An Observational Study of Paediatric Preoperative Transfusion Practice in a Resource-Limited Setting

World Journal of Surgery - Paediatric anaemia is highly prevalent in low–middle-income countries and can negatively impact postoperative outcomes. Currently, there are no guidelines for the...     

Effectiveness of delayed second dose of AZD1222 vaccine in patients with autoimmune rheumatic disease

Clinical Rheumatology - There is paucity of data on extended dosing interval between two doses of AZD1222 (AstraZeneca) in patients with Autoimmune Rheumatic Diseases (AIRD). We aimed to study the...     

TNF-Alpha Gene Polymorphisms in Iranian Azari Turkish Patients with Inflammatory Bowel Diseases

Context:

Crohn''s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the bowel (IBD) whose causes are not fully known. Emerging data indicate that alterations in cytokine synthesis may play a role in IBD pathogenesis.

Aims:

We aimed to determine the association between tumor necrosis factor-alfa (TNFα) promoter polymorphisms (at positions − 308 and − 1031) and susceptibility to IBD among Iranian Azari Turkish patients.

Settings and Design:

One hundred and one patients with IBD and 100 healthy subjects were analyzed.

Materials and Methods:

Both polymorphisms in the promoter region of the TNFα gene at positions -1031T/C and -308G/A were detected by polymerase chain reaction-restriction fragment length polymorphism assay. All statistical analyses were calculated with SPSS for Windows 16.0. The Fisher''s exact test was used to test for departure from Hardy–Weinberg equilibrium of the genotype frequencies (P > 0.05).

Results:

The allele frequency of the TNFα-308G and -1031T were higher in IBD patients but did not reach statistical significance. However, the homozygous TT genotype for the SNP-1031 T > C was significantly higher in UC patients than in healthy controls (P = 0.01) and the heterozygous CT genotype for the SNP -1031 T > C was significantly lower in UC patients than in healthy controls (P = 0.03).

Conclusions:

The TNFα-1031 T allele confers a significant risk for developing UC in Iranian Azeri Turkish patients. Also the frequency of TNFα-1031 C allele was considerably low among patients with UC and it may have protective role among them (OR = 0.43; P = 0.01).     

Proteome response to ochratoxin A-induced apoptotic cell death in mouse hippocampal HT22 cells

Mycotoxins are commonly encountered natural products, and are capable of poisoning animals or humans that inhale mold particles from mycotoxin-contaminated foods. Ochratoxin A (OTA) is produced by Aspergillu ochracus and Penicillium verrucosum, and is often found in cereals and agricultural products. Although previous studies have focused on the potent nephrotoxicity and renal carcinogenicity of OTA, more recent studies suggest that it accumulates in the brain and causes oxidative stress and DNA damage in various brain regions and neuronal populations. In the present study, we undertook to investigate the potential harm caused by environmental exposure to OTA in terms of its effects on neuronal cell viability and proteome profiles. OTA was found to significantly reduce the viabilities of human neuroblastoma SH-SY5Y and mouse hippocampal HT22 cells, as assessed by lactic dehydrogenase release into culture media. Generation of reactive oxygen species was detected in OTA-treated SH-SY5Y and HT22 cells, however, caspase activation and increase in p53 phosphorylation were only detected in HT22 cells, and the expressions of several proteins were found to be significantly altered after treating HT22 cells with OTA. Valosin containing protein, prolyl 4-hydroxylase, Atp5b protein, nucleophosmin 1, eukaryotic translation elongation factor 1 delta isoform, ornithine aminotransferase, prohibitin, and peroxiredoxin 6, which have been suggested to be implicated in the pathogenesis of neurodegenerative disorders, were up-regulated. Our findings suggest that coordinated regulations of molecular networks are involved in the OTA-induced cytotoxicity and that proteome response can be an indicative for neurodegeneration.     

Efficacy of rituximab in resistant palindromic rheumatism: first report in literature

Clinical Rheumatology - Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data...     

Novel NTRK1 mutations associated with congenital insensitivity to pain with anhidrosis verified by functional studies

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV, features loss of pain sensation, decreased or absent sweating (anhidrosis), recurrent episodes of unexplained fever, self‐mutilating behavior, and variable mental retardation. Mutations in neurotrophic receptor tyrosine kinase 1 (NTRK1) have been reported to be associated with CIPA. We identified four novel NTRK1 mutations in six Korean patients from four unrelated families. Of the four mutations, we demonstrated using a splicing assay that IVS14+3A>T causes aberrant splicing of NTRK1 mRNA, leading to introduction of a premature termination codon. An NTRK1 autophosphorylation assay showed that c.1786G>A (p.Asp596Asn) abolished autophosphorylation of NTRK1. In addition, Western blotting showed that c.704C>G (p.Ser235*) and c.2350_2363del (p.Leu784Serfs*79) blunted NTRK1 expression to undetectable levels. The four novel NTRK1 mutations we report here will expand the repertoire of NTRK1 mutations in CIPA patients, and further our understanding of CIPA pathogenesis.     

KITENIN-targeting MicroRNA-124 Suppresses Colorectal Cancer Cell Motility and Tumorigenesis

MicroRNAs are increasingly implicated in the modulation of the progression of various cancers. We previously observed that KAI1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in sporadic human colorectal cancer (CRC) tissues and hence the functional KITENIN complex acts to promote progression of CRC. However, it remains unknown that microRNAs target KITENIN and whether KITENIN-targeting microRNAs modulate CRC cell motility and colorectal tumorigenesis. Here, through bioinformatic analyses and functional studies, we showed that miR-124, miR-27a, and miR-30b negatively regulate KITENIN expression and suppress the migration and invasion of several CRC cell lines via modulation of KITENIN expression. Through in vitro and in vivo induction of mature microRNAs using a tetracycline-inducible system, miR-124 was found to effectively inhibit the invasion of CT-26 colon adenocarcinoma cells and tumor growth in a syngeneic mouse xenograft model. Constitutive overexpression of precursor miR-124 in CT-26 cells suppressed in vivo tumorigenicity and resulted in decreased expression of KITENIN as well as that of MYH9 and SOX9, which are targets of miR-124. Thus, our findings identify that KITENIN-targeting miR-124, miR-27a, and miR-30b function as endogenous inhibitors of CRC cell motility and demonstrate that miR-124 among KITENIN-targeting microRNAs plays a suppressor role in colorectal tumorigenesis.     

Serial evaluation of myocardial function using the myocardial performance index in Kawasaki disease

Background

Kawasaki disease (KD) is known as systemic vasculitis, and more than half of the patients with KD have myocarditis, which can induce ventricular dysfunction. In this study, we evaluate left ventricular (LV) dysfunction in patients with KD based on the myocardial performance index (MPI) using pulse Doppler (PD) and tissue Doppler imaging (TDI), from the acute to convalescent phases.

Methods

We retrospectively studied 89 children diagnosed with KD from January 2010 to August 2012. We assessed the presence of coronary artery lesions (CALs) and the LV ejection fraction, PD-MPI, and TDI-MPI at diagnosis, and 2, 14, and 56 days after intravenous immunoglobulin (IVIG) treatment. We enrolled 70 healthy children as a control group.

Results

The ejection fraction in patients with KD at diagnosis (67.3 ± 0.9%) was lower than that in the control group (69.8 ± 0.8%, P = 0.035), and the LV TDI-MPIs for patients with KD at diagnosis (0.49 ± 0.01) and 2 days after IVIG treatment (0.48 ± 0.01) were higher than those in the control group (0.45 ± 0.01, P = 0.002, P = 0.033, respectively). No significant differences were found in the LV dysfunction between the patients with complete and incomplete KD. Septal TDI-MPIs in patients with KD with CAL at diagnosis (0.52 ± 0.02) were higher than those in patients with KD without CAL (0.47 ± 0.01, P = 0.019).

Conclusions

Transient LV dysfunction occurred in patients with complete and incomplete KD in the acute stage. In patients with KD with CAL at diagnosis, the LV dysfunction was more prominent. The PD-MPI and TDI-MPI are useful parameters for assessing LV function in patients with KD.