Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating-protein associated with synucleinopathies, including Parkinson’s disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically-relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory-effect on α-synuclein aggregation, whilst not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. Histoplasmosis is typically self-limited and presents asymptomatically in most people. Nevertheless, histoplasmosis can cause severe pulmonary disease and death. Histoplasmosis is increasingly found worldwide; however, it is best documented in the endemic region of the Mississippi river valley system in the Eastern part of the United States (US). Epidemiological studies from the US detailing the morbidity, mortality, and cost associated with histoplasmosis underscore the need to develop a vaccine. Purpose of review: This review will detail some of the major developments in potential vaccines against histoplasmosis, with particular emphasis on those that could be used to immunize immunocompromised hosts. Additionally, this review will highlight some non-traditional vaccinelike ideas for the prevention of diverse mycoses. Recent findings: Historically, immunization strategies against histoplasmosis have largely focused on identifying immunogenic proteins that confer protection in animal models. More recently, novel active, therapeutic, and immunomodulatory strategies have been explored as potential alternatives for those with various immune-deficiencies. Summary: The studies summarized in this review demonstrate that more research is needed to clarify the immunobiology, clinical role and efficacy of each candidate vaccine in the everexpanding potential armamentarium against histoplasmosis.

Ameloblastomas are benign but locally aggressive odontogenic tumors that commonly present as expansile lesions in the tooth-bearing areas. Fine-needle aspiration (FNA) biopsies of ameloblastomas are rare in clinical practice, and only a handful of case reports and series have described their cytologic features. We present the case of a 70-year-old woman with a large and disfiguring maxillary sinus soft tissue mass sampled via transcutaneous FNA. Aspirate smears were composed of small clusters of cohesive and monotonous basaloid cells. The accompanying cellblock showed similar clusters of basaloid cells in gland-like, or "adenoid," configurations, eliciting a differential diagnosis that included sinonasal and salivary gland neoplasms. Excisional surgery material was consistent with ameloblastoma with adenoid morphology.Next-generation sequencing (NGS) analysis demonstrated FGFR2 and SMO pathogenic variants. This case exemplifies several uncommonly described features of ameloblastomas in cytology, including cyto-histologic correlation, adenoid morphology, and NGS findings. Awareness of the cytologic features of this neoplasm are important for cytopathologists confronted with maxillary sinus lesions.

Auto-reactivity in COVID-19 is increasingly being recognized and may identify a group of patients with inflammation severe enough to result in loss of self-tolerance. Corticosteroids are potent anti-inflammatory agents and now the standard of care for patients with severe Covid-19 requiring oxygen support/mechanical ventilation. We studied the outcomes of COVID-19 patients who demonstrated clinically identifiable auto-reactivity and received corticosteroid treatment. In this retrospective cohort study, we included 51 COVID-19 patients admitted between March 10, 2020 and May 2, 2020 who received corticosteroid treatment and also had serum sample in our institution bio-bank available for ANA and RF ELISA. Twelve patients (23.5%) had positive ANA or RF. Mortality rate among patients with positive autoantibodies was significantly higher than those without (9/12 or 75% versus 13/39 or 33.3%, p= 0.02). The high mortality rate in patients with auto-reactivity warrants further investigation and may be the subgroup where additional immunomodulation is effective.

The rationale of Convalescent Plasma (CP) is to provide passive immunity to acutely ill COVID-19 patients. However, there are other pathologies of COVID disease that may be alleviated by CP. COVID-19 coagulopathy has been hypothesized to be a form of disseminated intravascular coagulopathy, a type of thrombotic microangiopathy. Complement activation has also been implicated in COVID-19 coagulopathy. An alternative hypothesis for additional benefits of CP is replacement of inhibitors of complements. C1-esterase inhibitor (C1-INH) is a major regulator of complement activation. We hypothesized that COVID-19 patients have decreased C1-INH and that CP transfusion would restore intravascular C1-INH and complement levels. We studied serial C1-INH and complement levels in COVID-19 patients before and after CP transfusion (200 mL) and their association with overall mortality. Methods: We identified COVID-19 patients (n=91) that received CP within the first 72 hours after admission. We collected serum and/or plasma samples at day prior and post-day 1, 3, and 10. C1 inhibitor, C3 and C4 were tested in these samples as well as in the respective CP unit given to each patient. Results: C1-INH levels day before transfusion were increased in COVID-19 patients (201.5% +/- 53%) in comparison to CP (93.2% +/- 26.2%). C1-INH transiently increased post CP transfusion and remained relatively high through day 10. No statistical difference was observed in C1-INH between survivors (n=53) and non-survivors (n=39) at any time point before or after transfusion. C3 was higher in COVID-19 patients in comparison to CP (161.5 +/-47.0 vs. 89.6 +/-15.3 mg/dL). However, C3 levels were significantly lower in non-survivors compared to survivors the day before transfusion (131.9 +/- 38.0 vs. 180.9 +/- 45.1 mg/dL, p=2.8E-06). Following transfusion, C3 levels decreased and remained steady afterwards; at all subsequent time points C3 levels were significantly lower in non-survivors compared to survivors (post-day 1: 130.6+/- 33.0 vs. 158.5 +/- 51.5 mg/dL, p=0.006; post-day 3: 116.6+/-46.5 vs. 146.2+/-42.8 mg/dL, p=0.01; post-day 10: 120.8+/-40.9 vs. 150.3+/- 45.9 mg/dL, p=0.03). C4 levels trended lower in non-survivors compared to survivors the day before transfusion (30.8+/- 15.3 vs. 37.9 +/- 16.7 mg/dL, p=0.08). The day following CP, there was a significant decrease in C4 across the entire cohort (35.1+/- 16.4 vs. 27.9+/- 18.3 mg/dL, p=0.01); subsequent levels remained steady. In conclusion, a single CP transfusion does not appear to restore C1-INH, C3 and C4 levels in hospitalized COVID-19 patients. CP transfusion is associated with a transient increase in C1-INH and decreasing C3 and C4 levels. Contrary to our hypothesis, C1-INH levels are increased in COVID-19 patients. The relationship between C1-INH and complements in COVID-19 remains to be fully elucidated. Prospective studies are needed to further delineate these relationships especially in the context of ongoing clinical trials of recombinant C1-INH in COVID-19 patients.