OBJECTIVETo detect the function of proteolipid protein (PLP) peptide (residues 56 - 70)-specific CD(4)(+) T cells in experimental allergic encephalomyelitis (EAE) in Biozzi AB/H mice (H-2A(g7)).

METHODSBiozzi AB/H mice were immunized by synthetic PLP(56 - 70) peptide (DYEYLINVIHAFQYV) which was emulsified by sonication with complete Freund's adjuvant, a EAE model proven histologically and clinically. Murine splenocytes and spinal cord infiltrated (SCI) T cells were stimulated by PLP(56 - 70), then the CD(4)(+) T cells were isolated by Dynabeads, and confirmed by staining with anti-CD(4) antibody. Finally, the IL2 bioassay and IFN-gamma/IL4 ELISA were done to detect T cell proliferation and cytokine secretion after PLP(56 - 70) stimulation.

RESULTSThe histology of murine spinal cord showed a great number of lymphocytes infiltrated the spinal cord; the clinical signs showed high scores (4.3) on the peak, as well as a good EAE model. After being isolated by Dynabeads, CD(4)(+) T cells showed high purification (> 99%) by staining with anti-CD(4) antibody. IL2 bioassay showed that those T cells were PLP(56 - 70)-specific T cells. ELISA showed that those T cells had high IFN-gamma/IL4 ratio, indicating that they are T helper 1 (Th1) cells.

CONCLUSIONSPLP(56 - 70)-specific splenocytes and SCI CD(4)(+) T cells in EAE from Biozzi AB/H mice were detected and showed that both of them were PLP(56 - 70)-specific Th1 cells. It is beneficial to understand what kind of role these T cells play in the development of EAE.

Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes ; drug effects ; immunology ; metabolism ; Cell Line ; Encephalomyelitis, Autoimmune, Experimental ; immunology ; pathology ; Interferon-gamma ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Mice ; Mice, Inbred Strains ; Molecular Sequence Data ; Myelin Proteolipid Protein ; chemistry ; immunology ; Peptide Fragments ; administration & dosage ; immunology ; Spleen ; cytology ; immunology ; metabolism ; Th1 Cells ; drug effects ; immunology ; metabolism

OBJECTIVETo investigate the cross-reactivity between glutamic acid decarboxylase (GAD)-I-A(g7) and I-A(d) tetramer in diabetes-prone non-obese diabetic (NOD) mice (I-A(g7)) and diabetes-free Balb/c mice (I-A(d)).

METHODSTwo GAD peptide I-A(g7) and I-A(d) tetramers were generated and compared for phenotype and function of sorted GAD peptide I-A(g7) and I-A(d) tetramer-positive (tet+) T cells.

RESULTSThe cross-reactivity is shown in either tetramer positive percentage or tetramer staining intensity. The NOD and Balb/c derived-tet+ T cells were able to be cross-stained by GAD peptide I-A(g7) and I-A(d) tetramers, and responded to both irradiated NOD and Balb/c splenotyes under stimulation by synthetic and recombinant GAD peptides.

CONCLUSIONAlthough I-A(g7) and I-A(d) are closely related in biochemical and biological aspects, their most notable difference is the presence or absence of a negatively charged residue at position beta57 that links to insulin-dependent diabetes mellitus.

Amino Acid Sequence ; Animals ; Cross Reactions ; Female ; Glutamate Decarboxylase ; immunology ; Histocompatibility Antigens Class II ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Molecular Sequence Data ; T-Lymphocytes ; immunology

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed. Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed. Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31−2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users. Conclusion There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

INTRODUCTIONThe exposed section of a traditional nasogastric (NG) tube can interfere with patients' social activities and thereby result in distress. This study was conducted to evaluate the feasibility and safety of a novel two-piece NG tube for patients with dysphagia.

METHODSTen patients with dysphagia were recruited between November 2011 and May 2012. Patients who were unconscious or in critical condition, had a traditional NG tube < 50 cm or > 60 cm in fixed length, or were unable to follow instructions or sign consent forms were excluded. The two-piece NG tube, which was placed in the patients for one week, comprised a removable external tube that can be joined to an internal tube via a T-connector, which was placed close to the naris. Events related to safety (e.g. nasal pressure sores, number of unplanned extubation, displacement and spontaneous migration of the NG tube, other unpredictable injuries) and effectiveness (e.g. liquid food spills, tube obstruction, perfusion rate, other adverse circumstances) were assessed daily.

RESULTSAll patients received feeding without complication using the two-piece NG tube and none experienced premature removal of the tube. No serious NG tube complications or malfunctions were observed.

CONCLUSIONThe results of this study indicate that the two-piece NG feeding tube is a feasible option for patients with dysphagia. Future improvements to the connector may help enhance its performance. A rigorous randomised controlled trial to examine the effects of the two-piece NG tube on patients' quality of life and quality of medical care is being planned.

Aged ; Aged, 80 and over ; Deglutition Disorders ; therapy ; Enteral Nutrition ; instrumentation ; methods ; Equipment Design ; Female ; Humans ; Intubation, Gastrointestinal ; adverse effects ; methods ; Male ; Middle Aged

Background and Objectives: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. Methods: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. Results: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14–1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. Conclusions Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

Background and Objectives: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. Methods: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. Results: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14–1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. Conclusions Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

Background and Objectives: The impact of off-hours admission (such as weekends, nighttime, and non-working hours) vs. regular hours (weekdays and daytime working hours) on the mortality risk of patients undergoing surgery for type A aortic dissection (TAAD) repair is still uncertain. To address this uncertainty, we undertook a comprehensive systematic review and meta-analysis. We aimed to assess the potential link between off-hours admission and the risk of mortality in patients undergoing TAAD repair surgery. Methods: We conducted a thorough search of the PubMed, Embase, and Cochrane Library databases, covering the period from their inception to May 20, 2023. Our inclusion criteria encompassed all studies that examined the potential relationship between off-hour admission and mortality in individuals who had undergone surgery for TAAD repair. The odds ratios (ORs) were extracted and combined utilizing a random effects model for our synthesis. Results: Nine studies with 16,501 patients undergoing TAAD repair surgery were included in the meta-analysis. Overall, patients who underwent surgery during the weekend had higher in-hospital mortality (pooled OR, 1.41; 95% confidence interval [CI], 1.14–1.75; p=0.002) than those treated on weekdays. However, the mortality risks among patients who underwent TAAD surgery during nighttime and non-working hours were not significantly elevated compared to daytime and working hours admission. Conclusions Weekend surgery for TAAD was associated with a higher in-hospital mortality risk than weekday surgery. However, further studies are warranted to identify and develop strategies to improve the quality of round-the-clock care for patients with TAAD.

There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.