Differential Expression of the Circadian Clock in Maternal and Embryonic Tissues of Mice

BACKGROUND: Molecular feedback loops involving transcription and translation and several key genes are at the core of circadian regulatory cycles affecting cellular pathways and metabolism. These cycles are active in most adult animal cells but little is known about their expression or influence during development. METHODOLOGY/PRINCIPAL FINDINGS: To determine if circadian cycles are active during mammalian development we measured the expression of key circadian genes during embryogenesis in mice using quantitative real-time RT-PCR. All of the genes examined were expressed in whole embryos beginning at the earliest age examined, embryonic day 10. In contrast to adult tissues, circadian variation was absent for all genes at all of the embryonic ages examined in either whole embryos or individual tissues. Using a bioluminescent fusion protein that tracks translation of the circadian gene, per2, we also analyzed protein levels. Similar to mRNA, a protein rhythm was observed in adult tissue but not in embryonic tissues collected in-vivo. In contrast, when tissues were placed in culture for the continuous assay of bioluminescence, rhythms were observed in embryonic (E18) tissues. We found that placing embryonic tissues in culture set the timing (phase) of these rhythms, suggesting the importance of a synchronizing signal for the expression of circadian cycles in developing tissues. CONCLUSIONS/SIGNIFICANCE: These results show that embryonic tissues express key circadian genes and have the capacity to express active circadian regulatory cycles. In vivo, circadian cycles are not expressed in embryonic tissues as they are in adult tissues. Individual cells might express oscillations, but are not synchronized until later in development

Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart

Experimental data suggest that cell-based therapies may be useful for cardiac regeneration following ischaemic heart disease. Bone marrow (BM) cells have been reported to contribute to tissue repair after myocardial infarction (MI) by a variety of humoural and cellular mechanisms. However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs). To investigate whether BM cells contribute to repopulate the Kit+ CSCs pool, we transplanted BM cells from transgenic mice, expressing green fluorescent protein under the control of Kit regulatory elements, into wild-type irradiated recipients. Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate 'cardiospheres', a microtissue normally originating in vitro from CSCs. These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5. These findings indicate that, at least in conditions of local acute cardiac damage, BM cells can home into the heart and give rise to cells that share properties of resident Kit+ CSCs

Adolescent Oxytocin Exposure Causes Persistent Reductions in Anxiety and Alcohol Consumption and Enhances Sociability in Rats

Previous studies have suggested that administration of oxytocin (OT) can have modulatory effects on social and anxiety-like behavior in mammals that may endure beyond the time of acute OT administration. The current study examined whether repeated administration of OT to male Wistar rats (n = 48) during a key developmental epoch (early adolescence) altered their physiology and behavior in later-life. Group housed rats were given intraperitoneal injections of either 1 mg/kg OT or vehicle during early adolescence (post natal-days [PND] 33–42). OT treatment caused a transient inhibition of body weight gain that recovered quickly after the cessation of treatment. At PND 50, the rats pre-treated with OT displayed less anxiety-like behavior on the emergence test, while at PND 55 they showed greater levels of social interaction. A subgroup of OT pre-treated rats examined at PND 63 showed a strong trend towards increased plasma OT levels, and also displayed significantly increased OT receptor mRNA in the hypothalamus. Rats pre-treated with OT and their controls showed similar induction of beer intake in daily 70 min test sessions (PND 63 onwards) in which the alcohol concentration of beer was gradually increased across days from 0.44% to 4.44%. However, when given ad libitum access to beer in their home cages from PND 72 onwards (early adulthood), consumption of beer but not water was significantly less in the OT pre-treated rats. A “booster” shot of OT (1 mg/kg) given after 25 days of ad libitum access to beer had a strong acute inhibitory effect on beer intake without affecting water intake. Overall these results suggest that exogenous OT administered during adolescence can have subtle yet enduring effects on anxiety, sociability and the motivation to consume alcohol. Such effects may reflect the inherent neuroplasticity of brain OT systems and a feed-forward effect whereby exogenous OT upregulates endogenous OT systems

The CEOS Recovery Observatory Pilot

Over the course of the last decade, large populations living in vulnerable areas have led to record damages and substantial loss of life in mega-disasters ranging from the deadly Indian Ocean tsunami of 2004 and Haiti earthquake of 2010; the catastrophic flood damages of Hurricane Katrina in 2005 and the Tohoku tsunami of 2011, and the astonishing extent of the environmental impact of the Deepwater Horizon explosion in 2009. These major catastrophes have widespread and long-lasting impacts with subsequent recovery and reconstruction costing billions of euros and lasting years. While satellite imagery is used on an ad hoc basis after many disasters to support damage assessment, there is currently no standard practice or system to coordinate acquisition of data and facilitate access for early recovery planning and recovery tracking and monitoring. CEOS led the creation of a Recovery Observatory Oversight Team, which brings together major recovery stakeholders such as the UNDP and the World Bank/Global Facility for Disaster Reduction and Recovery, value-adding providers and leading space agencies. The principal aims of the Observatory are to: 1. Demonstrate the utility of a wide range of earth observation data to facilitate the recovery and reconstruction phase following a major catastrophic event; 2. Provide a concrete case to focus efforts in identifying and resolving technical and organizational obstacles to facilitating the visibility and access to a relevant set of EO data; and 3. Develop dialogue and establish institutional relationships with the Recovery phase user community to best target data and information requirements; The paper presented here will describe the work conducted in preparing for the triggering of a Recovery Observatory including support to rapid assessments and Post Disaster Needs Assessments by the EO community

A case report: Brugada syndrome in the setting of hypothermia.

Hypothermia is a common diagnosis in the Emergency Department. It can cause a multitude of symptoms and complications if not treated promptly. The following case report discusses Brugada pattern on an electrocardiogram in a patient with hypothermia and diabetic ketoacidosis. There was resolution of the Brugada pattern on the electrocardiogram after the patient was warmed to 35.3 °C

SUBCLINICAL RENAL DAMAGE IS ASSOCIATED WITH A REDUCED CHOROIDAL THICKNESS IN PATIENTS WITH PRIMARY HYPERTENSION

Objective: The retina is considered the easiest accessible window to study the state of the systemic microcirculation, even if the choroid is the most important vascular layer of the eye. Our understanding of the choroid has been greatly increased in last years since the introduction of advanced techniques of optical coherence tomography (OCT). Our study was aimed to assess choroidal thickness by using Swept-Source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without subclinical renal damage (SRD). Design and method: We enrolled 100 EHs of which 65 without kidney damage and 35 with SRD. In all the participants SS-OCT and a routine biochemical work-up were performed. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation (eGFR). SRD was defined, by the presence of microalbuminuria or eGFR between 30 and 60\u200amL/min/1.73 m2. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, that divides the macula into 9 subfields. The circular grid consists of 3 concentric rings. The inner and outer rings are further divided into quadrants: temporal, nasal, superior, and inferior. Design and method: Furthermore, we calculated the average of the individuals values of the four quadrants separately for the inner and the outer ring. The average of all the 9 regions of the ETRDS grid (including the inner, the outer and the central rings) was also calculated. Results: EHs with SRD showed thinner choroidal thicknesses than those without kidney damage (all p\u200a<\u200a0.05), even after adjustment for age (figure). Overall choroidal thickness correlated significantly and directly with eGFR (r\u200a=\u200a0.36) and negatively with urinary albumin excretion (r\u200a=\u200a- 0.39). The association of choroidal thickness with SRD was confirmed in multiple logistic regression analyses once the effect of age, anti-hypertensive therapy and triglycerides was accounted for. The odds ratio of having SRD associated with a standard deviation increase of overall choroidal thickness was 0.43 (0.24\u20130.75, 95% confidence interval; p\u200a=\u200a0.007). Conclusions: Our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction

WCDRR and the CEOS activities on disaters

Agencies from CEOS (Committee on Earth Observation Satellites) have traditionally focused their efforts on the response phase. Rapid urbanization and increased severity of weather events has led to growing economic and human losses from disasters, requiring international organisations to act now in all disaster risk management (DRM) phases, especially through improved disaster risk reduction policies and programmes. As part of this effort, CEOS agencies have initiated a series of actions aimed at fostering the use of Earth observation (EO) data to support disaster risk reduction and at raising the awareness of policy and decision-makers and major stakeholders of the benefits of using satellite EO in all phases of DRM. CEOS is developing a long-term vision for sustainable application of satellite EO to all phases of DRM. CEOS is collaborating with regional representatives of the DRM user community, on a multi-hazard project involving three thematic pilots (floods, seismic hazards and volcanoes) and a Recovery Observatory that supports resilient recovery from one major disaster. These pilot activities are meant as trail blazers that demonstrate the potential offered by satellite EO for comprehensive DRM. In the framework of the 2015 3rd World Conference on Disaster Risk Reduction (WCDRR), the CEOS space agencies intend to partner with major stakeholders, including UN organizations, the Group on Earth Observations (GEO), international relief agencies, leading development banks, and leading regional DRM organisations, to define and implement a 15-year plan of actions (2015- 2030) that responds to high-level Post-2015 Framework for Disaster Risk Reduction priorities. This plan of action will take into account lessons learned from the CEOS pilot activities

Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy

Background: Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. Objectives: The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. Methods: The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. Results: The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. Conclusions: COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population

Modulation of pain sensitivity by chronic consumption of highly palatable food followed by abstinence: emerging role of fatty acid amide hydrolase

There is a strong relationship between palatable diet and pain sensitivity, and the cannabinoid and opioid systems might play an important role in this correlation. The palatable diet used in many animal models of obesity is the cafeteria (CAF) diet, based on human food with high sugar, salt, and fat content. In this study, we investigated whether long-term exposure to a CAF diet could modify pain sensitivity and explored the role of the cannabinergic system in this modification. Male Sprague–Dawley rats were divided into two groups: one fed with standard chow only (CO) and the other with extended access (EA) to a CAF diet. Hot plate and tail flick tests were used to evaluate pain sensitivity. At the end of a 40-day CAF exposure, EA rats showed a significant increase in the pain threshold compared to CO rats, finding probably due to up-regulation of CB1 and mu-opioid receptors. Instead, during abstinence from palatable foods, EA animals showed a significant increase in pain sensibility, which was ameliorated by repeated treatment with a fatty acid amide hydrolase inhibitor, PF-3845 (10 mg/kg, intraperitoneally), every other day for 28 days. Ex vivo analysis of the brains of these rats clearly showed that this effect was mediated by mu-opioid receptors, which were up-regulated following repeated treatment of PF-3845. Our data add to the knowledge about changes in pain perception in obese subjects, revealing a key role of CB1 and mu-opioid receptors and their possible pharmacological crosstalk and reinforcing the need to consider this modulation in planning effective pain management for obese patients