Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis.

BACKGROUND: Measurement of beta-amyloid (Aß) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination. METHODS: A systematic search of prospective and retrospective studies investigating the association of Aß and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature. RESULTS: A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aß42 or Aß42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aß exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]). CONCLUSIONS: Identifying Aß-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aß, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aß decreases with age. TRIAL REGISTRATION: The study was registered in PROSPERO (ID: CRD42021288100).

Demographic predictors of bedtime procrastination in the Japanese population.

Bedtime procrastination (BP) is prevalent and problematic, with no previous study conducted in Japan. This study developed the Japanese version of the Bedtime Procrastination Scale (BPS), assessed its validity, and investigated the relationship between BP, demographic features, and sleep outcomes. Participants were divided into two samples (N = 252 and N = 630). Sample 1 involved a longitudinal study to confirm test-retest reliability of the BPS. Sample 2 involved a cross-sectional study to assess confirmatory factor analysis, criterion-related validity, construct validity, and determine the internal consistency of the BPS. The relationship between BP and demographic features (gender, age, and employment status) and sleep outcomes (Athens Insomnia Scale, sleep hours, sleep onset latency, and sleep efficiency) was investigated using Sample 2. The BPS showed good internal consistency (Cronbach's α coefficients = .90-91), test-retest reliability (ICC = .86), and one factor model was valid; CFI = .95, TLI = .94, RMSEA = .10, and SRMR = .04. The BPS had a moderate positive association with general procrastination, moderate negative associations with self-control, sleep quality, and sleep duration on weekdays, and those who answered "yes" to the item "Do you have trouble with bedtime procrastination?" had higher BPS scores. BPS scores were moderately higher for younger participants (≤ 40 years), slightly higher for females, and non-significantly different between employment statuses. The BPS showed a significant positive correlation with insomnia symptoms, weak positive association with sleep efficiency on weekdays and holidays, and no significant association with sleep onset latencies on holidays and weekdays. This study provides new data on demographic predictors of BP in Japan. No clear effects of gender and employment status were found, but age was a strong predictor of BP, where younger age groups had a higher BP risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00508-7.

Threshold of Surface Initiator Concentration for Polymer Brush Growth by Surface-Initiated Atom Transfer Radical Polymerization.

The surface modification of various materials by grafting functional molecules has attracted much attention from fundamental research to practical applications because of its ability to impart various physical and chemical properties to the surfaces. One promising approach is the use of polymer brushes synthesized by atom transfer radical polymerization (ATRP) from surface-tethered initiators (SIs). In this study, for the purpose of controlling the grafting amounts/densities of polymer brushes, we developed a facile method to precisely regulate SI concentrations of SI layers (SILs) by serial dilution based on a sol-gel method. By simply mixing organosilanes terminated with and without an initiator group ((p-chloromethyl) phenyltrimethoxysilane (CMPTMS) and phenyltrimethoxysilane (PTMS), respectively) with tetraethoxysilane (TEOS), SI concentrations of SILs could be arbitrarily tuned precisely by varying dilution factors of (CMPTMS + PTMS)/CMPTMS (DFs, 1-107). The resulting SILs prepared at different DFs were highly smooth and transparent. X-ray photoelectron spectroscopy (XPS) also confirmed that the SIs were homogeneously distributed at the topmost surface of the SILs and their concentrations were proven to be accurately and precisely controlled from high to extremely low, comparable to theoretical values. Subsequent SI-ATRP in air ("paint-on" SI-ATRP) of two different types of monomers (hydrophobic/nonionic (2,3,4,5,6-pentafluorostyrene) and hydrophilic/ionic (sodium 4-styrenesulfonate)) demonstrated that polymer brushes with different grafting amounts/densities were successfully grafted only from SILs with DFs of 1-104 (theoretical SI concentrations: 3.9 × 10-4 ∼ 3.5 units/nm2), while at DFs of 105 and above (theoretical SI concentrations: <3.9 × 10-5 units/nm2), no sign of polymer brush growth was confirmed by thickness, XPS, and water contact angle data. Therefore, we are the first to gather evidence that the approximate threshold of SI concentration required for "paint-on" SI-ATRP might be on the order of 10-4 ∼ 10-5 units/nm2.

Evaluation of an immunochromatography-based rapid antigen test, Inspecter Kowa® SARS-CoV-2, using saliva specimens for the detection of SARS-CoV-2.

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, a rapid and reliable point-of-care test is an essential tool for controlling the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, an immunochromatography test (ICT) that uses saliva specimens for rapid antigen detection not only reduces the risk of secondary infections but also reduces the burden on medical personnel. METHODS: The newly developed salivary antigen test kit "Inspecter Kowa® SARS-CoV-2" is an ICT to which saliva specimens can be directly applied. We evaluated its usefulness in comparison with reverse transcription quantitative PCR (RT-qPCR) and the Espline® SARS-CoV-2 Kit for the detection of SARS-CoV-2 using nasopharyngeal swab specimens. In this study, 140 patients with suspected symptomatic COVID-19 who visited our hospital were enrolled, and nasopharyngeal swab and saliva specimens were collected after they consented to participate in the study. RESULTS: Inspector Kowa SARS-CoV-2 was positive in 45 of 61 (73.8%) saliva that were positive by RT-qPCR and the Espline® SARS-CoV-2 Kit was also positive in 56 of 60 (93.3%) Np swabs that were positive by RT-qPCR. Good antigen detection was achieved by ICT with saliva and nasopharyngeal swab specimens when viral load was ≥105 copies/mL, whereas detection sensitivity was low when viral load was <105 copies/mL, especially in saliva specimens. CONCLUSION: This ICT for the detection of SARS-CoV-2 salivary antigen is an attractive tool that does not require specialized equipment and allows patients to perform the entire process from sample collection to self-diagnose and to reduce the burden on medical care during a pandemic.

Endovascular therapy and free flap transfer in chronic limb-threatening ischemia.

Although revascularization has evolved, treating foot gangrene with chronic limb-threatening ischemia remains challenging. There have been many reports on bypass surgery and free flap transfer. Meanwhile, few studies have reported on endovascular therapy and free flap transfer, with high flap survival rates and high wound complication rates. Wound complications are a serious problem that can lead to limb amputation, but previous studies have failed to identify risk factors for wound complications. In this study, we evaluated the results of endovascular therapy and free flap transfer for chronic limb-threatening ischemia and analyzed risk factors for wound complications. A total of 31 legs from 28 patients who underwent endovascular therapy and free flap transfer for lower limb salvage between August 2016 and April 2020 were retrospectively reviewed. The primary endpoints were flap survival and limb salvage rates and wound complication rates. In addition, we performed a statistical analysis of risk factors for wound complications. The flap survival rate was 100%, with partial necrosis in 6% of the patients. The limb salvage rate was 100%. The wound complication rate was 45%. The multivariate analysis showed end-stage renal failure on dialysis as a significant risk factor for wound complications (odds ratio = 133, 95% confidence interval = 2.74-6430, p = 0.014). Endovascular therapy and free flap transfer in chronic limb-threatening ischemia achieved high flap survival rate and limb salvage, but had a high incidence of wound complications. We identified end-stage renal failure on dialysis was a significant risk factor for wound complications.

In vivo measurement of three-dimensional load exerted on dental implants: a literature review.

BACKGROUND: For biomechanical consideration of dental implants, an understanding of the three-dimensional (3D) load exerted on the implant is essential, but little information is available on the in vivo load, including the measuring devices. PURPOSE: This review aimed to evaluate studies that used specific load-measuring devices that could be mounted on an implant to measure the functional load in vivo. MATERIALS AND METHODS: An electronic search utilizing the internet research databases PubMed, Google Scholar, and Scopus was performed. The articles were chosen by two authors based on the inclusion and exclusion criteria. RESULTS: In all, 132 studies were selected from the database search, and 16 were selected from a manual search. Twenty-three studies were finally included in this review after a complete full-text evaluation. Eleven studies were related to the force measurements using the strain gauges, and 12 were related to the piezoelectric force transducer. The principles of the two types of devices were completely different, but the devices produced comparable outcomes. The dynamics of the load magnitude and direction on the implant during function were clarified, although the number of participants in each study was small. CONCLUSIONS: The load exerted on the implant during function was precisely measured in vivo using specific measuring devices, such as strain gauges or piezoelectric force transducers. The in vivo load data enable us to determine the actual biomechanical status in more detail, which might be useful for optimization of the implant prosthetic design and development of related materials. Due to the limited data and difficulty of in vivo measurements, the development of a new, simpler force measurement device and method might be necessary.

Interventions for Co-occurring Cannabis Use and Depression.

This review aimed to investigate the effective intervention options for depression in patients with a history of cannabis use. The study eligibility criteria were as follows: English-language, peer-reviewed human studies; data not previously reported elsewhere; randomized controlled trials, non-randomized trials comparing an intervention group and a control group, and single-group trials. In total, eight studies of interventions for patients with depression who reported cannabis use were identified. Four studies evaluated the effectiveness of the following three pharmacological interventions: extended quetiapine release, extended venlafaxine release, and fluoxetine. However, all studies failed to demonstrate the effectiveness of these drugs. Four studies evaluated the following psychological interventions: motivational interviewing (MI) and cognitive behavior therapy (CBT). These studies found that CBT may improve depression symptoms and cannabis dependence, and MI was associated with improvements in cannabis dependence. CBT and MI may be effective in improving depression and reducing cannabis use. However, the conclusions of this review are limited because of the small number of studies and their low quality. Higher-quality research is required to evaluate the effectiveness of CBT, MI, and other interventions for comorbid cannabis use and depression.

Transparent Composite Films Showing Durable Antifogging and Repeatable Self-Healing Properties Based on an Integral Blend Method.

Antifogging coatings for infrastructures and transparent objects have attracted much attention lately from the perspective of safety and visibility. We have developed a one-pot process to fabricate transparent composite films showing long-lasting antifogging and fast repeatable self-healing properties based on an integral blend (IB) method. This method does not require any specific pretreatments of inorganic fillers/particles. Thus, the precursor solutions could be prepared in a single step by simply mixing raw materials, e.g., poly(vinylpyrrolidone) (PVP) having different molecular weights (MWs: 55, 360, and 1300 k), nano-clay particles (NCPs), and amino-terminated organosilane (AOS). In this study, to control the degree of cross-linking between the PVP matrices and NCPs, addition of AOS as a cross-linker to the PVP matrices (weight percentage of AOS to the PVP matrices, α = 0.01-300%) was carefully controlled. Transparency and self-healing abilities/kinetics of the resulting samples were found to be strongly influenced by both the MWs of PVP and α values. Samples spin-coated with the lowest MW of PVP (55 k) and α values of 0.01-1% gave highly transparent and durable antifogging performance. For example, no fogging was observed for 7 days under >80% relative humidity, and scratches about 30 µm in width could be completely self-healed within a few hours. However, samples with α > 10% gave opaque/grayish films that did not show any self-healing abilities because of an increase in cross-linking of the matrices. The optimized precursor solution was also deposited directly onto the glass slides covered with a transparent porous silica nano-framework (SNF) by a spray-coating method. Due to the formation of the hard and superhydrophilic/hygroscopic SNF with a large surface area, durability of antifogging and self-healing properties of the composite films were moderately improved, compared to those on the flat glass slides.

Clinical Trial for Evaluating the Effectiveness and Safety of a New Dental Plaque Removal Device: Microscale Mist Unit.

This study evaluates the effectiveness and safety of a microscale mist unit (MSM-UNIT) that sprays high-speed fine water droplets to remove dental plaque adhering to the oral mucosa (tongue and palate) and tooth surface. Fifteen patients who had difficulty self-managing sufficient oral care were included in this study. Effectiveness was evaluated for at least five patients' tongues, palate mucosas, and tooth surfaces, and safety evaluation was conducted at all three sites for all patients. Effectiveness was evaluated using the rate of degree of dental plaque removal. Safety was evaluated using a numerical rating scale (NRS) for pain and symptoms of inflammation. An operator who performed treatment and an evaluator who evaluated effectiveness and safety were designated. In addition, an image judgment committee judged effectiveness. Although evaluation of the tongue varied between the evaluators and the image judgment committee, the rates of degree for all plaque removal increased in all regions. In addition, low pain NRS results and minimal symptoms of inflammation were observed and within an acceptable range. The MSM-UNIT can be used effectively and safely for removing oral plaque not only from teeth, but also from the oral mucosa.

Real-world experience of treatment with thrombopoietin receptor agonists in anti-thymocyte globulin-naïve patients with aplastic anemia: an observational retrospective analysis in a single institution.

OBJECTIVE: To explore the efficacy and safety of thrombopoietin receptor agonists (TPO-RAs) without anti-thymocyte globulin (ATG) in ATG-naïve patients with aplastic anemia (AA) in a real-world setting. METHODS: We retrospectively evaluated treatment outcomes in 45 consecutive ATG-naïve patients with AA who received TPO-RAs between 2017 and 2021 at our hospital. RESULTS: ATG ineligibility was due to advanced age (≥ 70 years), n = 22; not recommended under Japanese guidelines due to mild symptoms, n = 13; patient preference, n = 6; uncontrolled heart failure, n = 2; uncontrolled diabetes mellitus, n = 2; chronic renal failure, n = 2; invasive aspergillosis, n = 1. Twenty-eight patients (62%) achieved hematologic response in at least unilineage after 6 months' treatment, while 38 (84% in unilineage response-eligible patients) and four (25% in trilineage response-eligible patients) patients achieved at least unilineage and trilineage responses, respectively, at any point during the follow-up period. Five patients switched from eltrombopag to romiplostim because of adverse events or lack of efficacy, and two developed hematologic malignancies. Eltrombopag was effective even in elderly ATG-ineligible patients with severe AA. The 2-year overall survival rate was 84.3%, with a median 26.3-month follow-up. Time from diagnosis to eltrombopag treatment initiation tended to affect the response (p = 0.0727), but no factors that significantly predicted hematologic response were identified. CONCLUSIONS: We found eltrombopag to be effective even in elderly ATG-naïve patients with severe AA, indicating that TPO-RA treatment should be considered in patients ineligible for ATG treatment because of age, complications, or severe AA.

Visibility of early gastric cancer in texture and color enhancement imaging.

Objective: There are little data regarding the efficacy of texture and color enhancement imaging (TXI) for early gastric cancer (EGC) diagnosis. This study aimed to compare the color difference and visibility of EGC between white light imaging (WLI) and TXI. Methods: This study included 20 EGCs of 18 patients undergoing endoscopic submucosal dissection. Still images of EGC in WLI, TXI mode 1 (with color enhancement), and TXI mode 2 (without color enhancement), which were consistent in distance, angle, and air insufflation, were constructed by computer simulation. The center of the lesion, eight equal peripheral points 5 mm outside the lesion, and eight inner points two-thirds of the distance from peripheral points to the EGC lesion center were annotated. Mean color differences (ΔE) of the area between peripheral and inner points per lesion in WLI, TXI mode 1, and TXI mode 2 were analyzed. In addition, four endoscopists independently scored the visibility of EGC images of TXI mode 1 and 2 compared with WLI. Results: Clinicopathological characteristics were as follows: 0-IIa/0-IIb/0-IIc/0-IIa+IIc = 6/1/11/2, reddish/pale = 10/10, differentiated/undifferentiated = 18/2, median tumor size = 13.5 mm. Mean ΔE ± SD = WLI/TXI mode1/TXI mode2 = 10.3 ± 4.7, 15.5 ± 7.8, and 12.7 ± 6.1, respectively. Mean ΔE was significantly higher in TXI mode 1 than in WLI. Visibility (improved/no change/decreased) was 7/13/0 and 4/16/0 in TXI mode 1 and 2, respectively. The visibility was significantly more commonly improved in the macroscopic type 0-IIc or 0-IIb than in 0-IIa or IIa+IIc in TXI mode 1. Conclusions: TXI could improve the visibility of EGC compared with WLI.

Glycogen synthase kinase 3ß/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO.

Multicentric Castleman disease-thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD-TAFRO)-is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine/chemokine profile referred to as "chemokine storm", the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD-TAFRO using serum cytokine/chemokine profiles. We performed the targeted cytokine/chemokine multiplex analysis in six cases of MCD-TAFRO with remission or non-remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase-3-like-1 in the MCD-TAFRO patients with active state compared to inactive state. Ingenuity pathway analysis revealed that glycogen synthase kinase 3 (GSK3) and CCR6, which is expressed in megakaryocytes, were detected as upstream positive regulators for activating MCD-TAFRO status. More GSK3ß+ CCR6+ cells like megakaryocytes were detected in the bone marrow of patients with MCD-TAFRO than in those with systemic lupus erythematosus, MCD-not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3ß+ CCR6+ cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3ß and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD-TAFRO and may act as diagnostic targets and therapeutic markers.

Acute Myocardial Infarction of the Left Main Coronary Artery Presenting with Cardiogenic Shock and Pulmonary Edema during Noncardiac Surgery.

Acute myocardial infarction (AMI) caused by severe stenosis of left main coronary artery (LMCA) presenting with cardiogenic shock and pulmonary edema during noncardiac surgery is uncommon, but a catastrophic event. A 77-year-old male with cholangiocarcinoma underwent hepatectomy. During the surgery, he presented with cardiogenic shock, which did not respond to infusion administration or vasopressor. A transesophageal echocardiogram revealed anterior, septal, and lateral severe hypokinesia and impaired left ventricular function. Emergent coronary angiogram showed severe stenosis of LMCA. The patient underwent primary percutaneous coronary intervention (PCI) under the support of intra-aortic balloon pump, followed by extracorporeal membrane oxygenation. The chest roentgenogram showed pulmonary edema. Two days after PCI, he successfully underwent hepatectomy and bile duct resection. Early identification of the cause of hemodynamic instability during noncardiac surgery and invasive strategy are important for minimizing the myocardial injury and improving clinical outcomes in AMI of LMCA.