-
World Journal of Gastroenterology Apr 2020Colorectal cancer (CRC) is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union. While the incidence and... (Review)
Review
Colorectal cancer (CRC) is the third most common diagnosed malignancy among both sexes in the United States as well as in the European Union. While the incidence and mortality rates in western, high developed countries are declining, reflecting the success of screening programs and improved treatment regimen, a rise of the overall global CRC burden can be observed due to lifestyle changes paralleling an increasing human development index. Despite a growing insight into the biology of CRC and many therapeutic improvements in the recent decades, preclinical models are still indispensable for the development of new treatment approaches. Since the development of carcinogen-induced rodent models for CRC more than 80 years ago, a plethora of animal models has been established to study colon cancer biology. Despite tenuous invasiveness and metastatic behavior, these models are useful for chemoprevention studies and to evaluate colitis-related carcinogenesis. Genetically engineered mouse models (GEMM) mirror the pathogenesis of sporadic as well as inherited CRC depending on the specific molecular pathways activated or inhibited. Although the vast majority of CRC GEMM lack invasiveness, metastasis and tumor heterogeneity, they still have proven useful for examination of the tumor microenvironment as well as systemic immune responses; thus, supporting development of new therapeutic avenues. Induction of metastatic disease by orthotopic injection of CRC cell lines is possible, but the so generated models lack genetic diversity and the number of suited cell lines is very limited. Patient-derived xenografts, in contrast, maintain the pathological and molecular characteristics of the individual patient's CRC after subcutaneous implantation into immunodeficient mice and are therefore most reliable for preclinical drug development - even in comparison to GEMM or cell line-based analyses. However, subcutaneous patient-derived xenograft models are less suitable for studying most aspects of the tumor microenvironment and anti-tumoral immune responses. The authors review the distinct mouse models of CRC with an emphasis on their clinical relevance and shed light on the latest developments in the field of preclinical CRC models.
Topics: Animals; Colorectal Neoplasms; Disease Models, Animal; Female; Male; Mice
PubMed: 32308343
DOI: 10.3748/wjg.v26.i13.1394 -
Medicine Sep 2022The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis.
BACKGROUND
The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE.
METHODS
A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes.
RESULTS
Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P = .04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated.
CONCLUSION
In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea.
Topics: Bacillus clausii; Child; Diarrhea; Gastroenteritis; Humans; Probiotics; Saccharomyces boulardii
PubMed: 36086703
DOI: 10.1097/MD.0000000000030500 -
Perspectives on Behavior Science Jun 2023In the history of the field, behavior analysts have used the operant chamber as an apparatus for both teaching and experimental investigations. In the early days of the...
In the history of the field, behavior analysts have used the operant chamber as an apparatus for both teaching and experimental investigations. In the early days of the field, students spent significant time in the animal laboratory, using operant chambers to conduct hands-on experiments. These experiences allowed students to see behavior change as an orderly process and drew many students toward careers in behavior analysis. Today, most students no longer have access to animal laboratories. However, the Portable Operant Research and Teaching Lab (PORTL) can fill this void. PORTL is a table-top game that creates a free-operant environment for studying the principles of behavior and their application. This article will describe how PORTL works and the parallels between PORTL and the operant chamber. Examples will illustrate how PORTL can be used to teach concepts such as differential reinforcement, extinction, shaping, and other basic principles. In addition to its use as a teaching tool, PORTL provides a convenient and inexpensive way for students to replicate research studies and even conduct their own research projects. As students use PORTL to identify and manipulate variables, they gain a deeper understanding for how behavior works.
PubMed: 37425989
DOI: 10.1007/s40614-023-00369-y -
Mikrochimica Acta Jun 2023High-throughput screening platforms are fundamental for the rapid and efficient processing of large amounts of experimental data. Parallelization and miniaturization of... (Review)
Review
High-throughput screening platforms are fundamental for the rapid and efficient processing of large amounts of experimental data. Parallelization and miniaturization of experiments are important for improving their cost-effectiveness. The development of miniaturized high-throughput screening platforms is essential in the fields of biotechnology, medicine, and pharmacology. Currently, most laboratories use 96- or 384-well microtiter plates for screening; however, they have disadvantages, such as high reagent and cell consumption, low throughput, and inability to avoid cross-contamination, which need to be further optimized. Droplet microarrays, as novel screening platforms, can effectively avoid these shortcomings. Here, the preparation method of the droplet microarray, method of adding compounds in parallel, and means to read the results are briefly described. Next, the latest research on droplet microarray platforms in biomedicine is presented, including their application in high-throughput culture, cell screening, high-throughput nucleic acid screening, drug development, and individualized medicine. Finally, the challenges and future trends in droplet microarray technology are summarized.
Topics: High-Throughput Screening Assays; Drug Evaluation, Preclinical; Microarray Analysis
PubMed: 37318602
DOI: 10.1007/s00604-023-05833-9 -
Communications Biology Sep 2023Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on... (Review)
Review
Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on surface-attached formations, but detached aggregates have received increasing attention in the past decade due to their pivotal role in chronic infections. Understanding their nature sparked fervent discussions in biofilm conferences and scientific literature. This review consolidates current insights on non-attached aggregates, offering examples of their occurrence in nature and diseases. We discuss their formation and dispersion mechanisms, resilience to antibiotics and immune-responses, drawing parallels to surface-attached biofilms. Moreover, we outline available in vitro models for studying non-attached aggregates.
Topics: Anti-Bacterial Agents; Biofilms; Molecular Weight
PubMed: 37658117
DOI: 10.1038/s42003-023-05281-4 -
Molecular Ecology Nov 2020Parallel evolution is one of the striking patterns in nature. The presence of repeated evolution of the same phenotypes, suites of traits, and adaptations suggests a...
Parallel evolution is one of the striking patterns in nature. The presence of repeated evolution of the same phenotypes, suites of traits, and adaptations suggests a strong role for natural selection in shaping biological diversity. The reasoning is straightforward: each instance of repeated evolution makes it less likely that these features evolved neutrally or due to stochastic forces in each population or species. With the growing sequencing capability, we are now poised to examine the genetic basis of parallel evolution in model and nonmodel systems. On pages 4102-4117 of this issue of Molecular Ecology, van Boheemen and Hodgins (2020) provide an exemplar study of this kind, using common ragweed (Ambrosia artemisiifolia; Figure 1a). Their study is noteworthy and ambitious in many respects, and we think will serve as a model for studying parallel adaptation, even in nonmodel species.
Topics: Adaptation, Physiological; Genomics; Metagenomics; Phenotype; Selection, Genetic
PubMed: 32997363
DOI: 10.1111/mec.15659 -
Lab on a Chip Jul 2022Microtoxicology is concerned with the toxic effects of small amounts of substances. This review paper discusses the application of small amounts of noxious substances... (Review)
Review
Microtoxicology is concerned with the toxic effects of small amounts of substances. This review paper discusses the application of small amounts of noxious substances for toxicological investigation in small volumes. The vigorous development of miniaturized methods in microfluidics over the last two decades involves chip-based devices, micro droplet-based procedures, and the use of micro-segmented flow for microtoxicological studies. The studies have shown that the microfluidic approach is particularly valuable for highly parallelized and combinatorial dose-response screenings. Accurate dosing and mixing of effector substances in large numbers of microcompartments supplies detailed data of dose-response functions by highly concentration-resolved assays and allows evaluation of stochastic responses in case of small separated cell ensembles and single cell experiments. The investigations demonstrate that very different biological targets can be studied using miniaturized approaches, among them bacteria, eukaryotic microorganisms, cell cultures from tissues of multicellular organisms, stem cells, and early embryonic states. Cultivation and effector exposure tests can be performed in small volumes over weeks and months, confirming that the microfluicial strategy is also applicable for slow-growing organisms. Here, the state of the art of miniaturized toxicology, particularly for studying antibiotic susceptibility, drug toxicity testing in the miniaturized system like organ-on-chip, environmental toxicology, and the characterization of combinatorial effects by two and multi-dimensional screenings, is discussed. Additionally, this review points out the practical limitations of the microtoxicology platform and discusses perspectives on future opportunities and challenges.
Topics: Bacteria; Cell Culture Techniques; Lab-On-A-Chip Devices; Microfluidics; Toxicity Tests
PubMed: 35678285
DOI: 10.1039/d2lc00268j -
Orthopaedics & Traumatology, Surgery &... Oct 2021Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since its introduction in the early 1960s, the multiple cannulated screw fixation method has been developed for use in femoral neck fractures (FNFs); however, the parallelism of screws remains controversial.
MATERIALS AND METHODS
MEDLINE, Embase, and the Cochrane Library were systematically searched for studies published before June 2, 2020, that compared the use of parallel and non-parallel screw fixation for the treatment of FNF. The pooled analysis was designed to identify differences between the two groups and focused on postoperative complications, including fracture nonunion and osteonecrosis of the femoral head (ONFH).
RESULTS
Over four studies, we enrolled 445 patients, including 195 patients with fixed FNF with parallel trajectory screws and 250 patients with fixed FNF with non-parallel screws. The pooled analysis showed no difference in the nonunion rates (odds ratio (OR)=0.91; 95% confidence interval (CI), 0.24-3.44; p=0.89) and no significant difference in the incidence of ONFH between parallel and non-parallel screw fixation (OR=0.74; 95% CI: 0.21-2.63; p=0.64).
CONCLUSIONS
The results of this meta-analysis reveal that screw parallelism in multiple cannulated screw fixation of FNF has no relationship with either the fracture nonunion rate or the incidence of postoperative ONFH.
LEVEL OF EVIDENCE
III; meta-analysis.
Topics: Bone Screws; Femoral Neck Fractures; Fracture Fixation, Internal; Fractures, Ununited; Humans; Postoperative Complications
PubMed: 34217865
DOI: 10.1016/j.otsr.2021.103005 -
Journal of Counseling Psychology Oct 2023Reports the retraction of "The triadic effect: Associations among the supervisory working alliance, therapeutic working alliance, and therapy session evaluation" by...
Reports the retraction of "The triadic effect: Associations among the supervisory working alliance, therapeutic working alliance, and therapy session evaluation" by Judith A. Gerstenblith, Kathryn V. Kline, Clara E. Hill and Dennis M. Kivlighan Jr. (, 2022[Mar], Vol 69[2], 199-210). The following article is being retracted (https://doi.org/10.1037/cou0000567). This retraction is at the request of coauthors Kivlighan and Hill after the results of an investigation by the University of Maryland Institutional Review Board (IRB). The IRB found that the study included data from between one and four therapy clients of the Maryland Psychotherapy Clinic and Research Laboratory (MPCRL) who either had not been asked to provide consent or had withdrawn consent for their data to be included in the research. Gerstenblith and Kline were not responsible for obtaining and verifying participant consent but agreed to the retraction of this article. (The following abstract of the original article appeared in record 2021-88607-001.) Several theorists (Bandura, 1969; Hackney & Goodyear, 1984; Searles, 1955) suggest parallels between the relationship in supervision and the relationship in therapy. We examined supervisor and therapist trainee ratings of supervisory working alliance (SWA) in 1 week predicting client-rated therapeutic working alliance (TWA) and client-rated therapy session evaluation (TSE) in the following week as well as TWA and TSE ratings in 1 week predicting SWA ratings in the following week. Our data included 663 weeks of therapy nested within 28 trainees nested within 15 supervisors, disaggregated into differences between supervisors, differences within supervisors, and differences within trainees. At the between-supervisor level, when supervisors' trainees rated the SWA higher on average compared with other supervisors' trainees' average SWA ratings, their clients' average TWA rating was higher. In contrast, when supervisors rated the SWA higher on average compared with other supervisors' average SWA ratings, their trainees' clients' average TSE rating was higher but the average TWA rating was lower. At the within-supervisor level, when trainees rated a higher SWA on average compared with other trainees' average SWA ratings with the same supervisor, their clients' average TSE rating was higher. The theoretical prediction of parallel relationships in supervision and therapy was supported, but only for between-supervisor and within-supervisor differences in SWA. We found no evidence that week-to-week changes in SWA or client-rated TWA or TSE reflected parallel relationships. We provide suggestions for further research, including exploring the mechanisms through which supervision relates to the therapy process and outcome. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
PubMed: 37747529
DOI: 10.1037/cou0000700 -
Journal of Evolutionary Biology Jun 2021Research on the genomics of adaptation is rapidly changing. In the last few decades, progress in this area has been driven by methodological advances, not only in the...
Research on the genomics of adaptation is rapidly changing. In the last few decades, progress in this area has been driven by methodological advances, not only in the way increasingly large amounts of molecular data are generated (e.g. with high-throughput sequencing), but also in the way these data are analysed. This includes a growing appreciation and quantitative treatment of covariation among units within the same data type (e.g. genes) or across data types (e.g. genes and phenotypes). The development and adoption of more and more integrative tools have resulted in richer and more interesting empirical work. This special issue - comprising methodological, empirical, and review papers - aims to capture a 'snapshot' of this rapidly evolving field. We discuss in particular three important themes in the study of adaptation: the genetic architecture of adaptive variation, protein-coding and regulatory changes, and parallel evolution. We highlight how more traditional key themes in the study of genetic architecture (e.g. the number of loci underlying adaptive traits and the distribution of their effects) are now being complemented by other factors (e.g. how patterns of linkage and number of loci interact to affect the ability to adapt). Similarly, apart from addressing the relative importance of protein-coding and regulatory changes, we now have the tools to look in-depth at specific types of regulatory variation to gain a clearer picture of regulatory networks. Finally, parallel evolution has always been central to the study of adaptation, but now we are often able to address the question of whether - and to what extent - parallelism at the organismal or phenotypic level is matched by parallelism at the genetic level. Perhaps most importantly, we can now determine what mechanisms are driving parallelism (or lack thereof) across levels of biological organization. All these recent methodological developments open up new directions for future studies of adaptive changes across traits, levels of biological organization, demographic contexts and time scales.
Topics: Adaptation, Biological; Biological Evolution; Genetic Variation; Genomics
PubMed: 34145685
DOI: 10.1111/jeb.13871