Multi-strain probiotic administration decreases necrotizing enterocolitis severity and alters the epigenetic profile in mice.

Background: Probiotic administration may decrease the incidence of necrotizing enterocolitis (NEC) through mechanisms that are largely unknown. We investigated the effects of probiotics on intestinal epigenetics and assessed their effects on intestinal inflammation and motility using both ileum-predominant and combined ileo-colitis mouse NEC models.

Methods: C57BL/6 J mice were gavage-fed a multi-strain probiotic from postnatal days 3-11, consisting of B.

Core Outcome Set for Necrotizing Enterocolitis Treatment Trials.

Background And Objectives: Variability in outcome reporting in necrotizing enterocolitis (NEC) treatment trials hinders conducting meta-analyses and implementing novel treatments. We aimed to develop a core outcome set (COS) for NEC treatment trials including outcome measures most relevant to patients and physicians, from NEC diagnosis to adulthood.

Methods: Clinicians and/or researchers from low-middle- and high-income countries were approached based on their scientific contributions to NEC literature, and patients and parents through local organizations.

Colitis-Induced Small Intestinal Hypomotility Is Dependent on Enteroendocrine Cell Loss in Mice.

Background & Aims: The abdominal discomfort experienced by patients with colitis may be attributable in part to the presence of small intestinal dysmotility, yet mechanisms linking colonic inflammation with small-bowel motility remain largely unexplored. We hypothesize that colitis results in small intestinal hypomotility owing to a loss of enteroendocrine cells (EECs) within the small intestine that can be rescued using serotonergic-modulating agents.

Methods: Male C57BL/6J mice, as well as mice that overexpress (EEC) or lack (EEC) NeuroD1+ enteroendocrine cells, were exposed to dextran sulfate sodium (DSS) colitis (2.

Outcome Reporting in Interventional Necrotizing Enterocolitis Studies: A Systematic Review.

Background: Despite an increasing necrotizing enterocolitis (NEC) incidence, treatment strategies have failed to make major advancements towards improved NEC outcomes. Heterogeneity in outcome reporting and a lack of treatment efficacy studies potentially hamper these advancements. We aimed to analyze outcome reporting in recent interventional NEC studies.

Hypermethylation of prior to necrotizing enterocolitis onset.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants. Epigenetic changes in DNA methylation may be present prior to NEC onset. 24 preterm infants with NEC and 45 matched controls were included.

Development of an international core outcome set for treatment trials in necrotizing enterocolitis-a study protocol.

Aim: Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies.

Fetal-neonatal exposure to antibiotics and NEC development: A systematic review and meta-analysis.

Background: Fetal and neonatal exposure to antibiotics may contribute to the development of necrotizing enterocolitis (NEC) in preterm infants. This systematic review and meta-analysis investigate whether exposure to third trimester maternal antibiotics (MAB) and/or prolongation of empirical antibiotics (PEAB) are associated with NEC development in preterms.

Method: We included observational and randomized controlled studies, including those on preterm or very low birth weight (VLBW) infants, from MEDLINE and EMBASE, published between 1990 and June 2021.

Amplification and sequencing of entire tick mitochondrial genomes for a phylogenomic analysis.

The mitochondrial genome (mitogenome) has proven to be important for the taxonomy, systematics, and population genetics of ticks. However, current methods to generate mitogenomes can be cost-prohibitive at scale. To address this issue, we developed a cost-effective approach to amplify and sequence the whole mitogenome of individual tick specimens.

Metallated phthalocyanines and their hydrophilic derivatives for multi-targeted oncological photodynamic therapy.

Background And Aim: A photosensitizer (PS) delivery and comprehensive tumor targeting platform was developed that is centered on the photosensitization of key pharmacological targets in solid tumors (cancer cells, tumor vascular endothelium, and cellular and non-cellular components of the tumor microenvironment) before photodynamic therapy (PDT). Interstitially targeted liposomes (ITLs) encapsulating zinc phthalocyanine (ZnPC) and aluminum phthalocyanine (AlPC) were formulated for passive targeting of the tumor microenvironment. In previous work it was established that the PEGylated ITLs were taken up by cultured cholangiocarcinoma cells.

Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.

Photodynamic therapy (PDT) is a minimally to noninvasive treatment modality that has emerged as a promising alternative to conventional cancer treatments. PDT induces hyperoxidative stress and disrupts cellular homeostasis in photosensitized cancer cells, resulting in cell death and ultimately removal of the tumor. However, various survival pathways can be activated in sublethally afflicted cancer cells following PDT.

Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.

Photodynamic therapy (PDT) is a non-to-minimally invasive treatment modality that utilizes photoactivatable drugs called photosensitizers to disrupt tumors with locally photoproduced reactive oxygen species (ROS). Photosensitizer activation by light results in hyperoxidative stress and subsequent tumor cell death, vascular shutdown and hypoxia, and an antitumor immune response. However, sublethally afflicted tumor cells initiate several survival mechanisms that account for decreased PDT efficacy.

DNA Methylation of , and Is Associated With Necrotizing Enterocolitis in Preterm Infants.

Epigenetic changes, such as DNA methylation, may contribute to an increased susceptibility for developing necrotizing enterocolitis (NEC) in preterm infants. We assessed DNA methylation in five NEC-associated genes, selected from literature: , and in infants with NEC and controls. Observational cohort study including 24 preterm infants who developed NEC (≥Bell Stage IIA) and 45 matched controls.

Attritional evaluation of lipophilic and hydrophilic metallated phthalocyanines for oncological photodynamic therapy.

Background And Aim: Oncological photodynamic therapy (PDT) relies on photosensitizers (PSs) to photo-oxidatively destroy tumor cells. Currently approved PSs yield satisfactory results in superficial and easy-to-access tumors but are less suited for solid cancers in internal organs such as the biliary system and the pancreas. For these malignancies, second-generation PSs such as metallated phthalocyanines are more appropriate.

De novo assembled salivary gland transcriptome and expression pattern analyses for Rhipicephalus evertsi evertsi Neuman, 1897 male and female ticks.

Ticks secrete proteins in their saliva that change over the course of feeding to modulate the host inflammation, immune responses, haemostasis or may cause paralysis. RNA next generation sequencing technologies can reveal the complex dynamics of tick salivary glands as generated from various tick life stages and/or males and females. The current study represents 15,115 Illumina sequenced contigs of the salivary gland transcriptome from male and female Rhipicephalus evertsi evertsi ticks of early, mid and late feeding stages from 1320 separate assemblies using three short read assemblers.

Local Rheology Relation with Variable Yield Stress Ratio across Dry, Wet, Dense, and Dilute Granular Flows.

Dry, wet, dense, and dilute granular flows have been previously considered fundamentally different and thus described by distinct, and in many cases incompatible, rheologies. We carry out extensive simulations of granular flows, including wet and dry conditions, various geometries and driving mechanisms (boundary driven, fluid driven, and gravity driven), many of which are not captured by standard rheology models. For all simulated conditions, except for fluid-driven and gravity-driven flows close to the flow threshold, we find that the Mohr-Coulomb friction coefficient μ scales with the square root of the local Péclet number Pe provided that the particle diameter exceeds the particle mean free path.

DNA methyltransferases expression in normal tissues and various human cancer cell lines, xenografts and tumors.

DNA methylation plays an important role in carcinogenesis and aberrant methylation patterns have been found in many tumors. Methylation is regulated by DNA methyltransferases (DNMT), catalyzing DNA methylation. Therefore inhibition of DNMT is an interesting target for anticancer treatment.

Transporter and Lysosomal Mediated (Multi)drug Resistance to Tyrosine Kinase Inhibitors and Potential Strategies to Overcome Resistance.

Tyrosine kinase inhibitors are a class of chemotherapeutic drugs that target specific protein kinases. These tyrosine kinase inhibitors constitute a relatively new class of drugs which target for instance Bcr-Abl, Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR). Despite some initial successes, the overall therapeutic benefit of tyrosine kinase inhibitors in the clinic has been mixed.

Argasid and ixodid systematics: Implications for soft tick evolution and systematics, with a new argasid species list.

The systematics of the genera and subgenera within the soft tick family Argasidae is not adequately resolved. Different classification schemes, reflecting diverse schools of scientific thought that elevated or downgraded groups to genera or subgenera, have been proposed. In the most recent classification scheme, Argas and Ornithodoros are paraphyletic and the placement of various subgenera remains uncertain because molecular data are lacking.

Integrative taxonomy of Afrotropical Ornithodoros (Ornithodoros) (Acari: Ixodida: Argasidae).

Afrotropical Ornithodoros (Ornithodoros) ticks are revised based on qualitative morphology of females and nymphs, as well as tarsus I shape outlines of females measured in a geometric morphometric framework. These lines of evidence corroborate lineages based on 16S rRNA nucleotide sequence data. Four previously unrecognized species are described, along with a revived nomen nudum that was previously considered a synonym.

Notes on maternal behaviour in soft ticks: Specifically observed in Argas (Argas) striatus Bedford, 1932 and Argas (Secretargas) transgariepinus White, 1846.

Maternal behaviour (carrying of larvae on the opisthosoma) in ticks has thus far only been observed in Antricola (Parantricola) marginatus and was considered a unique derived adaptation of this genus. The authors extend this observation to two additional argasid species, namely Argas (Argas) striatus and Argas (Secretargas) transgariepinus. In addition, brooding behaviour over eggs were observed with A.

Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne.

Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne.

Sialotranscriptomics of Rhipicephalus zambeziensis reveals intricate expression profiles of secretory proteins and suggests tight temporal transcriptional regulation during blood-feeding.

Background: Ticks secrete a diverse mixture of secretory proteins into the host to evade its immune response and facilitate blood-feeding, making secretory proteins attractive targets for the production of recombinant anti-tick vaccines. The largely neglected tick species, Rhipicephalus zambeziensis, is an efficient vector of Theileria parva in southern Africa but its available sequence information is limited. Next generation sequencing has advanced sequence availability for ticks in recent years and has assisted the characterisation of secretory proteins.

Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer.

Background: Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC.

Methods: The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy.

The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2.

Fluorocyclopentenylcytosine (RX-3117) is an orally available cytidine analog, currently in Phase I clinical trial. RX-3117 has promising antitumor activity in various human tumor xenografts including gemcitabine resistant tumors. RX-3117 is activated by uridine-cytidine kinase (UCK).