Search

Coccidioidomycosis, caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii, is recognized as an increasing threat both nationally and worldwide. This is in large part secondary to the expanding range of Coccidioides species and increased international travel to endemic regions. Most individuals exposed to airborne Coccidioides organisms do not need medical attention, but approximately 30% will demonstrate primary pulmonary coccidioidomycosis with signs and symptoms that mimic community-acquired pneumonia or other respiratory illnesses. Further, 5% of those with a diagnosis of pulmonary coccidioidomycosis will demonstrate serious and even life-threatening manifestations, including extrapulmonary or disseminated coccidioidomycosis. Of those who demonstrate pulmonary coccidioidomycosis, past evidence suggests that approximately 5% to 15% will experience long-term pulmonary sequelae in the form of nodules, abscesses, or cavitary lesions. These lesions may not be easily distinguished from malignancy or other infections, such as TB, and they add a substantial burden to both patients and the health care system. Despite the long-term consequences of cavitary coccidioidomycosis in some individuals, the current literature review and practice guidelines demonstrate a paucity of clear management strategies to treat these patients. In this report, we focus on cavitary lesions in coccidioidomycosis with the goal of presenting a description of the evaluation and management of their various forms, manifestations, and complications. These recommendations are derived from a multidisciplinary group of experts., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Although it is widely known that various pharmaceuticals affect the methylome, the knowledge of the effects from anesthesia is limited, and nearly nonexistent regarding the effects of obstetric anesthesia on the newborn child. Using sequencing based-methylation data and a reference-based statistical deconvolution approach we performed methylome-wide association studies (MWAS) of neonatal whole blood, and for each cell-type specifically, to detect methylation variations that are associated with the pain relief administered to the mother during delivery. Significant findings were replicated in a different dataset and followed-up with gene ontology analysis to pinpoint biological functions of potential relevance to these neonatal methylation alterations. The MWAS analyses detected methylome-wide significant (q<0.1) alterations in the newborn for laughing gas in granulocytes (two CpGs, p<5.50x10-9, q = 0.067), and for pudendal block in monocytes (five CpGs across three loci, p<1.51 x10-8, q = 0.073). Suggestively significant findings (p<1.00x10-6) were detected for both treatments for bulk and all cell-types, and replication analyses showed consistent significant enrichment (odds ratios ranging 3.47-39.02; p<4.00×10-4) for each treatment, suggesting our results are robust. In contrast, we did not observe any overlap across treatments, suggesting that the treatments are associated with different alterations of the neonatal blood methylome. Gene ontology analyses of the replicating suggestively significant results indicated functions related to, for example, cell differentiation, intracellular membrane-bound organelles and calcium transport. In conclusion, for the first time, we investigated and detected effect of obstetric pain-relief on the blood methylome in the newborn child. The observed differences suggest that anesthetic treatment, such as laughing gas or pudendal block, may alter the neonatal methylome in a cell-type specific manner. Some of the observed alterations are part of gene ontology terms that previously have been suggested in relation to anesthetic treatment, supporting its potential role also in obstetric anesthesia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural river flooding events can mobilize contaminants from the vadose zone and lead to increased concentrations in groundwater. Characterizing the mass and transport mechanisms of contaminants released from the vadose zone to groundwater during these recharge events is particularly challenging. Therefore, conducting highly-controlled in-situ experiments that simulate natural flooding events can help increase the knowledge of where contaminants can be stored and how they can move between hydrological compartments. This study specifically targets uranium pollution, which is accompanied by high sulfate levels in the vadose zone and groundwater. Two novel experimental river flooding events were conducted that utilized added non-reactive halides (bromide and iodide) and 2,6-difluorobenzoate tracers. In both experiments, about 8 m 3 of traced water from a nearby contaminant-poor river was flooded in a 3-m diameter basin and infiltrated through the vadose zone and into a contaminant-rich unconfined aquifer for an average of 10 days. The aquifer contained 13 temporary wells that were monitored for solute concentration for up to 40 days. The groundwater analysis was conducted for changes in contaminant mass using the Theissen polygon method and for transport mechanisms using temporal moments. The results indicated an increase in uranium (21 and 24%), and sulfate (24 and 25%) contaminant mass transport to groundwater from the vadose zone during both experiments. These findings confirmed that the vadose zone can store and release substantial amounts of contaminants to groundwater during flooding events. Additionally, contaminants were detected earlier than the added tracers, along with higher concentrations. These results suggested that contaminant-rich pore water in the vadose zone was transported ahead of the traced flood waters and into groundwater. During the first flooding event, elevated concentrations of contaminants were sustained, and that chloride behaved similarly. The findings implied that contaminant- and chloride-rich evaporites in the vadose zone were dissolved during the first flooding event. For the second flooding event, the data suggested that the contaminant-rich evaporites continued to dissolve whereas chloride-rich evaporites were previously flushed. Overall, these findings indicated that contaminant-rich pore water and evaporites in the vadose zone can play a significant role in contaminant transport during flooding events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Adverse neonatal outcomes are a prevailing risk factor for both short- and long-term mortality and morbidity in infants. Given the importance of these outcomes, refining their assessment is paramount for improving prevention and care. Here we aim to enhance the assessment of these often correlated and multifaceted neonatal outcomes. To achieve this, we employ factor analysis to identify common and unique effects and further confirm these effects using criterion-related validity testing. This validation leverages methylome-wide profiles from neonatal blood. Specifically, we investigate nine neonatal health risk variables, including gestational age, Apgar score, three indicators of body size, jaundice, birth diagnosis, maternal preeclampsia, and maternal age. The methylomic profiles used for this research capture data from nearly all 28 million methylation sites in human blood, derived from the blood spot collected from 333 neonates, within 72 h post-birth. Our factor analysis revealed two common factors, size factor, that captured the shared effects of weight, head size, height, and gestational age and disease factor capturing the orthogonal shared effects of gestational age, combined with jaundice and birth diagnosis. To minimize false positives in the validation studies, validation was limited to variables with significant cumulative association as estimated through an in-sample replication procedure. This screening resulted in that the two common factors and the unique effects for gestational age, jaundice and Apgar were further investigated with full-scale cell-type specific methylome-wide association analyses. Highly significant, cell-type specific, associations were detected for both common effect factors and for Apgar. Gene Ontology analyses revealed multiple significant biologically relevant terms for the five fully investigated neonatal health risk variables. Given the established links between adverse neonatal outcomes and both immediate and long-term health, the distinct factor effects (representing the common and unique effects of the risk variables) and their biological profiles confirmed in our work, suggest their potential role as clinical biomarkers for assessing health risks and enhancing personalized care., (© 2024. The Author(s).)

Background: Policy, societal, and system changes are prompting nursing programs to expand population health content in curricula. This study examined the current state of community, public, and population health (CPPH) education in nursing curricula throughout the United States., Method: This descriptive study examined CPPH education in nursing programs nationally. A survey was developed and distributed to nursing programs from January to May 2021., Results: CPPH content integration occurred across all program levels, and the majority of the participants were involved in the development of CPPH-specific curriculum. Programs experienced reductions in CPPH curriculum due to coronavirus disease 2019 (COVID-19), lack of experienced faculty, budget constraints, and an emphasis on acute care., Conclusion: The continuation of CPPH education in current nursing curricula is critical. National and academic nursing organizations must continue to monitor CPPH content in nursing curricula to assure a competent CPPH nursing workforce. [ J Nurs Educ . 2024;63(5):282-291.] .

Groundwater contamination at legacy uranium processing sites is an ongoing global challenge. Plumes at many uranium-contaminated sites are more persistent than originally predicted by groundwater modeling. Previous investigations of uranium plume persistence identified residual and secondary sources that contribute to plume longevity, but there is a remaining need to revise forecasted cleanup times using information about these ongoing sources. The purpose of this study is to investigate the quantitative impact of residual vadose zone sources of uranium on groundwater remediation time frame. This objective was approached by applying numerical uranium transport simulations and uncertainty analysis to a former uranium mill site in the southwestern United States. Information from recent site investigations provided details about the distribution and release characteristics of uranium accumulations in the vadose zone. The residual uranium characteristics were incorporated as decaying source terms in the transport model. A stochastic approach using an iterative ensemble smoother was applied for history matching, and the transport model was used to assess the impact of multiple remedial alternatives on forecasted time frame. The forecasted time frame to achieve the groundwater remediation goal for uranium by monitored natural attenuation is on the order of thousands of years, and treatment of the dissolved plume does not reduce the projected time frame. The large proportion of residual uranium mass remaining in the vadose zone and the gradual leaching rate due to the site's semiarid climate create a long-lived source that can sustain a dissolved plume for thousands of years despite an estimated 99% mass removal achieved during mill tailings disposal. Residual uranium in vadose zone sediments beneath former tailings impoundments could present comparable uranium plume persistence and remediation challenges at other legacy uranium mill sites in semiarid climates. Other remaining uranium-impacted sites are similarly complex, and forecasted remedial time frames are needed to effectively achieve compliance, manage risk, assess the benefits of additional treatment, manage and project costs, and support beneficial site reuse., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patient experience is positively associated with clinical effectiveness, quality care, and patient safety. This study examines the experience of care of adolescents and young adult (AYA) cancer patients from Australia and the United States, allowing a comparison of patient experiences in the context of different national models of cancer care delivery. Participants ( n  = 190) were aged 15-29 years and received cancer treatment from 2014 to 2019. Australians ( n  = 118) were recruited nationally by health care professionals. U.S. participants ( n  = 72) were recruited nationally via social media. The survey included demographic and disease variables, and questions regarding medical treatment, information and support provision, care coordination, and satisfaction across the treatment pathway. Sensitivity analyses examined the possible contribution of age and gender. Most patients from both countries were satisfied or very satisfied with their medical treatment (chemotherapy, radiotherapy, and surgery). There were significant differences between countries in the provision of fertility preservation services, age-appropriate communication, and psychosocial support. Our findings suggest when a national system of oversight with both state and federal funding is implemented, as is the case in Australia but not in the United States, significantly more AYAs with cancer receive age-appropriate information and support services, and improved access to specialist services such as fertility care. A national approach with government funding and centralized accountability appears to be associated with substantial benefits for the well-being of AYAs undergoing cancer treatment.

Background: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors., Methods: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2., Results: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists., Conclusions: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment., (© 2023. The Author(s).)

Interdisciplinary research teams can be extremely beneficial when addressing difficult clinical problems. The incorporation of conceptual and methodological strategies from a variety of research disciplines and health professions yields transformative results. In this setting, the long-term goal of team science is to improve patient care, with emphasis on population health outcomes. However, team principles necessary for effective research teams are rarely taught in health professional schools. To form successful interdisciplinary research teams in cardio-oncology and beyond, guiding principles and organizational recommendations are necessary. Cardiovascular disease results in annual direct costs of $220 billion (about $680 per person in the US) and is the leading cause of death for cancer survivors, including adult survivors of childhood cancers. Optimizing cardio-oncology research in interdisciplinary research teams has the potential to aid in the investigation of strategies for saving hundreds of thousands of lives each year in the United States and mitigating the annual cost of cardiovascular disease. Despite published reports on experiences developing research teams across organizations, specialties and settings, there is no single journal article that compiles principles for cardiology or cardio-oncology research teams. In this review, recurring threads linked to working as a team, as well as optimal methods, advantages, and problems that arise when managing teams are described in the context of career development and research. The worth and hurdles of a team approach, based on practical lessons learned from establishing our multidisciplinary research team and information gleaned from relevant specialties in the development of a successful team are presented., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Coccidioides species are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with symptomatic pneumonic diseases as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Elucidating the mechanisms of resistance to immunotherapy and developing strategies to improve its efficacy are challenging goals. Bioinformatics analysis demonstrates that high CDK6 expression in melanoma is associated with poor progression-free survival of patients receiving single-agent immunotherapy. Depletion of CDK6 or cyclin D3 (but not of CDK4, cyclin D1, or D2) in cells of the tumor microenvironment inhibits tumor growth. CDK6 depletion reshapes the tumor immune microenvironment, and the host anti-tumor effect depends on cyclin D3/CDK6-expressing CD8 + and CD4 + T cells. This occurs by CDK6 phosphorylating and increasing the activities of PTP1B and T cell protein tyrosine phosphatase (TCPTP), which, in turn, decreases tyrosine phosphorylation of CD3ζ, reducing the signal transduction for T cell activation. Administration of a PTP1B and TCPTP inhibitor prove more efficacious than using a CDK6 degrader in enhancing T cell-mediated immunotherapy. Targeting protein tyrosine phosphatases (PTPs) might be an effective strategy for cancer patients who resist immunotherapy treatment., Competing Interests: Declaration of interests P.S. has been a consultant at Novartis, Genovis, Guidepoint, The Planning Shop, ORIC Pharmaceuticals, Cedilla Therapeutics, Syros Pharmaceuticals, and Exo Therapeutics; his laboratory has received funding from Novartis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Gambling is a global public health issue that can cause harm to individuals, families, and communities. Older adults are vulnerable to gambling harm due to life-stage experiences. This study aimed to examine current research relating to individual, socio-cultural, environmental, and commercial determinants of gambling among older adults. A scoping review was conducted (PubMed, PsycInfo, SocIndex, CINAHL Complete, Web of Science, Social Science and Sociology databases available in ProQuest, Google Scholar, citation searching), with peer reviewed studies included that were published between 1 December 1999 and 28 September 2022. Included studies were published in English in peer-reviewed journals that examined the determinants of gambling in adults aged 55 and over. Records were excluded if they were experimental studies, prevalence studies or had a population wider than the required age group. Methodological quality was assessed using JBI critical appraisal tools. Data was extracted using a determinants of health framework and common themes were identified. Forty-four were included. Most literature examined individual and socio-cultural determinants including reasons for gambling, risk management strategies, and social motivations for gambling. Few studies investigated environmental or commercial determinants, and those that did focused on accessibility of venues or promotions as pathways to gambling. Further research is needed to understand the impact of gambling environments and industry, and effective public health responses for older adults., (© 2023. The Author(s).)

Disparities in care, treatment-related toxicity and health-related quality of life (HRQoL) for adolescents and young adults (AYAs, aged 15-39 years) with cancer are under-addressed partly because of limited collection of patient-reported outcomes (PROs) in cancer clinical trials (CCTs). The AYA years include key developmental milestones distinct from younger and older patients, and cancer interrupts attainment of critical life goals. Lack of consensus on a standardized approach to assess HRQoL and treatment-related toxicity in AYA CCTs has limited the ability to improve patient outcomes. The National Cancer Institute's Clinical Trials Network AYA PRO Task Force was assembled to reach consensus on a core set of PROs and foster its integration into AYA CCTs. Eight key considerations for selecting the core PRO AYA battery components were identified: relevance to AYAs; importance of constructs across the age continuum; prioritization of validated measures; availability of measures without licensing fees; availability in multiple languages; applicability to different cancer types and treatments; ability to measure different HRQoL domains and toxicities; and minimized burden on patients and sites. The Task Force used a modified Delphi approach to identify key components of the PRO battery. The Patient-Reported Outcomes Measurement Information System (PROMIS) and the PRO Common Terminology Criteria for Adverse Events Measurement System met all criteria and were selected to assess HRQoL and treatment toxicity, respectively. Investigators are rapidly incorporating the recommendations of the Task Force into AYA trials. Inclusion of a standardized assessment of HRQoL and treatment toxicities in AYA CCTs is a vital first step to develop interventions to improve health outcomes for AYAs diagnosed with cancer., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Herein described is a case of biofilm obstructing ventriculoperitoneal shunt due to Cutibacteirum acnes infection in a patient with coccidioidal meningitis. Cutibacterium acnes infects and obstructs cerebral shunts by the production of biofilm; however, diagnosis is usually missed by routine aerobic cultures. Obtaining anaerobic cultures routinely in patients with foreign body implants leading to central nervous system infections could prevent a missed diagnosis of this pathogen. Penicillin G is the first-line treatment.

The recharge of stream water below the baseflow water table can mobilize groundwater contaminants, particularly redox-sensitive and sorptive metals such as uranium. However, in-situ tracer experiments that simulate the recharge of stream water to uranium-contaminated groundwater are lacking, thus limiting the understanding of the potential mechanisms that control the mobility of uranium at the field scale. In this study, a field tracer test was conducted by injecting 100 gal (379 l) of oxic river water into a nearby suboxic and uranium-contaminated aquifer. The traced river water was monitored for 18 days in the single injection well and in the twelve surrounding observation wells. Mobilization of uranium from the solid to the aqueous phase was not observed during the tracer test despite its pre-test presence being confirmed on the aquifer sediments from lab-based acid leaching. However, strong evidence of oxidative immobilization of iron and manganese was observed during the tracer test and suggested that immobile uranium was likely in its oxidized state as U(VI) on the aquifer sediments; these observations ruled out oxidation of U(IV) to U(VI) as a potential mobilization mechanism. Therefore, desorption of U(VI) appeared to be the predominant potential mobilization mechanism, yet it was clearly not solely dependent on concentration as evident when considering that uranium-poor river water (<0.015 mg/L) was recharged to uranium-rich groundwater (≈1 mg/L). It was possible that uranium desorption was limited by the relatively higher pH and lower alkalinity of the river water as compared to the groundwater; both factors favor immobilization. However, it was likely that the immobile uranium was associated with a mineral phase, as opposed to a sorbed phase, thus desorption may not have been possible. The results of this field tracer study successfully ruled out two common mobilization mechanisms of uranium: (1) oxidative dissolution and (2) concentration-dependent desorption and ruled in the importance of advection, dispersion, and the mineral phase of uranium., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is characterised by the progressive loss of midbrain dopaminergic neurons and the presence of aggregated α-synuclein (α-syn). Pericytes and microglia, two non-neuronal cells contain α-syn in the human brain, however, their role in disease processes is poorly understood. Pericytes, found surrounding the capillaries in the brain are important for maintaining the blood-brain barrier, controlling blood flow and mediating inflammation. In this study, primary human brain pericytes and microglia were exposed to two different α-synuclein aggregates. Inflammatory responses were assessed using immunocytochemistry, cytometric bead arrays and proteome profiler cytokine array kits. Fixed flow cytometry was used to investigate the uptake and subsequent degradation of α-syn in pericytes. We found that the two α-syn aggregates are devoid of inflammatory and cytotoxic actions on human brain derived pericytes and microglia. Although α-syn did not induce an inflammatory response, pericytes efficiently take up and degrade α-syn through the lysosomal pathway but not the ubiquitin-proteasome system. Furthermore, when pericytes were exposed the ubiquitin proteasome inhibitor-MG132 and α-syn aggregates, there was profound cytotoxicity through the production of reactive oxygen species resulting in apoptosis. These results suggest that the observed accumulation of α-syn in pericytes in human PD brains likely plays a role in PD pathogenesis, perhaps by causing cerebrovascular instability, under conditions of cellular stress., (© 2022. The Author(s).)

Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis.

Automatic characterization of fluorescent labeling in intact mammalian tissues remains a challenge due to the lack of quantifying techniques capable of segregating densely packed nuclei and intricate tissue patterns. Here, we describe a powerful deep learning-based approach that couples remarkably precise nuclear segmentation with quantitation of fluorescent labeling intensity within segmented nuclei, and then apply it to the analysis of cell cycle dependent protein concentration in mouse tissues using 2D fluorescent still images. First, several existing deep learning-based methods were evaluated to accurately segment nuclei using different imaging modalities with a small training dataset. Next, we developed a deep learning-based approach to identify and measure fluorescent labels within segmented nuclei, and created an ImageJ plugin to allow for efficient manual correction of nuclear segmentation and label identification. Lastly, using fluorescence intensity as a readout for protein concentration, a three-step global estimation method was applied to the characterization of the cell cycle dependent expression of E2F proteins in the developing mouse intestine., Competing Interests: The authors have declared that no competing interests exist.