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Postepy Dermatologii I Alergologii Aug 2023Lipomas are usually sporadic, asymptomatic lesions, and their clinical and histologic presentation does not pose diagnostic difficulties. In ambiguous cases, however,... (Review)
Review
Lipomas are usually sporadic, asymptomatic lesions, and their clinical and histologic presentation does not pose diagnostic difficulties. In ambiguous cases, however, knowledge of genetics is necessary. HMGA2 expression in adipose cells enables the differentiation of normal adipose tissue from lipoma and liposarcoma. Moreover, lipomas can be associated with genetic diseases, such as multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson's disease, or mitochondrial diseases. Lipomas can run in families (familial multiple lipomatosis) or be a part of genetic syndromes such as PTEN hamartoma tumor syndrome, Proteus syndrome, and Pai syndrome. This study aims to present the genetic basis of lipomas and diseases in which these lesions occur in the clinical picture.
PubMed: 37692275
DOI: 10.5114/ada.2023.129529 -
Orphanet Journal of Rare Diseases Sep 2023Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to...
BACKGROUND
Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to life-threatening systemic anomalies. Till now, only a limited number of cases and mutations were reported in Chinese population. The purpose of this study was to describe the somatic mutation spectrum of a cohort of Chinese pediatrics with vascular malformations.
METHODS
Pediatrics diagnosed with various vascular malformations were collected between May 2019 and October 2020 from Beijing Children's Hospital. Genomic DNA of skin lesion of each patient was extracted and sequenced by whole-exome sequencing to identify pathogenic somatic mutations. Mutations with variant allele frequency less than 5% were validated by ultra-deep sequencing.
RESULTS
A total of 67 pediatrics (33 males, 34 females, age range: 0.1-14.8 years) were analyzed. Exome sequencing identified somatic mutations of corresponding genes in 53 patients, yielding a molecular diagnosis rate of 79.1%. Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L. Non-hotspot mutations were prevalent in patients with PIK3CA-related overgrowth spectrum, accounting for 50.0% (11/22) of detected mutations. The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge-Weber syndrome and venous malformation, respectively. In addition, we identified a novel AKT1 p.Q79K mutation in Proteus syndrome and MAP3K3 p.E387D mutation in verrucous venous malformation.
CONCLUSIONS
The somatic mutation spectrum of vascular malformations in Chinese population is similar to that reported in other populations, but non-hotspot PIK3CA mutations may also be prevalent. Molecular diagnosis may help the clinical diagnosis, treatment and management of these pediatric patients with vascular malformations.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Class I Phosphatidylinositol 3-Kinases; East Asian People; Hemangioma; Mutation; Vascular Malformations
PubMed: 37658401
DOI: 10.1186/s13023-023-02860-w -
Journal of Nuclear Medicine : Official... Sep 2023Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally...
Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells. Here, we report the use of human epidermal growth factor receptor 2 (HER2) Ac-pretargeted radioimmunotherapy (PRIT) to treat a mouse model of human EOC SKOV3 xenografts growing as peritoneal carcinomatosis (PC). On day 0, 10 SKOV3 cells transduced with a luciferase reporter gene were implanted intraperitoneally in nude mice, and tumor engraftment was verified by bioluminescent imaging (BLI). On day 15, treatment was started using 1 or 2 cycles of 3-step anti-HER2 Ac-PRIT (37 kBq/cycle as Ac- DOTA), separated by a 1-wk interval. Efficacy and toxicity were monitored for up to 154 d. Untreated PC-tumor-bearing nude mice showed a median survival of 112 d. We used 2 independent measures of response to evaluate the efficacy of Ac-PRIT. First, a greater proportion of the treated mice (9/10 1-cycle and 8/10 2-cycle; total, 17/20; 85%) survived long-term compared with controls (9/27, 33%), and significantly prolonged survival was documented (log-rank [Mantel-Cox] = 0.0042). Second, using BLI, a significant difference in the integrated BLI signal area to 98 d was noted between controls and treated groups ( = 0.0354). Of a total of 8 mice from the 2-cycle treatment group (74 kBq total) that were evaluated by necropsy, kidney radiotoxicity was mild and did not manifest itself clinically (normal serum blood urea nitrogen and creatinine). Dosimetry estimates (relative biological effectiveness-weighted dose, where relative biological effectiveness = 5) per 37 kBq administered for tumors and kidneys were 56.9 and 16.1 Gy, respectively. One-cycle and 2-cycle treatments were equally effective. With immunohistology, mild tubular changes attributable to α-toxicity were observed in both therapeutic groups. Treatment of EOC PC-tumor-bearing mice with anti-HER2 Ac-PRIT resulted in histologic cures and prolonged survival with minimal toxicity. Targeted α-therapy using the anti-HER2 Ac-PRIT system is a potential treatment for otherwise incurable EOC.
Topics: Humans; Animals; Mice; Radioimmunotherapy; Mice, Nude; Peritoneal Neoplasms; Radioisotopes; Cell Line, Tumor
PubMed: 37348919
DOI: 10.2967/jnumed.122.265095 -
Journal of the Association of Medical... Sep 2023There is a paucity of studies investigating the population-based epidemiology of (MPP) group infections. Our objective was to determine the incidence, risk factors, and...
BACKGROUND
There is a paucity of studies investigating the population-based epidemiology of (MPP) group infections. Our objective was to determine the incidence, risk factors, and outcome of MPP group bloodstream infections (BSI), and explore species-specific differences.
METHODS
Population-based surveillance was conducted in the western interior of British Columbia, Canada, between April 1, 2010 and March 30, 2020.
RESULTS
Sixty-two incident MPP group BSI occurred for an annual incidence of 3.4 per 100,000 residents; rates for , , and species were 0.5, 2.6, and 0.3 per 100,000 population, respectively. The median year of age was 72.5 and was different ( = 0.03) among the groups. Most (92%) MPP group BSIs were of community-onset. Significant differences were observed in the distribution of clinical focus of infection, with most notably 81% of BSI due to genitourinary focus as compared to 60% and 22% for species and , respectively. Comorbid illnesses that increased the risk for development of MPP group BSI (incidence rate ratio; 95% CI) were HIV infection (37.0; 4.4-139.6), dementia (11.5; 6.1-20.7), cancer (6.4; 3.2-11.9), stroke 6.5 (2.8-13.3), and diabetes 2.7 (1.3-5.0). Thirteen, one, and none of the cases with , , and species BSI died within 30 days of index culture for respective all cause case-fatalities of 27%, 11%, and 0% ( = 0.1).
CONCLUSIONS
Although collectively responsible for a substantial burden of illness, the epidemiology of MPP group BSI varies significantly by species.
PubMed: 38250289
DOI: 10.3138/jammi-2022-0038 -
Acute and Critical Care May 2024Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high...
Polymicrobial infections are the leading causes of complications incurred from injuries that burn patients develop. Such patients admitted to the hospital have a high risk of developing hospital-acquired infections, with longer patient stays leading to increased chances of acquiring such drug-resistant infections. Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis are the most common multidrug-resistant (MDR) Gram-negative bacteria identified in burn wound infections (BWIs). BWIs caused by viruses, like Herpes Simplex and Varicella Zoster, and fungi-like Candida spp. appear to occur occasionally. However, the preponderance of infection by opportunistic pathogens is very high in burn patients. Variations in the causative agents of BWIs are due to differences in geographic location and infection control measures. Overall, burn injuries are characterized by elevated serum cytokine levels, systemic immune response, and immunosuppression. Hence, early detection and treatment can accelerate the wound-healing process and reduce the risk of further infections at the site of injury. A multidisciplinary collaboration between burn surgeons and infectious disease specialists is also needed to properly monitor antibiotic resistance in BWI pathogens, help check the super-spread of MDR pathogens, and improve treatment outcomes as a result.
PubMed: 38863352
DOI: 10.4266/acc.2023.01571 -
MSystems Aug 2023is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike...
is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria, may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060 genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related genomes, and pan-genome annotation to identify genes of interest not present in the model strain HI4320. Within our cohort, is composed of 10 named species and 5 uncharacterized genomospecies. can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome. IMPORTANCE Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on , but similar to other Gram-negative bacteria, has a mosaic genome with a linkage between phylogenetic position and accessory genome content. encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.
Topics: Humans; Proteus mirabilis; Proteomics; Phylogeny; Virulence; Virulence Factors
PubMed: 37341494
DOI: 10.1128/msystems.00159-23 -
PloS One 2023Average Nucleotide Identity (ANI) is becoming a standard measure for bacterial species delimitation. However, its calculation can take orders of magnitude longer than...
Average Nucleotide Identity (ANI) is becoming a standard measure for bacterial species delimitation. However, its calculation can take orders of magnitude longer than similarity estimates based on sampling of short nucleotides, compiled into so-called sketches. These estimates are widely used. However, their variable correlation with ANI has suggested that they might not be as accurate. For a where-the-rubber-meets-the-road assessment, we compared two sketching programs, mash and dashing, against ANI, in delimiting species among Esterobacterales genomes. Receiver Operating Characteristic (ROC) analysis found Area Under the Curve (AUC) values of 0.99, almost perfect species discrimination for all three measures. Subsampling to avoid over-represented species reduced these AUC values to 0.92, still highly accurate. Focused tests with ten genera, each represented by more than three species, also showed almost identical results for all methods. Shigella showed the lowest AUC values (0.68), followed by Citrobacter (0.80). All other genera, Dickeya, Enterobacter, Escherichia, Klebsiella, Pectobacterium, Proteus, Providencia and Yersinia, produced AUC values above 0.90. The species delimitation thresholds varied, with species distance ranges in a few genera overlapping the genus ranges of other genera. Mash was able to separate the E. coli + Shigella complex into 25 apparent phylogroups, four of them corresponding, roughly, to the four Shigella species represented in the data. Our results suggest that fast estimates of genome similarity are as good as ANI for species delimitation. Therefore, these estimates might suffice for covering the role of genomic similarity in bacterial taxonomy, and should increase confidence in their use for efficient bacterial identification and clustering, from epidemiological to genome-based detection of potential contaminants in farming and industry settings.
Topics: Animals; Escherichia coli; Gammaproteobacteria; Dickeya; Genomics; Agriculture
PubMed: 37708115
DOI: 10.1371/journal.pone.0291492 -
Maedica Dec 2023Until now, there have been few investigations on the efficacy of fosfomycin in the treatment of patients with uncomplicated urinary tract infections (UTIs). The present...
Until now, there have been few investigations on the efficacy of fosfomycin in the treatment of patients with uncomplicated urinary tract infections (UTIs). The present study is aimed to examine how fosfomycin affects females with lower UTIs. A total of 200 female patients who visited the women's clinic at Amir-Al-Momenin Hospital between 2020 and 2021 were examined in the present study. Patients were randomly divided into two groups of 100 people each, with one group receiving fosfomycin (a single 3 g dose) and the other one receiving cephalexin (a five-day regimen at 0.5 g four times daily). Then, one week and one month after treatment, the patients underwent a urine culture test. The data were collected and further analyzed in SPSS statistics software version 26. According to the study findings, the mean age of females suffering from lower UTI was 25.45 ± 5.85 years. Besides, the collected data revealed that 85.5% of females diagnosed with lower UTI had E. coli. In addition, the frequency of females with Staphylococcus saprophyticus, Proteus spp and Klebsiella were 9%, 3% and 2.5%, respectively. Also, the frequency of women with UTI for E. coli, Staphylococcus saprophyticus, Proteus spp and Klebsiella were 85.5%, 9%, 3.2% and 2.5%, respectively. One month after treatment, urine culture showed positive results in 98% of patients who were treated with fosfomycin and 95% of those who received cephalexin. Fosfomycin can be administrated to treat uncomplicated UTIs in women with a high level of confidence, as an alternative to cephalexin.
PubMed: 38348083
DOI: 10.26574/maedica.2023.18.4.593 -
Translational Lung Cancer Research Nov 2023The tumor-resident microbiota in lung squamous cell carcinoma (LUSC) has been reported to be associated with the initiation and progression of cancer. And the gut...
BACKGROUND
The tumor-resident microbiota in lung squamous cell carcinoma (LUSC) has been reported to be associated with the initiation and progression of cancer. And the gut microbiome can modulate the efficacy of immunotherapies. However, it remains to be understood whether the tumor-resident microbiome promotes lymph node (LN) metastasis, which is important for clinical decision-making and prediction of a patient's prognosis. To investigate the potential role of tumor-resident microbiota in LN metastasis, we worked on the microbiota-geneset interaction profiles to characterize the molecular pathogenesis.
METHODS
RNA sequencing data and their matched clinical and genomic information were obtained from The Cancer Genome Atlas database. The matched microorganism quantification data were accessed via the cBioPortal database. The mutational signature analysis, transcriptome analysis, gene set enrichment analysis, immune infiltration, and microbiota-geneset network analysis were performed.
RESULTS
In this paper, we identified the tumor microbiota composition and microbial biomarkers in patients with and without LN metastases. In addition, significantly upregulated gene sets characterize the transcript profiles of patients with LN metastases, for example, Myc Targets, E2F Targets, G2M Checkpoint, Mitotic Spindle, DNA Repair, and Oxidative Phosphorylation. Finally, we found that and were strongly correlated with gene sets related to tumor development and energy metabolism in the networks of patients with LN metastases.
CONCLUSIONS
We found the associations between intratumor microbiota and transcripts. Our results shed light on the correlation network of and , which may serve as a novel strategy for modulating LN metastasis.
PubMed: 38090530
DOI: 10.21037/tlcr-23-357 -
Frontiers in Molecular Neuroscience 2023Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in...
INTRODUCTION
Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of ()-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.
METHODS
We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect -induced disease progression and pathology.
RESULTS AND DISCUSSION
Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for -induced pathological progression and provides evidence of metabolic alterations associated with -mediated pathology of brain neurodegeneration.
PubMed: 37635904
DOI: 10.3389/fnmol.2023.1201073