Phenotypic Characteristics Research Articles

Genomic epidemiology and phenotypic characterization of Staphylococcus aureus isolated from atopic dermatitis patients in South China

Atopic dermatitis (AD) is a multifactorial, chronic relapsing disease. Staphylococcus aureus is the key microbial factor in AD, linked to disease activity. However, there is limited knowledge of genomic prevalence characteristics and phenotypic features of S. aureus in AD patients in China. We investigated 108 S. aureus of AD in China and globally publicly available genome sequences of 579 S. aureus of AD. Sequence type (ST) 7, ST15 and ST188 were the major lineages in China. Genes esaC, esxB, and sea were only detected in ST7, potentially contributing to its prevalence in AD. ST188 exhibited high virulence and adhesion, possibly due to the cna gene. Phylogenetic and population structure analysis revealed that 579 strains of global AD were classified into 15 sequence clusters (SCs), with SC5, SC2, and SC7 dominating. S. aureus of Chinese AD patients was mainly distributed in SC2, SC7, and SC12. Comparative genomic highlighted genes linked to AD, including enterotoxins (seh, selk, selq, entH), adhesion genes (fnbA, fnbB, sdrD, map, fib, narH). From China and global perspectives, we analyzed S. aureus’s genomic epidemic traits, phylogeny, and population structure in AD skin. These findings contribute to understanding S. aureus-host interactions and genomic diversity in AD.

Combating enteropathogenic and multidrug resistant Escherichia coli using the lytic bacteriophage vB_EcoM_ECO78 which disrupts bacterial biofilm formation and exhibits a remarkable environmental stability.

The current study aimed to establish a phenotypic and genotypic characterization record of a novel lytic bacteriophage (phage) against multidrug-resistant (MDR) Escherichia coli (E. coli) infections. Phenotypic characterization of the isolated phage included the assessment of phage morphology, host range, stability, and antibiofilm activity. The isolated phage vB_EcoM_ECO78 demonstrated high lytic activity against MDR E. coli and E. coli serotypes O78:K80:H12 and O26:H11. Additionally, it showed a marked antibiofilm activity and high physical stability at a wide range of temperatures and pH. Genotypic investigations identified a double-stranded DNA genome of 165 912 base pairs (bp) spanning 258 open reading frames (ORFs), out of which 149 ORFs were identified and annotated. In vivo analysis further confirmed the therapeutic potential of vB_EcoM_ECO78 which effectively increased the survival of mice infected with MDR E. coli. The isolated phage vB_EcoM_ECO78 exhibits considerable stability and antibiofilm activity against MDR E. coli isolates, supported by notable environmental fitness and in vivo antibacterial capability.

Neural activity analysis of depressive disorder model mice using the Toyohashi probe

Abstract Major depressive disorder (MDD) is one of the most chronic disease and life-threatening 
illnesses globally. However, mainstay medications do not provide sufficient relief for 
depressive patients with MDD. Thus, there is an urgent need for the development of analysis 
methods that allow drug screening and observation of phenotypes. We developed a tiny 
microneedle electrode block module called the Toyohashi probe, which can be inserted into 
a mouse brain with minimal invasiveness using the vapor–liquid–solid method. Photo
response was measured in the primary visual cortex of Nrf2 knockout (KO) mice using the 
Toyohashi probe. We then successfully identified characteristic electrophysiological 
phenotypes, such as abnormal excitability of neurons and higher firing frequency and spikes, 
in Nrf2 KO mice. In conclusion, our new microneedle electrode can be used in vulnerable 
disease model mice to record stable neuronal activity stably in vulnerable disease model 
mice and observe characteristic phenotypes as indicators for drug efficacy.

Acidovorax sacchari sp. nov., a pathogen causing red stripe of sugarcane in Japan.

Phytopathogenic bacteria (MAFF 311311T and MAFF 311313) were isolated from sugarcane plants exhibiting leaf stripe symptoms associated with red stripe disease in Okinawa Prefecture, Japan. The strains were Gram-reaction-negative, aerobic, motile with one polar flagellum, rod-shaped and non-spore-forming. The genomic DNA G+C content was 69.0 mol%, and the major cellular fatty acids (>10 % of the total fatty acids) included summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0 and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). Phylogenomic analyses using whole-genome sequences consistently placed these strains within the genus Acidovorax. However, their phylogenetic positions did not correspond to any known species within this genus. Comparative analyses, including average nucleotide identity and digital DNA-DNA hybridization with closely related species, yielded values below the thresholds for prokaryotic species delineation (95-96 and 70 %, respectively), with the highest values observed for Acidovorax oryzae ATCC 19882T (93.98 and 54.3 %, respectively). Phenotypic characteristics, cellular fatty acid composition and a repertoire of secretion systems and their effectors can differentiate these strains from their closest relatives. The phenotypic, chemotaxonomic and genotypic data obtained in this study indicate that MAFF 311311T and MAFF 311313 constitute a novel species within the genus Acidovorax, for which we propose the name Acidovorax sacchari sp. nov., with MAFF 311311T (=ICMP 25276T) designated as the type strain.

Phenotypic Differences between Patients with Smoking Chronic Obstructive Pulmonary Disease and Non-smoking Chronic Obstructive Pulmonary Disease

ABSTRACT Background: In low- and middle-income countries, causes other than tobacco smoking contribute more to the development of chronic obstructive pulmonary disease (COPD). In India, non-smoking-related COPD (NS-COPD) is common due to the high prevalence of pulmonary tuberculosis and biomass fuel exposure. Our study aims to know the phenotypic differences between smoking-related COPD (S-COPD) and NS-COPD patients. Materials and Methods: The study included 217 patients, who visited the outdoor department of a tertiary care center. A detailed clinical history was obtained; radiological and hematological investigations, spirometry, and a 6-min walk test were performed. Results: Of 217 patients, 100 had S-COPD, and 117 had NS-COPD. Male patients were predominantly affected (P < 0.001) in both groups. There were significant differences in the age group (P < 0.001), body mass index (P < 0.045), blood hemoglobin levels (P < 0.02), forced vital capacity (FVC) (P = 0.02), postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) (P < 0.006), and FEV1/FVC ratio (P < 0.001) between patients with smoking and S-COPD and NS-COPD. Emphysema was more common in S-COPD, whereas COPD-bronchiectasis overlap was more common among NS-COPD patients. Cough was more common, and airflow obstruction was less severe in nonsmokers. There was no significant difference in the exercise capacity. Conclusion: The NS-COPD patients present at younger age, with more COPD-bronchiectasis overlap phenotype. They have less severe airflow obstruction and more postbronchodilator reversibility. Understanding phenotypic characteristics is necessary for accurate diagnosis and management of COPD in nonsmokers.

Heterologous expression of SpsTAC2 in Arabidopsis affected branch angle and secondary vascular system development

ABSTRACT To investigate the biological functions of Tiller Angle Control 2 (TAC2) in Salix psammophila. In this study, TAC2 was cloned from Salix psammophila, and an overexpression and subcellular localization expression vector for the SpsTAC2 gene was constructed. The SpsTAC2 gene was overexpressed in Arabidopsis and analyzed for phenotypic changes. The subcellular localization of SpsTAC2 was analyzed via Agrobacterium-mediated transient expression in onion (Allium cepa L.) epidermal cells. Phenotypic characterization of SpsTAC2 overexpressing Arabidopsis strains revealed that the branching angle of the transgenic strains was significantly greater than that of the wild type, and the anatomical structures of the stems and hypocotyls of the transgenic strains indicated that the vascular system of the transgenic strains developed more slowly than did that of the wild type. The subcellular localization of the SpsTAC2 gene revealed that the localization signals of the SpsTAC2 gene were mainly in the nucleus, and weak signals also appeared in the cell membrane, suggesting that the SpsTAC2 gene was mainly expressed mainly in the nucleus, with a small amount of expression in the cell membrane. This findings suggest that the SpsTAC2 gene influences the development of the branching angle of plants and xylem, and exerts its effects mainly in the nucleus and membrane. This study can help to characterize the regulatory effect of the TAC gene on the branching angle and explore its effect on the branching angle and vascular system development, and also help to explore the possible molecular regulatory mechanism, which can provide a theoretical basis for further elucidation of the mechanism of action of the IGT gene family.

Phenotypic and Molecular Characterization of Extended-Spectrum β-Lactamase, Plasmid-Mediated- AmpC, and Carbapenemase-Producing Enterobacteriaceae Isolated from Companion and Production Animals in Brazil.

The crisis of bacterial resistance is an emerging One Health challenge, driven by the overuse of antimicrobials in medical and agricultural settings. This study aimed to investigate extended-spectrum β-lactamase (ESBL), Ampicillinase (AmpC), and carbapenemase production, and the presence of genes encoding these enzymes in Escherichia coli, Klebsiella spp., and Proteus spp., major contributors to infections and resistance isolates from animals. From 2016 to 2021, 130 multidrug-resistant (MDR) or extensively drug-resistant (XDR) isolates were recovered from the secretions, excretions, and organs of companion and production animals with active infections. Antibacterial sensitivity tests, along with phenotypic and genotypic detection of resistance enzymes, were performed. To the best of our knowledge, this is the first study in Brazil to estimate the prevalence of XDR Enterobacteriales isolated from companion and production animals, which accounted for 13.8% of the strains. Statistically significant differences (P < 0.05) in resistant bacteria between different classes and within the same class of antibacterial bacteria were found. The statistical probability between genotypic detection of ESBL (OR = 3.1) and phenotypic tests for AmpC (OR = 2.3) was also established. Approximately 32.3%, 17.6%, and 16.8% of the strains had positive phenotypic tests for ESBL, AmpC, and carbapenemases, respectively. Genetic analysis revealed the presence of blaCTX-M (60.0%), blaAmpC (9.18%), blaKPC-2 (0.76%), and blaNDM (1.52%). AmpC genes were identified in 8.46% of the samples, with blaCMY being the most frequent (6.92%), followed by blaDHA (0.77%), and blaFOX (0.77%). The sequenced amplicons were deposited in NCBI. This study reveals critical data on Enterobacteriaceae with antibacterial resistance genes isolated from animals and may pose a significant threat to One health.

Recent advances in adipose-derived mesenchymal stem cell-derived exosomes for regulating macrophage polarization

Adipose-derived mesenchymal stem cells (ADSCs) exhibit superior immunomodulatory properties and have broad therapeutic applications. They induce macrophage M2 polarization for anti-inflammatory responses. Exosomes derived from ADSCs (ADSC-EXOs) exhibit biological functions similar to those of ADSCs but can circumvent the limitations associated with cellular injection therapies. Potent anti-inflammatory substances contained in exosomes include the glycoprotein MFGE8, the cytokines such as prostaglandin E2, IL-6, and IGF, as well as non-coding nucleotides (miR-451a, miR-23, miR-30d-5p, let-7, lncRNA DLEU2, circRps5, Circ-Ptpn4, and mmu_ circ_0001359). The anti-inflammatory and immunomodulatory properties of these exosomes provide new perspectives for therapeutic approaches for graft inflammation, bone healing, acute lung injury, kidney stones, myocardial infarction, and diabetes-related diseases. This review summarizes the contents and functions of ADSC-EXOs, outlines their properties and the characteristics of macrophage phenotypes, and emphasizes their impact on macrophage polarization and their contribution to immune-related diseases.

Characterization of the Cystic Phenotype Associated with Monoallelic ALG8 and ALG9 Pathogenic Variants.

Autosomal dominant polycystic kidney disease (ADPKD) is a common, inherited nephropathy often resulting in kidney failure. It is genetically heterogeneous; along with the major genes, PKD1 and PKD2, at least 8 others have been suggested. ALG8 pathogenic variants have been associated with autosomal dominant polycystic liver disease and implicated in ADPKD, while ALG9 has been suggested as an ADPKD gene, but details of the phenotypes and penetrance are unclear. We screened >3900 families with cystic kidneys and/or livers using global approaches to detect ALG8 or ALG9 pathogenic variants. In addition, population cohorts with sequence data (Genomics England 100kGP (100kGP), UK Biobank (UKBB), and Mayo Clinic Biobank (MCBB)), were screened for ALG8/ALG9 pathogenic variants. Multicenter screening of individuals with polycystic kidney and/or liver disease identified 51 (1.3%) ALG8 (7 multiplex) and 23 (0.6%) ALG9 (5 multiplex) families; frequencies that were ∼10x and ∼24x greater than non-polycystic kidney disease (PKD) controls. Analysis of individuals with PKD phenotypes in 100kGP, UKBB, and MCBB identified 9 ALG8 (0.39%) and 9 ALG9 (0.39%) families, an enriched frequency over controls. Two individuals had PKD1 and ALG8 pathogenic changes. Eighty-nine percent of individuals with ALG8 mutations with imaging in the entire MCBB had kidney cysts (56%, >10 cysts), with greater median kidney and liver cyst numbers than controls. For ALG9, 78% had kidney cysts (27%, >10 cysts). Individuals with ALG8 mutations typically had mild cystic kidneys with limited enlargement. Liver cysts were common (71%) with enlarged livers (>2L) found in 11/62 patients although surgical intervention was rare. The ALG9 kidney phenotype was also of mild cystic kidneys but enlarged livers were rare; for both genes chronic kidney disease or kidney failure were rare. ALG8 and ALG9 are defined as cystic kidney/liver genes but with limited penetrance for lower eGFR.

Generalizable Metamaterials Design Techniques Inspire Efficient Mycelial Materials Inverse Design.

Fungal mycelial materials can mimic numerous nonrenewable materials; they are even capable of outperforming certain materials at their own applications. Fungi's versatility makes mock leather, bricks, wood, foam, meats, and many other products possible. That said, there is currently a critical need to develop efficient mycelial materials design techniques. In mycelial materials, and the wider field of biomaterials, design is primarily limited to costly forward techniques. New mycelial materials could be developed faster and cheaper with robust inverse design techniques, which are not currently used within the field. However, computational inverse design techniques will not be tractable unless clear and concrete design parameters are defined for fungi, derived from genotype and bulk phenotype characteristics. Through mycelial materials case studies and a comprehensive review of metamaterials design techniques, we identify three critical needs that must be addressed to implement computational inverse design in mycelial materials. These critical needs are the following: 1) heuristic search/optimization algorithms, 2) efficient mathematical modeling, and 3) dimensionality reduction techniques. Metamaterials researchers already use many of these computational techniques that can be adapted for mycelial materials inverse design. Then, we suggest mycelium-specific parameters as well as how to measure and use them. Ultimately, based on a review of metamaterials research and the current state of mycelial materials design, we synthesize a generalizable inverse design paradigm that can be applied to mycelial materials or related design fields.

Role of metabolism, resistance, and/or antagonism as drivers of endomicrobiomes assemblage in Origanum heracleoticum L

The understanding of selective forces driving the compartmentalization of microbiota in plants remains limited. In this study, we performed a phenotypic characterization of bacterial endophytes isolated from the medicinal plant Origanum heracleoticum, together with the determination of the antibiotic resistance profiles and the antagonistic interactions of communities within and across different plant organs. Results revealed organ-related differences in the metabolic capabilities of bacteria, with those associated with stems displaying the highest metabolic activity for carbon sources. Contrarily, the patterns of antibiotic resistance appeared closely aligned with the taxonomical classification of the endophytes. The presence of antagonistic interactions, likely spurred by resource limitations, favor bacteria exhibiting greater metabolic plasticity. In conclusion, this research advances our comprehension of the intricate dynamics between plants and their associated microbiota, indicating that its composition is mainly influenced by forces contributing to the selection of distinct functions and phenotypic traits.

Human γδ T cells in the tumor microenvironment: Key insights for advancing cancer immunotherapy.

The role of γδ T cells in antitumor responses has gained significant attention due to their major histocompatibility complex (MHC)-independent killing mechanisms, which are functionally distinct from conventional αβ T cells. Notably, γδ tumor-infiltrating lymphocytes (TILs) have been identified as favorable prognostic markers in various cancers. However, the γδ TIL subsets, including Vδ1, Vδ2, and Vδ3, exhibit distinct prognostic implications and phenotypes within the tumor microenvironment (TME). Although the underlying mechanisms remain unclear, recent studies suggest that these subset-specific differences may arise from divergent activation pathways. Vδ1 TILs appear to be mainly activated by γδ T-cell receptor (TCR) signaling, whereas Vδ2 TILs seem to rely on alternative pathways, such as natural killer (NK) receptor-mediated activation. In addition to phenotypic studies, cancer immunotherapies, such as engineered γδ T cells, γδ T-cell engagers, and γδ TCR-based therapies, are under active development. However, despite these advancements, functional heterogeneity and limited persistence within TME remain significant challenges. Overcoming these obstacles could position γδ T-cell therapies as a transformative platform for cancer treatment. Here, we review recent findings on the prognostic significance of human γδ T cells, their phenotypic characteristics, and advances in γδ T-cell therapies, offering valuable insights for the development of novel cancer immunotherapies.

Clinical aspects and characterization of Pseudomonas aeruginosa isolated from patients infected with SARS-CoV-2.

This study aimed to identify and characterize Pseudomonas aeruginosa isolates from patients infected and uninfected with SARS-CoV-2, focusing on their phenotypic characteristics and antimicrobial resistance profiles. A total of 100P. aeruginosa isolates were obtained from patients admitted to a hospital in Presidente Prudente, SP, in 2021. The isolates were assessed for antimicrobial resistance, pyocyanin, lipase and phospholipase C production, biofilm formation, and the presence of virulence factor genes, including those associated with metallo-β-lactamase (MBL) production. Among the isolates, 58 were from patients infected with SARS-CoV-2 and 42 from non-infected patients. P. aeruginosa was predominantly isolated from tracheal secretion samples in infected patients, while urine samples were more common in non-infected patients. Notably, patients with SARS-CoV-2 exhibited a higher rate of resistance to aztreonam and used a wider range of antibiotics. Isolates from infected patients demonstrated higher phospholipase C production and a greater number classified as strong biofilm formers. Virulence factor genes were present in at least 70% of the isolates, while only three isolates showed genes for MBL production. The findings of this study indicate that the COVID-19 pandemic creates a favorable environment for the increase of secondary infections by P. aeruginosa. Understanding the characteristics and resistance profiles of these isolates is crucial for improving treatment strategies and patient outcomes.

Genomic insights into demographic history, structural variation landscape, and complex traits from 514 Hu sheep genomes

Hu sheep is an indigenous breed from the Taihu Lake Plain in China, known for its high fertility. Although Hu sheep belong to the Mongolian group, their demographic history and genetic architecture remain inconclusive. Here, we analyze 697 sheep genomes from representatives of Mongolian sheep breeds. Our study suggests that the ancestral Hu sheep first separated from the Mongolian group approximately 3000 years ago. As Hu sheep migrated from the north and flourished in the Taihu Lake Plain around 1000 years ago, they developed a unique genetic foundation and phenotypic characteristics, which are evident in the genomic footprints of selective sweeps and structural variation landscape. Genes associated with reproductive traits (BMPR1B and TDRD10) and horn phenotype (RXFP2) exhibit notable selective sweeps in the genome of Hu sheep. A genome-wide association analysis reveals that structural variations at LOC101110773, MAST2, and ZNF385B may significantly impact polledness, teat number, and early growth in Hu sheep, respectively. Our study offers insights into the evolutionary history of Hu sheep and may serve as a valuable genetic resource to enhance the understanding of complex traits in Hu sheep.

Developmental trajectories of atopic dermatitis with multi-omics approaches in the infant gut: COCOA birth cohort

An understanding of the phenotypes and endotypes of atopic dermatitis (AD) is essential for developing precision therapies. Recent studies have demonstrated evidence for the gut-skin axis in AD. We sought to determine the natural course and clinical characteristics of AD phenotypes and investigate their mechanisms on the basis of multiomics analyses. Latent class trajectory analysis was used to classify AD phenotypes in 2247 children who were followed until age 9 years from the COhort for Childhood Origin of Asthma and allergic diseases birth cohort study. Multiomics analyses (microbiome, metabolites, and gut epithelial cell transcriptome) using stool samples collected at age 6 months were performed to elucidate the underlying mechanisms of AD phenotypes. Five AD phenotypes were classified as follows: never/infrequent, early-onset transient, intermediate transient, late-onset, and early-onset persistent. Early-onset persistent and late-onset phenotypes showed increased risks of food allergy and wheezing treatment ever, with bronchial hyperresponsiveness evident only in the early-onset persistent phenotype. Multiomics analyses revealed a significantly lower relative abundance of Ruminococcus gnavus and a decreased gut acetate level in the early-onset persistent phenotype, with potential associations to ACSS2, Janus kinase-signal transducer and activator of transcription signaling, and systemic TH2 inflammation. The early-onset transient phenotype was associated with adenosine monophosphate-activated protein kinase (AMPK) and/or chemokine signaling regulation, whereas the late-onset phenotype was linked with IL-17 and barrier dysfunction. Multiomics profiling in early life may offer insights into different mechanisms underlying AD phenotypes in children.

Longitudinal characterization of impulsivity phenotypes boosts signal for genomic correlates and heritability.

Genomic correlates of impulsivity have been identified in several genome-wide association studies (GWAS) using cross-sectional designs, but no studies have investigated the molecular genetic correlates of impulsivity phenotypes using longitudinally constructed traits. In 3860 unrelated European participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), we constructed longitudinal phenotypes for delay discounting and impulsive personality traits (as measured by the UPPS-P impulsive behavior scales) via assessment at ages 24, 26, and 28. We conducted GWASs of impulsivity using both cross-sectional and longitudinal phenotypes, estimated heritability and their phenotypic and genetic correlations, and evaluated their association with recently-developed polygenic risk scores (PRSs) for the impulsivity indicators themselves and also related psychiatric conditions. Latent growth curve modeling revealed a stable intercept over time for all impulsivity phenotypes. High genetic correlation of cross-sectional measures over time suggested a stable genetic component for delay discounting (rg = 0.53-0.99) and sensation seeking (rg = 0.99). Heritability estimates of the stable longitudinal phenotypes substantively improved as compared to their cross-sectional counterparts, revealing a significant SNP-heritability for delay discounting (0.22; p = 0.03) and sensation seeking (0.35; p = 0.0007). Consistent with previous reports, GWAS and gene-based analyses revealed associations between specific longitudinal impulsivity indicators and CADM2 and NCAM1 genes. The PRSs for the impulsivity indicators and disorders related to self-regulation were also significantly associated with longitudinal impulsivity traits. Finally, we validated the associations between longitudinal impulsivity phenotypes and their PRSs in an independent 13-wave longitudinal study (n = 1019) and the benefit of longitudinal phenotypes in simulation studies. In this first longitudinal genetic study of impulsivity traits, the results revealed stable genomic correlates of delay discounting and sensation seeking over time and further validated the utility of recently-developed PRSs, both in relation to the observed traits and in connecting them to psychiatric disorders. More generally, these findings support using latent intercepts as novel longitudinal phenotypes to boost signal for heritability and genomic correlates of mechanisms contributing to psychiatric disease liability.

Multi-locus sequence typing of Candida tropicalis among Candiduria shows an outbreak in azole-susceptible isolates and clonal cluster enriched in azole-resistant isolates.

The increasing detection rate of C.tropicalis and its azole resistance have made clinical treatment difficult. The presence of candiduria seems to correlate with invasive candida infection, especially for patients admitted to ICUs. However, the prevalence and antifungal resistance of C.tropicalis isolates in urine samples has not been well studied. To retrospectively investigate the clinical features, antifungal resistance, and genetic relatedness of C.tropicalis isolates from urine samples. A total of 107 clinical C.tropicalis isolates were retrospectively studied, including phenotypes of isolates and characteristics of patients. The genetic profiles of 107 isolates were genotyped using multi-locus sequence typing (MLST). Phylogenetic analysis was inferred using unweighted pair group method with arithmetic averages. MLST clonal clusters (CCs) were analysed by goeBURST. Of the 107 isolates, 27.1% were resistant to fluconazole, and there was a notable increasing trend of fluconazole resistance from 16.1% in 2019 to 40.0% in 2021. Forty-seven diploid sequence types (DSTs) were assigned to ten major CCs. CC1 was the predominant fluconazole-susceptible group; 24 isolates from CC1 belonged to DST333, an outbreak clone in NICU ward. The azole-resistant CC4 contained 19 isolates, accounting for 65.5% of the azole-resistant isolates in this study. CC4 belongs to a prevalent FNS CC1 globally, of which the putative founder genotype was DST225. This study revealed an outbreak of azole-susceptible C.tropicalis isolates in urine specimens and a high azole resistance rate of C. tropicalis in candiduria, and the MLST type showed clonal aggregation in azole-resistant isolates from urine samples.

Chronic wounds and adaptive Pseudomonas aeruginosa: A phenotypic and genotypic characterization

Chronic wounds and adaptive Pseudomonas aeruginosa: A phenotypic and genotypic characterization

Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients.

Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.

The Impact of Active Ascertainment on Sex-Specific Differences in the Prevalence and Phenotype of Transthyretin Cardiac Amyloidosis: The SCAN-MP Study

Transthyretin cardiac amyloidosis (ATTR-CA) is disproportionately diagnosed in older men. However, studies suggest that the true prevalence of ATTR-CA in women may be greater than previously reported. The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study uses nuclear scintigraphy to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥60 years old with heart failure and left ventricular hypertrophy. We characterized the sex distribution and phenotypic characteristics of ATTR-CA in this active ascertainment cohort in comparison with a population of patients with ATTR-CA who were referred to a tertiary care academic center outpatient clinic. The active ascertainment SCAN-MP cohort had a greater proportion of women than did the referral clinic cohort (31.3% vs 13.3%, p = 0.016). This was mainly attributed to the greater proportion of women with wild-type ATTR-CA (27.8% vs 7.1%, p = 0.012). Women with ATTR-CA in the active ascertainment cohort exhibited higher left ventricular ejection fraction than did those in the referral cohort (61% vs 50%, p = 0.011), lower left ventricular mass index (110 vs 148 g/m2, p = 0.014), and smaller posterior wall thickness (1.4 vs 1.6 cm, p = 0.01). An active ascertainment strategy for ATTR-CA identification showed a greater proportion of women than did a referral cohort, driven predominantly by the greater proportion of women with wild-type ATTR-CA, and echocardiographic evidence of a less severe phenotype. In conclusion, efforts for early identification of ATTR-CA in women are critical for reducing sex disparities in this clinically treatable disease.