Pulmonary Co-Infections Detected Premortem Underestimate Postmortem Findings in a COVID-19 Autopsy Case Series.

Bacterial and fungal co-infections are reported complications of coronavirus disease 2019 (COVID-19) in critically ill patients but may go unrecognized premortem due to diagnostic limitations. We compared the premortem with the postmortem detection of pulmonary co-infections in 55 fatal COVID-19 cases from March 2020 to March 2021. The concordance in the premortem versus the postmortem diagnoses and the pathogen identification were evaluated. Premortem pulmonary co-infections were extracted from medical charts while applying standard diagnostic definitions. Postmortem co-infection was defined by compatible lung histopathology with or without the detection of an organism in tissue by bacterial or fungal staining, or polymerase chain reaction (PCR) with broad-range bacterial and fungal primers. Pulmonary co-infection was detected premortem in significantly fewer cases (15/55, 27%) than were detected postmortem (36/55, 65%; p < 0.0001). Among cases in which co-infection was detected postmortem by histopathology, an organism was identified in 27/36 (75%) of cases. Pseudomonas, Enterobacterales, and Staphylococcus aureus were the most frequently identified bacteria both premortem and postmortem. Invasive pulmonary fungal infection was detected in five cases postmortem, but in no cases premortem. According to the univariate analyses, the patients with undiagnosed pulmonary co-infection had significantly shorter hospital (p = 0.0012) and intensive care unit (p = 0.0006) stays and significantly fewer extra-pulmonary infections (p = 0.0021). Bacterial and fungal pulmonary co-infection are under-recognized complications in critically ill patients with COVID-19.

Predictors of COVID-19 Vaccine Uptake and Reasons for Vaccine Hesitancy Among New York State Refugees.

PURPOSE: Resettled refugees in the U.S. face a disproportionately high risk of COVID-19 exposure, infection, and death. This study examines COVID-19 vaccination status among adult participants and their minor children, reasons for vaccine hesitancy, and predictors of vaccine uptake, as well as sources of COVID-19 news and information and trust in those sources. METHOD: The data in this study were drawn from the Telehealth and COVID-19 Knowledge, Attitudes, and Practices in New York Refugee Communities Survey (N = 353), conducted March-May, 2022. RESULTS: The multivariate results indicate that in this sample of resettled refugees, those who reported higher levels of educational attainment, were from Afghanistan, and those who had fewer concerns about the vaccine were more likely to accept vaccination. The participants in this study identified local health workers, clinics, and community organizations - places where social workers are present - as both the largest source of nonsocial media COVID-19 news and information and the most trusted source of COVID-19 news and information. DISCUSSION: The implications from this study provide social workers with an understanding of the social and behavioral factors impacting vaccine uptake in refugee communities. CONCLUSION: According to the NASW Code of Ethics, social workers must challenge inequalities that persist against marginalized groups, such as racial and ethnic health disparities. Social work practitioners can play an essential role in decreasing unjust health disparities by providing accurate, culturally appropriate information on public health concerns such as COVID-19 to their refugee clients and within interprofessional collaboration.

Advancing Community-Based Participatory Research During the COVID-19 Pandemic: A Methods Commentary on the Lessons Learned from Working with Community Data Collectors on a Refugee Health Disparities Study.

This methods commentary focuses on lessons learned from working with community data collectors on a refugee health disparities study during the COVID-19 pandemic. While there is a strong literature base for community health workers in refugee or migrant communities, there is less known about the procedural elements, challenges, and effectiveness of using community data collectors (CDCs) in research with refugee or migrant communities. Recognizing the cultural wealth and unique strengths of local stakeholders in the refugee community, the research team employed a robust collaborative approach by partnering with CDCs to design and administer the Telehealth and COVID-19 Knowledge, Attitudes, and Practices in New York Refugee Communities Survey. The study's success was largely due to the CDC partnership. This methods commentary highlights the utility of Community-Based Participatory Research as a culturally-responsive framework well-suited to exploring health disparities as part of a broader agenda of public health communication research.

Essential but Excluded: Using Critical Race Theory to Examine COVID-19 Economic Relief Policies for Undocumented US Workers.

Following the onset of the COVID-19 pandemic, undocumented immigrants in the United States were vulnerable both to unemployment and to COVID-19 infection if they did remain employed, because of the sectors that employ them. Despite these heightened economic vulnerabilities, 7.8 million undocumented workers were excluded from federal economic relief policies. This article uses critical race theory (CRT) to examine the intentional and unjust exclusion of undocumented U.S. workers from COVID-19 economic relief aid within the larger context of economic marginalization and injustice. It also provides an overview of the major federal economic relief legislation and policy developments during the first year of the COVID-19 pandemic in the United States, between March 2020 and July 2021. While some states have enacted creative programs and policies related to COVID-19 economic relief, effective and comprehensive federal-level policies must be implemented to address the growing chasm of inequity in American society, particularly as experienced by often-essential undocumented immigrant workers. Specific standards related to work and quality of live are protected by the United Nations Universal Declaration of Human Rights (1948), but exclusionary federal policies render these minimum standards inaccessible for undocumented workers and deepen existing economic and social disparities. Social work aspires to provide a uniquely critical and social justice-minded perspective that considers systems of oppression, power dynamics, and human rights, and this perspective can contribute to socially just economic policy development.

A Disfiguring Rash.

Patients with rheumatologic conditions can have complex dermatologic manifestations. In addition, immunosuppressing treatment for autoimmune disorders can also increase incidence of infectious complications. Skin conditions in rheumatologic patients present particular challenges and this case highlights a rare infectious complication.

HIV-1 Engages a Dynein-Dynactin-BICD2 Complex for Infection and Transport to the Nucleus.

Human immunodeficiency virus type 1 (HIV-1) infection depends on efficient intracytoplasmic transport of the incoming viral core to the target cell nucleus. Evidence suggests that this movement is facilitated by the microtubule motor dynein, a large multiprotein complex that interacts with dynactin and cargo-specific adaptor proteins for retrograde movement via microtubules. Dynein adaptor proteins are necessary for activating dynein movement and for linking specific cargoes to dynein. We hypothesized that HIV-1 engages the dynein motor complex via an adaptor for intracellular transport. Here, we show that small interfering RNA depletion of the dynein heavy chain, components of the dynactin complex, and the dynein adaptor BICD2 reduced cell permissiveness to HIV-1 infection. Cell depletion of dynein heavy chain and BICD2 resulted in impaired HIV-1 DNA accumulation in the nucleus and decreased retrograde movement of the virus. Biochemical studies revealed that dynein components and BICD2 associate with capsid-like assemblies of the HIV-1 CA protein in cell extracts and that purified recombinant BICD2 binds to CA assemblies in vitro Association of dynein with CA assemblies was reduced upon immunodepletion of BICD2 from cell extracts. We conclude that BICD2 is a capsid-associated dynein adaptor utilized by HIV-1 for transport to the nucleus.IMPORTANCE During HIV-1 infection, the virus must travel across the cytoplasm to enter the nucleus. The host cell motor protein complex dynein has been implicated in HIV-1 intracellular transport. We show that expression of the dynein heavy chain, components of the dynein-associated dynactin complex, and the dynein adaptor BICD2 in target cells are important for HIV-1 infection and nuclear entry. BICD2 interacts with the HIV-1 capsid in vitro, suggesting that it functions as a capsid-specific adaptor for HIV-1 intracellular transport. Our work identifies specific host proteins involved in microtubule-dependent HIV-1 intracellular transport and highlights the BICD2-capsid interaction as a potential target for antiviral therapy.

A comparison of single quadrupole mass detection and diode array ultraviolet detection interfaced to ultra-high performance supercritical chromatography for the quantitative analysis of synthetic cathinones.

A comparison of single quadruple mass spectrometry and diode array-ultraviolet (PDA-UV) detection interfaced to ultra-high performance supercritical fluid chromatography was performed for the quantitative analysis of synthetic cathinones. Synthetic cathinones, also known as "bath salts", are derived from cathinone, a component of the khat plant. For 15 controlled solutes linearity, repeatability, and limits of detection were determined using both UV and MS detection. Quantitation studies were performed using the above detectors for 19 mixtures of up to 4 of the above compounds with an adulterant to simulate seized samples. MS detection provided approximately an order of magnitude greater linearity range and allowed for two to three orders of magnitude lower limits of detection than UV detection. Both detection techniques exhibited similar results of analysis and comparable repeatability. The latter detection mode which provided significantly high linearity correlation coefficients (0.9994 ≤ R2 ≤ 1.0000) would be preferred for quantitative analysis.

Inhibitors of the HIV-1 capsid, a target of opportunity.

PURPOSE OF REVIEW: To summarize recent advances in the discovery of chemical inhibitors targeting the HIV capsid and research on their mechanisms of action. RECENT FINDINGS: HIV infection is critically dependent on functions of the viral capsid. Numerous studies have reported the identification of a variety of compounds that bind to the capsid protein; some of these inhibit reverse transcription and nuclear entry, steps required for infection. Other capsid-targeting compounds appear to act by perturbing capsid assembly, resulting in noninfectious progeny virions. Inhibitors may bind to several different positions on the capsid protein, including sites in both protein domains. However, the antiviral activity of many reported capsid-targeting inhibitors has not been definitively linked to capsid binding. Until recently, the low-to-moderate potency of reported capsid-targeting inhibitors has precluded their further clinical development. In 2017, GS-CA1, a highly potent capsid inhibitor, was described that holds promise for clinical development. SUMMARY: Small molecules that bind to the viral capsid protein can be potent inhibitors of HIV infection. Capsid-targeting drugs are predicted to exhibit high barriers to viral resistance, and ongoing work in this area is contributing to an understanding of the molecular biology of HIV uncoating and maturation.

Comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones.

A comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones has been conducted. Nine different mixtures of bath salts were analyzed in this study. The three different chromatographic techniques were examined using a general set of controlled synthetic cathinones as well as a variety of other synthetic cathinones that exist as positional isomers. Overall 35 different synthetic cathinones were analyzed. A variety of column types and chromatographic modes were examined for developing each separation. For the ultra high performance supercritical fluid chromatography separations, analyses were performed using a series of Torus and Trefoil columns with either ammonium formate or ammonium hydroxide as additives, and methanol, ethanol or isopropanol organic solvents as modifiers. Ultra high performance liquid chromatographic separations were performed in both reversed phase and hydrophilic interaction chromatographic modes using SPP C18 and SPP HILIC columns. Gas chromatography separations were performed using an Elite-5MS capillary column. The orthogonality of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography was examined using principal component analysis. For the best overall separation of synthetic cathinones, the use of ultra high performance supercritical fluid chromatography in combination with gas chromatography is recommended.

The role of diode array ultraviolet detection for the identification of synthetic cathinones.

The utility of diode array ultraviolet (UV) detection for aiding in the identification of synthetic cathinones, including different sub-classes and positional isomers is presented. For 35 synthetic cathinones, unique UV spectra are obtained for seven sub-classes, including mostly beta ketones, where position and type of substitution on benzene rings give rise to differences in UV maxima and relative intensity of the spectral bands. This aspect is key to distinguishing positional isomers that contain differences in R substitution (mono and di) around the benzene ring, which provides complementary information to electron ionization mass spectrometry, where the latter technique cannot distinguish between these types of positional isomers. In addition, it is possible to ascertain the substitution position based on the UV spectra. For ten sets of positional isomers, it was possible to distinguish most of the positional isomers within a set. For ultra-high performance supercritical fluid chromatography (UHPSFC) versus reversed phase ultra-high performance liquid chromatography (UHPLC), there was at least a 10 nm blue shift in UV maximum (shift to shorter wavelengths). This highlights the importance of taking in account the effect of mobile phase on the UV maximum when performing method development in UHPSFC. Copyright © 2017 John Wiley & Sons, Ltd.

The far C-terminus of MCAK regulates its conformation and spindle pole focusing.

To ensure proper spindle assembly, microtubule (MT) dynamics needs to be spatially regulated within the cell. The kinesin-13 MCAK is a potent MT depolymerase with a complex subcellular localization, yet how MCAK spatial regulation contributes to spindle assembly is not understood. Here we show that the far C-terminus of MCAK plays a critical role in regulating MCAK conformation, subspindle localization, and spindle assembly in Xenopus egg extracts. Alteration of MCAK conformation by the point mutation E715A/E716A in the far C-terminus increased MCAK targeting to the poles and reduced MT lifetimes, which induced spindles with unfocused poles. These effects were phenocopied by the Aurora A phosphomimetic mutation, S719E. Furthermore, addition of the kinesin-14 XCTK2 to spindle assembly reactions rescued the unfocused-pole phenotype. Collectively our work shows how the regional targeting of MCAK regulates MT dynamics, highlighting the idea that multiple phosphorylation pathways of MCAK cooperate to spatially control MT dynamics to maintain spindle architecture.

Aurora B inhibits MCAK activity through a phosphoconformational switch that reduces microtubule association.

BACKGROUND: Proper spindle assembly and chromosome segregation rely on precise microtubule dynamics, which are governed in part by the kinesin-13 MCAK. MCAK microtubule depolymerization activity is inhibited by Aurora B-dependent phosphorylation, but the mechanism of this inhibition is not understood. RESULTS: Here, we develop the first Förster resonance energy transfer (FRET)-based biosensor for MCAK and show that MCAK in solution exists in a closed conformation mediated by an interaction between the C-terminal domain (CT) and the neck. Using fluorescence lifetime imaging (FLIM) we show that MCAK bound to microtubule ends is closed relative to MCAK associated with the microtubule lattice. Aurora B phosphorylation at S196 in the neck opens MCAK conformation and diminishes the interaction between the CT and the neck. Using FLIM and TIRF imaging, we find that changes in MCAK conformation are associated with a decrease in MCAK affinity for the microtubule. CONCLUSIONS: Unlike motile kinesins, which are open when doing work, the high-affinity binding state for microtubule-depolymerizing kinesins is in a closed conformation. Phosphorylation switches MCAK conformation, which inhibits its ability to interact with microtubules and reduces its microtubule depolymerization activity. This work shows that the conformational model proposed for regulating kinesin activity is not universal and that microtubule-depolymerizing kinesins utilize a distinct conformational mode to regulate affinity for the microtubule, thus controlling their catalytic efficiency. Furthermore, our work provides a mechanism by which the robust microtubule depolymerization activity of kinesin-13s can be rapidly modulated to control cellular microtubule dynamics.