Neuroscience-informed Auditory Training in Schizophrenia: A Final Report of the Effects on Cognition and Serum Brain-Derived Neurotrophic Factor.

ObjectiveWe previously reported the interim effects in a per protocol analysis of a randomized controlled trial of an innovative neuroscience-informed computerized cognitive training approach in schizophrenia. Here we report the effects of training on behavioral outcome measures in our final sample using an intent-to-treat analysis. We also report the effects on serum brain-derived neurotrophic factor (BDNF).MethodEighty-seven clinically stable participants with schizophrenia were randomly assigned to either targeted auditory training (AT, N=46) or a computer games control condition (CG, N=41). Participants were assessed on neurocognition, symptoms and functional outcome at baseline and after 50 hours of intervention delivered over 10 weeks. Serum BDNF was assessed at baseline, at 2 weeks, and at 10 weeks.ResultsAfter the intervention, AT participants showed significant gains in global cognition, speed of processing, verbal learning, and verbal memory, relative to CG participants, with no changes in symptoms or functioning. At baseline, schizophrenia participants had significantly lower-than-normal serum BDNF. AT participants showed a significant increase in serum BDNF compared to CG participants, and "normalized" levels by post training.ConclusionsParticipants with chronic schizophrenia made significant cognitive gains after 50 hours of intensive computerized training delivered as a stand-alone treatment, but no improvement in symptoms or functioning. Serum BDNF levels were significantly increased, and may serve as a peripheral biomarker for the effects of training. Future research must focus on: 1) Methods of integrating cognitive training with psychosocial treatments; 2) A deeper understanding of underlying neurophysiology in order to enhance critical mechanisms of action

Of sound mind and body: depression, disease, and accelerated aging

Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators

Improving Project Logistics by using IoT

This Bachelor´s thesis is made on behalf of Wärtsilä Energy Solutions, Project Logistics & Transport Management department whose main task is to coordinate and ensure that materials and products are transported to the right place and on time in Project Logistics. This thesis examines how you could improve Wärtsilä´s Project Logistics by using Internet of Things. By developing IoT, there has been an increased chance to get more information about transports than before and Wärtsilä is currently looking for new solutions to use that could improve their current logistics system. The purpose of this thesis is to review new, and used, solutions on the market, and then see what could work in practice at Wärtsilä. Material to this thesis are gathered from books, web pages and articles that reviewed interesting IoT solutions and which also gave examples on different solutions that are used by other companies in the same business. The Result is two different methods that could improve Wärtsilä´s Project Logistics in different occasions. These results are intended to give tips on how IoT could improve the department´s ways of coordinating and check transports and logistics within a project.Detta examensarbete är gjort i uppdrag av Wärtsilä Energy Solutions, Project logistics & Transport Management avdelningen vars huvuduppgift är att koordinera och se till att material och produkter transporteras till rätt plats i rätt tid inom projekt logistiken. Examensarbetet behandlar hur man kunde förbättra Wärtsiläs projekt logistik genom att använda Internet of Things. Genom att IoT har utvecklats har det uppstått möjligheter att få fram mer information om transporter än tidigare och Wärtsilä söker för tillfället nya lösningar som kunde användas för att förbättra deras nuvarande logistiksystem. Syftet med arbetet är att gå igenom nya, men även redan befintliga, lösningar som används på dagens marknad - för att sedan se vad som kunde fungera i praktiken hos Wärtsilä. Material till arbetet är samlat från böcker, webbsidor och artiklar som gick igenom intressanta IoT lösningar och som också gav exempel på hur olika system fungerar och används av andra företag inom samma bransch. Slutresultatet blev två olika metoder som kunde förbättra Wärtsiläs projekt logistik vid olika tillfällen. Dessa resultat är tänkta för att ge tips på hur IoT kunde förbättra avdelningens sätt hur man koordinerar och granskar transporter och logistiken inom ett projekt

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Cognition and resective surgery for diffuse infiltrative glioma: an overview

Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general assumption that cognitive assessment is time-consuming and burdensome contributes to this notion. Our understanding of the effects of brain surgery on cognition, for instance, is largely based on studies in surgical patients with refractory epilepsy, with only a limited number of studies in surgical patients with gliomas. The impact of other factors affecting cognition in glioma patients such as direct tumor effects, radiotherapy and chemotherapy, and medical treatment, including anti-epileptic drugs and steroids, have been studied more extensively. The purpose of this paper is to provide an overview of cognition in patients with diffuse infiltrative gliomas and the impact of resective surgery as well as other tumor and treatment-related factors

Is there Progress? An Overview of Select Biomarker Candidates for Major Depressive Disorder

Major Depressive Disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings