Publications by authors named "Naoki Hayashi"

239 Publications

Evaluation of radiophotoluminescent glass dosimeter response for therapeutic spot scanning proton beam: suggestion of linear energy transfer-based correction.

J Appl Clin Med Phys 2021 Aug 2. Epub 2021 Aug 2.

Faculty of Radiological Technology, School of Health Sciences, Fujita Health University, Toyoake, Japan.

A radiophotoluminescent glass dosimeter (RGD) is used for a postal audit of a photon beam because of its various excellent characteristics. However, it has not been used for scanning proton beams because its response characteristics have not been verified. In this study, the response of RGD to scanning protons was investigated to develop a dosimetry protocol using the linear energy transfer (LET)-based correction factor. The responses of RGD to four maximum-range-energy-pattern proton beams were verified by comparing it with ionization chamber (IC) dosimetry. The LET at each measurement depth was calculated via Monte Carlo (MC) simulation. The LET correction factor ( ) was the ratio between the uncorrected RGD dose ( ) and the IC dose at each measurement depth. can be represented as a function of LET using the following equation: . showed a linear under-response with increasing LET, and the maximum dose difference between the IC dose and was 15.2% at an LET of 6.07 keV/μm. The LET-based correction dose ( ) conformed within 3.6% of the IC dose. The mean dose difference (±SD) of and was -2.5 ± 6.9% and 0.0 ± 1.6%, respectively. To achieve accurate dose verification for scanning proton beams using RGD, we derived a linear regression equation based on LET. The results show that with appropriate LET correction, RGD can be used for dose verification of scanning proton beams.
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http://dx.doi.org/10.1002/acm2.13378DOI Listing
August 2021

Dosimetric effects of quality assurance-related setup errors in passive proton therapy for prostate cancer with and without a hydrogel spacer.

Radiol Phys Technol 2021 Jul 27. Epub 2021 Jul 27.

Faculty of Radiological Technology, School of Health Sciences, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.

The purpose of this study was to evaluate the effect of quality assurance (QA)-related setup errors in passive proton therapy for prostate cancer with and without a hydrogel spacer. We used 20 typical computed tomography (CT) images of prostate cancer: 10 patients with and 10 patients without spacers. The following 12 model errors were assumed: output error ± 2%, range error ± 1 mm, setup error ± 1 mm for three directions, and multileaf collimator (MLC) position error ± 1 mm. We created verification plans with model errors and compared the prostate-rectal (PR) distance and dose indices with and without the spacer. The mean PR distance at the isocenter was 1.1 ± 1.3 mm without the spacer and 12.9 ± 2.9 mm with the spacer (P < 0.001). The mean rectum V, V, and V in the original plan were 2.3%, 4.1%, and 12.1% without the spacer and 0.1%, 0.4%, and 3.3% with the spacer (P = 0.0011, < 0.001, and < 0.001). The effects of the range and lateral setup errors were small; however, the effects of the vertical/long setup and MLC error were significant in the cases without the spacer. The means of the maximum absolute change from original plans across all scenarios in the rectum V, V, and V were 1.3%, 1.5%, and 2.3% without the spacer, and 0.2%, 0.4%, and 1.3% with the spacer (P < 0.001, < 0.001, and = 0.0019). This study indicated that spacer injections were also effective in reducing the change in the rectal dose due to setup errors.
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http://dx.doi.org/10.1007/s12194-021-00632-4DOI Listing
July 2021

Design of synthetic polymer nanoparticles that inhibit glucose absorption from the intestine.

Biochem Biophys Res Commun 2021 Jul 15;561:1-6. Epub 2021 May 15.

Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8526, Japan.

Synthetic polymers prepared using several functional monomers have attracted attention as cost-effective protein affinity reagents and alternative to antibodies. We previously reported the synthesis of poly NIPAm-based nanoparticles (NPs) using several functional monomers that can capture target molecules. In this study, we designed NPs for capturing glucose and inhibiting intestinal absorption in living mice. For capturing glucose, we focused on the Maillard reaction between primary amines and aldehyde residues. We hypothesized that the primary amine-containing NPs can capture the open-chain structure of glucose via the Maillard reaction and inhibit intestinal absorption. NPs were prepared by the precipitation polymerization of NIPAm, N-tert-butylacrylamide (TBAm), trifluoroacetate-protected N-(3-aminopropyl)methacrylamide (T-APM), and N,N'-methylenebisacrylamide. Then, T-APM in NPs was deprotected by NH (aq). The amount of glucose captured by NPs depended on the percentage of TBAm and APM in vitro. After 24 h, only 2% of orally administered NPs remained in the body after administration, suggesting that many NPs were excreted without being absorbed. The prepared NPs significantly inhibited an increase in blood glucose concentration after the oral administration of glucose and NPs, indicating that NPs capture glucose and inhibit intestinal absorption. These results show the potential of using synthetic polymer nanoparticles for inhibiting postprandial hyperglycemia.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.005DOI Listing
July 2021

Early-phase migration dynamics of Echinococcus multilocularis in two mouse strains showing different infection susceptibilities.

Int J Parasitol 2021 May 13. Epub 2021 May 13.

Laboratory of Parasitology, Department of Disease Control, Graduate School of Infectious Diseases, Faculty of Veterinary Medicine, Hokkaido University, N 18 W 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan. Electronic address:

The early-phase migration dynamics of Echinococcus multilocularis in the intermediate hosts remain largely unknown. We compared the parasite burden in the intestine, liver and faeces of DBA/2 and C57BL/6 mouse strains using parasite-specific quantitative PCR. Our results indicated that the parasites invaded mainly from the middle segments of the small intestine and completed migration to the liver within 24 h p.i. C57BL/6 mice had lower parasite DNA burdens in the intestine and liver but higher in the faeces than DBA/2 mice, suggesting that parasite invasion of the intestine may be a critical stage regulating susceptibility to E. multilocularis infection in mice.
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http://dx.doi.org/10.1016/j.ijpara.2021.04.001DOI Listing
May 2021

Oral care and oral assessment guide in breast cancer patients receiving everolimus and exemestane: subanalysis of a randomized controlled trial (Oral Care-BC).

Ann Transl Med 2021 Apr;9(7):535

Department of Breast and Endocrine Surgery, Tokai University School of Medicine, Tokyo, Japan.

Background: Oral mucositis is a clinically significant adverse event linked to cancer therapy; it reduces the quality of life of patients and may result in the discontinuation of treatment and a poorer prognosis. Based on level 3 evidence, the Mucositis Study Group of Multinational Association for Supportive Care in Cancer and the International Society of Oral Oncology recommend oral care for all patients receiving cancer chemotherapy and radiotherapy, although no data from large-scaled randomized controlled trials support the efficacy of oral care in preventing oral mucositis. Therefore, this randomized, controlled, multicenter, open-label, phase III study sought to determine whether professional oral care reduces oral mucositis in everolimus and exemestane-treated estrogen receptor-positive metastatic breast cancer patients.

Methods: Altogether, 169 patients were randomized into the professional oral care (n=82) and control (n=87) groups. The professional oral care group received oral health instruction, professional mechanical tooth and tongue cleaning, gargling with a benzethonium chloride mouthwash, and dexamethasone ointment when grade 1 mucositis manifested. The control group received oral health instruction and gargling. Eight weeks after the everolimus and exemestane administration, the oral status (Oral Assessment Guide criteria) and oral mucositis status (Common Terminology Criteria for Adverse Events functional and clinical examinations) were evaluated.

Results: The incidence of oral mucositis of any grade and grade 2 severe mucositis was significantly lower in the professional oral care group, based on the Common Terminology Criteria for Adverse Events functional and clinical examinations. The total Oral Assessment Guide score, total Oral Assessment Guide grade, and Oral Assessment Guide score of teeth/dentures and mucous membranes were significantly different between the two groups. The Oral Assessment Guide grade for swallow, lip, teeth/dentures, mucous membrane, tongue, and saliva significantly correlated to oral mucositis severity.

Conclusions: Professional oral care may prevent oral mucositis and improve teeth/denture conditions in patients receiving everolimus and exemestane.
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http://dx.doi.org/10.21037/atm-20-6488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105828PMC
April 2021

Delusion progression process from the perspective of patients with psychoses: A descriptive study based on the primary delusion concept of Karl Jaspers.

PLoS One 2021 27;16(4):e0250766. Epub 2021 Apr 27.

Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Tokyo, Japan.

Background: Delusion occupies an important position in the diagnosis and treatment of patients with psychoses. Although Karl Jaspers' concept of the primary delusion (PD) is a key hypothesis in descriptive phenomenology concerning the primordial experience of delusion, to our knowledge it has not been verified in empirical studies of patients with psychosis, and the relationship between PDs and fully developed delusions remains unclear.

Methods: The subjects were 108 psychiatric patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder who had persisting delusions. This investigation used a newly devised semi-structured interview, the Delusion and its Origin Assessment Interview (DOAI), and the Positive and Negative Syndrome Scale. PDs enquired about in the DOAI were delusional perception, delusional memory, delusional mood, and delusional intuition. Associations of PDs with delusion themes and delusion features extracted from DOAI items by factor analysis were examined using correlational and MANCOVA regression analyses. Reliability studies of the DOAI were also conducted.

Results: The reliability and correlation analyses suggested robust psychometric properties of the DOAI. The percentages of subjects reporting PD phenomena as delusion origins and currently present were 93% and 84%, respectively. MANCOVA revealed several significant associations, including between delusional perception and delusional mood and persecutory themes, between delusional intuition and grandiose delusions, and between delusional perception and intuition and systematization of delusions.

Discussion: This study demonstrates that PDs can be considered as principal origins of delusions by subjects with psychosis, and have meaningful connections with the characteristics of their fully developed delusions. The associations between PDs and delusion characteristics can be interpreted in terms of progression processes of delusions, which are seen as intensification and generalization of cognitive and affective pathologies in PDs. The findings are also consistent with the neurobiological hypothesis that aberrant salience attribution to stimuli, as in PDs, is the primary phenomenon caused by abnormal dopamine system regulation. Further studies are needed to clarify delusion progression processes relating to PDs and to substantiate their clinical meanings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250766PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078756PMC
April 2021

Projections of disability-adjusted life years for major diseases due to a change in vegetable intake in 2017-2040 in Japan.

BMC Public Health 2021 04 21;21(1):770. Epub 2021 Apr 21.

Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Low vegetable intake is one of the key dietary risk factors known to be associated with a range of health problems, including cardiovascular diseases (CVDs), cancer, and diabetes and kidney diseases (DKDs). Using data from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017, this study aimed to forecast the impact of change in vegetable intake on disability-adjusted life years (DALYs) between 2017 and 2040 for three diseases.

Methods: We generated a three-component model of cause-specific DALYs, including changes in major behavioural and metabolic risk predictors, the socio-demographic index and an autoregressive integrated moving average model to project future DALY rates for 2017-2040 using the data between 1990 and 2016. Data on Vegetable consumption and risk predictors, and DALY rate were obtained from Japan's National Health and Nutrition Surveys and the Global Burden of Diseases Study in 2017. We also modelled three scenarios of better, moderate and worse cases to evaluate the impact of change in vegetable consumption on the DALY rates for three diseases (CVDs, cancer, and DKDs).

Results: Projected mean vegetable intake in the total population showed a decreasing trend through 2040 to 237.7 g/day. A significant difference between the reference scenario and the better case scenario was observed with un-overlapped 95% prediction intervals of DALY rates in females aged 20-49 years (- 8.0%) for CVDs, the total population for cancer (- 5.6%), and in males (- 8.2%) and females (- 13.7%) for DKDs.

Conclusions: Our analysis indicates that increased vegetable consumption would have a significant reduction in the burdens of CVDs, cancer and DKDs in Japan. By estimating the disease burden attributable to low vegetable intake under different scenarios of future vegetable consumption, our study can inform the design of targeted interventions for public health challenges.
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http://dx.doi.org/10.1186/s12889-021-10772-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061031PMC
April 2021

The exact asymptotic form of Bayesian generalization error in latent Dirichlet allocation.

Authors:
Naoki Hayashi

Neural Netw 2021 May 5;137:127-137. Epub 2021 Feb 5.

Simulation & Mining Division, NTT DATA Mathematical Systems Inc., 1F Shinanomachi Rengakan, 35, Shinanomachi, Shinjuku-ku, Tokyo, 160-0016, Japan; Department of Mathematical and Computing Science, Tokyo Institute of Technology, Mail-Box W8-42, 2-12-1, Oookayama, Meguro-ku, Tokyo, 152-8552, Japan. Electronic address:

Latent Dirichlet allocation (LDA) obtains essential information from data by using Bayesian inference. It is applied to knowledge discovery via dimension reducing and clustering in many fields. However, its generalization error had not been yet clarified since it is a singular statistical model where there is no one-to-one mapping from parameters to probability distributions. In this paper, we give the exact asymptotic form of its generalization error and marginal likelihood, by theoretical analysis of its learning coefficient using algebraic geometry. The theoretical result shows that the Bayesian generalization error in LDA is expressed in terms of that in matrix factorization and a penalty from the simplex restriction of LDA's parameter region. A numerical experiment is consistent with the theoretical result.
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http://dx.doi.org/10.1016/j.neunet.2021.01.024DOI Listing
May 2021

Clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with ductal carcinoma in situ (DCIS): a multi-institutional retrospective cohort study.

Breast Cancer 2021 Jul 18;28(4):896-903. Epub 2021 Feb 18.

Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Background: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS.

Patients And Methods: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records.

Results: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm.

Conclusion: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.
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http://dx.doi.org/10.1007/s12282-021-01225-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213581PMC
July 2021

Long-Term Oncologic Safety of Nipple-Sparing Mastectomy With Immediate Reconstruction.

Clin Breast Cancer 2021 Jan 6. Epub 2021 Jan 6.

Department of Breast Surgical Oncology, St Luke's International Hospital, Tokyo, Japan; Department of Breast Surgery, Watanabe Hospital, Tokyo, Japan. Electronic address:

Background: We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction.

Patients And Methods: Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD < 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed.

Results: The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43).

Conclusion: NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.
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http://dx.doi.org/10.1016/j.clbc.2021.01.002DOI Listing
January 2021

Dosimetric response of a glass dosimeter in proton beams: LET-dependence and correction factor.

Phys Med 2021 Jan 15;81:147-154. Epub 2021 Jan 15.

Fujita Health University, Faculty of Radiological Technology, School of Health Sciences, Japan.

A radiophotoluminescent glass dosimeter (RGD) is widely used in postal audit system for photon beams in Japan. However, proton dosimetry in RGDs is scarcely used owing to a lack of clarity in their response to beam quality. In this study, we investigated RGD response to beam quality for establishing a suitable linear energy transfer (LET)-corrected dosimetry protocol in a therapeutic proton beam. The RGD response was compared with ionization chamber measurement for a 100-225 MeV passive proton beam. LET of the measurement points was calculated by the Monte Carlo method. An LET-correction factor, defined as a ratio between the non-corrected RGD dose and ionization chamber dose, of 1.226×(LET) was derived for the RGD response. The magnitude of the LET-dependence of RGD increased with LET; for an LET of 8.2 keV/μm, the RGD under-response was up to 16%. The coefficient of determination, mean difference ± SD of non-corrected RGD dose, residual range-corrected RGD dose, and LET-corrected RGD dose to the ionization chamber are 0.923, 3.7 ± 4.2%, -2.4 ± 7.5%, and 0.04 ± 2.1%, respectively. The LET-corrected RGD dose was within 5% of the corresponding ionization chamber dose at all energies until 200 MeV, where it was 5.3% lower than the ionization chamber dose. A corrected LET-dependence of RGD using a correction factor based on a power function of LET and precise dosimetric verification close to the maximum LET were realized here. We further confirmed establishment of an accurate postal audit under various irradiation conditions.
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http://dx.doi.org/10.1016/j.ejmp.2020.12.001DOI Listing
January 2021

Secondary endpoints analysis in patients with estrogen receptor-positive metastatic breast cancer treated with everolimus and exemestane enrolled in Oral Care-BC.

BMC Cancer 2021 Jan 7;21(1):34. Epub 2021 Jan 7.

Department of Dentistry and Oral and Maxillofacial Surgery, Tokai University School of Medicine, Tokyo, Japan.

Background: The Oral Care BC-trial reported that professional oral care (POC) reduces the incidence and severity of oral mucositis in patients receiving everolimus (EVE) and exemestane (EXE). However, the effect of POC on clinical response among patients receiving EVE and EXE was not established. We compared outcomes for estrogen receptor-positive metastatic breast cancer patients who received POC to those who had not, and evaluated clinical prognostic factors. All patients simultaneously received EVE and EXE.

Methods: Between May 2015 and Dec 2017, 174 eligible patients were enrolled in the Oral Care-BC trial. The primary endpoint was the comparative incidence of grade 1 or worse oral mucositis, as evaluated for both the groups over 8 weeks by an oncologist. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collected after a follow-up period of 13.9 months.

Results: There were no significant differences in PFS between the POC and Control Groups (P = 0.801). A BMI <  25 mg/m and non-visceral metastasis were associated with longer PFS (P = 0.018 and P = 0.003, respectively) and the use of bone modifying agents (BMA) was associated with shorter PFS (P = 0.028). The PFS and OS between the POC and control groups were not significantly different in the Oral-Care BC trial.

Conclusions: POC did not influence the prognosis of estrogen receptor-positive metastatic breast cancer patients. Patients with non-visceral metastasis, a BMI <  25 mg/m, and who did not receive BMA while receiving EVE and EXE may have better prognoses.

Trial Registration: The study protocol was registered online at the University Hospital Medical Information Network (UMIN), Japan (protocol ID 000016109), on January 5, 2015 and at ClinicalTrials.gov ( NCT02376985 ).
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http://dx.doi.org/10.1186/s12885-020-07746-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791872PMC
January 2021

[Introduction of Medical Physics Education Course in Fujita Health University].

Igaku Butsuri 2020;40(4):147-151

Graduate school of Health Sciences, Fujita Health University.

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http://dx.doi.org/10.11323/jjmp.40.4_147DOI Listing
February 2021

Broad spectrum in vitro microbicidal activity of benzoyl peroxide against microorganisms related to cutaneous diseases.

J Dermatol 2021 Apr 28;48(4):551-555. Epub 2020 Dec 28.

Department of Microbiology and Infection Control Science, Kyoto Pharmaceutical University, Kyoto, Japan.

The in vitro microbicidal activity of benzoyl peroxide against Cutibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia furfur, Malassezia restricta, and Malassezia globosa was investigated. These strains were incubated for 1 h in the presence of 0.25, 0.5, 1, or 2 mmol/L benzoyl peroxide in phosphate buffered saline supplemented with 0.1% glycerol and 2% Tween 80. After exposure to benzoyl peroxide, counts of viable Gram-positive bacteria and fungi were markedly decreased, whereas counts of Gram-negative bacteria were unchanged. Transmission electron microscopy images showed a decrease in electron density and the destruction of C. acnes and M. restricta cell walls after exposure to 2 mmol/L benzoyl peroxide. In conclusion, this study showed that benzoyl peroxide has a potent and rapid microbicidal activity against Gram-positive bacteria and fungi that are associated with various cutaneous diseases. This suggests that the direct destruction of bacterial cell walls by benzoyl peroxide is an essential mechanism of its rapid and potent microbicidal activity against microorganisms.
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http://dx.doi.org/10.1111/1346-8138.15739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048985PMC
April 2021

Sulfated vizantin causes detachment of biofilms composed mainly of the genus Streptococcus without affecting bacterial growth and viability.

BMC Microbiol 2020 11 25;20(1):361. Epub 2020 Nov 25.

Division of Cariology, Operative Dentistry and Endodontics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274, Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.

Background: Sulfated vizantin, a recently developed immunostimulant, has also been found to exert antibiofilm properties. It acts not as a bactericide, but as a detachment-promoting agent by reducing the biofilm structural stability. This study aimed to investigate the mechanism underlying this activity and its species specificity using two distinct ex vivo oral biofilm models derived from human saliva.

Results: The biofilm, composed mainly of the genus Streptococcus and containing 50 μM of sulfated vizantin, detached significantly from its basal surface with rotation at 500 rpm for only 15 s, even when 0.2% sucrose was supplied. Expression analyses for genes associated with biofilm formation and bacterial adhesion following identification of the Streptococcus species, revealed that a variety of Streptococcus species in a cariogenic biofilm showed downregulation of genes encoding glucosyltransferases involved in the biosynthesis of water-soluble glucan. The expression of some genes encoding surface proteins was also downregulated. Of the two quorum sensing systems involved in the genus Streptococcus, the expression of luxS in three species, Streptococcus oralis, Streptococcus gordonii, and Streptococcus mutans, was significantly downregulated in the presence of 50 μM sulfated vizantin. Biofilm detachment may be facilitated by the reduced structural stability due to these modulations. As a non-specific reaction, 50 μM sulfated vizantin decreased cell surface hydrophobicity by binding to the cell surface, resulting in reduced bacterial adherence.

Conclusion: Sulfated vizantin may be a candidate for a new antibiofilm strategy targeting the biofilm matrix while preserving the resident microflora.
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http://dx.doi.org/10.1186/s12866-020-02033-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687742PMC
November 2020

Prediction of disability-adjusted life years for diseases due to low fruit intake in 2017-2040 in Japan.

Public Health Nutr 2021 Jul 13;24(10):3156-3166. Epub 2020 Nov 13.

Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Objective: The current study aimed to predict disability-adjusted life years (DALY) rate in Japan through 2040 with plausible future scenarios of fruit intake for neoplasms, cardiovascular diseases (CVD) and diabetes and kidney diseases (DKD).

Design: Data from National Health and Nutrition Surveys and the Global Burden of Diseases study in 2017 were used. We developed an autoregressive integrated moving average model with four future scenarios. Reference scenario maintains the current trend. Best scenario assumes that the goal defined in Health Japan 21 is achieved in 2023 and is kept constant afterwards. Moderate scenario assumes that the goal is achieved in 2040. Constant scenario applies the same proportion of 2016 for the period between 2017 and 2040.

Setting: DALY rates in Japan were predicted for the period between 2017 and 2040.

Participants: Population aged more than than 20 years old.

Results: In our reference forecast, the DALY rates in all-ages group were projected to be stable for CVD and continue increasing for neoplasms and DKD. Age group-specific DALY rates for these three disease groups were forecasted to decrease, with some exceptions. Among men aged 20-49 years, DALY attributable to CVD differed substantially between the scenarios, implying that there is a significant potential for reducing the burden of CVD by increasing fruit intake at the population level.

Conclusions: Our scenario analysis shows that higher fruit intake is associated with lower disease burden in Japan. Further research is required to assess which policies and interventions can be used to achieve an increase in fruit intake as modelled in the scenarios of the current study.
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http://dx.doi.org/10.1017/S1368980020004541DOI Listing
July 2021

Effect of protective glasses on radiation dose to eye lenses during whole breast irradiation.

J Appl Clin Med Phys 2020 Nov 30;21(11):272-277. Epub 2020 Oct 30.

Department of Radiology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.

Objectives: The efficacy of radiotherapy for breast cancer has greatly improved owing to better irradiation methods. Radiotherapy aims to deliver therapeutic doses to predetermined target volumes while sparing surrounding healthy tissues. However, there are few reports on radiation exposure to eye lenses, and the recommended exposure limits to ocular lens have been substantially reduced in recent years. This study aimed to investigate the amount of radiation exposure to eye lenses using optically stimulated luminescence dosimeters (OSLDs) and determine whether wearing special protective devices to protect the eyes, as an organ at risk, during whole breast irradiation, is necessary.

Methods: This experiment used OSLDs on water-equivalent phantom to measure the change in scattered radiation dose due to the difference of irradiation field while using 4- and 6-MV photons of TrueBeam linear accelerator. Using a total treatment dose of 50 Gy, a target was positioned to approximate the breast, and a plan was formulated to deliver 2 Gy per treatment by tangential irradiation. The mean (SD) irradiation dose at the lens position outside the irradiation field was reported.

Results: The scattered radiation dose outside the irradiation field was more affected by the irradiation field size than by the radiation energy. The out-of-field irradiation dose with a larger field of view was higher than that with a smaller field of view. The use of 0.07- and 0.83-mm-thick lead shield protective glasses reduced the radiation dose by 56.1% (P < .001) and 55.6% (P < .001), respectively.

Conclusions: In this experimental model, the amount of radiation the eye was exposed to during whole breast irradiation was determined by the distance of the eye from the radiation field edge and by wearing protective glasses. In clinical practice, the protection offered by eyeglasses may reduce the risk of long-term side effects and allow the use of higher intensive radiotherapy.
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http://dx.doi.org/10.1002/acm2.13073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700920PMC
November 2020

ASO Author Reflections: What will be Required to Safely Omit Breast Surgery for Early-Stage Breast Cancer?

Ann Surg Oncol 2021 May 12;28(5):2553-2554. Epub 2020 Oct 12.

Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1245/s10434-020-09195-xDOI Listing
May 2021

Response and Prognosis of Docetaxel and Cyclophosphamide as Neoadjuvant Chemotherapy in ER HER2 Breast Cancer: A Prospective Phase II Study.

Clin Breast Cancer 2020 12 18;20(6):462-468. Epub 2020 Sep 18.

Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan; Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.

Background: Although a docetaxel and cyclophosphomide (TC) regimen without anthracycline as adjuvant therapy became one of the standard regimens especially for ER-positive (ER)/human epidermal growth factor receptor 2-negative (HER2) primary breast cancer, the efficacy of TC as neoadjuvant chemotherapy (NAC) is not known. We conducted the prospective trial to assess the efficacy of a TC regimen in the neoadjuvant setting for stage II to III ER/HER2 primary breast cancer.

Patients And Methods: A TC regimen that included 75 mg/m of docetaxel and 600 mg/m of cyclophosphamide for 4 cycles every 3 weeks was administered as NAC. Primary endpoints are the rate of clinical response (clinical partial response and clinical complete response) and pathologic complete response; secondary endpoints are the disease-free survival and overall survival rates.

Results: Thirty (71.4%) of 42 tumors had clinical response. No patient achieved pathologic complete response. At the median follow-up period of 105.2 months (range, 12.1-119.7 months), the disease-free survival rate was 81.6%, and the distant disease-free survival rate was 86.8%. In terms of survival, only 1 patient died during the study period. The overall survival rate was 97.4% during the study period. Patients who developed distant recurrence had a trend to have progesterone receptor-negative or weakly positive compared with those who did not develop any recurrence (85.7% vs. 45.2%; P = .05).

Conclusions: Our prospective study showed that a TC regimen as NAC achieved a high clinical response rate in stage II to III ER/HER2 breast cancer. A TC regimen without anthracycline as NAC might be one of the options for patients with ER/HER2 breast cancer without high-risk factors including progesterone receptor negativity.
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http://dx.doi.org/10.1016/j.clbc.2020.09.007DOI Listing
December 2020

Risk Factors for Ipsilateral Breast Tumor Recurrence in Triple-Negative or HER2-Positive Breast Cancer Patients Who Achieve a Pathologic Complete Response After Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 May 6;28(5):2545-2552. Epub 2020 Oct 6.

Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan.

Background: Attention has been focused on attempts to eliminate breast surgery for breast cancer patients who achieve a pathologic complete response after neoadjuvant chemotherapy (NAC). However, there are few data on ipsilateral breast tumor recurrence (IBTR) among patients with triple-negative or epidermal growth factor receptor 2-positive (HER2+) tumors who achieve a pathologic complete response after NAC and breast-conserving treatment.

Methods: Using a multi-institutional retrospective database, this study evaluated the risk factors for IBTR among patients with newly diagnosed stages 1 to 3 breast cancer involving triple-negative or HER2+ tumors who achieved ypT0 after NAC and breast-conserving treatment.

Results: During a median follow-up period of 4.8 years (range, 0.1-15.5 years), the 5-year IBTR-free survival rate was 95.5%. The breast cancer subtype was not associated with IBTR-free survival. Patients younger than 40 years at diagnosis had significantly worse IBTR-free survival than those who were 40 years of age or older (5-year IBTR-free survival, 87.7 vs 96.9%; p = 0.002).

Conclusions: This retrospective study demonstrated that age at diagnosis was independently associated with IBTR-free survival. Special caution is needed when clinical trials analyzing omission of breast surgery after NAC are enrolling younger patients (UMIN-CTR No. UMIN000037067).
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http://dx.doi.org/10.1245/s10434-020-09176-0DOI Listing
May 2021

Severe myasthenia gravis with anti-LRP4 antibodies and Hodgkin lymphoma.

Muscle Nerve 2021 01 26;63(1):E2-E4. Epub 2020 Oct 26.

Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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http://dx.doi.org/10.1002/mus.27079DOI Listing
January 2021

Forecasting disability-adjusted life years for chronic diseases: reference and alternative scenarios of salt intake for 2017-2040 in Japan.

BMC Public Health 2020 Sep 29;20(1):1475. Epub 2020 Sep 29.

Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: In Japan, a high-sodium diet is the most important dietary risk factor and is known to cause a range of health problems. This study aimed to forecast Japan's disability-adjusted life year (DALYs) for chronic diseases that would be associated with high-sodium diet in different future scenarios of salt intake. We modelled DALY forecast and alternative future scenarios of salt intake for cardiovascular diseases (CVDs), chronic kidney diseases (CKDs), and stomach cancer (SC) from 2017 to 2040.

Methods: We developed a three-component model of disease-specific DALYs: a component on the changes in major behavioural and metabolic risk predictors including salt intake; a component on the income per person, educational attainment, and total fertility rate under 25 years; and an autoregressive integrated moving average model to capture the unexplained component correlated over time. Data on risk predictors were obtained from Japan's National Health and Nutrition Surveys and from the Global Burden of Disease Study 2017. To generate a reference forecast of disease-specific DALY rates for 2017-2040, we modelled the three diseases using the data for 1990-2016. Additionally, we generated better, moderate, and worse scenarios to evaluate the impact of change in salt intake on the DALY rate for the diseases.

Results: In our reference forecast, the DALY rates across all ages were predicted to be stable for CVDs, continuously increasing for CKDs, and continuously decreasing for SC. Meanwhile, the age group-specific DALY rates for these three diseases were forecasted to decrease, with some exceptions. Except for the ≥70 age group, there were remarkable differences in DALY rates between scenarios, with the best scenario having the lowest DALY rates in 2040 for SC. This represents a wide scope of future trajectories by 2040 with a potential for tremendous decrease in SC burden.

Conclusions: The gap between scenarios provides some quantification of the range of policy impacts on future trajectories of salt intake. Even though we do not yet know the policy mix used to achieve these scenarios, the result that there can be differences between scenarios means that policies today can have a significant impact on the future DALYs.
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http://dx.doi.org/10.1186/s12889-020-09596-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526266PMC
September 2020

Evaluation of differences and dosimetric influences of beam models using golden and multi-institutional measured beam datasets in radiation treatment planning systems.

Med Phys 2020 Nov 15;47(11):5852-5871. Epub 2020 Oct 15.

School of Medical Sciences, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.

Purpose: The beam model in radiation treatment planning systems (RTPSs) plays a crucial role in determining the accuracy of calculated dose distributions. The purpose of this study was to ascertain differences in beam models and their dosimetric influences when a golden beam dataset (GBD) and multi-institution measured beam datasets (MBDs) are used for beam modeling in RTPSs.

Methods: The MBDs collected from 15 institutions, and the MBDs' beam models, were compared with a GBD, and the GBD's beam model, for Varian TrueBeam linear accelerator. The calculated dose distributions of the MBDs' beam models were compared with those of the GBD's beam model for simple geometries in a water phantom. Calculated dose distributions were similarly evaluated in volumetric modulated arc therapy (VMAT) plans for TG-119 C-shape and TG-244 head and neck, at several dose constraints of the planning target volumes (PTVs), and organs at risk.

Results: The agreements of the MBDs with the GBD were almost all within ±1%. The calculated dose distributions for simple geometries in a water phantom also closely corresponded between the beam models of GBD and MBDs. Nevertheless, there were considerable differences between the beam models. The maximum differences between the mean energy of the energy spectra of GBD and MBDs were -0.12 MeV (-10.5%) in AcurosXB (AXB, Eclipse) and 0.11 MeV (7.7%) in collapsed cone convolution (CCC, RayStation). The differences in the VMAT calculated dose distributions varied for each dose region, plan, X-ray energy, and dose calculation algorithm. The ranges of the differences in the dose constraints were -5.6% to 3.0% for AXB and -24.1% to 2.8% for CCC. In several VMAT plans, the calculated dose distributions of GBD's beam model tended to be lower in high-dose regions and higher in low-dose regions than those of the MBDs' beam models.

Conclusions: We found that small differences in beam data have large impacts on the beam models, and on calculated dose distributions in clinical VMAT plan, even if beam data correspond within ±1%. GBD's beam model was not a representative beam model. The beam models of GBD and MBDs and their calculated dose distributions under clinical conditions were significantly different. These differences are most likely due to the extensive variation in the beam models, reflecting the characteristics of beam data. The energy spectrum and radial energy in the beam model varied in a wide range, even if the differences in the beam data were <±1%. To minimize the uncertainty of the calculated dose distributions in clinical plans, it was best to use the institutional MBD for beam modeling, or the beam model that ensures the accuracy of calculated dose distributions.
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http://dx.doi.org/10.1002/mp.14493DOI Listing
November 2020

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis.

Commun Biol 2020 09 23;3(1):526. Epub 2020 Sep 23.

Division of Neurology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.
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http://dx.doi.org/10.1038/s42003-020-01251-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511394PMC
September 2020

Genetic and functional analysis of KIF5A variants in Japanese patients with sporadic amyotrophic lateral sclerosis.

Neurobiol Aging 2021 01 17;97:147.e11-147.e17. Epub 2020 Jul 17.

Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Brain and Mind Research Center, Nagoya University, Nagoya, Japan; Aichi Medical University, Nagakute, Japan. Electronic address:

Two recent genetic studies reported that loss-of-function mutation of the C-terminal cargo-binding tail domain of the KIF5A gene cause amyotrophic lateral sclerosis (ALS). The aim of this study is to investigate the frequency of KIF5A variants in Japanese patients with sporadic ALS. In total, 807 sporadic ALS patients and 191 normal controls from a multicenter ALS cohort in Japan were included. Whole exome sequencing on an Illumina HiSeq 2000/2500 sequencer was used to identify and select variants within the KIF5A gene. Thirteen patients harbored a nonsynonymous variant in the KIF5A gene; These were considered variants of uncertain significance. One patient harbored a novel splice-site variant (c.2993-3C>A) in the C-terminal cargo-binding tail domain of the KIF5A gene. Functional analysis of this variant revealed that it caused skipping of exon 27. The frequency of KIF5A mutations in Japanese patients with sporadic ALS was 0.12% (1/807). This study reports a novel loss-of-function variant in KIF5A, and indicates that loss-of-function variant in KIF5A is a rare cause of sporadic ALS in Japanese patients.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.07.010DOI Listing
January 2021

Breast cancer survival among Japanese individuals and US residents of Japanese and other origins: a comparative registry-based study.

Breast Cancer Res Treat 2020 Nov 20;184(2):585-596. Epub 2020 Aug 20.

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

Background: Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO).

Method: Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status.

Results: We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45-0.47 for Japanese and 0.66 [95% CI 0.59-0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51-0.55] for Japanese and 0.53 [95% CI 0.52-0.74] for USJ).

Conclusions: In stage I-III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.
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http://dx.doi.org/10.1007/s10549-020-05869-yDOI Listing
November 2020

Annual report of the Japanese Breast Cancer Registry for 2017.

Breast Cancer 2020 Sep 24;27(5):803-809. Epub 2020 Jul 24.

Department of Breast Surgery, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.

Background: The Japanese Breast Cancer Society Registry started in 1975; it was transferred to the registry platform of the National Clinical Database in 2012. We provide the annual data and an analysis of the Breast Cancer Registry for 2017.

Methods: Patients' characteristics and pathological data of the 95,203 registered Japanese breast cancer patients from 1,427 institutes in 2017 were obtained. Trends in age at diagnosis and pathological stage were determined during the most recent 6 years (2012-2017).

Results: The mean onset age was 60.2 years with bimodal peaks at 45-49 years and 65-69 years. A short-term trend of the most recent 6 years of data caused the second, older peak. At diagnosis, 32.4% of breast cancer patients were premenopausal. The distribution of stages revealed that the proportion of early stage breast cancer (stage 0-I) increased up to 60%. At the initial diagnosis, 2.2% of patients presented with metastatic disease. Sentinel node biopsy without axillary node dissection was performed without neoadjuvant chemotherapy (NAC) in 68.8%, and with NAC in 31.1%, of patients. For patients without NAC, lymph node metastasis was less than 3% if the tumor size was less than 1 cm. The proportion of node-negativity decreased to 79.5% when tumor size was 2.1-5 cm.

Conclusions: This analysis of the registry provides new information for effective treatment in clinical practice, cancer prevention, and the conduct of clinical trials. Further development of the registry and progress in collecting prognostic data will greatly enhance its scientific value.
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http://dx.doi.org/10.1007/s12282-020-01139-3DOI Listing
September 2020

Late-onset ovarian hyperstimulation syndrome developing during ovarian stimulation in an ectopic pregnancy: a case report.

J Med Case Rep 2020 Jul 20;14(1):110. Epub 2020 Jul 20.

Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-3550, Japan.

Background: Ovarian hyperstimulation syndrome is normally induced by ovarian stimulation drugs. Severe cases of ovarian hyperstimulation syndrome involve complications such as renal failure and thrombosis. Evidence has recently been developed for a method to prevent ovarian hyperstimulation syndrome. Most cases of ovarian hyperstimulation syndrome are of an early-onset type, which occurs shortly after injection of human chorionic gonadotropin. However, late-onset ovarian hyperstimulation syndrome, which occurs in a pregnancy cycle, also requires caution. We report our experience in treating a woman who was transported to our hospital with a severe case of ovarian hyperstimulation syndrome occurring during ovarian stimulation and who was determined to have an ectopic pregnancy.

Case Presentation: Assisted reproductive technology was planned for a 29-year-old nulligravida Japanese woman diagnosed with bilateral fallopian tube obstruction and right-sided hydrosalpinx. On day 1 of controlled ovarian stimulation, the result of her human chorionic gonadotropin urine test was negative, and her serum levels of luteinizing hormone, estradiol, and progesterone were normal. On day 11 of controlled ovarian stimulation, the levels of estradiol and progesterone had risen to 9679 pg/ml and 16 ng/ml, respectively, prompting suspension of controlled ovarian stimulation. Eleven days after controlled ovarian stimulation was suspended, the patient demonstrated ascites that did not improve despite administration of cabergoline, and she was transported to our hospital 2 days after. Late-onset ovarian hyperstimulation syndrome suggested that she was pregnant, and her serum human chorionic gonadotropin level was 27,778 IU/ml. She underwent laparoscopic bilateral salpingectomy and was diagnosed with right tubal pregnancy.

Conclusion: In an ectopic pregnancy, human chorionic gonadotropin sometimes increases later than in an intrauterine pregnancy. In our patient's case, endogenous human chorionic gonadotropin following the start of controlled ovarian stimulation may have caused late-onset ovarian hyperstimulation syndrome. The key to early detection of similar cases may be to suspect pregnancy in the event of unexpectedly high progesterone levels during ovarian stimulation.
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http://dx.doi.org/10.1186/s13256-020-02439-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370457PMC
July 2020

Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1.

JCI Insight 2020 08 6;5(15). Epub 2020 Aug 6.

Laboratory of Innate Immunity and Inflammation, Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Macrolide antibiotics exert antiinflammatory effects; however, little is known regarding their immunomodulatory mechanisms. In this study, using 2 distinct mouse models of mucosal inflammatory disease (LPS-induced acute lung injury and ligature-induced periodontitis), we demonstrated that the antiinflammatory action of erythromycin (ERM) is mediated through upregulation of the secreted homeostatic protein developmental endothelial locus-1 (DEL-1). Consistent with the anti-neutrophil recruitment action of endothelial cell-derived DEL-1, ERM inhibited neutrophil infiltration in the lungs and the periodontium in a DEL-1-dependent manner. Whereas ERM (but not other antibiotics, such as josamycin and penicillin) protected against lethal pulmonary inflammation and inflammatory periodontal bone loss, these protective effects of ERM were abolished in Del1-deficient mice. By interacting with the growth hormone secretagogue receptor and activating JAK2 in human lung microvascular endothelial cells, ERM induced DEL-1 transcription that was mediated by MAPK p38 and was CCAAT/enhancer binding protein-β dependent. Moreover, ERM reversed IL-17-induced inhibition of DEL-1 transcription, in a manner that was dependent not only on JAK2 but also on PI3K/AKT signaling. Because DEL-1 levels are severely reduced in inflammatory conditions and with aging, the ability of ERM to upregulate DEL-1 may lead to a novel approach for the treatment of inflammatory and aging-related diseases.
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http://dx.doi.org/10.1172/jci.insight.136706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455085PMC
August 2020
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