species most frequently associated with human infections, <i>C. glabrata</i>, <i>C. parapsilosis</i>, <i>C. tropicalis</i>, and <i>C. krusei</i> also have been identified. Several antifungal drugs with different modes of action are approved for use in clinical settings to treat fungal infections. However, due to the common eukaryotic structure of humans and fungi, only a limited number of antifungal drugs are available for therapeutic use. Furthermore, drug resistance in <i>Candida</i> species has emerged as a result of the growing use of currently available antifungal drugs against fungal infections. Amphotericin B (AmB), a polyene class of antifungal drugs, is mainly used for the treatment of serious systemic fungal infections. AmB interacts with fungal plasma membrane ergosterol, triggering cellular ion leakage via pore formation, or extracting the ergosterol from the plasma membrane inducing cellular death. AmB resistance is primarily caused by changes in the content or structure of ergosterol. This review summarizes the antifungal drug resistance exhibited by <i>Candida</i> species, with a special focus on AmB.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"291-316"},"PeriodicalIF":2.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fang Zhou, Leilei Jiang, Xuankai Sun, Zhen Wang, Jialin Feng, Ming Liu, Zhao Ma
{"title":"Surgery of enlarging lesions after stereotactic radiosurgery for brain metastases in patients with non-small cell lung cancer with oncogenic driver mutations frequently reveals radiation necrosis: case series and review","authors":"Fang Zhou, Leilei Jiang, Xuankai Sun, Zhen Wang, Jialin Feng, Ming Liu, Zhao Ma","doi":"10.1111/apm.13402","DOIUrl":"10.1111/apm.13402","url":null,"abstract":"<p>In brain metastases, radiation necrosis (RN) is a complication that arises after single or multiple fractionated stereotactic radiosurgery (SRS/FSRS), which is challenging to distinguish from local recurrence (LR). Studies have shown increased RN incidence rates in non-small cell lung cancer (NSCLC) patients with oncogenic driver mutations (ODMs) or receiving tyrosine kinase inhibitors (TKIs). This study investigated enlarging brain lesions following SRS/FSRS, for which additional surgeries were performed to distinguish between RN and LR. We investigated seven NSCLC patients with ODMs undergoing SRS/FSRS for BM and undergoing surgery for suspicion of LR on MRI imaging. Descriptive statistics were performed. Among the seven patients, six were EGFR+, while one was ALK+. The median irradiation dose was 30 Gy (range, 20–35 Gy). The median time to develop RN after SRS/FSRS was 11.1 months (range: 6.3–31.2 months). Moreover, gradually enlarging lesions were found in all patients after 6 months post-SRS/FSR. Brain radiation necrosis was pathologically confirmed in all the patients. RN should be suspected in NSCLC patients when lesions keep enlarging after 6 months post-SRS/FSRS, especially for patients with ODMs and receiving TKIs. Further, this case series indicates that further dose reduction might be necessary to avoid RN for such patients.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"375-381"},"PeriodicalIF":2.8,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Understanding the biofilm development of Acinetobacter baumannii and novel strategies to combat infection","authors":"Naji Naseef Pathoor, Akshaya Viswanathan, Gulshan Wadhwa, Pitchaipillai Sankar Ganesh","doi":"10.1111/apm.13399","DOIUrl":"10.1111/apm.13399","url":null,"abstract":"<p><i>Acinetobacter baumannii</i> (<i>A. baumannii</i>) is a Gram-negative, nonmotile, and aerobic bacillus emerged as a superbug, due to increasing the possibility of infection and accelerating rates of antimicrobial agents. It is recognized as a nosocomial pathogen due to its ability to form biofilms. These biofilms serve as a defensive barrier, increase antibiotic resistance, and make treatment more difficult. As a result, the current situation necessitates the rapid emergence of novel therapeutic approaches to ensure successful treatment outcomes. This review explores the intricate relationship between biofilm formation and antibiotic resistance in <i>A. baumannii</i>, emphasizing the role of key virulence factors and quorum sensing (QS) mechanisms that will lead to infections and facilitate insight into developing innovative method to control <i>A. baumannii</i> infections. Furthermore, the review article looks into promising approaches for preventing biofilm formation on medically important surfaces and potential therapeutic methods for eliminating preformed biofilms, which can address biofilm-associated <i>A. baumannii</i> infections. Modern advances in emerging therapeutic options such as antimicrobial peptide (AMPs), nanoparticles (NPs), bacteriophage therapy, photodynamic therapy (PDT), and other biofilm inhibitors can assist readers understand the current landscape and future prospects for effectively treating <i>A. baumannii</i> biofilm infections.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"317-335"},"PeriodicalIF":2.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuwen Chu, Shuo Zhang, Wei Wan, Jialiang Yang, Yumeng Zhang, Chuanqi Nie, Weipeng Xing, Shanhe Tong, Jinyang Liu, Geng Tian, Bing Wang, Lei Ji
{"title":"Pathological image profiling identifies onco-microbial, tumor immune microenvironment, and prognostic subtypes of colorectal cancer","authors":"Yuwen Chu, Shuo Zhang, Wei Wan, Jialiang Yang, Yumeng Zhang, Chuanqi Nie, Weipeng Xing, Shanhe Tong, Jinyang Liu, Geng Tian, Bing Wang, Lei Ji","doi":"10.1111/apm.13387","DOIUrl":"10.1111/apm.13387","url":null,"abstract":"<p>Histology slide, tissue microbes, and the host gene expression can be independent prognostic factors of colorectal cancer (CRC), but the underlying associations and biological significance of these multimodal omics remain unknown. Here, we comprehensively profiled the matched pathological images, intratumoral microbes, and host gene expression characteristics in 527 patients with CRC. By clustering these patients based on histology slide features, we classified the patients into two histology slide subtypes (HSS). Onco-microbial community and tumor immune microenvironment (TIME) were also significantly different between the two subtypes (HSS1 and HSS2) of patients. Furthermore, variation in intratumoral microbes–host interaction was associated with the prognostic heterogeneity between HSS1 and HSS2. This study proposes a new CRC classification based on pathological image features and elucidates the process by which tumor microbes–host interactions are reflected in pathological images through the TIME.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 6","pages":"416-429"},"PeriodicalIF":2.8,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bryn Short, Christopher Delaney, William Johnston, Gary J. Litherland, John C. Lockhart, Craig Williams, William G. Mackay, Gordon Ramage
{"title":"Informed development of a multi-species biofilm in chronic obstructive pulmonary disease","authors":"Bryn Short, Christopher Delaney, William Johnston, Gary J. Litherland, John C. Lockhart, Craig Williams, William G. Mackay, Gordon Ramage","doi":"10.1111/apm.13386","DOIUrl":"10.1111/apm.13386","url":null,"abstract":"<p>Recent evidence indicates that microbial biofilm aggregates inhabit the lungs of COPD patients and actively contribute towards chronic colonization and repeat infections. However, there are no contextually relevant complex biofilm models for COPD research. In this study, a meta-analysis of the lung microbiome in COPD was used to inform development of an optimized biofilm model composed of genera highly associated with COPD. Bioinformatic analysis showed that although diversity matrices of COPD microbiomes were similar to healthy controls, and internal compositions made it possible to accurately differentiate between these cohorts (AUC = 0.939). Genera that best defined these patients included <i>Haemophilus</i>, <i>Moraxella</i> and <i>Streptococcus.</i> Many studies fail to account for fungi; therefore, <i>Candida albicans</i> was included in the creation of an interkingdom biofilm model. These organisms formed a biofilm capable of tolerating high concentrations of antimicrobial therapies with no significant reductions in viability. However, combined therapies of antibiotics and an antifungal resulted in significant reductions in viable cells throughout the biofilm (p < 0.05). This biofilm model is representative of the COPD lung microbiome and results from <i>in vitro</i> antimicrobial challenge experiments indicate that targeting both bacteria and fungi in these interkingdom communities will be required for more positive clinical outcomes.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"336-347"},"PeriodicalIF":2.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammatory mediators in bacterial vaginosis: The role of cytokines","authors":"Yuexin Zhang, Zhi He","doi":"10.1111/apm.13380","DOIUrl":"10.1111/apm.13380","url":null,"abstract":"<p>BV is a significant concern in women's health with a varying prevalence rate in different cities of China. The condition has been linked to the acquisition of STIs, including HIV and HPV, and can lead to infertility, adverse obstetric outcomes. We conducted a comprehensive literature search in the PubMed. The search was performed from 01/01/2018 to 01/09/2023. The following search terms were used: bacterial vaginosis and cytokine. We also manually searched the reference lists of included studies and relevant reviews to identify additional articles. The presence of <i>Gardnerella</i> spp. can lead to changes in cytokine levels. The immune system of the female reproductive tract consists of various immune cells and molecules that play a vital role in defending against infections. Cytokines, signaling molecules involved in immune cell recruitment and activation, have been identified as potential biomarkers for diagnosing BV and predicting STIs. Current treatments for BV primarily involve antibiotics, but there is a high recurrence rate posttreatment. BV is a complex condition that affects a significant number of women worldwide. The role of cytokines in the onset, progression, and treatment of BV offers promising avenues for future research and potential diagnostic and therapeutic advancements.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 4","pages":"245-255"},"PeriodicalIF":2.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autoimmune vulnerability of beta versus alpha cells might be due to increased 2′,5′ synthetase","authors":"Karsten Buschard, Martin Haupt-Jorgensen","doi":"10.1111/apm.13384","DOIUrl":"10.1111/apm.13384","url":null,"abstract":"","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"371-372"},"PeriodicalIF":2.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Humoral immune response of Galleria mellonella after mono- and co-injection with Hypericum perforatum extract and Candida albicans","authors":"Tülay Turgut Genç, Serhat Kaya, Melih Günay, Çağla Çakaloğlu","doi":"10.1111/apm.13383","DOIUrl":"10.1111/apm.13383","url":null,"abstract":"<p><i>Galleria mellonella</i> is used as a model organism to study the innate immune response of insects. In this study, the humoral immune response was assessed by examining phenoloxidase activity, fungal burden, and the expression of phenoloxidase and antimicrobial peptide genes at different time point following separate and combined injections of <i>Hypericum perforatum</i> extract and a nonlethal dose of <i>Candida albicans</i>. The administration of a plant extract at low doses increased phenoloxidase activity, while higher doses had no effect. Similarly, co-injection of a low dose of the extract with the pathogen allowed half of the yeast cells to survive after 24 h. Co-injection of plant extract with the pathogen decreased the phenoloxidase activity at the end of 4 h compared to <i>C. albicans</i> mono-injection. The phenoloxidase gene expressions was reduced in all experimental conditions with respect to the control. When plant extracts and the pathogen were administered together, gallerimycin and hemolin gene expressions were considerably higher compared to mono-injections of plant extracts and the pathogen. The results of this study reveal that gene activation and regulatory mechanisms may change for each immune gene, and that recognition and signaling pathways may differ depending on the involved immunoregulator.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 5","pages":"358-370"},"PeriodicalIF":2.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahnoor Sukaina, Syed Hasan Shuja, Syeda Tayyaba Rehan, Sidhant Ochani, Muhammad Sheryar
{"title":"Virology and safety profile of Molnupiravir at three different doses for treatment of SARS-CoV-2: a systematic review and meta-analysis","authors":"Mahnoor Sukaina, Syed Hasan Shuja, Syeda Tayyaba Rehan, Sidhant Ochani, Muhammad Sheryar","doi":"10.1111/apm.13373","DOIUrl":"10.1111/apm.13373","url":null,"abstract":"<p>Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication of SARS-CoV-2. Following PRISMA guidelines, a thorough literature search was performed on electronic and medical databases from December 2022 till January 2023. Molnupiravir 800 mg showed significance in creating viral RNA error rate at Day 5 (WMD: 4.91; 95% CI; [1.19, 8.63] p = 0.01; <i>I</i><sup>2</sup> = 0%). Similarly, at 400 mg, Molnupiravir creates an RNA error rate (WMD: 2.27; 95% CI; 2.27 [0.50, 4.65] p = 0.02; <i>I</i><sup>2</sup> = 0%). Furthermore, exhibit a significant outcome for mean change in SARS-CoV-2 RNA viral load from baseline in nasopharyngeal sample at 800 mg Molnupiravir on Day 3 (WMD: −0.22; 95% CI; [−0.35, −0.08] p = 0.002; <i>I</i><sup>2</sup> = 0%), Day 5 (WMD: −0.32; 95% CI; [−0.53, −0.11] p = 0.003; <i>I</i><sup>2</sup> = 24%) and overall pooled analysis (WMD: −0.17; 95% CI; [−0.29, 0.33] p = 0.003; <i>I</i><sup>2</sup> = 32%). Moreover, Molnupiravir 400 mg significantly reduced the incidence of death compared to the placebo group (RR: 0.17; 95% CI; [0.07, 0.43] p = 0.0002; <i>I</i><sup>2</sup> = 0%). Molnupiravir effectively treats SARS-CoV-2 patients by eliminating the virus from the host.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 3","pages":"139-151"},"PeriodicalIF":2.8,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}