Background levels of hydrogen cyanide in human breath measured by infrared cavity ring down spectroscopy

Hydrogen cyanide (HCN) in breath has been suggested as a diagnostic tool for cyanide poisoning and for cyanide-producing bacterial infections. To distinguish elevated levels of breath HCN, baseline data are needed. Background levels of HCN were measured in mixed exhaled air from 40 healthy subjects (26 men, 14 women, age 21–61 years; detection limit: 1.5?ppb; median: 4.4?ppb; range <1.5–14?ppb) by near-infrared cavity ring down spectroscopy (CRDS). No correlation was observed with smoking habits, recent meals or age. However, female subjects had slightly higher breath levels of HCN than male subjects. CRDS has not previously been used for this purpose.     

Toward Patient-Specific,Biologically Optimized Radiation Therapy Plans for the Treatment of Glioblastoma

Purpose

To demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol.

Methods and Materials

We integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics.

Results

The integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients.

Conclusions

Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.     

STEPS: A grid search methodology for optimized peptide identification filtering of MS/MS database search results

For bottom‐up proteomics, there are wide variety of database‐searching algorithms in use for matching peptide sequences to tandem MS spectra. Likewise, there are numerous strategies being employed to produce a confident list of peptide identifications from the different search algorithm outputs. Here we introduce a grid‐search approach for determining optimal database filtering criteria in shotgun proteomics data analyses that is easily adaptable to any search. Systematic Trial and Error Parameter Selection‐–referred to as STEPS‐–utilizes user‐defined parameter ranges to test a wide array of parameter combinations to arrive at an optimal “parameter set” for data filtering, thus maximizing confident identifications. The benefits of this approach in terms of numbers of true‐positive identifications are demonstrated using datasets derived from immunoaffinity‐depleted blood serum and a bacterial cell lysate, two common proteomics sample types.     

Bark beetle infestation impacts on nutrient cycling, water quality and interdependent hydrological effects

Bark beetle populations have drastically increased in magnitude over the last several decades leading to the largest-scale tree mortality ever recorded from an insect infestation on multiple wooded continents. When the trees die, the loss of canopy and changes in water and nutrient uptake lead to observable changes in hydrology and biogeochemical cycling. This review aims to synthesize the current research on the effects of the bark beetle epidemic on nutrient cycling and water quality while integrating recent and relevant hydrological findings, along with suggesting necessary future research avenues. Studies generally agree that snow depth will increase in infested forests, though the magnitude is uncertain. Changes in evapotranspiration are more variable as decreased transpiration from tree death may be offset by increased understory evapotranspiration and ground evaporation. As a result of such competing hydrologic processes that can affect watershed biogeochemistry along with the inherent variability of natural watershed characteristics, water quality changes related to beetle infestation are difficult to predict and may be regionally distinct. However, tree-scale changes to soil–water chemistry (N, P, DOC and base cation concentrations and composition) are being observed in association with beetle outbreaks which ultimately could lead to larger-scale responses. The different temporal and spatial patterns of bark beetle infestations due to different beetle and tree species lead to inconsistent infestation impacts. Climatic variations and large-scale watershed responses provide a further challenge for predictions due to spatial heterogeneities within a single watershed; conflicting reports from different regions suggest that hydrologic and water quality impacts of the beetle on watersheds cannot be generalized. Research regarding the subsurface water and chemical flow-paths and residence times after a bark beetle epidemic is lacking and needs to be rigorously addressed to best predict watershed or regional-scale changes to soil–water, groundwater, and stream water chemistry.     

Familial Creutzfeldt-Jakob Disease: Case report and role of genetic counseling in post mortem testing

Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ～1 y of symptom onset. The cause of death was reported as “rapid onset dementia.” The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD. The family had additional questions about the implications of this result and thus independently sought out genetic counseling.

?While rare, fCJD is likely underdiagnosed due to clinical heterogeneity, rapid onset, early non-specific symptomatology, and overlap in the differential diagnosis of Alzheimer disease and Lewy body dementias. When fCJD is identified, a multidisciplinary approach to return of results that includes the affected patient's provider, genetics professionals, and mental health professionals is key to the care of the family. We present an example case which discusses the psychosocial issues encountered and the role of genetic counseling in presymptomatic testing for incurable neurodegenerative conditions. Ordering physicians should be aware of the basic issues surrounding presymptomatic genetic testing and identify local genetic counseling resources for their patients.     

Immunochemical analysis of the structure of the signature domains of thrombospondin-1 and thrombospondin-2 in low calcium concentrations

Thrombospondins (TSPs) undergo conformational changes upon removal of calcium. The eight C-type and five N-type calcium-binding repeats of TSP-2 form a circuitous wire that, in 2 mm calcium, interacts at its ends with more N-terminal epidermal growth factor (EGF)-like modules, EGF2 and EGF3, and the C-terminal lectin-like module. These components, along with the other EGF-like module(s), form the signature domain of TSPs. Characterization of conformation-sensitive epitopes of monoclonal antibodies to human TSP-2 and its TSP-1 homolog have given insights into the structure of the signature domain in the absence of calcium. The epitope for 4B6.13 anti-TSP-2 was localized to His-722 and Leu-703 in repeat 1C of the wire; recognition only occurred in constructs that included EGF3, the rest of the wire, and the lectin-like module and in the presence of calcium. The epitope for C6.7 anti-TSP-1 was localized to Glu-609 in the EGF2 module. The C6.7 epitope was preferentially recognized when EGF2 was expressed in the context of EGF1, EGF3, the wire, and the lectin-like module. Preferential recognition of the C6.7 epitope did not require calcium. Rotary shadowing electron microscopy of TSP-1 has shown elongation of the stalk and diminution of the C-terminal globule. We propose a model whereby at low calcium concentrations the lectin-like module drops away from EGF3 concomitant with changes in conformation of the wire and loss of the 4B6.13 epitope. A critical feature of the model is interaction of repeat 12N of the wire with EGF2 in both the presence and absence of calcium.