Mercury accumulation in bats near hydroelectric reservoirs in Peninsular Malaysia

In large man-made reservoirs such as those resulting from hydroelectric dam construction, bacteria transform the relatively harmless inorganic mercury naturally present in soil and the submerged plant matter into toxic methylmercury. Methylmercury then enters food webs and can accumulate in organisms at higher trophic levels. Bats feeding on insects emerging from aquatic systems can show accumulation of mercury consumed through their insect prey. In this study, we investigated whether the concentration of mercury in the fur of insectivorous bat species was significantly higher than that in the fur of frugivorous bat species, sampled near hydroelectric reservoirs in Peninsular Malaysia. Bats were sampled at Temenggor Lake and Kenyir Lake and fur samples from the most abundant genera of the two feeding guilds—insectivorous (Hipposideros and Rhinolophus) and frugivorous (Cynopterus and Megaerops) were collected for mercury analysis. We found significantly higher concentrations of total mercury in the fur of insectivorous bats. Mercury concentrations also differed significantly between insectivorous bats sampled at the two sites, with bats from Kenyir Lake, the younger reservoir, showing higher mercury concentrations, and between the insectivorous genera, with Hipposideros bats showing higher mercury concentrations. Ten bats (H. cf. larvatus) sampled at Kenyir Lake had mercury concentrations approaching or exceeding 10 mg/kg, which is the threshold at which detrimental effects occur in humans, bats and mice.     

Predictive factors for latency period and a prognostic model for survival in patients with therapy‐related acute myeloid leukemia

Therapy‐related acute myeloid leukemia (t‐AML) is an increasingly recognized sequela in patients receiving chemotherapy or radiotherapy for a primary malignancy or autoimmune disease. This study assessed factors related to the latency period (LP) between the antecedent disorder (AD) and t‐AML diagnosis and developed a comprehensive prognostic model to predict overall survival (OS). We evaluated a cohort of newly diagnosed t‐AML patients treated with cytarabine‐based induction therapy from 2001 to 2011. Multivariable linear and proportional hazards models were used to assess the impact of different classes of chemotherapy on the LP and to identify independent prognostic factors for OS. Of 730 treated AML patients, 58 (7.9%) had t‐AML. Median LP to t‐AML was 5.6 years (range, 0.5–38.4). 64% of patients achieved CR and median OS was 10.7 months. Independent prognostic factors of short LP were age at AD (P < 0.0001) and prior treatment with mitotic inhibitors (P = 0.05). Unfavorable cytogenetics (P = 0.004), antecedent hematologic or autoimmune disease (P = 0.01), age >60 (P = 0.03), and platelet count <30,000 μL (P = 0.04) at the time of t‐AML diagnosis were prognostic for inferior OS. A prognostic model using these factors was developed that risk stratified t‐AML patients into two groups: favorable and unfavorable. Patients in the favorable group had a median OS of 37.6 months compared with 6.4 months in patients comprising the unfavorable group (P < 0.0001). Multicomponent prognostic models integrating disease or treatment‐related covariates can help better understand how t‐AML evolves; and can be clinically useful in risk stratifying t‐AML patients undergoing induction therapy. Am. J. Hematol. 89:168–173, 2014. © 2013 Wiley Periodicals, Inc.     

Shedding light on a potential hazard: Dental light-curing units

BackgroundDental light-curing units (LCUs) are powerful sources of blue light that can cause soft-tissue burns and ocular damage. Although most ophthalmic research on the hazards of blue light pertains to low levels from personal electronic devices, computer monitors, and light-emitting diode light sources, the amount of blue light emitted from dental LCUs is much greater and may pose a “blue light hazard.”MethodsThe authors explain the potential risks of using dental LCUs, identify the agencies that provide guidelines designed to protect all workers from excessive exposure to blue light, discuss the selection of appropriate eye protection, and provide clinical tips to ensure eye safety when using LCUs.ResultsWhile current literature and regulatory standards regarding the safety of blue light is primarily based on animal studies, sufficient evidence exists to suggest that appropriate precautions should be taken when using dental curing lights. The authors found it difficult to find on the U.S. Food and Drug Administration database which curing lights had been cleared for use in the United States or Europe and could find no database that listed which brands of eyewear designed to protect against the blue light has been cleared for use. The authors conclude that more research is needed on the cumulative exposure to blue light in humans. Manufacturers of curing lights, government and regulatory agencies, employers, and dental personnel should collaborate to determine ocular risks from blue light exist in the dental setting, and recommend appropriate eye protection. Guidance on selection and proper use of eye protection should be readily accessible.Conclusions and Practical ImplicationsThe Centers for Disease Control and Prevention Guidelines for Infection Control in the Dental Health-Care Setting–2003 and the Occupational Safety and Health Administration Bloodborne Pathogen Standard do not include safety recommendations or regulations that are directly related to blue light exposure. However, there are additional Occupational Safety and Health Administration regulations that require employers to protect their employees from potentially injurious light radiation. Unfortunately, it is not readily evident that these regulations apply to the excessive exposure to blue light. Consequently employers and dental personnel may be unaware that these Occupational Safety and Health Administration regulations exist.     

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off-site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off-site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off-site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co-factor (VWF:RCo), 122 (55%) were low off-site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off-site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off-site processing compared to onsite (McNemarʼs test P-value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.     

Frontal and temporal contributions to understanding the iconic co‐speech gestures that accompany speech

In everyday conversation, listeners often rely on a speaker's gestures to clarify any ambiguities in the verbal message. Using fMRI during naturalistic story comprehension, we examined which brain regions in the listener are sensitive to speakers' iconic gestures. We focused on iconic gestures that contribute information not found in the speaker's talk, compared with those that convey information redundant with the speaker's talk. We found that three regions—left inferior frontal gyrus triangular (IFGTr) and opercular (IFGOp) portions, and left posterior middle temporal gyrus (MTGp)—responded more strongly when gestures added information to nonspecific language, compared with when they conveyed the same information in more specific language; in other words, when gesture disambiguated speech as opposed to reinforced it. An increased BOLD response was not found in these regions when the nonspecific language was produced without gesture, suggesting that IFGTr, IFGOp, and MTGp are involved in integrating semantic information across gesture and speech. In addition, we found that activity in the posterior superior temporal sulcus (STSp), previously thought to be involved in gesture‐speech integration, was not sensitive to the gesture‐speech relation. Together, these findings clarify the neurobiology of gesture‐speech integration and contribute to an emerging picture of how listeners glean meaning from gestures that accompany speech. Hum Brain Mapp 35:900–917, 2014. © 2012 Wiley Periodicals, Inc.     

Changes in human brain glutamate concentration during hypoglycemia: insights into cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes

Hypoglycemia-associated autonomic failure (HAAF) is a condition in which patients with type 1 diabetes (T1D) who experience frequent hypoglycemia develop defective glucose counter-regulation and become unable to sense hypoglycemia. Brain glutamate may be involved in the mechanism of HAAF. The goal of this study was to follow the human brain glutamate concentration during experimentally induced hypoglycemia in subjects with and without HAAF. ¹H magnetic resonance spectroscopy was used to track the occipital cortex glutamate concentration throughout a euglycemic clamp followed immediately by a hypoglycemic clamp. T1D patients with HAAF were studied in comparison to two control groups, i.e., T1D patients without HAAF and healthy controls (n=5 per group). Human brain glutamate concentration decreased (P⩽0.01) after the initiation of hypoglycemia in the two control groups, but a smaller trend toward a decrease in patients with HAAF did not reach significance (P>0.05). These findings are consistent with a metabolic adaptation in HAAF to provide higher glucose and/or alternative fuel to the brain, eliminating the need to oxidize glutamate. In an exploratory analysis, we detected additional metabolite changes in response to hypoglycemia in the T1D patient without HAAF control group, namely, increased aspartate and decreased lactate.     

LEAP: Using machine learning to support variant classification in a clinical setting

Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence to Assess Pathogenicity (LEAP), a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and covariant information. L2‐regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer‐related genes and 5,398 variants from 30 cardiovascular‐related genes). Using 10‐fold cross‐validated predictions, the logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability make LEAP effective in the clinical setting as a high‐throughput quality control layer.