Updates in Coccidioidomycosis.

Coccidioidomycosis is the clinical disease caused by the dimorphic pathogenic fungi Coccidioides immitis and C posadasii. The number of clinically recognized coccidioidomycosis cases continues to increase yearly including in regions outside the traditional regions of endemicity. Following inhalation of Coccidioides spores, the course may range from asymptomatic exposure with resultant immunity, to a subacute pulmonary illness, to life-threatening disseminated infection.

Managing Cavitary Coccidioidomycosis Expert Opinions for Improving Patient Outcomes.

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.

Burden of Hospitalization for Coccidioidal Meningitis: An Analysis of the National Inpatient Sample, 2019-2021.

Coccidioidal meningitis (CM) requires lifelong aggressive management, often necessitating hospitalization. In the National Inpatient Sample (2019-2021), CM hospitalizations (N = 2305) were associated with frequent CM-related procedures (63.6% [95% confidence interval {CI}, 59.

AP2A2 mutation and defective endocytosis in a Malian family with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) comprises a large group of neurogenetic disorders characterized by progressive lower extremity spasticity. Neurological evaluation and genetic testing were completed in a Malian family with early-onset HSP. Three children with unaffected consanguineous parents presented with symptoms consistent with childhood-onset complicated HSP.

JAK inhibitors for inflammatory bowel disease: recent advances.

Inflammatory bowel disease (IBD) commonly requires immunosuppressive treatments to induce and maintain durable remission. Janus kinase inhibitors (JAKis) are a novel group of orally administered, small molecule drugs that work by attenuating multiple cytokine signalling pathways to mediate dysregulated immune responses involved in the pathogenesis of IBD. Tofacitinib, filgotinib and upadacitinib have demonstrated efficacy against placebo and are licensed for the treatment of moderate to severe ulcerative colitis; upadacitinib is the only JAKi also currently approved for the treatment of Crohn's disease.

FANCA c.3624C>T (p.Ser1208=) is a hypomorphic splice variant associated with delayed onset of Fanconi anemia.

Fanconi anemia (FA) is a hereditary, DNA repair deficiency disorder caused by pathogenic variants in any 1 of 22 known genes (FANCA-FANCW). Variants in FANCA account for nearly two-thirds of all patients with FA. Clinical presentation of FA can be heterogeneous and include congenital abnormalities, progressive bone marrow failure, and predisposition to cancer.

Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy.

Familial platelet disorder with associated myeloid malignancies (FPDMM) is caused by germline RUNX1 mutations and characterized by thrombocytopenia and increased risk of hematologic malignancies. We recently launched a longitudinal natural history study for patients with FPDMM. Among 27 families with research genomic data by the end of 2021, 26 different germline RUNX1 variants were detected.

Theoretical design of a space bioprocessing system to produce recombinant proteins.

Space-based biomanufacturing has the potential to improve the sustainability of deep space exploration. To advance biomanufacturing, bioprocessing systems need to be developed for space applications. Here, commercial technologies were assessed to design space bioprocessing systems to supply a liquid amine carbon dioxide scrubber with active carbonic anhydrase produced recombinantly.

Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis.

Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach.

Differential Regulation of Retinoic Acid Metabolism in Fanconi Anemia.

Fanconi anemia (FA) is a rare genetic disease characterized by heterogeneous congenital abnormalities and increased risk for bone marrow failure and cancer. FA is caused by mutation of any one of 23 genes, the protein products of which function primarily in the maintenance of genome stability. An important role for the FA proteins in the repair of DNA interstrand crosslinks (ICLs) has been established .

Utilizing teachers to enhance student recovery through emergency educational programming: A case study analysis of Hurricane Maria.

Emergency educational programing after disasters contributes to the physical, cognitive, and psychological protection of students when they are at their most vulnerable. The Inter-Agency Network for Education in Emergencies Minimum Standards for Education in Emergencies framework details the need to incorporate specific domains throughout implementation and asserts that teachers and educational institutions play a significant role in supporting disaster-affected youth in the classroom. Following the detrimental impact of Hurricane Maria on Puerto Rico, teachers became critical agents for maintaining the well-being of children at school, so the goals of this analysis are to (1) examine teachers' post-hurricane experiences to find out how the event impacted physical teaching environments and students' learning capacity, (2) investigate how teachers adapted and developed lesson plans to facilitate students' processing of the event, and (3) explore what resources, training, and emotional support teachers needed to continue their work in the classroom post-disaster.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

Cross-Sectional Study of Clinical Predictors of Coccidioidomycosis, Arizona, USA.

Demographic and clinical indicators have been described to support identification of coccidioidomycosis; however, the interplay of these conditions has not been explored in a clinical setting. In 2019, we enrolled 392 participants in a cross-sectional study for suspected coccidioidomycosis in emergency departments and inpatient units in Coccidioides-endemic regions. We aimed to develop a predictive model among participants with suspected coccidioidomycosis.

Studies of a mosaic patient with DBA and chimeric mice reveal erythroid cell-extrinsic contributions to erythropoiesis.

We follow a patient with Diamond-Blackfan anemia (DBA) mosaic for a pathogenic RPS19 haploinsufficiency mutation with persistent transfusion-dependent anemia. Her anemia remitted on eltrombopag (EPAG), but surprisingly, mosaicism was unchanged, suggesting that both mutant and normal cells responded. When EPAG was withheld, her anemia returned.

TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary .

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in infection remains poorly understood. The need to understand TNFα in infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice.

Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity.

Background: The risk of coccidioidomycosis (CM) as a life-threatening respiratory illness or disseminated CM (DCM) increases as much as 150-fold in immunosuppressed patients. The safety of biologic response modifiers (BRMs) as treatment for patients with autoimmune disease (AI) in CM-endemic regions is not well defined. We sought to determine that risk in the Tucson and Phoenix areas.

A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever).

Introduction: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection.