Movement disorder and neuronal migration disorder due to ARFGEF2 mutation

We report a child with a severe choreadystonic movement disorder, bilateral periventricular nodular heterotopia (BPNH), and secondary microcephaly based on compound heterozygosity for two new ARFGEF2 mutations (c.2031_2038dup and c.3798_3802del), changing the limited knowledge about the phenotype. The brain MRI shows bilateral hyperintensity of the putamen, BPNH, and generalized atrophy. Loss of ARFGEF2 function affects vesicle trafficking, proliferation/apoptosis, and neurotransmitter receptor function. This can explain BPNH and microcephaly. We hypothesize that the movement disorder and the preferential damage to the basal ganglia, specifically to the putamen, may be caused by an increased sensitivity to degeneration, a dynamic dysfunction due to neurotransmitter receptor mislocalization or a combination of both

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

<p>Abstract</p> <p>Background</p> <p>Cholelithiasis has become a major health problem in Taiwan. The predominant type of gallstone found in Asian populations differs from that in the West, indicating possible differences in the etiology and risk factors for cholelithiasis. The aim of this study is to investigate the risk factors for cholelithiasis using data representative of the general population.</p> <p>Methods</p> <p>We performed a population-based, case-control study in which we analyzed medical data for 3725 patients newly diagnosed with cholelithiasis and 11175 gender- and age-matched controls with no history of cholelithiasis, using information obtained from the 2005 Registry for Beneficiaries of the National Health Insurance Research Database. Coexisting medical conditions were included in the analysis. Relative risks were estimated by adjusted odds ratio (OR) and 95% confidence interval (CI) using a multivariate logistic regression analysis.</p> <p>Results</p> <p>After controlling for the other covariates, multivariate logistic regression analysis identified the following as risk factors for cholelithiasis (in descending order of contribution): Among all patients - hepatitis C (OR = 2.78), cirrhosis (OR = 2.47), hepatitis B (OR = 2.00), obesity (OR = 1.89), and hyperlipidemia (OR = 1.54); Among women - hepatitis C (OR = 3.05), cirrhosis (OR = 1.92), obesity (OR = 1.91), menopause (OR = 1.61), hepatitis B (OR = 1.54), and hyperlipidemia (OR = 1.49). Diabetes mellitus appeared to have a marked influence on the development of cholelithiasis but was not identified as a significant independent risk factor for cholelithiasis.</p> <p>Conclusions</p> <p>The risk factors for cholelithiasis were obesity, hyperlipidemia, hepatitis B infection, hepatitis C infection, and cirrhosis in both genders, and menopause in females. Despite differences in the predominate type of gallstone in Asian versus Western populations, we identified no unique risk factors among the population of Taiwan.</p

Tear secretion dysfunction among women workers engaged in light-on tests in the TFT-LCD industry

BACKGROUND: The TFT-LCD (thin film transistor liquid crystal display) industry is rapidly growing in Taiwan and many other countries. A large number of workers, mainly women, are employed in the light-on test process to detect the defects of products. At the light-on test workstation, the operator is generally exposed to low humidity (in the clean room environment), flashing light, and low ambient illumination for long working hours. Many workers complained about eye discomfort, and therefore we conducted a study to evaluate the tear secretion function of light-on test workers of a TFT-LCD company. METHODS: We recruited workers engaged in light-on tests in the company during their periodical health examination. In addition to a questionnaire survey of demographic characteristics and ophthalmic symptoms, we evaluated the tear secretion function of both eyes of each participant using the Schirmer's lacrimal basal secretion test with anaesthesia. A participant with one or both eyes yielding abnormal test results was defined as a case of tear secretion dysfunction. RESULTS: During the study period, a total of 371 light-on test workers received the health examination at the clinic of the park, and 52 of them were excluded due to having ophthalmic diseases and other systemic diseases that may affect ophthalmic function. All the remaining 319 qualified workers agreed to participate in this study, and they were all females working by 4-shift rotations. The average age was 24.2 years old (standard deviation [SD] = 3.8), and the average employment duration was 13.6 months (SD = 5.7). Among the 11 ophthalmic symptoms evaluated, eye dryness was the most prevalent (prevalence = 43.3%). In addition, the prevalence of tear secretion dysfunction in at least one eye was 40.1% (128 cases), and contact lens users had an odds ratio of 1.73 (95% confidence interval = 1.02–2.94) in comparison with non-contact lens users. Comparing the Schirmer's test results of those who also participated in the screening in the previous year, we found 40 of the 156 participants (17.2%) with normal test results in the previous year turned abnormal in 2001. In contrast, only 21 of the 76 participants (9.1%) with abnormal test results in the previous year turned normal, and the difference was statistically significant (p = 0.02 for McNemar's test). CONCLUSION: The prevalence of tear secretion dysfunction in woman workers engaged in light-on tests is high and increases with a one-year duration of employment. The use of contact lens may further increase the risk

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Low Expression of Bax Predicts Poor Prognosis in Resected Non-small Cell Lung Cancer Patients with Non-squamous Histology†

doi:10.1093/jjco/hyn089 Objective: The present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection. Methods: We investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) i

Host microenvironment in breast cancer development: Inflammatory cells, cytokines and chemokines in breast cancer progression: reciprocal tumor–microenvironment interactions

A comprehensive overview of breast cancer development and progression suggests that the process is influenced by intrinsic properties of the tumor cells, as well as by microenvironmental factors. Indeed, in breast carcinoma, an intensive interplay exists between the tumor cells on one hand, and inflammatory cells/cytokines/chemokines on the other. The purpose of the present review is to outline the reciprocal interactions that exist between these different elements, and to shed light on their potential involvement in breast cancer development and progression

Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression

Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase signaling induces apoptosis, and caspase inhibitors prevent pain-related behavior. The degree of DRG neuronal apoptosis is thought to play a role in pain behavior. We suggest that differences in pain behavior according to the injury sites within the DRG may be related to imbalances in apoptotic injuries. The aim of this study was to determine which compression injury was more painful and to compare behavior with expression of tumor necrosis factor (TNF)-alpha in DRG and apoptosis in the DRG following crush injury to the L5 nerve root or L5 spinal nerve. Sprague–Dawley rats received a crush injury to the L5 spinal nerve (distal to the DRG), crush injury to the L5 nerve root (proximal to the DRG), or no crush injury (sham). Mechanical allodynia was determined by the von Frey test. Expression of TNF-alpha was compared among three groups using immunoblot findings. Furthermore, we compared the percentage of neurons injured in the DRG using immunostaining for apoptotic cells and localization of activated caspase 3. Mechanical allodynia was observed in both crush injury groups. The duration of mechanical allodynia in the distal crush group was significantly longer than in the proximal crush group (P < 0.05). TNF-alpha expression was increased in DRG neurons following injury. DRG apoptosis in the distal crush group was significantly higher than in the proximal group at each time point (P < 0.05). This study suggests that spinal nerve crush injuries produce a greater degree of DRG apoptosis than do corresponding nerve root crush injuries, and that the former injuries are associated with longer lasting mechanical allodynia. Thus, differences in the time course of mechanical allodynia might be associated with an imbalance in DRG apoptosis