The association between retinal vascular fractal dimension and cognitive function in the community-dwelling older adults cohort TIGER.

BACKGROUND/PURPOSE: The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df), representing the complexity of the retinal microcirculation. However, the connection between retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between retinal vascular complexity and cognitive impairment over time in non-demented community-dwelling older adults. METHODS: This four-year prospective cohort study (2015-2019) is part of the ongoing Taiwan Initiative for Geriatric Epidemiological Research (TIGER, 2011 to present). Of the 434 older adults (age >65) recruited, 207 participants were included for analysis. The retinal vascular Df was assessed by baseline images from fundus photography (2015-2017). Global (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition were assessed at the baseline and 2-year follow-up (2017-2019). The multivariable linear regression models and generalized linear mixed models were used to evaluate the association of Df with cognitive decline/impairment over time. RESULTS: Decreased left retinal vascular complexity was associated with poor attention performance (ß = -0.40). As follow-up time increased, decreased vascular complexity was associated with poor memory performance (right: ß = -0.25; left: ß = -0.19), and decreased right vascular complexity was associated with poor attention performance (ß = -0.18). CONCLUSION: Low retinal vascular complexity of the right or left eye may be differentially associated with cognitive domains in community-dwelling older adults over two years. The retinal vascular Df of either eye may be served as a screening tool for detecting cognitive impairment in the preclinical phase of dementia.

The microRNA-210/Casp8ap2 Axis Alleviates Hypoxia-Induced Myocardial Injury by Regulating Apoptosis and Autophagy.

Coronary heart disease (CHD) is a serious condition comprising atherosclerosis-mediated ischaemic and hypoxic myocardial injury. This study aimed to investigate the mechanism of the miR-210/Casp8ap2 signalling pathway in hypoxic myocardial cells. mRNA and protein expression levels were determined by quantitative real-time PCR and western blotting, respectively. MTT was used to evaluate cell survival, and flow cytometry was used to assess apoptosis and the cell cycle distribution. The interaction between miR-210 and -Casp8ap2 was detected by dual-luciferase reporter assay. As a result, overexpression of miR-210 significantly inhibited apoptosis and reduced the proportion of cells in G1 phase. Moreover, miR-210 suppressed autophagy by upregulating p62 levels and reducing the LC3-II/I ratio in hypoxic cardiomyocytes. miR-210 regulated apoptosis and autophagy by directly targeting Casp8ap2. Furthermore, the expression levels of Casp8ap2, Cleaved caspase 8, Cleaved caspase 3and Beclin-1 were all decreased in response to miR-210. In short, our results suggest that miR-210 exerts anti-apoptotic and anti-autophagic effects in hypoxic cardiomyocytes, which alleviates myocardial injury in response to hypoxia.

Risk of developing diabetes in patients with atrial fibrillation taking non-vitamin K antagonist oral anticoagulants or warfarin: A nationwide cohort study.

AIM: To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head-to-head comparison. RESULTS: A total of 10 746 new-onset AF patients were included in our study. During the mean 2.4-year follow-up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68-0.94, P = .007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62-0.89, P = .002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58-0.84, P < .001). CONCLUSIONS: Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF.

Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed photobiomodulation (PBM) could effectively downregulate the process of inflammation with modification of macrophage polarization after SCI; however, the potential mechanism behind that is still unclear. In the presented study, we aimed to investigate the effect of PBM on the expression level of versican, a matrix molecular believed to be associated with inflammation, and tried to find the mechanism on how that could regulate the inflammation process. Using immunofluorescence technique and western blot, we found the expression level of versican is increased after injury and markedly downregulated by irradiation treatment. Using virus intrathecal injection, we found the knock-down of versican could produce the effect similar to that of PBM and might have an effect on inflammation and macrophage polarization after SCI. To further verify the deduction, we peptide the supernatant of astrocytes to induce M0, M1, and M2 macrophages. We found that the versican produced by astrocytes might have a role on the promotion of M2 macrophages to inflammatory polarization. Finally, we investigated the potential pathway in the regulation of M2 polarization with the induction of versican. This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI.

Fetal Aortic Blood Flow Velocity and Power Doppler Profiles in the First Trimester: A Comprehensive Study Using High-Definition Flow Imaging.

OBJECTIVES: This study aimed to establish reference values for fetal aortic isthmus blood flow velocity and associated indices during the first trimester, utilizing a novel ultrasonographic technique known as high-definition flow imaging (HDFI). Additionally, the correlation between Doppler profiles of aortic blood flow and key fetal parameters, including nuchal thickness (NT), crown-rump length (CRL), and fetal heartbeat (FHB), was investigated. METHODS: A total of 262 fetuses were included in the analysis between December 2022 and December 2023. Utilizing 2D power Doppler ultrasound images, aortic blood flow parameters were assessed, including aortic peak systolic velocity (PS), aortic end-diastolic velocity (ED), aortic time average maximal velocity (TAMV), and various indices such as aortic systolic velocity/diastolic velocity (S/D), aortic pulsatile index (PI), aortic resistance index (RI), aortic isthmus flow velocity index (IFI), and aortic isthmic systolic index (ISI). Concurrently, fetal FHB, NT, and CRL were evaluated during early trimester Down syndrome screening. RESULTS: Significant findings include a positive correlation between gestational age (GA) and PS (PS = 3.75 × (GA) - 15.4, r2 = 0.13, p < 0.01), ED (ED = 0.42 × (GA) - 0.61, r2 = 0.04, p < 0.01), PI (PI = 0.07 × (GA) + 1.03, r2 = 0.04, p < 0.01), and TAMV (TAMV = 1.23 × (GA) - 1.66, r2 = 0.08, p < 0.01). In contrast, aortic ISI demonstrated a significant decrease (ISI = -0.03 × (GA) + 0.57, r2 = 0.05, p < 0.05) with gestational age. No significant correlation was observed for aortic RI (p = 0.33), S/D (p = 0.39), and IFI (p = 0.29) with gestational age. Aortic PS exhibited positive correlations with NT (0.217, p = 0.001) and CRL (0.360, p = 0.000) but a negative correlation with FHB (-0.214, p = 0.001). Aortic PI demonstrated positive correlations with CRL (0.208, p = 0.001) and negative correlations with FHB (-0.176, p = 0.005). Aortic TAMV showed positive correlations with NT (0.233, p = 0.000) and CRL (0.290, p = 0.000) while exhibiting a negative correlation with FHB (-0.141, p = 0.026). Aortic ISI demonstrated negative correlations with NT (-0.128, p = 0.045) and CRL (-0.218, p = 0.001) but a positive correlation with FHB (0.163, p = 0.010). CONCLUSIONS: Power Doppler angiography with Doppler ultrasound demonstrates the ability to establish accurate reference values for fetal aortic blood flow during the first trimester of pregnancy. Notably, aortic PS, TAMV, and ISI exhibit significant correlations with NT, CRL, and FHB, with ISI appearing more relevant than IFI, PS, TAMV, and FHB. The utilization of HDFI technology proves advantageous in efficiently detecting the site of the aortic isthmus compared to traditional color Doppler mode in early second trimesters.

Gas tamponade for myopic foveoschisis with foveal detachment.

PURPOSE: To evaluate the effects of gas tamponade without vitrectomy in patients with myopic foveoschisis and foveal detachment. METHODS: We examined 10 eyes of 10 patients with myopic foveoschisis and foveal detachment. All patients received an intravitreal injection of 0.2-0.4 mL C3F8 and remained in the prone position for 5 to 7 days. The patients were followed up for at least 6 months after the procedure. The refractive status, best-corrected visual acuity (BCVA), fundus changes, premacular disorders, and anatomical results before and after the treatment were assessed and recorded. All participants underwent serial optical coherence tomography (OCT). RESULTS: All patients had myopia of more than -7 diopters in the lesion eye. Staphyloma with chorioretinal atrophy was noted in all 10 eyes. The best-corrected visual acuity (BCVA) ranged from logMAR 0.52-2.0 before treatment. After initial gas tamponade, foveal detachment had resolved completely in four eyes and partially in four eyes at the 1-month follow-up visit, and two of the partially resolved cases achieved anatomical success after repeated treatment. Another eye achieved reattachment 15 months later and the other had a persistent but decreased level of detachment. Vitrectomy was subsequently performed in the one eye that showed increased detachment, and complete resolution of the schisis-detachment was achieved. The final BCVA improved in seven eyes and none of the study subjects showed decreased visual acuity. CONCLUSION: Gas tamponade is an alternative treatment for myopic foveoschisis with foveal detachment. More than 50 % cases showed a positive response with increased visual acuity. Further, the procedure did not appear to interfere with subsequent vitrectomy, if this procedure must be performed.

Tramadol May Increase Risk of Hip Fracture in Older Adults with Post-Traumatic Osteoarthritis.

Tramadol, an analgesic widely used for arthritic pain, is known to have adverse effects. This study investigated the association between the long-term use of tramadol for pain control and subsequent hip fractures in patients aged 60 years or older with posttraumatic osteoarthritis. This population-based retrospective cohort study included patients with posttraumatic osteoarthritis who received tramadol for pain control for more than 90 days within a 1-year period. A control cohort was enrolled using propensity score matching. The primary outcome was a new diagnosis of hip fracture requiring surgery. In total, 3093 patients were classified into each cohort. Tramadol use was identified as a risk factor for hip fracture (adjusted hazard ratio (aHR): 1.41; 95% confidence interval (CI): 1.09-1.82; p = 0.008), especially among patients aged 60-70 years (aHR: 2.11; 95% CI: 1.29-3.47; p = 0.003) and among male patients (aHR: 1.83; 95% CI: 1.24-2.70; p = 0.002). This is the first cohort study focusing on the association between long-term tramadol use and hip fracture among older adults with posttraumatic osteoarthritis. Tramadol, as a long-term pain control analgesic for older adults with posttraumatic osteoarthritis, may increase the risk of hip fracture, especially among male patients and those aged 60-70 years.

Students' view upon graduation: a survey of medical education in Taiwan.

BACKGROUND: Improving the quality of medical education is a key goal of government policy in Taiwan. The aim of this study was to reflect the responses of medical education from the perspective of graduating medical students in Taiwan. This is the first survey study of medical education in Taiwan. METHODS: Using the Medical School Graduation Questionnaire from the Association of American Medical Colleges (AAMC), we distributed 406 questionnaires to medical students of four medical schools in their last semester, and received 270 back (response rate, 66.5%). There were 11 medical schools in Taiwan. Most questions were assessed on a 5-point Likert scale. RESULTS: Students identified genetics, biochemistry, and ethics as the three most important premedical subjects preparing them for medical education and gross anatomy, physiology, and pharmacology as the three most helpful basic science subjects preparing them for clinical clerkships and electives. Most Taiwanese students were satisfied with their learning experience in internal medicine. Only 55.9% of students were confident that they had acquired the clinical skills required to become a resident, and 70.7% were satisfied with the quality of their medical education. CONCLUSION: The study offers preliminary results on the views of graduating students on the medical education system in Taiwan. In particular, our government and medical educators need to continuously put more effort into building students' confidence in their clinical skills.

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a known complex, multi-organ system disorder with a sudden or subacute onset. ME/CFS occurs most commonly among women between 30 and 50 years of age. The current diagnostic criteria of ME/CFS, as defined by the Centers for Disease Control and Prevention, includes: profound fatigue and post-exertional malaise (>6 mo) unrelieved by rest, persistent cognitive impairment or orthostatic intolerance, and chronic unrefreshing sleep. Despite reported associations between ME/CFS onset and exposure to infectious agents (viral, bacterial, or fungal), the pathophysiology of ME/CFS remains unknown. In this prevalence study, we investigated the rates of Aspergillus-derived toxin levels, Aflatoxin (AF), Ochratoxin A (OTA), and Gliotoxin (GT), in the urinalysis of 236 ME/CFS patients with a history of chronic exposure to mold (i.e., from water-damaged buildings). Among ME/CFS patients reporting chronic exposure to mold, we found evidence of exposure in 92.4 percent of patients, with OTA being the most prevalent mycotoxin. Mold distributions (OTA, AF, and GT) in the urinalysis all demonstrated right skewness, while the distribution of age of ME/CFS patients diagnosed showed no deviation from normality. This study aims to provide preliminary, epidemiological evidence among ME/CFS patients who were diagnosed in South Florida with a history of exposure to mycotoxins. Based on these findings, we proposed how future control studies should approach investigating the association between chronic mold exposure and the diagnosis of ME/CFS.

Evaluating the "holiday season effect" of hospital care on the risk of mortality from pulmonary embolism: a nationwide analysis in Taiwan.

We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15-2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05-1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality.

A comparison of throwing kinematics between youth baseball players with and without a history of medial elbow pain.

Risk factors in throwing factors associated to little league elbow have not been adequately explored. Whether these factors also affect the players' performance is also important to elucidate while modifying throwing pattern to reduce injury. The purpose of this study was to compare the differences in throwing kinematics between youth baseball players with or without a history of medial elbow pain (MEP) and to determine the relationship between their throwing kinematics and ball speed. Fifteen players with previous MEP were matched with 15 healthy players by age, height and weight. Throwing kinematics was recorded by an electromagnetic motion analysis system. A foot switch was used for determining foot off and foot contact. Ball speed was recorded with a sports radar gun. The group with a history of MEP demonstrated less elbow flexion angle at maximum shoulder external rotation and had more lateral trunk tilt at ball release compared to the healthy group. The group with a history of MEP also had faster maximum upper torso rotation velocities, maximum pelvis rotation velocities and ball speeds. Maximum shoulder external rotation angle (r = 0.458, P = 0.011), elbow flexion angle at maximum shoulder external rotation (r = -0.637, P = 0.0003), and maximum upper torso rotation velocity (r = 0.562, P = 0.002) had significant correlation with ball speed. Findings of this study can be treated as elbow injury-related factors that clinicians and coaches can attend to when taking care of youth

Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms.

Drug-induced autoimmune hepatitis (DIH) is the most common hepatic drug-induced hypersensitization process observed in approximately 9 to 12% of patients with autoimmune hepatitis. The overwhelming majority of patients with DIH are women. The underlying mechanisms of these sex differences in prevalence are unclear because of the paucity of animal models that mimic human disease. Even so, underlying mechanisms are widely believed to be associated with human leukocyte antigen haplotypes and sex hormones. In contrast, using a DIH mouse model, we have uncovered that IL-4 initiated CD4+ T cells directed against an epitope of cytochrome P450 2E1 induces influx of neutrophils, macrophages and mast cells into the livers of female BALB/c mice. Using this model, we have also shown that IL-33-induced FoxP3+regulatory T cells confer protection against DIH in female and male mice. This DIH model is induced by immunizing mice with an epitope of CYP2E1 that has been covalently altered with a drug metabolite that has been associated with DIH. This epitope is recognized by patients with DIH. Our method induces robust and reproducible hepatitis and autoantibodies that can be utilized to study the pathogenesis of DIH. While in vivo studies can cause undue pain and distress in mice when done improperly, the advantage of an in vivo model is the ability to evaluate the pathogenesis of disease in a large number of mice. Additionally, biological effects of the altered liver proteins can be studied using invasive procedures. The addition of in vitro studies to the experimental design allows rapid repetition and mechanistic analysis at a cellular level. Thus, we will demonstrate our model protocol and how it can be utilized to study in vivo and in vitro mechanisms of DIH.

Effect of Vitamin D supplementation during pregnancy on maternal and perinatal outcomes.

Vitamin D deficiency is common globally with a higher prevalence in women, especially during pregnancy. Among the pregnant women, Vitamin D deficiency was reported up to 80% in the Asian group. Vitamin D deficiency was related to a higher risk of maternal complications including preeclampsia, impaired glucose tolerance, and cesarean section rate, and neonatal complications including low birthweight, neonatal hypocalcemia seizure, and impaired skeletal, lung and immune development. There were no data supporting Vitamin D deficiency screening routinely in pregnancy regarding cost-effectiveness or health benefits. The measurement of Vitamin D in the high-risk group of women is necessary. Subsequent supplement with Vitamin D with and without calcium supplement during pregnancy had been statistically significantly reported to decrease the risk of preeclampsia, preterm birth, and low birth body weight. However, due to a lack of studies, the strategies of dietary and nutritional supplement for fetal growth restriction prevention are not statistically effective and are not yet recommended. The present review is to provide an overview of the clinical and the experimental evidence of Vitamin D deficiency-related complication and review of available options for the prevention and management of these complications.

The outcome of skeletofacial reconstruction with mandibular rotation for management of asymmetric skeletal class III deformity: A three-dimensional computer-assisted investigation.

The mandibular proximal ramus segments should be moved and rotated during orthognathic surgery-based skeletofacial reconstruction for the correction of challenging patients with facial asymmetry and malocclusion, but quantitative data regarding this rotation were not sufficient to date. This 3D computer-assisted study measured the proximal ramus segment rotation after 3D simulation-guided two-jaw surgery in patients with facial asymmetric deformity and class III malocclusion (n = 31). Using 3D mandible models and a reliable proximal ramus segment-related plane, angular changes in pitch, roll and yaw directions were measured before and one month after surgery. Significant rotational changes (p < 0.01) were observed in the left and right sides and overall proximal ramus segments after surgery, with absolute differences of 4.1 ± 3.0 (range -7.8 to 6.9), 2.8 ± 2.3 (-8.8 to 5.0), and 2.7 ± 2.4 (-6.6 to 9.9) degrees in pitch, roll, and yaw rotations, respectively. Numbness and mouth opening limiting occurred within the first 6 months after surgery but the patients had an unremarkable long-term postoperative course, with no revisionary surgery required. This study contributes to the multidisciplinary-related literature by revealing that proximal ramus segment rotation and rigid fixation with no postoperative intermaxillary immobilization was practicable in skeletofacial surgery for the successful treatment of asymmetric deformity and class III malocclusion.

Postoperative outcomes of two- and three-dimensional planning in orthognathic surgery: A comparative study.

OBJECTIVE: Compared with conventional two-dimensional (2D) planning, three-dimensional (3D) planning in orthognathic surgery yields more accurate anatomical information and enables the precise positioning of maxillary and mandibular segments, particularly for patients with facial asymmetry. Accordingly, surgical outcomes achieved using 3D planning should be superior. This study determined the differences between the 2D and 3D planning techniques by comparing their surgical outcomes. MATERIALS AND METHODS: In this retrospective study, patients who underwent surgery following the traditional 2D planning technique were classified into the 2D planning group. Patients in whom the 2D plan was transferred to a 3D system after surgical simulation were classified into the 3D planning group. Surgical outcomes were compared using cephalometric measurements and patient perception of the results. RESULTS: In the 3D planning group, more favorable results were observed in frontal symmetry, change in the angle between the orbital and occlusal lines, frontal ramus inclination, and the distances from the mandibular central incisor and menton to the midsagittal line. No significant differences were observed in the lateral profiles (SNA, SNB, ANB, and angle convexity) of the two groups. Patient satisfaction was favorable in the two groups, but more patients in the 3D planning group reported being very satisfied. CONCLUSION: The 3D planning technique provided superior overall outcomes. The study findings can be used to augment clinical planning and surgical execution when using a conventional approach.

[Research progression in colorectal cancer stem cells].

Colorectal cancer (CRC) as a common malignancy in the digestive tract, its incidence and mortality increase significantly in China. Cancer stem cells (CSCs) are defined as a small fraction of tumor initiating cells that are endowed with both self-renewal and tumor growth potential. They may be responsible for tumor progression, metastasis, relapse and drug-resistance. Therefore, the isolation and characterization of tumorigenic CSCs in CRC may help to devise novel diagnostic and therapeutic procedures. This review briefly discusses the most recent advances in research on colorectal cancer stem cells including definition of the cancer stem cells, origin and specific markers of the colorectal CSCs. Transduction signal pathway involved in CSCs, potential therapeutic strategies targeting CSCs, and current issues in CSCs related research are also discussed.