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"Mah, Derek"
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Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study
The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS.
137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus.
MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7·4 [SD 4·2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11·2 [4·5] years; p<0·0001) or monofocal (12·0 [3·8] years; p=0·0005) presentations. Permanent physical disability (EDSS≥4·0) developed within 5 years in 15 (13%) of the 120 children for whom EDSS score was available. 23 (17%) had impaired academic performance, which was associated with increasing disease duration (p=0·02). Over 108 (86%) of the children with MS, irrespective of geographical residence, were seropositive for remote EBV infection, compared with only 61 (64%) of matched controls (p=0·025, adjusted for multiple comparisons). Children with MS did not differ from controls in seroprevalence of the other childhood viruses studied, nor with respect to month of birth, sibling number, sibling rank, or exposure to young siblings.
Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.
Journal Article
The Unknown and the Unexplored: Insights Into the Pacific Deep-Sea Following NOAA CAPSTONE Expeditions
Over a three-year period, the National Oceanic and Atmospheric Administration organized and implemented a Pacific-wide field campaign entitled CAPSTONE: Campaign to Address Pacific monument Science, Technology, and Ocean NEeds. Under the auspices of CAPSTONE, NOAA mapped 597,230 km 2 of the Pacific seafloor (with ~ 61% of mapped area located within US waters), including 323 seamounts, conducted 187 ROV dives totaling 189 hours of ROV benthic imaging time, and documented more than 347,000 individual organisms. This comprehensive effort yielded dramatic insight into differences in biodiversity across depths, regions, and features, at multiple taxonomic scales. For all deep sea taxonomic groups large enough to be visualized with the ROV, we found that fewer than 20% of the species were able to be identified. The most abundant and highest diversity taxa across the dataset were from one class and two phyla (Anthozoa, Porifera and Echinodermata). We further examined these phyla for taxonomic assemblage patterns by depth, geographic region, and geologic feature. Within each taxon, there were multiple genera with specific distribution and abundance by depth, region, and feature. Additionally, we observed multiple genera with broad abundance and distribution, which may focus future ecological research efforts. Novel taxa, records, and behaviors were observed, which are suggestive of new species interactions, drivers of community composition, and overall diversity patterns. To date, only 13.8% of the Pacific has been mapped using modern methods. Despite the many new contributions and insights to the Pacific deep-sea, CAPSTONE is far from the culminating experience the name suggests. Rather, it marks the beginning of a new era for exploration that will offer extensive opportunities via mapping, technology, analysis, and insights.
Journal Article
Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial
Background
Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery.
Methods
PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1–3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness.
Discussion
This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients.
Trial registration
This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).
Journal Article
Corrigendum: The Unknown and the Unexplored: Insights Into the Pacific Deep-Sea Following NOAA CAPSTONE Expeditions
Additionally, we observed multiple genera with broad abundance and distribution, which may focus future ecological research efforts. Novel taxa, records, and behaviors were observed, suggestive of many new types of species interactions, drivers of community composition, and overall diversity patterns. Brian R. C. Kennedy1,2*, Kasey Cantwell2,3, Mashkoor Malik2, Christopher Kelley2,4, Jeremy Potter5, Kelley Elliott2, Elizabeth Lobecker2,6, Lindsay McKenna Gray2,7, Derek Sowers2,6, Michael P. White2,6, Scott C. France8, Steven Auscavitch9, Christopher Mah10, Virginia Moriwake4, Sarah R. D. Bingo4, Meagan Putts4 and Randi D. Rotjan1* * 1Department of Biology, Boston University, Boston, MA, United States * 2NOAA Office of Ocean Exploration and Research, Silver Spring, MD, United States * 3MAXIMUS, Metro Center, Reston, VA, United States * 4University of Hawai'i at Manoa Joint Institute of Marine and Atmospheric Research (JIMAR), Honolulu, HI, United States * 5Bureau of Ocean Energy Management, Camarillo, CA, United States * 6Cherokee Nation Strategic Programs, Richmond Hwy Suite, Arlington, TX, United States * 7Athenium Analytics, Dover, DE, United States * 8Department of Biology, University of Louisiana at Lafayette, Lafayette, LA, United States * 9Department of Biology, Temple University, Philadelphia, PA, United States * 10Department of Invertebrate Zoology, National Museum of Natural History, Smithsonian Institution, Washington, DC, United States
Journal Article
Urethral Duplication with a Cystic Phallic Urethra Associated with a Uterus Didelphys, Partial Agenesis of the Tibia, and an Equinovarus Foot
Urethral duplication is a rare congenital malformation, especially in females. It may be associated with complex urogenital malformations, but the association with a cystic phallic urethra and a uterus didelphys is exceptional. We report a case of a newborn with urethral duplication, with the accessory urethra exteriorized by a large cyst, associated with a uterus didelphys and bone malformations. We discuss the clinical, radiographic, and therapeutic aspects as well as a literature review.
Journal Article
Characterizing the transcriptional regulation of let-721, a Caenorhabditis elegans homolog of human electron flavoprotein dehydrogenase
LET-721 is the Caenorhabditis elegans ortholog of electron-transferring flavoprotein dehydrogenase (ETFDH). We are studying this protein in C. elegans in order to establish a tractable model system for further exploration of ETFDH structure and function. ETFDH is an inner mitochondrial membrane localized enzyme that plays a key role in the beta-oxidation of fatty acids and catabolism of amino acids and choline. ETFDH accepts electrons from at least twelve mitochondrial matrix flavoprotein dehydrogenases via an intermediate dimer protein and transfers the electrons to ubiquinone. In humans, ETFDH mutations result in the autosomal recessive metabolic disorder, multiple acyl-CoA dehydrogenase deficiency. Mutants of let-721 in C. elegans are either maternal effect lethals or semi-sterile. let-721 is transcribed in the pharynx, body wall muscle, hypoderm, intestine and somatic gonad. In addition, the subcellular localization of LET-721 agrees with predictions that it is localized to mitochondria. We identified and confirmed three cis-regulatory sequences (pha-site, rep-site, and act-site). Phylogenetic footprinting of each site indicates that they are conserved between four Caenorhabditis species. The pha-site mapped roughly 1,300 bp upstream of let-721's translational start site and is necessary for expression in pharyngeal tissues. The rep-site mapped roughly 830 bp upstream of the translational start site and represses expression of LET-721 within pharyngeal tissues. The act-site mapped roughly 800 bp upstream of the translational start site and is required for expression within spermatheca, body wall muscle, pharynx, and intestine. Taken together, we find that LET-721 is a mitochondrially expressed protein that is under complex transcriptional controls.
Journal Article
High-Throughput Multiomics Profiling of Model Systems Using the AVITI24 Platform
We present a multiomics platform comprising Teton, a detection assay system, and AVITI24, a dual-flowcell instrument that performs both cellular imaging and sequencing readout. Teton integrates a compartmentalized flowcell for cell culture with methods to measure morphology, RNA, and protein at subcellular resolution. The platform quantifies morphological features through cell painting of 6 cellular components, RNA expression of up to 350 transcripts via sequencing of oligonucleotides hybridized to mRNA, and protein expression of up to 200 targets using antibody-linked oligonucleotide sequencing. The flow cell accommodates >1 million cells in a 10 cm sqaured open-well format or can be subdivided into 12 or 48 wells to support experiments with multiple conditions or time points. We describe and validate the detection methods of the platform and showcase its capabilities by co-culturing three cancer cell lines and elucidating the cellular pathways triggered by various drug treatments as a function of time. Using multiple time points enables us to capture the dynamics of cellular processes including receptor activation and signaling cascades. The results demonstrate how different cancer cells evade TNFalpha-induced apoptosis by activating compensatory signaling programs that maintain survival despite pro-apoptotic cues. Our model system replicates previously published results and highlights the versatility of the platform in enabling rapid, high-throughput analysis of complex cellular responses in varied biological contexts.
Paper
Local jobs outlook still positive; Staffing company's survey finds a slight edge in number of employers planning to hire
Local jobs outlook still positive; Staffing company's survey finds a slight edge in number of employers planning to hire
Newspaper Article