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1.
Nutr Res ; 87: 13-21, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33596507

RESUMEN

Vitamin D is a factor that regulates calcium and bone metabolism. However, the clinical effect of vitamin D on bone mineral density (BMD) remains controversial. We hypothesized that sufficient vitamin D is required to maintain optimal BMD in adolescents. Based on the Korea National Health and Nutritional Examination Survey, data of 1063 adolescents aged 12 to 18 years were analyzed. The association of vitamin D status and other variables, such as body mass index (BMI), calcium intake, physical activity, lean mass, and fat mass, with BMD Z-scores in the lumbar spine, whole body, total femur, and femur neck were examined. We defined vitamin D deficiency as < 12 ng/mL, vitamin D insufficiency as 12 to 20 ng/mL, and sufficiency as > 20 ng/mL according to the 25-hydroxyvitamin D (25-OHD) level. The mean 25-OHD concentration of subjects was below normal, at 16.28 ng/mL. Subjects with vitamin D deficiency, insufficiency, and sufficiency comprised 20.5%, 58.6%, and 20.9% of all subjects, respectively. The vitamin D sufficient group had higher BMD Z-scores compared to the insufficient group, and the insufficient group had higher BMD Z-scores compared to the deficient group. In linear regression analysis, 25-OHD level, BMI, calcium intake, physical activity, lean mass, and fat mass were positively associated with BMD Z-scores. 25-OHD level was positively associated with BMD Z-scores, even after adjusting for other factors. This study suggests that vitamin D status is positively associated with BMD in adolescents; therefore, maintaining sufficient vitamin D levels during adolescence is crucial to prevent low BMD.

2.
BMC Gastroenterol ; 21(1): 13, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407193

RESUMEN

BACKGROUND: Many patients with ulcerative colitis (UC) in clinical remission frequently complain of bowel symptoms such as increased stool frequency (SF) and rectal bleeding (RB). However, studies on these patient-reported outcomes in patients with inactive UC are limited, especially in Korea. Therefore, we investigated the prevalence and risk factors of bowel symptoms in Korean patients with inactive UC. METHODS: We investigated the prevalence of bowel symptoms in patients with endoscopically quiescent UC between June 1989 and December 2016 using a well-characterized referral center-based cohort. The Mayo clinic score (MCS) was used to evaluate bowel symptoms at the most recent visit near the date of endoscopy. Clinical characteristics of the patients were compared based on the presence or absence of bowel symptoms. RESULTS: Overall, 741 patients with endoscopically quiescent UC were identified, of whom 222 (30%) and 48 (6.5%) had an SF and RB subscore of ≥ 1, respectively. Patients with bowel symptoms (SF + RB ≥ 1; n = 244 [32.9%]) had higher rates of left-sided colitis (E2) or extensive colitis (E3) than patients without bowel symptoms (SF + RB = 0; n = 497 [67.1%]; P = 0.002). Multivariate analysis revealed that female sex (odds ratio [OR]: 1.568; 95% confidence interval [CI]: 1.023-2.402; P = 0.039) and E2 or E3 (OR 1.411; 95% CI 1.020-1.951; P = 0.038) were the significant risk factors for increased SF. CONCLUSIONS: This study revealed that one-third of patients with endoscopically quiescent UC reported increased SF. Female sex and disease extent may be associated with bowel symptoms.

3.
J Am Soc Nephrol ; 32(2): 502-516, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33323473

RESUMEN

BACKGROUND: Pharmacokinetic monitoring is insufficient to estimate the intensity of immunosuppression after transplantation. Virus-specific T cells correlate with both virus-specific and general cellular immune defense. Additional steering of immunosuppressive therapy by virus-specific T cell levels might optimize dosing of immunosuppressants. METHODS: In a multicenter, randomized, controlled trial, we randomized 64 pediatric kidney recipients to a control group with trough-level monitoring of immunosuppressants or to an intervention group with additional steering of immunosuppressive therapy by levels of virus-specific T cells (quantified by cytokine flow cytometry). Both groups received immunosuppression with cyclosporin A and everolimus in the same target range of trough levels. Primary end point was eGFR 2 years after transplantation. RESULTS: In the primary analysis, we detected no difference in eGFR for the intervention and control groups 2 years after transplantation, although baseline eGFR 1 month after transplantation was lower in the intervention group versus the control group. Compared with controls, patients in the intervention group received significantly lower daily doses of everolimus and nonsignificantly lower doses of cyclosporin A, resulting in significantly lower trough levels of everolimus (3.5 versus 4.5 µg/L, P<0.001) and cyclosporin A (47.4 versus 64.1 µg/L, P<0.001). Only 20% of patients in the intervention group versus 47% in the control group received glucocorticoids 2 years after transplantation (P=0.04). The groups had similar numbers of donor-specific antibodies and serious adverse events. CONCLUSIONS: Steering immunosuppressive therapy by virus-specific T cell levels in addition to pharmacokinetic monitoring seems safe, results in a similar eGFR, and personalizes immunosuppressive therapy by lowering exposure to immunosuppressive drugs, likely resulting in lower drug costs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: IVIST trial, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2009-012436-32 and ISRCTN89806912.

4.
Accid Anal Prev ; 150: 105899, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33285445

RESUMEN

The proliferation of digital textual archives in the transportation safety domain makes it imperative for the inventions of efficient ways of extracting information from the textual data sources. The present study aims at utilizing crash narratives complemented by crash metadata to discern the prevalence and co-occurrence of themes that contribute to crash incidents. Ten years (2009-2018) of Michigan traffic fatal crash narratives were used as a case study. The structural topic modeling (STM) and network topology analysis were used to generate and examine the prevalence and interaction of themes from the crash narratives that were mainly categorized into pre-crash events, crash locations and involved parties in the traffic crashes. The main advantage of the STM over the other topic modeling approaches is that it allows the researchers to discover themes from documents and estimate how the topic relates to the document metadata. Topics with the highest prevalence for the angle, head-on, rear-end, sideswipe and single motor vehicle crashes were crash at stop-sign, crossing the centerline, unable to stop, lane change maneuver and run-off-road crash, respectively. Eigenvector centrality measure in network topology showed that event-related topics were consistently central in articulating the crash occurrence. The centrality and association between topics varied across crash types. The efficacy of generated topics in classifying crashes by type was tested using a machine learning algorithm, Random Forest. The classification accuracy in the held-out sample ranged between 89.3 % for sideswipe crashes to 99.2 % for single motor vehicle crashes. High classification accuracy suggests that automation of crash typing and consistency checks can be accomplished effectively by using extracted latent themes from the crash narratives.

5.
Children (Basel) ; 7(12)2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33291623

RESUMEN

Sex hormone-binding globulin (SHBG) is associated with age, sex, and puberty. The association of SHBG with various diseases has been suggested nowadays, however, the relationships in prepubertal children have not been sufficiently investigated. This study analyzed the relationship of SHBG with body mass index (BMI) and plasma lipid levels in prepubertal children. We evaluated the association of SHBG with BMI among the 693 prepubertal children subdivided into normal, overweight, and obese groups, with plasma lipid levels among the children subdivided into normal and dyslipidemia groups. The obese and overweight group had lower SHBG levels than the normal BMI group in both sexes. The dyslipidemia group included subjects with low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TG), or a high atherogenic index of plasma (AIP); this group had lower SHBG than the normal lipid group. SHBG was positively correlated with HDL-C, and negatively correlated with TG and AIP. After adjusting for BMI, SHBG was positively correlated with HDL-C and negatively correlated with TG and AIP in all groups. In conclusion, SHBG levels are closely correlated with BMI in prepubertal children. SHBG may play a meaningful role in the decrease in HDL-C and increase in TG during prepubertal age.

6.
Pain Res Manag ; 2020: 7934164, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33294086

RESUMEN

Mannitol has recently been reported to be effective in enhancing the antinociceptive efficacy of lidocaine. No single study to date, however, has compared diphenhydramine with and without mannitol for nociceptive processing as an alternative local anesthetic. In this study, we examined the antinociceptive efficacy enhancements of diphenhydramine when combined with mannitol. Male Sprague-Dawley rats weighing 230-260 g were used in a hot plate test to evaluate the antinociceptive effects of diphenhydramine. All chemicals were dissolved in isotonic normal saline and administered subcutaneously into the plantar surface of the right hind paw at 10 min before the hot plate test. A subcutaneous injection of 0.5% or 1% diphenhydramine produced significant inhibition of the withdrawal latency time compared with the vehicle treatment. Antinociceptive effects appeared 10 min after the diphenhydramine injections and persisted for over 30 min. The antinociceptive effects of 1% diphenhydramine were not statistically different from those of 1% lidocaine. Although a subcutaneous injection of a 0.5 M mannitol solution alone did not affect the withdrawal latency time, 1% diphenhydramine with 0.5 M mannitol significantly enhanced antinociception. A subcutaneous injection of 1% diphenhydramine with epinephrine (1 : 100,000) solution did not increase the antinociceptive effect of the diphenhydramine. These results suggest that diphenhydramine with mannitol can be used as an alternative local anesthetic.

7.
Pediatr Transplant ; : e13955, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-33378587

RESUMEN

Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence.

8.
Children (Basel) ; 7(11)2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33228115

RESUMEN

Dyslipidemia is one of the important influencing factors of cardiovascular health in the youth, and thus, assessment of its etiology is important. We aimed to investigate the association of dyslipidemia with vitamin D and physical activity in Korean children and adolescents. Data of 3183 subjects aged 12-18 years in the Korea National Health and Nutrition Examination Survey were analyzed. Participants were divided into subgroups according to sex, body mass index, 25-hydroxyvitamin D levels, and lipid profile. The mean 25-hydroxyvitamin D level was 16.15 ng/mL, which was below normal. In total, 79.3% of the subjects had vitamin D deficiency. Females had lower vitamin D levels and a higher incidence of dyslipidemia compared to males. Vitamin D deficiency was significantly associated with high density lipoprotein cholesterol (HDL-C) levels. The low HDL-C group consisted of a higher proportion of subjects with vitamin D deficiency and low physical activity. This study suggests that vitamin D deficiency is prevalent in Korean children and adolescents. Vitamin D deficiency and low physical activity are related with low HDL-C levels. Maintaining sufficient vitamin D levels and physical activity may help prevent dyslipidemia.

9.
Sci Rep ; 10(1): 20349, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33230229

RESUMEN

Lithocholic bile acid (LCA) has been reported to selectively kill cancer cells within many tumor cell lines including neuroblastoma or glioblastoma. Wilms' tumor shares similarities with neuro- and glioblastoma. Hence, the aim of the study was to evaluate the effects of LCA on nephroblastoma. To test the effects of LCA, nephroblastoma cell line WT CLS1 was used. SK NEP1 was tested as well. It was originally classified as a nephroblastoma cell line but was meanwhile reclassified as an ewing sarcoma cell line. As control cell lines HEK 293 from embryonic kidney and RC 124 from adult kidney tissue as well as podocytes were used. The effects were evaluated using proliferation assay, caspase activity assay, FACS and Western blot. LCA showed a dose and time-dependent selective effect inducing apoptosis in nephroblastoma cells. However, these effects were not limited to the nephroblastoma cell line but also affected control kidney cell lines and the sarcoma cells; only podocytes are significantly less affected by LCA (at dosages < 200 µm). There were no significant differences regarding the TGR5 receptor expression. The study showed that LCA has a strong, yet unselective effect on all used in vitro cell-lines, sparing the highly differentiated podocytes in lower concentrations. Further studies are needed to verify our results before dismissing LCA as an anti-cancer drug.

10.
Antibiotics (Basel) ; 9(11)2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33233541

RESUMEN

Antibiotic resistance is an important issue affecting humans and livestock. Antimicrobial peptides are promising alternatives to antibiotics. In this study, the antimicrobial peptide Css54, isolated from the venom of C. suffuses, was found to exhibit antimicrobial activity against bacteria such as Listeria monocytogenes, Streptococcus suis, Campylobacter jejuni, and Salmonella typhimurium that cause zoonotic diseases. Moreover, the cytotoxicity and hemolytic activity of Css54 was lower than that of melittin isolated from bee venom. Circular dichroism assays showed that Css54 has an α-helix structure in an environment mimicking that of bacterial cell membranes. We examined the effect of Css54 on bacterial membranes using N-phenyl-1-naphthylamine, 3,3'-dipropylthiadicarbbocyanine iodides, SYTOX green, and propidium iodide. Our findings suggest that the Css54 peptide kills bacteria by disrupting the bacterial membrane. Moreover, Css54 exhibited antibiofilm activity against L. monocytogenes. Thus, Css54 may be useful as an alternative to antibiotics in humans and animal husbandry.

11.
Plants (Basel) ; 9(11)2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33182649

RESUMEN

Temperate japonica rice varieties exhibit wide variation in the phenotypes of several important agronomic traits, including disease resistance, pre-harvest sprouting resistance, plant architecture, and grain quality, indicating the presence of genes contributing to favorable agronomic traits. However, gene mapping and molecular breeding has been hampered as a result of the low genetic diversity among cultivars and scarcity of polymorphic DNA markers. Single nucleotide polymorphism (SNP)-based kompetitive allele-specific PCR (KASP) markers allow high-throughput genotyping for marker-assisted selection and quantitative trait loci (QTL) mapping within closely related populations. Previously, we identified 740,566 SNPs and developed 771 KASP markers for Korean temperate japonica rice varieties. However, additional markers were needed to provide sufficient genome coverage to support breeding programs. In this study, the 740,566 SNPs were categorized according to their predicted impacts on gene function. The high-impact, moderate-impact, modifier, and low-impact groups contained 703 (0.1%), 20,179 (2.7%), 699,866 (94.5%), and 19,818 (2.7%) SNPs, respectively. A subset of 357 SNPs from the high-impact group was selected for initial KASP marker development, resulting in 283 polymorphic KASP markers. After incorporation of the 283 markers with the 771 existing markers in a physical map, additional markers were developed to fill genomic regions with large gaps between markers, and 171 polymorphic KASP markers were successfully developed from 284 SNPs. Overall, a set of 1225 KASP markers was produced. The markers were evenly distributed across the rice genome, with average marker density of 3.3 KASP markers per Mbp. The 1225 KASP markers will facilitate QTL/gene mapping and marker-assisted selection in temperate japonica rice breeding programs.

12.
J Mater Sci Mater Med ; 31(12): 122, 2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33247775

RESUMEN

Device-related problems of drug-eluting stents, including stent thrombosis related to antiproliferative drugs and polymers, can cause adverse events such as inflammation and neointimal hyperplasia. Stent surface modification, wherein the drug and polymer are not required, may overcome these problems. We developed hydrophilic polyethylene glycol (PEG)-coating and hydrophobic octadecylthiol (ODT)-coating stents without a drug and polymer and evaluated their histopathologic response in a porcine coronary restenosis model. PEG-coating stents (n = 12), bare-metal stents (BMS) (n = 12), and ODT-coating stents (n = 10) were implanted with oversizing in 34 porcine coronary arteries. Four weeks later, the histopathologic response, arterial injury, inflammation, and fibrin scores were analyzed. A p value < 0.05 was considered statistically significant. There were significant differences in the internal elastic lamina area, lumen area, neointimal area, percent area of stenosis, arterial injury score, inflammation score, and fibrin score among the groups. Compared to the BMS or ODT-coating stent group, the PEG-coating stent group had significantly increased internal elastic lamina and lumen area (all p < 0.001) and decreased neointimal area and percent area of stenosis (BMS: p = 0.03 and p < 0.001, respectively; ODT-coating: p = 0.013 and p < 0.001, respectively). Similarly, the PEG-coating group showed significantly lower inflammation and fibrin scores than the BMS or ODT-coating groups (BMS: p = 0.013 and p = 0.007, respectively; ODT-coating: p = 0.014 and p = 0.008, respectively). In conclusion, hydrophilic PEG-coating stent implantation was associated with lower inflammatory response, decreased fibrin deposition, and reduced neointimal hyperplasia than BMS or hydrophobic ODT-coating stent implantation in the porcine coronary restenosis model.

13.
PLoS One ; 15(10): e0240446, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33108385

RESUMEN

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.

14.
Genes Genomics ; 42(12): 1419-1430, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33113112

RESUMEN

BACKGROUND: Information on the genetic variation of genetic resource collections is very important for both the conservation and utilization of crop germplasms in genebanks. Var. frutescens of Perilla crop is extensively cultivated in South Korea as both an oil crop and a vegetable crop. OBJECTIVES: We used SSR markers to evaluate the genetic diversity, genetic relationships, and population structure of 155 accessions of var. frutescens that have been selected as genetic resources for the development of leaf vegetable cultivars and preserved in the RDA-Genebank collection from South Korea. METHODS: A total of 155 accessions of var. frutescens of Perilla crop collected in South Korea were obtained from the RDA-Genebank of the Republic of Korea. We selected 20 SSR markers representing the polymorphism of and adequately amplifying all the Perilla accessions. RESULTS: The average GD and PIC values were 0.642 and 0.592, respectively, with ranges of 0.244-0.935 and 0.232- 0.931. The genetic variability in the southern region of South Korea was higher than that in the central region. The clustering patterns were not clearly distinguished between the accessions of var. frutescens from the central and southern regions of South Korea. CONCLUSION: These results regarding the genetic diversity and population structure of the 155 accessions of var. frutescens of South Korea provide useful information for understanding the genetic variability of this crop and selecting and managing core germplasm sets in the RDA-Genebank of the Republic of Korea.

15.
Artículo en Inglés | MEDLINE | ID: mdl-33007476

RESUMEN

OBJECTIVES: Investigation whether in depth characterization of virus variant patterns can be used for epidemiological analysis of the first SARS-CoV-2 infection clusters in Hamburg, Germany. METHODS: Metagenomic RNA- and amplicon-sequencing and subsequent variant calling in 25 respiratory samples from SARS-CoV-2 infected patients involved in the earliest infection clusters in Hamburg. RESULTS: Amplikon sequencing and cluster analyses of these SARS-CoV-2 sequences allowed the identification of the first infection cluster and five non-related infection clusters occurring at the beginning of the viral entry of SARS-CoV-2 in the Hamburg metropolitan region. Viral genomics together with epidemiological analyses revealed that the index patient acquired the infection in Northern Italy and transmitted it to two out of 134 contacts. Single nucleotide polymorphisms clearly distinguished the virus variants of the index and other clusters and allowed to track in which sequences worldwide these mutations were first described. Minor variant analyses identified the transmission of intra-host variants in the index cluster and household clusters. CONCLUSIONS: SARS-CoV-2 variant tracing allows the identification of infection clusters and the follow up of infection chains occurring in the population. Furthermore, the follow up of minor viral variants in infection cluster can provide further resolution on transmission events indistinguishable on consensus sequence level.

16.
Sci Rep ; 10(1): 16025, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32994492

RESUMEN

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (≤ 3 months; VEBNE) and early (4-15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ≤ 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort.

17.
iScience ; 23(9): 101513, 2020 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-32920488

RESUMEN

Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin-9 (GAL-9) expression is a possible mechanism promoting lymphocyte dysfunction. In this study, we measured the expression of inhibitory receptors and GAL-9 on T/NK cells of patients with chronic HCV with no to moderate fibrosis (F0-F2) and advanced fibrosis (F3-F4). To analyze their co-expression, we employed t-SNE analysis. Notably, we found that F3-F4 patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells. Moreover, F3-F4 patients manifest a higher frequency of NK cells co-expressing TIGIT and TIM-3, and CD4/NK cells co-expressing LAG-3 and GAL-9. In conclusion, we identified phenotypes of immune dysregulation that could explain the increased susceptibility to infection and HCC in patients with chronic HCV with advanced fibrosis.

18.
Front Immunol ; 11: 1833, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922395

RESUMEN

Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in circulation. Nevertheless, there is a growing body of evidence for additional sites of complement protein synthesis, including various cell types in the kidney. We hypothesized that podocytes are able to produce complement components and contribute to the local balance of complement activation and regulation. To investigate the relevant balance between inhibiting and activating sides, our studies focused on complement factor H (CFH), an important complement regulator, and on C3, the early key component for complement activation. We characterized human cultured podocytes for the expression and secretion of activating and regulating complement factors, and analyzed the secretion pathway and functional activity. We studied glomerular CFH and C3 expression in puromycin aminonucleoside (PAN) -treated rats, a model for proteinuria, and the physiological mRNA-expression of both factors in murine kidneys. We found, that C3 and CFH were expressed in cultured podocytes and expression levels differed from those in cultivated glomerular endothelial cells. The process of secretion in podocytes was stimulated with interferon gamma and located in the Golgi apparatus. Cultured podocytes could initiate the complement cascade by the splitting of C3, which can be shown by the generation of C3a, a functional C3 split product. C3 contributed to external complement activation. Podocyte-secreted CFH, in conjunction with factor I, was able to split C3b. Podocytes derived from a patient with a CFH mutation displayed impaired cell surface complement regulation. CFH and C3 were synthesized in podocytes of healthy C57Bl/6-mice and were upregulated in podocytes of PAN treated rats. These data show that podocytes produce functionally active complement components, and could therefore influence the local glomerular complement activation and regulation. This modulating effect should therefore be considered in all diseases where glomerular complement activation occurs. Furthermore, our data indicate a potential novel role of podocytes in the innate immune system.

19.
Am J Cardiol ; 136: 38-48, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32946862

RESUMEN

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.

20.
Am Heart J ; 228: 72-80, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32871327

RESUMEN

BACKGROUND: The clinical value of intracoronary imaging for percutaneous coronary intervention (PCI) guidance is well acknowledged. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most commonly used intravascular imaging to guide and optimize PCI in day-to-day practice. However, the comparative effectiveness of IVUS-guided versus OCT-guided PCI with respect to clinical end points remains unknown. METHODS AND DESIGN: The OCTIVUS study is a prospective, multicenter, open-label, parallel-arm, randomized trial comparing the effectiveness of 2 imaging-guided strategies in patients with stable angina or acute coronary syndromes undergoing PCI in Korea. A total of 2,000 patients are randomly assigned in a 1:1 ratio to either an OCT-guided PCI strategy or an IVUS-guided PCI strategy. The trial uses a pragmatic comparative effectiveness design with inclusion criteria designed to capture a broad range of real-world patients with diverse clinical and anatomical features. PCI optimization criteria are predefined using a common algorithm for online OCT or IVUS. The primary end point, which was tested for both noninferiority (margin, 3.1 percentage points for the risk difference) and superiority, is target-vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization) at 1 year. RESULTS: Up to the end of July 2020, approximately 1,200 "real-world" PCI patients have been randomly enrolled over 2 years. Enrollment is expected to be completed around the midterm of 2021, and primary results will be available by late 2022 or early 2023. CONCLUSION: This large-scale, multicenter, pragmatic-design clinical trial will provide valuable clinical evidence on the relative efficacy and safety of OCT-guided versus IVUS-guided PCI strategies in a broad population of patients undergoing PCI in the daily clinical practice.


Asunto(s)
Vasos Coronarios/diagnóstico por imagen , Intervención Coronaria Percutánea , Complicaciones Posoperatorias/prevención & control , Cirugía Asistida por Computador/métodos , Tomografía de Coherencia Óptica/métodos , Ultrasonografía Intervencional/métodos , Investigación sobre la Eficacia Comparativa , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Complicaciones Posoperatorias/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ajuste de Riesgo/métodos
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