scholarly journals Recent Developments in Treating Cognitive Impairment Associated with Schizophrenia

2021 ◽  
Author(s):  
Robert A Bittner ◽  
Catherine V Barnes-Scheufler ◽  
Meike D Hettwer ◽  
Andreas Reif ◽  
Mishal Qubad
Keyword(s):  
Cognitive Impairment ◽  
Neural Plasticity ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Cognitive Impairments ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Potential Effect ◽  
Current Evidence ◽  
Novel Treatment Strategies

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Cognitive Impairment in Children with Arachnoid Cyst of Sylvian Fissure: Does it Justify the Neurosurgical Treatment?

2020 ◽  
Vol 81 (04) ◽  
pp. 362-367 ◽  
Author(s):  
Karolina Kwiatkowska ◽  
Magdalena Dębicka ◽  
Agnieszka Maryniak ◽  
Stanisław Kwiatkowski
Keyword(s):  
Cognitive Impairment ◽  
Clinical Practice ◽  
Intracranial Hypertension ◽  
Cognitive Deficits ◽  
Cognitive Functions ◽  
Clinical Symptoms ◽  
Cognitive Impairments ◽  
Neurological Deficits ◽  
Neurosurgical Treatment ◽  
The Relationship

AbstractThis report discusses the relationship between arachnoid cysts (ACs) and cognitive deficits, and we ask if cognitive impairments could justify neurosurgical treatment. In clinical practice, only AC patients with symptoms of intracranial hypertension or focal neurological deficits are referred to surgery. Occasionally, one might assume that nonspecific problems such as impairment of learning, speech, or cognitive functions are caused by an AC and can be improved by surgery. We describe three patients, in which surgery was indicated on the basis of clinical symptoms such as headaches and the size of the cysts. A neuropsychological examination before AC surgery revealed reduced cognitive potential, and the same examination repeated after surgery showed improvement. We have not found any other reason for this change, except for the decompression of the AC.

Reward Circuits and Apathy in Schizophrenia: Neuroimaging and Treatment Strategies

2017 ◽  
Vol 41 (S1) ◽  
pp. S58-S58
Author(s):  
A. Aleman
Keyword(s):  
Behavioral Treatment ◽  
Negative Symptoms ◽  
Meta Analysis ◽  
Critical Role ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Reward Processing ◽  
Motivated Behavior ◽  
Novel Treatment Strategies ◽  
Quantitative Integration

Approximately 50% of patients with schizophrenia shows deficits in motivation and initiation of goal-directed behavior, which are suggestive of reward system dysfunction. We conducted a meta-analysis of neuroimaging studies reporting on the neural correlates of reward processing and negative symptoms in schizophrenia. A significant mean weighted correlation was observerd, revealing deficits in activation of reward neurocircuitry. A more specific findings is comprised activation of the ventral striatum, involved in anticipation of reward, and structures that play a critical role in the ability to represent the value of outcomes and plans. In a study of VTA connectivity in the resting state in a large group of patients with schizophrenia, we found reduced connectivity with lateral prefrontal, temporal and parietal regions to be associated with higher degrees of apathy. Apathy belongs to the most debilitating symptoms of schizophrenia and represents a significant unmet need in its treatment. Quantitative integration of published findings suggests that treatment with noninvasive magnetic brain stimulation can improve negative symptoms. Previous PET-studies have shown that such stimulation may target circuits with dopaminergic innervation. A behavioral treatment approach that may also target reward-related circuits will also be discussed briefly. It can be concluded that recent results regarding reward and motivated behavior in schizophrenia have clinical implications and may help develop novel treatment strategies.Disclosure of interestAA received speaker fees from Lundbeck.

scholarly journals Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1979
Author(s):  
Andrea Jess Josiah ◽  
Danielle Twilley ◽  
Sreejarani Kesavan Pillai ◽  
Suprakas Sinha Ray ◽  
Namrita Lall
Keyword(s):  
Cell Carcinoma ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Contributing Factors ◽  
Alternative Approach ◽  
Transdermal Drug Delivery Systems ◽  
Novel Treatment Strategies

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.

scholarly journals Identification of TNFR2 and IL-33 as therapeutic targets in localized fibrosis

2019 ◽  
Vol 5 (12) ◽  
pp. eaay0370 ◽  
Author(s):  
David Izadi ◽  
Thomas B. Layton ◽  
Lynn Williams ◽  
Fiona McCann ◽  
Marisa Cabrita ◽  
...  
Keyword(s):  
Immune Cells ◽  
Single Cell Analysis ◽  
Unmet Need ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Low Grade ◽  
Interleukin 33 ◽  
Target Disease ◽  
Novel Treatment Strategies ◽  
Molecular Landscape

Dissecting the molecular landscape of fibrotic disease, a major unmet need, will inform the development of novel treatment strategies to target disease progression and identify desperately needed therapeutic targets. Here, we provide a detailed single-cell analysis of the immune landscape in Dupuytren’s disease, a localized fibrotic condition of the hand, and identify a pathogenic signaling circuit between stromal and immune cells. We demonstrate M2 macrophages and mast cells as key cellular sources of tumor necrosis factor (TNF) that promotes myofibroblast development. TNF acts via the inducible TNFR2 receptor and stimulates interleukin-33 (IL-33) secretion by myofibroblasts. In turn, stromal cell IL-33 acts as a potent stimulus for TNF production from immune cells. Targeting this reciprocal signaling pathway represents a novel therapeutic strategy to inhibit the low-grade inflammation in fibrosis and the mechanism that drives chronicity.

scholarly journals Brain activation and connectivity in anorexia nervosa and body dysmorphic disorder when viewing bodies: relationships to clinical symptoms and perception of appearance

2020 ◽  
Author(s):  
Teena D Moody ◽  
Francesca Morfini ◽  
Gigi Cheng ◽  
Courtney L Sheen ◽  
Wesley Kerr ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Body Dysmorphic Disorder ◽  
Clinical Symptoms ◽  
Treatment Strategies ◽  
Brain Activation ◽  
Matching Task ◽  
Subjective Perception ◽  
Significant Activity ◽  
Global Features ◽  
Novel Treatment Strategies

AbstractAnorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared brain activation and connectivity in relevant networks when viewing images of others’ bodies and tested their relationships with clinical symptoms and subjective appearance evaluations. We acquired fMRI data from 64 unmedicated females (20 weight-restored AN, 23 BDD, 21 controls) during a matching task using photos of others’ bodies that were unaltered or spatial-frequency filtered. With general linear model and independent components analyses we compared brain activation and connectivity in visual, striatal, and parietal networks and performed univariate and partial least squares multivariate analyses to investigate relationships with clinical symptoms and appearance evaluations. BDD but not AN demonstrated hypoactivity in dorsal visual and parietal networks compared to controls. Yet, AN and BDD showed partially overlapping patterns of hyperconnectivity in the dorsal visual network and hypoconnectivity in parietal network compared with controls. Further, there were significant activity and connectivity differences between AN and BDD in both networks. In both groups, activity and/or connectivity were associated with symptom severity and appearance ratings of others’ bodies. AN and BDD demonstrate both distinct and partially overlapping aberrant neural phenotypes involved in body processing and visually encoding global features. Nevertheless, in each disorder, aberrant activity and connectivity show relationships to clinically relevant symptoms and subjective perception. Results have implications for understanding distinct and shared pathophysiology underlying perceptual distortions for appearance and may inform future novel treatment strategies.

scholarly journals Antimicrobial Treatment Strategies for Stenotrophomonas maltophilia: A Focus on Novel Therapies

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1226
Author(s):  
Jean Gibb ◽  
Darren W. Wong
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Treatment Strategies ◽  
Antimicrobial Treatment ◽  
Current Evidence ◽  
Antibiotic Development ◽  
Carbapenem Resistant ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Global Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Stenotrophomonas maltophilia is an urgent global threat due to its increasing incidence and intrinsic antibiotic resistance. Antibiotic development has focused on carbapenem-resistant Enterobacteriaceae, Pseudomonas, and Acinetobacter, with approved antibiotics in recent years having limited activity for Stenotrophomonas. Accordingly, novel treatment strategies for Stenotrophomonas are desperately needed. We conducted a systemic literature review and offer recommendations based on current evidence for a treatment strategy of Stenotrophomonas infection.

scholarly journals Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3429
Author(s):  
Aisling Forder ◽  
Chi-Yun Hsing ◽  
Jessica Trejo Vazquez ◽  
Cathie Garnis
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Metastatic Niche ◽  
Novel Treatment ◽  
Membrane Bound ◽  
Novel Treatment Strategies

Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.

scholarly journals Repurposing of α1-Adrenoceptor Antagonists: Impact in Renal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2442 ◽  
Author(s):  
Meredith Mihalopoulos ◽  
Zachary Dovey ◽  
Maddison Archer ◽  
Talia G. Korn ◽  
Kennedy E. Okhawere ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Metastatic Disease ◽  
Treatment Strategies ◽  
Metastatic Potential ◽  
Immune Checkpoint Blockade ◽  
Renal Tumors ◽  
Current Evidence ◽  
Anoikis Resistance ◽  
Mtor Inhibition ◽  
Novel Treatment Strategies

Renal cancer ranks twelfth in incidence among cancers worldwide. Despite improving outcomes due to better therapeutic options and strategies, prognosis for those with metastatic disease remains poor. Current systemic therapeutic approaches include inhibiting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition, but inevitably resistance develops for those with metastatic disease, and novel treatment strategies are urgently needed. Emerging molecular and epidemiological evidence suggests that quinazoline-based α1-adrenoceptor-antagonists may have both chemopreventive and direct therapeutic actions in the treatment of urological cancers, including renal cancer. In human renal cancer cell models, quinazoline-based α1-adrenoceptor antagonists were shown to significantly reduce the invasion and metastatic potential of renal tumors by targeting focal adhesion survival signaling to induce anoikis. Mechanistically these drugs overcome anoikis resistance in tumor cells by targeting cell survival regulators AKT and FAK, disrupting integrin adhesion (α5β1 and α2β1) and engaging extracellular matrix (ECM)-associated tumor suppressors. In this review, we discuss the current evidence for the use of quinazoline-based α1-adrenoceptor antagonists as novel therapies for renal cell carcinoma (RCC) and highlight their potential therapeutic action through overcoming anoikis resistance of tumor epithelial and endothelial cells in metastatic RCC. These findings provide a platform for future studies that will retrospectively and prospectively test repurposing of quinazoline-based α1-adrenoceptor-antagonists for the treatment of advanced RCC and the prevention of metastasis in neoadjuvant, adjuvant, salvage and metastatic settings.

Symptom severity and cognitive impairment in chronically hospitalised geriatric patients with affective disorders

1997 ◽  
Vol 170 (4) ◽  
pp. 369-374 ◽  
Author(s):  
Philip D. Harvey. Peter Powchik ◽  
Michael Parrella ◽  
Leonard White ◽  
Michael Davidson
Keyword(s):  
Cognitive Impairment ◽  
Affective Disorders ◽  
Geriatric Patients ◽  
Clinical Symptoms ◽  
Age Of Onset ◽  
Cognitive Impairments ◽  
Poor Outcome ◽  
Symptom Profiles ◽  
Two Samples ◽  
Schizophrenic Patients

BackgroundAffective disorders typically have a better outcome than schizophrenia, although recent evidence suggests that some patients with affective disorder have a relatively poor outcome, with cognitive impairments and persistent symptomatology.MethodFifty chronically hospitalised geriatric patients with mood disorders (major depression or bipolar disorder) were compared on the clinical symptoms and aspects of cognitive impairment with 308 geriatric schizophrenic patients who were hospitalised at the same institution. The two samples did not differ in current age or in premorbid education level, but the affective patients had a later age of onset and more females in the sample.ResultsThere were no overall differences in cognitive functioning between the groups, although the clinical symptom profiles resembled those seen in better outcome patients.ConclusionsCognitive impairment is present in poor-outcome patients with affective disorders as well as schizophrenia, suggesting that cognitive impairments predict poor outcome across psychiatric disorders and not just in schizophrenia.

scholarly journals Diagnostic Strategies for Treatment Selection in Advanced Prostate Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 345
Author(s):  
Ciara S. McNevin ◽  
Anne-Marie Baird ◽  
Ray McDermott ◽  
Stephen P. Finn
Keyword(s):  
Prostate Cancer ◽  
Treatment Strategies ◽  
Treatment Selection ◽  
High Rate ◽  
Current Evidence ◽  
Diagnostic Strategies ◽  
Novel Treatment ◽  
Proven Efficacy ◽  
Novel Treatment Strategies ◽  
Poor Outcomes

Prostate Cancer (PCa) is a leading cause of morbidity and mortality among men worldwide. For most men with PCa, their disease will follow an indolent course. However, advanced PCa is associated with poor outcomes. There has been an advent of new therapeutic options with proven efficacy for advanced PCa in the last decade which has improved survival outcomes for men with this disease. Despite this, advanced PCa continues to be associated with a high rate of death. There is a lack of strong evidence guiding the timing and sequence of these novel treatment strategies. This paper focuses on a review of the strategies for diagnostic and the current evidence available for treatment selection in advanced PCa.

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