Case Report: Disseminated Tuberculosis After Kidney Transplantation.

Tuberculosis (TB) can cause significant morbidity and mortality among solid organ transplant (SOT) recipients, including disseminated disease. Most TB cases after SOT occur in kidney transplant recipients, although data about TB in this population are sparse. Tuberculosis may present atypically in immunocompromised patients, underscoring why physicians must maintain high clinical suspicion when pertinent epidemiological risk factors are present, including birth or former residence in a country with endemic TB. We describe a unique case of disseminated TB in a 54-year-old Filipino woman who developed central nervous system tuberculoma, Pott's disease, chorioretinitis, and a perinephric fluid collection after kidney transplantation. Despite being a preventable and curable disease, TB remains a relevant and challenging infection with complex diagnostic and treatment guidelines.

The great imitator: Tuberculosis with lymphadenopathy and splenomegaly.

Tuberculosis (TB) is a leading infectious killer worldwide. Over two-thirds of new TB diagnoses in the United States occur among first-generation immigrants, especially within a year of migration. Hodgkin lymphoma (HL) accounts for a minority of lymphoma cases but presents similarly to disseminated or extrapulmonary TB. Clinical overlap between TB and HL increases patient risk of misdiagnosis. Concomitant presentation of both diseases is not uncommon but infrequently reported. We present a case of isoniazid-resistant TB with progressively worsening lymphadenopathy and splenomegaly despite appropriate TB treatment. The patient was diagnosed with HL following PET/CT and axillary lymph node biopsy.

Hantavirus Pulmonary Syndrome in an Adolescent from North Dakota.

Hantavirus pulmonary syndrome remains an uncommon yet emerging viral zoonosis that causes respiratory failure and hemodynamic instability in children and adolescents. Due to its acutely progressive course and high mortality rate, clinicians treating hantavirus pulmonary syndrome should understand its epidemiologic risk factors, clinical syndrome and radiographic findings. We present a case of hantavirus pulmonary syndrome in a 14-year-old female from North Dakota who survived the infection without sequelae.

Primary amebic meningoencephalitis: a review of Naegleria fowleri and analysis of successfully treated cases.

Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient's history of freshwater exposure and the physician's high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.

Dr. Allen Oldfather Whipple (1881-1963): Namesake of the pancreaticoduodenectomy.

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him.

Evaluating Impact of Implementing Order Questions on Appropriate Prescribing of Tolvaptan.

BackgroundTolvaptan poses a significant risk to patient safety due to its risk of overcorrection of hyponatremia, and its cost-effectiveness is not well established. Kettering Health implemented order questions into Epic in 2019 to drive appropriate use of tolvaptan. Objective: The primary objective was to determine the impact of implementing order questions on appropriate use of tolvaptan. The secondary objectives were to determine if providers are adhering to the order questions meant to ensure appropriate use, to identify if there is provider variance across the network constituting a higher proportion of use outside of network recommendations, and to look at patients with multiple orders for tolvaptan and discern if dose titration was appropriate based on sodium levels. Methods: This study was a retrospective chart review of all patients who received a dose of tolvaptan from 7/3/2019 to 10/15/2020. Results: From July 2019 to October 2020, 211 patients received tolvaptan for hyponatremia, resulting in 598 administrations. Use of urea powder or fluid restriction preceded 248/586 (42.3%) tolvaptan administrations and the patient's sodium level was < 125 mEq/L or 125-135 mEq/L with documentation of symptoms for 261/586 (44.5%) of the administrations. Medication safety concerns related to monitoring sodium levels were also identified. Conclusions: While tolvaptan use did significantly decrease in Kettering Health since the implementation of order questions, the answers to the questions displayed substantial variability. Further opportunity exists for directing appropriate use of tolvaptan within Kettering Health and additional emphasis should be placed on safe use of this medication.

Impact of animal programming on children's attitudes toward local wildlife.

Attitudes toward wildlife can have direct implications on children's interest in conservation behaviors. Animal programs are an example of interactive, educational experiences that have the potential to change attitudes by providing individuals the opportunity to get close to animal ambassadors and participate in engaging conversations about them. We conducted an animal program assessment with summer camps at the Ohio Wildlife Center to quantify changes in children's affiliation with local wildlife and their willingness to live near local wildlife. Campers showed an overall increase in affiliation and willingness scores from before to after an animal program, although with a small effect size. Overall willingness scores were lower than affiliation scores, but there was a significantly larger increase in willingness following the program. We found a strong correlation between affiliation and willingness scores. Overall, the study found that these animal programs positively influenced children's attitudes toward local wildlife and increased their willingness to live near them, suggesting animal programming could be used to decrease human-wildlife conflict. Visually seeing animals in the programs improved attitude scores, even for those not seen in this study, which suggests that program animals can act as an ambassador for other species. This opens the potential for utilizing animal ambassadors as powerful tools in conservation education about threatened and endangered species.

Perceived Anger in Clear and Conversational Speech: Contributions of Age and Hearing Loss.

A previous investigation demonstrated differences between younger adult normal-hearing listeners and older adult hearing-impaired listeners in the perceived emotion of clear and conversational speech. Specifically, clear speech sounded angry more often than conversational speech for both groups, but the effect was smaller for the older listeners. These listener groups differed by two confounding factors, age (younger vs. older adults) and hearing status (normal vs. impaired). The objective of the present study was to evaluate the contributions of aging and hearing loss to the reduced perception of anger in older adults with hearing loss. We investigated perceived anger in clear and conversational speech in younger adults with and without a simulated age-related hearing loss, and in older adults with normal hearing. Younger adults with simulated hearing loss performed similarly to normal-hearing peers, while normal-hearing older adults performed similarly to hearing-impaired peers, suggesting that aging was the primary contributor to the decreased anger perception seen in previous work. These findings confirm reduced anger perception for older adults compared to younger adults, though the significant speaking style effect-regardless of age and hearing status-highlights the need to identify methods of producing clear speech that is emotionally neutral or positive.

Effect of cleaning corn on mycotoxin concentration and nursery pig growth performance.

Mycotoxins are naturally produced hazards that result from molds grown on cereal grains and other commodities. These molds may produce carcinogenic mycotoxins, which can be harmful to humans and animals. Removing broken kernels has been demonstrated to reduce mycotoxin concentration, but with high variability. Therefore, two experiments were conducted to quantify the magnitude of natural mycotoxin concentration that may be reduced by cleaning corn. Two loads of corn that were naturally contaminated with mycotoxins were procured. Corn for Experiment 1 was contaminated with aflatoxin (1,074 parts per billion; ppb), fumonisin (8.3 parts per million; ppm), and ochratoxin A (206 ppb), while corn for Experiment 2 was contaminated with only fumonisin (5.5 ppm). Corn was cleaned by mechanical sieving. For each experiment, corn was divided into twenty 150 kg runs. Runs were randomly assigned to 1 of 4 experimental treatments: 1) no screen 2) 12.7 mm screen, 3) 4.8 mm screen, and 4) 12.7 + 4.8-mm screen. The corn cleaner was sanitized between runs. Three 5 kg corn samples were collected from each run, and analyzed for mycotoxin concentration. In Experiment 1, cleaning reduced (P < 0.05) aflatoxin and fumonisin concentration by an average of 26% and 45%, respectively, compared to the original uncleaned corn level, but did not impact (P > 0.10) ochratoxin A. The resultant screenings had nearly four times the aflatoxin (4,224 ppb) and 7.5 times the fumonisin concentration (60.4 ppm) as the uncleaned corn. In Experiment 2, cleaning reduced (P < 0.05) fumonisin concentration by 32%. The resultant screenings had 19.6 times the fumonisin concentration (65.4 ppm) as the uncleaned corn. To determine the effect that cleaning corn may have on nursery pig growth performance, 360 nursery pigs were used in Experiment 3 to evaluate the impact of cleaning or pelleting on growth performance. Treatments were arranged in a 2 × 3 factorial with corn type (uncleaned vs. cleaned) and feed form (mash vs. pelleted from either mill A or B). Neither cleaning corn nor pellet mill type affected (P > 0.19) nursery pig growth performance. Pelleting improved (P < 0.0001) gain to feed ratio (G:F) by 7.6% compared to mash diets. These data suggest that cleaning is an effective method to legally reduce aflatoxin and fumonisin concentration, but does not impact animal growth performance. Screenings should be used cautiously when feeding to animals.

Optimizing Fetal Aneuploidy Screening in an Austere Military Clinical Environment: A Prenatal Cost Comparison.

INTRODUCTION: Austere clinical settings, including remote military installations, face unique challenges in screening pregnant women for aneuploidy. The objective of this study was to compare the direct and indirect prenatal costs of traditional 2-part serum-based screening to cell-free DNA (cfDNA) for detection of trisomies 18 and 21 for a military treatment facility with limited in-house perinatal resources. MATERIALS AND METHODS: We identified Naval Hospital Guantanamo Bay as a surrogate for an austere clinical environment. A prenatal cost of care analysis incorporating direct and indirect expenses was performed to compare the 2 aneuploidy screening strategies for a theoretical cohort of 100 patients for detection of trisomies 18 and 21. The baseline aneuploidy uptake rate was determined using a historical cohort. Test performance characteristics were obtained from the contracting laboratory. Aneuploidy rates and costs were calculated using previously published data. RESULTS: Assuming a baseline screen uptake rate of 87%, initial screening using the traditional approach would directly cost $8,285.01 versus $44,140.32 with cfDNA. Considering indirect costs such as travel, consultative services, evaluation and follow-up testing of an abnormal screen result, and lost productivity, the cost difference narrows to $14,458.25 over a 5- to 6-year period. Cost equivalence is achieved when cfDNA is priced at $341.17 per test. CONCLUSION: Cell-free DNA as an initial screening strategy offers enhanced detection rates for trisomies 18 and 21 but remains more costly than traditional screening when incorporating direct and indirect expenses. In a low volume setting with limited resources, the added cost may be justified given the implications of unrecognized aneuploidy.

A Rapid, High-Throughput Validated Method for the Quantification of Atropine in Datura stramonium Seeds Using Direct Analysis in Real Time-High Resolution Mass Spectrometry (DART-HRMS).

The utility of direct analysis in real time-high resolution mass spectrometry (DART-HRMS) for quantification of a variety of compounds has been explored, but the number of reports of validated methods using this technique is limited. Furthermore, despite the increasing use in crime labs of DART-HRMS for the detection and identification of drugs of abuse, very few published reports have appeared describing how the method can be exploited for the analysis of small molecules of interest within complex matrices such as plant tissues. Herein we describe the steps to be taken to establish a validated quantification method for psychoactive compounds within complex plant matrices through its application to the detection and quantification of atropine in Datura stramonium seeds. Six calibration standard series are analyzed eight times over a period of several days to create a calibration curve. The resulting calibration curve is tested using six quality control samples and finally utilized to determine the concentration of atropine in a D. stramonium seed extract. The linear range for quantification of atropine in this study was found to be comparable to that reported previously using GC, LC, HPLC, and UHPLC-MS methods. Furthermore, the method can be applied to the quantification of other biomarkers in plant materials, despite the complexity of the plant matrix. The speed of the analysis (<10 min for duplicate analysis of 20 samples) and the ability to integrate peaks using accurate masses for specificity are advantages of the DART-HRMS quantification approach.

Rapid Species-level Identification of Salvias by Chemometric Processing of Ambient Ionisation Mass Spectrometry-derived Chemical Profiles.

INTRODUCTION: The Salvia genus contains numerous economically important plants that have horticultural, culinary and nutraceutical uses. They are often similar in appearance, making species determination difficult. Species identification of dried Salvia products is also challenging since distinguishing plant morphological features are no longer present. OBJECTIVE: The development of a simple high-throughput method of analysis of fresh and dried Salvia leaves that would permit rapid species-level identification and detection of diagnostic biomarkers. METHODOLOGY: Plant leaves were analysed in their native form by DART-MS without the need for any sample preparation steps. This furnished chemical fingerprints characteristic of each species. In the same experiment, in-source collision-induced dissociation was used to identify biomarkers. Biomarker presence was also independently confirmed by GC-MS. Chemometric processing of DART-MS profiles was performed by kernel discriminant analysis (KDA) and soft independent modelling of class analogy (SIMCA) to classify the fingerprints according to species. RESULTS: The approach was successful despite the occurrence of diurnal cycle and plant-age related chemical profile variations within species. In a single rapid experiment, the presence of essential oil biomarkers such as 3-carene, α-pinene, ß-pinene, ß-thujone, ß-caryophyllene, camphor and borneol could be confirmed. The method was applied to rapid identification and differentiation of Salvia apiana, S. dominica, S. elegans, S. officinalis, S. farinacea and S. patens. CONCLUSION: Species-level identification of Salvia plant material could be accomplished by chemometric processing of DART-HRMS-derived chemical profiles of both fresh and dried Salvia material. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry.

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

Initial Sequential Organ Failure Assessment score versus Simplified Acute Physiology score to analyze multiple organ dysfunction in infectious diseases in Intensive Care Unit.

AIMS: To investigate initial Sequential Organ Failure Assessment (SOFA) score of patients in Intensive Care Unit (ICU), who were diagnosed with infectious disease, as an indicator of multiple organ dysfunction and to examine if initial SOFA score is a better mortality predictor compared to Simplified Acute Physiology Score (SAPS). MATERIALS AND METHODS: Hospital-based study done in medical ICU, from June to September 2014 with a sample size of 48. Patients aged 18 years and above, diagnosed with infectious disease were included. Patients with history of chronic illness (renal/hepatic/pulmonary/  cardiovascular), diabetes, hypertension, chronic obstructive pulmonary disease, heart disease, those on immunosuppressive therapy/chemoradiotherapy for malignancy and patients in immunocompromised state were excluded. Blood investigations were obtained. Six organ dysfunctions were assessed using initial SOFA score and graded from 0 to 4. SAPS was calculated as the sum of points assigned to each of the 17 variables (12 physiological, age, type of admission, and three underlying diseases). The outcome measure was survival status at ICU discharge. RESULTS: We categorized infectious diseases into dengue fever, leptospirosis, malaria, respiratory tract infections, and others which included undiagnosed febrile illness, meningitis, urinary tract infection and gastroenteritis. Initial SOFA score was both sensitive and specific; SAPS lacked sensitivity. We found no significant association between age and survival status. Both SAPS and initial SOFA score were found to be statistically significant as mortality predictors. There is significant association of initial SOFA score in analyzing organ dysfunction in infectious diseases (P < 0.001). SAPS showed no statistical significance. There was statistically significant (P = 0.015) percentage of nonsurvivors with moderate and severe dysfunction, based on SOFA score. Nonsurvivors had higher SAPS but was not statistically significant (P = 0.094). CONCLUSIONS: Initial SOFA score is a superior mortality predictor. It easily measures degree of organ dysfunction in infectious diseases and complements other scoring systems.

Application of ambient ionization high resolution mass spectrometry to determination of the botanical provenance of the constituents of psychoactive drug mixtures.

A continuing challenge in analytical chemistry is species-level determination of the constituents of mixtures that are made of a combination of plant species. There is an added urgency to identify components in botanical mixtures that have mind altering properties, due to the increasing global abuse of combinations of such plants. Here we demonstrate the proof of principle that ambient ionization mass spectrometry, namely direct analysis in real time-high resolution mass spectrometry (DART-HRMS), and statistical analysis tools can be used to rapidly determine the individual components within a psychoactive brew (Ayahuasca) made from a mixture of botanicals. Five plant species used in Ayahuasca preparations were subjected to DART-HRMS analysis. The chemical fingerprint of each was reproducible but unique, thus enabling discrimination between them. The presence of important biomarkers, including N,N-dimethyltryptamine, harmaline and harmine, was confirmed using in-source collision-induced dissociation (CID). Six Ayahuasca brews made from combinations of various plant species were shown to possess a high level of similarity, despite having been made from different constituents. Nevertheless, the application of principal component analysis (PCA) was useful in distinguishing between each of the brews based on the botanical species used in the preparations. From a training set based on 900 individual analyses, three principal components covered 86.38% of the variance, and the leave-one-out cross validation was 98.88%. This is the first report of ambient ionization MS being successfully used for determination of the individual components of plant mixtures.