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1.
Medicine (Baltimore) ; 100(40): e27346, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622833

RESUMO

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.


Assuntos
Osteosclerose/genética , Criança , Códon sem Sentido , Feminino , Humanos , Osteosclerose/diagnóstico
2.
Appl Opt ; 60(24): 7446-7454, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613034

RESUMO

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.

3.
Medicine (Baltimore) ; 100(38): e26827, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559095

RESUMO

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.


Assuntos
Fios Ortopédicos , Luxações Articulares/cirurgia , Ligamentos Articulares/cirurgia , Articulação do Punho , Acidentes por Quedas , Idoso , Humanos , Luxações Articulares/diagnóstico por imagem , Osso Semilunar , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Osso Escafoide
4.
Nutrients ; 13(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34578886

RESUMO

Dietary choices may have differing effects on low-density lipoprotein cholesterol or triglyceride levels. The aim of this study was to investigate daily nutrient intake and dietary patterns of individuals with hyper-low-density lipoprotein cholesterolemia (hLDL) and hypertriglyceridemia (hTG) in a large Korean population-based study using propensity score (PS) matching. This study used data from the Korea National Health and Nutrition Examination Survey. Propensity score values for the predicted probability of patients with hLDL or hTG were estimated using logistic regression analysis, with age, sex, body mass index, alcohol consumption, smoking status, physical activity status, hypertension, and diabetes. After PS matching, intake of carbohydrates (%) was significantly lower (p = 0.021), and intake of fats (%) and saturated fatty acids (%) was significantly higher in the hLDL group than in the non-hLDL group (p = 0.025 and p = 0.013, respectively). The percentage of individuals with a high score for the Korean Healthy Eating Index (KHEI) "whole grains" or "saturated fatty acids" components was higher in the non-hLDL group than in the hLDL group (p < 0.05 for both). Dietary sodium/potassium ratio was significantly higher in the hTG than in the non-hTG (p = 0.049). Our results suggest that individualized dietary information and counseling require consideration of a person's specific lipid levels.

5.
Clin Ther ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34509304

RESUMO

PURPOSE: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. METHODS: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FINDINGS: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. IMPLICATIONS: We present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

6.
Sci Rep ; 11(1): 18130, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518578

RESUMO

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.

7.
Biosens Bioelectron ; 195: 113649, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34555637

RESUMO

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.

8.
Asia Pac J Clin Nutr ; 30(3): 512-521, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34587711

RESUMO

BACKGROUND AND OBJECTIVES: In adolescents, adequate nutrition education is essential for making decisions regarding healthy eating habits. We aimed to investigate differences in dietary habits and body image misperception according to nutrition education status. METHODS AND STUDY DESIGN: We analyzed 60,389 adolescents aged 12-18 years old, using the 2017 Korea Youth Risk Behavior Web-based Survey data. Participants were divided into nutrition-educated (EDU) and uneducated (non-EDU) groups, according to nutrition education status within the past year. Skipping breakfast was defined as skipping breakfast ≥5 times/week. Desirable dietary behaviors were divided into the frequency of consumption of 3 items: vegetables ≥1 time/day, milk ≥1 time/day, and fruits ≥1 time/day. Participants with normal weight who reported being slightly fat or very fat were defined as having body image misperception. RESULTS: Compared to the non-EDU group, the odds ratio (OR) and 95% confidence interval (CI) for desirable dietary behaviors in the EDU group were 1.08 (1.04-1.13), 1.14 (1.09-1.19), and 1.16 (1.12-1.20) for the intake of fruits, milk, and vegetables, respectively. The EDU group was less associated with skipping breakfast than the non-EDU group (OR=0.91, 95% CI: 0.87-0.95, p<0.001). The OR and 95% CI of body image misperception in the EDU group were lower than in the non-EDU group (OR=0.92, 95% CI: 0.87- 0.97, p<0.001). CONCLUSIONS: Nutrition education have positive effects on healthy dietary behaviors. It also shows a negative association with body image misperception, confirming the importance of nutrition education at school.

9.
Acta Psychiatr Scand ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34458979

RESUMO

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 cm2 ; 95% CI: 2.97-45.61) and VAT (MD = 33.73 cm2 , 95% CI: 4.19-63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm2 ; 95% CI: 11.33-52.64) and VAT (MD = 16.30 cm2 ; 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.

10.
J Hand Surg Asian Pac Vol ; 26(3): 425-431, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34380383

RESUMO

Background: Dorsal rotation or persistent displacement of the fracture fragment is frequently encountered in extension block pinning for mallet fractures. We reviewed nine irreducible mallet fracture patients treated with mini-open reduction and extension block pinning. Methods: A small V-shaped incision was made on the fracture gap when there was persistent displacement of fracture fragment despite closed maneuvers and percutaneous procedures while performing extension block pinning. Soft tissue or granulation tissue hampering reduction was removed through the incision. Anatomical reduction was guided with a freer elevator. The incision was closed by distal interphalangeal joint transfixation in extension without any suture. Pin tips were buried under the skin. The incision and pin entry sites were covered with skin adhesive, and the patients were allowed to wash their hands 1-2 days after the surgery. No splint was applied postoperatively. Mean follow-up period was 13 months. Results: Anatomical reduction was achieved in 7 out of 9 patients. In the rest 2 patients, postoperative step-off of the articular surface at the fracture site was less than 0.5 mm. Solid union was achieved in all cases. The mean extension lag at final follow-up was 0°. No patient developed postoperative external bleeding or other complications in the incision site or the pin site. Conclusions: Mini-open reduction and extension block pinning appears to be a good option for irreducible mallet fractures, which improves reduction quality and patients' convenience.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Ósseas , Redução Aberta , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Estudos Retrospectivos
11.
Genome Med ; 13(1): 136, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446064

RESUMO

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 × 10-8) 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.

12.
J Med Chem ; 64(16): 11934-11957, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34324343

RESUMO

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-d]pyrimidine derivatives. An intensive structure-activity relationship (SAR) study led to the identification of 26 as a lead. Moreover, 26, a multitargeted kinase inhibitor, possesses excellent potencies against FLT3 mutants as well as FAK. Gratifyingly, 26 remarkably inhibits recalcitrant FLT3 mutants, including F691L, that cause drug resistance. Importantly, 26 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, 26 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, 26 remarkably prevents metastasis of orthotopic tumors to lymph nodes. Taken together, the results indicate that 26 possesses potential therapeutic value against highly invasive cancers and relapsed AML.

13.
Circ Genom Precis Med ; 14(4): e003300, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34319147

RESUMO

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 (KCNQ1, KCNH2, and SCN5A), a controversial monogenic SCD gene (KCNE1), and novel genes (PAM and MFGE8) involved in cardiac conduction. Loss-of-function and pathogenic SCN5A variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (P=8.4×10-5). Similar variants in KCNQ1 and KCNH2 (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (P=4×10-25), 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.

14.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196304

RESUMO

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 (Galß1-4GalNAcß), 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.


Assuntos
Anticorpos Antivirais/biossíntese , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Proteínas Virais/imunologia , Adulto , Fatores Etários , Idoso , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Estudos de Coortes , Reações Cruzadas , Ovos/análise , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Pessoa de Meia-Idade , Polissacarídeos/imunologia , Vacinação
15.
PLoS One ; 16(6): e0253541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166440

RESUMO

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.

16.
J Intern Med ; 290(4): 866-877, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34114281

RESUMO

BACKGROUND: Associations among dietary fat, cholesterol intake and total mortality remain controversial, and most available data cover Western populations. The aim of this study was to assess associations for dietary fat and cholesterol in relation to total mortality in Koreans. METHODS: This study used data from three prospective Korean Genome and Epidemiology studies (conducted between June 2001 and December 2013). A total of 194,295 middle-aged and older Korean adults were included. Dietary fat intake was classified into quintiles. Dietary cholesterol intake was categorized into three groups based on cholesterol intake as follows: <200 mg, 200-299 mg and ≥300 mg. A multivariable Cox frailty model with random effects was applied to calculate hazard ratios (HR) and 95% confidence intervals (CIs) after adjusting for confounders. RESULTS: We documented 3866 deaths across a mean (min-max) follow-up period of 8.15 years (3-13 years). Higher fat intake was associated with lower total mortality (Q5 vs. Q1, HR 0.82 [95% CI 0.69, 0.98]; p trend < 0.01) after adjusting for age, sex, body mass index, alcohol, smoking, exercise and total calorie and protein (%) intake. Higher dietary cholesterol intake (≥300 mg/day) was associated with a higher risk of total mortality (HR 1.19 [95% CI 1.04, 1.37]) than lower cholesterol intake (<200 mg/day) in the multivariate model. CONCLUSIONS: In Koreans, high dietary fat intake is associated with a lower risk of total mortality, while dietary cholesterol intake above 300 mg/day is associated with a higher risk of total mortality.

17.
Am J Physiol Endocrinol Metab ; 321(1): E146-E155, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34097543

RESUMO

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.NEW & NOTEWORTHY 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.


Assuntos
Peso Corporal/fisiologia , Glucose/metabolismo , Homeostase/fisiologia , Neurônios/metabolismo , Receptor CB1 de Canabinoide/fisiologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Animais , Composição Corporal/fisiologia , Proteína 9 Associada à CRISPR , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Dieta Hiperlipídica , Metabolismo Energético/fisiologia , Feminino , Edição de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/metabolismo , Receptor CB1 de Canabinoide/deficiência , Receptor CB1 de Canabinoide/genética
18.
mBio ; 12(3): e0114421, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34060327

RESUMO

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. IMPORTANCE 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.

19.
Microscopy (Oxf) ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100544

RESUMO

The lamellar structure of bone, which endows biomechanical rigidity to support the host organism is observed in mammals, including humans. It is therefore essential to develop a quantitative analysis to evaluate the lamellarity of bone, which would especially useful for the pharmacological evaluation of anti-osteoporotic drugs. This study applied a current system for the semi-automatic recognition of fluorescence signals to the analysis of un-decalcified bone sections from rat and monkey specimens treated with teriparatide (TPTD). Our analyses on bone formation pattern and collagen topology indicated that TPTD augmented bone lamellarity and bone collagen linearity, which were possibly associated with the recovery of collagen crosslinking, thus endowing bone rigidity.

20.
Nutr Metab Cardiovasc Dis ; 31(6): 1774-1781, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975738

RESUMO

BACKGROUND AND AIMS: The new visceral adiposity index (NVAI) is an indirect marker of visceral adipose tissue recently developed using a Korean population. Here we examined the association of NVAI with coronary artery calcification and arterial stiffness in asymptomatic Korean patients. METHODS AND RESULTS: We analyzed data from 60,938 asymptomatic Korean adults. Odds ratios and 95% confidence intervals (CIs) for coronary artery calcification score (CACS) > 100 and brachial-ankle pulse wave velocity (baPWV) ≥14 m/s were calculated across NVAI tertiles using multiple logistic regression analysis. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to assess the ability of NVAI to predict moderate to high risk of cardiovascular disease. The prevalence of moderate and high risk of cardiovascular disease increased significantly as the NVAI tertile increased. The odds ratio (95% CI) of the highest NVAI tertile for CACS >100 was 5.840 (5.101-6.686) for men and 18.916 (11.232-31.855) for women, after adjusting for confounders. All NVAI AUC values were significantly higher than the AUC values for other visceral adiposity markers. CONCLUSIONS: This study provides the evidence that NVAI is independently and positively associated with coronary calcification and arterial stiffness in asymptomatic Korean adults.


Assuntos
Adiposidade , Doença da Artéria Coronariana/diagnóstico , Gordura Intra-Abdominal/fisiopatologia , Calcificação Vascular/diagnóstico , Rigidez Vascular , Adulto , Idoso , Índice Tornozelo-Braço , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Prevalência , Prognóstico , Análise de Onda de Pulso , Sistema de Registros , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Calcificação Vascular/epidemiologia , Calcificação Vascular/fisiopatologia
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