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PloS One 2023Debilitating symptoms of fatigue and accompanying "brain fog" are observed among patients with various chronic health conditions. Unfortunately, an efficient and...
Debilitating symptoms of fatigue and accompanying "brain fog" are observed among patients with various chronic health conditions. Unfortunately, an efficient and psychometrically sound instrument to assess these co-occurring symptoms is unavailable. Here, we report the development and initial psychometric properties of the Fatigue and Altered Cognition Scale (the FACs), a measure of self-reported central fatigue and brain fog. Traumatic brain injury (TBI) was chosen to model and develop the FACs due to research team expertise and established links between TBI and the symptom complex. Potential items were generated by researchers and clinicians with experience treating these symptoms, drawing from relevant literature and review of patient responses to measures from past and current TBI studies. The 20 candidate items for the FACs-ten each to assess altered cognition (i.e., brain fog) and central fatigue-were formatted on an electronic visual analogue response scale (eVAS) via an online survey. Demographic information and history of TBI were obtained. A total of 519 participants consented and provided usable data (average age = 40.23 years; 73% female), 204 of whom self-reported a history of TBI (75% reported mild TBI). Internal consistency and reliability values were calculated. Confirmatory factor analysis (CFA) examined the presumed two-factor structure of the FACs and a one-factor solution for comparison. A measurement invariance test of the two latent constructs (altered cognition, fatigue) among participants with and without TBI was conducted. All items demonstrated normal distribution. Cronbach's alpha coefficients indicated good internal consistency for both factors (α's = .95). Omega reliability values were favorable (α's = .95). CFA supported the presumed two-factor model and item loadings which outperformed the one-factor model. Measurement invariance found the two-factor structure was consistent between the two groups. Implications of these findings, study limitations, and potential use of the FACs in clinical research and practice are discussed.
Topics: Humans; Female; Adult; Male; Reproducibility of Results; Brain Injuries, Traumatic; Surveys and Questionnaires; Fatigue; Mental Fatigue; Cognition; Psychometrics
PubMed: 38079429
DOI: 10.1371/journal.pone.0295593 -
Aging Pathobiology and Therapeutics Mar 2021Genetic variation does not entirely address the consistent divergence of healthy and unhealthy aging in heterogeneous and homogeneous mammalian populations. The...
Genetic variation does not entirely address the consistent divergence of healthy and unhealthy aging in heterogeneous and homogeneous mammalian populations. The alteration of gene function through modification of histone DNA infrastructure is a logical extending explanation for this divergence. Since epigenetic alterations are reversible, therapeutic interventions that target the right gene or gene products could reverse aging, at the very least in the population of older people with poor health.
PubMed: 35083451
DOI: 10.31491/apt.2021.03.048 -
Frontiers in Psychiatry 2022Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of... (Review)
Review
Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost excitatory neurotransmitter: since the 1990s, studies have consistently reported altered levels of glutamate in MDD, as well as antidepressant effects following molecular targeting of glutamatergic receptors. Therapeutically, this has led to advances in the discovery, testing, and clinical application of a wide array of glutamatergic agents, particularly ketamine. Notably, ketamine has been demonstrated to rapidly improve mood symptoms, unlike monoamine-based interventions, and the neurobiological basis behind this rapid antidepressant response is under active investigation. Advances in brain imaging techniques, including functional magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, enable the identification of the brain network-based characteristics distinguishing rapid glutamatergic modulation from the effect of slow-acting conventional monoamine-based pharmacology. Here, we review brain imaging studies that examine brain connectivity features associated with rapid antidepressant response in MDD patients treated with glutamatergic pharmacotherapies in contrast with patients treated with slow-acting monoamine-based treatments. Trends in recent brain imaging literature suggest that the activity of brain regions is organized into coherent functionally distinct networks, termed intrinsic connectivity networks (ICNs). We provide an overview of major ICNs implicated in depression and explore how treatment response following glutamatergic modulation alters functional connectivity of limbic, cognitive, and executive nodes within ICNs, with well-characterized anti-anhedonic effects and the enhancement of "top-down" executive control. Alterations within and between the core ICNs could potentially exert downstream effects on the nodes within other brain networks of relevance to MDD that are structurally and functionally interconnected through glutamatergic synapses. Understanding similarities and differences in brain ICNs features underlying treatment response will positively impact the trajectory and outcomes for adults suffering from MDD and will facilitate the development of biomarkers to enable glutamate-based precision therapeutics.
PubMed: 35722550
DOI: 10.3389/fpsyt.2022.864902 -
Frontiers in Neuroscience 2014In this article we present a review of current literature on adaptations to altered head-related auditory localization cues. Localization cues can be altered through ear... (Review)
Review
In this article we present a review of current literature on adaptations to altered head-related auditory localization cues. Localization cues can be altered through ear blocks, ear molds, electronic hearing devices, and altered head-related transfer functions (HRTFs). Three main methods have been used to induce auditory space adaptation: sound exposure, training with feedback, and explicit training. Adaptations induced by training, rather than exposure, are consistently faster. Studies on localization with altered head-related cues have reported poor initial localization, but improved accuracy and discriminability with training. Also, studies that displaced the auditory space by altering cue values reported adaptations in perceived source position to compensate for such displacements. Auditory space adaptations can last for a few months even without further contact with the learned cues. In most studies, localization with the subject's own unaltered cues remained intact despite the adaptation to a second set of cues. Generalization is observed from trained to untrained sound source positions, but there is mixed evidence regarding cross-frequency generalization. Multiple brain areas might be involved in auditory space adaptation processes, but the auditory cortex (AC) may play a critical role. Auditory space plasticity may involve context-dependent cue reweighting.
PubMed: 25120422
DOI: 10.3389/fnins.2014.00219 -
Metabolites Jan 2022Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding...
Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens.
PubMed: 35050168
DOI: 10.3390/metabo12010047 -
Clinical and Experimental... 2015Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and abnormal bowel patterns. Alteration in gut... (Review)
Review
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and abnormal bowel patterns. Alteration in gut flora, visceral hypersensitivity, and abnormal bowel motility are among numerous factors in the complex pathophysiology of IBS. Antibiotics have been used adjunctively to treat IBS for many years but are associated with various systemic side effects. Rifaximin is a nonabsorbable, broad-spectrum antimicrobial that inhibits bacterial RNA synthesis by binding the β-subunit of microbial RNA polymerase. It targets the gastrointestinal tract and works by reducing the quantity of gas-producing bacteria and altering the predominant species of bacteria present. In vivo animal studies suggest additional beneficial mechanisms of rifaximin, including reducing mucosal inflammation and visceral hypersensitivity. Clinical studies have demonstrated that rifaximin improves symptoms associated with IBS, such as bloating, flatulence, stool consistency, and abdominal pain, and has a side-effect profile similar to placebo. Although additional investigation into optimal dosing, treatment duration, and potential resistance is required, rifaximin presents as a safe and beneficial addition to the current management options for IBS.
PubMed: 26089696
DOI: 10.2147/CEG.S67231 -
The Mental Health Clinician Nov 2016Schizophrenia is a severe disorder affecting approximately 1% of the population. Historically, alterations of dopaminergic function were considered the primary cause of...
Schizophrenia is a severe disorder affecting approximately 1% of the population. Historically, alterations of dopaminergic function were considered the primary cause of schizophrenia. However, for many patients, drugs that alter dopaminergic function do not consistently lead to resolution of the symptoms of schizophrenia. Thus, there is an increased interest in pathophysiologic processes that result in altered neurodevelopment and plasticity associated with schizophrenia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis, synaptic plasticity, cognition, and neurotransmission. Genetic polymorphism, expression, and function of BDNF have been implicated in psychiatric diseases, including schizophrenia. This review discusses BDNF, its role in neurologic processes, and the evidence implicating BDNF in schizophrenia.
PubMed: 29955483
DOI: 10.9740/mhc.2016.11.285 -
The Science of the Total Environment Feb 2023Anthropogenic stressors on the environment are increasing at unprecedented rates and include urbanization, nutrient pollution, water management, altered land use and...
Anthropogenic stressors on the environment are increasing at unprecedented rates and include urbanization, nutrient pollution, water management, altered land use and climate change. Their effects on disease vectors are poorly understood. A series of full factorial experiments investigated how key human induced abiotic pressures, and interactions between these, affect population parameters of the cosmopolitan disease vector, Culex pipiens s.l. Selected pressures include eutrophication, salinity, mean temperature, and temperature fluctuation. Data were collected for each individual pressure and for potential interactions between eutrophication, salinization and temperature. All experiments assessed survival, time to pupation, time to emergence, sex-ratio and ovipositioning behavior. The results show that stressors affect vector survival, may speed up development and alter female to male ratio, although large differences between stressors exist to quite different extents. While positive effects of increasing levels of eutrophication on survival were consistent, negative effects of salinity on survival were only apparent at higher temperatures, thus indicating a strong interaction effect between salinization and temperature. Temperature had no independent effect on larval survival. Overall, increasing eutrophication and temperatures, and the fluctuations thereof, lowered development rate, time to pupation and time to emergence while increasing levels of salinity increased development time. Higher levels of eutrophication positively impacted egg-laying behavior; the reverse was found for salinity while no effects of temperature on egg-laying behavior were observed. Results suggest large and positive impacts of anthropogenically induced habitat alterations on mosquito population dynamics. Many of these effects are exacerbated by increasing temperatures and fluctuations therein. In a world where eutrophication and salinization are increasingly abundant, mosquitoes are likely important benefactors. Ultimately, this study illustrates the importance of including multiple and combined stressors in predictive models as well as in prevention and mitigation strategies, particularly because they resonate with possible, but yet underdeveloped action plans.
Topics: Animals; Male; Female; Humans; Culicidae; Mosquito Vectors; Culex; Eutrophication; Larva; Temperature
PubMed: 36302419
DOI: 10.1016/j.scitotenv.2022.159716 -
Ecology and Evolution Dec 2021Trait and functional trait approaches have revolutionized ecology improving our understanding of community assembly, species coexistence, and biodiversity loss. Focusing... (Review)
Review
Trait and functional trait approaches have revolutionized ecology improving our understanding of community assembly, species coexistence, and biodiversity loss. Focusing on traits promotes comparability across spatial and organizational scales, but terms must be used consistently. While several papers have offered definitions, it remains unclear how ecologists operationalize "trait" and "functional trait" terms. Here, we evaluate how researchers and the published literatures use these terms and explore differences among subdisciplines and study systems (taxa and biome). By conducting both a survey and a literature review, we test the hypothesis that ecologists' working definition of "trait" is adapted or altered when confronting the realities of collecting, analyzing and presenting data. From 486 survey responses and 712 reviewed papers, we identified inconsistencies in the understanding and use of terminology among researchers, but also limited inclusion of definitions within the published literature. Discrepancies were not explained by subdiscipline, system of study, or respondent characteristics, suggesting there could be an inconsistent understanding even among those working in related topics. Consistencies among survey responses included the use of morphological, phonological, and physiological traits. Previous studies have called for unification of terminology; yet, our study shows that proposed definitions are not consistently used or accepted. Sources of disagreement include trait heritability, defining and interpreting function, and dealing with organisms in which individuals are not clearly recognizable. We discuss and offer guidelines for overcoming these disagreements. The diversity of life on Earth means traits can represent different features that can be measured and reported in different ways, and thus, narrow definitions that work for one system will fail in others. We recommend ecologists embrace the breadth of biodiversity using a simplified definition of "trait" more consistent with its common use. Trait-based approaches will be most powerful if we accept that traits are at least as diverse as trait ecologists.
PubMed: 34938447
DOI: 10.1002/ece3.8321 -
Journal of Animal Science May 2019In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from... (Review)
Review
In vitro embryo production (IVP) in cattle has gained worldwide interest in recent years, but the efficiency of using IVP embryos for calf production is far from optimal. This review will examine the pregnancy retention rates of IVP embryos and explore causes for pregnancy failures. Based on work completed over the past 25 yr, only 27% of cattle receiving IVP embryos will produce a live calf. Approximately 60% of these pregnancies fail during the first 6 wk of gestation. When compared with embryos generated by superovulation, pregnancy rates are 10% to 40% lower for cattle carrying IVP embryos, exemplifying that IVP embryos are consistently less competent than in vivo-generated embryos. Several abnormalities have been observed in the morphology of IVP conceptuses. After transfer, IVP embryos are less likely to undergo conceptus elongation, have reduced embryonic disk diameter, and have compromised yolk sac development. Marginal binucleate cell development, cotyledon development, and placental vascularization have also been documented, and these abnormalities are associated with altered fetal growth trajectories. Additionally, in vitro culture conditions increase the risk of large offspring syndrome. Further work is needed to decipher how the embryo culture environment alters post-transfer embryo development and survival. The risk of these neonatal disorders has been reduced by the use of serum-free synthetic oviductal fluid media formations and culture in low oxygen tension. However, alterations are still evident in IVP oocyte and embryo transcript abundances, timing of embryonic cleavage events and blastulation, incidence of aneuploidy, and embryonic methylation status. The inclusion of oviductal and uterine-derived embryokines in culture media is being examined as one way to improve the competency of IVP embryos. To conclude, the evidence presented herein clearly shows that bovine IVP systems still must be refined to make it an economical technology in cattle production systems. However, the current shortcomings do not negate its current value for certain embryo production needs and for investigating early embryonic development in cattle.
Topics: Animals; Cattle; Embryo Transfer; Embryo, Mammalian; Embryonic Development; Female; Oocytes; Placenta; Pregnancy; Pregnancy Rate; Uterus
PubMed: 30968113
DOI: 10.1093/jas/skz116