Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020-2021.

Objective: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance.

Design And Setting: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE).

Participants: All live births ≥34 weeks' gestation between September 2020 and August 2021.

Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases.

Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through "humanization" rescue and overexpression-based strategies.

Metformin-associated lactic acidosis.

A 58-year-old female with known type 2 diabetes mellitus continued to take her usual medications, including metformin, an ACE inhibitor and a non-steroidal anti-inflammatory drug, while suffering from diarrhoea and vomiting. On presentation to the emergency department, she was found to have a profound lactic acidosis, cardiovascular instability and acute kidney injury. Despite a pH of 6.

Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K channels.

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv fast-spiking interneurons in mouse and human.

haploinsufficiency impairs inhibition and mediates key neurological features of encephalopathy.

Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, with the majority affecting postsynaptic apparatuses and much fewer in presynaptic proteins. Syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1) is an essential component of the presynaptic neurotransmitter release machinery. De novo heterozygous pathogenic variants in are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies.

Transferring preterm infants into an open cot using a heated mattress at ≤ 1400 g.

Objective: The objective of this study is to evaluate the corrected age and weight that infants were transferred into an open cot using a heated mattress, in overall and within the subgroups of early (weight ≤ 1400 g) and standard transfer (weight > 1400 g).

Design: Retrospective cohort study in a tertiary neonatal unit RESULTS: One hundred and thirty-five preterm infants were analysed. The mean weight of moving into an open cot was 1370 ± 167 g at a corrected age 33 ± 1.

Measurement of gut oxygenation in the neonatal population using near-infrared spectroscopy: a clinical tool?

Context: Near-infrared spectroscopy (NIRS) is a non-invasive bedside monitor of tissue oxygenation that may be a useful clinical tool in monitoring of gut oxygenation in newborn infants.

Objective: To systematically review literature to determine whether NIRS is a reliable tool to monitor gut oxygenation on neonatal units.

Data Sources: PubMed and Embase databases were searched using the terms 'neonate', 'preterm infants', 'NIRS' and 'gut oxygenation' (2001-2018).

Plasma electrolyte imbalance in pediatric kidney transplant recipients.

Background: In current practice, pediatric kidney transplant recipients receive large volumes of intravenous fluid intraoperatively to establish allograft perfusion, and further fluid to replace urinary and insensible losses postoperatively. Acute electrolyte imbalance can result, with potential for neurological sequelae. We aimed to determine the incidence and severity of postoperative plasma electrolyte imbalance in pediatric kidney transplant recipients managed with the current standard intravenous crystalloid regimen.

Google Glass Glare: disability glare produced by a head-mounted visual display.

Purpose: Head mounted displays are a type of wearable technology - a market that is projected to expand rapidly over the coming years. Probably the most well known example is the device Google Glass (or 'Glass'). Here we investigate the extent to which the device display can interfere with normal visual function by producing monocular disability glare.

Rural Latino parents offer preschool children few nutrient-dense snacks: a community-based study in Western Illinois.

The aims of this descriptive study were to identify the snacks offered to preschool children by Latino parents living in a rural community, assess the overall healthfulness of those snacks, and measure related psychosocial correlates. Data were collected using Spanish-language questionnaires and interviews completed by 96 parents. Thirty-two percent of snack offerings were nutrient dense.

Biodistribution and excretion of radiolabeled 40 kDa polyethylene glycol following intravenous administration in mice.

The pharmacokinetics, excretion, and tissue distribution of [(14)C]-labeled polyethylene glycol-alanine (PEG-Ala) were determined after slow bolus administration into the femoral vein of male CD-1 mice. The pharmacokinetics of PEG-Ala in blood and plasma revealed a biphasic elimination with a terminal half-life of 20 h. Eighty-five percent of the excreted material was voided in the urine and the remaining amount was detected in the feces.

High-dose mannose-binding lectin therapy for Ebola virus infection.

Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents.

Effects of federal legislation on wellness policy formation in school districts in the United States.

The Reauthorization Act of 2004 required local education agencies sponsoring school meal programs to establish a wellness policy by the beginning of school year 2006-2007. The purpose of this study was to examine the process and outcome of wellness policy development in school districts. Phase 1 examined states' school nutrition legislation.

Expanding the roles for pregnane X receptor in cancer: proliferation and drug resistance in ovarian cancer.

Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its cognate ligand.

Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry.

The acceptability of home monitoring technology among community-dwelling older adults and baby boomers.

This pilot study investigated the willingness of two generational cohorts (current baby boomers and older adults) to accept home monitoring technology. Thirty individuals (15 baby boomers and 15 older adults) of both genders and living in the community participated in structured, mixed methods interviews. The participants' opinions and views on various technologies (e.

Inferred influence of human lateral profile on limb load asymmetry during a quiet standing balance test.

Although the identification and characterisation of a participant's lateral profile during quiet standing have not received much research attention, they have the potential to greatly extend our understanding of upright stance stability control. This study further examines limb load asymmetries during quiet bipedal stance. During voluntary frontal-plane weight shifting for 2 min, 300 centre-of-pressure displacements on 14 blindfolded right-handed young adults were recorded.

Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers.

CPT-11, also known as irinotecan, is a prodrug that is approved for the treatment of advanced colorectal cancer. The active metabolite of CPT-11, SN38 (7-ethyl-10-hydroxy-camptothecin), has 100- to 1000-fold more potent cytotoxic activity in tissue cell culture compared with CPT-11. However, parental administration of SN38 is not possible because of its inherently poor water solubility.

Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model.

Purpose: Clinical development of SN38, the active metabolite of camptothecin-11 (CPT-11), has been hampered due to its poor solubility. We have developed a novel polymer-drug conjugate, EZN-2208, made by linking SN38 with a multiarm polyethylene glycol via a glycine linker.

Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay.

Delivery of G3139 using releasable PEG-linkers: impact on pharmacokinetic profile and anti-tumor efficacy.

In order to overcome the problems of enzymatic degradation and short plasma half life, which can limit the delivery of antisense oligonucleotides, and the potential immuno-stimulatory effects of CpG motifs, we utilized a polyethylene glycol (PEG) technology that employed various releasable linkers (rPEG). 5'-20 kDa-PEGylation of an anti-Bcl-2 5'-aminoalkyl-oligonucleotide with the same sequence as G3139 (Compound 1) did not alter its binding to the heparin-binding protein bFGF, nor the release of cytochrome c from isolated mitochondria treated with the conjugates. However, in 518A2 melanoma cells in vitro, PEGylation resulted in greatly diminished cellular uptake.

Releasable PEGylation of mesothelin targeted immunotoxin SS1P achieves single dosage complete regression of a human carcinoma in mice.

Recombinant immunotoxins exhibit targeting and cytotoxic functions needed for cell-specific destruction. However, antitumor efficacy, safety, and pharmacokinetics of these therapeutics might be improved by further macromolecular engineering. SS1P is a recombinant anti-mesothelin immunotoxin in clinical trials in patients with mesothelin-expressing tumors.

Engineering an arginine catabolizing bioconjugate: Biochemical and pharmacological characterization of PEGylated derivatives of arginine deiminase from Mycoplasma arthritidis.

Arginine is an important metabolite in the normal function of several biological systems, and arginine deprivation has been investigated in animal models and human clinical trials for its effects on inhibition of tumor growth, angiogenesis, or nitric oxide synthesis. In order to design an optimal arginine-catabolizing enzyme bioconjugate, a novel recombinant arginine deiminase (ADI) from Mycoplasma arthritidis was prepared, and multi-PEGylated derivatives were examined for enzymatic and biochemical properties in vitro, as well as pharmacokinetic and pharmacodynamic behavior in rats and mice. ADI bioconjugates constructed with 12 kDa or 20 kDa monomethoxy-poly(ethylene glycol) polymers with linear succinimidyl carbonate linkers were investigated via intravenous, intramuscular, or subcutaneous administration in rodents.

Structure-function engineering of interferon-beta-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation.

Recombinant interferon-beta-1b (IFN-beta-1b) is used clinically in the treatment of multiple sclerosis. In common with many biological ligands, IFN-beta-1b exhibits a relatively short serum half-life, and bioavailability may be further diminished by neutralizing antibodies. While PEGylation is an approach commonly employed to increase the blood residency time of protein therapeutics, there is a further requisite for molecular engineering approaches to also address the stability, solubility, aggregation, immunogenicity and in vivo exposure of therapeutic proteins.

An unexpected amide bond cleavage: poly (ethylene glycol) transport forms of vancomycin. 2.

PEG-amide vancomycin derivatives (V(3) position) have been synthesized and found to behave as prodrugs in vivo, demonstrating anti-microbial activity in mice when challenged with Staphylococcus aureus. The corresponding PEG-carbamate derivatives do not manifest this in vivo activity, although both classes of compounds have similar in vitro rat plasma stability. Thus, it appears that extra vascular cleavage of the amide bond can occur if the condition of extended circulation of the conjugate is met, resulting in the release of vancomycin.