Whole‐exome sequencing of a unique brain malformation with periventricular heterotopia,cingulate polymicrogyria and midbrain tectal hyperplasia

We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR‐based sequencing. Whole‐exome sequencing confirmed the presence of novel gene variants for filamin B (FLNB), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X‐linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.     

One-phase vs 2-phase treatment for developing Class III malocclusion: A comparison of identical twins

Despite the known influence of early treatment on the facial appearance of growing patients with skeletal Class III malocclusion, few comparative reports on the long-term effects of different treatment regimens (1-phase vs 2-phase treatment) have been published. Uncertainty remains regarding the effects of early intervention on jaw growth and its effectiveness and efficiency in the long term. In this case report, we compared the effects of early orthodontic intervention as the first phase of a 2-phase treatment vs 1-phase fixed appliance treatment in identical twins over a period of 11 years. Facial and dental changes were recorded, and cephalometric superimpositions were made at 4 time points. In spite of the different treatment approaches, both patients showed identical dentofacial characteristics in the retention phase. Through this case report, we intended to clarify the benefits of undergoing 1-phase treatment against 2-phase treatment protocols for treating growing skeletal Class III patients.     

Incidence of tacrolimus-induced gingival overgrowth in the absence of calcium channel blockers: a short-term study

AIM: The aim of this study was to determine the incidence and severity of gingival overgrowth (GO) induced by tacrolimus (Tcr) compared with ciclosporin A (CiA) in the absence of calcium channel blockers (CCB) in renal transplant recipients. METHODS: Forty patients (20 Tcr and 20 CiA) were evaluated before and 30 and 90 days after kidney transplantation. Demographic (age, gender) and periodontal parameters were recorded for all patients. Patients taking CCB at any time during the study were excluded from the investigation. RESULTS: The mean GO score was significantly lower (p=0.014) in the Tcr group (6.4%) compared with the CiA group (17.9%) after 90 days of immunosuppressive therapy. At 90 days post-transplant, clinically significant GO was observed in four patients of the CiA group and in two of the Tcr group. This difference was not statistically significant (0.66). CONCLUSION: No significant difference in the incidence of clinically significant GO was observed between the CiA and Tcr groups up to 90 days of immunosuppressive therapy.     

Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice

High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.     

Prognostic Significance of Hiatal Hernia in Patients with Gastric Cancer Located within the Upper-Third of the Stomach

World Journal of Surgery - Gastric cancers located within the upper-third of the stomach (UGC), especially the esophagogastric junction GC (EGJGC), have distinct clinicopathological features due to...     

Castration-resistant prostate cancer without metastasis at presentation may achieve cancer-specific survival in patients who underwent prior radical prostatectomy

International Urology and Nephrology - Radical prostatectomy (RP) is relatively better oncological outcomes in patients with prostate cancer (PCa). However, the incidence of castration-resistant...     

Fibrosing Cholestatic Hepatitis Developing within One Month after Living Donor Liver Transplantation for Chronic Hepatitis C-related Cirrhosis: A Case Report

Fibrosing cholestatic hepatitis (FCH) is a life-threatening consequence of hepatitis C virus (HCV) infection occurring in a small minority of liver transplantation (LT) recipients. We herein report a case of early-onset FCH after living donor LT in a 47-year-old woman with HCV-related cirrhosis. The patient underwent balloon-occluded retrograde transvenous obliteration of a splenorenal shunt to treat an impaired portal flow on the sixth postoperative day (POD 6) and a bypass operation for hepatic artery thrombosis on POD 12. Thereafter, the serum bilirubin levels increased gradually; however, computed tomography revealed no evidence of biliary stricture. The serum HCV-RNA level on POD 27 was >7.8 log IU/mL. Histopathology of a needle graft biopsy performed on POD 28 revealed FCH with extensive portal fibrosis accompanied by mild inflammation, hepatocyte ballooning, and ductular proliferation with cholestasis. The patient received combination therapy with pegylated interferon, ribavirin, and double-filtration plasmapheresis for the treatment of early-onset FCH. Both the recipient and the donor carried the major genotype single nucleotide polymorphism (TT) at rs8099917 near the interleukin-28B gene. Furthermore, the HCV genotype was treatment-sensitive 2a. Nonetheless, the recipient died of hepatic failure on POD 211. Thus far, few cases of FCH occurring within 1 month after LT have been reported. In addition, the early onset of FCH may be an adverse prognostic factor.     

Stem cell factor‐activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration

Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with motor neuron death. Several experimental treatments, including cell therapy using hematopoietic or neuronal stem cells, have been tested in ALS animal models, but therapeutic benefits have been modest. Here we used a new therapeutic strategy, bone marrow transplantation (BMT) with stem cell factor (SCF)‐ or FMS‐like tyrosine kinase 3 (flt3)‐activated bone marrow (BM) cells for the treatment of hSOD1(G93A) transgenic mice. Motor function and survival showed greater improvement in the SCF group than in the group receiving BM cells that had not been activated (BMT alone group), although no improvement was shown in the flt3 group. In addition, larger numbers of BM‐derived cells that expressed the microglia marker Iba1 migrated to the spinal cords of recipient mice compared with the BMT‐alone group. Moreover, after SCF activation, but not flt3 activation or no activation, the migrating microglia expressed glutamate transporter‐1 (GLT‐1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis factor‐α and interleukin‐1β were suppressed and the neuroprotective molecule insulin‐like growth factor‐1 increased relative to nontreatment hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of the migrating donor BM cells, which resulted in neuroprotective effects. These studies have identified SCF‐activated BM cells as a potential new therapeutic agent for the treatment of ALS. © 2014 Wiley Periodicals, Inc.