Publications by authors named "Pooja Patel"

141 Publications

Preservation of eye movements in Parkinson's disease is stimulus and task specific.

J Neurosci 2021 Nov 29. Epub 2021 Nov 29.

Ophthalmology & Visual Sciences, University of British Columbia, Vancouver, BC, Canada.

Parkinson's disease (PD) is a neurodegenerative disease that includes motor impairments such as tremor, bradykinesia, and postural instability. Although eye movement deficits are commonly found in saccade and pursuit tasks, preservation of oculomotor function has also been reported. Here we investigate specific task and stimulus conditions under which oculomotor function in PD is preserved. Sixteen PD patients and eighteen healthy, age-matched controls completed a battery of movement tasks that included stationary or moving targets eliciting reactive or deliberate eye movements: pro-saccades, anti-saccades, visually-guided pursuit, and rapid go/no-go manual interception. Compared to controls, patients demonstrated systematic impairments in tasks with stationary targets: pro-saccades were hypometric and anti-saccades were incorrectly initiated toward the cued target in about 35% of trials compared to 14% errors in controls. In patients, task errors were linked to short latency saccades, indicating abnormalities in inhibitory control. However, patients' eye movements in response to dynamic targets were relatively preserved. PD patients were able to track and predict a disappearing moving target and make quick go/no-go decisions as accurately as controls. Patients' interceptive hand movements were slower on average but initiated earlier, indicating adaptive processes to compensate for motor slowing. We conclude that PD patients demonstrate stimulus- and task-dependency of oculomotor impairments and propose that preservation of eye and hand movement function in PD is linked to a separate functional pathway through the SC-brainstem loop that bypasses the fronto-basal ganglia network. Our results demonstrate that studying oculomotor and hand movement function in PD can support disease diagnosis and further our understanding of disease progression and dynamics.Eye movements are a promising clinical tool to aid in the diagnosis of movement disorders and to monitor disease progression. Although Parkinson's disease (PD) patients show some oculomotor abnormalities, it is not clear whether previously-described eye movement impairments are task specific. We assessed eye movements in PD under different visual (stationary vs. moving targets) and movement (reactive vs. deliberate) conditions. We demonstrate that PD patients are able to accurately track moving objects but make inaccurate eye movements towards stationary targets. The preservation of eye movements towards dynamic stimuli might enable patients to accurately act upon the predicted motion path of the moving target. These results can inform the development of tools for the rehabilitation or maintenance of functional performance.
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http://dx.doi.org/10.1523/JNEUROSCI.1690-21.2021DOI Listing
November 2021

Objective validity of patient-reported symptoms in aspirin-exacerbated respiratory disease patients.

Clin Exp Allergy 2021 Nov 25. Epub 2021 Nov 25.

Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1111/cea.14062DOI Listing
November 2021

Student perceptions of non-technical skills development during advanced pharmacy practice experiences.

Curr Pharm Teach Learn 2021 11 24;13(11):1510-1516. Epub 2021 Sep 24.

Pharmaceutical Sciences, Texas A&M Irma Lerma Rangel College of Pharmacy, 159 Reynolds Medical Building, College Station, TX 77843, United States. Electronic address:

Introduction: In today's workforce, non-technical skills (NTS) are essential in determining an employee's ability to fit into an organization. However, it is unknown whether pharmacy students consider these skills essential to their future work or believe they are sufficiently trained. Therefore, this study evaluated student perceptions of the value of NTS as a pharmacist and their satisfaction with NTS training.

Methods: A 45-item survey was distributed to 111 fourth-year pharmacy students at Texas A&M College of Pharmacy in March 2019. Given the diverse nature of NTS, this study collected student perceptions about the 2016 Accreditation Council for Pharmacy Education Standard 4 Key Elements: self-awareness, leadership, innovation, and professionalism. Results were analyzed utilizing descriptive statistics.

Results: Approximately 84% (n = 93) of students completed the survey. More students perceived professionalism as an important skill to have, followed by leadership, self-awareness, and innovation. Similar results were shown with students' satisfaction with NTS training. Also, results highlighted that students' satisfaction level with their NTS training and their belief regarding their strengths relied on two factors: the number of advanced pharmacy practice experiences (APPEs) where NTS training occurred and the amount of time spent practicing the NTS.

Conclusion: These data add to the existing literature to support NTS training in experiential pharmacy education. While APPEs should not be the only setting where these skills are practiced in the curriculum, our study's findings may further guide curricular priorities and assessment strategies for NTS in the experiential setting.
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http://dx.doi.org/10.1016/j.cptl.2021.09.016DOI Listing
November 2021

Analysis of reasons for loss to follow up in a prospective study in Chandigarh, India and impact from telecom changes.

BMC Res Notes 2021 Nov 18;14(1):419. Epub 2021 Nov 18.

Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.

Objective: Mobile phones are used in research studies, to enroll and follow-up participants, collect data, and implement mHealth initiatives. We conducted a longitudinal study in a birth cohort, where infants were required to make four scheduled visits by 12 months of age. Families of those failing to attend scheduled follow-up visits, were contacted telephonically to ascertain the reasons, which were categorized as: not interested to continue participating, migrated, phone disconnected due to telecom change, or other reason.

Results: A total of 413 mother-infant dyads were enrolled. The overall attrition was 56%, with majority occurring at the first follow-up visit. This temporally coincided with a telecom service provider announcing strong incentives to switch providers. Attrition monotonically decreased at subsequent visits. The reasons were: moved away (13%), no longer interested (8%), phone disconnected (7%), and multiple other reasons (28%), the majority of whom had unreachable phones. Those who remained in the study and those lost to follow-up were similar on most demographic variables. Among common reasons for attrition in cohort studies, we experienced a new dimension introduced by telecom changes. These findings underscore the need to consider unexpected reasons for attrition in longitudinal studies, and design more robust methods to follow-up participants.
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http://dx.doi.org/10.1186/s13104-021-05837-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600768PMC
November 2021

Rh(II)-Catalyzed Intermolecular -Aryl Aziridination of Olefins Using Nonactivated N Atom Precursors.

J Am Chem Soc 2021 Nov 8;143(45):19149-19159. Epub 2021 Nov 8.

Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, MC 111, Chicago, Illinois 60607, United States.

The development of the first intermolecular Rh(II)-catalyzed aziridination of olefins using anilines as nonactivated N atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. This reaction requires the transfer of an -aryl nitrene fragment from the iminoiodinane intermediate to a Rh(II) carboxylate catalyst; in the absence of a catalyst only diaryldiazene formation was observed. This -aryl aziridination is general and can be successfully realized by using as little as 1 equiv of the olefin. Di-, tri-, and tetrasubstituted cyclic or acylic olefins can be employed as substrates, and a range of aniline and heteroarylamine N atom precursors are tolerated. The Rh(II)-catalyzed N atom transfer to the olefin is stereospecific as well as chemo- and diastereoselective to produce the -aryl aziridine as the only amination product. Because the chemistry of nonactivated -aryl aziridines is underexplored, the reactivity of -aryl aziridines was explored toward a range of nucleophiles to stereoselectively access privileged 1,2-stereodiads unavailable from epoxides, and removal of the -2,4-dinitrophenyl group was demonstrated to show that functionalized primary amines can be constructed.
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http://dx.doi.org/10.1021/jacs.1c09229DOI Listing
November 2021

Controlled bimatoprost release from graphene oxide laden contact lenses: In vitro and in vivo studies.

Colloids Surf B Biointerfaces 2021 Dec 2;208:112096. Epub 2021 Sep 2.

School of Optometry and Vision, University of New South Wales, Sydney, New South Wales, 2052, Australia.

Ocular drug delivery using contact lenses may be able to substitute for eye drop therapy. However, issues with hydrophobic drugs (like bimatoprost that is used to treat glaucoma) such as low drug uptake using a simple soaking method into preformed contact lenses and alteration in the swelling and transmittance of lenses restricts the application for drug delivery. This research uses graphene oxide (GO) to control the release of bimatoprost from contact lenses along with improvements in the drug uptake, and lens swelling and transmittance. GO was loaded into silicone hydrogel contact lenses by adding the GO at the same time as lenses were polymerized. These lenses were soaked in bimatoprost. Alternatively contact lenses, either with or without GO, were produced by adding bimatoprost during lens polymerization. GO improved contact lens swelling due to its water binding capacity and lens transmittance due to the molecular dispersion of bimatoprost on the surface of the GO which prevented the local precipitation of the drug. The bimatoprost uptake was not improved in the presence of GO. However, its in vitro release profile was improved. Adding bimatoprost and GO at the same time as lenses were polymerized (DL-GO-BMT) significantly decreased the loss of drug during extraction and sterilization in comparison to contact lenses (DL-BMT) without GO. As the amount of GO was increased, the DL-GO-BMT lenses showed a significant decrease in the burst and cumulative release of bimatoprost. Ocular irritation and histopathology reports demonstrated the safety of GO contact lens. The in vivo pharmacokinetic studies in the rabbit tear fluid showed significant improvement in mean residence time (MRT) and area under the curve (AUC) with DL-GO-0.2 μg-BMT-100 contact lens in comparison to eye drop solution. The study demonstrated that the addition of GO to contact lenses can control the release of bimatoprost as well as improved the lens swelling and transmittance. However, further optimization is needed to modulate the release of drug within the therapeutic level to manage glaucoma.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112096DOI Listing
December 2021

A mom pharmacist working during the pandemic.

Authors:
Pooja H Patel

J Am Pharm Assoc (2003) 2021 Nov-Dec;61(6):647. Epub 2021 Aug 21.

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http://dx.doi.org/10.1016/j.japh.2021.08.017DOI Listing
August 2021

Immunization status of children in Nepal and associated factors, 2016.

Vaccine 2021 09 26;39(40):5831-5838. Epub 2021 Aug 26.

Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Infectious Disease, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address:

Background: Nepal has made substantial improvements in childhood immunization uptake. However, vaccination levels are still below the country-specific Sustainable Development Goal target of 94.8% coverage by 2025 for children aged 12-23 months who received all immunizations recommended in the national immunization schedule by their first birthday. A better understanding of the predictors of full immunization can inform successful programmatic interventions to improve coverage while also guiding resource allocation to ensure all children are fully vaccinated. This study estimates childhood immunization coverage in Nepal and characterizes the association between immunization status and various sociodemographic predictors.

Methods: Data from the 2016 Nepal Demographic and Health Survey were used to examine the immunization status of children aged 12-23 months. Immunization status was categorized as fully immunized (receiving all recommended doses), under-immunized (receiving at least one, but not all, recommended doses), and un-immunized (not receiving any doses of any vaccine). Associations between full and under-immunization and potential sociodemographic predictors were assessed using logistic regression.

Results: Among 976 children, 78.2% were fully immunized, 21% were under-immunized, and 0.8% were un-immunized. Retention of an immunization card was significantly associated with full immunization status. Mothers who had completed a formal education above secondary school and mothers who were working at time of interview had increased odds of full immunization. Birthing in an institutional setting was also associated with higher odds of full immunization.

Conclusions: Overall, immunization coverage in Nepal is relatively high, although it varies by dose and sociodemographic factors. Almost 25% of Nepalese children were not fully immunized, leaving them at increased risk for vaccine-preventable disease related morbidity and mortality. Nepal must continue focused efforts to reach every child and minimize the equity gap; programs may focus on advocating for the use of immunization cards, education and empowerment for girls, and delivery in institutional settings.
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http://dx.doi.org/10.1016/j.vaccine.2021.08.059DOI Listing
September 2021

Wearable myoelectric interface enables high-dose, home-based training in severely impaired chronic stroke survivors.

Ann Clin Transl Neurol 2021 09 20;8(9):1895-1905. Epub 2021 Aug 20.

Department of Neurology, Northwestern University, Chicago, Illinois, 60611, USA.

Background: High-intensity occupational therapy can improve arm function after stroke, but many people lack access to such therapy. Home-based therapies could address this need, but they don't typically address abnormal muscle co-activation, an important aspect of arm impairment. An earlier study using lab-based, myoelectric computer interface game training enabled chronic stroke survivors to reduce abnormal co-activation and improve arm function. Here, we assess feasibility of doing this training at home using a novel, wearable, myoelectric interface for neurorehabilitation training (MINT) paradigm.

Objective: Assess tolerability and feasibility of home-based, high-dose MINT therapy in severely impaired chronic stroke survivors.

Methods: Twenty-three participants were instructed to train with the MINT and game for 90 min/day, 36 days over 6 weeks. We assessed feasibility using amount of time trained and game performance. We assessed tolerability (enjoyment and effort) using a customized version of the Intrinsic Motivation Inventory at the conclusion of training.

Results: Participants displayed high adherence to near-daily therapy at home (mean of 82 min/day of training; 96% trained at least 60 min/day) and enjoyed the therapy. Training performance improved and co-activation decreased with training. Although a substantial number of participants stopped training, most dropouts were due to reasons unrelated to the training paradigm itself.

Interpretation: Home-based therapy with MINT is feasible and tolerable in severely impaired stroke survivors. This affordable, enjoyable, and mobile health paradigm has potential to improve recovery from stroke in a variety of settings. Clinicaltrials.gov: NCT03401762.
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http://dx.doi.org/10.1002/acn3.51442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419406PMC
September 2021

RNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage.

Nat Commun 2021 08 18;12(1):5016. Epub 2021 Aug 18.

Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

DNA damage prompts a diverse range of alterations to the chromatin landscape. The RNF168 E3 ubiquitin ligase catalyzes the mono-ubiquitination of histone H2A at lysine (K)13/15 (mUb-H2A), forming a binding module for DNA repair proteins. BRCA1 promotes homologous recombination (HR), in part, through its interaction with PALB2, and the formation of a larger BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex. The mechanism by which BRCA1-P is recruited to chromatin surrounding DNA breaks is unclear. In this study, we reveal that an RNF168-governed signaling pathway is responsible for localizing the BRCA1-P complex to DNA damage. Using mice harboring a Brca1 (coiled coil) mutation that blocks the Brca1-Palb2 interaction, we uncovered an epistatic relationship between Rnf168 and Brca1 alleles, which disrupted development, and reduced the efficiency of Palb2-Rad51 localization. Mechanistically, we show that RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain ubiquitin-dependent recruitment motif (BUDR). Subsequently, BARD1-BRCA1 accumulate PALB2-RAD51 at DNA breaks via the CC domain-mediated BRCA1-PALB2 interaction. Together, these findings establish a series of molecular interactions that connect the DNA damage signaling and HR repair machinery.
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http://dx.doi.org/10.1038/s41467-021-25346-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373961PMC
August 2021

Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein.

Parkinsonism Relat Disord 2021 Aug 19;89:41-47. Epub 2021 Jun 19.

Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA. Electronic address:

Background: Alpha-synuclein (α-syn) preformed fibril (PFF)-induced pathology can be used to study the features and progression of synucleinopathies, such as Parkinson's disease. Intrastriatal injection of mouse α-syn PFFs produce accumulation of α-syn pathology in both mice and rats. Previous studies in mice have revealed that greater sequence homology between the α-syn amino acid sequence used to produce PFFs with that of the endogenous host α-syn increases α-syn pathology in vivo.

New Methods: Based on the prediction that greater sequence homology will result in more α-syn pathology, PFFs generated from recombinant rat α-syn (rPFFs) were used instead of PFFs produced from recombinant mouse α-syn (mPFFs), which are normally used in the model. Rats received unilateral intrastriatal injections of either rPFFs or mPFFs and accumulation of α-syn phosphorylated at serine 129 (pSyn) was examined at 1-month post-surgery.

Results: Rats injected with mPFFs exhibited abundant accumulation of α-syn inclusions in the substantia nigra and cortical regions, whereas in rats injected with rPFFs had significantly fewer SNpc neurons containing pSyn inclusions (≈60% fewer) and little, if any, pSyn inclusions were observed in the cortex.

Conclusions: Our results suggest that additional factors beyond the degree of sequence homology between host α-syn and injected recombinant α-syn impact efficiency of seeding and subsequent inclusion formation. More practically, these findings caution against the use of rPFFs in the rat preformed fibril model.
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http://dx.doi.org/10.1016/j.parkreldis.2021.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429263PMC
August 2021

Occult Perforated Gangrenous Gallbladder Found on Magnetic Resonance Cholangiopancreatography.

Cureus 2021 Jun 19;13(6):e15754. Epub 2021 Jun 19.

Internal Medicine, Grand Strand Medical Center, Myrtle Beach, USA.

Acute gangrenous cholecystitis is a life-threatening disease that is most often diagnosed intraoperatively and can be missed on mildly symptomatic patients without the proper imaging modality. We present a case of a 69-year-old male with a history of hypertension, hyperlipidemia, and type 2 diabetes, and a recent right pontine infarct that arrived with 3 out of 10 right-sided abdominal pain. His liver ultrasound and computed tomography (CT) with contrast demonstrated acute cholecystitis. He was initially worked up conservatively and was scheduled for an elective cholecystectomy per surgery recommendation. However erring on the side of caution, the medical team had ordered a magnetic resonance cholangiopancreatography (MRCP), which demonstrated perforated gangrenous cholecystitis. Of note, the imaging modalities were ordered within a 24-hour window. The patient's antibiotics were promptly broadened, and he was emergently sent to the operating room. Moving forward, we will identify atypical clinical presentations of gangrenous cholecystitis and consider ordering an MRCP when clinical suspicion remains high and initial imaging is inconclusive. Perforated gangrenous cholecystitis is a severe disease and can cause rapid demise if not identified and treated early.
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http://dx.doi.org/10.7759/cureus.15754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214500PMC
June 2021

Immunotherapy-Induced Acute Tubulointerstitial Nephritis.

Cureus 2021 May 31;13(5):e15358. Epub 2021 May 31.

Nephrology, Grand Strand Medical Center, Myrtle Beach, USA.

Due to its minimal side-effect profile, immunotherapy has become a popular choice for the treatment of advanced melanoma as compared to conventional chemotherapy. The most common side effects associated with immunotherapy include gastrointestinal, pulmonary, and dermatologic manifestations. However, there have been very few documented occurrences of nephrotoxic side effects. We present a case of a 73-year-old male with a past medical history of chronic kidney disease (CKD) stage 3A, metastatic uveal melanoma, and gastroesophageal reflux disease on pantoprazole who arrived at the intensive care unit with altered mental status and creatinine of 27 gm/dl (baseline creatinine of 3 gm/dl about one year prior), after receiving his first dose of ipilimumab and nivolumab approximately 21 days prior. Kidney biopsy demonstrated acute tubulointerstitial nephritis (ATIN). This case highlights the importance of recognizing acute tubulointerstitial nephritis as a side effect of immunotherapy for prompt diagnosis and early treatment.
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http://dx.doi.org/10.7759/cureus.15358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214499PMC
May 2021

Hematologic Findings in Pregnancy: A Guide for the Internist.

Cureus 2021 May 21;13(5):e15149. Epub 2021 May 21.

Hematology and Oncology, Henry Ford Health System, Detroit, USA.

Hematologic changes in pregnancy are common and can potentially lead to maternal and fetal morbidity. Here, we present various hematologic manifestations seen in pregnant women. Iron deficiency anemia (IDA) is the most common cause of anemia in pregnancy. Physiologically, the state of pregnancy results in increased iron demand. Iron deficiency is important to diagnose and treat early for better maternal and fetal outcomes. An algorithmic approach is used for the repletion of iron storage, starting with oral elemental iron daily and escalating to intravenous iron if necessary. Folate and cobalamin are necessary elements for deoxyribonucleic acid (DNA) synthesis, fetal growth, and maternal tissue development, and deficiency in these elements can be a cause for anemia in pregnancy. Thrombocytopenia is currently the second most common hematologic condition in pregnancy after anemia. There is a wide range of etiology for thrombocytopenia in pregnancy from benign to life-threatening causes that require prompt diagnosis and treatment. These conditions include gestational thrombocytopenia, thrombotic thrombocytopenic purpura, pregnancy-associated atypical hemolytic-uremic syndrome, and immune thrombocytopenia. Acquired bleeding disorders that can cause major complications in pregnancy include von Willebrand disease (vWD) and coagulation factor deficiencies. Women with vWD are at increased risk of pregnancy bleeding and postpartum hemorrhage. Pregnancy can also produce a physiologic hypercoagulable state, leading to life-threatening conditions like thromboembolism. Diagnosis, treatment options, and guidelines for the management of these conditions will be explored in this review.
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http://dx.doi.org/10.7759/cureus.15149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214837PMC
May 2021

All-Cause Mortality and Incidence of Major Adverse Cardiac Events in Sickle Cell Nephropathy: A Comparative Study.

Cureus 2021 May 16;13(5):e15059. Epub 2021 May 16.

Internal Medicine, Grand Strand Medical Center, Myrtle Beach, USA.

Background Sickle cell disease (SCD) is an autosomal recessive disease resulting in hemolytic anemia and recurrent vaso-occlusive events. Consequently, it can result in a broad range of functional and structural renal and cardiac alterations. Chronic kidney disease (CKD), in SCD, is associated with proteinuria, microalbuminuria, and hemoglobinuria. Cardiac complications in SCD include pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, and sudden death. In patients with advancing age, cardio-renal dysfunction can have substantial effects on morbidity and mortality. Our primary aim was to compare the incidence of major adverse cardiac events (MACE) and all-cause mortality in sickle cell nephropathy (SCN). Methods In this retrospective study, we used International Classification of Diseases (ICD)-10 codes to identify admissions in 2019 with a diagnosis of MACE with a prior diagnosis of SCD and/or SCN. Our search of the HCA Healthcare Enterprise Data Warehouse for adult patients >18 years yielded 6,693 patients with SCD, of which 658 patients (9.8%) had SCN. Primary endpoints were incidence of MACE and all-cause mortality. Patients with MACE encompassed those with nonfatal stroke, nonfatal myocardial infarction, and congestive heart failure (CHF) exacerbations. A secondary endpoint was length of stay (LOS). Logistic regression analysis was used for MACE and all-cause mortality. LOS was analyzed using multiple linear regression analysis. Results were considered statistically significant for analyses showing p <0.05. All outcomes were adjusted for demographic variables and comorbidities. Results Logistic regression, after adjustment for comorbidities, demonstrated that SCN patients had significantly higher odds of all-cause mortality (odds ratio [OR] 2.343, p = 0.035, 95% confidence interval [CI] 1.063-5.166) compared to patients without SCN. Compared to those without SCN, those with SCN did not have a higher odds of MACE (OR 1.281, p = 0.265, 95% CI 0.828-1.982). Linear regression for LOS did not reveal a significant association with SCN (p = 0.169, 95% CI 0.157-0.899). Conclusion Based on the analysis of 6,693 patients with SCD, SCN was associated with significantly higher odds of all-cause mortality. SCN was not associated with significantly higher odds of MACE or prolonged LOS.
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http://dx.doi.org/10.7759/cureus.15059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205106PMC
May 2021

Agricultural workers in meatpacking plants presenting to an emergency department with suspected COVID-19 infection are disproportionately Black and Hispanic.

Acad Emerg Med 2021 09 2;28(9):1012-1018. Epub 2021 Jul 2.

Department of Emergency Medicine, University of Indiana School of Medicine, Indianapolis, Indiana, USA.

Objective: Facilities that process and package meat for consumer sale and consumption (meatpacking plants) were early sites of coronavirus disease 2019 (COVID-19) outbreaks. The aim of this study was to characterize the association between meatpacking plant exposure and clinical outcomes among emergency department (ED) patients with COVID-19 symptoms.

Methods: This was a retrospective cohort study of patients presenting to a single ED, from March 1 to May 31, 2020, who had: 1) symptoms consistent with COVID-19 and 2) a COVID-19 test performed. The primary outcome was COVID-19 positivity, and secondary outcomes included hospital admission from the ED, ventilator use, intensive care unit (ICU) admission, hospital length of stay (LOS; <48 or ≥48 h), and mortality.

Results: Patients from meatpacking plants were more likely to be Black or Hispanic than the ED patients without this occupational exposure. Patients with a meatpacking plant exposure were more likely to test positive for COVID-19 (adjusted relative risk [aRR] = 2.37, 95% confidence interval [CI] = 1.59 to 3.53) but had similar rates of hospital admission (aRR = 0.94, 95% CI = 0.82 to 1.07) and hospital LOS (aRR = 0.76, 95% CI = 0.45 to 1.23). There was no significant difference in ventilator use among patients with meatpacking and nonmeatpacking plant exposure (8.2% vs. 11.1%, p = 0.531), ICU admissions (4.1% vs. 12.0%, p = 0.094), and mortality (2.0% vs. 4.1%, p = 0.473).

Conclusions: Workers in meatpacking plants in Iowa had a higher rate of testing positive for COVID-19 but were not more likely to be hospitalized for their illness. These patients were disproportionately Black and Hispanic.
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http://dx.doi.org/10.1111/acem.14314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441647PMC
September 2021

Quantifying interfacial substrate interactions via surface energy analyses.

STAR Protoc 2021 Jun 21;2(2):100476. Epub 2021 Apr 21.

Department of Chemistry and Biochemistry, Lipscomb University, One University Park Drive, Nashville, TN 37217 USA.

Determination of a substrate's surface energy profile is a facile and inexpensive method to indicate the substrate's interfacial thermodynamics with another substance (e.g., microorganisms, biomacromolecules, medical devices, etc). The following protocol details a goniometric method to calculate a substrate's surface energy profile which (1) directly correlates to a substrate's interfacial Gibbs energy (ΔG) and (2) predicts the interfacial interactions with other substances. We also provide a calculation template using advanced mathematics to expedite surface energy profile determination. For complete details on the use and execution of this protocol, please refer to Cavitt et al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2021.100476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091927PMC
June 2021

Gut Microbiome Composition Is Associated with COVID-19 Disease Severity.

Gastroenterology 2021 Aug 13;161(2):722-724. Epub 2021 May 13.

Department of Medicine, Division of Gastroenterology, Duke University, Durham, North Carolina.

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http://dx.doi.org/10.1053/j.gastro.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116123PMC
August 2021

OPA1 deletion in brown adipose tissue improves thermoregulation and systemic metabolism via FGF21.

Elife 2021 05 4;10. Epub 2021 May 4.

Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, United States.

Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, which is activated independently of BAT thermogenic function.
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http://dx.doi.org/10.7554/eLife.66519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128440PMC
May 2021

Urine protein biomarkers of bladder cancer arising from 16-plex antibody-based screens.

Oncotarget 2021 Apr 13;12(8):783-790. Epub 2021 Apr 13.

Department Biomedical Engineering, University of Houston, Houston, TX, USA.

Purpose: The purpose of this study is to identify novel urine protein biomarkers of bladder cancer using a Luminex based screening platform.

Materials And Methods: The current study examines urine samples from 66 subjects, comprised of 31 Urology clinic controls and 35 bladder cancer patients, using a Luminex based screening platform. ELISA validation was carried out for the top 4 prospective urine biomarkers using an independent cohort of 20 Urology clinic controls and 60 bladder cancer (BC) subjects.

Results: Of the 16 proteins screened by Luminex, 10 showed significant elevation in BC compared to the controls. Eight of these urine proteins were able to differentiate BC from control urine with ROC AUC values exceeding 0.70 at < 0.0001, with specificity values exceeding 0.9. Upon ELISA validation, urine IL-1α, IL-1ra, and IL-8 were able to distinguish control urine from urine drawn from various bladder cancer stages, with IL-8 being the best discriminator. Compared to members of the IL-1 cytokine family, urine IL-8 was also best at discriminating T1 and/or T2-T4 from Ta BC (ROC AUC ≥ 0.83), as well as high grade from low grade BC (ROC AUC ≥ 0.82).

Conclusions: These findings suggest that urine IL-1α, IL-1ra and IL-8 are useful indicators of bladder cancer. Urine IL-8 not only distinguishes bladder cancer from controls, it also discriminates high grade from low grade disease, and the successive clinical stages of bladder cancer. While supportive of previous reports, these findings warrant further analysis in prospective cohorts.
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http://dx.doi.org/10.18632/oncotarget.27941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057279PMC
April 2021

Ischemic Nephropathy Following Occlusion of Abdominal Aortic Aneurysm Graft: A Case Report.

Cureus 2021 Mar 10;13(3):e13799. Epub 2021 Mar 10.

Internal Medicine, Grand Strand Medical Center, Myrtle Beach, USA.

In this report, we present a case of a 55-year-old female with a past medical history of abdominal aortic aneurysm (AAA) graft, femoral-femoral bypass graft, questionable history of chronic kidney disease (CKD), abdominal hernia repair, alcoholic pancreatitis, chronic abdominal pain on opioids, and tobacco abuse who presented with acute on chronic abdominal pain with an unexplained rise of creatinine and anuria. The patient was found to have complete occlusion of AAA graft and was determined to have ischemic nephropathy (IN).
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http://dx.doi.org/10.7759/cureus.13799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033647PMC
March 2021

Emergent robotic versus laparoscopic surgery for perforated gastrojejunal ulcers: a retrospective cohort study of 44 patients.

Surg Endosc 2021 Mar 24. Epub 2021 Mar 24.

Department of Surgery, Albany Medical Center, 43 New Scotland Avenue, Albany, NY, 12208, USA.

Background: Perforated gastrojejunal ulcers are a known complication following Roux-en-Y gastric bypass (RYGB) surgery requiring emergent surgical repair. The robotic approach has not been evaluated for emergency general surgery.

Methods: A retrospective cohort study from 2015 to 2019 was performed identifying all patients who underwent repair of perforated gastrojejunal ulcers after RYGB at a single institution. Patient characteristics and outcomes were compared by robotic or laparoscopic approach.

Results: Of the 44 patients analyzed, there were 24 robotic and 20 laparoscopic repairs of perforated gastrojejunal ulcers. No patients were initially approached with open surgery. In-room-to-surgery-start time was significantly faster in the robotic group than the laparoscopic group (25 versus 31 min, p = 0.01). Complication rate, complication severity, operating time, hospital length of stay, postoperative vasopressor requirement, discharge to home, hospital length of stay and 30-day readmission were all improved in the robotic group, although these were not statistically significant. Both total inpatient and procedural costs were more in the robotic group than the laparoscopic group.

Conclusion: Perforated hollow viscus is not a contraindication for the use of the surgical robot, which may improve outcomes.
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http://dx.doi.org/10.1007/s00464-021-08447-5DOI Listing
March 2021

Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management.

Cureus 2021 Jan 1;13(1):e12419. Epub 2021 Jan 1.

College of Pharmacy, Texas A&M University, Kingsville, USA.

Heart failure (HF) is a major public health problem in the United States as well as worldwide. Chronic heart failure is a syndrome of reduced cardiac output resulting from impaired ventricular function, impaired filling, or a combination of both. Associated symptoms include dyspnea, fatigue, and decreased exercise tolerance. HF has a marked effect on morbidity and mortality, given limited therapeutic choices. The first line of therapeutic agents indicated in heart failure are beta-blockers. Other drugs and therapeutic modalities employed in HF treatment include angiotensin-receptor blockers (ARBs), sacubitril (neprilysin inhibitor) combination with the ARB, valsartan, small doses of aldosterone receptor antagonists (ARAs) in the setting of angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers. Additionally, the sodium-glucose transporter-2 inhibitor, dapagliflozin in the setting of ACE inhibitors, ARBs, or sacubitril-valsartan plus beta-blocker have been employed. Other therapeutic modalities have included loop diuretics, digoxin, the hydralazine-isosorbide dinitrate combination, ivabradine, the inotropes, dobutamine, milrinone, and dopamine. Decreased cardiac contractility is central to the systolic HF. Therapeutic agents employed to increase cardiac contractility in HF are limited because of their mechanistic-related adverse effect profiles. Omecamtiv mecarbil (OM) is a first of its class cardiac myosin activator that increases the cardiac contractility by specifically binding to the catalytic S1 domain of cardiac myosin, to be employed in heart failure treatment. This agent has demonstrated benefit in reducing heart rate, peripheral vascular resistance, mean left arterial pressure, and left ventricular end-diastolic pressure in the animal models. Additionally, OM is known to improve systolic wall thickening, stroke volume (SV), and cardiac output (CO). OM increases systolic ejection time (SET), cardiac myocyte fractional shortening without significant increase of LV dP/dtmax, myocardial oxygen consumption, and myocyte intracellular calcium. The benefits of OM have been demonstrated through key trials, as (i) The Acute Treatment with Omecamtiv mecarbil to Increase Contractility in Acute Heart Failure (ATOMIC-AHF), and (ii) The Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF). The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial is ongoing and can help provide further clinical data. OM provides a novel mechanism and therapeutic approach to managing patients with HF. Preclinical and clinical data suggest that OM capability can improve cardiac function, decrease ventricular wall stress, reverse ventricular remodeling, and promote sympathetic withdrawal.
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http://dx.doi.org/10.7759/cureus.12419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847774PMC
January 2021

Successful treatment of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome with tofacitinib.

Pediatr Dermatol 2021 Mar 29;38(2):528-529. Epub 2021 Jan 29.

Baylor College of Medicine, Houston, TX, USA.

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a rare autoinflammatory disorder. Cutaneous manifestations of CANDLE syndrome include characteristic recurring violaceous annular plaques comprised of an immature dermal mononuclear cell infiltrate. In CANDLE syndrome, deleterious genetic mutations inhibit proteasome-immunoproteasome function, resulting in cellular accumulation of ubiquitinated waste proteins that activate type I interferon signaling to drive inflammation. We describe a report of successful treatment of a 12-year-old girl with CANDLE syndrome with tofacitinib.
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http://dx.doi.org/10.1111/pde.14517DOI Listing
March 2021

RPA complexes in Caenorhabditis elegans meiosis; unique roles in replication, meiotic recombination and apoptosis.

Nucleic Acids Res 2021 02;49(4):2005-2026

Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.

Replication Protein A (RPA) is a critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. The Caenorhabditis elegans genome encodes RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determined that RPA-2 is critical for germline replication and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for somatic replication, in contrast to other organisms that require both subunits. Six different hetero- and homodimeric complexes containing permutations of RPA-1, RPA-2 and RPA-4 can be detected in whole animal extracts. Our in vivo studies indicate that RPA-1/4 dimer is less abundant in the nucleus and its formation is inhibited by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibits RAD-51 filament formation and promotes apoptosis of a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes in C. elegans.
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http://dx.doi.org/10.1093/nar/gkaa1293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913698PMC
February 2021

An audit of brain tumor patients treated in 5 years at a single institute: Our regional cancer center experience.

J Cancer Res Ther 2020 Oct-Dec;16(6):1466-1469

Department of Radiotherapy, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.

Introduction: Brain tumors constitute a small presentation of all cancers (1.4%) and cancer related deaths (2.5%). Most of the brain tumors are malignant and carry bad prognosis and even if those which are benign still can interfere with brain functions that are required for daily living. We did an audit of brain tumor patients treated in our center and see their prognosis in correlation with different histological types.

Materials And Methods: We analyzed 497 patients treated at our center from June 2007 to June 2012 of different histological types. All the patients underwent complete central nervous system examination and thorough workup including hematological investigations, radiological investigations, and confirmation of histological type by biopsy. These patients were then treated with surgery followed by radiotherapy or upfront curative radiotherapy as per staging and then kept on regular follow-up as per institutional protocol.

Results: Majority of patients were astrocytomas (309 patients) followed by a pituitary adenoma (39 patients), oligodendroglioma (33 patients), medulloblastoma (22 patients), arteriovenous malformations (19 patients), craniopharyngioma (16 patients), and recurrent brain tumors (12 patients). There were few cases of central nervous lymphoma, meningioma, melanocytoma, ependymomas, schwannomas, hemangiopericytoma, gliosarcoma, and primitive neuroectodermal tumor. The histological types vary differently regarding presentation, treatment, and prognosis.

Conclusion: Astrocytomas are the most common tumors in presentation (309 patients) in which the high-grade astrocytomas carried worse prognosis. Benign tumors such as pituitary adenomas, schwannomas, and craniopharyngiomas had the best prognosis with survival seen up to almost last follow-up.
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http://dx.doi.org/10.4103/jcrt.JCRT_202_18DOI Listing
August 2021

Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia.

J Atten Disord 2020 Dec 17:1087054720978549. Epub 2020 Dec 17.

Deakin University, Geelong, VIC, Australia.

Objective: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD).

Methods: Parents of 213 Australian children (5-17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons).

Results: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3-0.6), less outdoor time (OR = 0.4; 95% 0.3-0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0-10.4), while television (OR = 4.0; 95% CI 2.5-6.5), social media (OR = 2.4; 95% CI 1.3-4.5), gaming (OR = 2.0; 95% CI 1.3-3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2-2.8), and loneliness (OR = 3.6; 95% CI 2.3-5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time.

Conclusions: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.
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http://dx.doi.org/10.1177/1087054720978549DOI Listing
December 2020

International travel is not a significant risk of exposure for patients at a Midwestern United States travel clinic.

Trop Dis Travel Med Vaccines 2020 Dec 10;6(1):25. Epub 2020 Dec 10.

Department of Emergency Medicine, University of Iowa, 200 Hawkins Drive, RCP 1008, Iowa City, IA, 52242, USA.

The Novel Coronavirus (SARS-CoV-2) was introduced into the United States via travel from Asia and Europe, although the extent of the spread of the disease was limited in the early days of the pandemic. Consequently, international travel may have played a role in the transmission of the disease into Iowa. This study seeks to determine how preferences for international travel changed as novel Coronavirus Disease (COVID-19) spread throughout the world and if any of these returning travelers developed COVID-19 as a result of their trips. This is a retrospective chart review of patients presenting to a travel clinic in Bettendorf, Iowa for pre-travel advice and vaccinations. From October 2019 to March 2020, four hundred twelve (n = 412) patients presented to the clinic. Intended travel to the Western Pacific region (China, Japan, Korea, etc.) decreased dramatically during the study period. All 412 patients were followed in the electronic medical record for the period after their planned travel and only three (3) presented for COVID-19 testing. Two (2) tested positive, and both of these infections were linked to workplace exposures and not due to travel. News of the growing pandemic and travel warnings likely altered patients' travel plans and decreased travel to the most affected regions of the world in the early months of the COVID-19 pandemic. Based on our study, travel was not a significant source of COVID-19 exposure for patients seen at this clinic.
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http://dx.doi.org/10.1186/s40794-020-00126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726604PMC
December 2020
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