British Journal of Biomedical Science最新文献

Background: Direct oral anticoagulants (DOACs) interfere with coagulation assays potentially leading to inaccurate results. This study determined the effectiveness of DOAC-stop® and DOAC-remove® in overcoming DOAC interference. It aimed to investigate the extent to which apixaban, rivaroxaban, and dabigatran had an effect on thrombophilia and lupus tests using normal plasma, as well as whether DOACs interfere with true-positive results by testing abnormal controls.

Methods: Apixaban (0.03 mg/mL), rivaroxaban (0.01 mg/mL), and dabigatran (0.019 mg/mL) stock solutions were made and added to the normal pool at three different concentrations (200, 400 and 600 ng/mL) and to the abnormal controls at a single concentration. These samples and untreated DOAC controls were tested before and after adding either DOAC-stop® or DOAC-remove®. The measured parameters included protein C, protein S, antithrombin III (ATIII), DRVVS, DRVVC, PTT-LA and DOAC concentration. The normal pool spiked with DOAC was repeated seven times for each DOAC at each concentration level and the abnormal controls spiked with DOAC were repeated four times at a single concentration level for each DOAC.

Results: In the normal pool, dabigatran and rivaroxaban affected all lupus anticoagulant tests, whereas apixaban only affected DRVVS and DRVVC. While dabigatran led to false-positive protein S deficiency and falsely elevated ATIII. Both DOAC-stop® and DOAC-remove® brought the thrombophilia results and all falsely elevated lupus anticoagulant results back within the normal range for apixaban and rivaroxaban. For dabigatran all the affected lupus anticoagulant tests remained abnormal following DOAC-remove®, unlike DOAC-stop® treatment, where only DRVVS and DRVVC at 600 ng/mL remained abnormal. In abnormal controls, all DOACs falsely elevated the lupus anticoagulant tests, whereas dabigatran caused false negative ATIII results, that were corrected (remained abnormal) with DOAC-stop® and DOAC-remove®. DOAC-stop® showed a greater reduction in lupus anticoagulant results than DOAC-remove®, causing a false-negative DRVVT ratio for rivaroxaban.

Conclusion: DOAC-stop® is more effective than DOAC-remove® in removing all DOACs below the reference range, whereas DOAC-remove® failed to remove dabigatran.

Background: Tuberculosis (TB) continues be the leading cause of death globally due to an infectious agent. There is a paucity of data describing the readability of patient-facing TB information for service users. The aim of this study was to calculate the readability of multiple global TB information sources.

Methods: Information on tuberculosis (n = 150 sources) included nine categories, Patient-facing information: WHO publications (n = 17), International governments (n = 19), Hospitals (n = 10), Non-government organisations (NGOs)/charities (n = 20), Cochrane Plain Language Summaries (n = 20); LabTestsOnlineUK (n = 4) and Scientific-facing information: Clinical trials (n = 20), Cochrane abstracts (n = 20), Scientific abstracts (n = 20). Readability was calculated using Readable software, defined by (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index and two text metrics [words/sentence, syllables/word].

Results: Mean readability values for TB information for the FRE and FKGL were 35.6 ± 1.6 (standard error of mean (SEM)) (US Target ≥60; UK Target ≥90) and 12.3 ± 0.3 (US Target ≤8; UK Target ≤6), respectively, with mean words per sentence and syllables per word of 17.2 and 1.8, respectively. Cochrane Plain Language Summaries had similar readability scores to their matching scientific abstract (p = 0.15). LabTestsOnlineUK yielded a mean FRE score of 51.5 ± 1.2, a mean FKGL score of 10.2 ± 0.5 and text metric scores of 16.7 ± 2.3 and 1.6, for words per sentence and syllables per word, respectively. In descending order, TB information from international governments, hospitals and LabTestsOnlineUK were the most readable (FRE = 57.9, 54.1 and 51.5, respectively), whereas scientific abstracts and Cochrane abstracts were the most difficult to read (13.0 and 30.2, respectively).

Conclusion: Patient-facing TB information analysed had poor readability. Effective communication of biomedical science concepts and information relating to TB is vital for service users to enhance their health literacy of tuberculosis, thereby promoting better clinical outcomes. Biomedical scientists are important custodians of scientific information for their service user populations, including other healthcare professionals within the TB multidisciplinary (MDT) team and patient service users. When preparing TB information, this should be checked and modified in real time employing readability calculators, to align with health readability targets.

Oral administration of protein-based therapeutics is highly desirable due to lower cost, enhanced patient compliance, and convenience. However, the harsh pH environment of the gastrointestinal tract poses significant challenges. Silica-based carriers have emerged as potential candidates for the delivery of protein molecules, owing to their tuneable surface area and pore volume. We explored the use of a commercial mesoporous silica carrier, SYLOID, for the delivery of octreotide and bovine serum albumin (BSA) using a solvent evaporation method in three different solvents. The loading of proteins into SYLOID was driven by diffusion, as described by the Stokes-Einstein equation. Various parameters were investigated, such as protein size, diffusion, and solubility. Additionally, 3D fluorescence confocal imaging was employed to identify fluorescence intensity and protein diffusion within the carrier. Our results indicated that the loading process was influenced by the molecular size of the protein as octreotide exhibited a higher recovery rate (71%) compared to BSA (32%). The methanol-based loading of octreotide showed uniform diffusion into the silica carrier, whereas water and ethanol loading resulted in the drug being concentrated on the surface, as shown by confocal imaging, and further confirmed by scanning electron microscopy (SEM). Pore volume assessment supported these findings, showing that octreotide loaded with methanol had a low pore volume (1.2 cc/g). On the other hand, BSA loading was affected by its solubility in the three solvents, its tendency to aggregate, and its low solubility in ethanol and methanol, which resulted in dispersed particle sizes of 223 and 231 μm, respectively. This reduced diffusion into the carrier, as confirmed by fluorescence intensity and diffusivity values. This study underscores the importance of protein size, solvent properties, and diffusion characteristics when using porous carriers for protein delivery. Understanding these factors allows for the development of more effective oral protein-based therapeutics by enhancing loading efficiency. This, in turn, will lead to advances in targeted drug delivery and improved patient outcomes.

This review delves into the entorhinal cortex (EC) as a central player in the pathogenesis of Alzheimer's Disease (AD), emphasizing its role in the accumulation and propagation of tau pathology. It elucidates the multifaceted functions of the EC, encompassing memory formation, spatial navigation, and olfactory processing, while exploring how disruptions in these processes contribute to cognitive decline in AD. The review discusses the intricate interplay between tau pathology and EC vulnerability, highlighting how alterations in neuronal firing patterns and synaptic function within the EC exacerbate cognitive impairments. Furthermore, it elucidates how specific neuronal subtypes within the EC exhibit differential susceptibility to tau-induced damage, contributing to disease progression. Early detection methods, such as imaging techniques and assessments of EC blood flow, are examined as potential tools for identifying tau pathology in the preclinical stages of AD. These approaches offer promise for improving diagnostic accuracy and enabling timely intervention. Therapeutic strategies targeting tau pathology within the EC are explored, including the clearance of pathological tau aggregates and the inhibition of tau aggregation processes. By understanding the molecular and cellular mechanisms underlying EC vulnerability, researchers can develop more targeted and effective interventions to slow disease progression. The review underscores the importance of reliable biomarkers to assess disease progression and therapeutic efficacy in clinical trials targeting the EC. Ultimately, it aims to contribute to the development of more effective management strategies for AD, emphasizing the translation of research findings into clinical practice to address the growing societal burden of the disease.

Background: Frequent chest CTs within a short period during follow-up of long COVID patients may increase the risk of radiation-related health effects in the exposed individuals. We aimed to assess the image quality and diagnostic accuracy of ultra-low-dose CT (ULDCT) chest compared to standard-dose CT (SDCT) in detecting lung abnormalities associated with long COVID.

Methods: In this prospective study, 100 long COVID patients with respiratory dysfunction underwent SDCT and ULDCT chest that were compared in terms of objective (signal-to-noise ratio, SNR) and subjective image quality (image graininess, sharpness, artifacts, and diagnostic accuracy along with the European guidelines on image quality criteria for CT chest), detection of imaging patterns of long COVID, CT severity score, and effective radiation dose. Additionally, the diagnostic performance of ULDCT was compared among obese (BMI≥30 kg/m²) and non-obese (BMI<30 kg/m²) subjects.

Results: The mean age of study participants was 53 ± 12.9 years, and 68% were male. The mean SNR was 31.4 ± 5.5 and 11.3 ± 4.6 for SDCT and ULDCT respectively (p< 0.0001). Common findings seen on SDCT included ground-glass opacities (GGOs, 77%), septal thickening/reticulations (67%), atelectatic/parenchymal bands (63%) and nodules (26%). ULDCT provided sharp images, with no/minimal graininess, and high diagnostic confidence in 81%, 82% and 80% of the cases respectively. The sensitivity of ULDCT for various patterns of long COVID was 72.7% (GGOs), 71.6% (interlobular septal thickening/reticulations), 100% (consolidation), 81% (atelectatic/parenchymal bands) and 76.9% (nodules). ULDCT scans in non-obese subjects exhibited a significantly higher sensitivity (88% vs. 60.3%, p < 0.0001) and diagnostic accuracy (97.7% vs. 84.9%, p < 0.0001) compared to obese subjects. ULDCT showed very strong correlation with SDCT in terms of CT severity score (r = 0.996, p < 0.0001). The mean effective radiation dose with ULDCT was 0.25 ± 0.02 mSv with net radiation dose reduction of 94.8% ± 1.7% (p < 0.0001) when compared to SDCT (5.5 ± 1.96 mSv).

Conclusion: ULDCT scans achieved comparable diagnostic accuracy to SDCT for detecting long COVID lung abnormalities in non-obese patients, while significantly reducing radiation exposure.

The global issue of antimicrobial resistance poses significant challenges to public health. The World Health Organization (WHO) has highlighted it as a major global health threat, causing an estimated 700,000 deaths worldwide. Understanding the multifaceted nature of antibiotic resistance is crucial for developing effective strategies. Several physiological and biochemical mechanisms are involved in the development of antibiotic resistance. Bacterial cells may escape the bactericidal actions of the drugs by entering a physiologically dormant state known as bacterial persistence. Recent findings in this field suggest that bacterial persistence can be one of the main sources of chronic infections. The antibiotic tolerance developed by the persister cells could tolerate high levels of antibiotics and may give rise to persister offspring. These persister offspring could be attributed to antibiotic resistance mechanisms, especially in chronic infections. This review attempts to shed light on persister-induced antibiotic resistance and the current therapeutic strategies.