Cytomegalovirus enteritis in immunocompetent patients: Report of two cases diagnosed using single-balloon enteroscopy

SummaryCytomegalovirus (CMV) infection of the gastrointestinal tract involves mostly the colon and rectum and mainly develops in immunocompromised patients. CMV infection in the small intestines has rarely been reported in immunocompetent patients. We report two cases of CMV enteritis that developed in immunocompetent patients and involved the ileum and jejunum, respectively. Both of them were diagnosed with single-balloon enteroscopy (SBE) and further confirmed with histopathology. The first case is a 71-year-old woman with a presentation of obscure gastrointestinal bleeding and severe anemia. Neither esophagogastroduodenoscopy nor colonoscopy identified any active bleeding. SBE and biopsy disclosed multiple scattered ulcers in the distal ileum and histopathology confirmed CMV ileitis. The hemorrhage subsided after conservative medical treatment. The second case is a 59-year-old woman with a presentation of progressive abdominal pain. SBE showed diffuse irregularly-shaped ulcers located from the upper to middle jejunum, and CMV jejunitis was confirmed with endoscopic biopsy and histopathological examination. Antiviral therapy was prescribed and her abdominal pain improved gradually. We discuss the clinical manifestations and management strategies of CMV infection that develops in the small intestines of immunocompetent patients. In addition, we highlight the endoscopic characteristics of CMV enteritis and the clinical utilities of SBE in the evaluation of patients with suspected CMV infection of the small intestines

Anatomical Asymmetry in Goiter: A Demonstration by Three-dimensional Power Doppler Ultrasound

The aim of the present study was to examine the anatomical differences in volumetric and intraparenchymal vascular parameters between the two thyroid lobes of patients with goiter, using three-dimensional power Doppler ultrasound. A total of 89 outpatients with goiter, including 55 with autoimmune thyroid disease (ATD) and 34 with simple goiter (SG), were evaluated by three-dimensional power Doppler ultrasound. Volumetric and intraparenchymal vascular indices including vascularization index, flow index and vascular flow index of each lobe were measured using the Virtual Organ Computer-Aided Analysis system. In all patients with goiter, the volume and vascular indices (vascularization index, flow index and vascular flow index) of the right thyroid lobe were significantly greater than those of the left lobe (p < 0.05). Differences in vascular indices were present in SG but not in ATD. ATD was associated with a larger thyroid volume and higher vascular indices compared with those of SG (p < 0.001), but there were no significant differences in volumetry and vascular indices between euthyroid ATD and SG. In conclusion, the right thyroid lobe was found to be significantly larger and more vascular than the left lobe in subjects with goiter, as measured by three-dimensional power Doppler ultrasound. In addition, ATD was associated with a higher thyroid volume and vascular indices compared with those of SG

Establishment of a Knock-In Mouse Model with the SLC26A4 c.919-2A>G Mutation and Characterization of Its Pathology

Recessive mutations in the SLC26A4 gene are a common cause of hereditary hearing impairment worldwide. Previous studies have demonstrated that different SLC26A4 mutations may have different pathogenetic mechanisms. In the present study, we established a knock-in mouse model (i.e., Slc26a4tm1Dontuh/tm1Dontuh mice) homozygous for the c.919-2A>G mutation, which is a common mutation in East Asians. Mice were then subjected to audiologic assessment, a battery of vestibular evaluations, and inner ear morphological studies. All Slc26a4tm1Dontuh/tm1Dontuh mice revealed profound hearing loss, whereas 46% mice demonstrated pronounced head tilting and circling behaviors. There was a significant difference in the vestibular performance between wild-type and Slc26a4tm1Dontuh/tm1Dontuh mice, especially those exhibiting circling behavior. Inner ear morphological examination of Slc26a4tm1Dontuh/tm1Dontuh mice revealed an enlarged endolymphatic duct, vestibular aqueduct and sac, atrophy of stria vascularis, deformity of otoconia in the vestibular organs, consistent degeneration of cochlear hair cells, and variable degeneration of vestibular hair cells. Audiologic and inner ear morphological features of Slc26a4tm1Dontuh/tm1Dontuh mice were reminiscent of those observed in humans. These features were also similar to those previously reported in both knock-out Slc26a4−/− mice and Slc26a4loop/loop mice with the Slc26a4 p.S408F mutation, albeit the severity of vestibular hair cell degeneration appeared different among the three mouse strains

High-level expression and molecular characterization of a recombinant prolidase from Escherichia coli NovaBlue

Long-term use of organophosphorus (OP) compounds has become an increasing global problem and a major threat to sustainability and human health. Prolidase is a proline-specific metallopeptidase that can offer an efficient option for the degradation of OP compounds. In this study, a full-length gene from Escherichia coli NovaBlue encoding a prolidase (EcPepQ) was amplified and cloned into the commercially-available vector pQE-30 to yield pQE-EcPepQ. The overexpressed enzyme was purified from the cell-free extract of isopropyl thio-β-D-galactoside IPTG-induced E. coli M15 (pQE-EcPepQ) cells by nickel-chelate chromatography. The molecular mass of EcPepQ was determined to be about 57 kDa by 12% sodium dodecyl sulfate–polyacrylamide gel electrophoresis and the result of size-exclusion chromatography demonstrated that the enzyme was mainly present in 25 mM Tris–HCl buffer (pH 8.0) as a dimeric form. The optimal conditions for EcPepQ activity were 60 °C, pH 8.0, and 0.1 mM Mn2+ ion. Kinetic analysis with Ala-Pro as the substrate showed that the Km and kcat values of EcPepQ were 8.8 mM and 926.5 ± 2.0 s−1, respectively. The thermal unfolding of EcPepQ followed a two-state process with one well-defined unfolding transition of 64.2 °C. Analysis of guanidine hydrochloride (GdnHCl)-induced denaturation by tryptophan emission fluorescence spectroscopy revealed that the enzyme had a [GdnHCl]0.5,N-U value of 1.98 M. The purified enzyme also exhibited some degree of tolerance to various water/organic co-solvents. Isopropanol and tetrahydrofuran were very detrimental to the enzymatic activity of EcPepQ; however, other more hydrophilic co-solvents, such as formamide, methanol, and ethylene glycol, were better tolerated. Eventually, the non-negative influence of some co-solvents on both catalytic activity and structural stability of EcPepQ allows to adjust the reaction conditions more suitable for EcPepQ-catalyzed bioprocess

Small-Size Meandered Loop Antenna for WLAN Dongle Devices

This paper proposes a loop-type USB dongle antenna, which is fabricated on a 1.6 mm thick FR-4 substrate for WLAN band systems. The front side of substrate consists of a 50-ohm coaxial line and a multiarm monopole antenna, while the back side has a meandered loop antenna connected to the ground by two via holes. The meandered loop resonates half-wavelength mode at about 2.4 GHz and its higher modes. The higher modes excited by the multiarm monopole form the 5.2 GHz frequency band. The bandwidth of the antenna covers the IEEE802.11 a/b/g WLAN applications. The overall dimensions of the antenna of 30 × 13.75 × 1.6 mm3 with an antenna area of 7.5 × 13.75 mm2 and a planar structure are exactly suitable for applying in dongle devices. The measured results of radiation patterns, antenna gain, and radiation efficiency are also proposed and discussed in the paper

Mycena genomes resolve the evolution of fungal bioluminescence

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life; yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies similar to 150 Mb are among the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were coexpressed across developmental stages, with the highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species

Identification of novel DNA methylation inhibitors via a two-component reporter gene system

<p>Abstract</p> <p>Background</p> <p>Targeting abnormal DNA methylation represents a therapeutically relevant strategy for cancer treatment as demonstrated by the US Food and Drug Administration approval of the DNA methyltransferase inhibitors azacytidine and 5-aza-2'-deoxycytidine for the treatment of myelodysplastic syndromes. But their use is associated with increased incidences of bone marrow suppression. Alternatively, procainamide has emerged as a potential DNA demethylating agent for clinical translation. While procainamide is much safer than 5-aza-2'-deoxycytidine, it requires high concentrations to be effective in DNA demethylation in suppressing cancer cell growth. Thus, our laboratories have embarked on the pharmacological exploitation of procainamide to develop potent DNA methylation inhibitors through lead optimization.</p> <p>Methods</p> <p>We report the use of a DNA methylation two-component enhanced green fluorescent protein reporter system as a screening platform to identify novel DNA methylation inhibitors from a compound library containing procainamide derivatives.</p> <p>Results</p> <p>A lead agent IM25, which exhibits substantially higher potency in <it>GSTp1 </it>DNA demethylation with lower cytotoxicity in MCF7 cells relative to procainamide and 5-aza-2'-deoxycytidine, was identified by the screening platform.</p> <p>Conclusions</p> <p>Our data provide a proof-of-concept that procainamide could be pharmacologically exploited to develop novel DNA methylation inhibitors, of which the translational potential in cancer therapy/prevention is currently under investigation.</p

Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization

Is the level of serum lactate dehydrogenase a potential biomarker for glucose monitoring with type 2 diabetes mellitus?

IntroductionType 2 diabetes mellitus (T2DM) is a metabolic disorder due to defects in insulin secretion or insulin resistance leading to the dysfunction and damage of various organs. To improve the clinical evaluation of short-term blood glycemic variability monitoring, it is critical to identify another blood cell status and nutritional status biomarker that is less susceptible to interference. This study identifies the significance of serum lactate dehydrogenase (LDH) level among T2DM patients treated in outpatient clinics and investigates the relationship of LDH level with other variables.MethodsThis study comprised 72 outpatients with T2DM over 20 years of age. Blood samples were collected followed by a hematological analysis of serum glycated albumin (GA), LDH, fasting blood glucose, glycosylated hemoglobin, C-peptide, and insulin antibodies (insulin Ab).ResultsSerum LDH level was significantly correlated with GA (p &lt; 0.001), C-peptide (p = 0.04), insulin Ab (p = 0.03), and thyroid-stimulating hormone (TSH) levels (p = 0.04). Hence, we performed a linear regression analysis of hematological markers. GA (p &lt; 0.001, r2 = 0.45) and insulin Ab (p &lt; 0.001, r2 = 0.40) were significantly associated with LDH level. Then, we classified patients into low (&lt;200 U/L) and high (≥200 U/L) serum LDH level groups, respectively. GA (p &lt; 0.001), C-peptide (p = 0.001), and TSH (p = 0.03) showed significant differences in patients with high LDH levels compared with those in patients with low LDH levels.ConclusionIn conclusion, we suggested that LDH level was independent of long-term but associated with short-term blood glucose monitoring. The results indicated that changes in serum GA induced cell damage and the abnormal elevation of the serum level of LDH may occur simultaneously with glycemic variability. It has been reported that many biomarkers are being used to observe glucose variability in T2DM. However, LDH could provide a more convenient and faster evaluation of glycemic variability in T2DM

Postchemoradiotherapy Pathologic Stage Classified by the American Joint Committee on the Cancer Staging System Predicts Prognosis of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

IntroductionTo determine whether the postchemoradiotherapy (post-CRT) pathologic stage predicts the outcomes of patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT followed by surgery.MethodsFrom three phase II trials of preoperative CRT for locally advanced ESCC, 140 patients were included. Preoperative CRT comprised twice weekly paclitaxel and cisplatin-based regimens and 40-Gy radiotherapy in 20 fractions. The post-CRT pathologic stage was classified according to the American Joint Committee on Cancer, 7th edition staging system. The prognostic effects of clinicopathologic factors were analyzed using Cox regression.ResultsWith a median follow-up of 61.9 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 24.5 and 30.9 months, respectively. The post-CRT pathologic stage was 0 in 34.5%, I in 12.9%, II in 29.3%, III in 13.6%, and ypT0N1-2 in 6.4% of the patients. The median PFS was 47.2, 25.9, 16.0, 9.4, and 15.1 months, and the median OS was 57.4, 34.1, 26.2, 14.1, and 17.6 months for patients with post-CRT pathologic stage 0, I, II, III, and ypT0N1-2, respectively. In multivariate analysis, performance status (p < 0.001), tumor location (p = 0.016), and extranodal extension (p = 0.024) were independent prognostic factors for PFS, whereas performance status (p < 0.001) and post-CRT pathologic stage (p = 0.027) were independent prognostic factors for OS.ConclusionsThe post-CRT pathologic stage classified by American Joint Committee on Cancer, 7th edition staging system predicted the survival of locally advanced ESCC patients who underwent preoperative paclitaxel and cisplatin-based CRT followed by esophagectomy