Flow Behavior of Heavy Silicone Oil During Eye Movements

PURPOSE. Currently there are various heavy silicone oil (HSO) tamponade agents available for treating inferior retinal diseases. Most of these HSO agents are either homogeneous liquids or a mixture of two components. Variations in their emulsification rates in vivo have been reported. In this study, we investigated their flow behaviors during eye-like movements. METHODS. A model eye chamber filled with various HSO agents was driven to perform eye-like movements. Five types of HSOs with different formulations together with 2 other tamponade agents were tested. Movements of various HSOs inside the chamber were captured by video recording and analyzed. RESULTS. Oxane HD has a larger movement and higher velocity relative to the eye chamber than the less viscous Densiron 68. The behavior of Densiron 68 is similar to that of homogeneous HSO 1.07 and HSO 1.20. Both Oxane HD and 11% silica fluid show very different behaviors compared to the other HSO agents. In addition, 11% silica fluid shows behavior similar to that of F6H8, a low-viscosity tamponade agent. CONCLUSIONS. The viscosity of HSO is not the sole parameter with which to determine the behavior of HSO during eye movements. Various HSOs that are manufactured by mixing different types of base SO and ''heavy'' additives show distinct flow behaviors. The solubility and stability of the heavy additives in the base SO alter its flow when subjected to eye movements, which may contribute to in vivo emulsification. Keywords: emulsification, eye movements, heavy silicone oil, tamponade S ilicone oil (SO) has been used in vitreoretinal surgery for a long time to repair complicated retinal detachment. 1 Conventional SO has a specific gravity lower than water and thus provides a good tamponade effect for breaks or holes in the superior retina. There is also a group of SO that has a specific gravity higher than water. That type of SO is designed initially for treating proliferative vitreoretinopathy, which has a propensity to affect the inferior part of the retina. 2 Those types are commonly called heavy silicone oil (HSO). The first generation of HSO was made by substituting a few methylated groups of conventional SO to fluorinated groups in order to increase its specific gravity. 3 However, that type of fluorosilicone oil was found to be toxic to ocular tissues

Promotion of knowledge and awareness of parents in HK about infant oral health care

Aim: To promote the knowledge and awareness of infant oral health (OH) care among Hong Kong parents with children aged 0 to 2 years through an interactive workshop and to evaluate its effectiveness. Methods: Parents were recruited from government-registered childcare centers and private playgroups. Interactive workshops consisted of a 30-minute PowerPoint presentation and 20 minutes of small-group activities, which included infant oral hygiene instruction with custom-made infant dentition models, diet analysis and question-and-answer session. Self-completed questionnaires used to evaluate the knowledge and attitude of parents were distributed before and after the workshops. Scores on general OH knowledge (range=0-18), infant OH knowledge (0-10) and parent’s attitude (0-4) were computed. Scores of at least 70% were considered proficient. Results: Among the 111 participants (aged 26 to 54 years, 64% mothers), 96% had a child aged 0 to 30 months. 30% had their children’s mouth cleaned at least twice a day. Only one participant had brought his/her child to see a dentist. Weaker aspects in parents’ OH knowledge and common misconceptions were identified in the pre-survey. Only 35% identified frequent meals as an increased caries risk; only 59% and 79% identified starchy food and formula milk as cariogenic food respectively. 58% did not know water fluoridation can prevent caries, while 33% of parents pointed out calcium supplement can prevent caries. Before the workshop, 41% had proficient general OH knowledge (mean=11.9) and 16% had proficient infant OH knowledge (mean=4.8). Over half of parents showed positive attitude (mean=3.4). Significant improvements in general OH knowledge (mean=15.6, p<0.001), infant OH knowledge (mean=8.8, p<0.001) and attitude (mean=3.9, p<0.001) were observed. Parents reflected the workshops were useful (94%) and they learned new practices to improve their infants’ OH (95%). Conclusion: Several deficiencies in oral health knowledge and behaviour are identified. The interactive workshops can effectively promote the knowledge and awareness of infant oral health care among parents with children aged 0 to 2 years. Large-scale infant oral health survey is needed. Interactive workshops with longer follow-up periods are recommended. More guidelines can be provided to parents and general dentists for prevention of caries.published_or_final_versio

Generation of induced pluripotent stem cell lines from 3 distinct laminopathies bearing heterogeneous mutations in lamin A/C

The term laminopathies defines a group of genetic disorders caused by defects in the nuclear envelope, mostly the lamins. Lamins are the main constituents of the nuclear lamina, a filamentous meshwork associated with the inner nuclear membrane that provides mechanical stability and plays important roles in processes such as transcription, DNA replication and chromatin organization. More than 300 mutations in lamin A/C have been associated with diverse clinical phenotypes, understanding the molecular basis of these diseases may provide a rationale for treating them. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient with inherited dilated cardiomiopathy and 2 patients with distinct accelerated forms of aging, atypical Werner syndrome and Hutchinson Gilford progeria, all of which are caused by mutations in lamin A/C. These cell lines were pluripotent and displayed normal nuclear membrane morphology compared to donor fibroblasts. Their differentiated progeny reproduced the disease phenotype, reinforcing the idea that they represent excellent tools for understanding the role of lamin A/C in normal physiology and the clinical diversity associated with these diseases

Antibody stabilization for thermally accelerated deep immunostaining

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining

Significance of Metastatic Lymph Node Ratio on Stimulated Thyroglobulin Levels in Papillary Thyroid Carcinoma after Prophylactic Unilateral Central Neck Dissection

Background: Prognostic significance of metastatic central lymph node ratio (CLNR) in papillary thyroid carcinoma (PTC) remains unknown. Because postsurgical detectable stimulated thyroglobulin (DsTg) after radioiodine ablation may imply persistent or recurrent disease, we evaluated the association between CLNR and rate of DsTg in patients with PTC who underwent unilateral prophylactic central neck dissection. Methods: To be eligible for analysis, the prophylactic central neck dissection specimen had to contain ≥3 central lymph nodes (CLNs) with ≥1 harboring metastasis. Of 129 specimens, 51 (39.5%) were eligible. CLNR was calculated as follows: (number of metastatic CLNs/number of CLNs retrieved) × 100. They were categorized into group 1 (CLNR 66.67%) (n = 22). Postablation sTg level was measured 6 months after radioiodine ablation. A multivariate analysis was conducted to identify factors for postablation DsTg. Results: Young age, palpable neck swelling, large tumor size, advanced tumor, node, metastasis system (TNM) stage, and large number of metastatic CLNs were significantly associated with high CLNR (Ppublished_or_final_versionSpringer Open Choice, 21 Feb 201

Probing the bradycardic drug binding receptor of HCN-encoded pacemaker channels

If (or Ih), encoded by the hyperpolarization-activated, cyclic nucleotide-gated (HCN1–4) channel gene family, contributes significantly to cardiac pacing. Bradycardic agents such as ZD7288 that target HCN channels have been developed, but the molecular configuration of their receptor is poorly defined. Here, we probed the drug receptor by systematically introducing alanine scanning substitutions into the selectivity filter (C347A, I348A, G349A, Y350A, G351A in the P-loop), outer (P355A, V356A, S357A, M358A in the P-S6 linker), and inner (M377A, F378A, V379A in S6) pore vestibules of HCN1 channels. When heterologously expressed in human embryonic kidney 293 cells for patch-clamp recordings, I348A, G349A, Y350A, G351A, P355A, and V356A did not produce measurable currents. The half-blocking concentration (IC50) of wild type (WT) for ZD7288 was 25.8 ± 9.7 μM. While the IC50 of M358A was identical to WT, those of C347A, S357A, F378A, and V379A markedly increased to 137.6 ± 56.4, 113.3 ± 34.1, 587.1 ± 167.5, and 1726.3 ± 673.4 μM, respectively (p < 0.05). Despite the proximity of the S6 residues studied, M377A was hypersensitive (IC50 = 5.1 ± 0.7 μM; p < 0.05) implicating site specificity. To explore the energetic interactions among the S6 residues, double and triple substitutions (M377A/F378A, M377A/V379A, F378A/V379A, and M377A/F378A/V379A) were generated for thermodynamic cycle analysis. Specific interactions with coupling energies (ΔΔG) >1 kT for M377–F378 and F378–V379 but not M377–V379 were identified. Based on these new data and others, we proposed a refined drug-blocking model that may lead to improved antiarrhythmics and bioartificial pacemaker designs

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication