Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

Hard X-ray microbeam lithography using a Fresnel zone plate with a long focal length.

Focused hard X-ray microbeams for use in X-ray nanolithography have been investigated. A 7.5 keV X-ray beam generated at an undulator was focused to about 3 µm using a Fresnel zone plate fabricated on silicon. The focused X-ray beam retains a high degree of collimation owing to the long focal length of the zone plate, which greatly facilitates hard X-ray nanoscale lithography. The focused X-ray microbeam was successfully utilized to fabricate patterns with features as small as 100 nm on a photoresist.

Treadmill exercise improves cognitive function and facilitates nerve growth factor signaling by activating mitogen-activated protein kinase/extracellular signal-regulated kinase1/2 in the streptozotocin-induced diabetic rat hippocampus.

This study aimed to investigate the effects of regular treadmill exercise on nerve growth factor (NGF) expression, the improvement of cognitive function in the hippocampus of diabetic rats, and to understand the molecular mechanisms through which the relevant signaling factors act. We investigated the effects of regular treadmill exercise for 6 weeks on NGF, tyrosine kinase receptor A (TrkA), p75 receptor, phosphatidylinositol 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (Erk1/2), cyclic AMP response element-binding protein (CREB), and caspase-3 protein levels; we also assessed cell survival and cognitive function. Forty male Sprague-Dawley rats were divided into four groups: (1) normal control group (NCG: n=10); (2) normal exercise group (NEG: n=10); (3) diabetes control group (DCG: n=10), and (4) diabetes exercise group (DEG: n=10). Diabetes was induced by injecting streptozotocin (STZ; 55 mg/kg dissolved in 0.05 M citrate buffer, pH 4.5, i.p.) into rats. Rats were subjected to treadmill exercise for 5 days a week over 6 weeks, and the speed of the treadmill was gradually increased. In a passive avoidance test, the retention latency in the DCG was significantly shorter than that in the DEG (P<0.05). Increased 5-bromo-2'-deoxyuridine-5'-mono-phosphate (BrdU)-labeled cells (P<0.001) and significant increases in NGF and TrkA protein levels were observed in the hippocampal dentate gyrus in the NEG and DEG (P<0.001 and P<0.01, respectively). The p75 receptor protein level significantly increased in the NEG but decreased in the DCG (P<0.001). The p-PI3-K and t-CREB protein levels significantly increased in the NEG (P<0.001 and P<0.05, respectively), whereas t-Erk1/2 significantly decreased in the DCG (P<0.01, P<0.01, respectively). p-Erk1/2 and p-CREB protein levels significantly increased in the NEG and DEG (P<0.001, P<0.001, and P<0.01, respectively). Caspase-3 protein levels significantly increased in the DCG (P<0.001). These results show that treadmill exercise improves cognitive function, increases the number of BrdU-labeled cells, and increases NGF levels, by the activation of the MAPK/Erk1/2 signaling pathway in the hippocampus of diabetic rats.

Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography.

OBJECTIVE: To evaluate the efficacy of F-18-fluoro-2-deoxy-D: -glucose positron emission tomography/computed tomography (FDG PET/CT) in differentiating malignant from benign pathologic fractures. MATERIALS AND METHODS: F-18 FDG PET/CT was performed on 34 patients with pathologic fractures between May 2004 and June 2007. Fractures were located in tubular bones (26), in the pelvis (six), in the spine (one) and in a rib (one). The FDG uptake pattern at the fracture site was described, whether FDG uptake occurred in the marrow or cortex and soft tissue. Maximum standardized uptake values (SUVmax, the largest value at the region of interest) were measured at the fracture site, including cortical bone, bone marrow and soft tissue. As a reference standard, biopsy was used for 12 patients and clinical follow-up for 22 patients. Sensitivity, specificity and diagnostic accuracy of PET/CT were calculated. RESULTS: There were 19 malignant and 15 benign fractures. In the malignant fractures, PET/CT demonstrated high (mean SUVmax 12.0, range 4.3 to 45.7) F-18 FDG uptake in bone marrow in most cases (17 of 19). In benign fractures, there was low FDG uptake (mean SUVmax 2.9, range 0.6 to 5.5) within cortical bone or adjacent soft tissue around the fracture, rarely in the marrow. There were significant differences in the pattern of intramedullary FDG uptake (P < 0.001) and in the mean SUVmax (P < 0.01) between malignant and benign fractures. The sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT were 89.5%, 86.7% and 88.2%, respectively, with a cut-off SUVmax set at 4.7. The time interval between fracture and PET/CT did not significantly influence FDG uptake at the fracture site. CONCLUSION: F-18 FDG PET/CT reliably differentiated between malignant and benign fractures based on the SUVmax and based on medullary uptake, which was characteristic for malignant fractures.

Spontaneous bone formation on the maxillary sinus floor in association with an extraction socket.

A case is reported of spontaneous bone formation on the maxillary sinus floor associated with the extraction socket of a maxillary impacted tooth. An impacted maxillary second premolar of a 20-year-old male had been pushed into the maxillary sinus during surgical extraction. The tooth was removed using the sinus elevation technique. After 5 months of healing, the space between the sinus floor and the socket was filled with new bone. Later, implant surgery was successfully carried out without any sinus augmentation. Osteogenic activity of sinus mucosa and the blood clot in the extraction socket beneath the elevated sinus would have been important factors in this spontaneous bone formation.

Effects of stress on female rat sexual function.

This study was undertaken to investigate whether prolonged stress interferes with sexual behavior and changes biochemical and physiologic mechanisms. Experiments were repeated three times with different rats in each period. In all, 63 female Sprague-Dawley rats were employed, with 21 rats in each period, and the control group was maintained at room temperature with free access to food and water. The stress group was maintained under a scheduled stress condition for 10 days, and seven rats from the group were randomly selected and exposed to the control environment for 10 days as the recovery group. Sexual behavior, hormonal values, and neuronal and endothelial nitric oxide synthase (nNOS and eNOS) expressions of vaginal tissue were analyzed and compared. Serum testosterone levels were significantly elevated in the stress and recovery groups (P<0.05). Female rats in the stress group showed reduced receptivity to their male mates (P<0.05). Western blot analysis demonstrated that nNOS and eNOS expressions were significantly lower in the stress group (P<0.05) than in the other groups. We conclude that chronic physical stress modifies the sexual behavior of female rats through a mechanism believed to involve complex changes in sex hormones, endocrine factors, and neurotransmitters.

Comparison of Tc-99m sestamibi and TI-201 uptake in multiple myeloma.

The authors report abnormal Tc-99m sestamibi (MIBI) and TI-201 uptake in a 62-year-old patient with histologically and biochemically proved myeloma. TI-201 imaging was undertaken for tumor evaluation, and 3 days later a Tc-99m MIBI study showed diffuse and focal marrow uptake with focal skull lesions, whereas TI-201 did not show skull lesions. After treatment, follow-up Tc-99m MIBI whole-body imaging was performed and the marrow uptake was decreased.

The malonate decarboxylase operon of Acinetobacter calcoaceticus KCCM 40902 is regulated by malonate and the transcriptional repressor MdcY.

A regulatory gene-like open reading frame oriented oppositely to mdcL, coined mdcY, was found upstream from the structural genes of the mdcLMACDEGBH operon in Acinetobacter calcoaceticus KCCM 40902. To elucidate the function of this gene, mdcY was expressed in Escherichia coli, and the MdcY protein was purified to homogeneity. Its DNA binding activity and binding site were examined by gel retardation and footprinting assays in vitro and by site-directed mutagenesis of the binding sites in vivo. The regulator bound target DNA regardless of the presence of malonate, and the binding site was found centered at -65 relative to the mdcL transcriptional start site and contains a 12-bp palindromic structure (5'-ATTGTA/TACAAT-3'). Using a promoter fusion to the reporter gene luc, we found that the promoter P(mdcY) is negatively regulated by MdcY independent of malonate. However, the promoter P(mdcL) recovered its activity in the presence of malonate. When mdcY was introduced into A. calcoaceticus KCCM 40902 in which the gene is inactivated by an IS3 family element, malonate decarboxylase was significantly repressed in cultures growing in acetate, succinate, or Luria-Bertani medium. However, in cells growing in malonate, malonate decarboxylase was induced, indicating that MdcY is a transcriptional repressor and that malonate or a product resulting from malonate metabolism should be the intracellular inducer of the mdc operon.

Radiation therapy for heterotopic ossification in a patient with traumatic brain injury.

Radiation therapy has been known to have a prophylactic effect for heterotopic ossification (HO), but until now it has not been known to have a therapeutic effect for established HO. We report a case of established HO compounded with a sudden increase in activity, that was improved with radiation therapy. A patient with traumatic brain injury had HO in both hips and thighs two months after the initial trauma. The existing level of HO activity suddenly increased seven months after the initial trauma, and was accompanied by severe pain that was refractory to indomethacin. We assumed that the pain was caused by the increased activity of HO on the basis of clinical symptoms and laboratory results. Initially, the patient received radiation therapy to the left lower extremity, with a total dose of 20 Gy in ten fractions. Next, the patient received radiation therapy at the same dosage to the right lower extremity, after which the pain and level of serum alkaline phosphatase significantly decreased. The patient experienced a mild pancytopenia as a side effect of the radiation therapy, but it was not severe enough to stop the radiation therapy, given the patient's suffering from the increased HO activity.

Viable tissue in an area of severely reduced perfusion demonstrated with I-123 iomazenil brain SPECT imaging of benzodiazepine receptors.

A 70-year-old woman who experienced transient left hemiparesis had 90% stenosis of the right internal carotid artery. CT revealed small low-density areas in the subcortical frontal area. Baseline cerebral blood flow was reduced, and vasoreactivity was poor in the right frontoparietal area according to I-123 IMP brain SPECT with acetazolamide. The distribution of I-123 iomazenil was normal on the delayed SPECT image but reduced in the early SPECT image, mimicking baseline cerebral blood flow. The distribution of I-123 iomazenil SPECT on the delayed image reflected the normal binding potential of the benzodiazepine receptor and thus identified viable tissue in an area of severely reduced perfusion. These findings were confirmed by positron emission tomography.

The influence of simultaneous versus delayed placement on the stability of titanium implants in onlay bone grafts. A histologic and biomechanic study in the rabbit.

A rabbit model was used to study the healing and stability of titanium implants in free bone grafts, placed simultaneously or after 8 weeks of healing and followed for 24 weeks. The skull bone was used as donor site and the tibial metaphysis as recipient site. Stability measurements were performed by using resonance frequency analysis (RFA) at implant placement and after 4, 8, 16 and 24 weeks of healing. Statistically significant higher resonance frequencies were measured at all time points for the delayed approach implants. Removal torque tests after 24 weeks revealed no differences between the two procedures. Histologic ground sections were prepared on specimens taken after 8, 16 and 24 weeks of healing. More bone-implant contacts were observed in the bone graft for the implants inserted in a delayed fashion, while there was no statistically significant difference in the degree of total bone-implant contact between the two groups. It is concluded that delayed implant placement in autogenous onlay bone grafts results in a better integration and stability of the implants.

Baumkuchen map analysis to detect postural cerebral hypoperfusion with upright 99Tcm-HMPAO brain SPET.

We have evaluated a polar cortical flow Baumkuchen map (BK map), constructed from projection data by inwardly layering cortical flow stripes from the base to the apex, to detect postural cerebral hypoperfusion using 99Tcm-HMPAO brain SPET. A circular cortical perfusion outline was constructed from sinogram data at a 20% threshold; a ring was then formed by constructing an inner line with a radius equal to half that of the outer line. This ring on the transaxial image was superimposed onto the cortical image, then divided into 60 portions at 6 degrees intervals from the centre. The maximal number of counts per pixel within each sector was determined, translated into polar coordinate profiles and displayed as a polar map. We studied 11 patients with unilateral stenosis of the internal carotid artery or middle cerebral artery (MCA) and 7 patients without stenosis, using upright and supine (rest) 99Tcm-HMPAO brain SPET Cerebral perfusion was visibly altered on the BK maps of all 11 patients with arterial stenosis and on the transaxial images of 8 of them. A semi-quantitative analysis of the BK maps using a ratio of the counts in the regions of interest over the right and left MCA areas, showed that the mean of the ratios was significantly lower in the upright images than in the upright + rest and rest images (P = 0.0044 and 0.0033, respectively). Although the difference in the means of the ratios between the upright and upright + rest images was significant for both the BK map and transaxial image data (P = 0.0044 and 0.0051, respectively), the BK map was accurate in detecting changes in perfusion in the upright position. We conclude that BK map analysis is useful for detecting changes in patients examined using upright brain SPET.

Visualization of pressure-dependent luxury perfusion in a patient with subacute cerebral infarction.

Luxury perfusion characterized by depressed metabolism compared with CBF might be changed by decreasing cerebral perfusion pressure during the sitting position. A 77-yr-old man with subacute cerebral infarction was studied with brain X-ray computed tomography (CT), raise-up test with 99mTc-d,1-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomography (SPECT) and positron emission tomography (PET). Brain X-ray CT revealed a low-density area in the left middle cerebral artery (MCA) anterior area. Raise-up 99mTc-HMPAO brain SPECT revealed decreased uptake in the left MCA anterior area in the sitting position and subsequent supine 99mTc-HMPAO brain SPECT revealed hot accumulation there. PET study in the supine position demonstrated some differences between CBF and the cerebral metabolic rate for oxygen in the left MCA anterior area, indicating luxury perfusion. CBF in the area of luxury perfusion might be decreased during the sitting or standing position and increased during the supine position by dysautoregulation of the cerebral vessels in the luxury perfusion during the subacute infarct.

Visualization of frontal postural hypoperfusion in patients with Takayasu arteritis with upright 99Tcm-HMPAO brain SPET.

Takayasu arteritis is a chronic inflammatory angiopathy involving the cerebral arteries. We performed upright and supine 99Tcm-HMPAO brain single photon emission tomography (SPET) to investigate the cerebral perfusion pattern in eight patients with Takayasu arteritis, and we compared the results with those acquired using 123I-IMP and acetazolamide in six patients. SPET images were evaluated visually and semi-quantitatively. Hypoperfusion was visually detected in all eight patients during the provocative upright test with 99Tcm-HMPAO, and in three of six tested using acetazolamide and 123I-IMP. Semiquantitative analysis revealed that the mean cortical-to-cerebellar ratio in the upright position was significantly changed compared to that in the supine position in the right frontal area (from 0.86 +/- 0.07 to 0.91 +/- 0.09; P < 0.05). Change was also seen in the left frontal area (from 0.85 +/- 0.08 to 0.91 +/- 0.08; P < 0.05). No significant change was seen in other cortical areas with the upright test or in any areas with the acetazolamide test. We postulate that reduced arterial compliance may cause frontal postural hypoperfusion in patients with Takayasu arteritis due to poor functioning of autoregulation and arterial stenosis or occlusion. We conclude that the provocative upright test with 99Tcm-HMPAO brain SPET can detect abnormal patterns of cerebral perfusion in patients with Takayasu arteritis that might be missed by brain SPET using 123I-IMP and acetazolamide.

All 4 bases of both strands at -9 and -8 in T7 promoter are needed to be substituted by SP6-specific bases to switch promoter specificity.

It has previously been shown that a substitution of two base pairs at -9 and -8 in T7 promoter by SP6 promoter-specific base pairs alone is sufficient to make the T7 variant become an SP6 promoter, abolishing T7 promoter activity [Lee, S. S., and Kang, C. (1992) Biochem. Int. 26, 1-5]. In order to determine which of the 4 bases on both strands at the two positions is involved in the discriminative specificity, each base or each pair of bases was substituted by SP6-specific base(s), allowing one or two mismatches. The results show that all-four-base substitution only is capable of switching promoter specificity, and that all the four bases are substantially involved in T7 promoter activity.