The origin of ultra diffuse galaxies: stellar feedback and quenching.

We test if the cosmological zoom-in simulations of isolated galaxies from the FIRE project reproduce the properties of ultra diffuse galaxies (UDGs). We show that outflows that dynamically heat galactic stars, together with a passively aging stellar population after imposed quenching, naturally reproduce the observed population of red UDGs, without the need for high spin haloes, or dynamical influence from their host cluster. We reproduce the range of surface brightness, radius, and absolute magnitude of the observed red UDGs by quenching simulated galaxies at a range of different times. They represent a mostly uniform population of dark matter-dominated dwarf galaxies with M * ~ 108 M☉, low metallicity, and a broad range of ages; the more massive the UDGs, the older they are. The most massive red UDG in our sample(M * ~ 3 × 108 M☉) requires quenching at z ~ 3 when its halo reached M h ~ 1011M☉. Our simulated UDGs form with normal stellar-to-halo ratios and match the central enclosed masses and the velocity dispersions of the observed UDGs. Enclosed masses remain largely fixed across a broad range of quenching times because the central regions of their dark matter haloes complete their growth early. If our simulated dwarfs are not quenched, they evolve into bluer low surface brightness galaxies with M/L similar to observed field dwarfs. While our simulation sample covers a limited range of formation histories and halo masses, we predict that UDG is a common, and perhaps even dominant, galaxy type around M * ~ 108 M☉, both in the field and in clusters.

Gas kinematics in FIRE simulated galaxies compared to spatially unresolved HI observations.

The shape of a galaxy's spatially unresolved, globally integrated 21-cm emission line depends on its internal gas kinematics: galaxies with rotationally supported gas discs produce double-horned profiles with steep wings, while galaxies with dispersion-supported gas produce Gaussian-like profiles with sloped wings. Using mock observations of simulated galaxies from the FIRE project, we show that one can therefore constrain a galaxy's gas kinematics from its unresolved 21-cm line profile. In particular, we find that the kurtosis of the 21-cm line increases with decreasing V/σ and that this trend is robust across a wide range of masses, signal-to-noise ratios, and inclinations. We then quantify the shapes of 21-cm line profiles from a morphologically unbiased sample of ~2000 low-redshift, HI-detected galaxies with Mstar = 107-11 M☉ and compare to the simulated galaxies. At Mstar ≳ 1010 M☉, both the observed and simulated galaxies produce double-horned profiles with low kurtosis and steep wings, consistent with rotationally supported discs. Both the observed and simulated line profiles become more Gaussian like (higher kurtosis and less-steep wings) at lower masses, indicating increased dispersion support. However, the simulated galaxies transition from rotational to dispersion support more strongly: at Mstar 108-10 M, most of the simulations produce more Gaussian-like profiles than typical observed galaxies with similar mass, indicating that gas in the low-mass simulated galaxies is, on average, overly dispersion supported. Most of the lower-mass-simulated galaxies also have somewhat lower gas fractions than the median of the observed population. The simulations nevertheless reproduce the observed line-width baryonic Tully-Fisher relation, which is insensitive to rotational versus dispersion support.

Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos.

The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies.

Early clinical experience with a new preloaded one-piece intraocular lens in paediatric cataract surgery.

PurposeTo report the clinical experience of using the Tecnis PCB00 (Abbott Medical Optics, Santa Ana, CA, USA) preloaded one-piece intraocular lens (IOL) in the setting of a tertiary referral centre for paediatric cataract.MethodsA retrospective case note review of all paediatric cataract surgeries using the Tecnis PCB00 IOL, at a single UK paediatric ophthalmology department.ResultsNine eyes in seven patients received the IOL between December 2014 and January 2016. All patients underwent lens aspiration and insertion of the IOL 'in the bag.' The indications for surgery included developmental cataract (8/9) and traumatic cataract (1/9). Mean age at the time of surgery was 7 years (range 2-14). The median improvement in logMAR best-corrected visual acuity was 0.475 (range 0.250-1.500). The mean follow-up duration was 5 months (range 1-13). No operative or post-operative complications occurred as a result of using the device.ConclusionThe Tecnis PCB00 preloaded IOL appears to be a safe and effective device in treating paediatric cataract.

Synthesis of embedded Au nanostructures by ion irradiation: influence of ion induced viscous flow and sputtering.

The ion-irradiation induced synthesis of embedded Au nanoparticles (NPs) into glass from islands of Au on a glass substrate is studied in the context of recoiling atoms, sputtering and viscous flow. Cross sectional transmission electron microscopy studies revealed the formation of Au NPs embedded in the glass substrates by the 50 keV Si(-) ion irradiation of irregularly shaped Au nanostructures on the glass surfaces at a fluence of 3 × 10(16) ions/cm(2). The depth profiles of Au in the samples were obtained from high-resolution Rutherford backscattering spectrometry studies. The results from TRIDYN simulation reveal the role of various ion-induced processes during the synthesis of the embedded Au NPs, viz. sputtering and recoiling atoms. Simulation and experimental results suggest that the viscous flow is one of the major factors that are responsible for the embedding of Au nanoparticles into the glass substrate.

'Toy' laser macular burns in children.

PURPOSE: Laser 'toys' can be purchased online and imported with relative ease; the variety of such devices is a potential public safety concern. We describe five children with maculopathy following exposure to laser 'toys'. METHODS: Case series of maculopathy following exposure to laser 'toys'. RESULTS: Five children were seen in our Ophthalmic Unit with macular injuries following exposure to laser 'toys'. Clinically, three children had an acute vitelliform-like maculopathy which resolved to leave sub-foveal retinal pigment epithelium changes with reduced vision. One case was complicated by a choroidal neovascular membrane. CONCLUSION: Laser 'toys', which resemble laser pointers, are increasingly available over the internet. Such 'toys' may not meet safety standards. Retinal injury in childhood following exposure to laser 'toys' is a public safety concern.

Low-dose subcutaneous alemtuzumab is a safe and effective treatment for chronic acquired pure red cell aplasia.

Three patients with pure red cell aplasia, with or without co-existing large granular lymphocytic leukaemia, who remained transfusion-dependent despite treatment with established first-line therapy, were treated with low-dose subcutaneous alemtuzumab 15 mg twice to thrice per week, for 3 to 4 weeks. The mean response time was 17 days compared with a response time of at least 61 days on standard first-line therapy. There were no serious side-effects and the mean duration of remission was 13 months. Low-dose subcutaneous alemtuzumab is a safe and effective treatment for pure red cell aplasia and further trials should be conducted to compare the long-term effectiveness of this treatment with conventional therapy.

Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity.

BACKGROUND AND PURPOSE: Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD. EXPERIMENTAL APPROACH: Andrographolide was given i.p. to BALB/c mice daily 2h before 4% cigarette smoke exposure for 1h over five consecutive days. Bronchoalveolar lavage fluid and lungs were collected for analyses of cytokines, oxidative damage markers and antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to cigarette smoke extract (CSE) and used to study the antioxidant mechanism of action of andrographolide. KEY RESULTS: Andrographolide suppressed cigarette smoke-induced increases in lavage fluid cell counts; levels of IL-1ß, MCP-1, IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3-nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to antioxidant response element (ARE) and total cellular glutathione level in response to CSE. Andrographolide up-regulated ARE-regulated gene targets including glutamate-cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR and heme oxygenase-1 in BEAS-2B cells in response to CSE. CONCLUSIONS: Andrographolide possesses antioxidative properties against cigarette smoke-induced lung injury probably via augmentation of Nrf2 activity and may have therapeutic potential for treating COPD.

Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models.

BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

Detection of paternal alleles in maternal plasma for non-invasive prenatal diagnosis of beta-thalassemia: a feasibility study in southern Chinese.

OBJECTIVE: To evaluate in maternal plasma, the efficacy of detecting the paternal beta-gene mutation and informative single nucleotide polymorphisms (SNPs) linked to the paternal-mutant or -normal allele in non-invasive prenatal diagnosis (NIPND). STUDY DESIGN: In 20 at-risk pregnancies, using the allele-specific arrayed primer extension (AS-APEX) technology of the previously published "Thalassemia" array, cyanine-5-deoxycytosine triphosphate (Cy5-dCTP) was incorporated into the extended strands to matched PCR-amplified maternal plasma DNA templates, to detect both the paternal beta-gene mutation and informative paternal SNPs. RESULTS: Sensitivity experiment showed that 5pg DNA as starting template gave detectable signals on the array. In 13 cases (65%), the paternal-derived beta-gene mutation and/or informative mutant-associated SNP were detected. A subsequent invasive procedure was required to determine if the fetus had a beta-thalassemia (thal) major or minor genotype. In 3 cases (15%), absence of the paternal mutant or mutant-associated SNP excluded a beta-thal major fetus; while in 4 cases (20%), this approach was non-discriminative as both parents carry the same mutation without any informative SNP. CONCLUSION: This approach was useful in 16 out of 20 (80%) pregnancies at risk for beta-thal in southern Chinese.

Antibiotics and postoperative abscesses in complicated appendicitis: is there any association?

INTRODUCTION: Complicated appendicitis has significant infective postoperative morbidity. There is no universally-accepted antibiotic regime, although traditionally, triple antibiotics are recommended. Our complicated appendicitis clinical pathway recommends ceftriaxone and metronidazole. The study aimed to determine if choice of antibiotics influenced the risk of infective complications. METHODS: We reviewed all paediatric appendicectomy patients between January 1, 2005 and December 31, 2005. All patients with intraoperative diagnosis of perforated appendicitis were recruited, excluding infants, immunocompromised patients, and patients allergic to the guideline antibiotics. All operations were performed by registrar/consultant surgeons and were laparoscopic, unless technically not feasible. RESULTS: There were 82 patients with perforated appendicitis. 62 patients (76 percent) followed pathway antibiotics, and 20 patients (24 percent) deviated from the pathway by receiving additional empiric gentamycin. We compared the pathway compliant and deviation groups, and found no significant differences in patient characteristics, clinical presentation, operation, length of stay and infective complications. Overall there was one wound infection and five (six percent) postoperative abscesses. Initial peritoneal cultures and subsequent drainage cultures of patients who developed abscesses were sensitive to treatment antibiotics. CONCLUSION: In complicated appendicitis, empirical perioperative addition of gentamycin to ceftriaxone and metronidazole did not reduce the risk of developing intra-abdominal abscess, compared to changing antibiotics on clinical grounds. Patients developed postoperative abscesses despite initial peritoneal cultures growing organisms sensitive to treatment antibiotics.

Localization of hRad9 in breast cancer.

BACKGROUND: hRad9 is a cell cycle checkpoint gene that is up-regulated in breast cancer. We have previously shown that the mRNA up-regulation correlated with tumor size and local recurrence. Immunohistochemical studies were made to better define the role of hRad9 in breast carcinogenesis. METHODS: Localisation of hRad9 protein were performed on paired tumor and normal breast tissues. Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells. RESULTS: Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. This nuclear protein existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1 complex. CONCLUSION: Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth.

Functional outcome of the hand following flexor tendon repair at the 'no man's land'.

PURPOSE: To evaluate the functional outcome of the hand following flexor tendon repair at 'no man's land' using 2 strands of a modified Kessler core suture and combined controlled motion rehabilitation protocol. METHODS: Records of 31 zone-2 flexor tendon injuries in 21 digits of 16 patients between July 2000 and June 2005 were reviewed retrospectively. The injured tendons were repaired within 24 hours using 2 strands of a modified Kessler core suture, reinforced by a continuous circumferential epitendon suture. All patients completed a rehabilitation protocol that included active extension against a rubber band, passive flexion, and controlled passive extension and passive flexion exercises. Functional outcome of the fingers was assessed using the Buck-Gramcko II score. Hand grip strength, rehabilitation period, and rupture rate were also measured. RESULTS: 17 (81%) out of 21 digits in 15 out of 16 patients achieved an excellent-to-good functional grade. The remaining patient with concomitant injuries to 4 (19%) digits attained a poor functional grade, attributable to poor compliance with the rehabilitation protocol. The mean rehabilitation period was 130 days and the mean grip strength was 78% that of the uninjured side. Concomitant digital nerve injury did not adversely affect the final outcome. Only one (4.8%) patient experienced a rupture. CONCLUSION: The surgical method and rehabilitation protocol used for zone-2 flexor tendon injury is safe and results in a reasonably good functional outcome.

Experience in preimplantation genetic diagnosis for exclusion of homozygous alpha degrees thalassemia.

OBJECTIVE: To report our experience in preimplantation genetic diagnosis (PGD) for the exclusion of homozygous alpha degrees thalassemia. PATIENTS AND METHODS: PGD was performed on nine couples with alpha degrees thalassemia genotype undergoing assisted reproduction. Oocytes were aspirated after ovarian stimulation and fertilized by intracytoplasmic sperm injection. One or two blastomeres were biopsied from the six- to eight-cell embryo. Single cell multiplex PCR of the normal and alpha degrees thalassemia alleles was performed for first round, followed by semi-nested PCR of the respective alleles using 5'-end labelled fluorescent primers. Only those embryos with a blastomere diagnosed as having at least one normal allele were selected for transfer. RESULTS: One hundred and twenty-six blastomeres from 82 embryos were analyzed. The rates of allele dropout was 10.2% and PCR failure 12.7%. Fifty-eight embryos (70.7%) had at least one normal allele, of which 31 were transferred to 13 prepared cycles and one triplet pregnancy achieved. The triplets showed no ultrasound features of homozygous alpha degrees thalassemia at 18 weeks and were delivered in healthy condition by caesarean section at 34 weeks. Their genotypes were confirmed by cord blood analysis. CONCLUSIONS: PGD for alpha degrees thalassemia is possible by single cell PCR. The transfer and successful implantation of unaffected embryos ensure birth of disease-free babies.

A thalassaemia array for Southeast Asia.

The alpha and beta thalassaemias are the commonest genetic disorders worldwide. The homozygous state is associated with high morbidity and mortality, thus screening of at-risk pregnancies and prenatal testing are strongly advocated. A thalassaemia (thal) array has been designed using allele-specific arrayed primer extension (AS-APEX) for the simultaneous analysis of 15 non-deletion alpha-gene defects and 23 beta-gene mutations commonly found in southeast Asian countries, where thalassaemias are highly prevalent. This overcomes the problem of using multiple reverse dot blot analysis. The array showed 100% sensitivity and specificity in the detection of 120 beta-thal mutants and 35 non-deletion alpha-thal mutants. It is robust enough to be produced in a single place and shipped to other laboratories for use. The production cost of the array is low, each slide can be used for three different test samples and is therefore amenable to large scale antenatal screening in southeast Asian countries.

Can defects in transferrin receptor 2 and hereditary hemochromatosis genes account for iron overload in HbH disease?

Iron overload was found to be the major cause of disability in Chinese HbH disease patients although they were not on regular blood transfusion. The transferrin receptor 2 (TFR2) and hereditary hemochromatosis (HFE) genes were examined to see if inheritance of these gene defects may be a possible cause of iron overload in 45 HbH patients. A novel intronic (IVS6 (+6) T-->A) mutation of the TFR2 gene was identified in one patient, and six others were found to carry a known missense mutation (exon 5, I238M) that was also present in one normal control subject. One HbH patient and one normal control carried the H63D mutation of the HFE gene. Since only eight out of 45 iron-overloaded HbH patients carry a defect in the TFR2 or HFE gene in the heterozygote state and their iron loading status was comparable to the matched controls without such defects, it would appear that the accumulation of excess iron in HbH disease is more likely a result of increase dietary absorption secondary to ineffective erythropoiesis.

Long-term survival of primary root canal treatment carried out in a dental teaching hospital.

AIM: This study aimed to examine clinically and radiographically the survival of primary root canal treatment completed in a dental teaching hospital between 10 and 20 years previously. METHODOLOGY: A data collection form was used to collate all information obtained from the written patients' records along with the results from clinical and radiographic examination of 608 teeth, out of a total of 986 randomly selected teeth that had been root filled in the Prince Philip Dental Hospital (PPDH), Hong Kong, between 1981 and 1989. The criteria for failure were extractions (except for documented nonendodontic reason), retreatments and presence of a periapical radiolucency. The survival function of the treated teeth was plotted against the calculated date of failure using the Kaplan-Meier (K-M) method. Covariables were examined further by Cox Regression analysis with a backward stepwise method. RESULTS: A total of 314 teeth (52%) were either documented or deemed to have failed after examination. The median survival time was 111 months. Cox Regression analysis indicated that the survival of root-filled teeth was significantly influenced by the tooth type, preoperative periapical status and the type of coronal restoration. The survival function declined with time, with a rapid drop in the first 18 months or so. The rate at which failures occurred appeared to slow down with a longer observation time. CONCLUSIONS: There was a nonlinear decline in the cumulative survival probability of primary root canal treatment. Tooth type, preoperative periapical status and type of post and final restoration significantly affected the long-term survival of the treated teeth.