Search

Eda Eken,1,2 David S Estores,3 Emily J Cicali,1,2 Kristin K Wiisanen,1,2 Julie A Johnson1,2 1Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA; 2Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA; 3Division of Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Julie A Johnson, University of Florida, Department of Pharmacotherapy and Translational Research, Box 100486, Gainesville, FL, 32610-0486, USA, Tel +1-352-273-6310, Email Julie.johnson@ufl.eduAbstract: Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of CYP2C19 genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of CYP2C19 prior to prescribing PPIs. There are strong data to support the influence of CYP2C19 genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on H. pylori and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.Keywords: CYP2C19, precision medicine, proton pump inhibitors, omeprazole, pantoprazole, lansoprazole

The aim of this study was to reveal biometric peculiarities of New Zealand white rabbit antebrachium (radius and ulna) by means of three-dimensional (3D) reconstruction of multidetector computed tomography (MDCT) images. Under general anesthesia, the antebrachiums of a total of sixteen rabbits of both sexes were scanned with a general diagnostic MDCT. Biometric measurements of the reconstructed models from high resolution MDCT images were analyzed statistically. Consequently, when biometric measurement values of corresponding bones of antebrachium were compared, it was revealed that there was no statistical significance within both sexes but there were statistically important differences between both sexes in some biometric measurements. It has been suggested that the results from the study can shed light on future studies on the skeletal system and can form a modern point of view to anatomical education. [ABSTRACT FROM AUTHOR]

In the past decade, pharmacogenomic (PGx) testing to predict drug response have emerged into clinical care. Clinical decision support (CDS) has and continues to play a key role in educating prescribers and facilitating the integration of pharmacogenomic results into routine clinical practice. The Epic Genomics module, an add-on to Epic's base clinical software, allows for storage of structured genomic data and provides electronic heath record tools designed with PGx CDS implementation in mind. In early 2022, the University of Florida Health deployed the Genomics module. This tutorial outlines the steps taken by the University of Florida Health Precision Medicine Program to implement Epic's Genomic Module at University of Florida Health and identifies key factors for a successful implementation., (© 2025 The Author(s). Clinical Pharmacology & Therapeutics © 2025 American Society for Clinical Pharmacology and Therapeutics.)

Purpose: Although it is known that alpha-adrenergic receptor antagonists have positive effects on metabolic parameters such as glucose metabolism, lipid profile, and insulin sensitivity, it is unclear whether this is a class effect. Tamsulosin is reported to have adverse effects on glucose metabolism and insulin resistance, and this may be because of its lack of glycolysis-enhancing effect compared with other alpha-adrenergic receptor antagonists with glycolysis-enhancing effects such as doxazosin, terazosin, and alfuzosin. The aim of this study was to compare the effect of tamsulosin on metabolic parameters with another alpha-1 adrenergic receptor antagonist, doxazosin., Methods: In this prospective, observational, controlled, 12-week clinical study, a total of 60 male patients aged ≥ 40 years who were first started on tamsulosin (n = 30; 0.4 mg/day, oral; mean age, 59.20 ± 8.97 years) or doxazosin (n = 30; 4 or 8 mg/day, oral; mean age, 58.50 ± 8.93 years) for benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) were enrolled. The groups were compared according to the changes in anthropometric and biochemical parameters (glycemia, lipid profile, and insulin sensitivity) at the end of treatment., Results: In intragroup analyses, systolic blood pressure, diastolic blood pressure, total cholesterol, and HbA1c levels decreased significantly in the doxazosin group compared with baseline (p < 0.05 for all), while no significant change was observed in the tamsulosin group. In comparisons between groups, systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels showed a significant decrease in the doxazosin group compared with the tamsulosin group (percent change: - 6.68 ± 13.08 vs. 0.53 ± 11.02, p = 0.025; - 3.63 ± 9.56 vs. 4.02 ± 10.86, p = 0.005; and - 5.62 ± 18.18 vs. 5.24 ± 15.42, p = 0.015, respectively)., Conclusion: Although these results do not support previous findings that tamsulosin has adverse effects on metabolic parameters, they suggest that doxazosin treatment may be a reason for preference in patients with BPH or LUTS accompanied by metabolic disorder., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The University of Florida Health Precision Medicine Program plays a crucial role in delivering pharmacogenomics (PGx) result notes to providers who request PGx testing. Despite this, there is currently a lack of a formal assessment of provider needs and established best practice design principles to guide the ongoing development of PGx result notes. This study aims to enhance the content and format of the PGx consult note at UF Health by incorporating valuable feedback from healthcare providers. Through in-depth user sessions involving 11 participants, we evaluated the usability of our consult note template. While overall satisfaction with the content was noted, specific sections, including those addressing phenoconversion and the medication list, were identified for revision to enhance clarity based on insightful provider feedback., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Desai, Ravindra, Hall, Al Alshaykh, Lemke, Eken, Cicali, Wiisanen, Cavallari and Nguyen.)

Stereology is a discipline that allows us to obtain quantitative information about the geometric structure of three-dimensional objects. In this study, the volume of grey matter (GM), white matter (WM), and lateral ventricle (LV) of the cerebral hemispheres (CH) in sheep and goats were calculated. For this purpose, six healthy male sheep and goat brains (1-2 years old) without any anomaly were used. Brains were fixed with 10% formaldehyde in the skull. The skull was opened using standard anatomical dissection methods, and the brains were carefully removed. Brain weight and volume were measured (using Archimedes' principle) after the meninges were removed. The cerebral hemispheres were separated from the other parts of the brain by a section made in front of the rostral colliculus. In the same way, the weight and volume of the cerebral hemispheres were measured. Afterward, the cerebral hemispheres were blocked with agar, and transversal cross sections (from rostral to caudal) with an average thickness of 3.42 mm were taken from the cerebral hemispheres. Grey matter was stained with Berlin blue macroscopic staining method. The stained cross sections were scanned at 600 dpi resolution, and a point counting grid was placed on the images with the ImageJ software. Cavalieri's principle calculated the surface area and volume measurements of the grey matter, white matter, and lateral ventricle. GM, WM, and LV volumes in sheep and goat cerebral hemispheres were calculated as 54.94, 21.48 and 3.06 mL in sheep, 57.46, 24.13 and 3.12 mL in goats, respectively. The percentages of these structures in the total hemisphere volume were 71.83%, 28.17% and 4.00% in sheep, 70.42%, 29.58% and 3.82% in goats, respectively. Asymmetry was not observed in cerebral hemispheres in both species. A difference was found in the WM, LV and LV: CH ratios in the right/left comparison of the goat (p < 0.05). In comparing sheep and goats, a significant difference was observed in WM right, WM left, WM total, CH left and CH total (p < 0.05). In conclusion, the cerebral hemispheres' grey matter and white matter ratio are frequently used to diagnose neurodegenerative diseases. In recent years, the increase in neurodegenerative disease models in farm animals has been enormous. It is thought that these values obtained from healthy animals in the current study will be important for such experimental studies in the future., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Purpose: To describe the implementation of CYP2C19 testing into clinical practice at University of Florida (UF) Health Gainesville hospital to guide proton pump inhibitor (PPI) dosing and the lessons learned from this experience., Summary: Different CYP2C19 genotypes are associated with variability in PPI plasma concentrations and intragastric pH, which may contribute to the risk of treatment failure due to subtherapeutic concentrations and adverse effects (eg, infection, bone fracture, renal dysfunction) with sustained supratherapeutic concentrations. Based on evidence available prior to the availability of pertinent Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, the UF Health Precision Medicine Program (PMP) developed clinical recommendations, provided through automated alerts at the time of a PPI order, to (1) increase the PPI dose for individuals with genotypes linked to increased CYP2C19 enzyme activity (ie, rapid and ultrarapid metabolizers) to improve the likelihood of drug effectiveness and (2) decrease the dose for individuals with decreased CYP2C19 activity (ie, intermediate and poor metabolizers) to reduce the risk of harm. The CYP2C19-PPI implementation was an iterative process that taught us key implementation lessons. Most notably, physician engagement is essential, problem lists in the medical record are unreliable, and special populations (eg, pediatric patients) need to be considered., Conclusion: Guiding PPI prescribing based on CYP2C19 genotype is a practical approach to potentially improve the benefit-risk ratio with PPI therapy. Physician engagement is key for successful implementation. A CPIC guideline on CYP2C19 genotype-guided PPI dosing is now available, and automated alerts may be instituted to facilitate implementation., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Insects vastly outnumber us in terms of species and total biomass, and are among the most efficient and voracious consumers of plants on the planet. As a result, to preserve crops, one of the primary tasks in agriculture has always been the need to control and reduce the number of insect pests. The current use of chemical insecticides leads to the accumulation of xenobiotics in ecosystems and a decreased number of species in those ecosystems, including insects. Sustainable development of human society is impossible without useful insects, so the control of insect pests must be effective and selective at the same time. In this article, we show for the first time a natural way to regulate the number of insect pests based on the use of extracellular double-stranded DNA secreted by the plant Pittosporum tobira . Using a principle similar to one found in nature, we show that the topical application of artificially synthesized short antisense oligonucleotide insecticides (olinscides, DNA insecticides) is an effective and selective way to control the insect Coccus hesperidum . Using contact oligonucleotide insecticide Coccus-11 at a concentration of 100 ng/μL on C. hesperidum larvae resulted in a mortality of 95.59 ± 1.63% within 12 days. Green oligonucleotide insecticides, created by nature and later discovered by humans, demonstrate a new method to control insect pests that is beneficial and safe for macromolecular insect pest management.

Objective: Recommendations for the treatment of cytokine release syndrome/macrophage activation syndrome (MAS) associated with coronavirus disease-2019 (COVID-19) are still of poor quality. IL-6 is an important therapeutic target as a main mediator of cytokine storm. The aim of our study was to evaluate the tocilizumab (TCZ) efficacy and factors affecting the therapy outcome., Methods: This retrospective study included 27 patients treated with TCZ for COVID-19-MAS. All patients in this study were treated with TCZ (intravenously, at a dose of 8 mg kg1 ) in addition to standard therapy. Clinical improvement (survival and decreased oxygen demand) on the 10-14th days and secondary infection rate were assessed., Results: In our 27 treated patients, 14 (51.8%) received TCZ in the intensive care unit (ICU) and seven (25.9%) were need to invasive mechanical ventilation (IMV). Fifteen (55.6%) of these patients revealed a good clinical response (four patients discharge from the ICU and 11 patients who followed-up in nonICU beds showed a decrease in oxygen demand). TCZ was significantly less effective in patients having high Murray lung injury score, low PO2/FiO2 ratio, IMV, and ICU admission (P < .05). Severity of hypoxemia was found as a single independent risk factor in the multivariable analysis (P < .05). Secondary bacterial infections rate was significantly higher in intubated patients (P < .01) or treated in the ICU (P ¼ .01)., Conclusion: TCZ was showed limited efficacy for COVID-19-related MAS. The most important predictive indicator for therapy outcome was found as the severity of hypoxemia. In addition, IMV and/or ICU was associated with the poor outcome and high side effect. So, controlled trials are still needed to confirm the indications and timing of TCZ therapy.

Mediterranean spotted fever (MSF) is a tick-borne acute endemic infectious disease caused by Rickettsia conorii. While MSF may progress asymptomatically, it may lead to clinical pictures like severe hemorrhagic fever. In this article, we are presenting an MSF case with signs of high fever, headache, nausea, weakness and generalized maculopapular rash. The diagnosis of the female patient who had a history of contact with a tick-infested dog was confirmed with her clinical and laboratory data. The clinical and laboratory findings of the patient who was given doxycycline by 200 mg/day for 7 days were improved in a short time. Rickettsia conorii serology by indirect immunofluorescence assay method confirmed the diagnosis of MSF. In cases of severe sepsis accompanied by high fever and generalized maculopapular rash where the source of the infection cannot be determined in the short term, carefully questioning exposure to ticks by considering the existing geographical, seasonal and endemic environmental factors may be life-saving in terms of early diagnosis and treatment of MSF, which may become fatal even in the absence of eschars (tache noire). The symptomatology of hemorrhagic fever associated with Rickettsia conorii may be confused with that of sepsis in clinical practice., Competing Interests: None

Three-dimensional (3D) reconstructive techniques are being used in many morphometric studies and clinical applications. The red fox is a wild animal localized in a wide geography. This study has been performed to determine morphometric properties of the pelvic cavity and reveal differences between sexes via 3D reconstruction obtained by multi-detector computed tomography images (MDCT) of the red fox. A total of 12 adult red foxes of both sexes were used in this study. Two-dimensional (2D) MDCT images of the pelvic cavity obtained and stored in DICOM format were used to reconstruct the 3D model. Mimics 13.1 program was used to perform the 3D reconstruction. A total of 24 dimensions were measured from the reconstructive model of the pelvic cavity. Twenty two dimensions were found to be significantly different (p < 0.05) between sexes. In conclusion, according to the pelvimetric data, it was determined that the red fox has sexual dimorphism and these data may be useful in wild animals morphological and gynaecological research. The authors hope to help in the diagnosis and treatment of the pelvic cavity-related orthopaedic and gynaecological disorders in the wild animals., (© 2021 Wiley-VCH GmbH.)

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.

A forty-seven-year-old female patient was admitted to our clinic with sudden ptosis and diplopia without pain. She had no trauma or systemic disease history. Ptosis and mydriasis were observed in her left eye. Eye movement was restricted all directions without lateral. Isolated oculomotor nerve paralysis was diagnosed based on clinical findings, and posterior communicating artery aneurysm was observed in magnetic resonance angiography.

Ticks are obligate blood-sucking arthropods that exist worldwide. Their targets include all vertebrates and humans. Ticks are harmful to people with regard to transmission in many viral, bacterial, and parasitic infections. In addition to these diseases and toxin-induced neurological complications, tick-induced paralysis is a syndrome related to neurotoxin production, and its mortality ratio in the literature is reported to be approximately 10%. Tick-induced isolated facial paralysis is a rare form of the disease developing because of attachment to the external auditory canal or attachment behind the ear. Our country and region are under risk in terms of included tick habitat for tick-induced paralysis that is responsible particularly for hard ticks. In our article, we aimed to present a case with isolated facial paralysis that occurred after the internal auditory canal was bitten by Hyalomma margintum species belonging to the hard ticks group and to probe the management of this disease.

The present study has been performed to reveal biometrical aspects and diameter-related differences in terms of sexes regarding pelvic cavity via three-dimensional (3D) reconstruction by using multidetector computed tomography (MDCT) images of pelvic cavity of the New Zealand rabbit. A total of 16 adult New Zealand rabbits, including 8 males and 8 females, were used in this study. Under anesthesia, the images obtained from MDCT were stacked and overlaid to reconstruct the 3D model of the pelvic cavity using 3D modeling software (Mimics 13.1). Measurements, such as the conjugate, transverse, and vertical diameters of the pelvic cavity, and the pelvic inclination were calculated and analyzed statistically. Biometrical differences of the pelvic diameters in New Zealand rabbits of both sexes were shown clearly. It was concluded that the pelvic diameters revealed by 3D modeling techniques can shed light on medical students who take both anatomy training and gynecological applications. The authors hope that the synchronization of medical approaches may give rise to novel diagnostic and therapeutic developments related to pelvic cavity.

This research investigates factors that may influence the secondary transfer of DNA. These include the type of biological substance deposited, the nature of the primary and secondary substrate, moisture content of the deposit and type of contact between the surfaces. Results showed that secondary transfer is significantly affected by both the type of primary substrate and the moisture (wetness) of the biological sample. Porous substrates and/or dry samples diminished transfer (with on average only 0.36% of biological material being transferred from one site to another), whereas non-porous substrates and/or wet samples facilitated transfer events (approximately 50-95% of biological material was transferred from one site to another). Further, the type of secondary substrate also influenced transfer rate, with porous surfaces, absorbing transferred biological substances more readily than non-porous ones. No significant differences were observed among the biological substances tested (pure DNA, blood and saliva). Friction contact between the two substrates significantly enhanced secondary transfer compared to either passive or pressure contact. These preliminary results will assist in developing general assumptions when estimating probability of a secondary DNA transfer event under simple conditions.

Background: Oxidative stress could play a role in pathogenesis of hepatitis C virus (HCV) infection. The aim of our study is to determine oxidant/antioxidant status of patients with chronic hepatitis C (CHC), and the effect of pegylated interferon alfa-2b plus ribavirin combination therapy on oxidative stress., Methods: Nineteen patients with chronic HCV infection and 28 healthy controls were included in the study. In control and patient groups, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte malondialdehyde (MDA) levels, erythrocyte CuZn-superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GSH-Px) activities were measured. After pegylated interferon alfa-2b and ribavirin combination therapy for 48 weeks, these parameters were measured again in the patient group., Results: Serum MDA levels increased significantly in CHC patients (n:19), before the treatment when compared with healthy subjects (n:28) 9.28 +/- 1.61, 4.20 +/- 1.47 nmol/ml, p < 0.001 respectively. MDA concentration decreased significantly (p < 0.001) after the treatment as well as ALT, AST activity, in erythrocytes of these patients. Average antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were significantly lower in erythrocytes of patients with CHC before treatment compared with the control group (both, p < 0.001). Chronic Hepatitis C patients after pegylated interferon alfa-2b and ribavirin therapy showed values of SOD, GSH-Px were significantly higher than pretreatment levels (both, p < 0.001)., Conclusion: Our results show that patients with chronic HCV infection are under the influence of oxidative stress associated with lower levels of antioxidant enzymes. These impairments return to level of healthy controls after pegylated interferon alfa-2b plus ribavirin combination therapy of CHC patients. Although interferon and ribavirin are not antioxidants, their antiviral capacity might reduce viral load, and inflammation, and perhaps through this mechanism might reduce virus-induced oxidative stress.

This study was carried out to describe morphologically and morphometrically the hypoglossal dorsal root and its ganglia, using heads of 20 adult Holstein cattle of both sexes. The dorsal root of the hypoglossal nerve (XII) has always an evident dorsal root ganglion (DRG) including the accessory in 30% (6 of heads) or satellite ganglia in 10% (2 of heads). There were statistically significant differences between the lengths (right: 8.64+/-0.22 mm, left: 7.91+/-0.31 mm, p<0.01) of peripheral roots of the DRG in male. Statistical significance existed in the lengths (right: 7.01+/-0.43, left: 8.27+/-0.47, p<0.05) of the central roots of the DRG in male. Since the histological findings showed that each ganglion placed on the dorsal root of the XII had the general feature of a spinal ganglion, it can be said that the XII has the intracranial peripheral (sensory) fibers and carry directly sensory input to the brain stem. In conclusion, the present study is the first to reveal the morphology of the hypoglossal dorsal root with ganglia in Holstein cattle.

This study was carried out to describe the arterial supply of Meckel's diverticulum (MD) in geese, using 36 adult healthy geese of both sexes, 50 to 52 weeks of age. The arterial supply of MD was classified into three types, In the first type, MD was supplied by a very distinct branch from the cranial mesenteric artery in 21 geese. In the second type, it was supplied by one terminal branch from the cranial mesenteric artery in 9 geese. In the third type, it was supplied both by one branch from the jejunal artery and by terminal branch from the cranial mesenteric artery in 6 geese. Based on the these types, we found significant differences (p < or = 0.01) in the length of MD between type I and II. The blood supply of the third type was observed more frequently in the male than in the female. Results from this study may contribute to the anatomical knowledge of arterial supply of MD in the geese.

To evaluate the formation of the external iliac vein in Akkaraman sheep and Angora goats, 8 adult healthy Akkaraman sheep and 8 Angora goats of both sexes, 3 to 4 years of age, were examined. The external iliac vein was formed by the deep femoral and femoral veins in 6 Akkaraman sheep and 7 Angora goats and by the medial circumflex femoral and femoral veins in 2 Akkaraman sheep and I Angora goat. Results from this study are thought to throw light on the future studies on the venous system, and to contribute considerably to the present anatomical knowledge concerning the external iliac vein of sheep and goats.

The aim of this study has been to describe the effect of varying degrees of fullness of the stomach on the topography of colon in cats by means of the sectional anatomy of the abdominal cavity. Twenty-four adult healthy cats of both sexes and of different ages were used. The cats were divided into two groups, of which group one had empty stomachs and the second filled stomachs. Eight cats were dissected. The remaining cats were frozen at -20 degrees C, the eight of which were sectioned paramedially and the other eight transversely. The ascending colon started at the level of the fifth lumbar vertebra, and the cranial boundary of the transverse colon was at the level of the second lumbar vertebra in cats with empty stomachs. The ascending colon started at the level of the sixth lumbar vertebra in cats with full stomachs, while the cranial boundary of the transverse colon was at the level of the fourth lumbar vertebra and had lost relationship to the right kidney resting directly on the vertebral column. In both groups, the descending colon was located in the left abdominal cavity up to the level of the sixth lumbar vertebra, at which point it curved medially and ran cranial to the seventh lumbar vertebra in the median plane. Results from this study are to throw light on computed tomography and magnetic resonance imaging.