Proton Magnetic Resonance Spectroscopic Evidence of Glial Effects of Cumulative Lead Exposure in the Adult Human Hippocampus

BACKGROUND: Exposure to lead is known to have adverse effects on cognition in several different populations. Little is known about the underlying structural and functional correlates of such exposure in humans. OBJECTIVES: We assessed the association between cumulative exposure to lead and levels of different brain metabolite ratios in vivo using magnetic resonance spectroscopy (MRS). METHODS: We performed MRS on 15 men selected from the lowest quintile of patella bone lead within the Department of Veterans Affairs’ Normative Aging Study (NAS) and 16 from the highest to assess in the hippocampal levels of the metabolites N-acetylaspartate, myoinositol, and choline, each expressed as a ratio with creatine. Bone lead concentrations—indicators of cumulative lead exposure—were previously measured using K-X-ray fluorescence spectroscopy. MRS was performed on the men from 2002 to 2004. RESULTS: A 20-μg/g bone and 15-μg/g bone higher patella and tibia bone lead concentration—the respective interquartile ranges within the whole NAS—were associated with a 0.04 [95% confidence interval (CI), 0.00–0.08; p = 0.04] and 0.04 (95% CI, 0.00–0.08; p = 0.07) higher myoinositol-to-creatine ratio in the hippocampus. After accounting for patella bone lead declines over time, analyses adjusted for age showed that the effect of a 20-μg/g bone higher patella bone lead level doubled (0.09; 95% CI, 0.01–0.17; p = 0.03). CONCLUSIONS: Cumulative lead exposure is associated with an increase in the myinositol-to-creatine ratio. These data suggest that, as assessed with MRS, glial effects may be more sensitive than neuronal effects as an indicator of cumulative exposure to lead in adults

A deformable model for the reconstruction of the neonatal cortex

We present a method based on deformable meshes for the reconstruction of the cortical surfaces of the developing human brain at the neonatal period. It employs a brain segmentation for the reconstruction of an initial inner cortical surface mesh. Errors in the segmentation resulting from poor tissue contrast in neonatal MRI and partial volume effects are subsequently accounted for by a local edge-based refinement. We show that the obtained surface models define the cortical boundaries more accurately than the segmentation. The surface meshes are further guaranteed to not intersect and subdivide the brain volume into disjoint regions. The proposed method generates topologically correct surfaces which facilitate both a flattening and spherical mapping of the cortex

Night shift work and risk of breast cancer in women: the Generations Study cohort.

Background It is plausible that night shift work could affect breast cancer risk, possibly by melatonin suppression or circadian clock disruption, but epidemiological evidence is inconclusive.Methods Using serial questionnaires from the Generations Study cohort, we estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for breast cancer in relation to being a night shift worker within the last 10 years, adjusted for potential confounders.Results Among 102,869 women recruited in 2003-2014, median follow-up 9.5 years, 2059 developed invasive breast cancer. The HR in relation to night shift work was 1.00 (95%CI: 0.86-1.15). There was a significant trend with average hours of night work per week (P = 0.035), but no significantly raised risks for hours worked per night, nights worked per week, average hours worked per week, cumulative years of employment, cumulative hours, time since cessation, type of occupation, age starting night shift work, or age starting in relation to first pregnancy.Conclusions The lack of overall association, and no association with all but one measure of dose, duration, and intensity in our data, does not support an increased risk of breast cancer from night shift work in women

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

One hundred years of neglect in paediatric schistosomiasis.

: Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel - PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.<br/

A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors

Resolving the extragalactic hard X-ray background

The origin of the hard (2-10 keV) X-ray background has remained mysterious for over 35 years. Most of the soft (0.5-2 keV) X-ray background has been resolved into discrete sources, which are primarily quasars; however, these sources do not have the flat spectral shape required to match the X-ray background spectrum. Here we report the results of an X-ray survey 30 times more sensitive than previous studies in the hard band and four times more sensitive in the soft band. The sources detected in our survey account for at least 75 per cent of the hard X-ray background. The mean X-ray spectrum of these sources is in good agreement with that of the background. The X-ray emission from the majority of the detected sources is unambiguously associated with either the nuclei of otherwise normal bright galaxies or optically faint sources, which could either be active nuclei of dust enshrouded galaxies or the first quasars at very high redshifts.Comment: Nature article in pres

Pathologic characteristics of resected squamous cell carcinoma of the trachea: prognostic factors based on an analysis of 59 cases

While squamous cell carcinoma (SCC) is the most common tracheal malignancy, few reports describe the pathologic considerations that may guide intraoperative decisions and prognostic assessment. We reviewed 59 tracheal SCC treated between 1985 and 2008 by segmental resection of the trachea, including resection of the carina in 24% and inferior larynx in 14%. We classified these tumors by grading histologic differentiation and microscopic features used in SCC of other sites. Of 59 tumors, 24% (14 of 59) were well differentiated, 49% (29 of 59) were moderately differentiated, and 27% (16 of 59) were poorly differentiated. Unfavorable prognostic factors were tumor extension into the thyroid gland (all of five so-afflicted patients died of tumor progression within 3 years) and lymphatic invasion (mean survival 4.6 versus 7.6 years). Keratinization, dyskeratosis, acantholysis, necrosis, and tumor thickness did not predict prognosis. As surgical resection is the only curative treatment; the surgeon should establish clean lines of resection using, as appropriate, intraoperative frozen section. The pathologist can provide additional important prognostic information, including tumor differentiation and extent, invasion of surgical margins, and extension into the thyroid

Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

The Influence of Different Stresses on Glomalin Levels in an Arbuscular Mycorrhizal Fungus—Salinity Increases Glomalin Content

Glomalin is a glycoprotein produced by arbuscular mycorrhizal (AM) fungi, and the soil fraction containing glomalin is correlated with soil aggregation. Thus, factors potentially influencing glomalin production could be of relevance for this ecosystem process and for understanding AM fungal physiology. Previous work indicated that glomalin production in AM fungi may be a stress response, or related to suboptimal mycelium growth. We show here that environmental stress can enhance glomalin production in the mycelium of the AM fungus Glomus intraradices. We applied NaCl and glycerol in different intensities to the medium in which the fungus was grown in vitro, causing salinity stress and osmotic stress, respectively. As a third stress type, we simulated grazing on the extraradical hyphae of the fungus by mechanically injuring the mycelium by clipping. NaCl caused a strong increase, while the clipping treatment led to a marginally significant increase in glomalin production. Even though salinity stress includes osmotic stress, we found substantially different responses in glomalin production due to the NaCl and the glycerol treatment, as glycerol addition did not cause any response. Thus, our results indicate that glomalin is involved in inducible stress responses in AM fungi for salinity, and possibly grazing stress