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MBio Jun 2024Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq is...
UNLABELLED
Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq is challenging. Dose limitations and host restrictions create bottlenecks that diminish the transposon mutant pool being screened. Here, we have developed a murine model with a disruption in that renders the resulting RECON mouse resistant to high-dose infection. We leveraged this model to perform a Tn-seq screen of the human pathogen . We identified 135 genes which were required for growth in mice including novel genes not previously identified for host survival. We identified organ-specific requirements for survival and investigated the role of the folate enzyme FolD in liver pathogenesis. A mutant lacking was impaired for growth in murine livers by 2.5-log compared to wild type and failed to spread cell-to-cell in fibroblasts. In contrast, a mutant in which encodes a transcription factor that represses an operon involved in D-allose catabolism, was attenuated in both livers and spleens of mice by 4-log and 3-log, respectively, but showed modest phenotypes in models. We confirmed that dysregulation of the D-allose catabolism operon is responsible for the growth defect, as deletion of the operon in the ∆ background rescued virulence. By undertaking an unbiased, genome-wide screen in mice, we have identified novel fitness determinants for host infection, which highlights the utility of the RECON mouse model for future screening efforts.
IMPORTANCE
is the gram-positive bacterium responsible for the food-borne disease listeriosis. Although infections with are limiting in healthy hosts, vulnerable populations, including pregnant and elderly people, can experience high rates of mortality. Thus, understanding the breadth of genetic requirements for survival will present new opportunities for treatment and prevention of listeriosis. We developed a murine model of infection using a RECON mouse that is restrictive to systemic infection. We utilized this model to screen for genes required via transposon sequencing. We identified the liver-specific gene and a repressor, , that only exhibits an growth defect. AlsR controls the expression of the D-allose operon which is a marker in diagnostic techniques to identify pathogenic . A better understanding of the role of the D-allose operon in human disease may further inform diagnostic and prevention measures.
PubMed: 38940553
DOI: 10.1128/mbio.01332-24 -
MSystems Jun 2024The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated...
UNLABELLED
The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors ( for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including -positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of and oral-associated bacteria was verified using fluorescence hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included , , and , was more abundant in the upper third of the GC. However, was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with in the lower third site of the GC tumoral tissue. Importantly, -negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in -positive GC patients showed no difference in overall survival. The prevalence of in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species and were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for -negative GCs.
IMPORTANCE
Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species and were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for -negative GCs.
PubMed: 38940519
DOI: 10.1128/msystems.00089-24 -
Nursing Open Jul 2024Family resilience and healthy family functioning are crucial for stroke survivors' rehabilitation. This study aimed to determine the mediating effects of self-efficacy...
AIM
Family resilience and healthy family functioning are crucial for stroke survivors' rehabilitation. This study aimed to determine the mediating effects of self-efficacy and confrontation coping on the relationship between family resilience and functioning among patients with first-episode stroke.
DESIGN
A cross-sectional design was applied.
METHODS
288 patients with first-episode stroke were recruited from 7 hospitals in Shangqiu and Shanghai, China, from July 2020 to October 2020. A shortened Chinese version of the Family Resilience Assessment Scale, family adaptation, partnership, growth, affection and resolve questionnaire, Medical Coping Modes Questionnaire, and Self-efficacy for Chronic Disease 6-item Scale were used to collect the self-reported data. The relationships among the studied variables were studied using spearman correlation and structural equation model.
RESULTS
The average level of family functioning among stroke patients was 7.87 (SD = 2.32). About 26.8% (n = 76) of patients reported family dysfunction. The structural equation model showed that family resilience directly affected patients' satisfaction with family functioning (r = 0.406, p < 0.001) and indirectly affected the mediating role of patients' self-efficacy and confrontation coping style (r = 0.119, p < 0.001). The model was with good fit (χ/df = 2.128, RMSEA = 0.065, GFI = 0.956, AGFI = 0.919, NFI = 0.949, and TLI = 0.956).
CONCLUSION
Family resilience and functioning among patients with first-episode stroke are positively associated with the mediating effects of the patients' confrontation coping style and self-efficacy between family resilience and functioning. The findings indicate that the professionals should pay special attention to families exhibiting poor family resilience or with patients who rarely use confrontation coping styles or with poor self-efficacy since they are more likely to suffer from low functioning.
Topics: Humans; Male; Female; Self Efficacy; Adaptation, Psychological; Cross-Sectional Studies; Middle Aged; Resilience, Psychological; Stroke; Survivors; Surveys and Questionnaires; China; Family; Aged; Adult
PubMed: 38940513
DOI: 10.1002/nop2.2230 -
Medeniyet Medical Journal Jun 2024sp. is considered an indispensable probiotic, and this probiotic has an effective role in maintaining the immune system. We evaluated the effect of the probiotic sp....
sp. is considered an indispensable probiotic, and this probiotic has an effective role in maintaining the immune system. We evaluated the effect of the probiotic sp. on modulating inflammation in several cases. In collecting the literature, we used databases from the Web of Science, the Cochrane Central Register of Controlled Trials, PubMed, and Embase. Studies that met the inclusion criteria were analyzed using Review Manager (version 5.4). A p-value of <0.05 of the total effect is considered statistically significant. Finally, 1895 references were retrieved and 20 were included in the meta-analysis. This meta-analysis suggested that most cases in this study were healthy elderly who received treatment with sp. sp. has a positive effect on B cells, eosinophils, IgE, NK cells, TNF-α, and IL-10. could regulate the immune system by modulating inflammation in the healthy elderly.
PubMed: 38940492
DOI: 10.4274/MMJ.galenos.2024.53822 -
Cancer Medicine Jul 2024Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and...
INTRODUCTION
Nucleoporin 98 (NUP98) fusion proteins are recurrently found in leukemia and are associated with unfavorable clinical outcomes. They are distributed to the nucleus and contribute to leukemogenesis via aberrant transcriptional regulation. We previously identified NUP98-BPTF (NB) fusion in patients with T-cell acute lymphoblastic leukemia (T-ALL) using next-generation sequencing. The FG-repeat of NUP98 and the PHD finger and bromodomain of bromodomain PHD finger transcription factor (BPTF) are retained in the fusion. Like other NUP98 fusion proteins, NB is considered to regulate genes that are essential for leukemogenesis. However, its target genes or pathways remain unknown.
MATERIALS AND METHODS
To investigate the potential oncogenic properties of the NB fusion protein, we lentivirally transduced a doxycycline-inducible NB expression vector into mouse NIH3T3 fibroblasts and human Jurkat T-ALL cells.
RESULTS
NB promoted the transformation of mouse NIH3T3 fibroblasts by upregulating the proto-oncogene Pim1, which encodes a serine/threonine kinase. NB transcriptionally regulated Pim1 expression by binding to its promoter and activated MYC and mTORC1 signaling. PIM1 knockdown or pharmacological inhibition of mTORC1 signaling suppressed NB-induced NIH3T3 cell transformation. Furthermore, NB enhanced the survival of human Jurkat T-ALL cells by inactivating the pro-apoptotic protein BCL2-associated agonist of cell death (BAD).
CONCLUSION
We demonstrated the pivotal role of NB in cell transformation and survival and identified PIM1as a key downstream target of NB. These findings propose a promising therapeutic strategy for patients with NB fusion-positive leukemia.
Topics: Humans; Proto-Oncogene Proteins c-pim-1; Animals; Mice; Cell Transformation, Neoplastic; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Jurkat Cells; Up-Regulation; NIH 3T3 Cells; Proto-Oncogene Mas; Transcription Factors; Apoptosis; Cell Proliferation
PubMed: 38940430
DOI: 10.1002/cam4.7445 -
Journal of Global Health Jun 2024Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that...
Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.
BACKGROUND
Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention.
METHODS
We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period.
RESULTS
A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up.
CONCLUSIONS
Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.
Topics: Humans; Female; Pulmonary Disease, Chronic Obstructive; Male; Bronchiectasis; Middle Aged; Prospective Studies; Aged; Prognosis; China; Risk Factors; Syndrome; Disease Progression
PubMed: 38940273
DOI: 10.7189/jogh.14.04129 -
The rapidly progressing and fatal outcome of rhombencephalitis by listeriosis in a 61-year-old male.Annals of Agricultural and... Jun 2024Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised...
Listeria monocytogenes is a Gram-positive facultative anaerobic bacterium that is ubiquitous in the environment and can cause severe infections in immunocompromised individuals, pregnant women, and newborns. Listeriosis can manifest as meningitis, encephalitis, or sepsis, and its diagnosis requires a high index of suspicion. The case is reported of a rare presentation of rhombencephalitis by listeriosis in a 61-year-old male who initially suffered from subacute gastric disturbances and fever. Neurological consultation showed abnormal functions of cranial nerves and meningeal signs were observed. MRI revealed a poorly demarcated focus of approximately 45 × 16 × 15mm, indicating possible inflammatory processes, necessitating a lumbar puncture. Assessment of the CSF indicated infection with the bacterium- Listeria Monocytogenes, with the final diagnosis of Listeriosis encephalitis. Despite antibiotic therapy of Ceftazidine and Ampicillin, the patient's condition deteriorated, followed by death.
Topics: Humans; Male; Listeriosis; Middle Aged; Fatal Outcome; Listeria monocytogenes; Encephalitis; Anti-Bacterial Agents; Rhombencephalon
PubMed: 38940119
DOI: 10.26444/aaem/178178 -
Annals of Agricultural and... Jun 2024Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body...
Morphological anomalies are considered a rare phenomenon among natural tick populations. New cases of abnormalities in ticks are being described, such as body assymetries, nanism, gynandromorphism and limb malformations. The tick removed from a cat was morphologically identified to species and developmental stage. The time of feeding on the host was determined. The specimen was tested using PCR and Real-Time PCR methods for the presence of the common tick-borne pathogens: , spp, spp., , spp. For visualisation of the anomalous structures, scanning electron microscopy (SEM) was performed. The tick was identified as a slightly engorged adult female of I. ricinus exhibiting ectromely of leg I on the left side of the idiosoma. The specimen was tested positive for two medically important pathogens: and . The case report describes a rare case of a morphological anomaly in an tick from Poland.
Topics: Animals; Poland; Ixodes; Female; Cats; Cat Diseases; Anaplasma phagocytophilum; Tick Infestations
PubMed: 38940115
DOI: 10.26444/aaem/172533 -
Annals of Agricultural and... Jun 2024Subtalar arthroereisis is a procedure commonly performed in children with flat feet. The procedure is performed when conservative treatment did not have the desired...
INTRODUCTION AND OBJECTIVE
Subtalar arthroereisis is a procedure commonly performed in children with flat feet. The procedure is performed when conservative treatment did not have the desired effect,or when the patient's abnormal symptoms are very severe and make it difficult for them to function normally in daily life. The aim of this study was to assess whether subtalar arthroereisis and physiotherapy improve the quality of life among children with flat feet.
MATERIAL AND METHODS
The study comprised 79 patients (140 operated feet) diagnosed with a flat foot defect who underwent a subtalar arthroereisis procedure. A self-administered questionnaire and a shortened version of the standardised WHOQOL-BREF questionnaire were used in the research.
RESULTS
The study confirmed that the patients' quality of life after surgery was high in all the areas regarding the somatic, psychological, social and environmental domains. In the group of children assessed 13-24 months after surgery. it was also found that rapid fatigue after exercise (30% ± 9%) and Achilles tendon contracture (7% ± 4%) were significantly reduced. The results of the study confirmed that subtalar arthroereisis contributes to a decreased demand for orthoses in children (9% ± 6%) and for orthopaedic footwear (11% ± 5%) than before surgery.
CONCLUSIONS
The employment of subtalars arthroereisis has a positive effect on the quality of life of children with flat feet. The surgery contributes to a reduction in pain and other abnormal symptoms that are associated with flat feet. In addition, physiotherapy performed after the procedure had a positive effect on the healing process and contributed to the improvement of the children's quality of life.
Topics: Humans; Quality of Life; Child; Flatfoot; Female; Male; Surveys and Questionnaires; Adolescent; Subtalar Joint; Child, Preschool
PubMed: 38940112
DOI: 10.26444/aaem/173220 -
Annals of Agricultural and... Jun 2024Smoking-free policies protect non-smokers from the negative effects of smoking, but many young adults still use products containing nicotine. The aim of this article is...
INTRODUCTION AND OBJECTIVE
Smoking-free policies protect non-smokers from the negative effects of smoking, but many young adults still use products containing nicotine. The aim of this article is to analyze the factors that influence young people's attitudes towards the ban on smoking in public places.
MATERIAL AND METHODS
Data were obtained from a representative sample of young adults aged 13-15 from the Global Youth Tobacco Survey (GYTS) conducted in the Czech Republic, Lithuania, Romania, Slovakia and Slovenia. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
At least a quarter of the adolescents were exposed to cigarette smoking, about 40% have parents who smoke and over 50% declared that they have peers who smoke. A higher proportion of adolescents have knowledge about the harmful effects of second-hand smoking (62.6-71.9%), but at least one-fifth of young people are still exposed to the marketing of tobacco products. Compared with current smoking, those with never smoked were significantly associated with positive attitude toward to restricting smoking in all five analyzed countries, with an AOR= 4.74 (95% CI: 3.61-6.23), AOR=4.33 (95% CI: 2.32-8.07), AOR=2.85 (95% CI: 2.19-3.70) and AOR=2.45 (95% CI: 1.65-3.64), respectively. Gender, age, smoking, exposure to second-hand smoke, knowledge about the harmful effects of smoking, anti-smoking education, seeing people using tobacco and exposure to tobacco marketing, were significantly associated with the attitudes of young people towards restricting smoking in public places.
CONCLUSIONS
The study provides useful information on factors that should be taken into account when planning anti-smoking strategies so that young people are able to resist the pressure to use tobacco products.
Topics: Humans; Adolescent; Male; Female; Lithuania; Slovakia; Smoke-Free Policy; Czech Republic; Surveys and Questionnaires; Tobacco Smoke Pollution; Romania; Slovenia; Smoking; Health Knowledge, Attitudes, Practice
PubMed: 38940106
DOI: 10.26444/aaem/173531