Cytosolic delivery of innate immune agonists.

Solute carrier proteins (SLCs) are pivotal for maintaining cellular homeostasis by transporting small molecules across cellular membranes. Recent discoveries have uncovered their involvement in modulating innate immunity, particularly within the cytosol. We review emerging evidence that links SLC transporters to cytosolic innate immune recognition and highlight their role in regulating inflammation.

Prophylactic Unfractionated Heparin in Antepartum Hospitalizations: A Randomized Controlled Trial.

Objective: To assess the effect of gestational age-based dosing of unfractionated heparin (UFH) compared with standard dosing of UFH for thromboprophylaxis on an elevated serum activated partial thromboplastin time (aPTT) during prolonged antepartum hospitalizations.

Methods: This was a randomized trial of pregnant persons who were admitted in the antepartum period for at least 72 hours. Participants were randomly allocated to the standard dose of UFH (5,000 units subcutaneously every 12 hours) or the gestational age-based dose of UFH (first trimester [less than 14 weeks]: 5,000 units subcutaneously every 12 hours; second trimester [14-27 6/7 weeks]: 7,500 units subcutaneously every 12 hours; third trimester (28 weeks or more): 10,000 units subcutaneously every 12 hours).

Rare case of total anomalous pulmonary venous return into the right atrium in situs solitus.

We report an uncommon case report of total anomalous pulmonary venous returns into the right atrium at the base of the superior caval vein's ostium without a sinus venosus defect, in situs solitus, without vertical vein or a posterior pulmonary venous confluence.

The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection.

Activation of endosomal Toll-like receptor (TLR) 7, TLR9, and TLR11/12 is a key event in the resistance against the parasite Toxoplasma gondii. Endosomal TLR engagement leads to expression of interleukin (IL)-12 via the myddosome, a protein complex containing MyD88 and IL-1 receptor-associated kinase (IRAK) 4 in addition to IRAK1 or IRAK2. In murine macrophages, IRAK2 is essential for IL-12 production via endosomal TLRs but, surprisingly, Irak2 mice are only slightly susceptible to T.

Sensitivity of antenatal ultrasound in diagnosing posterior placenta accreta spectrum disorders.

Objectives: Optimal management of placenta accreta spectrum (PAS) requires antenatal diagnosis. We sought to evaluate the sensitivity of ultrasound findings suggestive of PAS in detecting posterior PAS.

Methods: Cohort study of patients with posterior placentation and pathology-confirmed PAS from 2011 to 2020 at a tertiary center.

Society for Maternal-Fetal Medicine Consult Series #69: Hepatitis B in pregnancy: updated guidelines.

More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.

Synthesis and validation of click-modified NOD1/2 agonists.

NOD1 and NOD2 sense small bacterial peptidoglycan fragments, often called muropeptides, that access the cytosol. These muropeptides include iE-DAP and MDP, the minimal agonists for NOD1 and NOD2, respectively. Here, we synthesized and validated alkyne-modified muropeptides, iE-DAP-Alk and MDP-Alk, for use in click-chemistry reactions.

Group B Streptococcus in Pregnancy.

To decrease risk of early-onset neonatal sepsis from group B streptococcus (GBS), pregnant patients should undergo screening between 36 0/7 and 37 6/7 weeks' gestation. Patients with a positive vaginal-rectal culture, GBS bacteriuria , or history of newborn with GBS disease should receive intrapartum antibiotic prophylaxis (IAP) with an agent targeting GBS. If GBS status is unknown at time of labor, IAP should be administered in cases of preterm birth, rupture of membranes for >18 hours, or intrapartum fever.

Methotrexate suppresses psoriatic skin inflammation by inhibiting muropeptide transporter SLC46A2 activity.

Cytosolic innate immune sensing is critical for protecting barrier tissues. NOD1 and NOD2 are cytosolic sensors of small peptidoglycan fragments (muropeptides) derived from the bacterial cell wall. These muropeptides enter cells, especially epithelial cells, through unclear mechanisms.

Downregulation of Hsp90 and the antimicrobial peptide Mtk suppresses poly(GR)-induced neurotoxicity in C9ORF72-ALS/FTD.

GGGGCC repeat expansion in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat RNAs can be translated into dipeptide repeat proteins, including poly(GR), whose mechanisms of action remain largely unknown. In an RNA-seq analysis of poly(GR) toxicity in Drosophila, we found that several antimicrobial peptide genes, such as metchnikowin (Mtk), and heat shock protein (Hsp) genes are activated.

Dextran/eudragit S-100 based redox sensitive nanoparticles for colorectal cancer therapy.

Herein, we present disulfide crosslinked dextran/eudragit S-100 nanoparticles (DEEU NPs) (≈55 nm) for colorectal cancer treatment. These redox environment sensitive DEEU NPs are synthesized by simple oxidation of thiolated polymers in air. This approach allows avoiding the use of any additional chemical crosslinker.

The development and efficacy of a paediatric cardiology fellowship online preparatory course.

Background: The transition from residency to paediatric cardiology fellowship is challenging due to the new knowledge and technical skills required. Online learning can be an effective didactic modality that can be widely accessed by trainees. We sought to evaluate the effectiveness of a paediatric cardiology Fellowship Online Preparatory Course prior to the start of fellowship.

Functional assessment of atrial wall excursion and foramen ovale flap tracings in 3rd trimester as predictor of short-term hemodynamic stability in congenital heart defects fetuses.

Objectives: Right atrium and left atrium of the fetal heart play a fundamental role in fetal heart circulatory physiology.

Methods: Excursion of fetal atria walls and tracings of foramen ovale (FO) flap movement were analyzed by M-mode echocardiography by new FO index to determine fetal and neonatal outcome in the first week and month of life in various congenital heart defects. The study group was divided into 3 subgroups: group A: neonates stable after birth (all on I.

Retrotransposon activation during Drosophila metamorphosis conditions adult antiviral responses.

Retrotransposons are one type of mobile genetic element that abundantly reside in the genomes of nearly all animals. Their uncontrolled activation is linked to sterility, cancer and other pathologies, thereby being largely considered detrimental. Here we report that, within a specific time window of development, retrotransposon activation can license the host's immune system for future antiviral responses.

sabotages host cell SUMOylation for intracellular survival.

parasites use elaborate virulence mechanisms to invade and thrive in macrophages. These virulence mechanisms inhibit host cell defense responses and generate a specialized replicative niche, the parasitophorous vacuole. In this work, we performed a genome-wide RNAi screen in macrophage-like cells to identify the host factors necessary for infection.

The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways.

Interleukin-1 receptor-associated kinases (IRAKs) -4, -2, and -1 are involved in transducing signals from Toll-like receptors (TLRs) via the adaptor myeloid differentiation primary-response protein 88 (MYD88). How MYD88/IRAK4/2/1 complexes are formed, their redundancies, and potential non-enzymatic roles are subjects of debate. Here, we examine the hierarchical requirements for IRAK proteins in the context of TLR4 activation and confirmed that the kinase activity of IRAK4 is essential for MYD88 signaling.

Biodegradable disulfide crosslinked chitosan/stearic acid nanoparticles for dual drug delivery for colorectal cancer.

Herein, redox responsive chitosan/stearic acid nanoparticles (CSSA NPs) (≈200 nm) are developed for dual drug delivery. These degradable nanoparticles are prepared based on disulfide (SS) crosslinking chemistry avoiding the use of any external crosslinking agent. CSSA NPs are further loaded with both DOX (hydrophilic) and curcumin (hydrophobic) drugs with ≈86 % and ≈82 % encapsulation efficiency respectively.

The spatial variability of NDVI within a wheat field: Information content and implications for yield and grain protein monitoring.

Wheat is a staple crop that is critical for feeding a hungry and growing planet, but its nutritive value has declined as global temperatures have warmed. The price offered to producers depends not only on yield but also grain protein content (GPC), which are often negatively related at the field scale but can positively covary depending in part on management strategies, emphasizing the need to understand their variability within individual fields. We measured yield and GPC in a winter wheat field in Sun River, Montana, USA, and tested the ability of normalized difference vegetation index (NDVI) measurements from an unoccupied aerial vehicle (UAV) on spatial scales of ~10 cm and from Landsat on spatial scales of 30 m to predict them.

Risk Factors for Measles Nonimmunity in Rubella-Immune Pregnant Patients.

Objective: Measles immunity testing, unlike that for rubella, is not currently part of prenatal screening even though immunity to both is conferred by the measles-mumps-rubella (MMR) vaccine. Although endemic transmission of measles was declared eliminated in the United States in 2001, outbreaks have continued to occur. Given the risks associated with measles infection during pregnancy, we sought to identify risk factors for measles nonimmunity (MNI) in rubella-immune (RI) pregnant individuals.

Breaking the Rules: Left Common Carotid Artery from the Main Pulmonary Artery in an Infant with a Vascular Ring.

Anomalous left common carotid artery is a unique and rare abnormality. Most aortic arch anomalies can be explained by the totipotential aortic arch. Rare anomalies may not fit traditional arch regression models.

Prenatally diagnosed pseudoaneurysm of mitral-aortic intervalvular fibrous area.

The mitral-aortic intervalvular fibrosa (MAIVF) is an avascular, fibrous structure that provides continuity between the anterior leaflet of the mitral valve and the aortic valve. Pseudoaneurysm of the MAIVF is rare and has been most commonly described in adults and, more rarely, in children following cardiac surgery or endocarditis. Few reports have been published on cases with congenital pseudoaneurysm of the MAIVF.