Age-dependent ventilator-induced lung injury: Mathematical modeling, experimental data, and statistical analysis.

A variety of pulmonary insults can prompt the need for life-saving mechanical ventilation; however, misuse, prolonged use, or an excessive inflammatory response, can result in ventilator-induced lung injury. Past research has observed an increased instance of respiratory distress in older patients and differences in the inflammatory response. To address this, we performed high pressure ventilation on young (2-3 months) and old (20-25 months) mice for 2 hours and collected data for macrophage phenotypes and lung tissue integrity. Large differences in macrophage activation at baseline and airspace enlargement after ventilation were observed in the old mice. The experimental data was used to determine plausible trajectories for a mathematical model of the inflammatory response to lung injury which includes variables for the innate inflammatory cells and mediators, epithelial cells in varying states, and repair mediators. Classification methods were used to identify influential parameters separating the parameter sets associated with the young or old data and separating the response to ventilation, which was measured by changes in the epithelial state variables. Classification methods ranked parameters involved in repair and damage to the epithelial cells and those associated with classically activated macrophages to be influential. Sensitivity results were used to determine candidate in-silico interventions and these interventions were most impact for transients associated with the old data, specifically those with poorer lung health prior to ventilation. Model results identified dynamics involved in M1 macrophages as a focus for further research, potentially driving the age-dependent differences in all macrophage phenotypes. The model also supported the pro-inflammatory response as a potential indicator of age-dependent differences in response to ventilation. This mathematical model can serve as a baseline model for incorporating other pulmonary injuries.

Large Clusters of Invasive emm49 Group A Streptococcus Identified Within Arizona Health Care Facilities Through Statewide Genomic Surveillance System, 2019-2021.

A statewide genomic surveillance system for invasive Group A Streptococcus was implemented in Arizona in June 2019, resulting in 1046 isolates being submitted for genomic analysis to characterize emm types and identify transmission clusters. Eleven of the 32 identified distinct emm types comprised >80% of samples, with 29.7% of all isolates being typed as emm49 (and its genetic derivative emm151). Phylogenetic analysis initially identified an emm49 genomic cluster of 4 isolates that rapidly expanded over subsequent months (June 2019 to February 2020). Public health investigations identified epidemiologic links with 3 different long-term care facilities, resulting in specific interventions. Unbiased genomic surveillance allowed for identification and response to clusters that would have otherwise remained undetected.

Mathematical modeling of ventilator-induced lung inflammation.

Despite the benefits of mechanical ventilators, prolonged or misuse of ventilators may lead to ventilation-associated/ventilation-induced lung injury (VILI). Lung insults, such as respiratory infections and lung injuries, can damage the pulmonary epithelium, with the most severe cases needing mechanical ventilation for effective breathing and survival. Damaged epithelial cells within the alveoli trigger a local immune response. A key immune cell is the macrophage, which can differentiate into a spectrum of phenotypes ranging from pro- to anti-inflammatory. To gain a greater understanding of the mechanisms of the immune response to VILI and post-ventilation outcomes, we developed a mathematical model of interactions between the immune system and site of damage while accounting for macrophage phenotype. Through Latin hypercube sampling we generated a collection of parameter sets that are associated with a numerical steady state. We then simulated ventilation-induced damage using these steady state values as the initial conditions in order to evaluate how baseline immune state and lung health affect outcomes. We used a variety of methods to analyze the resulting parameter sets, transients, and outcomes, including a random forest decision tree algorithm and parameter sensitivity with eFAST. Analysis shows that parameters and properties of transients related to epithelial repair and M1 activation are important factors. Using the results of this analysis, we hypothesized interventions and used these treatment strategies to modulate the response to ventilation for particular parameters sets.

Suspected Locally Acquired Coccidioidomycosis in Human, Spokane, Washington, USA.

The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.

Impact of the Lattice on Magnetic Properties and Possible Spin Nematicity in the S=1 Triangular Antiferromagnet NiGa_{2}S_{4}.

NiGa_{2}S_{4} is a triangular lattice S=1 system with strong two dimensionality of the lattice, actively discussed as a candidate to host spin-nematic order brought about by strong quadrupole coupling. Using Raman scattering spectroscopy we identify a phonon of E_{g} symmetry which can modulate magnetic exchange J_{1} and produce quadrupole coupling. Additionally, our Raman scattering results demonstrate a loss of local inversion symmetry on cooling, which we associate with sulfur vacancies. This will lead to disordered Dzyaloshinskii-Moriya interactions, which can prevent long-range magnetic order. Using magnetic Raman scattering response we identify 160 K as a temperature of an upturn of magnetic correlations. The temperature range below 160 K, but above 50 K where antiferromagnetic correlations start to increase, is a candidate for spin-nematic regime.

Dynamical Bonding Driving Mixed Valency in a Metal Boride.

Samarium hexaboride is an anomaly, having many exotic and seemingly mutually incompatible properties. It was proposed to be a mixed-valent semiconductor, and later a topological Kondo insulator, and yet has a Fermi surface despite being an insulator. We propose a new and unified understanding of SmB6 centered on the hitherto unrecognized dynamical bonding effect: the coexistence of two Sm-B bonding modes within SmB6 , corresponding to different oxidation states of the Sm. The mixed valency arises in SmB6 from thermal population of these distinct minima enabled by motion of B. Our model simultaneously explains the thermal valence fluctuations, appearance of magnetic Fermi surface, excess entropy at low temperatures, pressure-induced phase transitions, and related features in Raman spectra and their unexpected dependence on temperature and boron isotope.

Hypervirulent emm59 Clone in Invasive Group A Streptococcus Outbreak, Southwestern United States.

The hyper-virulent emm59 genotype of invasive group A Streptococcus was identified in northern Arizona in 2015. Eighteen isolates belonging to a genomic cluster grouped most closely with recently identified isolates in New Mexico. The continued transmission of emm59 in the southwestern United States poses a public health concern.

Acute Appendicitis in the Setting of Infectious Mononucleosis: A Case Report.

Infectious mononucleosis (IM) is a viral illness caused by the Epstein-Barr virus that typically manifests with pharyngitis, lymphadenopathy, and fatigue. In rare cases, IM can cause acute appendicitis. We present the case of an 18-year-old female who arrived at the emergency department with worsening abdominal pain and an ongoing cough. Initial imaging showed a questionably dilated appendix, and a follow-up examination revealed cervical lymphadenopathy. She later returned to the ED with severe abdominal pain, clinical signs of acute appendicitis, and a positive monospot test, which led to an appendectomy. This case illustrates the need for complete history taking and thorough physical examination in patients with acute appendicitis, as their condition may be due to an atypical underlying cause.

Lumbar disc herniation with radiculopathy: a comparison of NASS guidelines and ChatGPT.

Background: ChatGPT is an advanced language AI able to generate responses to clinical questions regarding lumbar disc herniation with radiculopathy. Artificial intelligence (AI) tools are increasingly being considered to assist clinicians in decision-making. This study compared ChatGPT-3.5 and ChatGPT-4.0 responses to established NASS clinical guidelines and evaluated concordance. Methods: ChatGPT-3.5 and ChatGPT-4.0 were prompted with fifteen questions from The 2012 NASS Clinical Guidelines for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Clinical questions organized into categories were directly entered as unmodified queries into ChatGPT. Language output was assessed by two independent authors on September 26, 2023 based on operationally-defined parameters of accuracy, over-conclusiveness, supplementary, and incompleteness. ChatGPT-3.5 and ChatGPT-4.0 performance was compared via chi-square analyses. Results: Among the fifteen responses produced by ChatGPT-3.5, 7 (47%) were accurate, 7 (47%) were over-conclusive, fifteen (100%) were supplementary, and 6 (40%) were incomplete. For ChatGPT-4.0, ten (67%) were accurate, 5 (33%) were over-conclusive, 10 (67%) were supplementary, and 6 (40%) were incomplete. There was a statistically significant difference in supplementary information (100% vs. 67%; p=.014) between ChatGPT-3.5 and ChatGPT-4.0. Accuracy (47% vs. 67%; p=.269), over-conclusiveness (47% vs. 33%; p=.456), and incompleteness (40% vs. 40%; p=1.000) did not show significant differences between ChatGPT-3.5 and ChatGPT-4.0. ChatGPT-3.5 and ChatGPT-4.0 both yielded 100% accuracy for definition and history and physical examination categories. Diagnostic testing yielded 0% accuracy for ChatGPT-3.5 and 100% accuracy for ChatGPT-4.0. Nonsurgical interventions had 50% accuracy for ChatGPT-3.5 and 63% accuracy for ChatGPT-4.0. Surgical interventions resulted in 0% accuracy for ChatGPT-3.5 and 33% accuracy for ChatGPT-4.0. Conclusions: ChatGPT-4.0 provided less supplementary information and overall higher accuracy in question categories than ChatGPT-3.5. ChatGPT showed reasonable concordance to NASS guidelines, but clinicians should caution use of ChatGPT in its current state as it fails to safeguard against misinformation.

A Readability Study of Carpal Tunnel Release in 2023.

BACKGROUND: The National Institutes of Health (NIH) and the American Medical Association (AMA) recommend a sixth-grade reading level for patient-directed content. This study aims to quantitatively evaluate the readability of online information sources related to carpal tunnel surgery using established readability indices. METHODS: Web searches for "carpal tunnel release" and "carpal tunnel decompression surgery" queries were performed using Google, and the first 20 websites were identified per query. WebFX online software tools were utilized to determine readability. Indices included Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, Coleman Liau Index, Automated Readability Index, Gunning Fog Score, and the Simple Measure of Gobbledygook Index. Health-specific clickthrough rate (CTR) data were used in order to select the first 20 search engine results page from each query. RESULTS: "Carpal tunnel release" had a mean readability of 8.46, and "carpal tunnel decompression surgery" had a mean readability of 8.70. The range of mean readability scores among the indices used for both search queries was 6.17 to 14.0. The total mean readability for carpal tunnel surgery information was found to be 8.58. This corresponds to approximately a ninth-grade reading level in the United States. CONCLUSION: The average readability of carpal tunnel surgery online content is three grade levels above the recommended sixth-grade level for patient-directed materials. This discrepancy indicates that existing online materials related to carpal tunnel surgery are more difficult to understand than the standards set by NIH and AMA.

In vitro small molecule screening to inform novel candidates for use in fluconazole combination therapy in vivo against Coccidioides.

Identifying improved treatments for severe and refractory coccidioidomycosis (Valley fever) is needed. This endemic fungal disease is common in North and South America, and cases have increased substantially over the last 30 years. The current standard of care, oral daily fluconazole, often fails to completely eradicate Coccidioides infection; however, the high cost of identifying new compounds effective in treating Valley fever is a barrier to improving treatment. Therefore, repurposing existing pharmaceutical agents in combination with fluconazole therapy is an attractive option. We screened the Library of Pharmacologically Active Compounds (LOPAC) small molecule library for compounds that inhibited fungal growth in vitro and determined IC50 values for a subset of compounds. Based on these findings, we tested a small subset of these agents to validate the screen, as well as to test the performance of fluconazole in a combination therapy approach, as compared with fluconazole alone, in a murine model. We observed that combination therapy of tamoxifen:fluconazole and sertraline:fluconazole significantly reduced the burden of live fungus in the lung compared with fluconazole alone, and we observed reduced or nonexistent dissemination. These results suggest that tamoxifen and sertraline may be repurposed as adjunctive agents in the treatment of this important fungal disease. IMPORTANCE: Developing new drugs, especially for regional orphan diseases, such as Valley Fever, is a slow and costly endeavor. However, there is a wealth of FDA-approved drugs available for repurposing, offering a more economical and expedited approach to improve treatment. Those existing compounds with antifungal properties can become novel therapies with relative ease: a considerable advantage for patients in need of alternative treatment. Despite the scope of remaining tasks, our comprehensive screening of potential candidates has revealed promising combinations for further exploration. This effort outlines a practical pipeline for Valley fever drug screening and identifies viable drug combinations that could impact patients more rapidly than single drug development pathways.

An Unidentified Infiltrative Etiology of Spinal Cord Compression: A Case Report and Literature Review.

Spinal cord compression is a neurosurgical emergency. Symptoms of this disorder are highlighted as back pain, ambulatory difficulties, and bladder/bowel incontinence. Diagnostic imaging is not indicated in many circumstances of nonspecific back pain; however, the addition of neurologic deficits in the setting of back pain justifies radiologic imaging. Various pathologies can cause constriction of the spinal cord due to the delicate nature of spinal cord anatomy. Etiologies may include trauma, neoplasms, and infections. In this report, we present an unusual case of a 31-year-old male who presented to the emergency department with a history of chronic back pain accompanied by neurological deficits, ataxia, and bladder dysfunction. Contrast-enhanced MRI imaging heightened the suspicion of a neoplastic etiology; however, neuropathology revealed a non-neoplastic nature with abnormal lymphohistiocytic infiltrate suspicious for Langerhans cell histiocytosis or infectious etiology. A second opinion was provided by Mayo Clinic Laboratories, resulting in the definitive conclusion that the mass was non-neoplastic and tested negative for SD1a and Langerhin, biomarkers used to diagnose Langerhans cell histiocytosis. This unusual non-neoplastic lesion exemplifies one of many diverse and multifaceted pathologies that can precipitate spinal cord compression. Additionally, these findings underscore the importance of considering both neoplastic and non-neoplastic causes in the differential diagnosis of spinal cord compression, thereby enhancing clinical vigilance and improving patient outcomes for underlying spinal conditions.

Lyssa excreta: Defining parameters for fecal samples as a rabies virus surveillance method.

It is not possible to systematically screen the environment for rabies virus (RABV) using current approaches. We sought to determine under what conditions RABV is detectable from feces and other accessible samples from infected wildlife to broaden the number of biological samples that could be used to test for RABV. We employed a recently-developed quantitative RT-PCR assay called the "LN34 panlyssavirus real-time RT-PCR assay", which is highly sensitive and specific for all variants of RABV. We harvested and tested brain tissue, fecal, and/or mouth swab samples from 25 confirmed RABV positive bats of six species. To determine if rabies RNA lasts in feces sufficiently long post-defecation to use it as a surveillance tool, we tested fecal samples from 10 bats at the time of sample collection and after 24 hours of exposure to ambient conditions, with an additional test on six bats out to 72 hours. To assess whether we could pool fecal pellets and still detect a positive, we generated dilutions of known positives at 1:1, 1:10, 1:50, and 1:200. For six individuals for which matched brain, mouth swab, and fecal samples were tested, results were positive for 100%, 67%, and 67%, respectively. For the first time test to 24 hours, 63% of feces that were positive at time 0 were still positive after 24 hours, and 50% of samples at 72 hours were positive across all three replicates. Pooling tests revealed that fecal positives were detected at 1:10 dilution, but not at 1:50 or 1:200. Our preliminary results suggest that fecal samples hold promise for a rapid and non-invasive environmental screening system.

An Abnormal Presentation of Rocky Mountain Spotted Fever: A Case Report.

The intracellular coccobacilli Rickettsia rickettsii causes Rocky Mountain Spotted Fever, a potentially fatal illness. This bacterium is transmitted to humans through a tick vector. Patients classically present with a triad of symptoms, including fever, headache, and a rash that begins on the extremities and spreads proximally to the trunk. Diagnosis of this disease can prove difficult when patients have unusual symptoms, such as hypertensive crisis. In this case report, we present a 29-year-old male who arrived at the emergency room with altered mental status and a hypertensive crisis after his family reported one week of changes in his behavior. The patient had no evidence of ticks, tick bites, fever, or rash. Positive findings in the emergency room included a WBC of 14.9 × 109. All other physical exams, imaging, and laboratory findings were non-contributory. The patient was promptly given IV hydralazine to control his blood pressure and empiric IV ceftriaxone for potential infection, and he was admitted for observation. Over the course of three days, WBC levels decreased, and his altered mental status improved. On day 3, the patient remembered a tick crawling across his hand, and this prompted the ordering of immunoglobulin levels for tick-borne illnesses. IgM for RMSF was positive. This case presentation illustrates the need for clinicians to keep the potential diagnosis of RMSF high on the differential, even in the presence of a paucity of symptoms, as prompt treatment with doxycycline can be lifesaving. This case may also be one of the first reported in the literature of hypertension being a symptom of Rocky Mountain Spotted Fever. It is plausible, however, that this patient's hypertension was due to an acute stress response.

A Clinical Suspicion of Quetiapine-Induced Psychosis: A Case Report and Literature Review.

Quetiapine, a pharmacological agent within the class of atypical antipsychotics, is characterized by its efficacy in mood stabilization and its role in the modulation of serotonergic and dopaminergic pathways. Its therapeutic utility is broad, encompassing the management of acute psychotic episodes, schizophrenia, bipolar disorder, and treatment-resistant depressive states. Quetiapine's effectiveness extends to depressive disorders that do not exhibit classic psychotic features, with a side effect profile that is less burdensome than many alternative psychotropic medications. Its versatility in addressing a range of psychiatric conditions is useful in the psychopharmacological management of mood and thought disorders. However, like all drugs, quetiapine may have different effects relative to the individual. It is imperative to approach the administration of quetiapine carefully, ensuring any adverse effects are ameliorated for beneficial therapeutic outcomes. In this case report, we present a psychosis-naive 42-year-old male who developed psychotic symptoms after beginning a quetiapine regimen in order to manage major depressive disorder with suicidal ideation. Clinical suspicion of quetiapine-induced psychosis was a diagnosis considered due to symptom remission secondary to ziprasidone in the place of quetiapine. The determination of a suspected adverse drug reaction can utilize the Naranjo scale to demonstrate the likelihood of an adverse drug reaction. This patient scored a three on the Naranjo scale, indicating a possible adverse effect from quetiapine. Other potential etiologies of psychosis include medication-induced psychosis, major depressive disorder exacerbation, cocaine use/withdrawal, and brief psychotic disorder. Quetiapine-induced psychosis has not been described in the current literature, and therefore, this case report is solely based on clinical evaluation and is intended for educational purposes due to possible confounding factors and etiologies.

Heart Break or Headache: A Case Report of Sumatriptan-Induced Takotsubo Syndrome.

Takotsubo syndrome (TS) describes a transient type of dilated cardiomyopathy that mimics acute coronary syndrome (ACS) on initial presentation. Classic TS presents with marked dilation and ballooning of the left ventricular apex with hyperdynamic basal segments. The most frequent etiology is from emotional and stressful triggers; recently, evidence suggests neurologic and psychiatric involvement. There are increasing reports of TS occurring secondary to migraine abortives. We describe a unique case of TS in a woman after taking sumatriptan to abort her headache.

Levothyroxine Prescription Error: A Case Report.

Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes. General guidelines for treating exogenous thyrotoxicosis depend on the severity of symptoms. There is no standardized protocol; however, drug discontinuation, beta-blockers (specifically propranolol), and cholestyramine effectively manage overdose when needed, with most cases resolving independently without medical intervention.  Here, we present the case of a 26-year-old female with a history of supraventricular tachycardia, anxiety, depression, and Hashimoto thyroiditis who was accidentally overprescribed LT (300 mcg for one and a half months) that resulted in symptoms of lethargy, tremors, body temperature dysregulation, orthostatic hypotension, and diarrhea. This case, with limited evidence, suggests that excessive LT exacerbated the patient's underlying psychiatric symptoms, encouraging suicidal ideation.

Ollier Disease: A Case Report and Review of Treatment Options.

Ollier disease is a rare skeletal dysplasia characterized by the formation of multiple enchondromas (enchondromatosis), typically in the long bones of the extremities. These tumors are benign but can become complicated by the development of pathologic fractures, limb deformity, and malignant transformation to chondrosarcoma. Ollier disease has a highly variable presentation and is associated with a range of presenting findings; however, the most common presentation is a pathologic fracture. Surgical options include curettage and grafting of the enchondromas and, when displaced, fracture reduction and fixation. Of note, these fractures will heal without surgery. Regardless, all patients must be routinely monitored with yearly radiographs in order to detect malignant transformation as early as possible.  In this report, we describe the case of an 11-year-old female who presented to her physician with pain and swelling of her right ring and small fingers after playing in a swimming pool with no obvious mechanism of trauma. A routine, plain radiographic evaluation of her hand revealed the presence of multiple enchondromatosis. We hope to use this case to highlight the surgical management options for young patients with Ollier disease and discuss circumstances in which surgical management may not be indicated.

Hirschsprung Disease: A Literacy Analysis of Patient Information.

OBJECTIVE: Hirschsprung disease in newborns can be a potentially life-threatening condition, with risks for complications such as Hirschsprung-associated enterocolitis. Accessing health information in a readable format for complex diseases demonstrates an important outlet for families to address concerns. While it is important to seek out information from trusted providers, many individuals seek out ways to educate themselves further by using common search engines and turning to the internet. This article will evaluate the readability of relevant articles on Hirschsprung disease and information accessibility to the average health literacy individual. METHODS: A readability analysis of the first 20 Google search results from the keywords "Hirschsprung disease" and "aganglionic megacolon" was performed. Results were documented and averaged using standardized scoring systems. Scoring systems included an Automated Readability Index, Coleman Liau index, SMOG index, Gunning Fog score, Flesch Kinkaid grade level, Flesch Kinkaid reading ease, and average readability across all scoring systems. The number of sentences, number of words, number of complex words, percent of complex words, average words per sentence, and average syllables per word were included as a sample of criteria within scoring systems. RESULTS: The average readability score for the first 20 search results of keywords "Hirschsprung disease" and "aganglionic megacolon" was 9.4, indicating a reading level just above the ninth grade. Readability ease was scored separately due to its unique scoring system on a scale of 0-100. Flesch Kincaid Readability ease score was averaged and resulted in a score of 46.4, which is considered "college level" or "difficult." CONCLUSIONS: The average health consumer will turn to Google to find information about their own health, as well as the health of their loved ones. Hirschsprung disease in newborns presents a complex disease process and can be potentially life-threatening. Current resources available to the average health consumer averaged at a grade level of 9.4 relative to search results from keywords "Hirschsprung disease" and "aganglionic megacolon." Depending on the target audience for online information, more work needs to be done to improve readability for the average health information consumer.

Lower Back Pain Imaging: A Readability Analysis.

PURPOSE: The internet provides access to a myriad of educational health-related resources which are an invaluable source of information for patients. Lower back pain is a common complaint that is discussed extensively online. In this article, we aim to determine if the most commonly accessed articles about lower back pain imaging use language that can be understood by most patients. According to the American Medical Association (AMA) and National Institute of Health (NIH), this corresponds to a sixth-grade reading level. METHODS: Online searches were conducted from the most commonly used search engine, Google, to assess the present state of readability on radiograph imaging for LBP. Then the top 20 populated URL links from each search were utilized based on "health & fitness" search trends and click-through rates (CTRs). The readability of various websites was evaluated with WebFX online software that analyzed the unique websites' text when put into reader view on Firefox web browser version 116.0.3 (64-bit). Evaluation occurred via five common readability indices: the Automated Readability Index (ARI), the Coleman Liau Index (CLI), the SMOG index, the Gunning Fog Score Index (GFSI), and the Flesch Kincaid Grade Level Index (FKGLI). In addition, the Flesch Kincaid Reading Ease Index (FKREI) was also used but was excluded from the calculation due to its measuring scale outside of US grade levels. The number of samples was analyzed via health and fitness-specific CTR from an open-access database from July 2022 to July 2023. This was used to calculate the number of persons clicking and visiting positional URLs (first URL to the 20th URL) from each unique keyword search and the rational criteria for selecting the first 20 websites for each query. RESULTS: Online material that included LBP imaging information was calculated to have an overall readability score of 10.745 out of the 23 websites obtained from unique searches. The range was a mean readability score of 8 to 14. Notably, 17 websites were excluded from a total of 40 websites due to duplication of the same data (URLs that resulted from both unique searches) and accessibility requiring payment (specifically, an UpToDate link). A readability score of 10.745 refers to an 11th-grade reading level. That is to say, the most commonly visited sites on Google that contain information about lower back pain imaging are, on average, five grade levels higher than the sixth-grade reading level recommended by the AMA and the NIH. CONCLUSIONS: Most internet content regarding lower back pain imaging is written at a reading level that is above the recommended limit defined by the AMA and NIH. To improve education about lower back pain imaging and the patient-physician relationship, we recommend guiding patients to online material that contains a reading level at the sixth-grade level as suggested by the AMA and NIH.