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Article ; Online: Preterm birth by cesarean section: the gut-brain axis, a key regulator of brain development.

Morin, Cécile / Bokobza, Cindy / Fleiss, Bobbi / Hill-Yardin, Elisa L / Van Steenwinckel, Juliette / Gressens, Pierre

2023

Abstract: Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a "gut-brain axis" and the impact of an alteration of gut ... ...

Abstract	Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a "gut-brain axis" and the impact of an alteration of gut microbiota composition in brain diseases. Recent research has highlighted how gut microbiota could affect brain development and behavior. Many factors in early life such as the mode of delivery or preterm birth could lead to disturbance in the assembly and maturation of gut microbiota. Notably, global rates of cesarean sections (C-sections) have increased in recent decades and remain important when considering premature delivery. Both preterm birth and C-sections are associated with an increased risk of neurodevelopmental disorders such as autism spectrum disorders; with neuroinflammation a major risk factor. In this review, we explore links between preterm birth by C-sections, gut microbiota alteration, and neuroinflammation. We also highlight C-sections as a risk factor for developmental disorders due to alterations in the microbiome.
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	556887-0
ISSN	1421-9859 ; 0378-5866
ISSN (online)	1421-9859
ISSN	0378-5866
DOI	10.1159/000534124
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Article ; Online: Implications of zero-deforestation palm oil for tropical grassy and dry forest biodiversity.

Fleiss, Susannah / Parr, Catherine L / Platts, Philip J / McClean, Colin J / Beyer, Robert M / King, Henry / Lucey, Jennifer M / Hill, Jane K

Nature ecology & evolution

2022 Volume 7, Issue 2, Page(s) 250–263

Abstract: Many companies have made zero-deforestation commitments (ZDCs) to reduce carbon emissions and biodiversity losses linked to tropical commodities. However, ZDCs conserve areas primarily based on tree cover and aboveground carbon, potentially leading to ... ...

Abstract	Many companies have made zero-deforestation commitments (ZDCs) to reduce carbon emissions and biodiversity losses linked to tropical commodities. However, ZDCs conserve areas primarily based on tree cover and aboveground carbon, potentially leading to the unintended consequence that agricultural expansion could be encouraged in biomes outside tropical rainforest, which also support important biodiversity. We examine locations suitable for zero-deforestation expansion of commercial oil palm, which is increasingly expanding outside the tropical rainforest biome, by generating empirical models of global suitability for rainfed and irrigated oil palm. We find that tropical grassy and dry forest biomes contain >50% of the total area of land climatically suitable for rainfed oil palm expansion in compliance with ZDCs (following the High Carbon Stock Approach; in locations outside urban areas and cropland), and that irrigation could double the area suitable for expansion in these biomes. Within these biomes, ZDCs fail to protect areas of high vertebrate richness from oil palm expansion. To prevent unintended consequences of ZDCs and minimize the environmental impacts of oil palm expansion, policies and governance for sustainable development and conservation must expand focus from rainforests to all tropical biomes.
MeSH term(s)	Palm Oil ; Conservation of Natural Resources ; Poaceae ; Arecaceae ; Forests ; Biodiversity ; Carbon
Chemical Substances	Palm Oil (5QUO05548Z) ; Carbon (7440-44-0)
Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2397-334X
ISSN (online)	2397-334X
DOI	10.1038/s41559-022-01941-6
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Article ; Online: Key roles of glial cells in the encephalopathy of prematurity.

Van Steenwinckel, Juliette / Bokobza, Cindy / Laforge, Mireille / Shearer, Isabelle K / Miron, Veronique E / Rua, Rejane / Matta, Samantha M / Hill-Yardin, Elisa L / Fleiss, Bobbi / Gressens, Pierre

Glia

2023 Volume 72, Issue 3, Page(s) 475–503

Abstract: Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases ... ...

Abstract	Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotional regulation, and cognition. We are still severely limited in our abilities to prevent or predict preterm birth. No longer just the "support cells," we now clearly understand that during development glia are key for building a healthy brain. Glial dysfunction is a hallmark of EoP, notably, microgliosis, astrogliosis, and oligodendrocyte injury. Our knowledge of glial biology during development is exponentially expanding but hasn't developed sufficiently for development of effective neuroregenerative therapies. This review summarizes the current state of knowledge for the roles of glia in infants with EoP and its animal models, and a description of known glial-cell interactions in the context of EoP, such as the roles for border-associated macrophages. The field of perinatal medicine is relatively small but has worked passionately to improve our understanding of the etiology of EoP coupled with detailed mechanistic studies of pre-clinical and human cohorts. A primary finding from this review is that expanding our collaborations with computational biologists, working together to understand the complexity of glial subtypes, glial maturation, and the impacts of EoP in the short and long term will be key to the design of therapies that improve outcomes.
MeSH term(s)	Infant ; Pregnancy ; Animals ; Female ; Infant, Newborn ; Humans ; Premature Birth ; Infant, Premature ; Neuroglia ; Brain ; Brain Injuries
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639414-0
ISSN	1098-1136 ; 0894-1491
ISSN (online)	1098-1136
ISSN	0894-1491
DOI	10.1002/glia.24474
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Zs.A 2345: Show issues

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Article ; Online: Reducing MRSA Infection in a New NICU During the COVID-19 Pandemic.

Barrett, Renee E / Fleiss, Noa / Hansen, Caitlin / Campbell, Melissa M / Rychalsky, Michelle / Murdzek, Christina / Krechevsky, Kathy / Abbott, Meaghan / Allegra, Terese / Blazevich, Beth / Dunphy, Louise / Fox, Amy / Gambardella, Tracy / Garcia, Lindsey / Grimm, Natalie / Scoffone, Amy / Bizzarro, Matthew J / Murray, Thomas S

Pediatrics

2023 Volume 151, Issue 2

Abstract: Background and objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in most NICUs, with a high rate of skin colonization and subsequent invasive infections among hospitalized neonates. The effectiveness of interventions designed ... ...

Abstract	Background and objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is prevalent in most NICUs, with a high rate of skin colonization and subsequent invasive infections among hospitalized neonates. The effectiveness of interventions designed to reduce MRSA infection in the NICU during the coronavirus disease 2019 (COVID-19) pandemic has not been characterized. Methods: Using the Institute for Healthcare Improvement's Model for Improvement, we implemented several process-based infection prevention strategies to reduce invasive MRSA infections at our level IV NICU over 24 months. The outcome measure of invasive MRSA infections was tracked monthly utilizing control charts. Process measures focused on environmental disinfection and hospital personnel hygiene were also tracked monthly. The COVID-19 pandemic was an unexpected variable during the implementation of our project. The pandemic led to restricted visitation and heightened staff awareness of the importance of hand hygiene and proper use of personal protective equipment, as well as supply chain shortages, which may have influenced our outcome measure. Results: Invasive MRSA infections were reduced from 0.131 to 0 per 1000 patient days during the initiative. This positive shift was sustained for 30 months, along with a delayed decrease in MRSA colonization rates. Several policy and practice changes regarding personnel hygiene and environmental cleaning likely contributed to this reduction. Conclusions: Implementation of a multidisciplinary quality improvement initiative aimed at infection prevention strategies led to a significant decrease in invasive MRSA infections in the setting of the COVID-19 pandemic.
MeSH term(s)	Infant, Newborn ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Cross Infection/prevention & control ; Cross Infection/epidemiology ; Intensive Care Units, Neonatal ; Staphylococcal Infections/epidemiology ; Staphylococcal Infections/prevention & control ; Pandemics/prevention & control ; Infection Control ; COVID-19/prevention & control
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	207677-9
ISSN	1098-4275 ; 0031-4005
ISSN (online)	1098-4275
ISSN	0031-4005
DOI	10.1542/peds.2022-057033
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Um IV Zs.131: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 357: Show issues

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Article ; Online: Advances in neonatal cell therapies: Proceedings of the First Neonatal Cell Therapies Symposium (2022).

Malhotra, Atul / Thebaud, Bernard / Paton, Madison C B / Fleiss, Bobbi / Papagianis, Paris / Baker, Elizabeth / Bennet, Laura / Yawno, Tamara / Elwood, Ngaire / Campbell, Belinda / Chand, Kirat / Zhou, Lindsay / Penny, Tayla / Nguyen, Timothy / Pepe, Salvatore / Gunn, Alistair J / McDonald, Courtney A

Pediatric research

2023 Volume 94, Issue 5, Page(s) 1631–1638

Abstract: Despite considerable advances, there is a need to improve the outcomes of newborn infants, especially related to prematurity, encephalopathy and other conditions. In principle, cell therapies have the potential to protect, repair, or sometimes regenerate ...

Abstract	Despite considerable advances, there is a need to improve the outcomes of newborn infants, especially related to prematurity, encephalopathy and other conditions. In principle, cell therapies have the potential to protect, repair, or sometimes regenerate vital tissues; and improve or sustain organ function. In this review, we present highlights from the First Neonatal Cell Therapies Symposium (2022). Cells tested in preclinical and clinical studies include mesenchymal stromal cells from various sources, umbilical cord blood and cord tissue derived cells, and placental tissue and membrane derived cells. Overall, most preclinical studies suggest potential for benefit, but many of the cells tested were not adequately defined, and the optimal cell type, timing, frequency, cell dose or the most effective protocols for the targeted conditions is not known. There is as yet no clinical evidence for benefit, but several early phase clinical trials are now assessing safety in newborn babies. We discuss parental perspectives on their involvement in these trials, and lessons learnt from previous translational work of promising neonatal therapies. Finally, we make a call to the many research groups around the world working in this exciting yet complex field, to work together to make substantial and timely progress to address the knowledge gaps and move the field forward. IMPACT: Survival of preterm and sick newborn infants is improving, but they continue to be at high risk of many systemic and organ-specific complications. Cell therapies show promising results in preclinical models of various neonatal conditions and early phase clinical trials have been completed or underway. Progress on the potential utility of cell therapies for neonatal conditions, parental perspectives and translational aspects are discussed in this paper.
MeSH term(s)	Infant, Newborn ; Infant ; Humans ; Female ; Pregnancy ; Placenta ; Infant, Premature ; Mesenchymal Stem Cells
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-023-02707-x
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Heterogeneity of the GFP fitness landscape and data-driven protein design.

Gonzalez Somermeyer, Louisa / Fleiss, Aubin / Mishin, Alexander S / Bozhanova, Nina G / Igolkina, Anna A / Meiler, Jens / Alaball Pujol, Maria-Elisenda / Putintseva, Ekaterina V / Sarkisyan, Karen S / Kondrashov, Fyodor A

eLife

2022 Volume 11

Abstract: Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes ... ...

Abstract	Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design - instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.
MeSH term(s)	Genetic Fitness ; Models, Genetic ; Mutation ; Proteins/genetics
Chemical Substances	Proteins
Language	English
Publishing date	2022-05-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.75842
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Article: Midkine: The Who, What, Where, and When of a Promising Neurotrophic Therapy for Perinatal Brain Injury.

Ross-Munro, Emily / Kwa, Faith / Kreiner, Jenny / Khore, Madhavi / Miller, Suzanne L / Tolcos, Mary / Fleiss, Bobbi / Walker, David W

Frontiers in neurology

2020 Volume 11, Page(s) 568814

Abstract: Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and ... ...

Abstract	Midkine (MK) is a small secreted heparin-binding protein highly expressed during embryonic/fetal development which, through interactions with multiple cell surface receptors promotes growth through effects on cell proliferation, migration, and differentiation. MK is upregulated in the adult central nervous system (CNS) after multiple types of experimental injury and has neuroprotective and neuroregenerative properties. The potential for MK as a therapy for developmental brain injury is largely unknown. This review discusses what is known of MK's expression and actions in the developing brain, areas for future research, and the potential for using MK as a therapeutic agent to ameliorate the effects of brain damage caused by insults such as birth-related hypoxia and inflammation.
Language	English
Publishing date	2020-10-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2020.568814
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Article ; Online: Clinical and vital sign changes associated with late-onset sepsis in very low birth weight infants at 3 NICUs.

Sullivan, B A / Nagraj, V P / Berry, K L / Fleiss, N / Rambhia, A / Kumar, R / Wallman-Stokes, A / Vesoulis, Z A / Sahni, R / Ratcliffe, S / Lake, D E / Moorman, J R / Fairchild, K D

Journal of neonatal-perinatal medicine

2021 Volume 14, Issue 4, Page(s) 553–561

Abstract: Background: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start ... ...

Abstract	Background: In premature infants, clinical changes frequently occur due to sepsis or non-infectious conditions, and distinguishing between these is challenging. Baseline risk factors, vital signs, and clinical signs guide decisions to culture and start antibiotics. We sought to compare heart rate (HR) and oxygenation (SpO2) patterns as well as baseline variables and clinical signs prompting sepsis work-ups ultimately determined to be late-onset sepsis (LOS) and sepsis ruled out (SRO). Methods: At three NICUs, we reviewed records of very low birth weight (VLBW) infants around their first sepsis work-up diagnosed as LOS or SRO. Clinical signs prompting the evaluation were determined from clinician documentation. HR-SpO2 data, when available, were analyzed for mean, standard deviation, skewness, kurtosis, and cross-correlation. We used LASSO and logistic regression to assess variable importance and associations with LOS compared to SRO. Results: We analyzed sepsis work-ups in 408 infants (173 LOS, 235 SRO). Compared to infants with SRO, those with LOS were of lower GA and BW, and more likely to have a central catheter and mechanical ventilation. Clinical signs cited more often in LOS included hypotension, acidosis, abdominal distension, lethargy, oliguria, and abnormal CBC or CRP(p < 0.05). HR-SpO2 data were available in 266 events. Cross-correlation HR-SpO2 before the event was associated with LOS after adjusting for GA, BW, and postnatal age. A model combining baseline, clinical and HR-SpO2 variables had AUC 0.821. Conclusion: In VLBW infants at 3-NICUs, we describe the baseline, clinical, and HR-SpO2 variables associated with LOS versus SRO.
MeSH term(s)	Humans ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Intensive Care Units, Neonatal ; Oxygen Saturation ; Risk Factors ; Sepsis/diagnosis ; Vital Signs
Language	English
Publishing date	2021-01-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2435387-5
ISSN	1878-4429 ; 1934-5798
ISSN (online)	1878-4429
ISSN	1934-5798
DOI	10.3233/NPM-200578
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Article: Intraclass correlations: uses in assessing rater reliability.

Shrout, P E / Fleiss, J L

Psychological bulletin

2008 Volume 86, Issue 2, Page(s) 420–428

Abstract: Reliability coefficients often take the form of intraclass correlation coefficients. In this article, guidelines are given for choosing among six different forms of the intraclass correlation for reliability studies in which n target are rated by k ... ...

Abstract	Reliability coefficients often take the form of intraclass correlation coefficients. In this article, guidelines are given for choosing among six different forms of the intraclass correlation for reliability studies in which n target are rated by k judges. Relevant to the choice of the coefficient are the appropriate statistical model for the reliability and the application to be made of the reliability results. Confidence intervals for each of the forms are reviewed.
MeSH term(s)	Humans ; Models, Statistical ; Reproducibility of Results
Language	English
Publishing date	2008-09-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1321-3
ISSN	1939-1455 ; 0033-2909
ISSN (online)	1939-1455
ISSN	0033-2909
DOI	10.1037//0033-2909.86.2.420
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Zs.A 1403: Show issues

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Article ; Online: Agricultural groundwater with high nitrates and dissolved salts given to pregnant mice alters brain development in the offspring.

Schwendimann, Leslie / Sivaprakasam, Iswariya / Buvaneshwari, Sriramulu / Gurumurthy, Gundiga P / Mishra, Saumya / Ruiz, Laurent / Sekhar, Muddu / Fleiss, Bobbi / Riotte, Jean / Mani, Shyamala / Gressens, Pierre

Ecotoxicology and environmental safety

2021 Volume 224, Page(s) 112635

Abstract: Groundwater is the main source of drinking water for a significant portion of the human population. In many agricultural areas, diffuse pollution such as high levels of total dissolved salts including nitrate, puts the quality of this resource at risk. ... ...

Abstract	Groundwater is the main source of drinking water for a significant portion of the human population. In many agricultural areas, diffuse pollution such as high levels of total dissolved salts including nitrate, puts the quality of this resource at risk. However, the effect of exposure to these water contaminants on brain development is currently poorly understood. Here we characterised water from a borewell located in an intensely cultivated area (agricultural) or water from a borewell located in a nearby pristine forest. The agricultural borewell water was rich in nitrates with high total dissolved salts. We then studied the consequence of drinking the agricultural water on mouse brain development. For this, the agricultural borewell water or forest water was given to mice for 6 weeks before and during pregnancy and lactation. The brains of the offspring born to these dams were analysed at postnatal day (P)5 and P21 and compared using immunohistochemistry for changes in glial cells, neurons, myelin, and cell death across many brain regions. Brains from offspring born to dams who had been given agricultural water (versus forest control water) were significantly smaller, and at P21 had a significant degeneration of neurons and increased numbers of microglia in the motor cortex, had fewer white matter astrocytes and an increase in cell death, particularly in the dentate gyrus. This study shows that brain development is sensitive to water composition. It points to the importance of assessing neurodevelopmental delays when considering the effect of water contaminated with agricultural run offs on human health. MAIN FINDING: Pregnant and lactating mice were given borewell water from intensely cultivated land. Offspring brains reveal degeneration of neurons and a loss of astrocytes, increase in microglial cells and cell death, pointing to neurodevelopmental problems.
Language	English
Publishing date	2021-08-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	436536-7
ISSN	1090-2414 ; 0147-6513
ISSN (online)	1090-2414
ISSN	0147-6513
DOI	10.1016/j.ecoenv.2021.112635
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