Zoning for Conservation Easements

Richardson and Bernard talk about zoning for conservation easements. Most conservation easements are perpetual and may have a huge impact on the land use in a community. With few exceptions, however, conservation easements have not been incorporated in any meaningful way into local land-use planning

Does Cognitive Dysfunction in Bipolar Disorder Qualify as a Diagnostic Intermediate Phenotype?—A Perspective Paper

The present perspective paper addresses and discusses whether cognitive dysfunction in bipolar disorder qualifies as a diagnostic intermediate phenotype using the Robin and Guze criteria of diagnostic validity. The paper reviews current data within (1) delineation of the clinical intermediate phenotype, (2) associations of the intermediate phenotype with para-clinical data such as brain imaging and blood-based data, (3) associations to family history / genetics, (4) characteristics during long-term follow-up, and (5) treatment effects on cognition. In this way, the paper identifies knowledge gaps and suggests recommendations for future research within each of the five areas. Based on the current state of knowledge, we conclude that cognitive dysfunction does not qualify as a diagnostic intermediate phenotype or endophenotype for bipolar disorder, although promising new evidence points to emotion and reward processing abnormalities as possible putative endophenotypes

Characteristics of dental pulp in human upper first premolar teeth based on immunohistochemical and morphometric examinations

Teeth extracted for orthodontic reasons are commonly considered as healthy. Therefore, it is possible to examine structure of the dental pulp can be fully recognized and how it is affected by malocclusion. The aim of the study was to evaluate by immunohistochemistry (IHC) and morphometry dental pulp in human upper first premolar teeth extracted for orthodontic reasons. The material comprised 36 teeth of 20 patients in the age range 16–26 years. By the use of IHC markers the presence of immunocompetent cells (CD20, CD45RO, and CD68), blood vessels (CD31) and nerves (PGP9.5) were examined in the pulp. Inflammatory infiltrates and tissue atrophy were observed in 24 and 10 teeth, respectively. Strong positive correlation between the width of the odontoblastic layer, the number of rows of odontoblast nuclei and the increase of MVA (microvessel area) in the pulp of atrophic teeth was found. The cellular infiltrations found in H&E-stained sections were identified by IHC as memory T cells (CD45RO+) and B lymphocytes (CD20+) with macrophages (CD68+) present at the periphery. The CD20 antigen was intensively expressed in 13 teeth, CD45RO in 33 teeth, and CD68 in 20 teeth. Thus, despite the lack of any clinical signs of pulp disease many teeth extracted for orthodontic reasons show focal pulp inflammation and atrophy which probably results from the malocclusion stress accompanying teeth crowding

GSK3β:a plausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?

Abstract Mood disorders are associated with significant psychosocial and occupational disability. It is estimated that major depressive disorder (MDD) will become the second leading cause of disability worldwide by 2020. Existing pharmacological and psychological treatments are limited for targeting cognitive dysfunctions in mood disorders. However, growing evidence from human and animal studies has shown that treatment with erythropoietin (EPO) can improve cognitive function. A recent study involving EPO-treated patients with mood disorders showed that the neural basis for their cognitive improvements appeared to involve an increase in hippocampal volume. Molecular mechanisms underlying hippocampal changes have been proposed, including the activation of anti-apoptotic, antioxidant, pro-survival and anti-inflammatory signalling pathways. The aim of this review is to describe the potential importance of glycogen synthase kinase 3-beta (GSK3β) as a multi-potent molecular mechanism of EPO-induced hippocampal volume change in mood disorder patients. We first examine published associations between EPO administration, mood disorders, cognition and hippocampal volume. We then highlight evidence suggesting that GSK3β influences hippocampal volume in MDD patients, and how this could assist with targeting more precise treatments particularly for cognitive deficits in patients with mood disorders. We conclude by suggesting how this developing area of research can be further advanced, such as using pharmacogenetic studies of EPO treatment in patients with mood disorders

Neural and Behavioral Predictors of Treatment Efficacy on Mood Symptoms and Cognition in Mood Disorders: A Systematic Review

Background: The clinical and etiological heterogeneity of mood disorders impede identification of effective treatments for the individual patient. This highlights a need for early neuronal and behavioral biomarkers for treatment efficacy, which can provide a basis for more personalized treatments. The present systematic review aimed to identify the most consistent neuronal and behavioral predictors of treatment efficacy on mood symptoms and cognitive impairment in mood disorders.Methods: We identified and included 60 original peer-reviewed studies investigating neuroimaging and behavioral predictors of treatment efficacy within the domains of emotional and non-emotional cognition, structural neuroimaging, and resting state functional connectivity in patients with unipolar or bipolar disorder.Results: Lower baseline responsivity in limbic regions coupled with heightened medial and dorsal prefrontal responses to emotional stimuli were the most consistent predictors of response to pharmacotherapy for depression. In contrast, heightened limbic and ventral prefrontal reactivity to emotional stimuli seemed to predict efficacy of psychological interventions. Early modulation of fronto-limbic activity and reduction in negative bias were also associated with treatment response. Better performance on non-emotional tests at baseline was relatively consistently associated with efficacy on mood symptoms, whereas the association between neural activity during non-emotional tests and treatment response was less clear. Other baseline factors associated with treatment response were greater white matter integrity, resting state functional connectivity, more prefrontal gray matter volume as well as an early increase following short administered treatment. Finally, emerging evidence indicates that baseline cognitive deficits are associated with greater chances of achieving treatment efficacy on cognition.Conclusions: Patients' profile of emotional and non-emotional cognition and neural activity—and the early treatment-associated changes in neural and cognitive function—may be useful for guiding treatments for depression. While cognitive deficits at baseline seem to improve chances of treatment efficacy on cognition, more studies of this association are urgently needed

The Bipolar Illness Onset study: research protocol for the BIO cohort study

Introduction Bipolar disorder is an often disabling mental illness with a lifetime prevalence of 1%–2%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide and a substantial heritability. The course of illness is frequently characterised by progressive shortening of interepisode intervals with each recurrence and increasing cognitive dysfunction in a subset of individuals with this condition. Clinically, diagnostic boundaries between bipolar disorder and other psychiatric disorders such as unipolar depression are unclear although pharmacological and psychological treatment strategies differ substantially. Patients with bipolar disorder are often misdiagnosed and the mean delay between onset and diagnosis is 5–10 years. Although the risk of relapse of depression and mania is high it is for most patients impossible to predict and consequently prevent upcoming episodes in an individual tailored way. The identification of objective biomarkers can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Accurate diagnosis of bipolar disorder in its early stages could help prevent the long-term detrimental effects of the illness. The present Bipolar Illness Onset study aims to identify (1) a composite blood-based biomarker, (2) a composite electronic smartphone-based biomarker and (3) a neurocognitive and neuroimaging-based signature for bipolar disorder. Methods and analysis The study will include 300 patients with newly diagnosed/first-episode bipolar disorder, 200 of their healthy siblings or offspring and 100 healthy individuals without a family history of affective disorder. All participants will be followed longitudinally with repeated blood samples and other biological tissues, self-monitored and automatically generated smartphone data, neuropsychological tests and a subset of the cohort with neuroimaging during a 5 to 10-year study period. Ethics and dissemination The study has been approved by the Local Ethical Committee (H-7-2014-007) and the data agency, Capital Region of Copenhagen (RHP-2015-023), and the findings will be widely disseminated at international conferences and meetings including conferences for the International Society for Bipolar Disorders and the World Federation of Societies for Biological Psychiatry and in scientific peer-reviewed papers

Erythropoietin as candidate for supportive treatment of severe COVID-19

In light of the present therapeutic situation in COVID-19, any measure to improve course and outcome of seriously affected individuals is of utmost importance. We recap here evidence that supports the use of human recombinant erythropoietin (EPO) for ameliorating course and outcome of seriously ill COVID-19 patients. This brief expert review grounds on available subject-relevant literature searched until May 14, 2020, including Medline, Google Scholar, and preprint servers. We delineate in brief sections, each introduced by a summary of respective COVID-19 references, how EPO may target a number of the gravest sequelae of these patients. EPO is expected to: (1) improve respiration at several levels including lung, brainstem, spinal cord and respiratory muscles; (2) counteract overshooting inflammation caused by cytokine storm/ inflammasome; (3) act neuroprotective and neuroregenerative in brain and peripheral nervous system. Based on this accumulating experimental and clinical evidence, we finally provide the research design for a double-blind placebo-controlled randomized clinical trial including severely affected patients, which is planned to start shortly

Geographical and seasonal barriers to mammography services and breast cancer stage at diagnosis

Introduction: Routine mammography screening and early detection are important prognostic indicators for breast cancer. Geographical and seasonal barriers to mammography services and relationship to breast cancer stage at diagnosis were examined. Methods: Travel time to mammography center, seasonal distribution of mammogram use, mammography frequency, and stage of cancer were retrospectively examined in 1428 female patients diagnosed with primary breast cancer at a tertiary care clinic system in Wisconsin, USA, from 2002 to 2008. Results: Women with no missed mammograms before diagnosis lived a median of 15 minutes from the nearest facility, while those who missed five of their past five annual mammograms lived nearly twice as far, with a median travel time of 27 minutes (p<0.0001). There was a direct relationship between travel time to nearest mammogram facility and stage of breast cancer at diagnosis, with travel time increasing from 17 to 24 minutes for stage 0 and stage 4 breast cancers, respectively (p=0.0586). Women were less likely to undergo mammography screening during the winter months (p<0.0001), especially women with greater than 30 mi (48.3 km) to travel to the nearest mammogram facility (p=0.0448). Conclusions: In the studied service area, travel time to nearest mammogram center appears inversely related to regular mammography screening and breast cancer stage at diagnosis. Mammograms are less common in the winter, especially in women with further to travel. This is the first study to demonstrate that inclement winter weather may impact on screening behaviors in rural areas and demonstrates the importance of considering climate as part of geographical access to preventative care