MaSTR™: an effective probabilistic genotyping tool for interpretation of STR mixtures associated with differentially degraded DNA

International Journal of Legal Medicine - The recently developed probabilistic genotyping software package MaSTR™ (SoftGenetics LLC) was used to develop statistical weight estimates for a...     

A novel system to identify Myb target promoters in friend murine erythroleukemia cells

Friend murine erythroleukemia (MEL) cells provide an early erythroid precursor model that can be induced to terminally differentiate in cell culture and has been used to study erythroid differentiation as well as multistage tumorigenesis. During the chemically induced differentiation of MEL cells, expression of the c-myb protooncogene is downregulated in a biphasic fashion and forced expression of c-myb is able to block the differentiation process, suggesting that c-myb activity may be limiting for differentiation in MEL cells. We have recently produced stable transfectants in the C19 MEL cell line that carry a dominant interfering myb allele (MEnT) under the control of an inducible mouse metallothionein I (MTH) promoter. Upon inducing expression of MEnT, transfected cells enter a differentiation program and begin to produce alpha-globin mRNA, assemble hemoglobin, and stop proliferating. Differential display was used to compare mRNA expression between parental C19 MEL cells induced to differentiate with hexamethylene bisacetamide (HMBA) and stable transfectants induced to differentiate via expression of MEnT to identify potential Myb target promoters. We identified six candidate cDNAs in this fashion and present evidence that two of these represent genes that are dependent on c-Myb activity for maximal expression in MEL cells.     

Intramolecular general base-catalyzed ester hydrolyses by the imidazolyl group.

Intramolecular general base catalysis by the imidazolyl group was found in the hydrolyses of endo-5-[4;(5')-imidazolyl]-bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate in which the imidazolyl and trans-cinnamoyl groups are bound in close proximity to each other by rigid bicyclic rings. The rate constants for the intramolecular general base-catalyzed hydrolyses at 60 degrees are 6.4 X 10(-7) sec-1 for the former and 1.8 X 10(-7) sec-1 for the latter and the deuterium oxide solvent isotope effects are 3.0 for both. On the other hand, no intramolecular catalytic participation of the imidazolyl group was observed in the hydrolyses of the endo-exo isomers, exo- 5-[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5[4'(5')-imidazolyl]bicyclo[2.2.2]oct-exo-2-yl trans-cinnamate, in which the imidazolyl groups are located far from the trans-cinnamoyl groups. Intramolecular general base-catalyzed hydrolyses by the imidazolyl groups in endo-5[4'(5')-imidazolyl]bicyclo[2.2.1]hept-endo-2-yl trans-cinnamate and endo-5-[4'(5')-imidazolyl]bicyclo[2.2.2]oct-endo-2-yl trans-cinnamate can serve as models of serine esterase-catalyzed hydrolyses.     

A cross-over evaluation of different methods and devices to measure blood pressure in type 1 diabetic patients with nephropathy

BACKGROUND: In type 1 diabetic patients with nephropathy, tight blood pressure control has been shown to prevent the progression of the disease. Up until now, self-monitoring, ambulatory and office blood pressure values have not been compared in these patients. Thus, we have evaluated blood pressure values obtained in the office by a physician and at home by self-monitoring with those measured under ambulatory conditions in these patients. Additionally, for blood pressure self-monitoring, three different devices (the sphygmomanometer, upper-arm oscillometer and wrist oscillometer) were compared. METHODS: Twenty-one treated hypertensive type 1 diabetic patients [age 45+/-9 years, duration of diabetes 33+/-12 years (mean+/-SD)] with overt diabetic nephropathy participated in this study. At both baseline and the end of the study, daytime ambulatory blood pressure measurement was performed. Office blood pressure was measured at baseline. Additionally, all the patients measured their blood pressure over a 3-week period using each of the three different devices, in random order, for 1 week. RESULTS: The mean office blood pressure values (135+/-21/85+/-12mmHg) were higher than both the ambulatory (131+/-23/80+/-12, P<0.05) and self-monitoring values (130+/-14/78+/-10; P<0.05 for systolic and P<0.02 for diastolic values). The difference between the ambulatory and self-monitoring values were not statistically significant. Diastolic blood pressure values measured with the oscillometric wrist device showed a trend towards higher values when compared to those measured with the sphygmomanometer and with the oscillometric upper-arm device (P=0.065 for diastolic values). CONCLUSION: Office blood pressure measurements may over-estimate blood pressure in patients with type 1 diabetes and diabetic nephropathy. Because the oscillometric wrist device tends to over-estimate diastolic values, upper-arm devices should be preferred for blood pressure self-monitoring in these patients.     

Financial analysis of an inner-city helicopter service: charges versus collections

Trauma centers are now being perceived as financial burdens because of recent changes in trauma reimbursement for the Medicare Prospective Payment System population and the perception that collection rates are lower among trauma patients. We examined the demographic and clinical factors associated with the collection experience in a series of 114 trauma patients transferred by helicopter from the accident site to an inner-city trauma center. Factors affecting payment at 30, 60, 90, and 180 days included patient age, insurance class, and discharge status. While not as high as the collection rate for the facility as a whole, we found an average 71.2% collection rate for trauma patients at 180 days. As long as trauma reimbursement continues to be cost based for nonMedicare patients, collection rates remain an important consideration in determining the financial viability of trauma centers.     

Experiences with the human tumor colony-forming assay in gynecologic malignancies

Summary Tumor samples from 74 patients with gynecologic malignancies including breast cancer were processed in a soft agar colony-forming assay. None of the samples resulted in a pure single cell suspension. Of the 10 samples meeting our criteria of evaluability for chemosensitivity testing, only 5 samples showed in vitro sensitivity to any drug. Of the 3 evaluable correlations between in vitro and in vivo results, 2 were correct. Due to the low rate of evaluable samples the assay has only limited value in the assignment of chemotherapeutic drugs for patients treated at our institution.This work was supported in part by the Gesellschaft zur Bekämpfung der Krebskrankheiten Nordrhein-Westfalen     

Solid‐phase extraction–liquid chromatography–tandem mass spectrometry method for the qualitative analysis of 61 synthetic cannabinoid metabolites in urine

This article comprises the development and validation of a protocol for the qualitative analysis of 61 phase I synthetic cannabinoid metabolites in urine originating from 29 synthetic cannabinoids, combining solid‐phase extraction (SPE) utilizing a reversed phase silica‐based sorbent (phenyl) with liquid chromatography–tandem mass spectrometry (LC?MS/MS). Validation was performed according to the guidelines of the German Society of Toxicological and Forensic Chemistry. Sufficient chromatographic separation was achieved within a total runtime of 12.3 minutes. Validation included specificity and selectivity, limit of detection (LOD), recovery and matrix effects, as well as auto‐sampler stability of processed urine samples. LOD ranged between 0.025 ng/mL and 0.5 ng/mL in urine. Recovery ranged between 43% and 97%, with only two analytes exhibiting recoveries below 50%. However, for those two analytes, the LODs were 0.05 ng/mL in urine. In addition, matrix effects between 81% and 185% were determined, whereby matrix effects over 125% were observed for 10 non‐first‐generation synthetic cannabinoid metabolites. The developed method enables the rapid and sensitive detection of synthetic cannabinoid metabolites in urine, complementing the spectrum of existing analytical tools in forensic case work. Finally, application to 61 urine samples from both routine and autopsy case work yielded one urine sample that tested positive for ADB‐PINACA N‐pentanoic acid.     

Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies

Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions.     

A Lot of Action,But Not in the Right Direction: Systematic Review and Content Analysis of Smartphone Applications for the Prevention,Detection, and Management of Cancer

Background

Mobile phones have become nearly ubiquitous, offering a promising means to deliver health interventions. However, little is known about smartphone applications (apps) for cancer.

Objective

The purpose of this study was to characterize the purpose and content of cancer-focused smartphone apps available for use by the general public and the evidence on their utility or effectiveness.

Methods

We conducted a systematic review of the official application stores for the four major smartphone platforms: iPhone, Android, Nokia, and BlackBerry. Apps were included in the review if they were focused on cancer and available for use by the general public. This was complemented by a systematic review of literature from MEDLINE, Embase, and the Cochrane Library to identify evaluations of cancer-related smartphone apps.

Results

A total of 295 apps from the smartphone app stores met the inclusion criteria. The majority of apps targeted breast cancer (46.8%, 138/295) or cancer in general (28.5%, 84/295). The reported app purpose was predominantly to raise awareness about cancer (32.2%, 95/295) or to provide educational information about cancer (26.4%, 78/295), followed by apps to support fundraising efforts (12.9%, 38/295), assist in early detection (11.5%, 34/295), promote a charitable organization (10.2%, 30/295), support disease management (3.7%, 11/295), cancer prevention (2.0%, 6/295), or social support (1.0%, 3/295). The majority of the apps did not describe their organizational affiliation (64.1%, 189/295). Apps affiliated with non-profit organizations were more likely to be free of cost (χ² ₁=16.3, P<.001) and have a fundraising or awareness purpose (χ² ₂=13.3, P=.001). The review of the health literature yielded 594 articles, none of which reported an evaluation of a cancer-focused smartphone application.

Conclusions

There are hundreds of cancer-focused apps with the potential to enhance efforts to promote behavior change, to monitor a host of symptoms and physiological indicators of disease, and to provide real-time supportive interventions, conveniently and at low cost. However, there is a lack of evidence on their utility, effectiveness, and safety. Future efforts should focus on improving and consolidating the evidence base into a whitelist for public consumption.