Hippocampal denervation causes rapid forgetting of olfactory information in rats.

Rats were trained on a succession of two-odor discriminations for a water reward in a modified radial maze. A different odor pair was used each day. After three or four pairs, rats would learn to choose the correct odor in only 3-5 trials. Animals were then subjected to electrolytic lesions in the lateral entorhinal cortex, which is innervated by the lateral olfactory tract, or in the dorsal entorhinal cortex, which is not a target of the olfactory system. Lesions of the first type did not interfere with performance, provided a short interval (30 sec to 2 min) was used between trials. However, the rats were severely impaired when trials were separated by 3-10 min. Dorsal lesions had no effect on olfactory discrimination irrespective of length of delay. In additional experiments, the rats were trained for 10 trials with short inter-trial intervals and then tested 1 hr later with the significance of the cues reversed. Animals with dorsal lesions continued to respond to the formerly correct odor while those with lateral entorhinal damage immediately reversed their response choices. These results provide evidence that lesions to the hippocampal system produce a rapid forgetting syndrome in rats comparable with that reported for humans with temporal lobe damage or dysfunction.     

Hyaluronic acid and endothelial damage due to paracetamol‐induced hepatotoxicity

Abstract: Background: Damage to endothelial cells may be an important factor in the complications of acute liver failure, resulting in multi‐organ failure. The aim of this study was to assess endothelial cell function in patients with severe hepatotoxicity due to paracetamol ingestion. Patients and methods: Fifty‐eight patients with paracetamol‐induced hepatotoxicity were studied for up to 7 days. Serum hyaluronic acid (HA), as a marker of hepatic sinusoidal endothelial cell function, was determined using an enzyme‐linked binding assay. Plasma von Willebrand Factor, thrombomodulin and interleukin‐8 were also determined using ELISA. Results: Serum HA on admission was significantly increased (median 6777 ng/ml, range 24–50 967 ng/ml) as compared to normal controls (n = 10, median 21 ng/ml, range 0–50 ng/ml; P < 0.001). In non‐survivors (n = 21) HA levels peaked on day 2 after admission (P = 0.044), and then decreased. In the survivors (n = 37) the levels of HA did not increase further. Plasma von Willebrand Factor, plasma thrombomodulin and serum interleukin‐8 were significantly increased in the patients as compared to the normal controls (P < 0.001). Serum interleukin‐8 was significantly higher in non‐survivors in the first 2 days. Conclusions: Endothelial function is abnormal in paracetamol‐induced hepatotoxicity. Damage to hepatic sinusoidal endothelial cells assessed by serum HA was greater in non‐survivors than survivors.     

Acculturation and Nutritional Health of Immigrants in Canada: A Scoping Review

Although recent immigrants to Canada are healthier than Canadian born (i.e., the Healthy Immigrant Effect), they experience a deterioration in their health status which is partly due to transitions in dietary habits. Since pathways to these transitions are under-documented, this scoping review aims to identify knowledge gaps and research priorities related to immigrant nutritional health. A total of 49 articles were retrieved and reviewed using electronic databases and a stakeholder consultation was undertaken to consolidate findings. Overall, research tends to confirm the Healthy Immigrant Effect and suggests that significant knowledge gaps in nutritional health persist, thereby creating a barrier to the advancement of health promotion and the achievement of maximum health equity. Five research priorities were identified including (1) risks and benefits associated with traditional/ethnic foods; (2) access and outreach to immigrants; (3) mechanisms and coping strategies for food security; (4) mechanisms of food choice in immigrant families; and (5) health promotion strategies that work for immigrant populations.     

Antiproliferative Activity of King Cobra (Ophiophagus hannah) Venom l‐Amino Acid Oxidase

King cobra (Ophiophagus hannah) venom l ‐amino acid oxidase (LAAO), a heat‐stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF‐7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC₅₀ value of 0.04 ± 0.00 and 0.05 ± 0.00 μg/mL, respectively, after 72‐hr treatment. In comparison, its cytotoxicity was about 3–4 times lower when tested against human non‐tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF‐7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC₅₀ value of 0.18 ± 0.03 and 0.63 ± 0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7‐amino‐actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO‐treated tumour cells than in their non‐tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase‐3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H₂O₂ scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours.     

Detection of Chronic Wasting Disease in the Lymph Nodes of Free-Ranging Cervids by Real-Time Quaking-Induced Conversion

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic.     

Light exposure during sleep impairs cardiometabolic function

This study tested the hypothesis that acute exposure to light during nighttime sleep adversely affects next-morning glucose homeostasis and whether this effect occurs via reduced sleep quality, melatonin suppression, or sympathetic nervous system (SNS) activation during sleep. A total of 20 young adults participated in this parallel-group study design. The room light condition (n = 10) included one night of sleep in dim light (<3 lx) followed by one night of sleep with overhead room lighting (100 lx). The dim light condition (n = 10) included two consecutive nights of sleep in dim light. Measures of insulin resistance (morning homeostatic model assessment of insulin resistance, 30-min insulin area under the curve [AUC] from a 2-h oral glucose tolerance test) were higher in the room light versus dim light condition. Melatonin levels were similar in both conditions. In the room light condition, participants spent proportionately more time in stage N2 and less in slow wave and rapid eye movement sleep. Heart rate was higher and heart rate variability lower (higher sympathovagal balance) during sleep in the room light versus the dim light condition. Importantly, the higher sympathovagal balance during sleep was associated with higher 30-min insulin AUC, consistent with increased insulin resistance the following morning. These results demonstrate that a single night of exposure to room light during sleep can impair glucose homeostasis, potentially via increased SNS activation. Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health.

Exposure to artificial light during the night is widespread globally, particularly in industrialized countries (1–3). Given that light and dark exposure patterns play a key role in the timing of many behaviors and physiological functions (4), exposure to light in the evening and night has been posited to be deleterious for human health and well-being (1, 5–10). Impacts of light exposure during sleep are not as well studied as other kinds of nighttime light exposure. However, a recent cross-sectional observation study noted that, compared to no light exposure during sleep, any self-reported artificial light exposure in the bedroom during sleep (small nightlight in room, light from outside room, or television/light in room) was associated with obesity in women (11). Furthermore, the incidence of obesity was highest in those who reported sleeping with a television or light on in the bedroom (11). These findings suggest that light in the bedroom during nighttime sleep may negatively influence metabolic regulation.Emerging evidence indicates that light exposure plays a role in human metabolic regulation, with evening light exposure having unfavorable effects on metabolic functions including decreased glucose tolerance and decreased insulin sensitivity (12, 13). In line with these data, we have previously shown that blue-enriched light exposure in the morning and evening alters glucose metabolism, with an increase in insulin resistance compared to dim light exposure (14). In addition, evidence indicates that nighttime indoor light exposure during the habitual sleep period while awake (15), and during sleep itself (16), likely has deleterious metabolic effects. A recent study prospectively measured light exposure in the bedroom during nighttime sleep and showed that higher levels of bedroom light exposure were associated with a higher incidence of type 2 diabetes in an elderly population (16). However, the exact mechanisms by which light exposure, particularly during nighttime sleep, impacts metabolic regulation are not well understood.A proposed pathway to explain the relationship between nighttime light exposure and altered metabolic function is via changes in sleep. Robust evidence from epidemiological and experimental studies indicates that nighttime light exposure, either from outdoor or indoor sources, has negative impacts on subjective and objective sleep quality as indicated by actigraphy or polysomnography (PSG) measures of reduced total sleep time (TST), sleep efficiency (SE), increased wake after sleep onset (WASO), reduced amount of slow wave sleep (SWS), or increased arousal index (AI) (17–20). Given the well-established contribution of sleep disruptions to metabolic dysfunction (21), it is plausible that nighttime light exposure alters glucose metabolism due to disturbances to sleep. However, nighttime light exposure also appears to have a direct effect on glucose regulation that is independent of sleep loss, as shown by a study that subjected healthy male individuals to sleep deprivation in the dark or to sleep deprivation with nighttime light exposure (22). This study showed that a full night of sleep deprivation with nighttime light exposure increased postprandial levels of insulin and glucagon-like peptide-1, increased insulin resistance, and reduced nighttime melatonin; these changes were not observed under conditions of sleep deprivation in darkness.A second proposed mechanism to explain the impairment of glucose metabolism from nighttime light exposure is via light-induced changes to the endogenous circadian system, including suppression and phase shifting of the melatonin rhythm (23). It is well established that light exposure suppresses melatonin secretion (24, 25), and several studies have implicated suppression of nighttime melatonin with incidence of diabetes (26) and insulin resistance (27). The association between altered melatonin levels and changes in glucose regulation may be explained by evidence that melatonin plays a role in the secretion and action of insulin (28–30). In particular, lower melatonin levels resulting from light exposure during the nighttime sleep period, in a fasting condition, have been suggested to alter melatonin’s facilitation of pancreatic β-cell recovery (31). Moreover, evidence shows that light exposure, even of moderate intensity, during the nighttime sleep period can produce a phase shift of the internal circadian system (32, 33). Given the established role of the circadian system in the control of glucose metabolism, light exposure during the nighttime sleep period could facilitate the misalignment between the central clock and peripheral clocks in metabolic tissues, with consequent negative impact on glucose homeostasis (34).A third potential mechanism is the effect of light exposure on autonomic nervous system (ANS) activity. Light exposure has an arousing effect on the sympathetic autonomic system as revealed by the increase in cortisol or heart rate (HR) associated with light exposure mainly during the morning and/or nighttime hours as compared to evening hours (35–37). Beyond the direct excitatory effect exerted by light exposure on sympathetic activity (35), alterations of the ANS characterized by a shift toward an increased sympathetic drive have also been suggested to mediate the negative effects of sleep disruption on many physiological systems such as glucose metabolism (38). Thus, it is plausible that light-induced autonomic activation, either directly and/or mediated by sleep disruption, significantly contributes to the observed relationship between nighttime light exposure and altered glucose metabolism. Notably, sympathetic overactivity has been shown to precede the development of insulin resistance and prediabetes and contribute to the development of obesity and metabolic syndrome (39–41).Prior studies have reported that light exposure during sleep increases HR and decreases HR variability (HRV), consistent with increased sympathetic activation (42–44). These studies either examined bright light (1,000 lx) over the entire sleep period (42) or lower light levels (50 lx or dawn simulation) early or late in the sleep period (43, 44). However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period on autonomic activation and its impact on metabolic function has never been fully investigated.In the present study, we tested the hypothesis that room light exposure (100 lx) during habitual nighttime sleep is associated with increased insulin resistance as measured by the homeostatic model of insulin resistance (HOMA-IR), the Matsuda insulin sensitivity index, and impaired response to an oral glucose tolerance test (OGTT) the next morning. In addition, we hypothesized potential mechanisms of light-induced metabolic changes, such as reduced sleep quality, suppression of melatonin level, and elevated sympathetic activation (HR and HRV) during the sleep period.     

Cryo-EM Structure of a Possum Enterovirus

Enteroviruses (EVs) represent a substantial concern to global health. Here, we present the cryo-EM structure of a non-human enterovirus, EV-F4, isolated from the Australian brushtail possum to assess the structural diversity of these picornaviruses. The capsid structure, determined to ~3 Å resolution by single particle analysis, exhibits a largely smooth surface, similar to EV-F3 (formerly BEV-2). Although the cellular receptor is not known, the absence of charged residues on the outer surface of the canyon suggest a different receptor type than for EV-F3. Density for the pocket factor is clear, with the entrance to the pocket being smaller than for other enteroviruses.