Investigating somatic variants and pathways in mismatch repair-deficient (dMMR) colorectal carcinoma in South Africa.

Aims: Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide, and an emerging public health problem in sub-Saharan Africa. Several authors have described an increased frequency of mismatch repair-deficient (dMMR) CRC in sub-Saharan Africa, but these tumours remain poorly characterised molecularly. We sought to interrogate the somatic molecular genetic landscape of dMMR CRC in a cohort of young patients to better inform Lynch syndrome (LS) screening strategies and personalised medicine approaches in our setting.

Relationship between infectious screening and early unconjugated hyperbilirubinemia in well-appearing neonates.

Background: Neonatal hyperbilirubinemia (NH) may be the initial and solitary sign of infectious condition in neonates. This retrospective cohort study aims to evaluate the risk of sepsis or urinary tract infection in well-appearing infants with NH below 7 days old.

Methods: All neonates (n = 8779) born in Taipei Veterans General Hospital from 2013 to 2017 were evaluated retrospectively.

Ability of preschoolers to achieve maximal exercise and its correlation with oxygen uptake efficiency slope ∼ an observational study by direct cardiopulmonary exercise testing.

The oxygen uptake efficiency slope (OUES) is a well-established substitute for maximum oxygen uptake ((Equation is included in full-text article.)O2 max) in submaximal exercise effort among adolescents and adults. Few studies have analyzed the exercise capacity (EC) and OUES of children aged 4 to 6 (preschoolers).

Oxygen uptake efficiency slope and peak oxygen consumption predict prognosis in children with tetralogy of Fallot.

Background: Oxygen uptake efficiency slope (OUES) and peak oxygen consumption (VO2peak) are exercise parameters that can predict cardiac morbidity in patients with numerous heart diseases. But the predictive value in patients with tetralogy of Fallot is still undetermined, especially in children. We evaluated the prognostic value of OUES and VO2peak in children with total repair of tetralogy of Fallot.

Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen.

Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia.

2-Aminopyrazolo[1,5-a]pyrimidines as potent and selective inhibitors of JAK2.

Constitutive activation of the EPO/JAK2 signaling cascade has recently been implicated in a variety of myeloproliferative disorders including polycythemia vera, essential thrombocythemia and myelofibrosis. In an effort to uncover therapeutic potential of blocking the EPO/JAK2 signaling cascade, we sought to discover selective inhibitors that block the kinase activity of JAK2. Herein, we describe the discovery and structure based optimization of a novel series of 2-amino-pyrazolo[1,5-a]pyrimidines that exhibit potent inhibition of JAK2.

Estrogen effects on skeletal muscle insulin-like growth factor 1 and myostatin in ovariectomized rats.

Previous work showed that estrogen replacement attenuates muscle growth in immature rats. The present study examined muscle insulin-like growth factor-1 (IGF-1) and myostatin expression to determine whether these growth regulators might be involved in mediating estrogen's effects on muscle growth. IGF-1 and myostatin message and protein expression in selected skeletal muscles from 7-week-old sham-ovariectomized (SHAM) and ovariectomized rats that received continuous estrogen (OVX/E2) or solvent vehicle (OVX/CO) from an implant for 1 week or 5 weeks was measured.

Estrogen response element-independent regulation of gene expression by genistein in intestinal cells.

Isoflavone, genistein, was shown to have antioxidant and antitumor activities. We have reported the stimulatory effect of genistein on the expression of antioxidant and metal-binding protein, metallothionein IIA (MTIIA), in human intestinal Caco-2 cells. Genistein has been shown to up-regulate the expression of other genes through estrogen response element (ERE) but the ERE sequence is not in the MTIIA promoter.