Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content. Hepcidin, secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to plasma from intestinal iron absorption and from iron stores. Hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy. Hepcidin deficiency causes iron overload in hemochromatosis and anemias with ineffective erythropoiesis. Hepcidin excess causes iron-restrictive anemias including anemia of inflammation. The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Introduction. Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). Methods. We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. Results. Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = –0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions. As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.
Integrative medicine is an emerging field with many possible applications in Neurology. Patients living with neurological disease have been hungry for more guidance and study in this area. There is huge interest in wellness and helping patients make better lifestyle choices to influence the outcomes of their disease and to improve quality of life. We review the definitions, current literature and discuss limitations and identify questions for further research.
Major neurological and psychiatric diseases affect females and males differently, suggesting that inherent sex-biased biological factors affect disease incidence and progression. These factors are grouped into two major groups, hormones secreted by the gonads, and genes unequally encoded on X and Y sex chromosomes in the two sexes. Numerous rodent models of these diseases have been used to dissect the relative contributions of sex hormones and sex chromosomes, and studies of humans bear strongly on the factors that might account for the sex differences. Examples of research progress in this area are reviewed for multiple sclerosis and autoimmune diseases, stroke, Alzheimer's Disease, Parkinson's Disease, and autism spectrum disorder. The study of sex differences offers novel perspectives in the discovery of factors that may be targeted in the clinic to alleviate the burden of these diseases.
Hotel room cleaners are a vulnerable population at risk for cardiovascular disease. To evaluate their workload heart rate (HR), % heart rate reserve (%HRR), blood pressure (BP), metabolic equivalent (MET), and energy expenditure (EE) were measured over two workdays and two off-workdays. The mean age was 45.5 (SD 8.2) years with a mean 10.4 (SD 7.8) years of work experience. Mean average and peak HR, %HRR, MET, and EE were significantly higher during a workday than an off-workday for the entire work shift, first and last hour of work. Mean average HR and %HRR saw the largest increase between the lunch and post-lunch interim. One-fourth of subjects exceeded the recommended 30% HRR threshold for 8-hour shifts. Some workers experienced a substantial increase in HR and DBP over a workday indicating physiologic fatigue and thus may be at increased risk for cardiovascular disease and premature death due to excessive physical work demands.
The initiation and progression of various solid tumors have recently been linked to elevated BMI and obesity. Understanding this link is becoming increasingly important as obesity becomes more prevalent around the globe. However, the connection between obesity and brain tumors specifically is not currently well understood. Obesity-induced systemic inflammation and metabolic derangement may impact brain tumor risk and progression. However, clinical studies on this topic often reach conflicting results. This chapter explores obesity, brain tumor risk, and prognosis and includes analysis on related pathologies like pseudotumor cerebri and hypothalamic obesity. Analysis currently suggests that meningioma risk is increased in obese females, while conflicting data exists for other brain tumor types. Furthermore, it is uncertain whether obesity worsens prognosis or improves outcomes as an “obesity” paradox has been noted where obesity may lead to improved outcomes. These results signal that further study in this topic is necessary.
Recent preponderance of evidence suggests that adipose tissue is more than just a storage device but rather a complex organ with significant endocrine functions. Secretion of various adipokines has by this organ has been found to play a significant role in the balance between a systemic proinflammatory and antiinflammatory state. Obesity has been found to lead to dysregulation in this balance leading to a systemic proinflammatory state. Furthermore, various studies have found links between inflammation and CNS disorders. This chapter will focus on the links between the proinflammatory adipokines secreted in obesity and their link to disorders of the CNS with a particular focus on idiopathic intracranial hypertension, stroke, autoimmune CNS disorders, and finally dementia.
Of Being a First Generation (First Gen) college graduate is an important intersectionality which impacts the lens through which First Gen students learn to become physicians. In this Perspective, we define the First Gen identity and review some of the salient First Gen literature as it applies to the medical school experience. We discuss the conception, design and execution of First Gen initiatives and program development at our medical school as a call to action and model for other institutions to create communities for their First Gen populations, focusing on inclusion and tailored support. We describe the framework through which we envisioned our programming for First Gen medical students, trainees, staff, and faculty at the David Geffen School of Medicine at UCLA.
Hepatitis B virus (HBV) is a hepatotropic virus and an important human pathogen. There are an estimated 296 million people in the world that are chronically infected by this virus, and many of them will develop severe liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). HBV is a small DNA virus that replicates via the reverse transcription pathway. In this review, we summarize the molecular pathways that govern the replication of HBV and its interactions with host cells. We also discuss viral and non-viral factors that are associated with HBV-induced carcinogenesis and pathogenesis, as well as the role of host immune responses in HBV persistence and liver pathogenesis. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
The prevalence of obesity has risen to its highest values over the last two decades. While many studies have either shown brain or microbiome connections to obesity, few have attempted to analyze the brain-gut-microbiome relationship in a large cohort adjusting for cofounders. Therefore, we aim to explore the connection of the brain-gut-microbiome axis to obesity controlling for such cofounders as sex, race, and diet. Whole brain resting state functional MRI was acquired, and connectivity and brain network properties were calculated. Fecal samples were obtained from 287 obese and non-obese participants (males n = 99, females n = 198) for 16s rRNA profiling and fecal metabolites, along with a validated dietary questionnaire. Obesity was associated with alterations in the brain's reward network (nucleus accumbens, brainstem). Microbial diversity (p = .03) and composition (p = .03) differed by obesity independent of sex, race, or diet. Obesity was associated with an increase in Prevotella/Bacteroides (P/B) ratio and a decrease in fecal tryptophan (p = .02). P/B ratio was positively correlated to nucleus accumbens centrality (p = .03) and negatively correlated to fecal tryptophan (p = .004). Being Hispanic, eating a standard American diet, having a high Prevotella/Bacteroides ratio, and a high nucleus accumbens centrality were all independent risk factors for obesity. There are obesity-related signatures in the BGM-axis independent of sex, race, and diet. Race, diet, P/B ratio and increased nucleus accumbens centrality were independent risk factors for obesity. P/B ratio was inversely related to fecal tryptophan, a metabolite related to serotonin biosynthesis, and positively related to nucleus accumbens centrality, a region central to the brain's reward center. These findings may expand the field of therapies for obesity through novel pathways directed at the BGM axis.
The coronavirus disease-2019 (COVID-19) outbreak has been declared a global pandemic. COVID-19-associated acute kidney injury (COVID-19 AKI) is related to a high mortality rate and serves as an independent risk factor for hospital death in patients with COVID-19. Early diagnosis would allow for earlier intervention and potentially improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and several kidney injury biomarkers have been demonstrated to be beneficial in predicting COVID-19 AKI as well as disease progression in COVID-19. Furthermore, such data provide valuable insights into the molecular mechanisms underlying this complex and unique disease and serve as a molecular phenotyping tool that could be utilized to direct clinical intervention. This review focuses on a number of kidney injury biomarkers, such as CysC, NAGAL, KIM-1, L-FABP, IL-18, suPAR, and [TIMP-2] • [IGFBP7], which have been widely studied in common clinical settings, such as sepsis, cardiac surgery, and contrast-induced AKI. We explore the role of kidney injury biomarkers in COVID-19 and discuss what remains to be learned. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Background Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. Methods This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. Results Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization ( P = 0.828) between both treatment groups. Conclusions PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871
Objective Doppler ultrasonography of the common carotid artery is used to infer stroke volume change and a wearable Doppler ultrasound has been designed to improve this workflow. Previously, in a human model of hemorrhage and resuscitation comprising approximately 50,000 cardiac cycles, we found a strong, linear correlation between changing stroke volume, and measures from the carotid Doppler signal, however, optimal Doppler thresholds for detecting a 10% stroke volume change were not reported. In this Research Note , we present these thresholds, their sensitivities, specificities and areas under their receiver operator curves (AUROC). Results Augmentation of carotid artery maximum velocity time integral and corrected flowtime by 18% and 4%, respectively, accurately captured 10% stroke volume rise. The sensitivity and specificity for these thresholds were identical at 89% and 100%. These data are similar to previous investigations in healthy volunteers monitored by the wearable ultrasound.
Recording electric field evolution in single-shot with THz bandwidth is needed in science including spectroscopy, plasmas, biology, chemistry, Free-Electron Lasers, accelerators, and material inspection. However, the potential application range depends on the possibility to achieve sub-picosecond resolution over a long time window, which is a largely open problem for single-shot techniques. To solve this problem, we present a new conceptual approach for the so-called spectral decoding technique, where a chirped laser pulse interacts with a THz signal in a Pockels crystal, and is analyzed using a grating optical spectrum analyzer. By borrowing mathematical concepts from photonic time stretch theory and radio-frequency communication, we deduce a novel dual-output electro-optic sampling system, for which the input THz signal can be numerically retrieved—with unprecedented resolution—using the so-called phase diversity technique. We show numerically and experimentally that this approach enables the recording of THz waveforms in single-shot over much longer durations and/or higher bandwidth than previous spectral decoding techniques. We present and test the proposed DEOS (Diversity Electro-Optic Sampling) design for recording 1.5 THz bandwidth THz pulses, over 20 ps duration, in single-shot. Then we demonstrate the potential of DEOS in accelerator physics by recording, in two successive shots, the shape of 200 fs RMS relativistic electron bunches at European X-FEL, over 10 ps recording windows. The designs presented here can be used directly for accelerator diagnostics, characterization of THz sources, and single-shot Time-Domain Spectroscopy.
Migraine is a common, chronic, disorder that is typically characterized by recurrent disabling attacks of headache and accompanying symptoms, including aura. The aetiology is multifactorial with rare monogenic variants. Depression, epilepsy, stroke and myocardial infarction are comorbid diseases. Spreading depolarization probably causes aura and possibly also triggers trigeminal sensory activation, the underlying mechanism for the headache. Despite earlier beliefs, vasodilation is only a secondary phenomenon and vasoconstriction is not essential for antimigraine efficacy. Management includes analgesics or NSAIDs for mild attacks, and, for moderate or severe attacks, triptans or 5HT1B/1D receptor agonists. Because of cardiovascular safety concerns, unreliable efficacy and tolerability issues, use of ergots to abort attacks has nearly vanished in most countries. CGRP receptor antagonists (gepants) and lasmiditan, a selective 5HT1F receptor agonist, have emerged as effective acute treatments. Intramuscular onabotulinumtoxinA may be helpful in chronic migraine (migraine on ≥15 days per month) and monoclonal antibodies targeting CGRP or its receptor, as well as two gepants, have proven effective and well tolerated for the preventive treatment of migraine. Several neuromodulation modalities have been approved for acute and/or preventive migraine treatment. The emergence of new treatment targets and therapies illustrates the bright future for migraine management.
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