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Frontiers in Cellular and Infection... 2024Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the...
INTRODUCTION
Accurate identification of the etiology of orthopedic infection is very important for correct and timely clinical management, but it has been poorly studied. In the current study we explored the association of multiple bacterial pathogens with orthopedic infection.
METHODS
Hospitalized orthopedic patients were enrolled in a rural hospital in Qingdao, China. Wound or exudate swab samples were collected and tested for twelve bacterial pathogens with both culture and multiplex real time PCR.
RESULTS AND DISCUSSION
A total of 349 hospitalized orthopedic patients were enrolled including 193 cases presenting infection manifestations upon admission and 156 with no sign of infection. Orthopedic infection patients were mainly male (72.5%) with more lengthy hospital stay (median 15 days). At least one pathogen was detected in 42.5% (82/193) of patients with infection while 7.1% (11/156) in the patients without infection ( < 0.001). was the most prevalent causative pathogen (15.5%). Quantity dependent pathogen association with infection was observed, particularly for and , possibly indicating subclinical infection. Most of the patients with detected pathogens had a previous history of orthopedic surgery (odds ratio 2.8, = 0.038). Pathogen specific clinical manifestations were characterized. Multiplex qPCR, because of its high sensitivity, superior specificity, and powerful quantification could be utilized in combination with culture to guide antimicrobial therapy and track the progression of orthopedic infection during treatment.
Topics: Humans; Female; Male; Middle Aged; Aged; Multiplex Polymerase Chain Reaction; China; Adult; Bacteria; Bacterial Infections; Hospitalization; Aged, 80 and over; Real-Time Polymerase Chain Reaction; Hospitals, Rural
PubMed: 38938882
DOI: 10.3389/fcimb.2024.1394352 -
Frontiers in Cellular and Infection... 2024The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The...
The Asian citrus psyllid (ACP) Kuwayama is the leading vector of Liberibacter asiaticus (Las), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of Las within ACP are critical to understanding how the transmission, spread and infection of Las occurs within its host vector in nature. In this study, the distribution and titer changes of Las in various tissues of ACP 5 instar nymphs and adults were examined by (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5 instar nymphs and adults were infected with Las following feeding on infected plants, and that Las had widespread distribution in most of the tissues of ACP. The titers of Las within the midgut, salivary glands and hemolymph tissues were the highest in both 5 instar nymphs and adults. When compared with adults, the titers of Las in these three tissues of 5 instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of Las demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of Las with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of Las, which is of much importance for developing novel strategies to halt the spread of Las, and therefore contribute to the efficient prevention and control of HLB.
Topics: Animals; Hemiptera; Insect Vectors; Plant Diseases; Nymph; Citrus; In Situ Hybridization, Fluorescence; Rhizobiaceae; Real-Time Polymerase Chain Reaction; Salivary Glands; Hemolymph
PubMed: 38938879
DOI: 10.3389/fcimb.2024.1408362 -
Frontiers in Cellular and Infection... 2024Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in...
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in some cases. In general, when infection occurs, the body upregulates inflammatory responses to eliminate pathogenic microorganisms to protect the host from infection. However, EV71 may inhibit host's innate immunity to promote virus infection. At present, it is not fully understood how EV71 hijack the host cells for its own replication. Toll-like receptor 4 (TLR4), a natural immune receptor, historically associated with bacterial endotoxin-induced inflammatory responses. However, it is still unclear whether and how TLR4 is altered during EV71 infection. In this study, we observed a reduction in both TLR4 protein and gene transcript levels in RD, GES-1, and Vero cells following EV71 infection, as detected by RT-qPCR, immunofluorescence staining and western blot. Furthermore, we observed that the TLR4 downstream molecules of MYD88, p-NF-κB p65, p-TBK1 and related inflammatory cytokines were also reduced, suggesting that antiviral innate immune and inflammatory response were suppressed. To determine the impact of TLR4 changes on EV71 infection, we interfered EV71-infected RD cells with TLR4 agonist or inhibitor and the results showed that activation of TLR4 inhibited EV71 replication, while inhibition of TLR4 promote EV71 replication. Besides, EV71 replication was also promoted in TLR4 siRNA-transfected and EV71-infected RD cells. This suggests that down-regulation the expression of TLR4 by EV71 can inhibit host immune defense to promote EV71 self-replication. This novel mechanism may be a strategy for EV71 to evade host immunity.
Topics: Toll-Like Receptor 4; Enterovirus A, Human; Humans; Virus Replication; Signal Transduction; Animals; Vero Cells; Chlorocebus aethiops; Immunity, Innate; Host-Pathogen Interactions; Inflammation; Myeloid Differentiation Factor 88; Cell Line; Protein Serine-Threonine Kinases; Cytokines; NF-kappa B; Hand, Foot and Mouth Disease
PubMed: 38938877
DOI: 10.3389/fcimb.2024.1393680 -
JACC. Advances Mar 2024Patients with likely pathogenic/pathogenic desmoplakin () variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular...
BACKGROUND
Patients with likely pathogenic/pathogenic desmoplakin () variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting.
OBJECTIVES
The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (-TFC+).
METHODS
-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics.
RESULTS
Among 252 -TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank = 0.0239). History of nonsustained VT (aHR 2.097; = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age ( = 0.723) nor male sex ( = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]).
CONCLUSIONS
-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in -TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, -TFC+ patients with nonsustained VT should be considered as high-risk.
PubMed: 38938828
DOI: 10.1016/j.jacadv.2024.100832 -
Frontiers in Cardiovascular Medicine 2024This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old...
This case report details the identification of a novel likely pathogenic splicing variant in the TTN gene, associated with dilated cardiomyopathy (DCM), in a 42-year-old male patient presenting with early-onset heart failure and reduced ejection fraction. DCM is a nonischemic heart condition characterized by left biventricular dilation and systolic dysfunction, with approximately one-third of cases being familial and often linked to genetic mutations. The TTN gene, encoding the largest human protein essential for muscle contraction and sarcomere structure, is implicated in about 25% of DCM cases through mutations, especially truncating variants. Our investigation revealed a previously unreported G > C mutation at the splice acceptor site in intron 356 of TTN, confirmed by Sanger sequencing and not found in population databases, suggesting a novel contribution to the understanding of DCM etiology. The case emphasizes the critical role of the TTN gene in cardiac function and the genetic complexity underlying DCM. A comprehensive literature review highlighted the prevalence and significance of splice variants in the TTN gene, particularly those affecting the titin A-band, which is known for its role in muscle contraction and stability. This variant's identification underscores the importance of genetic screening in patients with DCM, offering insights into the disease's familial transmission and potential therapeutic targets. Our findings contribute to the expanding knowledge of genetic factors in DCM, demonstrating the necessity of integrating genetic diagnostics in cardiovascular medicine. This case supports the growing evidence linking splicing mutations in specific regions of the TTN gene to DCM development and underscores the importance of genetic counseling and testing in managing heart disease.
PubMed: 38938651
DOI: 10.3389/fcvm.2024.1387063 -
Frontiers in Plant Science 2024As an evergreen shrub, plays a crucial role in urban landscape construction, and its growth is affected by severe foliar anthracnose caused by spp. However, the...
As an evergreen shrub, plays a crucial role in urban landscape construction, and its growth is affected by severe foliar anthracnose caused by spp. However, the biodiversity of species associated with anthracnose on remains undetermined. This study involved a two-year collection of leaf samples with typical anthracnose symptoms from 9 districts in Beijing, China. A total of 194 isolates were obtained, and eight species were subsequently identified using morphological characteristics and molecular identification with the , , , , and genes, as well as the rDNA-ITS region. These species included , , , , , , , and with being the most prevalent (57%), followed by and . Furthermore, , and are reported for the first time as causal agents of anthracnose on worldwide, and is newly reported to be associated with anthracnose in China. Pathogenicity tests revealed that all tested isolates exhibited pathogenicity in the presence of wounds, emphasizing the need to avoid artificial or mechanical wounds to prevent infection in management. The EC values of five fungicides, namely difenoconazole, flusilazole, tebuconazole, hexaconazole, and prochloraz, were found to be less than 10 mg/L, indicating their strong potential for application. Notably, the EC of prochloraz was less than 0.05 mg/L for . These findings offer valuable insights for the management of anthracnose on .
PubMed: 38938640
DOI: 10.3389/fpls.2024.1411625 -
JACC. Advances Dec 2023Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the...
BACKGROUND
Recent evidence has shown that reproductive factors are associated with an increased risk of heart failure with preserved ejection fraction in women. However, the pathogenic pathways underlying this relationship are unclear. Subclinical myocardial fibrosis has been found to be a common pathway in a large proportion of patients with heart failure with preserved ejection fraction.
OBJECTIVES
This study examined the relationship between vital reproductive factors (parity, pregnancy, age at menopause, and use of hormone replacement therapy [HRT]) with interstitial myocardial fibrosis (IMF) and myocardial scar measured by cardiac magnetic resonance imaging (CMR) T1 mapping and late gadolinium enhancement, respectively.
METHODS
There were 596 female participants (mean age 67 ± 8 years) enrolled in MESA (Multi-Ethnic Study of Atherosclerosis) who had complete parity data and underwent CMR. Parity was categorized as 0 live births, 1 to 2, 3 to 4, and ≥5 live births. Multivariable regression models were constructed to assess the associations of parity status, history of null gravidity, age at menopause and HRT with CMR obtained measures of IMF (extracellular volume [ECV], native-T1 time) and myocardial scar.
RESULTS
Women with a history of nulliparity had greater ECV% (β = 0.95 ± 0.28, = 0.001) and native-T1 ms (β = 10.6 ± 4.9, = 0.03) than those who had 1 to 2 live births. These associations were independent of age, traditional cardiovascular risk factors, and interim cardiovascular events. Similar associations were found for women with a history of null gravidity compared to those with a history of pregnancy (ECV% [β = 0.7 ± 0.3, = 0.02] and native-T1 ms [β = 10.6 ± 5.2, = 0.04]). There was no association between age at menopause and HRT with markers of IMF. There were no associations between parity status, null gravidity, and age of menopause with the presence of myocardial scar; however, those who used HRT were independently associated with a lesser risk of myocardial scar (OR: 0.20; 95% CI: 0.05-0.82).
CONCLUSIONS
In a multiethnic cohort, women with a history of nulliparity or null gravidity had greater IMF defined by CMR, while those who used HRT were less likely to have myocardial scar.
PubMed: 38938498
DOI: 10.1016/j.jacadv.2023.100703 -
International Journal of Genomics 2024related hypertriglyceridemia occurs due to biallelic variants of this gene. Here, genotype-phenotype architecture of all pathogenic variants is investigated among...
related hypertriglyceridemia occurs due to biallelic variants of this gene. Here, genotype-phenotype architecture of all pathogenic variants is investigated among heterozygous and homozygous individuals. Clinical heterogeneity of various types of the variants is also described, and pancreatitis in more than half of homozygotes carrying chain-termination variants is highlighted as well. For this study, patients were selected who had a plasma triglyceride level above 250 mg/dL. The coding and intronic regions of the gene were amplified using the Sanger sequencing to investigate the presence of variants. The genotypes, lipid profiles, and detailed clinical features were documented for all -related patients and heterozygous individuals. Pathogenicity of the variants was predicted and categorized using available bioinformatics tools such as MutationTaster and PolyPhen-2 and ACMG criteria. MetaDome and Phyre2 were applied for structural and functional in silico analyses. 40% (12 out of 30) of variants were chain-termination (nonsense and frameshift) variants. These types of variants were determined in 60.53% of patients. 55% of these patients showed pancreatitis followed by lipemia retinalis (29%), abdominal pain (24%), hepatosplenomegaly (24%), and xanthomas (18%). The mean age of onset was about 22 years old. In at least 50% of 38 homozygous individuals, the TG level was more than 2000 mg/dL. More than 25% of heterozygous individuals showed at least one symptom. Pancreatitis and a severe form of HTG were found in 5 and 2% of heterozygous individuals, respectively. The main clinical features of -related hypertriglyceridemia include pancreatitis, lipemia retinalis, abdominal pain, hepatosplenomegaly, and xanthomas. Nonsense and frameshift homozygous variants usually lead to a severe form of hypertriglyceridemia. Pancreatitis is one of the main consequences of these types of mutations; thus, it is important to consider this point when evaluating asymptomatic individuals. Heterozygous individuals may become symptomatic due to the role of unknown modifying agent including environmental genetic factors.
PubMed: 38938447
DOI: 10.1155/2024/6653857 -
JACC. Advances Oct 2023Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications...
BACKGROUND
Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families.
OBJECTIVES
The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes.
METHODS
A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants.
RESULTS
Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up.
CONCLUSIONS
The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives.
PubMed: 38938358
DOI: 10.1016/j.jacadv.2023.100604 -
Case Reports in Obstetrics and... 2024Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. . A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient's serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-.
CONCLUSION
The presence of monoclonal IgG- in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.
PubMed: 38938323
DOI: 10.1155/2024/2223281