Publications by authors named "Jiwon Lee"

272 Publications

Novel WTX nonsense mutation in a family diagnosed with osteopathia striata with cranial sclerosis: Case report.

Medicine (Baltimore) 2021 Oct;100(40):e27346

Department of Orthopedic Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Abstract: Rationale: Osteopathia striata with cranial sclerosis is characterized by linear striations in the metaphysis of the long bones and pelvis with cranial sclerosis. It is an X-linked dominant sclerosing bone dysplasia and affected males show fetal or neonatal lethality. Mutations in the gene encoding Wilms tumor on the X chromosome (WTX) was identified as the cause of X-linked osteopathia striata with cranial sclerosis. About 30 pathogenic mutations in WTX have been reported recently. We have identified a novel nonsense mutation in the family diagnosed as osteopathia striata with cranial sclerosis.

Patient Concerns: The proband came to our attention at age 9 for the evaluation of toe-out gait and planovalgus deformity. Clinically, the proband showed coarse facial features including frontal bossing, ocular hypertelorism, wide depressed nasal bridge, dental malocclusion, mild macrocephaly and low set ears. Radiologically, sclerotic linear striations were seen in the X-rays of the pelvis and the metaphyseal region of femur and tibia and the cranial sclerosis was observed. The proband's mother presented similar facial features and the X-rays of the pelvis, femur, and tibia revealed same sclerotic linear striations as the proband's.

Diagnoses: Osteopathia striata with cranial sclerosis.

Interventions: A genetic analysis was conducted on genomic DNA isolated from peripheral blood leukocytes of the proband and the mother for confirming the clinical suspicion of osteopathia striata with cranial sclerosis. WTX on Xq11.2 gene was analyzed in direct sequencing for coding exons including intron-exon boundaries.

Outcomes: One novel nonsense mutation (c.1003C>T, p.Gln335∗) and known single nucleotide variant were observed in a heterozygous form.

Lessons: We found a novel nonsense mutation in a family diagnosed as osteopathia striata with cranial sclerosis. The relationship between various clinical features and genetic mutations can be clarified by accumulation of genetic database.
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http://dx.doi.org/10.1097/MD.0000000000027346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500662PMC
October 2021

Performance and limitation estimation of a three-tap gated imaging sensor in wide field time-gated fluorescence lifetime imaging systems.

Appl Opt 2021 Aug;60(24):7446-7454

In this paper, a computational performance analysis is presented of a wide-field time-gated fluorescence lifetime imaging microscope (FLIM) using practically realizable properties of the laser, sample, and a three-tap time-gated CMOS image sensor. The impact of these component-level properties on the accuracy and the precision of the measurement results are estimated and discussed based on Monte Carlo simulations. The correlation between the detector speed and the accuracy of the extracted fluorescence lifetime is studied, and the minimum required incident photoelectron number of each pixel is estimated for different detector speeds and different fluorescence lifetime measurements. In addition, the detection limits due to the dark current and the parasitic light sensitivity of the detector are also investigated. This work gives an overview of the required fluorescence emission condition as well as the required detector properties for a three-tap time-gated image sensor to achieve good FLIM data in biological applications.
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http://dx.doi.org/10.1364/AO.428590DOI Listing
August 2021

Scapholunate and lunotriquetral interosseous ligament augmentation with internal bracing in perilunate dislocation: Case reports.

Medicine (Baltimore) 2021 Sep;100(38):e26827

Department of Orthopaedic Surgery, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Rationale: The goals of surgical treatment of the perilunate dislocation (PLD) are confirmation of reduction, ligament repair, and supplemental fixation of the bony architecture. Open reduction and direct repair of the torn ligament are recommended for acute PLD. However, repair of the scapholunate interosseous ligament (SLIL) and lunotriquetral interosseous ligament (LTIL) is often unreliable, and secure repair is challenging. Internal bracing (IB) is an augmentation method that uses high-strength non-absorbable tape and enhances strength and support during the critical period of ligamentous healing. However, there is a paucity of data on the application of IB for PLD in the wrist. We report 3 cases of PLD that were augmented with IB after SLIL and LTIL repair.

Patient Concerns: All 3 cases were men who visited our emergency department with wrist after falling off a ladder.

Diagnoses: Initial radiographs revealed a dorsal PLD.

Interventions: Surgically, complete rupture of the SLIL and LTIL were confirmed. K-wires were placed into the scaphoid and lunate and used as joysticks to correct the intercalated segment instability pattern. This usually requires correcting scaphoid flexion and lunate extension and closing the scapholunate interval. Prior to SLIL and LTIL repair, temporary intercarpal fixation was performed with K-wires to maintain the carpal relationship. The dorsal SLIL and LTIL were carefully repaired using suture anchors. However, ligament repair was unreliable, and insecure. In view of the likelihood of insufficient repair, we performed IB augmentation using synthetic tape.

Outcomes: At the last follow-up, all cases were pain-free and had returned to all activities. The last follow-up radiographs showed good alignment of the carpal bones and no arthritic changes.

Lessons: IB augmentation can reduce the period of K-wire fixation and cast immobilization and can enable early joint motion. We believe that interosseous ligament augmentation using IB is a reasonable treatment option for PLD.
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http://dx.doi.org/10.1097/MD.0000000000026827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462623PMC
September 2021

Rapid, multiplexed, and nucleic acid amplification-free detection of SARS-CoV-2 RNA using an electrochemical biosensor.

Biosens Bioelectron 2021 Sep 17;195:113649. Epub 2021 Sep 17.

School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea. Electronic address:

Considering the worldwide health crisis associated with highly contagious severe respiratory disease of COVID-19 outbreak, the development of multiplexed, simple and rapid diagnostic platforms to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in high demand. Here, a nucleic acid amplification-free electrochemical biosensor based on four-way junction (4-WJ) hybridization is presented for the detection of SARS-CoV-2. To form a 4-WJ structure, a Universal DNA-Hairpin (UDH) probe is hybridized with two adaptor strands and a SARS-CoV-2 RNA target. One of the adaptor strands is functionalized with a redox mediator that can be detected using an electrochemical biosensor. The biosensor could simultaneously detect 5.0 and 6.8 ag/μL of S and Orf1ab genes, respectively, within 1 h. The biosensor was evaluated with 21 clinical samples (16 positive and 5 negative). The results revealed a satisfactory agreement with qRT-PCR. In conclusion, this biosensor has the potential to be used as an on-site, real-time diagnostic test for COVID-19.
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http://dx.doi.org/10.1016/j.bios.2021.113649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447555PMC
September 2021

Optimization of psoriasis assessment system based on patch images.

Sci Rep 2021 Sep 13;11(1):18130. Epub 2021 Sep 13.

Department of Software Convergence, Graduate School, Soonchunhyang University, 22, Soonchunhyang-ro, Asan City, Chungnam-do, 31538, Republic of Korea.

Psoriasis is a chronic inflammatory skin disease that occurs in various forms throughout the body and is associated with certain conditions such as heart disease, diabetes, and depression. The psoriasis area severity index (PASI) score, a tool used to evaluate the severity of psoriasis, is currently used in clinical trials and clinical research. The determination of severity is based on the subjective judgment of the clinician. Thus, the disease evaluation deviations are induced. Therefore, we propose optimal algorithms that can effectively segment the lesion area and classify the severity. In addition, a new dataset on psoriasis was built, including patch images of erythema and scaling. We performed psoriasis lesion segmentation and classified the disease severity. In addition, we evaluated the best-performing segmentation method and classifier and analyzed features that are highly related to the severity of psoriasis. In conclusion, we presented the optimal techniques for evaluating the severity of psoriasis. Our newly constructed dataset improved the generalization performance of psoriasis diagnosis and evaluation. It proposed an optimal system for specific evaluation indicators of the disease and a quantitative PASI scoring method. The proposed system can help to evaluate the severity of localized psoriasis more accurately.
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http://dx.doi.org/10.1038/s41598-021-97211-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437948PMC
September 2021

Adiposity in schizophrenia: A systematic review and meta-analysis.

Acta Psychiatr Scand 2021 Aug 30. Epub 2021 Aug 30.

Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.

Objective: Although a relationship between schizophrenia (SCZ), antipsychotic (AP) medication, and metabolic dysregulation is now well established, the effect of adiposity is less well understood. By synthesizing findings from imaging techniques that measure adiposity, our systematic review and meta-analysis (PROSPERO CRD42020192977) aims to determine the adiposity-related effects of illness and treatment in this patient population.

Methods: We searched MEDLINE, EMBASE, PsychINFO and Scopus for all relevant case-control and prospective longitudinal studies from inception until February 2021. Measures of adiposity including percent body fat (%BF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed as primary outcomes.

Results: Our search identified 29 articles that used imaging methods to quantify adiposity among patients with SCZ spectrum disorders. Analyses revealed that patients have greater %BF (mean difference (MD) = 3.09%; 95% CI: 0.75-5.44), SAT (MD = 24.29 cm ; 95% CI: 2.97-45.61) and VAT (MD = 33.73 cm , 95% CI: 4.19-63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm ; 95% CI: 11.33-52.64) and VAT (MD = 16.30 cm ; 95% CI: 8.17-24.44) with no effect on %BF. However, change in %BF was higher for AP-free/AP-naïve patients compared to treated patients.

Conclusion: Our findings indicate that patients with SCZ spectrum disorders have greater adiposity than healthy controls, which is increased by AP treatment. Young, AP-naïve patients may be particularly susceptible to this effect. Future studies should explore the effect of specific APs on adiposity and its relation to overall metabolic health.
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http://dx.doi.org/10.1111/acps.13365DOI Listing
August 2021

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

Genome Med 2021 Aug 26;13(1):136. Epub 2021 Aug 26.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.

Background: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.

Methods: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap.

Results: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways.

Conclusions: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.
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http://dx.doi.org/10.1186/s13073-021-00917-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394596PMC
August 2021

BinomiRare: A robust test for association of a rare genetic variant with a binary outcome for mixed models and any case-control proportion.

HGG Adv 2021 Jul 12;2(3). Epub 2021 Jun 12.

Framingham Heart Study, Framingham, MA, USA.

Whole-genome sequencing (WGS) and whole-exome sequencing studies have become increasingly available and are being used to identify rare genetic variants associated with health and disease outcomes. Investigators routinely use mixed models to account for genetic relatedness or other clustering variables (e.g., family or household) when testing genetic associations. However, no existing tests of the association of a rare variant with a binary outcome in the presence of correlated data control the type 1 error where there are (1) few individuals harboring the rare allele, (2) a small proportion of cases relative to controls, and (3) covariates to adjust for. Here, we address all three issues in developing a framework for testing rare variant association with a binary trait in individuals harboring at least one risk allele. In this framework, we estimate outcome probabilities under the null hypothesis and then use them, within the individuals with at least one risk allele, to test variant associations. We extend the BinomiRare test, which was previously proposed for independent observations, and develop the Conway-Maxwell-Poisson (CMP) test and study their properties in simulations. We show that the BinomiRare test always controls the type 1 error, while the CMP test sometimes does not. We then use the BinomiRare test to test the association of rare genetic variants in target genes with small-vessel disease (SVD) stroke, short sleep, and venous thromboembolism (VTE), in whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program.
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http://dx.doi.org/10.1016/j.xhgg.2021.100040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321319PMC
July 2021

Identification of Thieno[3,2-]pyrimidine Derivatives as Dual Inhibitors of Focal Adhesion Kinase and FMS-like Tyrosine Kinase 3.

J Med Chem 2021 Aug 29;64(16):11934-11957. Epub 2021 Jul 29.

Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Focal adhesion kinase (FAK) is overexpressed in highly invasive and metastatic cancers. To identify novel FAK inhibitors, we designed and synthesized various thieno[3,2-]pyrimidine derivatives. An intensive structure-activity relationship (SAR) study led to the identification of as a lead. Moreover, , a multitargeted kinase inhibitor, possesses excellent potencies against FLT3 mutants as well as FAK. Gratifyingly, remarkably inhibits recalcitrant FLT3 mutants, including F691L, that cause drug resistance. Importantly, is superior to PF-562271 in terms of apoptosis induction, anchorage-independent growth inhibition, and tumor burden reduction in the MDA-MB-231 xenograft mouse model. Also, causes regression of tumor growth in the MV4-11 xenograft mouse model, indicating that it could be effective against acute myeloid leukemia (AML). Finally, in an orthotopic mouse model using MDA-MB-231, remarkably prevents metastasis of orthotopic tumors to lymph nodes. Taken together, the results indicate that possesses potential therapeutic value against highly invasive cancers and relapsed AML.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00459DOI Listing
August 2021

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Circ Genom Precis Med 2021 Aug 28;14(4):e003300. Epub 2021 Jul 28.

Regeneron Genetics Center, Tarrytown, NY. Departments of Medicine, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.R.).

Background: Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.

Methods: Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).

Results: We found that rare variants associated with population-based electrocardiographic intervals identify established monogenic SCD genes (, , and ), a controversial monogenic SCD gene (), and novel genes ( and ) involved in cardiac conduction. Loss-of-function and pathogenic variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (=8.4×10). Similar variants in and (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (=4×10), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.

Conclusions: Our findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.
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http://dx.doi.org/10.1161/CIRCGEN.120.003300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373440PMC
August 2021

Influenza vaccination in the elderly boosts antibodies against conserved viral proteins and egg-produced glycans.

J Clin Invest 2021 07;131(13)

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas, USA.

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galβ1-4GalNAcβ), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.
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http://dx.doi.org/10.1172/JCI148763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245176PMC
July 2021

Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing.

PLoS One 2021 24;16(6):e0253541. Epub 2021 Jun 24.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.

Introduction: We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time.

Methods: Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets.

Results: Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies.

Conclusion: NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253541PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224885PMC
June 2021

CB1Rs in VMH neurons regulate glucose homeostasis but not body weight.

Am J Physiol Endocrinol Metab 2021 07 7;321(1):E146-E155. Epub 2021 Jun 7.

Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

Cannabinoid 1 receptor (CB1R) inverse agonists reduce body weight and improve several parameters of glucose homeostasis. However, these drugs have also been associated with deleterious side effects. CB1R expression is widespread in the brain and in peripheral tissues, but whether specific sites of expression can mediate the beneficial metabolic effects of CB1R drugs, while avoiding the untoward side effects, remains unclear. Evidence suggests inverse agonists may act on key sites within the central nervous system to improve metabolism. The ventromedial hypothalamus (VMH) is a critical node regulating energy balance and glucose homeostasis. To determine the contributions of CB1Rs expressed in VMH neurons in regulating metabolic homeostasis, we generated mice lacking CB1Rs in the VMH. We found that the deletion of CB1Rs in the VMH did not affect body weight in chow- and high-fat diet-fed male and female mice. We also found that deletion of CB1Rs in the VMH did not alter weight loss responses induced by the CB1R inverse agonist SR141716. However, we did find that CB1Rs of the VMH regulate parameters of glucose homeostasis independent of body weight in diet-induced obese male mice. Cannabinoid 1 receptors (CB1Rs) regulate metabolic homeostasis, and CB1R inverse agonists reduce body weight and improve parameters of glucose metabolism. However, the cell populations expressing CB1Rs that regulate metabolic homeostasis remain unclear. CB1Rs are highly expressed in the ventromedial hypothalamic nucleus (VMH), which is a crucial node that regulates metabolism. With CRISPR/Cas9, we generated mice lacking CB1Rs specifically in VMH neurons and found that CB1Rs in VMH neurons are essential for the regulation of glucose metabolism independent of body weight regulation.
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http://dx.doi.org/10.1152/ajpendo.00044.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321828PMC
July 2021

A Prevalent Focused Human Antibody Response to the Influenza Virus Hemagglutinin Head Interface.

mBio 2021 06 1;12(3):e0114421. Epub 2021 Jun 1.

Laboratory of Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.

Novel animal influenza viruses emerge, initiate pandemics, and become endemic seasonal variants that have evolved to escape from prevalent herd immunity. These processes often outpace vaccine-elicited protection. Focusing immune responses on conserved epitopes may impart durable immunity. We describe a focused, protective antibody response, abundant in memory and serum repertoires, to a conserved region at the influenza virus hemagglutinin (HA) head interface. Structures of 11 examples, 8 reported here, from seven human donors demonstrate the convergence of responses on a single epitope. The 11 are genetically diverse, with one class having a common, IGκV1-39, light chain. All of the antibodies bind HAs from multiple serotypes. The lack of apparent genetic restriction and potential for elicitation by more than one serotype may explain their abundance. We define the head interface as a major target of broadly protective antibodies with the potential to influence the outcomes of influenza virus infection. The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction of likely variants for an annual updating of influenza vaccines. The identification of human antibodies that recognize conserved surfaces on the influenza virus hemagglutinin (HA) has prompted efforts to design immunogens that might selectively elicit such antibodies. The recent discovery of a widely prevalent antibody response to the conserved interface between two HA "heads" (the globular, receptor-binding domains at the apex of the spike-like trimer) has added a new target for these efforts. We report structures of eight such antibodies, bound with HA heads, and compare them with each other and with three others previously described. Although genetically diverse, they all converge on a common binding site. The analysis here can guide immunogen design for preclinical trials.
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http://dx.doi.org/10.1128/mBio.01144-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262862PMC
June 2021

Relationship of domain-specific quality of life with body mass index and waist circumference in a Korean elderly population.

Aging Clin Exp Res 2021 May 24. Epub 2021 May 24.

Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: Obesity affects health-related quality of life (QoL); however, their relationship among elderly Asians is not well known.

Aims: Relationship of domain-specific QoL with body mass index (BMI) and waist circumference and the sex differences were investigated using a nationally representative sample of elderly Korean population.

Methods: In the Korea National Health and Nutrition Examination Survey phase VII (2016-2018), 3659 adults aged ≥ 65 years (1551 men and 2108 women) participated. BMI and waist circumference were classified according to Asian- and Korean-specific criteria. QoL was evaluated using the European Quality of Life Scale-Five Dimensions (EQ-5D). Multivariable logistic regressions were used to examine the relationship of QoL with BMI and waist circumference.

Results: Men with BMI < 18.5 kg/m and ≥ 25.0 kg/m had a significant association with poor QoL in mobility and self-care, but no relationship was found with the other domains. Women with BMI ≥ 25.0 kg/m had poor QoL in mobility and self-care, and those with BMI ≥ 30.0 kg/m had poor QoL in usual activities and pain/discomfort. There was no significant association with anxiety/depression. Both elderly men and women with abdominal obesity had a significant association with poor QoL in mobility, self-care, usual activities, and pain/discomfort; however, there was no significant relationship with waist circumference and anxiety/depression.

Conclusions: The association between QoL and BMI was different according to sex and the domains of QoL. Domain-specific QoL should be considered in the management of body weight of the elderly.
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http://dx.doi.org/10.1007/s40520-021-01876-1DOI Listing
May 2021

Micro- and nano-tomography analysis of mouse soleus muscle using radiation.

Microsc Res Tech 2021 May 21. Epub 2021 May 21.

Department of Software Convergence, Graduate School, Soonchunhyang University, Asan City, Chungnam, Republic of Korea.

In this study, we analyze radiation images of muscle structure of mice soleus muscles using radiation source-based microtomography and nanotomography. Soleus muscle samples were collected for analysis from 8-week-old male Institute of Cancer Research mice. First, phase-contrast X-ray microtomography was employed in these experiments. Then to obtain images with excellent contrast, imaging was performed using monochromatic light with excellent transmission power. To analyze additional muscle structures in higher magnification images than these images, nanotomography was performed, which facilitated obtaining high-magnification and high-resolution images. Muscle tissue microstructures were confirmed through three-dimensional images obtained from phase-contrast X-ray microtomography. Thus, the muscle tissue's overall shape at microscopic level can be captured. Additionally, a single muscle fiber was examined using hard X-ray nano-imaging, through which we could observe the alignment of countless myofibrils, that is, actin and myosin filaments in the muscle fibers. Thus, the methodology adopted here proved to be advantageous in analyzing the muscle tissue's overall structure with microtomography and in observing the myofibrils in detail using nanotomography.
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http://dx.doi.org/10.1002/jemt.23819DOI Listing
May 2021

A pilot study comparing three bend angles for lighted stylet intubation.

BMC Anesthesiol 2021 05 17;21(1):148. Epub 2021 May 17.

Department of Anesthesiology and Pain Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, 07061, Seoul, Republic of Korea.

Background: For successful lighted stylet intubation, bending the lighted stylet with an appropriate angle is a prerequisite. The purpose of this study was to compare three different bend angles of 70, 80, and 90 degrees for lighted stylet intubation.

Methods: The patient trachea was intubated with a lighted stylet bent at 70, 80, or 90 degrees according to the randomly allocated groups (group I, II, and III, respectively). A lighted stylet combined with a tracheal tube was prepared with a bend angle of 70, 80, or 90 degrees according to the assigned group. We checked the success rate at the first attempt and overall success rate for the two attempts. Additionally, we measured search time, which was time from insertion of the bent union into the patient mouth to the start of advancing the tracheal tube while separating it from the lighted stylet, and evaluated postoperative sore throat (POST) at 2, 4, and 24 h after the recovery from anesthesia.

Results: There was no statistically significant difference between group I, II, and III for success rate at first attempt (73.9 %, 88.2 %, and 94.7 %, respectively, p = 0.178), even though there was a trend of increasing success rate with increasing bend angles. For overall success rate, there was similar result to that in the first attempt between the groups I, II, and III (82.6 %, 94.1 %, and 100 %, respectively, p = 0.141). However, search time took significantly longer in group I than groups II and III (p < 0.001). When group II and III were compared for POST with numeric rating scale (0-10), it was significantly lower in group II than III at 2, 4 h after the recovery (0.5 vs. 2.3, p = 0.016, and 0.4 vs. 1.8, p = 0.011, respectively).

Conclusions: The bend angle of the lighted stylet affected the time required for tracheal intubation and POST in our study. 80 and 90 degrees as a bend angle seem to be acceptable for clinicians in regard to success rate of lighted stylet intubation. Considering the success rate of lighted stylet intubation and POST, the bend angle of 80 degrees might be better than 70 and 90 degrees.

Trial Registration: ClinicalTrials.gov Identifier NCT03693235 , registered on 30 September 2018.
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http://dx.doi.org/10.1186/s12871-021-01369-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127176PMC
May 2021

Novel and Potent Small Molecules against Melanoma Harboring BRAF Class I/II/III Mutants for Overcoming Drug Resistance.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.

Melanoma accounts for the majority of skin cancer deaths. About 50% of all melanomas are associated with BRAF mutations. BRAF mutations are classified into three classes with regard to dependency on RAF dimerization and RAS signaling. The most frequently occurring class I BRAF V600 mutations are sensitive to vemurafenib whereas class II and class III mutants, non-V600 BRAF mutants are resistant to vemurafenib. Herein we report six pyrimido[4,5-]pyrimidin-2-one derivatives possessing highly potent anti-proliferative activities on melanoma cells harboring BRAF class I/II/III mutants. Novel and most potent derivative, SIJ1777, possesses not only two-digit nanomolar potency but also 2 to 14-fold enhanced anti-proliferative activities compared with reference compound, GNF-7 against melanoma cells (SK-MEL-2, SK-MEL-28, A375, WM3670, WM3629). Moreover, SIJ1777 substantially inhibits the activation of MEK, ERK, and AKT and remarkably induces apoptosis and significantly blocks migration, invasion, and anchorage-independent growth of melanoma cells harboring BRAF class I/II/II mutations while both vemurafenib and PLX8394 have little to no effects on melanoma cells expressing BRAF class II/III mutations. Taken together, our six GNF-7 derivatives exhibit highly potent activities against melanoma cells harboring class I/II/III BRAF mutations compared with vemurafenib as well as PLX8394.
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http://dx.doi.org/10.3390/ijms22073783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038755PMC
April 2021

Genome-wide association study of neck circumference identifies sex-specific loci independent of generalized adiposity.

Int J Obes (Lond) 2021 07 27;45(7):1532-1541. Epub 2021 Apr 27.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background/objectives: Neck circumference, an index of upper airway fat, has been suggested to be an important measure of body-fat distribution with unique associations with health outcomes such as obstructive sleep apnea and metabolic disease. This study aims to study the genetic bases of neck circumference.

Methods: We conducted a multi-ethnic genome-wide association study of neck circumference, adjusted and unadjusted for BMI, in up to 15,090 European Ancestry (EA) and African American (AA) individuals. Because sexually dimorphic associations have been observed for anthropometric traits, we conducted both sex-combined and sex-specific analysis.

Results: We identified rs227724 near the Noggin (NOG) gene as a possible quantitative locus for neck circumference in men (N = 8831, P = 1.74 × 10) but not in women (P = 0.08). The association was replicated in men (N = 1554, P = 0.045) in an independent dataset. This locus was previously reported to be associated with human height and with self-reported snoring. We also identified rs13087058 on chromosome 3 as a suggestive locus in sex-combined analysis (N = 15090, P = 2.94 × 10; replication P =0.049). This locus was also associated with electrocardiogram-assessed PR interval and is a cis-expression quantitative locus for the PDZ Domain-containing ring finger 2 (PDZRN3) gene. Both NOG and PDZRN3 interact with members of transforming growth factor-beta superfamily signaling proteins.

Conclusions: Our study suggests that neck circumference may have unique genetic basis independent of BMI.
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http://dx.doi.org/10.1038/s41366-021-00817-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236408PMC
July 2021

A System for Phenotype Harmonization in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) Program.

Am J Epidemiol 2021 10;190(10):1977-1992

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948-2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.
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http://dx.doi.org/10.1093/aje/kwab115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485147PMC
October 2021

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P = 2 × 10). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P < 10). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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http://dx.doi.org/10.1038/s41380-021-01087-0DOI Listing
April 2021

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

Nat Commun 2021 04 12;12(1):2182. Epub 2021 Apr 12.

Division of Cardiology, George Washington University School of Medicine and Healthcare Sciences, Washington, DC, USA.

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
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http://dx.doi.org/10.1038/s41467-021-22339-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042019PMC
April 2021

Mitigating Dark Current for High-Performance Near-Infrared Organic Photodiodes via Charge Blocking and Defect Passivation.

ACS Appl Mater Interfaces 2021 Apr 6;13(14):16766-16774. Epub 2021 Apr 6.

IMEC, Kapeldreef 75, Leuven 3001, Belgium.

Thin-film organic near-infrared (NIR) photodiodes can be essential building blocks in the rapidly emerging fields including the internet of things and wearable electronics. However, the demonstration of NIR organic photodiodes with not only high responsivity but also low dark current density that is comparable to that of inorganic photodiodes, for example, below 1 nA cm for silicon photodiodes, remains a challenge. In this work, we have demonstrated non-fullerene acceptor-based NIR photodiodes with an ultralow dark current density of 0.2 nA cm at -2 V by innovating on charge transport layers to mitigate the reverse charge injection and interfacial defect-induced current generation. The same device also shows a high external quantum efficiency approaching 70% at 850 nm and a specific detectivity of over 10 Jones at wavelengths up to 940 nm. Furthermore, the versatility of our approach for mitigating dark current is demonstrated using a NIR photodetector utilizing different non-fullerene systems. Finally, the practical application of NIR organic photodiodes is demonstrated with an image sensor integrated on a silicon CMOS readout. This work provides new insight into the device stack design of low-dark current NIR organic photodiodes for weak light detection.
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http://dx.doi.org/10.1021/acsami.1c02080DOI Listing
April 2021

Pharmacological Interventions to Treat Antipsychotic-Induced Dyslipidemia in Schizophrenia Patients: A Systematic Review and Meta Analysis.

Front Psychiatry 2021 17;12:642403. Epub 2021 Mar 17.

Centre for Addiction and Mental Health, Toronto, ON, Canada.

Antipsychotic-induced dyslipidemia represents a common adverse effect faced by patients with schizophrenia that increases risk for developing further metabolic complications and cardiovascular disease. Despite its burden, antipsychotic-induced dyslipidemia is often left untreated, and the effectiveness of pharmacological interventions for mitigating dyslipidemia has not been well-addressed. This review aims to assess the effectiveness of pharmacological interventions in alleviating dyslipidemia in patients with schizophrenia. Medline, PsychInfo, and EMBASE were searched for all relevant English articles from 1950 to November 2020. Randomized placebo-controlled trials were included. Differences in changes in triglycerides, HDL cholesterol, LDL cholesterol, and VLDL cholesterol levels between treatment and placebo groups were meta-analyzed as primary outcomes. Our review identified 48 randomized controlled trials that comprised a total of 3,128 patients and investigated 29 pharmacological interventions. Overall, pharmacological interventions were effective in lowering LDL cholesterol, triglycerides, and total cholesterol levels while increasing the levels of HDL cholesterol. Within the intervention subgroups, approved lipid-lowering agents did not reduce lipid parameters other than total cholesterol level, while antipsychotic switching and antipsychotic add-on interventions improved multiple lipid parameters, including triglycerides, LDL cholesterol, HDL cholesterol, and total cholesterol. Off label lipid lowering agents improved triglycerides and total cholesterol levels, with statistically significant changes seen with metformin. Currently available lipid lowering agents may not work as well in patients with schizophrenia who are being treated with antipsychotics. Additionally, antipsychotic switching, antipsychotic add-ons, and certain off label interventions might be more effective in improving some but not all associated lipid parameters. Future studies should explore novel interventions for effectively managing antipsychotic-induced dyslipidemia. PROSPERO 2020 CRD42020219982; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020219982.
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http://dx.doi.org/10.3389/fpsyt.2021.642403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010007PMC
March 2021

The Long-Term Effect of Preterm Birth on Renal Function: A Meta-Analysis.

Int J Environ Res Public Health 2021 03 13;18(6). Epub 2021 Mar 13.

Department of Pediatrics, Chungnam National University Hospital, Daejeon 35015, Korea.

The preterm-born adult population is ever increasing following improved survival rates of premature births. We conducted a meta-analysis to investigate long-term effects of preterm birth on renal function in preterm-born survivors. We searched PubMed and EMBASE to identify studies that compared renal function in preterm-born survivors and full-term-born controls, published until 2 February 2019. A random effects model with standardized mean difference (SMD) was used for meta-analyses. Heterogeneity of the studies was evaluated using Higgin's statistics. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Of a total of 24,388 articles screened, 27 articles were finally included. Compared to full-term-born controls, glomerular filtration rate and effective renal plasma flow were significantly decreased in preterm survivors (SMD -0.54, 95% confidence interval (CI), -0.85 to -0.22, = 0.0008; SMD -0.39, 95% CI, -0.74 to -0.04, = 0.03, respectively). Length and volume of the kidneys were significantly decreased in the preterm group compared to the full-term controls (SMD -0.73, 95% CI, -1.04 to -0.41, < 0.001; SMD -0.82, 95% CI, -1.05 to -0.60, < 0.001, respectively). However, serum levels of blood urea nitrogen, creatinine, and cystatin C showed no significant difference. The urine microalbumin to creatinine ratio was significantly increased in the preterm group. Both systolic and diastolic blood pressures were also significantly elevated in the preterm group, although the plasma renin level did not differ. This meta-analysis demonstrates that preterm-born survivors may be subject to decreased glomerular filtration, increased albuminuria, decreased kidney size and volume, and hypertension even though their laboratory results may not yet deteriorate.
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http://dx.doi.org/10.3390/ijerph18062951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001027PMC
March 2021

Selective discrimination and classification of G-quadruplex structures with a host-guest sensing array.

Nat Chem 2021 05 1;13(5):488-495. Epub 2021 Apr 1.

Environmental Toxicology Graduate Program, University of California, Riverside, CA, USA.

The secondary structures of nucleic acids have an important influence on their cellular functions but can be difficult to identify and classify quickly. Here, we show that an arrayed suite of synthetic hosts and dyes is capable of fluorescence detection of oligonucleotide secondary structures. Multivariate analysis of different fluorescence enhancements-generated using cationic dyes that show affinity for both DNA G-quadruplexes and the synthetic hosts-enables discrimination between G-quadruplex structures of identical length and highly similar topological types. Different G-quadruplexes that display the same folding topology can also be easily differentiated by the number of G-quartets and sequence differences at the 3' or 5' ends. The array is capable of both differentiation and classification of the G-quadruplex structures at the same time. This simple non-invasive sensing method does not require the discovery and synthesis of specific G-quadruplex binding ligands, but employs a simple multicomponent approach to ensure wide applicability.
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http://dx.doi.org/10.1038/s41557-021-00647-9DOI Listing
May 2021

Emission of particulate and gaseous pollutants from household laser processing machine.

J Environ Sci (China) 2021 May 16;103:148-156. Epub 2020 Nov 16.

Department of Mechanical Engineering, Sejong University, Seoul 05006, Republic of Korea. Electronic address:

Indoor air quality (IAQ) directly affects the health of occupants. Household manufacturing equipment (HME) used for hobbies or educational purposes is a new and unexplored source of air pollution. In this study, we evaluated the characteristics of particulate and gaseous pollutants produced by a household laser processing equipment (HLPE). Various target materials were tested using a commercial HLPE under various operating conditions of laser power and sheath air flow rate. The mode diameters of the emitted particles gradually decreased as laser power increased, while the particle number concentration (PNC) and particle emission rate (PER) increased. In addition, as the sheath air flow rate quadrupled from 10 to 40 L/min, the mode diameter of the emitted particles decreased by nearly 25%, but the effect on the PNC was insignificant. When the laser induced the target materials at 53 mW, the mode diameters of particles were <150 nm, and PNCs were >2.0 × 10 particles/cm. Particularly, analyses of sampled aerosols indicated that harmful substances such as sulfur and barium were present in particles emitted from leather. The carcinogenic gaseous pollutants such as acrylonitrile, acetaldehyde, 1,3-butadiene, benzene, and C aromatics (ethylbenzene) were emitted from all target materials. In an actual indoor environment, the PNC of inhalable ultrafine particles (UFPs) was >5 × 10 particles/cm during 30 min of HLPE operation. Our results suggest that more meticulous control methods are needed, including the use of less harmful target materials along with filters or adsorbents that prevent emission of pollutants.
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http://dx.doi.org/10.1016/j.jes.2020.10.018DOI Listing
May 2021

A comparison of the analysis of 3 types of body fluids using the XN-350 hematology analyzer versus light microscopy assessment.

Medicine (Baltimore) 2021 Mar;100(11):e24852

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.

Abstract: We evaluated the capacity of the XN-350 instrument to analyze 3 different types of body fluid samples under "body fluid mode."The performance of XN-350 was evaluated in terms of precision, carryover, limit of blank, limit of detection, limit of quantification, and linearity. Cell enumeration and differential data produced by the XN-350 were compared to manual chamber counting results in 63 cerebrospinal fluid (CSF), 51 ascitic fluid, and 51 pleural fluid (PF) samples. Comparisons between XN-350 versus Cytospin data were also performed in PF samples.The precision, carry-over, limit of blank, and linearity of the XN-350 were acceptable. The limits of detection for white blood cells (WBCs) and red blood cells were 1.0/μL, and 1,000.0/μL, respectively; the corresponding limits of quantitation (LOQs) were 5.0/μL and 2,000.0/μL, respectively. The XN-350's cell enumeration and differential counting correlated well with those of manual chamber counting for all 3 sample types (except for differential counting in CSF samples), particularly parameters involving monocytes (r = 0.33) and mononuclear cells (MO- body fluid [BF]; r = 0.26), as well as total cell (TC-BF) enumeration (r = 0.50) and WBC-BF (r = 0.50) in PF samples. The MO-BF in CSF samples differed significantly from manual chamber counting results, but neither TC-BF nor WBC-BF in PF samples did. The XN-350 also showed good correlations with Cytospin analyses for differential counting of neutrophils, lymphocytes, and monocytes in PF samples. The differential counting of eosinophils via the XN-350 and Cytospin were not significantly correlated, but the difference between them was not significant.The XN-350 is an acceptable alternative to manual fluid analysis. Samples with low cellularity around the LOQ should be checked manually. Moreover, manual differential counting should be performed on CSF samples, particularity those with low cell numbers.
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http://dx.doi.org/10.1097/MD.0000000000024852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982217PMC
March 2021

Comparison of Sugammadex Dose for Intraoperative Neuromonitoring in Thyroid Surgery: A Randomized Controlled Trial.

Laryngoscope 2021 09 15;131(9):2154-2159. Epub 2021 Mar 15.

Department of Anesthesiology and Pain Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives/hypothesis: To compare effect of 1 and 2 mg/kg of sugammadex on the incidence of intraoperative bucking and intraoperative neuromonitoring (IONM) quality in thyroid surgery.

Study Design: Randomized controlled trial.

Methods: Patients qualified for thyroid surgery with IONM were eligible for this double-blind, randomized, controlled trial. After tracheal intubation with 0.6 mg/kg rocuronium, 1 or 2 mg/kg of sugammadex was administered to patients in group I or II, respectively. The quality of the IONM for the external branch of the superior laryngeal nerve (EBSLN) was evaluated (strong/intermediate/weak). The initial amplitude of electromyography for the vagus nerve (V1) and the recurrent laryngeal nerve (R1) were recorded. Intraoperative bucking movements was recorded.

Results: A total of 102 patients (51 in each group) completed the study. Time from sugammadex administration to initial checking for the EBSLN was not different between group I and II (25.0 ± 7.9 vs. 25.5 ± 9.0 minutes, P = .788). There was no difference in the neuromonitoring quality for the EBSLN between group I and II (strong/intermediate/weak: 46/5/0 vs. 50/1/0, P = .205). The amplitudes of V1 (1,086.3 ± 673.3 μV vs. 1,161.8 ± 727.5 μV, P = .588) and R1 (1,328.2 ± 934.1 μV vs. 1,410.5 ± 919.6 μV, P = .655) were comparable between the groups. Patients who experienced bucking were significantly fewer in the group I than the group II (13.7% vs. 35.3%, P = .020).

Conclusion: A dose of 1 mg/kg sugammadex induced less bucking than 2 m/kg while providing comparable IONM quality during thyroid surgery.

Level Of Evidence: 2 Laryngoscope, 131:2154-2159, 2021.
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http://dx.doi.org/10.1002/lary.29515DOI Listing
September 2021
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