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1.
Surgery ; 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38834400

BACKGROUND: It is unknown if the current minimum case volume recommendation of 20 cases per year per hospital is applicable to contemporary practice. METHODS: Patients undergoing esophageal resection between 2005 and 2015 were identified in the National Cancer Database. High, medium, and low-volume hospital strata were defined by quartiles. Adjusted odds ratios and adjusted 30-day mortality between low-, medium-, and high-volume hospitals were calculated using logistic regression analyses and trended over time. RESULTS: Only 1.1% of hospitals had ≥20 annual cases. The unadjusted 30-day mortality for esophagectomy was 3.8% overall. Unadjusted and adjusted 30-day mortality trended down for all three strata between 2005 and 2015, with disproportionate decreases for low-volume and medium-volume versus high-volume hospitals. By 2015, adjusted 30-day mortality was similar in medium- and high-volume hospitals (odds ratio 1.35, 95% confidence interval 0.96-1.91). For hospitals with 20 or more annual cases the adjusted 30-day mortality was 2.7% overall. To achieve this same 30-day mortality the minimum volume threshold had lowered to 7 annual cases by 2015. CONCLUSION: Only 1.1% of hospitals meet current volume recommendations for esophagectomy. Differential improvements in postoperative mortality at low- and medium- versus high-volume hospitals have led to 7 cases in 2015 achieving the same adjusted 30-day mortality as 20 cases in the overall cohort. Lowering volume thresholds for esophagectomy in contemporary practice would potentially increase the proportion of hospitals able to meet volume standards and increase access to quality care without sacrificing quality.

2.
J Chin Med Assoc ; 87(6): 643-652, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38838200

BACKGROUND: Early palliative care (EPC) benefits some cancers, but its clinical outcomes differ depending on patients' racial and ethnic disparities, and customs. To determine whether EPC improves symptoms, emotional distress, and quality of life among Taiwanese patients with early or advanced-stage head and neck cancer (HNC). METHODS: Based on participants' pathological stages, they were categorized as having early and advanced-stage HNC. Those willing and unwilling to undergo EPC were assigned to the EPC and standard groups, respectively. Their daily cancer-related symptoms were assessed using the Distress Thermometer (DT) and MD Anderson Symptom Inventory (MDASI), whose scores' concurrent validity was evaluated using the European Organization for Research and Treatment of Core Quality of Life (EORTC-QLQ-C30) and Head and Neck 35 (EORTC-QLQ-H&N35) questionnaires. RESULTS: Patients (n = 93) diagnosed with HNC at Taiwan's Chia-Yi Christian Hospital from November 2020 to October 2022 were recruited. The patients voluntarily split into two groups: EPC groups and standard groups (23 and 11 in early-stage; 46 and 13 in advanced-stage, respectively). DT assessment showed significant emotional distress improvements for all patients with HNC who received EPC. The EORTC-QLQ-C30 questionnaire indicated that, compared to standard interventions, EPC groups significantly improved the quality of life and some symptoms for both early and advanced-stage HNC patients. However, the EORTC-QLQ-H&N35 questionnaire found no significant difference between the two groups. Furthermore, advanced-stage patients' anticancer treatment completion rates with EPC and standard interventions were 95.35% and 75%, respectively. CONCLUSION: EPC improves symptoms, emotional distress, quality of life, and treatment completion rates in Taiwanese patients with early or advanced-stage HNC. Nonetheless, further extensive clinical studies are required for validation.


Head and Neck Neoplasms , Palliative Care , Quality of Life , Humans , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/psychology , Male , Female , Middle Aged , Aged , Taiwan , Adult , Surveys and Questionnaires
3.
Life Sci ; : 122764, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38838817

The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 µM for Y25A, 15.2 µM for T44A, and 25 µM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 µM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug.

5.
Opt Express ; 32(11): 19042-19056, 2024 May 20.
Article En | MEDLINE | ID: mdl-38859048

Lidar using active light illumination is capable of capturing depth and reflectivity information of target scenes. Among various technologies, streak tube imaging lidar (STIL) has garnered significant attention due to its high resolution and excellent precision. The echo signals of a STIL system using single laser pulse are often overwhelmed by noise in complex environments, making it difficult to discern the range of the target. By combining high-frequency laser pulses with the repetitive sweep circuit, the STIL system enables efficient detection of few-photons signal in weak-light environments. Additionally, we have developed a robust algorithm for estimating the depth and reflectivity images of targets. The results demonstrate that this lidar system achieves a depth resolution better than 0.5 mm and a ranging accuracy of 95 um. Furthermore, the imaging of natural scenes also validates the exceptional 3D imaging capability of this system.

6.
BMC Womens Health ; 24(1): 330, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38849887

BACKGROUND: Premenstrual syndrome (PMS) is a severe problem in women, and a well-balanced diet helps improve PMS symptoms. Eating disturbances are a major health problem in young women. Limited research has explored the correlation between eating behaviors and PMS symptoms in Japan. This study aimed to compare eating disturbances and the severity of PMS symptoms in college students. METHODS: This study was conducted among female college students using an online questionnaire. The questionnaire included basic information (age, height, and weight), PMS symptoms, and eating behaviors assessed using the Eating Attitudes Test 26. RESULTS: The proportion of those with PMS symptoms who were disturbed by PMS symptoms was significantly higher in the group with eating disturbance. Those who were affected by the physical symptoms of PMS had significantly higher scores on the subscales related to diet, bulimia and food preoccupation. CONCLUSION: The results showed an association between PMS symptom severity and eating disturbance. The findings of this study indicate that individuals with eating disturbances may experience adverse effects on PMS symptoms, even in cases where weight is not at the extremes of excessive underweight or obesity.


Feeding Behavior , Feeding and Eating Disorders , Premenstrual Syndrome , Students , Humans , Female , Premenstrual Syndrome/psychology , Cross-Sectional Studies , Students/statistics & numerical data , Students/psychology , Young Adult , Feeding and Eating Disorders/psychology , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/epidemiology , Surveys and Questionnaires , Japan/epidemiology , Universities , Feeding Behavior/psychology , Adult , Adolescent , Severity of Illness Index
7.
SLAS Technol ; 29(4): 100146, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38844139

Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.

8.
Sci Rep ; 14(1): 12716, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830933

To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that "extracellular matrix organization" ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMPs expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-ß1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-ß1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-ß1-induced myofibroblast activation.


Carotenoids , Hypertension, Pulmonary , Hypoxia , Matrix Metalloproteinase 2 , Tissue Inhibitor of Metalloproteinase-1 , Animals , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Mice , Hypoxia/metabolism , Hypoxia/complications , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/metabolism , Carotenoids/pharmacology , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Male , Signal Transduction/drug effects , Transforming Growth Factor beta1/metabolism , Disease Models, Animal , Cell Proliferation/drug effects , Mice, Inbred C57BL , Smad3 Protein/metabolism , Cell Movement/drug effects , Lung/pathology , Lung/metabolism , Lung/drug effects
9.
Aerosol Sci Technol ; 58(3): 264-275, 2024.
Article En | MEDLINE | ID: mdl-38706712

The ability to collect size-fractionated airborne particles that contain viable bacteria and fungi directly into liquid medium while also maintaining their viability is critical for assessing exposure risks. In this study, we present the BioCascade impactor, a novel device designed to collect airborne particles into liquid based on their aerodynamic diameter in three sequential stages (>9.74 µm, 3.94-9.74 µm, and 1.38-3.94 µm when operated at 8.5 L/min). Aerosol samples containing microorganisms - either Saccharomyces kudriavzevii or Micrococcus luteus, were used to evaluate the performance of the BioCascade (BC) paired with either the VIable Virus Aerosol Sampler (VIVAS) or a gelatin filter (GF) as stage 4 to collect particles <1.38 µm. Stages 2 and 3 collected the largest fractions of viable S. kudriavzevii when paired with VIVAS (0.468) and GF (0.519), respectively. Stage 3 collected the largest fraction of viable M. luteus particles in both BC+VIVAS (0.791) and BC+GF (0.950) configurations. The distribution function of viable microorganisms was consistent with the size distributions measured by the Aerodynamic Particle Sizer. Testing with both bioaerosol species confirmed no internal loss and no re-aerosolization occurred within the BC. Irrespective of the bioaerosol tested, stages 1, 3 and 4 maintained ≥80% of viability, while stage 2 maintained only 37% and 73% of viable S. kudriavzevii and M. luteus, respectively. The low viability that occurred in stage 2 warrants further investigation. Our work shows that the BC can efficiently size-classify and collect bioaerosols without re-aerosolization and effectively maintain the viability of collected microorganisms.

10.
Res Sq ; 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38699329

In bacteria, algae, fungi, and plant cells, the wall must expand in concert with cytoplasmic biomass production, otherwise cells would experience toxic molecular crowding1,2 or lyse. But how cells achieve expansion of this complex biomaterial in coordination with biosynthesis of macromolecules in the cytoplasm remains unexplained3, although recent works have revealed that these processes are indeed coupled4,5. Here, we report a striking increase of turgor pressure with growth rate in E. coli, suggesting that the speed of cell wall expansion is controlled via turgor. Remarkably, despite this increase in turgor pressure, cellular biomass density remains constant across a wide range of growth rates. By contrast, perturbations of turgor pressure that deviate from this scaling directly alter biomass density. A mathematical model based on cell wall fluidization by cell wall endopeptidases not only explains these apparently confounding observations but makes surprising quantitative predictions that we validated experimentally. The picture that emerges is that turgor pressure is directly controlled via counterions of ribosomal RNA. Elegantly, the coupling between rRNA and turgor pressure simultaneously coordinates cell wall expansion across a wide range of growth rates and exerts homeostatic feedback control on biomass density. This mechanism may regulate cell wall biosynthesis from microbes to plants and has important implications for the mechanism of action of antibiotics6.

11.
Aerosol Sci Technol ; 58(3): 217-243, 2024.
Article En | MEDLINE | ID: mdl-38764553

As SARS-CoV-2 swept across the globe, increased ventilation and implementation of air cleaning were emphasized by the US CDC and WHO as important strategies to reduce the risk of inhalation exposure to the virus. To assess whether higher ventilation and air cleaning rates lead to lower exposure risk to SARS-CoV-2, 1274 manuscripts published between April 2020 and September 2022 were screened using key words "airborne SARS-CoV-2 or "SARS-CoV-2 aerosol". Ninety-three studies involved air sampling at locations with known sources (hospitals and residences) were selected and associated data were compiled. Two metrics were used to assess exposure risk: SARS-CoV-2 concentration and SARS-CoV-2 detection rate in air samples. Locations were categorized by type (hospital or residence) and proximity to the sampling location housing the isolated/quarantined patient (primary or secondary). The results showed that hospital wards had lower airborne virus concentrations than residential isolation rooms. A negative correlation was found between airborne virus concentrations in primary-occupancy areas and air changes per hour (ACH). In hospital settings, sample positivity rates were significantly reduced in secondary-occupancy areas compared to primary-occupancy areas, but they were similar across sampling locations in residential settings. ACH and sample positivity rates were negatively correlated, though the effect was diminished when ACH values exceeded 8. While limitations associated with diverse sampling protocols exist, data considered by this meta-analysis support the notion that higher ACH may reduce exposure risks to the virus in ambient air.

12.
Heliyon ; 10(10): e30953, 2024 May 30.
Article En | MEDLINE | ID: mdl-38770312

Background: Acute dizziness is a common symptom in the emergency department (ED), with strokes accounting for 3 %-5 % of cases. We investigated the risk of stroke in ED patients with acute dizziness and compared stroke characteristics diagnosed during and after the ED visit. Methods: We identified adult patients with acute dizziness, vertigo, or imbalance using a hospital research-based database. Patients with abdominal or flank pain were used as the comparison group. Patients with dizziness were 1:1 matched to comparison patients. Each patient was traced for up to one year until being hospitalized for a stroke. Results: Out of the 24,266 eligible patients, 589 (2.4 %) were hospitalized for stroke during the ED visit. For the remaining 23,677 patients, the risk of stroke at 7, 30, 90, and 365 days after ED discharge was 0.40 %, 0.52 %, 0.71 %, and 1.25 % respectively. Patients with dizziness had a higher risk of stroke compared to the comparison group at 7, 30, 90, and 365 days. The risk ratios decreased from 5.69 (95 % confidence interval [CI], 3.34-9.68) to 2.03 (95 % CI, 1.65-2.49). Compared to patients hospitalized for stroke during the ED visit, those hospitalized for stroke after the ED visit had greater stroke severity despite a lower initial triage acuity. Patients with early stroke (≤7 days) after ED discharge were less likely to have hypertension, diabetes, hyperlipidemia, and atrial fibrillation. They mostly experienced posterior circulation stroke. Patients with late stroke (>7 days) were older and less likely to have hypertension and hyperlipidemia but more likely to have a history of prior stroke and ischemic heart disease. Their strokes were mainly located in the anterior circulation territory. Conclusions: The risk of stroke after ED discharge was higher in patients with dizziness than in the comparison group, with gradually decreasing risk ratios in the following year. Patients hospitalized for stroke during and after the ED visit had different profiles of vascular risk factors and clinical characteristics.

13.
J Med Virol ; 96(5): e29686, 2024 May.
Article En | MEDLINE | ID: mdl-38767142

Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays designed to discriminate genotype (GT)-1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV-viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next-generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%-98.5%) and 95.3% (95% CI: 93.4%-96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT-6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT-6a. Both assays demonstrated low accuracies for HCV GT-6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%-99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT-6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut-off viral load of 8.4% in minor genotype.


Genotype , Genotyping Techniques , Hepacivirus , Hepatitis C , High-Throughput Nucleotide Sequencing , Humans , Hepacivirus/genetics , Hepacivirus/classification , Hepacivirus/isolation & purification , Genotyping Techniques/methods , High-Throughput Nucleotide Sequencing/methods , Hepatitis C/diagnosis , Hepatitis C/virology , Molecular Diagnostic Techniques/methods , Sensitivity and Specificity , Reagent Kits, Diagnostic/standards , Female , Male , Middle Aged , Adult
14.
Hum Gene Ther ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38767504

Early diagnosis and intervention are pivotal in reducing colorectal cancer (CRC) incidence and enhancing patient outcomes. In this study, we focused on three genes, AQP8, GUCA2B, and SPIB, which exhibit high co-expression and play crucial roles in suppressing early-stage CRC. Our objective was to identify key miRNAs that can mitigate CRC tumorigenesis and modulate the co-expression network involving these genes. We conducted a comprehensive analysis using large-scale tissue mRNA data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus to validate the co-expression of AQP8, GUCA2B, and SPIB, and to assess their diagnostic and prognostic significance in CRC. mRNA-miRNA interactions were examined using MiRNet and the Encyclopedia of RNA Interactomes. Furthermore, using various molecular techniques, we conducted miRNA inhibitor transfection experiments in HCT116 cells to evaluate their effects on cell growth, migration, and gene/protein expression. Our findings revealed that, compared to normal tissues, AQP8, GUCA2B, and SPIB exhibited high co-expression and were downregulated in CRC, particularly during tumorigenesis. OncoMirs, hsa-miR-182-5p, and hsa-miR-27a-3p, were predicted to regulate these genes. MiRNA inhibition experiments in HCT116 cells demonstrated the inhibitory effects of miR-27a-3p and miR-182-5p on GUCA2B mRNA and protein expression. These miRNAs promoted the proliferation of CRC cells, possibly through their involvement in the GUCA2B-GUCY2C axis, which is known to promote tumor growth. While the expressions of AQP8 and SPIB were barely detectable, their regulatory relationship with hsa-miR-182-5p remained inconclusive. Our study confirms that hsa-miR-27a-3p and hsa-miR-182-5p are oncomiRs in CRC. These miRNAs may contribute to GUCY2C dysregulation by downregulating GUCA2B, which encodes uroguanylin. Consequently, hsa-miR-182-5p and hsa-miR-27a-3p show promise as potential targets for early intervention and treatment in the early stages of CRC.

15.
BMC Med ; 22(1): 206, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769523

BACKGROUND: Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. METHODS: We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8-11), moderate (4-7), and low (0-3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). RESULTS: The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger's test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P < 0.10, but the value of observed less than expected). And the article was demonstrated with high methodological quality using AMSTAR (score = 9). According to AMSTAR, 18, 32, and 11 studies were categorized as high, moderate, and low quality, respectively. Nine statistically significant associations reached moderate quality based on GRADE. CONCLUSIONS: Our findings suggest a potential relationship between ABO and Rh blood groups and adverse health outcomes. Particularly the association between blood group B and type 2 diabetes mellitus risk.


ABO Blood-Group System , Meta-Analysis as Topic , Observational Studies as Topic , Rh-Hr Blood-Group System , Systematic Reviews as Topic , Humans , Systematic Reviews as Topic/methods , Observational Studies as Topic/methods
16.
Cell Commun Signal ; 22(1): 266, 2024 May 13.
Article En | MEDLINE | ID: mdl-38741139

Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).


Glioblastoma , PPAR gamma , Temozolomide , Temozolomide/pharmacology , Temozolomide/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , Animals , PPAR gamma/metabolism , Mice , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Disease Progression , Serotonin/metabolism , Signal Transduction/drug effects , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , PPAR-gamma Agonists
17.
Front Endocrinol (Lausanne) ; 15: 1397512, 2024.
Article En | MEDLINE | ID: mdl-38745951

Background: The Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study. Methods: We included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC. Results: After adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC. Conclusion: Our study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.


Colorectal Neoplasms , Oxidative Stress , Humans , Male , Female , Middle Aged , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/blood , Prospective Studies , Incidence , Aged , Risk Factors , Life Style , Adult , Diet , Uric Acid/blood , United Kingdom/epidemiology , Follow-Up Studies
18.
J Vet Intern Med ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38752421

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment-associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non-associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

19.
Environ Technol ; : 1-10, 2024 May 16.
Article En | MEDLINE | ID: mdl-38753520

This study investigated the disinfection efficiency of a photoreactor equipped with a helical water flow channel and ultraviolet-C (UV-C) light emitting diodes (LEDs). Theoretical simulations and biodosimetry tests were conducted to investigate the effects of coil diameter and flow rate on the reactor's performance in inactivating Escherichia coli. The interplay between hydrodynamics and UV radiation was analyzed to determine the UV fluence absorbed by the microbes. The simulations revealed that, primarily due to the specific radiation pattern of the UV LEDs, the coil diameter strongly influenced the distribution of irradiance in the water and the UV fluence received by microbes. The experimental results indicated that the photoreactor achieved the highest inactivation value of 2.8 log when the coil diameter was 48 mm for a flow rate of 40 mL/min; this log value was superior to those for coil diameters of 16, 32, 64, and 80 mm by approximately 1.9, 0.4, 0.5, and 0.7 log units, respectively. This optimal coil diameter leading to the maximal UV irradiance and the highest degree of irradiance uniformity along the flow channel. This study offers design guidelines for constructing a high-efficiency water disinfection reactor with a helical flow channel configuration.

20.
Geriatr Nurs ; 58: 39-43, 2024 May 15.
Article En | MEDLINE | ID: mdl-38754197

Poor adherence to antidepressants increases the risk of suicide, while greater mental health awareness promotes seeking appropriate treatment, highlighting the urgent need to assess depression knowledge. This study aimed to develop and assess the psychometrics of a Geriatric Depression Knowledge Scale (GDKS) for older adults with depression. In phase 1, 18 items were generated through an intensive literature review and clinical experiences. Phase 2 involved assessing content and face validities of the GDKS. In phase 3, a cross-sectional study (206 older adults, 100 psychiatric professionals) determined construct validity, internal consistency, and test-retest reliability. GDKS demonstrated excellent content and face validity. Older participants scored significantly lower than psychiatric professionals, confirming excellent construct validity. Reliability was evident with a Kuder-Richardson formula 20 score of 0.72 and a 4-week test-retest reliability of 0.86 (p < 0.01). The GDKS provides a reliable tool for evaluating geriatric depression knowledge in psychiatric outpatient settings.

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