Assembly of anionic silver nanoclusters with controlled packing structures through site-specific ionic bridges.

The assembly of metal nanoclusters (NCs) into crystalline lattice structures is of interest in the development of NC-based functional materials. Here we demonstrate that the assembled structures of tri-anionic tetrahedral symmetric [Ag29(BDT)12]3- (Ag29 NC, BDT: 1,3-benzenedithiol) NCs are controlled into a polyethylene-like zigzag chain and a "poly-ring-fused-cyclohexane"-like honeycomb arrangement through ionic interactions with alkali metal cations such as K+ and Cs+. The site-specific binding of alkali metal ions on the tetrahedrally arranged binding sites of Ag29 NCs successfully connects the adjacent NCs into various packing modes. The number and type of bridges between NCs determine the Ag29 NC packing structures, which are affected by the solvent species, enabling the transformation of packing modes in the single-crystalline state. The photoluminescence (PL) properties of the crystals responded to the packing modes of the NCs in terms of anisotropy and bridge linkage style inducing a varied degree of relaxation of the excited state depending on the relocation mobility of alkali metal ions in the crystals.

Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly.

Pathobionts are commensal intestinal microbiota capable of causing systemic infections under specific conditions, such as environmental changes or aging. However, it is unclear how pathobionts are recognized by the intestinal mucosal immune system under physiological conditions. This study demonstrates that the gut pathobiont Klebsiella pneumoniae causes injury to the epithelium and translocates to the liver in specific pathogen-free mice treated with clodronate-liposomes that depleted macrophages. In the clodronate-liposome-treated mice, indigenous classical K. pneumoniae (cKp) with non-K1/K2 capsular serotypes were isolated from the liver, indicating that gut commensal cKp translocated from the gastrointestinal tract to the liver due to the depletion of intestinal macrophages. Oral inoculation of isolated cKp to clodronate-liposome-treated mice significantly reduced the survival rates compared to that of non-treated mice. Our findings demonstrate that intestinal mucosal macrophages play a pivotal role in sensing commensal cKp and suppressing their translocation to the liver. This study demonstrates that clodronate-liposome-treated mouse models are effective for screening and evaluating drugs that prevent the translocation of cKp to the liver, providing new insights into the development of preventive protocols against K. pneumoniae infection.

Soy-Based High-Protein Spheric Foods with the Appearance of Familiar Sugary Snacks.

Excessive consumption of sugary foods increases the likelihood of obesity, as well as the preventable risk of lifestyle illnesses such as diabetes and cardiovascular diseases. Frequent intake of sweet snacks is considered to increase the risk of overweight/obesity in industrial nations. However, we cannot stop snacking against our better judgment. Therefore, in this study, we sought to develop high-protein, low-carb "mock snacks" to satisfy snack lovers' appetites and nutrition. Soy protein-based, ball-shaped food products with 57.7% (w/w) protein and 3.6% sugar have been developed. The addition of canola oil made them melty in the mouth without sacrificing their crispiness. Moreover, evaluation of the surface topography of the "soy balls" by 3D laser scanning demonstrated their high degree of sphericity. Conclusively, the snacks developed here may be one of the healthy alternatives for the current sugary ones.

Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments.

BACKGROUND: Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn's disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown. RESULTS: This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain. CONCLUSIONS: Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD.

Selective Crystallization of Linkage Isomers, [RhIII(NCS)(SCN)5]3- and [RhIII(SCN)6]3-, to Investigate Structural Trans Influence and Thermal Stability.

Linkage isomers of homoleptic complexes, [RhIII(SCN)6]3- and [RhIII(NCS)(SCN)5]3-, formed in aqueous solution were successfully separated by employing methyltriphenylphosphonium (MePPh3+) and 1-ethylquinolinium (EtQu+) ions as countercations, respectively. The single-crystal X-ray analysis of (MePPh3)3[RhIII(SCN)6] (1) indicated that all of the SCN- ligands coordinate to the RhIII ion by S atoms with an octahedral symmetry, where the average bond length of Rh-S is 2.374(7) Å. On the other hand, the RhIII ion of (EtQu)3[RhIII(NCS)(SCN)5]·H2O (2) is coordinated by five S atoms and one N atom of the SCN- ligands with a C4v symmetry. Structural trans influence was observed in the shorter bond length of Rh-S at the trans position of Rh-N. The Rh-S bond length is 2.3398(13) Å significantly shorter than those of 1 by ca. 0.04 Å, although DFT calculations based on the crystal structures indicated that the effective bond order of Rh-N is higher than those of Rh-S. Thermal stability examination by thermogravimetric and differential thermal analyses (TG/DTA) and IR spectroscopy indicated that the linkage isomerization of [RhIII(SCN)6]3- to [RhIII(NCS)(SCN)5]3- proceeded after melting around 174 °C. These results clearly indicate that [RhIII(NCS)(SCN)5]3- is thermodynamically more stable than [RhIII(SCN)6]3- in solid states, although further linkage isomerization hardly occurs.

Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver.

Immunosenescence refers to the development of weakened and/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although Klebsiella pneumoniae is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why K. pneumoniae is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host's intestinal immune response to K. pneumoniae varies with age. To this end, the study analyzed an in vivo K. pneumoniae infection model using aged mice, as well as an in vitro K. pneumoniae infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize K. pneumoniae, inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under K. pneumoniae infection due to decreasing intestinal mucosal macrophages; therefore, K. pneumoniae can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of K. pneumoniae from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why K. pneumoniae can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.

Excited State Engineering in Ag29 Nanocluster through Peripheral Modification with Silver(I) Complexes for Bright Near-Infrared Photoluminescence.

The optical property of an ionic metal nanocluster (NC) is affected by the ionic interaction with counter ions. Here, we report that the modification of trianionic [Ag29(BDT)12(TPP)4]3- NC (BDT: 1.3-benzenedithiol; TPP: triphenylphosphine) with silver(I) complexes led to the intense photoluminescence (PL) in the near-infrared (NIR) region. The binding of silver(I) complexes to the peripheral region of Ag29 NC is confirmed by the single-crystal X-ray diffraction (SCXRD) measurement, which is further supported by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. The change of excited-state dynamics by the binding of silver(I) complexes is discussed based on the results of a transient absorption study as well as temperature-dependent PL spectra and PL lifetime measurements. The modification of Ag29 NCs with cationic silver(I) complexes is considered to give rise to a triplet excited state responsible for the intense NIR PL. These findings also afford important insights into the origin of the PL mechanism as well as the possible light-driven motion in Ag29-based NCs.

Adherent-invasive E. coli - induced specific IgA limits pathobiont localization to the epithelial niche in the gut.

Background and aim: Adherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn's disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive. Methods: Antibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium. Results: Persistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC - epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice. Conclusion: These results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.

Long-term safety and efficacy of belimumab in Japanese patients with SLE: A 7-year open-label continuation study.

OBJECTIVES: Evaluate long-term safety, tolerability, and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). METHODS: This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE Responder Index (SRI)-4 response rate, SRI-4 components, severe SLE flare, and use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first belimumab dose received in either parent or current study through to study end. RESULTS: Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index responders. The proportion of patients with no worsening in PGA (91.2-100.0%) and no new organ damage (92.6-100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. CONCLUSIONS: Favourable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

A potential pathogenic association between periodontal disease and Crohn's disease.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn's disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

Long-term effect of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (ß = - 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (ß = - 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss.

Predictors of Long-term Outcomes in Patients With Connective Tissue Disease Associated With Pulmonary Arterial Hypertension.

BACKGROUND/OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance that can lead to right-sided heart failure. Connective tissue disease-associated PAH (CTD-PAH) often has poorer outcomes than idiopathic or hereditary PAH, suggesting the presence of non-PAH factors that could affect the prognoses. This cohort study aimed to identify prognostic factors for CTD-PAH management. METHODS: Medical records from April 1999 to November 2014 were reviewed to determine the time from treatment initiation to the occurrence of a clinically worsening event and the time elapsed until death. Data at baseline and the final assessment were used to identify prognostic factors associated with events using univariate and multivariate analyses by the stepwise Cox regression method. RESULTS: In 36 patients with CTD-PAH analyzed, the proportions with no clinically worsening events at 1, 2, and 3 years after treatment initiation were 62%, 52%, and 45%, respectively, with survival rates of 88%, 77%, and 77%, respectively. The regression model showed that reduced hemoglobin at baseline, reduced qR pattern in electrocardiogram lead V1, increased 60-minute erythrocyte sedimentation rate, and increased mean pulmonary arterial pressure at the final assessment were risk factors that were significantly associated with clinical worsening. For survival, no prognostic factor was identifiable. CONCLUSIONS: Hemodynamic and non-PAH factors, such as anemia, nutritional status, and inflammatory activity of the underlying CTD, which are not listed in the risk assessment table of PAH guidelines, should be strictly controlled to improve the prognosis of patients with CTD-PAH. A more multifactorial treatment strategy should be developed.

Syntheses and Properties of (Nitronyl nitroxide)-substituted Tri-phenylamine ortho-Bridged by Two Oxygen and Sulfur Atoms.

A nitronyl nitroxide unit (NN) was linked with a triphenylamine-based condensed polycyclic skeleton DOTT to form a radical substituted donor NN-DOTT. X-ray crystal structure analysis demonstrated a flat bowl shape of the DOTT unit. EPR spectra showed the localization of electron spin on the NN unit. Chemical oxidation of the DOTT unit produced radical-substituted radical cation salts NN-DOTT+ ⋅ SbF6 - and NN-DOTT+ ⋅ FeBr4 - that are stable under ambient conditions. The magnetic behavior of NN-DOTT+ ⋅ SbF6 - is characterized by the strong intramolecular ferromagnetic interaction between NN and DOTT+ . The X-ray structural analysis of NN-DOTT+ ⋅ FeBr4 - shows planar structure of DOTT and 1D mixed-stack column of NN-DOTT+ and FeBr4 - . Magnetic measurements established that NN-DOTT+ ⋅ FeBr4 - undergoes magnetic phase transition into a weak ferromagnet at 7 K.

Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding.

Ectodomain shedding is a post-translational modification mechanism by which the entire extracellular domain of membrane proteins is liberated through juxtamembrane processing. Because shedding rapidly and irreversibly alters the characteristics of cells, this process is properly regulated. However, the molecular mechanisms governing the propensity of membrane proteins to shedding are largely unknown. Here, we present evidence that negatively charged amino acids within the stalk region, an unstructured juxtamembrane region at which shedding occurs, contribute to shedding susceptibility. We show that two activated leukocyte cell adhesion molecule (ALCAM) protein variants produced by alternative splicing have different susceptibilities to ADAM metallopeptidase domain 17 (ADAM17)-mediated shedding. Of note, the inclusion of a stalk region encoded by a 39-bp-long alternative exon conferred shedding resistance. We found that this alternative exon encodes a large proportion of negatively charged amino acids, which we demonstrate are indispensable for conferring the shedding resistance. We also show that the introduction of negatively charged amino acids into the stalk region of shedding-susceptible ALCAM variant protein attenuates its shedding. Furthermore, we observed that negatively charged amino acids residing in the stalk region of Erb-B2 receptor tyrosine kinase 4 (ERBB4) are indispensable for its shedding resistance. Collectively, our results indicate that negatively charged amino acids within the stalk region interfere with the shedding of multiple membrane proteins. We conclude that the composition of the stalk region determines the shedding susceptibility of membrane proteins.

Moyamoya syndrome related to systemic lupus erythematosus developing during pregnancy: a case-based review.

Moyamoya syndrome (MMS) is a chronic cerebrovascular disorder characterized by occlusion or stenosis of the internal carotid arteries with the formation of abnormal collateral vascular networks. Moreover, the development of MMS, which is a distinct category from "moyamoya disease," is attributed to the underlying disease, while some cases of MMS related to systemic lupus erythematosus (SLE) have been previously reported. Herein, we present the case of a 29-year-old Japanese woman with SLE in whom intracranial hemorrhage ascribable to MMS developed during pregnancy. Craniotomy was performed to remove hematoma, and prednisolone, tacrolimus, and hydroxychloroquine were consecutively administered. She ultimately achieved remission and childbearing without the relapse of cerebrovascular event. To our knowledge, this is the first report of MMS associated with SLE in pregnancy. Through reviewing published English articles and our case, it was suggested that the pathogenesis of SLE is implicated in the development of moyamoya vasculopathy leading to cerebrovascular events. Moreover, pregnancy may affect the bleeding from the fragile collateral vessel wall.

Redox-Induced Modulation of Exchange Interaction in a High-Spin Ground-State Diradical/Triradical System.

A triplet ground-state diradical molecule, bis(nitronyl nitroxide)-substituted diphenyldihydrophenazine (1.. ), that can be converted into a one-electron oxidized species, 1…+ , in the quartet ground state has been developed. Surprisingly, these species, 1.. and 1…+ , can be used under ambient conditions because they are reasonably stable under aerobic conditions, even in solution. The temperature-dependent magnetic susceptibilities reveal that 1.. and 1…+ are in the triplet state, with a weak exchange interaction (J1 /kB = +3.1 K) and quartet ground state with a strong exchange interaction (J2 /kB = +160 K), respectively. The interconversion between the neutral and one-electron oxidized species can be realized through electrochemical reactions. Significantly different absorption bands in the near-IR region newly appeared in the electronic spectra acquired during electrochemical oxidation/reduction.

Effects of self-guided e-counseling on health behaviors and blood pressure: Results of a randomized trial.

OBJECTIVE: 1) Evaluate the efficacy of e-Counseling vs. Control to promote lifestyle behaviors at 4 and 12-month follow-ups, 2) examine whether these behaviors changes were associated with lower blood pressure (BP), and Framingham Risk Index (FRI) at 12-month. METHODS: Hypertensive patients (n = 264) were randomized to the e-Counseling or the Control group. Primary trial outcome was BP and secondary outcomes included exercise and diet behaviors. This study presented the results of secondary outcomes. Linear mixed models evaluated treatment effects at 4 and 12-month. Treatment-by-sex exploratory analyses were conducted if no main treatment effect was observed. RESULTS: Daily steps significantly improved in e-Counseling vs. Controls at 12-month. Urinary sodium at 12-month did not significantly differ between the groups, but treatment-by-sex analysis showed that e-Counseling females lowered urinary sodium relative to Controls at 12 months. Improvements in steps and dietary sodium were significantly associated with improvements in BP and FRI at 12-month. CONCLUSION: This hypertension e-Counseling protocol can promote long-term lifestyle behavior changes. Adherence to the lifestyle behavior change was associated with BP and FRI reduction at 12-month. PRACTICE IMPLICATIONS: The hypertension e-counseling protocol has the potential to improve hypertension care and intervention reach.

Creation and stabilisation of tuneable open metal sites in thiocyanato-bridged heterometallic coordination polymers to be used as heterogeneous catalysts.

A series of thiocyanato-bridged heterometallic coordination polymers with a 3D reticular network have been synthesised by the reaction of [PtIV(SCN)6]2- with MII ions to form {MII[PtIV(SCN)6]}n and {[MII(CH3OH)2][PtIV(SCN)6]}n (MII = MnII, FeII, CoII, NiII or CuII) in water and methanol, respectively. Single-crystal X-ray analyses revealed the absence of open metal sites in {MII[PtIV(SCN)6]}ns and the formation of potential open metal sites at the MII ions of {[MII(CH3OH)2][PtIV(SCN)6]}ns by the coordination of methanol. One of the two coordinating methanol molecules in {[CoII(CH3OH)2][PtIV(SCN)6]}n was replaced with pyridine to stabilise the open metal sites, because the methanol molecules are too labile to maintain open metal sites in water. The heterogeneous catalysis of coordination polymers with and without open metal sites was examined for organophosphate hydrolysis and photocatalytic water oxidation to clarify the requisites for heterogeneous catalysts.

Transient multifocal genomic crisis creating chromothriptic and non-chromothriptic rearrangements in prezygotic testicular germ cells.

BACKGROUND: The co-occurrence of multiple de novo copy number variations (CNVs) is a rare phenomenon in the human genome. Recently, an "organismal CNV mutator phenotype" has been reported to result in transient genomic instability introducing multiple de novo CNVs in primary oocytes and early-stage zygotes. These findings opened a new area of human genome research. METHODS: We performed genome-wide copy number analysis for ~ 2100 individuals with various congenital defects. Furthermore, extensive molecular analyses, including synthetic long-read whole-genome sequencing and haplotype-phasing, were carried out for an individual with multiple de novo CNVs. RESULTS: A boy was found to have de novo rearrangements on five chromosomes. The rearrangements comprised simple duplication and inversion as well as chaotic changes, all of which affected paternally derived chromosomes. Postzygotic genomic instability was ruled out. The duplicated regions on 6q and 13q contained both diallelic and triallelic loci, indicating that the genomic rearrangements were initially created during premeiotic mitosis and subsequently modified by physiological cross-over during meiosis I. Breakpoints of the rearrangements were indicative of non-homologous end joining, replication-based errors, and/or chromothripsis. The mutagenic event was independent of specific local DNA motifs or de novo point mutations, but may be driven by spermatogenesis-specific factors. CONCLUSIONS: These results indicate that during spermatogenesis, a transient multifocal genomic crisis can introduce several chromothriptic and non-chromothriptic changes into the genome. These findings broaden the concept of the "organismal CNV mutator phenotype". This study provides insights into mechanisms for altering the global chromosomal architecture of human embryos.

[A case of angioedema with dysarthria mimicking transient ischemic attack].

An 85-year-old woman was transported to our emergency room by ambulance with a complaint of slurred speech. Neurological examination revealed dysarthria only. We considered that lingual edema identified on physical examination might have influenced dysarthria. However, we were unable to perform sufficient evaluation, since she could not open her mouth widely or push the tongue out beyond the lips. We considered the incidence of acute cerebrovascular disease because of the acute onset, and performed emergency brain MRI. Imaging revealed that although no abnormality was present in the brain parenchyma, edema of the tongue and soft palate was evident on T2-weighted sagittal imaging. We confirmed the dysarthria was caused by tongue edema due to angioedema. In addition, we diagnosed angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, because ACEI had been started 2 months earlier as pharmacotherapy for hypertension. Tongue swelling due to angioedema should be considered when examining patients with dysarthria.