The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the ...interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes.
Suicide is an important public health problem. The most frequent psychiatric illnesses associated with suicide or severe suicide attempt are mood and psychotic disorders. The purpose of this paper is ...to provide an educational overview of suicidal behavior in individuals with schizophrenia. A lifetime suicide rate in individuals with schizophrenia is approximately 10%. Suicide is the largest contributor to the decreased life expectancy in individuals with schizophrenia. Demographic and psychosocial factors that increase a risk of suicide in individuals with schizophrenia include younger age, being male, being unmarried, living alone, being unemployed, being intelligent, being well-educated, good premorbid adjustment or functioning, having high personal expectations and hopes, having an understanding that life's expectations and hopes are not likely to be met, having had recent (i.e., within past 3 months) life events, having poor work functioning, and having access to lethal means, such as firearms. Throughout the first decade of their disorder, patients with schizophrenia are at substantially elevated suicide risk, although they continue to be at elevated suicide risk during their lives with times of worsening or improvement. Having awareness of symptoms, especially, awareness of delusions, anhedonia, asociality, and blunted affect, having a negative feeling about, or non-adherence with, treatment are associated with greater suicide risk in patients with schizophrenia. Comorbid depression and a history of suicidal behavior are important contributors to suicide risk in patients with schizophrenia. The only reliable protective factor for suicide in patients with schizophrenia is provision of and compliance with comprehensive treatment. Prevention of suicidal behavior in schizophrenia should include recognizing patients at risk, delivering the best possible therapy for psychotic symptoms, and managing comorbid depression and substance misuse.
Our brain is a complex network in which information is continuously processed and transported between spatially distributed but functionally linked regions. Recent studies have shown that the ...functional connections of the brain network are organized in a highly efficient small-world manner, indicating a high level of local neighborhood clustering, together with the existence of more long-distance connections that ensure a high level of global communication efficiency within the overall network. Such an efficient network architecture of our functional brain raises the question of a possible association between how efficiently the regions of our brain are functionally connected and our level of intelligence. Examining the overall organization of the brain network using graph analysis, we show a strong negative association between the normalized characteristic path length lambda of the resting-state brain network and intelligence quotient (IQ). This suggests that human intellectual performance is likely to be related to how efficiently our brain integrates information between multiple brain regions. Most pronounced effects between normalized path length and IQ were found in frontal and parietal regions. Our findings indicate a strong positive association between the global efficiency of functional brain networks and intellectual performance.
Highlights • Sex and symptomatic state are crucial factors to consider when investigating cortisol stress reactivity in patients with a psychiatric disorder. • Women with current major depressive ...disorder or an anxiety disorder show blunting of the cortisol response to psychosocial stress. • Men with current major depressive disorder or social anxiety disorder show an increased cortisol response to psychosocial stress.
This paper was written to give veterinarians and decision-makers an overview of World Trade Organization (WTO) findings relevant to animal welfare. The article has a practical focus and does not ...attempt to provide a legal analysis of WTO dispute settlement. The author has simplified very technical legal language so that the paper will be useful to a broader audience. The global trade rules comprise a series of legal agreements that came into effect in 1995, when the WTO was established. The overarching objective of the WTO is to promote international trade by avoiding unjustified discrimination between trading partners. The harmonisation of national measures with relevant international standards is encouraged by the WTO to facilitate safe trade. The broad objective of the World Organisation for Animal Health (OIE) is to promote global improvements in animal health and welfare, and veterinary public health. To this end, the OIE sets intergovernmental standards and works to strengthen the capacities of Members to implement them. The OIE standards are recognised as WTO references with respect to animal health and zoonotic diseases and a significant number of WTO disputes have addressed the relevance of these OIE standards to international trade measures. In addition to animal health standards, the OIE also sets standards for animal welfare, and has implemented regional and global strategies to encourage their adoption by Members. In comparison with measures to protect animal health or food safety, few WTO disputes have considered animal welfare related measures. A lack of WTO case law has contributed to uncertainty about the consistency of WTO animal welfare measures. This paper considers some WTO disputes and findings relevant to animal welfare. The outcomes of these disputes suggest that WTO Panels and the Appellate Body are prepared to accept the right of Members to regulate for animal welfare purposes, providing that they respect the established WTO disciplines. This article draws two main conclusions. Firstly, regardless of whether measures are adopted to protect animal welfare or animal health, for WTO consistency, they must not result in unjustifiable, arbitrary or unnecessary discrimination. Secondly, regardless of how the WTO deals with animal welfare, governments must respond to the growing interest of consumers in farm animal welfare. The OIE standards, as recognised references for trading countries and the WTO, will continue to be influential in relation to global trade in animal products. It is important that the OIE update its animal welfare standards regularly, to ensure that they are consistent with latest scientific understanding and appropriate to consumer expectations for ethical food production.
Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these ...putative hub regions are mutually and densely interconnected, forming a “rich club” within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges (“path motifs”) that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.
Summary
Postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that develops in 20–50% of patients. PTS manifests as a spectrum of symptoms and signs of chronic venous ...insufficiency that can impose significant morbidity and have a negative impact on quality of life. Chronic venous hypertension caused by a combination of residual venous obstruction and valvular reflux is believed to play a major role in the pathophysiology of PTS. The Villalta scale is the most widely applied clinical scale used to diagnose and define PTS. Proximal DVT and recurrent ipsilateral DVT are the two principal established risk factors for PTS, and efforts in recent years have been focused on identifying a combination of clinical and biomarker predictors that will define high‐risk patients and possibly new therapeutic targets. The best way to prevent PTS is to prevent the occurrence of DVT, and to provide optimal anticoagulation for the acute phase of DVT once it occurs. Recent years have brought progress in our understanding of the role of endovascular techniques in the prevention and treatment of PTS and the subgroups of patients that may benefit from these modalities. Pharmacomechanical catheter‐directed thrombolysis is the most promising interventional modality for prevention of PTS. This review summarizes the current state of evidence on PTS of the lower limbs, and highlights areas where uncertainty still exists that require further research.
Brain regions are not independent. They are interconnected by white matter tracts, together forming one integrative complex network. The topology of this network is crucial for efficient information ...integration between brain regions. Here, we demonstrate that schizophrenia involves an aberrant topology of the structural infrastructure of the brain network. Using graph theoretical analysis, complex structural brain networks of 40 schizophrenia patients and 40 human healthy controls were examined. Diffusion tensor imaging was used to reconstruct the white matter connections of the brain network, with the strength of the connections defined as the level of myelination of the tracts as measured through means of magnetization transfer ratio magnetic resonance imaging. Patients displayed a preserved overall small-world network organization, but focusing on specific brain regions and their capacity to communicate with other regions of the brain revealed significantly longer node-specific path lengths (higher L) of frontal and temporal regions, especially of bilateral inferior/superior frontal cortex and temporal pole regions. These findings suggest that schizophrenia impacts global network connectivity of frontal and temporal brain regions. Furthermore, frontal hubs of patients showed a significant reduction of betweenness centrality, suggesting a less central hub role of these regions in the overall network structure. Together, our findings suggest that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs, resulting in a limited structural capacity to integrate information across brain regions.
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