Network crosstalk dynamically changes during neutrophil polarization.

How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or "crosstalk," among signaling modules involved in the cytoskeletal response of neutrophils to chemoattractant. We quantified the intensity and polarity of cytoskeletal marker proteins over time to characterize stereotyped cellular responses. Analyzing the effects of network disruptions revealed that, not only does crosstalk evolve rapidly during polarization, but also that intensity and polarity responses are influenced by different patterns of crosstalk. Interestingly, persistent crosstalk is arranged in a surprisingly simple circuit: a linear cascade from front to back to microtubules influences intensities, and a feed-forward network in the reverse direction influences polarity. Our approach provided a rational strategy for decomposing a complex, dynamically evolving signaling system and revealed evolving paths of causal influence that shape the neutrophil polarization response.

Frailty is Associated With Frontal Cortex-Related Cognitive Function in Patients With Alzheimer Disease.

OBJECTIVE: We compared the cognitive functions of Alzheimer disease (AD) patients who were robust, frail or pre-frail and hypothesized that declines in frontal cortex-related neuropsychological function would be associated with frailty. METHOD: One hundred and sixty outpatients aged 65 years or older with mild AD were enrolled. Cognitive function was assessed using the Cognitive Ability Screening Instrument and further classified into 4 clusters (recent memory, frontal cortex cluster, posterior cortex cluster, and orientation). Other variables included depressive mood, daily activities, body mass index, handgrip strength (HGS), and normal gait speed (NGS). RESULTS: Performance in daily activities, and slower NGS than robust group. Both the frail and pre-frail groups had lower HGS and more depressive symptoms than robust group. Generalized linear with ordinal logistic analysis showed that increment in age, slowing in NGS, and worse frontal cortex cluster function associated with being in a higher level of frailty. The patients with depression symptoms were the odds of being in a higher level of frailty compared to those without depression symptoms. CONCLUSIONS: In addition to physical and psychological symptoms, frailty is associated with specific cognitive domains in patients with AD. A multidimensional approach should be used to assess the impact of intervention programs focusing on frail patients with AD.

Reconstruction of the Instantaneous Earth Rotation Vector with Sub-Arcsecond Resolution Using a Large Scale Ring Laser Array.

Absolute rotation rate sensing with extreme sensitivity requires a combination of several large scale gyroscopes in order to obtain the full vector of rotation. We report on the construction and operation of a four-component, tetrahedral laser gyroscope array as large as a five story building and situated in a near surface, underground laboratory. It is demonstrated that reconstruction of the full Earth rotation vector can be achieved with sub-arcsecond resolution over more than six weeks.

Sarcopenia in female patients with Alzheimer's disease are more likely to have lower levels of haemoglobin and 25-hydroxyvitamin D.

AIM: Few studies have investigated sarcopenia in patients with cognitive impairment. However, identifying the characteristics and factors associated with sarcopenia in these patients may help to decrease the risk of falls, prevent disabilities, and maintain an independent life, all of which can affect the quality of life of both patient and caregiver. Therefore, the aim of this study was to investigate associated factors of sarcopenia in patients with mild to moderate Alzheimer's disease. METHODS: This cross-sectional study enrolled 125 outpatients aged 65 to 89 years (mean age 79.5 ± 7.9 years) from January 2018 to December 2018. In addition to demographic characteristics, cognitive status, depressive mood, activities of daily living, body mass index (BMI), handgrip strength, gait speed, muscle mass, and serum levels of 25-hydroxyvitamin D (Vit D), haemoglobin (Hb), albumin and creatinine were assessed. Sarcopenia was defined based on the presence of low muscle mass and either low muscle strength or low physical performance. RESULTS: Overall, 29.6% of the patients had sarcopenia. The patients with sarcopenia were mostly male, significantly older, and had a lower BMI and lower levels of Vit D. The female patients with sarcopenia were more likely to have lower levels of Hb. Multiple logistic regression showed that sarcopenia was associated with BMI in both genders. The level of Vit D was associated with sarcopenia in the female patients, whereas age was associated with sarcopenia in the male patients. CONCLUSIONS: A low BMI may be a dementia-related risk factor for sarcopenia. The female patients with sarcopenia were more likely to have lower levels of Hb and Vit D. There may be different risk profiles for sarcopenia in men and women with Alzheimer's disease. Further studies are needed to devise different nutritional support for muscle weakness in patients with cognitive decline by gender.

Higher levels of thyroxine may predict a favorable response to donepezil treatment in patients with Alzheimer disease: a prospective, case-control study.

BACKGROUND: Cholinergic hypothesis has been advanced as an etiology of Alzheimer disease (AD) on the basis of the presynaptic deficit found in the diseased brains, and cholinesterase inhibitors (ChEIs) are the treatment of choice for these patients. However, only about half of treatment efficacy was found. Because increasing evidence supports an extensive interrelationship between thyroid hormones (THs), cortisol level and the cholinergic system, the aim of the present study was to evaluate thyroid function and cortisol level in patients with mild to moderate AD before and after ChEIs treatment, and to identify possible variations in response. This was a prospective, case-control, follow-up study. Levels of cortisol and THs were evaluated in 21 outpatients with mild to moderate AD and 20 normal controls. All patients were treated with 5 mg/day of donepezil (DPZ) and were reevaluated after 24-26 weeks of treatment. RESULTS: The patients had worse cognitive function, higher cortisol level, and lower levels of triiodothyronine (T3) and its free fraction than the controls. There were no significant differences in global cognitive function or cortisol level after treatment, however, significant reductions in T3 and thyroxin (T4) levels were observed. Responders had higher levels of T4 than non-responders, followed by a significant reduction after treatment. CONCLUSIONS: These results suggest that relatively higher levels of T4 may predict a favorable response to DPZ treatment. Further studies are warranted to confirm the relationship between THs and ChEIs therapy in AD and to explore new therapeutic strategies. On the other hand, cortisol levels are more likely to respond to interventions for stress-related neuropsychiatric symptoms in patients with AD rather than ChEIs treatment. Further studies are warranted to investigate the association between cortisol level and the severity of stress-related neuropsychiatric symptoms in patients with AD.

Assessing and simulating the major pathway and hydrogeochemical transport of arsenic in the Beitou-Guandu area, Taiwan.

This study involved assessing and simulating the probable major pathways (surface and subsurface flow) and hydrogeochemical transport of arsenic (As) in the Beitou-Guandu area, Taiwan. A one-dimensional (1-D) generic, reactive, chemical transport model (PHREEQC) was adopted. The calibrated model showed that As transported to the downstream Guandu plain and Tan Shui river mouth accounted for 50.7 and approximately 100 % of the As in the subsurface flow pathway, respectively, suggesting that subsurface flow constituted a major As pathway. The highest As water concentration occurred near the Beitou geothermal valley because of the low pH and high redox potential in both the surface and subsurface pathways. However, As may be scavenged by aqueous Fe(II) in a reducing environment. The As concentrations in the downstream Guandu plain and Guandu wetland decreased as the simulated time increased, resulting in the adsorption of As on the surface of Fe oxydroxides and limiting the mobility of As in the surface flow pathway. The major retardation mechanism of As mobility in the subsurface flow pathway of the Guandu plain and Guandu wetland was governed by the adsorption reactions of iron-oxide and iron-sulfide minerals. The 1-D transport model was applied to predict the evolution of As in the subsurface flow pathway from 2013 to 2020. The results indicated that the As concentrations in all cells gradually increased. The geochemical redox reactions of As in the subsurface pathway subsequently led to the oxidization of As-bearing sulfides, causing As concentrations to rise substantially in the hillside area.

Association between antipsychotic use and risk of acute myocardial infarction: a nationwide case-crossover study.

BACKGROUND: Antipsychotic medications have been increasingly and more widely prescribed despite continued uncertainty about their association with the incidence of acute myocardial infarction (AMI). METHODS AND RESULTS: We investigated the risk of AMI associated with antipsychotic treatment in 56 910 patients with schizophrenia, mood disorders, or dementia first hospitalized or visiting an emergency room for AMI in 1999 to 2009. A case-crossover design was used to compare the distributions of antipsychotic exposure for the same patient across 1 to 30 and 91 to 120 days just before the AMI event. Adjustments were made for comedications and outpatient visits. The adjusted odds ratio of AMI risk was 2.52 (95% confidence interval, 2.37-2.68) for any antipsychotics, 2.32 (95% confidence interval, 2.17-2.47) for first-generation antipsychotics, and 2.74 (95% confidence interval, 2.49-3.02) for second-generation antipsychotics. The risk significantly increased (P<0.001) with elevations in dosage and in short-term use (≤30 days). Male patients, elderly patients, and patients with dementia were at significantly increased risk (all P<0.001). Physically healthier patients with no preexisting diabetes mellitus, hypertension, or dyslipidemia were at significantly greater risk (P<0.001), largely because they had been exposed to higher doses of antipsychotics (P<0.001). A study of the selected binding of antipsychotics to 14 neurotransmitter receptors revealed only dopamine type 3 receptor antagonism to be significantly associated with AMI risk (adjusted odds ratio, 2.59; 95% confidence interval, 2.43-2.75; P<0.0001). CONCLUSIONS: Antipsychotic use may be associated with a transient increase in risk for AMI, possibly mediated by dopamine type 3 receptor blockades. Further education on drug safety and research into the underlying biological mechanisms are needed.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and fluorouracil-based treatment in Taiwan colorectal cancer.

This study aimed to investigate the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and the prognosis of colorectal cancer (CRC) patients undergoing 5-fluorouracil (5-FU)-based chemotherapy in Taiwan. We investigated 126 CRC cases. The most common polymorphisms C677T (rs1801133) and A1298C (rs1801131) in MTHFR were genotyped using PCR-restriction fragment length polymorphism. The frequencies of C677T and A1298C were further compared with those in the HapMap database for Whites and Asians. In this study, we found that TT-homozygosity at MTHFR C677T was significantly associated with survival in CRC patients [P<0.001; 95% confidence interval (CI)=0.068-0.212]. In CRC patients receiving 5-FU-based chemotherapy, the TT genotype at C677T was also significantly associated with survival (P=0.001; 95% CI=0.113-0.400) and recurrence after surgery (P<0.001; 95% CI=0.295-0.609). The A1298C genotypes had a significant impact on survival (χ=7.103; P=0.029). The MTHFR A1298C CC genotype may increase the risk of death in Taiwanese CRC patients. The MTHFR C677T TT genotype was present at a lower frequency in our CRC patients than in the HapMap Asian population, but the frequency was similar to that in Whites in the HapMap database. The distribution of MTHFR A1298C genotypes was similar in our CRC and in the HapMap Asian population, but was different from that in the White population. This study suggested that MTHFR C677T and A1298C are associated with prognosis in CRC patients undergoing 5-FU-based chemotherapy.

Networks development between nicotinic chemical probes and Ca9-22 oral cancer cells by general proteomics analyses.

Tobacco includes thousands of chemicals such as nicotine, which causes numerous diseases including oral cancer. We synthesized nicotinic acid based probes by chemical modification to identify the proteins expressed by the oral cancer cell line Ca9-22 that interact with the nicotinic functional group. Proteins belonging to human oral squamous cell carcinoma were pulled down by a probe carrier based on nicotinic acid, which was reacted with 3-aminopropyltriethoxysilane to compose nicotinic acid linked 3-aminopropyltriethoxysilane exposed on the SiO2 surface. Oral cancer cell lysates were incubated with the nicotinic acid chemical probes to identify the interactions between the nicotinic group and oral cancer cell line extracted proteins. The interactions between the chemical probes and proteins identified as their targets were confirmed by consulting chemicals databases. Interestingly, chaperone proteins (e.g., heat-shock proteins and endoplasmin) that were found to interact with nicotinic acid were identified as binding partners in ribosomal and nucleosome assembly complexes.

A proteomics analysis to evaluate cytotoxicity in NRK-52E cells caused by unmodified Nano-Fe3O4.

We synthesized unmodified Fe3O4 nanoparticles (NPs) with particles size from 10 nm to 100 nm. We cultured NRK-52E cell lines (rat, kidney) and treated with Fe3O4 NPs to investigate and evaluate the cytotoxicity of NPs for NRK-52E cells. Through global proteomics analysis using dimethyl labeling techniques and liquid phase chromatography coupled with a tandem mass spectrometer (LC-MS/MS), we characterized 435 proteins including the programmed cell death related proteins, ras-related proteins, glutathione related proteins, and the chaperone proteins such as heat shock proteins, serpin H1, protein disulfide-isomerase A4, endoplasmin, and endoplasmic reticulum resident proteins. From the statistical data of identified proteins, we believed that NPs treatment causes cell death and promotes expression of ras-related proteins. In order to avoid apoptosis, NRK-52E cell lines induce a series of protective effects such as glutathione related proteins to reduce reactive oxygen species (ROS), and chaperone proteins to recycle damaged proteins. We suggested that, in the indigenous cellular environment, Fe3O4 NPs treatment induced an antagonistic effect for cell lines to go to which avoids apoptosis.

Phthalic acid chemical probes synthesized for protein-protein interaction analysis.

Plasticizers are additives that are used to increase the flexibility of plastic during manufacturing. However, in injection molding processes, plasticizers cannot be generated with monomers because they can peel off from the plastics into the surrounding environment, water, or food, or become attached to skin. Among the various plasticizers that are used, 1,2-benzenedicarboxylic acid (phthalic acid) is a typical precursor to generate phthalates. In addition, phthalic acid is a metabolite of diethylhexyl phthalate (DEHP). According to Gene_Ontology gene/protein database, phthalates can cause genital diseases, cardiotoxicity, hepatotoxicity, nephrotoxicity, etc. In this study, a silanized linker (3-aminopropyl triethoxyslane, APTES) was deposited on silicon dioxides (SiO2) particles and phthalate chemical probes were manufactured from phthalic acid and APTES-SiO2. These probes could be used for detecting proteins that targeted phthalic acid and for protein-protein interactions. The phthalic acid chemical probes we produced were incubated with epithelioid cell lysates of normal rat kidney (NRK-52E cells) to detect the interactions between phthalic acid and NRK-52E extracted proteins. These chemical probes interacted with a number of chaperones such as protein disulfide-isomerase A6, heat shock proteins, and Serpin H1. Ingenuity Pathways Analysis (IPA) software showed that these chemical probes were a practical technique for protein-protein interaction analysis.

Heat shock protein 90 stabilizes nucleolin to increase mRNA stability in mitosis.

Most studies on heat shock protein 90 (Hsp90) have focused on the involvement of Hsp90 in the interphase, whereas the role of this protein in the nucleus during mitosis remains largely unclear. In this study, we found that the level of the acetylated form of Hsp90 decreased dramatically during mitosis, which indicates more chaperone activity during mitosis. We thus probed proteins that interacted with Hsp90 by liquid chromatography/mass spectrometry (LC/MS) and found that nucleolin was one of those interacting proteins during mitosis. The nucleolin level decreased upon geldanamycin treatment, and Hsp90 maintained the cyclin-dependent kinase 1 (CDK1) activity to phosphorylate nucleolin at Thr-641/707. Mutation of Thr-641/707 resulted in the destabilization of nucleolin in mitosis. We globally screened the level of mitotic mRNAs and found that 229 mRNAs decreased during mitosis in the presence of geldanamycin. Furthermore, a bioinformatics tool and an RNA immunoprecipitation assay found that 16 mRNAs, including cadherin and Bcl-xl, were stabilized through the recruitment of nucleolin to the 3'-untranslated regions (3'-UTRs) of those genes. Overall, strong correlations exist between the up-regulation of Hsp90, nucleolin, and the mRNAs related to tumorigenesis of the lung. Our findings thus indicate that nucleolin stabilized by Hsp90 contributes to the lung tumorigenesis by increasing the level of many tumor-related mRNAs during mitosis.

Characteristics and impact of environmental shaking in the Taipei metropolitan area.

Examining continuous seismic data recorded by a dense broadband seismic network throughout Taipei shows for the first time, the nature of seismic noise in this highly populated metropolitan area. Using 140 broadband stations in a 50 km × 69 km area, three different recurring, strong noise signals characterized by dominant frequencies of 2-20 Hz, 0.25-1 Hz, and < 0.2 Hz are explored. At frequencies of 2-20 Hz, the seismic noise exhibits daily and weekly variations, and a quiescence during the Chinese New Year holidays. The largest amplitude occurred at a station located only 400 m from a traffic-roundabout, one of the busiest intersections in Taipei, suggesting a possible correlation between large amplitude and traffic flow. The median daily amplitude for the < 0.2 Hz and 0.2-1.0 Hz frequency bands is mostly synchronized with high similarity between stations, indicating that the sources are persistent oceanic or atmospheric perturbations across a large area. The daily amplitude for the > 2 Hz band, however, is low, indicating a local source that changes on shorter length scales. Human activities responsible for the 2-40 Hz energy in the city, we discovered, are able to produce amplitudes approximately 2 to 1500 times larger than natural sources. Using the building array deployed in TAIPEI 101, the tallest building in Taiwan, we found the small but repetitive ground vibration induced by traffic has considerable effect on the vibration behavior of the high-rise building. This finding urges further investigation not only on the dynamic and continuous interaction between vehicles, roads, and buildings, but also the role of soft sediment on such interaction.

The Cell Type-Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and TET2-Mutant Preleukemia.

The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that is mediated by ten-eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape of normal hematopoiesis and identify cell type-specific 5hmC profiles associated with active transcription and chromatin accessibility of key hematopoietic regulators. We utilized CRISPR/Cas9 to model TET2 loss-of-function mutations in primary human hematopoietic stem and progenitor cells (HSPC). Disrupted cells exhibited increased colonies in serial replating, defective erythroid/megakaryocytic differentiation, and in vivo competitive advantage and myeloid skewing coupled with reduction of 5hmC at erythroid-associated gene loci. Azacitidine and ascorbate restored 5hmC abundance and slowed or reverted the expansion of TET2-mutant clones in vivo. These results demonstrate the key role of 5hmC in normal hematopoiesis and TET2-mutant phenotypes and raise the possibility of utilizing these agents to further our understanding of preleukemia and clonal hematopoiesis. SIGNIFICANCE: We show that 5-hydroxymethylation profiles are cell type-specific and associated with transcriptional abundance and chromatin accessibility across human hematopoiesis. TET2 loss caused aberrant growth and differentiation phenotypes and disrupted 5hmC and transcriptional landscapes. Treatment of TET2 KO HSPCs with ascorbate or azacitidine reverted 5hmC profiles and restored aberrant phenotypes. This article is highlighted in the In This Issue feature, p. 265.

Quantitative phosphoproteomics studies using stable isotope dimethyl labeling coupled with IMAC-HILIC-nanoLC-MS/MS for estrogen-induced transcriptional regulation.

17ß-Estradiol (E2) regulates transcriptional activity partly by inducing protein-kinase cascades, leading to the phosphorylation of estrogen receptors (ERs) and other functional proteins. Many of these phosphorylation events are also modulated by growth factors. To gain an insight into E2-modulated protein phosphorylation, we applied quantitative phosphoproteomics to investigate global changes in protein phosphorylation induced by E2 in MCF-7 cells. Proteomic analyses using stable isotope dimethyl labeling coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography (IMAC-HILIC) fractionation and nanoLC-MS/MS identified and quantified 2857 unique phosphorylation sites in 1338 phosphoproteins from 1 mg of total cellular protein. In addition to S118 of ERα, a 30-min E2 treatment significantly altered the status of 403 phosphorylation sites, including 112 novel sites. Interestingly, the substrate motifs for ERK1/2 were largely enriched in both the up-regulated and down-regulated phosphorylation sites. An increase in the phosphorylation on either the T202 or Y204 sites of ERK1 was observed after E2 treatment, while dual phosphorylation on both sites were not detected, implying that a feedback loop to deactivate MAPK signaling was achieved during a 30-min E2 treatment. In contrast, the PKA and CKII substrate motifs were majorly enriched among the up-regulated phosphorylation sites. Western blot analysis confirmed that E2 increased the phosphorylation level of S226 within a CKII motif of HSP90ß by a factor of 2- to 3-fold without changing the total protein expression level. E2 also up-regulated phosphorylations of S255 in HSP90ß and S353 within a CKII motif of HSP90α. These results indicated that E2 may modulate gene transcription by affecting the stability, function, and activity of many regulators through a HSP90 phosphorylation-mediated chaperoning process. This study, using a quantitative, multidimensional separation phosphoproteomic approach that required a relatively low amount of cells, provides new insights into the diversity, variability, and dynamic nature of the protein phosphorylation/dephosphorylation elicited by E2.

Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities.

Phenotypic heterogeneity has been widely observed in cellular populations. However, the extent to which heterogeneity contains biologically or clinically important information is not well understood. Here, we investigated whether patterns of basal signaling heterogeneity, in untreated cancer cell populations, could distinguish cellular populations with different drug sensitivities. We modeled cellular heterogeneity as a mixture of stereotyped signaling states, identified based on colocalization patterns of activated signaling molecules from microscopy images. We found that patterns of heterogeneity could be used to separate the most sensitive and resistant populations to paclitaxel within a set of H460 lung cancer clones and within the NCI-60 panel of cancer cell lines, but not for a set of less heterogeneous, immortalized noncancer human bronchial epithelial cell (HBEC) clones. Our results suggest that patterns of signaling heterogeneity, characterized as ensembles of a small number of distinct phenotypic states, can reveal functional differences among cellular populations.

Relationship among sexual desire, sexual satisfaction, and quality of life in middle-aged and older adults.

The authors examined the association among sexual desire, sexual satisfaction, and quality of life in a sample of community participants. They predicted that quality of life would be positivity correlated with sexual satisfaction and that sexual desire would indirectly influence quality of life. This research showed that elderly adults' sexual desire and sexual satisfaction decrease with age and that nearly 40% of the interviewees still had sexual activity one or more times every month. The results revealed that sexual desire does not directly influence quality of life, but it does have a direct effect on sexual satisfaction; hence, sexual satisfaction will indirectly affect quality of life.

Robot technology in dentistry, part one of a systematic review: literature characteristics.

OBJECTIVES: To provide dental practitioners and researchers with a comprehensive and transparent evidence-based overview of the characteristics of literature regarding initiatives of robot technology in dentistry. DATA: All articles in which robot technology in dentistry is described, except for non-scientific articles and articles containing secondary data (reviews). Amongst others, the following data were extracted: type of study, level of technological readiness, authors' professional background and the subject of interaction with the robot. SOURCES: Bibliographic databases PubMed, Embase, and Scopus were surveyed. A reference search was conducted. The search timeline was between January 1985 and October 2020. STUDY SELECTION: A total of 911 articles were screened on title and abstract of which 161 deemed eligible for inclusion. Another 71 articles were excluded mainly because of unavailability of full texts or the sole use of secondary data (reviews). Four articles were included after hand searching the reference lists. In total, 94 articles were included for analysis. CONCLUSIONS: Since 2013 an average of six articles per year concern robot initiatives in dentistry, mostly originating from East Asia (57%). The vast majority of research was categorized as either basic theoretical or basic applied research (80%). Technology readiness levels did not reach higher than three (proof of concept) in 55% of all articles. In 84%, the first author of the included articles had a technical background and in 36%, none of the authors had a dental or medical background. The overall quality of literature, especially in terms of clinical validation, should be considered as low.

Robot technology in dentistry, part two of a systematic review: an overview of initiatives.

OBJECTIVES: To provide dental practitioners and researchers with a comprehensive and transparent evidence-based overview of physical robot initiatives in all fields of dentistry. DATA: Articles published since 1985 concerning primary data on physical robot technology in dentistry were selected. Characteristics of the papers were extracted such as the respective field of dentistry, year of publication as well as a description of its usage. SOURCES: Bibliographic databases PubMed, Embase, and Scopus were searched. A hand search through reference lists of all included articles was performed. STUDY SELECTION: The search timeline was between January 1985 and October 2020. All types of scientific literature in all languages were included concerning fields of dentistry ranging from student training to implantology. Robot technology solely for the purpose of research and maxillofacial surgery were excluded. In total, 94 articles were included in this systematic review. CONCLUSIONS: This study provides a systematic overview of initiatives using robot technology in dentistry since its very beginning. While there were many interesting robot initiatives reported, the overall quality of the literature, in terms of clinical validation, is low. Scientific evidence regarding the benefits, results and cost-efficiency of commercially available robotic solutions in dentistry is lacking. The rise in availability of open source control systems, compliant robot systems and the design of dentistry-specific robot technology might facilitate the process of technological development in the near future. The authors are confident that robotics will provide useful solutions in the future but, strongly, encourage an evidence-based approach when adapting to new (robot) technology.

Adverse effects following dental local anesthesia: a literature review.

Local anesthesia is indispensable in dentistry. Worldwide, millions of local anesthetic injections are administered annually, and are generally considered safe invasive procedures. However, adverse effects are possible, of which dentists should be aware of. This scoping review aimed to provide an extensive overview of the reported literature on the adverse effects of dental local anesthesia. The types of papers, what is reported, and how they are reported were reviewed. Additionally, the incidence and duration of adverse effects and factors influencing their occurrence were also reviewed. An electronic search for relevant articles was performed in PubMed and Embase databases from inception to January 2, 2020. The titles and abstracts were independently screened by two reviewers. The analysis was narrative, and no meta-analysis was performed. This study included 78 articles. Ocular and neurological adverse effects, allergies, hematomas, needle breakage, tissue necrosis, blanching, jaw ankylosis, osteomyelitis, and isolated atrial fibrillation have been described. Multiple adverse effects of dental local anesthesia have been reported in the literature. The results were heterogeneous, and detailed descriptions of the related procedures were lacking. Vital information concerning adverse effects, such as the dosage or type of anesthetic solution, or the type of needle used, was frequently missing. Therefore, high-quality research on this topic is needed. Finally, the adverse effects that are rarely encountered in real-world general practice are overrepresented in the literature.