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Sheng-Fen Wang,1,&ast; Shih-Feng Hung,2,&ast; Tsung-Ting Tsai,2 Yun-Da Li,2 Ping-Yeh Chiu,2 Ming-Kai Hsieh,2 Fu-Cheng Kao2,3 1Department of Anesthesiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Orthopaedic Surgery, Spine Section, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan&ast;These authors contributed equally to this workCorrespondence: Fu-Cheng KaoDepartment of Orthopaedic Surgery, Spine Section, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 5, Fusing St., Gueishan, Taoyuan, 333, TaiwanTel +886-3-3281200 ext. 3612Fax +886-3-3278113Email afogi73@gmail.comBackground: Even though percutaneous endoscopic transforaminal discectomy (PETD) has been widely used for the surgical treatment of lumbar herniated disc, there are only a few studies directly comparing the clinical outcomes between microdiscectomy (MD) and PETD. Therefore, further studies are needed in order to compare the clinical outcomes between PETD and MD on a single level more thoroughly.Methods: We proposed a far-lateral-outside-in technique for PETD to get an entry point without complex planning and facet violation. From September 2017 to September 2019, a total of 155 patients (69 with PETD and 86 with MD) were enrolled for this retrospective study, with the inclusion criteria: single level between L2 and S1, clinical sciatica for at least 6 weeks, and failed attempts with non-surgical treatments. Patients were excluded due to cauda equina syndrome, progressive neurologic deficits, history of lumbar spinal surgery, endplate modic changes, severe disc degeneration and less than 24 months of follow-up.Results: PETD showed significantly shorter surgery time and less intraoperative blood loss compared to MD. The difference between PETD and MD in VAS back pain (but not VAS leg pain) at follow-up time was significant. The ODI improvement in the follow-up time of 6 months between the 2 groups showed a significant difference (PETD: 31.23± 6.59, MD: 39.85± 7.81, p < 0.001). MD had a significantly higher chance of postoperative wound infection and poor healing, while PETD was more likely to have recurrence of the herniated disc.Conclusion: MD has been the gold standard procedure for LDH. However, with the advanced endoscopic technology and surgical technique, PETD has emerged as an alternative method due to higher functional outcome and less wound problems.Keywords: microdiscectomy, PETD, discectomy

Danshen-Gegen (DG) Decoction, an herbal formulation containing Radix Salviae miltiorrhizae and Radix Puerariae lobatae, has been used for the treatment of coronary artery disease in Chinese medicine. In the present study, the involvement of ERK- and PKC-mediated pathways in the cytoprotection against apoptosis afforded by DG pretreatment was investigated in H9c2 cardiomyocytes. Pretreatment with a methanol extract of aqueous DG decoction protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. The cytoprotection was associated the enhancement of cellular reduced glutathione and a reduced sensitivity to Ca(2+)-induced mitochondrial permeability transition. DG extract increased the production of cytochrome P-450 (CYP)-dependent reactive oxygen species (ROS) in H9c2 cardiomyocytes, which was accompanied by the concomitant activation of ERK1/2 and PKC. The DG-induced ERK1/2 activation was followed by the translocation of Nrf2 from the cytosol to the mitochondria accompanied by an increase in the expression of glutathione-related antioxidant proteins. In addition, the increased expression of hemeoxygenase-1 was associated with the activation of Akt and BAD, indicative of anti-apoptotic activity. In conclusion, DG treatment activated both ERK/Nrf2 and PKC pathways, presumably by ROS arising from CYP-catalyzed processes, with resultant inhibition of hypoxia/reoxygenation-induced apoptosis immediately after DG treatment or even after an extended time interval following DG treatment. [ABSTRACT FROM AUTHOR]

Abstract Danshen-Gegen (DG) decoction, an herbal formulation comprised of Radix Salvia Miltiorrhiza and Radix Puerariae Lobata, is prescribed for the treatment of coronary heart disease in Chinese medicine. Experimental and clinical studies have indicated that DG decoction can reduce the extent of atherosclerosis. In the present study, using an ex vivo rat model of myocardial ischemia/reperfusion (I/R) injury, we investigated the myocardial preconditioning effect of an aqueous DG extract prepared from an optimized weight-to-weight ratio of Danshen and Gegen. Long-term treatment with DG extract at increasing doses (including the equivalent of a human dose) protected against myocardial I/R injury in rats. The cardioprotection afforded by DG pretreatment was paralleled by enhancements in mitochondrial antioxidant status and membrane integrity, as well as a decrease in the sensitivity of mitochondria to Ca(2+)-stimulated permeability transition in vitro, particularly under I/R conditions. Long-term treatment with the DG extract enhanced the translocation of protein kinase C-epsilon (PKC) from the cytosol to mitochondria in rat myocardium, and this translocation was inhibited by [alpha]-tocopherol co-treatment with DG extract in rats. Long-term DG treatment may precondition the myocardium via a redox-sensitive PKC/mK(ATP) pathway, with resultant inhibition of the mitochondrial permeability transition. The results suggest that clinical studies examining the effectiveness of DG extract given prophylactically in affording protection against myocardial I/R injury would be warranted. [ABSTRACT FROM AUTHOR]

The effects of the schisandrin B stereoisomers, (+/-)gamma-schisandrin [(+/-)gamma-Sch] and (-)schisandrin B [(-)Sch B], on hypoxia/reoxygenation-induced apoptosis were investigated in AML12 hepatocytes. Changes in cellular reduced glutathione (GSH) levels, Ca(2+)-induced mitochondrial permeability transitions (MPTs) and mitochondrial membrane potentials (Deltapsi(m) values) were also examined in (+/-)gamma-Sch- and (-)Sch B-treated cells, without or with hypoxia/reoxygenation challenge. The (+/-)gamma-Sch/(-)Sch B pretreatments (2.5-5.0 microm) protected against hypoxia/reoxygenation-induced apoptosis in AML12 cells in a concentration-dependent manner, with the (-)Sch B effect being more potent. Drug antiapoptotic effects were further evidenced by suppression of hypoxia/reoxygenation-induced mitochondrial cytochrome c release and subsequent cleavage of caspase 3 and poly-ADP-ribose polymerase by (-)Sch B pretreatment. Whereas hypoxia/reoxygenation challenge increased the extent of Ca(2+)-induced MPT pore opening, and Deltapsi(m), in AML12 hepatocytes, cytoprotection afforded by (+/-)gamma-Sch/(-)Sch B pretreatment against hypoxia/reoxygenation-induced apoptosis was associated with a decreased sensitivity to Ca(2+)-induced MPT and an increased Deltapsi(m) in both unchallenged and challenged cells, compared with the drug-free control. The results indicate that (+/-)gamma-Sch/(-)Sch B pretreatment protected against hypoxia/reoxygenation-induced apoptosis in AML12 hepatocytes and that the cytoprotection afforded by (+/-)gamma-Sch/(-)Sch B may at least in part be mediated by a decrease in sensitivity to Ca(2+)-induced MPT, which may in turn result from enhancement of cellular GSH levels by drug pretreatments. [ABSTRACT FROM AUTHOR]

Reperfusion of the previously ischemic myocardium causes a burst of reactive oxygen species production that eventually leads to tissue damage. In the present study, the effect of long-term treatment with a red wine extract-containing antioxidant supplement (Super S.O.D) on myocardial ischemia/reperfusion (I/R) injury was examined in rats. To investigate the biochemical mechanism(s) involved in the cardioprotection, the effects of Super S.O.D treatment on myocardial mitochondrial antioxidant and structural parameters were also investigated. Long-term treatment with Super S.O.D (0.55 and 1.10 g/kg/day x 15) caused a dose-dependent protection against myocardial I/R injury in rats, as evidenced by the significant decrease in the extent of lactate dehydrogenase leakage. The cardioprotection was associated with increases in reduced glutathione level and antioxidant enzyme activities, including glutathione reductase, glutathione S-transferases and Mn-superoxide dismutase, and decreases in the extents of malodialdehyde production, Ca2+ loading and cytochrome c release, in non-ischemic and ischemic-reperfused rat hearts. The results indicated that long-term Super S.O.D treatment enhanced myocardial mitochondrial antioxidant status and structural integrity, thereby protecting against I/R injury. [ABSTRACT FROM AUTHOR]

The effect of electromagnetic manipulation (EM), consisting of an oscillating (50 Hz) high electrical potential (a maximum value of 20,000 V and an output current < 100 µA) and its associated alternating magnetic field (50-60 Guass), on the hepatoprotective action of schisandrin B (Sch B, an active ingredient isolated from the fruit of Schisandra chinensis) was examined in the mouse model of carbon tetrachloride (CCl4) hepatotoxicity and the AML12 cell model of menadione-induced toxicity. EM was found to enhance the Sch B-induced hepatoprotective action against CCl4 toxicity in mice and cytoprotective action against menadione toxicity in AML12 hepatocytes. The potentiating effect of EM on the pharmacological action of Sch B may be mediated by the increase in drug availability to tissues or cells and/or the pro-oxidant action of electromagnetic field in vivo. [ABSTRACT FROM AUTHOR]

Previous work in our laboratory has shown that long-term treatment with Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula used for the promotion of overall wellness in Chinese medicine, can enhance the mitochondrial functional ability and antioxidant capacity in various tissues of both male and female rats. To investigate whether the VI-28 treatment regimen could afford tissue protection against oxidative injury, the effects of long-term VI-28 treatment (80 or 240 mg/kg/d x 30) on oxidative stress-induced tissue damage in various organs (brain, heart, liver, and kidney) were examined in female rats. The results indicated that long-term VI-28 treatment invariably protected against oxidative tissue damage in the rat models of cerebral/myocardial ischemia-reperfusion injury, CCl4 hepatotoxicity, and gentamicin nephrotoxicity. The tissue protection was associated with increases in the levels and activities of mitochondrial antioxidant components as well as with the preservation of mitochondrial structural integrity. This was evidenced by decreases in the sensitivity of mitochondria to Ca2+-induced permeability transition, and in the levels of mitochondrial malondialdehyde production, Ca2+ loading, and cytochrome c release in the tissues examined. Interestingly, the VI-28 treatment increased red cell CuZn-superoxide dismutase (CuZn-SOD) levels, and these levels correlated positively with the degree of tissue protection afforded by long-term VI-28 treatment in rats. The generalized tissue protection afforded by long-term VI-28 treatment may have clinical implications in the prevention of age-related diseases, and VI-28 treatment may possibly delay the aging process. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess whether elderly patients (aged ≥ 70 years) face an elevated risk of complications following pedicle subtraction osteotomy (PSO) for adult spinal deformity (ASD) compared with younger patients (< 70 years) and to evaluate if clinical and radiological outcomes differ between these age groups., Methods: A retrospective analysis of 513 patients undergoing PSO for ASD by a single surgical team between January 2006 and January 2023 was conducted. Patients were categorized by age (≥ 70 years and < 70 years). Data on clinical, demographic, comorbidity, and radiographic details were collected and compared between the groups. For health-related quality of life assessment, the authors recorded the Oswestry Disability Index (ODI), numeric rating scale (NRS), and Scoliosis Research Society-22 revised (SRS-22r) scores preoperatively and at 6 weeks and 1 year postoperatively. Perioperative complications included major (neurological deficit, death, acute myocardial infarction, stroke), minor (ileus, arrhythmia, delirium), and intraoperative (durotomy, vascular injury)., Results: Of 513 patients, 412 were included in the study. Clinical outcomes, as measured by NRS, ODI, and SRS-22r scores, were comparable between groups, with both groups showing significant improvements postoperatively. Radiographic outcomes also showed significant and comparable improvements in sagittal balance and spinopelvic harmony in both groups. Deformity corrections were also well maintained at 1 year postoperatively. The elderly group (mean age 75.48 years) had a higher rate of perioperative complications (44.64%) than the younger group (mean age 59.60 years; 30.33%) (p = 0.0030), primarily minor complications such as delirium and arrhythmia (16.07% vs 8.61%, p = 0.0279). There was no significant difference between groups regarding the major complication rate (elderly group: 20.83% vs younger group: 14.34%, p = 0.1087), intraoperative complication rate (2.98% vs 3.69%, p = 0.6949), short-term complication rate (10.12% vs 8.20%, p = 0.5024), mechanical complication rate (30.95% vs 32.79%, p = 0.6949), and reoperation rate due to mechanical complications (38.46% vs 43.75% p = 0.5470)., Conclusions: Elderly patients undergoing PSO for ASD experience a higher rate of minor complications but can achieve clinical and radiological outcomes that are comparable to those of younger patients. The authors found no significant increase in major, intraoperative, short-term, or mechanical complication rates and their subsequent reoperation rates among the elderly. These findings underscore the effectiveness of PSO in improving the quality of life for patients with ASD across age groups, emphasizing the critical role of personalized perioperative management in enhancing outcomes and minimizing risks for all patients.

Purpose: To investigate efficacy of 3-month teriparatide(TPD) and compare this treatment with vertebroplasty in terms of clinical and radiographic outcomes after osteoporotic vertebral compression fractures (OVCFs)., Methods: This is a retrospective matched cohort study. Patients who received conservative treatment with at least 3-month TPD treatment for acute OVCF with at least 6 months follow-up were included. Each enrolled TPD case was matched with 2 vertebroplasty cases using age and gender. 30 TPD cases and 60 vertebroplasty cases were enrolled. Patient-reported pain scores were obtained at diagnosis and 1, 3, 6 months after diagnosis. Radiographic parameters including middle body height, posterior body height, wedge angle and kyphotic angle were measured at diagnosis and 6 months after diagnosis. Fracture non-union and subsequent vertebral fracture were evaluated., Results: TPD treatment showed inferior pain relief to vertebroplasty group at 1 month, but did not show difference at 3 and 6 months after diagnosis. In TPD cases, progression of vertebral body collapse was noted in terms of middle body height and wedge angle at final follow up. Instead, both middle body height and wedge angle increased significantly after operation in the vertebroplasty group. Fracture non-union was confirmed via MRI and 4 TPD patients were diagnosed with non-union (4/30, 13.3%). Subsequent compression fracture within 6 months was significant higher in vertebroplasty group (12/60, 20%) than in TPD group (1/30, 3.3%)., Conclusion: In acute OVCFs, 3-month TPD treatment alone showed comparable pain improvement and less subsequent spine fracture than vertebroplasty., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Adverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia., Methods: Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments., Results: Most associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R 2  = 0.003-0.006, p < 0.016, Šidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R 2  = 0.02-0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266-0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05)., Conclusion: These findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In this study, we demonstrate that palladium-platinum bimetallic nanoparticles (Pd@Pt NPs) as the nanozyme, combined with a multi-layer paper-based analytical device and DNA hybridization, can successfully detect Mycobacterium tuberculosis . This nanozyme has peroxidase-like properties, which can increase the oxidation rate of the substrate. Compared with horseradish peroxidase, which is widely used in traditional detection, the Michaelis constants of Pd@Pt NPs are fourteen and seventeen times lower than those for 3,3',5,5'-tetramethylbenzidine and H 2 O 2 , respectively. To verify the catalytic efficiency of Pd@Pt NPs, this study will execute molecular diagnosis of Mycobacterium tuberculosis . We chose the IS 6110 fragment as the target DNA and divided the complementary sequences into the capture DNA and reporter DNA. They were modified on paper and Pd@Pt NPs, respectively, to detect Mycobacterium tuberculosis on a paper-based analytical device. With the above-mentioned method, we can detect target DNA within 15 minutes with a linear range between 0.75 and 10 nM, and a detection limit of 0.216 nM. These results demonstrate that the proposed platform (a DNA-nanozyme integrated paper-based analytical device, dnPAD) can provide sensitive and on-site infection prognosis in areas with insufficient medical resources.

Background: The early detection of dementia depends on efficient methods for the assessment of cognitive capacity. Existing cognitive screening tools are ill-suited to the differentiation of cognitive status, particularly when dealing with early-stage impairment., Methods: The study included 8,979 individuals (> 50 years) with unimpaired cognitive functions, mild cognitive impairment (MCI), or dementia. This study sought to determine optimal cutoffs values for the Cognitive Abilities Screening Instrument (CASI) aimed at differentiating between individuals with or without dementia as well as between individuals with or without mild cognitive impairment. Cox proportional hazards models were used to evaluate the value of CASI tasks in predicting conversion from MCI to all-cause dementia, dementia of Alzheimer's type (DAT), or to vascular dementia (VaD)., Results: Our optimized cutoff scores achieved high accuracy in differentiating between individuals with or without dementia (AUC = 0.87-0.93) and moderate accuracy in differentiating between CU and MCI individuals (AUC = 0.67 - 0.74). Among individuals without cognitive impairment, scores that were at least 1.5 × the standard deviation below the mean scores on CASI memory tasks were predictive of conversion to dementia within roughly 2 years after the first assessment (all-cause dementia: hazard ratio [HR] = 2.81 - 3.53; DAT: 1.28 - 1.49; VaD: 1.58). Note that the cutoff scores derived in this study were lower than those reported in previous studies., Conclusion: Our results in this study underline the importance of establishing optimal cutoff scores for individuals with specific demographic characteristics and establishing profiles by which to guide CASI analysis., (© 2024. The Author(s).)

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination. Through machine learning and deep learning technology, we explored the feasibility of using the above clinical practice data to distinguish AD and VaD. We used the physiological data (33 features) and Tc-99m-ECD SPECT images of 112 AD patients and 85 VaD patients in the Taiwanese Nuclear Medicine Brain Image Database to train the classification model. The results, after filtering by the number of SVM RFE 5-fold features, show that the average accuracy of physiological data in distinguishing AD/VaD is 81.22% and the AUC is 0.836; the average accuracy of training images using the Inception V3 model is 85% and the AUC is 0.95. Finally, Grad-CAM heatmap was used to visualize the areas of concern of the model and compared with the SPM analysis method to further understand the differences. This research method can quickly use machine learning and deep learning models to automatically extract image features based on a small amount of general clinical data to objectively distinguish AD and VaD.

Objectives: Research has suggested that subjective memory complaints (SMC) are predictive of cognitive decline in cases of Alzheimer's disease; however, multidimensional characteristics of SMC make it difficult to formulate causal links. The Subjective Memory Complaints Questionnaire (SMCQ) has proven effective in capturing the nature of SMC. In this study, we developed a revised version of SMCQ (SMCQ-R) with corresponding normative data for application in Taiwan., Methods: This study recruited 100 cognitively normal participants (> 45 years) stratified according to demographic characteristics. Assessments were performed to evaluate test-retest reliability, criterion-related validity, and construct validity of SMCQ-R. SMCQ-R scores of 20 matched patients with mild cognitive impairment (MCI) were also compared with those of normal participants to test construct validity., Results: Reliability of SMCQ-R was satisfactory (0.81-0.95). Factor analysis revealed a three-factor structure: everyday memory problems (EMP), recent severe memory problems (RSMP), and long-term memory problems (LTMP). EMP and RSMP scores were negatively associated with objective cognitive function (r = -.20 to .39). Depressive symptoms were positively associated with all factors (r = .23-.33). Age was positively associated with total (b = 0.09, p < .05) and EMP scores (b = 0.06, p < .01). MCI patients obtained higher scores (p < .05) on all subscales. SMCQ-R scores discriminated between normal and MCI individuals (area under the curve = 0.77). This study established a norm based on scores adjusted to control for effects of age., Conclusions: SMCQ-R has sound psychometric properties and could potentially be used as a tool to assess SMC in clinical settings., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Over-distraction has been shown to be a risk factor for cage subsidence and postoperative neck pain after anterior cervical discectomy and fusion (ACDF). Biomechanical studies have demonstrated increased adjacent segment intradiscal pressure after ACDF. The purpose of this study is to determine if over-distraction of the index disc has an effect on adjacent segment pathology. A consecutive series of 145 patients who received primary ACDF for cervical degenerative pathologies from January 2010 to December 2017 were retrospectively reviewed. The patients were divided into: (1) Over-distraction group (postoperative-preoperative index disc height ≥ 2 mm), and (2) No-distraction group (postoperative-preoperative index disc height < 2 mm). Outcome measures included radiographic parameters, Japanese Orthopaedic Association (JOA) score, and incidences of cage subsidence, radiological and clinical adjacent segment pathologies (RASP and CASP) were compared between the two groups preoperatively, postoperatively, and at the final follow-up. The two groups were comparable with respect to age, follow-up length, JOA score, incidence of CASP, and radiographic parameters. The Over-distraction group (83 patients; 115 levels) had smaller preoperative index disc height (4.5 vs. 5.2 mm, p < 0.001), but taller postoperative index disc height (7.7 vs. 6.6 mm, p < 0.001) than No-distraction group (62 patients; 90 levels) Furthermore, significantly higher incidences of cage subsidence (47% vs. 31%, p = 0.04) and RASP (any progression: 48% vs. 15%, p < 0.001; progress ≥ 2 grades: 25% vs. 7%, p = 0.001) were observed in the Over-distraction group. The multivariate analysis indicated that over-distraction and multilevel fusion were independent risk factors for RASP. There were no clinical outcome differences between the Over-distraction group and the No-distraction group in ACDF. Over-distraction of the index level of ≥ 2 mm should be avoided because it significantly increases the incidences of RASP and cage subsidence., (© 2023. The Author(s).)

Previous studies revealed that hormone replacement therapy (HRT) probably has a protective effect for preventing dementia in post-menopausal women. However, the results were still controversial. The association between cholesterol levels and incident dementia in older women is not fully understood either. We conducted a retrospective analysis on a cohort of non-demented women aged older than 50 years, which was registered in the History-based Artificial Intelligence Clinical Dementia Diagnostic System database from September 2015 to August 2021. We followed this cohort longitudinally to examine the rates of conversion to dementia. Using a Cox regression model, we investigated the impact of the quartile of total cholesterol (TC) levels on incident dementia, adjusting for age, sex, education, neuropsychiatric symptoms, neuropsychological assessments, HRT, as well as various vascular risk factors and medications. We examined a cohort of 787 participants, comprising 539 (68.5%) individuals who did not develop dementia (non-converters). Among these non-converters, 68 individuals (12.6%) were treated with HRT. By contrast, there were 248 (31.5%) who did develop dementia (converters). Among the converters, 28 individuals (11.3%) were treated with HRT. The average follow-up durations were 2.9 ± 1.5 and 3.3 ± 1.6 years for non-converters and converters, respectively. Compared to the lowest quartile of TC levels (<153), the hazard ratios (HR) for converting to dementia were 0.61, 0.58, and 0.58 for the second (153-176), third (177-201), and highest (>201) quartiles, respectively (all p < 0.05). However, the low-density lipoprotein cholesterol (LDL-C) level and HRT did not alter the rate of conversion to dementia. In conclusion, the lowest quartile of TC increased incident dementia in post-menopausal women without dementia; however, HRT did not contribute to conversion to dementia. Some studies suggest that post-menopausal women who have reduced estrogen levels might have an increased risk of Alzheimer's disease if they also have high cholesterol. Nonetheless, the evidence is inconclusive, as not all studies support this finding. The "Lower LDL-C is better" strategy for preventing cardiac vascular disease should be re-examined for the possible serial adverse effects of new onset dementia due to very low cholesterol levels.

Robust evidence suggests that regular exercise, including walking more than 6000 steps, is effective for preventing dementia; however, such activity is less feasible in older people with osteoarthritis (OA) or other motor disabilities. Therefore, we aimed to test whether the minimal amount of exercise (MAE) could help prevent dementia in older adults with OA. A retrospective longitudinal study was performed and a non-demented cohort (≥ 50-years-old) of 242 people (155 [64.0%] non-converters and 87 [36.0%] converters) from three centers in Taiwan was analyzed with a mean follow-up of 3.1 (range 0.3-5.9) and 2.9 (range 0.5-6.0) years, respectively. MAE was defined as walking for approximately 15-30 min or 1500-3000 steps. Rate of MAE (0, 1-2, or ≥ 3) within one week were defined as MAE-no, MAE-weekly, or MAE-daily, respectively. The incidence rates of dementia were compared between groups. Multivariate logistic regression and Cox proportional hazards analyses were used to study the influence of MAE on dementia occurrence. Age, education, sex, activities of daily living, neuropsychiatric symptoms, cognition, multiple vascular risk factors, and related medications were adjusted. Compared to the MAE-no group, the odds ratios for the incidents of dementia were 0.48 and 0.19 in the MAE-weekly and MAE-daily groups, respectively. In addition, older age, poorer cognition, poorer ADL performance, and congestive heart failure increased the incidence of dementia. Daily and weekly MAE prevented dementia in older adults with OA. As such, an informative public health policy may help promote adequate exercise in at-risk groups., (© 2023. Springer Nature Limited.)

In recent years, the demand for rapid, sensitive, and simple methods for diagnosing deoxyribonucleic acid (DNA) has grown due to the increase in the variation of infectious diseases. This work aimed to develop a flash signal amplification method coupled with electrochemical detection for polymerase chain reaction (PCR)-free tuberculosis (TB) molecular diagnosis. We exploited the slightly miscible properties of butanol and water to instantly concentrate a capture probe DNA, a single-stranded mismatch DNA, and gold nanoparticles (AuNPs) to a small volume to reduce the diffusion and reaction time in the solution. In addition, the electrochemical signal was enhanced once two strands of DNA were hybridized and bound to the surface of the gold nanoparticle at an ultra-high density. To eliminate non-specific adsorption and identify mismatched DNA, the self-assembled monolayers (SAMs) and Muts proteins were sequentially modified on the working electrode. This sensitive and specific approach can detect as low as attomolar levels of DNA targets (18 aM) and is successfully applied to detecting tuberculosis-associated single nucleotide polymorphisms (SNPs) in synovial fluid. More importantly, as this biosensing strategy can amplify the signal in only a few seconds, it possesses a great potential for point-of-care and molecular diagnosis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Targeted temperature management (TTM) with therapeutic hypothermia (TH) has been used to improve neurological outcomes in patients after cardiac arrest; however, several trials have reported conflicting results regarding its effectiveness. This systematic review and meta-analysis assessed whether TH was associated with better survival and neurological outcomes after cardiac arrest., Method: We searched online databases for relevant studies published before May 2023. Randomized controlled trials (RCTs) comparing TH and normothermia in post-cardiac-arrest patients were selected. Neurological outcomes and all-cause mortality were assessed as the primary and secondary outcomes, respectively. A subgroup analysis according to initial electrocardiography (ECG) rhythm was performed., Result: Nine RCTs (4058 patients) were included. The neurological prognosis was significantly better in patients with an initial shockable rhythm after cardiac arrest (RR = 0.87, 95% confidence interval [CI] = 0.76-0.99, P = 0.04), especially in those with earlier TH initiation (<120 min) and prolonged TH duration (≥24 h). However, the mortality rate after TH was not lower than that after normothermia (RR = 0.91, 95% CI = 0.79-1.05). In patients with an initial nonshockable rhythm, TH did not provide significantly more neurological or survival benefits (RR = 0.98, 95% CI = 0.93-1.03 and RR = 1.00, 95% CI = 0.95-1.05, respectively)., Conclusion: Current evidence with a moderate level of certainty suggests that TH has potential neurological benefits for patients with an initial shockable rhythm after cardiac arrest, especially in those with faster TH initiation and longer TH maintenance., Competing Interests: Declaration of Competing Interest The study did not receive financial support from any institution or organization. All the authors have no potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A high hematocrit (HCT) level is strongly associated with the risk of cardiovascular disease. For early diagnosis of cardiovascular disease, it is vital to regularly measure the HCT, which is typically achieved by centrifuging a blood sample to measure the percentage of red blood cells. However, the centrifugal modalities are usually bulky, expensive, and require a stable electric input, which restrict the availability. This research develops a semi-automatic and portable centrifugal device for HCT measurement. This torque-actuated semi-automatic centrifuge, which we call the tFuge, is inspired by a music box, allowing different operators to generate the same rhythm. It is electricity-free and can be controlled based on a constant torque mechanism. Repeatable test results can be received from among different users regardless of their age, sex, and activity. With the assistance of the Boycott effect on the tFuge, we proved that the HCT level is in high linearity to the length of the sedimentation of the blood cells in a tube ( R 2 = 0.99, sample HCT range 10-60%). The tFuge takes less than 4 min and requires no more than 10 μL of blood that can be obtained by a less-invasive finger prick to complete the testing procedure. Calibrated gradient numbers are printed onto the rotation disc for instant HCT results that can be read by the naked eye. We expect this proposed point-of-care testing device possesses the potential to replace the microhematocrit centrifuge in the regions with limited resources.

Introduction: Anterior cervical discectomy and fusion (ACDF) has been considered as the gold standard surgical treatment for cervical degenerative pathologies. Some surgeons tend to use larger-sized interbody cages during ACDF to restore the index intervertebral disc height, hence, this study evaluated the effect of larger-sized interbody cages on the cervical spine with ACDF under both static and cyclic loading. Method: Twenty pre-operative personalized poro-hyperelastic finite element (FE) models were developed. ACDF post-operative models were then constructed and four clinical scenarios (i.e., 1) No-distraction; 2) 1 mm distraction; 3) 2 mm distraction; and 4) 3 mm distraction) were predicted for each patient. The biomechanical responses at adjacent spinal levels were studied subject to static and cyclic loading. Non-parametric Friedman statistical comparative tests were performed and the p values less than 0.05 were reflected as significant. Results: The calculated intersegmental range of motion (ROM) and intradiscal pressure (IDP) from 20 pre-operative FE models were within the overall ranges compared to the available data from literature. Under static loading, greater ROM, IDP, facet joint force (FJF) values were detected post ACDF, as compared with pre-op. Over-distraction induced significantly higher IDP and FJF in both upper and lower adjacent levels in extension. Higher annulus fibrosus stress and strain values, and increased disc height and fluid loss at the adjacent levels were observed in ACDF group which significantly increased for over-distraction groups. Discussion: it was concluded that using larger-sized interbody cages (the height of ≥2 mm of the index disc height) can result in remarkable variations in biomechanical responses of adjacent levels, which may indicate as risk factor for adjacent segment disease. The results of this comprehensive FE investigation using personalized modeling technique highlight the importance of selecting the appropriate height of interbody cage in ACDF surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cheng, Chiu, Chen, Niu and Nikkhoo.)

Background: Attenuation correction (AC) is an important correction method to improve the quantification accuracy of dopamine transporter (DAT) single photon emission computed tomography (SPECT). Chang's method was developed for AC (Chang-AC) when CT-based AC was not available, assuming uniform attenuation coefficients inside the body contour. This study aims to evaluate Chang-AC and different deep learning (DL)-based AC approaches on 99m Tc-TRODAT-1 brain SPECT using clinical patient data on two different scanners., Methods: Two hundred and sixty patients who underwent 99m Tc-TRODAT-1 SPECT/CT scans from two different scanners (scanner A and scanner B) were retrospectively recruited. The ordered-subset expectation-maximization (OS-EM) method reconstructed 120 projections with dual-energy scatter correction, with or without CT-AC. We implemented a 3D conditional generative adversarial network (cGAN) for the indirect deep learning-based attenuation correction (DL-AC μ ) and direct deep learning-based attenuation correction (DL-AC) methods, estimating attenuation maps (μ-maps) and attenuation-corrected SPECT images from non-attenuation-corrected (NAC) SPECT, respectively. We further applied cross-scanner training (cross-scanner indirect deep learning-based attenuation correction [cull-AC μ ] and cross-scanner direct deep learning-based attenuation correction [call-AC]) and merged the datasets from two scanners for ensemble training (ensemble indirect deep learning-based attenuation correction [eDL-AC μ ] and ensemble direct deep learning-based attenuation correction [eDL-AC]). The estimated μ-maps from (c/e)DL-AC μ were then used in reconstruction for AC purposes. Chang's method was also implemented for comparison. Normalized mean square error (NMSE), structural similarity index (SSIM), specific uptake ratio (SUR), and asymmetry index (%ASI) of the striatum were calculated for different AC methods., Results: The NMSE for Chang's method, DL-AC μ , DL-AC, cDL-AC μ , cDL-AC, eDL-AC μ , and eDL-AC is 0.0406 ± 0.0445, 0.0059 ± 0.0035, 0.0099 ± 0.0066, 0.0253 ± 0.0102, 0.0369 ± 0.0124, 0.0098 ± 0.0035, and 0.0162 ± 0.0118 for scanner A and 0.0579 ± 0.0146, 0.0055 ± 0.0034, 0.0063 ± 0.0028, 0.0235 ± 0.0085, 0.0349 ± 0.0086, 0.0115 ± 0.0062, and 0.0117 ± 0.0038 for scanner B, respectively. The SUR and %ASI results for DL-AC μ are closer to CT-AC, Followed by DL-AC, eDL-AC μ , cDL-AC μ , cDL-AC, eDL-AC, Chang's method, and NAC., Conclusion: All DL-based AC methods are superior to Chang-AC. DL-AC μ is superior to DL-AC. Scanner-specific training is superior to cross-scanner and ensemble training. DL-based AC methods are feasible and robust for 99m Tc-TRODAT-1 brain SPECT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Jiang, Lin, Peng, Sun, Chiu, Hung and Mok.)

Lipid-lowering drugs (LLDs) have protective effects against coronary artery disease (CAD) and cerebrovascular disease (CVD); however, a paradoxical association with cholesterol has been identified in several diseases, such as diabetes, dementia, and atrial fibrillation. We aimed to analyze the association between LLDs and cholesterol levels in older adults with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled consecutive patients aged ≥50 years from three centers in Taiwan. A multiple logistic regression model was used, and odds ratios (ORs) for different levels of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) compared with the highest level were adjusted for age, triglyceride level, sex, comorbidities, and medications. Among the 3688 participants, 572 with and 676 without T2DM used LLDs. After adjusting for age and sex, the non-T2DM group demonstrated better medical conditions, cognition, and daily function than the T2DM group, regardless of LLD use. Compared to the highest TC level (≥240 mg/dL), ORs were significantly increased as TC levels decreased. A similar pattern of T2DM prevalence was observed in LDL-C levels. Older people with T2DM demonstrated low cognitive and daily functions. Significantly reduced TC and LDL levels were associated with a higher T2DM prevalence in older adults regardless of LLD use. T2DM was associated with impaired cognitive and daily functioning. A higher prevalence of T2DM in older people with low cholesterol levels raises doubt surrounding cognition and daily function being jeopardized when the "lower is better" strategy is applied for the secondary prevention of CAD or CVD.

Objective: Early management of modifiable dementia-related factors is seen as a novel approach to preventing dementia onset; however, these efforts are often hindered by the complexity of interactions among these factors. In addition, different modifiable dementia-related factors may contribute to different etiologies of dementia., Design: The current study investigated the effects of common modifiable dementia-related factors on prediction of incident dementia, dementia of the Alzheimer's type (DAT), and vascular dementia (VaD)., Methods: Vascular- and lifestyle-related factors were used as predictors of incident dementia, DAT, and VaD among 1,285 elderly individuals without obvious signs of dementia or mild cognitive impairment. Cox proportional hazard models were used to evaluate the risks associated with each modifiable factor., Results: After controlling for factors other than stroke-related factors, hypercholesterolemia was correlated with a relatively low risk of all-cause incident dementia and DAT, whereas a vegetarian diet was correlated with an elevated risk of all-cause incident dementia and VaD. Hypertension was correlated with incident VaD. After controlling for stroke-related factors, a vegetarian diet was correlated with an elevated risk of all-cause dementia. A history of myocardiac infarction and the use of anti-platelet medication were, respectively, associated with a reduced risk of DAT and elevated risk of VaD. The use of anti-hypertensives was associated with a reduced risk of all-cause dementia, whereas the use of anti-lipid agents was associated with slow progression DAT (i.e. exceeding the average conversion time). Hypercholesterolemia was associated with an elevated risk for slow progression DAT., Conclusion: These findings could perhaps be used as clinical markers in predicting and preventing incident dementia, DAT, and VaD., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2023.)

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15-20%), leukemia (10%), and occasionally other cancer types. Here, we report using miRNA-708, which targets the distinct 3' untranslated region (3'UTR) of NRAS, to develop miRNA-based precision medicine to treat NRAS mutation-driven cancers. We first confirmed that NRAS is a direct target of miRNA-708. Overexpression of miRNA-708 successfully reduced NRAS protein levels in melanoma, leukemia, and lung cancer cell lines with NRAS mutations, resulting in suppressed cell proliferation, anchorage-independent growth, and promotion of reactive oxygen species-induced apoptosis. Consistent with the functional data, the activities of NRAS-downstream effectors, the PI3K-AKT-mTOR or RAF-MEK-ERK signaling pathway, were impaired in miR-708 overexpressing cells. On the other hand, cell proliferation was not disturbed by miRNA-708 in cell lines carrying wild-type NRAS. Collectively, our data unveil the therapeutic potential of using miRNA-708 in NRAS mutation-driven cancers through direct depletion of constitutively active NRAS and thus inhibition of its downstream effectors to decelerate cancer progression. Harnessing the beneficial effects of miR-708 may therefore offer a potential avenue for small RNA-mediated precision medicine in cancer treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis. Moreover, microRNA-708 expression correlates with better clinical outcomes in TNBC patients. Combination treatment with the hypomethylating agent decitabine and synthetic glucocorticoid significantly increased the expression of microRNA-708, reactivated DNMT-suppressed pathways, and decreased the expression of multiple metastasis-promoting genes such as matrix metalloproteinases (MMPs) and IL-1β, leading to the suppression of breast cancer cell proliferation, migration, and invasion, as well as reduced tumor growth and distant metastasis in the TNBC xenograft mouse model. Overall, our study reveals a therapeutic opportunity in which a combined regimen of decitabine with glucocorticoid may have therapeutic potential in treating TNBC patients., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2023 The Author(s).)

PI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved clinical outcomes. Prior phenotypic evaluation by CyTOF has identified increases in activated CD8 T cells with activation of Th17 T cells, as well as decreases in Tregs, particularly in patients with toxicity. Here we sought to further understand the effects of idelalisib and duvelisib in vitro, and demonstrate that both idelalisib and duvelisib can inhibit T cell proliferation as well as Th1 and Treg differentiation in vitro, while promoting Th2 and Th17 differentiation. We further demonstrate directly using intracellular flow cytometry that autoimmune toxicity in patients is associated with higher absolute numbers of CD4 and CD8 T cells with Th17 differentiation in peripheral blood prior to therapy, and that gastrointestinal tissues from patients with active autoimmune complications of PI3Kδ inhibitors show infiltration with Th17 +  T cells. These same tissues show depletion of Tregs as compared to CLL patients without toxicity, suggesting that loss of Tregs may be permissive for Th17 activation to lead to autoimmune toxicity. Clinical trials to restore this balance are warranted., (© 2023. The Author(s).)

Purpose: Bone graft extenders have been developed to prevent donor site morbidity associated with iliac crest bone graft, but few studies compared the efficacy of various substitutes. Our purpose was to determine fusion rate and clinical outcome in patients undergoing lumbar arthrodesis using demineralized bone matrix (DBM) and biphasic calcium phosphate (BCP)., Methods: Patients with degenerative spondylolisthesis undergoing one-level or two-level arthrodesis of lumbar spine were retrospectively reviewed. Two treatment groups placed either BCP or DBM, in addition to local autograft in lumbar posterolateral space. Three-dimensional CT exam and dynamic flexion-extension radiographs at postoperative 2-year were assessed for posterolateral fusion status and pain scale and Oswestry Disability Index (ODI) for clinical outcome., Results: Of the 148 patients reviewed (including 23 in one- and 58 patients in two-level in BCP group, and 47 in one- and 20 patients in two-level in DBM group), no significant differences were found in terms of age, sex, BMI, smoking, diabetes, steroids, number of level fused, non-union rate or revision surgery between BCP and DBM groups. Significantly improved pain scale of back and leg and ODI were found in both groups postoperatively without group difference. We found a comparable fusion rate in one-level surgery (100% versus 93.6%) and a superior fusion rate of BCP group in two-level surgery (98.3% versus 80.0%, p = 0.01)., Conclusion: Being a bone graft extender without osteoinductive property, with local autograft, BCP is comparable to DBM for one- and superior for two-level fusion. No significant difference was found in clinical outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Appropriate follow-up after treatment initiation in patients with osteoporosis is challenging. Serum biomarkers may offer more efficient monitoring of bone mineral density (BMD) than the currently used dual X-ray absorptiometry; however, significant changes in BMD often occur over at least 12 months. During teriparatide treatment for osteoporosis, monitoring with markers such as procollagen type I propeptide (PINP), which is derived from osteoblasts, can provide clinically useful information for disease management. However, rapid and cost-effective methods for detecting serum PINP are lacking, necessitating a point-of-care test (POCT) for enhanced follow-up efficiency in osteoporosis management. For the quantitative detection of PINP, we developed a high-sensitivity lateral flow immunoassay with a stacking pad (sLFIA). We established a calibration equation based on the test line/control line ratio obtained from our PINP sLFIA results of various nonspiked serum samples to calculate the PINP concentrations in 40 serum samples and compared the result with those obtained using a fully automated electrochemiluminescence immunoassay. PINP concentrations between these two methods exhibited excellent correlation (R = 0.991). In addition, we assessed the serum PINP concentrations of patients with osteoporosis treated with teriparatide. At the 3-month follow-up, their PINP levels were nearly twice as high as those at baseline, thus implying that our method can be used for osteoporosis treatment monitoring. Our findings thus indicate that the PINP sLFIA can serve as a POCT for monitoring medication response and managing osteoporosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Cognitive screening is often a first step to document cognitive status of patients suspected having Alzheimer's disease (AD). Unfortunately, screening neuropsychological tests are often insensitivity in the detection. The goal of this study was to develop a simple and sensitive screening neuropsychological test to facilitate early detection of AD. This study recruited 761 elderly individuals suspected of having AD and presenting various cognitive statuses (mean age: 77.69 ± 8.45 years; proportion of females: 65%; cognitively unimpaired, CU, n = 133; mild cognitive impairment, MCI, n = 231; dementia of Alzheimer's type, DAT, n = 397). This study developed a novel screening neuropsychological test incorporating assessments of the core memory deficits typical of early AD and an interview on memory function with an informant. The proposed History-based Artificial Intelligence-Show Chwan Assessment of Cognition (HAI-SAC) was assessed in terms of psychometric properties, test time, and discriminative ability. The results were compared with those obtained using other common screening tests, including Cognitive Abilities Screening Instrument (CASI), Montreal Cognitive Assessment (MoCA), and an extracted Mini-Mental State Examination score from CASI. HAI-SAC demonstrated acceptable internal consistency. Factor analysis revealed two factors: memory (semantic and contextual) and cognition-related information from informants. The assessment performance of HAI-SAC was strongly correlated with that of the common screening neuropsychological tests addressed in this study. HAI-SAC outperformed the other tests in differentiating CU individuals from patients with MCI (sensitivity: 0.87; specificity: 0.58; area under the curve [AUC]: 0.78) or DAT (sensitivity: 0.99; specificity: 0.89; AUC: 0.98). Performance of HAI-SAC on differentiating MCI from DAT was on par with performances of other tests (sensitivity: 0.78; specificity: 0.84; AUC: 0.87), while the test time was less than one quarter that of CASI and half that of MoCA. HAI-SAC is psychometrically sound, cost-effective, and sensitive in discriminating the cognitive status of AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chang, Chiu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: There is increasing evidence that arrhythmia is a risk factor for dementia; however, it appears that arrhythmia affects the cognitive function of individuals differentially across age groups, races, and educational levels. Demographic differences including educational level have also been found to moderate the effects of modifiable risk factors for cognitive decline., Methods: This study recruited 1,361 individuals including a group of cognitively unimpaired (CU) individuals, a group of patients with mild cognitive impairment (MCI), and a group of patients with dementia with low education levels. The participants were evaluated in terms of modifiable risk factors for dementia, including arrhythmia and neuropsychiatric symptoms., Results: Cox proportional hazard regression models revealed that among older MCI patients (>75 years), those with arrhythmia faced an elevated risk of dementia. Among younger MCI patients, those taking anti-hypertensive drugs faced a relatively low risk of dementia. Among younger MCI patients, male sex and higher educational level were associated with an elevated risk of dementia. Among CU individuals, those with coronary heart disease and taking anti-lipid compounds faced an elevated risk of MCI and those with symptoms of depression faced an elevated risk of dementia., Discussion: The risk and protective factors mentioned above could potentially be used as markers in predicting the onset of dementia in clinical settings, especially for individuals with low educational levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Liu, Liao, Chang and Chiu.)

Peptides, polymers of amino acids, comprise a vital and expanding therapeutic approach. Their rapid degradation by proteases, however, represents a major limitation to their therapeutic utility and chemical modifications to native peptides have been employed to mitigate this weakness. Herein, we describe functionalized thiocarbazate scaffolds as precursors of aza-amino acids, that, upon activation, can be integrated in a peptide sequence to generate azapeptides using conventional peptide synthetic methods. This methodology facilitates peptide editing-replacing targeted amino acid(s) with aza-amino acid(s) within a peptide-to form azapeptides with preferred therapeutic characteristics (extending half-life/bioavailability, while at the same time typically preserving structural features and biological activities). We demonstrate the convenience of this azapeptide synthesis platform in two well-studied peptides with short half-lives: FSSE/P5779, a tetrapeptide inhibitor of HMGB1/MD-2/TLR4 complex formation, and bradykinin, a nine-residue vasoactive peptide. This bench-stable thiocarbazate platform offers a robust and universal approach to optimize peptide-based therapeutics., (© 2022. The Author(s).)

In this study, we demonstrate how palladium@platinum nanoparticles (Pd@Pt NPs) can be used as a nanozyme for the detection of Staphylococcus aureus (S. aureus) on a paper-based analytical device. Pt was doped with Pd to form bimetallic NPs that serve as a peroxidase mimetic, which can enhance the reaction area with a substrate (3, 3', 5, 5'-tetramethylbenzidine, TMB). After material characterization, we show the peroxidase-like activity of the Pd@Pt NPs featured a 13-times higher binding affinity value (K m ) for TMB compared to horseradish peroxidase, which is currently widely used in immunoassays. By incorporating the Pd@Pt NPs in a paper-based immunoassay, we can detect protein A, the biomarker of S. aureus, within 30 min with a detection limit of 9.56 ng/mL. We have also successfully validated this nanozyme-immobilized paper-based analytical device (nPAD) for the detection of human immunoglobulin G to demonstrate the capability of the Pd@Pt NPs for different target analytes. This highly sensitive, rapid, and portable nPAD design has the potential for personalized medicine and point-of-care testing, which could expand on-site prognoses in resource-limited settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Amyloid plaques and tau tangles are pathological hallmarks of Alzheimer's disease (AD). Parkinson's disease (PD) results from the accumulation of α-synuclein. TAR DNA-binding protein (TDP-43) and total tau protein (T-Tau) play roles in FTD pathology. All of the pathological evidence was found in the biopsy. However, it is impossible to perform stein examinations in clinical practice. Assays of biomarkers in plasma would be convenient. It would be better to investigate the combinations of various biomarkers in AD, PD and FTD. Ninety-one subjects without neurodegenerative diseases, 76 patients with amnesic mild cognitive impairment (aMCI) or AD dementia, combined as AD family, were enrolled. One hundred and nine PD patients with normal cognition (PD-NC) or dementia (PDD), combined as PD family, were enrolled. Twenty-five FTD patients were enrolled for assays of plasma amyloid β 1-40 (Aβ 1-40 ), Aβ 1-42 , T-Tau, α-synuclein and TDP-43 using immunomagnetic reduction (IMR). The results show that Aβs and T-Tau are major domains in AD family. α-synuclein is highly dominant in PD family. FTD is closely associated with TDP-43 and T-Tau. The dominant plasma biomarkers in AD family, PD family and FTD are consistent with pathology. This implies that plasma biomarkers are promising for precise and differential assessments of AD, PD and FTD in clinical practice., (© 2022. The Author(s).)

Tunnel field-effect transistors (TFETs) are a promising candidate for low-power applications owing to their steep subthreshold swing of sub-60 mV per decade. For silicon- or germanium-based TFETs, the drive current is low due to the indirect band-to-band tunneling (BTBT) process. Direct-bandgap germanium-tin (GeSn) can boost the TFET performance since phonon participation is not required during the tunneling process. Esaki diodes with negative differential resistance (NDR) are used to characterize the BTBT properties and calibrate the tunneling rates for TFET applications. This work demonstrates high-performance GeSn Esaki diodes with clear NDR at room temperature with very high peak-to-valley current ratios of 15-53 from 300 K to 4 K. A record-high peak current density of 545 kA cm -2 at 4 K is also reported for the tensile-strained Ge 0.925 Sn 0.075 device (strain ≈0.6 %). By applying tensile stresses to n-GeSn epitaxial films, the direct BTBT process dominates, leading to high tunneling rates. Hall measurements further confirm that more electrons populate in the direct Γ valley in the tensile-strained n-GeSn epitaxial films., (© 2022 Wiley-VCH GmbH.)

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC)., Materials and Methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors., Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively ( p < 0.001)., Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tzeng, Yang, Hsu, Chang and Chiu.)

In the large full-thickness mouse skin regeneration model, wound-induced hair neogenesis (WIHN) occurs in the wound center. This implies a spatial regulation of hair regeneration. The role of mechanotransduction during tissue regeneration is poorly understood. Here, we created wounds with equal area but different shapes to understand if perturbing mechanical forces change the area and quantity of de novo hair regeneration. Atomic force microscopy of wound stiffness demonstrated a stiffness gradient across the wound with the wound center softer than the margin. Reducing mechanotransduction signals using FAK or myosin II inhibitors significantly increased WIHN and, conversely, enhancing these signals with an actin stabilizer reduced WIHN. Here, α-SMA was downregulated in FAK inhibitor-treated wounds and lowered wound stiffness. Wound center epithelial cells exhibited a spherical morphology relative to wound margin cells. Differential gene expression analysis of FAK inhibitor-treated wound RNAseq data showed that cytoskeleton-, integrin-, and matrix-associated genes were downregulated, while hair follicular neogenesis, cell proliferation, and cell signaling genes were upregulated. Immunohistochemistry staining showed that FAK inhibition increased pSTAT3 nuclear staining in the regenerative wound center, implying enhanced signaling for hair follicular neogenesis. These findings suggest that controlling wound stiffness modulates tissue regeneration encompassing epithelial competence, tissue patterning, and regeneration during wound healing.

Purpose: White matter hyperintensities (WMHs) are frequently found in elderly individuals with or without dementia. However, the association between WMHs and clinical presentations of dementia with Lewy bodies (DLB) has rarely been studied., Methods: We conducted a retrospective analysis of patients with DLB registered in a dementia database. WMHs were rated visually using the Fazekas scale, and its associated factors including dementia severity, cognitive functions, neuropsychiatric symptoms, and core clinical features were compared among different Fazekas scores. Domains in the Clinical Dementia Rating (CDR), Cognitive abilities Screening Instruments (CASI), and Neuropsychiatric Inventory (NPI) were compared among different Fazekas groups after adjusting for age, sex, education, and disease duration., Results: Among the 449 patients, 76, 207, 110, and 56 had Fazekas score of 0, 1, 2, and 3, respectively. There was a positive association between dementia severity and WMHs severity, and the mean sums of boxes of the Clinical Dementia Rating (CDR-SB) were 5.9, 7.8, 9.5, and 11.2 ( f = 16.84, p < 0.001) for the Fazekas scale scores 0, 1, 2, and 3, respectively. There was a negative association between cognitive performance and WMHs severity, and the mean CASI were 57.7, 45.4, 4.06, and 33.4 ( f = 14.22, p < 0.001) for the Fazekas scale scores 0, 1, 2, and 3, respectively. However, WMHs were not associated with the core clinical features of DLB. After adjustment, all cognitive domains in CDR increased as the Fazekas score increased. In addition, performance on all cognitive domains in CASI decreased as the Fazekas score increased (all p < 0.001). Among neuropsychiatric symptoms, delusions, euphoria, apathy, aberrant motor behavior, and sleep disorders were significantly worse in the higher Fazekas groups compared to those in the group with Fazekas score of 0 after adjustment., Conclusion: WMHs in DLB might contribute to deterioration of cognitive function, neuropsychiatric symptoms, and dementia stages. However, core clinical features were not significantly influenced by WMHs in DLB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chan, Tsai, Wei and Chiu.)

Objectives: Abnormal dopamine transporter (DAT) uptake is an important biomarker for diagnosing Lewy body disease (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We evaluated a machine learning-derived visual scale (ML-VS) for Tc99m TRODAT-1 from one center and compared it with the striatal/background ratio (SBR) using semiquantification for diagnosing LBD in two other centers. Patients and Methods: This was a retrospective analysis of data from a history-based computerized dementia diagnostic system. MT-VS and SBR among normal controls (NCs) and patients with PD, PD with dementia (PDD), DLB, or Alzheimer’s disease (AD) were compared. Results: We included 715 individuals, including 122 NCs, 286 patients with PD, 40 with AD, 179 with DLB, and 88 with PDD. Compared with NCs, patients with PD exhibited a significantly higher prevalence of abnormal DAT uptake using all methods. Compared with the AD group, PDD and DLB groups exhibited a significantly higher prevalence of abnormal DAT uptake using all methods. The distribution of ML-VS was significantly different between PD and NC, DLB and AD, and PDD and AD groups (all p < 0.001). The correlation coefficient of ML-VS/SBR in all participants was 0.679. Conclusions: The ML-VS designed in one center is useful for differentiating PD from NC, DLB from AD, and PDD from AD in other centers. Its correlation with traditional approaches using different scanning machines is also acceptable. Future studies should develop models using data pools from multiple centers for increasing diagnostic accuracy.

Corni fructus is consumed as food and herbal medicine in Chinese culture. Studies have revealed that corni fructus exhibits potent antioxidant activity; however, few studies have investigated the ability of corni fructus to lower uric acid concentrations. In this study, the xanthine oxidase (XO) inhibition and uric acid-lowering effect of corni fructus extract (CFE) were evaluated in mice with potassium oxonate-induced hyperuricemia. Hyperuricemia is a chronic disease prevalent worldwide and is associated with high recurrence rates. In addition, drugs used to treat hyperuricemia induce side effects that discourage patient compliance. Hyperuricemia induces metabolic imbalances resulting in accumulative uric acid deposition in the joints and soft tissues. Hyperuricemia not only induces gout but also interrupts hepatic and renal function, thereby trigging severe inflammation and various complications, including obesity, nonalcoholic fatty liver disease, diabetes, and metabolic diseases. In this study, the ethyl acetate fraction (EAF) of CFE resulted in yields of antioxidant photochemical components significantly higher than those of CFEs formed using other substances. The EAF of CFE exhibited high free radical scavenging activity and XO inhibition and effectively lowered uric acid concentrations in the animal model of chemically induced hyperuricemia. The results of this study can serve as a reference for the prevention of preclinical gout as well as for functional food research.

Background: Minimally invasive surgery (MIS) has become a feasible option for patients with spinal metastasis, but the effectiveness of percutaneous pedicle screw fixation (PPSF) without decompression in patients with severe cord compression remains unknown. We compared PPSF without decompression with debulking surgery in patients with radiosensitive, unstable, metastatic thoracolumbar spinal cord compression., Methods: A retrospective study of surgically treated spinal metastasis and spinal cord compression patients was conducted between October 2014 and June 2019. Demographic and pre- and postoperative data were collected and compared between patients treated with minimally invasive percutaneous fixation and external beam radiotherapy (EBRT) (the PPSF group) and those treated with debulking surgery (the debulking group)., Results: We included 50 patients in this study. The PPSF group had a significantly shorter operative time (143.56 ± 49.44 min vs. 181.47 ± 40.77 min; p < 0.01), significantly lower blood loss (116.67 ± 109.92 mL vs. 696.55 ± 519.43 mL; p < 0.01), and significantly shorter hospital stay (11.90 ± 9.69 vs. 25.35 ± 20.65; p < 0.01) than did the debulking group. No significant differences were observed between the groups in age, sex, spinal instability neoplastic score, ESCC, Tomita scores, numeric rating scale scores, American Spinal Injury Association Impairment Scale scores, survival rates, and complication rates. Postoperative neurologic function and decrease in pain were similar between the groups., Conclusion: The PPSF group had a shorter operation time, shorter length of hospital stay, and less blood loss than did the debulking group. PPSF followed by EBRT is pain relieving, relatively safe and appropriate as palliative therapy., Competing Interests: Conflicts of interest The authors have no financial or ethical conflicts of interest to report., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Postoperative immunosuppression is associated with blood loss and surgical trauma during surgery and subsequently predisposes patients to increased morbidity. Spine endoscopic surgery has been accepted as an effective surgical technique with less surgical trauma and less blood loss for the complication of infectious spondylodiscitis. Therefore, the aim of this study was to investigate whether PEIDF could reduce the morbidity rates for patients with infectious spondylodiscitis. Methods: We launched a retrospective cohort study on the comparison of the perioperative prognosis between PEIDF and conventional open surgery for single-level lumbar infectious spondylodiscitis in patients with poor physical health (ASA ≥ 4) from 2014 to 2019. Results: Forty-four patients were included in this study. Fifteen of them underwent PEIDF, and the rest of the 29 patients were treated with open surgery. Less surgical blood loss (p < 0.001) and intraoperative transfusions (p < 0.001) with a better decline of CRP (p = 0.017) were statistically significant in patients receiving PEIDF. Patients undergoing conventional open surgery encountered more postoperative sepsis (p = 0.030), a higher qSOFA score (p = 0.044), and prolonged-time for CRP normalization (p = 0.001). Conclusions: PEIDF minimizes a poor postoperative outcome due to less surgical trauma, intraoperative blood loss, and the need for a blood transfusion.

Emergency department visits (EDV) are common among older adults with and without dementia. The risk factors and demands of EDVs for people with dementia have been well studied; however, the association between EDVs and conversion to dementia among people with predementia has not been thoroughly explored. To study the predictive value of EDVs in predementia's progression to dementia. The baseline predementia cohort registered from September 2015 to August 2017, with longitudinal follow-up in the History-based Artificial Intelligent Clinical Dementia Diagnostic System database, was retrospectively analyzed. The rates of conversion among the different EDVs were compared. Multivariate logistic regression and Cox proportional hazards analyses were applied to study the influence of EDVs on progression. Age, education, sex, neuropsychological tests, activities of daily living, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors were adjusted for. A total of 512 participants were analyzed, including 339 (66.2%) non-converters and 173 (33.8%) converters with a mean follow-up of 3.3 (range 0.4-6.1) and 2.8 (range 0.5-5.9) years, respectively. Compared to people without EDV (EDV 0), the hazard ratios for conversion to dementia were 3.6, 5.9, and 6.9 in those with EDV once (EDV 1), twice (EDV 2), and more than twice (EDV >2), respectively. In addition, older age, lower education, poorer cognition, poorer ADL performance, and longer follow-up periods also increased the conversion rates. EDVs in the predementia stages highly predict progression to dementia. Therefore, a sound public health as well as primary healthcare system that provide strategies for better management of mental and physical condition might help prevention of EDVs among older people in the predementia stages., Competing Interests: The authors have declared that no competing interests exist.