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TIMELESS (TIM) was first identified as a molecular cog in the Drosophila circadian clock. Almost three decades of investigations have resulted in an insightful model describing the critical role of Drosophila TIM (dTIM) in circadian timekeeping in insects, including its function in mediating light entrainment and temperature compensation of the molecular clock. Furthermore, exciting discoveries on its sequence polymorphism and thermosensitive alternative RNA splicing have also established its role in regulating seasonal biology. Although mammalian TIM (mTIM), its mammalian paralog, was first identified as a potential circadian clock component in 1990s due to sequence similarity to dTIM, its role in clock regulation has been more controversial. Mammalian TIM has now been characterized as a DNA replication fork component and has been shown to promote fork progression and participate in cell cycle checkpoint signaling in response to DNA damage. Despite defective circadian rhythms displayed by mtim mutants, it remains controversial whether the regulation of circadian clocks by mTIM is direct, especially given the interconnection between the cell cycle and circadian clocks. In this review, we provide a historical perspective on the identification of animal tim genes, summarize the roles of TIM proteins in biological timing and genomic stability, and draw parallels between dTIM and mTIM despite apparent functional divergence.

BACKGROUND Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.

People in Mexico speak of the medicinal properties of Moringa oleifera (“moringa”), but they know less about its nutritive properties. A qualitative, participatory approach was utilized to explore the use of moringa as a vegetable in Agua Caliente Nueva, Jalisco, by enrolling 14 female participants (mothers over 18) who were nutritional gatekeepers of the family and were responsible for preparing family meals using moringa leaves. Participants prepared meals with moringa and participated in semi‐structured interviews to record their perceptions of foods, shopping habits, and knowledge and experience using moringa. The study objectives were to assess the regional acceptability and feasibility of introducing a readily available and nutritious plant into diets, and to examine whether moringa could potentially serve as part of a solution to the double burden of malnutrition in Mexico. Findings suggest that given its ability to thrive in this dry tropical region, moringa has the potential to be recognized as a viable component in the traditional diet in this small “ejido” communal farming community.

Determining the fate of nitroaromatic compounds (NACs) in the environment requires the use of predictive models for compounds and conditions for which experimental data are insufficient. Previous studies have developed linear free energy relationships (LFERs) that relate the thermodynamic energy of NAC reduction to its corresponding rate constant. Here we present a comprehensive LFER that incorporates both the reduction and oxidation half reactions through Quantum Chemically (QC) calculated energies. This article is protected by copyright. All rights reserved.

The metallation of nucleic acids is key to wide‐ranging applications, from anticancer medicine to nanomaterials, yet there is a lack of understanding of the molecular‐level effects of metallation. Here, we apply single‐molecule fluorescence methods to study the reaction of an organo‐osmium anticancer complex and DNA. Individual metallated DNA hairpins are characterized using Förster resonance energy transfer (FRET). Although ensemble measurements suggest a simple two‐state system, single‐molecule experiments reveal an underlying heterogeneity in the oligonucleotide dynamics, attributable to different degrees of metallation of the GC‐rich hairpin stem. Metallated hairpins display fast two‐state transitions with a two‐fold increase in the opening rate to ~2 s‐1, relative to the unmodified hairpin, and relatively static conformations with long‐lived open (and closed) states of 5 s to ≥ 50 s. These studies show that a single‐molecule approach can provides new insight into metallation‐induced changes in DNA structure and dynamics.

Global climate change and acquired resistance to insecticides are threats to world food security. Drosophila suzukii, a devastating invasive pest in many parts of the world, causes substantial economic losses to fruit production industries, forcing farmers to apply broad-spectrum insecticides frequently. This could lead to the development of insecticide resistance. We determined the Lethal Concentration 50 (median lethal concentration, LC50 ) values of zeta-cypermethrin, spinosad, and malathion insecticides against D. suzukii colonies established from Clarke and Pierce county Georgia, United States. The LC50 values were 3 fold higher in the Pierce county population for all insecticide treatments. We then used RNA sequencing to analyze the responses of Pierce and Clarke population flies surviving a LC50 treatment of the 3 insecticides. We identified a high number of differentially expressed genes that are likely involved in detoxification and reduced cuticular penetration, especially in the Pierce population, with extensive overlap in differentially expressed genes between the 3 insecticide treatments. Finally, we predicted fewer nonsynonymous single nucleotide variants having deleterious effects on protein function among detoxification, insecticide target, and cuticular protein encoding genes in Pierce flies. Thus a combination of increased gene expression and fewer deleterious single nucleotide variants highlights molecular mechanisms underlying the higher LC50 values for Pierce population flies.

The experiments described in this paper look to further transient electronic device development by exploring the fracturing capabilities of aluminum copper (II) oxide and aluminum bismuth (III) oxide nanothermites. In particular, a quick, inexpensive test was developed that was able to characterize the substrate fracturing capability of these selectively deposited energetic materials. Using this test, aluminum bismuth (III) oxide nanothermite with near stoichiometric composition was shown to be an effective material for fracturing silicon wafers of two different thicknesses for the configuration considered. Nanothermites were deposited at various equivalence ratios, resulting in a range of damage, which enables material preparation in a given practical application to be based on the desired level of resultant fracturing. This data was subsequently compared with thrust measurements and gas shock formation in an effort to correlate thrust production to the severity of fracturing produced.

The diffusiophoresis of a charged sphere along the axis of a circular microtube filled with an electrolyte solution is studied theoretically. The tube wall may be either nonconductive and impermeable or prescribed with a linear electrolyte concentration distribution. The electric double layers at the solid surfaces are thin, but the diffuse-layer polarization effect over the particle surface is considered. The general solutions to the electrokinetic differential equations are expressed in spherical and cylindrical coordinates, whereas the boundary conditions at the particle surface are satisfied by a collocation technique. The collocation solutions for the diffusiophoretic velocity of the particle, which are in good agreement with the asymptotic formula derived from a reflection method, are obtained for various values of the radius ratio and zeta potential ratio between the particle and the microtube and of other relevant parameters. The contributions from the diffusioosmotic flow along the tube wall and wall-corrected diffusiophoretic driving force to the particle velocity can be superimposed due to the linearity. Although the diffusiophoretic velocity in an uncharged microtube is in general a decreasing function of the particle-to-tube radius ratio and can reverse its direction, it can increase with increases in this ratio due to the competition of the wall effects of possible electrochemical enhancement and hydrodynamic retardation to the particle motion. When the zeta potentials associated with the tube and particle are equivalent, the diffusioosmotic flow induced by the tube wall dominates the diffusiophoretic motion.

Transient changes in wettability complicate the prediction of biochar's hydrologic effects. Biochar wetting properties were characterized from poultry litter biochar (PLBC) produced from slow pyrolysis at temperatures between 300 and 600°C with water drop penetration time (persistence of hydrophobicity) and contact angle (CA; severity of hydrophobicity) measurements. Hydrophobicity was associated with semivolatile organic compounds coating PLBC surfaces, which resulted in 24.4 carbon layers and CAs of 101.1 ± 2.9° at a pyrolysis temperature of 300°C but only 0.4 layers of surface coverage and CAs of 20.6 ± 1.3° when pyrolyzed at 600°C. Mixing PLBC with water removed organic coatings, and storage in water for 72 h decreased CA as much as 81° for the most hydrophobic PLBCs. When mixed with quartz sand of the same particle size, CAs of PLBC-sand mixtures increased from 6.6 ± 1.4° at 0% PLBC mass fraction to 48.3 ± 2.0° at 15% mass fraction. Hydrophobic and hydrophilic PLBCs increased CA by nearly identical amounts at 2 and 5% mass fractions, which was explained by the influence of PLBC particle topology on macroscopic surface roughness of PLBC-sand mixtures. For environmentally relevant situations, PLBC-sand mixtures at mass fractions ≤15% remained water wetting. However, all PLBC additions increased CA, which may alter infiltration rates and induce preferential water flow.

Aim The aim of the present study was to investigate the preference and willingness-to-pay (WTP) of older Chinese adults for community end-of-life care in a nursing home rather than a hospital. Methods A total of 1540 older Chinese adults from 140 nursing homes were interviewed. Four hypothetical questions were asked to explore their preferences for end-of-life care. Using a discrete choice approach, specific questions explored acceptable trade-offs between three attributes: availability of doctors onsite, attitude of the care staff and additional cost of care per month. Results Approximately 35% of respondents preferred end-of-life care in the nursing home, whereas 23% of them would consider it in a better nursing home. A good attitude of staff was the most important attribute of the care site. Respondents were willing to pay an extra cost of US$5 (HK$39) per month for more coverage of doctor's time, and US$49 (HK$379) for a better attitude of staff in the nursing home. The marginal WTP for both more coverage of doctor's time and better attitude of staff amounted to US$54 (HK$418). Respondents on government subsidy valued the cost attribute more highly, as expected, validating the hypothesis that those respondents would be less willing to pay an additional cost for end-of-life care. Conclusions Older Chinese adults living in nursing homes are willing to pay an additional fee for community end-of-life care services in nursing homes. Both the availability of the doctor and attitudes of nursing home staff are important, with the most important attribute being the staff attitudes. Geriatr Gerontol Int 2013; 14: 273–284.

Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA-DRB1 alleles and Taiwanese children with GD by both case-control and family-based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA-DRB1 genotyping was performed by polymerase chain reaction and sequence-based typing assays. We found that DRB1*09:01 (OR = 2.60, 95% CI 2.02–3.35, Pc = 6.55 × 10−13) was associated with GD risk, while DRB1*12:02 (OR = 0.32, 95% CI 0.20–0.53, Pc = 4.55 × 10−5) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13–6.22, Pc = 1.0 × 10−5) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05–0.42, Pc = 1.7 × 10−3). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.

Eur J Clin Invest 2011; 41 (11): 1195–1201 Abstract Background Both obesity and type 2 diabetes are associated with hypovitaminosis D. We investigated the impact of body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin sensitivity. Design This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) and beta-cell function were assessed by using hyperglycaemic clamps. Serum 25OHD concentration was determined in the fasting samples. Results The correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 0·5271, P 40 ng mL−1, the association between serum 25D concentrations and insulin sensitivity plateaued. Conclusions We observed stronger associations of serum 25OHD with insulin sensitivity in overweight than normal weight subjects, suggesting that overweight subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects. Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL−1. As more than 60% of the US population is overweight and hypovitaminosis D is highly prevalent in overweight subjects, hypovitaminosis D has a large population attributable risk for type 2 diabetes.

Nitroaromatic compounds (NACs) are widespread environmental contaminants, and the one-electron reduction potential (E oH) is an important parameter used in modeling their environmental fate. We have identified a method that is both accurate and efficient to predict E oH values for NACs, using gas-phase quantum mechanics (QM) calculations combined with empirical correlations. First, the adiabatic electron affinity (EA) at 0 K is calculated using the B98/MG3S method, and the predictions are scaled by a factor of 0.802 to account for systematic errors in the density functional calculations. Second, the E oH values are predicted from a linear correlation between E oH and EA. Using this method, E oH values were predicted with a mean absolute deviation from measured values of 0.021 V for the 14 NACs used to obtain the correlation and 0.029 V for six additional NACs. This represents a substantial improvement in accuracy over predictions by other QM methods, which are affected by large errors in solvation or aqueous-phase calculations for some compounds.

Summary: In typical scanning probe microscope experiment a three-dimensional image of a substrate is obtained. For a given scanning mechanism, the time needed to image an area depends mainly on the number of samples and the size of the image. The imaging speed is further compromised by drifts associated with the substrate and the piezoscanner. It is therefore desirable to improve the imaging speed with limited impact to the effective resolution of the resulting image. By utilizing an adaptive sampling scheme with fractal compression technique, we have demonstrated that the number of the required samples can be significantly reduced with minimal impact to the image quality. SCANNING 30: 463–473, 2008. r 2008 Wiley Periodicals, Inc.

Aim: To review the outcome of homozygous alpha-thalassaemia without prior intra-uterine therapy treated in neonatal intensive care unit and identify the factors associated with survival. Methods: The hospital records of all patients with homozygous alpha-thalassaemia treated in our neonatal intensive care unit in the last 15 years were reviewed. A literature search beginning in the year 1980 was done to identify homozygous alpha-thalassaemia actively treated in neonatal intensive care units. Those receiving prior intra-uterine therapy were excluded. The following information was collected: the severity of hydrops, sizes of liver and spleen, haemoglobin level, Apgar score at 5 min, ventilator settings, timing and forms of red blood cell transfusion and presence of persistent hypoxaemia. The survivors and the non-survivors were compared. Results: In our centre, in the last 15 years there were six infants born with homozygous alpha-thalassaemia who did not receive intra-uterine therapy; one survived and five succumbed despite aggressive respiratory therapy. In our literature search there were more reports of survivors (10) than non-survivors (six) for these infants, suggesting a reporting bias towards selection of rare cases of survival. Apgar score of four or above occurred in seven of the eight survivors with data available in the reports, whereas this occurred in four of the 11 non-survivors (P = 0.035, Fisher Exact test). Five of the 11 survivors had abnormal neurological outcome including developmental delay and spastic quadriplegia. Conclusion: Without prior intra-uterine therapy, homozygous alpha-thalassaemia has grave outlook in terms of mortality and morbidity despite aggressive respiratory therapy.

Post-translational modification (PTM) such as phosphorylation is an integral step in protein regulation. Poly-ubiquitylation is a PTM carried out by E3 Ubiquitin Ligases (E3), which is important fo...

Aims: To identify the subjects of interest and to examine the modes as well as means of study for continuing professional dental education amongst general dental practitioners who attended the 26th Asia Pacific Dental Congress, 28 May—1 June 2004, Hong Kong. Methods: A total of 381 general dental practitioners as the registered conference delegates from Hong Kong, Mainland China and other Asia-Pacific regions were randomly selected for the present survey. The survey was conducted through face-to-face interviews by a group of practising dentists in Hong Kong. Results: Overall, orthodontics and prosthodontics were the most popular subjects for clinical degree programmes, whilst oral implantology and cosmetic dentistry were the highly preferred subjects for continuing education courses. Concerning the preferred mode of study for degree programmes, the part-time study mode was chosen by 68.3% of the participating dentists. A didactic teaching approach was preferred by most of the participants (81.7%) for postgraduate study. The majority of the interviewees (76.5%) were interested in a proposed clinical degree programme to be offered jointly by The University of Hong Kong and a leading university in the Mainland. Overall, there was no marked difference in the preference for continuing dental education amongst the respondents from Hong Kong, Mainland China and other Asia-Pacific regions. Conclusions: The present survey shows the currently preferred specialty areas and subjects for continuing professional dental education amongst the general dental practitioners who attended the 26th Asia Pacific Dental Congress, with didactic teaching as the most preferred mode of study on a part-time basis.

The objective of the present study was to assess the effect of the addition of 0.2% anticaking agent "silicon dioxide" (S) and of 70.0% reduction of the headspace in the package (H) both individually and combined (SH), on the sensory and physicochemical characteristics of a powdered-drink mix over a shelf-life period of 120 days. The "difference from control" test was applied to 10 trained panelists in order to assess the four treatments at 30-day intervals throughout the experimental period, according to visual aspect of the powdered mix and drink flavor. The results demonstrated that a reduction of 70% of the headspace was the most effective treatment for product sensory stability. Water activity (A w ) was a more sensitive parameter than moisture content and ascorbic acid degradation. Although A w has shown a significant difference over time, the sensory properties still seemed to be a better shelf-life indicator for powdered mixes. Based on the sensory alterations of the aspect of the powder, a reduction of headspace and the limiting of shelf life to between 60 and 90 days could be recommended for powdered-drink mixes packaged in polypropylene containers.

As part of a study to evaluate an integrated zero-valent iron (Fe(0))-biological oxidation process for treating azo dye wastewaters, we conducted batch and column experiments with the azo dye orange G to assess the effects of solution conditions on the performance of iron pretreatment. The influence of iron type and surface area, solution pH, dissolved inorganic salts, and phosphate ion on the reduction (decolorization) of orange G solution were examined. In batch experiments, increased iron surface area, decreased pH, and chloride and sulfate salts enhanced dye decolorization, whereas high pH (9.9) and phosphate concentrations (> 3 mg/L PO4-P) inhibited dye reduction. Results from batch experiments were confirmed in column experiments. An increase in temperature from 22 to 35 degrees C resulted in a near doubling of the reduction rate constant in a column study. The abiotic reduction results illustrate the feasibility and potential limitations of an integrated iron column, activated sludge treatment process for wastewaters containing azo dyes.

Aim Apolipoprotein AV (APOA5) is an important determinant of plasma triglyceride concentration. This study aimed to investigate the relationship of an amino acid substitution at position 182 (G182C) of the apolipoprotein AV (APOA5) gene with triglyceride concentration in a Taiwanese population. Methods This study enrolled two cohorts: non-diabetic subjects (112 males and 89 females) aged 50.3 ± 11.0 years (mean ± sd) and diabetic subjects (106 males and 96 females) aged 62.1 ± 10.3 years. The relationship between the G182C polymorphism (rs 2075291) and plasma triglycerides was examined. Demographic and metabolic parameters including age, sex, body mass index, fasting plasma glucose and total cholesterol were also obtained. Results The G182C polymorphism was a determinant of plasma triglycerides in both non-diabetic (P = 0.022) and diabetic (P = 0.003) groups, independent of age, gender, fasting plasma glucose, body mass index and total cholesterol. In the diabetic group, this genetic polymorphism interacts significantly (P = 0.032) with fasting plasma glucose concentration on plasma triglycerides after adjustment for age, sex, body mass index and total cholesterol. Conclusions In conclusion, the G182C polymorphism of the APOA5 gene affects plasma triglycerides in both non-diabetic and diabetic populations. The observed interaction of gene and glycaemic control further indicates a multifactorial nature of clinical phenotypes in subjects with Type 2 diabetes. Diabet. Med. (2005)

Summary Design Prevalence of type 2 diabetes and glucose intolerance increase with age. It has been demonstrated that beta cell function declines at about 1% per year in glucose tolerant Caucasians. However, this relationship is not known to exist in other ethnic groups. Subjects and Measurements We investigated the relationship of age to beta cell function (%B) and insulin sensitivity (%S), estimated by the homeostasis model assessment, in a nationally representative sample of healthy US adults who participated in a cross-sectional study, the third National Health and Nutrition Examination Survey. Only those subjects who had never been told to have diabetes by a physician, with HbA1C

Chronic HBsAg carriers are known to have a higher risk of hepatitis-related mortality and morbidity when undergoing kidney transplantation. Immunosuppressants might flare up the infection that could be fulminating. Lamivudine and mycophenolate mofetil (MMF) have been shown to be effective in inhibiting replication of hepatitis B virus (HBV). With these two drugs, hepatitis related adverse outcome might be preventable when these patients are being transplanted. Four Chinese adolescents with chronic HBV infection were transplanted in our Department from 1999 to 2001. Immunosuppresants included prednisolone, cyclosporin A and MMF; azathioprine was not used for its potentially liver toxic effect. Prophylactic lamivudine 3 mg/kg and maximum 100 mg daily was given just before transplantation and was continued afterwards. HBV status and liver enzymes were monitored serially. Patients were followed up for 26.0 ± 10.3 (11–34) months post-transplant and no mortality was reported. All grafts were functioning and no rejection was noted. MMF and lamivudine were well tolerated. Alanine transaminase was only transiently elevated in the first 2 months post-transplant in all patients and became normal afterwards. The patients were clinically well and liver function was normal at the last follow-up. However, HBV DNA became positive in three patients after the transplantation. YMDD mutant HBV was negative in one patient and undeterminable in the other three due to low virus load. In summary, with prophylactic lamivudine and MMF, short-term follow-up showed that renal transplant might be feasible and safe in chronic HBV carriers.

Problem: The physiological role of antibody-binding proteins in human seminal plasma and the potential role of these proteins in infertility is relatively unknown. Method of study: Literature on antibody-binding proteins. Results: Human seminal plasma has a diverse effect on immune function of the reproductive tracts. This review describes (1) the presence of receptors like proteins that can react with monoclonal antibodies against Fcγ receptors III (Fcγ RIII) but are distinctly different from Fcγ RIII; (2) IgG binding factors (IgGBF), a group of low molecular weight proteins that are capable of binding human IgG; (3) other proteins that can bind antibodies, such as prolactin-inducible protein and three other novel proteins that we have discovered. These proteins potentially all have the ability to reduce the interactions between antisperm antibodies and effector components of the immune system, such as phagocytic cells. Conclusions: Human seminal plasma contains proteins that can bind antibodies. However, to date our knowledge of these proteins especially, whether they have a physiological role in either the male and female reproductive tracts is limited.

Summary Cryptococcal meningitis is an uncommon but often fatal complication of systemic lupus erythematosus (SLE). We report on a 13-year-old girl with SLE using high-dose prednisolone for several months, presented to us with low grade fever, intermittent vomiting and headache. Physical examination, including papilloedema and meningeal irritation, was unremarkable. Serum and cerebrospinal fluid (CSF) cryptococcal antigen titer was 1 : 128 by latex agglutination method. CSF culture yielded Cryptococcus neoformans. We used amphotericin B deoxycholate (a cumulative dose of 1.95 gm) and fluconazole (200 mg day−1) for 6 weeks. Clinical response was good. Then, we continued fluconazole 200 mg per qd as suppressive therapy for thirty-four months. There were no neurological sequelae or relapse after 20-month follow-up. Timely diagnosis and effective antifungal therapy could improve the prognosis of cryptococcal meningitis in SLE patients. Zusammenfassung Wir berichten uber ein 13jahriges Madchen mit systemischem Lupus erythematodes, das uber mehrere Monate hochdosiert Prednisolon bekam und bei uns mit leichtem Fieber, intermittierendem Erbrechen und Kopfschmerzen vorgestellt wurde. In Serum und Liquor konnte Cryptococcus-Antigen nachgewiesen werden. Aus dem Liquor wurde Cryptococcus neoformans isoliert. Die Patientin wurde mit Amphotericin B (kumulative Dosis 1,95 g) und nachfolgend 6 Wochen lang mit Fluconazol (200 mg day−1) behandelt. Die Weiterbehandlung erfolgte 34 Monate Lang mit Fluconazol 200 mg/qd als Suppressionstherapie.

BACKGROUND Hurthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hurthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hurthle cell carcinomas that predict disease progression or death. METHODS The authors reviewed medical records of patients who were treated for Hurthle cell carcinoma (HCC) and Hurthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS The authors identified 127 patients with Hurthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy. Cancer 2003;97:1186–94. © 2003 American Cancer Society. DOI 10.1002/cncr.11176

Summary objective The significance of the association of amino terminal polymorphisms in β2-adrenoreceptor (ADRB2) with obesity and type 2 diabetes is controversial and differs among ethnic groups. In this study, the association of ADRB2 with risk and age of onset of type 2 diabetes has been examined in a Taiwanese population. design The study design is a case–control study to investigate the impact of the two amino acid polymorphisms in ADRB2. patients and measurements This study includes 130 patients with type 2 diabetes [female : male = 1 : 1, age: 52·4 ± 10·0 years; body mass index (BMI): 24·2 ± 2·9 kg/m2; mean ± SD] and 130 controlled subjects matched for gender, age and BMI with normal glucose tolerance (female : male = 1 : 1, age: 51·7 ± 10·6 years; BMI: 23·9 ± 2·7 kg/m2). The Arg16Gly and Gln27Glu polymorphisms of ADRB2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) assays. The genotypic and allelic frequencies between two groups were compared and the relationship between the genotypes and clinical phenotypes was examined. results A difference in genotypic frequency in the Arg16Gly polymorphism was noted between groups in this gender-, age- and BMI-matched case–control study (P = 0·039). Multivariate regression analysis revealed that the Arg16Gly polymorphism was the only independent factor for development of type 2 diabetes (P = 0·021). In addition, we utilized the log-rank test to compare the differences in age of onset between wild-type and nonwild-type polymorphisms. The Arg16Gly polymorphism was independently associated with age of onset in type 2 diabetes (P = 0·017). There was no difference in the Gln27Glu polymorphism between diabetic and control groups in this study. conclusions In a Taiwanese population, homozygosity of Arg16 in the ADRB2 gene was associated with a higher frequency (odds ratio 1·87, 95% confidence interval 1·34–2·40) for development of type 2 diabetes. Moreover, this polymorphism was also associated with an earlier onset of type 2 diabetes. However, the Glu27Gln polymorphism had no impact on either BMI or type 2 diabetes in a Taiwanese population.

PROBLEM: The significance of antibody-mediated infertility is unclear and complicated by the finding of that antisperm antibodies are found both in fertile and infertile couples. Seminal plasma contains immunosuppressive factors, one such factor may be antibody-binding proteins (ABP's). METHOD OF STUDY: Antibody-binding-proteins were purified using human IgG or IgG-Fc affinity chromatography columns. The purified antibody-binding proteins were characterized by their molecular weights, partial amino acid sequences, and immunoreactivities. RESULTS: Three proteins of molecular weight 74, 70 and 55 kDa and other low molecular weight proteins specifically bound to the IgG or IgG-Fc affinity columns demonstrating Fc-binding specificities. These proteins were not FcγRIII, IgG, or fragments of these proteins by their behaviors under reducing conditions, Western blot, and partial amino acid sequence analyses. Amino acid sequence data demonstrated some of these proteins to be novel. CONCLUSIONS: We have isolated and partially characterized several ABP's from seminal plasma. The IgG-binding proteins we have identified may protect spermatozoa against antibody-mediated damage by conferring protection to antibody-coated spermatozoa. If this hypothesis holds true, differences in the level or function of these ABP's may alter the status of fertility.

The effect of adsorption to elemental iron on the reductive transformation of 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (royal demolition explosive (RDX)) in aqueous solution was studied with scrap iron and high-purity iron. In batch experiments with the same total iron surface area and a mixing rate of 100 rpm, TNT and RDX were removed from the solution within 30 min. With high-purity iron, adsorbed TNT was reduced to 2,4,6-triaminotoluene (TAT) rapidly, with little accumulation of intermediates at the surface. With scrap iron, the extent of adsorption of TNT and its daughter products was more significant and reduction of these adsorbed molecules to TAT was slower. Distribution of the intermediates indicated that the reaction with scrap iron occurred primarily through reduction of the ortho nitro group. Kinetic analysis suggests that mass transfer or adsorption of TNT controlled the overall rate of TNT reduction to TAT with pure iron, whereas with scrap iron, the rate of TAT formation was probably limited by other processes. Compared to TNT, transformation of adsorbed RDX was more rapid and less affected by iron type. The RDX was reduced to an unidentified, water-soluble intermediate and NH 4 + , which accounted for approximately 50% of the RDX nitrogen. No total organic carbon reduction was observed before and after RDX transformation with scrap iron.

The use of the Rapid Visco Analyser (RVA) for application in the screening of wheat breeding lines for starch quality and potential noodle quality has been limited by relatively low sample throughput. Current methods generally enable only 20–30 samples to be tested each day. This study sought to develop a more rapid time-temperature profile that could be applied to whole meal samples. A profile that involved a total analysis time of 7.5 min/sample gave measurements of peak viscosity (PV) and breakdown (BD) on whole meal that were highly correlated with corresponding measurements obtained using a more conventional profile that had been applied to low-extraction flours. BD and PV were also highly correlated with the total texture score of ramen (Chinese-style alkaline noodles as manufactured in Japan), but only when 1 mM AgNO3 was used to eliminate the effects of α-amylase.

A nodavirus was isolated from diseased yellow grouper, Epinephelus awoara, larvae cultured in southern Taiwan. The histopathology and RT–PCR results confirmed that it was a fish nodavirus; its coat protein gene sequence was similar to that of red spotted grouper nervous necrosis virus (RGNNV) and it is named yellow grouper nervous necrosis virus (YGNNV). A new nodavirus-susceptible cell line, grouper brain (GB) was established and characterized from the brain tissue of yellow grouper. The GB cells multiplied well in Leibovitz’s L-15 medium supplemented with 10% foetal bovine serum at temperatures between 24 and 32 °C, and have been subcultured more than 80 times, becoming a continuous cell line. The GB cell line consists of fibroblast-like cells and some epithelioid cells. The cell line yielded titres of YGNNV up to 108.5 TCID50 mL–1. The GB cells effectively replicated the virus at 28 °C, which could be purified to homogeneity by caesium chloride gradient centrifugation. Electron microscopy studies showed that purified virus particles were 25–30 nm in diameter. The cytoplasm of infected cells was filled with aggregates of virus particles. These results indicate that the GB cell line is a significant tool for the study of fish nodaviruses.

CHIU, C.C., et al.: Clinical Use of Permanent Pacemaker for Conversion of Intraatrial Reentry Tachycardia in Children. The use of the implanted atrial-based pacemaker to overdrive postsurgical intraatrial reentry tachycardia (IART) was evaluated in a large group of pediatric patients over a 14-year study period. The authors sought to determine the feasibility of this noninvasive technique in the management of this specialized population and to determine factors associated with successful conversion. They examined 128 manual overdrive attempts performed on 22 consecutive patients. There were 10 patients with post-Fontan repair, 7 with post-Mustard/Senning procedure, and 5 with miscellaneous lesion types. The number of IART episodes for overdrive pacing per patient ranged from 1 to 15. The first overdrive pacing attempt was successful in 63% (14/22) of the patients. The mean IART cycle length was 278 ± 59 ms. The mean pacing rate for effective conversion of IART was 66 ± 10% faster than the IART rate. By controlling for repeated measures for individual patients, three factors were found to be independently associated with a successful outcome: (1) lesion type other than Fontan surgery (P = 0.007), (2) lack of acceleration of IART with the overdrive attempt (P < 0.001), and (3) patient use of amiodarone with attempt (P = 0.005). There were three procedural complications: two inadvertent overdrive pacing episodes, and one episode of acceleration of IART cycle length and conduction resulting in need for cardioversion. Manual pacemaker overdrive conversion of IART is a useful adjunct in the management of postsurgical IART in the pediatric population and should be considered as an initial treatment option.

Background An A54T polymorphism of the fatty acid binding protein 2 (FABP2) gene was found to be associated with insulin resistance in nondiabetic Pima Indians. Design This is a cross-sectional study to examine the role of this polymorphism in insulin resistance in 71 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S, ISIM, ISIS) and beta-cell function (%B, dI/dG, 1stPHS, 2ndPHS) were estimated based on published models. Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotypes and phenotypes was examined. Results After genotyping, we identified 34 AA, 32 AT and five TT subjects. The TT subjects were pooled together with the AT subjects during the analysis due to their low number. No difference was noted in gender distribution, clinical features, or fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had lower %S and ISIS than the AA group (P = 0·0118 and P = 0·0170, respectively). The difference in ISIM was marginal (P = 0·0544). However, no difference was noted in beta-cell function between the two groups. Multivariate analysis revealed that this polymorphism was an independent but modest determinant for %S (P = 0·0149), ISIM (P = 0·0489) and ISIS (P = 0·0175). It independently contributed 6·04% (95% CI, 0·02–20·53%), 4·28% (95% CI, 0·08–17·63%) and 4·94% (95% CI, 0·01–18·75%) of the variation of %S, ISIM and ISIS, respectively. Conclusions We demonstrated that the A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population.