Experimental realization of a π/2 vortex mode converter for electrons using a spherical aberration corrector.

In light optics, beams with orbital angular momentum (OAM) can be produced by employing a properly-tuned two-cylinder-lens arrangement, also called π/2 mode converter. It is not possible to convey this concept directly to the beam in an electron microscope due to the non-existence of cylinder lenses in commercial transmission electron microscopes (TEMs). A viable work-around are readily-available electron optical elements in the form of quadrupole lenses. In a proof-of-principle experiment in 2012, it has been shown that a single quadrupole in combination with a Hilbert phase-plate produces a spatially-confined, transient vortex mode. Here, an analogue to an optical π/2 mode converter is realized by repurposing a CEOS DCOR probe corrector in an aberration corrected TEM in a way that it resembles a dual cylinder lens using two quadrupoles. In order to verify the presence of OAM in the output beam, a fork dislocation grating is used as an OAM analyser. The possibility to use magnetic quadrupole fields instead of, e.g., prefabricated fork dislocation gratings to produce electron beams carrying OAM enhances the beam brightness by almost an order of magnitude and delivers switchable high-mode purity vortex beams without unwanted side-bands.

[CART therapy followed by allo-HSCT for patients with B-cell acute lymphoblastic leukemia relapsing after the first hematopoietic stem cell transplantation].

Objective: To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT. Methods: Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia. Results: A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95%CI 23.0%-70.6%) , 41.8% (95%CI 17.3%-64.9%) , 8.8% (95%CI 2.9%-26.4%) , and 51.1% (95%CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95%CI 12.7%-73.5%) and 75.0% (95%CI 51.4% -88.8%) (P=0.017) , respectively. Conclusion: CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Vitamin B12 for herpetic neuralgia: A meta-analysis of randomised controlled trials.

BACKGROUND: Postherpetic neuralgia (PHN) is the most distressful complication of herpes zoster. PHN results in an impaired quality of life and higher healthcare utilization. Vitamin B12 has been proven to be effective in pain relief for various conditions. OBJECTIVE: We conducted a systematic review and a meta-analysis to evaluate the efficacy of vitamin B12 supplementation in PHN patients. METHODS: PubMed, Embase, Cochrane Library, CINAHL, and ClinicalTrials.gov registry were searched. Randomised control trials evaluating the efficacy and safety of vitamin B12 in PHN patients were selected. Eligible trials were abstracted and assessed for the risk of bias by two reviewers, and the results of pain indicators in the selected trials were analysed. RESULTS: Four trials including 383 participants were published between 2013 and 2016. Compared with the placebo group, the Vitamin B12 group exhibited a significant decrease in the Numeric Rating Scale score, with a mean difference of -4.01 (95% confidence interval = -4.70 to -3.33). Vitamin B12 administration improved the quality of life of PHN patients with moderate quality evidence and significantly decreased the number of patients using analgesics. CONCLUSION: Vitamin B12 appears to be an attractive complementary therapy for PHN patients. Further investigation is needed before conclusive recommendations can be made.

[Clinical characteristics and prognosis of 34 cases of acute myeloid leukemia with FLT3 internal tandem duplication and MLL gene rearrangement].

Objective: To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement. Methods: The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT). Results: Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×10(9)/L, 39.4% greater than 50 × 10(9)/L respectively on admission. M(5) (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×10(9)/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%). Conclusion: AML patients with FLT3-ITD and MLL gene rearrangement often presented with M(5), accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Survival without peripheral neuropathy after massive acute arsenic poisoning: Treated by 2,3-dimercaptopropane-1-sulphonate.

WHAT IS KNOWN AND OBJECTIVE: Massive acute arsenic poisoning is rare yet potentially life-threatening. 2,3-dimercaptopropane-1-sulphonate (DMPS) appears to have the appropriate chelating property. However, clinical experience on the use of DMPS in massive arsenic poisoning is limited. CASE DESCRIPTION: A 37-year-old woman attempted suicide by ingesting 37.5 g of arsenic trioxide. DMPS was promptly initiated based on history and clinical symptoms. The patient recovered completely, with no complications or side effects of the therapy. WHAT IS NEW AND CONCLUSION: TDMPS is useful for the treatment of massive acute arsenic poisoning.

Ghrelin level negatively predicts quality of life in obese women.

A cross-sectional cohort study was conducted to investigate whether ghrelin level in obese women predicts the quality of life (QOL). A total of 307 subjects fulfilled the criteria: (1) age between 20 and 65 years old, (2) body mass index ≥27 kg/m2 (3) waist circumference ≥80 cm were enrolled in the study. All subjects were assigned to one of the plasma ghrelin level categories according to the quartiles. The median of age and BMI of the 307 obese women were 45 ± 18 years and 29.9 ± 4.1 kg/m2, respectively. The main outcome evaluated is the associations of plasma ghrelin level and QOL, which were evaluated using multiple linear regression analysis. Results of linear trend test show significant statistical difference in plasma lipoproteins (triglyceride, cholesterol, HDL-cholestero and LDL-cholesterol = and levels of obesity-related hormone peptides, including leptin, adiponectin, insulin among quartiles of ghrelin. Multiple liner regression analysis of serum obesity-related hormone peptide level and QOL using stepwise method shows ghrelin concentration was the only predictor of QOL, including PCS-12 level (ß = -0.18, p = 0.001), MCS-12 level (ß = -0.14, p = 0.009), WHOQOL-BREF scores: physical (ß = -0.13, p = 0.03), psychological (ß = -0.16, p = 0.007), social (ß = -0.21, p =  < 0.001), and environmental (ß = -0.22, p =  <0.001), after adjusting other factors for obese female subjects. This study demonstrated that ghrelin concentration is strongly associated with QOL level among obese women. Hence, ghrelin concentration might be a valuable marker to be monitored in obese women.

Does supplementation with green tea extract improve acne in post-adolescent women? A randomized, double-blind, and placebo-controlled clinical trial.

BACKGROUND: Green tea is believed to have beneficial effects in the prevention and treatment of acne. OBJECTIVE: To examine the effects of a decaffeinated green tea extract (GTE), providing a daily dose of 856 mg of epigallocatechin gallate (EGCG) upon women with post-adolescent acne. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from May 2012 through October 2013. A final group of 80 subjects were randomly assigned to receive either 1500 mg of decaffeinated GTE or placebo (cellulose) daily for 4 weeks. Inflammatory lesion counts were used as the major outcome measurement. At baseline and after 4 weeks of treatment, anthropometric measurements, fasting glucose levels and a lipid profile were measured from both groups. RESULTS: Sixty-four of 80 women, from 25 to 45 years of age with moderate-to-severe acne completed the study. Statistically significant differences were noted in inflammatory lesion counts distributed on the nose, periorally and on the chin between the two groups. However, there were no significant differences between groups for total lesion counts. Within-group comparison revealed that the GTE group had significant reductions in inflammatory lesions distributed on the forehead and cheek, and significant reductions in total lesion counts. GTE resulted in significant reductions in total cholesterol levels within the GTE group. CONCLUSIONS: GTE resulted in significant reductions in lesions located on the nose, perioral area and chin. More research is required to determine whether a decaffeinated GTE standardized for EGCG content will provide clinical benefits in women with post-adolescent acne.

Body mass index is negatively associated with acne lesion counts in Taiwanese women with post-adolescent acne.

BACKGROUND: Acne in adult women tends to be chronic, refractory to treatment and associated with psychosocial problems. Body mass index (BMI) has been reported to be a risk factor for acne in school children and adolescents, but not in adult women. OBJECTIVES: The aim of this study was to demonstrate the relationship between BMI and acne lesion counts in women with post-adolescent acne. METHODS: Hundred and four women between 25 and 45 years of age, with moderate or severe acne vulgaris were enrolled in this study. The main outcome evaluated was the number of acne lesions, which were then assessed using multiple linear regression analysis. RESULTS: The coefficients of multiple regression analysis with stepwise model showed that BMI (ß = -0.36; p = 0.001) and family history (ß = 0.21; p = 0.04) were the main predictors of the number of acne lesions. CONCLUSION: Initial findings indicate that BMI is negatively associated with the number of acne lesions in Taiwanese women with moderate to severe post-adolescent acne.

Gefitinib-induced epidermal growth factor receptor-independent keratinocyte apoptosis is mediated by the JNK activation pathway.

BACKGROUND: Gefitinib (ZD1839) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with a significant antitumour effect on various cancers. Skin toxicity induced by gefitinib is common, and has been shown to be related to the inhibition of EGFR signalling pathways. However, other mechanisms may be involved in gefitinib-induced skin toxicity. OBJECTIVES: To study the possible EGFR-independent mechanisms of gefitinib-induced skin toxicity. METHODS: The human immortalized keratinocyte cell line HaCaT and human lung adenocarcinoma cell lines (A549 and PC9) were treated with different concentrations of gefitinib for 24, 48 and 72 h. Cell viability was measured by MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] after EGFR gene silencing. The signalling pathways were investigated by immunoblot analysis. Keratinocyte apoptosis was evaluated by nuclear condensation and flow cytometric analysis. RESULTS: Gefitinib maintained its cytotoxicity to HaCaT cells after EGFR gene silencing, indicating that an EGFR-independent mechanism exists. Increased phosphorylation of p38 mitogen-activated protein kinase and JNK by gefitinib was observed in a dose-dependent manner in HaCaT cells. The JNK inhibitor, SP600125, attenuated the gefitinib-induced cytotoxicity and apoptosis of HaCaT cells. Immunohistochemical examination of patient specimens showed an increased expression of phosphorylated JNK in lesional epidermis compared with nonlesional epidermis. CONCLUSIONS: Gefitinib can induce keratinocyte apoptosis through an EGFR-independent JNK activation pathway.

Combined NgR vaccination and neural stem cell transplantation promote functional recovery after spinal cord injury in adult rats.

AIMS: after spinal cord injury (SCI), there are many adverse factors at the lesion site such as glial scar, myelin-derived inhibitors, cell loss and deficiency of neurotrophins that impair axonal regeneration. Therefore, combination therapeutic strategies might be more effective than a single strategy for promoting functional recovery after SCI. In the present study, we investigated whether a Nogo66 receptor (NgR) vaccine, combined with neural stem cell (NSC) transplantation, could promote better functional recovery than when NgR vaccine or NSCs were used alone. METHODS: adult rats were immunized with NgR vaccine at 1 week after a contusive SCI at the thoracic level, and the NSCs, obtained from green fluorescent protein transgenic rats, were transplanted into the injury site at 8 weeks post injury. The functional recovery of the animals under various treatments was evaluated by three independent behavioural tests, that is, Basso, Beattie and Bresnahan locomotor rating scale, footprint analysis and grid walking. RESULTS: the combined therapy with NgR vaccination and NSC transplantation protected more ventral horn motor neurones in the injured spinal cord and greater functional recovery than when they were used alone. Furthermore, NgR vaccination promoted migration of engrafted NSCs along the rostral-caudal axis of the injured spinal cords, and induced their differentiation into neurones and oligodendrocytes in vivo. CONCLUSIONS: the combination therapy of NgR vaccine and NSC transplantation exhibited significant advantages over any single therapy alone in this study. It may represent a potential new therapy for SCI.

Outcome evaluation of carotid stenting in high-risk patients with symptomatic carotid near occlusion.

Management of symptomatic carotid near occlusion especially in high-risk patients is different from outcome analysis of NASCET. We evaluated outcome in high-risk patients with symptomatic near occlusion. For 48 patients with near occlusion out of 166 symptomatic high-risk patients who underwent carotid stenting, we assessed the procedural success defined as residual stenosis <30%, modified Rankin Scale (mRS) at one and six months following stenting, and the 13 cerebrovascular factors related to the outcome. Initial National Institutes of Health Stroke Scale (NIHSS) ≥4, 1-3 and 0 were 13, 14 and 21 patients each. We compared the outcome with patients who underwent CAS (n=118) due to symptomatic stenosis without near occlusion during the same period. Our procedural success rate was 98%. A good outcome (mRS ≤2) was achieved in 44 patients (92%) at six months. There were five events (10%) within six months, i.e. three minor strokes, one major stroke caused by hemorrhage, and one death excluding two deaths not related to stroke. Hyperperfusion (n=4) was the most common cause of events leading to two minor strokes and a major stroke. Although initial NIHSS (P = .012) was related to poor outcome (mRS >2) compared to the CAS group, there was no statistical significance between two groups in the event rate of stroke, death or restenosis. The outcome of carotid stenting in high-risk patients with symptomatic near occlusion did not reveal any difference compared with CAS. Poor outcome was related to the initial NIHSS (≥4). Hyperperfusion tended to be more commonly related to an event occurring after stenting.

Donepezil delays progression to AD in MCI subjects with depressive symptoms.

OBJECTIVE: To determine whether the presence of depression predicts higher rate of progression to Alzheimer disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and whether donepezil treatment beneficially affect this relationship. METHODS: The study sample was composed of 756 participants with aMCI from the 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study drug trial of donepezil and vitamin E. Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and participants were followed either to the end of study or to the primary endpoint of progression to probable or possible AD. RESULTS: Cox proportional hazards regression, adjusted for age at baseline, gender, apolipoprotein genotype, and NYU paragraph delayed recall score, showed that higher BDI scores were associated with progression to AD (p = 0.03). The sample was stratified into depressed (BDI score > or =10; n = 208) and nondepressed (BDI <10; n = 548) groups. Kaplan-Meier analysis showed that among the depressed subjects, the proportion progressing to AD was lower for the donepezil group than the combined vitamin E and placebo groups at 1.7 years (p = 0.023), at 2.2 years (p = 0.025), and remained marginally lower at 2.7 years (p = 0.070). The survival curves among the three treatment groups did not differ within the nondepressed participants. CONCLUSIONS: Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms.

Serine-385 phosphorylation of inwardly rectifying K+ channel subunit (Kir6.2) by AMP-dependent protein kinase plays a key role in rosiglitazone-induced closure of the K(ATP) channel and insulin secretion in rats.

AIMS/HYPOTHESIS: Rosiglitazone, an insulin sensitiser, not only improves insulin sensitivity but also enhances insulin secretory capacity by ameliorating gluco- and lipotoxicity in beta cells. Rosiglitazone can stimulate insulin secretion at basal and high glucose levels via a phosphatidylinositol 3-kinase (PI3K)-dependent pathway. We hypothesised that regulation of phosphorylation of the ATP-sensitive potassium (K(ATP)) channel might serve as a key step in the regulation of insulin secretion. METHODS: Insulin secretory responses were studied in an isolated pancreas perfusion system, cultured rat islets and MIN6 and RINm5F beta cells. Signal transduction pathways downstream of PI3K were explored to link rosiglitazone to K(ATP) channel conductance with patch clamp techniques and insulin secretion measured by ELISA. RESULTS: Rosiglitazone stimulated AMP-activated protein kinase (AMPK) activity and induced inhibition of the K(ATP) channel conductance in islet beta cells; both effects were blocked by the PI3K inhibitor LY294002. Following stimulation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a pharmacological activator, both AICAR-stimulated insulin secretion and inhibition of K(ATP) channel conductance were unaffected by LY294002, indicating that AMPK activation occurs at a site downstream of PI3K activity. The serine residue at amino acid position 385 of Kir6.2 was found to be the substrate phosphorylation site of AMPK when activated by rosiglitazone or AICAR. CONCLUSIONS/INTERPRETATION: Our data indicate that PI3K-dependent activation of AMPK is required for rosiglitazone-stimulated insulin secretion in pancreatic beta cells. Phosphorylation of the Ser(385) residue of the Kir6.2 subunit of the K(ATP) channel by AMPK may play a role in insulin secretion.

Platelet-derived growth factor-AA mediates oligodendrocyte lineage differentiation through activation of extracellular signal-regulated kinase signaling pathway.

Platelet-derived growth factor-AA (PDGF-AA) has been used as a potent mitogen for the proliferation of oligodendrocyte progenitor cells (OPCs). Whether it plays a role in oligodendrocyte lineage differentiation of neural stem cells (NSCs) is unclear. Here we report that PDGF-AA is an instructional signal required for the differentiation of embryonic forebrain NSCs into O4-positive oligodendrocytes. Moreover, such PDGF-AA-induced oligodendrocyte differentiation appears to be mediated by the extracellular signal-regulated kinases 1 and 2 (Erk1/2) but not phosphatidylinositol-3 kinase (PI3K) pathway. Finally, PDGF-AA treatment resulted in a significant increase in the expression of the oligodendrocyte-specific transcriptional factor Olig2 in an Erk1/2-dependent mechanism at early stages of oligodendrogliogenesis. Together, our studies provide cellular and molecular evidence to suggest that PDGF-AA is a key molecule that regulates the differentiation of embryonic NSCs into oligodendrocytes. The action of PDGF-AA is mediated by the activation of Erk pathway which involves the downstream upregulation of transcriptional factor Olig2.

Region-specific growth properties and trophic requirements of brain- and spinal cord-derived rat embryonic neural precursor cells.

To determine whether neural precursor cells have region-specific growth properties, we compared the proliferation, mitogenicity, and differentiation of these cells isolated from the embryonic day 16 rat forebrain and spinal cord. Neural precursor cells isolated from both regions were cultured in growth medium supplemented with epidermal growth factor, basic fibroblast growth factor, or epidermal growth factor+basic fibroblast growth factor. Under all three conditions, both neural precursor cell populations proliferated for multiple passages. While spinal cord-derived neural precursor cells proliferated moderately faster in epidermal growth factor-enriched growth medium, brain-derived cells proliferated much faster in basic fibroblast growth factor-enriched growth medium. When exposed to both epidermal growth factor and basic fibroblast growth factor, the two neural precursor cell populations expanded and proliferated more rapidly than when exposed to a single factor, with brain-derived neural precursor cells expanding significantly faster than spinal cord-derived ones (P<0.0001). Differentiation studies showed that both neural precursor cell populations were multi-potent giving rise to neurons, astrocytes, and oligodendrocytes. However, neuronal differentiation from brain-derived neural precursor cells was greater than spinal cord-derived ones (11.95+/-5.00% vs 1.92+/-1.13%; passage 2). Further, the two neural precursor cell populations differentiated into a similar percentage of oligodendrocytes (brain: 8.66+/-5.85%; spinal cord: 7.69+/-3.91%; passage 2). Immunofluorescence and Western blot studies showed that neural precursor cells derived from both regions expressed receptors for basic fibroblast growth factor and epidermal growth factor. However, brain-derived neural precursor cells expressed higher levels of the two receptors than spinal cord-derived ones in growth medium containing epidermal growth factor+basic fibroblast growth factor. Thus, our results showed that neural precursor cells isolated from the two regions of the CNS have distinct properties and growth requirements. Identifying phenotypic differences between these neural precursor cell populations and their growth requirements should provide new insights into the development of cell therapies for region-specific neurological degenerative diseases.

Differential gene expression after complete spinal cord transection in adult rats: an analysis focused on a subchronic post-injury stage.

In an attempt to characterize changes in transcription after a sub-chronic spinal cord injury (SCI), we investigated gene expression profiles using cDNA microarray. Among 7523 genes and expressed sequence tags (ESTs) examined, 444 transcripts, including 218 genes and 226 ESTs, were identified to be either up-regulated (373 of 444) or down-regulated (71 of 444) greater than 2.0-fold in the spinal cord at 14 days after a complete spinal transection at the 11th thoracic level in adult rats. Based on their potential function, these differentially expressed genes were categorized into seven classes which include cell division-related protein, channels and receptors, cytoskeletal elements, extracellular matrix proteins, metalloproteinases and inhibitors, growth-associated molecules, metabolism, intracellular transducers and transcription factors, as well as others. Strong expressional changes were found in all classes revealing the complexity and diversity of gene expression profiles following SCI. We verified array results with RT-PCR for eight genes, Northern blotting for nine genes, and in situ hybridization for one gene and immunohistochemistry for four genes. These analyses confirmed, to a large extent, that the array results have accurately reflected the molecular changes occurring at 14 days post-SCI. Importantly, the current study has identified a number of genes, including annexins, heparin-binding growth-associated protein (HB-GAM), P9ka (S100A4), matrix metalloproteinases, and lysozyme, that may shed new light on SCI-related inflammation, neuroprotection, neurite-outgrowth, synaptogenesis, and astrogliosis. In conclusion, the identification of molecular changes using the large-scale microarray analysis may lead to a better understanding of underlying mechanisms, thus, the development of new repair strategies for SCI.

Comparisons of metal leachability for various wastes by extraction and leaching methods.

The objective of this research was to evaluate three extraction tests, i.e., toxicity characteristic leaching procedures (TCLP), extraction procedure (EP), and American Society for Testing and Materials (ASTM) methods, for their ability to extract metals in chemical sludge and incineration bottom ash, in terms of the precision of analytical results. Typical chemical sludges, including the electroplating and dye-stuff sludges, the municipal solid waste incineration bottom ash, the leather debris, and the steel-mill bottom residue containing Cd, Cr, Cu, Pb, and Zn were prepared for the lysimetry test (dynamic testing) to compare with the extraction results. Results show that for bottom residue and dye-stuff sludge, the concentration of metal leached was almost the same between the lysimetry leaching and the TCLP tests. The metal concentration followed the order: TCLP approximately = EP > ASTM. TCLP and EP exhibited almost the same relative standard deviation (RSD) value. Therefore, the results of the TCLP tests for bottom residue and dye-stuff sludge, which have a low metal content and alkalinity, can be used to estimate the metal concentration leached by typical acid rain in Taiwan; whereas the ASTM extraction test may be a better indicator of the lysimetry test.

Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study.

BACKGROUND: Imaging and postmortem studies provide converging evidence that, beginning in adolescence, gray matter volume declines linearly until old age, while cerebrospinal fluid volumes are stable in adulthood (age 20-50 years). Given the fixed volume of the cranium in adulthood, it is surprising that most studies observe no white matter volume expansion after approximately age 20 years. We examined the effects of the aging process on the frontal and temporal lobes. METHODS: Seventy healthy adult men aged 19 to 76 years underwent magnetic resonance imaging. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray vs white matter contrast. The volumes of total frontal and temporal lobes as well as the gray and white matter subcomponents were evaluated. RESULTS: Age-related linear loss in gray matter volume in both frontal (r = -0.62, P<.001) and temporal (r = -0.48, P<.001) lobes was confirmed. However, the quadratic function best represented the relationship between age and white matter volume in the frontal (P<.001) and temporal (P<.001) lobes. Secondary analyses indicated that white matter volume increased until age 44 years for the frontal lobes and age 47 years for the temporal lobes and then declined. CONCLUSIONS: The changes in white matter suggest that the adult brain is in a constant state of change roughly defined as periods of maturation continuing into the fifth decade of life followed by degeneration. Pathological states that interfere with such maturational processes could result in neurodevelopmental arrests in adulthood.