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Alternative Therapies in Health and... Jun 2024Colorectal cancer is a malignant tumor with high mortality, but is hard to detect at its early stage. Recent studies highlighted the crucial roles of Ezrin protein and...
OBJECTIVE
Colorectal cancer is a malignant tumor with high mortality, but is hard to detect at its early stage. Recent studies highlighted the crucial roles of Ezrin protein and MMP-9 in the development and malignancy of colorectal cancer, but Ezrin protein and MMP-9 in early diagnosis of colorectal cancer require further investigation. Therefore, we aimed to investigate their roles in the occurrence and metastasis of colorectal cancer, and to analyze their clinical significance in diagnosing and treating colorectal cancer.
METHOD
The diagnosis of collected colorectal cancer tissue and adjacent tissue samples from colorectal cancer patients confirmed by clinical symptoms was performed using Hematoxylin Eosin staining. The expression levels of Ezrin and MMP-9 in 50 colorectal cancer tissue and 50 cases adjacent colorectal cancer tissue were detected by the immuno-histochemical MaxVision method. The relationship between the positive expression rate of Ezrin and MMP-9 in colorectal cancer tissue and clinical pathological factors was analyzed, and the correlation between Ezrin and MMP-9 was examined.
RESULTS
The positive expression rate of Ezrin in colorectal cancer tissue (78%) was significantly higher compared to adjacent non-cancerous tissues (6.0%) (P < .05). There was no significant correlation of gender/age and Ezrin/MMP-9 expressions (P > .05). The expression level of Ezrin exhibited statistically significant differences in the pathological factors including tumor diameter, depth of invasion, degree of differentiation, presence or absence of lymph node metastasis, and distant metastasis (P < .05). Additionally, the positive expression rate of MMP-9 in colorectal cancer tissue (76%) was markedly elevated compared to adjacent tissues (8.0%) (P < .05). The expression level of MMP-9 showed statistically significant differences in the pathological factors including tumor diameter, depth of invasion, degree of differentiation, presence or absence of lymph node metastasis, and distant metastasis (P < .05). In addition, the expression of Ezrin and MMP-9 in colorectal cancer tissue showed a significant positive correlation (r=0.637, P < .01).
CONCLUSION
Ezrin and MMP-9 may synergistically participate in the occurrence, invasion, and metastasis of colorectal cancer. The combined assessment of Ezrin and MMP-9 expression levels in colorectal cancer patients holds significant potential for clinical diagnosis and personalized therapeutic applications.
PubMed: 38940787
DOI: No ID Found -
Alternative Therapies in Health and... Jun 2024The research aims to investigate the impact of narrative nursing on the psychological well-being of nursing personnel in the context of the normalization of epidemic.
OBJECTIVE
The research aims to investigate the impact of narrative nursing on the psychological well-being of nursing personnel in the context of the normalization of epidemic.
METHODS
A cohort of 170 frontline nursing staff at our institution was selected for this clinical study from January 1st to October 31st of 2023. The Symptom Checklist-90 (SCL-90) was employed to evaluate the psychological health of these frontline nursing personnel, compared to the standard norms for nurses in mainland China. Employing a randomized selection method, the cohort was divided into two groups: a control group (85 cases) receiving conventional nursing care and a research group (85 cases) receiving narrative nursing care. The duration of nursing intervention in both groups was set at 12 weeks. Various aspects of psychological well-being, work-related stress, psychological resilience, post-traumatic stress disorder, occupational burnout, job satisfaction, and coping strategies were assessed both before and after the nursing intervention.
RESULTS
Among the positive projects of 170 frontline nursing personnel, 32 exhibited positive symptoms, resulting in a positive rate of 18.82%. With the exception of the paranoia dimension score, the scores for other dimensions in the SCL-90 scale within the clinical group were notably higher than those observed in the norm group (P < .05). Among the ten items with the highest frequency of positive symptoms, anxiety, obsessive-compulsive symptoms, and hostility were identified as the most prevalent psychological health issues among frontline nursing personnel. Post-nursing intervention, the research group exhibited lower scores in dimensions other than paranoia in the SCL-90 scale compared to the control group (P < .05). The research group also displayed lower scores in SAS, SDS, SRQ, PCL-C, MBI-HSS and higher scores in CD-RISC and JWS post-intervention (P < .05). In the post-nursing intervention phase, the research group demonstrated lower scores in negative coping and higher scores in positive coping as per the SCSQ scale in comparison to the control group (P < .05).
CONCLUSIONS
Amidst the ongoing normalization of the epidemic, the psychological well-being of frontline nursing staff was lower than the established norms for nurses in mainland China. Notably, somatization, anxiety, and depression emerged as predominant manifestations. Narrative nursing was identified as an effective intervention to enhance nursing personnel's psychological well-being and coping strategies, ultimately regulating negative emotions, reducing post-traumatic stress disorder and occupational burnout, reducing stress levels, and enhancing job satisfaction and psychological resilience.
PubMed: 38940786
DOI: No ID Found -
Clinical Transplantation and Research Jun 2024Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase...
Perioperative optic nerve sheath diameter variations in patients with end-stage renal failure undergoing robotic-assisted kidney transplant: a prospective observational study.
BACKGROUND
Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase optic nerve sheath diameter (ONSD) and intracranial pressure. The impact of robotic-assisted kidney transplant (RAKT) on ONSD is complicated by the presence of CKD, the administration of furosemide and mannitol, and the manipulation of hemodynamics. We examined ONSD variations in patients undergoing RAKT over a 1-year period at our institution. Furthermore, we attempted to identify any perioperative hemodynamic factors influencing these changes.
METHODS
This prospective study included 20 patients undergoing RAKT. ONSD, heart rate, central venous pressure, systolic blood pressure, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured following intubation (T1), after assuming the steep Trendelenburg position (T2), 1 hour after docking (T3), upon reperfusion (T4), after transition to the supine position (T5), and 3 hours postextubation (T6). Repeated measures analysis of variance with post hoc Bonferroni correction was employed to compare variables at each time point. Pearson correlation analysis was utilized to assess relationships between variables. P-values ≤0.05 were considered to indicate statistical significance.
RESULTS
ONSD (in mm) increased from T1 (3.60±0.44) to T3 (4.06±0.45, P=0.002) and T4 (3.99±0.62, P=0.046), before falling to its lowest value at T6 (3.42±0.64, P=0.002). Pearson correlation analysis revealed significant correlations (P<0.05) between changes in ONSD at T3 and both DBP (r=0.637) and MAP (r=0.522).
CONCLUSIONS
During RAKT with open ureteric anastomosis, ONSD initially increased, then decreased following reperfusion. DBP and MAP displayed positive correlations with ONSD changes at T3.
PubMed: 38940687
DOI: 10.4285/ctr.24.0007 -
Microbiology Spectrum Jun 2024The hospital environmental microbiome, which can affect patients' and healthcare workers' health, is highly variable and the drivers of this variability are not well...
UNLABELLED
The hospital environmental microbiome, which can affect patients' and healthcare workers' health, is highly variable and the drivers of this variability are not well understood. In this study, we collected 37 surface samples from the neonatal intensive care unit (NICU) in an inpatient hospital before and after the operation began. Additionally, healthcare workers collected 160 surface samples from five additional areas of the hospital. All samples were analyzed using 16S rRNA gene amplicon sequencing, and the samples collected by healthcare workers were cultured. The NICU samples exhibited similar alpha and beta diversities before and after opening, which indicated that the microbiome there was stable over time. Conversely, the diversities of samples taken after opening varied widely by area. Principal coordinate analysis (PCoA) showed the samples clustered into two distinct groups: high alpha diversity [the pediatric intensive care unit (PICU), pathology lab, and microbiology lab] and low alpha diversity [the NICU, pediatric surgery ward, and infection prevention and control (IPAC) office]. Least absolute shrinkage and selection operator (LASSO) classification models identified 156 informative amplicon sequence variants (ASVs) for predicting the sample's area of origin. The testing accuracy ranged from 86.37% to 100%, which outperformed linear and radial support vector machine (SVM) and random forest models. ASVs of genera that contain emerging pathogens were identified in these models. Culture experiments had identified viable species among the samples, including potential antibiotic-resistant bacteria. Though area type differences were not noted in the culture data, the prevalences and relative abundances of genera detected positively correlated with 16S sequencing data. This study brings to light the microbial community temporal and spatial variation within the hospital and the importance of pathogenic and commensal bacteria to understanding dispersal patterns for infection control.
IMPORTANCE
We sampled surface samples from a newly built inpatient hospital in multiple areas, including areas accessed by only healthcare workers. Our analysis of the neonatal intensive care unit (NICU) showed that the microbiome was stable before and after the operation began, possibly due to access restrictions. Of the high-touch samples taken after opening, areas with high diversity had more potential external seeds (long-term patients and clinical samples), and areas with low diversity and had fewer (short-term or newborn patients). Classification models performed at high accuracy and identified biomarkers that could be used for more targeted surveillance and infection control. Though culturing data yielded viability and antibiotic-resistance information, it disproportionately detected the presence of genera relative to 16S data. This difference reinforces the utility of 16S sequencing in profiling hospital microbiomes. By examining the microbiome over time and in multiple areas, we identified potential drivers of the microbial variation within a hospital.
PubMed: 38940596
DOI: 10.1128/spectrum.00296-24 -
Microbiology Spectrum Jun 2024Many methods are being tried for rapid and accurate identification of sepsis-causing microorganisms. We analyzed the performance of three different preparation methods...
UNLABELLED
Many methods are being tried for rapid and accurate identification of sepsis-causing microorganisms. We analyzed the performance of three different preparation methods [MBT Sepsityper IVD Kit (Bruker Daltonics GmbH, Germany), sodium dodecyl sulfate (SDS) lysis, and differential centrifugation with protein extraction (Centrifugation +PE)] and compared in standard and Sepsityper modules of the Bruker Biotyper MALDI-TOF MS for direct identification of bacteria from 240 positive blood culture bottles of BACTEC FX (Becton Dickinson, USA). By using the standard module, correct identification at species level (score ≥2) was done in 46.7% of the samples with SDS lysis, 44.2% with centrifugation +PE, and 25.4% with the Sepsityper kit. These ratios at the genus level (score range 1.70-1.99) were 34.6%, 31.3%, and 32.5%, respectively. With SDS lysis (195), more bacteria were identified correctly than centrifugation +PE (181) and the Sepsityper kit (139). A statistically significant difference was found between SDS and the Sepsityper kit and Centrifugation +PE and the Sepsityper kit ( < 0.001, both). By using the Sepsityper module, correct identification at species level (score ≥1.8) was determined in 74.2% of the samples with SDS lysis and centrifugation +PE each and 55% with the Sepsityper kit. These ratios at the genus level (score range 1.60-1.79) were 16.3%, 10%, and 19.2%, respectively. SDS lysis (217) had significantly higher identification rates than centrifugation +PE (202) and the Sepsityper kit (178) ( = 0.028 and < 0.001). A statistically significant difference was also observed between centrifugation +PE and the Sepsityper kit ( < 0.001). Best performance was obtained with SDS lysis among the methods. Although better performance was achieved by using Sepsityper software module, risk of misidentification should not be ignored.
IMPORTANCE
Sepsis is a life-threatening condition, and rapid and accurate identification of the causative microorganisms from blood cultures is crucial for timely and effective treatment. Although there are many studies on direct identification from blood cultures with MALDI-TOF MS, further standardization is still needed. In our study, we analyzed the performance of three different preparation methods and compared by using two analysis modules of the Bruker Biotyper MALDI-TOF MS for direct identification of bacteria from numerous positive blood culture bottles. The literature reports a limited number of studies that compare different preparation methods for direct blood culture identification, processing a large number of blood samples concurrently and evaluating the same samples as in our study. Moreover, although SDS is used very frequently in medical laboratories, there are few studies on direct identification from blood culture bottles. In our study, the highest correct identification rate was observed with the SDS method.
PubMed: 38940589
DOI: 10.1128/spectrum.00638-24 -
MBio Jun 2024Conjugative type 4 secretion systems (T4SSs) are the main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. To deliver the DNA...
Conjugative type 4 secretion systems (T4SSs) are the main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. To deliver the DNA substrate to recipient cells, it must cross the cell envelopes of both donor and recipient bacteria. In the T4SS from the enterococcal conjugative plasmid pCF10, PrgK is known to be the active cell wall degrading enzyme. It has three predicted extracellular hydrolase domains: metallo-peptidase (LytM), soluble lytic transglycosylase (SLT), and cysteine, histidine-dependent amidohydrolases/peptidases (CHAP). Here, we report the structure of the LytM domain and show that its active site is degenerate and lacks the active site metal. Furthermore, we show that only the predicted SLT domain is functional and that it unexpectedly has a muramidase instead of a lytic transglycosylase activity. While we did not observe any peptidoglycan hydrolytic activity for the LytM or CHAP domain, we found that these domains downregulated the SLT muramidase activity. The CHAP domain was also found to be involved in PrgK dimer formation. Furthermore, we show that PrgK interacts with PrgL, which likely targets PrgK to the rest of the T4SS. The presented data provides important information for understanding the function of Gram-positive T4SSs.IMPORTANCEAntibiotic resistance is a large threat to human health and is getting more prevalent. One of the major contributors to the spread of antibiotic resistance among different bacteria is type 4 secretion systems (T4SS). However, mainly T4SSs from Gram-negative bacteria have been studied in detail. T4SSs from Gram-positive bacteria, which stand for more than half of all hospital-acquired infections, are much less understood. The significance of our research is in identifying the function and regulation of a cell wall hydrolase, a key component of the pCF10 T4SS from . This system is one of the best-studied Gram-positive T4SSs, and this added knowledge aids in our understanding of horizontal gene transfer in as well as other medically relevant Gram-positive bacteria.
PubMed: 38940556
DOI: 10.1128/mbio.00488-24 -
MBio Jun 2024Merkel cell polyomavirus (MCPyV) is a double-stranded tumor virus that is the main causative agent of Merkel cell carcinoma (MCC). The MCPyV large T antigen (LT), an...
UNLABELLED
Merkel cell polyomavirus (MCPyV) is a double-stranded tumor virus that is the main causative agent of Merkel cell carcinoma (MCC). The MCPyV large T antigen (LT), an essential viral DNA replication protein, maintains viral persistence by interacting with host Skp1-Cullin 1-F-box (SCF) E3 ubiquitin ligase complexes, which subsequently induces LT's proteasomal degradation, restricting MCPyV DNA replication. SCF E3 ubiquitin ligases require their substrates to be phosphorylated to bind them, utilizing phosphorylated serine residues as docking sites. The MCPyV LT unique region (MUR) is highly phosphorylated and plays a role in multiple host protein interactions, including SCF E3 ubiquitin ligases. Therefore, this domain highly governs LT stability. Though much work has been conducted to identify host factors that restrict MCPyV LT protein expression, the kinase(s) that cooperates with the SCF E3 ligase remains unknown. Here, we demonstrate that casein kinase 1 alpha (CK1α) negatively regulates MCPyV LT stability and LT-mediated replication by modulating interactions with the SCF β-TrCP. Specifically, we show that numerous CK1 isoforms (α, δ, ε) localize in close proximity to MCPyV LT through proximity ligation assays (PLA) and CK1α overexpression mainly resulted in decreased MCPyV LT protein expression. Inhibition of CK1α using short hairpin RNA (shRNA) and treatment of a CK1α inhibitor or an mTOR inhibitor, TORKinib, resulted in decreased β-TrCP interaction with LT, increased LT expression, and enhanced MCPyV replication. The expression level of the gene transcripts is higher in MCPyV-positive MCC, suggesting a vital role of CK1α in limiting MCPyV replication required for establishing persistent infection.
IMPORTANCE
Merkel cell polyomavirus (MCPyV) large tumor antigen is a polyphosphoprotein and the phosphorylation event is required to modulate various functions of LT, including viral replication. Therefore, cellular kinase pathways are indispensable for governing MCPyV polyomavirus infection and life cycle in coordinating with the immunosuppression environment at disease onset. Understanding the regulation mechanisms of MCPyV replication by viral and cellular factors will guide proper prevention strategies with targeted inhibitors for MCPyV-associated Merkel cell carcinoma (MCC) patients, who currently lack therapies.
PubMed: 38940554
DOI: 10.1128/mbio.01117-24 -
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 -
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