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2.
Cancer Med ; 13(12): e7213, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888352

ABSTRACT

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.


Subject(s)
Elective Surgical Procedures , Length of Stay , Mouth Neoplasms , Tracheotomy , Humans , Tracheotomy/methods , Male , Female , Middle Aged , Mouth Neoplasms/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Aged , Elective Surgical Procedures/methods , Length of Stay/statistics & numerical data , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cohort Studies , Adult
3.
Gait Posture ; 113: 145-150, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38901386

ABSTRACT

BACKGROUND: Turning difficulties have been reported in stroke persons, but studies have indicated that fall history might not significantly affect turning performance. Fear of falling (FOF) is common after a fall, although it can occur in individuals without a fall history. RESEARCH QUESTION: Could FOF have an impact on turning performance among chronic stroke patients? METHODS: This cross-sectional study recruited 97 stroke persons. They were instructed to perform 180° and 360° turns, and their performance was represented by angular velocity. FOF was evaluated using the Falls Efficacy Scale-International (FES-I). Falls that occurred 12 months prior to the study assessment were recorded. RESULTS: A higher FES-I score was significantly correlated with a decline in angular velocity in all turning tasks after adjustment for demographic data. The correlation remained significant after controlling for falls history. Participants with a high level of FOF exhibited significantly slower angular velocities during all turning tasks compared with those with a low level of FOF. Participants with a moderate level of FOF had a significantly slower angular velocity than did those with a low level of FOF during the 360° turn to the paretic side only. SIGNIFICANCE: A higher level of FOF, regardless of fall history, was significantly associated with a reduced angular velocity during turning. A high level of FOF affected turning performance in all tasks. Turning performance may not be affected by fall experience. Anxiety about falling may have a greater effect on turning performance than does fall history.

4.
Cancer Med ; 13(10): e7127, 2024 May.
Article in English | MEDLINE | ID: mdl-38770540

ABSTRACT

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.


Subject(s)
Mouth Neoplasms , Humans , Male , Female , Mouth Neoplasms/radiotherapy , Mouth Neoplasms/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Middle Aged , Aged , Taiwan/epidemiology , Neoplasm Staging , Radiotherapy Dosage , Treatment Outcome , Propensity Score , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Adult , Retrospective Studies , Survival Rate , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/surgery , Squamous Cell Carcinoma of Head and Neck/pathology
5.
Prehosp Emerg Care ; 28(5): 669-679, 2024.
Article in English | MEDLINE | ID: mdl-38820136

ABSTRACT

OBJECTIVE: Various prediction scores have been developed to predict mortality in trauma patients, such as the shock index (SI), modified SI (mSI), age-adjusted SI (aSI), and the shock index (SI) multiplied by the alert/verbal/painful/unresponsive (AVPU) score (SIAVPU). The SIAVPU is a novel scoring system but its prediction accuracy for trauma outcomes remains in need of further validation. Therefore, we investigated the accuracy of four scoring systems, including SI, mSI, aSI, and SIAVPU, in predicting mortality, admission to the intensive care unit (ICU), and prolonged hospital length of stay ≥ 30 days (LOS). METHODS: This retrospective multicenter study used data from the Tzu Chi Hospital trauma database. The area under the receiver operating characteristic curve (AUROC) was determined for each outcome to assess their discrimination capabilities and comparing by Delong's test. Subgroup analyses were conducted to investigate the prediction accuracy of the SIAVPU in different patient populations. RESULTS: In total, 5355 patients were included in the analysis. The median of SIAVPU were significantly higher among patients at those with major injury (1.47 vs 0.63), those admitted to the ICU (0.73 vs 0.62), those with prolonged hospital LOS≥ 30 days (0.83 vs 0.64), and those with mortality (1.08 vs 0.64). The AUROC of the SIAVPU was significantly higher than that of the SI, mSI, and aSI for 24-h mortality (AUROC: 0.845 vs 0.533, 0.540, and 0.678), 3-day mortality (AUROC: 0.803 vs 0.513, 0.524, and 0.688), 7-day mortality (AUROC: 0.755 vs 0.494, 0.505, and 0.648), in-hospital mortality (AUROC: 0.722 vs 0.510, 0.524, and 0.667), ICU admission (AUROC: 0.635 vs 0.547, 0.551, and 0.563). At the optimal cutoff value of 0.9, the SIAVPU had an accuracy of 82.2% for predicting 24-h mortality, 82.8% for predicting 3-day mortality, of 82.8% for predicting 7-day mortality, of 82.5% for predicting in-hospital mortality, of 73.9% for predicting Intensive Care Unit (ICU) admission, and of 81.7% for predicting prolonged hospital LOS ≥30 days. CONCLUSIONS: Our results reveal that SIAVPU has better accuracy than the SI, mSI, and aSI for predicting 24-h, 3-day, 7-day, and in-hospital mortality; ICU admission; and prolonged hospital LOS ≥30 days among patients with traumatic injury.


Subject(s)
Wounds and Injuries , Humans , Retrospective Studies , Male , Female , Wounds and Injuries/mortality , Middle Aged , Adult , Emergency Medical Services , Length of Stay/statistics & numerical data , Predictive Value of Tests , Aged , Intensive Care Units/statistics & numerical data , Shock/mortality , ROC Curve , Injury Severity Score , Hospital Mortality
6.
Child Care Health Dev ; 50(3): e13270, 2024 May.
Article in English | MEDLINE | ID: mdl-38706405

ABSTRACT

INTRODUCTION: Chronic physical disease (CPD) makes life filled with many negative events in adolescents, but not all adolescents experiencing negative life events proceed to develop emotional distress, only those with low emotional distress tolerance (EDT). A valid and reliable scale to measure EDT in CPD adolescents is important for caring for their emotional distress. Therefore, the purpose of this study is to translate the 15-item English version Distress Tolerance Scale (DTS) into a Chinese version and then validate the scale for measuring EDT of adolescents with CPD. METHODS: The 15-item English version DTS was translated into a Chinese version using the translation guidelines for cross-cultural research. Two cohorts of adolescents with CPD were recruited from four hospitals in southern Taiwan, with the first cohort including 124 adolescents with CPD employed to conduct exploratory factor analysis, corrected item-total correlation and reliability testing, while the second cohort, consisting of 238 adolescents with CPD, was utilized to examine confirmatory factor analysis and concurrent validity. RESULTS: The two-factor nine-item Chinese version DTS for Adolescents with CPD (C-DTS-A) was developed. Lower scores of the C-DTS-A were significantly associated with higher diabetes distress, poorer self-management, and worse glycaemic control; their correlation coefficients sequentially were -.40, .17 and -.23. Cronbach's α and the test-retest reliability of the two-factor C-DTS-A ranged from .81 to .87 and from .79 to .89, respectively. CONCLUSION: The two-factor nine-item C-DTS-A with good cross-cultural translation quality was a reliable and valid scale to assess EDT for adolescents with CPD.


Subject(s)
Cross-Cultural Comparison , Psychological Distress , Psychometrics , Translations , Humans , Adolescent , Female , Male , Reproducibility of Results , Chronic Disease , Taiwan , Surveys and Questionnaires/standards , Stress, Psychological/diagnosis , Factor Analysis, Statistical , Translating
7.
Lab Anim Res ; 40(1): 16, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649958

ABSTRACT

BACKGROUND: Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. RESULTS: The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37-38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. CONCLUSIONS: We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

8.
Sci Rep ; 14(1): 8716, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38622170

ABSTRACT

Artificial selection has been widely applied to genetically fix rare phenotypic features in ornamental domesticated animals. For many of these animals, the mutated loci and alleles underlying rare phenotypes are known. However, few studies have explored whether these rare genetic mutations might have been fixed due to competition among related mutated alleles or if the fixation occurred due to contingent stochastic events. Here, we performed genetic crossing with twin-tail ornamental goldfish and CRISPR/Cas9-mutated goldfish to investigate why only a single mutated allele-chdS with a E127X stop codon (also called chdAE127X)-gives rise to the twin-tail phenotype in the modern domesticated goldfish population. Two closely related chdS mutants were generated with CRISPR/Cas9 and compared with the E127X allele in F2 and F3 generations. Both of the CRISPR/Cas9-generated alleles were equivalent to the E127X allele in terms of penetrance/expressivity of the twin-tail phenotype and viability of carriers. These findings indicate that multiple truncating mutations could have produced viable twin-tail goldfish. Therefore, the absence of polymorphic alleles for the twin-tail phenotype in modern goldfish likely stems from stochastic elimination or a lack of competing alleles in the common ancestor. Our study is the first experimental comparison of a singular domestication-derived allele with CRISPR/Cas9-generated alleles to understand how genetic fixation of a unique genotype and phenotype may have occurred. Thus, our work may provide a conceptual framework for future investigations of rare evolutionary events in domesticated animals.


Subject(s)
CRISPR-Cas Systems , Goldfish , Animals , Goldfish/genetics , Alleles , Biological Evolution , Mutation , Phenotype , Animals, Domestic/genetics
9.
Nurse Educ Today ; 138: 106155, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38603829

ABSTRACT

BACKGROUND: Good nursing leadership management positively correlates with patient care quality and an organization's performance. Plans to nurture top-notch talents and strengthen management functions are essential to retain key talents and achieve sustainability. The leadership training for nursing staff should begin early to cope with complex clinical situations. OBJECTIVES: To compare the impact of leadership training on high-performing young nurses' (young nursing elite) management functions and team behavior. SETTING: A public teaching hospital in Taipei, Taiwan. METHODS: This research implemented a longitudinal quasi-experimental study with a fixed time series design; the target subjects were youth nursing elites who received training, along with their direct managers and peers, for a total of 102 participants. The training course intervention included the classroom teaching of leadership management functions, arranging internships in the hospital's internal administrative units and professional nursing institutions, and the direct managers sharing their experiences during teaching. We measured the outcome indicators before the course intervention, at the end of the course intervention, and three months after using the management function and team behavior scales. RESULTS: The mean score of the direct managers' assessments regarding the youth nursing elite's pre-test team behavior was 4.18. This improved by 0.68 points (p < .001) after the program intervention and improved by 0.65 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the two groups as analyzed using GEE. The mean score of the pre-test self-assessment management function of the young nursing elite was 3.27. This improved by 1.06 points (p < .001) after the program intervention and by 1.14 points (p < .001) three months after the program compared to the pre-test. There was no statistically significant difference between the three groups using GEE analysis. CONCLUSIONS: Leadership training enhances young nursing professionals' leadership function and team behavior.


Subject(s)
Hospitals, Teaching , Leadership , Humans , Taiwan , Longitudinal Studies , Female , Male , Adult , Nursing Staff, Hospital/education
10.
Singapore Med J ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478735

ABSTRACT

INTRODUCTION: Perioperative hypothermia (PH) is common in children and associated with adverse clinical outcomes. Guidelines to prevent PH are mainly developed for adults and differ among institutions. We aimed to evaluate the effectiveness of customised guidelines in reducing PH in our paediatric population and the impact of cost considerations on physician practice. METHODS: Patients aged ≤16 years undergoing general anaesthesia in our tertiary paediatric hospital were prospectively recruited in this cohort study. Patient demographics, surgical procedures, anaesthesia details and temperature control measures were recorded. Data collection occurred over four phases: Phases 1 and 2 comprised standard management, while Phases 3 and 4 occurred following guidelines implementation. Sensors for continuous core temperature monitoring were provided free to patients during Phases 1 and 3, but were charged during Phases 2 and 4. The main outcome was occurrence of PH, defined as core temperature <36°C at any point from induction of anaesthesia to discharge from the postanaesthetic care unit. The impact of guidelines implementation and cost considerations influencing physician practice on PH outcomes was also analysed. RESULTS: Data from 3917 patients was analysed (1766 in Phase 1, 679 in Phase 2, 706 in Phase 3 and 766 in Phase 4). Guidelines implementation decreased PH incidence from 11.0% to 6.79% (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.50-0.80, P = 0.0002). Free sensors increased the odds of detecting PH (OR 1.48, 95% CI 1.17-1.88, P = 0.001). With guidelines implementation, there was greater reduction in PH with free sensors (OR 0.64, 95% CI 0.47-0.88, P = 0.0055) compared to chargeable sensors (OR 0.75, 95% CI 0.50-1.11, P = 0.1471). CONCLUSIONS: Customised guidelines facilitated a sustained reduction of hypothermia in our paediatric surgical patients, although its impact was reduced by cost considerations.

11.
Creat Nurs ; 30(2): 133-144, 2024 May.
Article in English | MEDLINE | ID: mdl-38533549

ABSTRACT

Aims: This review aimed to identify and map the evidence about sarcopenia among older Filipinos. Methods: Studies about sarcopenia among Filipinos aged 60 and above were included. All studies regardless of type, setting, language, and timeframe were reviewed. The Cochrane Library, Cumulative Index of Nursing and Allied Health, Embase, PubMed, and Health Research and Development Information Network were searched. The study was conducted per an a priori protocol and utilized the Joanna Briggs Institute guidance for scoping reviews. Results: From the 87 records identified, 20 studies published from 2013 to 2023 were eligible (≥ 5424 participants). The studies were varied; 11 cross-sectional, 2 conference lectures, 2 consensus reports, 1 meta-analysis, cohort study, case series, posthoc analysis, and continuing education. As to setting, 11 studies were conducted in the hospital and 4 in the community. On the level of prevention, 5 studies addressed the primary level, 10 studies secondary, and 2 studies both tertiary and secondary. The studies focused on: sarcopenia in a specific group (13 studies), consensus (4 studies), and education (3 studies). Conclusions: Sarcopenia studies among older Filipinos were limited. Most were hospital-based and involved patients with comorbidities. Some studies used sarcopenia assessment guidelines with Filipino normative references. Sarcopenia impacts the overall well-being of older Filipinos; hence more studies and health promotion programs are necessary.


Subject(s)
Sarcopenia , Humans , Philippines/epidemiology , Sarcopenia/epidemiology , Aged , Female , Male , Middle Aged , Aged, 80 and over , Cross-Sectional Studies
12.
Oral Oncol ; 151: 106745, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38460286

ABSTRACT

BACKGROUND: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm. METHODS: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted. RESULTS: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398). CONCLUSIONS: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Child, Preschool , Squamous Cell Carcinoma of Head and Neck/pathology , Retrospective Studies , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Prognosis , Head and Neck Neoplasms/pathology , Neoplasm Staging
14.
Prim Care Diabetes ; 18(3): 257-267, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38490914

ABSTRACT

AIMS: To explore the effectiveness of the Taiwanese Diabetes Shared Care Program (DSCP) on improving the metabolic indicators of people with type 2 diabetes. METHODS: Relevant studies published between January 2002 and August 2021 were retrieved from Chinese- and English-language electronic databases, including PubMed, MEDLINE, CINAHL, ProQuest, Cochrane Library, Airiti Library, and Taiwan Periodical Literature System. After screening, studies that met inclusion criteria were included in the literature review. RevMan 5.4 was employed for a meta-analysis. RESULTS: Ten studies published between 2007 and 2021 were included in the systematic review, with nine of them contributing to the meta-analysis. In total, 1506 and 1388 participants were classified into DSCP and non-DSCP groups, respectively, for the meta-analysis. The results revealed that the DSCP significantly improved glycated hemoglobin levels (mean difference [MD]: -0.50, 95% Confidence Interval [CI]: -0.83 to -0.17) and body weights (MD: -0.83, 95% CI: -1.29 to -0.38) within 1-year follow-up. However, it did not show significant improvement in other metabolic indicators. CONCLUSIONS: Taiwanese DSCP led to improvements in glycated hemoglobin levels and body weights among people with type 2 diabetes. This study suggests that people with diabetes and health-care institutions should consider participating in the DSCP.


Subject(s)
Biomarkers , Delivery of Health Care, Integrated , Diabetes Mellitus, Type 2 , Glycated Hemoglobin , Glycemic Control , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Humans , Glycated Hemoglobin/metabolism , Biomarkers/blood , Middle Aged , Female , Male , Treatment Outcome , Blood Glucose/metabolism , Aged , Taiwan/epidemiology , Program Evaluation , Adult , Time Factors , Hypoglycemic Agents/therapeutic use , Body Weight
15.
J Neuroimmune Pharmacol ; 19(1): 11, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530514

ABSTRACT

Neuro-inflammation involves distinct alterations of microglial phenotypes, containing nocuous pro-inflammatory M1-phenotype and neuroprotective anti-inflammatory M-phenotype. Currently, there is no effective treatment for modulating such alterations. M1/M2 marker of primary microglia influenced by Melatonin were detected via qPCR. Functional activities were explored by western blotting, luciferase activity, EMSA, and ChIP assay. Structure interaction was assessed by molecular docking and LIGPLOT analysis. ER-stress detection was examined by ultrastructure TEM, calapin activity, and ERSE assay. The functional neurobehavioral evaluations were used for investigation of Melatonin on the neuroinflammation in vivo. Melatonin had targeted on Peroxisome Proliferator Activated Receptor Delta (PPARδ) activity, boosted LPS-stimulated alterations in polarization from the M1 to the M2 phenotype, and thereby inhibited NFκB-IKKß activation in primary microglia. The PPARδ agonist L-165,041 or over-expression of PPARδ plasmid (ov-PPARδ) showed similar results. Molecular docking screening, dynamic simulation approaches, and biological studies of Melatonin showed that the activated site was located at PPARδ (phospho-Thr256-PPARδ). Activated microglia had lowered PPARδ activity as well as the downstream SIRT1 formation via enhancing ER-stress. Melatonin, PPARδ agonist and ov-PPARδ all effectively reversed the above-mentioned effects. Melatonin blocked ER-stress by regulating calapin activity and expression in LPS-activated microglia. Additionally, Melatonin or L-165,041 ameliorated the neurobehavioral deficits in LPS-aggravated neuroinflammatory mice through blocking microglia activities, and also promoted phenotype changes to M2-predominant microglia. Melatonin suppressed neuro-inflammation in vitro and in vivo by tuning microglial activation through the ER-stress-dependent PPARδ/SIRT1 signaling cascade. This treatment strategy is an encouraging pharmacological approach for the remedy of neuro-inflammation associated disorders.


Subject(s)
Melatonin , PPAR delta , Rats , Mice , Animals , Microglia , PPAR delta/metabolism , PPAR delta/pharmacology , PPAR delta/therapeutic use , Melatonin/pharmacology , Lipopolysaccharides/pharmacology , Sirtuin 1/metabolism , Molecular Docking Simulation , Inflammation/metabolism
16.
ACS Appl Mater Interfaces ; 16(12): 15394-15404, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38489480

ABSTRACT

External stimuli-responsive DNA hydrogels present interesting platforms for drug loading and triggered release. Typically, drug molecules are encapsulated within three-dimensionally hybridized DNA networks. However, the utilization of drug molecules as cofactors to facilitate the directed assembly of DNA strands into hydrogel frameworks and their subsequent controlled release remains to be explored. Herein, we introduce the guided assembly of oligo-adenine (A-strand) into an acidic pH-responsive DNA hydrogel using an anticancer drug, coralyne (COR), as a low-molecular-weight cofactor. At pH 7, COR orchestrates the assembly of A-strand into an antiparallel duplex configuration cross-linked by A-COR-A units at a stoichiometric ratio of one COR cofactor per four adenine bases, resulting in a DNA hydrogel characterized by A-COR-A duplex bridges. At pH 4-5, the instability of A-COR-A units results in the disintegration of the duplex into its constituent components, leading to the release of COR and simultaneous dissociation of the DNA hydrogel matrix. This study introduces a method by which drug molecules, exemplified here by COR, facilitate the direct formation of a supramolecular cofactor-DNA complex, subsequently leading to the creation of a stimuli-responsive DNA hydrogel. This approach may inspire future investigations into DNA hydrogels tailored for controlled drug encapsulation and release applications.


Subject(s)
Adenine , Berberine Alkaloids , Hydrogels , Hydrogels/chemistry , DNA/chemistry , Hydrogen-Ion Concentration
17.
J Formos Med Assoc ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38331637

ABSTRACT

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

18.
Cancer Med ; 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38169115

ABSTRACT

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

20.
Ophthalmol Retina ; 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38280425

ABSTRACT

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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