Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Reallocating desk workers' sitting time to standing or stepping: associations with work performance.

BACKGROUND: Studies have suggested that sitting time at work may lead to underperformance but they may underestimate the benefits to desk workers' performance of reducing occupational sitting time without considering the relative effects of the specific activities replaced. AIMS: To estimate differences in work performance (presenteeism, absenteeism and engagement) when occupational sitting time is reallocated to standing/stepping in desk workers. METHODS: Data for middle-aged desk workers were from a Japan-wide online survey (n = 2228). Self-report proportion of occupational sitting and standing/stepping, work hours and work performance indicators, including absolute (ratings relating only to self) and relative (ratings of self, compared to others) presenteeism and absenteeism, and dimensions of work engagement, were collected. Partition and isotemporal substitution models were used to investigate the associations of occupational sitting and standing/stepping time with work performance, including their reallocation effects. RESULTS: In partition models, longer occupational sitting time was associated with a lower absolute presenteeism score (i.e. less productivity), lower absolute absenteeism (i.e. longer-than-expected work hours), and lower engagement. Longer occupational standing/stepping time was associated with lower absolute absenteeism and more engagement. Isotemporal substitution models showed that each hour of occupational sitting reallocated to standing/stepping was favourably associated with overall work engagement (B = 0.087; 95% confidence interval 0.051, 0.122) and its dimensions (B ranged from 0.078 to 0.092), but was not associated with presenteeism or absenteeism. CONCLUSIONS: These findings suggest that management support and practical initiatives to encourage desk workers to replace portions of their sitting time with standing/stepping may contribute to enhanced work engagement.

Infantile outcome at 3 years of age among monochorionic twins with Type-II or -III selective fetal growth restriction with isolated oligohydramnios who underwent fetoscopic laser photocoagulation.

OBJECTIVE: This study aimed to examine infantile outcomes at 3 years of age with selective fetal growth restriction (sFGR) Types II and III with isolated oligohydramnios who underwent fetoscopic laser photocoagulation (FLP). METHODS: This multicenter prospective cohort study included monochorionic diamniotic twins who underwent FLP for sFGR between 16 and 25 weeks of gestation. The indication for performing FLP was in cases of sFGR Type II or III with oligohydramnios, where the maximal vertical pocket was ≤2 cm among twins with FGR. This was done in the absence of a typical twin-twin transfusion syndrome diagnosis. The primary outcome was the intact survival (IS) rate of infants at the corrected age of 40 weeks and 3 years. IS at the corrected age of 40 weeks was defined as survival without grade III or IV intraventricular hemorrhage or cystic periventricular leukomalacia, and IS at 3 years of age was defined as survival without neurodevelopmental morbidity, including cerebral palsy, neurodevelopmental impairment with a total developmental quotient of ≤70, bilateral deafness, or bilateral blindness. RESULTS: Among 45 patients with sFGR, 30 (66.7%) were classified as having Type II and 15 (33.3%) as Type III sFGR. The prevalence of IS at the corrected age of 40 weeks was 51.1% (n=23) in FGR twins and 95.5% (n=42) in larger twins. The prevalence of IS at 3 years of age was 46.7% (n=21) in FGR twins and 86.4% (n=38) in larger twins. Among the 24 FGR twins who were not diagnosed with IS at 3 years of age, 91.7% (22 of 24 cases) suffered fetal or infantile demise other than miscarriage and neurodevelopmental impairment. All larger twins who were not diagnosed with IS at 3 years of age (n=6, 13.6%) had neurological morbidity, in addition to one case of miscarriage. CONCLUSIONS: FGR twins and larger twins, when subjected to FLP due to sFGR coupled with umbilical artery Doppler abnormalities and isolated oligohydramnios, exhibit low rates of neurological morbidity and low mortality, respectively. Therefore, FLP for Type II or III sFGR with oligohydramnios may be a feasible and preferable management option. This article is protected by copyright. All rights reserved.

RENEB Inter-Laboratory Comparison 2021: Inter-Assay Comparison of Eight Dosimetry Assays.

Tools for radiation exposure reconstruction are required to support the medical management of radiation victims in radiological or nuclear incidents. Different biological and physical dosimetry assays can be used for various exposure scenarios to estimate the dose of ionizing radiation a person has absorbed. Regular validation of the techniques through inter-laboratory comparisons (ILC) is essential to guarantee high quality results. In the current RENEB inter-laboratory comparison, the performance quality of established cytogenetic assays [dicentric chromosome assay (DCA), cytokinesis-block micronucleus assay (CBMN), stable chromosomal translocation assay (FISH) and premature chromosome condensation assay (PCC)] was tested in comparison to molecular biological assays [gamma-H2AX foci (gH2AX), gene expression (GE)] and physical dosimetry-based assays [electron paramagnetic resonance (EPR), optically or thermally stimulated luminescence (LUM)]. Three blinded coded samples (e.g., blood, enamel or mobiles) were exposed to 0, 1.2 or 3.5 Gy X-ray reference doses (240 kVp, 1 Gy/min). These doses roughly correspond to clinically relevant groups of unexposed to low exposed (0-1 Gy), moderately exposed (1-2 Gy, no severe acute health effects expected) and highly exposed individuals (>2 Gy, requiring early intensive medical care). In the frame of the current RENEB inter-laboratory comparison, samples were sent to 86 specialized teams in 46 organizations from 27 nations for dose estimation and identification of three clinically relevant groups. The time for sending early crude reports and more precise reports was documented for each laboratory and assay where possible. The quality of dose estimates was analyzed with three different levels of granularity, 1. by calculating the frequency of correctly reported clinically relevant dose categories, 2. by determining the number of dose estimates within the uncertainty intervals recommended for triage dosimetry (±0.5 Gy or ±1.0 Gy for doses <2.5 Gy or >2.5 Gy), and 3. by calculating the absolute difference (AD) of estimated doses relative to the reference doses. In total, 554 dose estimates were submitted within the 6-week period given before the exercise was closed. For samples processed with the highest priority, earliest dose estimates/categories were reported within 5-10 h of receipt for GE, gH2AX, LUM, EPR, 2-3 days for DCA, CBMN and within 6-7 days for the FISH assay. For the unirradiated control sample, the categorization in the correct clinically relevant group (0-1 Gy) as well as the allocation to the triage uncertainty interval was, with the exception of a few outliers, successfully performed for all assays. For the 3.5 Gy sample the percentage of correct classifications to the clinically relevant group (≥2 Gy) was between 89-100% for all assays, with the exception of gH2AX. For the 1.2 Gy sample, an exact allocation to the clinically relevant group was more difficult and 0-50% or 0-48% of the estimates were wrongly classified into the lowest or highest dose categories, respectively. For the irradiated samples, the correct allocation to the triage uncertainty intervals varied considerably between assays for the 1.2 Gy (29-76%) and 3.5 Gy (17-100%) samples. While a systematic shift towards higher doses was observed for the cytogenetic-based assays, extreme outliers exceeding the reference doses 2-6 fold were observed for EPR, FISH and GE assays. These outliers were related to a particular material examined (tooth enamel for EPR assay, reported as kerma in enamel, but when converted into the proper quantity, i.e. to kerma in air, expected dose estimates could be recalculated in most cases), the level of experience of the teams (FISH) and methodological uncertainties (GE). This was the first RENEB ILC where everything, from blood sampling to irradiation and shipment of the samples, was organized and realized at the same institution, for several biological and physical retrospective dosimetry assays. Almost all assays appeared comparably applicable for the identification of unexposed and highly exposed individuals and the allocation of medical relevant groups, with the latter requiring medical support for the acute radiation scenario simulated in this exercise. However, extreme outliers or a systematic shift of dose estimates have been observed for some assays. Possible reasons will be discussed in the assay specific papers of this special issue. In summary, this ILC clearly demonstrates the need to conduct regular exercises to identify research needs, but also to identify technical problems and to optimize the design of future ILCs.

Outcome of laser photocoagulation in monochorionic diamniotic twin pregnancy complicated by Type-II selective fetal growth restriction.

OBJECTIVES: To evaluate the outcome of monochorionic diamniotic (MCDA) twins complicated by Type-II selective fetal growth restriction (sFGR) who underwent fetoscopic laser photocoagulation and to validate a previously proposed subclassification system for Type-II sFGR in a large multicenter cohort. METHODS: This retrospective multicenter cohort study included all MCDA twins complicated by Type-II sFGR who underwent laser photocoagulation of placental anastomoses at four large tertiary fetal-care centers between 2006 and 2020. Cases were subclassified according to a recently proposed system based on Doppler evaluation of the ductus venosus (DV) and middle cerebral artery (MCA) into Type-IIA (normal DV flow and MCA peak systolic velocity (PSV) of the growth-restricted fetus) or Type-IIB (absent or reversed flow in the DV during atrial contraction and/or MCA-PSV ≥ 1.5 multiples of the median of the growth-restricted fetus). Demographic characteristics and pregnancy outcomes were compared between the groups. Data are presented as mean ± SD or n (%) as appropriate. P-values < 0.05 were considered statistically significant. RESULTS: A total of 98 patients with MCDA twins met our inclusion criteria, with 56 subclassified as Type IIA and 42 as Type IIB. Demographic characteristics were similar between the groups; however, Type-IIB cases had a significantly earlier gestational age at diagnosis and at laser surgery, as well as larger intertwin estimated fetal weight discordance, which may be a reflection of disease severity. Postnatal survival of the growth-restricted fetus to 30 days of age was significantly lower in Type-IIB compared to Type-IIA cases (23.8% vs 46.4%; P = 0.034). CONCLUSIONS: In MCDA twins complicated by Type-II sFGR and treated with laser photocoagulation of placental anastomoses, preoperative Doppler assessment of the DV and MCA helped identify a subset of patients at increased risk of demise of the growth-restricted fetus following intervention. This study provides valuable information for guiding surgical management and patient counseling. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

MRI features of extraocular muscle metastases compared to those of other extraocular muscle diseases of non-thyroid origin.

AIM: To identify the magnetic resonance imaging (MRI) features of metastases to the extraocular muscles (EOM metastases). MATERIAL AND METHODS: The MRI features of 19 patients with EOM metastases were compared with those of 24 patients with EOM diseases of non-thyroid origin. MRI was used to assess the number of tumours, morphology, signal intensity on T2-weighted images, enhancement patterns, and apparent diffusion coefficient (ADC) values. RESULTS: Single muscular involvement was observed in 10 patients, and multiple muscular involvement was observed in nine patients. The morphology was focally discrete in nine patients, and diffuse infiltrative in 10 patients; all the nine patients with focal discrete morphology presented with single muscular lesions. On T2-weighted images, the signal intensities were intermediate or low in 15 patients and a mixture of high and intermediate in four patients. In 14 patients for whom contrast-enhanced images were available, ring enhancement (n=5), heterogeneous diffuse enhancement (n=5), and homogeneous enhancement (n=4) were seen. The mean ADC value was 0.98 × 10-3 mm2/s. Compared to other EOM diseases of non-thyroid origin, single muscular presentation, focal discrete morphology, the presence of hyperintensity on T2-weighted images, and ring or heterogeneous enhancement were significantly more frequent in EOM metastases. CONCLUSION: The MRI features of EOM metastases showed two main patterns: a single discrete mass and multiple infiltrative masses. In addition to the presentation as a single discrete mass, the presence of hyperintensity on T2-weighted images and ring or heterogeneous enhancement can aid in the differentiation of EOM metastases from other EOM diseases.

CHEMORESISTANCE RELATED TO HYPOXIA ADAPTATION IN MESOTHELIOMA CELLS FROM TUMOR SPHEROIDS.

BACKGROUND: Hypoxia has been noted as a key factor for induction and maintenance of cancer stemness thereby leading to therapy resistance. Three-dimensional (3D) spheroid models demonstrate a heterogeneity of hypoxic regions replicating the in vivo situation within tumors. Utilizing an established 3D spheroid model, we investigated whether extrinsic hypoxia reinforced chemoresistance in malignant pleural mesothelioma (MPM) spheroids. MATERIALS AND METHODS: Tumor spheres were generated from Meso-1 (a typical human MPM cell line) cells having high spheroid-forming ability. To induce hypoxia condition, we utilized a hypoxia chamber with regulation of O2 and CO2 levels. Cell viability was estimated by a WST-8 assay. Real-time polymerase chain reaction and Western blot were performed to evaluate the expression at mRNA and protein levels. RESULTS: Compared with cells cultured in the two-dimensional monolayer model, tumor sphere cells showed elevated mRNA levels of cancer stemness markers (CD26, CD44 and ABCG2) and protein levels of the stemness and hypoxia adaptation markers (ABCG2, ALDH1A1 and HIFs). Correlating with this, 3D spheroid cells were more resistant to permetrexed and topotecan than the two-dimensional cells, indicative of their potential for hypoxic adaptation. Furthermore, significantly stronger resistance to both chemotherapeutic agents was observed in spheroid cells upon hypoxic challenge compared to spheroid cells under normoxia. CONCLUSION: From the present data, it is concluded that hypoxia adaptation of MPM cells from tumor spheres could enhance their chemoresistance.

Exposure to aerosol extract from heated tobacco products causes a drastic decrease of glutathione and protein carbonylation in human lung epithelial cells.

Heated tobacco products (HTPs) are an emerging class of tobacco goods that claim to have lower health risks than those of smoking combustible tobacco products. In this study, we exposed human lung epithelial cell lines to extracts prepared from HTP aerosols and combustible cigarette smoke to compare cytotoxicity. We focused on the effects of aldehydes present in the aerosols of HTPs at levels close to those in combustible cigarette smoke. Significant toxicity was confirmed for the HTP extract, albeit to a lesser extent than that with the combustible cigarette extract. When redox balance was evaluated by the oxidative loss of low-molecular-weight thiols in the cells, we found that total glutathione (GSH) contents and low-molecular-weight thiol levels were significantly decreased after exposure to the aerosol extract of HTPs. These results indicated that GSH is rapidly consumed during the detoxification of xenobiotics, such as aldehydes from tobacco extracts. Accordingly, exposure to the aerosol extract of HTPs resulted in the enhanced carbonylation of many proteins. In a simple comparison, the results for HTPs were significantly different from those obtained with combustible cigarette smoke, suggesting reduced toxicity of HTPs. However, we found significant and harmful effects after exposing lung epithelial cells to the aerosol extract of HTPs. Thus, a further comprehensive study is needed to clarify the lung damage induced via the long-term inhalation of aerosols from HTPs.

Analysis of clinical characteristics, prognosis and antibody pathogenicity of pemphigus patients positive for anti-desmoglein IgG autoantibodies in remission: a retrospective cohort study.

BACKGROUND: The detection of serum anti-desmoglein (Dsg) IgG autoantibodies has been reported to be useful for assessment of disease activity in pemphigus. However, previous studies have reported that anti-Dsg autoantibodies remain detectable in some patients without active pemphigus lesions. OBJECTIVES: To investigate the clinical characteristics and antibody pathogenicity of pemphigus patients positive for anti-Dsg IgG autoantibodies in remission. METHODS: We retrospectively investigated pemphigus patients with a history of clinical remission who visited the Department of Dermatology of Keio University during 2019 and 2020. The antibody pathogenicity was assessed by bead aggregation assay. RESULTS: When patients were recognized as having entered remission (PDAI = 0 and PSL ≦ 10 mg/day for 2 months), serum autoantibodies against Dsg were detected in 72 of 132 patients (54.5%, positive group; PG), but were not detected in 60 patients (45.5%, negative group; NG). Anti-Dsg antibody titres in remission declined from the active phase in 33 patients in the PG for whom data were available. There were no differences in the chance of reducing PSL to 5 mg/day (P = 0.885) and rate of relapse (P = 0.279) between PG and NG, but fewer patients in PG discontinued corticosteroids (P = 0.004). The ability of patients' sera to block aggregation of Dsg/desmocollin beads was significantly reduced in remission compared to the active phase. However, our results revealed that whole sera in remission still had pathogenic activity in seven of nine patients, and the approximately equal amounts of anti-Dsg antibodies in active phase and remission showed similar pathogenicity. CONCLUSIONS: This study will provide guidance in cases where autoantibodies are found to be positive in pemphigus patients during remission or steroid reduction.

A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer's Disease.

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the "ATN" (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer's disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aß1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

Bayesian Estimation of CBF Measured by DSC-MRI in Patients with Moyamoya Disease: Comparison with 15O-Gas PET and Singular Value Decomposition.

BACKGROUND AND PURPOSE: CBF analysis of DSC perfusion using the singular value decomposition algorithm is not accurate in patients with Moyamoya disease. This study compared the Bayesian estimation of CBF against the criterion standard PET and singular value decomposition methods in patients with Moyamoya disease. MATERIALS AND METHODS: Nineteen patients with Moyamoya disease (10 women; 22-52 years of age) were evaluated with both DSC and 15O-gas PET within 60 days. DSC-CBF maps were created using Bayesian analysis and 3 singular value decomposition analyses (standard singular value decomposition, a block-circulant deconvolution method with a fixed noise cutoff, and a block-circulant deconvolution method that adopts an occillating noise cutoff for each voxel according to the strength of noise). Qualitative and quantitative analyses of the Bayesian-CBF and singular value decomposition-CBF methods were performed against 15O-gas PET and compared with each other. RESULTS: In qualitative assessments of DSC-CBF maps, Bayesian-CBF maps showed better visualization of decreased CBF on PET (sensitivity = 62.5%, specificity = 100%, positive predictive value = 100%, negative predictive value = 78.6%) than a block-circulant deconvolution method with a fixed noise cutoff and a block-circulant deconvolution method that adopts an oscillating noise cutoff for each voxel according to the strength of noise (P < .03 for all except for specificity). Quantitative analysis of CBF showed that the correlation between Bayesian-CBF and PET-CBF values (ρ = 0.46, P < .001) was similar among the 3 singular value decomposition methods, and Bayesian analysis overestimated true CBF (mean difference, 47.28 mL/min/100 g). However, the correlation between CBF values normalized to the cerebellum was better in Bayesian analysis (ρ = 0.56, P < .001) than in the 3 singular value decomposition methods (P < .02). CONCLUSIONS: Compared with previously reported singular value decomposition algorithms, Bayesian analysis of DSC perfusion enabled better qualitative and quantitative assessments of CBF in patients with Moyamoya disease.

Decreased regional cerebral blood flow in patients with diphenylarsinic acid intoxication.

BACKGROUND AND PURPOSE: Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar-brainstem and temporo-occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA-contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single-photon emission computed tomography (CBF-SPECT). METHODS: The DPAA-exposed inhabitants (n = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high-performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF-SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF-SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects. RESULTS: Compared with control subjects, CBF in symptomatic DPAA-exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF. CONCLUSION: These data suggest that CBF-SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.

Differential interference contrast microscopy for cells using hard x-ray holography.

We propose a differential interference contrast method for cells using hard x-ray Gabor holography and knife-edge filtering in the spatial frequency domain, without relying on beam shearing. A phase object is holographically recorded and reconstructed by computer. Interference between the wavefronts of zeroth order weighted by ejπ/2 in the positive frequency region produces a dark image. Similarly, interference between the wavefronts of the zeroth order weighted by ej3π/2 in the negative frequency region produces a bright image. By adding these two intensity distributions, good quality phase-contrast images of 8-µm-diameter polystyrene beads and human HeLa cells were obtained.

Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

The comparative anatomy of the folds, fossae, and adhesions around the duodenojejunal flexure in mammals.

BACKGROUND: Anatomical knowledge of the duodenojejunal flexure is necessary for abdominal surgeries, and also important for physiologic studies about the duodenum. But little is known about the anatomy of this region in mammals. Here, we examined comparative anatomy to understand the anatomical formation of the duodenojejunal flexure in mammals. MATERIALS AND METHODS: The areas around the duonenojejunal flexure were ob-served in mouse, rat, dog, pig, and human, and the anatomical structures around the duodenojejunal junction in the animals were compared with those in human. RESULTS: The superior and inferior duodenal folds, and the superior and inferior duodenal fossae were identified in all examined humans. In pig, the structures were not clearly identified because the duodenum strongly adhered to the retroperitoneum and to the mesocolon. In mouse, rat, and dog, only the plica duodenocolica, which is regarded as the animal counterpart of the superior duo-denal fold in human, was identified, and other folds or fossae were not observed, probably because the duodenum was not fixed to the parietal peritoneum in those animals. Transection of the plica duodenocolica could return the normally rotated intestine back to the state of non-rotation in rat. CONCLUSIONS: This study showed the anatomical similarities and dissimilarities of the duodenojejunal flexure among the mammals. Anatomical knowledge of the area is useful for duodenal and pancreatic surgeries, and for animal studies about the duodenum. (Folia Morphol 2018; 77, 2: 286-292).

Contact urticaria syndrome with IgE antibody against a cefotiam-unique structure, evoked by nonapparent exposure to cefotiam.

A 26-year-old woman presented with recurrent attacks of widespread urticaria and systemic symptoms. The patient was a nurse, and the attacks occurred only in her workplace, without an apparent trigger. A patch test to cefotiam (CTM) induced an immediate skin reaction. ELISA detected the patient's serum IgE antibody binding to CTM conjugated with human serum albumin (CTM-HSA), and her basophils released histamine in response to CTM-HSA in a histamine release assay (HRA). Both reactions in ELISA and HRA were inhibited by pretreatment of the patient's serum or basophils with cefotiam. No crossreactivity in skin tests or in vitro assays was observed against other antibiotics, even those containing a beta-lactam ring and/or side chains similar to CTM. Certain antibiotics including CTM may cause extremely sensitive and specific contact urticaria syndrome, which is mediated by IgE and evoked even without apparent skin contact with the culprit drug and in the absence of any history of an allergic reaction against other antibiotics with similar structures.

Hard x-ray photoemission study of Yb1-x Zr x B12: the effects of electron doping on the Kondo insulator YbB12.

We have carried out hard x-ray photoemission spectroscopy (HAXPES) of Yb1-x Zr x B12 ([Formula: see text]) to study the effects of electron doping on the Kondo insulator YbB12. The Yb valences of Yb1-x Zr x B12 at 300 K estimated from the Yb 3d HAXPES spectra decreased after substituting Yb with Zr from 2.93 for YbB12 to 2.83 for Yb0.125Zr0.875B12. A temperature dependent valence decrease was found upon cooling for all doping concentrations. We found peak shifts of the B 1s and Zr 3d5/2, and Yb3+ 4f spectra toward the deeper binding-energy with increasing Zr concentration, which indicates a shift of the Fermi level to the higher energy and that of the Yb 4f hole level close to the Fermi level, respectively, due to electron doping. These results qualitatively show the enhanced hybridization between the Yb 4f and conduction-band states with Zr substitution, consistent with magnetic susceptibility measurements.

Noninvasive Evaluation of CBF and Perfusion Delay of Moyamoya Disease Using Arterial Spin-Labeling MRI with Multiple Postlabeling Delays: Comparison with 15O-Gas PET and DSC-MRI.

BACKGROUND AND PURPOSE: Arterial spin-labeling MR imaging with multiple postlabeling delays has a potential to evaluate various hemodynamic parameters. To clarify whether arterial spin-labeling MR imaging can identify CBF and perfusion delay in patients with Moyamoya disease, we compared arterial spin-labeling, DSC, and 15O-gas PET in terms of their ability to identify these parameters. MATERIALS AND METHODS: Eighteen patients with Moyamoya disease (5 men, 13 women; ages, 21-55 years) were retrospectively analyzed. CBF values of pulsed continuous arterial spin-labeling using 2 postlabeling delays (short arterial spin-labeling, 1525 ms; delayed arterial spin-labeling, 2525 ms) were compared with CBF values measured by 15O-gas PET. All plots were divided into 2 groups by the cutoff of time-based parameters (the time of the maximum observed concentration, TTP, MTT, delay of MTT to cerebellum, and disease severity [symptomatic or not]). The ratio of 2 arterial spin-labeling CBFs (delayed arterial spin-labeling CBF to short arterial spin-labeling CBF) was compared with time-based parameters: time of the maximum observed concentration, TTP, and MTT. RESULTS: The short arterial spin-labeling-CBF values were significantly correlated with the PET-CBF values (r = 0.63; P = .01). However, the short arterial spin-labeling-CBF value dropped in the regions with severe perfusion delay. The delayed arterial spin-labeling CBF overestimated PET-CBF regardless of the degree of perfusion delay. Delayed arterial spin-labeling CBF/short arterial spin-labeling CBF was well correlated with the time of the maximum observed concentration, TTP, and MTT (ρ = 0.71, 0.64, and 0.47, respectively). CONCLUSIONS: Arterial spin-labeling using 2 postlabeling delays may detect PET-measured true CBF and perfusion delay in patients with Moyamoya disease. Provided its theoretic basis and limitations are considered, noninvasive arterial spin-labeling could be a useful alternative for evaluating the hemodynamics of Moyamoya disease.

Clinical application of apparent diffusion coefficient mapping in voxel-based morphometry in the diagnosis of Alzheimer's disease.

AIM: To evaluate the performance of apparent diffusion coefficient (ADC) mapping compared with voxel-based morphometry and to demonstrate the clinical usefulness of ADC mapping in the diagnosis of Alzheimer's disease (AD). MATERIALS AND METHODS: The study population comprised 31 patients with AD (group A) and 24 patients without dementia (group B) who underwent three-dimensional (3D) T1-weighted imaging (WI) and two-dimensional (2D) echo-planar diffusion-weighted imaging (DWI) at 3 T. The volume and ADC of the regional grey matter (GM) in the bilateral hippocampi, precunei, and the anterior and posterior cingulate gyri were calculated using a voxel-based method for automatic segmentation of brain structures. The significance of intergroup differences in each volume and ADC of all regional GM was tested using analysis of variance (ANOVA) with Bonferroni correction. Intergroup regional GM differences in each volume and ADC were evaluated using statistical parametric mapping (SPM). RESULTS: In group A, the volumes of the precunei (mean value: group A/B=18.93/21.48 cm3) and the anterior cingulate gyri (mean value: group A/B=6.1/7.81 cm3) were significantly less than in group B (p<0.05). The ADC in group A was significantly larger than that in group B in the bilateral hippocampi (mean value: group A/B=right 1020.79×10-6/877.23×10-6 mm2/s; left 1072.89×10-6/900.2×10-6 mm2/s) and posterior cingulate gyri (mean value: group A/B=1006.77×10-6/876.88×10-6 mm2/s; p<0.05). SPM showed that the areas of increased ADC were more extensive than the areas of decreased volume in the bilateral hippocampi, precunei, and posterior cingulate gyri in group A, compared with those in group B (p<0.001). CONCLUSION: Evaluation of ADC mapping can quantify changes in brain water diffusivity and may improve the performance of automatic morphometric diagnosis of AD.

Geographic distribution and environmental control of vertebral count in Ammodytes spp. along the northern Pacific coast of Japan.

To examine species composition and population structures in sand lance (Ammodytidae) along the northern Pacific coast of Japan, genetic analysis were carried out for specimens collected in 2014 from Otsuchi Bay, Iwate, Ishinomaki Bay, Miyagi, off Soma, Fukushima and Ise-Mikawa Bays, Aichi. The samples consisted of Ammodytes japonicus and Ammodytes heian, of which the latter is a recently described species. Neither species exhibited significant genetic differences among localities. Only A. japonicus was found in the most southern locality at Aichi, but it decreased northward to <90% in Miyagi and Fukushima and the two species occurred almost evenly in Iwate suggesting a latitudinal cline in their species composition along the northern Pacific coast of Japan, off Tohoku. The vertebral counts differed between A. japonicus and A. heian with modes of 65 and 63, respectively, but this characteristic did not differ significantly within a locality (Iwate). This suggests that the vertebral counts of Ammodytes spp. in Japanese waters are probably strongly determined by the environment than by a species-specific genetic trait.