Coccidioides immitis presenting with acute hydropneumothorax in an immunocompetent patient from South Texas

Coccidioidomycosis is a disease caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii that predominates in dry climates and it is endemic in Southern California and Arizona. Coccidioides is also found in parts of West Texas and a long the Rio Grande River, however, incidence tends to decrease in areas close to the Gulf of Mexico due to increased humidity. Coccidioidomycosis is more commonly a subclinical and self-limited disease in up to sixty percent of cases. Acute pneumonia (Valley fever), extra thoracic disseminated infection and complications occur more frequently in immunocompromised hosts. We present a case of severe coccidiomycosis in an immunocompetent host who lived in central California for two months, 2 years prior to manifesting severe respiratory compromise. Clinicians should be able to recognize differential diagnoses for cavitary-like lung lesions, paying close attention to social history and CDC epidemiology data

Predictive Markers of Coagulopathy in COVID-19 Infection: A Meta Narrative Review

In late 2019, COVID was initially discovered in Wuhan, China, and the COVID-19 pandemic primarily began in early 2020. Along with respiratory distress, COVID-19 patients had an increased risk of forming abnormal clotting. In ICU COVID-19 patients, abnormal clotting increases the risk of mortality by approximately 74% (Montiel et al., 2022). The aim for this meta-narrative review was to identify what hemostatic parameters are predictive of coagulopathy in COVID-19 patients. Determining predictive markers of coagulopathy in COVID-19 infection may allow for early identification of severe cases before bleeding and thrombotic manifestations occur. The review included articles primarily from PubMed and were published between 2020 and 2022. After screening for eligibility, seven articles were deemed fit to be included. Our findings indicate that elevated D-dimer levels were the most common predictive hemostatic parameter utilized, along with elevated Von Willebrand Factor, elevated Factor VIII, and decreased fibrinogen levels. COVID-19 patients that presented with these parameters upon admission were highly likely to experience clotting events such as deep vein thrombosis and pulmonary embolism. Although many of the articles in this review focused on elevated D-dimer as an early marker of coagulopathy, one study found that elevated soluble thrombomodulin was the best predictor of coagulopathy in COVID patients. Future research will be needed to confirm soluble thrombomodulin’s ability as a predictive parameter and compare its suggestive power to D-dimer levels. Clinical trials will also be needed to assess how these predictive markers can be used to inform prophylactic treatment in COVID-19 patients.https://openworks.mdanderson.org/rmps/1003/thumbnail.jp

High infestation of invasive Aedes mosquitoes in used tires along the local transport network of Panama

Background: The long‑distance dispersal of the invasive disease vectors Aedes aegypti and Aedes albopictus has intro‑ duced arthropod‑borne viruses into new geographical regions, causing a significant medical and economic burden. The used‑tire industry is an effective means of Aedes dispersal, yet studies to determine Aedes occurrence and the factors influencing their distribution along local transport networks are lacking. To assess infestation along the primary transport network of Panama we documented all existing garages that trade used tires on the highway and surveyed a subset for Ae. aegypti and Ae. albopictus. We also assess the ability of a mass spectrometry approach to classify mos‑ quito eggs by comparing our findings to those based on traditional larval surveillance. Results: Both Aedes species had a high infestation rate in garages trading used tires along the highways, providing a conduit for rapid dispersal across Panama. However, generalized linear models revealed that the presence of Ae. aegypti is associated with an increase in road density by a log‑odds of 0.44 (0.73 ± 0.16; P = 0.002), while the presence of Ae. albopictus is associated with a decrease in road density by a log‑odds of 0.36 (0.09 ± 0.63; P = 0.008). Identifica‑ tion of mosquito eggs by mass spectrometry depicted similar occurrence patterns for both Aedes species as that obtained with traditional rearing methods. Conclusions: Garages trading used tires along highways should be targeted for the surveillance and control of Aedes‑mosquitoes and the diseases they transmit. The identification of mosquito eggs using mass spectrometry allows for the rapid evaluation of Aedes presence, affording time and cost advantages over traditional vector surveil‑ lance; this is of importance for disease risk assessment.Background: The long‑distance dispersal of the invasive disease vectors Aedes aegypti and Aedes albopictus has intro‑ duced arthropod‑borne viruses into new geographical regions, causing a significant medical and economic burden. The used‑tire industry is an effective means of Aedes dispersal, yet studies to determine Aedes occurrence and the factors influencing their distribution along local transport networks are lacking. To assess infestation along the primary transport network of Panama we documented all existing garages that trade used tires on the highway and surveyed a subset for Ae. aegypti and Ae. albopictus. We also assess the ability of a mass spectrometry approach to classify mos‑ quito eggs by comparing our findings to those based on traditional larval surveillance. Results: Both Aedes species had a high infestation rate in garages trading used tires along the highways, providing a conduit for rapid dispersal across Panama. However, generalized linear models revealed that the presence of Ae. aegypti is associated with an increase in road density by a log‑odds of 0.44 (0.73 ± 0.16; P = 0.002), while the presence of Ae. albopictus is associated with a decrease in road density by a log‑odds of 0.36 (0.09 ± 0.63; P = 0.008). Identifica‑ tion of mosquito eggs by mass spectrometry depicted similar occurrence patterns for both Aedes species as that obtained with traditional rearing methods. Conclusions: Garages trading used tires along highways should be targeted for the surveillance and control of Aedes‑mosquitoes and the diseases they transmit. The identification of mosquito eggs using mass spectrometry allows for the rapid evaluation of Aedes presence, affording time and cost advantages over traditional vector surveil‑ lance; this is of importance for disease risk assessment

In vivo imaging of lung inflammation with neutrophil-specific Ga-68 nano-radiotracer

In vivo detection and quantification of inflammation is a major goal in molecular imaging. Furthermore, cell-specific detection of inflammation would be a tremendous advantage in the characterization of many diseases. Here, we show how this goal can be achieved through the synergistic combination of nanotechnology and nuclear imaging. One of the most remarkable features of this hybrid approach is the possibility to tailor the pharmacokinetics of the nanomaterial-incorporated biomolecule and radionuclide. A good example of this approach is the covalent binding of a large amount of a neutrophil-specific, hydrophobic peptide on the surface of Ga-68 core-doped nanoparticles. This new nano-radiotracer has been used for non-invasive in vivo detection of acute inflammation with very high in vivo labelling efficiency, i.e. a large percentage of labelled neutrophils. Furthermore, we demonstrate that the tracer is neutrophil-specific and yields images of neutrophil recruitment of unprecedented quality. Finally, the nano-radiotracer was successfully detected in chronic inflammation in atherosclerosis-prone ApoE(-/-) mice after several weeks on a high-fat diet

Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.National Institutes of HealthRevisión por pare

Gametogenesis in the Pacific Oyster Crassostrea gigas: A Microarrays-Based Analysis Identifies Sex and Stage Specific Genes

Background: The Pacific oyster Crassostrea gigas (Mollusca, Lophotrochozoa) is an alternative and irregular protandrous hermaphrodite: most individuals mature first as males and then change sex several times. Little is known about genetic and phenotypic basis of sex differentiation in oysters, and little more about the molecular pathways regulating reproduction. We have recently developed and validated a microarray containing 31,918 oligomers (Dheilly et al., 2011) representing the oyster transcriptome. The application of this microarray to the study of mollusk gametogenesis should provide a better understanding of the key factors involved in sex differentiation and the regulation of oyster reproduction. Methodology/Principal Findings: Gene expression was studied in gonads of oysters cultured over a yearly reproductive cycle. Principal component analysis and hierarchical clustering showed a significant divergence in gene expression patterns of males and females coinciding with the start of gonial mitosis. ANOVA analysis of the data revealed 2,482 genes differentially expressed during the course of males and/or females gametogenesis. The expression of 434 genes could be localized in either germ cells or somatic cells of the gonad by comparing the transcriptome of female gonads to the transcriptome of stripped oocytes and somatic tissues. Analysis of the annotated genes revealed conserved molecular mechanisms between mollusks and mammals: genes involved in chromatin condensation, DNA replication and repair, mitosis and meiosis regulation, transcription, translation and apoptosis were expressed in both male and female gonads. Most interestingly, early expressed male-specific genes included bindin and a dpy-30 homolog and female-specific genes included foxL2, nanos homolog 3, a pancreatic lipase related protein, cd63 and vitellogenin. Further functional analyses are now required in order to investigate their role in sex differentiation in oysters. Conclusions/Significance: This study allowed us to identify potential markers of early sex differentiation in the oyster C. gigas, an alternative hermaphrodite mollusk. We also provided new highly valuable information on genes specifically expressed by mature spermatozoids and mature oocytes

Remission of obesity and insulin resistance is not sufficient to restore mitochondrial homeostasis in visceral adipose tissue

Metabolic plasticity is the ability of a biological system to adapt its metabolic phenotype to different environmental stressors. We used a whole-body and tissue-specific phenotypic, functional, proteomic, metabolomic and transcriptomic approach to systematically assess metabolic plasticity in diet-induced obese mice after a combined nutritional and exercise intervention. Although most obesity and overnutrition-related pathological features were successfully reverted, we observed a high degree of metabolic dysfunction in visceral white adipose tissue, characterized by abnormal mitochondrial morphology and functionality. Despite two sequential therapeutic interventions and an apparent global healthy phenotype, obesity triggered a cascade of events in visceral adipose tissue progressing from mitochondrial metabolic and proteostatic alterations to widespread cellular stress, which compromises its biosynthetic and recycling capacity. In humans, weight loss after bariatric surgery showed a transcriptional signature in visceral adipose tissue similar to our mouse model of obesity reversion. Overall, our data indicate that obesity prompts a lasting metabolic fingerprint that leads to a progressive breakdown of metabolic plasticity in visceral adipose tissue

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery