21,939 results match your criteria huntington's disease


Detection of Protein Aggregation using Fluorescence Correlation Spectroscopy.

J Vis Exp 2021 Apr 25(170). Epub 2021 Apr 25.

Laboratory for Molecular Cell Dynamics, Faculty of Advanced Life Science, Hokkaido University.

Protein aggregation is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and so on. To detect and analyze soluble or diffuse protein oligomers or aggregates, fluorescence correlation spectroscopy (FCS), which can detect the diffusion speed and brightness of a single particle with a single molecule sensitivity, has been used. However, the proper procedure and know-how for protein aggregation detection have not been widely shared. Read More

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Outcomes of a novel pharmacy screening intervention to address the burden of type 2 diabetes and cardiovascular disease in an Arabic-speaking country.

Diabet Med 2021 May 9:e14598. Epub 2021 May 9.

IRD Global, 15 Beach Road #02-01, 189677, Singapore.

Aims: To evaluate the capacity of a pharmacist-delivered screening model for type 2 diabetes and cardiovascular disease (CVD) in identifying and referring individuals at risk.

Method: A screening program was implemented in 12 community pharmacies in three cities in the United Arab Emirates. Trained pharmacists screened adults (≥40 years) without a previous diagnosis of diabetes or CVD. Read More

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Lifetime neuropsychiatric symptoms in Huntington's disease: Implications for psychiatric nursing.

Arch Psychiatr Nurs 2021 Jun 26;35(3):284-289. Epub 2021 Mar 26.

Department of Psychiatry, Vanderbilt University Medical Center, 1601 23rd Avenue South, Suite 3068, Nashville, TN 37212, USA.

Neuropsychiatric manifestations of Huntington's disease (HD) can present years before motor symptoms. Nurses with specialized training provide superior care for HD patients, but HD exposure in nursing education is limited. Here we aimed to describe the historical neuropsychiatric burden in 50 HD patients and discuss implications for psychiatric nurses. Read More

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An apparent core/shell architecture of polyQ aggregates in the aging C. elegans neuron.

Protein Sci 2021 May 9. Epub 2021 May 9.

Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY, United States.

Huntington's disease is caused by a polyglutamine (polyQ) expansion in the huntingtin protein which results in its abnormal aggregation in the nervous system. Huntingtin aggregates are linked to toxicity and neuronal dysfunction, but a comprehensive understanding of the aggregation mechanism in vivo remains elusive. Here, we examine the morphology of polyQ aggregates in C. Read More

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Delivering clinical trials at home: protocol, design and implementation of a direct-to-family paediatric lupus trial.

Lupus Sci Med 2021 May;8(1)

Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA

Introduction: Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE. Read More

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A Systematic Review and Network Meta-analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide-refractory Multiple Myeloma.

Clin Lymphoma Myeloma Leuk 2021 Mar 26. Epub 2021 Mar 26.

Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS.

Introduction: Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis.

Methods: We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens. Read More

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Methylation as a key regulator of Tau aggregation and neuronal health in Alzheimer's disease.

Cell Commun Signal 2021 May 7;19(1):51. Epub 2021 May 7.

Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, 411008,, Pune, India.

Neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's disease involves abnormal aggregation and accumulation of toxic proteins aggregates. Post-translational modifications (PTMs) of the causative proteins play an important role in the etiology of disease as they could either slow down or accelerate the disease progression. Alzheimer disease is associated with the aggregation and accumulation of two major protein aggregates-intracellular neurofibrillary tangles made up of microtubule-associated protein Tau and extracellular Amyloid-β plaques. Read More

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Impaired inhibitory GABAergic synaptic transmission and transcription studied in single neurons by Patch-seq in Huntington's disease.

Proc Natl Acad Sci U S A 2021 May;118(19)

NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany;

Transcriptional dysregulation in Huntington's disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-sequencing (Patch-seq) in an in vitro HD model to investigate the effects of mutant Huntingtin (Htt) on synaptic transmission and gene transcription in single striatal neurons. We found that expression of mutant decreased the synaptic output of striatal neurons in a cell autonomous fashion and identified a number of genes whose dysregulation was correlated with physiological deficiencies in mutant Htt neurons. Read More

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Proteomic analysis of human frontal and temporal cortex using iTRAQ-based 2D LC-MS/MS.

Chin Neurosurg J 2021 May 5;7(1):27. Epub 2021 May 5.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South Fourth Ring Road, Beijing, 100070, China.

Background: The human brain is the most complex organ in the body, and it is important to have a better understanding of how the protein composition in the brain regions contributes to the pathogenesis of associated neurological disorders.

Methods: In this study, a comparative analysis of the frontal and temporal cortex proteomes was conducted by isobaric tags of relative and absolute quantification (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS). Brain protein was taken from relatively normal tissue that could not be avoided of damage during emergent surgery of the TBI (traumatic brain injury) patients admitted in Beijing Tiantan Hospital from 2014 to 2017. Read More

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NMR illuminates intrinsic disorder.

Curr Opin Struct Biol 2021 May 2;70:44-52. Epub 2021 May 2.

Department of Integrative Structural and Computational Biology and Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA. Electronic address:

Nuclear magnetic resonance (NMR) has long been instrumental in the characterization of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). This method continues to offer rich insights into the nature of IDPs in solution, especially in combination with other biophysical methods such as small-angle scattering, single-molecule fluorescence, electron paramagnetic resonance (EPR), and mass spectrometry. Substantial advances have been made in recent years in studies of proteins containing both ordered and disordered domains and in the characterization of problematic sequences containing repeated tracts of a single or a few amino acids. Read More

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Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models.

Hum Mol Genet 2021 May 5. Epub 2021 May 5.

Guangdong Key Laboratory of Non-Human Primate Models, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632.

Our previous work has established a huntingtin knock-in (KI) pig model that displays striatal neuronal loss, allowing us to examine if somatic CAG expansion in striatum accounts for the preferential neurodegeneration in Huntington disease (HD). We found that HD KI pigs do not display somatic CAG expansion in striatum as HD KI mice and that the majority of polyQ repeats in exon 1 HTT in the striatum of HD KI mice are fairly stable. We also found that striatal MSH2 and MLH3, which are involved in DNA repair, are more abundant in mouse brains than pig brains. Read More

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High spatial-resolution imaging of label-free protein aggregates by VISTA.

Analyst 2021 May 5. Epub 2021 May 5.

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Amyloid aggregation, formed by aberrant proteins, is a pathological hallmark for neurodegenerative diseases, including Alzheimer's disease and Huntington's disease. High-resolution holistic mapping of the fine structures from these aggregates should facilitate our understanding of their pathological roles. Here, we achieved label-free high-resolution imaging of the polyQ and the amyloid-beta (Aβ) aggregates in cells and tissues utilizing a sample-expansion stimulated Raman strategy. Read More

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Profiling Social Cognition in Premanifest Huntington's Disease.

J Int Neuropsychol Soc 2021 May 5:1-13. Epub 2021 May 5.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Objective: Discrepancies exist in reports of social cognition deficits in individuals with premanifest Huntington's disease (HD); however, the reason for this variability has not been investigated. The aims of this study were to (1) evaluate group- and individual-level social cognitive performance and (2) examine intra-individual variability (dispersion) across social cognitive domains in individuals with premanifest HD.

Method: Theory of mind (ToM), social perception, empathy, and social connectedness were evaluated in 35 individuals with premanifest HD and 29 healthy controls. Read More

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Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.

Neuromolecular Med 2021 May 4. Epub 2021 May 4.

Applied Biology Division, CSIR- Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500007, Telangana, India.

Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X-linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. Read More

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CAG RNAs induce DNA damage and apoptosis by silencing expression in polyglutamine degeneration.

Proc Natl Acad Sci U S A 2021 May;118(19)

Laboratory of Drosophila Research, The Chinese University of Hong Kong, Hong Kong, China;

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the () gene was down-regulated in mutant CAG RNA-expressing cells. Read More

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Huntington's disease mice and human brain tissue exhibit increased G3BP1 granules and TDP43 mislocalization.

J Clin Invest 2021 May 4. Epub 2021 May 4.

Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, United States of America.

Chronic cellular stress associated with neurodegenerative disease can result in the persistence of stress granule (SG) structures, membraneless organelles that form in response to cellular stress. In Huntington's disease (HD), chronic expression of mutant huntingtin generates various forms of cellular stress, including activation of the unfolded protein response and oxidative stress. However, it has yet to be determined whether SGs are a feature of HD neuropathology. Read More

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Effects of Low-dose Mercury Exposure in Newborns on mRNA Expression Profiles.

Bull Environ Contam Toxicol 2021 May 4. Epub 2021 May 4.

School of Public Health/Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, 550025, Guiyang, China.

This study was designed to investigate the molecular mechanism of mercury (Hg) toxicity in the newborns by mRNA sequencing (mRNA-seq). A questionnaire survey, routine blood parameters of pregnant women, and umbilical cord blood (UCB) of newborns were collected. The median (25th percentile, 75th percentile) of total Hg (THg) concentrations in UCB of newborns was 3. Read More

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Health gains and financial protection from human papillomavirus vaccination in Ethiopia: findings from a modelling study.

Health Policy Plan 2021 May 4. Epub 2021 May 4.

Center for Health Decision Science, Harvard T.H. Chan School of Public Health, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115, USA.

High out-of-pocket (OOP) medical expenses for cervical cancer (CC) can lead to catastrophic health expenditures (CHEs) and medical impoverishment in many low-resource settings. There are 32 million women at risk for CC in Ethiopia, where CC screening is extremely limited. An evaluation of the population health and financial risk protection benefits, and their distributional consequences across socioeconomic groups, from human papillomavirus (HPV) vaccination will be critical to support CC prevention efforts in this setting. Read More

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Normalization of Calcium Balance in Striatal Neurons in Huntington's Disease: Sigma 1 Receptor as a Potential Target for Therapy.

Biochemistry (Mosc) 2021 Apr;86(4):471-479

Laboratory of Molecular Neurodegeneration, Peter the Great Saint-Petersburg Polytechnic University, Saint-Petersburg, 195251, Russia.

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established. Read More

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Plasma neurofilament light in Huntington's disease: A marker for disease onset, but not symptom progression.

Parkinsonism Relat Disord 2021 Apr 28;87:32-38. Epub 2021 Apr 28.

Department of Epidemiology, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA, USA. Electronic address:

Objective: To investigate whether plasma NfL levels correlate with clinical symptom severity in premanifest (PM) and manifest HD (HD) individuals, and whether a NfL cut-point could distinguish PM from HD patients with reasonable accuracy.

Method: 98 participants (33 control, 26 PM, 39 HD), underwent blood sample collection and clinical assessment, using both UHDRS and non-UHDRS measures, at one academic HD Center. Years to onset (YTO), probability of disease onset in 5 years, and predicted years until 60% onset probability were also calculated. Read More

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Exosomes as a potential messenger unit during heterochronic parabiosis for amelioration of Huntington's disease.

Neurobiol Dis 2021 Apr 30;155:105374. Epub 2021 Apr 30.

Department of Neurology, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Protein Metabolism and Neuroscience Dementia Medical Research Center, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Neuroscience and dementia Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Huntington's disease (HD) starts its pathology long before clinical manifestation, however, there is no therapy to cure it completely and only a few studies have been reported for delaying the progression of HD. Recently, it has been shown that heterochronic parabiosis can modulate the neurodegenerative diseases. Despite the importance of the transportation process of positive factors during heterochronic parabiosis, there were limited understandings because the transportation process is nanoscale, which makes it difficult to identify the messenger unit. Read More

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Prevalence and Mortality due to COVID-19 in HIV Co-Infected Population: A Systematic Review and Meta-Analysis.

Infect Dis Ther 2021 May 3. Epub 2021 May 3.

Department of Respiratory and Critical Care Medicine, Maoming People's Hospital, Maoming, China.

Introduction: The coronavirus disease 2019 (COVID-19) was defined as a species of beta coronavirus causing atypical respiratory disease in humans. The COVID-19 pandemic has resulted in an unprecedented health and economic crisis worldwide. Little is known about the specifics of its influence on people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA). Read More

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Algorithms for segmenting cerebral time-of-flight magnetic resonance angiograms from volunteers and anemic patients.

J Med Imaging (Bellingham) 2021 Mar 28;8(2):024005. Epub 2021 Apr 28.

Rudi Schulte Research Institute, Santa Barbara, California, United States.

To evaluate six cerebral arterial segmentation algorithms in a set of patients with a wide range of hemodynamic characteristics to determine real-world performance. Time-of-flight magnetic resonance angiograms were acquired from 33 subjects: normal controls ( ), sickle cell disease ( ), and non-sickle anemia ( ) using a 3 Tesla Philips Achieva scanner. Six segmentation algorithms were tested: (1) Otsu's method, (2) K-means, (3) region growing, (4) active contours, (5) minimum cost path, and (6) U-net machine learning. Read More

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Validating Automated Segmentation Tools in the Assessment of Caudate Atrophy in Huntington's Disease.

Front Neurol 2021 14;12:616272. Epub 2021 Apr 14.

Department of Neurodegenerative Disease, Huntington's Disease Centre, University College London Queen Square Institute of Neurology, University College London, London, United Kingdom.

Neuroimaging shows considerable promise in generating sensitive and objective outcome measures for therapeutic trials across a range of neurodegenerative conditions. For volumetric measures the current gold standard is manual delineation, which is unfeasible for samples sizes required for large clinical trials. Using a cohort of early Huntington's disease (HD) patients ( = 46) and controls ( = 35), we compared the performance of four automated segmentation tools (FIRST, FreeSurfer, STEPS, MALP-EM) with manual delineation for generating cross-sectional caudate volume, a region known to be vulnerable in HD. Read More

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Role of MicroRNAs, Aptamers in Neuroinflammation and Neurodegenerative Disorders.

Cell Mol Neurobiol 2021 May 1. Epub 2021 May 1.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, Hyderabad, Telangana, 500037, India.

Exploring the microRNAs and aptamers for their therapeutic role as biological drugs has expanded the horizon of its applicability against various human diseases, explicitly targeting the genetic materials. RNA-based therapeutics are widely being explored for the treatment and diagnosis of multiple diseases, including neurodegenerative disorders (NDD). Latter includes microRNA, aptamers, ribozymes, and small interfering RNAs (siRNAs), which control the gene expression mainly at the transcriptional strata. Read More

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Suppressor of cytokine signaling 2 is induced in Huntington's disease and involved in autophagy.

Biochem Biophys Res Commun 2021 Apr 29;559:21-27. Epub 2021 Apr 29.

Department of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea; Samsung Biomedical Research Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, South Korea.

Suppressor of cytokine signaling (SOCS) proteins are primarily feedback inhibitors of cytokine signaling. The two conserved domains of SOCS proteins have distinct functions. Src homology 2 (SH2) domain inhibits cytokine receptor, while SOCS box acts as an E3 ubiquitin ligase. Read More

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The Mediterranean lifestyle (MEDLIFE) index and metabolic syndrome in a non-Mediterranean working population.

Clin Nutr 2021 Mar 31;40(5):2494-2503. Epub 2021 Mar 31.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA; Occupational Medicine, The Cambridge Health Alliance/Harvard Medical School, Boston, MA, 02139, USA. Electronic address:

Background & Aims: The Mediterranean lifestyle (MEDLIFE), as an overall lifestyle pattern, may be associated with a lower prevalence of metabolic syndrome. We assessed the association of a validated MEDLIFE index with metabolic syndrome and its components in a non-Mediterranean working population.

Methods: A cross-sectional analysis was conducted at baseline among 249 US career firefighters in Feeding America's Bravest 2016-2018. Read More

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Seasonal variation in fluorescence characteristics of dissolved organic matter in wastewater and identification of proteins through HRLC-MS/MS.

J Hazard Mater 2021 Jul 18;413:125453. Epub 2021 Feb 18.

Environmental Science and Engineering Department (ESED), IIT Bombay, Mumbai, India. Electronic address:

In the present study, wastewater samples acquired from five wastewater treatment plants (WWTPs), located in western India were characterized using fluorescence spectroscopy, and resin-based fractionation was conducted to fractionate DOM into hydrophobic and hydrophilic base, acid, and neutral fractions. Among several fractions, the hydrophilic acid (HIA) and hydrophilic neutral (HIN) fractions were present in higher abundance (more than 50% of DOC) compared to the hydrophilic base (HIB) fraction in both influent and effluent wastewater stream obtained from WWTPs. Tryptophan-like and tyrosine-like substances were also abundant in the influent and effluent stream of WWTPs. Read More

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Association of transcutaneous CO with respiratory support: a prospective double blind observational study in children with bronchiolitis and reactive airway disease.

J Clin Monit Comput 2021 Apr 29. Epub 2021 Apr 29.

Department of Pediatrics, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave., Peoria, IL, 61637, USA.

The use of clinical scoring to assess for severity of respiratory distress and respiratory failure is challenging due to subjectivity and interrater variability. Transcutaneous Capnography (TcpCO) can be used as an objective tool to assess a patient's ventilatory status. This study was designed to assess for any correlation of continuous monitoring of TcpCO with the respiratory clinical scores and deterioration in children admitted for acute respiratory distress. Read More

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