A γ-β frequency transition generated by inter-areal communication in the hippocampus in vitro

Gamma oscillations are generated in area CA3 of the hippocampus both in vitro and in vivo (Fisahn et al., 1998; Csicsvari et al., 2003). Here we present experimental and network simulation data to elucidate the mechanism of the generation of CA3-driven gamma and beta oscillations in area CA1. (1) The frequency of area CA1 output generated by gamma input from area CA3 was dependent on the degree of recruitment of CA1 principal cells. Passive involvement of area CA1 principal cells resulted in a gamma frequency oscillation. Active involvement of CA1 principal cells transformed this gamma oscillation into one at beta frequencies. (2) This beta oscillation in area CA1 was dependent on CA1 recurrent excitation. (3) It was also dependent on the temporal relationship between feedforward excitation of CA1 interneurons (by CA3 output) and feedback excitation of CA1 interneurons (by CA1 output). That is, the network beta oscillation in area CA1 depended on doublet firing of certain interneurons driven by area CA3. (4) The interneuron doublet rate during beta corresponded to whether or not dendrites are oriented horizontally or vertically: Interneurons with vertically oriented dendrites (eg. basket cells and - to a lesser extent - bistratified cells, all receiving input from CA3) fired considerably more doublets than interneurons with horizontally oriented dendrites (horizontal alveus cells or olm cells) which are not contacted by area CA3 and hardly ever fired doublets during beta. Taken together the findings demonstrate that different interneurons can serve different purposes during a given network oscillation, that single interneuron subtypes can mediate multiple network frequencies, and that the frequency of output from a cortical region serves to signal the degree of principal cell recruitment

A γ-β frequency transition generated by inter-areal communication in the hippocampus in vitro

Gamma oscillations are generated in area CA3 of the hippocampus both in vitro and in vivo (Fisahn et al., 1998; Csicsvari et al., 2003). Here we present experimental and network simulation data to elucidate the mechanism of the generation of CA3-driven gamma and beta oscillations in area CA1. (1) The frequency of area CA1 output generated by gamma input from area CA3 was dependent on the degree of recruitment of CA1 principal cells. Passive involvement of area CA1 principal cells resulted in a gamma frequency oscillation. Active involvement of CA1 principal cells transformed this gamma oscillation into one at beta frequencies. (2) This beta oscillation in area CA1 was dependent on CA1 recurrent excitation. (3) It was also dependent on the temporal relationship between feedforward excitation of CA1 interneurons (by CA3 output) and feedback excitation of CA1 interneurons (by CA1 output). That is, the network beta oscillation in area CA1 depended on doublet firing of certain interneurons driven by area CA3. (4) The interneuron doublet rate during beta corresponded to whether or not dendrites are oriented horizontally or vertically: Interneurons with vertically oriented dendrites (eg. basket cells and - to a lesser extent - bistratified cells, all receiving input from CA3) fired considerably more doublets than interneurons with horizontally oriented dendrites (horizontal alveus cells or olm cells) which are not contacted by area CA3 and hardly ever fired doublets during beta. Taken together the findings demonstrate that different interneurons can serve different purposes during a given network oscillation, that single interneuron subtypes can mediate multiple network frequencies, and that the frequency of output from a cortical region serves to signal the degree of principal cell recruitment

Effect of pragmatic versus explanatory interventions on medication adherence in people with cardiometabolic conditions: a systematic review and meta-analysis

Objective To synthesise findings from randomised controlled trials (RCTs) of interventions aimed at increasing medication adherence in individuals with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). And, in a novel approach, to compare the intervention effect of studies which were categorised as being more pragmatic or more explanatory using the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool, to identify whether study design affects outcomes. As explanatory trials are typically held under controlled conditions, findings from such trials may not be relatable to real-world clinical practice. In comparison, pragmatic trials are designed to replicate real-world conditions and therefore findings are more likely to represent those found if the intervention were to be implemented in routine care. Design Systematic review and meta-analysis. Data sources Ovid Medline, Ovid Embase, Web of Science and CINAHL from 1 January 2013 to 31 December 2018. Eligibility criteria for selecting studies RCTs lasting ≥3 months (90 days), involving ≥200 patients in the analysis, with either established CVD and/or T2DM and which measured medication adherence. From 4403 citations, 103 proceeded to full text review. Studies published in any language other than English and conference abstracts were excluded. Main outcome measure Change in medication adherence. Results Of 4403 records identified, 34 studies were considered eligible, of which 28, including 30 861 participants, contained comparable outcome data for inclusion in the meta-analysis. Overall interventions were associated with an increase in medication adherence (OR 1.57 (95% CI: 1.33 to 1.84), p<0.001; standardised mean difference 0.24 (95% CI: −0.10 to 0.59) p=0.101). The effectiveness of interventions did not differ significantly between studies considered pragmatic versus explanatory (p=0.598), but did differ by intervention type, with studies that included a multifaceted rather than a single-faceted intervention having a more significant effect (p=0.010). The analysis used random effect models and used the revised Cochrane Risk of Bias Tool to assess study quality. Conclusions In this meta-analysis, interventions were associated with a significant increase in medication adherence. Overall multifaceted interventions which included an element of education alongside regular patient contact or follow-up showed the most promise. Effectiveness of interventions between pragmatic and explanatory trials was comparable, suggesting that findings can be transferred from idealised to real-word conditions. PROSPERO registration number CRD42017059460

The impact of neighbourhood walkability on the effectiveness of a structured education programme to increase objectively measured walking

Background: Incorporating physical activity into daily activities is key for the effectiveness of lifestyle education interventions aimed at improving health outcomes; however, consideration of the environmental context in which individuals live is not always made. Walkability is a characteristic of the physical environment, and may be a potential facilitator to changing physical activity levels.  Methods: Using data collected during the Walking Away from Diabetes randomised controlled trial, we examined the association between the walkability of the home neighbourhood and physical activity of participants. We also determined whether home neighbourhood walkability of participants was associated with the intervention effect of the education programme.  Results: Data from 706 participants were available for analysis. Neighbourhood walkability was not significantly associated with any of the physical activity measures at baseline, or at 12, 24 or 36 months following the intervention (p>0.05 for all). There was no association between walkability and change in purposeful steps/ day from baseline to 36months in the usual care or intervention arm; 25.77 (-99.04, 150.58) and 42.97 (-327.63, 413.45) respectively.  Conclusion: Neighbourhood walkability appeared to have no association with objectively-measured physical activity in this population. Furthermore, the walkability of participant’s neighbourhood did not influence the effectiveness of a lifestyle programme

Mapping the stray domestic cat (Felis catus) population in New Zealand: Species distribution modelling with a climate change scenario and implications for protected areas

Species distribution models of stray cats were developed using two types of occurrence data: (i) a combined dataset of stray cats and cat colonies in Auckland and projected to the wider New Zealand area; and (ii) population density as an analogue for country-wide stray cat occurrence. These occurrence data, together with sets of environmental variables were used as input to the Maxent modelling tool to produce maps of suitability for the species. Environmental variables used in the models consist of current bioclimatic conditions, and a future climate scenario (RCP8.5 for year 2070 CCSM model). Commonly occurring bias in the modelling process due to latitude, the area for selecting background points in model evaluation, inherent spatial autocorrelation of occurrence points, and correlated bioclimatic variables were explicitly addressed. Results show that the North Island consistently provide more suitable areas for stray cats with increased suitability in a high emission climate change condition. Key protected areas at risk from the increased suitability to stray cats are also presented

Association of smoking and cardiometabolic parameters with albuminuria in people with type 2 diabetes mellitus: a systematic review and meta-analysis

AIMS: Smoking is a strong risk factor for albuminuria in people with type 2 diabetes mellitus (T2DM). However, it is unclear whether this sequela of smoking is brought about by its action on cardiometabolic parameters or the relationship is independent. The aim of this systematic review is to explore this relationship. METHODS: Electronic databases on cross-sectional and prospective studies in Medline and Embase were searched from January 1946 to May 2018. Adult smokers with T2DM were included, and other types of diabetes were excluded. RESULTS: A random effects meta-analysis of 20,056 participants from 13 studies found that the odds ratio (OR) of smokers developing albuminuria compared to non-smokers was 2.13 (95% CI 1.32, 3.45). Apart from smoking, the odds ratio of other risk factors associated with albuminuria were: age 1.24 (95% CI 0.84, 1.64), male sex 1.39 (95% CI 1.16, 1.67), duration of diabetes 1.78 (95% CI 1.32, 2.23), HbA1c 0.63 (95% CI 0.45, 0.81), SBP 6.03 (95% CI 4.10, 7.97), DBP 1.85 (95% CI 1.08, 2.62), total cholesterol 0.06 (95% CI - 0.05, 0.17) and HDL cholesterol - 0.01 (95% CI - 0.04, 0.02), triglyceride 0.22 (95% CI 0.12, 0.33) and BMI 0.40 (95% CI 0.00-0.80). When the smoking status was adjusted in a mixed effect meta-regression model, the duration of diabetes was the only statistically significant factor that influenced the prevalence of albuminuria. In smokers, each year's increase in the duration of T2DM was associated with an increased risk of albuminuria of 0.19 units (95% CI 0.07, 0.31) on the log odds scale or increased the odds approximately by 23%, compared to non-smokers. Prediction from the meta-regression model also suggested that the odds ratios of albuminuria in smokers after a diabetes duration of 9 years and 16 years were 1.53 (95% CI 1.10, 2.13) and 5.94 (95% CI 2.53, 13.95), respectively. CONCLUSIONS: Continuing to smoke and the duration of diabetes are two strong predictors of albuminuria in smokers with T2DM. With a global surge in younger smokers developing T2DM, smoking cessation interventions at an early stage of disease trajectory should be promoted