Prime Time Research Articles

Aldosterone synthase inhibitors for cardiorenal protection: ready for prime time?

Background: Aldosterone, through its genomic and non-genomic effects, plays an important role in cardiovascular and renal injury. Steroidal mineralocorticoid receptor antagonists (MRAs) are fundamental to offset the aldosterone-mediated cardiorenal damage, but side effects may limit their use in a substantial proportion of patients. On the other hand, non-steroidal mineralocorticoid receptor antagonists (NS-MRA) showed improved selectivity and safety profile. However, interfering with the MRA could only partially inhibit aldosterone mediated effect both because of escaping mechanisms and potential non-genomic activity. Summary: Inhibiting aldosterone synthesis could be a promising strategy to abolish aldosterone-mediated cardiovascular side effects. Aldosterone is primarily synthesized by the CYP11B2 enzyme, which is very similar to CYP11B1, a key enzyme involved in glucocorticoid production. Lack of specificity for CYP11B2 and consequent off-target effects hampered the development of first-generation aldosterone synthase inhibitors (ASIs). The subsequent development of highly specific ASIs led to successful clinical trials in patients with resistant and uncontrolled hypertension. Key Messages: A recent randomized clinical trial showed a significant benefit of ASIs in patients with chronic kidney disease and albuminuria. However, further outcome based clinical trials are needed to confirm the promising role of ASIs in cardiorenal damage.

Molecular imaging of renal cell carcinomas: ready for prime time.

The clinical diagnosis of renal cell carcinoma (RCC) is constantly evolving. Diagnostic imaging of RCC relying on enhanced computed tomography (CT) and magnetic resonance imaging (MRI) is commonly used for renal mass characterization and assessment of tumour thrombosis, whereas pathology is the gold standard for establishing diagnosis. However, molecular imaging is rapidly improving the clinical management of RCC, particularly clear-cell RCC. Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.

Personalized clinical management of patients with atrial fibrillation: is a biomarker-based strategy for prediction of sinus rhythm persistence ready for prime time?

Personalized clinical management of patients with atrial fibrillation: is a biomarker-based strategy for prediction of sinus rhythm persistence ready for prime time?

Pre-emptive therapeutic decisions based on measurable residual disease status in acute myeloid leukemia: ready for prime time?

The use of measurable residual disease (MRD) as a biomarker for prognostication, risk stratification, and therapeutic decision-making in acute myeloid leukemia (AML) is gaining prominence. MRD monitoring for NPM1-mutated and core-binding factor AML using PCR techniques is well-established for assessing disease after intensive chemotherapy. AML with persistent FLT3-ITD MRD post-intensive chemotherapy and pre-allogeneic hematopoietic cell transplantation (pre-allo-HCT) is associated with an increased risk of relapse and lower survival. Pre-allo-HCT MRD is an independent risk factor for post-allo-HCT outcomes, including relapse and death. Therefore, preemptive interventions on the natural history of MRD positivity are an active area of research beyond its initial prognostic function. Targeting MRD in AML with innovative treatment strategies can improve patient outcomes.

Is Neonatal Delirium Ready for Prime Time Quality Improvement?

Is Neonatal Delirium Ready for Prime Time Quality Improvement?

ASSESSMENT AND TECHNICAL CONSTRAINT IDENTIFICATION OF SMALLHOLDER IRRIGATION PUMP IN ARSI AND EAST SHEWA ZONE, OROMIA

Efficient irrigation begins with properly installed and maintained pumps, motors, and engines. For this, the study was conducted on potential irrigation pump users of the Arsi and East Shewa zones with the objective of identifying the technical constraints of smallholder irrigation pump users. Doddota from Arsi and Dugda and Bora woreda from the East Shewa zone were selected. 211 samples size from 2321 pump users were used for data collection. The constraints listed by respondents, like pump damage, pump cost, long priming, and fuel, were the most common bottlenecks in pump irrigation schemes. Pump damage was positively correlation with use of un-recommended suction and delivery head, age of pump, long priming time and continues operation time but negatively correlation with pump maintenance, experience in irrigation farming and educational level of the household. Long priming and fuel consumption was positively (+Ve) correlation with use of un-recommended suction and delivery head, age of pump, operation time and pump size. From the existing pump type respondent responses, KAMA pumps were highly available on the market, vulnerable to damage, and had sufficient spare parts with values of 60.66, 64.45 and 44.08%, respectively. The lowest were Cushion their values were 1.42%, 3.32% and 3.78%, respectively. The respondents also reply, due to absence of governmental pump maintaining organization, cost of maintenance at local and private garage were very expensive (68.25%) and expensive (26.07%). This makes another problem on small holder irrigation pump. Therefore, it is recommended to government to add pump maintaining structure at engineering center which serves' closely to scheme users and providing regular training on maintenance checklist. It is also recommended for engineering and socio-economic researchers to conduct research collaboratively to assess the gap frequently for other kebele pump user and technical performance evaluation for pump that have problems.

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was >50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p<0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

Enhancing physio-biochemical characteristics in okra genotypes through seed priming with biogenic zinc oxide nanoparticles synthesized from halophytic plant extracts

Poor seedling germination and growth can result in large financial losses for farmers, thus, there is an urgent need for sustainable agricultural techniques to enhance seed germination and early growth. As an outcome, sustainable agriculture-which emphasizes the smart and effective utilization of resources-has gained popularity worldwide. At numerous levels, the field of nanotechnology is capable of significant benefit in achieving sustainable agricultural practices. Zinc oxide nanoparticles (ZnO NPs) have been shown to have biostimulatory properties and serve as effective solutions for addressing environmental and biotic stressors. The purpose of this study, investigating Salvadora persica halophytic leaf extract -synthesized zinc oxide nanoparticles (S-ZnONPs) as nano-priming agents to ensure okra seeds germinated under stress-free conditions. From an application perspective, we examined the effect of seed priming with varying concentrations of S-ZnO NPs (0, 20 and 40 ppm) for 18 and 24 h of soaking. Results indicated that the germination rate of hybrid variety improved with 20 ppm at 18 h, increasing by 58.22%, while mean germination time reduced by 24.62%. An enhancement trend was observed in the shoot, root length, shoot and root fresh weight, shoot and root dry weight of hybrid variety at 20ppm with 18 h priming by 34.2, 84.3, 80.2, 47.4, 50.3, and 36.2%, respectively. However, chlorophyll pigments chl a, chl b, and carotenoids was significantly raised in desi variety by 42.4, 79.31, and 142.29% with 20 ppm at 18 h priming. Hydrogen per oxide decreased up to 87.8% with 40 ppm at 24 h in hybrid variety, while, in desi variety H2O2 was reduced 88.3% with 20 ppm at 24 h. Non enzymatic antioxidant activities such as ascorbic acid, was highly increased 130.6% in hybrid at 24 h priming with 20 ppm dose. Flavonoids raised in same variety by 166.1% with 20 ppm at 18 h. Proline content was increased by 144.5% with 40ppm at 18 h. Moreover, Antioxidant enzymes, superoxide dismutase, peroxidase and catalase were significantly increased in both varieties with both levels of S-ZnO NPs and priming time. This cost-effective and environmentally safe technique to produce nanoparticles of different halophytic plants can maximize resource utilization, supporting sustainable agriculture by minimizing adverse environmental effects without compromising efficiency.

Thoracic ultrasound: Ready for prime time

Thoracic ultrasound: Ready for prime time

The effect of second screening on repeat viewing: Insights from large-scale mobile diary data

AbstractThis paper examines the effect of second screening, the common practice of using another digital device while watching a television show, on repeat show viewing. We leveraged large-scale individual-level data from mobile diaries of 1,702 US TV viewers on 2,755 prime time shows. We used causal forest analysis for estimation, focusing on the moderating role of viewing preferences and show loyalty, and captured heterogeneity in viewer preferences using latent-class segmentation. We found that overall, show-related second screening has a positive effect on the attitude toward the show, as well as on actual repeat viewing. Show-unrelated second screening diminishes the viewer’s attitude. These effects are especially pronounced in the heavy viewer segment and among infrequent show viewers. Interestingly, our analysis did not provide evidence that second screening harms actual repeat viewing, countering potential concerns of negative distraction effects.

First reported human use of wireless laparoscopic system: is it ready for prime time?

ObjectiveDuring the advent of laparoscopy, surgeons directly explored the abdominal cavity with a telescope-like device through a small incision. Since then, numerous technological advances have transformed minimally invasive surgery (MIS). Yet, in our wireless world, various devices crowd the surgical field, with long wires and light sources posing fall and fire risks. The primary objective of this study was to analyze the first reported human use of a novel wireless laparoscopy system or WLS (ArthroFree™, Lazurite®, Cleveland, Ohio).MethodsThe utility and convenience of the WLS was assessed via two avenues: (1) by analyzing surgical outcomes from first human use and (2) by surveying healthcare professionals regarding its quality and utility.ResultsEighteen patients (mean age 44.2, 83.3% female, mean BMI 33.4) underwent operations with the WLS. Operations included gynecologic and general surgical procedures. There were no intraoperative or postoperative complications, and no conversions to traditional laparoscopy or laparotomy. Mean operating time was 71.94 ± 20.41 min, and estimated blood loss was minimal. Survey results revealed varied individual experiences. Strengths included adequate illumination, improved ergonomics, and simplicity of setup and ease of operation. One respondent criticized the image resolution. Feedback indicated an overall positive impact, and 67% of respondents supported inclusion of the device at their facility. Moreover, its deployment in resource-limited settings abroad has demonstrated its efficacy in global surgery, indicating its potential in various healthcare environments.ConclusionsThis is the first reported human use of a novel WLS. Clinical results supported efficiency and safety of the technology. The successful deployment of the WLS in diverse surgical environments, including resource-limited settings, highlights its potential as a universally adaptable tool in global surgery. This report represents a strong first step toward a wireless operating room with the promise of redefining surgical standards as well as bridging gaps in surgical care worldwide.Graphical abstract

Optimization of The Priming Time of Mannitol Solution for Mungbean Seed Treatment

Abstract not available Bangladesh Agron. J. 2024, 26(2): 100-103

Thermal priming of Saccharina latissima: a promising strategy to improve seaweed production and restoration in future climates

Saccharina latissima is a brown algal kelp species of ecological and economic importance. As the rise in sea surface temperature will threaten not only wild populations of S. latissima but also the productivity of kelp farms, crop enhancement techniques will become crucial to mitigate this threat. Priming is a common strategy in crop plants, in which seeds are pre-exposed to moderate stress to improve the performance and tolerance of plants when exposed to harsher conditions. We investigated the potential of thermal priming to improve growth and tolerance of S. latissima. Kelp gametophytes primed at 20°C for 2, 4 and 6 wk and then re-transferred to 5°C were compared to a naïve treatment maintained at 5°C. Gametophyte priming increased growth of subsequently formed sporophytes by up to 30% (for 4 wk priming) compared to the naïve treatment. Female gametophyte growth in the priming environment was positively correlated to offspring sporophyte growth, indicating a maternal effect. Sporophytes were exposed to heat stress of 20°, 22°, 23° and 24°C for 2 wk. Sporophytes from 4 and 6 wk primed gametophytes exhibited 11 d longer tolerance at 22°C, 7 d longer tolerance at 23°C and 1°C higher thermal tolerance over 7 d compared to naïve sporophytes and sporophytes from 2 wk priming. A priming time of 4 wk was optimal for both sporophyte growth and thermal tolerance. Our results suggest that priming is a promising crop enhancement technique that could improve yield for seaweed farmers and restoration of kelp forests threatened by warming climates.

Dedicated Breast CT: Getting Ready for Prime Time.

Dedicated breast CT is an imaging modality that provides true 3D imaging of the breast with many advantages over current conventional breast imaging modalities. The addition of intravascular contrast increases the sensitivity of breast CT substantially. As such, there are immediate potential applications in the clinical workflow. These include using breast CT to replace much of the traditional diagnostic workup when faced with indeterminate breast lesions. Contrast-enhanced breast CT may be appropriate as a supplemental screening tool for women at high risk of breast cancer, similar to breast MRI. In addition, emerging studies are demonstrating the utility of breast CT in neoadjuvant chemotherapy tumor response monitoring as well as planning for surgical treatment options. While short exam times and fully 3D imaging in a noncompressed position are advantages of this modality, limited coverage of chest wall/axilla due to prone positioning and use of ionizing radiation are drawbacks. To date, several studies have reported on the performance characteristics of this promising modality.

Dihydrorhodamine-123 flow cytometry method: time for substantial revision in technical procedure.

The dihydrorhodamine 123 assay is generally applied to measure the production of intracellular reactive oxygen species in neutrophils using flow cytometry and is considered a diagnostic evaluation for chronic granulomatous disease. In fact, there is a broad range of variables that can directly or indirectly affect test results, either individually or collectively. It is therefore crucial to identify the ideal requirements to achieve reliable results as well as using these requirements to provide standard operating procedures that should be taken into account. Therefore, we focus on aligning optimum results by comparing preanalytical and analytical phases that influence test results, such as the effect of various anticoagulants, transport and maintaining temperature (24°C or 4°C) of samples, test prime run time, appropriate solution concentrations, and effect of incubation temperature (24°C or 37°C) during the test run.

114 Prime Time of Life: A multimodal physical activity and health education programme for middle-aged and older adults

Abstract Prime Time of Life is inclusive of people living with clinical conditions and differing fitness and functional abilities. Health screening was conducted preprogramme, and specific clinical exercise advice and support was provided to participants by Dr Diane Cooper, Clinical Exercise Physiologist. Participants completed two 60-minute multimodal (cardiovascular fitness, strength, balance, flexibility) exercise classes per week and were also encouraged to complete additional classes in their purpose built on-demand exercise library. In all 60-minute exercise classes the exercise instructor demonstrated three different options for each exercise to cater for participants who were working at beginner, intermediate and advanced levels of fitness. Participants appreciated the adaptations and progressions that were available for all exercises as it enabled them to work to their ownability and progress and monitor progress throughout the programme. Each week a 20-minute health education workshop relevant to participants was delivered online via Zoom. The workshop was recorded, edited, and uploaded to YouTube to view on-demand. The link for each video was shared with participants weekly via email to support on-demand learning in addition to any other relevant supporting material such as a training diary. The Prime Time of Life programme increased participants upper and lower body strength, aerobic fitness and perceptions of physical and mental health (see chapter 3). This was in addition to increased confidence and feelings of positivity around the participants’ own management of healthy functional ageing (see chapter 3). Participants commented that they really enjoyed the Prime Time of Life programme. It increased their awareness on the importance of multimodal exercise for healthy ageing and that they felt empowered to continue training and improve their health in the long term. Following on from this successful programme a full train the trainer programme has been developed and piloted with 9 Local Sports Partnerships, 20 participants with further plans for upscaling.

Editorial Comment: Screening Imaging for Early Detection of Pancreatic Ductal Adenocarcinoma in High-Risk Individuals: Is It Ready for Prime Time?

Editorial Comment: Screening Imaging for Early Detection of Pancreatic Ductal Adenocarcinoma in High-Risk Individuals: Is It Ready for Prime Time?

Using conversant artificial intelligence to improve diagnostic reasoning: ready for prime time?

Using conversant artificial intelligence to improve diagnostic reasoning: ready for prime time?

Pharmacogenomics polygenic risk score: Ready or not for prime time?

Pharmacogenomic Polygenic Risk Scores (PRS) have emerged as a tool to address the polygenic nature of pharmacogenetic phenotypes, increasing the potential to predict drug response. Most pharmacogenomic PRS have been extrapolated from disease-associated variants identified by genome wide association studies (GWAS), although some have begun to utilize genetic variants from pharmacogenomic GWAS. As pharmacogenomic PRS hold the promise of enabling precision medicine, including stratified treatment approaches, it is important to assess the opportunities and challenges presented by the current data. This assessment will help determine how pharmacogenomic PRS can be advanced and transitioned into clinical use. In this review, we present a summary of recent evidence, evaluate the current status, and identify several challenges that have impeded the progress of pharmacogenomic PRS. These challenges include the reliance on extrapolations from disease genetics and limitations inherent to pharmacogenomics research such as low sample sizes, phenotyping inconsistencies, among others. We finally propose recommendations to overcome the challenges and facilitate the clinical implementation. These recommendations include standardizing methodologies for phenotyping, enhancing collaborative efforts, developing new statistical methods to capitalize on drug-specific genetic associations for PRS construction. Additional recommendations include enhancing the infrastructure that can integrate genomic data with clinical predictors, along with implementing user-friendly clinical decision tools, and patient education. Ethical and regulatory considerations should address issues related to patient privacy, informed consent and safe use of PRS. Despite these challenges, ongoing research and large-scale collaboration is likely to advance the field and realize the potential of pharmacogenomic PRS.

Are Blood Tests for Alzheimer Disease Ready for Prime Time?

Are Blood Tests for Alzheimer Disease Ready for Prime Time?