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Background: The mainstay of treatment for melasma is topical hydroquinone or preparations containing hydroquinone. In recent years, cysteamine cream has gained popularity in the treatment of hyperpigmentation disorders. Objectives: This study aimed to compare the efficacy of combined hydroquinone/betamethasone to cysteamine in the treatment of melasma. Methods: Eighteen patients had completed this open-label controlled trial. Subjects received either 5% cysteamine cream or a combination of 4% hydroquinone cream and 0.06% betamethasone valerate for 12 weeks according to standardized protocols. Patients were assessed at recruitment, 4 weeks, and 12 weeks after treatment for Melasma Area and Severity Index (MASI) scores. Other parameters relating to skin complexions and patient satisfaction were also assessed. Results: Patients treated with hydroquinone (n = 7) and cysteamine (n = 11) both showed significant decreases in MASI score at week 12: 33.1% (P = 0.009) and 37.9% (P = 0.009), respectively. There was no statistically significant difference between the two treatment groups (P = 0.236). Melanin content at week 12 decreased by 8.8% (P = 0.016) in the hydroquinone group and 11.5% (P = 0.046) in the cysteamine group, with no significant difference between the groups (P = 0.253). No significant differences were observed between the groups for other parameters or patient satisfaction. Conclusion: Cysteamine cream may provide an alternative treatment option for individuals with melasma, offering fewer side effects while delivering comparable results.

Abstract Background Mild cognitive impairment (MCI) is the transition stage between the cognitive decline expected in normal aging and more severe cognitive decline such as dementia. The early diagnosis of MCI plays an important role in human healthcare. Current methods of MCI detection include cognitive tests to screen for executive function impairments, possibly followed by neuroimaging tests. However, these methods are expensive and time-consuming. Several studies have demonstrated that MCI and dementia can be detected by machine learning technologies from different modality data. This study proposes a multi-stream convolutional neural network (MCNN) model to predict MCI from face videos. Results The total effective data are 48 facial videos from 45 participants, including 35 videos from normal cognitive participants and 13 videos from MCI participants. The videos are divided into several segments. Then, the MCNN captures the latent facial spatial features and facial dynamic features of each segment and classifies the segment as MCI or normal. Finally, the aggregation stage produces the final detection results of the input video. We evaluate 27 MCNN model combinations including three ResNet architectures, three optimizers, and three activation functions. The experimental results showed that the ResNet-50 backbone with Swish activation function and Ranger optimizer produces the best results with an F1-score of 89% at the segment level. However, the ResNet-18 backbone with Swish and Ranger achieves the F1-score of 100% at the participant level. Conclusions This study presents an efficient new method for predicting MCI from facial videos. Studies have shown that MCI can be detected from facial videos, and facial data can be used as a biomarker for MCI. This approach is very promising for developing accurate models for screening MCI through facial data. It demonstrates that automated, non-invasive, and inexpensive MCI screening methods are feasible and do not require highly subjective paper-and-pencil questionnaires. Evaluation of 27 model combinations also found that ResNet-50 with Swish is more stable for different optimizers. Such results provide directions for hyperparameter tuning to further improve MCI predictions.

IntroductionResearch has shown that speech analysis demonstrates sensitivity in detecting early Alzheimer’s disease (AD), but the relation between linguistic features and cognitive tests or biomarkers remains unclear. This study aimed to investigate how linguistic features help identify cognitive impairments in patients in the early stages of AD.MethodThis study analyzed connected speech from 80 participants and categorized the participants into early-AD and normal control (NC) groups. The participants underwent amyloid-β positron emission tomography scans, brain magnetic resonance imaging, and comprehensive neuropsychological testing. Participants’ speech data from a picture description task were examined. A total of 15 linguistic features were analyzed to classify groups and predict cognitive performance.ResultsWe found notable linguistic differences between the early-AD and NC groups in lexical diversity, syntactic complexity, and language disfluency. Using machine learning classifiers (SVM, KNN, and RF), we achieved up to 88% accuracy in distinguishing early-AD patients from normal controls, with mean length of utterance (MLU) and long pauses ratio (LPR) serving as core linguistic indicators. Moreover, the integration of linguistic indicators with biomarkers significantly improved predictive accuracy for AD. Regression analysis also highlighted crucial linguistic features, such as MLU, LPR, Type-to-Token ratio (TTR), and passive construction ratio (PCR), which were sensitive to changes in cognitive function.ConclusionFindings support the efficacy of linguistic analysis as a screening tool for the early detection of AD and the assessment of subtle cognitive decline. Integrating linguistic features with biomarkers significantly improved diagnostic accuracy.

Objectives: This study aimed to explore the relationship between multidimensional factors, such as environment, health status, behavior, social support, and the well-being of middle-aged and older adults. Methods: This study utilized data from 2 waves of the nationally representative Taiwan Longitudinal Study on Aging Survey Report (TLSA) conducted in 2015 and 2019. The TLSA assesses socioeconomic status, physical and health status, the 5-item World Health Organization Well-Being Index (WHO-5 index), and social support. Data regarding the degree of digital development were obtained from the 2020 Township Digital Development Report. We applied a generalized estimating equation (GEE) to analyze the influencing factors. Results: This study included 4796 participants. Residing in areas with a higher degree of digital development, having a higher socioeconomic status, and experiencing better physical and mental health were significantly associated with well-being. Furthermore, emotional and attentive support mediated the association between physical and mental status and well-being. Conclusion: People’s awareness of searching for and receiving social support and medical resources is important for enhancing their well-being. It is also crucial to pay attention to the living environment and maintain one’s health status to promote well-being.

Background: Air pollution is recognized as a modifiable risk factor for dementia, and recent evidence suggests that improving air quality could attenuate cognitive decline and reduce dementia risk. However, studies have yet to explore the effects of improved air quality on brain structures. This study aims to investigate the impact of air pollution reduction on cognitive functions and structural brain differences among cognitively normal older adults. Methods: Four hundred and thirty-one cognitively normal older adults were from the Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT), a community-based cohort of adults aged 60 and older, between year 2017– 2021. Annual concentrations of PM2.5, NO2, O3, and PM10 at participants’ residential addresses during the 10 years before enrollment were estimated using ensemble mixed spatial models. The yearly rate of change (slope) in air pollutants was estimated for each participant. Cognitive functions and structural brain images were collected during enrollment. The relationships between the rate of air pollution change and cognitive functions were examined using linear regression models. For air pollutants with significant findings in relation to cognitive function, we further explored the association with brain structure. Results: Overall, all pollutant concentrations, except O3, decreased over the 10-year period. The yearly rates of change (slopes) in PM2.5 and NO2 were correlated with better attention (PM2.5: r = -0.1, p = 0.047; NO2: r = -0.1, p = 0.03) and higher white matter integrity in several brain regions. These regions included anterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, and inferior fronto-occipital fasciculus. Conclusions: Greater rate of reduction in air pollution was associated with better attention and attention-related white matter integrity. These results provide insight into the mechanism underlying the relationship between air pollution, brain health, and cognitive aging among older adults.

IntroductionThe microbiota-gut-brain axis is implicated in Alzheimer’s disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences.MethodsA nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3–V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures.ResultsThere was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function.ConclusionThis study provides insights into the role of gut microbiota in the neurodegenerative process.

Background and objectivesAmong individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways.MethodsFrom 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating—Sum of Boxes (CDR-SB).ResultsAfter adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group.ConclusionsCarriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.

Background: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. Method: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. Results: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p

Abstract Home blood pressure (BP) monitoring is a useful tool for hypertension management. BP variability (BPV) has been associated with an increased risk of cardiovascular events. However, little is known about the correlation between BPV and different measurement patterns of long‐term home BP monitoring. This longitudinal cohort study aimed to assess the associations between dynamic BP measurement patterns and BPV. A total of 1128 participants (mean age, 77.4 ± 9.3 years; male, 51%) with 23 269 behavior measuring units were included. We used sliding window sampling to classify the home BP data with a regular 6‐month interval into units in a sliding manner until the data are not continuous. Three measurement patterns (stable frequent [SF], stable infrequent [SI], and unstable [US]) were assessed based on the home BP data obtained within the first 3 months of the study, and the data in the subsequent 3 months were used to assess the BPV of that unit. We used linear mixed‐effects model to assess the association between BP measurement patterns and BPV with adjustment for possible confounding factors including average BP. Average real variability and coefficient variability were used as measures of the BPV. No significant differences were observed in average BP between the SF, SI, and US patterns. However, BPV in the SF group was significantly lower than that in the US and SI groups (all p‐values

Abstract Background Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear. Method 523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry. Result Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status. Conclusion The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.

Abstract Background Chronic kidney disease (CKD) and kidney stones are common in Taiwan; in particular, CKD has a high prevalence but low self-awareness rate. CKD-related risk factors such as diabetes, hypertension, and nephrotoxic drugs are well-known and uncontested; however, kidney stones are relatively less studied and easily overlooked as a risk factor. The objective of this study was to investigate whether kidney stones are a risk factor for CKD. Methods We conducted a nationwide population-based matched cohort study to assess the risk of incident CKD in people with kidney stones. Data on incident stones formers in the year 2001—excluding those with a history of CKD—were obtained from Taiwan’s National Health Insurance database. Stone formers were matched (1:4) to control subjects according to sex, age, and index date. The total observation period of the study was 10 years, and the primary end-point was the occurrence of CKD. Student’s t-test and Chi-squared test were used to compare continuous and categorical data, respectively. Logistic regression was used to calculate the odds ratio of kidney stone patients with incident CKD relative to the control group. Cox proportional hazard regression model was used to obtain the hazard ratio for development of incident CKD among patients with kidney stones. Results The incidence of CKD in the kidney stone cohort was 11.2%, which was significantly higher than that of the control group (P

Background: Chronic kidney disease exhibits a prominent premature aging phenotype in many different organ systems, including the brain. Nevertheless, a comprehensive characterization of brain aging in non-demented patients with end-stage renal disease (ESRD) is lacking and it remains unclear if the collective changes of cognitive functions and brain structures in ESRD is compatible with aging. Methods: We compared 56 non-demented, independently living dialysis patients (mean age 59.4 ± 11.0 years; mean dialysis vintage of 5.9 years) and 60 non-dialysis controls on a battery of neuropsychological tests, brain MRI T1 imaging and diffusion tensor imaging. Participants with diagnosis of dementia, Mini-Mental State Examination

Background: Evidence-based care has become critical in raising the quality of medical facilities. The implementation of evidence-based practice helps medical practitioners make better clinical decisions. Objective: The objective of this study was to investigate whether the innovative flipped teaching model could be as effective as the conventional teaching model in terms of knowledge, attitude, and practice and to confirm the continuous effect. Design: A quasi-experimental design using the flipped and conventional learning groups concurrently with repeat measurements was used. Setting: The setting was a 475-bed regional teaching hospital in Taiwan, from March to July 2020. Participants: The study included 114 licensed nurses who had worked longer than three months, with 57 participants each in two groups. Methods: The participants were assigned to two groups using a block randomization method. All participants completed questionnaires related to knowledge, attitude, and practice of EBP at four-time points: pre-test (T0) and immediately after intervention (T1), at month 1 (T2), and at month 3 (T3). Analysis of repeated generalized estimating equations was used. Results: The flipped and conventional learning groups had significant differences in knowledge, attitude, and practice at the T0 and T1 (p < 0.05). The flipped group was higher than the conventional group at T3 in the knowledge score (p = 0.001) and lower than the conventional group at T2 in the attitude score (p = 0.010). There were no significant differences between the two groups’ practice scores at different time points. There were no significantly different score changes for knowledge, attitude, and practice (p > 0.05). The interaction term only at T3 vs. T0 in the knowledge score was slightly different (p = 0.049) in primary outcome. Conclusion: The intervention methods of both groups were effective. Flipped learning is more flexible and has more time for discussion, which nurses favor. Under the policy promoted in the hospital, EBP combined with the nursing advancement system was standardized, and conventional learning also improved the learning effect.

Abstract Background Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. Results Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. Conclusions Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.

Abstract Background Accumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown. Results Among 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- TEMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease. Conclusion This is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population.

The ventral tegmental area (VTA) receives phenotypically distinct innervations from the pedunculopontine tegmental nucleus (PPTg). While PPTg-to-VTA inputs are thought to play a critical role in stimulus-reward learning, direct evidence linking PPTg-to-VTA phenotypically distinct inputs in the learning process remains lacking. Here, we used optogenetic approaches to investigate the functional contribution of PPTg excitatory and inhibitory inputs to the VTA in appetitive Pavlovian conditioning. We show that photoinhibition of PPTg-to-VTA cholinergic or glutamatergic inputs during cue presentation dampens the development of anticipatory approach responding to the food receptacle during the cue. Furthermore, we employed in vivo optetrode recordings to show that photoinhibition of PPTg cholinergic or glutamatergic inputs significantly decreases VTA non-dopamine (non-DA) neural activity. Consistently, photoinhibition of VTA non-DA neurons disrupts the development of cue-elicited anticipatory approach responding. Taken together, our study reveals a crucial regulatory mechanism by PPTg excitatory inputs onto VTA non-DA neurons during appetitive Pavlovian conditioning.

Abstract Background The adverse impact of obesity has been extensively studied in the general population; however, the added risk of obesity on trauma-related mortality remains controversial. This study investigated and compared mortality as well injury patterns and length of stay (LOS) in obese and normal-weight patients hospitalized for trauma in the hospital and intensive care unit (ICU) of a Level I trauma center in southern Taiwan. Methods Detailed data of 880 obese adult patients with body mass index (BMI) ≥ 30 kg/m2 and 5391 normal-weight adult patients (25 > BMI ≥ 18.5 kg/m2) who had sustained a trauma injury between January 1, 2009 and December 31, 2013were retrieved from the Trauma Registry System. Pearson’s chi-squared, Fisher’s exact, and independent Student’s t-tests were used to compare differences between groups. Propensity score matching with logistic regression was used to evaluate the effect of obesity on mortality. Results In this study, obese patients were more often men, motorcycle riders and pedestrians, and had a lower proportion of alcohol intoxication compared to normal-weight patients. Analysis of Abbreviated Injury Scale scores revealed that obese trauma patients presented with a higher rate of injury to the thorax, but a lower rate of facial injuries than normal-weight patients. No significant differences were found between obese and normal-weight patients regarding Injury Severity Score (ISS), Trauma-Injury Severity Score (TRISS), mortality, the proportion of patients admitted to the ICU, or LOS in ICU. After propensity score matching, logistic regression of 66 well-matched pairs did not show a significant influence of obesity on mortality (odds ratio: 1.51, 95 % confidence interval: 0.54–4.23 p = 0.438). However, significantly longer hospital LOS (10.6 vs. 9.5 days, respectively, p = 0.044) was observed in obese patients than in normal-weight patients, particularly obese patients with pelvic, tibial, or fibular fractures. Conclusion Compared to normal-weight patients, obese patients presented with different injury characteristics and bodily injury patterns but no difference in mortality.

Orthognathic surgery alters the position of maxilla and mandible, and consequently changes the nasal shape. The nasal change remains a concern to Asian patients. The aim of this study was to measure the nasal changes using a novel three-dimensional photographic imaging method. Methods: A total of 38 patients with Class III malocclusion and prognathism were enrolled. All patients underwent two-jaw surgery with the standard technique. A nasal alar cinching suture was included at the end of procedure. Facial landmarks and nasal morphology were defined and measured from pre- and postoperative three-dimensional photographic images. Intra-rater errors on landmark identification were controlled. Patient's reports of perceptual nasal changes were recorded. Results: The average width of the alar base and subalare remained similar after surgery. Alar width was increased by 0.74 mm. Nasal height and length remained the same. Nasolabial angle increased significantly. The area of nostril show revealed a significant increase and was correlated with a decrease of columella inclination. Nasal tip projection decreased significantly, by 1.99 mm. Preoperative nasal morphology was different between patients with and without cleft lip/palate, but most nasal changes were concordant. In the self-perception, 37% of patients reported improved nasal appearance, 58% reported no change, and 5% were not satisfied with the nasal changes. Conclusion: After the surgery, characteristic nasal changes occurred with an increase of nasolabial angle and nostril show, but a preserved nasal width. The majority of patients did not perceive adverse nasal changes.