Pharmacokinetics and in vitro effects of imipramine hydrochloride on the vas deferens in cattle

This project was divided into two studies. The first investigated the pharmacokinetics of imipramine hydrochloride (IMI) in bulls. IMI was administered intravenously to three bulls (600-705.5 kg) at a dose of 2mg/kg body weight (BW). Intravenous plasma concentrations of IMI over time were determined by fluorescence polarization immunoassay (FPIA). IMI plasma concentration versus time profile was best described by a two compartmental open model with first-order rate constants. IMI distributed rapidly, (t½a) at 7.2 ± 4.2 min, exhibited a very large apparent steady state volume of distribution (Vdss) of 4.2 ± 0.9 l/kg BW, had a very short terminal elimination half-life (t½b) of 140 ± 15 min and showed a rapid total body clearance (Cl) of 22.7 ± 7 ml/min/kg. Both IMI and the pharmacologically active metabolite, desipramine was negligible in serum at 24 hours. All three bulls treated with IMI showed pronounced central nervous system signs immediately post injection. Signs of generalised weakness and ataxia were evident. All CNS signs dissipated 15-20 minutes post injection and should therefore not influence the treatment interval. An interval of at least 23 hours between repeat treatments of IMI, representing a period of at least 10 half-lives, is recommended. The dose of 2 mg/kg BW used in this study was similar to that routinely used in stallions without fatal side effects. One of the three bulls exhibited spontaneous emission and ejaculation with this dose. The second study investigated the effects of IMI on ampullar strips of bulls in organ baths. Vasa deferentia were collected from 16 freshly slaughtered post-puberal bulls of various breeds. Longitudinal ampullar strips were prepared and placed into 20 ml modified Krebs bicarbonate solution, aerated with a mixture of 02 (95 %) and CO2 (5 %) in water-jacketed organ baths. The effect on the smooth muscle tissue of noradrenaline (NA) alone, NA in combination with IMI and IMI alone was evaluated. NA alone consistently produced dose-dependant smooth muscle tissue contractions. IMI doses equivalent to 0.1 mg to <1 mg/kg bwe partially blocked NA stimulating effects. Amplitude of rhythmic contractions increased while contraction frequency decreased at this level. This study supports the adrenergic potentiating effects of IMI at doses of 0.05-0.2 mg/kg bwe with higher doses having paradoxical effects. Doses of IMI < 2 mg/kg bwe completely blocked NA effects. Tissue response to NA, after IMI blockade, started to recover 146-186 minutes after application of IMI at <2 mg/kg bwe. In the absence of NA, IMI had no effect on smooth muscle activity. The time to an IMI effect on NA initiated smooth muscle activity was 8 minutes. On the basis of the results of this in vitro study, we propose that IMI can be used to enhance semen collection by means of electro-stimulation in domestic bulls and immobilised wildlife species such as buffalo, provided that the correct dose is used.Dissertation (MMedVet (Gyn))--University of Pretoria, 2005.Production Animal Studiesunrestricte

Calder\'on Strategies for the Convolution Quadrature Time Domain Electric Field Integral Equation

In this work, we introduce new integral formulations based on the convolution quadrature method for the time-domain modeling of perfectly electrically conducting scatterers that overcome some of the most critical issues of the standard schemes based on the electric field integral equation (EFIE). The standard time-domain EFIE-based approaches typically yield matrices that become increasingly ill-conditioned as the time-step or the mesh discretization density increase and suffer from the well-known DC instability. This work presents solutions to these issues that are based both on new Calder\'on strategies and quasi-Helmholtz projectors regularizations. In addition, to ensure an efficient computation of the marching-on-in-time, the proposed schemes leverage properties of the Z-transform -- involved in the convolution quadrature discretization scheme -- when computing the stabilized operators. The two resulting formulations compare favorably with standard, well-established schemes. The properties and practical relevance of these new formulations will be showcased through relevant numerical examples that include canonical geometries and more complex structures.Comment: 11 pages, 9 images, 1 table, Journal paper submitted to IEEE OJAP (Open Journal of Antennas and Propagation

Application for White Spot Syndrome Virus (WSSV) Monitoring using Edge Machine Learning

The aquaculture industry, strongly reliant on shrimp exports, faces challenges due to viral infections like the White Spot Syndrome Virus (WSSV) that severely impact output yields. In this context, computer vision can play a significant role in identifying features not immediately evident to skilled or untrained eyes, potentially reducing the time required to report WSSV infections. In this study, the challenge of limited data for WSSV recognition was addressed. A mobile application dedicated to data collection and monitoring was developed to facilitate the creation of an image dataset to train a WSSV recognition model and improve country-wide disease surveillance. The study also includes a thorough analysis of WSSV recognition to address the challenge of imbalanced learning and on-device inference. The models explored, MobileNetV3-Small and EfficientNetV2-B0, gained an F1-Score of 0.72 and 0.99 respectively. The saliency heatmaps of both models were also observed to uncover the "black-box" nature of these models and to gain insight as to what features in the images are most important in making a prediction. These results highlight the effectiveness and limitations of using models designed for resource-constrained devices and balancing their performance in accurately recognizing WSSV, providing valuable information and direction in the use of computer vision in this domain.Comment: 6 pages, 7 figures, conferenc

Baybayin Character Instance Detection

The Philippine Government recently passed the "National Writing System Act," which promotes using Baybayin in Philippine texts. In support of this effort to promote the use of Baybayin, we present a computer vision system which can aid individuals who cannot easily read Baybayin script. In this paper, we survey the existing methods of identifying Baybayin scripts using computer vision and machine learning techniques and discuss their capabilities and limitations. Further, we propose a Baybayin Optical Character Instance Segmentation and Classification model using state-of-the-art Convolutional Neural Networks (CNNs) that detect Baybayin character instances in an image then outputs the Latin alphabet counterparts of each character instance in the image. Most existing systems are limited to character-level image classification and often misclassify or not natively support characters with diacritics. In addition, these existing models often have specific input requirements that limit it to classifying Baybayin text in a controlled setting, such as limitations in clarity and contrast, among others. To our knowledge, our proposed method is the first end-to-end character instance detection model for Baybayin, achieving a mAP50 score of 93.30%, mAP50-95 score of 80.50%, and F1-Score of 84.84%

Management of tuberculosis: are the practices homogeneous in high-income countries?

Objectives: to evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: a survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum (n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% (n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: this study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed

Acetaminophen Protects Against Iron-Induced Cardiac Damage in Gerbils

There are few effective agents that safely remove excess iron from iron-overloaded individuals. Our goal was to evaluate the iron-removing effectiveness of acetaminophen given ip or orally in the gerbil iron-overload model. Male gerbils were divided into 5 groups: saline controls, iron-overloaded controls, iron-overloaded treated with ip acetaminophen, iron-overloaded treated with oral acetaminophen, and iron-overloaded treated with ipdeferoxamine. Iron dextran was injected iptwice/wk for 8 wk. Acetaminophen and deferoxamine treatments were given on Mondays, Wednesdays, and Fridays during the same 8 wk and continued for 4 wk after completion of iron-overloading. Echocardiograms were performed after completion of the iron-overloading and drug treatments. Liver and cardiac iron contents were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Iron-overloaded controls had 232-fold and 16-fold increases in liver and cardiac iron content, respectively, compared to saline controls. In iron-overloaded controls, echocardiography showed cardiac hypertrophy, right and left ventricular distension, significant reduction in left ventricular ejection fraction (−22%), and fractional shortening (−31%) during systole. Treatments with acetaminophen (ip or oral) or deferoxamine (ip) were equally effective in reducing cardiac iron content and in preventing cardiac structural and functional changes. Both agents also significantly reduced excess hepatic iron content, although acetaminophen was less effective than deferoxamine. The results suggest that acetaminophen may be useful for treatment of iron-induced pathology

Increase in Docetaxel-Resistance of Ovarian Carcinoma-Derived RMG-1 Cells with Enhanced Expression of Lewis Y Antigen

Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (LeY) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of LeY. We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-LeY antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of LeY were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance

Time delays in the diagnosis and treatment of malaria in non-endemic countries: a systematic review

Background Delays in diagnosis and treatment for malaria are associated with an increased risk for severe disease and mortality. Identifying the extent of patient and health system delay can provide a benchmark against which interventions to reduce delays can be measured. Methods We performed an electronic search in PubMed, EMBASE, Web of Science and LILACS for studies reporting time to diagnosis and treatment after return from travel, onset of symptoms and seeking healthcare in non-endemic countries. Additionally, theses, conference proceedings and nationally reported surveillance data were also searched for information on time delays. There were no language restrictions and all the studies were assessed for methodological quality. Results Data from 69 papers out of 1719 identified records published between 2005 and 2017 were extracted; our findings show that median diagnosis delays of four or more days are common and patient delays accounted for a large proportion of diagnostic delay. There were limited data available on medical diagnostic delay. Conclusion Patient delays accounted for a large proportion of the overall diagnostic delay; however the retrospective nature of the studies could have overestimated patient delay since previous healthcare contacts were not included. Additionally, the high frequency of studies reporting a clinically significant delay is a major concern

A Two-Way Interactive Text Messaging Application for Low-Income Patients with Chronic Medical Conditions: Design-Thinking Development Approach

Background: Two-way interactive text messaging between patient and community health workers (CHWs) through mobile phone SMS (short message service) text messaging is a form of digital health that can potentially enhance patient engagement in young adults and families that have a child with chronic medical conditions such as diabetes mellitus, sickle cell disease, and asthma. These patients have complex needs, and a user-centered way can be useful for designing a tool to address their needs. Objective: The aim of this study was to utilize the user-centered approach of design thinking to develop a two-way interactive communication SMS text messaging tool for communication between patients or caregivers and CHWs. Methods: We applied a design thinking methodology for development of the SMS text messaging tool. We collected qualitative data from 127 patients/caregivers and 13 CHWs, health care professionals, and experts. In total, 4 iterative phases were used to design the final prototype. Results: The design thinking process led to the final SMS text messaging tool that was transformed from a one-dimensional, template-driven prototype (phases 1 and 2) into a dynamic, interactive, and individually tailored tool (phases 3 and 4). The individualized components consider social factors that influence patients’ ability to engage such as transportation issues and appointment reminders. SMS text messaging components also include operational factors to support staff such as patient contact lists, SMS text messaging templates, and technology chat support. Conclusions: Design thinking can develop a tool to meet the engagement needs of patients with complex health care needs and be user-friendly for health care staff