Disinfection Byproducts in Drinking Water from the Tap: Variability in Household Calculated Additive Toxicity (CAT)

Recent studies have implemented a calculated additive toxicity (CAT) approach that sums measured disinfection byproduct (DBP) concentrations weighted by their respective in vitro bioassay potencies to estimate their associated risk in disinfected waters. In this study, the CAT approach was used to systematically investigate 21 regulated and unregulated DBPs measured in drinking water at the household level. Water samples from the tap were collected from over 120 randomly selected participants supplied by eight public water systems using four distinct source water types, two types of disinfection processes, and across two seasons. The purpose of this study was to compare CAT using multiple biological end points, examine household variability, identify DBPs driving toxicity, and assess if current regulated DBPs are adequate predictors of unregulated DBPs. Our results support the significance of unregulated DBPs, particularly haloacetonitriles and iodoacetic acid, as drivers of toxicity. Simple linear models between regulated versus unregulated concentrations and CAT were overall weak with 67% considered poor (r 2 < 0.3). These results reveal that current regulatory monitoring approaches may not be adequately capturing true household exposure due to higher contribution of unregulated DBPs to CAT and poor predictability between regulated and unregulated DBP-mediated CAT

Letter to editor: A new core gross anatomy syllabus for medicine

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Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?

Down's syndrome (DS, trisomy 21) represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD). We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42) burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of Aβ42 could relate to the cases' similar life-time accumulation of Aβ due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP). The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of Aβ42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary). Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis

43 W, 1.55 μm and 12.5 W, 3.1 μm dual-beam, sub-10 cycle, 100 kHz optical parametric chirped pulse amplifier

We present a 100 kHz optical parametric chirped pulse amplifier (OPCPA) developed for strong-field attosecond physics and soft-x-ray transient absorption experiments. The system relies on noncollinear potassium titanyl arsenate booster OPCPAs and is pumped by a 244 W, 1.1 ps Yb:YAG Innoslab chirped pulse laser amplifier. Two optically synchronized infrared output beams are simultaneously available: a 430 μJ, 51 fs, carrier-envelope phase stable beam at 1.55 μm and an angular-dispersion-compensated, 125 μJ, 73 fs beam at 3.1 μm

The Misdiagnosis of Hypertension: The Role of Patient Anxiety

Background: The white coat effect (defined as the difference between blood pressure [BP] measurements taken at the physician's office and those taken outside the office) is an important determinant of misdiagnosis of hypertension, but little is known about the mechanisms underlying this phenomenon. We tested the hypothesis that the white coat effect may be a conditioned response as opposed to a manifestation of general anxiety. Methods: A total of 238 patients in a hypertension clinic wore ambulatory blood pressure monitors on 3 separate days 1 month apart. At each clinic visit, BP readings were manually triggered in the waiting area and the examination room (in the presence and absence of the physician) and were compared with the mercury sphygmomanometer readings taken by the physician in the examination room. Patients completed trait and state anxiety measures before and after each BP assessment. Results: A total of 35% of the sample was normotensive, and 9%, 37%, and 19% had white coat, sustained, and masked hypertension, respectively. The diagnostic category was associated with the state anxiety measure (F3,237 = 6.4, P < .001) but not with the trait anxiety measure. Patients with white coat hypertension had significantly higher state anxiety scores (t = 2.67, P < .01), with the greatest difference reported during the physician measurement. The same pattern was observed for BP changes, which generally paralleled the changes in state anxiety (t = 4.86, P < .002 for systolic BP; t = 3.51, P < .002 for diastolic BP). Conclusions: These findings support our hypothesis that the white coat effect is a conditioned response. The BP measurements taken by physicians appear to exacerbate the white coat effect more than other means. This problem could be addressed with uniform use of automated BP devices in office settings

Seroprevalence of Zika virus in wild African green monkeys and baboons

ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available

Examining the impact of audience response systems on student performance in anatomy education: a randomized controlled trial

Background and Aims: Electronic audience response systems (ARSs) offer the potential to enhance learning and improve performance. However, objective research investigating the use of ARSs in undergraduate education has so far produced mixed, inconclusive results. We investigated the impact of ARSs on short- and long-term test performance, as well as student perceptions of the educational experience, when integrated into undergraduate anatomy teaching. Methods and Results: A cohort of 70 undergraduate medical students were randomly allocated to one of two groups. Both groups received the same anatomy lecture, but one group experienced the addition of ARSs. Multiple-choice tests were conducted before, immediately after the lecture and again 10 weeks later. Self-perceived post-lecture subject knowledge, confidence and enjoyment ratings did not differ between groups. Test performance immediately following the lecture improved when compared against baseline and was modestly but significantly superior in the group taught with ARSs (mean test score of 17.3/20 versus 15.6/20 in the control group, p = 0.01). Tests conducted 10 weeks after the lecture showed no difference between groups (p = 0.61) although overall a small improvement from the baseline test was maintained (p = 0.02). Conclusions: Whilst ARSs offer opportunities to deliver novel education experiences to students, an initial superiority over standard methods does not necessarily translate into longer-term gains in student performance when employed in the context of anatomy education. Key words: medical education; education methodology; education technology; audience response systems; anatomy

Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury.

A major portion of individuals affected by traumatic spinal cord injury (SCI) experience one or more types of chronic neuropathic pain (NP), which is often intractable to currently available treatments. The availability of reliable behavioral assays in pre-clinical models of SCI-induced NP is therefore critical to assess the efficacy of new potential therapies. Commonly used assays to evaluate NP-related behavior in rodents, such as Hargreaves thermal and von Frey mechanical testing, rely on the withdrawal response to an evoked stimulus. However, other assays that test spontaneous/non-evoked NP-related behavior or supraspinal aspects of NP would be highly useful for a more comprehensive assessment of NP following SCI. The Mouse Grimace Scale (MGS) is a tool to assess spontaneous, supraspinal pain-like behaviors in mice; however, the assay has not been characterized in a mouse model of SCI-induced chronic NP, despite the critical importance of mouse genetics as an experimental tool. We found that beginning 2 weeks after cervical contusion, SCI mice exhibited increased facial grimace features compared to laminectomy-only control mice, and this grimace phenotype persisted to the chronic time point of 5 weeks post-injury. We also found a significant relationship between facial grimace score and the evoked forepaw withdrawal response in both the Hargreaves and von Frey tests at 5 weeks post-injury when both laminectomy-only and SCI mice were included in the analysis. However, within only the SCI group, there was no correlation between grimace score and Hargreaves or von Frey responses. These results indicate both that facial grimace analysis can be used as an assay of spontaneous NP-related behavior in the mouse model of SCI and that the information provided by the MGS may be different than that provided by evoked tests of sensory function