Macerated stillbirth

Stillbirth is defined as the birth of a viable baby without signs of life. They account for more than 2.5 million intrauterine deaths per year worldwide and are associated with a number of risk factors, the most important of which are maternal and placental factors. Autopsy provides information that may be of use in determining time since death, gestational age of the fetus, mode of death, cause of fetal demise, and the likelihood of recurrence. The format of the autopsy is guided by parental consent, but even when consent is limited, valuable information may be obtained by careful consideration of antemortem test results, imaging, and genetic testing. Where there is a delay between death and delivery, fetuses are affected by maceration, which may increase the technical complexity of the autopsy and impart a number of artefactual changes, which should not be misinterpreted as genuine pathology. The most common pathologies encountered at autopsy are placental abnormalities, changes related to maternal disorders, malformations, and central nervous system pathology. © Springer Nature Switzerland AG 2022. All rights reserved.

Quantitative proteomics and biological activity of extracellular vesicles engineered to express SARS-CoV-2 spike protein.

SARS-CoV-2 viral infection led to the devastating COVID-19 pandemic, where illness stemmed from interactions between virions and recipient host cells resulting in multi-layered pathological consequences. The role of the infection portal is now understood to be the cellular angiotensin converting enzyme-2 (ACE2) receptor, which binds to viral spike (S) protein initiating virion internalisation process. Since SARS-CoV-2 virions bear some resemblance to endogenously produced small extracellular vesicles (sEVs) we reasoned that EVs engineered to express S protein (viral mimics) may interfere with viral infection. Here, we report generation of HEK293T cells producing sEVs enriched for transmembrane S-protein tagged with green fluorescent protein (S/GFP). Strikingly, S protein drove the GFP tag to the membrane of sEVs, while GFP alone was not efficiently included in the sEV cargo. High-throughput quantitative proteomics revealed that S/GFP sEVs contained over 1000 proteins including canonical components of the exosomal pathway such as ALIX, syntenin-1, and tetraspanins (CD81, CD9), but depleted for calnexin and cytochrome c. We found that 84 sEV proteins were significantly altered by the presence of S/GFP. S protein expressing EVs efficiently adhered to target cells in an ACE2-dependent manner, but they were poorly internalised. Importantly, prolonged administration of S/GFP EV to K18-hACE2 mice provided a significant protection against SARS-CoV-2 infection. Thus, the generation of sEV containing S protein can be considered as a novel therapeutic approach in reducing the transmission of SARS-CoV-2.

A Case-Control Study of Distinguishing Between Stroke Mimics and True Strokes.

This study was conducted with the primary aim to distinguish patients with a true stroke versus a stroke mimic based on clinical features and imaging. We conducted a retrospective case-control study on 116 adult patients who received alteplase (tPA) to treat acute stroke at our hospital. We further analyzed 79 patients with a normal computed tomography angiography (CTA). Based on their magnetic resonance imaging (MRI) of the brain, they were divided into cases (stroke mimics) and controls (true strokes). Data were collected retrospectively by reviewing individual medical charts on the electronic medical record (EMR), including age, gender, history of stroke, seizure, hypertension, diabetes, atrial fibrillation, hyperlipidemia, presenting NIH Stroke Scale/Score, hemorrhagic conversion, history of migraine, history of depression, sidedness of symptoms and aphasia. Data were categorized to separate those who were later diagnosed to be stroke mimics by being-postictal, encephalopathic, in acute migraine, suffered post-stroke recrudescence (PSR) due to metabolic insult, or had conversion disorder when symptoms could not be attributed to any medical condition or mental illness. Of the 79 study subjects, 48 (60%) were stroke mimics. The mean age of the cohort was 68.67 years, and 46.8% of the study subjects were females. Based on the multivariate logistic regression analysis, factors associated with being a stroke mimic were older age, history of migraine, and a history of prior stroke. In conclusion, increased attention to history and clinical examination as the first step can aid in the proper diagnosis of strokes versus stroke mimics. Identifying stroke mimics early could help expedite hospital workup and prevent inadvertent investigations, reducing hospital occupancy during the ongoing COVID-19 pandemic. We could potentially avoid the administration of tPA to such patients, reducing both the cost and adverse effects of it. Every stroke can cause neurological deficits, but every deficit need not be a stroke.

The striking mimics between COVID-19 and malaria: A review.

Objectives: COVID-19 is a transmissible illness triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its onset in late 2019 in Wuhan city of China, it continues to spread universally, leading to an ongoing pandemic that shattered all efforts to restrain it. On the other hand, in Africa, the COVID-19 infection may be influenced by malaria coinfection. Hence, in this review article, we aimed to give a comprehensive account of the similarities between COVID-19 and malaria in terms of symptoms, clinical, immunological, and molecular perspectives. Methodology: In this article, we reviewed over 50 research papers to highlight the multilayered similarities between COVID-19 and malaria infections that might influence the ontology of COVID-19. Results: Despite the poor health and fragile medical system of many sub-Saharan African countries, they persisted with a statistically significantly low number of COVID-19 cases. This was attributed to many factors such as the young population age, the warm weather, the lack of proper diagnosis, previous infection with malaria, the use of antimalarial drugs, etc. Additionally, population genetics appears to play a significant role in shaping the COVID-19 dynamics. This is evident as recent genomic screening analyses of the angiotensin-converting enzyme 2 (ACE2) and malaria-associated-variants identified 6 candidate genes that might play a role in malaria and COVID-19 incidence and severity. Moreover, the clinical and pathological resemblances between the two diseases have made considerable confusion in the diagnosis and thereafter curb the disease in Africa. Therefore, possible similarities between the diseases in regards to the clinical, pathological, immunological, and genetical ascription were discussed. Conclusion: Understanding the dynamics of COVID-19 infection in Sub-Saharan Africa and how it is shaped by another endemic disease like malaria can provide insights into how to tailor a successful diagnostic, intervention, and control plans that lower both disease morbidity and mortality.

Smaller, Stronger, More Stable: Peptide Variants of a SARS-CoV-2 Neutralizing Miniprotein.

Based on the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, we have generated and characterized truncated peptide variants of LCB1, which present only two of the three LCB1 helices, and which fully retained the virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC). This antiviral activity was even 10-fold stronger for a cyclic variant of the two-helix peptides, as compared to the full-length peptide. Furthermore, the proteolytic stability of the cyclic peptide was substantially improved, rendering it a better potential candidate for SARS-CoV-2 therapy. In a more mechanistic approach, the peptides also served as tools to dissect the role of individual mutations in the RBD for the susceptibility of the resulting virus variants to neutralization by the peptides. As the peptides reported here were generated through chemical synthesis, rather than recombinant protein expression, they are amenable to further chemical modification, including the incorporation of a wide range of non-proteinogenic amino acids, with the aim to further stabilize the peptides against proteolytic degradation, as well as to improve the strength, as well the breadth, of their virus neutralizing capacity.

Virus-inspired surface-nanoengineered antimicrobial liposome: A potential system to simultaneously achieve high activity and selectivity.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local "burst" release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6-6.3 µg mL-1), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

Mimics of vasculitis.

While prompt diagnosis of vasculitis is important, recognition of vasculitis mimics is equally essential. As in the case of vasculitis, an approach to mimics based on the anatomic size of vessels can be useful. Infections can mimic vasculitis of any vessel size, including the formation of aneurysms and induction of ANCAs. Genetic disorders and vasculopathies are important considerations in large and medium vessel vasculitis. Cholesterol emboli, thrombotic conditions and calciphylaxis typically affect the medium and small vessels and, like vasculitis, can cause cutaneous, renal and CNS manifestations. Reversible cerebral vasoconstriction syndrome is important to distinguish from primary angiitis of the CNS. As an incorrect diagnosis of vasculitis can result in harmful consequences, it is imperative that the evaluation of suspected vasculitis includes consideration of mimics. We discuss the above mimics and outline a systematic and practical approach for differentiating vasculitis from its mimics.

Bioinspired Spiky Peroxidase-Mimics for Localized Bacterial Capture and Synergistic Catalytic Sterilization.

Besides the pandemic caused by the coronavirus outbreak, many other pathogenic microbes also pose a devastating threat to human health, for instance, pathogenic bacteria. Due to the lack of broad-spectrum antibiotics, it is urgent to develop nonantibiotic strategies to fight bacteria. Herein, inspired by the localized "capture and killing" action of bacteriophages, a virus-like peroxidase-mimic (V-POD-M) is synthesized for efficient bacterial capture (mesoporous spiky structures) and synergistic catalytic sterilization (metal-organic-framework-derived catalytic core). Experimental and theoretical calculations show that the active compound, MoO3 , can serve as a peroxo-complex-intermediate to reduce the free energy for catalyzing H2 O2 , which mainly benefits the generation of •OH radicals. The unique virus-like spikes endow the V-POD-M with fast bacterial capture and killing abilities (nearly 100% at 16 µg mL-1 ). Furthermore, the in vivo experiments show that V-POD-M possesses similar disinfection treatment and wound skin recovery efficiencies to vancomycin. It is suggested that this inexpensive, durable, and highly reactive oxygen species (ROS) catalytic active V-POD-M provides a promising broad-spectrum therapy for nonantibiotic disinfection.

Impact of Covid-19 on Stroke Code Activations, Process Metrics, and Diagnostic Error.

BACKGROUND AND PURPOSE: In a comprehensive stroke center, we analyzed the stroke code activations (SCA), assessed the impact of Covid-19, and the measures taken by the local government to lessen the spread of the disease. METHODS: We retrospectively reviewed SCA and classified them into 2 groups: pre-pandemic activations (February 15 to March 10) and Covid-19 pandemic activations (March 11 to April 30). The primary outcome was the ratio of true positive diagnoses of stroke relative to the total number of SCA in the 2 time periods. RESULTS: Among the 212 SCA, 83 (39.2%) were from the pre-pandemic period, whereas 129 (60.8%) were from the pandemic period, 147 (69.3%) in the Emergency Department (ED) versus 65 (30.7%) in the inpatient service. In the ED cohort, a rapid decrease in the number of SCA at the beginning of the pandemic was followed by a gradual increase to pre-pandemic levels and a significant increase in the number of true positive strokes over time (44.2% vs 61.1%, p = 0.037). An increase in door-to-CT time (p = 0.001) and an increase in the rate of diagnostic error in patients admitted from the ED (p = 0.016) were also seen. The in-hospital cohort had a sustained decrease in the number of SCA following the pandemic declaration, with no difference in the rate of true positive stroke. CONCLUSIONS: We observed a rapid decline and slow recovery in ED SCA with a shift toward increased true positive cases following the Covid-19 pandemic. Also, delays in obtaining CT and diagnostic error was increased, however, no difference in early clinical outcomes were seen between groups.