Diligent Design Enables Antibody-ASO Conjugates with Optimal Pharmacokinetic Properties.

Antisense-oligonucleotides (ASOs) are a promising drug modality for the treatment of neurological disorders, but the currently established route of administration intrathecal delivery is a major limitation to its broader clinical application. An attractive alternative is the conjugation of the ASO to an antibody that facilitates access to the central nervous system (CNS) after peripheral application and target engagement at the blood-brain barrier, followed by transcytosis. Here, we show that the diligent conjugate design of Brainshuttle-ASO conjugates is the key to generating promising delivery vehicles and thereby establishing design principles to create optimized molecules with drug-like properties.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

Background: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility.

Methods: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

Background: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported.

Objectives: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1β, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia.

Potential role of circulating microRNAs (486-5p, 497, 509-5p and 605) in metabolic syndrome Egyptian male patients.

This study aims to evaluate the expression pattern of circulating microRNAs (miR)-486-5p, miR-497, miR-509-5p, and miR-605 in the serum of metabolic syndrome (MetS) Egyptian male patients. In this study, the circulating miR-486-5p, miR-497, miR509-5p, and miR-605 were amplified and quantitatively detected by quantitative real-time polymerase chain reaction in sera of 55 MetS male patients in comparison to 20 male controls. The level of fasting plasma glucose and triacylglycerol (TAG) were measured using calorimetric assay.

Transversus Abdominis Plane Block Versus Wound Infiltration for Analgesia After Cesarean Delivery: A Randomized Controlled Trial.

Background: Transversus abdominis plane (TAP) block and local anesthetic wound infiltration provide analgesia after cesarean delivery. Studies comparing the 2 techniques are scarce, with conflicting results. This double-blind, randomized controlled trial aimed to compare bilateral ultrasound-guided TAP block with single-shot local anesthetic wound infiltration for analgesia after cesarean delivery performed under spinal anesthesia.

Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition.

Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation.

Brucellosis in Qatar: A retrospective cohort study.

Background: We conducted a retrospective cohort study to evaluate the clinical manifestations, laboratory findings, complications and treatment of brucellosis in the State of Qatar.

Methods: The medical records of patients in Hamad Medical Corporation, Doha, Qatar were reviewed from January 2000 to December 2006. History, various socio-demographic features, clinical and biochemical parameters, therapeutic features, and complications were retrospectively collected from the patient database.