Nigral dopaminergic projections to the striatum are targeted in Parkinson's disease (PD). The extent of the degeneration of the dopaminergic system in PD can be visualised by dopamine transporter imaging using single-photon emission tomography (SPET). In this study in 188 patients with PD, we analysed the image patterns and compared them with the clinical features in order to verify the usefulness of technetium-99m TRODAT-1 brain SPET in the evaluation of patients with PD. Two independent readers visually assessed SPET slices from three brain axes according to a "fine" visual scale; results were also grouped according to a "rough" visual scale. Results of both visual and semi-quantitative analyses were compared among patients with different stages of PD and healthy controls. There was good agreement between the readers in the interpretation of the image patterns [kappa statistic (kappa)=0.85 for the presence of PD; kappa=0.88 for the rough scale and 0.81 for the fine scale]. Good concordance was obtained when visual interpretation was used to evaluate the presence of PD (sensitivity = 98%, specificity = 86%, kappa = 0.85). Semi-quantitative analyses revealed significant negative correlations between both striatal and putaminal uptake and disease severity as assessed using the Hoehn and Yahr scale (rho = -0.89 and -0.93 respectively). An apparent decrease in striatal uptake in early PD, hardly discernible from the uptake level in advanced PD, was commonly found in visual analyses. The results suggest that both visual and semi-quantitative analyses of 99mTc-TRODAT-1 SPET images reflect neurodegeneration in PD, and that 99mTc-TRODAT-1 SPET represents an adequate means for evaluation of the status of patients with PD.

Medical images usually suffer from a partial volume effect (PVE), which may degrade the accuracy of any quantitative information extracted from the images. Our aim was to recreate accurate radioactivity concentration and time-activity curves (TACs) by microPET R4 quantification using ensemble learning independent component analysis (EL-ICA). We designed a digital cardiac phantom for this simulation and in order to evaluate the ability of EL-ICA to correct the PVE, the simulated images were convoluted using a Gaussian function (FWHM = 1-4 mm). The robustness of the proposed method towards noise was investigated by adding statistical noise (SNR = 2-16). During further evaluation, another set of cardiac phantoms were generated from the reconstructed images, and Poisson noise at different levels was added to the sinogram. In real experiments, four rat microPET images and a number of arterial blood samples were obtained; these were used to estimate the metabolic rate of FDG (MR(FDG)). Input functions estimated using the FastICA method were used for comparison. The results showed that EL-ICA could correct PVE in both the simulated and real cases. After correcting for the PVE, the errors for MR(FDG), when estimated by the EL-ICA method, were smaller than those when TACs were directly derived from the PET images and when the FastICA approach was used.

Previous studies have shown that the experimental models of hypoxia-reoxygenation (H/R) mimics the physiological conditions of ischemia-reperfusion and induce oxidative stress and injury in various types of organs, tissues, and cells, both in vivo and in vitro, including human lung adenocarcinoma epithelial cells. Nonetheless, it had not been reported whether H/R affected proliferation, apoptosis, and expression of stem/progenitor cell markers in the bronchial epithelial cells. In this study, we investigated differential effects of consecutive hypoxia and intermittent 24/24-h cycles of H/R on human bronchial epithelial (HBE) cells derived from the same-race and agematched healthy subjects (i.e., NHBE) and subjects with chronic obstructive pulmonary disease (COPD) (i.e., DHBE). To analyze gene/protein expression during differentiation, both the NHBE and DHBE cells at the 2nd passage were cultured at the air-liquid interface (ALI) in the differentiation medium under normoxia for 3 days, followed by either culturing under hypoxia (1% O 2) for consecutively 9 days and then returning to normoxia for another 9 days, or culturing under 24/24-h cycles of H/R (i.e., 24 h of 1% O 2 followed by 24 h of 21% O 2 , repetitively) for 18 days in total, so that all differentiating HBE cells were exposed to hypoxia for a total of 9 days. In both the normal and diseased HBE cells, intermittent H/R significantly increased HIF1A, BMP4, NOTCH1, MKI67, OCT4, and MUC5AC expression, while consecutive hypoxia significantly decreased NKX2-1, NOTCH3, HEY1, CC10, and FOXJ1 expression.

The effective management and therapies for Parkinson’s disease (PD) require appropriate clinical evaluation. The Parkinson’s KinetiGraph (PKG) is a wearable sensor system that can monitor the motion characteristics of PD objectively and continuously. This study was aimed to assess the correlations between PKG data and clinical scores of bradykinesia, rigidity, tremor, and fluctuation. It also aims to explore the application value of identifying early motor symptoms. An observational study of 100 PD patients wearing the PKG for ≥ 6 days was performed. It provides a series of data, such as the bradykinesia score (BKS), percent time tremor (PTT), dyskinesia score (DKS), and fluctuation and dyskinesia score (FDS). PKG data and UPDRS scores were analyzed, including UPDRS III total scores, UPDRS III-bradykinesia scores (UPDRS III-B: items 23–26, 31), UPDRS III-rigidity scores (UPDRS III-R: item 22), and scores from the Wearing-off Questionnaire (WOQ-9). This study shows that there was significant correlation between BKS and UPDRS III scores, including UPDRS III total scores, UPDRS III-B, and UPDRS III-R scores ( r = 0.479–0.588, p ≤ 0.001), especially in the early-stage group ( r = 0.682, p < 0.001). Furthermore, we found that BKS in patients with left-sided onset (33.57 ± 5.14, n = 37) is more serious than in patients with right-sided onset (29.87 ± 6.86, n = 26). Our findings support the feasibility of using the PKG to detect abnormal movements, especially bradykinesia in PD. It is suitable for the early detection, remote monitoring, and timely treatment of PD symptoms.

No abstract

Chromosome 17p13.3 microduplication syndrome is considered a multisystem disorder that results in a wide variety of clinical manifestations including dysmorphic facial characteristics, brain structural malformations, developmental restriction, growth restriction, and neurocognitive disorders. The two major classes of chromosome 17p13.3 microduplication, which have different clinical presentations, are associated with specific genetic regions. Among the various known phenotypes, scattered cases with congenital heart disease (CHD) have been reported for both classes of chromosome 17p13.3 microduplication syndrome. Unfortunately, there is insufficient understanding of the correlation between chromosome anomaly induced alterations in gene expression and aberrant cardiac development, and thus early diagnosis of CHD among patients with chromosome 17p13.3 microduplication is difficult without routine prenatal cardiac assessment. One such congenital heart anomalies known to affect a substantial number of newborns worldwide is ventricular septal defect (VSD), which has been found in 17p13.3 microduplication carriers, and seems to sometimes undergo spontaneous closure. We report an unprecedented case of moderate sized perimembranous-outlet VSD and congestive heart failure (CHF) in a Chinese Han male infant with a class II chromosome 17p13.3 microduplication. Despite the fact that cytogenic testing and fetal echocardiography confirmed a 249-Kb chromosome duplication within 17p13.3 that encompassed the PAFAH1B1 gene and showed the presence of VSD during prenatal period, this patient still developed a range of symptoms including sustained prolonged feeding, dyspnea, diaphoresis and retarded growth. A physical examination indicated hepatomegaly and a grade III/VI pan-systolic murmur along the left upper sternal border. Laboratory testing showed a high serum pro–B-type natriuretic peptide (pro-BNP). Imaging studies revealed cardiomegaly and a persistent VSD with related pulmonary stenosis. Since the clinical findings were compatible with CHF, we provided mainline treatment with digoxin, captopril, and furosemide, as well as fluid restriction. Despite sustained poor weight gain, the feeding behavior and the respiratory conditions of the patient improved gradually. This case report and literature review suggest that patients carrying chromosome 17p13.3 microduplication who have VSD may have an increased risk of developing CHF as young infants and hence a comprehensive cardiac evaluation is warranted to allow the early diagnosis and management of any severe heart anomalies.

A 35-year-old woman with unintentional weight gain, hyperpigmentation of bilateral palms, and general fatigue was initially suspected of Cushing’s syndrome or adrenal insufficiency based on the isolated elevation of the plasma adrenocorticotropic hormone (ACTH) level (113.0 pg/mL) in the Siemens ACTH Immulite assay (ACTH [Immulite]). However, both of the diagnoses were excluded by screening tests including the overnight dexamethasone suppression test, the 24-hour urinary free cortisol excretion, and the ACTH stimulation test in spite of the consistent elevation of the plasma ACTH levels. We speculated that the existence of the immunoassay interference may be the underlying cause because the plasma ACTH level analyzed by the CIS Bio International ELSA-ACTH immunoassay (ELSA-ACTH) was within the normal range. After reviewing our case and several reported cases of falsely elevated plasma ACTH levels, we conclude that when discrepancy between clinical symptoms and laboratory measurements exists, medical practitioners ought to rely on formal diagnostic criteria rather than misleading laboratory results to avoid misdiagnosis or even unnecessary invasive testing and procedures. In addition, current methods for investigation and elimination of immunoassay interferences should be applied with caution due to variable efficacy and inevitable deviations.

Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS. In order to determine any precipitating causes of ASAS, we also extensively investigated established potential risk factors for ASAS in our patient and noticed that she had a marked folate deficiency requiring folic acid supplementation to prevent future episodes of ASAS as well as to repair the patient’s injured spinal cord. Interestingly, the patient did not display elevated levels of homocysteine nor did she possess the three pathogenic MTHFR mutations characteristic of ASAS. Although her folate deficiency did not cause responsive hyperhomocysteinemia, and she did not have pathogenic MTHFR mutations that impair the function of methylenetetrahydrofolate reductase in folate cycle, we suggest that isolated folate deficiency may play a role in adolescent cases of ASAS that, once identified, would require prompt identification and early intervention to improve the prognosis of these patients.