"I Have to Ask": A Mixed-Methods Study on the Collection of Sexual Orientation and Gender Identity Data Within the San Francisco County COVID-19 Case Investigation and Contact Tracing Program.

OBJECTIVE: To understand how the San Francisco (SF) COVID-19 case investigation and contact tracing (CICT) workforce documented sexual orientation and gender identity (SOGI) data, as well as a qualitative assessment of the workforce's capacity to successfully collect that data. METHODS: This mixed-methods project analyzed data from 2 sources: SOGI item completeness among adult completed/partially completed interviews in the SF digital CICT COVID-19 database, and a secondary data analysis of qualitative data from 16 semistructured 90-minute virtual interviews with the SF CICT workforce, between November 14, 2020, and April 14, 2021. RESULTS: Among 15 416 COVID-19 cases and 7836 close contacts, sexual orientation data are missing from 20% of cases and 17% of contacts. The proportion of transgender/nonbinary individuals was 0.32% and 0.5%, respectively. The SF CICTs participants discussed challenges in collecting SOGI data, not understanding SOGI measure rationale, and feeling uncomfortable asking the questions. CONCLUSION: Qualitative interviews with the COVID-19 CICT workforce and quantitative data on SOGI parameters in COVID-19 surveillance suggest that these data may have been underreported. Our results strongly suggest that comprehensive training is crucial in the collection of SOGI data among COVID-19 cases and their close contacts. If SOGI data are not collected accurately, the true impact of COVID-19 among lesbian, gay, bisexual, transgender, and queer populations remains unknown, preventing data-driven allocation of COVID-19 funds to lesbian, gay, bisexual, transgender, and queer communities.

Evolutionary history of orangutan plasmodia revealed by phylogenetic analysis of complete mtDNA genomes and new biogeographical divergence dating calibration models.

During the past 15 years, researchers have shown a renewed interest in the study of the Plasmodium parasites that infect orangutans. Most recently, studies examined the phylogenetic relationships and divergence dates of these parasites in orangutans using complete mitochondrial DNA genomes. Questions regarding the dating of these parasites, however, remain. In the present study, we provide a new calibration model for dating the origins of Plasmodium parasites in orangutans using a modified date range for the origin of macaques in Asia. Our Bayesian phylogenetic analyses of complete Plasmodium sp. mitochondrial DNA genomes inferred two clades of plasmodia in orangutans (Pongo 1 and Pongo 2), and that these clades likely represent the previously identified species Plasmodium pitheci and Plasmodium silvaticum. However, we cannot identify which Pongo clade is representative of the morphologically described species. The most recent common ancestor of both Pongo sp. plasmodia, Plasmodium. hylobati, and Plasmodium. inui dates to 3-3.16 million years ago (mya) (95% highest posterior density [HPD]: 2.09-4.08 mya). The Pongo 1 parasite diversified 0.33-0.36 mya (95% HPD: 0.12-0.63), while the Pongo 2 parasite diversified 1.15-1.22 mya (95% HPD: 0.63-1.82 mya). It now seems likely that the monkey Plasmodium (P. inui) is the result of a host switch event from the Pongo 2 parasite to sympatric monkeys, or P. hylobati. Our new estimates for the divergence of orangutan malaria parasites, and subsequent diversification, are all several hundred thousand years later than previous Bayesian estimates.

COVID-19 and global equity for health: The good, the bad, and the wicked.

Elvin Geng and co-authors discuss monitoring and achieving equity in provision of vaccines for COVID-19.

Establishment and Evaluation of a Large Contact-Tracing and Case Investigation Virtual Training Academy.

During the COVID-19 pandemic, the Virtual Training Academy (VTA) was established to rapidly develop a contact-tracing workforce for California. Through June 2021, more than 10 000 trainees enrolled in a contact-tracing or case investigation course at the VTA. To evaluate program effectiveness, we analyzed trainee pre- and postassessment results using the Wilcoxon signed-rank test. There was a statistically significant (P < .001) improvement in knowledge and self-perceived skills after course completion, indicating success in training a competent contact-tracing workforce. (Am J Public Health. 2021;111(11):1934-1938. https://doi.org/10.2105/AJPH.2021.306468).

Comparison of Inhibitor and Substrate Selectivity between Rodent and Human Vascular Adhesion Protein-1.

Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that functions as a copper-containing amine oxidase and is involved in leukocyte adhesion at sites of inflammation. Inhibition of VAP-1 oxidative deamination has become an attractive target for anti-inflammatory therapy with demonstrated efficacy in rodent models of inflammation. A previous comparison of purified recombinant VAP-1 from mouse, rat, monkey, and human gene sequences predicted that rodent VAP-1 would have higher affinity for smaller hydrophilic substrates/inhibitors because of its narrower and more hydrophilic active site channel. An optimized in vitro oxidative deamination fluorescence assay with benzylamine (BA) was used to compare inhibition of five known inhibitors in recombinant mouse, rat, and human VAP-1. Human VAP-1 was more sensitive compared to rat or mouse VAP-1 (lowest IC50 concentration) to semicarbazide but was least sensitive to hydralazine and LJP-1207. Hydralazine had a lower IC50 in rats compared to humans, although not significant. However, the IC50 of hydralazine was significantly higher in the rat compared to mouse VAP-1. The larger hydrophobic compounds from Astellas (compound 35c) and Boehringer Ingelheim (PXS-4728A) were hypothesized to have higher binding affinity for human VAP-1 compared to rodent VAP-1 since the channel in human VAP-1 is larger and more hydrophobic than that in rodent VAP-1. Although the sensitivity of these two inhibitors was the lowest in the mouse enzyme, we found no significant differences between mouse, rat, and human VAP-1. Michaelis-Menten kinetics of the small primary amines phenylethylamine and tyramine were also compared to the common marker substrate BA demonstrating that BA had the highest affinity among the substrates. Rat VAP-1 had the highest affinity for all three substrates and mouse VAP-1 had intermediate affinity for BA and phenylethylamine, but tyramine was not a substrate for mouse VAP-1 under these assay conditions. These results suggest that comparing oxidative deamination in mouse and rat VAP-1 may be important if using these species for preclinical efficacy models.

Is 2020 the year when primatologists should cancel fieldwork?

Year 2020 has brought the greatest global pandemic to hit the world since the end of the First World War. The severe acute respiratory syndrome coronavirus 2 and the resulting disease named coronavirus disease 2019 has brought the world to its knees both financially and medically. The American Society of Primatologists has postponed their annual meetings from the end of May 2020 until the end of September 2020, while the International Primatological Society have postponed their biennial congress from August 2020 to August 2021, which has also resulted in their 2022 meetings in Malaysia being pushed back until 2023. Here, I explore the potential dangers of pursuing any primate fieldwork during this pandemic on our study species, their ecosystems, and local peoples. I believe that the risk of bringing this virus into our study ecosystems is too great and that primatologists should cancel all field research until the pandemic ends or a vaccine/reliable treatment is widely available. This is the year we all must become One Health practitioners!

Identifying research priorities for health professions education research in sub-Saharan Africa using a modified Delphi method.

BACKGROUND: Recent increases in health professions education (HPE) research in sub-Saharan Africa (SSA), though substantial, have predominantly originated from single institutions and remained uncoordinated. A shared research agenda can guide the implementation of HPE practices to ultimately influence the recruitment and retention of the health workforce. Thus, the authors aimed to generate and prioritise a list of research topics for HPE research (HPER) in SSA. METHODS: A modified Delphi process was designed to prioritise a shared agenda. Members of the African Forum for Research and Education in Health (AFREhealth) technical working group (TWG) were asked to first list potential research topics. Then, members of the same TWG and attendees at the annual AFREhealth academic symposium held in Lagos, Nigeria in August 2019 rated the importance of including each topic on a 3-point Likert scale, through two rounds of consensus seeking. Consensus for inclusion was predefined as ≥70% of respondents rating the topic as "must be included." RESULTS: Health professions educators representing a variety of professions and 13 countries responded to the survey rounds. Twenty-three TWG members suggested 26 initial HPER topics; subsequently 90 respondents completed round one, and 51 completed round 2 of the modified Delphi. The final list of 12 research topics which met predetermined consensus criteria were grouped into three categories: (1) creating an enabling environment with sufficient resources and relevant training; (2) enhancing student learning; and (3) identifying and evaluating strategies to improve pedagogical practice. CONCLUSIONS: Establishing research priorities for HPE is important to ensure efficient and appropriate allocation of resources. This study serves as a reminder of how the prevailing context within which HPE, and by implication research in the field, is undertaken will inevitably influence choices about research foci. It further points to a potential advocacy role for research that generates regionally relevant evidence.

Oxidative Deamination of Emixustat by Human Vascular Adhesion Protein-1/Semicarbazide-Sensitive Amine Oxidase.

Emixustat potently inhibits the visual cycle isomerase retinal pigment epithelium protein 65 (RPE65) to reduce the accumulation of toxic bisretinoid by-products that lead to various retinopathies. Orally administered emixustat is cleared rapidly from the plasma, with little excreted unchanged. The hydroxypropylamine moiety that is critical in emixustat's inhibition of RPE65 is oxidatively deaminated to three major carboxylic acid metabolites that appear rapidly in plasma. These metabolites greatly exceed the plasma concentrations of emixustat and demonstrate formation-rate-limited metabolite kinetics. This study investigated in vitro deamination of emixustat in human vascular membrane fractions, plasma, and recombinant human vascular adhesion protein-1 (VAP-1), demonstrating single-enzyme kinetics for the formation of a stable aldehyde intermediate (ACU-5201) in all in vitro systems. The in vitro systems used herein established sequential formation of the major metabolites with addition of assay components for aldehyde dehydrogenase and cytochrome P450. Reaction phenotyping experiments using selective chemical inhibitors and recombinant enzymes of monoamine oxidase, VAP-1, and lysyl oxidase showed that only VAP-1 deaminated emixustat. In individually derived human vascular membranes from umbilical cord and aorta, rates of emixustat deamination were highly correlated to VAP-1 marker substrate activity (benzylamine) and VAP-1 levels measured by enzyme-linked immunosorbent assay. In donor-matched plasma samples, soluble VAP-1 activity and levels were lower than in aorta membranes. A variety of potential comedications did not strongly inhibit emixustat deamination in vitro.

Disposition, profiling and identification of emixustat and its metabolites in humans.

1. Emixustat is a small molecule that potently inhibits retinal pigment epithelium 65 isomerohydrolase. Emixustat is in clinical development for the treatment of various retinopathies (i.e. Stargardt disease and diabetic retinopathy). 2. A human absorption, distribution, metabolism, and excretion (ADME) study was conducted with a single dose of [14C]-emixustat in healthy male subjects. Total 14C content in plasma, urine, and faeces was determined using accelerator mass spectrometry (AMS), and metabolic profiles in pooled plasma and urine were investigated by both HPLC-AMS and 2D LC-MS/MS. 3. After a single, oral 40-mg dose of [14C]-emixustat, recovery of total 14C was nearly complete within 24 h. Urine was the major route of 14C elimination; accounting for > 90% of the administered dose. 4. Biotransformation of emixustat occurred primarily at two structural moieties; oxidation of the cyclohexyl moiety and oxidative deamination of the 3R-hydroxypropylamine, both independently and in combination to produce secondary metabolites. Metabolite profiling in pooled plasma samples identified 3 major metabolites: ACU-5124, ACU-5116 and ACU-5149, accounting for 29.0%, 11.5%, and 10.6% of total 14C, respectively. Emixustat was metabolized in human hepatocytes with unchanged emixustat accounting for 33.7% of sample radioactivity and predominantly cyclohexanol metabolites observed.

Staphylococcus aureus nasal colonization among HIV-infected adults in Botswana: prevalence and risk factors.

We sought to determine the clinical and epidemiologic determinants of Staphylococcus aureus nasal colonization in HIV-infected individuals at two outpatient centers in southern Botswana. Standard microbiologic techniques were used to identify S. aureus and methicillin-resistant S. aureus (MRSA). In a sample of 404 HIV-infected adults, prevalence of S. aureus nasal carriage was 36.9% (n = 152) and was associated with domestic overcrowding and lower CD4 cell count. MRSA prevalence was low (n = 13, 3.2%), but more common among individuals with asthma and eczema. The implications of these findings for HIV management are discussed.

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: Case report and review of the literature.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Baylisascaris procyonis-Associated Meningoencephalitis in a Previously Healthy Adult, California, USA.

After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.

Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.

OBJECTIVE: Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis. METHODS: We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent. RESULTS: Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive. INTERPRETATION: The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.

Assessing the impact of one million COVID-19 deaths in America: economic and life expectancy losses.

Between February 2020 and May 2022, one million Americans have died of COVID-19. To determine the contribution of those deaths to all-cause mortality in terms of life expectancy reductions and the resulting economic welfare losses, we calculated their combined impact on national income growth and the added value of lives lost. We estimated that US life expectancy at birth dropped by 3.08 years due to the million COVID-19 deaths. Economic welfare losses estimated in terms of national income growth supplemented by the value of lives lost, was in the order of US$3.57 trillion. US$2.20 trillion of these losses were in in the non-Hispanic White population (56.50%), US$698.24 billion (19.54%) in the Hispanic population, and US$579.93 billion (16.23%) in the non-Hispanic Black population. The scale of life expectancy and welfare losses underscores the pressing need to invest in health in the US to prevent further economic shocks from future pandemic threats.