Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Living in a bubble with profound difficulties-parents' experiences of extremely preterm survivors.

Aim: To analyse the challenges faced by parents of extremely preterm infants born before 24 weeks of gestation and the potential buffering effect of perceived resources on the family's health continuum.

Methods: The qualitative data were obtained from 70 parents of 70 infants born before 24 weeks of gestation, through open-ended questions in a survey. An inductive content analysis was conducted to identify themes and patterns in the parents' experiences.

Platelet characteristics in extremely preterm infants after fatty acid supplementation: a randomized controlled trial.

Background: Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.

Method: Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal enteral AA/DHA supplementation or standard care (controls).

Postnatal betamethasone treatment in extremely preterm infants and risk of neurodevelopmental impairment: a cohort study.

Objective: To evaluate if postnatal treatment with betamethasone in extremely preterm infants was associated with neurodevelopmental impairment (NDI) at 6.5 years of age.

Design: Prospective cohort study.

Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain.

Reduced serum level of insulin-like growth factor 1 (IGF-1), a major regulator of perinatal development, in extremely preterm infants has been shown to be associated with neurodevelopmental impairment. To clarify the mechanism of IGF-1 transport at the blood-cerebrospinal fluid (CSF) barrier of the immature brain, we combined studies of in vivo preterm piglet and rabbit models with an in vitro transwell cell culture model of neonatal primary murine choroid plexus epithelial (ChPE) cells. We identified IGF-1-positive intracellular vesicles in ChPE cells and provided data indicating a directional transport of IGF-1 from the basolateral to the apical media in extracellular vesicles (EVs).

Respiratory support and bronchopulmonary dysplasia in infants born at 22-26 weeks gestation in Sweden, 2004-2007 and 2014-2016.

Background: Our aim was to evaluate if increased survival and new ventilation strategies were accompanied by a changed incidence of bronchopulmonary dysplasia (BPD) in Sweden over a decade.

Methods: Data from two Swedish population-based studies of live-born infants with gestational age (GA) 22-26 weeks, born during 2004-2007 (n=702) and 2014-2016 (n=885), were compared for survival, any BPD, moderate BPD and severe BPD and the composite outcomes of any BPD or death and severe BPD or death at 36 weeks postmenstrual age (PMA). Ventilation strategies and interventions were analysed.

Efficacy of vedolizumab and ustekinumab in pediatric-onset inflammatory bowel disease: A real-world multicenter study.

Objectives: Vedolizumab and ustekinumab are effective in inducing and maintaining corticosteroid-free clinical remission (CFR) in adult patients with inflammatory bowel disease (IBD). This study describes the efficacy and safety of vedolizumab and ustekinumab in pediatric IBD.

Methods: All patients ≤18 years of age with Crohn's disease (CD) or ulcerative colitis (UC) treated with vedolizumab or ustekinumab in three centers in Northern France were followed retrospectively.

Centralisation of extremely preterm births and decreased early postnatal mortality in Sweden, 2004-2007 versus 2014-2016.

Aim: We evaluated the increased centralisation of extremely preterm (EPT) births in Sweden in relation to the changes in mortality and morbidity.

Methods: Population-based data covering Swedish live births from 22 + 0 to 26 + 6 weeks of gestation during 2004-2007 and 2014-2016 were analysed for associations between time-period, birth within (inborn) or outside (outborn) regional centres, and outcomes.

Results: Among 1626 liveborn infants, 703 were born in 2004-2007 and 923 in 2014-2016.

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells.

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Challenges of parenting children born before 24 weeks of gestation.

Aim: To assess experience of care, well-being of parents and children's development in a cohort of extremely premature infants born <24 weeks of gestation in Sweden from 2007 to 2018.

Methods: A survey based on multiple questionnaires answered by 124/349 (35.5%) parents.

High Rates of Seroprotection to Hepatitis B After a Hepatitis B Challenge Dose in Previously Vaccinated Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy.

Background: Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD.

Donor human milk treated by high-pressure processing improves the body growth of growth-restricted mice pups.

Introduction: Pasteurized human donor milk (DM) is frequently used for feeding preterm newborns and extrauterine growth-restricted (EUGR) infants. Most human milk banks performed a pasteurization of DM using the standard method of Holder pasteurization (HoP) which consists of heating milk at 62.5°C for 30 min.

Risk factors for surgery in stricturing small bowel Crohn's disease: A retrospective cohort study from the GETAID pédiatrique.

Objectives: Previous studies have shown rates of surgical resection of up to 41% in stricturing pediatric Crohn's disease (CD). In this retrospective multicenter study, our aims were to identify clinical risk factors and magnetic resonance enterography (MRE) features of small bowel strictures associated with surgery.

Methods: Pediatric patients with symptomatic stricturing small bowel CD (defined as obstructive symptoms or proximal dilatation on MRE) confirmed by MRE between 2010 and 2020 were recruited from 12 French tertiary hospitals.

Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants.

Background & Aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants.

Methods: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity.

Home enteral nutrition does not decrease oral feeding in children during the first year of nutritional support.

Background: Enteral nutrition is necessary when nutritional status is poor and oral intake is insufficient or impossible. Although it has been suspected to reduce spontaneous oral feeding, no study has formally assessed the influence of enteral nutrition on pediatric oral intake. The present study aimed to evaluate variation in oral feeding intake after enteral nutrition initiation, and to identify factors influencing oral feeding.

High hydrostatic pressure is similar to Holder pasteurization in preserving donor milk antimicrobial activity.

Background: The microbiological safety of donor milk (DM) is commonly ensured by Holder pasteurization (HoP, 62.5 °C for 30 min) in human milk banks despite its detrimental effects on bioactive factors. We compared the antimicrobial properties of DM after Holder pasteurization treatment or High Hydrostatic Pressure processing (HHP, 350 MPa at 38 °C), a non-thermal substitute for DM sterilization.

An Overview of the Influence of Breastfeeding on the Development of Inflammatory Bowel Disease.

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period early in life, there is growing evidence that the establishment of healthy gut microbiota plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of the gut microbiota colonisation depends on several dietary factors, including breastfeeding.