Effects of childhood experiences of parental attitude, depressive rumination, and sleep disturbances on adulthood depressive symptoms.

Aim: Various factors are thought to be involved in the development of depression, but the mechanisms are not yet clear. Although several reports have demonstrated that parental attitude experienced in childhood, depressive rumination, and sleep disturbances each influence depressive symptoms, and the association between two of these four variables, to our knowledge, no reports to date have investigated the association among the four variables. Methods: A questionnaire survey was administered to 576 adults who agreed to participate in this study between April 2017 and April 2018. Questionnaires assessed parental attitudes experienced in childhood, depressive rumination, sleep disturbances, and depressive symptoms in adulthood. The associations among the four variables were tested by structural equation modeling. Results: Regarding the direct effects, the parental attitude of "care" had a negative influence on depressive rumination and depressive symptoms, whereas "overprotection" had a positive influence on depressive rumination. Depressive rumination had a positive influence on sleep disturbance and depressive symptoms, whereas sleep disturbances had a positive influence on depressive symptoms. Regarding indirect effects, depressive rumination mediated the association between parental attitudes and sleep disturbances or depressive symptoms. Furthermore, sleep disturbances mediated the association between depressive rumination and depressive symptoms. Care and overprotection showed opposite effects. The goodness of fit of this model was high. Conclusion: The results of this study demonstrated that there were associations among the four variables. Clinical assessment and intervention of depressive rumination and sleep disturbances that are closely associated with previous parental attitudes may lead to an improvement of depressive symptoms.

Effects of Peer Victimization in Childhood and Trait Anxiety on Job Stress in Adulthood.

Background: The experience of peer victimization in childhood increases the risk of developing anxiety disorders and depression, risk of suicide, as well as sensitivity to stress, in adulthood. Various personality traits are known to be associated with these effects. However, the influence of trait anxiety on job stress has not yet been reported. In the present study, we tested the hypothesis that the experience of peer victimization in childhood and trait anxiety influence job stress in adulthood. Methods: A questionnaire survey, including State-Trait Anxiety Inventory, Childhood Victimization Rating Scale, and Brief Job Stress Questionnaire, was administered to 566 adult workers. The interrelationship between multiple variables was analyzed by multiple regression analysis and path analysis. Results: In the path model, childhood peer victimization had a positive direct effect on trait anxiety and the psychological and physical stress response (PPSR). Trait anxiety had a positive direct effect on job stressors and PPSR, and job stressors had a positive direct effect on PPSR. Regarding indirect effects, childhood peer victimization had a significant adverse effect on job stressors and PPSR via trait anxiety. Conclusion: Our results showed that childhood peer victimization has a negative impact on job stress in adulthood, which is influenced by trait anxiety. Interventions to address peer victimization in childhood and trait anxiety may reduce job stress in adulthood, and thus contribute to improved occupational mental health and productivity in the workplace.

NMR Studies of Genomic RNA in 3' Untranslated Region Unveil Pseudoknot Structure that Initiates Viral RNA Replication in SARS-CoV-2.

In the 3' untranslated region of the SARS-CoV-2 virus RNA genome, genomic RNA replication is initiated in the highly conserved region called 3'PK, containing three stem structures (P1pk, P2, and P5). According to one proposed mechanism, P1pk and distal P2 stems switch their structure to a pseudoknot through base-pairing, thereby initiating transcription by recruiting RNA-dependent RNA polymerase complexed with nonstructural proteins (nsp)7 and nsp8. However, experimental evidence of pseudoknot formation or structural switching is unavailable. Using SARS-CoV-2 3'PK fragments, we show that 3'PK adopted stem-loop and pseudoknot forms in a mutually exclusive manner. When P1pk and P2 formed a pseudoknot, the P5 stem, which includes a sequence at the 3' end, exited from the stem-loop structure and opened up. Interaction with the nsp7/nsp8 complex destabilized the stem-loop form but did not alter the pseudoknot form. These results suggest that the interaction between the pseudoknot and nsp7/nsp8 complex transformed the 3' end of viral genomic RNA into single-stranded RNA ready for synthesis, presenting the unique pseudoknot structure as a potential pharmacological target.

Interpersonal Sensitivity as a Mediator of the Effect of Childhood Parenting Quality on Depressive Symptoms.

ABSTRACT: The aim of this study was to analyze whether interpersonal sensitivity mediates the effect of qualitative parenting characteristics experienced during childhood on the appraisal of life experiences and depression severity during adulthood in adult community volunteers. A total of 404 Japanese adult volunteers answered the following four self-report questionnaires: Parental Bonding Instrument, Interpersonal Sensitivity Measure, Life Experiences Survey, and Patient Health Questionnaire-9. Structural equation modeling was performed to analyze whether childhood parenting quality increases depressive symptom severity through interpersonal sensitivity, which then affects the appraisal of recent life events. In the two structural equation models, inadequate care and excessive overprotection received during childhood were associated with the negative evaluation of life experiences and depression severity in adulthood through high interpersonal sensitivity. Our findings indicate interpersonal sensitivity as a mediator of the effect of inadequate care and excessive overprotection experienced in childhood on the negative evaluation of life experiences and depression severity in adulthood.

Enzymatic and selective production of alkyl α-d-glucopyranosides by the α-glucosyl transfer enzyme derived from Xanthomonas campestris WU-9701.

Several alkyl glucosides exhibit various bioactivities. 1-Octyl ß-d-glucopyranoside produced by organic synthesis is used as a nonionic surfactant. However, no convenient method has been developed for the selective production of alkyl α-glucosides (α-AGs), such as 1-octyl α-d-glucopyranoside (α-OG). Therefore, we developed a simple method for selective production of α-AGs using the glucosyl transfer enzyme XgtA, (E.C. 3.2.1.20), derived from Xanthomonas campestris WU-9701. When 0.80 M alkyl alcohol and 2.5 units XgtA were incubated in 2.0 mL of 30 mM HEPES-NaOH buffer (pH 8.0) containing 1.2 M maltose at 45 °C, a specific α-AG corresponding to each alkyl alcohol (C2-C10) was detected. Under the standard conditions, we examined the selective production of α-OG from 1-octanol and maltose using XgtA. The reaction product was isolated and identified as α-OG via 1H nuclear magnetic resonance and nuclear overhauser effect spectroscopy analyses. No other glucosylated products, such as maltotriose, were detected in the reaction mixture. Under the standard conditions at 45 °C for 96 h, 243 mM α-OG (71 g/L) was produced in one batch production. Moreover, the addition of glucose isomerase to the reaction mixture decreased the concentration of glucose released via the reaction and increased the amount of α-OG produced; 359 mM α-OG (105 g/L) was maximally produced at 96 h. In conclusion, this study demonstrates the selective production of α-AGs using a simple enzymatic reaction, and XgtA has the potential to selectively produce various α-AGs.

Trait anxiety and depressive rumination mediate the effect of perceived childhood rearing on adulthood presenteeism.

AIM: Productivity loss in the workplace due to physical or mental health problems, which is called presenteeism, leads to large financial losses. Personal and work environment factors, as well as physical and mental illnesses are associated with presenteeism, but the detailed underlying mechanism remains unclear. In this study, we analyzed the effects of perceived childhood rearing on the presenteeism of adult workers, and the mediating effects of trait anxiety and depressive rumination. METHODS: In 2017 and 2018, a cross-sectional paper-based survey was conducted, and written consent from 447 adult workers was obtained. Demographic information and results from the Parental Bonding Instrument, trait anxiety of State-Trait Anxiety Inventory Form Y, Ruminative Responses Scale, and Work Limitations Questionnaire were surveyed. Multiple regression analyses and structural equation modeling were conducted. RESULTS: The low perceived quality of rearing from parents in childhood, i.e., low care and high overprotection, indirectly worsened current presenteeism via trait anxiety and depressive rumination. Presenteeism was directly worsened by trait anxiety and depressive rumination, and the low perceived quality of rearing from parents directly affected trait anxiety and depressive rumination, and trait anxiety affected depressive rumination. CONCLUSION: The results of this study clarified the long-term influences of the low perceived quality of rearing experienced in childhood on adulthood presenteeism via trait anxiety and depressive rumination. Therefore, assessing the quality of childhood rearing, trait anxiety, and depressive rumination of individuals may help to elucidate the causes of presenteeism in the workplace, and how to manage it effectively.

Depressive rumination and trait anxiety mediate the effects of childhood victimization on adulthood depressive symptoms in adult volunteers.

BACKGROUND: Prior studies have reported that childhood victimization experiences substantially augment the risk of depression and suicide in adulthood. Several of our previous studies suggested that childhood experiences of victimization interact with the quality of parenting experienced in childhood, childhood experiences of abuse, neuroticism, and other factors to influence depressive symptoms in adulthood. In this study, it was hypothesized that "childhood victimization" worsens "trait anxiety" and "depressive rumination", and that "trait anxiety" and "depressive rumination" are mediators that worsen "depressive symptoms in adulthood". SUBJECTS AND METHODS: The following self-administered questionnaires were completed by 576 adult volunteers: Patient Health Questionnaire-9, State-Trait Anxiety Inventory form Y, Ruminative Responses Scale, and Childhood Victimization Rating Scale. Statistical analyses were performed by Pearson correlation coefficient analysis, t-test, multiple regression analysis, path analysis, and covariance structure analysis. RESULTS: Path analysis demonstrated that the direct effect was statistically significant for the paths from childhood victimization to trait anxiety, depressive rumination, and depressive symptom severity. Moreover, the indirect effect of childhood victimization on depressive rumination mediated by trait anxiety was statistically significant. The indirect effects of childhood victimization on depressive symptom severity mediated by trait anxiety and depressive rumination were statistically significant. Furthermore, the indirect effect of childhood victimization on depressive symptom severity mediated by both trait anxiety and depressive rumination was statistically significant. CONCLUSIONS: We found that childhood victimization directly and adversely influenced each of the above factors, and indirectly worsened adulthood depressive symptoms with trait anxiety and depressive ruminations as mediating factors. The present study is the first to clarify these mediation effects. Therefore, the results of this study suggest the importance of preventing childhood victimization and the importance of identifying and addressing childhood victimization in patients with clinical depression.

Groin and anterolateral thigh flaps for hemiglossectomy reconstruction: A comparison based on Japanese speech intelligibility.

OBJECTIVE: The differences in speech function between groin flap reconstruction and anterolateral thigh (ALT) flap reconstruction after hemiglossectomy have not been clarified to date. This study aimed to compare Japanese speech intelligibility after hemiglossectomy reconstruction using groin and ALT flaps of similar thickness. METHODS: Data of patients who underwent hemiglossectomy reconstruction with groin or ALT flaps between April 2010 and March 2020 were collected from the medical chart database. The ALT flap was the first choice for hemiglossectomy reconstruction, and a groin flap was used when the ALT flap was >10 mm. Cases in which speech intelligibility assessments based on Hirose's 10-point scoring system, the TKR speech test, and the Japanese speech intelligibility test for 100 monosyllables were performed after 6 months postoperatively were extracted. The per-patient scores for each assessment were initially compared between the two flap groups. Then, the results of the Japanese speech intelligibility test for 100 monosyllables were reanalyzed on a syllable-by-syllable basis. RESULTS: Among the 44 hemiglossectomy patients who underwent free-flap reconstruction during the study period, 14 (seven each in the groin flap and ALT flap groups) underwent all three conventional speech intelligibility assessments after 6 months postoperatively. The two groups showed no significant difference in postoperative speech intelligibility in any of the three patient assessment methods. However, in intergroup comparisons based on per-syllable accuracy for each of the 100 monosyllables, the groin flap group showed 19 syllables with a significantly higher accuracy, whereas the ALT flap group showed one such syllable. In particular, five out of the six alveolar consonants (/t/ and /d/) were more accurately articulated in the groin flap group. Per-syllable accuracy was significantly higher in the groin flap group (74.6% vs. 66.7%; 95% confidence interval: 4.6-11.1, p < 0.001). CONCLUSION: In patients undergoing hemiglossectomy reconstruction, our new analysis method, which compared intelligibility by syllables, showed that the groin flap yielded higher speech intelligibility than the ALT flap. This difference was evident at all four articulation points involving the tongue, whereas there was no significant difference at the two articulation points without tongue involvement.

Interpersonal sensitivity mediates the effects of perceived parenting styles on state anxiety and negative assessment of life events in adult volunteers from the community.

Aim: The association of parenting experiences in childhood with anxiety symptoms in adulthood has yet to be clarified. We hypothesized that interpersonal sensitivity (IPS) mediates the impacts of parenting experiences in childhood on anxiety symptoms and negative assessment of life events in adulthood. Methods: An observational cross-sectional study was carried out from January 2014 to August 2014 on 853 adults. Participants provided their demographic information and answered the following four self-administered questionnaires: Parental Bonding Instrument (PBI), Interpersonal Sensitivity Measure (IPSM), Life Experiences Survey (LES), and State-Trait Anxiety Inventory Form Y (STAI-Y). The data of a total of 404 participants who agreed to take part in this study were analyzed. Results: Multiple regression analysis with the State Anxiety subscale of STAI-Y as the dependent variable identified the following five out of the 15 independent variables as being statistically significant: IPSM total, LES positive and negative, PBI paternal overprotection, and employment status. This model explains 17.8% of the State Anxiety subscale score. In the structural equation models, the Care subscale showed significant indirect negative effects on State Anxiety subscale and LES negative score through a decrease in IPSM total score (ß = -0.061 and -0.042, respectively). The former indirect effect accounted for 31.6%, and the latter accounted for 56.8% of the total effects. In contrast, Overprotection subscale had opposite effects to Care subscale. Conclusion: These results suggest that parenting experiences in childhood are related to adult anxiety symptoms and the negative assessment of life events indirectly through IPS.

Association between psychotropics use and occurrence of falls in hospitalized patients: A matched case-control study.

Aim: Understanding the appropriate prescription of psychotropics for hospitalized patients in terms of preventing falls is an important issue. The aim of this study was to assess the associations between the occurrence of falls and the use of various individual psychotropics in hospitalized patients. Methods: A retrospective matched case-control study was conducted on adult patients admitted to every department of Tokyo Medical University Hospital, with the outcome being in-hospital falls. A total of 447 hospitalized patients who had had in-hospital falls at some point in their hospitalization between January 2016 and December 2016 were included as cases. A total of 447 hospitalized patients who did not have in-hospital falls, and were individually matched to the cases by sex, age, and clinical department, were included as controls. All data were extracted from electronic medical records. Conditional logistic regression analyses were conducted to assess the association between the exposure to 16 psychotropic medications and the occurrence of in-hospital falls. The multivariable logistic regression model adjusted sex, age, clinical department, body mass index, fall risk score on the fall risk assessment measure, and use of psychotropic medications. Results: The multivariable conditional logistic regression model showed a significant association between the use of risperidone (odds ratio [OR] = 3.730; 95% confidence interval [CI] = 1.229-11.325) and flunitrazepam (OR = 4.120; 95% CI = 1.105-15.364) and an increased OR of falls among hospitalized patients. Conclusion: The use of risperidone and flunitrazepam were identified as risk factors for falls among hospitalized patients.

High-Field Nuclear Magnetic Resonance Studies Reveal New Structural Landscape of Sulfur-Vulcanized Natural Rubber.

Despite intensive research efforts over the past 3 decades, the structural analysis of sulfur-vulcanized natural rubber (NR) remains challenging owing to the complexity and low population of its sulfur moieties. Herein, solid vulcanized NR samples and NR samples reacted with sulfur and other reactants in an organic solvent were analyzed by solid-state NMR with fast magic-angle spinning and solution NMR, respectively. The present high-field two-dimensional NMR analysis revealed six novel sulfur moieties in these samples, including cyclic sulfides, cyclic di/polysulfides, and crosslinked structures with a vinylidene group. While previous studies reported a variety of sulfur-crosslinked structures in NR, our analysis identified only two dominant types of crosslinked structures that matched those reported previously. Our NMR assignments for the crosslinked structures were inconsistent to a large extent with those presented in the previous studies; thus, in the current work, the crosslinked structures were reassigned using the new data. Based on quantitative NMR analysis, this study also provides the first tangible evidence that cyclic rather than crosslinked sulfides can be the dominant sulfur moieties in vulcanized NR. These results may drastically alter the previously established structural landscape of sulfur-vulcanized NR.

Selective and high-yield production of ethyl α-d-glucopyranoside by the α-glucosyl transfer enzyme of Xanthomonas campestris WU-9701 and glucose isomerase.

Ethyl α-d-glucopyranoside (α-EG) is detected in sake (Japanese rice wine), that has moisturizing and skin conditioning effects. The production of α-EG by fermentation or enzymatic synthesis to date generates unwanted by-products such as maltooligosaccharides and/or organic acids. In this study, we employed a reaction involving selective α-glucosylation of ethanol by the α-glucosyl transfer enzyme (XgtA) of Xanthomonas campestris WU-9701. Under standard conditions, when 0.80 M ethanol and 1.2 M maltose were used as substrates with XgtA (2.5 units) and incubated in 30 mM HEPES-NaOH buffer (pH 8.0) at 45°C, only one form of ethyl glucopyranoside was selectively obtained as a product. The isolated product was identified as ethyl α-d-glucopyranoside by 1H NMR, 1H-1H COSY, and NOESY analyses. In the reaction mixture, other glucosylated products such as maltotriose and ethylmaltoside were not detected. Under optimum conditions, 180 mM (37.5 g/L) α-EG was produced in one batch production for 80 h. Further, the reaction rate of α-EG production decreased with an increase in glucose, especially more than 500 mM. In contrast, the addition of glucose isomerase decreased the concentration of glucose and was useful for maintaining a glucose concentration of less than 500 mM in the reaction mixture. Thus, owing to the enzymatic reaction with XgtA and glucose isomerase, as much as 260 mM (54.1 g/L) α-EG was produced in one batch production for 100 h. Altogether, this study reports the highest concentration of α-EG produced by enzymatic reaction.

Victimization in Childhood Influences Presenteeism in Adulthood via Mediation by Neuroticism and Perceived Job Stressors.

BACKGROUND: Victimization in childhood profoundly influences the mental health of individuals in adulthood, causing depression, anxiety disorder, suicidality, and self-harm, which leads to productivity loss in the workplace, ie, presenteeism. However, the specific effects of victimization on presenteeism remain unclear. We hypothesized that victimization affects the presenteeism of workers through neuroticism and perceived job stressors and analyzed the association among these factors by path analysis. METHODS: A questionnaire survey, including demographic and clinical data, Japanese versions of victimization scale in childhood, Brief Job Stress Questionnaire, and Work Limitations Questionnaire (WLQ), was administered to 443 adult volunteers between April 2017 and April 2018 in Tokyo, Japan. Multiple variables were analyzed by multiple regression analysis and path analysis. The Institutional Review Board of Tokyo Medical University approved this study. RESULTS: Path analysis demonstrated that neuroticism and perceived job stressors had direct effects on presenteeism in the WLQ. Victimization indirectly increased presenteeism via neuroticism and its subsequent effects on perceived job stressors. This model accounted for 18% of the variability of presenteeism (R 2 = 0.180). LIMITATIONS: There may be possible recall bias owing to the self-administration of the questionnaire. In addition, this study had a cross-sectional design, and hence the causal associations among variables should be validated in a prospective study. CONCLUSION: The present study indicates that the experience of victimization in childhood is a risk factor of adulthood presenteeism, and this effect is mediated by neuroticism and adverse effects on job stressors. These results suggest that multiple factors, including childhood victimization, neuroticism, and job stressors, should be considered when assessing and preventing presenteeism.

Complex effects of childhood abuse, subjective social status, and trait anxiety on presenteeism in adult volunteers from the community.

Background: Presenteeism, which is reduced productivity levels owing to physical or mental problems, causes substantial economic loss. It is known to be associated with personal and working environment factors, but the mechanism has not been fully clarified to date. Therefore, we analyzed the effects of childhood abuse on presenteeism of general adult workers, and the mediating effects of subjective social status and trait anxiety. Methods: From 2017 to 2018, a cross-sectional survey was performed, and 469 adult workers provided written consent. Demographic information, and results from the Child Abuse and Trauma Scale, Subjective Social Status, State-Trait Anxiety Inventory form Y, and Work Limitations Questionnaire were investigated. Multiple linear regression and path analyzes were performed. Results: Childhood abuse indirectly affected current presenteeism via subjective social status and trait anxiety. Presenteeism was directly affected only by trait anxiety, childhood abuse directly affected subjective social status and trait anxiety, and subjective social status affected trait anxiety. Conclusion: This study clarified the long-term effects of childhood abuse on presenteeism in adulthood via trait anxiety. Therefore, assessing childhood abuse, subjective social status, and trait anxiety may help to elucidate the mechanism of workplace presenteeism and develop measures against it.

Efficient solvent suppression with adiabatic inversion for 1H-detected solid-state NMR.

This study introduces a conceptually new solvent suppression scheme with adiabatic inversion pulses for 1H-detected multidimensional solid-state NMR (SSNMR) of biomolecules and other systems, which is termed "Solvent suppression of Liquid signal with Adiabatic Pulse" (SLAP). 1H-detected 2D 13C/1H SSNMR data of uniformly 13C- and 15N-labeled GB1 sample using ultra-fast magic angle spinning at a spinning rate of 60 kHz demonstrated that the SLAP scheme showed up to 3.5-fold better solvent suppression performance over a traditional solvent-suppression scheme for SSNMR, MISSISSIPPI (Zhou and Rienstra, J Magn Reson 192:167-172, 2008) with 2/3 of the average RF power.

Victimization in Childhood Mediates the Association Between Parenting Quality, Stressful Life Events, and Depression in Adulthood.

BACKGROUND: Various stressors during childhood and adulthood, such as experiencing poor parenting, abuse, and harassment, have long-lasting effects on depression. The long-term effects of childhood stressors, such as childhood abuse and inappropriate parenting experiences, on adult depression are mediated by personality traits. In the present study, we hypothesized that parental bonding in childhood influences adulthood depression, and that this association is mediated by childhood victimization experiences and negative life event evaluations in adulthood. To test this hypothesis, multiple regression analysis and structural equation modeling were performed. METHODS: A questionnaire survey, including Patient Health Questionnaire-9, victimization scale in childhood, Parental Bonding Instrument (PBI), and Life Experiences Survey was administered to 449 general adult volunteers (age: 41.1 ± 11.7 years; 196 men and 253 women). Multiple variables were analyzed by multiple regression analysis and structural equation modeling. RESULTS: Multiple regression analysis demonstrated that victimization experiences in childhood affect adulthood depression independently of several other factors. Structural equation modeling showed that the "parental care" subscale of the PBI decreased adulthood depression directly, as well as indirectly through its effects on victimization experiences in childhood and negative life events. On the other hand, the "parental overprotection" subscale of the PBI increased adulthood depression directly, as well as indirectly through its effects on the experience of victimization in childhood and negative life events. CONCLUSION: The present study indicates that the experience of victimization in childhood is a risk factor of adulthood depression. Furthermore, we found that parenting quality experienced in childhood influences adulthood depression, and that these effects are mediated by the experiences of victimization in childhood and negative life events in adulthood.

Sensitivity-Enhanced Solid-State NMR Detection of Structural Differences and Unique Polymorphs in Pico- to Nanomolar Amounts of Brain-Derived and Synthetic 42-Residue Amyloid-ß Fibrils.

Amyloid-ß (Aß) fibrils in neuritic plaques are a hallmark of Alzheimer's disease (AD). Since the 42-residue Aß (Aß42) fibril is the most pathogenic among different Aß species, its structural characterization is crucial to our understanding of AD. While several polymorphs have been reported for Aß40, previous studies of Aß42 fibrils prepared at neutral pH detected essentially only one structure, with an S-shaped ß-sheet arrangement (e.g., Xiao et al. Nat. Struct. Mol. Biol. 2015, 22, 499). Herein, we demonstrate the feasibility of characterizing the structure of trace amounts of brain-derived and synthetic amyloid fibrils by sensitivity-enhanced 1H-detected solid-state NMR (SSNMR) under ultrafast magic angle spinning. By taking advantage of the high sensitivity of this technique, we first demonstrate its applicability for the high-throughput screening of trace amounts of selectively 13C- and 15N-labeled Aß42 fibril prepared with ∼0.01% patient-derived amyloid (ca. 4 pmol) as a seed. The comparison of 2D 13C/1H SSNMR data revealed marked structural differences between AD-derived Aß42 (∼40 nmol or ∼200 µg) and synthetic fibrils in less than 10 min, confirming the feasibility of assessing the fibril structure from ∼1 pmol of brain amyloid seed in ∼2.5 h. We also present the first structural characterization of synthetic fully protonated Aß42 fibril by 1H-detected 3D and 4D SSNMR. With procedures assisted by automated assignments, main-chain resonance assignments were completed for trace amounts (∼42 nmol) of a fully protonated amyloid fibril in the 1H-detection approach. The results suggest that this Aß42 fibril exhibits a novel fold or polymorph structure.

Atomic-level differences between brain parenchymal- and cerebrovascular-seeded Aß fibrils.

Alzheimer's disease is characterized by neuritic plaques, the main protein components of which are ß-amyloid (Aß) peptides deposited as ß-sheet-rich amyloid fibrils. Cerebral Amyloid Angiopathy (CAA) consists of cerebrovascular deposits of Aß peptides; it usually accompanies Alzheimer's disease, though it sometimes occurs in the absence of neuritic plaques, as AD also occurs without accompanying CAA. Although neuritic plaques and vascular deposits have similar protein compositions, one of the characteristic features of amyloids is polymorphism, i.e., the ability of a single pure peptide to adopt multiple conformations in fibrils, depending on fibrillization conditions. For this reason, we asked whether the Aß fibrils in neuritic plaques differed structurally from those in cerebral blood vessels. To address this question, we used seeding techniques, starting with amyloid-enriched material from either brain parenchyma or cerebral blood vessels (using meninges as the source). These amyloid-enriched preparations were then added to fresh, disaggregated solutions of Aß to make replicate fibrils, as described elsewhere. Such fibrils were then studied by solid-state NMR, fiber X-ray diffraction, and other biophysical techniques. We observed chemical shift differences between parenchymal vs. vascular-seeded replicate fibrils in select sites (in particular, Ala2, Phe4, Val12, and Gln15 side chains) in two-dimensional 13C-13C correlation solid-state NMR spectra, strongly indicating structural differences at these sites. X-ray diffraction studies also indicated that vascular-seeded fibrils displayed greater order than parenchyma-seeded fibrils in the "side-chain dimension" (~ 10 Å reflection), though the "hydrogen-bond dimensions" (~ 5 Å reflection) were alike. These results indicate that the different nucleation conditions at two sites in the brain, parenchyma and blood vessels, affect the fibril products that get formed at each site, possibly leading to distinct pathophysiological outcomes.

Utility of the evaluation of blood flow of remnant esophagus with indocyanine green in esophagectomy with jejunum reconstruction: Case series.

BACKGROUND: Pedicled jejunal flap can be utilized with various tips for esophageal reconstruction in patients with a history of gastrectomy or those who have undergone synchronous esophagogastrectomy. However, the rate of anastomosis leakage is high; therefore, we considered the evaluation of blood flow of the remnant esophagus with indocyanine green in setting the anastomosis site. METHODS: Fifty patients who underwent radical esophagectomy with pedicled jejunal flap between January 2011 and June 2020 were identified. From June 2019, blood flow in the pedicled jejunum and remnant esophagus were evaluated to set the anastomosis site of the latter. Usually, the second and third jejunal vessels are transected, and if the jejunal flap cannot reach to the anastomosis point, we actively transect the marginal vessels to stretch the jejunal flap. Microvascular anastomosis between the jejunal branches and the internal thoracic vessels is usually made, and the anastomosis site is set at the well-stained part of the esophagus. RESULTS: Overall, 39 patients underwent the procedure before June 2019 (Group A), and 11 patients underwent the procedure since June 2019 (Group B). No significant difference was found in the patients' background, type of preoperative therapy, presence or absence of ligation of marginal vessels and two-stage operation between the groups. Group A had 16 cases of anastomosis leakage; B had only 1 case (p < 0.05). There were no cases of pedicled jejunum graft necrosis. CONCLUSION: Assessing remnant esophageal perfusion by indocyanine green imaging in pedicled jejunum reconstruction resulted in a lower anastomotic leak rate.

Decoherence optimized tilted-angle cross polarization: A novel concept for sensitivity-enhanced solid-state NMR using ultra-fast magic angle spinning.

Ultra-fast magic-angle spinning (UFMAS) at a MAS rate (ωR/2π) of 60 kHz or higher has dramatically improved the resolution and sensitivity of solid-state NMR (SSNMR). However, limited polarization transfer efficiency using cross-polarization (CP) between 1H and rare spins such as 13C still restricts the sensitivity and multi-dimensional applications of SSNMR using UFMAS. We propose a novel approach, which we call decoherence-optimized tilted-angle CP (DOTA CP), to improve CP efficiency with prolonged lifetime of 1H coherence in the spin-locked condition and efficient band-selective polarization transfer by incorporating off-resonance irradiation to 1H spins. 13C CP-MAS at ωR/2π of 70-90 kHz suggested that DOTA CP notably outperformed traditional adiabatic CP, a de-facto-standard CP scheme over the past decade, in sensitivity for the aliphatic-region spectra of 13C-labeled GB1 protein and N-formyl-Met-Leu-Phe samples by up to 1.4- and 1.2-fold, respectively. 1H-detected 2D 1H/13C SSNMR for the GB1 sample indicated the effectiveness of this approach in various multidimensional applications.