Retinoic acid is required for endodermal pouch morphogenesis and not for pharyngeal endoderm specification.

Because tissues from all three germ layers contribute to the pharyngeal arches, it is not surprising that all major signaling pathways are involved in their development. We focus on the role of retinoic acid (RA) signaling because it has been recognized for quite some time that alterations in this pathway lead to craniofacial malformations. Several studies exist that describe phenotypes observed upon RA perturbations in pharyngeal arch development; however, these studies did not address whether RA plays multiple roles at distinct time points during development. Here, we report the resulting phenotypes in the hindbrain, the neural crest-derived tissues, and the pharyngeal endoderm when RA synthesis is disrupted during zebrafish gastrulation and pharyngeal arch morphogenesis. Our results demonstrate that RA is required for the post-gastrulation morphogenesis and segmentation of endodermal pouches, and that loss of RA does not affect the length of the pharyngeal ectoderm or medial endoderm along the anterior-posterior axis. We also provide evidence that RA is not required for the specification of pharyngeal pouch endoderm and that the pharyngeal endoderm consists of at least two different cell populations, of which the pouch endoderm is sensitive to RA and the more medial pharyngeal endoderm is not. These results demonstrate that the developmental processes underlying pharyngeal arch defects differ depending on when RA signaling is disturbed during development.     

Early appearance of inhibitory input to the MNTB supports binaural processing during development

Despite the peripheral and central immaturities that limit auditory processing in juvenile animals, they are able to lateralize sounds using binaural cues. This study explores a central mechanism that may compensate for these limitations during development. Interaural time and level difference processing by neurons in the superior olivary complex depends on synaptic inhibition from the medial nucleus of the trapezoid body (MNTB), a group of inhibitory neurons that is activated by contralateral sound stimuli. In this study, we examined the maturation of coding properties of MNTB neurons and found that they receive an inhibitory influence from the ipsilateral ear that is modified during the course of postnatal development. Single neuron recordings were obtained from the MNTB in juvenile (postnatal day 15-19) and adult gerbils. Approximately 50% of all recorded MNTB neurons were inhibited by ipsilateral sound stimuli, but juvenile neurons displayed a much greater suppression of firing as compared with those in adults. A comparison of the prepotential and postsynaptic action potential indicated that inhibition occurred at the presynaptic level, likely within the cochlear nucleus. A simple linear model of level difference detection by lateral superior olivary neurons that receive input from MNTB suggested that inhibition of the MNTB may expand the response of LSO neurons to physiologically realistic level differences, particularly in juvenile animals, at a time when these cues are reduced.     

Quantitative aspects of enhanced liver tumour formation in CF-1 mice by dieldrin

The dose-response characteristics of dieldrin-mediated enhancementof liver tumour formation in CF-1 mice were analysed, usingexisting tumour data from chronic feeding studies at six levelsof continuous exposure, involving a total of > 1500 animals.The dose-response relationship can be expressed as: D_x x T_x= D₀ x T₀ = constant, where T₀ = the median liver tumour inductionperiod in control CF-1 mice, T_x = the median liver tumour inductionperiod in dieldrin-treated mice at a dose level D_x, D₀ = thebackground dose equivalent for the induction of ‘spontaneous’liver tumours, D_x = the sum of background dose (D₀) and actualdieldrin dose (_x). The relationship, which is a Druckrey equation(D x Tⁿ = constant) where n = 1, indicates that: (i) the velocityof liver tumour development is proportional to the daily doselevel (D_x), (ii) the total tumourigenic dose is constant acrossall doses, (iii) the effects of dieldrin on the neo-plasticprocess in mouse liver are essentially irreversible and cumulative,and (iv) there is no evidence for a threshold level. However,when _x «D₀, the actual contribution of dieldrin to tumourformation is expected to be negligible.     

Analytical studies on illicit heroin

The recovery of heroin in fumes was investigated. In the Netherlands the common mode of heroin smoking is the chasing the dragon procedure: heroin is heated on an aluminium foil by a lighter and the fumes are inhaled. The efficiency of the volatilization of heroin using this procedure was studied under laboratory conditions using thin layer chromatography, gas chromatography and high pressure liquid chromatography. A considerable influence of the form (salt or base) of the heroin was found as well as strong influences of other substances that may be present in illicit heroin samples as diluents. The danger of the inhalation of fumes containing unknown pyrolysis products is mentioned and a hypothesis is given for the phenomenon of heroin-leucoencephalopathy that was observed in heroin smokers in Amsterdam in 1981. The types of heroin encountered in the Netherlands are discussed with regard to their suitability for smoking.     

Between a hygiene rock and a hygienic hard place: Avoiding SARS-CoV-2 while needing environmental exposures for immunity

Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers.Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene.     

Association between Fruit and Vegetable Intakes and Mental Health in the Australian Diabetes Obesity and Lifestyle Cohort

Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS (p < 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46–0.75) of MCS below population average (<47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects.     

Promotion of knowledge transfer and retention in year 2 medical students using an online training exercise

Advances in Health Sciences Education - It was recently shown that novice medical students could be trained to demonstrate the speed-to-diagnosis and diagnostic accuracy typical of System-1-type...