Lessons identified from initiating a thalassaemia programme in a conflict setting: a case study from northeast Syria.

Background: Thalassaemia affects many families in Northeast Syria, an area devastated by over a decade of conflict which has significantly impacted their health system. People with thalassaemia require holistic multidisciplinary care for the clinical complications of thalassaemia. The risks of thalassaemia treatment include blood-borne viral infections secondary to unsafe transfusion, increased vulnerability to serious bacterial infection following splenectomy, and complications of both iron overload and iron chelation therapy.

Mumps-specific IgG, IgG subclasses and neutralization titres to the vaccine and outbreak mumps strains differ in vaccinated healthy controls, breakthrough mumps infection cases and naturally infected individuals.

Background: Despite widespread use of the mumps vaccine resulting in significant reduction in the incidence of symptomatic mumps infection, large outbreaks continue to occur in highly vaccinated populations.

Objectives: We examined the mumps-specific IgG, IgG subclasses and neutralization titres to the outbreak Genotype G5 and Jeryl Lynn vaccine (Genotype A) mumps strains.

Study Design: Sera from 207 individuals were classified into five distinct cohorts: healthy controls and mumps cases of 5-17 years and 18-25 years, and naturally infected individuals of 50+ years.

The psychological impact of childhood homelessness-a literature review.

In August 2019, 3848 children in Ireland were faced with emergency homelessness [1]. In recent years, lack of affordable housing, unemployment and shortage of rental properties have been the primary driving factors for the potentially devastating impact of familial homelessness in our society [1]. Our aim was to evaluate current knowledge on the psychological impact of homelessness in children.

Physical illnesses associated with childhood homelessness: a literature review.

Background: Childhood homelessness is a growing concern in Ireland [1] creating a paediatric subpopulation at increased risk of physical illnesses, many with life-long consequences [2].

Aim: Our aim was to identify and categorize the physical morbidities prevalent in homeless children.

Methods: A review of the English-language literature on physical morbidities affecting homeless children (defined as ≤ 18 years of age) published from 1999 to 2019 was conducted.

Readmission to hospital following laparoscopic cholecystectomy: a meta-analysis.

Background: Laparoscopic cholecystectomy (LC) is one of the most commonly performed surgical procedures. Despite this, patterns of readmission following LC are not well defined. This meta-analysis aimed to determine rates and predictors of readmission.

Inhibition of NGLY1 Inactivates the Transcription Factor Nrf1 and Potentiates Proteasome Inhibitor Cytotoxicity.

Proteasome inhibitors are used to treat blood cancers such as multiple myeloma (MM) and mantle cell lymphoma. The efficacy of these drugs is frequently undermined by acquired resistance. One mechanism of proteasome inhibitor resistance may involve the transcription factor Nuclear Factor, Erythroid 2 Like 1 (NFE2L1, also referred to as Nrf1), which responds to proteasome insufficiency or pharmacological inhibition by upregulating proteasome subunit gene expression.

Complementary Assays Reveal a Low Level of CA Associated with Viral Complexes in the Nuclei of HIV-1-Infected Cells.

Unlabelled: During uncoating, the conical capsid of HIV disassembles by dissociation of the p24 capsid protein (CA). Uncoating is known to be required for HIV replication, but the mechanism is poorly defined. Here, we examined the timing and effect of two capsid binding drugs (PF74 and BI2) on infectivity and capsid integrity in HIV-1-infected cells.

The polysialyltransferases interact with sequences in two domains of the neural cell adhesion molecule to allow its polysialylation.

The neural cell adhesion molecule (NCAM) is the major substrate for the polysialyltransferases (polySTs), ST8SiaII/STX and ST8SiaIV/PST. The polysialylation of NCAM N-glycans decreases cell adhesion and alters signaling. Previous work demonstrated that the first fibronectin type III repeat (FN1) of NCAM is required for polyST recognition and the polysialylation of the N-glycans on the adjacent Ig5 domain.

Sequences at the interface of the fifth immunoglobulin domain and first fibronectin type III repeat of the neural cell adhesion molecule are critical for its polysialylation.

Polysialic acid is an anti-adhesive glycan that modifies a select group of mammalian proteins. The primary substrate of the polysialyltransferases (polySTs) is the neural cell adhesion molecule (NCAM). Polysialic acid negatively regulates cell adhesion, is required for proper brain development, and is expressed in specific areas of the adult brain where it promotes on-going cell migration and synaptic plasticity.

Sequences from the first fibronectin type III repeat of the neural cell adhesion molecule allow O-glycan polysialylation of an adhesion molecule chimera.

Polysialic acid is a developmentally regulated, anti-adhesive polymer that is added to N-glycans on the fifth immunoglobulin domain (Ig5) of the neural cell adhesion molecule (NCAM). We found that the first fibronectin type III repeat (FN1) of NCAM is required for the polysialylation of N-glycans on the adjacent Ig5 domain, and we proposed that the polysialyltransferases recognize specific sequences in FN1 to position themselves for Ig5 N-glycan polysialylation. Other studies identified a novel FN1 acidic surface patch and α-helix that play roles in NCAM polysialylation.

Structure and mutagenesis of neural cell adhesion molecule domains: evidence for flexibility in the placement of polysialic acid attachment sites.

The addition of alpha2,8-polysialic acid to the N-glycans of the neural cell adhesion molecule, NCAM, is critical for brain development and plays roles in synaptic plasticity, learning and memory, neuronal regeneration, and the growth and invasiveness of cancer cells. Our previous work indicates that the polysialylation of two N-glycans located on the fifth immunoglobulin domain (Ig5) of NCAM requires the presence of specific sequences in the adjacent fibronectin type III repeat (FN1). To understand the relationship of these two domains, we have solved the crystal structure of the NCAM Ig5-FN1 tandem.

Identification of sequences in the polysialyltransferases ST8Sia II and ST8Sia IV that are required for the protein-specific polysialylation of the neural cell adhesion molecule, NCAM.

The polysialyltransferases ST8Sia II and ST8Sia IV polysialylate the glycans of a small subset of mammalian proteins. Their most abundant substrate is the neural cell adhesion molecule (NCAM). An acidic surface patch and a novel alpha-helix in the first fibronectin type III repeat of NCAM are required for the polysialylation of N-glycans on the adjacent immunoglobulin domain.

Use of a panel of novel genes for differentiating breast cancer from non-breast tissues.

Existing serum markers for breast cancer such as CA 15-3, BR 27.29 and CEA lack sensitivity and specificity. The aim of this study was to evaluate the value of new putative breast-specific markers for differentiating breast cancer from non-breast tissues.

Membrane topology of the endoplasmic reticulum to Golgi transport factor Erv29p.

Secretory proteins are transported from the endoplasmic reticulum to the Golgi apparatus via COPII-coated intermediates. Yeast Erv29p is a transmembrane protein cycling between these compartments. It is conserved across species, with one ortholog found in each genome studied, including the surf-4 protein in mammals.

Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.

Background: Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin.