Spatial Similarity of MRI-Visible Perivascular Spaces in Healthy Young Adult Twins.

PURPOSE: This study aimed to determine whether genetic factors affect the location of dilated perivascular spaces (dPVS) by comparing healthy young twins and non-twin (NT) siblings. MATERIALS AND METHODS: A total of 700 healthy young adult twins and NT siblings [138 monozygotic (MZ) twin pairs, 79 dizygotic (DZ) twin pairs, and 133 NT sibling pairs] were collected from the Human Connectome Project dataset. dPVS was automatically segmented and normalized to standard space. Then, spatial similarity indices [mean squared error (MSE), structural similarity (SSIM), and dice similarity (DS)] were calculated for dPVS in the basal ganglia (BGdPVS) and white matter (WMdPVS) between paired subjects before and after propensity score matching of dPVS volumes between groups. Within-pair correlations for the regional volumes of dVPS were also assessed using the intraclass correlation coefficient. RESULTS: The spatial similarity of dPVS was significantly higher in MZ twins [higher DS (median, 0.382 and 0.310) and SSIM (0.963 and 0.887) and lower MSE (0.005 and 0.005) for BGdPVS and WMdPVS, respectively] than in DZ twins [DS (0.121 and 0.119), SSIM (0.941 and 0.868), and MSE (0.010 and 0.011)] and NT siblings [DS (0.106 and 0.097), SSIM (0.924 and 0.848), and MSE (0.016 and 0.017)]. No significant difference was found between DZ twins and NT siblings. Similar results were found even after the subjects were matched according to dPVS volume. Regional dPVS volumes were also more correlated within pairs in MZ twins than in DZ twins and NT siblings. CONCLUSION: Our results suggest that genetic factors affect the location of dPVS.

Exploring the exponential sensitivity of risk perception in the COVID-19 pandemic.

Individual's risk perception regarding specific hazards is a dynamic process that evolves over time. This study analyzed the relationship between the number of COVID-19 cases and the South Korean public's risk perceptions from the outset of the pandemic to the recent past. More than 70 repeated cross-sectional surveys were conducted biweekly to measure individuals' risk perception. An autoregressive integrated moving average with explanatory variable time series analysis was used to characterize the relationship between the number of COVID-19 cases and level of risk perceptions. It revealed that individuals' risk perception and the number of COVID-19 cases were not linearly related but were logarithmically correlated. This finding can be understood as a psychic numbing effect, suggesting that people's perception of risk is not linear but rather exponentially sensitive to changes. The findings also revealed a significant influence of individuals' trust in local governments on their risk perceptions, highlighting the substantial role played by local governments in direct risk management during the COVID-19 pandemic.

Malignancy risk stratification and subcategorization of K-TIRADS intermediate suspicion thyroid nodules: a retrospective multicenter study.

PURPOSE: This study aimed to develop the ultrasonography (US) criteria for risk stratification of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) 4 nodules, and to evaluate the diagnostic yield of a modified biopsy criterion in a multicenter cohort. METHODS: In total, 1,542 K-TIRADS 4 nodules (≥1 cm) were included in the study. US criteria for the subcategorization of K-TIRADS 4 nodules were developed based on high-risk US features. The diagnostic yields and false referral rates of biopsy criterion 1 (size cut-off of 1 cm), biopsy criterion 2 (size cut-off of 1.5 cm), and modified biopsy criterion 3 (size cut-off of 1 cm for K-TIRADS 4B and 1.5 cm for K-TIRADS 4A) were evaluated. RESULTS: The five high-risk US features (solid composition, marked hypoechogenicity, macrocalcification, punctate echogenic foci, and irregular margin) independently increased the malignancy risk of the K-TIRADS 4 nodules (P<0.001). The K-TIRADS 4 nodules could be subcategorized into higher- and lower-risk subcategories according to the number of high-risk US features: K-TIRADS 4B (≥2 US features) and K-TIRADS 4A (≤1 US feature). The modified biopsy criterion increased the diagnostic yield by 7.8% compared with criterion 2 and reduced the false referral rate by 15.3% compared with criterion 1 (P<0.001). CONCLUSION: The K-TIRADS 4 nodules were subcategorized as K-TIRADS 4B and K-TIRADS 4A based on high-risk US features. The modified biopsy criterion 3 showed a similar diagnostic yield and reduced false referral rate compared to criterion 1.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

3D printing of drug-eluting bioactive multifunctional coatings for orthopedic applications.

Three-dimensional (3D) printing is implemented for surface modification of titanium alloy substrates with multilayered biofunctional polymeric coatings. Poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL) polymers were embedded with amorphous calcium phosphate (ACP) and vancomycin (VA) therapeutic agents to promote osseointegration and antibacterial activity, respectively. PCL coatings revealed a uniform deposition pattern of the ACP-laden formulation and enhanced cell adhesion on the titanium alloy substrates as compared to the PLGA coatings. Scanning electron microscopy and Fourier-transform infrared spectroscopy confirmed a nanocomposite structure of ACP particles showing strong binding with the polymers. Cell viability data showed comparable MC3T3 osteoblast proliferation on polymeric coatings as equivalent to positive controls. In vitro live/dead assessment indicated higher cell attachments for 10 layers (burst release of ACP) as compared to 20 layers (steady release) for PCL coatings. The PCL coatings loaded with the antibacterial drug VA displayed a tunable release kinetics profile based on the multilayered design and drug content of the coatings. Moreover, the concentration of active VA released from the coatings was above the minimum inhibitory concentration and minimum bactericidal concentration, demonstrating its effectiveness against Staphylococcus aureus bacterial strain. This research provides a basis for developing antibacterial biocompatible coatings to promote osseointegration of orthopedic implants.

Bioactive Synthetic Polymer-Based Polyelectrolyte LbL Coating Assembly on Surface Treated AZ31-Mg Alloys.

Polyelectrolyte layer-by-layer (LbL) films on pretreated Mg containing 3 wt.% Al and 1 wt.% Zn (MgAZ31) alloy surfaces were prepared under physiological conditions offering improved bioresponse and corrosive protection. Pretreatments of the model MgAZ31 substrate surfaces were performed by alkaline and fluoride coating methods. The anti-corrosion and cytocompatibility behavior of pretreated substrates were evaluated. The LbL film assembly consisted of an initial layer of polyethyleneimine (PEI), followed by alternate layers of poly (lactic-co-glycolic acid) (PLGA) and poly (allylamine hydrochloride) (PAH), which self-arrange via electrostatic interactions on the pretreated MgAZ31 alloy substrate surface. The physicochemical characterization, surface morphologies, and microstructures of the LbL films were investigated using Fourier-transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The in vitro stability studies related to the LbL coatings confirmed that the surface treatments are imperative to achieve the lasting stability of PLGA/PAH layers. Electrochemical impedance spectroscopy measurements demonstrated that pretreated and LbL multilayered coated substrates enhanced the corrosion resistance of the bare MgAZ31 alloy. Cytocompatibility studies using human mesenchymal stem cells seeded directly over the substrates showed that the pretreated and LbL-generated surfaces were more cytocompatible, displaying reduced cytotoxicity than the bare MgAZ31. The release of bovine serum albumin protein from the LbL films was also studied. The initial data presented cooperatively demonstrate the promise of creating LbL layers on Mg-related bioresorbable scaffolds to obtain improved surface bio-related activity.

Diagnosis of parathyroid incidentaloma detected on thyroid ultrasonography: the role of fine-needle aspiration cytology and washout parathyroid hormone measurements.

PURPOSE: The aim of this study was to assess the diagnostic role of fine-needle aspiration cytology (FNAC) and analyze factors associated with false-negative FNAC results in patients with parathyroid incidentaloma who were referred for ultrasonography (US)-guided fine-needle aspiration (FNA) of thyroid nodules. METHODS: In this study, 121 patients with suspected parathyroid lesions were enrolled. The patients underwent US-guided FNAC with measurements of washout parathyroid hormone (PTH) between January 2015 and May 2020. The diagnostic performance of FNAC for the diagnosis of parathyroid lesions was assessed using surgical results and elevated washout PTH as a reference standard. The clinical and radiologic features associated with false-negative results on FNAC for the diagnosis of parathyroid lesions were evaluated. RESULTS: Among the 121 nodules assessed, 38 were parathyroid lesions (31.4%), and 83 were non-parathyroid lesions (68.6%). The diagnostic performance of FNAC for parathyroid incidentaloma showed a sensitivity of 31.6% (12/38), specificity of 100% (83/83), positive predictive values of 100% (12/12), negative predictive values of 76.1% (83/109), and accuracy of 78.5% (95/121). The FNAC results of non-parathyroid lesions included thyroid nodules, lymph nodes, neurogenic tumors, and fat tissue. True-positive results on FNAC were significantly associated with performing FNA twice (58.3% vs. 23.1%, P=0.043). CONCLUSION: Considering the low sensitivity of FNAC, measuring washout PTH in addition to FNAC may help accurately diagnose parathyroid incidentaloma on thyroid US. Further, the falsenegative rate for FNAC can be reduced by obtaining two or more FNA samples.

Comparison of Safety and Diagnostic Efficacy of Iohexol 240 mgI/mL, Iopamidol 250 mgI/mL, and Iodixanol 270 mgI/mL in Cerebral Angiography: A Prospective, Multicenter Study.

PURPOSE: This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease. MATERIALS AND METHODS: Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal-Wallis tests to assess the image quality and safety profiles of the contrast agents. RESULTS: Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection. CONCLUSION: Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

Malignancy risk stratification of thyroid nodules according to echotexture and degree of hypoechogenicity: a retrospective multicenter validation study.

Various risk stratification systems show discrepancies in the ultrasound lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity. From June to September 2015, we retrospectively evaluated 5601 thyroid nodules with final diagnoses from 26 institutions. Nodules were stratified according to the echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We calculated the malignancy risk according to composition and suspicious features. Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017), except in partially cystic nodules. Malignancy risks were not significantly different between homogeneous versus heterogeneous nodules in both hypoechoic (P ≥ 0.086) and iso- hyperechoic nodules (P ≥ 0.05). Heterogeneous iso-hyperechoic nodules without suspicious features showed a low malignancy risk. The malignancy risks of markedly and moderately hypoechoic nodules were not significantly different in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) nodules. The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. The degree of hypoechogenicity could be stratified as mild versus moderate to marked hypoechogenicity.

Risk factors for reoperation after lumbar spine surgery in a 10-year Korean national health insurance service health examinee cohort.

Degenerative lumbar spine disease is becoming increasingly prevalent in the aging population. Surgical treatment is the standard treatment modality for intractable cases, but the reoperation rate remains high. We conducted this study to longitudinally evaluate the impact of health risk factors on the risk of lumbar spine reoperation in Koreans aged over 40 years. Subjects aged > 40 years who underwent their first lumbar spinal surgery between January 2005 and December 2008 were selected and followed up until 2015. A total of 6300 people were included. The reoperation rate during the 10-year follow-up period was 13.2% (831/6300 patients). The reoperation rate was the highest in patients in their 60 s (15.4%, P < 0.05). The reoperation rates were also significantly higher in men (vs. women: 14.7% vs. 11.7%, P < 0.05), smokers (vs. non-smokers: 15.2% vs. 12.7%, P < 0.05), alcohol drinkers (vs. non-drinkers: 14.7% vs. 12.4%, P < 0.05), and those with a higher Charlson Comorbidity Index (CCI) score (CCI 0, 11.6%; 1-2, 13.2%; and ≥ 3, 15%; P < 0.05). Among patients undergoing lumbar spine surgery, reoperation is performed in 13.2% of patients within 10 years. Male sex, age in the 60 s, alcohol use, smoking, higher Hgb and a high CCI score increased the risk of reoperation after lumbar spine operation.

Intradiploic Encephalocele at the Parietal Bone: A Case Report and Literature Review.

Intradiploic encephalocele is a rare condition of herniation of the brain parenchyma through the diploic space. A 52-year-old man presented with a parietal intradiploic encephalocele manifesting as an intermittent headache for 7 months. CT revealed an osteolytic lesion involving the right parietal bone. MRI demonstrated brain herniation within the diploic space. Surgery may be unnecessary in the absence of concurrent symptoms or neurological deficits. After 2 years of follow-up, symptoms were improved without neurological deficits and CT findings. We report the X-ray, CT, and MRI findings of an extremely rare case of parietal intradiploic encephalocele in adulthood.

Recapitulation of First Pass Metabolism Using 3D Printed Microfluidic Chip and Organoid.

The low bioavailability of oral drugs due to first pass metabolism is a major obstacle in drug development. With significant developments in the field of in vitro organ modeling and microfluidic chip three-dimensional (3D) printing, the challenge is to apply these for the production and evaluation of new drug candidates. This study aimed to produce a microfluidic chip to recapitulate and assess the feasibility of the first pass metabolism. The infill condition of the polycarbonate transparent filament and layer height was optimized to visualize and maintain the organoid or spheroid on the chip. Next, the chip was fabricated using a 3D printer after a computer-aided design (CAD). The chip consisted of three wells of different heights. The small intestinal (SI) organoid and colorectal adenocarcinoma spheroids were placed on the second and third wells, respectively. No additional equipment was assembled, and the tilted tunnel was connected to each well to transport the material by gradient force. The chip was fabricated using 50% and 0.1 um thickness. Among the three different prototypes of chip (chips 1, 2, and 3), the highest distribution of plasmids in the Matrigel of the second well was observed in Chip 2 at 48 h. The effect of first pass metabolism was analyzed using docetaxel. In the chip without an SI organoid, there was a marked decrease in the viability of colorectal adenocarcinoma spheroids due to drug efficacy. However, in the chip with the SI organoid, no significant change in viability was observed because of first pass metabolism. In conclusion, we presented a simple, fast, and low-cost microfluidic chip to analyze the efficacy change of candidate drug by the first pass metabolism.

Radiologic Differentiation between Granulomatosis with Polyangiitis and Its Mimics Involving the Skull Base in Humans Using High-Resolution Magnetic Resonance Imaging.

Granulomatosis with polyangiitis (GPA) can involve the skull base or the Eustachian tubes. GPA is diagnosed on the basis of clinical manifestations and serological tests, although it is challenging to discriminate GPA from infectious processes driving skull base osteomyelitis (SBO) and malignant processes such as nasopharyngeal carcinoma (NPC). Moreover, current serological tests have a low sensitivity and cannot distinguish GPA from these other conditions. We hypothesized that certain MRI characteristics would differ significantly among conditions and aimed to evaluate whether the features could differentiate between GPA, SBO, and NPC involving the skull base. We retrospectively evaluated the MRI findings of patients with GPA, SBO, and NPC. We performed univariable logistic regression analyses to identify the predictive variables for differentiating between conditions and evaluated their diagnostic values. We showed, for the first time, that certain MRI findings significantly differed between patients with GPA and those with SBO or NPC, including the lesion morphology and extent, the apparent diffusion coefficient (ADC) values, the contrast enhancement patterns, the presence or absence of necrosis, and retropharyngeal lymphadenopathy. In conclusion, utilizing certain MRI features can improve the diagnostic performance of MRI by differentiating GPA with skull base involvement from other conditions with similar radiologic findings, including SBO and NPC, facilitating treatment plans and, thus, improving patient outcomes.

Association between prenatal polycyclic aromatic hydrocarbons and infantile allergic diseases modified by maternal glutathione S-transferase polymorphisms: results from the MOCEH birth cohort.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study. METHODS: The study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed. RESULTS: The risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP µg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP µg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant. CONCLUSIONS: The present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Temporalis muscle thickness as an indicator of sarcopenia predicts progression-free survival in head and neck squamous cell carcinoma.

Temporalis muscle thickness (TMT) on brain magnetic resonance imaging (MRI) is correlated with sarcopenia and can be a predictive marker for survival in patients with brain tumors, but the association of TMT on head and neck computed tomography (CT) with survival in head and neck squamous cell carcinoma (HNSCC) remains unclear. We investigated whether TMT on CT could predict progression-free survival (PFS) in patients with HNSCC. A total of 106 patients with newly diagnosed HNSCC were included in this retrospective study. The patients underwent baseline head and neck CT and/or MRI between July, 2008 and August, 2018. The correlation between TMT on CT and MRI was tested using intraclass correlation coefficient (ICC). The cut-off value of TMT on CT for determining tumor progression was identified using receiver-operating characteristic curve analysis. Uni- and consecutive multi-variable Cox regression models were used to verify the association between TMT and PFS. TMT on CT and MRI showed excellent correlation (ICC, 0.894). After a mean follow-up of 37 months, 49 out of 106 patients showed locoregional recurrence and/or distant metastasis. The cut-off TMT of 6.47 mm showed good performance in predicting tumor progression (area under the curve, 0.779). The Cox regression model showed that TMT ≤ 6.24 mm (median value in study population) was a significant contributing factor for predicting shorter PFS (hazard ratio 0.399; 95% confidence interval 0.209-0.763; P = .005). TMT may be used as a surrogate parameter for pre-treatment sarcopenia and could help predict PFS in patients with HNSCC.

Construction of an MRI-based decision tree to differentiate autoimmune and autoinflammatory inner ear disease from chronic otitis media with sensorineural hearing loss.

Autoimmune and autoinflammatory inner ear diseases (AIED/AID) are characterized by the symptom of sensorineural hearing loss (SNHL). To date, standardized diagnostic tools for AIED/AID are lacking, and clinically differentiating AIED/AID from chronic otitis media (COM) with SNHL is challenging. This retrospective study aimed to construct a magnetic resonance imaging (MRI)-based decision tree using classification and regression tree (CART) analysis to distinguish AIED/AID from COM. In total, 67 patients were enrolled between January 2004 and October 2019, comprising AIED/AID (n = 18), COM (n = 24), and control groups (n = 25). All patients underwent 3 T temporal bone MRI, including post-contrast T1-weighted images (postT1WI) and post-contrast FLAIR images (postFLAIR). Two radiologists evaluated the presence of otomastoid effusion and inner ear contrast-enhancement on MRI. A CART decision tree model was constructed using MRI features to differentiate AIED/AID from COM and control groups, and diagnostic performance was analyzed. High-intensity bilateral effusion (61.1%) and inner ear enhancement (postFLAIR, 93.8%; postT1WI, 61.1%) were the most common findings in the AIED/AID group. We constructed two CART decision tree models; the first used effusion amount as the first partitioning node and postT1WI-inner ear enhancement as the second node, whereas the second comprised two partitioning nodes with the degree of postFLAIR-enhancement of the inner ear. The first and second models enabled distinction of AIED/AID from COM with high specificity (100% and 94.3%, respectively). The amount of effusion and the degree of inner ear enhancement on MRI may facilitate the distinction between AIED/AID and COM with SNHL using decision tree models, thereby contributing to early diagnosis and intervention.

Joint association of prenatal bisphenol-A and phthalates exposure with risk of atopic dermatitis in 6-month-old infants.

BACKGROUND: Prenatal exposure to bisphenol A (BPA) and phthalates could trigger immune response. Few studies have investigated the association between prenatal BPA and phthalate exposure and atopic dermatitis (AD) in infants. OBJECTIVE: We aimed to clarify the joint association of prenatal exposure to BPA and phthalate metabolites with AD incidence in 6-month-old infants. METHODS: We included 413 mother-child pairs from the Mothers and Children's Environmental Health (MOCEH) in a prospective birth cohort study. Maternal urinary BPA, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) concentrations were measured during early and late pregnancy. We applied the Bayesian kernel machine regression (BKMR) with probit regression to estimate the association of BPA and phthalate metabolites with AD incidence after adjusting for potential confounders. Individual association was estimated by differences in predicted probabilities comparing each individual chemical concentration at 75th versus 25th percentiles, while other chemicals were set at their median. Overall joint effect was estimated by differences in predicted probabilities comparing all chemical concentrations at 75th versus 25th percentiles. RESULTS: Individual effect of MEHHP in late pregnancy was strongly associated with incident AD [Difference: 0.244 (95% credible interval: -0.066, 0.554)] in the model including both early and late exposures. Furthermore, we confirmed overall joint association of urinary BPA and phthalate metabolites during pregnancy with a higher risk of AD [0.347 (0.168, 0.526) for late pregnancy exposure, and 0.307 (0.094, 0.521) for both early and late pregnancy]. Additionally, the joint association was more prominent among girls than that in boys. CONCLUSIONS: The joint association of prenatal exposure to BPA and phthalates could be associated with the incident AD in 6-month-old infants. Further studies are needed to confirm the synergistic effect of BPA and phthalate exposures on AD in children.

Evaluation of Substituted N-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands.

N-phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted N-phenylpiperazine analogs were evaluated. Compound 6a was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound 6a was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound 6a was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease.

High-resolution MR imaging of cranial neuropathy in patients with anti-GQ1b antibody syndrome.

OBJECTIVE: The value of conventional MRI in patients anti-GQ1b antibody syndrome is subject to debate. Our purpose was to evaluate the diagnostic accuracy of high-resolution MRI for detecting cranial nerve abnormalities in patients with anti-GQ1b antibody syndrome. MATERIALS AND METHODS: This retrospective cohort study enrolled 15 anti-GQ1b-positive patients diagnosed with MFS and related disorders and 17 age-matched controls, all of whom underwent high-resolution MR imaging including pre-contrast and contrast-enhanced (CE) 3D FLAIR and 3D CE T1-weighted turbo field echo (T1-TFE) between 2010 and 2016. The diagnostic performance of high-resolution MRI was assessed using the area under the curve (AUC) of the receiver operating characteristics curve. Inter- and intraobserver agreements were calculated using kappa statistics and intraclass correlation coefficients (ICC), respectively. RESULTS: Ophthalmoplegia, ataxia, and hypo/areflexia were present in 100%, 60%, and 67%, respectively. Other neurologic findings included ptosis (40%), mydriasis (13%), and facial (27%) and bulbar (13%) palsy. Fourteen of sixteen (88%) MR examinations in 15 patients demonstrated at least one cranial nerve abnormality corresponding to the clinical findings. The involved cranial nerves on MRI were the IIIrd cranial nerve in 14 patients, VIth in nine, VIIth in four, Vth in one, and VIIIth in one. AUC values for detecting cranial neuropathy on high-resolution MRI were 0.938 (95% CI: 0.795-0.992) on a per patient basis. Inter- and intraobserver agreements were 0.842 and 0.945, respectively. CONCLUSION: High-resolution 3D FLAIR and CE 3D T1-TFE MRI has high reliability and accuracy for demonstrating cranial neuropathy in patients with anti-GQ1b antibody syndrome.

Cancer cluster among small village residents near the fertilizer plant in Korea.

OBJECTIVES: In Jang-jeom, a small village in Hamra-myeon, Iksan-si, Jeollabuk-do, South Korea, residents raised concerns about a suspected cancer cluster that they attributed to a fertilizer plant near the village. We aimed to investigate whether the cancer incidence in the village was higher than that in the general Korean population when the factory was in operation (2001-2017) and whether living in the village was associated with a higher risk of cancer. METHODS: Using national population data and cancer registration data of South Korea, we estimated the standardized incidence ratios (SIRs) in the village to investigate whether more cancer cases occurred in the village compared to other regions. The SIRs were standardized by age groups of 5 years and sex. In order to investigate whether residence in the village increased the risk of cancer, a retrospective cohort was constructed using National Health Insurance Service (NHIS) databases. We estimated the cancer hazard ratios (HRs) using the Cox proportional hazard model, and defined the exposed area as the village of Jang-jeom, and the unexposed or control area as the village neighborhood in Hamra-myeon. We considered potential confounding variables such as age, sex, and income index in the models. Additionally, we measured polycyclic aromatic hydrocarbons (PAHs) and tobacco-specific nitrosamines (TSNAs), suspected carcinogens that may have caused the cancer cluster, in samples collected from the plant and the village. RESULTS: Twenty-three cancer cases occurred in Jang-jeom from 2001 to 2017. Between 2010 and 2016, the incidence rates of all cancers (SIR: 2.05, except thyroid cancer: 2.22), non-melanoma skin cancer (SIR: 21.14, female: 25.41), and gallbladder (GB) and biliary tract cancer in men (SIR: 16.01) in the village were higher than those in the national population in a way that was statistically significant. In our cohort analysis that included only Hamra-myeon residents who have lived there for more than 7 years, we found a statistically significant increase in the risk of all cancers (HR: 1.99, except thyroid cancer: 2.20), non-melanoma skin cancer (HR: 11.60), GB and biliary tract cancer (HR: 15.24), liver cancer (HR: 6.63), and gastric cancer (HR: 3.29) for Jang-jeom residents compared to other Hamra area residents. We identified PAHs and TSNAs in samples of deposited dust and residual fertilizer from the plant and TSNAs in dust samples from village houses. CONCLUSIONS: The results of the SIR calculation and cancer risk analyses of Jang-jeom village residents from the retrospective cohort design showed consistency in the effect size and direction, suggesting that there was a cancer cluster in Jang-jeom. This study would be a good precedent for cancer cluster investigation.