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To explore associations between histoplasmosis and race and ethnicity, socioeconomic status, and rurality, we conducted an in-depth analysis of social determinants of health and histoplasmosis in 8 US states. Using the Minority Health Social Vulnerability Index (MH SVI), we analyzed county-level histoplasmosis incidence (cases/100,000 population) from the 8 states by applying generalized linear mixed hurdle models. We found that histoplasmosis incidence was higher in counties with limited healthcare infrastructure and access as measured by the MH SVI and in more rural counties. Other social determinants of health measured by the MH SVI tool either were not significantly or were inconsistently associated with histoplasmosis incidence. Increased awareness of histoplasmosis, more accessible diagnostic tests, and investment in rural health services could address histoplasmosis-related health disparities.

Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.

Mycetoma is a debilitating neglected tropical disease that affects individuals worldwide, particularly in regions where there is poverty and limited health care access. The Mycetoma Research Center (MRC), based in Khartoum, Sudan, provides a sustainable, holistic approach to patient care as the only World Health Organization collaborating center for mycetoma. We describe MRC activities that align with the United Nations' Sustainable Development Goals to control mycetoma in Sudan and globally.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

During 2016–2022, Medicare part D beneficiaries filled 8,674,460 clotrimazole-betamethasone dipropionate prescriptions. Annual rates were stable (30.9 prescriptions/1,000 beneficiary-years in 2022, enough for one in every 33 beneficiaries). Diagnostic testing was infrequent, particularly among internal medicine, family medicine, and general practitioners, suggesting potential opportunities to improve diagnostic and prescribing practices.

The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, nirmatrelvir/ritonavir (Paxlovid™) fixed-dose combination is recommended by the World Health Organization for treatment of COVID-19. The ritonavir component is an inhibitor of cytochrome P450 (CYP) 3A, which is used in this combination to achieve needed therapeutic concentrations of nirmatrelvir. Because of the critical pharmacokinetic effect of this mechanism of action for Paxlovid™, co-administration with needed medications that inhibit or induce CYP3A is contraindicated, reflecting concern for interactions with the potential to alter the efficacy or safety of co-administered drugs that are also metabolized by CYP3A. Some herbal medicines are known to interact with drug metabolizing enzymes and transporters, including but not limited to inhibition or induction of CYP3A and P-glycoprotein. As access to these COVID-19 medications has increased in low- and middle-income countries (LMICs), understanding the potential for herb-drug interactions within these regions is important. Many studies have evaluated the utility of herbal medicines for COVID-19 treatments, yet information on potential herb-drug interactions involving Paxlovid™, specifically with herbal medicines commonly used in LMICs, is lacking. This review presents data on regionally-relevant herbal medicine use (particularly those promoted as treatments for COVID-19) and mechanism of action data on herbal medicines to highlight the potential for herbal medicine interaction Herb-drug interaction mediated by ritonavir-boosted antiviral protease inhibitors This work highlights potential areas for future experimental studies and data collection, identifies herbal medicines for inclusion in future listings of regionally diverse potential HDIs and underscores areas for LMIC-focused provider-patient communication. This overview is presented to support governments and health protection entities as they prepare for an increase of availability and use of Paxlovid™.

Background: Blastomycosis is an environmentally acquired fungal disease that can cause severe illness, with approximately 65% of reported cases requiring hospitalization. Recent trends in blastomycosis-associated hospitalizations in the United States have not been described. Methods: We analyzed hospital discharge data from the Healthcare Cost and Utilization Project (HCUP) National (Nationwide) Inpatient Sample. We calculated hospitalization rates per 100,000 population using U.S. census data and examined factors associated with in-hospital mortality. Results: An estimated 11,776 blastomycosis-associated hospitalizations occurred during 2010–2020 (average yearly rate 0.3 per 100,000 persons), with no apparent temporal trend. Rates were consistently highest among persons ≥65 years old and males. In-hospital death occurred in 7.9% and approximately doubled from 3.9% in 2010 to 8.5% in 2020. Older age, chronic obstructive pulmonary disease, and malignancy were associated with mortality. Conclusions: Blastomycosis-associated hospitalizations can result in poor outcomes, underscoring the continued need for attention to early detection and treatment of blastomycosis and monitoring of disease trends.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.

Abstract Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Histoplasmosis is an environmentally acquired fungal disease caused by Histoplasma species. In the United States, Histoplasma most commonly lives in central and eastern states, but infections also have been acquired [...]

Atriplex hortensis (2n = 2x = 18, 1C genome size ∼1.1 gigabases), also known as garden orach and mountain-spinach, is a highly nutritious, broadleaf annual of the Amaranthaceae-Chenopodiaceae alliance (Chenopodiaceae sensu stricto, subfam. Chenopodioideae) that has spread in cultivation from its native primary domestication area in Eurasia to other temperate and subtropical regions worldwide. Atriplex L. is a highly complex but, as understood now, a monophyletic group of mainly halophytic and/or xerophytic plants, of which A. hortensis has been a vegetable of minor importance in some areas of Eurasia (from Central Asia to the Mediterranean) at least since antiquity. Nonetheless, it is a crop with tremendous nutritional potential due primarily to its exceptional leaf and seed protein quantities (approaching 30%) and quality (high levels of lysine). Although there is some literature describing the taxonomy and production of A. hortensis, there is a general lack of genetic and genomic data that would otherwise help elucidate the genetic variation, phylogenetic positioning, and future potential of the species. Here, we report the assembly of the first high-quality, chromosome-scale reference genome for A. hortensis cv. “Golden.” Long-read data from Oxford Nanopore’s MinION DNA sequencer was assembled with the program Canu and polished with Illumina short reads. Contigs were scaffolded to chromosome scale using chromatin-proximity maps (Hi-C) yielding a final assembly containing 1,325 scaffolds with a N50 of 98.9 Mb – with 94.7% of the assembly represented in the nine largest, chromosome-scale scaffolds. Sixty-six percent of the genome was classified as highly repetitive DNA, with the most common repetitive elements being Gypsy-(32%) and Copia-like (11%) long-terminal repeats. The annotation was completed using MAKER which identified 37,083 gene models and 2,555 tRNA genes. Completeness of the genome, assessed using the Benchmarking Universal Single Copy Orthologs (BUSCO) metric, identified 97.5% of the conserved orthologs as complete, with only 2.2% being duplicated, reflecting the diploid nature of A. hortensis. A resequencing panel of 21 wild, unimproved and cultivated A. hortensis accessions revealed three distinct populations with little variation within subpopulations. These resources provide vital information to better understand A. hortensis and facilitate future study.

Dermatophytosis (i.e., ringworm, tinea) is a common superficial fungal skin infection caused by dermatophyte molds (1). In the past decade, widespread outbreaks of antifungal-resistant dermatophytosis have occurred in South Asia [...]

BACKGROUND:Taenia solium, a parasitic cestode that affects humans and pigs, is the leading cause of preventable epilepsy in the developing world. T. solium eggs are released into the environment through the stool of humans infected with an adult intestinal tapeworm (a condition called taeniasis), and cause cysticercosis when ingested by pigs or other humans. A control strategy to intervene within high-risk foci in endemic communities has been proposed as an alternative to mass antihelminthic treatment. In this ring strategy, antihelminthic treatment is targeted to humans and pigs residing within a 100 meter radius of a pig heavily-infected with cysticercosis. Our aim was to describe the roaming ranges of pigs in this region, and to evaluate whether the 100 meter radius rings encompass areas where risk factors for T. solium transmission, such as open human defecation and dense pig activity, are concentrated. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we used Global Positioning System (GPS) devices to track pig roaming ranges in two rural villages of northern Peru. We selected 41 pigs from two villages to participate in a 48-hour tracking period. Additionally, we surveyed all households to record the locations of open human defecation areas. We found that pigs spent a median of 82.8% (IQR: 73.5, 94.4) of their time roaming within 100 meters of their homes. The size of home ranges varied significantly by pig age, and 93% of the total time spent interacting with open human defecation areas occurred within 100 meters of pig residences. CONCLUSIONS/SIGNIFICANCE:These results indicate that 100 meter radius rings around heavily-infected pigs adequately capture the average pig's roaming area (i.e., home range) and represent an area where the great majority of exposure to human feces occurs.

Dermatophytosis, also called ringworm or tinea, is a common superficial fungal skin infection most often caused by Trichophyton, Microsporum, or Epidermophyton fungi and often treated using over-thecounter topical antifungal agents [...]

It is important that preservice and in-service teachers use effective supports for English language learners (ELLs) in science classes to enhance learning. ELLs with limited English proficiency may need more supports to address language barriers that affect student learning. Literature circles can be used to enhance understanding of content when embedded into instructional strategies. This grant-funded study collected data on effective instructional approaches to support ELL students in upper elementary science classes from October, 2017 through May, 2018. During a lesson on phases of the moon, researchers incorporated literature circles into instruction embedded with metacognitive strategies to assess student learning outcomes. Student-participants: (1) took a researcher-designed, pre-assessment; (2) received direct instruction in phases of the moon; (3) were engaged in literature circles; (4) created "Phases of the Moon" booklets; and (5) took a post-assessment. For the collaborative activity, students were grouped with peers who had similar English proficiency levels; and each group was given a book in English, a book in Spanish, or a book that had text in both Spanish and English. Students were asked to read, identify cognates/clarify unknown words, develop a summary/gist, and create questions to ask peers after a group presentation (Klingner & Vaughn, 1999; Palincsar & Brown, 1984).

On 6 January 2022, a cluster of cases of COVID-19 (1) due to the SARS-CoV-2 Omicron variant was detected in Hong Kong Special Administrative Region of China (Hong Kong SAR), [...]

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021–2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy. [ABSTRACT FROM AUTHOR]

Background: Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare‐associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. Methods: After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case‐mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next‐generation sequencing (mNGS) and fungal‐specific polymerase chain reaction and in plasma by mNGS. Results: Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1‐3)‐β‐d‐glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. Conclusion: Antifungal prophylaxis may be useful in preventing donor‐derived infections in recipients of organs from donors that are found to have Fusarium meningitis. [ABSTRACT FROM AUTHOR]

Older adults are especially unlikely to seek mental health services, and internalized stigma is a key reason why. However, little research has investigated which older adults are particularly likely to have stigma influence help-seeking. To address this, we tested whether perceived control (PC) moderates an internalized stigma model in which public stigma is internalized as self-stigma, which negatively predicts help-seeking attitudes and help-seeking intentions. We employed moderated mediation analysis of cross-sectional, secondary data from 348 psychologically distressed Canadian adults aged 65 years and older. Participants completed an online survey that included measures of public stigma of help-seeking, self-stigma of help-seeking, help-seeking attitudes, conditional help-seeking intentions, psychological distress, and PC. PC emerged as a moderator of the internalized stigma model. Those lower in PC were more likely to have public stigma negatively predict help-seeking intentions through the serial mediation of (a) self-stigma and (b) help-seeking attitudes. Further, those lower in PC were more likely to have public stigma internalized as self-stigma and more likely to have negative help-seeking attitudes predict lower help-seeking intentions. Finally, those lower in PC also had lower help-seeking intentions in the face of low levels of self-stigma. These results contribute to a nuanced understanding of which older adults are unlikely to seek help. Identifying PC as a moderator of the internalized stigma model suggests that interventions that enhance PC should protect against public stigma's internalization and improve help-seeking behaviors for older adults who need such help. Public Significance Statement: This study demonstrates that if distressed older adults are low in perceived control (i.e., they feel they have little control over influencing outcomes and events), they are more likely to avoid seeking psychological help when exposed to help-seeking stigma. This is important because older adults are the age demographic least likely to seek help for mental health concerns, and enhancing perceptions of control is one way to improve treatment seeking. [ABSTRACT FROM AUTHOR]

Mycetoma is a neglected tropical disease (NTD) with devastating morbidity and stigma. Despite increased awareness and international collaboration, the burden of mycetoma is largely unknown and diagnosis and treatment are difficult. Addressing mycetoma globally aligns with several United Nation's Sustainable Development Goals (SDGs). Little progress has been made since the WHO's NTD roadmap publication in 2020. The Global Mycetoma Working Group proposes an enhanced mycetoma-control roadmap to meet the SDGs, stimulate progress and improve the lives of patients experiencing mycetoma. By aligning mycetoma management with the goals and targets of this enhanced roadmap, it becomes possible to leverage existing resources, infrastructure and partnerships to improve the lives of affected individuals and communities. This updated assessment is designed for the benefit of health workers and providers in mycetoma-endemic areas, NTD government officials, civil society and funding and implementing agencies. [ABSTRACT FROM AUTHOR]

Mycetoma is a debilitating neglected tropical disease that affects individuals worldwide, particularly in regions where there is poverty and limited health care access. The Mycetoma Research Center (MRC), based in Khartoum, Sudan, provides a sustainable, holistic approach to patient care as the only World Health Organization collaborating center for mycetoma. We describe MRC activities that align with the United Nations' Sustainable Development Goals to control mycetoma in Sudan and globally. [ABSTRACT FROM AUTHOR]

This study developed an animal model of gestational obesity and prediabetes in Sprague Dawley rats using 35% sucrose supplementation (SS). Postprandially, insulin stimulates glucose uptake and nutrient partitioning via insulin-dependent action as well as hepatic insulin sensitizing substance (HISS) - dependent action. HISS is glycogenic in heart, kidney, and skeletal muscle (contrasting insulin's lipogenic actions in liver and adipose tissue) and is responsible for the vasodilatory action of insulin. Postprandial insulin sensitivity was quantified using the rapid insulin sensitivity test (RIST). Animals at 15-day gestation and virgin animals received SS for 8 weeks (with a 2-week recovery), 10 weeks, or 22 weeks. SS in pregnant and virgin rats eliminated HISS-dependent glucose uptake, resulting in compensatory hyperinsulinemia and resultant hypertriglyceridemia and obesity. In groups with SS for 8 weeks followed by a 2-week recovery, there was spontaneous partial recovery of HISS-dependent glucose uptake in virgins and complete recovery in pregnancy. The 10-week SS resulted in complete absence of HISS-dependent glucose uptake and produced a model of gestational obesity and prediabetes. The 22-week SS did not produce hyperglycemia or worsen hyperinsulinemia but did increase hypertriglyceridemia above 10-week SS. This substantiates the use of 10-week SS as a model of gestational obesity and (or) prediabetes, allowing further studies into treatments of gestational obesity and insulin resistance. Key words: HISS, sucrose, pregnancy, insulin resistance, gestational obesity. Dans ces travaux, nous avons mis au point un modele d'obesite et de prediabete gestationnels a l'aide d'une supplementation en saccharose (SS) a 35 % chez le rat Sprague Dawley. A l'etat postprandial, l'insuline stimule l'absorption de glucose et le partitionnement de nutriments par une action dependante de l'insuline ainsi que dependante de la substance sensibilisant a l'insuline hepatique (SSIH). La SSIH est dotee d'un pouvoir glycogenique dans le coeur, les reins et le muscle squelettique (contrastant avec les actions lipogeniques de l'insuline dans le foie et le tissu adipeux), et il est responsable des proprietes vasodilatatrices de l'insuline. Nous avons quantifie la sensibilite a l'insuline postprandiale a l'aide du test rapide de sensibilite a l'insuline (TRSI). Chez des rates vierges et a 15 jours de gestation, nous avons administre la SS pendant 8 semaines (avec retablissement de 2 semaines), 10 semaines ou 22 semaines. Chez les rates vierges et gestantes, la SS entrainait une inhibition complete de l'absorption de glucose dependante de la SSIH, ce qui menait a une hyperinsulinemie compensatoire ainsi qu'a une hypertriglyceridemie et une obesite consecutives. Dans les groupes de SS sur 8 semaines suivies d'un retablissement de 2 semaines, nous avons observe un retablissement spontane partiel de l'absorption de glucose dependante de la SSIH chez les vierges, mais un retablissement complet avec la gestation. La SS sur 10 semaines a mene a une absence complete d'absorption de glucose dependante de la SSIH, ce qui permettait d'obtenir un modele d'obesite et de prediabete gestationnels. La SS sur 22 semaines n'a pas entraine d'hyperglycemie ni d'aggravation de l'hyperinsulinemie, mais bien une augmentation de l'hypertriglyceridemie apres 10 semaines de SS. Ces resultats appuient l'utilisation de la SS sur 10 semaines comme modele d'obesite et de prediabete gestationnels, ce qui permettra de realiser d'autres etudes sur les traitements de l'obesite et de la resistance a l'insuline gestationnelles. [Traduit par la Redaction] Mots-cles : substance sensibilisant a l'insuline hepatique, saccharose, grossesse, resistance a l'insuline, obesite gestationnelle., Introduction By the 15th day of pregnancy in the Sprague Dawley rat (equivalent to the third trimester in humans), there is a mixed hepatic insulin sensitizing substance (HISS)--dependent and insulin-dependent [...]

Background Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown. Methods We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019–29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends. Results Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%–74%) and blastomycosis (42%–68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases. Conclusions Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden. [ABSTRACT FROM AUTHOR]

Background Public health officials are responding to an outbreak of fungal meningitis among patients who received procedures under epidural anesthesia at 2 clinics (River Side Surgical Center and Clinica K-3) in Matamoros, Mexico, during 1 January to 13 May 2023. This report describes outbreak epidemiology and outlines interim diagnostic and treatment recommendations. Methods Interim recommendations for diagnosis and management were developed by the Mycoses Study Group Research Education and Consortium (MSGERC) based on the clinical experience of clinicians caring for patients during the current outbreak or during previous outbreaks of healthcare-associated fungal meningitis in Durango, Mexico, and the United States. Results As of 7 July 2023, the situation has evolved into a multistate and multinational fungal meningitis outbreak. A total of 185 residents in 22 US states and jurisdictions have been identified who might be at risk of fungal meningitis because they received epidural anesthesia at the clinics of interest in 2023. Among these patients, 11 suspected, 10 probable, and 10 confirmed US cases have been diagnosed, with severe vascular complications and 8 deaths occurring. Fusarium solani species complex has been identified as the causative agent, with antifungal susceptibility testing of a single isolate demonstrating poor in vitro activity for most available antifungals. Currently, triple therapy with intravenous voriconazole, liposomal amphotericin B, and fosmanogepix is recommended. Conclusions Efforts to understand the source of this outbreak and optimal treatment approaches are ongoing, but infectious diseases physicians should be aware of available treatment recommendations. New information will be available on the Centers for Disease Control and Prevention's (CDC's) website. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia. This guidance is intended to help outpatient clinicians test for these fungal diseases in patients with community-acquired pneumonia to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes. [ABSTRACT FROM AUTHOR]