Computational modeling of multiscale collateral blood supply in a whole-brain-scale arterial network.

The cerebral arterial network covering the brain cortex has multiscale anastomosis structures with sparse intermediate anastomoses (O[102] µm in diameter) and dense pial networks (O[101] µm in diameter). Recent studies indicate that collateral blood supply by cerebral arterial anastomoses has an essential role in the prognosis of acute ischemic stroke caused by large vessel occlusion. However, the physiological importance of these multiscale morphological properties-and especially of intermediate anastomoses-is poorly understood because of innate structural complexities. In this study, a computational model of multiscale anastomoses in whole-brain-scale cerebral arterial networks was developed and used to evaluate collateral blood supply by anastomoses during middle cerebral artery occlusion. Morphologically validated cerebral arterial networks were constructed by combining medical imaging data and mathematical modeling. Sparse intermediate anastomoses were assigned between adjacent main arterial branches; the pial arterial network was modeled as a dense network structure. Blood flow distributions in the arterial network during middle cerebral artery occlusion simulations were computed. Collateral blood supply by intermediate anastomoses increased sharply with increasing numbers of anastomoses and provided one-order-higher flow recoveries to the occluded region (15%-30%) compared with simulations using a pial network only, even with a small number of intermediate anastomoses (≤10). These findings demonstrate the importance of sparse intermediate anastomoses, which are generally considered redundant structures in cerebral infarction, and provide insights into the physiological significance of the multiscale properties of arterial anastomoses.

Chloroquine regulates the lipopolysaccharide-induced inflammatory response in RAW264.7 cells.

INTRODUCTION AND OBJECTIVES: Macrophage-induced inflammation plays a key role in defense against injury and harmful pathogens. Autophagy and the inflammatory response are associated; however, the relationship between the autophagy pathway and lipopolysaccharide (LPS)- induced inflammatory responses remains unknown. We aimed to determine the effect of autophagy on the LPS-induced myeloid differentiation factor 88 (MyD88)/nuclear transcription factor kB (NF-kB) pathway-mediated inflammatory response in RAW264.7 cells. MATERIALS AND METHODS: To determine the effect of autophagy on the LPS-induced inflammatory response, using various in vitro assays, we determined the effect of autophagy inhibitors and inducers on the inflammatory response in RAW264.7 cells. RESULTS: Chloroquine (CQ), an autophagy inhibitor, suppressed pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNFα) in LPS-stimulated RAW264.7 cells. CQ also affected inflammatory mediators such as myeloid differentiation factor 88 and NF-kB in LPS-stimulated RAW264.7 cells. CONCLUSION: This study demonstrated that CQ regulates the LPS-induced inflammatory response in RAW264.7 cells. We propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators using CQ is a promising therapeutic approach for preventing inflammatory injury. CQ serves as a potential therapeutic target for treating various inflammatory diseases.

The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.

Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed-all-nominated-in-one-BRCA (MANO-B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition.

Spatial-photonic Ising machine by space-division multiplexing with physically tunable coefficients of a multi-component model.

This paper proposes a space-division multiplexed spatial-photonic Ising machine (SDM-SPIM) that physically calculates the weighted sum of the Ising Hamiltonians for individual components in a multi-component model. Space-division multiplexing enables tuning a set of weight coefficients as an optical parameter and obtaining the desired Ising Hamiltonian at a time. We solved knapsack problems to verify the system's validity, demonstrating that optical parameters impact the search property. We also investigated a new dynamic coefficient search algorithm to enhance search performance. The SDM-SPIM would physically calculate the Hamiltonian and a part of the optimization with an electronics process.

Low-Rank Combinatorial Optimization and Statistical Learning by Spatial Photonic Ising Machine.

The spatial photonic Ising machine (SPIM) [13D. Pierangeli et al., Large-Scale Photonic Ising Machine by Spatial Light Modulation, Phys. Rev. Lett. 122, 213902 (2019).PRLTAO0031-900710.1103/PhysRevLett.122.213902] is a promising optical architecture utilizing spatial light modulation for solving large-scale combinatorial optimization problems efficiently. The primitive version of the SPIM, however, can accommodate Ising problems with only rank-one interaction matrices. In this Letter, we propose a new computing model for the SPIM that can accommodate any Ising problem without changing its optical implementation. The proposed model is particularly efficient for Ising problems with low-rank interaction matrices, such as knapsack problems. Moreover, it acquires the learning ability of Boltzmann machines. We demonstrate that learning, classification, and sampling of the MNIST handwritten digit images are achieved efficiently using the model with low-rank interactions. Thus, the proposed model exhibits higher practical applicability to various problems of combinatorial optimization and statistical learning, without losing the scalability inherent in the SPIM architecture.

In Vitro Phagocytosis of Different Dinoflagellate Species by Coral Cells.

Coral-dinoflagellate symbiosis is a unique biological phenomenon, in which animal cells engulf single-celled photosynthetic algae and maintain them in their cytoplasm mutualistically. Studies are needed to reveal the complex mechanisms involved in symbiotic processes, but it is difficult to answer these questions using intact corals. To tackle these issues, our previous studies established an in vitro system of symbiosis between cells of the scleractinian coral Acropora tenuis and the dinoflagellate Breviolum minutum, and showed that corals direct phagocytosis, while algae are likely engulfed by coral cells passively. Several genera of the family Symbiodiniaceae can establish symbioses with corals, but the symbiotic ratio differs depending on the dinoflagellate clades involved. To understand possible causes of these differences, this study examined whether cultured coral cells show phagocytotic activity with various dinoflagellate strains similar to those shown by intact A. tenuis. We found that (a) A. tenuis larvae incorporate Symbiodinium and Breviolum, but not Cladocopium, and very few Effrenium, (b) cultured coral cells engulfed all four species but the ratio of engulfment was significantly higher with Symbiodinium and Breviolum than Cladocopium and Effrenium, (c) cultured coral cells also phagocytosed inorganic latex beads differently than they do dinoflagellates . It is likely that cultured coral cells preferentially phagocytose Symbiodinium and Breviolum, suggesting that specific molecular mechanisms involved in initiation of symbiosis should be investigated in the future.

Computer-aided detection improves brain metastasis identification on non-enhanced CT in less experienced radiologists.

BACKGROUND: Brain metastases (BMs) are the most common intracranial tumors causing neurological complications associated with significant morbidity and mortality. PURPOSE: To evaluate the effect of computer-aided detection (CAD) on the performance of observers in detecting BMs on non-enhanced computed tomography (NECT). MATERIAL AND METHODS: Three less experienced and three experienced radiologists interpreted 30 NECT scans with 89 BMs in 25 cases to detect BMs with and without the assistance of CAD. The observers' sensitivity, number of false positives (FPs), positive predictive value (PPV), and reading time with and without CAD were compared using paired t-tests. The sensitivity of CAD and the observers were compared using a one-sample t-test. RESULTS: With CAD, less experienced radiologists' sensitivity significantly increased from 27.7% ± 4.6% to 32.6% ± 4.8% (P = 0.007), while the experienced radiologists' sensitivity did not show a significant difference (from 33.3% ± 3.5% to 31.9% ± 3.7%; P = 0.54). There was no significant difference between conditions with CAD and without CAD for FPs (less experienced radiologists: 23.0 ± 10.4 and 25.0 ± 9.3; P = 0.32; experienced radiologists: 18.3 ± 7.4 and 17.3 ± 6.7; P = 0.76) and PPVs (less experienced radiologists: 57.9% ± 8.3% and 50.9% ± 7.0%; P = 0.14; experienced radiologists: 61.8% ± 12.7% and 64.0% ± 12.1%; P = 0.69). There were no significant differences in reading time with and without CAD (85.0 ± 45.6 s and 73.7 ± 36.7 s; P = 0.09). The sensitivity of CAD was 47.2% (with a PPV of 8.9%), which was significantly higher than that of any radiologist (P < 0.001). CONCLUSION: CAD improved BM detection sensitivity on NECT without increasing FPs or reading time among less experienced radiologists, but this was not the case among experienced radiologists.

Antiproliferative Effect of N-Heterocyclo-Coumarin Derivatives against Multidrug-Resistant Cells.

Chemotherapy refers principally to the use of small molecules to treat cancer, and natural product derivatives have been main sources of clinically using anticancer drugs. While the coumarin skeleton does not inhibit cell growth, its derivatives are often active, and numerous coumarins have been examined for antiproliferative activity against human cancer cell lines. In this study, 16 novel coumarin derivatives (1, 1a-5a, 1b, 2b, 6b, 7b, 8-13) with attached N-heterocycles, including aminopyrrolidine, aminopiperidine, aminoazepane, and indoline, were prepared and ultimately esterified or amidated with alcohols or amines, respectively. All synthesized N-heterocycles containing coumarin derivatives with alcohols, amines, and carboxylic acids were assessed for antiproliferative activity against several human cancer cell lines, containing triple-negative breast cancer (TNBC) as well as a P-glycoprotein (P-gp) overexpressing multidrug-resistant (MDR) KB subline KB-VIN. Five coumarin derivatives (3a-5a, 12, 13) showed no effect (IC50 >40 µM) against all tested cell lines. In contrast, derivative 1a showed broad-spectrum activity against four cell lines, while 1b and 10 were nearly twice as selective for KB-VIN cells as the parent KB. The coumarin derivatives 1a, 1b, and 10 were optimal for antiproliferative activity in this study and could provide a new avenue for overcoming MDR tumors. Derivatives 1a, 1b, and 10 showed MDR cell-selective antiproliferative activity, indicating that N-heterocycle-coumarins exert previously unexplored bioactivity with selective action on MDR cancer cells.

Eighteen Coral Genomes Reveal the Evolutionary Origin of Acropora Strategies to Accommodate Environmental Changes.

The genus Acropora comprises the most diverse and abundant scleractinian corals (Anthozoa, Cnidaria) in coral reefs, the most diverse marine ecosystems on Earth. However, the genetic basis for the success and wide distribution of Acropora are unknown. Here, we sequenced complete genomes of 15 Acropora species and 3 other acroporid taxa belonging to the genera Montipora and Astreopora to examine genomic novelties that explain their evolutionary success. We successfully obtained reasonable draft genomes of all 18 species. Molecular dating indicates that the Acropora ancestor survived warm periods without sea ice from the mid or late Cretaceous to the Early Eocene and that diversification of Acropora may have been enhanced by subsequent cooling periods. In general, the scleractinian gene repertoire is highly conserved; however, coral- or cnidarian-specific possible stress response genes are tandemly duplicated in Acropora. Enzymes that cleave dimethlysulfonioproprionate into dimethyl sulfide, which promotes cloud formation and combats greenhouse gasses, are the most duplicated genes in the Acropora ancestor. These may have been acquired by horizontal gene transfer from algal symbionts belonging to the family Symbiodiniaceae, or from coccolithophores, suggesting that although functions of this enzyme in Acropora are unclear, Acropora may have survived warmer marine environments in the past by enhancing cloud formation. In addition, possible antimicrobial peptides and symbiosis-related genes are under positive selection in Acropora, perhaps enabling adaptation to diverse environments. Our results suggest unique Acropora adaptations to ancient, warm marine environments and provide insights into its capacity to adjust to rising seawater temperatures.

Deep-learning 2.5-dimensional single-shot detector improves the performance of automated detection of brain metastases on contrast-enhanced CT.

PURPOSE: This study aims to develop a 2.5-dimensional (2.5D) deep-learning, object detection model for the automated detection of brain metastases, into which three consecutive slices were fed as the input for the prediction in the central slice, and to compare its performance with that of an ordinary 2-dimensional (2D) model. METHODS: We analyzed 696 brain metastases on 127 contrast-enhanced computed tomography (CT) scans from 127 patients with brain metastases. The scans were randomly divided into training (n = 79), validation (n = 18), and test (n = 30) datasets. Single-shot detector (SSD) models with a feature fusion module were constructed, trained, and compared using the lesion-based sensitivity, positive predictive value (PPV), and the number of false positives per patient at a confidence threshold of 50%. RESULTS: The 2.5D SSD model had a significantly higher PPV (t test, p < 0.001) and a significantly smaller number of false positives (t test, p < 0.001). The sensitivities of the 2D and 2.5D models were 88.1% (95% confidence interval [CI], 86.6-89.6%) and 88.7% (95% CI, 87.3-90.1%), respectively. The corresponding PPVs were 39.0% (95% CI, 36.5-41.4%) and 58.9% (95% CI, 55.2-62.7%), respectively. The numbers of false positives per patient were 11.9 (95% CI, 10.7-13.2) and 4.9 (95% CI, 4.2-5.7), respectively. CONCLUSION: Our results indicate that 2.5D deep-learning, object detection models, which use information about the continuity between adjacent slices, may reduce false positives and improve the performance of automated detection of brain metastases compared with ordinary 2D models.

The Usefulness of Computer-Aided Detection of Brain Metastases on Contrast-Enhanced Computed Tomography Using Single-Shot Multibox Detector: Observer Performance Study.

OBJECTIVE: This study aimed to test the usefulness of computer-aided detection (CAD) for the detection of brain metastasis (BM) on contrast-enhanced computed tomography. METHODS: The test data set included whole-brain axial contrast-enhanced computed tomography images of 25 cases with 62 BMs and 5 cases without BM. Six radiologists from 3 institutions with 2 to 4 years of experience independently reviewed the cases, both in conditions with and without CAD assistance. Sensitivity, positive predictive value, number of false positives, and reading time were compared between the conditions using paired t tests. Subanalysis was also performed for groups of lesions divided according to size. A P value <0.05 was considered statistically significant. RESULTS: With CAD, sensitivity significantly increased from 80.4% to 83.9% ( P = 0.04), whereas positive predictive value significantly decreased from 88.7% to 84.8% ( P = 0.03). Reading time with and without CAD was 112 and 107 seconds, respectively ( P = 0.38), and the number of false positives was 10.5 with CAD and 7.0 without CAD ( P = 0.053). Sensitivity significantly improved for 6- to 12-mm lesions, from 71.2% without CAD to 80.3% with CAD ( P = 0.02). The sensitivity of the CAD (95.2%) was significantly higher than that of any reader (with CAD: P = 0.01; without CAD: P = 0.005). CONCLUSIONS: Computer-aided detection significantly improved BM detection sensitivity without prolonging reading time while marginally increased the false positives.

Unique environmental Symbiodiniaceae diversity at an isolated island in the northwestern Pacific.

Dinoflagellates in the family Symbiodiniaceae are intensively investigated as algal symbionts of corals and other invertebrates, underpinning coral reef ecosystems as primary producers. Diversity, including regional diversification, of free-living communities is less studied. In this study, an environmental Symbiodiniaceae community at an isolated island, Okinotori Island, Japan, was investigated to determine whether the community is endemic or common with other locations near continents and major ocean currents. Symbiotic algae in common corals at the island were the same type as those of the corals from other Japanese waters. In the environmental samples, genera Symbiodinium (formerly clade A), Cladocopium (clade C), Durusdinium (clade D), and clades F (including Freudenthalidium), G, and I, were identified through analysis of internal transcribed spacer region 2 of nuclear ribosomal RNA gene (ITS2) sequences. Interestingly, some sequences found were genetically different from those of previously reported genera/clades. These unknown sequences were genetically included in the Symbiodiniaceae linage, but they were differentiated from the previously known nine clades. The sequences formed a cluster in the phylogenetic tree based on 28S nrDNA. These sequences were thus considered members of a novel clade in the family (clade J). In total, 120 kinds of ITS2 sequences were produced; while 10 were identical to previously reported sequences, the majority were highly divergent. These genetically unique Symbiodiniaceae types, including novel clade J, may have evolved in isolation and reflect the environmental characteristics of the Okinotori Island.

FXTAS is difficult to differentiate from neuronal intranuclear inclusion disease through skin biopsy: a case report.

BACKGROUND: Both fragile X-associated tremor/ataxia syndrome (FXTAS) and late-onset neuronal intranuclear inclusion disease (NIID) show CGG/GGC trinucleotide repeat expansions. Differentiating these diseases are difficult because of the similarity in their clinical and radiological features. It is unclear that skin biopsy can distinguish NIID from FXTAS. We performed a skin biopsy in an FXTAS case with cognitive dysfunction and peripheral neuropathy without tremor, which was initially suspected to be NIID. CASE PRESENTATION: The patient underwent neurological assessment and examinations, including laboratory tests, electrophysiologic test, imaging, skin biopsy, and genetic test. A brain MRI showed hyperintensity lesions along the corticomedullary junction on diffusion-weighted imaging (DWI) in addition to middle cerebellar peduncle sign (MCP sign). We suspected NIID from the clinical picture and the radiological findings, and performed a skin biopsy. The skin biopsy specimen showed ubiquitin- and p62-positive intranuclear inclusions, suggesting NIID. However, a genetic analysis for NIID using repeat-primed polymerase chain reaction (RP-PCR) revealed no expansion detected in the Notch 2 N-terminal like C (NOTCH2NLC) gene. We then performed genetic analysis for FXTAS using RP-PCR, which revealed a repeat CGG/GGC expansion in the FMRP translational regulator 1 (FMR1) gene. The number of repeats was 83. We finally diagnosed the patient with FXTAS rather than NIID. CONCLUSIONS: For the differential diagnosis of FXTAS and NIID, a skin biopsy alone is insufficient; instead, genetic analysis, is essential. Further investigations in additional cases based on genetic analysis are needed to elucidate the clinical and pathological differences between FXTAS and NIID.

Automated detection of brain metastases on non-enhanced CT using single-shot detectors.

PURPOSE: To develop and investigate deep learning-based detectors for brain metastases detection on non-enhanced (NE) CT. METHODS: The study included 116 NECTs from 116 patients (81 men, age 66.5 ± 10.6 years) to train and test single-shot detector (SSD) models using 89 and 27 cases, respectively. The annotation was performed by three radiologists using bounding-boxes defined on contrast-enhanced CT (CECT) images. NECTs were coregistered and resliced to CECTs. The detection performance was evaluated at the SSD's 50% confidence threshold using sensitivity, positive-predictive value (PPV), and the false-positive rate per scan (FPR). For false negatives and true positives, binary logistic regression was used to examine the possible contributing factors. RESULTS: For lesions 6 mm or larger, the SSD achieved a sensitivity of 35.4% (95% confidence interval (CI): [32.3%, 33.5%]); 51/144) with an FPR of 14.9 (95% CI [12.4, 13.9]). The overall sensitivity was 23.8% (95% CI: [21.3%, 22.8%]; 55/231) and PPV was 19.1% (95% CI: [18.5%, 20.4%]; 98/ of 513), with an FPR of 15.4 (95% CI [12.9, 14.5]). Ninety-five percent of the lesions that SSD failed to detect were also undetectable to radiologists (168/176). Twenty-four percent of the lesions (13/50) detected by the SSD were undetectable to radiologists. Logistic regression analysis indicated that density, necrosis, and size contributed to the lesions' visibility for radiologists, while for the SSD, the surrounding edema also enhanced the detection performance. CONCLUSION: The SSD model we developed could detect brain metastases larger than 6 mm to some extent, a quarter of which were even retrospectively unrecognizable to radiologists.

N-Acetyl-d-Glucosamine-Binding Lectin in Acropora tenuis Attracts Specific Symbiodiniaceae Cell Culture Strains.

Many corals establish symbiosis with Symbiodiniaceae cells from surrounding environments, but very few Symbiodiniaceae cells exist in the water column. Given that the N-acetyl-d-glucosamine-binding lectin ActL attracts Symbiodiniaceae cells, we hypothesized that corals must attract Symbiodiniaceae cells using ActL to acquire them. Anti-ActL antibody inhibited acquisition of Symbiodiniaceae cells, and rearing seawater for juvenile Acropora tenuis contained ActL, suggesting that juvenile A. tenuis discharge ActL to attract these cells. Among eight Symbiodiniaceae cultured strains, ActL attracted NBRC102920 (Symbiodinium tridacnidorum) most strongly followed by CS-161 (Symbiodinium tridacnidorum), CCMP2556 (Durusdinium trenchii), and CCMP1633 (Breviolum sp.); however, it did not attract GTP-A6-Sy (Symbiodinium natans), CCMP421 (Effrenium voratum), FKM0207 (Fugacium sp.), and CS-156 (Fugacium sp.). Juvenile polyps of A. tenuis acquired limited Symbiodiniaceae cell strains, and the number of acquired Symbiodiniaceae cells in a polyp also differed from each other. The number of Symbiodiniaceae cells acquired by juvenile polyps of A. tenuis was correlated with the ActL chemotactic activity. Thus, ActL could be used to attract select Symbiodiniaceae cells and help Symbiodiniaceae cell acquisition in juvenile polyps of A. tenuis, facilitating establishment of symbiosis between A. tenuis and Symbiodiniaceae cells.

Comparison of the benefits and hemodynamic side effects of oxytocin between intravenous infusion with and without bolus injection during caesarean section.

The aim of this study was to compare the benefits and hemodynamic side effects of oxytocin between intravenous infusion with and without a bolus injection during a caesarean section. Women with singleton pregnancies who underwent caesarean sections under spinal anaesthesia were included. Oxytocin was administered by an iv bolus injection (5 U) followed by an intravenous infusion (10 U of oxytocin in 500 mL normal saline); this was switched to just an intravenous infusion. The amount of blood loss did not differ between the groups. In a multivariate analysis, the adjusted odds ratios for the risk of hypotension (≥20% reduction of systolic BP) and tachycardia (heart rate ≥100 bpm) were 4.5 (95% confidence interval [CI], 1.6-12.5) and 3.7 (95%CI 1.9-7.2) in the iv bolus group, respectively, compared with the just the infusion group. The oxytocin administration by iv bolus injection did not decrease blood loss and increased the rate of hemodynamic side effects.Impact statementWhat is already known on this subject? Oxytocin is used as the first-line uterotonic treatment to prevent a postpartum haemorrhage in women undergoing Caesarean Sections. Oxytocin is known to relax vascular smooth muscle, which can cause hypotension and tachycardia. The protocols for administering oxytocin during CS vary by institution.What do the results of this study add? Combined treatment with oxytocin by iv bolus injection (5 U) followed by iv infusion (10 U of oxytocin in 500 mL normal saline) during CS increased the risk of developing adverse hemodynamic side effects, including hypotension, tachycardia, and the need for vasopressors, without any benefit in the control of intraoperative blood loss in comparison to iv infusion alone.What are the implications of these findings for clinical practice and/or further research? We should abandon the iv bolus injection of oxytocin during CS, especially for women undergoing an elective CS who are not in labour.

The Insular Cortex, Alzheimer Disease Pathology, and Their Effects on Blood Pressure Variability.

Recent findings indicate that the human cardiovascular system is regulated by a cortical network comprised of the insular cortex (Ic), anterior cingulate gyrus, and amygdala which is necessary for the regulation of the central autonomic network system. Alzheimer disease (AD) affects the Ic at a preclinical stage. The pathology of AD at the Ic is suggested to predispose the cardiovascular system to detrimental changes such as increased blood pressure variability (BPV). In this review article, we focus on the physiology of the Ic in the relationship between the central autonomic network and BPV. We provide a summary of the published evidence regarding the relationship between Ic damage and exaggerated BPV in the context of AD pathology.

Fetal sex and maternal insulin resistance during mid-pregnancy: a retrospective cohort study.

BACKGROUND: Recent studies have suggested that fetal sex influences maternal glucose and insulin metabolism during pregnancy. We examined whether fetal sex is associated with maternal insulin resistance and the ß-cell function during mid-pregnancy. METHODS: This retrospective study included singleton pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) at 24-34 weeks of gestation due to positive diabetic screening. In addition to plasma glucose (PG), we measured plasma insulin during the OGTT to obtain surrogate indices associated with insulin resistance (IR), including homeostasis assessment model (HOMA) -IR and insulin sensitivity index (IsOGTT), and ß-cell function, including insulinogenic index (II), HOMA-ß, and area under the curve of insulin response. We compared these indices between women carrying male fetuses to those carrying female fetuses. RESULTS: The study population included 617 women (mean age, 32.4 ± 4.9 years) with a mean pre-pregnancy body mass index (BMI) of 22.6±4.5. They underwent the 75g-OGTT at 29.0 ± 2.5 weeks. Two hundred fifty-eight (42%) women were diagnosed with gestational diabetes (GDM). There was no significant difference in maternal age, pre-pregnancy BMI, gestational age at OGTT, PG at OGTT, or the prevalence of GDM between women with a male fetus (n=338) (male group) and those with a female fetus (n=279) (female group). Regarding the indices of IR, IR was significantly higher and insulin sensitivity was lower in the female group than in the male group (HOMA-IR: 7.0 [5-9.6] vs. 6.2 [4.6-8.8], p< 0.05; IsOGTT: 5.86 [4.29-7.83] vs. 6.29 [4.59-8.84], p< 0.01) (median [quartile range]). These differences remained significant after adjustment for maternal age, pre-pregnancy BMI, gestational age and fasting PG at OGTT, and the diagnosis of GDM. In contrast, the ß-cell function did not differ between the two groups. CONCLUSION: Maternal IR during mid-pregnancy was significantly higher in women carrying a female fetus than in those with a male fetus. The sex of the fetus may affect maternal insulin sensitivity during mid-pregnancy.

Clinical characteristics of boys with comorbid autism spectrum disorder and attention deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention deficit / hyperactivity disorder (ADHD) are frequently comorbid and, as both are defined as neurodevelopmental disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, simultaneous diagnosis is possible. However, despite the frequency of this comorbid state, its endophenotypic features remain unclear. This study thus aimed to describe the behavioral and emotional problems in boys with comorbid ASD and ADHD using the Strengths and Difficulties Questionnaire (SDQ). METHODS: In total, 102 boys (age, 6-12 years) diagnosed with one or both disorders were divided into three groups according to their clinical diagnosis: ASD + ADHD (N = 39), ASD (N = 37), and ADHD (N = 25). Symptoms and related behaviors were compared among the groups using parents' ratings of the autism spectrum quotient, ADHD rating scale-IV, and SDQ. RESULTS: In the ASD + ADHD group, the proportion of "clinical-range" cases was as high as 76.9% for the SDQ total difficulties score (TDS). The ASD + ADHD and ADHD groups had significantly higher TDS as well as behavioral problems and hyperactivity subscale scores than did the ASD group; however, the ASD + ADHD group did not have significantly different scores on any subscale compared with the other two groups. The ASD + ADHD and ASD groups also had significantly lower prosocial behavior scores than the ADHD group. CONCLUSIONS: When using the SDQ as a screening tool for neurodevelopmental disorders, a high TDS, conduct problems, hyperactivity, and low prosocial behavior can be considered characteristic of ASD and ADHD comorbidity in 6- to 12-year-old boys.

Intracardiac metastasis from unknown uterine cervical cancer with severe thrombocytopenia.

INTRODUCTION: Cardiac metastasis is relatively common in malignant neoplasms, such as lung cancers, breast cancers, melanomas, lymphomas, and leukemias. In contrast, cardiac metastasis of uterine cervical cancer, solitary metastasis to the heart, and tumors inducing severe thrombocytopenia are rare. CASE REPORT: The present patient was a 52-year-old female who was diagnosed with a solitary cardiac tumor prior to uterine cervical cancer and presented with severe thrombocytopenia. Our case had two remarkable aspects: 1) successful treatment under the condition of severe thrombocytopenia in association with the presence of a cardiac tumor, and survival without recurrence of the carcinoma one year after surgery; and 2) a solitary cardiac metastatic tumor larger than the primary uterine cervix carcinoma. COMMENT: we report an extremely rare case of solitary cardiac metastasis of uterine cervical cancer, which wassuccessfully treated. One year after cardiac surgery, the patient is alive without recurrence of the carcinoma.