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1.
Nat Sci Sleep ; 16: 461-471, 2024.
Article in English | MEDLINE | ID: mdl-38737461

ABSTRACT

Aim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30-74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as "low" (<6%), "intermediate" (6-20%), or "high" (>20%). Groups were compared on symptom and polysomnographic variables. Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI. Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.

2.
Bioact Mater ; 38: 486-498, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38779592

ABSTRACT

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

3.
Sleep Med Rev ; 75: 101930, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38761649

ABSTRACT

There is no consensus on the definition of sleep hygiene and its components. We examined the definition of sleep hygiene based on its use in published studies. Four databases (Medline, EMBASE, PsycINFO and CINAHL) were searched from inception until December 31, 2021 for the phrase 'sleep hygiene' in the title or abstract. We identified 548 relevant studies in adults: 250 observational and 298 intervention studies. A definition of sleep hygiene was provided in only 44% of studies and converged on three themes: behavioural factors, environmental factors, and an aspect of control. Sleep hygiene components were explicitly defined in up to 70% of observational studies, but in only 35% of intervention studies. The most commonly considered components of sleep hygiene were caffeine (in 51% of studies), alcohol (46%), exercise (46%), sleep timing (45%), light (42%), napping (39%), smoking (38%), noise (37%), temperature (34%), wind-down routine (33%), stress (32%), and stimulus control (32%), although the specific details of each component varied. Lack of consistency in definitions of sleep hygiene and its components may hinder communication between researchers, clinicians, and the public, and likely limits the utility of sleep hygiene as an intervention.

4.
Korean J Intern Med ; 39(3): 513-523, 2024 May.
Article in English | MEDLINE | ID: mdl-38649159

ABSTRACT

BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.


Subject(s)
COVID-19 , Cross Infection , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Incidence , Retrospective Studies , Cross Infection/epidemiology , Cross Infection/prevention & control , Cross Infection/diagnosis , Cross Infection/microbiology , Republic of Korea/epidemiology , Male , Female , Middle Aged , Infection Control , Aged , Adult , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/diagnosis , Hematology , SARS-CoV-2
5.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 22-28, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38650160

ABSTRACT

This study aimed to evaluate the physiological role of NAMPT associated with MDPC-23 odontoblast cell proliferation. Cell viability was measured using the (DAPI) staining, caspase activation analysis and immunoblotting were performed. Visfatin promoted MDPC-23 odontoblast cell growth in a dose-dependent manner. Furthermore, the up-regulation of Visfatin promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers in MDPC-23 cells. However, FK-866 cell growth in a dose-dependent manner induced nuclear condensation and fragmentation. FK-866-treated cells showed H&E staining and increased apoptosis compared to control cells. The expression of anti-apoptotic factors components of the mitochondria-dependent intrinsic apoptotic pathway significantly decreased following FK-866 treatment. The expression of pro-apoptotic increased upon FK-866 treatment. In addition, FK-866 activated caspase-3 and PARP to induce cell death. In addition, after treating FK-866 for 72 h, the 3/7 activity of MDPC-23 cells increased in a concentration-dependent manner, and the IHC results also confirmed that Caspase-3 increased in a concentration-dependent. Therefore, the presence or absence of NAMPT expression in dentin cells was closely related to cell proliferation and formation of extracellular substrates.


Subject(s)
Apoptosis , Cell Proliferation , Nicotinamide Phosphoribosyltransferase , Odontoblasts , Nicotinamide Phosphoribosyltransferase/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Odontoblasts/drug effects , Odontoblasts/cytology , Odontoblasts/metabolism , Animals , Mice , Cell Line , Cytokines/metabolism , Caspase 3/metabolism , Cell Differentiation/drug effects , Cell Survival/drug effects , Acrylamides/pharmacology , Odontogenesis/drug effects
6.
Sci Rep ; 14(1): 9660, 2024 04 26.
Article in English | MEDLINE | ID: mdl-38671196

ABSTRACT

Analyzing the correlation between cephalometric measurements is important for improving our understanding of the anatomy in the oral and maxillofacial region. To minimize bias resulting from the design of the input data and to establish a reference for malocclusion research, the aims of this study were to construct the input set by integrating nine cephalometric analyses and to study the correlation structure of cephalometric variables in Korean adults with normal occlusion. To analyze the complex correlation structure among 65 cephalometric variables, which were based on nine classical cephalometric analyses, network analysis was applied to data obtained from 735 adults (368 males, 367 females) aged 18-25 years with normal occlusion. The structure was better revealed through weighted network analysis and minimum spanning tree. Network analysis revealed cephalometric variable clusters and the inter- and intra-correlation structure. Some metrics were divided based on their geometric interpretation rather than their clinical significance. It was confirmed that various classical cephalometric analyses primarily focus on investigating nine anatomical features. Investigating the correlation between cephalometric variables through network analysis can significantly enhance our understanding of the anatomical characteristics in the oral and maxillofacial region, which is a crucial step in studying malocclusion using artificial intelligence.


Subject(s)
Cephalometry , Humans , Cephalometry/methods , Male , Female , Adult , Adolescent , Republic of Korea , Young Adult , Dental Occlusion , East Asian People
7.
Article in English | MEDLINE | ID: mdl-38536685

ABSTRACT

Causal effect estimation of individual heterogeneity is a core issue in the field of causal inference, and its application in medicine poses an active and challenging problem. In high-risk decision-making domain such as healthcare, inappropriate treatments can have serious negative impacts on patients. Recently, machine learning-based methods have been proposed to improve the accuracy of causal effect estimation results. However, many of these methods concentrate on estimating causal effects of continuous outcome variables under binary intervention conditions, and give less consideration to multivariate intervention conditions or discrete outcome variables, thus limiting their scope of application. To tackle this issue, we combine the double machine learning framework with Light Gradient Boosting Machine (LightGBM) and propose a double LightGBM model. This model can estimate binary causal effects more accurately and in less time. Two cyclic structures were added to the model. Data correction method was introduced and improved to transform discrete outcome variables into continuous outcome variables. Multivariate Cyclic Double LightGBM model (MCD-LightGBM) was proposed to intelligently estimate multivariate treatment effects. A visual human-computer interaction system for heterogeneous causal effect estimation was designed, which can be applied to different types of data. This paper reports that the system improved the Logarithm of the Minimum Angle of Resolution (LogMAR) of visual acuity change after Vascular Endothelial Growth Factor (anti-VEGF) treatment in patients with diabetic macular degeneration. The improvement was observed in two clinical problems, from 0.05 to 0.33, and the readmission rate of diabetic patients after cure was reduced from 48.4% to 10.5%. The results above demonstrate the potential of the proposed system in predicting heterogeneous clinical drug treatment effects.

8.
Sleep ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38531670

ABSTRACT

STUDY OBJECTIVES: Recent studies suggest sleepy patients with OSA are at higher risk for incident cardiovascular disease. This study assessed cardiac autonomic function in sleepy versus non-sleepy patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. We hypothesised that HRV profiles of sleepy patients would indicate higher cardiovascular risk. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) collected by the Sydney Sleep Biobank were used to study HRV in groups of sleepy (ESS≥10) and non-sleepy OSA patients (ESS<10). HRV parameters were averaged across available ECG signal during N2 sleep. RESULTS: A total of 421 patients were evaluated, with mean age of 54 (14) years, body mass index (BMI) of 33 (9) kg/m2, apnoea hypopnoea index (AHI) of 21 (28) events/h and, 66% male. The sleepy group consisted of 119 patients, and the non-sleepy group 302 patients. Sleepy patients exhibited lower HRV values for: root mean square successive difference (RMSSD, p= 0.028); total power (TP, p= 0.031); absolute low frequency (LF, p= 0.045); and high frequency (HF, p= 0.010) power compared to Non-Sleepy patients. Sleepy patients with moderate to severe OSA exhibited lower HRV values for: (RMSSD, p= 0.045; TP, p= 0.052) ; absolute LF (p= 0.051); and HF power (p= 0.025). There were no differences in other time and frequency domain HRV markers. CONCLUSIONS: This study shows a trend towards parasympathetic withdrawal in sleepy OSA patients, particularly in moderate to severe cases, lending mechanistic support to the link between the sleepy phenotype and CVD risk in OSA.

9.
Article in English | MEDLINE | ID: mdl-38534063

ABSTRACT

An 82-year-old woman presented with a 6-month history of an enlarging brow mass that developed after trauma. Clinical and MRI appearance of the lesion appeared consistent with epidermal inclusion cyst. However, excisional biopsy demonstrated invasive squamous cell carcinoma, which recurred 6 weeks later and required repeat surgical excision. To our knowledge, this represents the first case of squamous cell carcinoma arising from a posttraumatic epidermal inclusion cyst.

10.
Sleep Med ; 116: 62-70, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38430792

ABSTRACT

INTRODUCTION: Understanding how persons with narcolepsy conceptualize symptoms, daily impact and illness experience is key to facilitating dialogue between patients and healthcare professionals. These concepts are usually explored from the perspective of healthcare professionals/researchers and rarely from the perspective of those with narcolepsy. METHODS: 127 self-reported persons with narcolepsy were recruited from an Australian patient support group. A short demographic survey was completed. All agreed to participate in a subsequent 1:1 semi-structured interview. Saturation was reached after 24 interviews (mean age = 33 years (SD 11) with 44% reporting cataplexy). A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Participants perceived physical fatigue, sleepiness, and two separate experiences of 'falling asleep/sleep attacks' as distinct symptoms rather than a multidimensional construct (i.e. excessive daytime sleepiness). We also identified two experiences of cataplexy, one triggered by acute emotion and another by a stressor. Participants determined their narcolepsy to be 'well-managed' by the level of functional impairment rather than the frequency of any symptom. Almost all participants described experiencing anticipated stigma and internalized or 'self-' stigma, likely stemming from societal devaluation of sleep and the conflation of sleepiness with laziness. CONCLUSION: Descriptions of common symptoms often differed between participants and the existing literature. These differences likely impact patient-physician communication, with both parties utilizing the same terminology to communicate different concepts. The characterization of stigma in narcolepsy presents opportunities for future research exploring the impact and possible development of interventions to reduce the substantial psychological comorbidity in persons with narcolepsy.


Subject(s)
Cataplexy , Disorders of Excessive Somnolence , Narcolepsy , Humans , Adult , Cataplexy/diagnosis , Sleepiness , Australia , Narcolepsy/diagnosis , Disorders of Excessive Somnolence/diagnosis
11.
Cell Mol Immunol ; 21(4): 349-361, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38311677

ABSTRACT

Distinct neutrophil populations arise during certain pathological conditions. The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear. In this study, using an experimental sepsis model that features immunosuppression, we identified a novel population of pathogenic CD200Rhigh neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (Treg) cells. Compared to their CD200Rlow counterparts, sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production. Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis, and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200Rhigh neutrophils. The administration of an α-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200Rhigh neutrophils expressed high levels of Igf1, which elicits the generation of Treg cells, while the administration of an α-CD200R antibody inhibited Treg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200Rhigh neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.


Subject(s)
Coinfection , Sepsis , Humans , T-Lymphocytes, Regulatory , Neutrophils , Immunosuppression Therapy , Antibodies , Autophagy
12.
J Chest Surg ; 57(2): 205-212, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38419583

ABSTRACT

Background: Postoperative atrial fibrillation (A-fib) is a serious complication of cardiac surgery that is associated with increased mortality and morbidity. Traditional 24-hour Holter monitors have limitations, which have prompted the development of innovative wearable electrocardiogram (ECG) monitoring devices. This study assessed a patch-type wearable ECG device (MobiCARE-MC100) for monitoring A-fib in patients undergoing cardiac surgery and compared it with 24-hour Holter ECG monitoring. Methods: This was a single-center, prospective, investigator-initiated cohort study that included 39 patients who underwent cardiac surgery between July 2021 and June 2022. Patients underwent simultaneous monitoring with both conventional Holter and patchtype ECG devices for 24 hours. The Holter device was then removed, and patch-type monitoring continued for an additional 48 hours, to determine whether extended monitoring provided benefits in the detection of A-fib. Results: This 72-hour ECG monitoring study included 39 patients, with an average age of 62.2 years, comprising 29 men (74.4%) and 10 women (25.6%). In the initial 24 hours, both monitoring techniques identified the same number of paroxysmal A-fib in 7 out of 39 patients. After 24 hours of monitoring, during the additional 48-hour assessment using the patch-type ECG device, an increase in A-fib burden (9%→38%) was observed in 1 patient. Most patients reported no significant discomfort while using the MobiCARE device. Conclusion: In patients who underwent cardiac surgery, the mobiCARE device demonstrated diagnostic accuracy comparable to that of the conventional Holter monitoring system.

13.
NPJ Vaccines ; 9(1): 34, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38360752

ABSTRACT

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

14.
Neurol Sci ; 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38400888

ABSTRACT

OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

15.
J Clin Sleep Med ; 20(5): 699-707, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38169428

ABSTRACT

STUDY OBJECTIVES: Parents/carers of a child with narcolepsy are often required to become experts in narcolepsy and navigate health care, education, and welfare systems on behalf of their child. Managing pediatric narcolepsy is complex and challenges the child and the entire family, yet few studies have explored carers' experiences. METHODS: Twenty mothers (50% had a child with narcolepsy < 18 years at the time of interview; 85% narcolepsy with cataplexy) participated in a 1:1 semistructured interview. Participation from fathers was sought; however, none were recruited. A multidisciplinary team of researchers/clinicians analyzed interview transcripts using thematic analysis. RESULTS: Mothers perceived that most people misunderstood the whole-person impact of narcolepsy, including their child's peers, teachers, and support networks. Narcolepsy had a substantial psychological impact on both the child and the whole family yet was largely unaddressed by health care professionals, leaving mothers unsure of where to turn for help. Most parents described negative experiences with their child's specialist, often perceiving the specialists to lack knowledge specific to narcolepsy. Information about illness trajectory and support services was limited or inaccessible, fueling many mothers' hopes and fears for their child's future. Mothers also frequently described feelings of abandonment by the health care system. CONCLUSIONS: Our results contextualize the whole-person impact of narcolepsy from the perspective of parents and carers, highlighting the need for proactive inclusion of parents/carers in developing health care policy and practice. It calls for developing tools and resources to capture "well-managed" narcolepsy from the perspective of parents/carers for use in research and clinical practice. CITATION: Schokman A, Cheung J, Klinner C, et al. A qualitative exploration of the lived experience of mothers caring for a child with narcolepsy. J Clin Sleep Med. 2024;20(5):699-707.


Subject(s)
Caregivers , Mothers , Narcolepsy , Qualitative Research , Humans , Narcolepsy/psychology , Mothers/psychology , Female , Child , Caregivers/psychology , Adult , Male , Adolescent , Child, Preschool , Middle Aged
16.
J Proteome Res ; 23(3): 905-915, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38293943

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Animals , Humans , AMP-Activated Protein Kinases , Chromatography, Liquid , Proteomics , Cell Proliferation , Cell Movement , Tandem Mass Spectrometry , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , Disease Models, Animal , Protein Serine-Threonine Kinases , Intracellular Signaling Peptides and Proteins
17.
Curr Med Sci ; 44(1): 110-120, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38277017

ABSTRACT

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.


Subject(s)
Asthma , Leukocytes, Mononuclear , Animals , Mice , Asthma/drug therapy , Asthma/genetics , Immunoglobulin E , Immunoglobulin G , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , RNA, Small Interfering/genetics
18.
Sleep Breath ; 28(1): 349-357, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37770793

ABSTRACT

PURPOSE: This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. METHODS: Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30 s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). RESULTS: In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56 ± 11 years, BMI 29.8 ± 5.3 kg/m2, and treatment duration was 4.0 ± 3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (ß(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. CONCLUSION: The study findings suggest that successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.


Subject(s)
Mandibular Advancement , Sleep Apnea, Obstructive , Male , Humans , Middle Aged , Aged , Female , Occlusal Splints , Prospective Studies , Sleep Apnea, Obstructive/therapy , Heart , Heart Rate/physiology
19.
Midwifery ; 129: 103903, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38056099

ABSTRACT

OBJECTIVE: To explore the levels and predictors of body image dissatisfaction among women at different stages of pregnancy. DESIGN: This was a cross-sectional study design. SETTING AND PARTICIPANTS: A total of 863 Chinese pregnant women were recruited from a tertiary hospital via a convenience sampling method. MEASUREMENT AND FINDINGS: Eligible participants completed a demographic questionnaire and self-reported measures of body image dissatisfaction, pregnancy-related anxiety, prenatal depression, and appearance comparison. Results showed no statistical difference in body image dissatisfaction levels among early-mid pregnancy (47.6 ± 6.17), late-mid pregnancy (47.3 ± 7.56), and late pregnancy stages (48.4 ± 6.22). The generalized linear model showed that gestational weight gain, pregnancy-related anxiety, own/family's perception of pregnancy weight, and current ideal weight change were predictors of body image dissatisfaction in the early-mid pregnancy stage. In addition, pre-pregnancy BMI, appearance comparison, own /family's perception of pregnancy weight, current ideal weight change, and overeating during pregnancy significantly predicted body image dissatisfaction in the late-mid pregnancy stage. Predictors of body image dissatisfaction in the late pregnancy stage comprised planned pregnancy, pre-pregnancy eating disorders, own perception of pregnancy weight, current ideal weight change, pregnancy-related anxiety, and prenatal depression. KEY CONCLUSION AND IMPLICATION FOR PRACTICE: The findings suggest that predictors of body image dissatisfaction differed according to pregnancy stage. Self-perception of pregnancy weight was primary predictor of body image dissatisfaction. Healthcare professionals are recommended to provide prenatal health education to reduce own/family's negative perception of pregnancy weight, so as to alleviate the body image dissatisfaction level of pregnant women.


Subject(s)
Body Dissatisfaction , Female , Pregnancy , Humans , Body Image , Cross-Sectional Studies , Pregnant Women , Self Concept , Body Mass Index
20.
Horm Behav ; 157: 105450, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37923628

ABSTRACT

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.


Subject(s)
Depressive Disorder, Major , Humans , Adolescent , Female , Estradiol , Depression , Emotions/physiology , Affect , Facial Expression
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