Interview with Mary Glick

An interview with Marie Glick regarding her experiences in a one-room school house.https://scholars.fhsu.edu/ors/1100/thumbnail.jp

Efficacy of antifungal agents against fungal spores: an in vitro study using microplate laser nephelometry and an artificially infected 3D skin model

Dermal fungal infections seem to have increased over recent years. There is further a shift from anthropophilic dermatophytes to a growing prevalence of zoophilic species and the emergence of resistant strains. New antifungals are needed to combat these fungi and their resting spores. This study aimed to investigate the sporicidal effects of sertaconazole nitrate using microplate laser nephelometry against the microconidia of Trichophyton , chlamydospores of Epidermophyton , blastospores of Candida , and conidia of the mold Scopulariopsis brevicaulis . The results obtained were compared with those from ciclopirox olamine and terbinafine. The sporicidal activity was further determined using infected three‐dimensional full skin models to determine the antifungal effects in the presence of human cells. Sertaconazole nitrate inhibited the growth of dermatophytes, molds, and yeasts. Ciclopirox olamine also had good antifungal activity, although higher concentrations were needed compared to sertaconazole nitrate. Terbinafine was highly effective against most dermatophytes, but higher concentrations were required to kill the resistant strain Trichophyton indotineae . Sertaconazole nitrate, ciclopirox olamine, and terbinafine had no negative effects on full skin models. Sertaconazole nitrate reduced the growth of fungal and yeast spores over 72 h. Ciclopirox olamine and terbinafine also inhibited the growth of dermatophytes and molds but had significantly lower effects on the yeast. Sertaconazole nitrate might have advantages over the commonly used antifungals ciclopirox olamine and terbinafine in combating resting spores, which persist in the tissues, and thus in the therapy of recurring dermatomycoses

Quantification of gold nanoparticle cell uptake under controlled biological conditions and adequate resolution

Aim: We examined cellular uptake mechanisms of fluorescently labeled polymer-coated gold nanoparticles (NPs) under different biological conditions by two quantitative, microscopic approaches. Materials & methods: Uptake mechanisms were evaluated using endocytotic inhibitors that were tested for specificity and cytotoxicity. Cellular uptake of gold NPs was analyzed either by laser scanning microscopy or transmission electron microscopy, and quantified by means of stereology using cells from the same experiment. Results: Optimal inhibitor conditions were only achieved with chlorpromazine (clathrin-mediated endocytosis) and methyl-β-cyclodextrin (caveolin-mediated endocytosis). A significant methyl-β-cyclodextrin-mediated inhibition (63–69%) and chlorpromazine-mediated increase (43–98%) of intracellular NPs was demonstrated with both imaging techniques, suggesting a predominant uptake via caveolin-medicated endocytois. Transmission electron microscopy imaging revealed more than 95% of NPs localized in intracellular vesicles and approximately 150-times more NP events/cell were detected than by laser scanning microscopy. Conclusion: We emphasize the importance of studying NP–cell interactions under controlled experimental conditions and at adequate microscopic resolution in combination with stereology

Explaining Myanmar's Regime Transition: The Periphery is Central

In 2010, Myanmar (Burma) held its first elections after 22 years of direct military rule. Few compelling explanations for this regime transition have emerged. This article critiques popular accounts and potential explanations generated by theories of authoritarian ‘regime breakdown’ and ‘regime maintenance’. It returns instead to the classical literature on military intervention and withdrawal. Military regimes, when not terminated by internal factionalism or external unrest, typically liberalise once they feel they have sufficiently addressed the crises that prompted their seizure of power. This was the case in Myanmar. The military intervened for fear that political unrest and ethnic-minority separatist insurgencies would destroy Myanmar’s always-fragile territorial integrity and sovereignty. Far from suddenly liberalising in 2010, the regime sought to create a ‘disciplined democracy’ to safeguard its preferred social and political order twice before, but was thwarted by societal opposition. Its success in 2010 stemmed from a strategy of coercive state-building and economic incorporation via ‘ceasefire capitalism’, which weakened and co-opted much of the opposition. Having altered the balance of forces in its favour, the regime felt sufficiently confident to impose its preferred settlement. However, the transition neither reflected total ‘victory’ for the military nor secured a genuine or lasting peace

Enacting a Culture of Access in Our Conference Spaces

The article offers information on periodical\u27s rhetoric and writing studies conference held in September 2020. Topics discussed include prioritizing access in the service of love, justice, connection and liberation; proposing expansive frameworks for access in designing accessible writing classrooms and professional events; and major principles of definition of access, which reflect access\u27s complexity and liberatory potential such as dynamic, relational and intersectional

FAM111A is a novel molecular marker for oocyte aging

Aging is the main cause of decline in oocyte quality, which can further trigger the failure of assisted reproductive technology (ART). Exploring age-related genes in oocytes is an important way to investigate the molecular mechanisms involved in oocyte aging. To provide novel insight into this field, we performed a pooled analysis of publicly available datasets, using the overlapping results of two statistical methods on two Gene Expression Omnibus (GEO) datasets. The methods utilized in the current study mainly include Spearman rank correlation, the Wilcoxon signed-rank test, t-tests, Venn diagrams, Gene Ontology (GO), Protein–Protein Interaction (PPI), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and receiver operating characteristic (ROC) curve analysis. We identified hundreds of age-related genes across different gene expression datasets of in vitro maturation-metaphase II (IVM-MII) oocytes. Age-related genes in IVM-MII oocytes were involved in the biological processes of cellular metabolism, DNA replication, and histone modifications. Among these age-related genes, FAM111A expression presented a robust correlation with age, seen in the results of different statistical methods and different datasets. FAM111A is associated with the processes of chromosome segregation and cell cycle regulation. Thus, this enzyme is potentially an interesting novel marker for the aging of oocytes, and warrants further mechanistic study

Comparison of efficacy in patients with metastatic melanoma treated with ipilimumab and nivolumab who did or did not discontinue treatment due to immune-related adverse events:A real-world data study

SIMPLE SUMMARY: This retrospective study of real-world patients with metastatic melanoma shows that discontinuing treatment with combination immunotherapy due to adverse events does not result in a poorer outcome compared to patients that did not discontinue due to toxicity. This is important knowledge for clinicians and patients, as discontinuing treatment may cause great anxiety for patients because they believe that it may limit the response. ABSTRACT: Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma