rudyvdbrink/CitationDatabase huggingface dataset:
Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway.
International journal of molecular sciences, 2020

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to the abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes, which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of KP alterations observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota in the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.
Prion protein disease and neuropathology of prion disease.
Neuroimaging clinics of North America, 2008

Human prion diseases, in common with other neurodegenerative diseases, may be sporadic or inherited and are characterized by the accumulation of cellular proteins accompanied by neuronal death and synaptic loss. Prion diseases are, however, unique in being transmissible. Central to the pathogenesis of all forms of prion disease is the prion protein. This article provides a brief overview of the biology of human prion diseases followed by a more in-depth discussion of the neuropathology of these diseases, including features of neuroradiologic relevance.
Research on aging during the Venezuelan humanitarian crisis: the experience of the Maracaibo aging study.
BMC public health, 2021

Venezuela is in the throes of a complex humanitarian crisis that is one of the worst in decades to impact any country outside of wartime. This case analysis describes the challenges faced by the ongoing Maracaibo Aging Study (MAS) during the deteriorating conditions in Venezuela. When the MAS began in 1997, it focused on memory-related disorders. Since then, strategic planning and proactive community participation allowed us to anticipate and address logistical, funding, and ethical challenges, and facilitated the enrollment and retention of more than 2500 subjects over 55 years of age. All participants, who are residents of the city of Maracaibo, Venezuela, underwent various assessments on several occasions. Here, we discuss how our approach to implementing a longitudinal, population-based study of age-related conditions has allowed our research program to continue throughout this period of political, economic, and social upheaval.
Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife).
BMC ophthalmology, 2021

Early detection of glaucoma is paramount to maintain patients' eyesight, however glaucomatous vision loss tends to begin in the periphery with up to 50% of patients unaware they are affected. Because glaucomatous vision loss is permanent, screening appears attractive, but currently is not cost-effective. Therefore we aim to investigate the utility of genetic pre-screening for glaucoma in a population-based setting, called EyeLife.
Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor MT-3014 in rats.
Pharmacology, biochemistry, and behavior, 2020

Phosphodiesterase (PDE) 10A is an attractive therapeutic target for schizophrenia. Here, we investigated the antipsychotic-like effects of a novel PDE10A inhibitor, 1-({2-(7-fluoro-3-methylquinoxalin-2-yl)-5-[(3R)-3-fluoropyrrolidin-1-yl]pyrazolo[1,5-α]pyrimidin-7-yl}amino)-2-methylpropan-2-ol hydrochloride (MT-3014) in rats. MT-3014 showed a potent and selective inhibitory effect against PDE10A (IC
Prevalence and risk factors of erectile dysfunction in patients with hepatitis B virus or hepatitis C virus or chronic liver disease: results from a prospective study.
Sexual health, 2018

Background Approximately 300million people are affected by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection worldwide. Erectile dysfunction (ED) is a frequent condition that impairs the quality of life and can be associated with several chronic disorders (type 2 diabetes mellitus, atherosclerosis, depression). Few studies have evaluated the prevalence of ED in patients with HBV and HCV chronic infection. The aim of this study was to evaluate the prevalence and the risk factors of ED in a cohort of patients with HBV or HCV-related chronic liver diseases.
Metabolic characteristics of Appalachian children.
Clinical nutrition ESPEN, 2017

The purpose of this investigation is to assess the physiological characteristics and the resting metabolic rates of a representative population of children in Buchanan County in order to identify those factors that may be contributing to the predisposition for being overweight or obese and provide nutritional and physical activity guidance for prevention.
Facilitation of antagonist motor output through short-latency sensory pathways during postnatal development in the mouse.
Neuroscience letters, 2018

Reciprocal inhibition of motor neurons via Ia inhibitory interneurons recruited by stimulation of proprioceptive afferents supplying antagonist muscles has been well described. Changes in the efficacy of inhibition, and sometimes even a switch from inhibition to facilitation, have been reported in the literature after disruption of descending pathways. We sought to test whether such facilitation could be expressed in normal animals by evaluating the presence of facilitation in acute preparations from uninjured animals. Using an isolated spinal cord preparation from neonatal mice, changes in the monosynaptic stretch reflex response in knee flexor motor neurons (posterior biceps semitendinosus; PBST) were monitored following conditioning stimulation of proprioceptive sensory afferents in other muscle nerves. As expected for reciprocal inhibition, conditioning by stimulation of quadriceps (knee extensors and PBST antagonists) sensory afferents resulted in inhibition of the stretch reflex response. Facilitation, however, of the stretch reflex response by quadriceps conditioning stimulation was observed when the glycinergic reciprocal inhibitory pathway was blocked by application of strychnine. Facilitation was elicited by low-threshold proprioceptive afferents and occurred at latencies consistent with a disynaptic circuit. The magnitude of facilitation was larger at birth than at one week postnatal. Our results also suggest reciprocal facilitation is restricted to antagonist muscle pairs, as facilitation of PBST responses was not observed when conditioned with the obturator nerve supplying the adductor muscles. Overall, these data suggest the efficacy of facilitation is modulated during the first postnatal week, while the specificity of facilitation is already established by birth.
Ciliary melanin-concentrating hormone receptor 1 (MCHR1) is widely distributed in the murine CNS in a sex-independent manner.
Journal of neuroscience research, 2020

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.
Changes in microRNA Expression in the Cochlear Nucleus and Inferior Colliculus after Acute Noise-Induced Hearing Loss.
International journal of molecular sciences, 2020

Noise-induced hearing loss (NIHL) can lead to secondary changes that induce neural plasticity in the central auditory pathway. These changes include decreases in the number of synapses, the degeneration of auditory nerve fibers, and reorganization of the cochlear nucleus (CN) and inferior colliculus (IC) in the brain. This study investigated the role of microRNAs (miRNAs) in the neural plasticity of the central auditory pathway after acute NIHL. Male Sprague-Dawley rats were exposed to white band noise at 115 dB for 2 h, and the auditory brainstem response (ABR) and morphology of the organ of Corti were evaluated on days 1 and 3. Following noise exposure, the ABR threshold shift was significantly smaller in the day 3 group, while wave II amplitudes were significantly larger in the day 3 group compared to the day 1 group. The organ of Corti on the basal turn showed evidence of damage and the number of surviving outer hair cells was significantly lower in the basal and middle turn areas of the hearing loss groups relative to controls. Five and three candidate miRNAs for each CN and IC were selected based on microarray analysis and quantitative reverse transcription PCR (RT-qPCR). The data confirmed that even short-term acoustic stimulation can lead to changes in neuroplasticity. Further studies are needed to validate the role of these candidate miRNAs. Such miRNAs may be used in the early diagnosis and treatment of neural plasticity of the central auditory pathway after acute NIHL.
Programmable C-to-U RNA editing using the human APOBEC3A deaminase.
The EMBO journal, 2020

Programmable RNA cytidine deamination has recently been achieved using a bifunctional editor (RESCUE-S) capable of deaminating both adenine and cysteine. Here, we report the development of "CURE", the first cytidine-specific C-to-U RNA Editor. CURE comprises the cytidine deaminase enzyme APOBEC3A fused to dCas13 and acts in conjunction with unconventional guide RNAs (gRNAs) designed to induce loops at the target sites. Importantly, CURE does not deaminate adenosine, enabling the high-specificity versions of CURE to create fewer missense mutations than RESCUE-S at the off-targets transcriptome-wide. The two editing approaches exhibit overlapping editing motif preferences, with CURE and RESCUE-S being uniquely able to edit UCC and AC motifs, respectively, while they outperform each other at different subsets of the UC targets. Finally, a nuclear-localized version of CURE, but not that of RESCUE-S, can efficiently edit nuclear RNAs. Thus, CURE and RESCUE are distinct in design and complementary in utility.
Developing a protocol for determining the competitive advantage of clinical specialty and sub-specialty mission differentiation in Iran.
Journal of advances in medical education & professionalism, 2020

The differentiation as a process occurs when new functions emerge in a system, and for this reason the university system is bound to diversify. With the advancement of knowledge and increase in competition, it has become a challenging issue and an inevitable necessity. This study aimed at identifying the dimensions of the differentiation of Iran's medical sciences universities through determining a protocol of the competitive advantage and scientific strength of clinical specialty and sub-spatiality departments of research activities.
Chemotherapy-induced neuropathy.
Journal of the peripheral nervous system : JPNS, 2008

Neurotoxic side effects of cancer therapy are second in frequency to hematological toxicity. Unlike hematological side effects that can be treated with hematopoietic growth factors, neuropathies cannot be treated and protective treatment strategies have not been effective. For the neurologist, the diagnosis of a toxic neuropathy is primarily based on the case history, the clinical and electrophysiological findings, and knowledge of the pattern of neuropathy associated with specific agents. In most cases, toxic neuropathies are length-dependent, sensory, or sensorimotor neuropathies often associated with pain. The platinum compounds are unique in producing a sensory ganglionopathy. Neurotoxicity is usually dependent on cumulative dose. Severity of neuropathy increases with duration of treatment and progression stops once drug treatment is completed. The platinum compounds are an exception where sensory loss may progress for several months after cessation of treatment ("coasting"). As more effective multiple drug combinations are used, patients will be treated with several neurotoxic drugs. Synergistic neurotoxicity has not been extensively investigated. Pre-existent neuropathy may influence the development of a toxic neuropathy. Underlying inherited or inflammatory neuropathies may predispose patients to developing very severe toxic neuropathies. Other factors such as focal radiotherapy or intrathecal administration may enhance neurotoxicity. The neurologist managing the cancer patient who develops neuropathy must answer a series of important questions as follows: (1) Are the symptoms due to peripheral neuropathy? (2) Is the neuropathy due to the underlying disease or the treatment? (3) Should treatment be modified or stopped because of the neuropathy? (4) What is the best supportive care in terms of pain management or physical therapy for each patient? Prevention of toxic neuropathies is most important. In patients with neuropathy, restorative approaches have not been well established. Symptomatic and other management are necessary to maintain and improve quality of life.
Are there "local hotspots?" When concepts of cognitive psychology do not fit with physiological results.
The Behavioral and brain sciences, 2016

Mather and colleagues' arguments require rethinking at the mechanistic level. The arguments on the physiological effects of norepinephrine at the cortical level are inconsistent with large parts of the literature. There is no evidence that norepinephrine induces local "hotspots": Norepinephrine mainly decreases evoked responses; facilitating effects are rare and not localized. More generally, the idea that perception benefits from "local hotspots" is hardly compatible with the fact that neural representations involve largely distributed activation of cortical and subcortical networks.
Disentangling the lasting effects of adolescent cannabinoid exposure.
Progress in neuro-psychopharmacology & biological psychiatry, 2021

Cannabis is the most widely used illicit substance among adolescents, and adolescent cannabis use is associated with various neurocognitive deficits that can extend into adulthood. A growing body of evidence supports the hypothesis that adolescence encompasses a vulnerable period of development where exposure to exogenous cannabinoids can alter the normative trajectory of brain maturation. In this review, we present an overview of studies of human and rodent models that examine lasting effects of adolescent exposure. We include evidence from meta-analyses, longitudinal, or cross-sectional studies in humans that consider age of onset as a factor that contributes to the behavioral dysregulation and altered structural or functional development in cannabis users. We also discuss evidence from preclinical rodent models utilizing well-characterized or innovative routes of exposure, investigating the effects of dose and timing to produce behavioral deficits or alterations on a neuronal and behavioral level. Multiple studies from both humans and animals provide contrasting results regarding the magnitude of residual effects. Combined evidence suggests that exposure to psychoactive cannabinoids during adolescence has the potential to produce subtle, but lasting, alterations in neurobiology and behavior.
The Impact of the Global SARS-CoV-2 (COVID-19) Pandemic on Neuroanesthesiology Fellowship Programs Worldwide and the Potential Future Role for ICPNT Accreditation.
Journal of neurosurgical anesthesiology, 2021

The COVID-19 pandemic is an international crisis placing tremendous strain on medical systems around the world. Like other specialties, neuroanesthesiology has been adversely affected and training programs have had to quickly adapt to the constantly changing environment.
Effect of Core Temperature and Embolic Load During Cardiac Surgery on Motion Perception.
Heart, lung & circulation, 2016

Cognitive decline post-cardiac surgery is of clinical concern. To better understand it a sensitive and specific measure of post-surgery brain impairment is required. The cerebral territory most likely to be adversely affected by surgery is the posterior "watershed" territory.
Caregiver self-efficacy to talk about sex predicts conversations about HIV transmission risk with perinatally infected young people in Zimbabwe.
AIDS care, 2020

Given advances in care and treatment for HIV, perinatally infected young people are surviving into adolescence. These young people are making decisions about engaging in sexual relationships and it is critical to ensure they have the information they need to engage responsibly in sexual activity, particularly in an era where adherence to treatment could make their virus undetectable. The main objective of this analysis was to examine whether an HIV-positive young person's knowledge about forward transmission is associated with caregiver self-efficacy to talk about sex and general caregiver communication. Using data from a 12-month prospective cohort of caregivers of HIV-positive children aged 9-15 on ART and pre-ART in rural Zimbabwe, we found that caregiver self-efficacy to talk about sex predicted whether conversations about HIV transmission would occur between caregiver and the young person. However, by the end of 12-months, nearly two-thirds of caregivers of HIV-positive teenagers in our sample had still not explained how their adolescents could spread the virus to others despite these caregivers saying their adolescent should know this information at baseline. We discuss the implications for designing sexual and reproductive health (SRH) programs among populations of young people perinatally infected with HIV to ensure that this breakthrough generation receives the SRH support they need.
Perinatal Nicotine Reduces Chemosensitivity of Medullary 5-HT Neurons after Maturation in Culture.
Neuroscience, 2020

Perinatal exposure to nicotine produces ventilatory and chemoreflex deficits in neonatal mammals. Medullary 5-HT neurons are putative central chemoreceptors that innervate respiratory nuclei and promote ventilation, receive cholinergic input and express nicotinic acetylcholine receptors (nAChRs). Perforated patch clamp recordings were made from cultured 5-HT neurons dissociated from the medullary raphé of 0-3 day old mice expressing enhanced yellow fluorescent protein driven by the enhancer region for PET1 (ePet-EYFP). The effect of exposure to low (6 mg kg
Chronic hyperalgesia induced by repeated acid injections in muscle is abolished by the loss of ASIC3, but not ASIC1.
Pain, 2003

Clinically, chronic pain and hyperalgesia induced by muscle injury are disabling and difficult to treat. Cellular and molecular mechanisms underlying chronic muscle-induced hyperalgesia are not well understood. For this reason, we developed an animal model where repeated injections of acidic saline into one gastrocnemius muscle produce bilateral, long-lasting mechanical hypersensitivity of the paw (i.e. hyperalgesia) without associated tissue damage. Since acid sensing ion channels (ASICs) are found on primary afferent fibers and respond to decreases in pH, we tested the hypothesis that ASICs on primary afferent fibers innervating muscle are critical to development of hyperalgesia and central sensitization in response to repeated intramuscular acid. Dorsal root ganglion neurons innervating muscle express ASIC3 and respond to acidic pH with fast, transient inward and sustained currents that resemble those of ASICs. Mechanical hyperalgesia produced by repeated intramuscular acid injections is prevented by prior treatment of the muscle with the non-selective ASIC antagonist, amiloride, suggesting ASICs might be involved. ASIC3 knockouts do not develop mechanical hyperalgesia to repeated intramuscular acid injection when compared to wildtype littermates. In contrast, ASIC1 knockouts develop hyperalgesia similar to their wildtype littermates. Extracellular recordings of spinal wide dynamic range (WDR) neurons from wildtype mice show an expansion of the receptive field to include the contralateral paw, an increased response to von Frey filaments applied to the paw both ipsilaterally and contralaterally, and increased response to noxious pinch contralaterally after the second intramuscular acid injection. These changes in WDR neurons do not occur in ASIC3 knockouts. Thus, activation of ASIC3s on muscle afferents is required for development of mechanical hyperalgesia and central sensitization that normally occurs in response to repeated intramuscular acid. Therefore, interfering with ASIC3 might be of benefit in treatment or prevention of chronic hyperalgesia.