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An untargeted metabolomic study using MALDI-mass spectrometry imaging reveals region-specific biomarkers associated with bowel inflammation

Metabolomics. 2024 Dec 14;21(1):5. doi: 10.1007/s11306-024-02200-4.

ABSTRACT

INTRODUCTION: Inflammatory bowel diseases (IBDs) are chronic immune driven intestinal disorders with marked metabolic alteration. Mass spectrometry imaging (MSI) enables the direct visualization of biomolecules within tissues and facilitates the study of metabolic changes. Integrating multiple spatial information sources is a promising approach for discovering new biomarkers and understanding biochemical alteration within the context of the disease.

OBJECTIVE: This study evaluates the metabolomic changes in gut tissue samples from a preclinical model of spontaneous colitis, the HLA-B27/hβ2m transgenic rat, to uncover disease biomarkers.

METHODS: We applied MSI to study the biochemical profile of bowel samples from HLA-B27/hβ2m transgenic and WT control rats in an unbiased manner. Statistical comparison was used to identify discriminative features. Some features were annotated using LC-MS/MS. The significance of these discriminative features was evaluated based on their distribution within histological layers and the presence of immune infiltration.

RESULTS: We identified spatially resolved changes in the metabolomic pattern of HLA-B27+ samples compared to WT controls. Out of the 275 discriminative features identified, 83 were annotated as metabolites. Two functional groups of discriminative metabolites were discussed as markers of gut barrier impairment and immune cell infiltration.

CONCLUSION: MS imaging’s spatial dimension provides insights into disease mechanisms through the identification of spatially resolved biomarkers.

PMID:39674857 | DOI:10.1007/s11306-024-02200-4

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Biomolecule-functionalized polydiacetylene assembly for visual and on-site sensing of (E)-2-hexenal in fruits

J Food Sci. 2024 Dec 14. doi: 10.1111/1750-3841.17395. Online ahead of print.

ABSTRACT

(E)-2-Hexenal (E2H) is an important volatile organic compound (VOC) that can serve as a marker for fruit quality sensing and shelf-life evaluation. However, visual and portable sensors for E2H have not been reported mainly because of the difficulty in selective response to E2H while avoiding interference from other VOC, especially isomers. Herein, we developed a novel colorimetric sensor based on thiol-functionalized polydiacetylene assembly (PDA-SH/PDA) for the quantitative and selectivity of E2H. The mechanism was that E2H underwent a Michael addition reaction with sulfhydryl groups in PDA-SH/PDA. The Michael addition reaction destroyed the hydrogen bond and distorted the conjugated molecular system, resulting in colorimetric responses. Under optimal conditions, a good linear relationship was observed between E2H concentration and red colorimetric shift (R2 = 0.9679). The E2H sensor yields a high analytical sensitivity of 1.5203% and a limit of detection of 0.015 g L-1. Besides, the PDA-SH/PDA sensor can be used to visually distinguish E2H and its isomer (Z)-3-hexenal. The PDA-SH/PDA sensor yielded a statistically significant difference in red colorimetric shift (p < 0.01) between the pairs of isomers in the ripeness of fruits. At last, the sensor was utilized for detecting E2H in grapes from different shelf lives. We found that the E2H concentration increased from 66.16 ± 1.54 to 67.56 ± 1.30 µg L-1 as storage time was prolonged. The results of this research not only demonstrated the feasibility of visual and on-site detection of E2H but also provided potential promise for portable fruit quality sensing and shelf-life evaluation.

PMID:39674853 | DOI:10.1111/1750-3841.17395

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Application of modified Curie and SIOPEN skeleton scoring systems in 18F-AlF-NOTA-octreotide PET/CT for neuroblastoma

Ann Nucl Med. 2024 Dec 15. doi: 10.1007/s12149-024-02006-3. Online ahead of print.

ABSTRACT

OBJECTIVE: The study aimed to explore the role of fluorine-18-aluminum fluoride-1,4,7-triazacyclononane-1,4,7-triacetic acid-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT) in neuroblastoma (NB) and compared it with Iodine-123 labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy with single photon emission computed tomography/computed tomography (SPECT/CT), as well as to investigate the feasibility of the modified Curie scoring system and International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) skeleton scoring system applied in 18F-OC PET/CT.

METHODS: Patients with pathologically confirmed NB underwent 123I-MIBG scintigraphy with SPECT/CT and 18F-OC PET/CT according the standard imaging protocols. The interval between the two imaging techniques ranged from 0 to 22 days (median interval: 9 days). The number of lesions in modified Curie scoring system and SIOPEN skeleton scoring system applied on 123I-MIBG SPECT/CT and 18F-OC PET/CT was compared.

RESULTS: A total of 50 NB patients (male: female = 25:25) with a median age of 62-month-old were enrolled. 123I-MIBG and 18F-OC imaging were positive in 22 patients and negative in 27 patients. 1 patient had positive 18F-OC but negative 123I-MIBG results (p = 1.000). In lesion-based analysis, 18F-OC PET/CT revealed more positive lesions than 123I-MIBG scintigraphy with SPECT/CT (57 vs. 44, p < 0.001), regardless of bone/bone marrow lesions (43 vs. 37, p = 0.031) or soft tissue lesions (14 vs. 7, p = 0.016). The Curie scores of the two imaging techniques showed a significant difference (p = 0.047), whereas no statistic difference for SIOPEN scores (p = 0.688). The Curie and SIOPEN scores were significantly higher in patients with the presence of MYCN amplification or positive bone marrow puncture result (p < 0.05).

CONCLUSION: 18F-OC could be used in the evaluation of NB, and the modified Curie scoring system could be used to semi-quantify the disease extent of NB in 18F-OC PET/CT.

PMID:39674843 | DOI:10.1007/s12149-024-02006-3

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Demographic profile of surgical approaches to obstructive sleep apnea in the United States from 2004 to 2020: a descriptive study

Sleep Breath. 2024 Dec 15;29(1):60. doi: 10.1007/s11325-024-03197-9.

ABSTRACT

OBJECTIVES: This study aims to evaluate the quantity, types, and trends of surgical procedures used to treat obstructive sleep apnea (OSA) within a diverse national population, utilizing a comprehensive proprietary healthcare database.

METHODS: This descriptive observational study analyzed longitudinal data from the Optum Clinformatics® Data Mart databases, covering the period from January 2004 to December 2020. The study included patients aged 18 to 89 years, both male and female, with a confirmed diagnosis of OSA. These patients were either treated with continuous positive airway pressure (CPAP) or underwent surgical interventions.

RESULTS: Throughout the study period, 1,250,273 individuals were diagnosed with OSA. The average age at diagnosis was 62 years (SD = 16), with a male predominance of 62.3%, and 75% of the patients were identified as Caucasian. The most frequently performed surgical procedure for OSA was Uvulopalatopharyngoplasty (UPPP). However, the implantable hypoglossal nerve stimulator was more commonly utilized among older patients.

CONCLUSIONS: This study provides essential insights into the prevalence and characteristics of surgical procedures used in OSA treatment across a diverse national population. The findings underscore the significance of understanding surgical intervention patterns and trends to enhance patient care and outcomes.

PMID:39674840 | DOI:10.1007/s11325-024-03197-9

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Transitioning medically complex infants home: lessons learned from quality improvement efforts

J Perinatol. 2024 Dec 14. doi: 10.1038/s41372-024-02189-7. Online ahead of print.

ABSTRACT

OBJECTIVE: Decrease: 1) time from tracheostomy or gastrostomy tube placement to discharge home, and 2) avoidable readmissions within 7 days post-discharge, for medically complex infants.

STUDY DESIGN: Five neonatology units and representatives from Medicaid and Managed Care Organizations participated. Measures included length of stay (LOS) from surgery to discharge, readmissions, and time from surgery to identifying home nursing. We used statistical process control (SPC) methods and bivariate tests for post-hoc before-after comparisons.

RESULT: Among 421 infants, no avoidable readmissions occurred in the final 25 months. LOS and all-cause readmissions were unchanged (SPC). LOS changes were variable, ranging from -39.5 days (tracheostomy and ventilator) to +30.8 days (tracheostomy without ventilator) and not significant. Median time to identify home nursing was 70.1 days (range 2-428).

CONCLUSION: Although lack of skilled home nursing precluded improving transitions from NICU to home in medically complex infants, all avoidable readmissions were eliminated for 25 months.

PMID:39674835 | DOI:10.1038/s41372-024-02189-7

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The long-lasting impacts of the COVID-19 pandemic on population-based cancer survival: what are the implications for data analysis?

Br J Cancer. 2024 Dec 14. doi: 10.1038/s41416-024-02931-0. Online ahead of print.

ABSTRACT

Monitoring trends of cancer incidence, mortality and survival is vital for the planning and delivery of health services, and the evaluation of diagnostics and treatment at the population level. Furthermore, comparisons are often made between population subgroups to explore inequalities in outcomes. During the COVID-19 pandemic routine delivery of health services were severely disrupted. Resources were redeployed to COVID-19 services and patient risk of COVID-19 infection required serious consideration. Cancer screening services were paused, the availability of healthcare providers was reduced and, in some cases, patients faced difficulty in accessing optimal treatment in a timely manner. Given these major disruptions, much care should be taken when interpreting changes in cancer survival estimates during this period. The impact on cancer incidence and mortality statistics that have already been reported in some jurisdictions should drive further thought on the corresponding impact on cancer survival, and whether any differences observed are real, artificial or a combination of the two. We discuss the likely impact on key cancer metrics, the likely implications for the analysis of cancer registration data impacted by the pandemic and the implications for comparative analyses between population groups and other risk factor groups when using data spanning the pandemic period.

PMID:39674825 | DOI:10.1038/s41416-024-02931-0

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Significance of diagnostic and therapeutic potential of serum endothelial and inflammatory biomarkers in defining disease severity of dengue infected patients

Med Microbiol Immunol. 2024 Dec 14;214(1):3. doi: 10.1007/s00430-024-00810-2.

ABSTRACT

Dengue virus (DENV) mediated disease severity leads to fatality among infected patients. Immune sentinels recognize DENV thereby secreting inflammatory mediators, endothelial biomarkers and anticoagulation factors. Absence of any diagnostic biomarkers for early identification of severe dengue (SD) patients has hindered disease management. Present study is aimed to evaluate diagnostic potential of these biomarkers along with their therapeutic targets for disease severity. Dengue infection was screened among 214 symptomatic patients and 25 healthy individuals by qRT-PCR, NS1-antigen, anti-dengue-IgM, anti-dengue-IgG ELISA and categorized them according to WHO-classification, 2009. Dengue viral-load and serotypes were determined by qRT-PCR. Serum-protein concentrations of inflammatory mediators (MIF, PAF, MMP2, MMP9, MCP1, RANTES, STNFRI, ST2, EOTAXIN), endothelial biomarkers (SDC1, VEGF, ANGPT2), anticoagulation factors (sTM, vWF, TF, PAI) were determined by sandwich ELISA. Statistical, PPI-network, hub-proteins, drug prediction analysis were performed by GraphPad-Prism9, STRING, Cytoscape-cytoHubba, DrugBank online, TTD, respectively. Among 81 dengue infected patients, significantly higher levels of MIF, PAF, sTNFRI, MMP9, VEGF, ANGPT2, MMP2, RANTES, SDC1 were detected among SD patients compared to non-severe ones, with excellent and good diagnostic potential of first (> 77.11, > 57.57 ng/ml, > 3226 pg/ml) and next three (> 105.3 ng/ml, > 12,380, > 8284 pg/ml) biomarkers, respectively. Serum MIF, PAF, MMP9, sTNFRI levels were significantly higher among hospitalized (p-value: 0.0081-0.0499), high-viral-load (p-value: 0.0266-0.0466) and DENV-2, 4 (p-value: < 0.0001-0.0298) infected patients. PPI-network analysed MMP9, PAI, vWF, ANGPT2, sTM, sTNFRI, MIF as hub-proteins targeted by FDA-approved/experimental drugs. This study recognized serum-biomarkers: MIF, PAF, sTNFRI, MMP9, VEGF, ANGPT2 to have significant diagnostic potential for identification of SD cases.

PMID:39674822 | DOI:10.1007/s00430-024-00810-2

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High-dose-rate (2 fractions of 13.5 Gy) and low-dose-rate brachytherapy as monotherapy in prostate cancer. Long term outcomes and predictive value of nadir prostate-specific antigen

Brachytherapy. 2024 Dec 13:S1538-4721(24)00443-4. doi: 10.1016/j.brachy.2024.10.014. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to evaluate the outcomes of patients treated for low-risk (LR) and favorable intermediate risk (FIR) prostate cancer with brachytherapy (BT) in monotherapy with LDR or HDR and its relationship with nadir PSA (nPSA).

MATERIALS AND METHODS: We retrospectively analyzed 139 patients (2005-2019) with exclusive LDR (46%. 145/160 Gy) /HDR (54%. 2 implants of 13.5 Gy each separated 10 days). 69% LR and 31% FIR. PSA nadir was grouped into two categories: ≤ 0.2 ng/mL and > 0.2 ng/mL.

RESULTS: Median patient age was 69 years (46-84). Seventy-six patients (55%) received androgen deprivation therapy, and 37% received neoadjuvant therapy. Median follow-up period was 90 months. Actuarial biochemical failure-free survival (BFFS), local control (LC), overall survival (OS), and cause-specific survival (CSS) rates for the total cohort were 78%, 87%, 68%, and 98% at 10 years, respectively. BFFS, LC, OS and CSS in nPSA ≤ 0,2 ng/ml was 90%, 96%, 67%, 100% at 10 years respectively, whereas, those with a nPSA > 0.2 ng/ml had a BFFS, LC, OS and CSS of was 37%, 51%, 72%, 90% at 10 years respectively Statistical significance between both groups was reached in BFFS (p=0,000), LC (p=0,000) and CSS (p=0,007)). In the univariate analysis, there was no difference between risk stratification, BT technique, ADT, or the development of bouncing.

CONCLUSIONS: Prostate brachytherapy as monotherapy (LDR and HDR) is an effective treatment option for patients with LR and FIR prostate cancer. nPSA ≤0,2 ng/ml is a representative value that provides prognostic information for favorable outcomes in this group of patients.

PMID:39674772 | DOI:10.1016/j.brachy.2024.10.014

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Peripheral Percutaneous Electrical Nerve Stimulation for Neuropathies: A Systematic Review and Meta-analysis

Pain Manag Nurs. 2024 Dec 13:S1524-9042(24)00308-4. doi: 10.1016/j.pmn.2024.11.005. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective of this review is to demonstrate the use of Peripheral Percutaneous Electrical Nerve Stimulation (PENS), together with its most up-to-date protocols, for the treatment of neuropathies.

DESIGN: We conducted a systematic search for randomised clinical trials evaluating the effectiveness of PENS on pain intensity, sleep quality, oral analgesic intake and depression in patients with neuropathic pain.

DATA SOURCES: The search was performed in Pubmed, PEDro and Cochrane databases.

ANALYSIS METHODS: The meta-analysis was conducted using RevMan 5.4 software. The mean difference was applied for variables with the same measurement scale, while the standardized mean difference was used for different scales. The inverse variance method was employed for statistical analysis, with heterogeneity assessed using the I² and Cochrane Q statistics.

RESULTS: Four articles that met the search requirements were included. After qualitative and quantitative synthesis, the results obtained were an improvement in pain intensity (-3.57 [-4.01, -3.13]; p < .05) and sleep quality (2.48 [1.96, 3.00]; p < .05) and a reduction in medication intake (-2.37 [-4.26, -0.47]; p < .05) and depressive behaviours (-1.10 [-1.55, -0.66]; p < .05). The overall methodological quality was rated as moderate and the risk of bias as unclear.

CONCLUSIONS: The scientific evidence found is still limited for the use of PENS in neuropathies. However, this study suggests an encouraging future for the use of this therapy as a treatment tool in physiotherapy.

NURSING PRACTICE IMPLICATIONS: PENS requires nurse education on electrode/needle placement and patient instruction, with documentation of key parameters. This review emphasizes the need for further research to establish standardized protocols and optimal application parameters for different neuropathic pain conditions.

PMID:39674759 | DOI:10.1016/j.pmn.2024.11.005

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Validity evidence for a French version of the Stigma of Occupational Stress Scale for Doctors (SOSS-D)

Encephale. 2024 Dec 13:S0013-7006(24)00209-4. doi: 10.1016/j.encep.2024.10.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Physicians demonstrate low rates of help seeking for psychiatric disorders, occupational stress, and burnout due to perceived stigma. The Stigma of Occupational Stress Scale for Doctors (SOSS-D) is a brief standardized tool designed to measure stigma (personal, perceived other, and perceived structural) in physicians. The aim of this study was to gather validity evidence for a French version of the SOSS-D.

METHODS: The SOSS-D was translated into French and piloted with 12 physicians. The scale was administered to physicians at the Geneva University Hospitals. We computed descriptive statistics and internal consistency coefficients. Construct validity was analyzed using exploratory (EFA) and confirmatory factor (CFA) analyses.

RESULTS: In total, 323 physicians participated in the survey. The internal consistency coefficient for the French SOSS-D was 0.72, 0.55 for the personal stigma subscale, 0.66 for the perceived other stigma subscale, and 0.65 for the perceived structural stigma subscale. CFA indicated a marginal fit. EFA revealed three factors: personal, perceived other, and perceived structural stigma.

DISCUSSION: Our findings support the hypothesis that stigma is a multi-dimensional construct. However, the French version of the SOSS-D scale did demonstrate some differences when compared to its English version. Identifying stigmatization beliefs among physicians may allow for increased identification of physicians at risk, and increased communication concerning preventive actions. Moreover, being aware of and fighting stigma can reduce barriers to help seeking and increased access to care resources for burnt-out physicians.

CONCLUSION: The results provide evidence of the validity and reliability of the French version of the SOSS-D indicating its suitability for use in a French-speaking physician population.

PMID:39674755 | DOI:10.1016/j.encep.2024.10.002