The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited ...statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the ...Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.
Interparticle forces in granular materials are intimately linked to mechanical properties and are known to self-organize into heterogeneous structures, or force chains, under external load. Despite ...progress in understanding the statistics and spatial distribution of interparticle forces in recent decades, a systematic method for measuring forces in opaque, three-dimensional (3D), frictional, stiff granular media has yet to emerge. In this Letter, we present results from an experiment that combines 3D x-ray diffraction, x-ray tomography, and a numerical force inference technique to quantify interparticle forces and their heterogeneity in an assembly of quartz grains undergoing a one-dimensional compression cycle. Forces exhibit an exponential decay above the mean and partition into strong and weak networks. We find a surprising inverse relationship between macroscopic load and the heterogeneity of interparticle forces, despite the clear emergence of two force chains that span the system.
In recent years, there has been a rapid increase in the number of CT scans performed, both in the US and the UK, which has fuelled concern about the long-term consequences of these exposures, ...particularly in terms of cancer induction. Statistics from the US and the UK indicate a 20-fold and 12-fold increase, respectively, in CT usage over the past two decades, with per caput CT usage in the US being about five times that in the UK. In both countries, most of the collective dose from diagnostic radiology comes from high-dose (in the radiological context) procedures such as CT, interventional radiology and barium enemas; for these procedures, the relevant organ doses are in the range for which there is now direct credible epidemiological evidence of an excess risk of cancer, without the need to extrapolate risks from higher doses. Even for high-dose radiological procedures, the risk to the individual patient is small, so that the benefit/risk balance is generally in the patients' favour. Concerns arise when CT examinations are used without a proven clinical rationale, when alternative modalities could be used with equal efficacy, or when CT scans are repeated unnecessarily. It has been estimated, at least in the US, that these scenarios account for up to one-third of all CT scans. A further issue is the increasing use of CT scans as a screening procedure in asymptomatic patients; at this time, the benefit/risk balance for any of the commonly suggested CT screening techniques has yet to be established.
Reovirus is an oncolytic virus (OV), which acts by both direct tumor cell killing and priming of antitumor immunity. A major obstacle for effective oncolytic virotherapy is effective delivery of OV ...to tumor cells. Ovarian cancer is often confined to the peritoneal cavity and therefore i.p. delivery of reovirus may provide the ideal locoregional delivery, avoiding systemic dissemination. However, ovarian cancer is associated with an accumulation of ascitic fluid, which may interfere with oncolytic viral therapy. Here, we investigated the effect of ascites on reovirus‐induced oncolysis against primary ovarian cancer cells and ovarian cancer cell lines. In the absence of ascites, reovirus was cytotoxic against ovarian cancer cells; however, cytotoxicity was abrogated in the presence of ascitic fluid. Neutralizing antibodies (NAb) were identified as the cause of this inhibition. Loading OV onto cell carriers may facilitate virus delivery in the presence of NAb and immune cells which have their own antitumor effector activity are particularly appealing. Immature dendritic cells (iDC), Lymphokine‐activated killer (LAK) cells and LAKDC cocultures were tested as potential carriers for reovirus for tumor cell killing and immune cell priming. Reovirus‐loaded LAKDC, and to a lesser degree iDC, were able to: (i) protect from NAb and hand‐off reovirus for tumor cell killing; (ii) induce a proinflammatory cytokine milieu (IFNɣ, IL‐12, IFNα and TNFα) and (iii) generate an innate and specific antitumor adaptive immune response. Hence, LAKDC pulsed with reovirus represent a novel, clinically practical treatment for ovarian cancer to maximise both direct and innate/adaptive immune‐mediated tumor cell killing.
What's new?
Oncolytic viruses (OVs) specifically infect and kill tumor cells. In this study, the authors began to examine whether intraperitoneal delivery of an OV could be effective against ovarian cancer. They found that, while the virus does kill ovarian‐cancer cells in vitro, this effect is blocked when ascites fluid is added. Cytotoxicity can be restored, however, by using a combination of lymphokine‐activated killer and dendritic cells (LAKDC) as carriers, which protect the virus from neutralizing antibodies in the ascites. The LAKDC combination may also support subsequent adaptive immune priming.
Balanced fishing across a range of species, stocks, and sizes could mitigate adverse effects and address food security better than increased selectivity.
Concern about the impact of fishing on ...ecosystems and fisheries production is increasing (
1
,
2
). Strategies to reduce these impacts while addressing the growing need for food security (
3
) include increasing selectivity (
1
,
2
): capturing species, sexes, and sizes in proportions that differ from their occurrence in the ecosystem. Increasing evidence suggests that more selective fishing neither maximizes production nor minimizes impacts (
4
–
7
). Balanced harvesting would more effectively mitigate adverse ecological effects of fishing while supporting sustainable fisheries. This strategy, which challenges present management paradigms, distributes a moderate mortality from fishing across the widest possible range of species, stocks, and sizes in an ecosystem, in proportion to their natural productivity (
8
), so that the relative size and species composition is maintained.
Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and ...diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T(1)-weighted MRI) and integrity (DTI) was ascertained. Subjects with the risk-associated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.
Hopping Hotspots: Global Shifts in Marine Biodiversity Renema, W.; Bellwood, D. R.; Braga, J. C. ...
Science (American Association for the Advancement of Science),
08/2008, Letnik:
321, Številka:
5889
Journal Article
Recenzirano
Hotspots of high species diversity are a prominent feature of modern global biodiversity patterns. Fossil and molecular evidence is starting to reveal the history of these hotspots. There have been ...at least three marine biodiversity hotspots during the past 50 million years. They have moved across almost half the globe, with their timing and locations coinciding with major tectonic events. The birth and death of successive hotspots highlights the link between environmental change and biodiversity patterns. The antiquity of the taxa in the modern Indo-Australian Archipelago hotspot emphasizes the role of pre-Pleistocene events in shaping modern diversity patterns.
Aims/hypothesis
Weight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated ...dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines.
Methods
First, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions ROBINS-I), with GRADE applied (PROSPERO CRD42020208878).
Results
We identified 19 meta-analyses of weight-loss diets, involving 2–23 primary trials (
n
= 100–1587), published 2013–2021. Twelve were ‘critically low’ or ‘low’ AMSTAR 2 quality, with seven ‘high’ quality. Greatest weight loss was reported with very low energy diets, 1.7–2.1 MJ/day (400–500 kcal) for 8–12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI −9.5, −3.7) greater weight loss than low-energy diets (4.2–6.3 MJ/day 1000–1500 kcal). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3–2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low.
Conclusions/interpretation
Published meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.
Graphical abstract
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