Additive Manufacturing by Heating at a Patterned Photothermal Interface.

Direct additive manufacturing (AM) of commercial silicones is an unmet need with high demand. We report a new technology, heating at a patterned photothermal interface (HAPPI), which achieves AM of commercial thermoset resins without any chemical modifications. HAPPI integrates desirable aspects of stereolithography with the thermally driven chemical modalities of commercial silicone formulations. In this way, HAPPI combines the geometric advantages of vat photopolymerization with the materials properties of, for example, injection molded silicones. We describe the realization of the new technology, HAPPI printing using a commercial Sylgard 184 polydimethylsiloxane resin, comparative analyses of material properties, and demonstration of HAPPI in targeted applications.

Old Age, Female Sex, and Psychotropic Medications Predict Hyposalivation But Not Heart Rate Variability.

OBJECTIVE: To explore risk factors for dry mouth and examine the clinical utility of the heart rate variability (HRV) test in the prediction of dry mouth. METHODS: Every outpatient, who underwent tests for both unstimulated salivary flow and HRV, was retrospectively reviewed. After excluding seven subjects, the demographics and clinical factors in 70 total patients were collected. Based on objective salivary flow rates, patients were classified into normal (≥0.2 mL/min) or hyposalivation groups (<0.2 mL/min), and inter-group comparisons were performed with a two-tailed statistical significance of 0.05. RESULTS: Patients with subjective dry mouth were significantly more likely to show hyposalivation. Advanced age, female sex, and current use of psychotropic medications were identified as risk factors for dry mouth. However, dry mouth was not associated with any HRV parameters. CONCLUSION: HRV test did not demonstrate a clinical utility in predicting dry mouth. Because subjective dry mouth is significantly associated with objective hyposalivation, a simple probing question would be useful for early recognition of dry mouth. Clinical attention is required for patients meeting criteria of older age, female, and/or using psychotropic prescriptions. Prompt management of hyposalivation may improve quality of life and clinical outcome by enhanced treatment adherence.

Late-life depression, subjective cognitive decline, and their additive risk in incidence of dementia: A nationwide longitudinal study.

OBJECTIVE: Late-life depression and subjective cognitive decline (SCD) are significant risk factors for dementia. However, studies with a large sample size are needed to clarify their independent and combined risks for subsequent dementia. METHODS: This nationwide population-based cohort study included all individuals aged 66 years who participated in the National Screening Program between 2009 and 2013 (N = 939,099). Subjects were followed from the day they underwent screening to the diagnosis of dementia, death, or the last follow-up day (December 31, 2017). RESULTS: Depressive symptom presentation, recent depressive disorder, and SCD independently increased dementia incidence with adjusted hazard ratio (aHR) of 1.286 (95% CI:1.255-1.318), 1.697 (95% CI:1.621-1.776), and 1.748 (95% CI: 689-1.808) respectively. Subjects having both SCD and depression had a higher risk (aHR = 2.466, 95% CI:2.383-2.551) of dementia than having depression (aHR = 1.402, 95% CI:1.364-1.441) or SCD (aHR = 1.748, 95% CI:1.689-1.808) alone. CONCLUSIONS: Depressive symptoms, depressive disorder, and SCD are independent risk factors for dementia. Co-occurring depression and SCD have an additive effect on the risk of dementia; thus, early intervention and close follow up are necessary for patients with co-occurring SCD and depression.

Impact of Transcranial Direct Current Stimulation on Cognitive Function, Brain Functional Segregation, and Integration in Patients with Mild Cognitive Impairment According to Amyloid-Beta Deposition and APOE ε4-Allele: A Pilot Study.

Anodal transcranial direct current stimulation (anodal-tDCS) is known to improve cognition and normalize abnormal network configuration during resting-state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). We aimed to evaluate the impact of sequential anodal-tDCS on cognitive functions, functional segregation, and integration parameters in patients with MCI, according to high-risk factors for Alzheimer's disease (AD): amyloid-beta (Aß) deposition and APOE ε4-allele status. In 32 patients with MCI ([18 F] flutemetamol-: n = 10, [18 F] flutemetamol+: n = 22; APOE ε4-: n = 13, APOE ε4+: n = 19), we delivered anodal-tDCS (2 mA/day, five times/week, for 2 weeks) over the left dorsolateral prefrontal cortex and assessed the neuropsychological test battery and resting-state fMRI measurements before and after 2 weeks stimulation. We observed a non-significant impact of an anodal-tDCS on changes in neuropsychological battery scores between MCI patients with and without high-risk factors of AD, Aß retention and APOE ε4-allele. However, there was a significant difference in brain functional segregation and integration parameters between MCI patients with and without AD high-risk factors. We also found a significant effect of tDCS-by-APOE ε4-allele interaction on changes in the functional segregation parameter of the temporal pole. In addition, baseline Aß deposition significantly associated negatively with change in global functional integrity of hippocampal formation. Anodal-tDCS might help to enhance restorative and compensatory intrinsic functional changes in MCI patients, modulated by the presence of Aß retention and the APOE ε4-allele.

Hand grip strength can predict clinical outcomes and risk of falls after decompression and instrumented posterolateral fusion for lumbar spinal stenosis.

BACKGROUND CONTEXT: There has been limited research on the association between hand grip strength (HGS) as one of the diagnostic criteria for sarcopenia and surgical outcomes of lumbar spinal stenosis (LSS). PURPOSE: We aimed to determine the effect of HGS on surgical outcomes and risk of fall in patients with LSS. STUDY DESIGN: This is a retrospective observational study. PATIENT SAMPLE: We included 200 patients who underwent spinal surgery for LSS. OUTCOME MEASURES: We recorded clinical outcome parameters, including Oswestry Disability Index (ODI), Euro-QOL (EQ-5D), and visual analog scale (VAS) scores for back or leg pain. To assess the risk of fall we used HGS and four functional mobility tests (alternative step test, six-meter walk test, timed up and go test, sit-to-stand test). MATERIALS AND METHODS: ODI, EQ-5D, and VAS scores for back and leg pain were assessed preoperatively and 1 year after surgery. The four functional mobility tests were assessed at each time point during the 1-year follow-up period to assess the risk of fall in patients with LSS. We divided the patient cohort according to sex and allocated them into two different groups based on HGS: high HGS (≥26 kg for men, n=26; ≥18 kg for women, n=35), and low HGS (<26 kg for men, n=48; <18 kg for women, n=91). The pre- and postoperative ODI, EQ-5D, and VAS scores for back and leg pain, as well as the functional mobility test results, and demographic data were compared between the two groups using independent t tests. Correlations between HGS and clinical outcome parameters were analyzed using Pearson correlation. RESULTS: In women and men, HGS correlated with the preoperative/postoperative ODI (r1=-0.217/r2=-0.345 in women, and r1=-0.384/r2=-0.411 in men) and EQ-5D scores (r1=0.190/r2=0.309 in women, and r1=0.373/r2=0.467 in men). HGS also correlated with the four postoperative results for the functional mobility tests: alternative step test (r=-0.238 in women, r=-0.431 in men), six-meter walk test (r=-0.232 in women, r=-0.282 in men), timed up and go test (r=-0.285 in women, r=-0.359 in men), and sit-to-stand test (r=-0.238 in women, r=-0.251 in men). The preoperative and postoperative ODI and EQ-5D scores in the high HGS group were superior to those in the low HGS group. Among the four functional mobility tests, preoperative and postoperative six-meter walk test results showed improvements in the high HGS group. CONCLUSIONS: Considering the multifactorial nature of falls, HGS may be a useful surrogate marker for predicting the risk of falls and clinical outcomes in patients with LSS.

100th Anniversary of Macromolecular Science Viewpoint: Integrating Chemistry and Engineering to Enable Additive Manufacturing with High-Performance Polymers.

Additive manufacturing (AM) with high-performance polymers (HPPs) represents simultaneously one of the most desirable and challenging feats in the AM arena. The very properties that make HPPs so attractive in a broad range of applications also make them nearly impossible to process using common AM equipment. Furthermore, when AM is achieved, it often brings the caveat of compromised mechanical properties of the final parts, in comparison with those made via injection molding. The demand to have advanced fabrication methods, rapid prototyping, and customization of parts while maintaining high performance in the finished products has inspired creative innovations that integrate chemical synthesis, materials science, mechanical engineering, and other fields into a multidisciplinary approach to advance AM with the seemingly "unprintable" HPPs. In this Viewpoint, we summarize several standout developments in the area and offer our perspective on future directions and challenges.

Stem cell therapies for Alzheimer's disease: is it time?

PURPOSE OF REVIEW: Stem cell therapy has the potential to modify the disease of Alzheimer's disease. This article aims to describe the mechanisms of action, preclinical animal studies, human clinical trials, and challenges for the future direction of stem cell therapy for Alzheimer's disease. RECENT FINDINGS: Stem cells of diverse origins (embryonic, placental or umbilical cord blood, and induced pluripotent stem cells) and cell types (neural and mesenchymal stem cells) are widely studied in both animals and humans. SUMMARY: In terms of mechanism of actions, recent research focused on the interplay between amyloid-beta Aß (and tau), neurons, and glia. Stem cells can induce direct regeneration of neurons and synapses. They can also prevent activation of pro-inflammatory microglia, promote activation of anti-inflammatory microglia, inhibit astrogliosis, and promote nonreactive astrocytes. These effects in return may increase amyloid-beta (Aß) degradation, decrease the risk of the Aß cascade, repair injured neurons, and enhance synaptogenesis. Two completed and nine ongoing clinical trials using diverse stem cells and administration methods (intravenous, subcutaneous, and intra-cranial) were found for the treatment of Alzheimer's disease. Although stem cell therapy shows great potential to become a prospective treatment for Alzheimer's disease in the future, these studies are still in their early stages and more studies showing safety and efficacy are needed.

Alterations in Intra- and Interregional Intrinsic Brain Connectivity Are Differentially Associated with Memory Performance in Amnestic Mild Cognitive Impairment.

BACKGROUND: Previous research has separated spatial patterns of intra- and interregional intrinsic brain connectivity, as evaluated by regional homogeneity (ReHo) and functional connectivity (FC), respectively, in prodromal Alzheimer's disease (AD). Moreover, the intra- and interregional intrinsic brain connectivities have been demonstrated to have a significant relationship with each other. OBJECTIVE: To explore FCs from brain regions which display a difference in ReHo between an amnestic mild cognitive impairment (aMCI) group and healthy controls (HC) and to examine the relationship of intra- and interregional intrinsic brain connectivity to cognitive function in both groups. METHODS: Thirty-four subjects with aMCI and 38 HC underwent 3T MRI scanning and a battery of neuropsychological tests. RESULTS: The aMCI group exhibited significantly higher ReHo in the left putamen and lower ReHo in the left inferior temporal gyrus than the HC. Furthermore, both groups showed a distinctive functional connectivity pattern seeded from 2 regions of interest which exhibited significant ReHo differences between the groups. In the HC group, only ReHo exhibited significant associations with memory performance, but in the aMCI group, only FC seeded from the left inferior temporal gyrus showed significant correlations with memory performance. CONCLUSIONS: By approaching both intra- and interregional intrinsic brain activities in the early stages of AD, the findings of this research provide insights into the early pathogenesis of AD as related to memory performance.

Relationship between Delusion of Theft and Cognitive Functions in Patients with Mild Alzheimer's Disease.

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer's disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD.

Feasibility of Psychosocial Distress Screening and Management Program for Hospitalized Cancer Patients.

OBJECTIVE: Although the diagnosis and treatment of cancer is associated with psychosocial distress, routine distress screening is difficult in hospitalized oncology settings. We developed a consecutive screening program for psychosocial distress to promote psychiatric treatment of cancer patients and evaluated the feasibility of our program by Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). METHODS: Among 777 cancer inpatients recruited from the Catholic Comprehensive Institute of Seoul St. Mary's Hospital, 499 agreed to complete primary distress screening through DT. We conducted secondary distress screening through HADS in 229 patients who had high scores of DT. RESULTS: Of the 499 participants, 270 patients with low scores of DT were included in the distress education program. 229 patients with high scores of DT received secondary distress screening through HADS. Among 115 patients with low scores of HADS, 111 patients received distress management. Among 114 patients with high scores in the secondary distress screening, 38 patients received psychiatric consultation service whereas 76 patients refused psychiatric consultation. CONCLUSION: Using consecutive screening for psychosocial distress appeared to be feasible in an inpatient oncology setting. Nevertheless, the low participation rate of psychiatric consultation service in cancer patients with high distress level should be improved.

Whole Brain Voxel-Wise Analysis of Cerebral Retention of Beta-Amyloid in Cognitively Normal Older Adults Using 18F-Florbetaben.

OBJECTIVE: Recently developed 18F-labelled amyloid beta (Aß) positron emission tomography (PET) tracers have demonstrated potentials to enable more prevalent application of amyloid imaging in the clinical setting. The aim of this study is to demonstrate cerebral retention of Aß in cognitively normal older adults, by implementing voxel-based analysis on images acquired from 18F-Florbetaben amyloid PET. METHODS: Fifty cognitive normal elderly subjects were recruited and included in the study. Demographic data and cognitive measurements were collected. Magnetic resonance imaging (MRI) and 18F-Florbetaben PET data were obtained followed by whole brain voxel-based analysis. RESULTS: Compared to the florbetaben (FBB) (-) counterpart, FBB (+) showed significantly higher Aß deposition in the brain regions comprising anterior cingulate, middle cingulate, posterior cingulate and precuneus (family wise error corrected p<0.05). There was no significant correlation between amyloid retention and cognitive functions. CONCLUSION: Our results confirms previous results regarding Aß deposition by using 18F-Florbetaben, demonstrating potentials in application of 18F-Florbetaben PET imaging in clinical settings.

Erratum to "Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease".

[This corrects the article on p. 698 in vol. 14.].

Association between mental health status and bone mineral density: Analysis of the 2008-2010 Korea national health and nutrition examination survey.

The current study aimed to investigate the association between mental health status and bone mineral density (BMD) using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2010. We enrolled 15,876 South Korean participants (4,010 postmenopausal females, 4,836 premenopausal females, and 7,016 males, all aged 20 years or older). BMD was measured using dual-energy radiography absorptiometry at the femoral neck (NK), lumbar spine (LSP), and total femur (TFM). Mental health status data were obtained from a self-report questionnaire that assessed psychological stress, depressed mood, and suicidal ideation. Psychological stress was negatively correlated with BMD in the LSP, NK, and TFM for the male group. Depressed mood was associated with lower BMD in the LSP, NK and TFM for the premenopausal female group, and in the LSP for the male group. Suicidal ideation was associated with lower BMD in the NK and TFM for the male group. Mental health problems were associated with lower BMD, especially in premenopausal females and males. Future investigations should focus on the shared pathophysiology between mental health problems and BMD, and the interrelationship between increased BMD and recovery from mental health problems.

Prediction of Treatment Response to Donepezil using Automated Hippocampal Subfields Volumes Segmentation in Patients with Mild Alzheimer's Disease.

Previous studies reported some relationships between donepezil treatment and hippocampus in Alzheimer's disease (AD). However, due to methodological limitations, their close relationships remain unclear. The aim of this study is to predict treatment response to donepezil by utilizing the automated segmentation of hippocampal subfields volumes (ASHS) in AD. Sixty four AD patients were prescribed with donepezil and were followed up for 24 weeks. Cognitive function was measured to assess whether there was a response from the donepezil treatment. ASHS was implemented on non-responder (NR) and responder (TR) groups, and receiver operator characteristic (ROC) analysis was conducted to evaluate the sensitivity, specificity, and accuracy of hippocampal subfields in predicting response to donepezil. The left total hippocampus and the CA1 area of the NR were significantly smaller than those of the TR group. The ROC curve analysis showed the left CA1 volumes showed highest area under curve (AUC) of 0.85 with a sensitivity of 88.0%, a specificity of 74.0% in predicting treatment response to donepezil treatment. We expect that hippocampal subfields volume measurements that predict treatment responses to current AD drugs will enable more evidence-based, individualized prescription of medications that will lead to more favorable treatment outcomes.

A Case Report of a 37-Year-Old Alzheimer's Disease Patient with Prominent Striatum Amyloid Retention.

With recent advancement in amyloid imaging, diagnostic application of this new modality has become a great interest among researchers. New ligands, such as 18F- florbetaben, florbetapir and flutemetamol, have been discovered to overcome limitations of preexisting ligand Pittsburgh compound B. We report here a case of a 37-year-old male patient whose initial complaints comprised of gradual cognitive decline, apraxia, disorientation and sleep disturbances. 18F-Florbetaben amyloid imaging of the patient showed diffuse amyloid retention with prominent striatal uptake. This finding supports the clinical utility of amyloid imaging in diagnostic process of early-onset AD. Moreover, striatal dominant uptake pattern demonstrated in this patient include some meaningful clinical implications that warrant special attention among clinicians.

Amphiphilic Copolymers Capable of Concomitant Release of HNO and Small Molecule Organics.

We demonstrate concomitant release of HNO and small molecule organics from amphiphilic poly(norbornene)-based copolymers. This key function was achieved by incorporation of thermally labile oxazine units within random and block copolymer architectures. Upon thermolysis, we observed generation of HNO and release of a small molecule conjugate. Importantly, the release kinetics of HNO and a UV-active small molecule (4-nitroaniline) were found to be 1:1, signifying an ability to monitor HNO production indirectly, or to simultaneously release organic therapeutics (e.g., nonsteroidal anti-inflammatory drugs) along with HNO. To our knowledge, these are the first reported polymeric materials demonstrating HNO release from covalently attached HNO donors.

Thalamic Shape and Cognitive Performance in Amnestic Mild Cognitive Impairment.

OBJECTIVE: This study aimed to investigate thalamic shape alterations and their relationships with various episodic memory impairments in subjects with amnestic mild cognitive impairment (aMCI). METHODS: We compared volumes and morphological alterations of the thalamus between aMCI subjects and healthy controls. In addition, we investigated the correlation between thalamic deformations and various memory impairments in aMCI subjects using a comprehensive neuropsychological battery. RESULTS: The normalized left thalamic volumes of the aMCI group were significantly smaller than those of the healthy control group (p<0.0001). aMCI subjects exhibited significant thalamic deformations in the left thalamic dorso-medial and antero-medial areas compared with healthy individuals. CERAD-K Word List Memory scores were significantly correlated with the left dorso-medial areas in aMCI subjects. There were no significant correlations between verbal fluency, Boston naming test, constructional praxis, Word List Recognition, and Visuospatial Recall scores and thalamic shape in aMCI subjects. Verbal delayed recall scores were also significantly correlated with the left dorso-medial areas in the aMCI group. CONCLUSION: Structural alterations in the thalamic deformations in the left dorso-medial and antero-medial areas might be core underlying neurobiological mechanisms of thalamic dysfunction related to Word List Memory and delayed verbal recall in individuals with aMCI.

Thermoreversible and Injectable ABC Polypeptoid Hydrogels: Controlling the Hydrogel Properties through Molecular Design.

A series of ABC triblock copolypeptoids [i.e., poly(N-allyl glycine)-b-poly(N-methyl glycine)-b-poly(N-decyl glycine) (AMD)] with well-defined structure and varying composition have been synthesized by sequential primary amine-initiated ring-opening polymerization of the corresponding N-substituted N-carboxyanhydride monomers (Al-NCA, Me-NCA, and De-NCA). The ABC block copolypeptoids undergo sol-to-gel transitions with increasing temperature in water and biological media at low concentrations (2.5-10 wt %). The sol-gel transition is rapid and fully reversible with a narrow transition window, evidenced by the rheological measurements. The gelation temperature (Tgel) and mechanical stiffness of the hydrogels are highly tunable: Tgel in the 26.2-60.0 °C range, the storage modulus (G') and Young's modulus (E) in the 0.2-780 Pa and 0.5-2346 Pa range, respectively, at the physiological temperature (37 °C) can be readily accessed by controlling the block copolypeptoid composition and the polymer solution concentration. The hydrogel is injectable through a 24 gauge syringe needle and maintains their shape upon in contact with surfaces or water baths that are kept above the sol-gel transition temperature. The hydrogels exhibit minimal cytotoxicity toward human adipose derived stem cells (hASCs), evidenced from both alamarBlue and PicoGreen assays. Furthermore, quantitative PCR analysis revealed significant up-regulation of the Col2a1 gene and down-regulation of ANGPT1 gene, suggesting that the hydrogel exhibit biological activity in inducing chondrogenesis of hASCs. It was also demonstrated that the hydrogel can be used to quantitatively encapsulate water-soluble enzymes (e.g., horseradish peroxidase) by manipulating the sol-gel transition. The enzymatic activity of HRP remain unperturbed after encapsulation at 37 °C for up to 7 d, suggesting that the hydrogel does not adversely affect the enzyme structure and thereby the enzymatic activity. These results suggest that the polypeptoid hydrogel a promising synthetic platform for tissue engineering or protein storage applications.

Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders.

OBJECTIVE: Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. METHODS: A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. RESULTS: The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. CONCLUSIONS: Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay.

Visual Hallucinations and Amyloid Deposition in Parkinson's Disease Dementia: A Case Report.

Parkinson's disease dementia (PDD) is notorious for its debilitating clinical course and high mortality rates. Consequently, various attempts to investigate predictors of cognitive decline in Parkinson's disease (PD) have been made. Here we report a case of a 75-year-old female patient with PD who visited the clinic with complaints of recurrent visual hallucinations and cognitive decline, whose symptoms were ameliorated by the titration of rivastigmine. Imaging results showed pronounced diffuse cortical amyloid deposition evidenced by 18F-florbetaben amyloid positron emission tomography (PET) imaging. This observation suggests that pronounced amyloid deposition and visual hallucinations in PD patients could be clinically significant predictors of cognitive decline in PD patients. Future research should concentrate on accumulating more evidence for possible predictors of cognitive decline and their association with PD pathology that can enable an early intervention and standardized treatment in PDD patients.