Focal ischemic myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). METHODS: The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. RESULTS: We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P < 0.0001) than HCM with NI-LGE or without LGE. In addition, HCM with I-LGE had a larger LV end- systolic volume (P = 0.045), lower LV ejection fraction (LVEF) (P = 0.026), higher LV myocardial mass (P < 0.001) and thicker LV wall (P < 0.001) more than HCM without LGE alone. The I-LGE were significantly associated with LVEF (OR: 0.961; P = 0.016), LV mass (OR: 1.028; P < 0.001), and maximal end-diastolic LVWT (OR: 1.567; P < 0.001). On multivariate analysis, LVEF (OR: 0.948; P = 0.013) and maximal end-diastolic LVWT (OR: 1.548; P = 0.001) were associated with higher risk for I-LGE compared to HCM without LGE. Noticeably, the maximal end-diastolic LVWT (OR: 1.316; P = 0.011) was the only associated with NI-LGE compared to HCM without LGE. CONCLUSIONS: I-LGE is not uncommon in patients with HCM. HCM with I-LGE was associated with significant LV hypertrophy, extensive LGE and poor LV ejection fraction. We should consider focal ischemic myocardial fibrosis when applying LGE to risk stratification for HCM.

Standardized lymph node dissection for gallbladder cancer under laparoscopy: en-bloc resection technique.

PURPOSE: Positive lymph node (LN) is a key prognostic factor in radically resected gallbladder cancer (GBCA). However, only a few underwent an adequate lymphadenectomy, and the number and extent of lymph node dissection (LND) have not been standardized. This study aims to develop an en bloc and standardized surgical procedure of LND for GBCA under laparoscopy. METHODS: Data of patients with GBCA underwent laparoscopic radical resection using a standardized and en bloc technique for LND were collected. Perioperative and long-term outcomes were retrospectively analyzed. RESULTS: A total of 39 patients underwent laparoscopic radical resection using standardized and en bloc technique for LND except one case (open conversion rate: 2.6%). Patients with stage T1b had significantly lower LNs involved rate than patients with stage T3 (P = 0.04), whereas median LN count in stage T1b was significantly higher than that in stage T2 (P = 0.04), which was significantly higher than that in stage T3 (P = 0.02). Lymphadenectomy with ≥ 6 LNs accounted for 87.5% in stage T1b, up to 93.3% in T2 and 81.3% in T3, respectively. All the patients in stage T1b were alive without recurrence at this writing. The 2-year recurrence-free survival rate was 80% for T2 and 25% for T3, and the 3-year overall survival rate was 73.3% for T2 and 37.5% for T3. CONCLUSION: The standardized and en bloc LND permits complete and radical removal of lymph stations for patients with GBCA. This technique is safe and feasible with low complication rates and good prognosis. Further studies are required to explore its value and long-term outcomes compared to conventional approaches.

Pediatric Cardiac Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

Cardiac lymphoma is rare in children. Treatment typically includes chemotherapy, combination of radiotherapy, or surgery. We report a case of stage IV precursor B lymphoblastic lymphoma with secondary involvement of the heart in an 11-year-old girl who was treated with acute lymphoblastic leukemia-based chemotherapy. Also, we review the literature on this uncommon malignancy.

Dual-tracer positron emission tomography/computed tomography as an imaging probe of de novo lipogenesis in preclinical models of hepatocellular carcinoma.

Background: De novo lipogenesis is upregulated in many cancers, and targeting it represents a metabolic approach to cancer treatment. However, the treatment response is unpredictable because lipogenic activity varies greatly among individual tumors, thereby necessitating the assessment of lipogenic activity before treatment. Here, we proposed an imaging probe, positron emission tomography/computed tomography (PET/CT) with dual tracers combining 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG), to assess the lipogenic activity of hepatocellular carcinoma (HCC) and predict the response to lipogenesis-targeted therapy. Methods: We investigated the association between 11C-acetate/18F-FDG uptake and de novo lipogenesis in three HCC cell lines (from well-differentiated to poorly differentiated: HepG2, Hep3B, and SkHep1) by examining the expression of lipogenic enzymes: acetyl-CoA synthetase 2 (ACSS2), fatty acid synthase (FASN), and ATP citrate lyase (ACLY). The glycolysis level was determined through glycolytic enzymes: pyruvate dehydrogenase expression (PDH). On the basis of the findings of dual-tracer PET/CT, we evaluated the treatment response to a lipase inhibitor (orlistat) in cell culture experiments and xenograft mice. Results: Dual-tracer PET/CT revealed the lipogenic activity of various HCC cells, which was positively associated with 11C-acetate uptake and negatively associated with 18F-FDG uptake. This finding represents the negative association between 11C-acetate and 18F-FDG uptake. Because these two tracers revealed the lipogenic and glycolytic activity, respectively, which implies an antagonism between lipogenic metabolism and glucose metabolism in HCC. In addition, dual-tracer PET/CT not only revealed the lipogenic activity but also predicted the treatment response to lipogenesis-targeted therapy. For example, HepG2 xenografts with high 11C-acetate but low 18F-FDG uptake exhibited high lipogenic activity and responded well to orlistat treatment, whereas SkHep1 xenografts with low 11C-acetate but high 18F-FDG uptake exhibited lower lipogenic activity and poor response to orlistat. Conclusion: The proposed non-invasive dual-tracer PET/CT imaging can reveal the lipogenesis and glycolysis status of HCC, thus providing an ideal imaging probe for predicting the therapeutic response of HCC to lipogenesis-targeted therapy.

Transcriptome analysis reveals differing response and tolerance mechanism of EPSPS and GAT genes among transgenic soybeans.

BACKGROUND: Glyphosate is a broad-spectrum, non-selective systemic herbicide. Introduction of glyphosate tolerance genes such as EPSPS or detoxification genes such as GAT can confer glyphosate tolerance on plants. Our previous study revealed that co-expression of EPSPS and GAT genes conferred higher glyphosate tolerance without "yellow flashing". However, the plant response to glyphosate at the transcriptional level was not investigated. METHODS AND RESULTS: To investigate the glyphosate tolerance mechanism, RNA-seq was conducted using four soybean genotypes, including two non-transgenic (NT) soybeans, ZH10 and MD12, and two GM soybeans, HJ698 and ZH10-6. Differentially expressed genes (DEGs) were identified in these soybeans before and after glyphosate treatment. Similar response to glyphosate in the two NT soybeans and the different effects of glyphosate on the two GM soybeans were identified. As treatment time was prolonged, the expression level of some DEGs involved in shikimate biosynthetic pathway and herbicide targeted cross-pathways was increased or declined continuously in NT soybeans, and altered slightly in HJ698. However, the expression level of some DEGs was altered in ZH10-6 at 12 hpt, while similar expression level of some DEGs involved in shikimate biosynthetic pathway and herbicide targeted cross-pathways was observed in ZH10-6 at 0 hpt and 72 hpt. These observations likely explain the higher glyphosate tolerance in ZH10-6 than in HJ698 and NT soybeans. CONCLUSIONS: These results suggested that GAT and EPSPS genes together play a crucial role in response to glyphosate, the GAT gene may work at the early stage of glyphosate exposure, whereas the EPSPS gene may be activated after the uptake of glyphosate by plants. These findings will provide valuable insight for the molecular basis underlying glyphosate tolerance or glyphosate detoxication.

Micro-PET imaging of [18F]fluoroacetate combined with [18F]FDG to differentiate chronic Mycobacterium tuberculosis infection from an acute bacterial infection in a mouse model: a preliminary study.

BACKGROUND: Mycobacterium tuberculosis (TB) infection is one of the deadliest infectious diseases worldwide and is responsible for 1.7 million deaths per year. The increase in multidrug-resistant TB poses formidable challenges to the global control of tuberculosis. TB infection could easily yield false-positive results in fluorine-18-fluorodeoxyglucose ([F]FDG) PET imaging for cancer detection because of its high [F]FDG uptake. We describe the combined [F]FDG PET with fluorine-18-fluoroacetate ([F]FAC), a promising analog of carbon-11-acetate, for targeting glycolysis and de novo lipogenesis, respectively, to determine the metabolic differences between chronic TB infection and acute infection. MATERIALS AND METHODS: Six-month-old BALB/c mice were inoculated with Mycobacterium bovis to induce chronic TB infection, and Escherichia coli as well as Staphylococcus aureus to induce acute infection for an in-vivo imaging study. Eighteen days after inoculation for chronic TB infection and 5 days for acute infection, both [F]FDG and [F]FAC micro-PET were performed on the infected mice. Analysis of variance and the Tukey honest ad-hoc test were carried out to determine differences among treatment with different bacterial infections. RESULTS: TB infection showed much lower [F] FAC accumulation than acute infection. However, both TB infection and acute infection exhibited high [F]FAC accumulation. CONCLUSION: The marked metabolic differences in de novo lipogenesis and glycolysis in [F]FDG and [F]FAC uptakes in micro-PET imaging, respectively, help to differentiate chronic TB infection from acute infection.

Changes of Atrial Natriuretic Peptides after Defibrillation Threshold Testing Predicted Future Ventricular Arrhythmia Event.

BACKGROUND: We investigated the change of natriuretic peptides during defibrillation threshold (DFT) testing and its relationship with future ventricular arrhythmia (VA) events in patients implanted with an implantable cardioverter defibrillator (ICD). METHODS: Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP) were measured in 21 patients (mean age 61 ± 13 years; 67% male) undergoing ICD implantation. Blood samples of the patients were drawn at pre-implantation, 30 minutes, 60 minutes, and 24 hours after DFT testing. The patients were followed and divided into two groups according to the occurrence of VA in 18 months. The biomarker levels and their changes were compared in patients with and without further VA. RESULTS: The pre-implantation ANP levels were higher at pre-implantation and increased significantly at 30 minutes after DFT testing (Δ30minANP) among patients with VA events. The BNP and CNP levels did not change significantly after DFT testing in both groups. The area under curve was 0.82 for the change in Δ30minANP determining further ventricular events. The optimal Δ30minANP cutoff value was 0.51 pg/ml, with sensitivity of 0.83 and specificity of 0.68. Multivariable analysis confirmed that patients with Δ30minANP more than 0.51 pg/ml have a higher risk of further ventricular events (hazard ratio 39.8, 95% confidence interval: 2.87-553.01, p = 0.006). The pre-implantation ANP level could not predict future VA events (hazard ratio 1.06, 95% CI: 1.00-1.14, p = 0.06). CONCLUSIONS: The increase of ANP concentration after DFT testing predicted future VA events after ICD implantation while the BNP and CNP levels did not predict future VA events.

Optimizing Technology Use for Chronic Lower-Extremity Wound Healing: A Consensus Document.

Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

[Comparisons of Microbial Numbers, Biomasses and Soil Enzyme Activities Between Paddy Field and Drvland Origins in Karst Cave Wetland].

The purpose of this study is to compare microbial number, microbial biomass as well as soil enzyme activity between paddy field and dryland originated karst wetland ecosystems. The soil samples (0-20 cm) of uncultivated wetland, paddy field and dryland were collected in Huixian karst cave wetland, Guilin, China. Microbial numbers and biomass were detected using dilute plate incubation counting and chloroform fumigation-extraction, respectively. Microbial DNA was extracted according to the manufacturer's instructions of the kit. Microbial activity was examined using soil enzyme assays as well. The result showed that the bacteria number in paddy filed was (4.36 +/- 2.25) x 10(7) CFU x g(-1), which was significantly higher than those in wetland and dryland. Fungi numbers were (6.41 +/- 2.16) x 10(4) CFU x g(-1) in rice paddy and (6.52 +/- 1.55) x 10(4) CFU x g(-1) in wetland, which were higher than that in dryland. Actinomycetes number was (2.65 +/- 0.72) x 10(6) CFU x g(-1) in dryland, which was higher than that in wetland. Microbial DNA concentration in rice paddy was (11.92 +/- 3.69) microg x g(-1), which was higher than that in dryland. Invertase activity was (66.87 +/- 18.61) mg x (g x 24 h)(-1) in rice paddy and alkaline phosphatase activity was (2.07 +/- 0.99) mg x (g x 2 h)(-1) in wetland, both of which were higher than those in dryland. Statistical analysis showed there was a significant positive correlation of microbial DNA content, alkaline phosphatase activity and microbial carbon with soil pH, soil organic carbon (SOC), total nitrogen, alkali-hydrolyzable nitrogen, soil moisture, exchangeable Ca2+ and exchangeable Mg2+, as well as a significant positive correlation of intervase activity with the former three microbial factors. The above results indicated that microbial biomass and function responded much more sensitively to land-use change than microbial number in karst cave wetland system. Soil moisture, SOC and some factors induced by land-use change could affect mainly microbiological characteristics. We suggest that rice paddy, a kind of constructed wetland, should be kept and protected in experimental area or buffer area of Huixian karst cave wetland in the light of its similar property with the natural wetland.

α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium.

The spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and ß-Spectrin are essential to maintain a monolayered FE, but, contrary to previous work, spectrins are not required to control proliferation. Furthermore, spectrin mutant cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-Spectrin and integrin mutant cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-Myosin II pathway enhances and decreases multilayering of α-Spectrin cells, respectively. Similarly, higher Myosin II activity enhances the integrin multilayering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequate forces, in order to maintain a monolayered epithelium.

Responses of cardiac natriuretic peptides after paroxysmal supraventricular tachycardia: ANP surges faster than BNP and CNP.

Atrial natriuretic peptide (ANP) secretion increases after 30 min of paroxysmal supraventricular tachycardia (PSVT). Whether this phenomenon also applies to brain or C-type natriuretic peptides (BNP or CNP) remains unknown. Blood samples of 18 patients (41 ± 11 yr old; 4 men) with symptomatic PSVT and normal left ventricular systolic function (ejection fraction 65 ± 6%) were collected from the coronary sinus (CS) and the femoral artery (FA) before and 30 min after the induction, and 30 min after the termination of PSVT. The results showed that the ANP levels rose steeply after the PSVT and then reduced at 30 min after the termination (baseline vs. post-PSVT vs. posttermination: CS: 34.0 ± 29.6 vs. 74.1 ± 42.3 vs. 46.1 ± 32.9; FA: 5.9 ± 3.24 vs. 28.2 ± 20.7 vs. 10.0 ± 4.6 pg/ml; all P < 0.05). In contrast, compared with ANP, the increases of BNP and CNP in CS after the PSVT were less sharp, but continued to rise after the termination of tachycardia (BNP, 10.2 ± 6.4 vs. 11.3 ± 7.1 vs. 11.8 ± 7.9; CNP, 4.5 ± 1.2 vs. 4.9 ± 1.4 vs. 5.0 ± 1.4 pg/ml; all P < 0.05). The rise of BNP and CNP in FA was similarly less sharp after the PSVT and remained stationary after the termination. PSVT exerted differential effects on cardiac natriuretic peptide levels. ANP increased greater after a 30-min induced PSVT, but dropped faster after termination of PSVT, compared with BNP and CNP.

Potential Role of Tc-99m DTPA Diuretic Renal Scan in the Diagnosis of Calyceal Diverticulum in Children.

The aim of the study was to assess the usefulness of Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) diuretic scan to diagnose calyceal diverticulum (CD). From January 2000 to June 2014, children with evidence of renal cystic lesions of undetermined diagnosis on ultrasound were enrolled. Computed tomography urography (CTU) and Tc-99m DTPA diuretic scan were performed to characterize the precise anatomy. The diagnosis of CD depended on visualization of a renal cystic lesion with filling of contrast material or radiotracer from the collecting system on CTU or diuretic renal scan. Children who had positive findings of CD on 1 or both imaging studies were selected and analyzed. Both CTU and Tc-99m DTPA diuretic renal scan were performed in 39 children. A total of 9 (23.1 %) children with CD were diagnosed. All 9 children had positive diagnosis of CD on diuretic renal scan. Only 6 (66.7%) children could be diagnosed by CTU, and CD was missed by CTU in 3 subjects. The differential renal functions in patients with CD were 46% to 55%. The time of radiotracer appearance in the CD ranged from the 8th to the 24th minute. Seven patients had persistent accumulation of radiotracer in their CD at the end of the study. Tc-99m DTPA diuretic renal scan seems to be more sensitive than CTU in diagnosing CD. The possible reasons of higher sensitivity are discussed. Additional advantages that Tc-99m DTPA diuretic renal scan provides include the following: continuous monitoring, less radiation doses, and information on renal function, making it an attractive alternative to CTU for diagnosis of CD.

The Role of MicroRNA, miR-24, and Its Target CHI3L1 in Osteomyelitis Caused by Staphylococcus aureus.

Osteomyelitis is a debilitating infectious disease of the bone which is predominantly caused by Staphylococcus aureus (S. aureus). MicroRNAs (miRNAs) have been shown to play a regulatory role in osteogenesis. In the present study, the expression levels of miRNAs proposed to potentially play a regulatory role in bone formation or differentiation (miR-24, miR-29b, miR-200a, miR-208, miR-322) were analyzed in the whole blood of patients with bacterial osteomyelitis or healthy controls, and in MC3T3-E1 cells infected with S. aureus by qRT-PCR. The expression of miR-24 was significantly down-regulated in osteomyelitis patients and S. aureus-infected MC3T3-E1 cells compared with the healthy controls or untreated control cells. Moreover, our results showed that S. aureus inhibited MC3T3-E1 cell proliferation, induced osteoblast apoptosis and prohibited bone formation and mineralization. We found that overexpression of miR-24 could reduce the effects of S. aureus, while inhibition of miR-24 intensified the effects. We also demonstrated that miR-24 suppressed the expression of chitinase 3-like 1 (CHI3L1) mRNA, thought to mediate multiple signaling pathways, by directly binding to the 3'-untranslated region.

Reappraisal of the effectiveness of 99mTc-dimercaptosuccinic acid scans for selective voiding cystourethrography in children with a first febrile urinary tract infection.

Recent studies have yielded conflicting results regarding the ability of technetium-99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scans for identifying high-grade vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). This study aimed to reevaluate the effectiveness of (99m)Tc-DMSA renal scans for selective voiding cystourethrography (VCUG) in children with a first febrile UTI. The medical records of children aged ≤ 5 years who were admitted with a first febrile UTI were retrospectively reviewed. Ultrasonography (US) and DMSA renal scans were performed within 3-5 days after admission, and VCUG was performed 7-10 days after antibiotics treatment. A total of 653 children were enrolled for analysis, including 579 patients aged < 2 years (Group A) and 74 patients aged 2-5 years (Group B). In Group A, DMSA scans were abnormal for 346 patients (59.8%), and normal for 233 patients (40.2%). High-grade VUR was present in 99 of 346 patients (28.9%) with abnormal DMSA scans, but present in only 16 of 233 patients (6.9%) with normal DMSA scans (p < 0.001). Regarding the prediction of high-grade VUR, the sensitivity and negative predictive value (NPV) for the DMSA scans were 86.1% and 93.1%, respectively. In Group B, DMSA scans were abnormal for 36 patients (48.6%), and normal for 38 patients (51.4%). High-grade VUR was present in 12 of 36 patients (33.3%) with abnormal DMSA scans, whereas none of the 38 patients with normal DMSA scans had high-grade VUR (p < 0.001). The sensitivity and NPV of the DMSA scans were both 100%. Using the selective VCUG strategy, approximately 40% of Group A patients and 50% of Group B patients could be spared an unnecessary VCUG, respectively. Our study results suggest that (99m)Tc-DMSA renal scans are effective in identifying children with a first febrile UTI for selective VCUG.

The auto-inhibitory domain and ATP-independent microtubule-binding region of Kinesin heavy chain are major functional domains for transport in the Drosophila germline.

The major motor Kinesin-1 provides a key pathway for cell polarization through intracellular transport. Little is known about how Kinesin works in complex cellular surroundings. Several cargos associate with Kinesin via Kinesin light chain (KLC). However, KLC is not required for all Kinesin transport. A putative cargo-binding domain was identified in the C-terminal tail of fungal Kinesin heavy chain (KHC). The tail is conserved in animal KHCs and might therefore represent an alternative KLC-independent cargo-interacting region. By comprehensive functional analysis of the tail during Drosophila oogenesis we have gained an understanding of how KHC achieves specificity in its transport and how it is regulated. This is, to our knowledge, the first in vivo structural/functional analysis of the tail in animal Kinesins. We show that the tail is essential for all functions of KHC except Dynein transport, which is KLC dependent. These tail-dependent KHC activities can be functionally separated from one another by further characterizing domains within the tail. In particular, our data show the following. First, KHC is temporally regulated during oogenesis. Second, the IAK domain has an essential role distinct from its auto-inhibitory function. Third, lack of auto-inhibition in itself is not necessarily detrimental to KHC function. Finally, the ATP-independent microtubule-binding motif is required for cargo localization. These results stress that two unexpected highly conserved domains, namely the auto-inhibitory IAK and the auxiliary microtubule-binding motifs, are crucial for transport by Kinesin-1 and that, although not all cargos are conserved, their transport involves the most conserved domains of animal KHCs.

[Microbial community abundance and diversity in typical karst ecosystem to indicate soil carbon cycle].

The soil microbial characteristics were detected to clarify their indications in organic carbon cycle in karst system. Soil samples from three karst types (saddle, depression and slop) at 0-10 cm, 10-20 cm and 20-30 cm layers were collected in the Yaji Karst Experimental Site, a typical karst ecosystem. The microbial diversity and abundance were assayed using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescence quantitative PCR. The data showed that the highest abundance of 16S rRNA and 18S rRNA were in depression with 1.32 x 10(11) copies x g(-1) and in saddle with 1.12 x 10(10) copies x g(-1), respectively. The abundance of 16S rRNA in saddle and depression decreased from top to bottom, while that of 18S rRNA in three karst forms decreased, which showed that the abundance changed consistently with soil organic carbon (SOC). The 3 diversity indices of 16S rRNA and 6 diversity indices of 18S rRNA increased from top to bottom in soil profiles of three karst forms. These results showed that microbial diversity changed conversely with the abundance and SOC in soil profile. It can be concluded that the abundance was more important than the diversity index for soil carbon cycle in karst system.

Polo-mediated phosphorylation of Maelstrom regulates oocyte determination during oogenesis in Drosophila.

In Drosophila, Maelstrom is a conserved component of the perinuclear nuage, a germline-unique structure that appears to serve as a site for Piwi-interacting RNA (piRNA) production to repress deleterious transposons. Maelstrom also functions in the nucleus as a transcriptional regulator to repress the expression of microRNA-7, a process that is essential for the proper differentiation of germline stem cells. In this paper, we report another function of Maelstrom in regulating oocyte determination independently of its transposon silencing and germline stem cell differentiation activities. In Drosophila, the conserved serine 138 residue in Maelstrom is required for its phosphorylation, an event that promotes oocyte determination. Phosphorylation of Maelstrom is required for the repression of the pachytene checkpoint protein Sir2, but not for transposon silencing or for germline stem cell differentiation. We identify Polo as a kinase that mediates the phosphorylation of Maelstrom. Our results suggest that the Polo-mediated phosphorylation of Maelstrom may be a mechanism that controls oocyte determination by inactivating the pachytene checkpoint via the repression of Sir2 in Drosophila ovaries.

Screening high-grade vesicoureteral reflux in young infants with a febrile urinary tract infection.

BACKGROUND: The lack of good evidence for improved outcomes in children and young infants with febrile urinary tract infection (UTI) after aggressive treatment for vesicoureteral reflux (VUR) has raised doubts regarding the need for routine voiding cystourethrography (VCUG), and the appropriate imaging evaluation in these children remains controversial. OBJECTIVES: This prospective study aimed to determine whether abnormalities found on acute dimercaptosuccinic acid (DMSA) scan and ultrasound (US) can help indicate the necessity of voiding cystourethrography (VCUG) in young infants. METHODS: For 3.5 years, all infants younger than 3 months presenting with first febrile UTI were prospectively studied. All infants were hospitalized and investigated using US (<3 days after admission), DMSA scan (<5 days after admission), and VCUG (7-10 days after antibiotic treatment) after diagnosis. The association among findings of US, DMSA scan, and VCUG were evaluated. RESULTS: From 220 infants, there were abnormal results in 136 (61.8%) US and in 111 (50.5%) DMSA scans. By US, ten infants (4.5%) with abscess or structural abnormalities other than VUR were diagnosed. High-grade (III-V) VUR was present in 39 patients (17.7%). The sensitivities for high-grade VUR of renal US alone (76.9%) or DMSA scan alone (82.1%) were not as good as that of the "OR rule" strategy, which had 92.3% sensitivity and 94.3% negative predictive value. CONCLUSIONS: To screen high-grade VUR in young infants with febrile UTI, US and acute DMSA scan could be performed first. VCUG is only indicated when abnormalities are apparent on either US or DMSA scan or both.

Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults.

Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1), were measured in 25 healthy volunteers (mean age: 30.1 ± 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 ± 3.1 vs. 3.40 ± 2.0%; P < 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased (P < 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect.

Association of polymorphisms in genes involved in the dopaminergic pathway with blood pressure and uric acid levels in Chinese females.

Since the high degree of heritability of physiological traits was demonstrated by twin and adoption studies, contemporary researchers in the fields of clinical medicine, behavioral science, and genetics have acknowledged the crucial role of genetic factors in human physiology. The study described herein explores the association between physiological parameters and the dopaminergic system using molecular genetic techniques. A total of 558 Taiwanese female volunteers, ranging from 16 to 17 years, were recruited. Single nucleotide polymorphisms in genes involved in the dopaminergic pathway were selected for analysis. Systolic blood pressure and diastolic blood pressure were associated significantly with the catechol-O-methyltransferase (COMT) Val158Met polymorphism and the dopamine ß-hydroxylase (DBH) C1021T polymorphism. Furthermore, plasma uric acid was associated significantly with the COMT Val158Met polymorphism. Our study suggests the possible involvement of genetic polymorphisms in COMT and DBH in the regulation of blood pressure and plasma uric acid.