Complex competitive and non-competitive inhibition of rat lung angiotensin-converting enzyme by inhibitors containing thiol groups: captopril and SA 446.
1. The kinetics of the inhibitory action of four different angiotensin-converting enzyme inhibitors was evaluated in vitro with rat lung enzyme and the substrate hippuryl-histidyl-leucine. 2. Enzyme velocity against substrate concentration curves were fitted squares to hyperbolae by a weighted least squares iterative method to obtain apparent values of Km, Vmax. and K/V at each concentration of inhibitor. 3. The inhibitory constants Ki and Ki' were obtained by weighted linear regressions of K/V against i and 1/V against i respectively. 4. Teprotide was the least potent inhibitor with a Ki of near 20 nmol/l whereas captopril (SQ 14 225) and SA 446 were both approximately 10 times and MK 421 approximately 20 times more potent. 5. Two inhibitors which lacked thiol groups [teprotide or SQ 20 881 and N-(1-S-1-carboxy-3-phenylpropyl)-L-Ala-L-Pro or MK 421] produced a purely competitive pattern of inhibition with increased apparent Km but no change in apparent Vmax.. 6. Two inhibitors containing thiol groups [captopril or SQ 14 225 and 2-(2'-hydroxyphenyl)-3-(3-mercaptopropanoyl)-4-thiazolidine carboxylic acid or SA 446] both produced a mixed competitive and non-competitive pattern of inhibition with increased apparent Km and decreased Vmax.. 7. It is possible that thiol-containing inhibitors might produce non-competitive inhibition of converting enzyme by forming strong bonds with zinc near the active site of the enzyme.


Bulk-mediated surface transport in the presence of bias.
Surface transport, when the particle is allowed to leave the surface, travel in the bulk for some time, and then return to the surface, is referred to as bulk-mediated surface transport. Recently, we proposed a formalism that significantly simplifies analysis of bulk-mediated surface diffusion [A. M. Berezhkovskii, L. Dagdug, and S. M. Bezrukov, J. Chem. Phys. 143, 084103 (2015)]. Here this formalism is extended to bulk-mediated surface transport in the presence of bias, i.e., when the particle has arbitrary drift velocities on the surface and in the bulk. A key advantage of our approach is that the transport problem reduces to that of a two-state problem of the particle transitions between the surface and the bulk. The latter can be solved with relative ease. The formalism is used to find the Laplace transforms of the first two moments of the particle displacement over the surface in time t at arbitrary values of the particle drift velocities and diffusivities on the surface and in the bulk. This allows us to analyze in detail the time dependence of the effective drift velocity of the particle on the surface, which can be highly nontrivial.


Liposome-Protamine-DNA Nanoparticle-Mediated Delivery of Short Hairpin RNA Targeting Brachyury Inhibits Chordoma Cell Growth.
Recent evidence suggests that brachyury is a crucial molecular driver in the initiation and propagation of chordoma. However, no small molecules have been used to specifically target brachyury. Short hairpin RNA (shRNA) has therapeutic promise for the genetic treatment of cancer, but the usage of shRNA therapeutics is limited by obstacles related to effective delivery into the nuclei of target cancer cells due to their inherent sensitivity to nucleases and large polyanionic characteristics. To overcome instability and low transfection efficiency, liposome-protamine-DNA (LPD) nanoparticles were synthesized and investigated as a non-viral carrier of shRNA targeting brachyury in chordoma cells. The size, zeta potential, affinity and transfection efficiency of LPD-shRNA complexes were characterized, and their biological functions in chordoma cells were evaluated. The transfection efficiency of LPD-shRNA was significant higher than naked shRNA. LPD delivered brachyury shRNA into chordoma cells and inhibited brachyury expression, induced apoptosis, upregulated the epithelial biomarker, E-cadherin, downregulated the mesenchymal biomarker, Snail and Slug, and suppressed cell growth. These data indicate that LPD might be a promising non-viral carrier for shRNA in gene targeted therapy of chordoma.


Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.
1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.


[Disease modifying antirheumatic drugs with inhibitory effect on osteoclastogenesis].
Suppression of bone destruction is a requirement for effective therapeutic strategies for autoimmune arthritis. Although numerous antirheumatic drugs are in clinical use, little is known about whether they ameliorate bone destruction by acting on activated T cells or other cell types, such as bone-resorbing osteoclasts. Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1, the master switch regulator for osteoclast differentiation. We show that the direct inhibitory action of leflunomide on osteoclast differentiation constitutes an important aspect to ameliorate bone destruction, and that RANKL dependent NFATc1 induction pathway is an auspicious target for pharmacological intervention into arthritic bone destruction.


Evaluating pictogram prediction in a location-aware augmentative and alternative communication system.
This study compared the performance of two statistical location-aware pictogram prediction mechanisms, with an all-purpose (All) pictogram prediction mechanism, having no location knowledge. The All approach had a unique language model under all locations. One of the location-aware alternatives, the location-specific (Spec) approach, made use of specific language models for pictogram prediction in each location of interest. The other location-aware approach resulted from combining the Spec and the All approaches, and was designated the mixed approach (Mix). In this approach, the language models acquired knowledge from all locations, but a higher relevance was assigned to the vocabulary from the associated location. Results from simulations showed that the Mix and Spec approaches could only outperform the baseline in a statistically significant way if pictogram users reuse more than 50% and 75% of their sentences, respectively. Under low sentence reuse conditions there were no statistically significant differences between the location-aware approaches and the All approach. Under these conditions, the Mix approach performed better than the Spec approach in a statistically significant way.


Consideration of alternative causes of lactic acidosis: Thiamine deficiency in malignancy.
Lactic acidosis is a common metabolic acidosis characterized by increased serum lactate and is usually associated with a decreased blood pH. Lactic acidosis has many different causes but has been differentiated into type A, hypoxic causes, and type B, non-hypoxic causes. Tissue hypoxia, type A, is the most common cause, usually secondary to processes such as sepsis and multi-organ failure. Type A must be differentiated from type B in the correct clinical setting as treatments are vastly different. Type B causes may include drug side-effects, toxins, enzymatic defects, inherited or acquired, any of which may lead to overproduction or underutilization of lactate. However, as most clinicians are more familiar, and likely more initially concerned with hypoxic etiologies, evaluation is directed toward finding the source of hypoperfusion or hypoxia, and thus generally leading to a delay in discovering a type B cause (or mixed type A and type B). Here we describe a case of lactic acidosis in the setting of thiamine deficiency thought to be secondary to advanced lung cancer. The purpose of this paper is to bring awareness to the clinician to consider other causes of lactic acidosis when evaluating a patient.


Alternative Solvents for the Biorefinery of Spirulina: Impact of Pretreatment on Free Fatty Acids with High Added Value.
The growing demand for molecules of interest from microalgal biomass, such as phycobiliproteins, has led to an accumulation of unused by-products. For example, phycocyanin, obtained by the extraction of Spirulina, generated cakes rich in non-polar molecules of interest, such as free fatty acids (FFAs). These FFAs were generally considered as markers of lipidome degradation, but represented a relevant alternative to topical antibiotics, based on a biomimetic approach. In order to develop a sustainable Spirulina biorefinery scheme, different pretreatments and alternative solvents were screened to identify the best combination for the valorization of FFAs. Thus, five pre-treatments were studied including a phycocyanin extraction by-product. The following three biobased solvents were selected: ethyl acetate (EtOAc), dimethyl carbonate (DMC) and a fatty acid-based natural deep eutectic solvent (NaDES). The pigment and fatty acid profiles were established by spectroscopic and chromatographic approaches. NaDES demonstrated superior extraction capacity and selectivity compared to other biobased solvents, regardless of pretreatment. In contrast, EtOAc and DMC showed a greater diversity of FFAs, with a predominance of polyunsaturated fatty acids (PUFAs). The by-product has also been highlighted as a relevant raw material facilitating the recovery of FFAs. These results pave the way for a green biorefinery of the lipid fraction and phycobiliproteins of microalgae.


Monoclonal antibodies reacting with endo-beta-galactosidase-resistant epitopes on keratan sulfate-bearing fragments of bovine nasal cartilage proteoglycan.
Six monoclonal antibody-producing cell lines were derived from mice immunized with keratan sulfate (KS)-bearing tryptic fragments of the core protein of bovine nasal cartilage proteoglycan monomer digested with KS-specific endo-beta-galactosidase. The monoclonal antibodies were characterized by solid-phase ELISA competition studies and SDS-PAGE immunoblotting. Two of them resemble previously described monoclonal antibodies that are directed to epitopes containing both KS and core protein. In contrast, the remaining four monoclonal antibodies are unprecedented in being directed to epitopes whose reactivity is unaffected or enhanced by endo-beta-galactosidase degradation of KS. SDS-PAGE immunoblots revealed two large KS-bearing tryptic fragments of cartilage proteoglycan and a heterogeneous population of smaller fragments not evident by non-immunological techniques. Some of the antibodies used react with all KS-bearing fragments, others react only with the two largest fragments.


Cardiac electronic implantable devices: A call for a new coding system.
Over the last decades, cardiac electronic implantable devices (CEID) have incorporated a myriad of technological capabilities that are not conveniently inferred by using the conventional ICHD and NBG coding systems. We propose a new coding system (i.e., the C-ARL-A coding system) aimed at overcoming this important limitation.


Renal microangiopathy of the hemolytic-uremic syndrome in childhood.
18 children with clinical and laboratory findings characteristic of the hemolytic uremic syndrome were retrospectively studied. Thrombocytopenia due to platelet destruction was accompanied by only minimal changes in fibrinogen turnover and fibrinolytic degradation products. The most consistent pathologic feature was severe renal endothelial cell injury, which was postulated to produce both platelet and red cell destruction. Despite initially severe renal damage, 90% of the patients ultimately recovered normal renal function if adequately supported during the acute phase of the disease.


Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model.
The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582).


Signatures of beta-sheet secondary structures in linear and two-dimensional infrared spectroscopy.
Using idealized models for parallel and antiparallel beta sheets, we calculate the linear and two-dimensional infrared spectra of the amide I vibration as a function of size and secondary structure. The model assumes transition-dipole coupling between the amide I oscillators in the sheet and accounts for the anharmonic nature of these oscillators. Using analytical and numerical methods, we show that the nature of the one-quantum vibrational eigenstates, which govern the linear spectrum, is, to a large extent, determined by the symmetry of the system and the relative magnitude of interstrand interactions. We also find that the eigenstates, in particular their trends with system size, depend sensitively on the secondary structure of the sheet. While in practice these differences may be difficult to distinguish in congested linear spectra, we demonstrate that they give rise to promising markers for secondary structure in the two-dimensional spectra. In particular, distinct differences occur between the spectra of parallel and antiparallel beta sheets and between beta hairpins and extended beta sheets.


Complex Phase Behavior of GUVs Containing Different Sphingomyelins.
Understanding the lateral organization of biological membranes plays a key role on the road to fully appreciate the physiological functions of this fundamental barrier between the inside and outside regions of a cell. Ternary lipid bilayers composed of a high and a low melting temperature lipid and cholesterol represent a model system that mimics some of the important thermodynamical features of much more complex lipid mixtures such as those found in mammal membranes. The phase diagram of these ternary mixtures can be studied exploiting fluorescence microscopy in giant unilamellar vesicles, and it is typically expected to give rise, for specific combinations of composition and temperature, to regions of two-phase coexistence and a region with three-phase coexistence, namely, the liquid-ordered, liquid-disordered, and solid phases. Whereas the observation of two-phase coexistence is routinely possible using fluorescence microscopy, the three-phase region is more elusive to study. In this article, we show that particular lipid mixtures containing diphytanoyl-phosphatidylcholine and cholesterol plus different types of sphingomyelin (SM) are prone to produce bilayer regions with more than two levels of fluorescence intensity. We found that these intensity levels occur at low temperature and are linked to the copresence of long and asymmetric chains in SMs and diphytanoyl-phosphatidylcholine in the lipid mixtures. We discuss the possible interpretations for this observation in terms of bilayer phase organization in the presence of sphingolipids. Additionally, we also show that in some cases, liposomes in the three-phase coexistence state exhibit extreme sensitivity to lateral tension. We hypothesize that the appearance of the different phases is related to the asymmetric structure of SMs and to interdigitation effects.


The Influence of Copolymer Composition on PLGA/nHA Scaffolds' Cytotoxicity and In Vitro Degradation.
The influence of copolymer composition on Poly(Lactide-co-Glycolide)/nanohydroxyapatite (PLGA/nHA) composite scaffolds is studied in the context of bone tissue engineering and regenerative medicine. The composite scaffolds are fabricated by thermally-induced phase separation and the effect of bioactive nanoparticles on their in vitro degradation in phosphate-buffered solution at 37 °C is analyzed over eight weeks. The indirect cytotoxicity evaluation of the samples followed an adaptation of the ISO 10993-5 standard test method. Based on the measurement of their molecular weight, molar mass, pH, water absorption and dimensions, the porous scaffolds of PLGA with a lower lactide/glycolide (LA/GA) molar ratio degraded faster due to their higher hydrophilicity. All of the samples without and with HA are not cytotoxic, demonstrating their potential for tissue engineering applications.


Does seasonal employment in grain elevators increase nonspecific airways responsiveness?
Grain handling and increased airways responsiveness (AR) have been independently associated with an accelerated decline in forced expiratory volume in 1 sec. We performed methacholine inhalation bronchial challenge tests in 45 river port grain handlers during layoff and again during employment to determine whether short-term exposure increased AR. To assess bias, due to seasonal/temporal influences, AR was also measured in 56 nonexposed men of similar age and socioeconomic status. AR, slightly higher among laid-off grain handlers than the comparison group, fell more among grain handlers during employment than among the comparison group during the same time period. Our results do not support the hypothesis that seasonal exposure to grain dust increases AR.


Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status.
Objective: Overweight (body mass index or BMI ≥ 25 kg/m2) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function.


Global research trends in immunotherapy for glioma: a comprehensive visualization and bibliometric analysis.
Glioma is a prevalent and lethal brain malignancy; despite current treatment options, the prognosis remains poor. Therefore, immunotherapy has emerged as a promising therapeutic strategy. However, research trends and hotspots in glioma immunotherapy have not been systematically analyzed. This study aimed to elucidate global research trends and knowledge structures regarding immunotherapy for glioma using bibliometric analysis. Publications related to immunotherapy for glioma from 2000-2023 were retrieved from Web of Science Core Collection database (WoSCC). We conducted quantitative analysis and visualization of research trends using various tools, including VOSviewer (1.6.18), CiteSpace (5.7 R3), Microsoft Charticulator, and the Bibliometrix package in R. A total of 4910 publications were included. The number of annual publications exhibited an obvious upward trend since 2019. The USA was the dominant country in terms of publication output and centrality. Frontiers in Immunology published the most articles. Harvard Medical School ranked first in productivity among institutions. Sampson, John H. Ph.D. is the most prolific author in the field with 88 articles and a total of 7055 citations. Clinical Cancer Research has the largest total number and impact factor. Analysis of keywords showed immunotherapy, glioblastoma, immunotherapy, and clinical trials as hot topics. The tumor microenvironment, cell death pathways, chimeric antigen receptor engineering, tumor-associated macrophages, and nivolumab treatment represent indicating shifts in the direction of future glioma immunotherapy development. This bibliometric analysis systematically delineated global landscapes and emerging trends in glioma immunotherapy research. This study highlighted the prominence of Chimeric Antigen Receptor T-cell (CAR-T), Programmed Death-1 (PD-1), and nivolumab in current glioma immunotherapy research. The growing emphasis on specific neoantigens and prognostic tumor markers suggests potential avenues for future exploration. Furthermore, the data underscores the importance of strengthened international collaboration in advancing the field.


Mercury content in tinned molluscs (mussel, cockle, variegated scallop, and razor shell) normally consumed in Spain, 2005.
Concentrations of mercury were determined for tinned molluscs (Mollusca, Bivalvia), i.e., mussels (Mytilus spp.), cockles (Cerastoderma edule), variegated scallops (Chlamys varia), and razor shells (Ensis spp.), consumed in Spain. A total of 220 samples were analyzed: 120 mussels, 40 cockles, 24 variegated scallops, and 36 razor shells. Samples were obtained weekly from markets in Santa Cruz de Tenerife (Canary Islands) over a period of 12 months. All observed concentrations of mercury were below the maximum permitted for human consumption (0.5 mg/kg) as defined by European Community Decision 93/ 351/CE. Mercury concentrations were 27.28 +/- 12.43 microg/kg for mussels, 66.59 +/- 23.53 microg/kg for cockles, 33.68 +/- 15.76 microg/kg for variegated scallops, and 21.26 +/- 12.24 microg/kg for razor shells. To evaluate the importance of mercury as a food contaminant, the percentage ingested daily, the weight of mercury in the diet, and the calculated percentage of this metal in the diet contributed by reference species were estimated.


Structural characterization and in vitro immunogenicity evaluation of amphibian-derived collagen type II from the cartilage of Chinese Giant Salamander (Andrias davidianus).
Collagen type II (CT-II) has unique biological activities and functions, yet the knowledge on amphibian-derived CT-II is rare. Herein, acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) were successfully isolated and characterized from the cartilage of Chinese Giant Salamander (CGS). The in vitro immunogenicity of collagen was then evaluated and compared with that of the standard bovine CT-II (SCT-II) by T-lymphocyte cell proliferation activity. Results demonstrated that ASC and PSC were predominantly CT-II along with minor collagen type I and maintained intact triple-helical structure of nature collagen. Compared with SCT-II, higher glycine content (337.80 and 339.93 residues/1000 residues) and lower degree of proline hydroxylation (51.81% and 52.52%) were observed in ASC and PSC. Additionally, PSC showed comparable Td (63 °C) and higher Tm (109 °C) than SCT-II (64 °C and 103 °C, respectively), indicating its high thermal and structural stability. SEM revealed that the lyophilized ASC and PSC had interconnected porous network structures of collagen-based materials. Moreover, different from SCT-II, both ASC and PSC presented no immunogenicity because they did not cause obvious proliferation of murine T-lymphocyte regardless of the induced concentration of collagen increased from 8 to 417 μg/mL. These data suggested that the amphibian-derived CGS cartilage collagens avoid the immunogenic risk of terrestrial animal collagen, and show high thermal stability and potential advantage in biomedical application.


Domains of initiator tRNA and initiation codon crucial for initiator tRNA selection by Escherichia coli IF3.
Initiation factors are used by Escherichia coli to select the initiator tRNA over elongator tRNAs during translation initiation. IF3 appears to "inspect" the anticodon end of the tRNA, probably along with the initiation codon. The anticodon stem and loop of the initiator tRNA, together with part of the initiation codon of the mRNA, can be thought of as a unit. Changes made in the anticodon stem, the anticodon loop, or the anticodon of an initiator tRNA fragment result in a loss of selection by IF3 in an in vitro assay for translation initiation. IF3 allows the selection of an initiator tRNA anticodon stem and loop fragment on GUG and UUG codons but does not select that tRNA fragment in response to AUU.


Codon reassignment to facilitate genetic engineering and biocontainment in the chloroplast of Chlamydomonas reinhardtii.
There is a growing interest in the use of microalgae as low-cost hosts for the synthesis of recombinant products such as therapeutic proteins and bioactive metabolites. In particular, the chloroplast, with its small, genetically tractable genome (plastome) and elaborate metabolism, represents an attractive platform for genetic engineering. In Chlamydomonas reinhardtii, none of the 69 protein-coding genes in the plastome uses the stop codon UGA, therefore this spare codon can be exploited as a useful synthetic biology tool. Here, we report the assignment of the codon to one for tryptophan and show that this can be used as an effective strategy for addressing a key problem in chloroplast engineering: namely, the assembly of expression cassettes in Escherichia coli when the gene product is toxic to the bacterium. This problem arises because the prokaryotic nature of chloroplast promoters and ribosome-binding sites used in such cassettes often results in transgene expression in E. coli, and is a potential issue when cloning genes for metabolic enzymes, antibacterial proteins and integral membrane proteins. We show that replacement of tryptophan codons with the spare codon (UGG→UGA) within a transgene prevents functional expression in E. coli and in the chloroplast, and that co-introduction of a plastidial trnW gene carrying a modified anticodon restores function only in the latter by allowing UGA readthrough. We demonstrate the utility of this system by expressing two genes known to be highly toxic to E. coli and discuss its value in providing an enhanced level of biocontainment for transplastomic microalgae.


Neural oscillations associated with auditory duration maintenance in working memory.
The neural representation of auditory duration remains unknown. Here, we used electroencephalogram (EEG) recordings to investigate neural oscillations during the maintenance of auditory duration in working memory (WM). EEG analyses indicated that the auditory duration length was not associated with changes in the theta band amplitude, whereas the alpha band amplitudes during 3-s and 4-s auditory duration conditions were lower than during the 1-s and 2-s conditions. Moreover, the alpha band amplitude and accuracy were positively correlated in the 2-s duration condition. We also found that the neural representation of auditory duration is segmented, with a critical threshold point of approximately 2 s, which is shorter than that for visual duration (3 s). The results emphasised the involvement of the alpha band in auditory duration maintenance in WM. Our study's findings indicate that different internal representations of auditory durations are maintained in WM below and above 2 s from the perspective of electrophysiology. Additionally, the critical threshold point is related to the sensory modality of duration.


Similarities and differences between DNA of Cryptosporidium parvum and C. wrairi detected by the polymerase chain reaction.
The objective of this study was to determine if primers, probes, and pHC1, a plasmid containing a 2.3 kilobase insert of genomic DNA from Cryptosporidium parvum, would be useful for the detection of Cryptosporidium wrairi DNA using the polymerase chain reaction. C. wrairi DNA was prepared from oocysts recovered from guinea pigs and C. parvum DNA was prepared from the Iowa strain of C. parvum. Two 26-(bp) primers were used to amplify a 452-base pair bp target sequence within the cloned DNA. Similarly-sized PCR products were obtained with the pHC1 plasmid DNA, C. parvum DNA, and C. wrairi DNA. However, a 20-base pair probe did not detect C. wrairi DNA. Sequencing of C. wrairi DNA homologous with the 452-bp segment of C. parvum DNA showed 18 bp changes including bp changes in the segment homologous with the probe. A new probe based on homologous sequences was useful for detection of both species of cryptosporidia. The sequences of the homologous 452-bp segment from the Iowa strain of C. parvum and that segment of C. parvum DNA from the pHC1 plasmid were very similar. Nine base pairs identical in the homologous bp segment of the Iowa strain of C. parvum, C. wrairi and the pHC1 plasmid differed from those previously reported. Previously reported primers and a newly designed probe proved to be useful for detecting C. wrairi DNA.


Disability and the Family in South Wales Coalfield Society, c.1920-1939.
This article utilises the south Wales coalfield in the interwar period as a case study to illustrate the applicability of two sociological theories - family systems theory and the social ecology of the family - to impairment in the past. It demonstrates that a theoretically-informed approach can help to situate impairment in its particular contexts, most especially the family and the community, and give a better sense of the lived experience of disability. It also demonstrates the complexity of the experience of disability as the family and economic circumstances of each impaired individual varied and led to different forms of care-giving or the utilisation of different sources of support. The article also sheds further light on the ubiquity of disability as many families included a number of individuals with different impairments and this too had consequences for experiences and coping strategies.


Electroluminescent Devices: Extremely Stretchable Electroluminescent Devices with Ionic Conductors (Adv. Mater. 22/2016).
An extremely stretchable electroluminescent device is fabricated by P. S. Lee and co-workers, as described on page 4490. The stretchable alternating-current electroluminescent (ACEL) device possesses extremely high stretchability, and can be linearly stretched to 700% with the luminance being maintained at 70% of the initial value before stretching. The device can be repeatedly stretched to 400% with stable emission behavior. The presented device will provide new opportunities in stretchable lighting, volumetric 3D displays, interactive readout systems, and other unprecedented applications.


The Relationship of Symptoms of Anxiety and Depression with Disease Severity and Treatment Modality in Myasthenia Gravis: A Cross-sectional Study.
Findings about the relationship between psychopathology and severity of myasthenia gravis (MG) seem scarce and conflicting. The aim of this study was to investigate the relationship of depressive and anxiety symptoms with disease severity and treatment modalities among a cohort of patients with MG. Sixty-seven patients, who presented to the neuromuscular outpatient clinic, at a neuropsychiatry hospital in Istanbul, Turkey in a two-month period, were recruited consecutively. A total of 42 patients with MG were invited to participate in the study. None of the patients refused to participate. Severity of MG was assessed according to the Osserman and Genkins classification. The participants were evaluated by a sociodemographic form, the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Hamilton Depression Rating Scale 17-item version (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). The patients with stage IIB MG had significantly higher scores on the BAI, HAM-D, HAM-A total and somatic anxiety than those with stage I and IIA MG (p<0.05). Likewise, the patients taking a combination of prednisolone+pyridostigmine/azathioprine had significantly higher scores on the BAI, HAM-D, HAM-A total and somatic anxiety than those taking only prednisolone (p<0.05). Linear regression analysis revealed that disease severity and stressful life events were the factors associated with the HAM-D scores. Disease severity, treatment modalities, and gender were the factors associated with the HAM-A scores. The results of the present study may suggest that patients with relatively more severe MG or those taking a combination of immunosupressive and anticholinesterase medications need psychiatric/psychological evaluation.


Selected lactobacilli and bifidobacteria development in solid state fermentation using soybean paste.
At present, consumers are looking for more natural foods so as to improve health through their active compounds. Within this context, soybean is an excellent substrate due to its beneficial effects on consumers' health. Moreover, lactic cultures are widely used in the food industry to improve the technological, nutritional and functional characteristics of fermented foods. It is interesting to find new matrices in which to transport these starter cultures (potentially probiotic microorganisms). The aim of this research was to obtain a solid state fermentation system from soybean to analyze the behavior of selected lactobacilli and bifidobacteria, with the potential to develop a functional vegetarian food to serve as carrier for the microorganisms. A soybean solid substrate system was optimized by selecting the relationship of the main processing parameters. Homogeneous soybean pastes with different moisture content (60-80%) were obtained and used as substrate and support for solid substrate fermentation. Moisture, inoculum size and temperature were optimized: 80%, 4%, 37°C, respectively. L. rhamnosus CRL 981 was chosen as the best starter to use in this kind of fermentation, showing high acidification and cell counts at 24h of fermentation and increased specific growth rate in tested soybean pastes. It was demonstrated that the selected soybean paste could be used as a carrier of these microorganisms having probiotic potential for the production of vegetarian foods. Moreover, these microorganisms are able to modify the substrate to enhance their nutritional and functional characteristics, which would change the soybean into a more attractive product for consumers.


The Effect of Inhibitory Signals on the Priming of Drug Hapten-Specific T Cells That Express Distinct Vβ Receptors.
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO-specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ-restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO-specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO-induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.


Cytomorphologic diagnosis of adult granulosa cell tumors at the metastatic sites with an emphasis on the cytologic mimics.
Adult granulosa cell tumor (AGCT) is a rare ovarian sex-cord malignancy notorious for late recurrences and metastases. The cytologic features of AGCT at the metastatic sites have been documented sporadically. Hence, knowledge of the characteristic cytomorphologic features is essential for an accurate diagnosis and distinguishing it from its pathologic mimics, especially at the metastatic sites. This was a retrospective study conducted over six years. The cytopathology electronic database was searched for the fine needle aspirates (FNA) reported as metastatic AGCT. A detailed cytomorphologic assessment was done for multiple cytologic features, including overall cellularity, cellular arrangement of the tumor cells, cell size, cell shape, nuclear pleomorphism, nuclear grooving, chromatin pattern, nucleolar prominence, mitotic figures, amount and character of cytoplasm, and the extracellular background. There were 6 cases reported as metastatic AGCT on aspiration cytology. The smears in all the cases were cellular, with tumor cells arranged in loose aggregates, three-dimensional clusters, perivascular papillary fronds, and scattered singly. The most consistent cytologic features included microfollicular arrangement of monomorphic tumor cells with round-oval nuclei, fine chromatin, longitudinal nuclear grooving, and scant cytoplasm. Typical Call-Exner bodies and metachromatically stained extracellular hyaline material were noted sporadically. None of the smears showed anaplasia, prominent macronucleoli, atypical mitoses, or necrosis. The current study not only outlines the distinct cytologic attributes of AGCTs across various metastatic locations but also highlights its prevalent cytologic mimics. Additionally, it outlines key clinicopathologic traits that can aid in distinguishing and precisely diagnosing these tumors through cytological analysis.


The vibrational spectrum of fanlike ScC(3) in solid Ar.
Fourier transform infrared spectra of fanlike (C(2v)) ScC(3) have been obtained by trapping the vapor from the Nd:YAG (yttrium aluminum garnet) laser ablation of (13)C-enriched graphite and Sc rods in solid Ar at approximately 10 K. Three vibrational fundamentals, the nu(5)(b(2))=1478.0 cm(-1) asymmetric carbon stretch, the nu(3)(a(1))=557.0 cm(-1) symmetric metal-carbon stretch, and the nu(1)(a(1))=1190.7 cm(-1) symmetric carbon stretch have been observed for the first time. The measured isotopic spectra are in good agreement with DFT-B3LYP/6-311G(3df,3pd) simulated spectra and indicate a (2)A(2) ground state rather than (4)B(1) as suggested by other theoretical calculations. The frequency of the nu(3)(a(1)) fundamental is consistent with a frequency of 560+/-30 cm(-1) reported in a photoelectron spectroscopy investigation of ScC(3).


Timing of Debridement and Infection Rates in Open Fractures of the Hand: A Systematic Review.
Background: Literature on open fracture infections has focused primarily on long bones, with limited guidelines available for open hand fractures. In this study, we systematically review the available hand surgery literature to determine infection rates and the effect of debridement timing and antibiotic administration. Methods: Searches of the MEDLINE, EMBASE, and Cochrane computerized literature databases and manual bibliography searches were performed. Descriptive/quantitative data were extracted, and a meta-analysis of different patient cohorts and treatment modalities was performed to compare infection rates. Results: The initial search yielded 61 references. Twelve articles (4 prospective, 8 retrospective) on open hand fractures were included (1669 open fractures). There were 77 total infections (4.6%): 61 (4.4%) of 1391 patients received preoperative antibiotics and 16 (9.4%) of 171 patients did not receive antibiotics. In 7 studies (1106 open fractures), superficial infections (requiring oral antibiotics only) accounted for 86%, whereas deep infections (requiring operative debridement) accounted for 14%. Debridement within 6 hours of injury (2 studies, 188 fractures) resulted in a 4.2% infection rate, whereas debridement within 12 hours of injury (1 study, 193 fractures) resulted in a 3.6% infection rate. Two studies found no correlation of infection and timing to debridement. Conclusions: Overall, the infection rate after open hand fracture remains relatively low. Correlation does exist between the administration of antibiotics and infection, but the majority of infections can be treated with antibiotics alone. Timing of debridement, has not been shown to alter infection rates.


Structure and activity of CPNGRC: a modified CD13/APN peptidic homing motif.
Asn-Gly-Arg peptides have been designed as vehicles for the delivery of chemotherapeutics, magnetic resonance imaging contrast agents, and fluorescence labels to tumor cells, and cardiac angiogenic tissue. Specificity is derived via an interaction with aminopeptidase N, also known as CD13, a cell surface receptor that is highly expressed in angiogenic tissue. Peptides containing the CNGRC homing sequence tethered to a pro-apoptotic peptide sequence have the ability to specifically induce apoptosis in tumor cells. We have now identified a modification to the Asn-Gly-Arg homing sequence motif that improves overall binding affinity to aminopeptidase N. Through the addition of a proline residue, the new peptide with sequence, CPNGRC, inhibits aminopeptidase N proteolytic activity with an IC(50) of 10 microM, a value that is 30-fold lower than that for CNGRC. Both peptides are cyclized via a disulfide bridge between cysteines. Steady-state kinetic experiments suggest that efficient aminopeptidase N inhibition is achieved through the highly cooperative binding of two molecules of CPNGRC. We have used NMR-derived structural constraints for the elucidation of the solution structures CNGRC and CPNGRC. Resulting structures of CNGRC and CPNGRC have significant differences in the backbone torsion angles, which may contribute to the enhanced binding affinity and demonstrated enzyme inhibition by CPNGRC.


Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study.
Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H(+)-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.


Ethical issues in human prion diseases.
Prion diseases or transmissible spongiform encephalopathies are a group of closely related transmissible neurodegenerative conditions of humans and animals, all of which are incurable. In recent years, they have captured public attention with the emergence of the bovine spongiform encephalopathy (BSE) epidemic in Europe, and more recently with the appearance of variant CJD (vCJD) in humans, a novel form of Creutzfeldt-Jakob disease (CJD) that is linked to dietary exposure to BSE. In this chapter, we outline ethical questions posed by research, diagnostic procedures and therapy in the field of prion diseases.


Delivery of mitogen-activated protein kinase inhibitor for hepatocellular carcinoma stem cell therapy.
Hepatocellular carcinoma (HCC) is one of the most common malignant human tumors worldwide, but no effective therapeutic options are currently available. The cancer stem cell (CSC) has proven to play a central role in the development, metastasis, and recurrence of HCC. In this study, we report a dual functional mitogen-activated protein kinase inhibitor (U0126)-based therapy for treating both bulk HCC and HCC CSCs, using poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles as the drug carrier. It is demonstrated that nanoparticle encapsulation enhanced the cell uptake of U0126 in HCC CSCs and that enhanced endocytosis lead to augmented cytotoxicity of U0126 in HCC CSCs. Moreover, the nanoparticle encapsulation increased the inhibition of self-renewal capability, prolonged the circulation time, and increased the tumor accumulation of U0126 when compared with the use of the free inhibitor. The systemic delivery of U0126 remarkably enhanced the suppression of tumor development with decreased CSCs in the HepG2 xenograft simultaneously with reduced systemic toxicity.


Influence of physico-mechanical properties of elastomeric material for different cell growth.
The tunable mechanical and physical properties of polydimethylsiloxane (PDMS) are commonly utilized for studying cellular dynamics. However, the inherent hydrophobic nature of PDMS limits its application as a cell culture film. Various surface modification techniques render PDMS films hydrophilic, altering their surface chemistry, elasticity, roughness and the cell attachment of anchorage-dependent cell types to the films. The surface properties of thin films lead to the alteration of the biomechano-physical properties of cells, so they can be used as a mechanical signature for the viability testing of different types of cell, such as normal and cancerous ones. In this study, 3T3 fibroblast and HaCaT keratinocyte cells were grown on different pristine and oxidized PDMS compositions by varying their base-to-curing-agent ratios (w/w). The enhanced wettability favors the cell spreading and growth rate of both 3T3 and HaCaT cells, and it varies with the film's surface chemistry and elasticity. This study focuses on the importance of understanding how various surface modification methods, like oxygen plasma and piranha treatment, can impact cell-cell and cell-substrate interaction for different cell types, thereby assisting in the preparation of various PDMS-based biomedical devices.


High Glucose Promotes Epithelial-Mesenchymal Transition of Uterus Endometrial Cancer Cells by Increasing ER/GLUT4-Mediated VEGF Secretion.
Uterus endometrial cancer (UEC) is the common malignancy among gynecologic cancers, and most of them are type I estrogen-dependent UEC. Diabetes is well-known risk factor for the development of UEC. However, the underlying link between high glucose (HG) and the estrogen receptor in UEC remains unclear. Epithelial-mesenchymal transition (EMT) has also been shown to occur during the initiation of metastasis in cancer progression. The aim of this study was to determine the relationships and roles of HG, estrogen receptor and EMT in the growth and migration of UEC. The expression of glucose transport protein 4 (GLUT4) in the control endometrium and UEC tissues was detected by immunohistochemistry (IHC); the cell viability and invasion were analyzed through CCK-8 and Matrigel invasion assays; the transcriptional level of EMT-related genes was evaluated through real-time PCR; and the effect of HG and / or GLUT4 on estrogen receptors, vascular endothelial growth factor (VEGF) and its receptor VEGFR was analyzed through western blotting, ELISA and flow cytometry (FCM) assay, respectively. In addition, Ishikawa-xenografted nude mice were constructed and were used to analyze the effect of estrogen and GLUT4 on the growth of UEC in vivo. Here, we found that exposure to HG led to a high level of viability and invasion of UEC cell lines (UECC, Ishikawa and RL95-2 cells). Compared with the normal endometrium, a higher level of GLUT4 was observed in UEC tissues. Silencing GLUT4 obviously inhibited the HG-promoted viability, invasion and expression of EMT-related genes (TWIST, SNAIL and CTNNB1) of UECC promoted by HG. Further analysis showed that HG and GLUT4 promoted the secretion of VEGF and expression of VEGFR in UECC. Treatment with HG led to the increase of estrogen receptor α (ERα) and β (ERβ) in UECC, blocking ERα or ERβ resulted in the decreases in GLUT4 expression, TWIST, SNAIL and CTNNB1 transcription, and VEGF and VEGFR expression in UECC. Treatment with anti-human VEGF neutralizing antibody restricted the viability and invasion of UECC that was induced by HG and estrogen. Exposure to estrogen accelerated growth, VEGF production, and TWIST and CTNNB1 expression in UEC in Ishikawa-xenografted nude mice, and silencing GLUT4 restricted these effects. These data suggest that HG increases GLUT4 and VEGF/VEGFR expression, further promotes EMT process and accelerates the development of UEC by up-regulating ER.


[Evaluation of a linear TEOAE protocol in hearing screening of neonates: feasibility study].
The audiological screening of newborns based on recording TEOAEs--the expression of anatomical-functional integrity of the cochlea--has unanimously gained importance. The prevalence of severe of genetic or congenital hearing loss in the healthy infant population and in the population at risk for audiological disorders, as well as the consequent psycholinguist and socialization problems such children have to deal with, have led the authors to set up a preliminary protocol for the audiological screening of neonates. The purpose of this protocol is to improve the feasibility of applying such a program. To this purpose, the preliminary protocol called for the recording of the TEOAE in both non linear (NL) and linear (L) modes. Examination was performed in 347 newborns (30% of all the children born during 1997) the second day of life and during spontaneous sleep. The ILO 92 was used for the screening. The results obtained with the two methods were statistically compared using the 9 parameters considered response indicators. Using the linear method of a function-window and improving the signal-to-noise ratio, the study showed a significant difference in the quality of the TEOAE using the linear method as compared with the non linear method, although this did not modify response reliability. This lead to the definition, through free distribution statistical analysis, of broader than normal criteria by which to evaluate the responses evoked with the L method. All this is aimed at increasing system specificity and reducing the number of false positives which feeds family anxiety.


Acetylation of trehalose mycolates is required for efficient MmpL-mediated membrane transport in Corynebacterineae.
Pathogenic species of Mycobacteria and Corynebacteria, including Mycobacterium tuberculosis and Corynebacterium diphtheriae, synthesize complex cell walls that are rich in very long-chain mycolic acids. These fatty acids are synthesized on the inner leaflet of the cell membrane and are subsequently transported to the periplasmic space as trehalose monomycolates (TMM), where they are conjugated to other cell wall components and to TMM to form trehalose dimycolates (TDM). Mycobacterial TMM, and the equivalent Corynebacterium glutamicum trehalose corynomycolates (TMCM), are transported across the inner membrane by MmpL3, or NCgl0228 and NCgl2769, respectively, although little is known about how this process is regulated. Here, we show that transient acetylation of the mycolyl moiety of TMCM is required for periplasmic export. A bioinformatic search identified a gene in a cell wall biosynthesis locus encoding a putative acetyltransferase (M. tuberculosis Rv0228/C. glutamicum NCgl2759) that was highly conserved in all sequenced Corynebacterineae. Deletion of C. glutamicum NCgl2759 resulted in the accumulation of TMCM, with a concomitant reduction in surface transport of this glycolipid and syntheses of cell wall trehalose dicorynomycolates. Strikingly, loss of NCgl2759 was associated with a defect in the synthesis of a minor, and previously uncharacterized, glycolipid species. This lipid was identified as trehalose monoacetylcorynomycolate (AcTMCM) by mass spectrometry and chemical synthesis of the authentic standard. The in vitro synthesis of AcTMCM was dependent on acetyl-CoA, whereas in vivo [(14)C]-acetate pulse-chase labeling showed that this lipid was rapidly synthesized and turned over in wild-type and genetically complemented bacterial strains. Significantly, the biochemical and TMCM/TDCM transport phenotype observed in the ΔNCgl2759 mutant was phenocopied by inhibition of the activities of the two C. glutamicum MmpL3 homologues. Collectively, these data suggest that NCgl2759 is a novel TMCM mycolyl acetyltransferase (TmaT) that regulates transport of TMCM and is a potential drug target in pathogenic species.


Epidemiology of Pediatric Convulsive Status Epilepticus With Fever in the Emergency Department: A Cohort Study of 381 Consecutive Cases.
Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children's hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P < .001). These results provide for the first time the pretest probability of final diagnoses in children with convulsive status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever.


A case of video-assisted retroperitoneal debridement in a patient with HELLP syndrome.
Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome describes a cohort of disease processes that may have devastating consequences for the peripartum patient. Although the hemopoetic and hepatic systems are classically involved, we illustrate a case of walled-off pancreatic necrosis occurring in a woman with HELLP syndrome. Initially managed with resuscitation, steroids, and plasmapheresis, the patient developed necrotizing pancreatitis that overtime became walled-off. Despite attempts at percutaneous drainage, the patient ultimately had a video-assisted retroperitoneal debridement. As there are no descriptions in the literature of walled-off pancreatic necrosis stemming from HELLP syndrome, this case provides a new avenue from which to study the pathophysiology and provides a management strategy for this problem.


Lutein supplements are not bioavailable in the Mongolian gerbil while consuming a diet with or without cranberries.
Lutein is a carotenoid that may be involved in the prevention of macular degeneration and is available as supplements. Cranberries are a potential "functional food" due to anti-adhesion and antioxidant properties. This study was designed to determine the bioavailability of lutein supplements in Mongolian gerbils, as prior studies have focused on beta-carotene, and to investigate any interactions between a lutein supplement and a diet containing cranberries. Gerbils (n = 28) were divided into treatment groups: lutein + cranberry; lutein + control; cottonseed oil + cranberry; and cottonseed oil + control. The lutein supplement (50 microg lutein in oil) was delivered orally for 14 days, and then blood, livers, and eyes were collected. Samples were analyzed by high-performance liquid chromatography (HPLC) and total antioxidant status was determined. Serum and liver were analyzed for lutein, retinol, and alpha-tocopherol. Serum lutein concentrations were extremely low in all four groups. Serum total antioxidants did not differ (p > 0.2) among diet groups. Serum retinol concentrations were significantly lower in the cranberry groups (p = 0.0024). In conclusion, gerbils are able to thrive on a high cranberry diet. However, this study showed that lutein, as a daily supplement in oil, is not bioavailable in Mongolian gerbils.


Nutrition and Health: Survey on Food Awareness in Teenagers.
According to the WHO, 86% of deaths and 75% of healthcare costs in Europe are attributable to diseases, which share risk factors, including obesity, overweight and high blood pressure. Common point to these factors is their modifiability, adopting correct life habits. It is, therefore, appropriate to investigate teenagers' eating habits, in order to familiarize them with the risks associated with incorrect diet, develop their critical thinking regarding sources of information and strengthen their life skills. The chosen approach to achieve these goals is to develop food education programs focused on Peer education. To collect the necessary data, Focus groups have been run in November 2017, in "Da Vigo Nicoloso High School" in Rapallo (Genoa). A random selection of participants, within homogeneous groups (ages 13-14 and 17-18), has been applied. Eating choices among teenagers represent a strong element of identity. Sharing experiences produces consequences on individual and collective tastes. Awareness in young people regarding correct food choices grows with increasing age; so does sensitivity to being conditioned by interpersonal relationships and messages conveyed through the mass media. It is advisable to develop education programs, specifically aimed at individuals in the age range 13-18. This will both develop their skills in the field of food awareness, and it will enable them to become the source of positive influences within their families and among their acquaintances. Nurse plays a fundamental role as an active subject in this field of primary prevention, transmitting knowledge to the recipients, coordinating with other professional figures (psychologists/professional educators).


[Intravesical cidofovir--instillation therapy for polyomavirus-associated hemorrhagic cystitis after bone marrow transplantation].
Viral infections of the urogenital tract are a potential problem in patients taking immunosuppressive medication. We report a 14 year old male patient with hemorrhagic cystitis who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia. Attempts at coagulation as well as instillation treatment and continuous bladder irrigation were not sufficient to stop bleeding. Sequential to these procedures, local instillation with cidofovir into the bladder was started to treat a suspected infection with polyomavirus and the gross hematuria stopped within a few days.


Prevalence of Human Immunodeficiency Virus and Sexually Transmitted Infections Among Cisgender and Transgender Women Sex Workers in Greater Kuala Lumpur, Malaysia: Results From a Respondent-Driven Sampling Study.
Sex workers face a disproportionate burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STI) worldwide. For cisgender women sex workers (CWSW), global HIV prevalence is over 10%, whereas transgender women sex workers (TWSW) face an HIV burden of 19% to 27%. We used respondent-driven sampling to recruit 492 sex workers, including CWSW (n = 299) and TWSW (n = 193) in Greater Kuala Lumpur, Malaysia. Participants completed an in-depth survey and were screened for HIV, syphilis, Chlamydia trachomatis, and Neisseria gonorrhoeae. Sample characteristics stratified by gender identity and interview site are presented. Bivariate analyses comparing CWSW and TWSW were conducted using independent samples t tests for continuous variables and χ tests for categorical variables. Pooled HIV prevalence was high (11.7%; 95% confidence interval [CI], 8.8-14.5), and was similar for CWSW (11.1%) and TWSW (12.4%). Rates of syphilis 25.5% (95% CI, 21.6-29.5), C. trachomatis (14.8%; 95% CI, 11.6-18.0) and N. gonorrhoeae (5.8%; 95% CI, 3.7-7.9) were also concerning. Both groups reported lifetime HIV testing (62.4%), but CWSW were less likely to have ever been HIV tested (54.5%) than TWSW (74.6%). Median time since last HIV test was 24 months. Previous screening for STI was low. Inconsistent condom use and drug use during sex work were not uncommon. High HIV and STI prevalence, coupled with infrequent HIV and STI screening, inconsistent condom use, and occupational drug use, underscore the need for expanded HIV and STI prevention, screening, and treatment efforts among CWSW and TWSW in Malaysia.


Thrombotic complications of umbilical artery catheters: A clinical and radiographic study.
Catheterization of the aorta via the umbilical artery provides a convenient route for monitoring arterial blood pressure, for obtaining blood specimens for measurement of blood gas tensions and chemistries, and for the infusion of fluids and pharmacologic preparations in sick newborn infants. Use of this technique may be accompanied by a number of complications of which thrombotic phenomena are the most common. Twenty-three of 98 (24%) newborn infants undergoing umbilical artery catheterization were found to have thrombotic complication determined by aortography. No correlation was present between the duration of time that the umbilical artery catheters were in place and the occurrence of thrombotic complications. From paired aortographic or aortographic and autopsy studies in 24 patients, it was concluded that if a thrombotic complication did not occur early, none was likely to occur subsequently. One patient was considered to have died as a direct result of a thrombotic complication. Aortography is a safe, simple, and reliable technique for the early detection of thrombotic complications of umbilical artery catheters. Umbilical artery catheterization is not without risk and careful selection of patients for this procedure is indicated.


University general practices in Australasia.
The nature of the general practice departments in the medical schools of Australian and New Zealand universities, and the role of general practice conducted by these departments, are discussed. A number of arguments for, and against, the establishment of university general practice units, and comments on these, are listed. A greater involvement in the general practice and primary care units by the university departments over the next decade is predicted.


Born too small: who survives in the public hospitals in Lilongwe, Malawi?
Malawi has the highest estimated preterm birth rate in the world. The survival rate of these babies is not known. The main objective of this study was to demonstrate the short-term survival of infants with birth weight below 2500 g nursed in Bwaila Hospital, a district hospital, and the tertiary level Kamuzu Central Hospital (KCH) in Lilongwe. The specific objectives were to calculate birth weight specific survival rates, compare the two hospitals regarding the chances of survival and review the use of antenatal corticosteroids. 1496 babies were included prospectively in the study between June and November 2012. Survival was defined as discharge from the nursery or postnatal ward. Survival was 7% for extremely low birth weight infants, 52% for very low birth weight and 90% for low birth weight (1500-2499 g). There was a marked increase in survival from 1100 g. Survival was significantly higher in KCH only for babies weighing below 1200 g. The majority of deaths occurred within the first 3 days of life. Only 98 of the babies had a mother who had received antenatal corticosteroids. With the current resources, we suggest focusing efforts on preventing early neonatal deaths in low birth weight infants above 1100 g in the hospitals in Lilongwe. The coverage of antenatal steroids for mothers at risk of preterm delivery can be improved. Further studies are needed on the quality of the obstetric and neonatal care at the hospitals and how to reduce the high rate of preterm birth in Malawi.


Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways.
The U.S. National Research Council (NRC) introduced new approaches to report toxicity studies. The NRC vision is to explore the toxicity pathways leading to the adverse effects in intact organisms by the exposure of the chemicals. This study examines the toxicity profiling of the naphthalene-2-yl 2-chloro-5-dinitrobenzoate (SF5) by adopting the vision of NRC that moves from traditional animal studies to the cellular pathways. Acute, subacute, and developmental toxicity studies were assayed according to the Organization for Economic Cooperation and Development (OECD) guidelines. The stress response pathway, toxicity pathway, and adverse effects outcome parameters were analyzed by using their standard protocols. The results showed that the acute toxicity study increases the liver enzyme levels. In a subacute toxicity study, alkaline phosphatase (ALP) levels were raised in both male and female animals. SF5 significantly increases the normal sperm count in the male animals corresponding to a decrease in the abnormality count. Developmental toxicity showed the normal skeletal and morphological parameters, except little hydrocephalus was observed in developmental toxicity. Doses of 20 mg/kg in males and 4 mg/kg in females showed decreased glutathione (GSH) levels in the kidney and liver. MDA levels were also increased in the kidney and liver. However, histopathological studies did not show any cellular change in these organs. No statistical difference was observed in histamine levels, testosterone, nuclear factor erythroid two-related factor-2 (Nrf2), and nuclear factor-kappa B (NF-κB), which showed no initiation of the stress response, toxicity, and adverse effect pathways. Immunomodulation was observed at low doses in subacute toxicity studies. It was concluded that SF5 did not produce abrupt and high-toxicity levels in organs and biochemical parameters. So, it is safe for further studies.


Systematic Bandgap Engineering of Graphene Quantum Dots and Applications for Photocatalytic Water Splitting and CO2 Reduction.
Graphene quantum dots (GQDs), which is the latest addition to the nanocarbon material family, promise a wide spectrum of applications. Herein, we demonstrate two different functionalization strategies to systematically tailor the bandgap structures of GQDs whereby making them snugly suitable for particular applications. Furthermore, the functionalized GQDs with a narrow bandgap and intramolecular Z-scheme structure are employed as the efficient photocatalysts for water splitting and carbon dioxide reduction under visible light. The underlying mechanisms of our observations are studied and discussed.


Genetic and clinical considerations in six cases with neurofibromatosis type 1.
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, caused by mutations in the NF1 gene. The NF1 gene encoding neurofibromin protein, which is strongly expressed in the nervous system and with the role as a negative regular of the ras proteins signal. All six cases with neurofibromatosis type 1 were clinical and laboratory investigated. The frequently symptoms are "café au lait" spots and neurofibromas. In two cases, the disease is associated with essential hypertension and, in other two cases with kyphoscoliosis. The novo mutations in NF1 gene cause the disease in three cases, and in other three cases, the mutation is inherited (two cases on father side and one case on mother side).


3D MRI in multiple sclerosis: a study of three sequences at 3 T.
The objective of this study was to assess the feasibility of using 3D acquisition at 3 T for imaging patients with multiple sclerosis (MS). Feasibility was assessed by three criteria based on acquisition time, specific absorption rate (SAR) and image quality. 47 patients with clinically definite MS underwent imaging in a Siemens 3T Trio MR scanner. Patient safety data were obtained following the scan sessions. The study had local ethics approval. The following three-dimensional (3D) sequences, all acquired coronally, were used: T2 fluid attenuated inversion recovery (FLAIR) (repetition time (TR) 6000 ms, echo time (TE) 353 ms, inversion time (TI) 2200 ms), 0.5x0.5x1 mm voxels, acquisition time 10 min 38 s; T2 turbo spin echo (TSE) (TR 3000 ms, TE 354 ms), 1x1x1 mm voxels, acquisition time 8 min 29 s; T1 inversion recovery (IR) (TR 2040 ms, TE 5.56 ms, TI 1100 ms), matrix 512x448 (0.5x0.5 mm pixels), 0.5x0.5x1 mm voxels, acquisition time 7 min 38 s. Total acquisition time was 26 min 45 s. Example images are presented. 3D scanning at 3 T provides highly detailed, high quality images with acquisition times tolerated by MS patients, even by those with severe disability. The volumetric data are suitable for a wide variety of post-processing techniques; the authors suggest that 3D studies at 3 T should be considered as the possible brain imaging protocol for either cross-sectional or longitudinal studies in MS and that the 3D T2 FLAIR sequence should be considered for the purposes of radiological diagnosis.


Synthesis of cystine peptides 21-25/70-73 and 35-39/56-59 of the beta-subunit of human choriogonadotropin.
Syntheses of two asymmetrical cystine peptides with the amino acid residues 21-25/70-73 and 35-39/56-59, based on the linear amino acid sequence and the disulfide bond assignment in the beta-subunit of human choriogonadotropin (hCG-beta), are described. S-trityl and S-acetamidomethyl peptide fragments of each cystine peptide were prepared in solution phase and were subjected to oxidation with I2/MeOH to form the disulfide bridge. The cystine peptides were characterized by their amino acid analyses and fast atom bombardment mass spectrometry. Immunological characterization by several homologous radioimmunoassay systems showed that peptide 21-25/70-73 had significant hCG, hCG-beta, and hLH activities while peptide 35-39/56-59 failed to reveal any immunoreactivity.


Pictorial essay: thoracic cardiovascular complications of acquired immunodeficiency syndrome.
Patients with acquired immunodeficiency syndrome frequently develop complications of cardiac, pericardial, and thoracic vascular origin. The purpose of this pictorial essay is to review the most common etiologic and diagnostic imaging findings of these diseases. Patients with acquired immunodeficiency syndrome often demonstrate enlargement of the cardiac silhouette on the chest radiograph. While the cause of this finding may be clinically evident, the authors share cases in which chest computed tomography, echocardiography, and nuclear medicine studies better reveal the nature of underlying cardiac and pericardial abnormalities. Thoracic vascular complications, including pulmonary hypertension, pulmonary thromboembolism, and the sequelae of indwelling venous catheters, are also addressed.


Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.
Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.


A national profile of the health care experiences and family impact of autism spectrum disorder among children in the United States, 2005-2006.
We sought to examine the health care experiences of children with autism spectrum disorder and the impact of autism spectrum disorder on the family and to assess whether having a medical home is associated with less family impact. We used the 2005-2006 National Survey of Children With Special Health Care Needs to compare 2088 children with special health care needs, aged 3 to 17 years, reported by their parents to have autism spectrum disorder, with children with special health care needs with "other emotional, developmental, or behavioral problems" (excluding autism spectrum disorder; n=9534) and 26751 other children with special health care needs. We used weighted logistic regression to examine unmet needs for specific health care and support services, delayed care, no usual care source or personal physician, difficulty receiving referrals, and financial, employment, or time problems because of child's care. Nationally, an estimated 535000 children have special health care needs and autism spectrum disorder, a prevalence of 86 per 10000 children aged 3 to 17 years. Among children with special health care needs, 5.6% have autism spectrum disorder. Compared with other children with special health care needs without emotional, developmental, or behavioral problems, children with special health care needs with autism spectrum disorder were more likely to have unmet needs for specific health care services, family support services, delayed or foregone care, difficulty receiving referrals, and care that is not family centered. Children with special health care needs with autism spectrum disorder were more likely to live in families that report financial problems, need additional income for the child's medical care, reduce or stop work because of the child's condition, spend >or=10 hours per week providing or coordinating care, and paid more than $1000 in the previous year for the child's care. The financial impacts of autism spectrum disorder were significantly more burdensome when children with special health care needs did not have a medical home. Children with special health care needs with autism spectrum disorder are significantly more likely to have problems regarding access to care and unmet needs, and their families have greater financial, employment, and time burdens compared with other children with special health care needs. Receipt of primary care in a medical home may reduce these burdens.


Tetraodon palustris, a new freshwater pufferfish (Tetraodontiformes: Tetraodontidae) from the Mekong Basin of Thailand.
Tetraodon palustris, new species, is described from the Mekong basin of Thailand. Tetraodon palustris differs from T cochinchinensis and T. fangi in having no ocellus on the flank and spinules dorsally from the interorbital region to the end of the dorsal-fin base. T. etraodon cochinchinensis is distinguished from T. fangi by having a longer snout (43.5-49.2% HL in T. cochinchinensis vs. 37.9-41.1% HL in T. fangi) and is covered with spinules dorsally from the front of the nasal organs to the end of the dorsal-fin base (vs. from the front of the eyes to the end of the dorsal-fin base in T. fangi).


The fine structure of the placenta and chorionic vesicles of the bush baby, Galago crassicaudata.
The fine structure of the placental villi and the chorionic vesicles of the bush baby, Galago crassicaudata, were examined. The placenta was of the diffuse epitheliochorial type. The trophoblastic epithelium of the placental villi consisted of cells joined by tight junctions and desmosomes. The apical borders of these cells interdigitated with corresponding processes on the uterine epithelial cells. The fetal capillaries indented the trophoblastic cells later in gestation, and the trophoblast over the capillaries was correspondingly thinner with advancing gestation. The trophoblast of the villi was characterized by numerous lipid droplets and moderate amounts of granular endoplasmic reticulum (ER). The apical cytoplasm often had many mitochondria as well as small electron-dense vesicles and tubules. Uterine epithelial cells contained agranular ER and a well-developed Golgi apparatus. The apical cytoplasm contained numerous granules often with an electron-dense content. The uterine epithelial cells appeared to be secretory, contributing to the electron-dense material found between the fetal and maternal cells. Fetal capillaries were of the continuous type, whereas occasional fenestrae were observed in maternal capillaries. Recesses in the trophoblastic epithelium occurred at the tips, sides, and bases of the villi. These areas had taller trophoblastic cells that appeared to be more active in phagocytosing uterine content. The chorionic vesicles are invaginations of the chorion opposite the mouths of uterine glands. A layer of columnar trophoblastic cells covered the villi of the vesicles. These cells had abundant vacuoles and coated pits and vesicles. The mesodermal component of the chorionic vesicles included a capillary network and a layer of smooth muscle cells in the wall of the vesicle. It was concluded that the trophoblast of the placental villi is engaged in both hemotrophic and histotrophic nourishment of the embryo. The specialized chorionic vesicles are particularly important in providing histotrophic nutrients to the embryo, especially the secretions of the uterine glands. The similarity of the chorionic vesicles to the areolae of other species suggests they may be the pathway by which iron is transported from mother to fetus, perhaps by receptor-mediated endocytosis of macromolecules derived from uterine gland secretions.


Effects of isoprenaline on tonic tension and Na-Ca exchange in frog atrial fibres.
The action of isoprenaline, a purely beta-agonist, was investigated on frog atrial fibres under voltage clamp conditions; tonic tension was induced by long depolarizing pulses and the outward delayed current simultaneously developed. The cumulative dose-response curves showed that isoprenaline increased the peak of tonic tension in the concentration range 10(-8) to 3. 10(-6) mol.l-1, with a maximum effect for 10(-6) mol.l-1. The positive inotropic action of isoprenaline was associated with an increase in the rates of tension rise and of relaxation. Isoprenaline also increased the amplitude of the outward delayed current in a dose-dependent manner. The effects of isoprenaline (10(-6) mol.l-1) on tonic tension and outward delayed current were not observed in the presence of propranolol (10(-7) mol.l-1). Experiments carried out in low-sodium solution demonstrated that the action of isoprenaline on tonic tension can be explained by activation of Na-Ca exchange; the enhanced relaxation might result from the same process. These results suggested that the positive inotropic action of isoprenaline is mediated not only by the well-known increase in the slow inward current but also by activation of the Na-Ca exchange mechanism.


[Effects of continuous adenosine infusion on pulmonary hypertension in chronically hypoxic rats].
To observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats. Twenty-four SD rats were randomized into normoxic group, hypoxic group and adenosine-treated hypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 microg kg(-1) min(-1) via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days of hypoxia, pulmonary artery pressure and tail-cuff blood pressure were measured, with the plasma rennin activity (RA), angiotensin II (AngII), endothelin (ET)-1, and nitric oxide (NO) determined. Inducible nitric oxide synthase (iNOS) expression in the pulmonary artery of the rats was detected using immunohistochemical method. The mean pulmonary artery pressure (mPAP) was significantly higher in the hypoxic group than that in the normoxic group (P<0.01) and in the adenosine-treated group (P<0.01). Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group (P<0.01) and the adenosine-treated group (P<0.01). iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group (P<0.01), and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups (P<0.01). Plasma RA and AngII in the hypoxic group were significantly higher than those in the normoxic group (P<0.01) and the adenosine-treated (P<0.01). Adenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.


Effects of ginkgolide A on okadaic acid-induced tau hyperphosphorylation and the PI3K-Akt signaling pathway in N2a cells.
Alzheimer's disease is the most common form of dementia leading to the irreversible loss of neurons, and Tau hyperphosphorylation has an important role in the pathology of Alzheimer's disease. Ginkgolide A is one of the active components of Ginkgo biloba extracts which has been proven to have neuroprotective effects, but the effect of ginkgolide A on Tau hyperphosphorylation has not yet been reported. In this study, the effects of ginkgolide A on cell viability, Tau hyperphosphorylation, and the PI3K-Akt signaling pathway in N2a cell lines were explored, and methods such as the MTT assay, ELISA, and Western blots techniques were used. The results showed that ginkgolide A could increase cell viability and suppress the phosphorylation level of Tau in cell lysates, meanwhile, GSK3β was inhibited with phosphorylation at Ser9. Moreover, treatment of the cells with ginkgolide A promoted phosphorylation of PI3K and Akt, suggesting that the activation of the PI3K-Akt signaling pathway may be the mechanism for ginkgolide A to prevent the intracellular accumulation of p-Tau induced by okadaic acid and to protect the cells from Tau hyperphosphorylation-related toxicity.


Recognition gradients for random shapes following distinctive or equivalent verbal association training.
The effect of distinctive and equivalent verbal label training on a subsequent test of recognition memory for random shapes were assessed. Shape continua, systematically relating the labeled shapes, were used in the memory test so that gradients of recognition memory were obtained. Distinctive-nonrepresentative-label training produced symmetrical recognition gradients with a single mode at the correct target shape. Equivalent-label training produced symmetrical gradients that were as steep as the distinctive-label gradients, but the mode of the equivalent-label gradients was shifted to a distractor shape that varied from the target in the direction of the equivalent-label shape. The results offered support to a Gestalt/configurational account of the effects of verbal labels on memory for form, but the data were also consistent with an extension of Ellis' conceptual coding hypothesis. It was concluded that, rather than being a competing alternative account, the conceptual coding hypothesis may be viewed as an updated, more analytic statement of the older Gestalt view.


Phototherapy and photochemotherapy in dermatologic diseases.
Phototherapy and photochemotherapy have been shown to be effective treatments in a number of cutaneous disorders, but they are not without risk. PUVA has revolutionized the treatment of psoriasis and stimulated major improvements in the administration of UVB therapy. Successful treatment depends on careful patient selection and evaluation. Accurate dosimetry and close supervision are necessary to avoid complications. Regular and careful follow-up, both during and after therapy, can help to identify and treat long-term side effects such as non-melanoma skin cancers. In order to achieve the necessary balance between benefits and risks with these valuable forms of therapy, patients should be referred to dermatologists with special training.


Tuning the photoisomerization of a N^C-chelate organoboron compound with a metal-acetylide unit.
To examine the impact of metal moieties that have different triplet energies on the photoisomerization of B(ppy)Mes2 compounds (ppy = 2-phenyl pyridine, Mes = mesityl), three metal-functionalized B(ppy)Mes2 compounds, Re-B, Au-B, and Pt-B, have been synthesized and fully characterized. The metal moieties in these three compounds are Re(CO)3(tert-Bu2 bpy)(C≡C), Au(PPh3)(C≡C), and trans-Pt(PPh3)2(C≡C)2, respectively, which are connected to the ppy chelate through the alkyne linker. Our investigation has established that the Re(I) unit completely quenches the photoisomerization of the boron unit because of a low-lying intraligand charge transfer/MLCT triplet state. The Au(I) unit, albeit with a triplet energy that is much higher than that of B(ppy)Mes2 , upon conjugation with the ppy chelate unit, substantially increases the contribution of the π→π* transition, localized on the conjugated chelate backbone in the lowest triplet state, thereby leading to a decrease in the photoisomerization quantum efficiency (QE) of the boron chromophore when excited at 365 nm. At higher excitation energies, the photoisomerization QE of Au-B is comparable to that of the silyl-alkyne-functionalized B(ppy)Mes2 (TIPS-B), which was attributable to a triplet-state-sensitization effect by the Au(I) unit. The Pt(II) unit links two B(ppy)Mes2 together in Pt-B, thereby extending the π-conjugation through both chelate backbones and leading to a very low QE of the photoisomerization. In addition, only one boron unit in Pt-B undergoes photoisomerization. The isomerization of the second boron unit is quenched by an intramolecular energy transfer of the excitation energy to the low-energy absorption band of the isomerized boron unit. TD-DFT computations and spectroscopic studies of the three metal-containing boron compounds confirm that the photoisomerization of the B(ppy)Mes2 chromophore proceeds through a triplet photoactive state and that metal units with suitable triplet energies can be used to tune this system.


Personal digital video: a method to monitor drug regimen adherence during human clinical investigations.
1. Maintaining patient adherence to a drug regimen has proven to be difficult. Missed doses can impact drug efficacy and disease control, leading to increased health-care costs. 2. During clinical drug trials, poor adherence could lead to false conclusions regarding drug efficacy. Therefore, the purpose of the present study was to determine the feasibility of using personal digital video cameras to monitor adherence to a medication regimen during a clinical investigation. 3. Older men and women (60-78 years) participated in a double-blind, placebo-controlled trial to determine the effect of ibuprofen or paracetamol on skeletal muscle adaptations to chronic resistance exercise training. Patients took three daily doses of either a placebo or the maximal daily over-the-counter dose of ibuprofen (1.2 g/day) or paracetamol (4.0 g/day) for 12 weeks. Prior to beginning the study, subjects were trained to use a personal digital video camera to record their drug consumption. 4. Subjects correctly recorded 4,956 of 5,375 doses, resulting in an average camera compliance rate of 92% (71-100%). 5. We describe a method of monitoring adherence to a prescribed drug regimen during a clinical investigation. Camera compliance rates, which directly confirm drug consumption, were higher than what is typically obtained with other methods of monitoring adherence. This camera compliance method provides the investigator with a simple and convenient means to generate direct evidence of drug consumption.


From waste carbonated beverages to high performance electrochromic devices: a green and low-cost synthetic method for self-doped metal oxides.
Metal oxides with reversible optical modulation capability are in the spotlight for smart windows and other emerging optoelectronic devices. Improving the electrochromic performance at a low cost is the only way to popularize their applications. Herein, we demonstrate a facile and versatile strategy to synthesize high-performance electrochromic metal oxides, in which waste carbonated beverages are used as the raw materials for the first time. It can not only reduce the production cost of electrochromic materials, but also alleviate the environmental pollution caused by such liquid waste. With an ingenious carbonization pre-step, both nanoscale pores and oxygen vacancies are created in an annealed tungsten oxide thin film. Multiscale structure optimization endows the self-doped WO3-x films with excellent electrochromic properties such as large transmittance modulation (81.2%), high coloration efficiency (98.7 cm2 C-1) and good cycling stability. DFT calculations show that oxygen vacancies reduce the Li+ ion insertion energy barrier, which is conducive to the interfacial reaction in coloring and bleaching processes. Moreover, this approach is universal to other oxides such as vanadium pentoxide, molybdenum oxide and nickel oxide. The waste-to-value concept paves the way for cost-effective electrochromic materials and sheds light on the multiscale optimization of superior metal oxides.


Secondary radical attack on DNA nucleotides: reaction by addition to DNA bases and abstraction from sugars.
In this work radicals generated by dissociative electron attachment to iodoacetamide (H2NCOCH2.) and 6-chloromethyluracil (U5CH2.) are suggested to react with DNA nucleotides in frozen aqueous solutions via either hydrogen abstraction or addition to the double bonds of the bases. Methyl hydrogens of TMP are the preferential sites of the attack by H2NCOCH2. radical. For dCMP the C1' site on the sugar group is found to be the preferred site of hydrogen abstraction by H2NCOCH2. while for dGMP and to a lesser extent dAMP attack at the C8 position of the purine ring is found to be competitive with sugar attack. In general allylic U6CH2. and U5CH2. radicals are found to be poor hydrogen abstractors and the only reaction pathway found is the addition to double bonds at C6 in thymine and C8 in adenine and guanine. Whereas, the cytosine 5,6 double bond appears to be unreactive towards addition at low temperatures. Some evidence is found for sugar radical addition to the adenine C8 position.


Radioiodine treatment outcomes in thyroid glands previously irradiated for Graves' hyperthyroidism.
Persistent or recurrent Graves' hyperthyroidism after an initial treatment dose of radioactive iodine (RAI) is not uncommon and usually necessitates additional administrations. The radiation sensitivity of the previously irradiated thyroid gland is unknown but is of importance in selecting the retreatment dose. A retrospective analysis of patients receiving RAI for Graves' hyperthyroidism was undertaken. A first treatment dose was given to 1076 patients, and 168 of these patients subsequently required a second dose for persistent or recurrent hyperthyroidism (interval between RAI treatments, 8.5 +/- 17.1 mo). Paired comparisons for retreated patients showed similar RAI doses (291 +/- 95 MBq and 283 +/- 129 MBq; p = ns) and treatment intensities (3.26 +/- 1.87 MBq g(-1) and 3.48 +/- 1.88 MBq g(-1); p = ns) for first and second treatments. Hypothyroidism occurred significantly earlier and more frequently after the first RAI dose (p = 0.002), but there was no difference for persistent or recurrent hyperthyroid events (p = 0.14). Multivariate regression established that the RAI treatment number (first or second) was a significant independent determinant of hypothyroid (p = 0.008) and combined (p = 0.001) events, whereas RAI dose and dose intensity were not. We conclude that previous RAI treatment failure does not lessen the chance of successfully eradicating Graves' hyperthyroidism with additional RAI treatment. Furthermore, the previously irradiated thyroid gland may be less susceptible to early hypothyroidism than the RAI-naive thyroid gland.


[Quantitative assessment of vascular calcification--Potential for diagnosis of vascular aging].
Quantitative assessment of vascular calcification is important in understanding the mechanisms of vascular aging. To elucidate the progress of calcification with aging, we measured calcium contents in various blood vessels by atomic emission spectrometry and analysis of X-ray CT image. These quantitative assessments revealed that the progress of calcification was different by arterial region. A novel diagnosis considering the difference of calcification progress will provide useful information for understanding vascular ageing.


Speculations on the roles of RB1 in tissue-specific differentiation, tumor initiation, and tumor progression.
Studies of retinoblastoma clearly identify mutation of the RB1 gene on chromosome 13 as the primary cause of this cancer. However, all retinoblastoma tumors have an abnormal karyotype (1, 2) indicating the presence of additional mutations and suggesting that mutation of both RB1 alleles is insufficient for development of retinoblastoma. In addition, analysis of RB1 expression and of RB1 mutations in different tumors leads to the following dilemma: while the RB1 gene product, p110RB1, is expressed in most dividing cells, germline mutations inactivating the function of p110RB1 predispose primarily to retinoblastoma and to a lesser extent to osteosarcoma, but do not predispose to cancer in general. However, many tumors contain somatic mutations that disrupt RB1 function. Thus, we are faced with the unusual situation in which germline mutations in the RB1 gene predispose to a very limited set of cancers, but somatic mutations in RB1 appear to contribute to malignancy in many tissues. We propose that the role of the RB1 gene is to maintain the cells in a stable, quiescent state required for terminal differentiation and that the effect of RB1 mutations in different tissues depends on the pattern of differentiation in that tissue. In tissues where differentiation follows a linear process from undifferentiated precursors to fully differentiated cells, loss of RB1 function during early stages of differentiation may lead to uncontrolled growth and the development of cancer. On the other hand, in cell renewal systems where cell number is usually maintained by a process of programmed cell death (PCD) or apoptosis, loss of RB1 function may lead to cell death.