Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of ...the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation.
Summary Background Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the ...effects of diet and physical activity on blood pressure and glucose concentrations. Methods We did a randomised, controlled trial in southwest England in adults aged 30–80 years in whom type 2 diabetes had been diagnosed 5–8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A1c (HbA1c ) concentration and blood pressure at 6 months. Analysis was done by intention to treat. This study is registered, number ISRCTN92162869. Findings Of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA1c percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA1c −0·28%, 95% CI −0·46 to −0·10; p=0·005) and diet plus activity group (−0·33%, −0·51 to −0·14; p<0·001). These differences persisted to 12 months, despite less use of diabetes drugs. Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups. Blood pressure was similar in all groups. Interpretation An intensive diet intervention soon after diagnosis can improve glycaemic control. The addition of an activity intervention conferred no additional benefit. Funding Diabetes UK and the UK Department of Health.
Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and Ser(2)exendin(1-9) ...(HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. Ser(2)exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of Ser(2)exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Sedentary behaviour is any waking behaviour characterised by an energy expenditure of ≤1.5 metabolic equivalent of task while in a sitting or reclining posture. Prolonged bouts of sedentary behaviour ...have been associated with negative health outcomes in all age groups. We examined qualitative research investigating perceptions and experiences of sedentary behaviour and of participation in non-workplace interventions designed to reduce sedentary behaviour in adult populations.
A systematic search of seven databases (MEDLINE, AMED, Cochrane, PsychINFO, SPORTDiscus, CINAHL and Web of Science) was conducted in September 2017. Studies were assessed for methodological quality and a thematic synthesis was conducted. Prospero database ID: CRD42017083436.
Thirty individual studies capturing the experiences of 918 individuals were included. Eleven studies examined experiences and/or perceptions of sedentary behaviour in older adults (typically ≥60 years); ten studies focused on sedentary behaviour in people experiencing a clinical condition, four explored influences on sedentary behaviour in adults living in socio-economically disadvantaged communities, two examined university students' experiences of sedentary behaviour, two on those of working-age adults, and one focused on cultural influences on sedentary behaviour. Three analytical themes were identified: 1) the impact of different life stages on sedentary behaviour 2) lifestyle factors influencing sedentary behaviour and 3) barriers and facilitators to changing sedentary behaviour.
Sedentary behaviour is multifaceted and influenced by a complex interaction between individual, environmental and socio-cultural factors. Micro and macro pressures are experienced at different life stages and in the context of illness; these shape individuals' beliefs and behaviour related to sedentariness. Knowledge of sedentary behaviour and the associated health consequences appears limited in adult populations, therefore there is a need for provision of accessible information about ways in which sedentary behaviour reduction can be integrated in people's daily lives. Interventions targeting a reduction in sedentary behaviour need to consider the multiple influences on sedentariness when designing and implementing interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present the first full Holocene palaeomagnetic secular variation record from New Zealand. The 11 500 year-long record, from the sediments of Mavora Lakes, comprises composite declination, ...inclination and relative palaeointensity logs, compiled from two six-metre long cores and the uppermost 1.5 m of another. An age model has been developed from 28 AMS radiocarbon age determinations on fragments of southern beech (Lophozonia menziesii and Fuscospora cliffortioides) leaves. The excellent between-core correlation in all three components of the field results in a high-resolution palaeosecular variation record, with precise and accurate age control. The variations change in character from high amplitude in-phase declination and inclination swings in the earliest part of the record to low amplitude variations in the middle part and declination and inclination swings that are 90° out of phase, leading to broad looping of the vector in the upper part of the record, that is consistent with westward drifting sources in the outer core. The present-day field at the site (Dec = 24.2°E, Inc=−70.7°, F=59 μT) represents a rare steep and easterly extreme direction, but close to average intensity. The palaeointensity is inferred to have varied between about 40 and 90 μT, with variations that, to some extent, mirror variations in the virtual axial geomagnetic dipole moment seen from global data, but also show some notable differences, particularly in the past few thousand years.
•This is the first full Holocene palaeosecular variation record for New Zealand.•High precision age control comes from 28 14C dates on leaf fragments.•Palaeomagnetic directions and RPI are composites from three correlated cores.•The record will be central to new global models of the geomagnetic field.•It may be used as a dating tool for geological and archaeological materials.
Aims/hypothesis
We investigated whether objectively measured sedentary time and interruptions in sedentary time are associated with metabolic factors in people with type 2 diabetes.
Methods
We ...studied 528 adults (30–80 years) with newly diagnosed type 2 diabetes, who were participants in a diet and physical activity intervention. Waist circumference (WC), fasting HDL-cholesterol, insulin and glucose levels, HOMA of insulin resistance (HOMA-IR) and physical activity (accelerometer) were measured at baseline and at 6 months follow-up. Linear regression models were used to investigate cross-sectional and longitudinal associations of accelerometer-derived sedentary time and breaks in sedentary time (BST) with metabolic variables.
Results
In cross-sectional analyses each hour of sedentary time was associated with larger WC (unstandardised regression coefficient
B
95% CI 1.89 cm 0.94, 2.83;
p
< 0.001), higher insulin (
B
= 8.22 pmol/l 2.80, 13.65;
p
= 0.003) and HOMA-IR (
B
= 0.42 0.14, 0.70;
p
= 0.004), and lower HDL-cholesterol (
B
= −0.04 mmol/l −0.06, −0.01;
p
= 0.005). Adjustment for WC attenuated all associations. Each BST was associated with lower WC (
B
= −0.15 cm − 0.24, −0.05;
p
= 0.003) and there was evidence of a weak linear association with HDL-cholesterol, but no association with insulin levels or HOMA-IR. Volume of sedentary time at baseline predicted HDL-cholesterol (
B
= −0.05 mmol/l −0.08, −0.01;
p
= 0.007), insulin levels (
B
= 8.14 pmol/l 0.1.51, 14.78;
p
= 0.016) and HOMA-IR (
B
= 0.49 0.08, 0.90;
p
= 0.020) at 6 months, though not WC. Baseline BST did not substantially predict any metabolic variables at follow-up. No change was seen in sedentary time or BST between baseline and 6 months follow-up.
Conclusions/interpretation
Higher sedentary time is associated with a poorer metabolic profile in people with type 2 diabetes.
The Ramsar Convention (or the Convention on Wetlands), signed in 1971, was one of the first international conservation agreements, promoting global wise use of wetlands. It has three primary ...objectives: national designation and management of wetlands of international importance; general wise use of wetlands; and international cooperation. We examined lessons learnt for improving wetland conservation after Ramsar’s nearly five decades of operation. The number of wetlands in the Ramsar Site Network has grown over time (2,391 Ramsar Sites, 2.5 million km
2
, as at 2020-06-09) but unevenly around the world, with decreasing rate of growth in recent decades. Ramsar Sites are concentrated in countries with a high Gross Domestic Product and human pressure (e.g., western Europe) but, in contrast, Ramsar Sites with the largest wetland extent are in central-west Africa and South America. We identified three key challenges for improving effectiveness of the Ramsar Site Network: increasing number of sites and wetland area, improved representation (functional, geographical and biological); and effective management and reporting. Increasing the number of sites and area in the Ramsar network could benefit from targets, implemented at national scales. Knowledge of representativeness is inadequate, requiring analyses of functional ecotypes, geographical and biological representativeness. Finally, most countries have inadequate management planning and reporting on the ecological character of their Ramsar Sites, requiring more focused attention on a vision and objectives, with regular reporting of key indicators to guide management. There are increasing opportunities to rigorously track ecological character, utilizing new tools and available indicators (e.g., remote sensing). It is critical that the world protect its wetlands, with an effective Ramsar Convention or the Convention on Wetlands at the core.
The COVID-19 pandemic has had profound implications for continuing medical education. Travel restrictions, lockdowns and social distancing in an effort to curb spread have meant that medical ...conferences have been postponed or cancelled. When the Australian and New Zealand College of Anaesthetists made the decision to commit to a fully virtual 2021 Annual Scientific Meeting, the organising committee investigated the viability of presenting a virtual 'Can't intubate, can't oxygenate' workshop. A workshop was designed comprising a lecture, case scenario discussion and demonstration of emergency front-of-neck access techniques broadcast from a central hub before participants separated into ZoomVR (Zoom Video Communications, San Jose, CA, USA) breakout rooms for hands-on practice, guided by facilitators working virtually from their own home studios. Kits containing equipment including a 3D printed larynx, cannula, scalpel and bougie were sent to workshop participants in the weeks before the meeting. Participants were asked to complete pre- and post-workshop surveys. Of 42 participants, 32 responded, with the majority rating the workshop 'better than expected'. All except two respondents felt the workshop met learning objectives. Themes of positive feedback included being impressed with the airway model, the small group size, content and delivery. Feedback focused on previously unperceived advantages of virtual technical skills workshops, including convenience, equitable access and the reusable airway model. Disadvantages noted by respondents included lack of social interaction, inability to trial more expensive airway equipment, and some limitations of the ability of facilitators to review participants' technique. Despite limitations, in our experience, virtual workshops can be planned with innovative solutions to deliver technical skills education successfully.
We examined stressors that have led to profound ecological changes in the Lake Ontario ecosystem and its fish community since 1970. The most notable changes have been reductions in phosphorus ...loading, invasion by Dreissena spp., fisheries management through stocking of exotic salmonids and control of sea lamprey (Petromyzon marinus), and fish harvest by anglers and double-crested cormorants (Phalacrocorax auritus). The response to these stressors has led to (i) declines in both algal photosynthesis and epilimnetic zooplankton production, (ii) decreases in alewife (Alosa pseudoharengus) abundance, (iii) declines in native Diporeia and lake whitefish (Coregonus clupeaformis), (iv) behavioral shifts in alewife spatial distribution benefitting native lake trout (Salvelinus namaycush), threespine stickleback (Gasterosteus aculeatus), and emerald shiner (Notropis atherinoides) populations, (v) dramatic increases in water clarity, (vi) predation impacts by cormorants on select fish species, and (vii) lake trout recruitment bottlenecks associated with alewife-induced thiamine deficiency. We expect stressor responses associated with anthropogenic forces like exotic species invasions and global climate warming to continue to impact the Lake Ontario ecosystem in the future and recommend continuous long-term ecological studies to enhance scientific understanding and management of this important resource.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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