Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

Background The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed phenotypic delineation of interstitial 16p13.3 duplications is hampered by the scarcity of such patients. Objectives To delineate the phenotypic spectrum associated with interstitial 16p13.3 duplications, and perform a genotype-phenotype analysis. Results The present report describes the genotypic and phenotypic delineation of nine submicroscopic interstitial 16p13.3 duplications. The critically duplicated region encompasses a single gene, CREBBP, which is mutated or deleted in Rubinstein-Taybi syndrome. In 10 out of the 12 hitherto described probands, the duplication arose de novo. Conclusions Interstitial 16p13.3 duplications have a recognizable phenotype, characterized by normal to moderately retarded mental development, normal growth, mild arthrogryposis, frequently small and proximally implanted thumbs and characteristic facial features. Occasionally, developmental defects of the heart, genitalia, palate or the eyes are observed. The frequent de novo occurrence of 16p13.3 duplications demonstrates the reduced reproductive fitness associated with this genotype. Inheritance of the duplication from a clinically normal parent in two cases indicates that the associated phenotype is incompletely penetrant

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Evaluation of Bioactivities and Phenolic Content of Selected Edible Mushrooms in Malaysia

Purpose: To determine the radical scavenging, metal chelating, antibacterial and cytotoxic activities of five edible mushrooms in Malaysia.Methods: Mushrooms (H. tessulatus, P. eryngii, P. florida, A. polytricha and F. velutipes) were ovendried and extracted with 90 % ethanol. Radical scavenging and metal chelating assays were based on the measurement of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferrozine absorbance at 517 and 562 nm, respectively. Mushrooms total phenolic and flavonoid contents were determined by spectrophotometric methods. Antimicrobial activity was measured using Kirby-Bauer Susceptibility Test. Cytotoxicity was assessed using brine shrimp toxicity assay.Results: Total phenolic and flavonoid contents ranged from 0.90 - 6.03 mg GAE per g of dry sample and 0.17 - 6.95 mg QE per g of dry sample, respectively. A. polytricha demonstrated the strongest radical scavenging and metal chelating activities. Moderate antimicrobial activity was found for extracts of both P. florida and A. polytricha. Cytotoxicity LD50 ranged from 46.9 - 115.8 μg/ml.Conclusion: The results suggest that A. polytricha is a suitable candidate for chemoprevention and would safe for use in large doses.Keywords: Cytotoxicity, Flavonoid, Free radical scavenging, Metal chelating, Mushroom, Phenoli

A Retrospective Review of 25 cases of Lethal Fetal Anomalies

Introduction: To review the gestational age at diagnosis, method of diagnosis, pregnancy outcome and maternal complications of prenatally diagnosed lethal foetal anomalies. Methods: Retrospective review of 25 women who had aborted or delivered foetuses with lethal anomalies in a tertiary hospital in 2011 based on patient medical records. Results: There were a total of 10,088 deliveries, in which 25 (0.24%) women were found to have conceived foetuses with lethal anomalies. All of them were diagnosed by prenatal ultrasound and only 7 (28.0%) had both prenatal ultrasound and genetic study done. The women’s mean age was 29.9 years old. The mean gestational age at diagnosis of lethal foetal anomalies was 25.5 weeks (SD=12.5) and mean gestational age at termination of pregnancy (TOP) or delivery was 28.5 weeks (SD=12.5). Seven (28%) women had early counseling and TOP at the gestation of < 22 weeks. Beyond 22 weeks of gestation, eight (32%) women had TOP and ten (40%) women had spontaneous delivery. Twenty (80%) women delivered or aborted vaginally, three (12%) women with assisted breech delivery and two (8%) women with abdominal delivery which were performed due to transverse foetal lie in labour and a failed induction, leading to emergency hysterotomy complicated by hysterectomy due to intraoperative finding of ruptured uterus. Overall, the associated post-partum adverse events included post-partum haemorrhage (12%), retained placenta (12%), blood transfusion (8%), uterine rupture (4%) and endometritis (4%). Mean duration of hospital stay was 6.6 days (SD 3.7 days). Conclusion: Late diagnosis of lethal foetal anomalies leads to various maternal morbidities, in this case series , which could have been prevented if they were diagnosed and terminated at early trimester. A new direction is needed in our local practice

Acute symptomatic hypoglycaemia mimicking ischaemic stroke on imaging:a systemic review

<p>Abstract</p> <p>Background</p> <p>Acute symptomatic hypoglycaemia is a differential diagnosis in patients presenting with stroke-like neurological impairment, but few textbooks describe the full brain imaging appearances. We systematically reviewed the literature to identify how often hypoglycaemia may mimic ischaemic stroke on imaging, common patterns and relationships with hypoglycaemia severity, duration, clinical outcome and add two new cases.</p> <p>Methods</p> <p>We searched EMBASE and Medline databases for papers reporting imaging in adults with symptomatic hypoglycaemia. We analysed the clinical presentation, outcome, brain imaging findings, duration and severity of hypoglycaemia, time course of lesion appearance, including two new cases.</p> <p>Results</p> <p>We found 42 papers describing computed tomography or magnetic resonance imaging in 65 patients, plus our two cases with symptomatic hypoglycaemia. Imaging abnormalities on computed tomography and magnetic resonance were uni or bilateral, cortical or sub-cortical. Thirteen (20%) mimicked cortical or lacunar stroke. Acute lesions had restricted diffusion on magnetic resonance or low attenuation on computed tomography, plus swelling; older lesions showed focal atrophy or disappeared, as with ischaemic stroke. The association between the depth or duration of hypoglycaemia, the severity or extent of neurological deficit, and the imaging abnormalities, was weak.</p> <p>Conclusion</p> <p>Imaging abnormalities in patients with hypoglycaemia are uncommon but very variable, weakly associated with neurological deficit, and about a fifth mimic acute ischaemic stroke. Blood glucose testing should be routine in all patients with acute neurological impairment and hypoglycaemia should be included in the differential diagnosis of imaging appearances in patients presenting with acute stroke.</p

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: Findings from the Shanghai cohort study

Background: N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods: A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results: Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion: The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection

Application of a high density adsorbent in expanded bed adsorption of lipase from Burkholderia pseudomallei

The application of STREAMLINE Direct HST adsorbent in expanded bed adsorption of lipase from Burkholderia pseudomallei was explored in this study. Scouting of optimum binding and elution condition was performed in batch binding mode. The addition of 0.2 M salt in acetate buffer (pH 5)during adsorption has increased the specificity and quantity of lipase binding onto the adsorbent. The addition of 0.4 M salt in phosphate buffer (pH 7) achieved the highest purification fold (2.5) in elution. The high density of the adsorbent allowed the EBA to be operated at linear velocity as high as 657 cm/h with feedstock containing 4.5% (w/v) wet biomass. The Richardson-Zaki correlation obtained for this EBA system at the presence of 4.5% (w/v) wet biomass is 5.14, a value closed to the laminar flow regime of 4.8, demonstrated that a stable bed is achieved under this operating condition. Meanwhile, a flow velocity of 343 cm/h with bed expansion of 3.2 gave highest dynamic binding capacity (4979.28 U/ml)and productivity (61.52 U/ml.min) for this EBA operation. It also demonstrated that biomass concentration up to 4.5% (w/v) wet weight showed slightly drop of sorption efficiency (0.82) compared to lower biomass concentration (0.94). Further increase of biomass concentration above 4.5% (w/v) wet weight has greatly decreased the equilibrium and dynamic capacity. Application of high density adsorbent tolerated to high density and biomass has reduced the processing time and increased theproductivity

Uranium bioprecipitation mediated by yeasts utilizing organic phosphorus substrates

In this research, we have demonstrated the ability of several yeast species to mediate U(VI) biomineralization through uranium phosphate biomineral formation when utilizing an organic source of phosphorus (glycerol 2-phosphate disodium salt hydrate (C3H7Na2O6P·xH2O (G2P)) or phytic acid sodium salt hydrate (C6H18O24P6·xNa+·yH2O (PyA))) in the presence of soluble UO2(NO3)2. The formation of meta-ankoleite (K2(UO2)2(PO4)2·6(H2O)), chernikovite ((H3O)2(UO2)2(PO4)2·6(H2O)), bassetite (Fe++(UO2)2(PO4)2·8(H2O)), and uramphite ((NH4)(UO2)(PO4)·3(H2O)) on cell surfaces was confirmed by X-ray diffraction in yeasts grown in a defined liquid medium amended with uranium and an organic phosphorus source, as well as in yeasts pre-grown in organic phosphorus-containing media and then subsequently exposed to UO2(NO3)2. The resulting minerals depended on the yeast species as well as physico-chemical conditions. The results obtained in this study demonstrate that phosphatase-mediated uranium biomineralization can occur in yeasts supplied with an organic phosphate substrate as sole source of phosphorus. Further understanding of yeast interactions with uranium may be relevant to development of potential treatment methods for uranium waste and utilization of organic phosphate sources and for prediction of microbial impacts on the fate of uranium in the environment.</p

A multicomponent intervention for the management of chronic pain in older adults: study protocol for a randomized controlled trial

Background: Studies have shown that physical interventions and psychological methods based on the cognitive behavioral approach are efficacious in alleviating pain and that combining both tends to yield more benefits than either intervention alone. In view of the aging population with chronic pain and the lack of evidence-based pain management programs locally, we developed a multicomponent intervention incorporating physical exercise and cognitive behavioral techniques and examined its long-term effects against treatment as usual (i.e., pain education) in older adults with chronic musculoskeletal pain in Hong Kong. Methods/design: We are conducting a double-blind, cluster-randomized controlled trial. A sample of 160 participants aged ≥ 60 years will be recruited from social centers or outpatient clinics and will be randomized on the basis of center/clinic to either the multicomponent intervention or the pain education program. Both interventions consist of ten weekly sessions of 90 minutes each. The primary outcome is pain intensity, and the secondary outcomes include pain interference, pain persistence, pain self-efficacy, pain coping, pain catastrophizing cognitions, health-related quality of life, depressive symptoms, and hip and knee muscle strength. All outcome measures will be collected at baseline, postintervention, and at 3 and 6 months follow-up. Intention-to-treat analysis will be performed using mixed-effects regression to see whether the multicomponent intervention alleviates pain intensity and associated outcomes over and above the effects of pain education (i.e., a treatment × time intervention effect). Discussion: Because the activities included in the multicomponent intervention were carefully selected for ready implementation by allied health professionals in general, the results of this study, if positive, will make available an efficacious, nonpharmacological pain management program that can be widely adopted in clinical and social service settings and will hence improve older people’s access to pain management services

Electron shuttle-mediated microbial Fe(III) reduction under alkaline conditions

Purpose: Extracellular Fe(III) reduction plays an important role in a variety of biogeochemical processes. Several mechanisms for microbial Fe(III) reduction in pH-neutral environments have been proposed, but pathways of microbial Fe(III) reduction within alkaline conditions have not been clearly identified. Alkaline soils are vastly distributed; thus, a better understanding of microbial Fe(III) reduction under alkaline conditions is of significance. The purpose of this study is to explore the dominant mechanism of bacterial iron reduction in alkaline environments. Materials and methods: We used antraquinone-2,6-disulfonate (AQDS) as a representative of quinone moities of humic substances and elemental sulfur and sulfate as sulfur species to investigate the potential role of humic substances and sulfur species in mediating microbial Fe(III) reduction in alkaline environments. We carried out thermodynamic calculations to predict the ability of bacteria to reduce Fe(III) (oxyhydr)oxides under alkaline conditions and the ability of AQDS and sulfur species to serve as electron acceptors for microbial anaerobic respiration in an assumed alkaline soil environments. A series of incubation experiments with two model dissimilatory metal reducing bacteria, Shewanella oneidensis MR-1 and Geobacter sulfurreducens PCA as well as mixed bacteria enriched from a soil were performed to confirm the contribution of AQDS and sulfur species to Fe(III) reduction under alkaline conditions. Results and discussion: Based on thermodynamic calculations, we predicted that, under alkaline conditions, the enzymatic reduction of Fe(III) (oxyhydr)oxides would be thermodynamically feasible but very weak. In our incubation experiments, the reduction of ferrihydrite by anaerobic cultures of Shewanella oneidensis MR-1, Geobacter sulfurreducens PCA or microbes enriched from a soil was significantly increased in the presence of S0 or AQDS. Notably, AQDS contributed more to promoting Fe(III) reduction as a soluble electron shuttle than S0 did under the alkaline conditions probably because of different mechanisms of microbial utilization of AQDS and S0. Conclusions: These results suggest that microbial reduction of Fe(III) (oxyhydr)oxides under alkaline conditions may proceed via a pathway mediated by electron shuttles such as AQDS and S0. Considering the high ability of electron shuttling and vast distribution of humic substances, we suggest that humic substance-mediated Fe(III) reduction may potentially be the dominant mechanism for Fe(III) reduction in alkaline environments