Susceptibility of Bacillus subtilis to Zinc Oxide Nanoparticles Treatment.

Aim: With the characteristics such as low toxicity, high total surface, ability to inhibit the growth of pathogenic microorganisms, zinc oxide nanoparticles (ZnO NPs), as one of the metallic nanoparticles, have been chosen as an antibacterial agent to treat various skin infections. The present study was aimed to determine the antibacterial potential of ZnO NPs on Bacillus subtilis, the Gram-positive bacterium that can cause skin and wound infections. Methods: B. subtilis was exposed to 5 to 150 µg/mL of ZnO NPs for 24 h. The parameters employed to evaluate the antimicrobial potential of ZnO NPs were the growth inhibitory effect on B. subtilis, the surface interaction of ZnO NPs on the bacterial cell wall, and also the morphological alterations in B. subtilis induced by ZnO NPs. Results: The results demonstrated a significant (p <0.05) inhibition of ZnO NPs on B. subtilis growth and it was in a dose-dependent manner for all the tested concentrations of ZnO NPs from 5 to 150 µg/mL at 24 h. Fourier transformed infrared (FTIR) spectrum confirmed the involvement of polysaccharides and polypeptides of bacterial cell wall in surface binding of ZnO NPs on bacteria. The scanning electron microscopy (SEM) was used to visualize the morphological changes, B. subtilis illustrated several surface alterations such as distortion of cell membrane, roughening of cell surface, aggregation and bending of cells, as well as, the cell rupture upon interacting with ZnO NPs for 24 h. Conclusion: The results indicated the potential of ZnO NPs to be used as an antibacterial agent against B. subtilis. The findings of the present study might bring insights to incorporate ZnO NPs as an antibacterial agent in the topical applications against the infections caused by B. subtilis.

Validity and Reliability of Surface Electromyography Features in Lower Extremity Muscle Contraction in Healthy and Spinal Cord-Injured Participants.

Background: Spinal cord injury (SCI) has a significant impact on motor control and active force generation. Quantifying muscle activation following SCI may help indicate the degree of motor impairment and predict the efficacy of rehabilitative interventions. In healthy persons, muscle activation is typically quantified by electromyographic (EMG) signal amplitude measures. However, in SCI, these measures may not reflect voluntary effort, and therefore other nonamplitude-based features should be considered. Objectives: The purpose of this study was to assess the correlation of time-domain EMG features with the exerted joint torque (validity) and their test-retest repeatability (reliability), which may contribute to characterizing muscle activation following SCI. Methods: Surface EMG (SEMG) and torque were measured while nine uninjured participants and four participants with SCI performed isometric contractions of tibialis anterior (TA) and soleus (SOL). Data collection was repeated at a subsequent session for comparison across days. Validity and test-retest reliability of features were assessed by Spearman and intraclass correlation (ICC) of linear regression coefficients. Results: In healthy participants, SEMG features correlated well with torque (TA: ρ > 0.92; SOL: ρ > 0.94) and showed high reliability (ICCmean = 0.90; range, 0.72-0.99). In an SCI case series, SEMG features also correlated well with torque (TA: ρ > 0.86; SOL: ρ > 0.86), and time-domain features appeared no less repeatable than amplitude-based measures. Conclusion: Time-domain SEMG features are valid and reliable measures of lower extremity muscle activity in healthy participants and may be valid measures of sublesional muscle activity following SCI. These features could be used to gauge motor impairment and progression of rehabilitative interventions or in controlling assistive technologies.

Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices.

BACKGROUND: Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality. OBJECTIVES: To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally invasive, user-friendly and targeted fashion. METHODS: Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin. RESULTS: Cell viability and functionality are maintained after injection through hollow microneedles with a bore size ≥ 75 µm. Healthy cells are delivered into the skin at clinically relevant depths. CONCLUSIONS: Hollow microneedles provide an innovative and minimally invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin repigmentation, wound repair, scar and burn remodelling, immune therapies and cancer vaccines.

The surface chemistry of sapphire-c: A literature review and a study on various factors influencing its IEP.

A wide range of isoelectric points (IEPs) has been reported in the literature for sapphire-c (α-alumina), also referred to as basal plane, (001) or (0001), single crystals. Interestingly, the available data suggest that the variation of IEPs is comparable to the range of IEPs encountered for particles, although single crystals should be much better defined in terms of surface structure. One explanation for the range of IEPs might be the obvious danger of contaminating the small surface areas of single crystal samples while exposing them to comparatively large solution reservoirs. Literature suggests that factors like origin of the sample, sample treatment or the method of investigation all have an influence on the surfaces and it is difficult to clearly separate the respective, individual effects. In the present study, we investigate cause-effect relationships to better understand the individual effects. The reference IEP of our samples is between 4 and 4.5. High temperature treatment tends to decrease the IEP of sapphire-c as does UV treatment. Increasing the initial miscut (i.e. the divergence from the expected orientation of the crystal) tends to increase the IEP as does plasma cleaning, which can be understood assuming that the surfaces have become less hydrophobic due to the presence of more and/or larger steps with increasing miscut or due to amorphisation of the surface caused by plasma cleaning. Pre-treatment at very high pH caused an increase in the IEP. Surface treatments that led to IEPs different from the stable value of reference samples typically resulted in surfaces that were strongly affected by subsequent exposure to water. The streaming potential data appear to relax to the reference sample behavior after a period of time of water exposure. Combination of the zeta-potential measurements with AFM investigations support the idea that atomically smooth surfaces exhibit lower IEPs, while rougher surfaces (roughness on the order of nanometers) result in higher IEPs compared to reference samples. Two supplementary investigations resulted in either surprising or ambiguous results. On very rough surfaces (roughness on the order of micrometers) the IEP lowered compared to the reference sample with nanometer-scale roughness and transient behavior of the rough surfaces was observed. Furthermore, differences in the IEP as obtained from streaming potential and static colloid adhesion measurements may suggest that hydrodynamics play a role in streaming potential experiments. We finally relate surface diffraction data from previous studies to possible interpretations of our electrokinetic data to corroborate the presence of a water film that can explain the low IEP. Calculations show that the surface diffraction data are in line with the presence of a water film, however, they do not allow to unambiguously resolve critical features of this film which might explain the observed surface chemical characteristics like the dangling OH-bond reported in sum frequency generation studies. A broad literature review on properties of related surfaces shows that the presence of such water films could in many cases affect the interfacial properties. Persistence or not of the water film can be crucial. The presence of the water film can in principle affect important processes like ice-nucleation, wetting behavior, electric charging, etc.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

COMETARY SCIENCE. 67P/Churyumov-Gerasimenko surface properties as derived from CIVA panoramic images.

The structure and composition of cometary constituents, down to their microscopic scale, are critical witnesses of the processes and ingredients that drove the formation and evolution of planetary bodies toward their present diversity. On board Rosetta's lander Philae, the Comet Infrared and Visible Analyser (CIVA) experiment took a series of images to characterize the surface materials surrounding the lander on comet 67P/Churyumov-Gerasimenko. Images were collected twice: just after touchdown, and after Philae finally came to rest, where it acquired a full panorama. These images reveal a fractured surface with complex structure and a variety of grain scales and albedos, possibly constituting pristine cometary material.

Electrolyte layering at the calcite(104)-water interface indicated by Rb(+)- and Se(VI) K-edge resonant interface diffraction.

Calcite-water interface reactions are of major importance in various environmental settings as well as in industrial applications. Here we present resonant interface diffraction results on the calcite(104)-aqueous solution interface, measured in solutions containing either 10 mmol L(-1) RbCl or 0.5 mmol L(-1) Se(VI). Results indicate that Rb(+) ions enter the surface adsorbed water layers and adsorb at the calcite(104)-water interface in an inner-sphere fashion. A detailed analysis based on specular and off-specular resonant interface diffraction data reveals three distinct Rb(+) adsorption species: one 1.2 Å above the surface, the second associated with surface adsorbed water molecules 3.2 Å above the surface, and the third adsorbed in an outer-sphere fashion 5.6 Å above the surface. A peak in resonant amplitude between L = 1.5 and L = 3.0 is interpreted as signal from a layered electrolyte structure. The presence of a layered electrolyte structure seems to be confirmed by data measured in the presence of Se(VI).

Age-dependent sting recurrence and outcome in immunotherapy-treated children with anaphylaxis to Hymenoptera venom.

BACKGROUND: Data on outcome of insect venom immunotherapy in children are rare. OBJECTIVE: We investigated the rate of sting recurrence and outcome of Hymenoptera venom anaphylaxis in children of different age groups treated with immunotherapy. METHODS: Data from children consecutively referred for anaphylaxis to Hymenoptera venom were collected using a standardized questionnaire. RESULTS: During mean follow-up of 7.7 years after commencement of immunotherapy, 45 of 83 children (56%) were re-stung 108 times by the insect they were allergic to. This corresponds to a rate of 0.23 stings per child and year of follow-up. The younger the subject, the higher was the prevalence of re-stings, with rates of 0.41 in children < 6 years, 0.21 at school age and 0.15 in adolescents (P = 0.001). In contrast, prevalence of systemic allergic reactions to field stings was significantly lower in pre-school (3.4%) and school-age children (4.3%) compared with adolescents (15.6%; P < 0.05). Overall, prevalence of systemic allergic reactions at re-sting was 15.6% in the honey bee venom and 5.9% in the Vespula venom allergic group (P = ns). Younger boys with anaphylaxis to honey bee venom predominated in our cohort (P = 0.019). CONCLUSION AND CLINICAL RELEVANCE: A majority of children with anaphylaxis to Hymenoptera venom (56%) in our cohort were re-stung, equally by honey bees or Vespula species. Younger children were more likely to be re-stung, but less likely to have a systemic reaction. Venom immunotherapy induces long-term protection in most children: 84.4% of subjects with anaphylaxis to honey bee and 94.1% of those to Vespula venom were completely protected at re-stings.

Perspectives on allergen-specific immunotherapy in childhood: an EAACI position statement.

This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen-specific immunotherapy in childhood. Unmet needs are identified. To fill the gaps and to bridge the different points of view, recommendations are made to researchers, to scientific and patient organizations and to regulators and ethical committees. Working together for the benefit of the community is essential. The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation.

[Diagnosis and treatment of food allergies in preschool children]. / Nahrungsmittelallergien im Vorschulalter - aktueller Stand der Diagnostik und Therapie.

The prevalence of food allergies in preschool children has increased in the last few decades. Depending on the triggering allergen, children may outgrow many hypersensitivity reactions to food proteins by the age of 3 - 5 years. Despite improved diagnosis and knowledge, food allergies are still restricting the quality of life in affected subjects and their families. There is a wide spectrum of clinical manifestation from mild cutaneous symptoms to life-threatening anaphylactic reaction. Food proteins are the most frequent cause of anaphylactic reactions in childhood and adolescence. The task of primary care physicians includes identification of at-risk patients, early diagnosis and advice to family members concerning preventive measures and emergency treatment (e. g. adrenaline) in case of accidental ingestion of the culprit food. There is still no causal treatment of food allergy available. Therefore, strict avoidance of the causative food remains the most important measure to date.

A new x-ray interface and surface scattering environmental cell design for in situ studies of radioactive and atmosphere-sensitive samples.

We present a novel design of a purpose-built, portable sample cell for in situ x-ray scattering experiments of radioactive or atmosphere sensitive samples. The cell has a modular design that includes two independent layers of containment that are used simultaneously to isolate the sensitive samples. Both layers of containment can be flushed with an inert gas, thus serving a double purpose as containment of radiological material (either as a solid sample or as a liquid phase) and in separating reactive samples from the ambient atmosphere. A remote controlled solution flow system is integrated into the containment system that allows sorption experiments to be performed on the diffractometer. The cell's design is discussed in detail and we demonstrate the cell's performance by presenting first results of crystal truncation rod measurements. The results were obtained from muscovite mica single crystals reacted with 1 mM solutions of Th(IV) with 0.1 M NaCl background electrolyte. Data were obtained in specular as well as off-specular geometry.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

BACKGROUND: For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. METHODS: This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. RESULTS: Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. CONCLUSION: Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development.

We report an ~1.3 Mb tandem duplication at Xp11.23p11.3 in an 11-year-old boy with pleasant personality, hyperactivity, learning and visual-spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X-linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over-expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams-Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co-localize to presynaptic active zones, and play important roles in neurotransmitter release.

Human immunodeficiency virus testing in patients with newly-diagnosed tuberculosis in Singapore.

INTRODUCTION: Infection with human immunodeficiency virus (HIV) is the most well-known risk factor for the development of tuberculosis (TB). The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with TB undergo testing for HIV infection after counselling. We looked at physician compliance with this recommendation in Singapore. METHODS: A retrospective review of the case records of all patients diagnosed with microbiologically-proven TB between September 2005 and December 2006 (inclusive) at the Singapore General Hospital was conducted. RESULTS: Between September 2005 and December 2006, 493 patients were diagnosed with tuberculosis at our institution. HIV testing was performed in 184 patients (37.3 percent), of whom 15 (8.2 percent) was seropositive. Univariate analysis showed that an age equal to or younger than 60 years, male gender, non-pulmonary tuberculosis, inpatient location at diagnosis, and having an infectious diseases physician as the attending doctor were all significantly associated with HIV testing (p-value is less than 0.05). CONCLUSION: Compliance with HIV testing in all newly-diagnosed tuberculosis patients is poor, with less than 40 percent of patients being tested at our institution. We need to address the factors associated with failure to test, and reinforce to our physicians the importance of HIV testing in these patients.

Risk of hyperkalemia in women taking ethinylestradiol/drospirenone and other oral contraceptives.

BACKGROUND: The oral contraceptive ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin component that possesses potassium-sparing diuretic activity similar to spironolactone. We sought to determine whether EE/DRSP use might lead to adverse effects possibly attributable to hyperkalemia. STUDY DESIGN: This was a matched cohort study in which we identified oral contraceptive (OC) initiators between July 2001 and June 2004 within a large, US health plan. We matched EE/DRSP initiators to other OC initiators in a 1:2 ratio on the basis of a prediction model (propensity score) of EE/DRSP initiation that incorporated dozens of characteristics. We identified insurance claims mentioning hyperkalemia, related clinical outcomes (electrolyte disturbances, arrhythmia, syncope, myocardial infarction) and verified the underlying condition through medical record review. RESULTS: There were 22,429 EE/DRSP initiators matched to 44,858 other OC initiators, with an average follow-up of 7.6 months. A composite clinical surrogate hyperkalemia end point occurred with equal frequency in the compared groups [118 cases in EE/DRSP and 260 in comparators; rate ratio (RR) 0.9, 95% confidence interval (CI) 0.7-1.1]. The individual hyperkalemia surrogate end points exhibited similar results. One EE/DRSP initiator and four comparators were diagnosed specifically with hyperkalemia (RR 0.5, 95% CI 0.0-4.9). The results were not different when we accounted for changes in OC use during follow-up. CONCLUSION: EE/DRSP initiators are no more likely than other OC initiators to experience hyperkalemia or related clinical outcomes which could be caused by hyperkalemia during follow-up.

Supplementary data collection with case-cohort analysis to address potential confounding in a cohort study of thromboembolism in oral contraceptive initiators matched on claims-based propensity scores.

PURPOSE: Residual confounding is a potential limitation of pharmacoepidemiologic studies, and in particular, studies based on administrative claims data that do not capture lifestyle and clinical confounders. We describe an application of the case-cohort design to assess residual confounding by thromboembolic risk factors (e.g., smoking and obesity) not captured in claims data in a claims-based cohort study of thromboembolism among matched oral contraceptive (OC) initiators. METHODS: This study was conducted using the Ingenix Research Data Mart, a database containing medical claims for approximately 12 million members of a large health plan of the United States. We randomly sampled 701 OC initiators from cohorts of ethinyl estradiol/drospirenone (n = 22,429) and other OC initiators (n = 44,858) identified in the years 2001-2004 and matched by propensity score in a claims-based cohort study. Supplementary data on risk factors not measured in the cohort study were collected from medical records for the sample. We estimated the risk ratio of thromboembolism adjusted for the supplementary variables using Cox regression modified for a case-cohort design, and compared it to the rate ratio from the cohort study. RESULTS: The risk ratio adjusted for the supplementary variables was 0.90 (95 per cent (%) confidence interval (CI): 0.49, 1.68) which was similar to the rate ratio (0.92; 95%CI: 0.50, 1.63), indicating negligible confounding by the supplementary variables in the cohort study. CONCLUSIONS: Case-cohort methods were used to assess residual confounding in a claims-based cohort study. This approach adds to a growing number of methods to evaluate residual confounding in cohort studies.

Point-of-care blood ketone testing: screening for diabetic ketoacidosis at the emergency department.

INTRODUCTION: We piloted the use of a blood beta-hydroxybutyrate meter as a point-of-care testing in an emergency department (ED) to establish its role in distinguishing ketosis/ketoacidosis from simple hyperglycaemia, and develop guidelines for its use in the ED. METHODS: 111 consecutive patients presenting with capillary glucose levels exceeding 14 mmol/L had a simultaneous blood ketone measurement at triage. This was correlated with clinical diagnosis, venous bicarbonate levels and urine ketone testing. RESULTS: The median beta-hydroxybutyrate levels was 5.7 (range 4.3-6.0) mmol/L for patients with diabetic ketoacidosis (DKA) and 0.1 (0.0-3.2) mmol/L for the remaining patients. Only 47.7 percent could provide urine samples in the ED. A blood ketone result of 3.5 mmol/L yielded 100 percent specificity and sensitivity for the diagnosis of DKA. CONCLUSION: This is a useful tool that allows clinicians to immediately distinguish between simple hyperglycaemia and potentially life-threatening ketotic states. We formulated simple guidelines for its utilisation in an ED setting.