Renal outcomes after contrast exposure in patients with diabetes who use sodium-glucose cotransporter 2 inhibitors.

BACKGROUND: Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear. METHODS: Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders. RESULTS: This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs. CONCLUSIONS: SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Pressure-impedance analysis: Assist the diagnosis and classification of ineffective esophageal motility disorder.

BACKGROUND AND AIM: We elucidated the clinical significance of distal contractile integral-to-esophageal impedance integral (EII) ratio (DCIIR) in ineffective esophageal motility (IEM) adult patients. METHODS: We recruited 101 patients with IEM (48.38 ± 1.58 years) and 42 matched healthy volunteers (44.28 ± 1.85 years) in this case-control study. All subjects underwent esophageal high-resolution impedance manometry from October 2014 to May 2018. The diagnosis of IEM was based on the Chicago Classification version 3.0. The EII, EII ratio, and DCIIR were analyzed by matlab software. RESULTS: The EII, EII ratio, and DCIIR calculated at an impedance threshold of 1500 Ω (EII1500, EII ratio1500, and DCIIR1500, respectively) were significantly lower in the IEM group than in healthy controls (P < 0.0001, < 0.0001, and < 0.0001, respectively). Receiver operating characteristic analysis showed that DCIIR1500 < 0.008 mmHg/Ω, EII1500 > 71 000 Ω.s.cm, and EII ratio1500 > 0.43 were all predictive of IEM. Only DCIIR1500 < 0.008 mmHg/Ω remained significant in diagnosing IEM in the multivariate logistic regression analysis (odds ratio = 72.13, P < 0.001). The DCIIR1500 is negatively correlated with Eckardt score and the Reflux Disease Questionnaire (correlation coefficient = -0.2844 and -0.3136; P = 0.0006 and 0.0002, respectively). Receiver operating characteristic analysis further showed that a DCIIR1500 cut-off of 0.002 mmHg/Ω achieved the best differentiation between the IEM-alternans and IEM-persistens subtypes among IEM patients (P < 0.001). CONCLUSIONS: The novel pressure-impedance parameter of high-resolution impedance manometry, DCIIR1500, may assist in the diagnosis and classification of IEM and correlated with clinical symptoms.

Quantitative analysis of genetically modified soya using multiple reaction monitoring mass spectrometry with endogenous peptides as internal standards.

A simple label-free method was developed for the quantification of the herbicide-resistant gene-related protein 5-enolpyruvylshikimate-3-phosphate synthase using multiple reaction monitoring liquid chromatography-mass spectrometry. Sample pretreatment procedures including ion exchange chromatography and CaCl2 precipitation were used to purify the 5-enolpyruvylshikimate-3-phosphate synthase protein. Quantification of various percentages of genetically modified soya (0.5-100%) was performed by selecting suitable endogenous soybean peptides as internal standards. Results indicated that Gly P (QGDVFVVPR) and Lec P (LQLNK) are useful internal standards for the quantification of low and high percentages of genetically modified soya, respectively. Linear regression analysis of both calibration curves yielded good linearity with R2 of 0.99. This approach is a convenient and accurate quantification method for genetically modified soya at a level as low as 0.5% (less than the current EU threshold for labeling genetically modified soya).

Distal contractile to impedance integral ratio assist the diagnosis of pediatric ineffective esophageal motility disorder.

OBJECTIVES: We investigated the diagnostic utility of distal contractile integral (DCI) to esophageal impedance integral (EII) ratio (DCIIR) in high-resolution impedance manometry (HRIM) of ineffective esophageal motility (IEM) in children. METHODS: We performed HRIM in 31 children with dysphagia, odynophagia, chronic vomiting, chest pain, or heartburn sensation. Based on the Chicago classification version 3.0, 20 subjects were diagnosed with IEM, and 11 subjects were normal. We analyzed the EII and DCIIR using MATLAB software. RESULTS: The DCIIR calculated at the impedance cutoff at 1500 Ω (DCIIR1500) were significantly lower in IEM group than patients with normal motility (P = 0.007). Receiver operating characteristic (ROC) curve analysis showed that a DCIIR1500 < 0.009 mmHg/Ω best predicted IEM in children (P < 0.001). A DCIIR1500 < 0.008 mmHg/Ω is associated with significant body weight loss > 10% within 6 months in children. (P < 0.001). CONCLUSIONS: The calculation of DCIIR1500 may assist the automatic analysis of bolus transit in HRIM study to diagnose IEM in children. An DCIIR1500 < 0.009 mmHg/Ω may assist in the diagnosis of IEM in children, and DCIIR1500 < 0.008 mmHg/Ω correlated with significant body weight loss. The calculation of DCIIR may serve as possible parameters for HRIM.

Rear interface engineering of hybrid organic-silicon nanowire solar cells via blade coating.

In this work, we investigate blade-coated organic interlayers at the rear surface of hybrid organic-silicon photovoltaics based on two small molecules: Tris(8-hydroxyquinolinato) aluminium (Alq(3)) and 1,3-bis(2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl) benzene (OXD-7). In particular, soluble Alq(3) resulting in a uniform thin film with a root-mean-square roughness < 0.2nm is demonstrated for the first time. Both devices with the Alq(3) and OXD-7 interlayers show notable enhancement in the open-circuit voltage and fill-factor, leading to a net efficiency increase by over 2% from the reference, up to 11.8% and 12.5% respectively. The capacitance-voltage characteristics confirm the role of the small-molecule interlayers resembling a thin interfacial oxide layer for the Al-Si Schottky barrier to enhance the built-in potential and facilitate charge transport. Moreover, the Alq(3) interlayer in optimized devices exhibits isolated phases with a large surface roughness, in contrast to the OXD-7 which forms a continuous uniform thin film. The distinct morphological differences between the two interlayers further suggest different enhancement mechanisms and hence offer versatile functionalities to the advent of hybrid organic-silicon photovoltaics.

Ligand-doped liquid crystal sensor system for detecting mercuric ion in aqueous solutions.

We developed a liquid crystal (LC) sensor system for detecting mercuric ion (Hg(2+)) in aqueous solutions. In this system, 4-cyano-4'-pentyl biphenyl (5CB) was doped with a sulfur- and nitrogen-containing ligand 5-(pyridine-4-yl)-2-(5-(pyridin-4-yl)thiophen-2-yl)thiazole (ZT) as the Hg(2+) specific LCs. When the system was immersed in the solution containing Hg(2+), the complex of ZT and Hg(2+) formed, which disrupted the orientation of LC and lead to a dark-to-bright transition of the image of LCs. From mercuric binding titrations monitored by UV-vis spectroscopy, it was found that 1:1 Hg(2+)/ZT complexes were formed. The limit of detection (LOD) of the system to Hg(2+) is 10 µM, and it did not respond to Cd(2+), Zn(2+), Cu(2+), Pb(2+), Fe(+), Mg(2+), Ca(2+), Na(+), and K(+). Besides, we also demonstrated that this system is capable of detecting Hg(2+) in tap water and pond water. Because the signal of this system is colorful under ambient light, which is readily understood by normal users, it can be used as a portable device to monitor the water quality at any location.

Cingulum correlates of cognitive functions in patients with mild cognitive impairment and early Alzheimer's disease: a diffusion spectrum imaging study.

Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.

Low-dose aspirin for prevention of cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease: A real-world nationwide cohort study.

AIMS/INTRODUCTION: Cardiovascular mortality risk is elevated among patients with diabetes and concurrent chronic kidney disease. However, controversy surrounds the use of aspirin for primary prevention within this population. This study aims to assess the effectiveness and safety of low-dose aspirin for primary prevention in patients with diabetes and pre-end-stage renal disease. MATERIALS AND METHODS: This was a retrospective population-based cohort study using the National Health Insurance Research Database in Taiwan. The study included adults with type 2 diabetes who were enrolled in the pre-end-stage renal disease pay-for-performance program and had no atherosclerotic cardiovascular disease. We used propensity score analysis to control baseline characteristics between the two groups. Clinical outcomes including cardiovascular mortality, all-cause mortality, major bleeding, and renal disease progression were compared between patients who first received aspirin and those who did not. RESULTS: Between January 2012 and December 2015, a total of 2,155 low-dose aspirin users and 6,737 nonaspirin users were identified. Following propensity score adjustment, aspirin use exhibited a comparable risk of cardiovascular death compared with nonaspirin users (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.65-1.95; P = 0.681). The risk of all-cause mortality was similar between the two groups (aHR 1.07; 95% CI 0.92-1.24; P = 0.385). Similar risks were observed in terms of major bleeding and renal disease progression. CONCLUSIONS: In patients with diabetes and pre-end-stage renal disease who lacked atherosclerotic cardiovascular disease, low-dose aspirin did not demonstrate a reduction in mortality. These findings do not support the use of aspirin for primary prevention in this high-risk population.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Platelet-Rich Fibrin-Augmented Gap-Bridging Strategy in Rabbit Anterior Cruciate Ligament Repair.

BACKGROUND: We assessed the efficacy of a novel platelet-rich fibrin (PRF)-augmented repair strategy for promoting biological healing of an anterior cruciate ligament (ACL) midsubstance tear in a rabbit model. The biological gap-bridging effect of a PRF scaffold alone or in combination with rabbit ligamentocytes on primary ACL healing was evaluated both in vitro and in vivo. HYPOTHESIS: A PRF matrix can be implanted as a provisional fibrin-platelet bridging scaffold at an ACL defect to facilitate functional healing. STUDY DESIGN: Controlled laboratory study. METHODS: The biological effects of PRF on primary rabbit ligamentocyte proliferation, tenogenic differentiation, migration, and tendon-specific matrix production were investigated for treatment of cells with PRF-conditioned medium (PRFM). Three-dimensional (3D) lyophilized PRF (LPRF)-cell composite was fabricated by culturing ligamentocytes on an LPRF patch for 14 days. Cell-scaffold interactions were investigated under a scanning electron microscope and through histological analysis. An ACL midsubstance tear model was established in 3 rabbit groups: a ruptured ACL was treated with isolated suture repair in group A, whereas the primary repair was augmented with LPRF and LPRF-cell composite to bridge the gap between ruptured ends of ligaments in groups B and C, respectively. Outcomes-gross appearance, magnetic resonance imaging, and histological analysis-were evaluated in postoperative weeks 8 and 12. RESULTS: PRFM promoted cultured ligamentocyte proliferation, migration, and expression of tenogenic genes (type I and III collagen and tenascin). PRF was noted to upregulate cell tenogenic differentiation in terms of matrix production. In the 3D culture, viable cells formed layers at high density on the LPRF scaffold surface, with notable cell ingrowth and abundant collagenous matrix depositions. Moreover, ACL repair tissue and less articular cartilage damage were observed in knee joints in groups B and C, implying the existence of a chondroprotective phenomenon associated with PRF-augmented treatment. CONCLUSION: Our PRF-augmented strategy can facilitate the formation of stable repair tissue and thus provide gap-bridging in ACL repair. CLINICAL RELEVANCE: From the translational viewpoint, effective primary repair of the ACL may enable considerable advancement in therapeutic strategy for ACL injuries, particularly allowing for proprioception retention and thus improved physiological joint kinematics.

Comparison of clinical outcomes of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction.

BACKGROUND: Angiotensin receptor blockers (ARBs) are considered an alternative to angiotensin-converting enzyme inhibitors (ACEIs) in patients with acute myocardial infarction (AMI), but in the era of extensive use of preventive therapies and percutaneous coronary intervention, this has not been adequately evaluated in Asians. METHODS: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. In total, 52,620 patients initially hospitalized due to AMI between 2002 and 2015 were assessed. RESULTS: After propensity score matching, 14,993 patients each were assigned to ACEI and ARB groups. Patients who received ARBs had significantly lower all-cause mortality (adjusted hazard ratio [aHR]: 0.82; 95% confidence interval [CI]: 0.75-0.90) and hospitalization for heart failure (aHR: 0.92; 95% CI: 0.85-0.99) compared with those who received ACEIs at 18 month follow-up. No significant difference was observed between the two groups in terms of major adverse cardiovascular events (aHR: 098; 95% CI: 0.90-1.07), cardiovascular death (aHR: 0.82; 95% CI: 0.68-1.00), ischemia stroke (aHR: 0.93; 95% CI: 0.77-1.11), and nonfatal myocardial infarction (aHR: 1.04; 95% CI: 0.93-1.17). ARBs showed benefits in many subgroups in terms of all-cause mortality and cardiovascular death. CONCLUSIONS: Real-world data demonstrate that ARBs might be associated with lower all-cause mortality and hospitalization for heart failure compared with ACEIs among patients with AMI.

Correlation between Subchondral Insufficiency Fracture of the Knee and Osteoarthritis Progression in Patients with Medial Meniscus Posterior Root Tear.

A medial meniscus posterior root tear (MMPRT) contributes to knee joint degeneration. Arthroscopic transtibial pullout repair (ATPR) may restore biomechanical integrity for load transmission. However, degeneration persists after ATPR in certain patients, particularly those with preoperative subchondral insufficiency fracture of the knee (SIFK). We explored the relationship between preoperative SIFK and osteoarthritis (OA) progression in retrospectively enrolled patients who were diagnosed as having an MMPRT and had received ATPR within a single institute. Based on their preoperative magnetic resonance imaging (MRI), these patients were then categorized into SIFK and non-SIFK groups. OA progression was evaluated by determining Kellgren-Lawrence (KL) grade changes and preoperative and postoperative median joint widths. SIFK characteristics were quantified using Image J (Version 1.52a). Both groups exhibited significant post-ATPR changes in medial knee joint widths. The SIFK group demonstrated significant KL grade changes (p < 0.0001). A larger SIFK size in the tibia and a greater lesion-to-tibia length ratio in the coronal view were positively correlated with more significant KL grade changes (p = 0.008 and 0.002, respectively). Thus, preoperative SIFK in patients with an MMPRT was associated with knee OA progression. Moreover, a positive correlation was observed between SIFK lesion characteristics and knee OA progression.

Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease.

OBJECTIVE: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m2), which have been excluded from the landmark trials. PATIENTS AND METHODS: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints. RESULTS: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m2) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m2 vs 21.4±17.5 mL/min per 1.73 m2; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users. CONCLUSION: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.

Exploring the dynamics of reaction C(3P) + C2H4 with crossed beam/photoionization experiments and quantum chemical calculations.

We investigated the title reaction at collision energy 3.5 kcal mol(-1) in a crossed molecular beam apparatus using undulator radiation as an ionization source. Time-of-flight (TOF) spectra of product C(3)H(3) were measured in laboratory angles from 20° to 100° using two photoionization energies 9.5 and 11.6 eV. These two sets of experimental data exhibit almost the same TOF distributions and laboratory angular distributions. From the best simulation, seven angle-specific kinetic-energy distributions and a nearly isotropic angular distribution are derived for product channel C(3)H(3) + H that has an average kinetic-energy release of 15.5 kcal mol(-1), corresponding to an average internal energy of 33.3 kcal mol(-1) in C(3)H(3). Furthermore, TOF spectra of product C(3)H(3) were measured at laboratory angle 52° with ionizing photon energies from 7 to 12 eV. The appearance of TOF spectra remains almost the same, indicating that a species exclusively contributes to product C(3)H(3); the species is identified as H(2)CCCH (propargyl) based on the ionization energy of 8.6 ± 0.2 eV and the maximal kinetic-energy release of 49 kcal mol(-1). Theoretical calculations indicate that the rapid inversion mechanism and rotation in intermediate H(2)CCCH(2) can result in a forward-backward symmetric angular distribution for product C(3)H(3) + H. The present work avoids the interference of reactions of C((1)D) and C(2) radicals with C(2)H(4) and rules out the probability of production of other isomers like c-C(3)H(3) and H(3)CCC proposed in the previous work at least at the investigated collision energy.

Frequency-Dependent Effects of Cerebellar Repetitive Transcranial Magnetic Stimulation on Visuomotor Accuracy.

The cerebellum plays a critical role in acquiring visuomotor skills. Visuomotor task mastery requires improving both visuomotor accuracy and stability; however, the cerebellum's contribution to these processes remains unclear. We hypothesized that repetitive transcranial magnetic stimulation (rTMS) of the cerebellum exerts frequency-dependent modulatory effects on both accuracy and stability in subjects performing a visuomotor coordination task (i.e., pursuit rotor task). We recruited 43 healthy volunteers and randomly assigned them to the high-frequency (HF), low-frequency (LF), and sham rTMS groups. We calculated changes in performance of the pursuit rotor task at the highest rotation speed and the minimum distance from target as indices of accuracy. We also calculated the intertrial variability (standard deviations) of time on target and distance from target as indices of stability. Visuomotor accuracy was significantly enhanced in the HF group and disrupted in the LF group compared to the sham group, indicating frequency-dependent effects of rTMS. In contrast, both HF and LF rTMS demonstrated no significant change in visuomotor stability. Surprisingly, our findings demonstrated that the accuracy and stability of visuomotor performance may be differentially influenced by cerebellar rTMS. This suggests that visuomotor accuracy and stability have different underlying neural mechanisms and revealed the possibility of training strategies based on cerebellar neuromodulation.

The Clinical Course of Early and Late Mild Cognitive Impairment.

Introduction: Amnestic mild cognitive impairment (MCI) can be classified as either early MCI (EMCI) or late MCI (LMCI) according to the severity of memory impairment. The aim of this study was to compare the prognosis and clinical course between EMCI and LMCI. Methods: Between January 2009 and December 2017, a total of 418 patients with MCI and 146 subjects with normal cognition were recruited from a memory clinic. All the patients received at least two series of neuropsychological evaluations each year and were categorized as either EMCI or LMCI according to Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) criteria. Results: In total, our study included 161 patients with EMCI, 258 with LMCI, and 146 subjects with normal cognition as controls (NCs). The mean follow-up duration was 3.55 ± 2.18 years (range: 1-9). In a first-year follow-up assessment, 54 cases (32.8%) of EMCI and 16 (5%) of LMCI showed a normal cognitive status. There was no significant difference between the first year EMCI reverter and NCs in terms of dementia-free survival and further cognitive decline. However, first-year LMCI reverters still had a higher risk of cognitive decline during the following evaluations. Until the last follow-up, annual dementia conversion rates were 1.74, 4.33, and 18.6% in the NC, EMCI, and LMCI groups, respectively. The EMCI and LMCI groups showed a higher rate of progression to dementia (log-rank test, p < 0.001) than normal subjects. Compared with NCs, patients in the LMCI group showed a significantly faster annual decline in global cognition [annual rate of change for the mini-mental status examination (MMSE) score: -1.035, p < 0.001]) and all cognitive domains, while those in the EMCI group showed a faster rate of decline in global cognitive function (annual rate of change for the MMSE score: -0.299, p = 0.001). Conclusion: It is important to arrange follow-up visits for patients with MCI, even in the EMCI stage. One-year short-term follow-up may provide clues about the progression of cognitive function and help to identify relatively low-risk EMCI subjects.

Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning.

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research.