Cystatin B and its EPM1 mutants are polymeric and aggregate prone in vivo.
Progressive myoclonus epilepsy type 1 (EPM1) is a neurodegenerative disease correlating with mutations of the cystatin B gene. Cystatin B is described as a monomeric protein with antiprotease function. This work shows that, in vivo, cystatin B has a polymeric structure, highly resistant to SDS, urea, boiling and sensitive to reducing agents and alkaline pH. Hydrogen peroxide increases the polymeric structure of the protein. Mass spectrometry analysis shows that the only component of the polymers is cystatin B. EPM1 mutants of cystatin B transfected in cultured cells are also polymeric. The banding pattern generated by a cysteine-minus mutant is different from that of the wild-type protein as it contains only monomers, dimers and some very high MW bands while misses components of MW intermediate between 25 and 250 kDa. Overexpression of wild-type or EPM1 mutants of cystatin B in neuroblastoma cells generates cytoplasmic aggregates. The cysteine-minus mutant is less prone to the formation of inclusion bodies. We conclude that cystatin B in vivo has a polymeric structure sensitive to the redox environment and that overexpression of the protein generates aggregates. This work describes a protein with a physiological role characterized by highly stable polymers prone to aggregate formation in vivo.


[Seasonal dynamics of hydrochemical characteristics of streams under different forest types].
Stream water samples under the Korean pine broad-leaved forest, spruce-fir forest, and larch plantation in Liangshui Nature Reserve of Xiaoxing' an Mountains were collected monthly from March to October 2006 to study the dynamic changes of their hydrochemical characteristics. The results indicated that the content of major cations in the streams was in the sequence of Ca2+ > Na+ > K+ > Mg2+, and that of anions was HCO3(-) > SO4(2-) > NO3(-) > Cl(-). The average content of Na+, Ca2+, Mg2+, Fe2+ and Fe3+ was in the order of spruce-fir forest > larch plantation > Korean pine broad-leaved forest, while that of K+ was in the order of larch plantation > spruce-fir forest > Korean pine broad-leaved forest. The average monthly content of anions in stream water was the highest under larch plantation.


DMSO/t-BuONa/O2-Mediated Aerobic Dehydrogenation of Saturated N-Heterocycles.
Aromatic N-heterocycles such as quinolines, isoquinolines, and indolines are synthesized via sodium tert-butoxide-promoted oxidative dehydrogenation of the saturated heterocycles in DMSO solution. This reaction proceeds under mild reaction conditions and has a good functional group tolerance. Mechanistic studies suggest a radical pathway involving hydrogen abstraction of dimsyl radicals from the N-H bond or α-C-H of the substrates and subsequent oxidation of the nitrogen or α-aminoalkyl radicals.


Evaluation of a dynamic ankle foot orthosis in hemiplegic gait: A case report.
This investigation utilized a single case design to evaluate the effects of a dynamic AFO on ambulation in post stroke hemiplegia. A single patient with stroke related hemiplegia using a dynamic AFO underwent gait analysis while walking on level ground. Outcome measures included temporal-spatial gait parameters and bilateral kinematic joint angles at the ankle, knee, and hip with and without AFO. Walking speed, stride length, step length and cadence increased with the dynamic AFO. Step width and double support decreased, while single support remained unchanged on the affected limb with the dynamic AFO. With the dynamic AFO there was increased hip flexion at foot strike and toe-off, increased hip sagittal plane angular velocity during swing, and decreased abduction. The dynamic AFO had a positive effect on the participant's overall gait which included improved temporal-spatial parameters and gait velocity which is likely due to a decrease in the overall energy cost of walking. Kinematic angles at the hip were most notably affected by brace utilization and this effect should be more fully explored. Further research with a larger sample utilizing dynamic AFOs is indicated to explore the generalizability of these findings and to determine the potential utility of these braces as an alternative to the traditionally prescribed solid AFO.


Non-Hodgkin's lymphoma of the thyroid gland occurring after treated Hodgkin's lymphoma.
To present a case report of the occurrence of non-Hodgkin's lymphoma in the thyroid gland of a patient who had previously undergone successful treatment of Hodgkin's lymphoma. We describe pertinent historical features and current symptoms and laboratory findings in a 62-year-old man who had had successful treatment of Hodgkin's lymphoma 10 years previously and had been free of disease for a decade. We also review the related medical literature on the course of patients after therapy for Hodgkin's lymphoma. Because of a progressively enlarging anterior neck mass, hoarseness, and difficulty with breathing, a patient sought medical attention. Ten years previously, he had undergone irradiation and splenectomy for treatment of Hodgkin's lymphoma. In the current assessment, fine-needle aspiration and open biopsy yielded the diagnosis of non-Hodgkin's lymphoma, for which the patient received irradiation and chemotherapy. Review of the literature pertaining to diseases after treated Hodgkin's lymphoma, including second cancers, failed to identify any such prior reported case. Because the clinical profile of our patient was consistent with primary non-Hodgkin's lymphoma of the thyroid gland developing after radiation-treated Hodgkin's lymphoma, we conclude that this represents the first such reported example.


[Research on mutual collation between Japan Cabinet Edition and National Beijing Library Edition of Shang han lun (Treatise on Cold Pathogenic Disease)].
Through textual research on the Song Dynasty block-printed large-character and small-character editions of Shang han lun (Treatise on Cold Pathogenic Disease), it can be definitely verified that Yang Shoujing's so-called 'facsimile handwritten copy of Northern Song edition' was an apocrypha fabricated by Yang himself. Japanese Horikawa's An zheng edition, the original edition adopted by Yun Tieqiao's photocopy, did exert a profound and lasting influence on China. After collating the Song Dynasty block-printed edition collected in Japan National Cabinet Library with the one collected in the National Beijing Library thoroughly, and checking the prefaces and postscripts carefully, it has been found, for the first time, that these two editions, both called 'Song edition', differ dramatically.


The effects of electrode impedance on data quality and statistical significance in ERP recordings.
To determine whether data quality is meaningfully reduced by high electrode impedance, EEG was recorded simultaneously from low- and high-impedance electrode sites during an oddball task. Low-frequency noise was found to be increased at high-impedance sites relative to low-impedance sites, especially when the recording environment was warm and humid. The increased noise at the high-impedance sites caused an increase in the number of trials needed to obtain statistical significance in analyses of P3 amplitude, but this could be partially mitigated by high-pass filtering and artifact rejection. High electrode impedance did not reduce statistical power for the N1 wave unless the recording environment was warm and humid. Thus, high electrode impedance may increase noise and decrease statistical power under some conditions, but these effects can be reduced by using a cool and dry recording environment and appropriate signal processing methods.


Functional Capacity, Lipid Profile, and Associated Factors in Older Adults Living in Urban and Rural Areas.
This study aimed to analyze the relationship between sociodemographic and lifestyle variables, functional strength, aerobic capacity, and lipid profile of older adults living in urban and rural areas. For this purpose, 208 older adults were evaluated (132 living in rural areas and 73 living in urban areas). Sociodemographic data were collected, and functional strength, aerobic capacity, and lipid profile of older adults living in the southern region of Brazil were evaluated. Only total cholesterol and LDL cholesterol were associated with place of residence (p < 0.05), and living in the countryside was associated with low aerobic capacity (p=0.010). The use of medication (OR = 3.01; p=0.012) and smoking (OR = 0.30; p=0.027) were the only variables that explained aerobic performance, regardless of place of residence. In conclusion, place of residence is not a factor that, alone or in combination with other conditions, affects the functional performance or lipid profile of the older adult population.


SKF83959 produces antidepressant effects in a chronic social defeat stress model of depression through BDNF-TrkB pathway.
SKF83959 stimulates the phospholipase Cβ/inositol phosphate 3 pathway, resulting in the activation of Ca(2+)/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway.


Long-term Results of Scandinavian Total Ankle Replacement.
The purpose of this study was to evaluate the long-term results of the Scandinavian Total Ankle Replacement (STAR) implant in a single center. Between 1997 and 2002, 34 consecutive ankles were replaced with the STAR ankle prosthesis and reviewed in 2016. Patients were followed both radiologically and clinically; clinical outcomes were measured with the Kofoed ankle score and subjective measurements. The median follow-up period was 159 months (13.3 years; range, 13-202 months). The implant survival rate was 93.9% (95% confidence interval [CI], 92.2%-86.7%) at 5 years, 86.7% (95% CI, 69.3%-96.2%) at 10 years, and 63.6% (95% CI, 30.8%-89.0%) at 15 years. A total of 15 ankles (44%) had been revised: 2 by fusion, 3 by further replacement, 5 by insert exchange, and 5 by bone grafting for marked osteolysis. The improvements in the Kofoed ankle score and Kofoed ankle score for pain were statistically significant at every postoperative evaluation point compared to the preoperative values (all P < .0001), and subjective patient satisfaction was high. Our results were satisfactory and in agreement with previously reported findings of STAR implants. Level IV, retrospective case series.


Time-Varying Association of Individual BP Components with eGFR in Late-Stage CKD.
The association of individual BP components with changes in eGFR in patients with late-stage CKD is unknown. The objectives of our study were to examine the associations of systolic BP, diastolic BP, and pulse pressure with continuous temporal changes in eGFR and an eGFR decline ≥30% in late-stage CKD. We performed a retrospective cohort study (2010-2015) of patients with CKD in a multidisciplinary CKD clinic with an eGFR≤30. The associations of repeat measures of BP (systolic BP, diastolic BP, and pulse pressure) with eGFR were examined using general linear mixed models. The associations of BP components and eGFR decline ≥30% were examined with time-varying Cox models. In total, 1203 patients were followed for a median of 548 days (interquartile range, 292-913), with an average of 6.7 visits and BP measures per patient. Mean baseline systolic BP, diastolic BP, pulse pressure, and eGFR were 139.2 mmHg, 73.2 mmHg, 64.9 mmHg, and 16.8 ml/min, respectively. Systolic BP and diastolic BP measures over time were statistically significantly associated with changes in eGFR (P<0.001), whereas pulse pressure was not. Patients with extremes of systolic BP (<105 or >170) and high diastolic BP (>90) measures were at a higher risk of GFR decline ≥30% (systolic BP <105: hazard ratio, 1.51; 95% confidence interval, 0.98 to 2.34; systolic BP >170: hazard ratio, 1.62; 95% confidence interval, 1.05 to 2.49; referent systolic BP =121-130; diastolic BP =81-90: hazard ratio, 1.40; 95% confidence interval, 0.99 to 1.86; diastolic BP >90: hazard ratio, 1.83; 95% confidence interval, 1.21 to 2.77; referent diastolic BP =61-70). The findings were consistent after multiple sensitivity analyses. Pulse pressure was not significantly associated with risk of eGFR decline. In patients referred to a multidisciplinary care clinic with late-stage CKD, only extremes of systolic BP and elevations of diastolic BP were associated with eGFR decline.


Predicting the earnings of supported employees with mental retardation: a longitudinal study.
A random sample (N = 197) of supported employees with mental retardation was examined in a longitudinal study. Results indicate that intelligence, prior earnings, and federal job subsidy predicted future earnings. Statistical controls applied to the stratified sample show that job placement, job type, subsidy, and means of transportation had little influence on earnings.


GAG depletion increases the stress-relaxation response of tendon fascicles, but does not influence recovery.
Cyclic and static loading regimes are commonly used to study tenocyte metabolism in vitro and to improve our understanding of exercise-associated tendon pathologies. The aims of our study were to investigate if cyclic and static stress relaxation affected the mechanical properties of tendon fascicles differently, if this effect was reversible after a recovery period, and if the removal of glycosaminoglycans (GAGs) affected sample recovery. Tendon fascicles were dissected frombovine-foot extensors and subjected to 14% cyclic (1Hz) or static tensile strain for 30min. Additional fascicles were incubated overnight in buffer with 0.5U chondroitinase ABC or in buffer alone prior to the static stress-relaxation regime. To assess the effect of different stress-relaxation regimes, a quasi-static test to failure was carried out, either directly post loading or after a 2h recovery period, and compared with unloaded control fascicles. Both stress-relaxation regimes led to a significant reduction in fascicle failure stress and strain, but this was more pronounced in the cyclically loaded specimens. Removal of GAGs led to more stress relaxation and greater reductions in failure stress after static loading compared to controls. The reduction in mechanical properties was partially reversible in all samples, given a recovery period of 2h. This has implications for mechanical testing protocols, as a time delay between fatiguing specimens and characterization of mechanical properties will affect the results. GAGs appear to protect tendon fascicles from fatigue effects, possibly by enabling sample hydration.


Solving time-independent inhomogeneous optoacoustic wave equation numerically with a modified Green's function approach.
The purpose of the paper is twofold. First, a modified Green's function (MGF) approach is described for solving the time-independent inhomogeneous optoacoustic (OA) wave equation. The performance of this technique has been assessed with respect to the exact, traditional Born series and convergent Born series methods for an acoustically inhomogeneous spherical source. Second, we apply the same approach for calculating time domain signal from a blood vessel network consisting of an ensemble of acoustically homogeneous/inhomogeneous randomly positioned disks resembling cells. The predicted signals have been compared with those generated by the exact method and a freely available standard software. The OA spectra for a spherical source demonstrated excellent agreement with the exact results when sound-speed for the source was varied from -20% to 30% compared to that of the surrounding medium. The simulated OA signals also followed the same trend as that of the exclusively used software for the acoustically homogeneous blood vessel network. Future work will focus inclusion of a suitable phase factor within the MGF facilitating OA pulses building up at correct temporal locations for an acoustically inhomogeneous source.


Distribution Amplitudes of K^{*} and ϕ at the Physical Pion Mass from Lattice QCD.
We present the first lattice QCD calculation of the distribution amplitudes of longitudinally and transversely polarized vector mesons K^{*} and ϕ using large momentum effective theory. We use the clover fermion action on three ensembles with 2+1+1 flavors of highly improved staggered quarks action, generated by the MIMD Lattice Computation Collaboration, at physical pion mass and {0.06,0.09,0.12} fm lattice spacings and choose three different hadron momenta P_{z}={1.29,1.72,2.15} GeV. The resulting lattice matrix elements are nonperturbatively renormalized in a recently proposed hybrid scheme. An extrapolation to the continuum and infinite momentum limit is carried out. We find that, while the longitudinal distribution amplitudes tend to be close to the asymptotic form, the transverse ones deviate rather significantly from the asymptotic form. Our final results provide crucial ab initio theory inputs for analyzing pertinent exclusive processes.


Reconsidering Depression in the Elderly.
The authors present a literature review and a scientific commentary. The prevalence of depressive disorders in the elderly and their association with significant morbidity and mortality are discussed in relation to study of clinical heterogeneity, which may provide useful insights into etiologic and pathophysiologic variability. The authors summarize findings regarding clinical and associated features of late-life depression, explore the limitations of current factual knowledge and conceptual approaches, and propose directions for future research. They argue that current sample selection procedures minimize the variability of the very phenomena under study; therefore, few phenomenologic differences or risk factors for long-term outcome have been noted consistently. Factors such as medical illness account for much of the observed heterogeneity in presentation and outcome. Future studies must include a broader range of subjects and carefully examine in a multidimensional fashion a wider range of "comorbid" conditions, personality and social assessments, and neuropsychologic and neurobiologic measures. Such approaches will enhance our understanding of the pathophysiologic mechanisms of depression in the elderly and across the lifespan.


CW-OSL measurement protocols using optical fibre Al2O3:C dosemeters.
A new system for in vivo dosimetry during radiotherapy has been introduced. Luminescence signals from a small crystal of carbon-doped aluminium oxide (Al2O3:C) are transmitted through an optical fibre cable to an instrument that contains optical filters, a photomultiplier tube and a green (532 nm) laser. The prime output is continuous wave optically stimulated luminescence (CW-OSL) used for the measurement of the integrated dose. We demonstrate a measurement protocol with high reproducibility and improved linearity, which is suitable for clinical dosimetry. A crystal-specific minimum pre-dose is necessary for signal stabilisation. Simple background subtraction only partially removes the residual signal present at long integration times. Instead, the measurement protocol separates the decay curve into three individual components and only the fast and medium components were used.


Inhibitor of peritoneal mononuclear phagocyte colony forming cells.
We investigated an inhibitory factor present in mouse L-cell conditioned medium. This soluble factor, colony inhibitory factor (CIF), selectively inhibits the clonal growth of mouse peritoneal exudate (PE) macrophages in vitro. CIF appears to be a non-dialyzable macromolecule which was eluted by Sephadex G200 gel filtration at post-albumin fractions. It can be fractionated by ammonium sulfate precipitation within the range of 60%--70% saturated solution at room temperature. CIF is moderately heat labile and is destroyed by incubation at high pH. CIF is more effective on PE cells from C57 mice than on those from C3H or DBA mice. It also inhibits the clonal growth of committed stem cells for both granulocytes and macrophages present in bone marrow but to a much lesser degree. CIF is not interferon since no antiviral activity is demonstrable in the CIF preparation.


Pretreatment of polyamide monofilament with hydrochloric acid improves sensitivity of three-dimensional microarray, Bio-Strand.
A single-nucleotide-polymorphism-typing method using a novel three-dimensional DNA microarray, Bio-Strand, is promising because it is rapid, inexpensive and easily automated. It has been developed with the intent to overcome the drawbacks of conventional DNA microarrays, which use flat surfaces and impermeable materials such as glass slides; Bio-Strand as a novel DNA microarray, with its permeability, has a significantly improved stability compared with conventional DNA microarrays that use impermeable materials. In this study, we have developed a simple method of pretreating a polyamide monofilament to increase its surface area and to make it permeable, which makes Bio-Strand more sensitive and stable, allowing it to be adapted for clinical diagnostic applications. The fluorescence signal obtained with a nylon 6 monofilament pretreated under optimal conditions (hydrolysis by 5 M HCl/ethanol followed by washing with 50% ethanol and 100% ethanol) was significantly stronger than that obtained with an untreated monofilament.


Pulmonary hypertension, pulmonary edema, and decreased pulmonary compliance produced by increased ICP in cats.
Cats, anesthetized with sodium pentobarbital, were cannulated to measure pulmonary, systemic, and left atrial pressures and pulmonary ventilation, compliance, and resistance. Intracranial pressure was elevated to 30 mm Hg by injecting silicone oil into the extradural space. After an average time of 56 minutes, pulmonary systolic and diastolic pressures more than doubled, systemic systolic pressure sometimes rose and sometimes fell, and diastolic pressure rose 5%. Left atrial pressure never exceeded 8 cm of saline. Pulmonary compliance decreased by one-half, but airway resistance was unchanged. Pulmonary edema was estimated from histological sections. The pulmonary hypertension may be the result of a sympathetic discharge confined to the lung, since no remarkable changes in heart rate or systemic blood pressure occurred. The decrease in pulmonary compliance followed the rise in pulmonary arterial pressure, and is interpreted as the result of interstitial edema. There was no evidence that left heart failure or elevated left atrial pressure caused the pulmonary edema.


Traceability of Italian Protected Designation of Origin (PDO) table olives by means of microsatellite molecular markers.
The aim of this work was to develop a DNA microsatellite-based method of analysis to allow traceability of the three Italian Protected Designation of Origin (PDO) table olives in comparison with fruits of another seven highly diffused table olive cultivars. The analyses were carried out by using 16 primer pairs, with a mean of five different alleles detected per primer set, and power of discrimination from 0.56 to 0.90. Allelic error rates in the range of 0-3.8% were observed. By combining data from the most reliable and highly informative microsatellites (DCA3, DCA16, DCA17, DCA18, UDO-043, and GAPU101), it was possible to identify the PDO fruits over the panel of 10 cultivars, with the probability of a chance match between different cultivars as low as 10(-9) and with 0.5% error rate. The amplification profile is independent of environmental and processing conditions and is helpful to verify the authenticity of PDO samples.


Therapies of mucopolysaccharidosis IVA (Morquio A syndrome).
Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA) is one of the lysosomal storage diseases and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced by chondrocytes, and therefore, the undegraded substrates accumulate mainly in cells and extracelluar matrix (ECM) of cartilage. This has a direct impact on cartilage and bone development, leading to systemic skeletal dysplasia. In patients with Morquio A, cartilage cells are vacuolated, and this results in abnormal chondrogenesis and/or endochondral ossification. This article describes the advanced therapies of Morquio A, focused on enzyme replacement therapy (ERT) and gene therapy to deliver the drug to avascular bone lesions. ERT and gene therapies for other types of MPS are also discussed, which provide therapeutic efficacy to bone lesions. ERT, gene therapy and hematopietic stem therapy are clinically and/or experimentally conducted. However, there is no effective curative therapy for bone lesion to date. One of the limitations for Morquio A therapy is that targeting avascular cartilage tissues remains an unmet challenge. ERT or gene therapy with bone-targeting system will improve the bone pathology and skeletal manifestations more efficiently.


Off-label use of drugs in Italy: a prospective, observational and multicentre study.
The aims of the study were to measure the paediatric, off-label use of drugs in the Italian hospital setting and to reveal areas for priority intervention by investigating the therapeutic indications most involved. Prescriptions given to all children admitted to nine general paediatric hospital wards from December 1998 to February 1999 were analysed. In total, 4265 prescriptions were given to 1461 children, 10 of which were unlicensed and excluded from further analysis. Sixty percent of prescriptions (range between centres: 44-71%) were off-label and concerned 89% of children receiving medications (80-96%). The main drug classes were antibacterials, antiasthmatics and analgesics, and represented 56% of off-label prescriptions. Paracetamol (385 prescriptions) and beclomethasone (339) were the generic substances most often used off-label. The most common off-label categories were dosage/frequency (50% of prescriptions), indication and lack of paediatric licence (7% each). Fifty-four per cent of all indications that led to off-label prescribing involved only respiratory problems, fever, respiratory tract infections and bronchospasm. Despite prescription profile differences among centres, off-label use was high everywhere. Immediate action for more rational drug use is necessary and requires not only regulatory intervention but also a more evidence-based, therapeutic approach.


Glucosamine enhances proliferation, barrier, and anti-oxidative functions in porcine trophectoderm cells.
Trophectoderm (TE) is the first epithelium that appears during mammalian embryogenesis, and is a polarized transporting single cell layer that comprises the wall of the blastocyst. Previous studies have revealed the functional roles of glucose (Gluc), fructose (Fruc), and glutamine (Gln), which play a positive role in porcine trophectoderm (pTr) cell proliferation and migration, suggesting the importance of nutrients for normal development of the conceptus and implantation. This work was conducted to test the hypothesis that glucosamine (GlcN), which is synthesized from Gln and Fruc-6-phosphate through the hexosamine biosynthesis pathway (HBP), can stimulate proliferation and sustain the barrier and anti-oxidative functions of pTr cells. Cells were treated with 0, 0.25, or 0.5 mmol L-1 GlcN in the presence or absence of adiquat (DQ) for the indicated time points. The results showed that 0.25 or 0.5 mmol L-1 GlcN stimulated pTr cell viability and DNA replication compared to the control group. The addition of 0.25 mmol L-1 GlcN enhanced the phosphorylation of mTOR signaling proteins, which can be inhibited by the inhibitor of phosphatidylinositol 3-kinase (PI3K), LY294002. Transepithelial electrical resistance (TEER) was increased, and paracellular permeability was correspondingly reduced in GlcN treatment. GlcN attenuated DQ-induced cell death and reduced the level of reactive oxygen species (ROS). The decreased TEER values and increased paracellular permeability caused by DQ treatment were also inhibited by GlcN treatment. The addition of 0.5 mmol L-1 GlcN increased the protein expression of zonula occludens-3 (ZO-3), claudin-3, and claudin-4 in pTr cells, while inhibited the downregulation protein of claudin-1 and claudin-3 brought about by oxidative stress. Collectively, GlcN plays an important role in promoting proliferation and stimulating the mTOR cell signaling pathway, as well as ameliorating oxidative stress and augmenting barrier functions in pTr cells.


The WWW as a tool to obtain molecular parameters.
This article analyses molecular property calculation resources available on the Internet. The first section summarizes the on-line database resources that could be useful to search molecular and biological properties of chemicals, and indicates some principal databases with physicochemical, thermochemical, toxicity, cancer and HIV data. The second section overviews popular standalone programs for calculation of molecular descriptors. Some of these programs can be downloaded for free and used as standalone applications for calculation of molecular descriptors. The third section describes on-line tools for the prediction of molecular properties, activities and calculation of molecular descriptors. Analysis of emerging tools that can be useful to developing new on-line servers for the prediction of molecular parameters and properties is also given.


Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease.
The lack of healthy HLA-identical sibs limits the use of allogeneic hematopoietic cell transplantation in children with high-risk sickle cell disease (SCD). We evaluated unrelated placental blood cell transplantation (UPBCT) after a preparative regimen of busulfan, cyclophosphamide and antithymocyte globulin in three children with SCD who had cerebrovascular accidents (CVAs) and did not have HLA-matched sib donors. The placental blood cell units were matched with the recipients at four of six HLA-A, HLA-B and HLA-DRB1 antigens. Neutrophil levels above 0.5 x 10(9)/l occurred at 23, 38 and 42 days after UPBCT, and platelet levels above 50 x 10(9)/l without transfusions occurred at 62, 81 and 121 days after UPBCT. All patients developed acute graft-versus-host disease (GVHD; two grade II, one grade III), and one developed extensive chronic GVHD. One patient had graft failure and autologous hematopoietic recovery. Two patients have complete donor hematopoietic chimerism without detectable hemoglobin S or symptoms of SCD at 40 and 61 months, respectively, after UPBCT. These observations demonstrate the feasibility of UPBCT in children with SCD. Further studies of UPBCT for SCD are needed but, because of risks of procedure-related morbidity and graft rejection, should be restricted to pediatric patients with high-risk manifestations of SCD.


Somatic mutational mechanisms involved in intestinal tumor formation in Min mice.
We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc) allele and that intestinal tumor multiplicity in B6 Min/+ mice can be significantly increased by treatment with a single dose of N-ethyl-N-nitrosourea (ENU). Here, we show that some tumors from ENU-treated Min/+ mice can form without complete elimination of Apc+. At least 25% of these tumors acquired somatic Apc truncation mutations. Interestingly, some ENU-induced tumors demonstrated loss of the Apc+ allelic marker examined by the quantitative PCR assay used here. Using two methods of mutation detection, we identified no Apc mutations in at least 12% of the tumors from ENU-treated B6 Min/+ mice. Finally, no H- or K-ras-activating mutations were detected in intestinal tumors from either untreated or ENU-treated Min/+ mice. The majority of somatic human APC mutations in intestinal tumors lead to APC truncation. Our results demonstrate that somatic Apc truncation mutations also frequently occur in ENU-induced intestinal tumors in Min mice.


Treatment of melasma using tranexamic acid: what's known and what's next.
Tranexamic acid is a procoagulant agent that is approved by the US Food and Drug Administration for treatment of menorrhagia and to prevent hemorrhage in patients with hemophilia undergoing tooth extractions. Through its inhibitory effects on the plasminogen activation pathway, tranexamic acid also mitigates the UV radiation-induced pigmentation response. Systemic tranexamic acid has consistently been reported as an effective treatment of melasma, though its broad use may be limited by the risk for thromboembolism. Limited studies have investigated the efficacy of topical tranexamic acid, with or without the use of adjunctive therapies to increase uptake. This review summarizes the effects of tranexamic acid on the pathophysiology of melasma and the available evidence on the off-label treatment of melasma using systemic and topical tranexamic acid.


Age-related non-Gaussian diffusion patterns in the prefrontal brain.
To characterize age-related MR diffusion patterns of the prefrontal brain cortex microstructure using a new method for investigating the non-Gaussian behavior of water diffusion called diffusional kurtosis imaging (DKI). Measures of mean diffusivity (MD), fractional anisotropy (FA) and mean kurtosis (MK) were compared in the prefrontal brain cortex of 24 healthy volunteers (adolescents, young adults, and elderly) ranging from age 13 to 85 years. A Mann-Whitney test was used to compare subject groups with respect to the diffusion measures, and linear regression was used to characterize the change in each diffusion measure as a function of age. We found significant age-related changes in the elderly adult group, with increase of MD and decrease of FA. The current study demonstrates distinct mean kurtosis patterns for different age-ranges, with significant age-related correlation for mean kurtosis (MK) and MK peak position, showing that diffusional kurtosis is able to characterize and measure age-related diffusion changes for both grey and white matter, in the developing and aging brain.


Elevated glucagon-like peptide-1 plasma levels, as a possible adaptive response, in diabetic NOD mice.
The incretin glucagon-like peptide-1 (GLP-1) and other GLP-1 receptor agonists have been shown to cause both antiapoptotic as well as regenerative effects on beta-cells in different animal models for diabetes. Our aim of this study was to test the hypothesis that spontaneously diabetic non obese diabetic (NOD) mice show an altered expression of GLP-1 compared to normoglycemic age-matched controls as a consequence of a diabetic state. To do this we used an ELISA prototype for mouse GLP-1 to measure plasma total GLP-1 from recently diabetic NOD mice as well as from age-matched normoglycemic NOD mice (controls). We also stained sections of pancreatic glands for GLP-1 from diabetic NOD mice and controls. We found increased levels of plasma total GLP-1 in diabetic NOD mice, when compared to control mice, both from non-fasted mice and from mice fasted for 2h. Furthermore, diabetic NOD mice displayed a higher GLP-1 response to an oral glucose tolerance test, compared to control mice. We also found that sections of pancreatic glands from diabetic NOD mice had an increased GLP-1 positive islet area in regard to relative islet area (i.e. total islet area / total pancreas area of the sections) compared to control mice. To our knowledge, this study is the first to show increased levels of GLP-1 in plasma in spontaneously diabetic NOD mice. We suggest that these results might represent a compensatory mechanism of the diabetic NOD mice to counteract beta-cell loss and hyperglycemia.


Treatment of multifocal motor neuropathy.
Multifocal motor neuropathy (MMN) is a treatable immune disorder of the peripheral nerves that is characterized clinically by slowly progressive or stepwise asymmetric distal > proximal, upper > lower limb weakness in multiple motor nerve distributions; electrophysiologically by multifocal motor demyelination, specifically partial motor conduction block; laboratory evidence of high serum anti-GM1 IgM antibodies; and remarkable treatment response to intravenous immunoglobulin (IVIG). IVIG has become the treatment of choice, and the U.S. Food and Drug Administration (FDA) has approved Gammagard Liquid 10 % [immune globulin infusion (human)] as a treatment for multifocal motor neuropathy (MMN). Response to IVIG in MMN is dose- and frequency-dependent, most patients needing high (2 g/kg) and frequent (every 4-8 weeks) doses for several years. Over time, response to IVIG may decrease despite higher and more frequent dosing of IVIG treatment. Subcutaneous immunoglobulin (dose equivalent to IVIG) given in weekly fashion has recently been used with equal efficacy and fewer side effects. There are some case reports and non-randomized trials suggesting variable results from therapeutic or adjunctive use of other immunosuppressive or immunomodulatory agents such as cyclophosphamide, cyclosporine, methotrexate, azathioprine, interferon beta-1a, and rituximab. Of these, cyclophosphamide and rituximab are the only immune treatments that have shown some benefits in case reports. One randomized controlled trial of mycophenolate mofetil used as adjunctive agent did not prove efficacious in altering the disease course. Although MMN, like chronic inflammatory demyelinating polyneuropathy (CIDP), is a chronic immune-mediated demyelinating neuropathy, the use of corticosteroids and plasma exchange - two other therapies used in CIDP - is not beneficial for MMN. Further investigations are warranted to evaluate the immunopathogenesis of MMN and to explore options for dose, frequency, and duration of IVIG treatment as well as the use of alternative immunomodulatory agents either as primary therapeutic or adjunctive agents.


Experimental and theoretical investigations of four 3d-4f butterfly single-molecule magnets.
The syntheses, structures, and characterization of four 3d-4f butterfly clusters are described. With different polyhydroxy Schiff-base ligands 2-(((2-hydroxy-3-methoxyphenyl)methylene)amino)-2-(hydroxymethyl)-1,3-propanediol (H4L1) and 2-(2,3-dihydroxpropyliminomethyl)-6-methoxyphenol (H3L2), three heterotetranuclear NiLn complexes (NiDy-L1 (1), NiTb-L2 (2), NiDy-L2 (3)) and one heterohexanuclear CoDy complex (4) were obtained. The three heterotetranuclear NiLn complexes display a central planar butterfly topology. The heterohexanuclear complex was built from butterfly CoDy clusters and two Dy(III) ions by the bridging of pivalate. The vertices of the body positions of the butterfly are occupied by transition metal ions in all four complexes. Magnetic analyses indicate that the complexes exhibit typical single-molecule magnet behaviour with anisotropy barriers of 33.7 cm(-1), 60.3 cm(-1), 39.6 cm(-1), and 18.4 cm(-1) for 1-4, respectively. Ab initio calculations were performed on these complexes, and the low lying electronic structure of each Ln(III) (Ln = Dy, Tb) ion and the magnetic interactions were determined. It was found that the two Ln ions may have much more contribution to the total relaxation barrier through the stronger 3d-4f exchange couplings compared to weak Ln-Ln interactions.


Pulmonary inflammatory cells in ventilated preterm infants: effect of surfactant treatment.
The aim of this study was to determine the effect of surfactant treatment on the number and distribution of inflammatory cells in bronchoalveolar lavage fluid (BALF) from mechanically ventilated preterm infants over the first week of life in relation to the subsequent development of chronic lung disease (CLD). The study included 25 babies who received surfactant on clinical grounds and 29 babies of similar severity who did not. BALF was collected on days 1, 3, 5, and 7 after birth. Cell counts were performed and differentials were calculated on 300 cells. CLD was equally common in both treatment groups. Of the 54 infants, 29 (53%) who developed CLD had a higher incidence of patent ductus arteriosus and air leak and needed a higher concentration of inspired oxygen on the fifth and seventh days of life. Babies who developed CLD had more polymorphonuclear leucocytes and fewer macrophages on days 5 and 7 than those who recovered. Surfactant treatment was associated with a higher total white cell count on day 3. Between days 3 and 7, macrophage numbers were higher in surfactant treated babies, whatever the pulmonary outcome. This data suggests that CLD was associated with persistence of high numbers of polymorphonuclear leucocytes in BALF at the end of the first week. Surfactant treatment caused a persistent increase in macrophage numbers. The association between persistent neutrophilia and CLD was unaffected by surfactant treatment.


Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation.
It was hypothesized that endothelial glycocalyx perturbation contributes to increased vulnerability of the arterial wall exposed to atherogenic risk factors. Glycocalyx and intima-to-media ratios (IMR) were studied at a low- and a high-risk region within the murine carotid artery (common region) and internal carotid branch (sinus region) in control C57BL/6J (C57BL6) and age-matched C57BL/6J/apoE*3-Leiden (apoE*3; on an atherogenic diet) mice. Electron micrographs revealed significantly thinner glycocalyces [73 (SD 36) vs. 399 (SD 174) nm, P < 0.05] and greater IMR [0.096 (SD 0.045) vs. 0.044 (SD 0.023), P < 0.05] at the sinus region of C57BL6 mice than in the common region. Thinner glycocalyces [100 (SD 27) vs. 399 (SD 174) nm, P < 0.05] and greater IMR [0.071 (SD 0.024) vs. 0.044 (SD 0.023), P < 0.05] were also observed in the common region of age-matched apoE*3 mice on an atherogenic diet for 6 wk vs. C57BL6 mice on a normal diet. Greater IMR were due to greater intima layers, without significant changes in media layer dimension. In addition, atherogenic diet resulted in increased endothelial cell thickness at the sinus region [0.85 (SD 0.49) vs. 0.53 (SD 0.28) microm, P < 0.05] but not at the common region [0.66 (SD 0.37) vs. 0.62 (SD 0.32) microm]. It is concluded that both regional and diet-induced increases in atherogenic risk are associated with smaller glycocalyx dimensions and greater IMR and that vascular sites with diminished glycocalyx are more vulnerable to proinflammatory and atherosclerotic sequelae.


[Cytomegalovirus colitis simulating neoplasm in a patient with HIV infection].
Cytomegalovirus colitis occurs in at least 5-10% of patients with AIDS. The most usual form of clinical presentation is that of a chronic picture of diarrhea, fever and abdominal pain in a patient with AIDS with a CD4 lymphocyte count lower than 100/mm3, although it can be the diagnostic index for AIDS up to in 25% of the cases. Cytomegalovirus colitis in a patient with AIDS was diagnosed by endoscopy and colonic biopsy. The clinical was diagnosed by endoscopy and colonic biopsy. The clinical picture consisted of abdominal pain, without the findings of fever and diarrhea described in almost 80% and 100% respectively of the cases published in the literature. The barium enema carried out showed a stenotic appearance, like serviette ring, in the ascending colon, which suggested neoplasia of the colon. Induction therapy with ganciclovir was effective. However, the patient was readmitted one year later for chorioretinitis due to cytomegalovirus, without any evidence of gastro-intestinal involvement. Although unusual, cytomegalovirus colitis can be present with an abdominal clinical picture without diarrhea. Radiological and/or endoscopic pseudotumoral forms which this entity can adopt are often described. Endoscopy with digestive biopsy in essential for diagnosis. Therapy with ganciclovir can be effective although the reappearance of findings from cytomegalovirus can occur at another area, or as a gastrointestinal recurrence.


Structural and Biochemical Studies on Product Inhibition of S-Adenosylmethionine Synthetase from Corynebacterium glutamicum.
S-Adenosylmethionine (SAM) acts as a methyl donor in living organisms, and S-adenosylmethionine synthetase (MetK) is an essential enzyme for cells, as it synthesizes SAM from methionine and adenosine triphosphate (ATP). This study determined the crystal structures of the apo form and adenosine/triphosphate complex form of MetK from Corynebacterium glutamicum (CgMetK). Results showed that CgMetK has an allosteric inhibitor binding site for the SAM product in the vicinity of the active site and is inhibited by SAM both competitively and noncompetitively. Through structure-guided protein engineering, the CgMetKE68A variant was developed that exhibited an almost complete release of inhibition by SAM with rather enhanced enzyme activity. The crystal structure of the CgMetKE68A variant revealed that the formation of a new hydrogen bond between Tyr66 and Glu102 by the E68A mutation disrupted the allosteric SAM binding site and also improved the protein thermal stability by strengthening the tetramerization of the enzyme.


A Novel Fusion-Based Ship Detection Method from Pol-SAR Images.
A novel fusion-based ship detection method from polarimetric Synthetic Aperture Radar (Pol-SAR) images is proposed in this paper. After feature extraction and constant false alarm rate (CFAR) detection, the detection results of HH channel, diplane scattering by Pauli decomposition and helical factor by Barnes decomposition are fused together. The confirmed targets and potential target pixels can be obtained after the fusion process. Using the difference degree of the target, potential target pixels can be classified. The fusion-based ship detection method works accurately by utilizing three different features comprehensively. The result of applying the technique to measured Airborne Synthetic Radar (AIRSAR) data shows that the novel detection method can achieve better performance in both ship's detection and ship's shape preservation compared to the result of K-means clustering method and the Notch Filter method.


Protective effects of a polysaccharide from Hizikia fusiformis against ethanol toxicity in rats.
Hizikia fusiformis is an edible brown alga that is widely consumed in Korea, Japan, and China and possesses a number of potentially beneficial compounds, including antioxidants and anticoagulants. No reports have investigated potential H. fusiformis protectants against ethanol-induced peptic injury. We extracted a polysaccharide from H. fusiformis (Hf-PS-1) that exhibited protective effects against ethanol-induced peptic injury and related mechanisms in rats. Experimental animals were divided into three groups: control, ethanol-only, and ethanol+Hf-PS-1. The ethanol-only group exhibited decreased levels of total glutathione (GSH) and increased levels of jun N-terminal kinase (JNK) phosphorylation relative to the control group, whereas levels were significantly increased and decreased, respectively, in the ethanol+Hf-PS-1 group. The ethanol-only group also exhibited increased levels of extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation relative to the control group; these levels were not significantly different in the ethanol+Hf-PS-1 group. Hf-PS-1 appeared to reduce ethanol-induced gastric injury. Therefore, we suggest that Hf-PS-1 could protect against ethanol-induced peptic ulcers primarily through a mechanism associated with the inhibition of JNK activation.


Regression of medial elastocalcinosis in rat aorta: a new vascular function for carbonic anhydrase.
We sought to determine whether carbonic anhydrase (CA), which plays an important role in bone resorption, contributes to vascular mineral loss induced by an endothelin receptor antagonist. Wistar rats were compared with rats receiving warfarin and vitamin K1 (WVK) for 8 weeks alone or in association with the endothelin receptor antagonist darusentan (30 mg/kg per day), the CA inhibitor acetazolamide (100 mg/kg per day), or both for the last 4 weeks. Rats were also treated with WVK for 5 or 6 weeks, and darusentan was added for the last week or last 2 weeks of treatment, respectively. Treatment with WVK produced medial elastocalcinosis in the aorta and carotid arteries. Immunohistochemistry revealed that CA II was already abundant in the adventitia and in calcified areas of aortic sections from WVK-treated rats. Darusentan did not significantly modify its abundance or distribution. In contrast, CA IV immunostaining, which was weak in WVK-treated rats, became apparent after 1 week of darusentan treatment and declined toward basal levels thereafter. These findings were confirmed by a parallel increase in CA IV protein abundance and activity in the aorta. The mineral loss induced by darusentan was blunted by acetazolamide treatment, confirming the functional relevance of the biochemical findings. Moreover, CA IV immunostaining was enhanced much later in the carotids, where darusentan did not cause regression of elastocalcinosis. Vascular mineral loss induced by the blockade of endothelin receptors seems dependent on the activation of membrane-bound CA IV, suggesting that mineral loss may proceed via local changes in pH similar to that seen in bone resorption.


Tuning the excited-state energy of the organic chromophore in bichromophoric systems based on the Ru(II) complexes of tridentate ligands.
A series of new heteroleptic and homoleptic Ru(II) complexes containing variously substituted bis(pyridyl)triazine ligands has been prepared and their absorption spectra, redox behaviour and luminescence properties (both in fluid solution at room temperature and in a rigid matrix at 77 K) have been investigated. For some compounds, X-ray structures have also been determined. The new bis(pyridyl)triazines incorporate additional chromophores, such as biphenyl, phenanthrene, anthracene and bromoanthracene derivatives, so the Ru(II) species can be considered as multichromophoric species. The absorption spectra and redox properties of all the metal complexes have been assigned to features belonging to specific subunits, thus suggesting that these species can be regarded as multicomponent, supramolecular assemblies from an electronic coupling point of view. Whereas most of the complexes exhibit luminescence properties that can be attributed to metal-to-ligand charge-transfer (MLCT) states involving the metal-based subunit(s), the species containing the anthryl and, even more, the brominated anthryl chromophores exhibit complicated luminescence behaviour. For example, 2 d (the anthryl-containing heteroleptic metal compound) exhibits MLCT emission at room temperature and emission from the anthracene triplet at 77 K; 2 e (the bromo-substituted anthryl-containing heteroleptic metal compound) exhibits anthryl-based emission at 77 K and MLCT emission at room temperature, but with a prolonged lifetime, thus suggesting equilibration between two triplet states that belong to different chromophores. The equilibration regime between MLCT and aromatic hydrocarbon triplet states is therefore reached by suitable substitution on the organic chromophore.


Mitral valve surgery under perfused ventricular fibrillation with moderate hypothermia.
The safety and myocardial protective effect of perfused ventricular fibrillation (VF) under moderate hypothermia were investigated. Through a midline sternotomy and opening the left atrium from the right side, isolated mitral valve surgery was performed under aortic cross-clamping (ACC) and cardioplegic arrest using Bretschneider HTK solution in 96 patients, and under perfused VF in 20 patients (VF Group). Patient characteristics, clinical outcomes, and perioperative variables were compared. A satisfactory surgical view was obtained in all VF Group patients. Patient characteristics in the 2 groups were similar, and both groups had comparable results for mortality and morbidity, operation time, cardiopulmonary bypass time, peak levels of creatine kinase (CK) and its myocardial fraction, hours of mechanical ventilation, intensive care unit stay, and postoperative left ventricular ejection fraction. Even in VF Group patients with preoperative critical hemodynamic compromise, inotropes could be discontinued within 3 days. Thus, no detrimental effect of perfused VF was observed. On the other hand, in patients who underwent ACC and cardioplegic arrest of 120min or longer, peak levels of CK and its myocardial fraction were significantly higher than those of the rest of C group patients and VF Group patients. Perfused VF under moderate hypothermia can be a good alternative myocardial protection strategy during mitral valve surgery, particularly in patients in whom ACC is unsuitable or the duration of ACC is expected to be long.


[When in pregnancy should screening for Chlamydia be carried out?].
One goal of every prenatal care should be the diagnosis of a cervical infection with Chlamydia trachomatis and the prevention of its transmission to the neonate. Therefore, we studied the questions (1) at which gestational age a screening would be most meaningful and (2) whether the woman's medical history, a vaginal smear or cervical cerclage suggests any risk of infection. 11 of 121 pregnant women (9.1%) had a positive test for cervical infection with Chlamydia trachomatis at their booking visit. More than half of them had a spontaneous remission at the follow-up visit. Practically, all newborns to infected mothers (at follow-up visits) had a positive test as well. We did not find any relationship between the medical history, vaginal smear or cervical cerclage and the incidence of Chlamydia trachomatis infection. In conclusion, we propose a screening for Chlamydia trachomatis infection of all pregnant women between the 34th and 38th week of gestation and treatment of infected individuals with erythromycin (4 x 500 mg t.i.d.).


[Procedures and technical aptitude of primary care physicians: which education?].
To ascertain the educational goals of internal medicine teachers in the domain of clinical skills, the realization of these objectives and their pertinence for the practice of primary care physicians. Questionnaire containing 44 clinical skills sent to the chiefs of the services of internal medicine of public hospitals in French-speaking Switzerland and the 5 Swiss university hospitals. Comparison of these results with an earlier study concerning the practice of clinical skills of the primary care physicians. The participation was 82%. The educational goals were identical for all the chiefs of internal medicine independently of whether they were university-dependent or not, or in a large or small hospital. 22 of the proposed clinical skills were considered as teaching goals for > or = 70% of the heads of medicine. However, they thought that only 8 of these 22 skills were acquired by the majority of their residents. 8 of these 22 skills were considered to be indispensable for proper functioning of the service. There was a good correlation between the acquired skills and those considered to be indispensable for proper functioning of the service. The medical chiefs considered most of the skills practiced by the primary care physicians were also educational objectives. However, they thought that only 23% of these skills were acquired by their residents. Only half of the skills considered as acquired were practiced by a majority of the primary care physicians. Many clinical skills are considered as educational goals by the medical chiefs of hospital services in internal medicine. However, they consider only a third of these goals as acquired by their residents at the end of their residency. There was a good correlation between the skills thought to be acquired and those considered to be indispensable for proper functioning of their service, and a poor correlation between the skills considered as acquired and those practiced by primary care physicians.


[Current indications for resection of tuberculoid lung changes--relics of the pre-chemotherapy era?].
The spectrum of indications for elective resection of pulmonary tuberculosis was considerably reduced by clinical evaluation of the effective antituberculous chemotherapy and is limited only to a few pathomorphological processes and clinical situations today. The same estimation is valid in case of nontuberculous mycobacteriosis with clinical importance. The combined therapy with new macrolid antibiotics, quinoloses and Rifampicin-derivatives current enlarged the options of conservative therapy. Thus the surgery of pulmonary tuberculosis are rare operations and are essentially limited to the therapy of late complications of a former collapse therapy, of destroyed lungs and bronchiectasis with recurrent infect exacerbations and life threatening or massive recurrent haemoptysis.


Plasma Homocysteine Levels and Cardiovascular Events in Patients With End-Stage Renal Disease: A Systematic Review.
Patients with chronic renal disease or failure are at a heightened risk of mortality due to cardiovascular disease (CVD), which is a predominant cause of death in this population. Hyperhomocysteinemia is prevalent in patients with end-stage renal disease (ESRD), which may increase their susceptibility to CVD. We conducted a comprehensive search of PubMed, Science Direct, and Google Scholar for articles published between 2003 and February 2023, using a combination of keywords such as "plasma homocysteine levels," "hyperhomocysteinemia," "end-stage renal disease," "renal failure," "kidney failure," "cardiovascular events," "cardiovascular disease," "myocardial infarction," "coronary artery disease," and "stroke." Our inclusion criteria were studies that investigated the association between total homocysteine (Hcy) level and CVD or total mortality, as well as the impact of vitamin supplementation on cardiovascular or mortality risk. We restricted our search to English-language studies that included ESRD patients and provided data on plasma Hcy levels and associated CVD events. This systematic review includes 11 articles published between 2003 and 2023 that enrolled a total of 3,953 subjects, of whom 79.15% were male patients. All studies included in the review were either quantitative randomized trials or non-randomized studies, such as cross-sectional, cohort, or case-control studies. Of the total studies included, 10 reported either cardiovascular mortality or CVD events, including cardiovascular death, myocardial infarction (MI), angina, and stroke. One study reported the CVD risk score of the patients, and most of them had higher total homocysteine (tHcy) levels. Overall, a total of 817 CVD events were reported across the studies. In conclusion, the relationship between Hcy and cardiovascular events in ESRD patients is not straightforward and requires further research. However, our review suggests that Hcy could be a predictor of cardiovascular events in this population, and its nutritional characteristics as well as other associated comorbidities may contribute to its inverse association with outcomes.


Research on Multifeature Intelligent Correction of Spoken English.
For a long time, college English teaching in many Chinese universities has focused on cultivating students' reading abilities while ignoring the cultivation of students' speaking abilities, leaving many non-English majors unable to communicate in English even after years of English study. This paper outlines the entire design and development process for an intelligent correction system for spoken English, with a focus on the methods for implementing the functions of spoken English examination, question bank management, and marking. A multifeature fusion of SE (sample entropy) and MFCC (Mel frequency cepstrum coefficient) based speech emotion recognition method is proposed. It denotes the rate at which the SE nonlinear dynamic system generates new data. It can be used to describe the dynamic fluctuation of speech signals in response to various emotions. To process SE and its statistics, as well as MFCC, and calculate the probability that they belong to one of six emotions, the support vector machine is used. The spoken English recognition algorithm described in this paper has obvious performance improvements in many indicators, according to the experimental evaluation.


It's all in the detail: intentional forgetting of autobiographical memories using the autobiographical think/no-think task.
Using a novel autobiographical think/no-think procedure (ATNT; a modified version of the think/no-think task), 2 studies explored the extent to which we possess executive control over autobiographical memory. In Study 1, 30 never-depressed participants generated 12 positive and 12 negative autobiographical memories. Memories associated with cue-personal word pairings were learned to criterion. Participants were then asked to recall the memory associated with some of the cue-personal word pairs (i.e., think condition) or to avoid saying or thinking about the memory associated with others (i.e., no-think condition). In a subsequent test of recall, systematic forgetting effects emerged for no-think autobiographical memories compared to baseline that received neither no-think nor think instructions. These findings were extended and replicated in a second ATNT study (using a further 30 never-depressed participants), which showed that the forgetting of autobiographical memories in the no-think condition was unlikely to be a function of thought substitution or demand characteristics.


Comparison of Minimally Invasive Surgery Transforaminal Lumbar Interbody Fusion and TLIF for Treatment of Lumbar Spine Stenosis.
With the development of minimally invasive technology, minimally invasive surgery transforaminal lumbar interbody fusion has become an effective way to treat lumbar spinal stenosis. Lumbar spinal stenosis is one of the common diseases that cause backache or lumbago and sciatica. This article compares and analyzes the clinical efficacy of 60 patients with lumbar spinal stenosis surgery. It can be seen that the wound by MIS-TLIF is significantly less than that of traditional open surgery, and the postoperative recovery of MIS-TLIF is faster. So, MIS-TLIF is one of the concepts of minimally invasive surgery. The age distribution ranged from 56 to 78 years, with an average of 65.7 years. 31 cases were treated with MIS-TLIF (MIS-TLIF group), and 29 were treated with traditional posterior open surgery (TLIF group). The operation time, intraoperative blood loss, and postoperative drainage of the operation area were recorded. After statistical testing, the intraoperative blood loss, incision size, and postoperative drainage volume of the wound in the MIS-TLIF group were significantly less than those in the TLIF group. The results of JOA score, ODI score, and VAS score during the postoperative follow-up period were comparable to those of open surgery. Therefore, minimally invasive transforaminal lumbar interbody fusion is effective in treating lumbar spinal stenosis.


Characterisation of mumps virus genotype C among patients with mumps in India.
Measles, mumps and rubella (MMR) vaccine failure had been reported globally and here, we report that it occurs in India now. MMR vaccinated people have developed acute mumps accompanied by anti-mumps immunoglobulin M. Genotypic characterisation revealed that the circulating mumps strain was genotype C, which is distinct from the vaccine strain of genotype N (L-Zagreb). This is the first report in India to suggest that genotype C is responsible for the present mumps infection. Thus, the present MMR vaccine must be revamped and optimised for its efficacy to prevent any future mumps epidemics.


Stem cells, cell therapies, and bioengineering in lung biology and diseases. Comprehensive review of the recent literature 2010-2012.
A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," was held July 25 to 28, 2011 at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.


Enhanced electrochemical performance of Li-Co-BTC ternary metal-organic frameworks as cathode materials for lithium-ion batteries.
Metal-organic frameworks (MOFs) with diverse structures have been projected as futuristic electrode materials for lithium-ion batteries (LIBs). In this work, two ternary Li-Co-MOFs of three-dimensional (3D) porous structures were synthesized, inspired by LiCoO2 inorganic metal salts, through a simple solvothermal method and further applied as active cathode materials for the first time in lithium-ion batteries. In these MOF structures, the lithium atoms are located at the same (SNNU-73) or different (SNNU-76) sites as cobalt atoms, and the four-coordinated tetrahedron mode is used to coordinate with the oxygen atoms. The 3D porous frameworks provide a good channel for the embedding and de-embedding of lithium ions. The experimental results suggest that porous Li-Co-MOF ternary composites show excellent cycling stability. Particularly, the discharge capacity and average coulombic efficiency of SNNU-73 reach 155.6 mA h g-1 and nearly 100% for 50 cycles at a rate of 50 mA g-1. This synergistic effect of mixed Li and Co sites demonstrates great potential of MOFs as advanced electrode materials, and provides a promising route to designing porous materials for lithium-ion batteries in the future.


Trial of scar.
It is becoming increasingly common to attempt vaginal delivery in women whose previous delivery or deliveries have been by caesarean section. The outcome in these "trials of scar" is generally good, with reported vaginal delivery rates ranging from 60% to 94% and few complications.


Solution-Processed Gold Nanorods Integrated with Graphene for Near-Infrared Photodetection via Hot Carrier Injection.
Graphene-based photodetectors have attracted wide interest due to their high-speed, wide-band photodetection and potential as highly energy-efficient integrated devices. However, the inherently low-absorption cross-section and nonselective spectra response hinder its utilization as a high-performance photodetector. Here, we report a solution-processed and high-spectral-selectivity photodetector based on a gold nanorods (Au NRs)-graphene heterojunction with near-infrared (NIR) detection. Au NRs are used as a subwavelength scattering source, and nanoantennas with wide light absorption range from ultraviolet to near-infrared via tuning their geometry. Photons couple into Au NRs, exciting resonant plasmas and generating hot carriers that pump into graphene, resulting in selective NIR photodetection. A flexible NIR photodetector is also demonstrated based on this simple structure. Au NRs can achieve variable resonance frequencies by the design of different aspect ratios as nanoantennae for graphene, which promises the selective amplifying of the photoresponsivity and enables highly specific detection.


Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: The TRAINING-HF Trial.
Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF. A total of 61 stable symptomatic patients (New York Heart Association II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes. Mean age and peak exercise oxygen uptake were 74 ± 9 years and 9.9 ± 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 6 months (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found. In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life. This trial was registered at ClinicalTrials.gov (Identifier: NCT02638961)..


Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1.
Cyclooxygenase (COX) inhibitors have antitumorigenic activity and increase the expression of the early growth response gene Egr-1, a tumor suppressor gene and transcription factor. In this study, we have investigated the gene regulatory and anti-invasive activity of two traditional nonsteroidal anti-inflammatory drugs (NSAID), sulindac sulfide and indomethacin. These compounds inhibited tumor cell invasion and induced Egr-1 expression in lung adenocarcinoma A549 cells. Overexpression of Egr-1 reduced cellular invasion in the Matrigel system, whereas suppression of Egr-1 by small interference RNA (siRNA) attenuated the inhibition of Matrigel invasion by these compounds, indicating that Egr-1 is responsible for the decrease in invasion reported following treatment with NSAIDs. Egr-1-overexpressing cells were analyzed for genes involved in invasion and metastasis. Thrombospondin-1 (TSP-1) an antiangiogenic and anti-invasion protein was up-regulated by Egr-1 overexpression, which was confirmed following treatment with sulindac sulfide. Furthermore, the induction of TSP-1 by sulindac sulfide was blocked by Egr-1 siRNA. When TSP-1 was sequestered by the addition of anti-TSP-1 antibody, the inhibition of invasion by sulindac sulfide was attenuated, indicating that TSP-1 is involved in the inhibition of invasion by NSAIDs. We used the Min mouse model to determine if sulindac sulfide would increase Egr-1 and TSP-1 in vivo, because this model is widely used to study the effects of NSAIDs on tumor formation. Treatment of Min mice with concentrations of sulindac sulfide that inhibit tumor formation increased the expression of Egr-1 and TSP-1 in colonic tissues and in the polyps of these mice. This is the first report suggesting that COX inhibitors suppress tumor cell invasion via TSP-1, which occurs downstream of Egr-1.


Sleep disturbances associated with gastro-oesophageal reflux disease: prevalence and impact of treatment in French primary care patients.
To evaluate the prevalence of sleep disturbances in French patients with gastro-oesophageal reflux disease and the impact of gastro-oesophageal reflux disease treatment on sleep. A registry was compiled of all gastro-oesophageal reflux disease patients seen during a 2-week period by 1983 French primary care physicians. Data from the first two patients with nocturnal gastro-oesophageal reflux disease symptoms and gastro-oesophageal reflux disease-related sleep disturbances seen by each physician were derived from physician questionnaires and medical records. These patients completed a questionnaire during the initial consultation and after 1-month treatment. A total of 33,391 patients were included in the study: physician questionnaires were available for 3269 patients and patient questionnaires for 2876. Nocturnal gastro-oesophageal reflux disease symptoms were reported by 21,337 patients (63.9%) and regular (at least once weekly) gastro-oesophageal reflux disease-related sleep disturbances by 19,313 (61.7%). Multivariate analysis showed that nocturnal gastro-oesophageal reflux disease symptoms, use of hypnotic drugs, and age over 50 years were significant independent predictors of sleep disturbances. The proportion of patients reporting at least one nocturnal gastro-oesophageal reflux disease symptom during the previous week decreased following treatment, from 98.8% to 39.3% (P<0.001). Nocturnal gastro-oesophageal reflux disease symptoms are common in the French population and are associated with sleep disturbances. Effective treatment can significantly improve sleep duration and quality.


Actions of domperidone on the opioid system in isolated guinea-pig ileum: differences between dopamine antagonists on opioid system.
1. To validate the relationship between the dopaminergic, opioidergic and cholinergic nervous systems, we evaluated the effect of domperidone, a dopamine (D2) antagonist, on the opioid system in myenteric plexus-longitudinal muscle preparation isolated from the guinea-pig ileum. 2. One micromolar of domperidone did not affect the 0.1 Hz-evoked (duration 0.5 ms, maximum intensity) twitch response, but concentration dependently inhibited the twitch response between concentrations of 2 and 20 microM, and the inhibition was maximum after 20-30 min at the highest concentration used (20 microM). 3. Acetylcholine-evoked contraction on basal tension was also not inhibited by 1 microM domperidone, but the contraction was concentration dependently inhibited at concentrations of 10-100 microM in a non-competitive manner. 4. One micromolar of domperidone, however, increased post-tetanic twitch inhibition, an indicator of the release of endogenous opioids. This increase was completely antagonized by 1 microM naloxone. Twitch inhibition induced by dynorphin 1-13 (0.1-10 nM) was not affected by 1 microM domperidone, but increased the maximum twitch inhibition caused by morphine (0.1-1 microM). 6. These results might reflect the existence of an interaction between the dopaminergic and opioidergic system without the inhibition of the cholinergic system. Dopamine antagonists increased opioid action, an action that may depend more on the increased release of endogenous opioids than on supersensitivity of the opioid receptor.


Etiology, Severity, Audiogram Type, and Device Usage in Patients with Unilateral Moderate to Profound Sensorineural Hearing Loss in Japan.
Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant.


Elbow Arthrodesis as a Salvage Procedure for Combat-Related Upper Extremity Trauma.
Upper extremity amputation is associated with significant disability. Elbow arthrodesis (EA) is a rarely indicated salvage procedure with a narrow set of indications. The purpose of this case series is to describe the clinical course of those patients undergoing an EA following severe combat-related, upper extremity trauma. 5 patients treated for combat-related upper extremity injuries treated with an EA between 2003 and 2012 were identified. Demographic information, injury characteristics, and treatment course were evaluated. 5 male patients with a mean age of 23.8 years were treated with an EA in relative extension following severe upper extremity trauma. 3 patients undergoing EA had concomitant bilateral above-knee amputations and 2 patients underwent fusion of their dominant arm. Successful arthrodesis was achieved in all patients. All patients reported good pain control without evidence of deep infection, the mean time from injury to arthrodesis was 305 days, and the mean time to arthrodesis was 714 days. The mean fusion angle among these patients was 138°. EA following severe combat-related, upper extremity trauma is a viable treatment option. In the multiply injured patient, arthrodesis in a position of extension may be advantageous to accommodate transfers and mobility.


SWAMP: Sliding Window Alignment Masker for PAML.
With the greater availability of genetic data, large genome-wide scans for positive selection increasingly incorporate data from a range of sources. These data sets may be derived from different sequencing methods, each of which has potential sources of error. Sequencing errors, compounded by alignment errors, greatly increase the number of false positives in tests for adaptive evolution. Genome-wide analyses often fail to fully address these issues or to provide sufficient detail on postalignment masking/filtering. Here, we introduce a Sliding Window Alignment Masker for Phylogenetic Analysis by Maximum Likelihood (SWAMP) that scans multiple-sequence alignments for short regions enriched with unreasonably high rates of nonsynonymous substitutions caused, for example, by sequence or alignment errors. SWAMP prevents their inclusion in downstream evolutionary analyses and therefore increases the reliability of downstream analyses. It is able to effectively mask short stretches of erroneous sequence, particularly prevalent in low-coverage genomes, which may not be detected by existing methods based on filtering by sitewise conservation or alignment confidence. SWAMP offers a flexible masking approach, and the user can apply different masking regimens to specific branches or sequences in the phylogeny allowing the stringency of masking to vary according to branch length, expected divergence levels, or assembly quality. We exemplify SWAMPs effectiveness on a dataset of 6,379 protein-coding genes from primate species, including data of variable quality. Full reporting of the software parameters will further improve the reproducibility of genome-wide analyses, as well as reduce false-positive rates.


A neural classification method for supporting the creation of BioVerbNet.
VerbNet, an extensive computational verb lexicon for English, has proved useful for supporting a wide range of Natural Language Processing tasks requiring information about the behaviour and meaning of verbs. Biomedical text processing and mining could benefit from a similar resource. We take the first step towards the development of BioVerbNet: A VerbNet specifically aimed at describing verbs in the area of biomedicine. Because VerbNet-style classification is extremely time consuming, we start from a small manual classification of biomedical verbs and apply a state-of-the-art neural representation model, specifically developed for class-based optimization, to expand the classification with new verbs, using all the PubMed abstracts and the full articles in the PubMed Central Open Access subset as data. Direct evaluation of the resulting classification against BioSimVerb (verb similarity judgement data in biomedicine) shows promising results when representation learning is performed using verb class-based contexts. Human validation by linguists and biologists reveals that the automatically expanded classification is highly accurate. Including novel, valid member verbs and classes, our method can be used to facilitate cost-effective development of BioVerbNet. This work constitutes the first effort on applying a state-of-the-art architecture for neural representation learning to biomedical verb classification. While we discuss future optimization of the method, our promising results suggest that the automatic classification released with this article can be used to readily support application tasks in biomedicine.


Zinc-mediated C-C bond sigmatropic rearrangement: a new and efficient methodology for the synthesis of beta-diketones.
A new and efficient methodology has been developed for the synthesis of beta-diketones from aromatic alpha-bromo ketones in the presence of Furukawa reagent under mild conditions. The present transformation is proposed to proceed via a Reformatsky-type reaction of alpha-bromo ketones, followed by C-C bond sigmatropic rearrangement of the aldolate intermediate to give beta-diketones in moderate to good isolated yields, while aliphatic alpha-bromomethyl ketones resulted in the formation of 2,4-disubstituted furans or cis-1,2-disubstituted cyclopropanols in moderate yields. The scope of this process was investigated, and a tentative mechanism was proposed.


Evaluation on quantum illumination radar with quantum limited amplification.
Based on Quantum illumination (QI) protocol, researcshers have developed prototypes of quantum radar and demonstrated its quantum enhancement. Nevertheless, there are still difficulties in the practical application for QI radar, especially the trade-off between the detection range and quantum enhancement, as well as the construction of the optimized receiver. Some studies have suggested that the potential solutions to these difficulties are to deploy the quantum limited amplifiers in QI radars, and have envisioned different amplification schemes. In this paper, we establish a universal and effective method to evaluate the signal-to-noise ratio of QI radar. It connects QI radar theory with classical radar signal processing theory, providing support for researchers to evaluate the performance of various QI radar schemes from a radar perspective. Based on this method, we prove that any quantum limited phase-insensitive amplification scheme will seriously weaken the quantum enhancement of QI radar. Furthermore, we also demonstrate that the QI radar with phase-sensitive amplified idler has no advantage over the optimal classical illumination. These results can help us avoid some unreasonable QI radar schemes. In addition, we believe that the proposed method can also be applied to explore other potential QI radar schemes and contribute to promoting the application development of QI radar.


Candida albicans-conditioned medium protects yeast cells from oxidative stress: a possible link between quorum sensing and oxidative stress resistance.
Candida albicans, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that C. albicans is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a C. albicans stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of C. albicans cells to oxidants. Relative reverse transcription-PCR analysis indicates that Candida-conditioned growth medium induces the expression of CAT1, SOD1, SOD2, and SOD4, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in C. albicans.


Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of human skin in vivo: apoptosis versus migration.
Ultraviolet B radiation can suppress cellular immunity. One of the mechanisms related to this immunosuppression is the disappearance of Langerhans cells from the epidermis. The aim of this study was to establish the mechanism of ultraviolet B-induced Langerhans cell disappearance in healthy individuals. The two most likely mechanisms for Langerhans cell disappearance are apoptosis and migration. Apoptosis was assessed in vivo by exposing buttock skin of 10 healthy volunteers to six minimal erythema doses of ultraviolet B. Only very few apoptotic Langerhans cells could be observed in sections from the ultraviolet B-exposed skin. Migration of Langerhans cells cannot be established in skin sections and suction blisters were therefore raised in an attempt to trap migrating Langerhans cells in the sub-basal membrane blister fluid. Blisters were raised on the flexor side of the lower arm of 30 healthy volunteers at several time points after exposure of the skin to six minimal erythema doses of ultraviolet B. Blister fluid was collected and blister roofs were removed to check for Langerhans cell disappearance. Langerhans cells were detected in the blister fluid of the ultraviolet B-exposed skin and not of the unexposed skin. The number of Langerhans cells in the blister fluid peaked at about 18 h after ultraviolet exposure, which coincided with the largest depletion of Langerhans cells in the blister roof. A fraction (20-30%) of the Langerhans cells in the blister fluid stained positive for DNA damage (cyclobutyl pyrimidine dimers), showing that they originated from the epidermis. Ultraviolet B-induced Langerhans cell disappearance appears to be mainly attributable to migration.


Attenuation of UV-B exposure-induced inflammation by abalone hypobranchial gland and gill extracts.
Exposure to solar ultraviolet B (UV-B) is a known causative factor for many skin complications such as wrinkles, black spots, shedding and inflammation. Within the wavelengths 280‑320 nm, UV-B can penetrate to the epidermal level. This investigation aimed to test whether extracts from the tropical abalone [Haliotis asinina (H. asinina)] mucus-secreting tissues, the hypobranchial gland (HBG) and gills, were able to attenuate the inflammatory process, using the human keratinocyte HaCaT cell line. Cytotoxicity of abalone tissue extracts was determined using an AlamarBlue viability assay. Results showed that HaCaT cells could survive when incubated in crude HBG and gill extracts at concentrations between <11.8 and <16.9 µg/ml, respectively. Subsequently, cell viability was compared between cultured HaCaT cells exposed to serial doses of UV-B from 1 to 11 (x10) mJ/cm2 and containing 4 different concentrations of abalone extract from both the HBG and gill (0, 0.1, 2.5, 5 µg/ml). A significant increase in cell viability was observed (P<0.001) following treatment with 2.5 and 5 µg/ml extract. Without extract, cell viability was significantly reduced upon exposure to UV-B at 4 mJ/cm2. Three morphological changes were observed in HaCaT cells following UV-B exposure, including i) condensation of cytoplasm; ii) shrunken cells and plasma membrane bubbling; and iii) condensation of chromatin material. A calcein AM‑propidium iodide live‑dead assay showed that cells could survive cytoplasmic condensation, yet cell death occurred when damage also included membrane bubbling and chromatin changes. Western blot analysis of HaCaT cell COX‑2, p38, phospho‑p38, SPK/JNK and phospho‑SPK/JNK following exposure to >2.5 µg/ml extract showed a significant decrease in intensity for COX‑2, phospho‑p38 and phospho‑SPK/JNK. The present study demonstrated that abalone extracts from the HGB and gill can attenuate inflammatory proteins triggered by UV-B. Hence, the contents of abalone extract, including cellmetabolites and peptides, may provide new agents for skin anti‑inflammation, preventing damage due to UV-B.


Controversies in medical mycology.
Questions and controversies involving many aspects of medical mycology have increased in recent years. Case histories are described in which fungal infection causes unexpected and atypical problems. Molecular techniques of diagnosis need to be used alongside traditional culture methods. Increased drug use has led to genuine concerns and differing views regarding the definition and development of resistance by fungi. The use and value of combinational antifungal therapy and the employment of immunomodulatory agents concomitant with antimycotics have been debated. Nonetheless, good standards have been developed in the testing of antifungal agents. These, together with the commercial viability of antifungal drugs and hence increased interest in their development, mean that although we have entered the golden age of mycology we have also entered the golden age of antifungal therapy.


Experiments on elastomechanical wave functions in chaotic plates and their statistical features.
We measure the amplitude of the elastomechanical displacement at a fine grid of points on a free plate having the shape of a Sinai stadium. The obtained displacement field formally corresponds to a wave function in a quantum system. While the distribution of the squared amplitudes agrees with the prediction of random matrix theory (RMT), there is a strong deviation of the spatial correlator from the standard prediction for quantum chaotic systems. We show that this is due to the presence of two modes, leading to a beating phenomenon. We construct a proper extension of the spatial correlator within the framework of RMT.


Structural intermediate in the photocycle of a BLUF (sensor of blue light using FAD) protein Slr1694 in a Cyanobacterium Synechocystis sp. PCC6803.
Slr1694 in Synechocystis sp. PCC6803 is a family of blue-light photoreceptors based on flavin adenine dinucleotide (FAD) called BLUF (sensor of blue light using FAD) proteins, which include AppA from Rhodobacter sphaeroides and PAC from Euglena gracilis. Illumination of dark-state Slr1694 at 15 degrees C reversibly induced a signaling light state characterized by the red shift in the UV-visible spectrum and by the light-induced Fourier transform infrared (FTIR) difference spectrum for structural changes of a bound flavin and apo protein. Illumination at the medium-low temperature (-35 degrees C) led to the red shift in the UV-visible spectrum despite some small difference in the light-induced changes. In contrast, the -35 degrees C illumination resulted in a completely different light-induced FTIR spectrum, in which almost all of the bands were suppressed with the exception of the bands for the change of C4=O bonding of the FAD isoalloxazine ring. The C4=O bands were induced at -35 degrees C with almost the same intensity, but the band frequency for the light state was upshifted by 6 cm(-)(1). The changes in frequency of the light-state C4=O band and in amplitude of other bands showed the same temperature dependence with a half-change temperature at approximately -20 degrees C. It was indicated that the light-induced structural changes of apo protein and FAD were inhibited at low temperature with the exception of the change in hydrogen bonding to the C4=O group. The light-induced formation of the FTIR bands was similarly inhibited by sample dehydration. We discussed the possibility that this constrained light state is a trapped intermediate state in the photocycle of Slr1694.


Occupational health in Mexico.
The authors discuss the maquiladoras and child labor, and offer an overview of the history of occupational safety and health in Mexico that covers laws and regulations, social security, unions, and enforcement of legislation. The organization and structure of the various institutions responsible for occupational safety and health (OSH), as well as administrative procedures, are described. This article concludes with a list of the new challenges for OSH in Mexico.


Visualization of individual DNA molecules in solution by light microscopy: DAPI staining method.
A method was developed to visualize individual DNA molecules in solution under a fluorescent microscope connected to a highly sensitive video camera. DNA stained with a fluorescent dye, DAPI, revealed thin extended filaments, thicker filaments and rapidly transforming folded structures dependent upon the solution conditions. Structural transitions were observed and recorded as video images. Our observations indicated the possibility that DNA has the ability of supercoiling itself. This DAPI staining method will have wide possible application in the study of DNA and chromatin.


The native-invasive balance: implications for nutrient cycling in ecosystems.
We conducted single- and mixed-litter experiments in a hardwood forest in Long Island, New York, using leaf litter from phylogenetically paired native and invasive species. We selected long-established, abundant invasive species with wide-ranging distributions in the eastern United States that likely make substantial contributions to the litter pool of invaded areas. Overall, leaf litter from invasive species differed from native litter, though differences varied by phylogenetic grouping. Invasive litter had lower carbon:nitrogen ratios (30.9 ± 1.96 SE vs. 32.8 ± 1.36, P = 0.034) and invasive species lost 0.03 ± 0.007 g of nitrogen and had 23.4 ± 4.9 % of their starting mass remaining at the end of 1 year compared with a loss of 0.02 ± 0.003 g nitrogen and 31.1 ± 2.6 % mass remaining for native species. Mixing litter from two species did not alter decomposition rates when native species were mixed with other native species, or when invasive species were mixed with other invasive species. However, mixing litter of native and invasive species resulted in significantly less mass and nitrogen loss than was seen in unmixed invasive litter. Mixtures of native and invasive litter lost all but 47 ± 2.2 % of initial mass, compared to 37 ± 5.8 % for invasive litter and 50 ± 5.1 % for native litter. This non-additive effect of mixing native and invasive litter suggests that an additive model of metabolic characteristics may not suffice for predicting invasion impacts in a community context, particularly as invasion proceeds over time. Because the more rapid decomposition of invasive litter tends to slow to rates typical of native species when native and invasive litters are mixed together, there may be little impact of invasive species on nutrient cycling early in an invasion, when native leaf litter is abundant (providing litter deposition is the dominant control on nutrient cycling).


Assessment of the obstetric flying squad in an urban area.
The experience of an obstetric flying squad in an urban area over one year was reviewed. Very few calls were found to be justifiable, and it is concluded that few if any circumstances in modern obstetric practice merit continuing the flying squad in the urban area.


Ciliated foregut cyst of the gall bladder: the largest ever described.
A 78-year-old man presented to the accident and emergency department with acute abdominal pain. A CT scan done to investigate the pain showed an intra-abdominal abscess medial to the caecum and an incidental exophytic lesion in the gall bladder. This was excised during surgery and sent for histological examination. Histology showed a ciliated foregut cyst of the gall bladder. A literature review revealed that this was the 13th case worldwide, as ciliated foregut cysts are usually found either above the diaphragm or in the liver. It was also the largest cyst described, with 45 mm diameter. So far none of these cysts found in the gall bladder have shown malignant transformation, though those found in the liver have been known to become malignant. Due to histological similarity, excision of ciliated foregut cysts of the gall bladder should be considered as there is still a risk of malignant transformation.