Coping While Black: Comparing Coping Strategies Across COVID-19 and the Killing of Black People.

In the same year the world was thrown into turmoil with COVID-19, the USA also experienced a surge in attention given to the plight of Black people in the policing system, following the killing of George Floyd. Both the COVID-19 pandemic and the ongoing "pandemic" of police and White violence against Black people in the USA cause significant amounts of stress, disproportionately affecting Black people. Utilizing qualitative analysis of responses from 128 Black-identifying participants to an online survey, this investigation seeks to understand how the coping strategies of Black people in the USA compare between the racism-related stressor of police killings of Black people and the generalized stressor of the COVID-19 pandemic. Findings demonstrate that while Black people use overlapping strategies to deal with stress, clear patterns exist with regard to differences across racism-related and non-racism-related stressors. We report important implications for understanding the impact of COVID-19 on Black people, cultural understandings of research on coping, and Black mental health more broadly.

Biofluorescent sexual dimorphism revealed in a southern Appalachian endemic salamander, Plethodon metcalfi.

Biofluorescence occurs when a living organism absorbs high energy light and reemits it at longer wavelengths. Many species within clades of vertebrates are known to fluoresce including mammals, reptiles, birds, and fish. Most, if not all, amphibians exhibit biofluorescence when exposed to either blue (440-460 nm) or ultra-violet (360-380 nm) wavelengths of light. Salamanders (Lissamphibia: Caudata) appear to consistently fluoresce in green wavelengths (520-560 nm) when excited by blue light. Biofluorescence is theorized to have many ecological functions including mate signaling, camouflage, and mimicry. Despite the discovery of their biofluorescence, its role in salamander ecology and behavior remains unresolved. In this study we present the first case of biofluorescent sexual dimorphism within Amphibia and the first documentation of the biofluorescent pattern of a salamander within the Plethodon jordani species complex. This sexually dimorphic trait was discovered in the southern Appalachian endemic species, Southern Gray-Cheeked Salamander (Plethodon metcalfi, Brimley in Proc Biol Soc Wash 25:135-140, 1912), and may extend into other species within the Plethodon jordani and Plethodon glutinosus species complexes. We propose that this sexually dimorphic trait could be related to fluorescence of ventral modified granular glands used in plethodontid chemosensory communication.

An Examination of Discrimination on Stress, Depression, and Oppression-Based Trauma During the COVID-19 Pandemic and the Racial Awakening of 2020.

Background: Discrimination is a pervasive societal issue that monumentally impacts people of color (POC). Many Black, Asian, and Hispanic/Latinx individuals report experiencing race-based discrimination in their lifetime. Discrimination has previously been linked to adverse health outcomes among POC, including stress, depressive, and posttraumatic stress disorder symptoms. These health disparities are posited to have become exacerbated by COVID-19 and the racial awakening of 2020. The current study examined the short- and long-term effects of discrimination on stress, depression, and oppression-based trauma among POC. Methods: Participants were (n = 398) who identified as Black, Indigenous, Hispanic/Latinx, and Asian completed an online self-report survey assessing discrimination, depression, stress, and oppression-based trauma collected at 3 time points: (T1) beginning of the COVID-19 pandemic (May 2020), (T2) 6 weeks later during the racial awakening of 2020 (June 2020), (T3) one year later (June 2021). Results: Significant positive paths were revealed from T1 discrimination to T2 depression, T2 stress, and T3 oppression-based trauma. The association between T1 discrimination and T3 oppression-based trauma was partially mediated by T2 depression, but not by stress; total and total indirect effects remained significant. The final model accounted for a significant proportion of the variance in T3 oppression-based trauma, T2 depression, and T2 stress. Conclusion: Findings are consistent with prior research linking discriminatory experiences with mental health symptomatology and provide evidence that race-based discrimination poses harmful short-and long-term mental health consequences. Further research is necessary to better understand oppression-based trauma to improve the accuracy of clinical diagnosis and treatment of POC.

Manuka honey in combination with azithromycin shows potential for improved activity against Mycobacterium abscessus.

Mycobacterium abscessus is an increasingly prevalent opportunistic pathogen causing both pulmonary and skin and soft tissue infections. It is of increasing concern for immunocompromised individuals, such as those with cystic fibrosis, due to its highly drug resistant nature and ability to evade the host immune system. Current treatments for M. abscessus pulmonary infections are largely ineffective and treatment outcomes are generally poor, thus we urgently require new treatments to combat these infections. Recently, it has been demonstrated that manuka honey is effective against M. abscessus and can improve the inhibitory effect of amikacin. Here, we explore the potential improvement of both azithromycin and tobramycin with the addition of manuka honey against M. abscessus complex. Improved growth inhibition was observed for azithromycin with manuka honey against all M. abscessus subspecies. Improved bactericidal activity was also observed. Importantly, the macrolide resistant M. abscessus subsp. bolletii showed improved inhibition and bactericidal activity was obtained in response to 0.117 g/mL manuka honey MGO40 with 16 µg/mL azithromycin. No improved activity was observed for tobramycin and manuka honey against any of the M. abscessus isolates tested. This demonstrates the potential for antibiotic enhancement by the addition of manuka honey, furthering the applications of therapeutic manuka honey.

In vitro synergy between manuka honey and amikacin against Mycobacterium abscessus complex shows potential for nebulisation therapy.

Mycobacterium abscessusis an opportunistic human pathogen of increasing concern, due to its ability to cause aggressive pulmonary infections (especially in cystic fibrosis patients), as well as skin and soft tissue infections. M. abscessus is intrinsically drug resistant and treatment regimens are lengthy, consisting of multiple antibiotics with severe side effects and poor patient success rates. New and novel strategies are urgently required to combat these infections. One such strategy thus far overlooked for mycobacteria is manuka honey. For millennia manuka honey has been shown to have wide ranging medicinal properties, which have more recently been identified for its broad spectrum of antimicrobial activity. Here we demonstrate that manuka honey can be used to inhibit M. abscessus and a variety of drug resistant clinical isolates in vitro. We also demonstrate using a microbroth dilution checkerboard assay that manuka honey works synergistically with amikacin, which is one of the current front line antibiotics used for treatment of M. abscessus infections. This was further validated using an in vitro inhalation model, where we showed that with the addition of manuka honey, the amikacin dosage can be lowered whilst increasing its efficacy. These findings demonstrate the utility of manuka honey for incorporation into nebulised antibiotic treatment for respiratory infections, in particular M. abscessus. These results pave the way for a change of strategy for M. abscessus management, offering new therapeutic options for this deadly infection.

Indole-containing arene-ruthenium complexes with broad spectrum activity against antibiotic-resistant bacteria.

Antimicrobial resistant (AMR) bacteria are emerging and spreading globally, threatening our ability to treat common infectious diseases. The development of new classes of antibiotics able to kill or inhibit the growth of such AMR bacteria through novel mechanisms of action is therefore urgently needed. Here, a new family of indole-containing arene ruthenium organometallic compounds are screened against several bacterial species and drug resistant strains. The most active complex [(p-cym)Ru(O-cyclohexyl-1H-indole-2-carbothioate)Cl] (3) shows growth inhibition and bactericidal activity against different organisms (Acinetobacter baumannii, Mycobacterium abscessus, Mycobacterium tuberculosis, Staphylococcus aureus, Salmonella enterica serovar Typhi and Escherichia coli), demonstrating broad-spectrum inhibitory activity. Importantly, this compound series exhibits low toxicity against human cells. Owing to the novelty of the antibiotic family, their moderate cytotoxicity, and their inhibitory activity against Gram positive, Gram negative and acid-fast, antibiotic resistant microorganisms, this series shows significant promise for further development.

Cholesterol-dependent activity of dapsone against non-replicating persistent mycobacteria.

One-third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis. This reservoir of bacteria is largely resistant to antimicrobial treatment that often only targets actively replicating mycobacteria, with current treatment for latent infection revolving around inhibiting the resuscitation event rather than preventing or treating latent infection. As a result, antimicrobials that target latent infection often have little to no activity in vivo. Here we report a method of in vitro analysis of physiologically relevant non-replicating persistence (NRP) utilizing cholesterol as the sole carbon source, alongside hypoxia as a driver of Mycobacterium bovis BCG into the NRP state. Using the minimal cholesterol media NRP assay, we observed an increased state of in vitro resistance to front-line anti-tubercular compounds. However, following a phenotypic screen of an approved-drug library, we identified dapsone as a bactericidal active molecule against cholesterol-dependent NRP M. bovis BCG. Through an overexpression trial of probable antimicrobial target enzymes, we further identified FolP2, a non-functional dihydropteroate synthase homologue, as the likely target of dapsone under cholesterol-NRP due to a significant increase in bacterial resistance when overexpressed. These results highlight the possible reason for little in vivo activity seen for current front-line anti-NRP drugs, and we introduce a new methodology for future drug screening as well as a potential role for dapsone inclusion within the current treatment regime.

An Investigation of Associations Between Race, Ethnicity, and Past Experiences of Discrimination with Medical Mistrust and COVID-19 Protective Strategies.

This study investigates the associations between three forms of discrimination, race and ethnicity, general medical mistrust, health-specific COVID-19 conspiracy beliefs, and adherence to COVID-19 protective behaviors. Participants (n = 963) completed an online survey during May 2020, when stay-at-home orders and other government mandates were implemented in many states. Results indicate that everyday discrimination and healthcare discrimination were associated with significantly higher general medical mistrust, and healthcare discrimination and structural discrimination were associated with higher endorsement of health-specific COVID-19 conspiracy beliefs. Higher endorsement of health-specific COVID-19 conspiracy beliefs, but not general medical mistrust, was associated with significantly lower engagement in health-specific COVID-19 conspiracy beliefs. This study helps to contextualize racial health disparities during the COVID-19 pandemic and the widespread impact of everyday, structural, and healthcare discrimination in society.

Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery.

Tuberculosis (TB) remains a global healthcare crisis, with an estimated 5.8 million new cases and 1.5 million deaths in 2020. TB is caused by infection with the major human pathogen Mycobacterium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models that capably mimic all physiological conditions of the infection, and high-throughput drug screening platforms. Microfluidic-based techniques provide single-cell analysis which reduces experimental time and the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review outlines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculosis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB.

In vitro efficacy of relebactam versus avibactam against Mycobacterium abscessus complex.

Infections resulting from Mycobacterium abscessus are increasing in prevalence worldwide, with the greatest risk posed to patients with underlying respiratory conditions. Treatment for infections is difficult due to wide ranging intrinsic antimicrobial resistance, which is compounded by the existence of a range of subspecies within the M. abscessus complex, each with varying additional antimicrobial resistance profiles. Previously, the use of ß-lactam/ß-lactamase inhibitors within a combination therapy has been proposed as an effective treatment option for pulmonary M. abscessus infections. Here, we assess the in vitro efficacy of two non-ß-lactam based inhibitors, relebactam and avibactam, as agents against M. abscessus with their respective partner drugs imipenem and ceftazidime, as well as in triplicate combinations with additional ß-lactam antibiotics against the M. abscessus complex. We have shown that the commercially available ratio of imipenem to relebactam is the appropriate ratio for bactericidal activity against M. abscessus, whereas the ratio between ceftazidime and avibactam is redundant, due to inactivity of ceftazidime to inhibit the bacteria. We have identified that the use of imipenem and meropenem alongside either relebactam or avibactam yield low minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for each M. abscessus subspecies, which are within the therapeutically achievable concentration ranges within the epithelial lining fluid of the lungs. We propose the implementation of imipenem with relebactam in place of stand-alone imipenem into the current treatment regime, alongside meropenem, as a future front-line treatment option for M. abscessus complex infections.

Drug Susceptibility Screening Using In Vitro Models of Hypoxic Non-Replicating Persistent Mycobacteria.

Non-replicating persistence (NRP) is a functional adaptation that mycobacteria undergo in response to the stresses of the granuloma, facilitating antibiotic tolerance and long-term infection. These stresses, or NRP-inducing factors, include hypoxia, nutrient deprivation, and nitric oxide assault, which mycobacteria are well evolved to tolerate through a series of metabolic and physiological adaptations producing the NRP state. Most attempts to replicate these conditions in vitro have focused on only one of these factors at a time for ease and simplicity, but as a result, do not necessarily produce physiologically relevant phenotypes. Here, we provide the methods for two different in vitro NRP strategies that are useful for drug susceptibility testing and high-throughput screening.

Olfactory flow in the sea catfish, Ariopsis felis (L.): Origin, regulation, and resampling.

The olfactory epithelium of the sea catfish, Ariopsis felis, is found on a pinnate array of lamellae (the olfactory rosette) housed within a nasal chamber. The nasal anatomy of A. felis suggests an ability to capture external water currents. We prepared models from X-ray micro-computed tomography scans of two preserved specimens of A. felis. We then used dye visualisation and computational fluid dynamics to show that an external current induced a flow of water through a) the nasal chamber and b) the sensory channels of the olfactory rosette. The factors responsible for inducing flow through the nasal chamber are common to fishes from two other orders. The dye visualisation experiments, together with observations of sea catfishes in vivo, indicate that flow through the nasal chamber is regulated by a mobile nasal flap. The position of the nasal flap - elevated (significant flow) or depressed (reduced flow) - is controlled by the sea catfish's movements. Flow in the sensory channels of the olfactory rosette can pass through either a single channel or, via multiple pathways, up to four consecutive channels. Flow through consecutive sensory channels (olfactory resampling) is more extensive at lower Reynolds numbers (200 and 300, equivalent to swimming speeds of 0.5-1.0 total lengths s-1), coinciding with the mean swimming speed of the sea catfishes observed in vivo (0.6 total lengths s-1). Olfactory resampling may also occur, via a vortex, within single sensory channels. In conclusion, olfactory flow in the sea catfish is regulated and thoroughly sampled by novel mechanisms.

Improving Undergraduate Epidemiology Education: An Example Using Instructional Teams.

Epidemiology is a core component of the undergraduate public health curriculum and a critical component of a healthy community and a comprehensive education. Evidence-based, collaborative instructional practices improve student success, reach diverse student populations, and improve learning outcomes. Here we describe the pedagogical approach of an instructional team with which we observed an 18% greater learning gain (95% confidence interval: 6.5, 29.5; t = -3.08; P = 0.002), based on pre-/posttesting in a large (approximately 120 students) undergraduate course, than with the prior course offering. There were no differences in DEW rates (defined as receiving a grade of D (scoring 60%-69%) or E (scoring <60%) or withdrawing (W)) between the 2 offerings, but the ratio of "A" to "B" grades was higher (by approximately 10%) after deployment of the instructional team (Pearson's χ2 (1 degree of freedom) = 4.17, P = 0.041). In addition, students reported greater satisfaction with the course deploying an instructional team (80.4% positive sentiment in course evaluation comments compared with 76.1% in the prior offering). As students and faculty become more familiar with effective evidence-based instructional practices, improvements in student learning can be achieved and the goal of creating an educated citizenry ready to build a healthy society will be more attainable.

Clinical Significance of Manuka and Medical-Grade Honey for Antibiotic-Resistant Infections: A Systematic Review.

Antimicrobial resistance is an ever-increasing global issue that has the potential to overtake cancer as the leading cause of death worldwide by 2050. With the passing of the "golden age" of antibiotic discovery, identifying alternative treatments to commonly used antimicrobials is more important than ever. Honey has been used as a topical wound treatment for millennia and more recently has been formulated into a series of medical-grade honeys for use primarily for wound and burn treatment. In this systematic review, we examined the effectiveness of differing honeys as an antimicrobial treatment against a variety of multidrug-resistant (MDR) bacterial species. We analysed 16 original research articles that included a total of 18 different types of honey against 32 different bacterial species, including numerous MDR strains. We identified that Surgihoney was the most effective honey, displaying minimum inhibitory concentrations as low as 0.1% (w/v); however, all honeys reviewed showed a high efficacy against most bacterial species analysed. Importantly, the MDR status of each bacterial strain had no impact on the susceptibility of the organism to honey. Hence, the use of honey as an antimicrobial therapy should be considered as an alternative approach for the treatment of antibiotic-resistant infections.

Development of a novel secondary phenotypic screen to identify hits within the mycobacterial protein synthesis pipeline.

BACKGROUND: Whole-cell phenotypic screening is the driving force behind modern anti-tubercular drug discovery efforts. Focus has shifted from screening for bactericidal scaffolds to screens incorporating target deconvolution. Target-based screening aims to direct drug discovery toward known effective targets and avoid investing resources into unproductive lines of enquiry. The protein synthesis pipeline, including RNA polymerase and the ribosome, is a clinically proven target in Mycobacterium tuberculosis. Screening for new hits of this effective target pathway is an invaluable tool in the drug discovery arsenal. METHODS: Using M. tuberculosis H37Rv augmented with anhydrotetracycline-inducible expression of mCherry, a phenotypic screen was developed for the identification of protein synthesis inhibitors in a medium throughput screening format. RESULTS: The assay was validated using known inhibitors of protein synthesis to show a dose-dependent reduction in mCherry fluorescence. This was expanded to a proprietary screen of hypothetical protein synthesis hits and modified to include quantitative viability measurement of cells using resazurin. CONCLUSION: Following the success of the proprietary screen, a larger scale screen of the GlaxoSmithKline anti-tubercular library containing 2799 compounds was conducted. Combined single shot and dose-response screening yielded 18 hits, 0.64% of all screened compounds.

Looking good but feeling bad: "Camouflaging" behaviors and mental health in women with autistic traits.

LAY ABSTRACT: Women who try to hide or "camouflage" their autistic traits are likely to report that they feel distressed, think of suicide, and/or struggle to function in everyday life. We asked 58 women with autistic traits to complete questionnaires about camouflaging and mental health. Most of these women did not have a formal diagnosis of autism, yet a majority reported that they camouflaged autistic traits, and a large majority reported significant mental health challenges. Some researchers have suggested that women with autistic traits are more likely than autistic men to experience mental health challenges because women may try more to "fit in" socially by camouflaging their autistic traits. Analyses showed that camouflaging was associated with feeling distressed (depressed, anxious, and/or stressed). For women who reported above-average levels of camouflaging, camouflaging was also associated with having thoughts about suicide and struggling to function in everyday life. Trying to camouflage autistic traits was associated with mental health challenges, regardless of whether those traits were very mild or more severe. The findings of this study may influence how mental health professionals evaluate and treat women with autistic traits.

The functional nasal anatomy of the pike, Esox lucius L.

Olfactory flow in fishes is a little-explored area of fundamental and applied importance. We investigated olfactory flow in the pike, Esox lucius, because it has an apparently simple and rigid nasal region. We characterised olfactory flow by dye visualisation and computational fluid dynamics, using models derived from X-ray micro-computed tomography scans of two preserved specimens. An external current induced a flow of water through the nasal chamber at physiologically relevant Reynolds numbers (200-300). We attribute this externally-induced flow to: the location of the incurrent nostril in a region of high static pressure; the nasal bridge deflecting external flow into the nasal chamber; an excurrent nostril normal to external flow; and viscous entrainment. A vortex in the incurrent nostril may be instrumental in viscous entrainment. Flow was dispersed over the olfactory sensory surface when it impacted on the floor of the nasal chamber. Dispersal may be assisted by: the radial array of nasal folds; a complementary interaction between a posterior nasal fold and the ventral surface of the nasal bridge; and the incurrent vortex. The boundary layer could delay considerably (up to ~ 3 s) odorant transport from the external environment to the nasal region. The drag incurred by olfactory flow was almost the same as the drag incurred by models in which the nasal region had been replaced by a smooth surface. The boundary layer does not detach from the nasal region. We conclude that the nasal bridge and the incurrent vortex are pivotal to olfaction in the pike.