Journal of biological methods最新文献

Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. Being the largest possible meta-analysis at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results were not artifacts of resistant test-animal species and showed orders of magnitude beyond the 1.6 logs (40-fold change) range of lethal dose documented in the literature between amphibians, lizards, and mice.

Methods: A total of 1003 lethal dose study results for 160 of the most lethal venomous ophidian species in the world were analyzed.

Results: LDLo was not different from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that, for the route of inoculation, IC < IV < IP < IM < SC was well supported (R² = 0.90). However, 5% of ICs were the highest dose, and 7% of SC inoculations were the lowest dose. Within the mouse test species, for one route of inoculation, the widest LD range was 2.96 logs (917-fold change, N = 20). Within mouse species, for multiple routes of inoculation, the widest LD range was 3.6 logs (4,150-fold change, N = 20). The strongest correlation for the range of lethal dose results was the number of studies (R² = 0.56), followed by the number of test-animal species (R² = 0.55) and then the number of routes of inoculation (R² = 0.43).

Conclusion: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate mean, median, minimum, range, and standard deviation as shown in the supplement spreadsheet, and the equations we provide. Standard deviation multiples may provide the desired safety for experimenters. For estimating the LD50 range and minimum lethal dose for species with little data, we recommend curating a meta-dataset of related snakes, and computational research to strengthen this estimation.

Background: Menopause, characterized by cessation of menstruation, is accompanied by various physiological and psychological changes. This randomized controlled trial (RCT) investigated the efficacy of a multi-domain lifestyle modification program in alleviating menopausal symptoms and promoting health behaviors among postmenopausal women residing in urban slums of Hyderabad, India.

Methods: Eighty-two women aged 45-60 years experiencing menopausal symptoms were recruited. Participants were randomly assigned to either a 45-day lifestyle intervention group or a control group receiving standard care. The intervention program addressed six domains: health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, and stress management. The menopause rating scale (MRS) and a modified health-promoting lifestyle II (HPBII) questionnaire assessed menopausal symptoms and health behaviors at baseline and during follow-up.

Results: The intervention group showed significant improvements (P < 0.05) in terms of overall HPBII scores compared to baseline, with the most notable changes observed in health responsibility, nutrition, and stress management domains. In addition, MRS scores indicating menopausal symptoms were significantly lowered (P < 0.05) in the intervention group. No significant changes were found in the control group in either health behaviors or menopausal symptoms. After the intervention, the experimental group showed a significant improvement in HPBII scores compared to the control group, particularly in health responsibility, nutrition, interpersonal relationships, and stress management sub-domains.

Conclusion: This RCT suggested that a comprehensive lifestyle modification program could effectively improve health behaviors and alleviate menopausal symptoms in postmenopausal women residing in under-resourced settings. Further research is warranted to explore the program's long-term sustainability and generalizability.

In this study, we assessed the precision and repeatability of the daily patient positioning for three distinct immobilization devices used for head-and-neck patients undergoing RapidArc radiation therapy using cone beam computed tomography (CBCT). An analysis was conducted on the accuracy of patient setup for three distinct immobilization devices, resulting in 1204 CBCT images for 189 patients in total. Using a typical posifix supine headrest and five fixation point podcast-plus-thermoplastic masks, the first group of 39 patients (125 CBCTs) was immobilized. The identical method was used to immobilize the second group of 19 patients (158 CBCTs) in the same posture (supine), and AccuFormTM custom headrests were employed as an added measure. Over 65% of the patients in the third group had a double shell positioning system (DSPS) covering their entire head and neck. Patient-alignment-accuracy or couch shifts in the vertical, longitudinal, and lateral directions from CT-CBCT fusions were recorded from ARIA. Our results showed that in 90% of the anteriorposterior (AP), 90% of the superior-inferior (SI), and 92.7% of the right-left (RL) population in the first group, patient-alignment-accuracy or couch shifts were within 2 mm. For 99.4% (AP), 100% (SI), and 98.7% (RL) of the second group's total population, patient-alignment-accuracy was within 2 mm. In the third group, it was within 2 mm for 92.1% (AP), ~89% (SI), and 93.3% (RL) of the total population. In conclusion, a significant improvement was seen with the application of a mouth bite and a tailored backrest cushion to the five fixation point posicast mask. In addition, significant improvement in the alignment of the lower neck area was observed with the use of DSPS. Virtually 100% of the head-and-neck patients were aligned within an accuracy of 3 mm, which is the PTV margin in our department.

This study aimed to investigate the role of the nigrostriatal dopaminergic system in the modulation of absence epilepsy. Immunochemical analysis of the rostral pole of the substantia nigra pars compacta (SNpc) was conducted on 13 adult male Wistar Albino rats from Rijswijk rats. The rostral pole of the SNpc included the dorsal and lateral parts. The neuronal density in the dorsal part was higher than in the lateral part. The ratio of dopaminergic to non-dopaminergic neurons in the lateral part of the SNpc was 1:1, while in the dorsal part, it was around 1.9:1. All rats exhibited spontaneous spike-wave discharges (SWDs) on their electrocorticograms. SWDs are known to be a hallmark of absence seizures in both human patients and rat models. In this study, we found that the number and duration of SWDs were negatively correlated with dopaminergic and non-dopaminergic neurons only in the lateral part of the SNpc. However, in the dorsal part of the SNpc, no correlations were found between neuronal density and the severity of absence epilepsy. Our findings suggest that the lateral SNpc may be involved in modulating the severity of absence epilepsy in genetically prone subjects. This contributes to a better understanding of the role of the nigrostriatal dopaminergic system in the absence of epilepsy.

The aim of this meta-analysis was to analyze allele and genotype pattern frequencies of five different gene polymorphisms associated with endurance athlete status. Endurance sports require prolonged physical performance, and it is well known that physiological and genetic characteristics play a prominent role in this performance. In recent years, research on the impact of genetic factors on endurance athlete status has been on the rise, suggesting that various gene polymorphisms may be associated with physical performance. Specifically, the gene polymorphisms, activin receptor type-1B (A9CVR1B) rs2854464, angiotensinogen (AGT) rs699, fat mass and obesity-associated (FTO) rs9939609, interleukin-6 (IL-6) rs1800795, and nuclear factor erythroid 2 (NRF2) rs12594956, are thought to be related to endurance athlete status. Each of these genes plays a part in different biological processes, such as muscle development, energy metabolism, inflammation, and antioxidant defense mechanisms. For example, the NRF2 gene is a critical player in the regulation of cellular stress responses and may contribute to adaptive responses that enhance performance in endurance athletes. This meta-analysis included a total of 20 articles published between 2009 and 2023. The specific gene polymorphisms explored in this study, i.e., ACVR1B rs2854464, AGT rs699, FTO rs9939609, IL-6 rs1800795, and NRF2 rs12594956, were selected due to their reported associations with physical performance and endurance. A comprehensive search was conducted in the Web of Science and PubMed databases using specific keywords, preliminarily identifying 329 articles. Upon analysis of the abstracts, and full texts, 20 articles were deemed eligible for inclusion in this meta-analysis. Articles lacking control and endurance athlete groups or clear allele/genotype data were excluded. The findings indicated no significant differences in allele and genotype frequencies for ACVR1B, AGT, FTO, and IL-6 gene polymorphisms between endurance athletes and control groups. However, the NRF2 rs12594956 gene polymorphism showed a significantly higher frequency of the major allele (A) and the AA genotype in endurance athletes than in controls. In conclusion, the NRF2 rs12594956 polymorphism may be a genetic variant of interest in determining the status of endurance athletes. These findings highlight the potential clinical implications for genetic screening and personalized training programs in sport genetics. More extensive studies with larger cohorts are needed to further confirm these associations.

Lung cancer is the leading cause of cancer-related mortality globally, making early detection crucial for reducing death rates. Low-dose computed tomography (LDCT) screening helps detect lung cancer early but often identifies indeterminate pulmonary nodules (PNs), leading to potential overtreatment. This study aimed to develop a diagnostic test that accurately differentiates malignant from benign PNs detected on LDCT scans by analyzing non-coding RNAs, DNA methylation, and bacterial DNA in patient samples. Using droplet digital polymerase chain reaction, we analyzed samples from a training set of 150 patients with malignant PNs and 250 smokers with benign PNs. Individual biomarkers in plasma and sputum showed moderate effectiveness, with sensitivities ranging from 62% to 77% and specificities from 54% to 87%. We developed an integromic signature by combining two plasma biomarkers and one sputum biomarker, along with additional clinical data, which demonstrated a sensitivity of 90% and specificity of 95%. The signature's diagnostic performance was further validated in a cohort consisting of 30 patients with malignant PNs and 50 smokers with benign PNs. The integromic signature showed high sensitivity and specificity in distinguishing malignant from benign PNs identified through LDCT. This tool has the potential to significantly lower both mortality and health-care costs associated with the overtreatment of benign nodules, offering a promising approach to improving lung cancer screening protocols.

CaptureSelect CH1-XL and Praesto 70 CH1 are two affinity media that specifically bind to the CH1 domain of an antibody. In the current work, we first demonstrated that these two CH1-specific affinity media bound to different monoclonal antibodies (mAbs) with varied strengths under identical conditions. We previously had observed the same on a Protein L-conjugated resin and showed that such a property could facilitate homodimer removal in asymmetric bispecific antibody (bsAb) purification. Next, using Praesto 70 CH1, we showed that a small difference in binding between two mAbs could be significantly exaggerated by adding sodium chloride to the mobile phase, further demonstrating this resin can potentially play a role in bsAb purification. Finally, with a concrete bsAb case study, we showed that, like Protein L, Praesto 70 CH1 could separate the target heterodimer from the homodimer by-product. Homodimers are common product-related impurities associated with the recombinant production of asymmetric bsAbs, which can be difficult to remove. Their removal, even a partial one, at the capture stage is a big advantage as it can alleviate the purification burden on subsequent polishing steps and render the overall process more robust. Therefore, Praesto 70 CH1's unique property is highly desirable, and this affinity resin can be a better alternative than Protein A for product capture in asymmetric bsAb purification.

The regulation of chromatin structure and gene transcription in eukaryotic cells is an involved process mediated by histone modifications, chromatin-binding proteins, and transcription factors. Studying the distribution of histone modifications and transcription factors at the whole-genome level is crucial for understanding the mechanisms of gene transcription. Cleavage under targets and tagmentation (CUT&Tag) is a novel chromatin analysis method that has rapidly gained popularity in the field of epigenetics since its introduction. It has been widely used for the detection of chromatin modifications and transcription factors in different species. Furthermore, CUT&Tag has also been adapted to simultaneously detect multiple epigenetic modifications. Its integration with single-cell transcriptome, and spatial transcriptome analysis allows for a comprehensive examination of cell fate and functions. In this review, we aimed to provide an overview of the recent developments and applications of CUT&Tag and its derivatives, highlighting their significance in advancing our understanding of epigenetic regulation.

Prostate cancer (PCa) remains a significant health challenge, necessitating diverse therapeutic interventions to manage the disease effectively. While these treatments offer promising outcomes, they are often accompanied by a range of side effects that can impact patient quality of life and treatment compliance. This review provides an overview of the common side effects associated with various PCa therapies, including prostatectomy, radiation therapy, thermal therapy, hormone therapy, chemotherapy, and targeted drug therapy, among others. We summarized and discussed the reported side effects encompassing ureteral problems, sexual issues, gastrointestinal symptoms, fatigue, anemia, thrombocytopenia, hematologic abnormalities, nausea, vomiting, and liver enzyme elevation. Specific managements, such as personalized treatment plans, proactive symptom monitoring, supportive care interventions, and hematological assessments, are crucial in mitigating these side effects and optimizing treatment outcomes. By prioritizing patient-centered care and tailored interventions, health-care providers can enhance treatment efficacy and improve the overall well-being of individuals undergoing PCa therapies.