scholarly journals Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus

2020 ◽  
Vol 42 (4) ◽  
pp. 413-429 ◽  
Author(s):  
Ella Shana Green ◽  
Petra Clara Arck
Keyword(s):  
Preterm Birth ◽  
Animal Models ◽  
Mouse Models ◽  
Current Knowledge ◽  
Human Studies ◽  
Morbidity And Mortality ◽  
Early Prediction ◽  
Effective Strategies ◽  
Bidirectional Communication ◽  
Maternal Tolerance

Abstract Preterm birth (PTB) complicates 5–18% of pregnancies globally and is a leading cause of maternal and fetal morbidity and mortality. Most PTB is spontaneous and idiopathic, with largely undefined causes. To increase understanding of PTB, much research in recent years has focused on using animal models to recapitulate the pathophysiology of PTB. Dysfunctions of maternal immune adaptations have been implicated in a range of pregnancy pathologies, including PTB. A wealth of evidence arising from mouse models as well as human studies is now available to support that PTB results from a breakdown in fetal-maternal tolerance, along with excessive, premature inflammation. In this review, we examine the current knowledge of the bidirectional communication between fetal and maternal systems and its role in the immunopathogenesis of PTB. These recent insights significantly advance our understanding of the pathogenesis of PTB, which is essential to ultimately designing more effective strategies for early prediction and subsequent prevention of PTB.

scholarly journals Overview of current mouse models of autism and strategies for their development using CRISPR/Cas9 technology

2018 ◽  
Vol 112 (1) ◽  
pp. 19
Author(s):  
Anja DOMADENIK
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Genome Engineering ◽  
New Technologies ◽  
Current Knowledge ◽  
Autism Spectrum ◽  
Phenotypic Traits ◽  
Knock Out ◽  
Sgrna Design ◽  
Spectrum Disorders

<p>Autism spectrum disorders (ASD) are a group of highly heterogenous neurological disorders that are believed to have strong genetic component. Due to the limited use of approaches of functional genomics in human medicine, creating adequate animal models for the study of complex human diseases shows great potential. There are several already established mouse models of autism that offer insight into single phenotypic traits, although causes for its complex phenotype have not yet been fully understood. Development of new technologies, such as CRISPR/Cas9, represent great capability for targeted genome engineering and establishment of new animal models. This article provides an up to date overview of current knowledge in the area of autism genomics and describes the potential of CRISPR/Cas9 technology for the establishment of new mouse models, representing sgRNA design as one of the initial steps in planning a CRISPR/Cas9 single knock-out experiment. In addition, it offers an overview of current approaches to behavioural studies, explaining how relevant animal models could be developed.</p>

Subduing the killer - sepsis; through simulation

2018 ◽  
Vol 24 (1) ◽  
pp. 26-29 ◽  
Author(s):  
Jonathan B T Herron ◽  
Andrew Harbit ◽  
James A T Dunbar
Keyword(s):  
Knowledge Base ◽  
Teaching Methods ◽  
Simulation Training ◽  
Current Knowledge ◽  
Morbidity And Mortality ◽  
Constructivist Teaching ◽  
Effective Strategies ◽  
Poor Outcomes ◽  
Current Knowledge Base ◽  
Level Of Experience

Few pathophysiological processes have a higher morbidity and mortality than sepsis. Implementing effective strategies to improve these poor outcomes remains a challenge. Previous work has shown improvements using single and multifaceted approaches, many with inclusion of sepsis training for doctors and nurses. However, previous work has not necessarily trained all those involved in the recognition and treatment of sepsis. After sepsis simulation training using cognitive-constructivist teaching methods, reaudit demonstrated highly significant improvement in ‘sepsis-six’ delivery. This study found inclusion of healthcare assistants in sepsis training is of great importance. This training should be tailored to personnel’s current knowledge base and level of experience.

scholarly journals The genomics of preterm birth: from animal models to human studies

10.1186/gm438 ◽  
2013 ◽  
Vol 5 (4) ◽  
pp. 34 ◽  
Author(s):  
Katherine Y Bezold ◽  
Minna K Karjalainen ◽  
Mikko Hallman ◽  
Kari Teramo ◽  
Louis J Muglia
Keyword(s):  
Preterm Birth ◽  
Animal Models ◽  
Human Studies

scholarly journals Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Ricardo Pereira-Moreira ◽  
Elza Muscelli
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Current Knowledge ◽  
Sglt2 Inhibitor ◽  
Proximal Tubules ◽  
Human Studies ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Insulin Effect ◽  
Renal Gluconeogenesis

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.

scholarly journals Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

2021 ◽  
Vol 22 (8) ◽  
pp. 3860
Author(s):  
Elisa Ren ◽  
Giulia Curia
Keyword(s):  
Animal Models ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Current Knowledge ◽  
Focal Epilepsy ◽  
Ex Vivo ◽  
Hippocampal Sclerosis ◽  
Control Group ◽  
Epileptogenic Zone ◽  
Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

scholarly journals A birth population-based survey of preterm morbidity and mortality by gestational age

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaojing Guo ◽  
Xiaoqiong Li ◽  
Tingting Qi ◽  
Zhaojun Pan ◽  
Xiaoqin Zhu ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Birth Defects ◽  
Gestational Age ◽  
Death Rate ◽  
Preterm Births ◽  
Mortality Rates ◽  
Morbidity And Mortality ◽  
Hospital Death

Abstract Background Despite 15–17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai’an in 2015, an emerging prefectural region of China. Methods Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai’an Women and Children’s Hospital (HWCH) and non-HWCH hospitals in 2018–2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression. Results The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks. Conclusions The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.

scholarly journals Consideration of Gut Microbiome in Murine Models of Diseases

2021 ◽  
Vol 9 (5) ◽  
pp. 1062
Author(s):  
Chunye Zhang ◽  
Craig L. Franklin ◽  
Aaron C. Ericsson
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Biomedical Research ◽  
Gut Microbiome ◽  
Close Association ◽  
Disease Model ◽  
Potential Contributor ◽  
Potential Factors ◽  
Models Of Disease ◽  
The Impact

The gut microbiome (GM), a complex community of bacteria, viruses, protozoa, and fungi located in the gut of humans and animals, plays significant roles in host health and disease. Animal models are widely used to investigate human diseases in biomedical research and the GM within animal models can change due to the impact of many factors, such as the vendor, husbandry, and environment. Notably, variations in GM can contribute to differences in disease model phenotypes, which can result in poor reproducibility in biomedical research. Variation in the gut microbiome can also impact the translatability of animal models. For example, standard lab mice have different pathogen exposure experiences when compared to wild or pet store mice. As humans have antigen experiences that are more similar to the latter, the use of lab mice with more simplified microbiomes may not yield optimally translatable data. Additionally, the literature describes many methods to manipulate the GM and differences between these methods can also result in differing interpretations of outcomes measures. In this review, we focus on the GM as a potential contributor to the poor reproducibility and translatability of mouse models of disease. First, we summarize the important role of GM in host disease and health through different gut–organ axes and the close association between GM and disease susceptibility through colonization resistance, immune response, and metabolic pathways. Then, we focus on the variation in the microbiome in mouse models of disease and address how this variation can potentially impact disease phenotypes and subsequently influence research reproducibility and translatability. We also discuss the variations between genetic substrains as potential factors that cause poor reproducibility via their effects on the microbiome. In addition, we discuss the utility of complex microbiomes in prospective studies and how manipulation of the GM through differing transfer methods can impact model phenotypes. Lastly, we emphasize the need to explore appropriate methods of GM characterization and manipulation.

scholarly journals The Genomic Architecture of Bladder Exstrophy Epispadias Complex

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1149
Author(s):  
Glenda M. Beaman ◽  
Raimondo M. Cervellione ◽  
David Keene ◽  
Heiko Reutter ◽  
William G. Newman
Keyword(s):  
Urinary Tract ◽  
Animal Models ◽  
Abdominal Wall ◽  
Current Knowledge ◽  
Bladder Exstrophy ◽  
Genomic Architecture ◽  
Developmental Mechanisms ◽  
Anatomical Characterization

The bladder exstrophy–epispadias complex (BEEC) is an abdominal midline malformation comprising a spectrum of congenital genitourinary abnormalities of the abdominal wall, pelvis, urinary tract, genitalia, anus, and spine. The vast majority of BEEC cases are classified as non-syndromic and the etiology of this malformation is still unknown. This review presents the current knowledge on this multifactorial disorder, including phenotypic and anatomical characterization, epidemiology, proposed developmental mechanisms, existing animal models, and implicated genetic and environmental components.

Oxidative stress in phenylketonuria—evidence from human studies and animal models, and possible implications for redox signaling

2021 ◽  
Vol 36 (4) ◽  
pp. 523-543
Author(s):  
Vanessa Trindade Bortoluzzi ◽  
Carlos Severo Dutra Filho ◽  
Clovis Milton Duval Wannmacher
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Redox Signaling ◽  
Human Studies
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