scholarly journals The Microbiome and Preterm Birth: A Change in Paradigm with Profound Implications for Pathophysiologic Concepts and Novel Therapeutic Strategies

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Birte Staude ◽  
Frank Oehmke ◽  
Tina Lauer ◽  
Judith Behnke ◽  
Wolfgang Göpel ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Neonatal Intensive Care ◽  
Early Stage ◽  
Amniotic Cavity ◽  
Balanced Development ◽  
Global Challenge ◽  
Stage Of Development ◽  
Lower Genital Tract ◽  
Therapeutic Concepts ◽  
Novel Therapeutic Strategies

Preterm birth poses a global challenge with a continuously increasing disease burden during the last decades. Advances in understanding the etiopathogenesis did not lead to a reduction of prematurely born infants so far. A balanced development of the host microbiome in early life is key for the maturation of the immune system and many other physiological functions. With the tremendous progress in new diagnostic possibilities, the contribution of microbiota changes to preterm birth and the acute and long-term sequelae of prematurity have come into the research focus. This review summarizes the latest advances in the understanding of microbiomes in the amniotic cavity and the female lower genital tract and how changes in microbiota structures contribute to preterm delivery. The exhibition of these highly vulnerable infants to the hostile environment in the neonatal intensive care unit necessarily entails the rapid colonization with a nonbalanced microbiome in a situation where the organism is still very prone and at an early stage of development. The global research efforts to decipher pathologic changes will pave the way to new pre- and postnatal therapeutic concepts.

scholarly journals Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michelle Coleman ◽  
Blair Armistead ◽  
Austyn Orvis ◽  
Phoenicia Quach ◽  
Alyssa Brokaw ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Preterm Labor ◽  
Bacterial Invasion ◽  
Group B Streptococci ◽  
Primate Model ◽  
Amniotic Cavity ◽  
Human Pregnancy ◽  
Lower Genital Tract ◽  
Group B ◽  
Maternal Fetal Interface

ABSTRACT Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated preterm labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy. IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.

scholarly journals Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection

2015 ◽  
Vol 1 (6) ◽  
pp. e1400225 ◽  
Author(s):  
Claire Gendrin ◽  
Jay Vornhagen ◽  
Lisa Ngo ◽  
Christopher Whidbey ◽  
Erica Boldenow ◽  
...  
Keyword(s):  
Mast Cell ◽  
Preterm Birth ◽  
Genital Tract ◽  
Mast Cell Degranulation ◽  
Microbial Infection ◽  
Amniotic Cavity ◽  
Proinflammatory Mediators ◽  
Ascending Infection ◽  
Lower Genital Tract ◽  
Deficient Mice

Ascending infection of microbes from the lower genital tract into the amniotic cavity increases the risk of preterm birth, stillbirth, and newborn infections. Host defenses that are critical for preventing ascending microbial infection are not completely understood. Group BStreptococcus(GBS) are Gram-positive bacteria that frequently colonize the lower genital tract of healthy women but cause severe infections during pregnancy, leading to preterm birth, stillbirth, or early-onset newborn infections. We recently described that the GBS pigment is hemolytic, and increased pigment expression promotes GBS penetration of human placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and hyperpigmented GBS strains induce mast cell degranulation, leading to the release of preformed and proinflammatory mediators. Mast cell–deficient mice exhibit enhanced bacterial burden, decreased neutrophil mobilization, and decreased immune responses during systemic GBS infection. In a vaginal colonization model, hyperpigmented GBS strains showed increased persistence in mast cell–deficient mice compared to mast cell–proficient mice. Consistent with these observations, fewer rectovaginal GBS isolates from women in their third trimester of pregnancy were hyperpigmented/hyperhemolytic. Our work represents the first example of a bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the role of mast cells in limiting genital colonization by hyperpigmented GBS.

The Application of UX Research in New Energy Vehicle Innovation

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Menghan TAO ◽  
Ning XIAO ◽  
Xingfu ZHAO ◽  
Wenbin LIU
Keyword(s):  
Early Stage ◽  
Rapid Expansion ◽  
The Other ◽  
Innovative Product ◽  
Stage Of Development ◽  
New Energy ◽  
New Energy Vehicle ◽  
The One ◽  
New Energy Vehicles ◽  
Degree Of Innovation

New energy vehicles(NEV) as a new thing for sustainable development, in China, on the one hand has faced the rapid expansion of the market; the other hand, for the new NEV users, the current NEVs cannot keep up with the degree of innovation. This paper demonstrates the reasons for the existence of this systematic challenge, and puts forward the method of UX research which is different from the traditional petrol vehicles research in the early stage of development, which studies from the user's essence level, to form the innovative product programs which meet the needs of users and being real attractive.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals Learning health systems in primary care: a systematic scoping review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Danielle M. Nash ◽  
Zohra Bhimani ◽  
Jennifer Rayner ◽  
Merrick Zwarenstein
Keyword(s):  
Primary Care ◽  
Quality Improvement ◽  
Health Systems ◽  
Scoping Review ◽  
Early Stage ◽  
Point Of Care ◽  
The United States ◽  
Stage Of Development ◽  
Integrated Health ◽  
Google Search

Abstract Background Learning health systems have been gaining traction over the past decade. The purpose of this study was to understand the spread of learning health systems in primary care, including where they have been implemented, how they are operating, and potential challenges and solutions. Methods We completed a scoping review by systematically searching OVID Medline®, Embase®, IEEE Xplore®, and reviewing specific journals from 2007 to 2020. We also completed a Google search to identify gray literature. Results We reviewed 1924 articles through our database search and 51 articles from other sources, from which we identified 21 unique learning health systems based on 62 data sources. Only one of these learning health systems was implemented exclusively in a primary care setting, where all others were integrated health systems or networks that also included other care settings. Eighteen of the 21 were in the United States. Examples of how these learning health systems were being used included real-time clinical surveillance, quality improvement initiatives, pragmatic trials at the point of care, and decision support. Many challenges and potential solutions were identified regarding data, sustainability, promoting a learning culture, prioritization processes, involvement of community, and balancing quality improvement versus research. Conclusions We identified 21 learning health systems, which all appear at an early stage of development, and only one was primary care only. We summarized and provided examples of integrated health systems and data networks that can be considered early models in the growing global movement to advance learning health systems in primary care.

scholarly journals Open Research Data and Open Peer Review: Perceptions of a Medical and Health Sciences Community in Greece

Publications ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 14
Author(s):  
Eirini Delikoura ◽  
Dimitrios Kouis
Keyword(s):  
Peer Review ◽  
Evaluation System ◽  
Early Stage ◽  
Open Science ◽  
Health Sciences ◽  
Research Data ◽  
Stage Of Development ◽  
Open Research ◽  
Proper Training ◽  
To Receive

Recently significant initiatives have been launched for the dissemination of Open Access as part of the Open Science movement. Nevertheless, two other major pillars of Open Science such as Open Research Data (ORD) and Open Peer Review (OPR) are still in an early stage of development among the communities of researchers and stakeholders. The present study sought to unveil the perceptions of a medical and health sciences community about these issues. Through the investigation of researchers` attitudes, valuable conclusions can be drawn, especially in the field of medicine and health sciences, where an explosive growth of scientific publishing exists. A quantitative survey was conducted based on a structured questionnaire, with 179 valid responses. The participants in the survey agreed with the Open Peer Review principles. However, they ignored basic terms like FAIR (Findable, Accessible, Interoperable, and Reusable) and appeared incentivized to permit the exploitation of their data. Regarding Open Peer Review (OPR), participants expressed their agreement, implying their support for a trustworthy evaluation system. Conclusively, researchers need to receive proper training for both Open Research Data principles and Open Peer Review processes which combined with a reformed evaluation system will enable them to take full advantage of the opportunities that arise from the new scholarly publishing and communication landscape.

scholarly journals Primary Care Networks and Starfield’s 4Cs: A Case for Enhanced Chronic Disease Management

2021 ◽  
Vol 18 (6) ◽  
pp. 2926
Author(s):  
Chuan De Foo ◽  
Shilpa Surendran ◽  
Geronimo Jimenez ◽  
John Pastor Ansah ◽  
David Bruce Matchar ◽  
...  
Keyword(s):  
Primary Care ◽  
Chronic Disease ◽  
Disease Management ◽  
Chronic Disease Management ◽  
Early Stage ◽  
Healthcare Delivery ◽  
Stage Of Development ◽  
Facilitators And Barriers ◽  
Design Options ◽  
First Contact

The primary care network (PCN) was implemented as a healthcare delivery model which organises private general practitioners (GPs) into groups and furnished with a certain level of resources for chronic disease management. A secondary qualitative analysis was conducted with data from an earlier study exploring facilitators and barriers GPs enrolled in PCN’s face in chronic disease management. The objective of this study is to map features of PCN to Starfield’s “4Cs” framework. The “4Cs” of primary care—comprehensiveness, first contact access, coordination and continuity—offer high-quality design options for chronic disease management. Interview transcripts of GPs (n = 30) from the original study were purposefully selected. Provision of ancillary services, manpower, a chronic disease registry and extended operating hours of GP practices demonstrated PCN’s empowering features that fulfil the “4Cs”. On the contrary, operational challenges such as the lack of an integrated electronic medical record and disproportionate GP payment structures limit PCNs from maximising the “4Cs”. However, the enabling features mentioned above outweighs the shortfalls in all important aspects of delivering optimal chronic disease care. Therefore, even though PCN is in its early stage of development, it has shown to be well poised to steer GPs towards enhanced chronic disease management.

scholarly journals Relationship between vaginal group B streptococcus colonization in the early stage of pregnancy and preterm birth: a retrospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sho Tano ◽  
Takuji Ueno ◽  
Michinori Mayama ◽  
Takuma Yamada ◽  
Takehiko Takeda ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Early Stage ◽  
Group B Streptococcus ◽  
Multivariable Logistic Regression Analysis ◽  
Simple Method ◽  
Group B ◽  
Singleton Pregnancies

Abstract Background Although infection and inflammation within the genital tract during pregnancy is considered a major risk factor for spontaneous preterm birth (PTB), there are few studies on association between vaginal microorganisms in the early stage of pregnancy and PTB. The aim of this study was to investigate relationship between vaginal Group B streptococcus (GBS) colonization, a leading cause of infection during pregnancy, in the early stage of pregnancy and PTB. Methods This single-center, retrospective cohort study utilized data from 2009 to 2017 obtained at TOYOTA Memorial Hospital. Women with singleton pregnancies who underwent vaginal culture around 14 weeks of gestation during their routine prenatal check-up were included. Vaginal sampling for Gram staining and culture was performed regardless of symptoms. GBS colonization was defined as positive for GBS latex agglutination assay. Statistical analysis was performed to determine the factors associated with PTB. Results Overall 1079 singleton pregnancies were included. GBS (5.7%) and Candida albicans (5.5%) were the most frequently observed microorganisms. The incidence of PTB (before 34 and before 37 weeks of gestation) were significantly higher in the GBS-positive group than in the GBS-negative group (6.6% vs 0.5%, p = 0.001 and 9.8% vs 4.3%, p = 0.047). Our multivariable logistic regression analysis revealed that GBS colonization was a factor associated with PTB before 34 and before 37 weeks of gestation (Odds ratio [OR] 15.17; 95% confidence interval [CI] 3.73–61.74), and OR 2.42; 95%CI 1.01–5.91, respectively). Conclusions The present study found that vaginal GBS colonization in the early stage of pregnancy was associated with PTB. Our study indicates that patients at a high risk for PTB can be extracted by a simple method using conventional culture method.

The magic bullet for rural development? Exploring the impacts of community telecenters in Bangladesh

2021 ◽  
pp. 026666692199750
Author(s):  
Noore Alam Siddiquee ◽  
Md Gofran Faroqi
Keyword(s):  
Service Delivery ◽  
Rural Areas ◽  
Early Stage ◽  
Rural Livelihoods ◽  
Value Added ◽  
Magic Bullet ◽  
Government Information ◽  
Individual Interviews ◽  
Stage Of Development ◽  
Marginalized Groups

This paper explores the impacts of Bangladesh’s Union Digital Centers (UDCs) as government information and service delivery hubs in rural areas. Drawing on user-surveys and semi-structured individual interviews it demonstrates that the UDCs have produced generally positive yet modest impacts on governance of service delivery. It shows that the UDCs are at an early stage of development, and that they offer only a limited set of services. While they helped extend ICT-enabled services to sections of population that would otherwise have missed them, the UDCs do not have much to do with rural livelihoods and empowerment of the poor and marginalized groups. These findings point to current inadequacies and pitfalls of the UDC approach to development. We argue that enhanced viability and effectiveness of the UDC experiment would warrant embedding more value-added governmental services and further strengthening of their capacity, mandate, and connectivity with government agencies at various levels, among others.

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