Influences of −482C&gt;T and 3238G&gt;C polymorphisms of the <Emphasis Type="Italic">Apolipoprotein C3</Emphasis> gene on prevalence of metabolic syndrome

Apolipoprotein C3 (ApoC3) plays a regulatory role in triglyceride (TG) metabolism. The higher level of TG can be a cause in pathogenesis of the vascular diseases or metabolic syndrome (MetS). In this study, we examined the associations of ApoC3 polymorphisms (?482C>T rs2854117 and 3238G>C rs5128) with Korean MetS patients. A total of 835 subjects were investigated, including 320 patients with MetS and 515 healthy subjects. The genotype analysis of the ApoC3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism methods. Of the two polymorphisms studied, we observed a significant difference in the ?482C>T polymorphism between the MetS and control groups. The TT genotype of the ?482C>T polymorphism was associated with increased risk for MetS, compared with the controls (OR 1.627, 95 % CI 1.075–2.463, P = 0.021). The association was female-specific. No associations were found for the risk of MetS in the 3238G>C polymorphism. Haplotypes composed of two polymorphisms, however, were associated with MetS susceptibility in only male group. The 3238G>C polymorphism was significantly associated with TG levels (P = 0.013). Our data suggest that the ApoC3 ?482C>T polymorphism is associated with increased MetS susceptibility in the Korean population.     

L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice

New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (T_CM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R⁺ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R⁺ T_CM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R⁺ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.     

Assessing Seasonal and Inter-Annual Variations of Lake Surface Areas in Mongolia during 2000-2011 Using Minimum Composite MODIS NDVI

A minimum composite method was applied to produce a 15-day interval normalized difference vegetation index (NDVI) dataset from Moderate Resolution Imaging Spectroradiometer (MODIS) daily 250 m reflectance in the red and near-infrared bands. This dataset was applied to determine lake surface areas in Mongolia. A total of 73 lakes greater than 6.25 km²in area were selected, and 28 of these lakes were used to evaluate detection errors. The minimum composite NDVI showed a better detection performance on lake water pixels than did the official MODIS 16-day 250 m NDVI based on a maximum composite method. The overall lake area detection performance based on the 15-day minimum composite NDVI showed -2.5% error relative to the Landsat-derived lake area for the 28 evaluated lakes. The errors increased with increases in the perimeter-to-area ratio but decreased with lake size over 10 km². The lake area decreased by -9.3% at an annual rate of -53.7 km² yr^-1 during 2000 to 2011 for the 73 lakes. However, considerable spatial variations, such as slight-to-moderate lake area reductions in semi-arid regions and rapid lake area reductions in arid regions, were also detected. This study demonstrated applicability of MODIS 250 m reflectance data for biweekly monitoring of lake area change and diagnosed considerable lake area reduction and its spatial variability in arid and semi-arid regions of Mongolia. Future studies are required for explaining reasons of lake area changes and their spatial variability.     

Altered Gut Microbiota Composition Associated with Eczema in Infants

Eczema is frequently the first manifestation of an atopic diathesis and alteration in the diversity of gut microbiota has been reported in infants with eczema. To identify specific bacterial communities associated with eczema, we conducted a case-control study of 50 infants with eczema (cases) and 51 healthy infants (controls). We performed high-throughput sequencing for V3–V4 hypervariable regions of the 16S rRNA genes from the gut fecal material. A total of 12,386 OTUs (operational taxonomic units) at a 97% similarity level were obtained from the two groups, and we observed a difference in taxa abundance, but not the taxonomic composition, of gut microbiota between the two groups. We identified four genera enriched in healthy infants: Bifidobacterium, Megasphaera, Haemophilus and Streptococcus; and five genera enriched in infants with eczema: Escherichia/Shigella, Veillonella, Faecalibacterium, Lachnospiraceae incertae sedis and Clostridium XlVa. Several species, such as Faecalibacterium prausnitzii and Ruminococcus gnavus, that are known to be associated with atopy or inflammation, were found to be significantly enriched in infants with eczema. Higher abundance of Akkermansia muciniphila in eczematous infants might reduce the integrity of intestinal barrier function and therefore increase the risk of developing eczema. On the other hand, Bacteroides fragilis and Streptococcus salivarius, which are known for their anti-inflammatory properties, were less abundant in infants with eczema. The observed differences in genera and species between cases and controls in this study may provide insight into the link between the microbiome and eczema risk.     

Senecio changii (Asteraceae: Senecioneae), a New Species from Sichuan,China

Senecio changii (Asteraceae: Senecioneae), a new species from Muli, Sichuan, southwestern China, is described. It is distinguished in Chinese Senecio s.s. by having lyrate-pinnatisect to pinnatisect leaves and a single terminal large discoid capitulum which is somewhat nodding. Evidence from floral micromorphology, karyology and molecular phylogenetic analyses based on the nuclear ITS/ETS sequence data all support its membership within Senecio s.s.     

Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis

Introduction

In response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson''s disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.

Methods

We conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.

Results

Eleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).

Conclusions

Results of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.     

Genotype–phenotype correlation of Charcot-Marie-Tooth type 1E patients with <Emphasis Type="Italic">PMP22</Emphasis> mutations

Charcot-Marie-Tooth disease type 1E (CMT1E) is a demyelinating motor and sensory neuropathy with peripheral myelin protein 22 (PMP22) point mutations. The objective of this study was to identify genetic causes and determine genotype–phenotype correlation in two Korean demyelinating CMT patients based on whole exome sequencing (WES), histological examination of distal sural nerve, and magnetic resonance imaging (MRI) of leg. WES revealed two de novo PMP22 mutations in the two demyelinating CMT patients, including one novel p.Leu82Pro (c.245T>A) mutation in one patient and one previously reported p.Ser72Leu (c.215C>T) mutation in the other patient. Both mutation sites were located in the well conserved second transmembrane domain. No control had the same mutations. The affected individual with the novel p.Leu82Pro mutation showed early onset, scoliosis, and sensory ataxia with ability to walk without assistance. Histopathological examination showed severe damage of myelin and axons. No compound muscle action potentials (CMAPs) were evoked in the upper or lower limb nerves. Leg MRIs revealed mild fatty infiltration of the bilateral peronei muscles consistent with clinical manifestations. The patient with the p.Ser72Leu mutation showed developmental delay in infancy. No CMAPs were elicited. However, she was also able to walk without assistance. In spite of markedly severe electrophysiological defects, leg MRIs showed almost normal findings except slight muscle atrophies of the lower legs. Both patients presented similar clinical features including no CMAPs in electrophysiological tests and mild fatty replacement in the lower leg MRI. Therefore, there was a good genotype–phenotype correlation in both cases.     

Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012–2013. Risk factors for mortality were evaluated using multivariable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC.     

The Influence of Perioperative Dexmedetomidine on Patients Undergoing Cardiac Surgery: A Meta-Analysis

BackgroundThe use of dexmedetomidine may have benefits on the clinical outcomes of cardiac surgery. We conducted a meta-analysis comparing the postoperative complications in patients undergoing cardiac surgery with dexmedetomidine versus other perioperative medications to determine the influence of perioperative dexmedetomidine on cardiac surgery patients.MethodsRandomized or quasi-randomized controlled trials comparing outcomes in patients who underwent cardiac surgery with dexmedetomidine, another medication, or a placebo were retrieved from EMBASE, PubMed, the Cochrane Library, and Science Citation Index.ResultsA total of 1702 patients in 14 studies met the selection criteria among 1,535 studies that fit the research strategy. Compared to other medications, dexmedetomidine has combined risk ratios of 0.28 (95% confidence interval [CI] 0.15, 0.55, P = 0.0002) for ventricular tachycardia, 0.35 (95% CI 0.20, 0.62, P = 0.0004) for postoperative delirium, 0.76 (95% CI 0.55, 1.06, P = 0.11) for atrial fibrillation, 1.08 (95% CI 0.74, 1.57, P = 0.69) for hypotension, and 2.23 (95% CI 1.36, 3.67, P = 0.001) for bradycardia. In addition, dexmedetomidine may reduce the length of intensive care unit (ICU) and hospital stay.ConclusionsThis meta-analysis revealed that the perioperative use of dexmedetomidine in patients undergoing cardiac surgery can reduce the risk of postoperative ventricular tachycardia and delirium, but may increase the risk of bradycardia. The estimates showed a decreased risk of atrial fibrillation, shorter length of ICU stay and hospitalization, and increased risk of hypotension with dexmedetomidine.     

Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro

Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections.