Search

Coccidioidomycosis is a disease caused by soil fungi of the genus Coccidioides, divided genetically into Coccidioides immitis (California isolates) and Coccidioides posadasii (isolates outside California). Coccidioidomycosis is transmitted through the inhalation of fungal spores, arthroconidia, which can cause disease in susceptible mammalian hosts, including humans. Coccidioidomycosis is endemic to the western part of the United States of America, including the central valley of California, Arizona, New Mexico, and parts of western Texas. Cases have been reported in other regions in different states, and endemic pockets are present in these states. The incidence of reported cases of coccidioidomycosis has notably increased since it became reportable in 1995. Clinically, the infection ranges from asymptomatic to fatal disease due to pneumonia or disseminated states. The recognition of coccidioidomycosis can be challenging, as it frequently mimics bacterial community-acquired pneumonia. The diagnosis of coccidioidomycosis is frequently dependent on serologic testing, the results of which can take several days or longer to obtain. Coccidioidomycosis continues to present challenges for clinicians, and suspected cases can be easily missed. The challenges of coccidioidomycosis disease, from presentation to diagnosis to treatment, remain a hurdle for clinicians, and further research is needed to address these challenges.

BackgroundCoccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations.Materials and methodsWe identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci.ResultsUsing univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making.ConclusionsCareful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

BACKGROUND: Although trust is central to successful physician-family relationships in ICUs, little is known about how to promote surrogates trust of ICU physicians in this setting. RESEARCH QUESTION: Does the conduct of family conferences and physicians use of shared decision-making (SDM) within family conferences impact surrogates trust in the physician? STUDY DESIGN AND METHODS: A mixed-methods secondary analysis was done of a multicenter prospective cohort study of 369 surrogate decision-makers of 204 decisionally incapacitated patients at high risk of death or severe functional impairment within 13 ICUs at six US medical centers between 2008 and 2012. Surrogates completed the Abbreviated Wake Forest Physician Trust Scale (range, 5-25) before and after an audio-recorded family conference conducted within 5 days of ICU admission. We qualitatively coded transcribed conferences to determine physicians use of five SDM behaviors: discussing surrogates role, explaining medical condition and prognosis, providing emotional support, assessing understanding, and eliciting patients values and preferences. Using multivariable linear regression with adjustment for clustering, we assessed whether surrogates trust in the physician increased after the family meeting; we also examined whether the number of SDM behaviors used by physicians during the family meeting impacted trust scores. RESULTS: In adjusted models, conduct of a family meeting was associated with increased trust (average change, pre- to post family meeting: 0.91 point [95% CI, 0.4-1.4; P < .01]). Every additional element of SDM used during the family meeting, including discussing surrogates role, providing emotional support, assessing understanding, and eliciting patients values and preferences, was associated with a 0.37-point increase in trust (95% CI, 0.08-0.67; P = .01). If all four elements were used, trust increased by 1.48 points. Explaining medical condition or prognosis was observed in nearly every conference (98.5%) and was excluded from the final model. INTERPRETATION: The conduct of family meetings and physicians use of SDM behaviors during meetings were both associated with increases in surrogates trust in the treating physician.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including typical, indeterminate, and atypical appearance for COVID-19, or negative for pneumonia, adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Objective: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Results: Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. Conclusion: This study suggests which types of interventions are more effective in addressing depression in heart failure patients.

CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, Cx3cr1 deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a comparable fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.

ObjectivesOptimistic expectations about prognosis by surrogate decision-makers in ICUs are common, but there are few data about the causes and clinical consequences. Our objective was to determine the causes of optimistic expectations about prognosis among surrogates and whether it is associated with more use of life support at the end of life.DesignProspective, multicenter cohort study from 2009 to 2012.SettingTwelve ICUs from multiple regions of the United States.SubjectsThe surrogates and physicians of 275 incapacitated ICU patients at high risk of death.InterventionsNone.Measurements and main resultsSurrogates and physicians completed a validated instrument assessing their prognostic expectations for hospital survival. We determined the proportion of surrogates with optimistic expectations, defined as a prognostic estimate that was at least 20% more optimistic than the physician's, then determined how frequently this arose from surrogates miscomprehending the physicians' prognosis versus holding more hopeful beliefs compared with the physician. We used multivariable regression to examine whether optimistic expectations were associated with length of stay, stratified by survival status, and time to withdrawal of life support among nonsurvivors. Overall, 45% of surrogates (95% CI, 38-51%) held optimistic expectations about prognosis, which arose from a combination of misunderstanding the physician's prognostic expectations and from holding more hopeful beliefs compared with the physician. Optimistic expectations by surrogates were associated with significantly longer duration of ICU treatment among nonsurvivors before death (β coefficient = 0.44; 95% CI, 0.05-0.83; p = 0.027), corresponding to a 56% longer ICU stay. This difference was associated with a significantly longer time to withdrawal of life support among dying patients whose surrogates had optimistic prognostic expectations compared with those who did not (β coefficient = 0.61; 95% CI, 0.16-1.07; p = 0.009).ConclusionsThe prevalent optimism about prognosis among surrogates in ICUs arises both from surrogates' miscomprehension of physicians' prognostications and from surrogates holding more hopeful beliefs. This optimism is associated with longer duration of life support at the end of life.

Coccidioidomycosis (CM) is a fungal infection endemic in the southwestern United States (US). In California, CM incidence increased more than 213% (from 6.0/100,000 (2014) to 18.8/100,000 (2017)) and continues to increase as rates in the first half of 2018 are double that of 2017 during the same period. This cost-of-illness study provides essential information to be used in health planning and funding as CM infections continue to surge. We used a "bottom-up" approach to determine lifetime costs of 2017 reported incident CM cases in California. We defined CM natural history and used a societal approach to determine direct and discounted indirect costs using literature, national datasets, and expert interviews. The total lifetime cost burden of CM cases reported in 2017 in California is just under $700 million US dollars, with $429 million in direct costs and $271 million in indirect costs. Per person direct costs were highest for disseminated disease ($1,023,730), while per person direct costs were lowest for uncomplicated CM pneumonia ($22,039). Cost burden varied by county. This is the first study to estimate total costs of CM, demonstrating its huge cost burden for California.

To assess and compare the diagnostic performance of magnitude-reconstruction chemical-shift-encoded magnetic resonance imaging (MRI-M) and complex-reconstruction chemical-shift-encoded magnetic resonance imaging (MRI-C) for diagnosis of hepatic steatosis in subjects with severe obesity without known non-alcoholic fatty liver disease (NAFLD), using contemporaneous histology as reference. This is an IRB-approved, HIPAA-compliant, two-center, cross-sectional study of a larger prospective trail that recruited patients without known NAFLD consecutively between October 2010 and March 2015 to undergo research MRI exams 1-2 days prior to clinical-care weight-loss surgery. Proton denisty fat fraction (PDFF) was estimated using MRI-M and MRI-C. Liver biopsies were obtained intraoperatively. Using histologically-determined presence of steatosis as the reference standard, receiver operating characteristics (ROC) analyses were used to identify MRI-M- and MRI-C-derived PDFF thresholds for diagnosing steatosis. Bootstrapped-based tests were used to compare their diagnostic performace. A total of 81 patients (67 female, 14 maile, average age 48.2) were recruited for this study. MRI-M and MRI-C had areas under the ROC curve of 0.951 and 0.947, respectively, for diagnosing hepatic steatosis. for MRI-M, the Youden-index-based PDFF threshold of 6.5% provided 0.87 sensitivity (95% confidence internal: 0/75, 0.95), 0.96 specificity (0.81, 0.99), and 0.90 total accuracy (0.82, 0.96). For MRI-C, a PDFF threshold of 6.8%, provided a 0.90 sensitivity (0.77, 0.96), 0.96 specificity (0.81, 0.99), and 0.91 total accuracy (0.83, 0.97). Differences in performance parameters between MRI-M and MRI-C were not statistically significant. Conclusion: MRI-M- and MRI-C-derived PDFF is accurate for non-invasive diagnosis of hepatic steatosis in subjects with severe obesity.

ObjectiveChanges in slow waves during non-rapid eye movement (NREM) sleep in response to acute total sleep deprivation are well-established measures of sleep homeostasis. This investigation utilized high-density electroencephalography (hdEEG) to examine topographic changes in slow waves during repeated partial sleep deprivation.MethodsTwenty-four participants underwent a 6-day sleep restriction protocol. Spectral and period-amplitude analyses of sleep hdEEG data were used to examine changes in slow wave energy, count, amplitude, and slope relative to baseline.ResultsChanges in slow wave energy were dependent on the quantity of NREM sleep utilized for analysis, with widespread increases during sleep restriction and recovery when comparing data from the first portion of the sleep period, but restricted to recovery sleep if the entire sleep episode was considered. Period-amplitude analysis was less dependent on the quantity of NREM sleep utilized, and demonstrated topographic changes in the count, amplitude, and distribution of slow waves, with frontal increases in slow wave amplitude, numbers of high-amplitude waves, and amplitude/slopes of low amplitude waves resulting from partial sleep deprivation.ConclusionsTopographic changes in slow waves occur across the course of partial sleep restriction and recovery.SignificanceThese results demonstrate a homeostatic response to partial sleep loss in humans.

BackgroundThe negative symptoms of schizophrenia include deficits in emotional expression and motivation. These deficits are stable over the course of illness and respond poorly to current medications. Previous studies have focused on negative symptoms as a single category; however, individual symptoms might be related to separate neurological disturbances. We analyzed data from the Functional Biomedical Informatics Research Network dataset to explore the relationship between individual negative symptoms and functional brain activity during an auditory oddball task.MethodsFunctional magnetic resonance imaging was conducted on 89 schizophrenia patients and 106 healthy controls during a two-tone auditory oddball task. Blood oxygenation level-dependent (BOLD) signal during the target tone was correlated with severity of five negative symptom domains from the Scale for the Assessment of Negative Symptoms.ResultsThe severity of alogia, avolition/apathy and anhedonia/asociality was negatively correlated with BOLD activity in distinct sets of brain regions associated with processing of the target tone, including basal ganglia, thalamus, insular cortex, prefrontal cortex, posterior cingulate and parietal cortex.ConclusionsIndividual symptoms were related to different patterns of functional activation during the oddball task, suggesting that individual symptoms might arise from distinct neural mechanisms. This work has potential to inform interventions that target these symptom-related neural disruptions.

As top predators in the northeast Pacific Ocean, northern elephant seals (Mirounga angustirostris) are vulnerable to bioaccumulation of persistent organic pollutants (POPs). Our study examined a suite of POPs in blubber (inner and outer) and blood (serum) of free-ranging northern elephant seals. For adult females (N=24), we satellite tracked and sampled the same seals before and after their approximately seven month long foraging trip. For males, we sampled different adults and sub-adults before (N=14) and after (N=15) the same foraging trip. For females, we calculated blubber burdens for all compounds. The highest POP concentrations in males and females were found for ∑DDTs and ∑PCBs. In blubber and serum, males had significantly greater concentrations than females for almost all compounds. For males and females, ∑DDT and ∑PBDEs were highly correlated in blubber and serum. While ∑PCBs were highly correlated with ∑DDTs and ∑PBDEs in blubber and serum for males, ∑PCBs showed weaker correlations with both compounds in females. As females gained mass while foraging, concentrations of nearly all POPs in inner and outer blubber significantly decreased; however, the absolute burden in blubber significantly increased, indicating ingestion of contaminants while foraging. Additionally, we identified three clusters of seal foraging behavior, based on geography, diving behavior, and stable carbon and nitrogen isotopes, which corresponded with differences in ∑DDTs, ∑PBDEs, MeO-BDE 47, as well as the ratio of ∑DDTs to ∑PCBs, indicating the potential for behavior to heighten or mitigate contaminant exposure. The greatest concentrations of ∑DDTs and ∑PBDEs were observed in the cluster that foraged closer to the coast and had blood samples more enriched in (13)C. Bioaccumulation of POPs by elephant seals supports mesopelagic food webs as a sink for POPs and highlights elephant seals as a potential sentinel of contamination in deep ocean food webs.

PurposeTo determine per-lesion sensitivity and positive predictive value (PPV) of gadoxetic acid-enhanced 3-T magnetic resonance (MR) imaging for the diagnosis of malignant lesions by using matched (spatially correlated) hepatectomy pathologic findings as the reference standard. Materials andMethodsIn this prospective, institutional review board-approved, HIPAA-compliant study, 20 patients (nine men, 11 women; mean age, 59 years) with malignant liver lesions who gave written informed consent underwent preoperative gadoxetic acid-enhanced 3-T MR imaging for surgical planning. Two image sets were independently analyzed by three readers to detect liver lesions (set 1 without and set 2 with hepatobiliary phase [HBP] images). Hepatectomy specimen ex vivo MR imaging assisted in matching gadoxetic acid-enhanced 3-T MR imaging findings with pathologic findings. Interreader agreement was assessed by using the Cohen κ coefficient. Per-lesion sensitivity and PPV were calculated.ResultsCohen κ values were 0.64-0.76 and 0.57-0.84, and overall per-lesion sensitivity was 45% (42 of 94 lesions) to 56% (53 of 94 lesions) and 58% (55 of 94 lesions) to 64% (60 of 94 lesions) for sets 1 and 2, respectively. The addition of HBP imaging did not affect interreader agreement but significantly improved overall sensitivity for one reader (P < .05) and almost for another (P = .05). Sensitivity for 0.2-0.5-cm lesions was 0% (0 of 26 lesions) to 8% (two of 26 lesions) for set 1 and 4% (one of 26 lesions) to 12% (three of 26 lesions) for set 2. Sensitivity for 0.6-1.0-cm lesions was 28% (nine of 32 lesions) to 59% (19 of 32 lesions) for set 1 and 66% (21 of 32 lesions) to 69% (22 of 32 lesions) for set 2. Sensitivity for lesions at least 1.0 cm in diameter was at least 81% (13 of 16 lesions) for set 1 and was not improved for set 2. PPV was 98% (56 of 57 lesions) to 100% (60 of 60 lesions) for all readers without differences between image sets or lesion size.ConclusionGadoxetic acid-enhanced 3-T MR imaging provides high per-lesion sensitivity and PPV for preoperative malignant liver lesion detection overall, although sensitivity for 0.2-0.5-cm malignant lesions is poor.

PurposeTo investigate in adults the associations between histologic features of nonalcoholic fatty liver disease (NAFLD) and quantitative measures derived from diffusion-weighted imaging (DWI).Materials and methodsEighty-nine adults undergoing standard-of-care liver biopsy for NAFLD were recruited for DWI. Biopsies were scored for histologic features of NAFLD. DWI was performed using b-values of 0, 100, and 500 s/mm(2) . Images were reconstructed using either conventional magnitude averaging (CMA) or a method to address bulk motion artifacts (Beta*LogNormal, BLN). The apparent diffusion coefficient (ADC) and the diffusivity (D) and perfusion fraction (F) of the intravoxel incoherent motion (IVIM) model were measured in the right hepatic lobe using both reconstructions. Associations between histologic features and DWI-derived measures were tested statistically with several methods including multiple linear regression.ResultsUsing CMA and BLN reconstructions, respectively, the means (and ranges) were 1.7 (1.1-3.5) and 1.4 (1.0-3.2) × 10(-3) mm(2) /s for ADC, 1.1 (0.84-1.4) and 0.84 (0.53-1.1) × 10(-3) mm(2) /s for D, and 17 and 18 (2.3-35)% for F. For both reconstruction methods, D decreased with steatosis and F decreased with fibrosis (P < 0.05). ADC was not independently associated with any histologic feature.ConclusionSteatosis and fibrosis have significant independent effects on D and F in adults undergoing biopsy for NAFLD.

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

Rapid real-time PCR (RT-PCR) can be performed in a community hospital setting to identify Coccidioides species using the new Becton Dickinson molecular instrument BD Max. Following sample preparation, DNA extraction and PCR were performed on the BD Max using the BD Max extraction kit ExK-DNA-1 test strip and a master mix prepared by BioGX (Birmingham, AL). Sample preparation took 2 h, and testing on the BD Max took an additional 2 h. Method sensitivity and specificity were evaluated along with the limits of detection to confirm that this convenient method would provide medically useful information. Using serial dilutions, the lower limit of detection was determined to be 1 CFU/μl. Testing with this method was validated using samples from various body sites, including bronchial alveolar lavage (BAL) fluid; sputum and lung tissue samples; and pleural and spinal fluids. Safety protocols were established, and specimen preparation processes were developed for the various types of specimens. The range for the cycle threshold (CT) indicating adequate fluorescent signal to signify a positive result was established along with the acceptable range for the internal standard. Positive controls run with each batch were prepared by spiking a pooled BAL fluid specimen with a known dilution of Coccidioides immitis organism. Our experience with testing >330 patient samples shows that clinically relevant information can be available within 4 h using an RT-PCR method on the BD Max to identify Coccidioides spp., with sensitivity equivalent to culture.

Background & aimsLittle is known about how weight loss affects magnetic resonance imaging (MRI) of liver fat and volume or liver histology in patients with nonalcoholic steatohepatitis (NASH). We measured changes in liver fat and liver volume associated with weight loss by using an advanced MRI method.MethodsWe analyzed data collected from a previous randomized controlled trial in which 43 adult patients with biopsy-proven NASH underwent clinical evaluation, biochemical tests, and MRI and liver biopsy analyses at the start of the study and after 24 weeks. We compared data between patients who did and did not have at least 5% decrease in body mass index (BMI) during the study period.ResultsTen of 43 patients had at least a 5% decrease in BMI during the study period. These patients had a significant decrease in liver fat, which was based on MRI proton density fat fraction estimates (18.3% ± 7.6% to 13.6% ± 13.6%, P = .03), a relative 25.5% reduction. They also had a significant decrease in liver volume (5.3%). However, no significant changes in levels of alanine aminotransferase or aspartate aminotransferase were observed with weight loss. Thirty-three patients without at least 5% decrease in BMI had insignificant increases in estimated liver fat fraction and liver volume.ConclusionsA reduction in BMI of at least 5% is associated with significant decrease in liver fat and volume in patients with biopsy-proven NASH. These data should be considered in assessing effect size in studies of patients with nonalcoholic fatty liver disease or obesity that use MRI-estimated liver fat and volume as end points.

In this article, the author introduces whole schooling and its role within: to work towards positive change in schooling. The author discusses what led educators to the idea of creating schools that are more effective, engaging, and joyful places of growth and development for children.

This study examined the impact of the American Cancer Society's (ACS's) media based peer education program, Message Magic: Selling Healthy Eating and Physical Activity, on participant self-reported dietary and physical activity behaviors and advocacy skill development. High school students participating in the program were required to work as a team to examine advertising techniques and then develop a media-based message to be presented to peers. Results indicated that significant nutritional improvements in girls and physical activity improvements in boys were realized. The majority (76%) of participants expressed that their media messages had made a positive difference in their school and the program enhanced their advocacy skills. Students rated their experience in the program favorably. Findings suggest the ACS media-based program may be a viable option for a high school health curriculum. (Contains 3 tables.)