Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

The utility of on-site ultrasound screening in population at high risk for deep venous thrombosis in temporary housing after the great East Japan Earthquake.

BACKGROUND: To evaluate the diagnostic performance of ultrasonography for screening of a population at risk for deep vein thrombosis (DVT) in a post-disaster setting. METHODS: Ultrasonography was applied as a screening technique to the residents of a temporary housing facility who were displaced following the Great East Japan Earthquake. Thirty DVT screening sessions were held from April 2013 to June 2015. Individuals were invited to participate if they were identified as "high risk" for DVT, defined as those with low activity levels, a history of lower limb trauma, baseline lower limb pain or swelling, a cancer-bearing status, or a history of venous thromboembolic event. Ultrasonographic examinations were performed from the calf to the popliteal veins using portable devices. RESULTS: Of the 3,316 subjects screened (682 men and 2,634 women) with a mean age of 71 ± 9.7 years, DVT was diagnosed in 382 (11.5%). DVT was more likely in older, symptomatic, or female patients with a history of venous thromboembolism and attempting to perform daily exercise. The rate of DVT diagnosis increased from 9.9% in 2013 to 13.5% in 2015. CONCLUSIONS: Ultrasonography is efficient for screening at-risk populations in challenging settings. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:566-574, 2017.

Familial Mediterranean fever with P369S/R408Q exon3 variant in pyrin presenting as symptoms of PFAPA.

Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome-like symptoms have been found in atypical type carrying P369S-R408Q mutations in the responsible gene MEFV. A 28-year-old female with recurrent fever and her young sisters and mother, all of whom had tonsillectomy for tonsillitis, carried heterozygous alterations involving E148Q/P369S/R408Q. A diagnosis of atypical FMF, MEFV exon3 variants with PFAPA syndrome-like symptoms, was made.

Oxygen reduction reaction activity and structural stability of Pt-Au nanoparticles prepared by arc-plasma deposition.

The oxygen reduction reaction (ORR) activity and durability of various Au(x)/Pt100 nanoparticles (where x is the atomic ratio of Au against Pt) are evaluated herein. The samples were fabricated on a highly-oriented pyrolytic graphite substrate at 773 K through sequential arc-plasma depositions of Pt and Au. The electrochemical hydrogen adsorption charges (electrochemical surface area), particularly the characteristic currents caused by the corner and edge sites of the Pt nanoparticles, decrease with increasing Au atomic ratio (x). In contrast, the specific ORR activities of the Au(x)/Pt100 samples were dependent on the atomic ratios of Pt and Au: the Au28/Pt100 sample showed the highest specific activity among all the investigated samples (x = 0-42). As for ORR durability evaluated by applying potential cycles between 0.6 and 1.0 V in oxygen-saturated 0.1 M HClO4, Au28/Pt100 was the most durable sample against the electrochemical potential cycles. The results clearly showed that the Au atoms located at coordinatively-unsaturated sites, e.g. at the corners or edges of the Pt nanoparticles, can improve the ORR durability by suppressing unsaturated-site-induced degradation of the Pt nanoparticles.

[Examination for deep vein thrombosis in the Iwate Sanriku coastal area stricken by the Great East Japan Earthquake Disaster in 2011--measurement of D-dimer using POCT apparatus].

After the Great East Japan Earthquake Disaster in 2011, examinations for below the-knee deep vein thrombosis (BK-DVT) were carried out to prevent victims from secondary health damage by Iwate Prophylactic Examination Organization from economy-class syndrome. In this examination, D-dimer was measured using cobas h 232, a point-of-care testing (POCT) apparatus, in addition to medical interview, blood pressure measurement, and lower limb vein sonography. In the BK-DVT examination carried out in Tanohata in October and in Miyako in November 2012, the BK-DVT-positive number(percentage) in lower limb vein sonography was six (13.3%) in Tanohata and four (4.1%) in Miyako among 136 subjects (average age of 69.0 +/- 11.9, male:female sex ratio of 28:108). D-dimer in BK-DVT-positive subjects was 1.31 +/- 1.27 microg/mL, significantly higher than that in BK-DVT-negative subjects without cardiac diseases (0.46 +/- 0.50 microg/mL, p < 0.05). Eight subjects (5.6%) with higher D-dimer values were immediately referred to the nearest hospital. It was shown that the POCT apparatus was very useful when lifelines were not available and when the examination was performed in refuges since they are small, light and simple to operate, and the medical technologists played important roles in various examinations because of their high skill and abilities.

Association between administration or recommendation of the human papillomavirus vaccine and primary care physicians' knowledge about vaccination during proactive recommendation suspension: a nationwide cross-sectional study in Japan.

OBJECTIVE: The Japanese government suspended the proactive recommendation of the human papillomavirus vaccine (HPVv) in 2013, and the vaccination rate of HPVv declined to <1% during 2014-2015. Previous studies have shown that the recommendation by a physician affects a recipient's decision to receive a vaccine, and physicians' accurate knowledge about vaccination is important to increase vaccine administration. This study aimed to evaluate the association between physicians' knowledge of vaccination and the administration or recommendation of HPVv by primary care physicians (PCPs) in the absence of proactive recommendations from the Japanese government. DESIGN: Cross-sectional study analysed data obtained through a web-based, self-administered questionnaire survey. SETTING: The questionnaire was distributed to Japan Primary Care Association (JPCA) members. PARTICIPANTS: JPCA members who were physicians and on the official JPCA mailing list (n=5395) were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary and secondary outcomes were the administration and recommendation of HPVv, respectively, by PCPs. The association between PCPs' knowledge regarding vaccination and each outcome was determined based on their background and vaccination quiz scores and a logistic regression analysis to estimate the adjusted ORs (AORs). RESULTS: We received responses from 1084 PCPs and included 981 of them in the analysis. PCPs with a higher score on the vaccination quiz were significantly more likely to administer the HPVv for routine and voluntary vaccination (AOR 2.28, 95% CI 1.58 to 3.28; AOR 2.71, 95% CI 1.81 to 4.04, respectively) and recommend the HPVv for routine and voluntary vaccination than PCPs with a lower score (AOR 2.17, 95% CI 1.62 to 2.92; AOR 1.88, 95% CI 1.32 to 2.67, respectively). CONCLUSIONS: These results suggest that providing accurate knowledge regarding vaccination to PCPs may improve their administration and recommendation of HPVv, even in the absence of active government recommendations.

Factors associated between behavior of administrating or recommending mumps vaccine and primary care physicians' knowledge about vaccination: A nationwide cross-sectional study in Japan.

BACKGROUND: In Japan, the mumps-containing vaccine was withdrawn from routine vaccination in 1993, and it became a voluntary vaccination. This study aimed to evaluate the association between the physicians' knowledge about vaccinations and the administration or recommendation of the mumps vaccine. METHODS: We conducted a nationwide cross-sectional study targeting primary care physicians (PCPs) in Japan. We used a web-based self-administered questionnaire by Preventive Medicine and Health Promotion Committee Vaccine Team, the Japan Primary Care Association (JPCA), from March to June in 2019. The outcome of the study was the association between PCPs' knowledge about vaccine and the administration or recommendation of mumps vaccine. We obtained the information on background, subsidies of mumps vaccination for children from the local government, and vaccination quiz scores. We performed logistic regression analysis to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 10,470 PCPs in JPCA, 5075 were excluded. We received responses from 1084 PCPs (20.1%) and enrolled 981 participants in the analysis. PCPs with a higher score on the vaccination quizzes were significantly more likely to administrate the mumps vaccine for adults (adjusted odds ratio [AOR] 1.93, 95% CI 1.45-2.59, p < 0.001) and recommend mumps vaccine to adults than PCPs with a lower score (AOR 1.78, 95% CI 1.33-2.40, p < 0.001). CONCLUSIONS: We revealed an association between the administration or recommendation of mumps vaccine and PCPs' better vaccination knowledge.

Long-Term Prevalence of Disaster-Related Deep Vein Thrombosis in Minamiaso Village After the 2016 Kumamoto Earthquakes: A Prospective Cross-Sectional Analysis.

OBJECTIVE: This study aimed to examine the prevalence of deep vein thrombosis (DVT) among evacuees in Minamiaso, a village which was temporarily isolated after the earthquakes, from the acute to recovery phase after the 2016 Kumamoto Earthquakes (GLIDE no: EQ-2016-000033-JPN). METHODS: This prospective study, which was approved by Fukui University Medical Research Ethics Committee (approval no. 20160024 and 20160089), enrolled 181 evacuees (73.9 ± 11.6 y) who participated in a series of 3 DVT screenings using portable ultrasound machines conducted over 19 mo. All participants completed a questionnaire before the screenings, and none of the participants attended all 3 screenings. Data analysis was performed using EZR version 1.41. RESULTS: The DVT prevalence was 14.3% (79.4 ± 8.2 y) at first screening of evacuees staying in shelters and 18.5% (71.5 ± 13.1 y) and 12.2% (72.8 ± 10.9 y) in second and third screenings of evacuees staying in temporary housing, respectively. Multivariate analysis revealed age ≥75 y and alcohol consumption as independent risk factors in the entire cohort and in patients aged ≤74 y, respectively. CONCLUSIONS: A high DVT prevalence over a long time period of 19 mo was observed where survivors were temporarily isolated after the disaster.

Localized Right Subclavian Artery Dissection Detected by Accident on an Ultrasound Examination: A Case Report and Literature Review.

Right subclavian artery dissection was detected in a 78-year-old female victim of the Kumamoto earthquake during a carotid artery ultrasound examination. She was subsequently taken to hospital and diagnosed with localized subclavian artery dissection (LSAD) by contrast-enhanced computed tomography. There have been no previous reports of LSAD detected at a medical checkup. LSAD may progress and become severe, even in asymptomatic patients or patients with mild symptoms, and careful long-term follow-up is therefore required in all patients diagnosed with LSAD.

[Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations].

Pneumonia is a major cause of morbidity and mortality in elderly people, especially in those with chronic medical conditions such as chronic heart and lung diseases. We prospectively examined the effect of influenza and pneumococcal vaccinations on the rate of hospitalization for and complications of pneumonia, all respiratory tract conditions and mortality in elderly bedridden patients and found that both febrile days and pneumonia cases decreased. Thus, these results show that it is valuable to vaccinate for influenza elderly people even if they are confined to bed. Furthermore, the tuberculin skin test is an easy method to check the cell-mediated immunity in the elderly people. In the tuberculin skin test, all Japanese over 65 years old should have positive status. A negative result indicates depressed cell-mediated immunity. We undertook a trial to vaccinate tuberculin negative elderly people with BCG vaccine and found that the risk of pneumonia is decreased to a similar degree to that in subjects with positive tuberculin test results. We conclude that vaccination might be an effective strategy for the prevention of pneumonia in elderly people with limited activities of daily living.

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.

Efficient synthesis of poly(phenylazomethine) dendrons allowing access to higher generation dendrimers.

We have developed a novel synthetic method of phenylazomethine dendrons that uses 4,4'-methylenedianiline instead of 4,4'-diaminobenzophenone to synthesize the precursor of the phenylazomethine dendron and then oxidized the precursor to the next-generation dendron. For this method, the productivity of the dendrons has been significantly increased. Furthermore, as the synthesis of high-generation dendrons becomes easier, synthesis of DPA G5 was achieved. [structure--see text]

Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP-2, MMP-3, and MMP-9) activity in a rabbit preterm delivery model.

AIM: To investigate the effect of recombinant human lactoferrin (rh-LF) on the expression of matrix metalloproteinase as a marker of cervical maturation, using a rabbit preterm delivery model in which preterm labor was induced by bacteria. METHODS: We used cervical tissues that had been excised in a previous study in which rabbits were randomly assigned to receive either inoculation with Escherichia coli (E. coli) or saline solution and to receive pretreatment with or without rh-LF inserted into the cervix two hours before bacterial inoculation (Condition A: saline + saline; Condition B: rh-LF + E. coli; Condition C: saline +E. coli). E. coli, saline solution, and rh-LF were inserted into the cervix using a hysteroscope and a sterile polyethylene cannula. Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out and preserved, and expression of matrix metalloproteinases MMP-2,-3, and -9 in the cervix was evaluated using Western blot. RESULTS: MMP-2,-3, and -9 levels in the cervix under Conditions A and B were significantly lower than that under Condition C. CONCLUSIONS: These results suggest that the prevention of preterm delivery by rh-LF in a rabbit model has been achieved through inhibition of cervical maturation promoted by matrix metalloproteinase activity.

Cell-free mRNA concentrations of plasminogen activator inhibitor-1 and tissue-type plasminogen activator are increased in the plasma of pregnant women with preeclampsia.

BACKGROUND: Detection of placental mRNA in maternal plasma has been reported in high-risk pregnancies. We attempted to investigate the concentrations of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) mRNA in maternal plasma in preeclampsia. METHODS: Peripheral blood samples were obtained from healthy pregnant women before and after delivery and also from women with or without preeclampsia. Plasma was isolated from these samples, and RNA was extracted. Plasma PAI-1 and tPA mRNA concentrations were then measured by use of reverse transcription PCR assays. The concentrations were converted into multiples of the median (MoM) of the controls adjusted for gestational age. Data were stratified and analyzed according to the clinical severity of preeclampsia and quantitative distribution of blood pressure and proteinuria. RESULTS: The median (minimum-maximum) PAI-1 mRNA MoM values for women with preeclampsia and controls were 2.48 (0.82-8.53) and 1.00 (0.41-2.33), respectively, whereas the median (minimum-maximum) tPA mRNA MoM values were 3.33 (1.01-10.58) and 1.00 (0.95-1.20), respectively. The concentrations of both PAI-1 and tPA mRNA were significantly increased in cases of preeclampsia, compared with controls (P <0.0001). The MoM values of both mRNA species were directly correlated with the severity of preeclampsia and were greatest among a subgroup of hemolysis, increased liver enzymes, and low platelets pregnancies. CONCLUSION: Maternal plasma PAI-1 and tPA mRNAs are significantly increased in patients with preeclampsia and are positively correlated with the severity of preeclampsia.

Characterization of DLC films by EELS and electron holography.

Thickness measurements of diamond-like carbon (DLC) films by electron energy-loss spectroscopy (EELS) and electron holography are discussed. In order to evaluate the thickness by EELS and electron holography, the mean free path for inelastic scattering and mean inner potential of DLC films were determined precisely, respectively. It is found that both the mean free path for inelastic electron scattering and the mean inner potential are sensitive to the preparation methods, namely the density of DLC films. The present work has demonstrated that thickness measurement by EELS is available to DLC films thicker than 20 nm, while electron holography can be applied to thinner films ( approximately 5 nm). Furthermore, close relations are observed between the density of DLC films and the energy-loss spectra.

Preventive effect of recombinant human lactoferrin in a rabbit preterm delivery model.

OBJECTIVE: Lactoferrin, an iron-binding glycoprotein found in cervical mucus and amniotic fluid, plays a defensive role against mucosal infections. This study examined the effect of recombinant human lactoferrin on preterm delivery in a rabbit model. STUDY DESIGN: Anesthetized rabbits were randomly assigned to receive either inoculation with Escherichia coli or saline solution and to receive treatment with or without recombinant human lactoferrin inserted into the cervix 2 hours before bacterial inoculation (condition A: saline + saline; condition B: E coli + saline; condition C: E coli + recombinant human lactoferrin). E coli , saline solution, and recombinant human lactoferrin were inserted into the cervix using a hysteroscope and a sterile polyethylene cannula. Fetus survival rate and days to delivery after inoculation were monitored and tumor necrosis factor-alpha concentrations were measured in maternal serum and amniotic fluid. RESULTS: Fetus survival for conditions A, B, and C were 95.7%, 0%, and 32.6%, respectively, whereas pregnancy continuation was 7.00 +/- 0 days, 3.25 +/- 0.43 days, and 4.85 +/- 1.77 days, respectively. CONCLUSION: Cervical recombinant human lactoferrin administration increased fetal survival and extended pregnancy. Lactoferrin has an anti-inflammatory action as well as an antibacterial action, suggesting that recombinant human lactoferrin has the potential to prevent preterm delivery originating from cervical infection in the clinical setting.

Recombinant human lactoferrin has preventive effects on lipopolysaccharide-induced preterm delivery and production of inflammatory cytokines in mice.

OBJECTIVE: The following animal studies have been conducted to investigate whether recombinant human lactoferrin (rh-LF) has the same effect as bovine lactoferrin (b-LF) in the prevention of preterm delivery. STUDY DESIGN: Female C3H/HeNCrj mice were pair-mated with male Crj:B6D2F1 mice. On day 15 of gestation, as a model of preterm delivery, a 50 microg/kg intraperitoneal injection of lipopolysaccharide (LPS) was administered twice with a 3-h interval between injections (2:00 and 5:00 PM). One hour prior to each LPS injection (1:00 and 4:00 PM), an intraperitoneal injection of saline, b-LF, or rh-LF (1 mg/body) was administered. In non-LPS-treated controls, an intraperitoneal injection of saline was administered 4 times (1:00, 2:00, 4:00 and 5:00 PM). Body weights and delivery times were recorded. To compare plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) between experimental and other pregnant mice, prepared as above, were sacrificed 6 h after the second LPS injection, and then blood samples were obtained and analyzed. RESULTS: Preterm delivery occurred (16.2+/-0.4 days of gestation) in all LPS-treated mice that were not administered LF. LF significantly prolonged gestation of LPS-treated mice: b-LF+LPS, 17.8+/-0.3 days; rh-LF+LPS, 18.0+/-0.8 days (P<0.05). LF (1 mg/body) significantly suppressed plasma IL-6 in LPS-treated mice:b-LF+LPS, 1060+/-154; rh-LF+ LPSF, 244+/-59; LPS without LF, 1628+/-115 pg/mL (P<0.05). As well, LF (1 mg/body) significantly suppressed plasma TNF-alpha in LPS-treated mice: b-LF+LPS, 88+/-36; rh-LF+LPS, 37+/-30; LPS without LF, 114+/-49 pg/mL (P<0.05). CONCLUSIONS: Rh-LF may prolong gestation in LPS-induced preterm delivery in mice, by suppressing LPS-induced plasma IL-6 and TNF-alpha augmentation.

Stepwise radial complexation of imine groups in phenylazomethine dendrimers.

Dendrimers are highly branched organic macromolecules with successive layers or 'generations' of branch units surrounding a central core. Organic-inorganic hybrid versions have also been produced, by trapping metal ions or metal clusters within the voids of the dendrimers. The unusual, tree-like topology endows these nanometre-sized macromolecules with a gradient in branch density from the interior to the exterior, which can give rise to an energy gradient that directs the transfer of charge and energy from the dendrimer periphery to its core. Here we show that tin ions, Sn(2+), complex to the imine groups of a spherical polyphenylazomethine dendrimer in a stepwise fashion. This behaviour reflects a gradient in the electron density associated with the imine groups, with complexation in a more peripheral generation proceeding only after complexation in generations closer to the core has been completed. By attaching an electron-withdrawing group to the dendrimer core, we are able to change the complexation pattern, so that the core imines are complexed last. By further extending this strategy, it should be possible to control the number and location of metal ions incorporated into dendrimer structures, which might find uses as tailored catalysts or building blocks for advanced materials.