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The release of engineered titanium dioxide nanoparticles in the environment is nowadays continuously increasing due to their wide range of industrial applications. Their potential toxicity effects became of major concern and several assessment studies in natural waters were already undertaken. However, no consensus arised about the environmental factors influencing their hazardous impact, but rather contrary conclusions were drawn. In this study, the acute toxicity of commercial TiO2 nanoparticles suspensions at different concentrations on microcrustacean (Daphnia magna), marine rotifers (Brachionus plicatilis) and marine microalgae (Phaeodactylum tricornutum) under environmental conditions, in synthetic fresh and marine water, was investigated. Factors driving TiO2 adverse effects on aquatic environment, such as allotropic form, primary particle size, surface area, particle concentration and agglomerate size were studied. A thorough characterization of both surface and bulk properties of nano-sized TiO2 particles was therefore performed. Our results showed that Daphnia magna test is the most sensitive test for assessing toxicity of TiO2 samples on aquatic organisms. For anatase samples, toxicity towards aquatic organisms depends (i) on the primary particle size and the extent of agglomeration (mass median diameter d50), and consequently on surface reactivity (total surface site concentration, specific surface area, pHIEP) (ii) on the presence of rutile impurities in the sample. Toxicity results of rutile and anatase samples of comparable primary particle size (sub micrometric range) are of same order of magnitude and remained less toxic than nanometric particles. Rutile agglomeration was found to be higher than anatase agglomeration, toxicity results obtained for rutile could be attribute to the shape of particles, or it could be due to the presence of BaTiO3 impurities. This work emphasized the importance of studying the effects of different bulk and surface parameters of engineered TiO2 nanoparticles to understand their reactivity towards micro-organisms under environmental conditions.

Background The development of technical dexterity is a critical for surgeons in training. This study describes and assesses the feasibility of an objective method for the evaluation of procedure-specific technical dexterity in hepatopancreatobiliary (HPB) surgery using cumulative sum (CUSUM) analysis. Methods Dry-lab HPB procedures were divided into procedural steps with binary outcomes (success or failure). Two HPB fellows completed 20 dry lab hepaticojejunostomy (HJ) procedures. Participant progress was tracked over time with CUSUM analytics to establish a learning curve for procedural proficiency. Results The CUSUM charts for 20 consecutive dry-lab HJ procedures were analysed. A learning curve was created and used to identify areas of weakness to facilitate improvement in technical proficiency. Conclusions CUSUM is effective tool for objective evaluation of technical dexterity offering both simplicity and adaptability. We demonstrate its use and feasibility for surgical education and plan to expand its' application to assess residents performing general surgery procedures.

DNA G-quadruplex structures were recently discovered to provide reliable scaffolding for two-dimensional organic frameworks due to the strong hydrogen-bonding ability of guanine. Herein, 2,7-diaryl pyrene building blocks with high HOMO energies and large optical gaps are incorporated into G-quadruplex organic frameworks. The adjustable substitution on the aryl groups provides an opportunity to elucidate the framework formation mechanism; molecular non-planarity is found to be beneficial for restricting interlayer slippage, and the framework crystallinity is highest when intermolecular interaction and non-planarity strike a fine balance. When guanine-functionalized pyrenes are co-crystallized with naphthalene diimide, charge-transfer (CT) complexes are obtained. The photophysical properties of the pyrene-only and CT frameworks are characterized by UV/Vis and steady-state and time-resolved photoluminescence spectroscopies, and by EPR spectroscopy for the CT complex frameworks.

Cabozantinib is an oral small-molecule multitargeted tyrosine kinase inhibitor (TKI) that may confer an advantage over other TKIs that target a single receptor. It was approved by the U.S. Food and Drug Administration for the treatment of both advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, and it is being investigated for a wide array of other malignancies. Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article. Common adverse events are reviewed, and management strategies for select adverse events are discussed. Implications for contemporary practitioners are also provided because use of this novel agent is likely to increase as more studies are completed.

It is not always practical to hand-measure body size of free-ranging animals. In recent years, parallel-laser photogrammetry has become increasingly common for obtaining remote estimates of body size. However, it is unknown how well this technique might capture variation in body size of curvilinear features or whether the distance between parallel-laser calipers is altered when projected onto a curved surface. We describe a photogrammetric system that may be useful for obtaining body-size measurements from unrestrained large mammals that permit approach. We tested the use of parallel-laser photogrammetry to estimate the size of curvilinear features in domestic horses (Equus ferus caballus) and identified morphometrics that explained variation in body weight. Despite projecting the lasers onto a curved surface (the barrel of a horse), we achieved accurate photogrammetric estimates of linear hand-measurements. The curvilinear hand-measurements also showed strong correlations (R2 ≥ 0.996) with their respective linear photogrammetric estimates, and most photogrammetric estimates had high reliability. Using 3 variables of body size, photogrammetric estimates and hand-measurements explained 86.0% and 96.2% of the variation in weight, respectively. © 2015 The Wildlife Society.

Summary Background In adults, depressive symptoms are positively associated with insulin resistance. Objective To determine whether an association exists between depressive symptoms and markers of insulin resistance in youth. Methods This study used a retrospective review of data from an obesity clinic. We evaluated the association between depressive symptoms (Children's Depression Inventory, CDI) and fasting insulin and homeostatic model assessment-insulin resistance (HOMA-IR) in obese youth (n = 207, age 10–18 years). Individuals with lower vs. higher CDI T-scores (

Background Pediatric studies examining the association between obstructive sleep apnea (OSA) and insulin sensitivity/cardiometabolic risk are limited and conflicting.

Introduction Clinical heterogeneity of limb-girdle muscular dystrophies (LGMDs, 24 known subtypes), which includes overlapping phenotypes and varying ages of onset and morbidity, adds complexity to clinical and molecular diagnoses. Methods To diagnose LGMD subtype, protein analysis, using immunohistochemistry (IHC) and immunoblotting, was followed by gene sequencing through a panel approach (simultaneous sequencing of known LGMD genes) in 9 patients from unrelated families of the Indian Agarwal community. Haplotype studies were performed by targeted SNP genotyping to establish mutation segregation. Results We identified 2 founder mutations in CAPN3, a missense (c.2338G>C; p.D780H) and a splice-site (c.2099-1G>T) mutation, on 2 different haplotype backgrounds. The patients were either heterozygous for both or homozygous for either of these mutations. Conclusions Founder mutations have immediate clinical application, at least in selected population groups. Clinically available gene panels may provide a definitive molecular diagnosis for heterogeneous disorders such as LGMD. Muscle Nerve 47: 931–937, 2013

Background Depression is common during and after breast cancer treatment. However, the role of specific therapeutic modalities and related biological mechanisms remains unclear. Radiation is an essential component of breast conserving therapy and may contribute to depression in breast cancer patients through activation of inflammatory pathways.

Small changes in the flux of energy, chemicals, and water to mountain catchments may invoke large changes in the local climate, ecosystem dynamics, and water quantity and quality. The Landscape Continuum Model (LCM) was developed in part to improve our understanding of how high-elevation ecosystems might respond to future perturbations. We sampled water chemistry along the main stem of Boulder Creek in the Colorado Front Range from the foothills to the Continental Divide, along with four headwater catchments, to address two questions: (i) Is there value in extending the LCM concept to lower-elevation headwater catchments? (ii) Is a “space-for-time” substitution along an elevational gradient appropriate when there are changes in ecosystem type? Our results show that the hydrochemistry of headwater catchments along the elevational gradient of Boulder Creek was different when compared to the main stem. Headwater catchments amplified the fluxes of inorganic and organic solutes when compared with sites at similar elevations along the main stem of Boulder Creek, consistent with the LCM. Our results also suggest a space-for-time substitution along an elevational gradient is warranted for at least some biogeochemical processes when there is a switch from the snow to rain transition in annual precipitation. For example, the high concentrations of base cations and dissolved organic carbon in the foothills catchment when compared with higher elevation catchments is consistent with increased rates of biogeochemical cycling with increasing air temperature at lower elevations. However, the low-elevation catchment had a lower specific discharge than other catchments with similar annual precipitation, but higher percentages as snowfall, resulting in decreased fluxes of these products.

Summary: Using antigens from three strains of Aspergillus fumigatus (AF), 97 sera were studied for specific antibodies by agar gel double diffusion (DD), indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). The results showed wide variation in the reactivity of the different antigens and different methods. It is also evident from the results that several different AF antigens and serological methods are useful in demonstrating antibodies in the sera and in avoiding false positive and negative results. However, it is not possible to make a diagnosis solely from the serological results, as a majority of the sera from non-AF-induced lung diseases showed comparable reactions to those of aspergilloma and allergic bronchopulmonary aspergillosis (ABPA). This study confirms the necessity of standardized antigens for reliable and dependable results irrespective of the methods employed. Zusammenfassung: Unter Verwendung der Antigene von drei Stammen von Aspergillus fumigatus (AF) wurden 97 Seren mit Hilfe der folgenden Methoden auf spezifische Antikorper untersucht: Agar-Gel-Doppeldiffusion (DD), indirekte Imminfluoreszenz (IIF) und Enzyme-linked immunosorbent assay (ELISA). Die Ergebnisse zeigten eine grose Streubreite der Reaktionen unter Verwendung verschiedener Antigene und verschiedener Methoden. Aus den Ergebnissen ist weiterhin ablesbar, das eine Reihe verschiedener AF-Antigene und verschiedener serologischer Methoden fur den Nachweis von Antikorpern benutzt werden konnen und dasihre Kombination nutzlich ist fur die Vermeidung falsch positiver oder falsch negativer Ergebnisse. Dennoch ist es nicht moglich, eine Diagnose ausschlieslich aufgrund der serologischen Befunde zu stellen, da eine grose Zahl der Seren von Patienten mit Lungenerkrankungen, die nicht durch AF hervorgerufen waren, Reaktionen zeigten, wie sie auch beim Aspergillom oder bei der allergischen bronchopulmonalen Aspergillose auftraten. Aus der Studie wird deutlich, das es unabhangig von der angewendeten Methode erforderlich ist, zur Gewinnung verlaslicher Ergebnisse standardisierte Antigene zu benutzen.

Summary: One thousand three hundred and ten samples of human sera were studied for the presence of antibodies against Aspergillus fumigatus using antigen extracts from 3 selected strains of A. fumigatus. Fifty sera gave strong precepitin reactions while 221 gave weakly positive reactions. However, only 50 and 11 percent of the strongly positive and weakly positive sera were positive to all 3 extracts. The use of antigenic preparations from several strains of A. fumigatus is proposed to avoid false negative reactions. Zusammenfassung: 1310 Patientenseren wurden auf die Anwesenheit von Antikorpern gegen Aspergillus fumigatus unter Verwendung von Antigenextrakten aus drei ausgewahlten Stammen von Aspergillus fumigatus untersucht. 50 Seren zeigten starke Prazipitinreaktionen, wahrend 221 Seren nur schwach positive Reaktionen aufwiesen. Von den stark bzw. schwach positiven Seren reagierten jedoch nur 50 bzw. 11% auf alle drei Anti-genextrakte. Es wird daher vorgeschlagen, zur Vermeidung falsch negativer Reaktionen Antigenpraparate von mehreren Aspergillus fumigatus Stammen gleichzeitig einzusetzen.

Upon variation of the steric and electronic properties of the starting sulfolenes four unique bi- or tricyclic ring-systems are constructed as single diastereomers with up to five stereogenic centers.

BACKGROUND Aspergillus fumigatus, a ubiquitous fungus, is responsible for a number of lung disorders in atopic and non-atopic individuals. Standardized, pure, and relevant allergens are desirable for reliable immunodiagnosis of the disease and to understand the structural and functional properties of these allergens and the role they play in causing ABPA. OBJECTIVE Molecular cloning and characterization of a relevant allergen from A. fumigatus cDNA library. MATERIALS AND METHODS A cDNA library was constructed from 96 h old mycelium of A. fumigatus using lambda ZAP expression vector. A novel gene encoding an A. fumigatus allergen was identified by screening the library with sera from ABPA patients. The gene was cloned and the allergen over-expressed in Escherichia coli. This recombinant allergen, Asp f 16, was evaluated in ELISA and Western blots using sera from patients and normal subjects and peripheral blood mononuclear cells (PBMC) for antigen-induced stimulation. RESULTS Seventy percent of the patients with ABPA demonstrated high levels of serum IgE antibodies to Asp f 16, a 43-kDa protein, whereas patients with allergic asthma, Aspergillus skin test-positive asthmatics without clinical evidence of ABPA, and normal controls failed to show Asp f 16-specific IgE binding by ELISA. The deduced amino acid sequences of Asp f 16 showed extensive sequence homology to 30.6-kDa Asp f 9 at the N-terminal region of the protein. PBMC from the majority of patients with ABPA exhibited significant proliferation with the recombinant Asp f 16 allergen. CONCLUSION Specific humoral and cell-mediated immune responses of Af-sensitized patients against Asp f 16 suggest its usefulness in the immunodiagnosis of hypersensitivity diseases due to Af and understanding the pathophysiology of ABPA.

Background Latex allergy is largely an occupational allergy due to sensitization to natural rubber latex allergens present in a number of health care and household products. Although several purified allergens are currently available for study, information on the usefulness of these purified, native or recombinant allergens in the demonstration of specific immunoglobulin (Ig) E in the sera of patients is lacking. Objective To evaluate the purified latex allergens and to demonstrate specific IgE antibody in the sera of health care workers and spina bifida patients with clinical latex allergy. Methods Two radioallergosorbent and an enzyme-linked immunosorbent assay (ELISA) using latex proteins Hev b 1, 2, 3, 4, 6 and 7 along with two glove extracts and Malaysian nonammoniated latex (MNA) were evaluated to demonstrate IgE in the sera of health care workers and spina bifida with latex allergy and controls with no history of latex allergy. Results ELISA using the purified latex allergens demonstrated specific IgE in 32–65% health care workers and 54–100% of spina bifida patients with latex allergy. The corresponding figures for RAST were 13–48 and 23–85 for RAST-1 and 19–61 and 36–57 for RAST-2. These results were comparable with the results obtained with glove extracts and crude rubber latex proteins. Conclusions When used simultaneously, latex proteins Hev b 2 and Hev b 7 reacted significantly with specific serum IgE in 80% of health care workers and 92% of spina bifida patients with latex allergy by ELISA technique, while this combination gave lower positivity when the RASTs were used. By the addition of Hev b 3, specific IgE was detected in all spina bifida patients with latex allergy. Both RASTs failed to show specific IgE in the control subjects, while the ELISA showed significant latex-specific IgE in 22% of controls.

Pigeon serum (PS) is one of the most common causes of hypersensitivity pneumonitis (HP). PS-induced HP was examined in a dog model. The dogs (n = 6) were immunized by i.m. injections of PS, followed by insufflation with aerosolized PS, while all control dogs (n = 3) received saline only. All animals insufflated with PS developed tachypnea 2-4 h after PS inhalation. After PS insufflation, a significant decrease in arterial oxygen tension (PaO2) was detected in sensitized dogs. No change in PaO2 was detected in sensitized dogs after saline or in the controls after PS insufflation. In intradermal skin tests with PS antigen, a positive skin reaction was found in 3/6 dogs in 30 min, and in 5/6 dogs in 6 and 48 h after the PS injections. Sensitized dogs showed a significant increase in PS-specific IgG in serum and lavage fluid (LF). In LF of sensitized dogs, an increase in the percentage of lymphocytes, eosinophils, and neutrophils was detected. Sensitized dogs developed chronic interstitial inflammation with lymphocytes, macrophages, plasma cells, and eosinophils in lungs. Granulomas with lymphocytes, histiocytes, and giant cells were detected in both the interstitium and the bronchiolar wall in the lungs of sensitized dogs. PaO2 was lowest in dogs showing the most severe interstitial inflammation in the lungs. The results indicate that dogs can be successfully used in immunologic and physiologic studies of PS-induced HP.

Immunoelectron microscopy (IEM) was used to determine the binding of six monoclonal antibodies (MoAbs) produced against Aspergillus fumigatus antigens present on or within the conidia and hyphae of the fungus. Antigen-antibody complexes were demonstrated in EM using labelled colloidal gold particles (15 nm). Three out of 6 MoAbs (C9, F12 and H10) reacted only with the cytoplasmic components of A. fumigatus while the remaining three (B12, F6G5 and D6E6) showed reactivity to both cytoplasm and cell wall of the conidia and hyphae. The results indicate that IEM is of considerable value in determining and selecting monoclonal antibodies having specific reactivity with diverse antigenic components.