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1.
Adv Physiol Educ ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695081

RESUMO

OBJECTIVE: It is essential for modern medical students to continuously enhance their clinical thinking abilities. This study aims to evaluate the efficacy of the combined World Café discussion and case-based learning (CBL) approach within the clinical thinking training course. METHODS: The clinical thinking training course incorporated the combined World Café discussion and CBL approach. The assessment of the accuracy and rationality of clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use was conducted through case-related queries. Feedback from students and instructors regarding the teaching content, teaching process, and teaching effect was gathered through questionnaires. RESULTS: The findings indicate that the students achieved high marks in all assessed areas, including clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use. The feedback from students and instructors on the teaching content, teaching process, and teaching effect was positive. CONCLUSION: Medical educators can use our findings to implement the combined World Café discussion and CBL mode to enhance student engagement.

2.
Biotechnol Bioeng ; 121(5): 1543-1553, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38293815

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-based screening has emerged as a powerful tool for identifying new gene targets for desired cellular phenotypes. The construction of guide RNA (gRNA) pools largely determines library quality and is usually performed using Golden Gate assembly or Gibson assembly. To date, library construction methods have not been systematically compared, and the quality check of each batch has been slow. In this study, an in-house nanopore sequencing workflow was established for assessing the current methods of gRNA pool construction. The bias of pool construction was reduced by employing the polymerase-mediated non-amplifying method. Then, a small gRNA pool was utilized to characterize stronger activation domains, specifically MED2 (a subunit of mediator complex) and HAP4 (a heme activator protein), as well as to identify better gRNA choices for dCas12a-based gene activation in Saccharomyces cerevisiae. Furthermore, based on the better CRISPRa tool identified in this study, a custom gRNA pool, which consisted of 99 gRNAs targeting central metabolic pathways, was designed and employed to screen for gene targets that could improve ethanol utilization in S. cerevisiae. The nanopore sequencing-based workflow demonstrated here should provide a cost-effective approach for assessing the quality of customized gRNA library, leading to faster and more efficient genetic and metabolic engineering in S. cerevisiae.


Assuntos
Sequenciamento por Nanoporos , RNA Guia de Sistemas CRISPR-Cas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ativação Transcricional , Clonagem Molecular , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos
3.
J Gastrointest Oncol ; 14(5): 2249-2259, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969835

RESUMO

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers. A major recent advance has been the identification of a subset of patients with PDAC who harbor inherited or somatic genetic alterations that result in homologous recombination deficiency (HRD) in tumor cells. These patients often respond favorably to drugs that can exploit this vulnerability. This review outlines the biomarkers that have been developed to predict HRD and their performance related specifically to PDAC, as well as novel HRD-targeted therapies for PDAC. Methods: We conducted a narrative review of the HRD in PDAC based on PubMed, Google Scholar, website and citation searches. Key Content and Findings: Germline mutations in BRCA1 and BRCA2 remains the only validated biomarker for the HRD state but various platforms are now available to define HRD beyond BRCA1/2 alterations. Currently, the available evidence supports the use of platinum-based chemotherapy as well as PARP inhibitors, and there is also emerging data that immune checkpoint inhibitors can produce some durable responses in these patients. Conclusions: Consistently detecting clinically significant the HRD status in PDAC has remained challenging with current commercially available platforms. Multiple novel HRD-targeted therapies for PDAC are currently in development and clinical trials, offering new opportunities for these patients.

4.
Womens Health (Lond) ; 19: 17455057231206312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37899602

RESUMO

BACKGROUND: Studies had compared single-embryo transfer to double-embryo transfer with cleavage stage embryos and found that while single-embryo transfer was less costly, it was also associated with a lower live birth rate than double-embryo transfer. A single blastocyst transfer has been shown to improve the live birth rate per cycle compared to single-embryo transfer at cleavage stage. OBJECTIVES: To compare live birth rates and real costs of elective single-embryo transfer to double-embryo transfer and to determine the incremental cost-effectiveness ratio of these two strategies in an unselected pool of women in a single center. DESIGN: Retrospective study. METHODS: We analyzed data of 4232 women who underwent their first fresh in vitro fertilization/intra-cytoplasmic sperm injection cycles with at least two embryos available for transfer in KK Women's and Children's Hospital from 2010 to 2017. RESULTS: Five hundred and sixty-four women underwent elective single-embryo transfer and 3668 women underwent double-embryo transfer. One hundred and fifty-six women who failed to achieve a live birth in their fresh elective single-embryo transfer cycle underwent a sequential thaw single-embryo transfer cycle. Live birth rate of fresh elective single-embryo transfer was significantly higher at 41.3% than that of double-embryo transfer at 32.6%. Cumulative live birth rate for sequential elective single-embryo transfer (fresh elective single-embryo transfer + thaw single-embryo transfer) was 47.9%. After accounting for variables which may affect live birth rates such as age and stage of embryo transfer, the odds of achieving a live birth from double-embryo transfer was 24% lower than that from sequential single-embryo transfer, although not statistically significant. For every live birth gained from an elective single-embryo transfer compared to double-embryo transfer, cost savings were S$20,172 per woman. If a woman had to have a sequential single-embryo transfer after a failed single-embryo transfer in her fresh cycle, cost savings were reduced to S$1476 per woman. CONCLUSION: Single-embryo transfer is a dominant strategy in an unselected population and adopting it in assisted reproductive treatments (ART) can produce cost savings without compromising on live birth rates.


Assuntos
Transferência Embrionária , Sêmen , Masculino , Gravidez , Criança , Feminino , Humanos , Taxa de Gravidez , Estudos Retrospectivos , Fertilização in vitro , Custos e Análise de Custo
5.
Antibiotics (Basel) ; 11(12)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36551422

RESUMO

Fracture-related infection is a serious complication in orthopedic surgery with severe consequences for the patient. We evaluated whether a novel noble metal nail-coating technology can prevent bacterial adhesion and biofilm formation without interfering with bony union. In this retrospective, single-center case series, we described the incidence of fracture-related infections and bony union achievement in patients who had Gustilo type IIIa or IIIb femoral or tibial fractures treated with noble metal alloy-coated titanium nails. Patients were treated between January 2017 and January 2019 at the Sultanah Aminah Hospital, Johor Bahru, Malaysia. Information on fracture-related infections and bone healing assessments was collected from patient records. Additionally, three independent experts retrospectively reviewed patient X-ray images from follow-up visits to further evaluate bony union achievement. Thirty-five patients were included. Infection developed in 3/35 (8.6%) patients; all cases were resolved by antibiotic therapy. Radiographs were available for 32 patients; these confirmed the presence of bone healing in 30/32 (93.8%) patients. However, according to patient records, bony union was achieved in all patients. No safety issues were recorded. This case series suggests that a noble metal alloy-coated titanium nail can prevent infection and facilitate bony union achievement in patients undergoing surgery for severe open fractures.

6.
Huan Jing Ke Xue ; 43(11): 5180-5191, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36437090

RESUMO

In order to explore the spatial and temporal changes in spatial patterns and source changes in heavy metals in Xiangzhou District, 395 and 326 soil samples were collected from cultivated soil in Xiangzhou District in November 2009 and November 2019, respectively. The contents of Cr, Pb, As, Hg, and Cd during these two years were measured. The spatial pattern and variation distribution of five types of heavy metals during these two years were obtained by using the empirical Bayesian Kriging (EBK) method. The effect (q-statistic) of 19 environmental factors and 5 types of heavy metals was calculated by using the geographical detector model (GDM), and the changes over the two years were compared. The results showed that compared with that in 2009, the heavy metal contents of Cr, Pb, Hg, and As in Xiangzhou District were decreased as a whole in 2019, whereas the Cd content increased overall. The spatial differentiation of heavy metals in the soil in Xiangzhou District in 2019 was more complicated than that in 2009. Pb, Hg, and Cd in the south and Hg in the central urban area and surrounding areas also increased. The content of each element decreased to the north and northwest. Compared with that in 2009, the explanatory power of natural factors and the distance between pollution enterprises on the single factor of the five soil heavy metal contents in 2019 decreased, and the influence on the contents under the control of single factors decreased significantly. The superposition influence of human activity factors increased, especially the distance between residential land, road, and land for pollution enterprises and environmental factors on soil heavy metal elements. These results indicated that the changes in soil heavy metal sources in 2019 tended to be complex, with structural factors as the main influencing factor. The influence of the emission of polluting enterprises on heavy metal elements decreased, whereas the influence of human activities on heavy metal content increased.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Humanos , Solo/química , Poluentes do Solo/análise , Teorema de Bayes , Cádmio , Chumbo , Monitoramento Ambiental/métodos , Metais Pesados/análise , Análise Espacial
7.
Front Mol Biosci ; 9: 991308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330220

RESUMO

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers.

8.
iScience ; 25(12): 105459, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36425765

RESUMO

The efficacy of cisplatin in treating advanced non-small cell lung cancer is limited mainly because of insensitivity and/or acquired resistance. MAPK15, previously shown by us to enhance the sensitivity of the anti-cancer drug arsenic trioxide, could also enhance the sensitivity of other anti-cancer drugs. Here, we explore the potential role of MAPK15 in chemosensitivity to cisplatin in human lung cancer cells. Our results indicated that the expression level of MAPK15 was positively correlated with cisplatin sensitivity through affecting the DNA repair capacity of cisplatin-treated cells. The expression of MAPK15 was transcriptionally regulated by the TNF-α-activated NF-κB signaling pathway, and TNF-α synergized with cisplatin, in a MAPK15-dependent manner, to exert cytotoxicity in vitro and in vivo. Therefore, levels of TNF-α dictate the responsiveness/sensitivity of lung cancer cells to cisplatin by transcriptionally upregulating MAPK15 to enhance chemosensitivity, suggesting manipulation of MAPK15 as a strategy to improve the therapeutic efficacy of chemotherapeutic drugs.

9.
BMC Med Inform Decis Mak ; 22(1): 161, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35725445

RESUMO

BACKGROUND: In developing countries where both high rates of smoking and endemic tuberculosis (TB) are often present, identification of early lung cancer can be significantly confounded by the presence of nodules such as those due to latent TB (LTB). It is very challenging to distinguish lung cancer and LTB without invasive procedures, which have their own risks of morbidity and even mortality. METHODS: Our method uses a customized VGG16-based 15-layer 2-dimensional deep convolutional neural network (DNN) architecture with transfer learning. The DNN was trained and tested on sets of CT images set extracted from the National Lung Screening Trial and the National Institute of Allergy and Infectious Disease TB Portals. Performance of the DNN was evaluated under locked and step-wise unlocked pretrained weight conditions. RESULTS: The DNN with unlocked pretrained weights achieved an accuracy of 90.4% with an F score of 90.1%. CONCLUSIONS: Our findings support the potential for a DNN to serve as a noninvasive screening tool capable of reliably detecting and distinguishing between lung cancer and LTB.


Assuntos
Aprendizado Profundo , Neoplasias Pulmonares , Tuberculose , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Redes Neurais de Computação
10.
J Med Syst ; 46(7): 48, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35670870

RESUMO

Justifications for the widespread adoption and integration of an electronic health record (EHR) have long leaned on the purported benefits of the technology. However, the performance of the EHR has been underwhelming relative to the promises of immediate access to relevant patient information, clinical decision supports, computerized ordering, and transferable patient data. In this narrative review, we provide an overview of the historical problems and limitations of the EHR, detail the core principles that define agile processes that may overcome the barriers faced by the current EHR, and re-imagine what an integrated, seamless EHR that serves its users and patients might look like. Moving forward, the EHR should be redesigned using a middle-out framework and empowering dual-type champions to maintain the sustainable diffusion of future innovations.


Assuntos
Registros Eletrônicos de Saúde , Humanos
11.
Brain Behav ; 12(1): e2453, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878231

RESUMO

INTRODUCTION: Social rank has a profound influence on the behavior and health of humans and animals. METHODS: To explore the effect of a combination of living Bifidobacterium, Lactobacillus and Streptococcus (CLB) on anxiety- and depression-like behaviors and social rank, mice were subjected to a social dominance tube test (SDTT). The behaviors, rank, gut microbiota, and expression of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus were measured. RESULTS: The results indicated that CLB improved the SDTT ranking score of the losers and alleviated anxiety-like behaviors of the winners. CLB decreased the level of Desulfovibrio and augmented the level of Mollicutes in the feces, increased BDNF content, and reduced the level of tumor necrosis factor-α in the hippocampus. CONCLUSION: These findings indicated that CLB may be used for the treatment of anxiety and improvement of the rank score via regulation of gut microbiota and anti-inflammatory effects.


Assuntos
Bifidobacterium , Lactobacillus , Animais , Ansiedade/metabolismo , Ansiedade/terapia , Depressão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Predomínio Social , Streptococcus
12.
Int J Mol Sci ; 22(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34768831

RESUMO

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.


Assuntos
Cádmio/metabolismo , Proteínas de Transporte de Cátions/genética , Selênio/metabolismo , Transporte Biológico , Proteínas de Transporte de Cátions/metabolismo , Bases de Dados Genéticas , Doença/genética , Células HeLa , Homeostase , Humanos , Ferro/metabolismo , Manganês/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Zinco/metabolismo
13.
Expert Rev Proteomics ; 18(11): 925-938, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34812694

RESUMO

INTRODUCTION: The outbreak of the newly discovered human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has disrupted the normal life of almost every civilization worldwide. Studies have shown that the coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 can affect multiple human organs and physiological systems, but the respiratory system remains the primary location for viral infection. AREAS COVERED: We summarize how omics technologies are used in SARS-CoV-2 research and specifically review the current knowledge of COVID-19 from the aspect of human bronchial-pulmonary proteomics. Also, knowledge gaps in COVID-19 that can be fulfilled by proteomics are discussed. EXPERT OPINION: Overall, human bronchial-pulmonary proteomics plays an important role in revealing the dynamics, functions, tropism, and pathogenicity of SARS-CoV-2, which is crucial for COVID-19 biomarker and therapeutic target discoveries. To more fully understand the impact of COVID-19, research from various angles using multi-omics approaches should also be conducted on the lungs as well as other organs.


Assuntos
Brônquios/metabolismo , COVID-19/metabolismo , Pulmão/metabolismo , Pandemias , Proteômica , SARS-CoV-2/patogenicidade , Animais , COVID-19/virologia , Humanos , Terapia de Alvo Molecular
14.
World J Clin Cases ; 9(20): 5737-5743, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34307633

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant epithelial tumor originating from adrenocortical cells that carries a very poor prognosis. Metastatic or inoperable diseases are often considered incurable, and treatment remains a challenge. Especially for advanced cases such as ACC complicated with renal venous cancer thrombus, there are few cumulative cases in the literature. CASE SUMMARY: The patient in this case was a 39-year-old middle-aged male who was admitted to the hospital for more than half a month due to dizziness and chest tightness. Computed tomography (CT) findings after admission revealed a left retroperitoneal malignant space-occupying lesion, but the origin of the formation of the left renal vein cancer thrombus remained to be determined. It was speculated that it originated from the left adrenal gland, perhaps a retroperitoneal source, and left adrenal mass + left nephrectomy + left renal vein tumor thrombus removal + angioplasty were performed under general anesthesia. Postoperative pathology results indicated a diagnosis of ACC. Postoperative steroid therapy was administered. At 3 mo after surgery, abdominal CT reexamination revealed multiple enlarged retroperitoneal lymph nodes and multiple low-density shadows in the liver, and palliative radiotherapy and mitotane were administered, considering the possibility of metastasis. The patient is currently being followed up. CONCLUSION: ACC is a highly malignant tumor. Even if the tumor is removed surgically, there is still the possibility of recurrence. Postoperative mitotane and adjuvant chemoradiotherapy have certain benefits for patients, but they cannot fully offset the poor prognosis of this disease.

15.
Nat Biotechnol ; 39(12): 1521-1528, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34312500

RESUMO

Whole-brain mesoscale mapping in primates has been hindered by large brain sizes and the relatively low throughput of available microscopy methods. Here, we present an approach that combines primate-optimized tissue sectioning and clearing with ultrahigh-speed fluorescence microscopy implementing improved volumetric imaging with synchronized on-the-fly-scan and readout technique, and is capable of completing whole-brain imaging of a rhesus monkey at 1 × 1 × 2.5 µm3 voxel resolution within 100 h. We also developed a highly efficient method for long-range tracing of sparse axonal fibers in datasets numbering hundreds of terabytes. This pipeline, which we call serial sectioning and clearing, three-dimensional microscopy with semiautomated reconstruction and tracing (SMART), enables effective connectome-scale mapping of large primate brains. With SMART, we were able to construct a cortical projection map of the mediodorsal nucleus of the thalamus and identify distinct turning and routing patterns of individual axons in the cortical folds while approaching their arborization destinations.


Assuntos
Mapeamento Encefálico , Encéfalo , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento Tridimensional/métodos , Macaca mulatta
16.
ORL J Otorhinolaryngol Relat Spec ; 83(4): 258-262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34148048

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the fourth common cancer in Malaysia. A few studies have looked into the incidence of NPC in Malaysia in general, but there has been no published data on its incidence in Sabah specifically, where NPC is very common among the population. The aim of this study is to present the first report on the incidence of NPC in the state of Sabah, Borneo. METHODS: Data of all patients diagnosed with NPC over a 5-year period from January 2015 to December 2019 inclusive were collected from the NPC registry of 3 main hospitals in Sabah. Age-standardized rates (ASRs) for different genders, ethnicities, and districts of origin were calculated. RESULTS: 215 NPC patients were identified with a mean age at diagnosis of 49 (range 9-82). The ASR of NPC was 7.9/100,000 where the average age-adjusted male-to-female ratio was 2.4. The highest ASR was found in Dusun ethnicity in both male (3.19/100,000) and female (1.69/100,000) individuals, followed by Chinese (both genders), and Kadazan (for male individuals) and Bajau (for female individuals). The highest ASR was found in patients originating from Sandakan, Kota Kinabalu, Keningau, and Tawau. CONCLUSION: This is the first report on the incidence of NPC in Sabah, Borneo. The data suggest high ASRs among the population, especially in male Dusun and Chinese ethnic groups. Further research looking into NPC in this state, especially on risk factors and ways to improve diagnosis and prevention among the population, is recommended.


Assuntos
Neoplasias Nasofaríngeas , Bornéu , Feminino , Humanos , Incidência , Malásia/epidemiologia , Masculino , Carcinoma Nasofaríngeo/epidemiologia , Neoplasias Nasofaríngeas/epidemiologia
17.
Rambam Maimonides Med J ; 12(2)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33938804

RESUMO

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.

18.
Drug Metab Pharmacokinet ; 38: 100390, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33836300

RESUMO

The combination of antiarrhythmic agents, amiodarone or dronedarone, with the anticoagulant rivaroxaban is used clinically in the management of atrial fibrillation for rhythm control and secondary stroke prevention respectively. Renal drug-drug interactions (DDIs) between amiodarone or dronedarone and rivaroxaban were previously ascribed to inhibition of rivaroxaban secretion by P-glycoprotein at the apical membrane of renal proximal tubular epithelial cells. Benzbromarone, a known inhibitor of organic anion transporter 3 (OAT3), shares a benzofuran scaffold with amiodarone and dronedarone. However, inhibitory activity of amiodarone and dronedarone against OAT3 remains arcane. Here, we conducted in vitro transporter inhibition assays in OAT3-transfected HEK293 cells which revealed amiodarone, dronedarone and their respective major pharmacologically-active metabolites N-desethylamiodarone and N-desbutyldronedarone possess inhibitory activity against OAT3, with corrected Ki values of 0.042, 0.019, 0.028 and 0.0046 µM respectively. Protein binding effects and probe substrate dependency were accounted for in our assays. Static modelling predicted 1.29-, 1.01-, 1.29- and 1.16-fold increase in rivaroxaban exposure, culminating in a predicted 1.29-, 1.01-, 1.28- and 1.15-fold increase in major bleeding risk respectively, suggesting potential OAT3-mediated DDI between amiodarone and rivaroxaban. Future work involving physiologically-based pharmacokinetic modelling is crucial in holistically predicting the complex DDIs between the benzofuran antiarrhythmic agents and rivaroxaban.


Assuntos
Antiarrítmicos/farmacologia , Benzofuranos/farmacologia , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Amiodarona/análogos & derivados , Amiodarona/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Linhagem Celular , Dronedarona/farmacologia , Interações Medicamentosas/fisiologia , Células HEK293 , Humanos , Rivaroxabana/farmacologia
19.
Plants (Basel) ; 10(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808386

RESUMO

Organically-derived biofertilizers and biostimulants, developed from harvested materials such as seaweed and waste from animal and fish processing, are currently the subject of much fundamental and applied research. These products have significant potential in reducing synthetic fertilizer inputs to horticultural, arable, and pasture-based agricultural systems, although there is frequently some ambiguity over the magnitude and consistency of any positive effects these products may have on plant performance. This study examined the effects of organically-derived plant growth promoters (PGPs) available in New Zealand on the early vegetative growth of 16 plant species maintained under glasshouse conditions. When applied as a root drench to low nutrient potting mix, the effects of the PGPs on seedling shoot growth were strongly related to the NPK contents of the applied solutions. Any positive effects on shoot growth were, on average, reduced when the seedlings were maintained in higher nutrient growing media. Applying the PGPs at concentrations twice, and four times, the recommended concentration, only caused further growth responses when the PGPs contained high levels of nutrients. Applying the PGPs as a foliar spray had negligible effects on shoot growth. Overall, the results of these trials suggest that the positive effects of applying some organically-derived PGPs on seedling growth are a function of the PGP nutrient content, and not due to any indirect effects related to phytohormone pathways or modification of rhizosphere microorganisms.

20.
Int J Surg Case Rep ; 81: 105723, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33713999

RESUMO

BACKGROUND: Hypopharyngeal carcinoma can involve thyroid gland due to their close proximity. However, an initial presentation as a thyroid abscess is rare in this malignancy. To our knowledge, this is the second reported case in the English literature. CASE PRESENTATION: We described a 45-year-old female who presented with dysphagia, hoarseness and anterior neck swelling. The initial CT scan revealed a right thyroid abscess which was incised and drained with no malignancy found in the biopsy of the thyroid tissue. Patient presented one month later with worsening dysphagia, weight loss and a fungating anterior neck mass. Further investigation revealed a locally advanced hypopharyngeal squamous cell carcinoma extending to the right thyroid, upper oesophagus, prevertebral muscles and bilateral cervical lymph nodes (T4bN2cM0). Unfortunately, the patient passed away prior to initiation of treatment. CONCLUSION: Clinicians should have raised index of suspicion of a possible underlying hypopharyngeal carcinoma in patients presenting with thyroid abscess and proceed to further investigations in order to ensure early diagnosis and treatment of the malignancy.

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