University of California, Los Angeles
  • Los Angeles, CA, United States
Recent publications
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.
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.
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.
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.
Background: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These malignant tumours have a high metastatic rate and limited chemotherapeutic options. The multi-receptor tyrosine kinase inhibitor sunitinib malate has benefit in the treatment of metastatic insulinoma in people. Toceranib phosphate, an analogous veterinary agent, may provide benefit for dogs. Methods: A retrospective study describing the extent and duration of clinical outcomes and adverse events (AEs) in dogs diagnosed with insulinoma and receiving toceranib. Results: Records for 30 dogs diagnosed with insulinoma and having received toceranib were identified from a medical record search of five university and eight referral hospitals. The median progression-free interval and overall survival time were 561 days (95% confidence interval (CI): [246, 727 days]) and 656 days (95% CI: [310, 1045 days]), respectively. Of the dogs for which the canine Response evaluation criteria for solid tumours tool could be applied, the majority (66.7%) showed either a complete response, partial response or stable disease. Time to clinical progression was associated with prior intervention and type of veterinary practice. Larger dogs were at increased risk for disease progression and death. No novel AEs were reported. Conclusions: Most dogs diagnosed with insulinoma and receiving toceranib appeared to have a clinical benefit. Randomised, prospective studies are needed to better elucidate and objectively quantify the potential effect and survival benefit of toceranib therapy for management of insulinoma in dogs.
Imaging through diffusers presents a challenging problem with various digital image reconstruction solutions demonstrated to date using computers. Here, we present a computer-free, all-optical image reconstruction method to see through random diffusers at the speed of light. Using deep learning, a set of transmissive diffractive surfaces are trained to all-optically reconstruct images of arbitrary objects that are completely covered by unknown, random phase diffusers. After the training stage, which is a one-time effort, the resulting diffractive surfaces are fabricated and form a passive optical network that is physically positioned between the unknown object and the image plane to all-optically reconstruct the object pattern through an unknown, new phase diffuser. We experimentally demonstrated this concept using coherent THz illumination and all-optically reconstructed objects distorted by unknown, random diffusers, never used during training. Unlike digital methods, all-optical diffractive reconstructions do not require power except for the illumination light. This diffractive solution to see through diffusers can be extended to other wavelengths, and might fuel various applications in biomedical imaging, astronomy, atmospheric sciences, oceanography, security, robotics, autonomous vehicles, among many others.
Conventional vision-based systems, such as cameras, have demonstrated their enormous versatility in sensing human activities and developing interactive environments. However, these systems have long been criticized for incurring privacy, power, and latency issues due to their underlying structure of pixel-wise analog signal acquisition, computation, and communication. In this research, we overcome these limitations by introducing in-sensor analog computation through the distribution of interconnected photodetectors in space, having a weighted responsivity, to create what we call a computational photodetector. Computational photodetectors can be used to extract mid-level vision features as a single continuous analog signal measured via a two-pin connection. We develop computational photodetectors using thin and flexible low-noise organic photodiode arrays coupled with a self-powered wireless system to demonstrate a set of designs that capture position, orientation, direction, speed, and identification information, in a range of applications from explicit interactions on everyday surfaces to implicit activity detection.
Background: Whilst cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalalgias (TAC's), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management. Methods: Migraineurs seen in a tertiary headache service between 2014 and 2018 (n = 340): cohort one, and a separate cohort of headache patients seen between 2014-May 2021 reporting voice change, or throat swelling, or both, as CAS were selected (n = 64): cohort two. We performed a service evaluation of our records regarding age, sex, diagnosis, headache and CAS frequency and laterality as acquired from the first consultation, during which a detailed headache history is taken by a headache trained physician. Results: Cohort 1: Mean age 43 (range 14-94, SD 15). The most common diagnosis was chronic migraine (78%). Median monthly headache frequency was 26 days (IQR 15-75). At least one CAS was reported in 74%, with a median of two (IQR 0-3). The most common were nasal congestion (32%), lacrimation (31%) and aural fullness (25%). Most patients reported their most common headache as unilateral (80%) and with it strictly unilateral CAS (64%). There was a positive association between headache and CAS laterality (χ21 = 20.7, P < 0.001), with a positive correlation between baseline headache frequency and number of CAS reported (r = 0.11, P = 0.047). Cohort two: mean age 49 (range 23-83, SD 14). Diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described trigeminal distribution pain; 25% involving all three divisions. Throat swelling was reported by 54, voice change by 17, and both by 7. The most common CAS reported were lacrimation (n = 47), facial swelling (n = 45) and rhinorrhoea (n = 37). There was significant agreement between the co-reporting of throat swelling (χ21 = 7.59, P = 0.013) and voice change (χ21 = 6.49, P = 0.02) with aural fullness. Conclusions: CAS are common in migraine, are associated with increasing headache frequency and tend to lateralise with headache. Voice change and throat swelling should be recognized as possible parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic endophenotype.
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26,302 members
Daniel Braas
  • Department of Pharmacology
Eric Robert Scerri
  • Department of Chemistry and Biochemistry
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