Facile catalytic combustion of rice husk and burning temperature dependence of the ashes.
In this work, it was discovered and demonstrated that the combustion of rice husk is a catalytic process by the thermoanalytical technique. The catalyst involves the oxides of such transition metals as Mn, Fe, and Cu, which are mainly formed in the initial stage of rice husk combustion and remain in the rice husk ash as an impurity. Mn(2+) ions of various concentrations were reloaded into the HCl-washed husk for cocombustion. As a result, the complete combustion temperature of the husk was decreased exponentially depending on the Mn(2+) concentration. By the facile Mn loading technique using a 0.5 M solution, the combustion temperature can be decreased by approximately 100 degrees C, and the resulting ashes themselves can be a good catalyst in the complete combustion of many other organic compounds. The physicochemical properties and amorphous structure of the ashes from both the raw and HCl-washed husks were found to be strongly dependent on the burning temperature. A decreased complete rice husk combustion temperature can be beneficial in preparing porous amorphous silica with high surface area, high densification, and small Si-O-Si band angles.


Nongonococcal tysonitis.
Tyson's glands are sebaceous glands located on each side of the frenulum that communicate with the preputial sac, and their inflammation can be an infrequent complication of urethritis. We describe a rare case that presented with urethral discharge and parafrenular swelling with mucopurulent discharge a week after an unprotected sexual encounter. The patient was empirically treated with 500 mg of ceftriaxone intramuscularly and 100 mg of doxycycline every 12 h for 14 days with symptomatic resolution. The urethral swab culture and the urine polymerase chain reaction (PCR) were negative for Neisseria gonorrhoeae and Chlamydia trachomatis, therefore, and given the response to treatment, nongonococcal tysonitis was diagnosed.


Self-Assembled Minimalist Multifunctional Theranostic Nanoplatform for Magnetic Resonance Imaging-Guided Tumor Photodynamic Therapy.
Minimalist multifunctional platforms for delivering diagnostic and therapeutic agents effectively and safely into tumor sites are highly desired in nanomedicine. Herein, we describe the fabrication of a supramolecular nanoplatform via the amphiphilic amino acid (9-fluorenylmethyloxycarbonyl-l-leucine, Fmoc-l-L)-modulated self-assembly of a magnetic resonance imaging (MRI) contrast agent (ionic manganese, Mn2+) and photosensitive drug (chlorin e6, Ce6). Coordination drives the coassembly of Fmoc-l-L and Mn2+ to generate a nanoscale supramolecular network to adaptively encapsulate Ce6. The obtained biometal-organic nanoparticles exhibit a high drug loading capability, inherent good biocompatibility, robust stability, and smart disassembly in response to glutathione (GSH). The cooperative assembly of the multiple components is synchronously dynamic in nature and enables enhanced photodynamic therapy (PDT) to damage tumor cells and tissue by efficiently delivering the photosensitizer and improving the reductive tumor microenvironment via the competitive coordination of GSH with Mn2+. The antitumor effect can also be monitored and evaluated in vivo by MRI through the long-term intracellular biochelation of Mn2+. Therefore, this work presents a one-pot and robust method for the self-assembly of a multifunctional theranostic nanoplatform capable of MRI-guided PDT starting from minimalist biological building blocks.


Bone demineralization mechanisms at level of free radicals and nanoscale subsystems of bone tissue.
Influence of simulated microgravity on characteristics of rat bones was investigated by electron paramagnetic resonance (EPR). For simulation of microgravity condition the hanging of animal by tail was used. The main measurements were performed for diaphysis of femoral bones. The quantity of native radicals Rn, localized in an organic matrix, and carbonate radicals CO2-, localized on a surface of bioapatite nanocrystals, were determined. The decrease of CO2- radical quantity in bones of experimental animals have shown, that due to simulation of microgravity the decrease of "collagen-nanocrystals" interaction takes place. It is shown that the EPR method open possibilities to receive the unique information about bone demineralization processes at level of free radicals and nanoscale subsystems of bone tissue.


von Recklinghausen's disease associated with somatostatin-rich duodenal carcinoid (somatostatinoma), medullary thyroid carcinoma and diffuse adrenal medullary hyperplasia.
This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type IIa or IIb.


Multivariate-based classification of predicting cooking quality ideotypes in rice (Oryza sativa L.) indica germplasm.
For predicting texture suited for South and South East Asia, most of the breeding programs tend to focus on developing rice varieties with intermediate to high amylose content in indica subspecies. However, varieties within the high amylose content class may still be distinguishable by consumers, who are able to distinguish texture that cannot be differentiated by proxy cooking quality indicators. This study explored a suite of assays to capture viscosity, rheometric, and mechanical texture parameters for characterising cooked rice texture in a set of 211 rice accessions from a diversity panel and employed multivariate approaches to classify rice varieties into distinct cooking quality classes. Results suggest that when the amylose content range is narrowed to the intermediate to high classes, parameters determined by rheometry and RVA become diagnostic. Modeled parameters distinguishing cooking quality ideotypes within the same range of amylose classes differ in textural parameters scored by a descriptive sensory panel. Our results reinforced the notion that it is important to define cooking quality classes in indica subtypes based on multidimensional parameters, by going beyond amylose predictions. These predictive cooking models will be handy in capturing cooking and eating quality properties that address consumer preferences in future breeding programs. Policy implications of such findings may lead to changes in criteria used in assessing grain quality in the intermediate to high amylose classes.


Anemia in infancy and childhood.
The definition, clinical manifestations, and causes of anemia in childhood are age-related and reflect the dynamic processes of growth and development during this period. Although the possible causes of anemia in children are extensive, the etiology is usually unifactorial. Thus, systematic evaluation of the anemia will usually result in the diagnosis of a specific anemia, which can then be effectively treated in a gratifying number of children.


The proposed role of suppression in simultaneous interpretation.
In this paper we suggest that the cognitive mechanism of suppression attenuates interference in many language comprehension phenomena, and is particularly crucial when comprehension must share processing capacity with other cognitive tasks, as is manifestly the case in simultaneous interpreting. During lexical access, the mechanism of suppression attenuates the interference caused by the activation of other lexical information, such as the inappropriate meanings of homonyms. During anaphoric reference, the mechanism of suppression attenuates the interference caused by the activation of other potential referents. In this way, the referent to which the anaphor does refer becomes the most activated concept. During syntactic parsing, the mechanism of suppression attenuates the interference caused by a previous syntactic form. During metaphor comprehension, the mechanism of suppression attenuates the interference caused by a literal interpretation. During inferencing, the mechanism of suppression attenuates the interference caused by an initial but inappropriate inference. We propose therefore that suppression - a general, cognitive mechanism that attenuates interference - plays a crucial role in language comprehension and simultaneous interpretation.


Child, adolescent and youth suicide and undetermined deaths in England and Wales compared with Australia, Canada, France, Germany, Italy, Japan and the USA for the 1974-1999 period.
Successive British Governments have aimed to reduce suicide, especially amongst younger people. Using WHO standardised data for the age bands "child" (5-14 years) and "adolescent and youth" (15-24 years) suicide rates for England and Wales were compared with the other major Western countries with end-points being average of 1974-1976 and average 1997-1999, by gender. "Undetermined deaths" were also analysed to consider any "hidden suicides". Over the period there was little change in child suicide for both genders in any country. Female "adolescent and youth" suicide rates fell in most countries, in contrast to male "adolescent and youth" rates, which rose substantially in six countries, including England & Wales. With the exception of Spain, there was little statistical significant difference between female Anglo-Welsh rates and the other countries. Apart from Spain and Australia, Anglo-Welsh youth rates were significantly worse than Canada, France, Germany and Japan. "Undetermined" deaths showed marked variation across many countries, but Anglo-Welsh rates were up substantially for both males and females [116% and 83%, respectively], whilst falling substantially in six countries. Child suicide continues to be a statistical rarity with little change in either suicide or "undetermined" deaths over the period. The dichotomy between male and female young people's suicide is a matter of concern, as the improvements in female rates are not matched in the male rates--the majority of which rose substantially. The "undetermined deaths" results continue to be problematic, especially regarding the substantial rises in England and Wales. Country-specific research is required to determine, why Anglo-Welsh adolescent and youth rates have deteriorated relative to other countries.


Polyfunctional radiosensitizers IV. The effect of contact time and temperature on sensitization of hypoxic Chinese hamster cells in vitro by bifunctional nitroxyl compounds.
Three biradical nitroxyl compounds have been shown to modify the slope and shoulder region of the hypoxic cell survival curve of V79 cells to different degrees. The amount of sensitization produced by these compounds is dependent on the cell-drug contact time at both 20 degree and 37 degree C whereas sensitization by the monoradical nitroxyl, NPPN, is independent of these factors. The results suggest that biradicals may modify cellular biochemistry in such a way as to change the repair capacity of the cells. This could be responsible for changes in the shape of survival curves when cell-drug contact times are increased.


Rate Control for Video-based Point Cloud Compression.
Rate control is a necessary tool for video-based point cloud compression (V-PCC). However, there is no solution specified on this topic yet. In this paper, we propose the first rate control algorithm for V-PCC. Generally, a rate control algorithm is divided into two processes: bit allocation and bitrate control. In V-PCC, the total bits are composed of three parts: the header information including the auxiliary information and occupancy map, the geometry video, and the attribute video. The bit allocation aims to assign the total bits to these three parts. Since the auxiliary information and occupancy map are encoded losslessly, the bit cost of the header information is fixed. Therefore, we only need to assign bits between the geometry and attribute videos. Our first key contribution is the proposed video-level bit allocation algorithm between the geometry and attribute videos to optimize the overall reconstructed point cloud quality. Then we assign geometry and attribute video bits to each group of pictures (GOP), each frame, and each basic unit (BU). Our second key contribution is that we assign zero bits to the BUs with only unoccupied pixels. The unoccupied pixels are useless for the reconstructed quality of the point cloud and therefore should be assigned zero bits. In the bitrate control process, the encoding parameters are determined, and the model parameters are updated for each frame and BU to achieve the target bits. Our third key contribution is that we propose a BU-level model updating scheme to handle the case where various patches may be placed in different positions in neighboring frames. We use the auxiliary information to find the corresponding BU in the previous frame and apply its model parameters to the current BU. The proposed algorithms are implemented in the V-PCC and High Efficiency Video Coding (HEVC) reference software. The experimental results show that the proposed rate control algorithm can achieve significant bitrate savings compared with the state-of-the-art method.


Effect of Laparoscopic Peritoneal Lavage and Drainage and Continuous Venovenous Diahemofiltration on Severe Acute Pancreatitis.
Severe acute pancreatitis (SAP), one severe and fatal disease, the therapy of which is pretty hard. This study aimed to study the effect of laparoscopic peritoneal lavage and drainage (LPLD) and continuous venovenous diahemofiltration (CVVDH) on SAP. Two hundred forty-five patients with SAP in total were randomly assigned into four groups according to the therapeutic plan: basic treatment; LPLD; CVVDH; or LPLD+CVVDH. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the ratios of multiple organ dysfunction syndrome (MODS), mortality, hospitalization time, hospitalization cost, ratios of complications, the abdominal distention relief time, abdominal pain relief time, plasma concentration of endotoxin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8 were evaluated. Ratios of MODS, mortality, hospitalization time, hospitalization cost, the abdominal distention relief time, abdominal pain relief time, concentration of endotoxin, TNF-α, IL-6, IL-8, and APACHE II scores were significantly decreased in the CVVDH, LPLD, and CVVDH+LPLD groups, while ratios of recovery were significantly increased in the CVVDH, LPLD, and CVVDH+LPLD groups, especially in the CVVDH+LPLD group. LPLD and CVVDH are effective in the treatment of SAP by eliminating endotoxin, TNF-α, IL-6, and IL-8. The combination of CVVDH and LPLD can further improve the treatment effect.


Focal liver disease: neural network-aided diagnosis based on clinical and laboratory data.
The purpose of this study was to evaluate the use of clinical and laboratory data in the diagnosis of benign or malignant focal liver disease. Diagnosis was made by artificial neural network (NN), a system of simple computing units connected in a specific structural network. Seven clinical and laboratory variables were retrospectively studied in 172 patients with a liver mass (93 benign, 79 malignant) detected with ultrasound. The diagnostic efficacy of NN was compared with a score based on the logistic regression model (Beaujon score). Although the sensitivity of the Beaujon score and the neural network was similar (4 malignant tumors inversely classified), neural network-aided diagnosis was characterized by higher specificity and accuracy (respectively 98.9% vs 82.5%, P < 0.001, and 97.1% vs 88.4%, P < 0.002). In patients with a hepatic mass, neural network is a valuable method for differentiating malignant and benign tumors.


Functional organization of respiratory neurones: a brief review of current questions and speculations.
This article presents a short overview of current knowledge about the medullary respiratory neurones and the generation of breathing rhythm. The background respiratory neurophysiology of the medulla and pons is briefly reviewed, with some current ideas about the organization of the pontine-medullary respiratory control system and its development. Questions and speculations about the organization and generation of respiratory rhythm are included, with a view to stimulating experiments to provide answers.


Screening of Intestinal Crypt Organoids: A Simple Readout for Complex Biology.
Oral and intestinal mucositis is a debilitating side effect of radiation treatment. A mouse model of radiation-induced mucositis leads to weight loss and tissue damage, reflecting the human ailment as it responds to keratinocyte growth factor (KGF), the standard-of-care treatment. Cultured intestinal crypt organoids allowed the development of an assay monitoring the effect of treatments of intestinal epithelium to radiation-induced damage. This in vitro assay resembles the mouse model as KGF and roof plate-specific spondin-1 (RSPO1) enhanced crypt organoid recovery following radiation. Screening identified compounds that increased the survival of organoids postradiation. Testing of these compounds revealed that the organoids changed their responses over time. Unbiased transcriptome analysis was performed on crypt organoid cultures at various time points in culture to investigate this adaptive behavior. A number of genes and pathways were found to be modulated over time, providing a rationale for the altered sensitivity of the organoid cultures. This report describes an in vitro assay that reflects aspects of human disease. The assay was used to identify bioactive compounds, which served as probes to interrogate the biology of crypt organoids over prolonged culture. The pathways that are changing over time may offer potential targets for treatment of mucositis.


Measurements of the Absolute Branching Fractions of B^{±}→K^{±}X_{cc[over ¯]}.
A study of the two-body decays B^{±}→X_{cc[over ¯]}K^{±}, where X_{cc[over ¯]} refers to one charmonium state, is reported by the BABAR Collaboration using a data sample of 424 fb^{-1}. The absolute determination of branching fractions for these decays are significantly improved compared to previous BABAR measurements. Evidence is found for the decay B^{+}→X(3872)K^{+} at the 3σ level. The absolute branching fraction B[B^{+}→X(3872)K^{+}]=[2.1±0.6(stat)±0.3(syst)]×10^{-4} is measured for the first time. It follows that B[X(3872)→J/ψπ^{+}π^{-}]=(4.1±1.3)%, supporting the hypothesis of a molecular component for this resonance.


CPred: a web server for predicting viable circular permutations in proteins.
Circular permutation (CP) is a protein structural rearrangement phenomenon, through which nature allows structural homologs to have different locations of termini and thus varied activities, stabilities and functional properties. It can be applied in many fields of protein research and bioengineering. The limitation of applying CP lies in its technical complexity, high cost and uncertainty of the viability of the resulting protein variants. Not every position in a protein can be used to create a viable circular permutant, but there is still a lack of practical computational tools for evaluating the positional feasibility of CP before costly experiments are carried out. We have previously designed a comprehensive method for predicting viable CP cleavage sites in proteins. In this work, we implement that method into an efficient and user-friendly web server named CPred (CP site predictor), which is supposed to be helpful to promote fundamental researches and biotechnological applications of CP. The CPred is accessible at http://sarst.life.nthu.edu.tw/CPred.


Effect of temperature and chain length on the bimodal emission properties of single polyfluorene copolymer molecules.
Fluorescence emission spectra were recorded for isolated polymer chains of the polyfluorene copolymer, F8BT [poly(9,9-di-n-octylfluorene-alt-benzothiadiazole)], at 298 and 20 K for two molecular weights (chain lengths). For long-chain F8BT at 298 K, the observed distribution of single-molecule emission maxima G(Emax) is bimodal, with peaks at approximately 2.35 eV ("blue") and approximately 2.25 eV ("red"). Previously, the red forms have been assigned to polymer chains that possess intrachain contacts, which lowers the local singlet exciton energy. At approximately 20 K, G(Emax) collapses into a single broad distribution centered at approximately 2.3 eV for long-chain F8BT. However, this distribution can be further divided into a high-energy edge that is dominated by the "blue" form, while the remainder of the distribution is composed of the "red" form. Low-molecular-weight F8BT samples emit exclusively from the blue form, and no shift in peak maxima with low temperature was observed. A Franck-Condon analysis reveals a decrease in emitting state displacements between spectra measured at 298 and 20 K, suggesting that temperature-induced structural displacements are responsible for the change in the bimodal emission.


Lessons learnt from 20 years surveillance of malaria drug resistance prior to the policy change in Burkina Faso.
The history of drug resistance to the previous antimalarial drugs, and the potential for resistance to evolve to Artemisinin-based combination therapies, demonstrates the necessity to set-up a good surveillance system in order to provide early warning of the development of resistance. Here we report a review summarizing the history of the surveillance of drug resistance that led to the policy change in Burkina Faso. The first Plasmodium falciparum Chloroquine-Resistance strain identified in Burkina Faso was detected by an in vitro test carried out in Koudougou in 1983. Nevertheless, no further cases were reported until 1987, suggesting that resistant strains had been circulating at a low prevalence before the beginning of the systematic surveillance system from 1984. We observed a marked increase of Chloroquine-Resistance in 2002-2003 probably due to the length of follow-up as the follow-up duration was 7 or 14 days before 2002 and 28 days from 2002 onwards. Therefore, pre-2002 studies have probably under-estimated the real prevalence of Chloroquine-Resistance by not detecting the late recrudescence. With a rate of 8.2% treatment failure reported in 2003, Sulfadoxine-Pyrimethamine was still efficacious for the treatment of uncomplicated malaria in Burkina Faso but this rate might rapidly increase as the result of its spreading from neighboring countries and due to its current use for both the Intermittent Preventive Treatment in pregnant women and Seasonal Malaria Chemoprophylaxis. The current strategy for the surveillance of the Artemisinin-based combination treatments resistance should build on lessons learnt under the previous period of 20 years surveillance of Chloroquine and Sulfadoxine-Pyrimethamine resistance (1994-2004). The most important aspect being to extend the number of sentinel sites so that data would be less patchy and could help understanding the dynamic of the resistance.


Organotypic Models for Functional Drug Testing of Human Cancers.
In the era of personalized oncology, there have been accelerated efforts to develop clinically relevant platforms to test drug sensitivities of individual cancers. An ideal assay will serve as a diagnostic companion to inform the oncologist of the various treatments that are sensitive and insensitive, thus improving outcome while minimizing unnecessary toxicities and costs. To date, no such platform exists for clinical use, but promising approaches are on the horizon that take advantage of improved techniques in creating human cancer models that encompass the entire tumor microenvironment, alongside technologies for assessing and analyzing tumor response. This review summarizes a number of current strategies that make use of intact human cancer tissues as organotypic cultures in drug sensitivity testing.


Free-viewpoint images captured using phase-shifting synthetic aperture digital holography.
Free-viewpoint images obtained from phase-shifting synthetic aperture digital holography are given for scenes that include multiple objects and a concave object. The synthetic aperture technique is used to enlarge the effective sensor size and to make it possible to widen the range of changing perspective in the numerical reconstruction. The lensless Fourier setup and its aliasing-free zone are used to avoid aliasing errors arising at the sensor edge and to overcome a common problem in digital holography, namely, a narrow field of view. A change of viewpoint is realized by a double numerical propagation and by clipping the wave field by a given pupil. The computational complexity for calculating an image in the given perspective from the base complex-valued image is estimated at a double fast Fourier transform. The experimental results illustrate the natural change of appearance in cases of both multiple objects and a concave object.


Can we spin straw into gold? An evaluation of immigrant legal status imputation approaches.
Researchers have developed logical, demographic, and statistical strategies for imputing immigrants' legal status, but these methods have never been empirically assessed. We used Monte Carlo simulations to test whether, and under what conditions, legal status imputation approaches yield unbiased estimates of the association of unauthorized status with health insurance coverage. We tested five methods under a range of missing data scenarios. Logical and demographic imputation methods yielded biased estimates across all missing data scenarios. Statistical imputation approaches yielded unbiased estimates only when unauthorized status was jointly observed with insurance coverage; when this condition was not met, these methods overestimated insurance coverage for unauthorized relative to legal immigrants. We next showed how bias can be reduced by incorporating prior information about unauthorized immigrants. Finally, we demonstrated the utility of the best-performing statistical method for increasing power. We used it to produce state/regional estimates of insurance coverage among unauthorized immigrants in the Current Population Survey, a data source that contains no direct measures of immigrants' legal status. We conclude that commonly employed legal status imputation approaches are likely to produce biased estimates, but data and statistical methods exist that could substantially reduce these biases.


Investigations on the nature of the cost of reproduction: susceptibility to heat stress in fruitflies.
Studies in various species have shown that changes in reproductive activity result in inverse changes in life span. It is interesting to know how this "cost of reproduction" is incurred. It is possible that reproductive activity renders the organism more vulnerable to stress and that accumulated damage has a role in the observed decrease in life span. Previously, other investigators had shown that mated female fruitflies have significantly shorter life spans than virgin females. We compare mated and virgin young fruitflies for susceptibility to lethal heat stress. Preliminary results suggest that mated fruitflies are significantly more susceptible to heat stress than virgin ones.


A report of cutaneous tuberculosis in siblings.
Cutaneous tuberculosis is rarely seen in the United States, and we are unaware of any reports of siblings sharing the diagnosis. We report an instance of cutaneous tuberculosis affecting two sisters. The first sibling had skin biopsy specimen findings suggestive of an infectious source, but special stains and cultures were negative. Only with further evaluation using polymerase chain reaction (PCR) was the diagnosis established. The second sibling had positive staining for acid-fast bacilli, though her cultures were also negative. A high level of suspicion for tuberculosis should be maintained in otherwise healthy children with nonspecific, granulomatous disorders of the skin. PCR may be a useful tool for selected cases in which a high level of clinical suspicion exists, but special stains and cultures are negative.


[Transitory vision loss by orbital osteoma].
The authors present a case of a 50-year-old woman with orbital osteoma complaining of gaze-evoked transitory vision loss of the right eye lasting for 6 months. The patient presented with normal visual acuity, pupils, eye movements, color vision, visual evoked potentials and visual fields. Orbital ultrasound showed a nasal intraorbitary neoformation, with low echogenicity and well-defined borders, suggesting an ethmoidal mucocele. Only a computed tomographic scan allowed the correct diagnosis, revealing a 2.7 cm x 2.2 cm calcified mass in the medial half of the right orbit, compatible with an osteoma. The x-ray view of the orbit confirmed the diagnosis. Although osteomas are slow-growing tumors, we decided to remove it because of the size, the complaints, and the patient's wishes. The tumor was approached and excised through an anterior medial orbitotomy. It was histopathologically shown to be a compact osteoma. The transitory vision loss resolved after surgery.


Orbital Transitions and Frustrated Magnetism in the Kagome-Type Copper Mineral Volborthite.
Volborthite Cu3V2O7(OH)2·2H2O is a copper mineral that materializes a two-dimensional quantum magnet comprising a kagome net of spin-1/2 Cu2+ ions. We prepared single crystals of volborthite using hydrothermal conditions and investigated their crystal structures and magnetic properties. Unusual orbital "switching" and "flipping" transitions were observed: in the former type of transition (switching), the Cu 3d orbital occupied by an unpaired electron changes between the d(3z2-r2) and d(x2-y2) types, and in the latter type of transition (flipping), the d(x2-y2)-type orbitals change their directions. Their origin is ascribed to variations in the orientation of water molecules in the gap between the kagome layers and the accompanying changes of hydrogen bonding. These orbital transitions dramatically modify the magnetic interactions between Cu2+ spins, from the anisotropic kagome type to the formation of spin trimers over the kagome net. The effective spin 1/2 generated on the trimers exhibits a frustrated magnetism, resulting in a rich phase diagram in the magnetic fields. Volborthite is a unique compound showing an exceptional interplay between the orbital and spin degrees of freedom.


Endomyocardial biopsy technique for orthotopic heart transplantation and cardiac stem-cell harvesting.
Orthotopic heart transplantation (OHT) is performed using the bicaval and pulmonary venous anastomoses or the standard (biatrial) anastomoses. The special considerations of endomyocardial biopsy after OHT using the bicaval technique, and after myocardial infarction for harvesting of cardiac stem cells, have not been described. When approached via the right or left internal jugular vein, important technical considerations were ultrasound guidance for vascular access; a soft, 80-cm, 0.035-inch, J-tipped guidewire; a long (23-cm), 7-Fr sheath; and a flexible 7-Fr, 50-cm bioptome. These technical aspects were helpful to avoid disruption of the superior vena cava suture line, avoid entry into the right atrial appendage or coronary sinus, avoid right ventricular free wall perforation, and provide ready access to the right ventricular septal wall. We used the same principles and technical considerations when obtaining the cardiac stem cells after myocardial infarction in patients enrolled in the CADUCEUS trial. From January 2002 to December 2005, 754 biopsy procedures were performed in 179 patients after OHT with the bicaval technique, using bioptome A. There was 1 occurrence of ventricular fibrillation requiring cardioversion, and no occurrence of cardiac tamponade during the procedure. From January 2006 to September 2013, 2818 biopsy procedures were performed in 1064 patients using bioptome B. No patient developed ventricular fibrillation or cardiac tamponade during the procedure. In 2010 and 2011, 23 biopsy procedures were performed in 23 patients after acute myocardial infarction, using bioptome B. No immediate complications occurred while performing these biopsies. The late occurrence of tricuspid regurgitation was not evaluated in this study. Endomyocardial biopsy procedures can be safely performed after OHT with the bicaval technique and after myocardial infarction for harvesting of cardiac stem cells. Ultrasound guidance for vascular access, a long guidewire and sheath, and a flexible bioptome are important features for the safe conduct of the biopsy procedure.


GSK-3β Overexpression Alters the Dendritic Spines of Developmentally Generated Granule Neurons in the Mouse Hippocampal Dentate Gyrus.
The dentate gyrus (DG) plays a crucial role in hippocampal-related memory. The most abundant cellular type in the DG, namely granule neurons, are developmentally generated around postnatal day P6 in mice. Moreover, a unique feature of the DG is the occurrence of adult hippocampal neurogenesis, a process that gives rise to newborn granule neurons throughout life. Adult-born and developmentally generated granule neurons share some maturational aspects but differ in others, such as in their positioning within the granule cell layer. Adult hippocampal neurogenesis encompasses a series of plastic changes that modify the function of the hippocampal trisynaptic network. In this regard, it is known that glycogen synthase kinase 3β (GSK-3β) regulates both synaptic plasticity and memory. By using a transgenic mouse overexpressing GSK-3β in hippocampal neurons, we previously demonstrated that the overexpression of this kinase has deleterious effects on the maturation of newborn granule neurons. In the present study, we addressed the effects of GSK-3β overexpression on the morphology and number of dendritic spines of developmentally generated granule neurons. To this end, we performed intracellular injections of Lucifer Yellow in developmentally generated granule neurons of wild-type and GSK-3β-overexpressing mice and analyzed the number and morphologies of dendritic spines (namely, stubby, thin and mushroom). GSK-3β overexpression led to a general reduction in the number of dendritic spines. In addition, it caused a slight reduction in the percentage, head diameter and length of thin spines, whereas the head diameter of mushroom spines was increased.


Pre-Ramadan diabetes risk stratification and patient education.
The fast (Sawm) is one of the religious obligations "Pillars" of Islam. The target audience of pre-Ramadan diabetes risk stratification and pre-education are the healthcare providers (particularly the Primary care physicians), diabetic patients and community members including general public. As per IDF-DAR (International Diabetes Federation & Diabetes and Ramadan International Alliance) guideline, it is advisable that healthcare providers should arrange pre-Ramadan session (appointment) at least 6-8 weeks prior to Ramadan quantify/stratify the patient risk category and educate all the diabetic patients on Ramadan aspects of Diabetes Mellitus. Diabetic patients are classified in to three risk groups (very high risk, moderate risk and low risk) based on specific patient characteristics. The physician should estimate the effect of fast on the patient, whether he will be able to fast or not, and the patient will estimate his ability and endurance to fast. The mode of Pre-Ramadan diabetes patient education could be group sessions or one to one consultation. Patient education should include information on risks, glucose monitoring, nutrition, exercise and medication adjustment. Studies have shown that pre-Ramadan counseling reduces the incidence of hypoglycaemia. Altering the drug dosage, dietary counseling and patient education, together with regular blood glucose monitoring enables the patients to fast without major complications. Patients classified as very high/high risk including T1DM and pregnant women with diabetes need close medical supervision and focused Ramadan-specific education if they insist on fasting. With the correct advice and support from healthcare providers most people with T2DM can fast safely during Ramadan.


Quantitative evaluation of diaphragmatic motion during forced breathing in chronic obstructive pulmonary disease patients using dynamic chest radiography.
To quantitatively evaluate the bilateral diaphragmatic motion difference during forced breathing between chronic obstructive pulmonary disease (COPD) patients and healthy individuals using dynamic chest radiography technique. This prospective study included the COPD patients (n: 96, f/m: 17/79, age: 66 ± 8 years old) and healthy individuals (n: 50, f/m: 42/8, age: 53 ± 5 years old) that underwent dynamic chest radiography with a flat panel X-ray detector system during forced breathing in a standing position. After analyzing the excursions, duration and velocity of diaphragmatic motion were automatically calculated using the postprocessing software. The parameters of diaphragmatic motion including excursion, duration, velocity, inhalation/exhalation times were assessed in all subjects for both diaphragms. The correlation between lung function parameters and diaphragmatic motion excursions were further evaluated. The excursions of diaphragmatic motion in COPD patients were significantly decreased in COPD patients compared with healthy individuals during forced breathing (P < 0.05). The excursion in COPD patients was 35.93 ± 13.07 mm vs. 41.49 ± 12.07 mm in healthy individuals in the left diaphragm, and 32.05 ± 12.29 mm in COPD patients vs. 36.88 ± 10.96 mm in healthy individuals in the right diaphragm. The duration of diaphragmatic motion significantly decreased in COPD patients, compared with the healthy individuals (P < 0.05). The inhalation time in COPD patients was 2.03 ± 1.19 s vs. 2.53 ± 0.83 s in healthy individuals in the left diaphragm and 1.94 ± 1.32 s in COPD patients vs. 2.23 ± 1.21 s in healthy individuals in the right diaphragm. The exhalation time was 4.77 ± 1.32 s in COPD patients vs. 6.40 ± 2.73 s in healthy individuals in the left diaphragm and 4.94 ± 3.30 s in COPD patients vs. 6.72 ± 2.58 s in healthy individuals in the right diaphragm. The peak velocity of diaphragmatic motion showed no significant difference between COPD and healthy groups. The excursions of bilateral diaphragmatic motion showed moderate correlation with FEV1/FVC (r = 0.44, P < 0.001). Multi-linear regression analysis showed that the excursions of bilateral diaphragm are significantly associated with COPD occurrence (P < 0.05). The excursions and duration of diaphragmatic motion during forced breathing are significantly decreased in COPD patients, compared with healthy individuals. Our study showed that precise bilateral diaphragmatic motion activity can be evaluated by dynamic chest radiography.


Developing and implementing a community intergenerational program.
Although intergenerational programs are becoming increasingly popular, there has been little documentation linking independent yet isolated seniors with children. This article discusses the development and implementation of a community intergenerational program. Elementary school students interacted with seniors at a nearby senior citizen apartment complex during eight 2-hr after-school meetings. Various recruitment strategies were needed to reach this vulnerable senior population, and activities had to be carefully monitored to promote intergenerational exchange. Evaluation of the program showed both the value of such interaction to the students and seniors and the importance of the nurse's role in ensuring that the program's benefits were realized.


Resident Memory-Like Tumor-Infiltrating Lymphocytes (TILRM): Latest Players in the Immuno-Oncology Repertoire.
Resident memory T cells (TRM) are a recently identified subset of long-lived memory T cells that are characterized in terms of their unique surface phenotype combined with a non-recirculating pattern of localization to non-lymphoid, peripheral tissues. TRM have quickly become a key area of focus in understanding immune responses to microbial infection in so-called "barrier" tissues, and appear to be particularly critical for protection against repeat exposure at the same site. More recently, tumor-infiltrating T cells with canonical TRM features are being identified in human cancers, in particular cancers of epithelial origin, and their presence is broadly found to be associated with favorable long-term prognosis. Moreover, recent studies have shown that these "resident memory-like" tumor-infiltrating lymphocytes (referred to herein as TILRM) are uniquely activated in melanoma patients undergoing PD-1 directed checkpoint blockade therapy. Accordingly, there is much interest at present regarding the biology of these cells and their precise role in anti-cancer immunity. Herein, we review the current state of the literature regarding TILRM with a specific emphasis on their specificity, origins, and relationship to conventional pathogen-specific TRM and speculate upon the way(s) in which they might contribute to improved prognosis for cancer patients. We discuss the growing body of evidence that suggests TILRM may represent a population of bona-fide tumor-reactive T cells and the attractive possibility of leveraging this cell population for future immunotherapy.


Generation of synthetic EEG data for training algorithms supporting the diagnosis of major depressive disorder.
Major depressive disorder (MDD) is the most common mental disorder worldwide, leading to impairment in quality and independence of life. Electroencephalography (EEG) biomarkers processed with machine learning (ML) algorithms have been explored for objective diagnoses with promising results. However, the generalizability of those models, a prerequisite for clinical application, is restricted by small datasets. One approach to train ML models with good generalizability is complementing the original with synthetic data produced by generative algorithms. Another advantage of synthetic data is the possibility of publishing the data for other researchers without risking patient data privacy. Synthetic EEG time-series have not yet been generated for two clinical populations like MDD patients and healthy controls. We first reviewed 27 studies presenting EEG data augmentation with generative algorithms for classification tasks, like diagnosis, for the possibilities and shortcomings of recent methods. The subsequent empirical study generated EEG time-series based on two public datasets with 30/28 and 24/29 subjects (MDD/controls). To obtain baseline diagnostic accuracies, convolutional neural networks (CNN) were trained with time-series from each dataset. The data were synthesized with generative adversarial networks (GAN) consisting of CNNs. We evaluated the synthetic data qualitatively and quantitatively and finally used it for re-training the diagnostic model. The reviewed studies improved their classification accuracies by between 1 and 40% with the synthetic data. Our own diagnostic accuracy improved up to 10% for one dataset but not significantly for the other. We found a rich repertoire of generative models in the reviewed literature, solving various technical issues. A major shortcoming in the field is the lack of meaningful evaluation metrics for synthetic data. The few studies analyzing the data in the frequency domain, including our own, show that only some features can be produced truthfully. The systematic review combined with our own investigation provides an overview of the available methods for generating EEG data for a classification task, their possibilities, and shortcomings. The approach is promising and the technical basis is set. For a broad application of these techniques in neuroscience research or clinical application, the methods need fine-tuning facilitated by domain expertise in (clinical) EEG research.


Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study].
A first pilot study of interleukin-1 blockade in ST-segment elevation acute myocardial infarction showed improved remodeling. In the present second pilot study, we enrolled 30 patients with clinically stable ST-segment elevation acute myocardial infarction randomized to anakinra, recombinant interleukin-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blind fashion. The primary end point was the difference in the interval change in left ventricular (LV) end-systolic volume index between the 2 groups within 10 to 14 weeks. The secondary end points included changes in the LV end-diastolic volume index, LV ejection fraction, and C-reactive protein levels. No significant changes in end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction were seen in the placebo group. Compared to placebo, treatment with anakinra led to no measurable differences in these parameters. Anakinra significantly blunted the increase in C-reactive protein between admission and 72 hours (+0.8 mg/dl, interquartile range -6.4 to +4.2, vs +21.1 mg/dl, interquartile range +8.7 to +36.6, p = 0.002), which correlated with the changes in LV end-diastolic volume index and LV end-systolic volume index at 10 to 14 weeks (R = +0.83, p = 0.002, and R = +0.55, p = 0.077, respectively). One patient in the placebo group (7%) died. One patient (7%) in the anakinra group developed recurrent acute myocardial infarction. More patients were diagnosed with new-onset heart failure in the placebo group (4, 27%) than in the anakinra group (1, 7%; p = 0.13). When the data were pooled with those from the first Virginia Commonwealth University-Anakinra Remodeling Trial (n = 40), this difference reached statistical significance (30% vs 5%, p = 0.035). In conclusion, interleukin-1 blockade with anakinra blunted the acute inflammatory response associated with ST-segment elevation acute myocardial infarction. Although it failed to show a statistically significant effect on LV end-systolic volume index, LV end-diastolic volume index, or LV ejection fraction in this cohort of clinically stable patients with near-normal LV dimensions and function, anakinra led to a numerically lower incidence of heart failure.


The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: A study in the Swedish AMORIS cohort.
Metabolic syndrome (MetS) is associated with non-alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end-date December 2011), aged ≥20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio-economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA-I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA-I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis.


The prediction of facial growth.
In the two contrasting malocclusions, the open bite and the deep overbite, statistically significant differences are shown in the anterior, middle and posterior endocranial regions. In open bite there is an association between the lower face height and the size of the anterior, middle and posterior cranial regions, but in deep overbite the associations between face height and the endocranial size are less strong. These and other associations if brougth together in a multiple regression analysis may prove useful in prognosticating the final face height in the growing child, particularly in the open-bite case.


[Clinical effectiveness and systemic toxicity of various mixtures of prilocaine and bupivacaine in axillary plexus block].
The presently existing local anesthetics (LA) do not guarantee a rapid onset and simultaneously a long duration of action. The combination of a medium-long acting LA with bupivacaine, a long-acting LA with slow onset, could be means to achieve these aims. Prilocaine was chosen as the medium-long acting LA because it has the lowest toxicity of this group and for pharmacological reasons. METHODS. In a prospective, controlled double-blind study 100 patients scheduled for axillary block for elective surgical procedures of the hand or wrist were randomly assigned to five groups. Twenty patients in each group received either 40 ml prilocaine 1.5%; 40 ml bupivacaine 0.375%; 20 ml prilocaine 1% + 20 ml bupivacaine 0.5%; 20 ml prilocaine 2% + 20 ml bupivacaine 0.5%; or 20 ml prilocaine 2% + 20 ml bupivacaine 0.375%. The LA mixtures were freshly mixed 15 min prior to the axillary block. The blocks were performed using an immobile, short-beveled needle by anesthesiologists who were familiar with this technique. Analgesia was classified using the pin-prick method with 0 = no analgesia, 1 = analgesia, 2 = anesthesia. Motor blockade was classified with 0 = no motor block, 1 = paresis, 2 = paralysis. The following nerves were analyzed: ulnar, radial, median, musculocutaneous, and medial antebrachial. In 6 patients of each group plasma levels of the LA were measured by gas chromatography and methemoglobinemia was determined. Statistical analysis of the data was performed using the Student t-test and chi-square test on a level of significance of P less than 0.05. Results. All surgical procedures could be performed as planned in regional anesthesia. Twenty minutes after injection of the LA only 15% of the blocks were sufficient in the bupivacaine group, while in the other four groups 40%-50% of the blocks were complete (P less than 0.05). The degree of analgesia was deeper in the groups with 2% prilocaine and prilocaine alone than in the group with 1% prilocaine. Forty minutes after injection there were no significant differences between the groups. Motor blockade after 20 min was significantly lower in the bupivacaine group than in the prilocaine group (P less than 0.05). After 4 h all three prilocaine-bupivacaine mixtures showed a significantly more pronounced analgesia of the median nerve than the prilocaine group (P less than 0.02-0.001).(ABSTRACT TRUNCATED AT 400 WORDS)


JN-2, a C-X-C motif chemokine receptor 3 antagonist, ameliorates arthritis progression in an animal model.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by uncontrolled joint inflammation and destruction of bone and cartilage. Previous studies have shown that C-X-C motif chemokine 10 (CXCL10) has important roles in RA development and that blocking CXCL10 expression effectively inhibits arthritis progression in animal models. However, clinical study using anti-CXCL10 monoclonal antibody (MDX-1100) to block CXCL10 expression in patients with RA did not show significant effectiveness. Therefore, we turned our attention to C-X-C motif chemokine receptor 3 (CXCR3), which is a receptor for CXCL9, CXCL10, and CXCL11, to treat RA. In the present study, administration of JN-2, our newly developed CXCR3 antagonist, ameliorated the progression of arthritis in a collagen-induced arthritis animal model. JN-2 also inhibited CXCR3-induced cell migration and pro-inflammatory cytokine expression of bone marrow-derived macrophages and CD4+ T cells in vitro. In addition, we found that CXCL10 formed an auto-amplification loop through activation of NFκB. Furthermore, Phosphorylation of p65 at serine 536 played an important role in the auto-amplification of CXCL10. Overall, the present results demonstrated that JN-2 decreased inflammation by inhibiting CXCR3-enhanced cell migration and pro-inflammatory cytokine expression, which then ameliorated arthritis progression.


Multidrug resistance gene and its relationship to ulcerative colitis and immune status of ulcerative colitis.
We examined the relationship among the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp), ulcerative colitis, and immune status under ulcerative colitis. MDR1 P-gp expression and interleukin-8 levels in ulcerative colitis were determined using immunohistochemistry and a double-antibody sandwich avidin-biotin complex-enzyme-linked immunosorbent assay, respectively. Nitric oxide content and nitric oxide synthase activity in the colonic mucosa were determined using a colorimetric method; CD4(+) and CD25(+) T cell subset percentages in the peripheral blood were determined by flow cytometry. The positive expression rate of P-gp in patients with ulcerative colitis (17.4%) was significantly lower than that in the control group (31.4%). The expression rate decreased to 10.1, 9.2, and 8.3% after 12, 18, and 24 months of treatment, respectively, which were significantly lower than the expression rate before treatment (17.4%). P-gp expression levels during the remission phase and active phase of ulcerative colitis were 15.2 and 17.1%, respectively, which were significantly lower than that in normal controls (31.4%). Compared with P-gp-negative patients, nitric oxide content, nitric oxide synthase activity, and interleukin-8 levels were significantly higher in P-gp-positive patients with moderately active, severely active, early onset, chronic relapsing, chronic persistent, and acute fulminant ulcerative colitis. CD4(+) and CD25(+) T cell subsets were significantly lower in the peripheral blood of patients with severely active and acute fulminant ulcerative colitis than in control subjects. Expression of the multidrug resistance gene and its product P-gp was observed in normal colon tissues and may be closely related to ulcerative colitis.


Intersubunit distances in full-length, dimeric, bacterial phytochrome Agp1, as measured by pulsed electron-electron double resonance (PELDOR) between different spin label positions, remain unchanged upon photoconversion.
Bacterial phytochromes are dimeric light-regulated histidine kinases that convert red light into signaling events. Light absorption by the N-terminal photosensory core module (PCM) causes the proteins to switch between two spectrally distinct forms, Pr and Pfr, thus resulting in a conformational change that modulates the C-terminal histidine kinase region. To provide further insights into structural details of photoactivation, we investigated the full-length Agp1 bacteriophytochrome from the soil bacterium Agrobacterium fabrum using a combined spectroscopic and modeling approach. We generated seven mutants suitable for spin labeling to enable application of pulsed EPR techniques. The distances between attached spin labels were measured using pulsed electron-electron double resonance spectroscopy to probe the arrangement of the subunits within the dimer. We found very good agreement of experimental and calculated distances for the histidine-kinase region when both subunits are in a parallel orientation. However, experimental distance distributions surprisingly showed only limited agreement with either parallel- or antiparallel-arranged dimer structures when spin labels were placed into the PCM region. This observation indicates that the arrangements of the PCM subunits in the full-length protein dimer in solution differ significantly from that in the PCM crystals. The pulsed electron-electron double resonance data presented here revealed either no or only minor changes of distance distributions upon Pr-to-Pfr photoconversion.


Rapid and sensitive screening of sulfamethazine in porcine urine with an enzyme-linked immunosorbent assay and a field-portable immunofiltration assay.
An enzyme-linked immunosorbent assay (ELISA) and an enzyme-linked immunofiltration assay (ELIFA) were developed for the screening of sulfamethazine (SMZ) in porcine urine. Incurred urine samples were measured by ELISA with a working range of 0 to 10 ng of SMZ per ml. The assay showed good accuracy and precision, with recoveries above 99.8% and intra- and interassay coefficients of variation (CVs) ranging from 2.6 to 5.6% and from 5.9 to 12.7%, respectively. Good agreement was observed when the results of the immunoassay were compared with those of liquid chromatography/tandem mass spectrometry analysis. For the ELIFA, a nylon membrane is placed on top of an absorbent material and covalently coated with rabbit anti-rat immunoglobulins. Free binding sites are blocked, and monoclonal anti-SMZ antibodies, SMZ standard or urine, and SMZ-horse radish peroxidase conjugate are subsequently dropped onto the membrane. During the assay, the reactants are drawn through the membrane because of its close contact with the absorbent pad. Finally, a substrate solution is added for blue color development. The blue spot produced can be visually evaluated or instrumentally measured (numeric deltaE*ab value), and the intensity of its color is inversely proportional to the analyte concentration. When a blue dot appears on the membrane, even if its color is less intense than that of the negative control, the sample is considered "negative," i.e., it is thought to contain a concentration of SMZ that is below the visual detection limit. If no color appears on the test membrane, the sample is considered "positive," i.e., it is thought to contain a concentration of SMZ that is equal to or above the visual detection limit. Validation of the assay showed good inter- and intra-assay precision (CV < 10%). Because samples can be analyzed after a simple dilution in <30 min with this assay format, it has strong potential for application in the field.


Genetic factors in the pathogenesis of breast cancer: their role and relative importance.
Aggregation of breast cancer in families is an established risk factor associated with increased incidence of the disease, which is a leading cause of morbidity and mortality among women in this country. Three genes have now been identified that confer increased susceptibility in families with a clear hereditary (i.e., Mendelian) pattern of expression: BRCA1, BRCA2 and p53. However, a significant number of women have an identified family history of breast cancer without clear Mendelian patterns of disease. Such patterns are consistent with the effect of more common genes with lower associated risk. Some evidence is available to implicate three additional genes that fit this category: AT, ESR and HRAS1. An area of active interest is genetically mediated variation in the metabolism of estrogens, a process controlled by several genes, each with more modest effects. The interaction of genes and environmental factors in breast cancer pathogenesis is of considerable public health importance.


A quantitative trait GWAS on lens thickness identifies novel risk loci on PTPRM in the narrow angle individuals susceptible to PACG.
PACG is one of the leading causes of blindness where lens thickness is a major risk factor for narrow-angle individuals. To our knowledge, no literature has been reported on candidate gene for lens thickness as a quantitative trait (QT). Here, we performed a genome-wide association analysis on lens thickness in the narrow-angle individuals. We conducted a genome-wide association study (GWAS) in the narrow angle individuals to investigate comprehensive genetic insights on lens thickness. In QT-GWAS, we identified 145 genome-wide suggestive significant loci in the discovery cohort. Subsequently, we observed 13 SNPs that showed statistical significance around the region of PTRRM. Regional association analysis for top significant genotyped variants identified PTPRM as the most likely candidate for increased LT. Integrative bioinformatic analyses confirmed that the associated genomic region has potential regulatory roles for modulating transcription as enhancers. In the replication cohort, the sentinel genotype SNP was further associated significantly (P-value =0.000448) with high LT individuals. In both cohorts, the T allele of rs1941137 in the PTPRM gene indicates as a risk allele for the increased LT. In this study, we discovered evidence of a genomic association between chromosomal areas around the PTPRM and increased lens thickness, resulting in a narrow angle. The regulatory components corresponding to PTPRM variations might have a role in the thicker lens. We report that the genomic region near PTPRM, a gene of potential interest, is associated with increased lens thickness.


Pilot study evaluating ureteric physiological changes with a novel 'ribbon stent' design using electromyographic and giant magnetoresistive sensors.
To test a novel 'ribbon stent' (RS) design using an extraluminal bipolar electromyographic (EMG) and giant magnetoresistive (GMR) sensor system to characterize ureteric responses. In all, 11 female domestic pigs were divided into three groups to evaluate ureteric physiology: group 1 (two pigs) with an unstented ureter, group 2 (three) with a standard 6 F ureteric stent, and group 3 (six) with the RS. For all groups EMG/GMR evaluation was performed at baseline, immediately after stenting, and at 3 and 7 days after stenting. All pigs underwent standardized retrograde ureteropyelogram evaluation at these time points, and after the final evaluation the pigs were killed and the urinary tract was harvested for histopathological evaluation. One stent in group 3 could not be deployed due to a problem with ureteric access. For groups 1, 2 and 3 the ureteric peristaltic activity was 109, 63, 72 events/h at baseline (P = 0.49); 61, 70, and 66 events/h immediately after stenting (P = 0.97); 66, 0, 8 events/h at 3 days after stenting (P = 0.002); and 61, 12, 0 events/h at 7 days after stenting, respectively (P = 0.049). The RS was deployed easily and safely in the porcine model using a standard technique. As with a standard stent, there was significant ureteric dilation and decrease in peristalsis with the RS.


Complex and magnitude-only preprocessing of 2D and 3D BOLD fMRI data at 7 T.
A challenge to ultra high field functional magnetic resonance imaging is the predominance of noise associated with physiological processes unrelated to tasks of interest. This degradation in data quality may be partially reversed using a series of preprocessing algorithms designed to retrospectively estimate and remove the effects of these noise sources. However, such algorithms are routinely validated only in isolation, and thus consideration of their efficacies within realistic preprocessing pipelines and on different data sets is often overlooked. We investigate the application of eight possible combinations of three pseudo-complementary preprocessing algorithms - phase regression, Stockwell transform filtering, and retrospective image correction - to suppress physiological noise in 2D and 3D functional data at 7 T. The performance of each preprocessing pipeline was evaluated using data-driven metrics of reproducibility and prediction. The optimal preprocessing pipeline for both 2D and 3D functional data included phase regression, Stockwell transform filtering, and retrospective image correction. This result supports the hypothesis that a complex preprocessing pipeline is preferable to a magnitude-only pipeline, and suggests that functional magnetic resonance imaging studies should retain complex images and externally monitor subjects' respiratory and cardiac cycles so that these supplementary data may be used to retrospectively reduce noise and enhance overall data quality.


GAPcare: The Geriatric Acute and Post-Acute Fall Prevention Intervention for Emergency Department Patients - A Qualitative Evaluation.
Three million US emergency department (ED) visits occur for falls each year. The mortality of falls is increasing and only one fourth of older adults report their fall to their primary care provider, suggesting that valuable preventative opportunities are missed. A fall prevention intervention initiated in the ED immediately after a fall has the potential to reduce subsequent falls, but ED providers lack the time and resources to complete fall risk assessments on their patients. GAPcare, the Geriatric Acute and Post-Acute Fall Prevention Intervention, was developed to address this need. GAPcare combines a pharmacist-led medication therapy management intervention with a physical therapist (PT)-administered fall risk assessment and disposition planning. A key objective of this pilot randomized controlled trial (RCT) was to create a patient and caregiver-centric intervention. This manuscript reports on the results of the qualitative companion study in which we conducted in-depth interviews with patients and caregivers to determine their lived experience with the intervention, barriers and perceived impact of the intervention, and to obtain their recommendations for the improvement of GAPcare. We recruited patients and their caregivers from the RCT into 30 minutes interviews in the participants' home singularly or in dyads (patient and caregiver together). Interviews were audio-recorded, transcribed, and double-coded. We used applied thematic analysis to guide the data analysis. We conducted 20 interviews; patients (n=12), caregivers (n=11). Patients were on average 83 years old, 7/12 were female, and 2/14 had cognitive impairment. 6/11 caregiver interviews were in reference to a patient with dementia. Patients and caregivers reported they embraced the experience of motivational interviewing elements, citing its collaborative and inclusive nature. Caregivers in particular said they felt that PT helped their loved one recognize and overcome functional limitations. Barriers included lack of time, the burden of coordinating multiple service providers once home, and concerns that PT would be ineffective or increase pain. Areas for improvement included better screening for those who would benefit from the individual components (pharmacy vs. PT consultation), improving identification of GAPcare pharmacists and PTs vs. other hospital staff in the ED, and expanding the role of GAPcare personnel to provide culturally competent, comprehensive care to improve adherence and medication education. We found that GAPcare, a new team-based intervention for fall prevention in the ED, was welcomed by patients and their caregivers. Several suggestions to improve the intervention were made that will inform the screening, content, and communication with patients in GAPcare.


Calculations of substituent and solvent effects on the kinetic isotope effects of Menshutkin reactions.
Nitrogen, deuterium, halogen, and carbon kinetic isotope effects have been modeled for the Menshutkin reaction between methyl halides and substituted N,N-dimethylaniline at the HF/6-31G(d) level of theory augmented by the C-PCM continuum solvent model for several solvents. Systematic changes in geometries of the transition states and Gibbs free energies of activation have been found with phenyl ring substituents, solvent, and the leaving group. Kinetic isotope effects also change systematically; however, these changes are predicted to be small, inside the usual precision of the experimental measurements. On the contrary, no correlation has been found between the kinetic isotope effects and the Hammett constants for para substituents. Thus opposite to previous assumptions, our results indicate that kinetic isotope effects on the Menshutkin reaction cannot be used to predict the position of the transition state on the reaction coordinate.


Navigational range lights: effect of stimulus configuration on alignment accuracy.
The use of range lights in nautical navigation involves the visual determination of the vertical alignment of two points of light, in order to indicate the centre of the channel. In two experiments it is shown that this vernier alignment task is more accurate if illuminated linear stimuli are used as range lights. Experiment 1 involved a laboratory simulation and experiment 2 involved a field test with full sized range lights. The average reduction of error through the use of linear stimuli over the standard point stimuli, for navigational alignments at a distance of one-half nautical mile from the range lights, was 69-4%. This suggests that a marked safety advantage might accrue from the use of linear range lights for nautical navigation purposes.


[Intratesticular calcifications: clinical significance].
[corrected] To evaluate the clinical-pathological significance of the intratesticular calcification. We analyzed by scrotal U.S., transducer 6.5 Mhz, the patients that consulted about testicular painful, infertility or intrascrotal deformity. Biopsy was effectuated when detected size modification of testicles, and central or focal calcifications. Also was done the classics tumoral markers. We founds 16 patients with microlithiasis over 24 testicles with these pathology. Previous antecedents: infertility 6 cases, testicular devolvulations surgery 5c, bilateral orchidopexy 3c and unilateral epididymitis 2c. The calcifications was classified in: peripheric or central follow-up 26.4 months. Associated pathology: a) Bilateral cryptorchidism: 4 testicles. b) Testicular tumors: 5 testicles. These tumors were biopsed: 3 seminomas, 1 embryonary carcinoma and 1 ca in situ. Both with negative biologic markers. The association with testicular tumor had an incidence of 20.83%. The central localization was detected in the 5 tumors, while the peripheric were 4 testis (cryptorchidism) and 15 with aspect of "snow storm". Histopathologically was observed eosinophilic bodies, with calcified nucleus, but not a exclusive features. Is a benign condition, casual, whose clinical significance is a still enigma. The association with testicular tumor is 20.83% and associated pathology is 33%. We proposed a testicular biopsy in cases of microlithiasis focal, central or with previous pathology.


Effects of substituting wheat by rye in diets for young fattening pigs on nutrient digestibility, performance, products of intestinal fermentation, and fecal characteristics.
Climate change and increasing demands to reduce the environmental impact of feed production are major challenges for animal nutritionists. Compared to wheat, which is commonly used in high levels in European piglet diets, rye is more efficient in using limited resources, most importantly, water and phosphorus. As a result, its cultivation has a relatively low carbon footprint. The high amounts of non-starch polysaccharides of rye might lead to an increased intestinal fermentation with potential beneficial effects on gut health. However, the high levels of non-starch polysaccharides in rye, which have a major impact on the physico-chemical conditions of the digesta, might affect digestibility and performance especially in young animals. It was therefore of interest to compare the effects of isoenergetic diets with increasing levels of rye as a replacement for wheat fed to young fattening pigs (bodyweight: 16-40 kg). The control diet contained 69% of wheat, while in the other three experimental diets, the amount of wheat was gradually replaced (by a third in each case) with rye. Thus, the experimental diets contained 23, 46, and 69% of rye. A total of 40 young pigs were housed individually in four dietary treatment groups. During a 4 week trial, effects on performance, digestibility, products of intestinal fermentation, and fecal characteristics were evaluated. There were no negative effects on feed intake and gains, even though the feed conversion ratio increased with the highest dietary rye level (69%). Digestibility rates of organic matter and crude protein did not differ significantly. Without affecting the characteristics of the feces, numerically higher amounts of intestinal fermentation products and higher colonic digesta mass were observed.


PrEP awareness and engagement among transgender women in South Africa: a cross-sectional, mixed methods study.
The South African national HIV plan recommends pre-exposure prophylaxis (PrEP) for transgender women, whose HIV prevalence estimates are as high as 25% in sub-Saharan Africa. The aim of this study was to explore PrEP awareness, uptake, and willingness, as well as associated barriers and facilitators, in order to inform PrEP implementation efforts with transgender women in South Africa. Using a community-engaged, convergent parallel mixed methods design, trained local transgender women data collectors recruited 213 transgender women participants (aged >18 years, assigned male sex at birth, and identifying as a gender different from male), via network referral and word-of-mouth in Cape Town, East London, and Johannesburg. A subset of 36 transgender women also participated in qualitative in-depth interviews. Quantitative analyses included descriptive statistics and negative binomial regression models to assess correlates of PrEP willingness. Qualitative interviews were audio-recorded, transcribed verbatim, and coded. Thematic content analysis was used to identify key themes. Quantitative and qualitative data were integrated for interpretation. Participants were recruited between June 1 and Nov 30, 2018. 57 (45%) of 127 HIV-negative participants were PrEP-aware and only 14 (11%) of 129 were currently taking PrEP. HIV-negative participants experiencing social (eg, violence, poverty) and interpersonal (eg, discrimination, low transgender women community connectedness) hardship reported PrEP awareness more frequently than HIV-negative transgender women who did not. Willingness to take PrEP was low, at 56 (55%) of 102, among HIV-negative participants who were not currently taking PrEP, and negatively associated with transgender women community connectedness (multivariable prevalence ratio 0·87; 95% CI 0·77-0·99). Barriers to PrEP included taking a daily pill, side-effects, and cost. Participants urged greater education and engagement of transgender women in PrEP implementation. South Africa is poised to scale up PrEP services for transgender women. Dedicated transgender clinics are planned to provide comprehensive care, including PrEP, for transgender women. It is critical to ensure transgender women are aware of and have accurate information about PrEP, and that health-care sites are prepared to provide quality care for transgender women. Gilead Sciences.


[A case of concurrent bilateral adrenocortical adenoma causing Cushing's syndrome].
A 43-year-old woman presented with obesity and lumbago. Endocrinological examinations revealed normal plasma cortisol levels and a suppressed serum adrenocorticotropic hormone (ACTH) level. On venous sampling, markedly elevated plasma cortisol levels were observed for bilateral adrenal veins (243 and 62.3 micrograms/dl on the right and left sides, respectively). Although the computed tomogram revealed bilaterally enlarged adrenal glands, 131I-adosterol scintigram showed a strong uptake only on the right side. Right adrenalectomy successfully relieved Cushing's syndrome. Pathological diagnosis was adrenocortical adenoma, 3.5 cm in diameter. Cushing's syndrome recurred in 9 years. At that time, she underwent left subtotal adrenalectomy including a 3-cm adrenocortical adenoma. Postoperative convalescence has been uneventful with oral steroid supplementation. All 14 previously reported cases of bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome as well as the present case were concurrent and dominant in females of reproductive age. This suggests that some cofactors other than ACTH, such as estrogen, contribute to the pathogenesis of BAA.


An optical intervention for visual hallucinations associated with visual impairment in an elderly patient.
A case study of a 100-year-old patient with visual hallucinations and visual impairment is presented. The patient was fit with optical aids in an effort to reduce the hallucinations, operating on the "phantom vision" theory, which postulates that visual hallucinations associated with visual impairment result from the brain's attempt to "fill in" for compromised visual input.


4-tert-Butyl-2-[2-(1,3,3-trimethyl-indolin-2-yl-idene)ethyl-idene]cyclo-hexa-none.
The title mol-ecule, C(23)H(31)NO, has two alternative cyclo-hexa-none configurations at the 4-position in a ratio of 0.663 (3):0.337 (3). The plane of the five-membered planar ring in the indolin-2-yl-idene subtends an angle of 2.19 (7)° with its fused aromatic ring, an angle of 16.24 (8)° with the plane of the major cyclo-hexa-none configuration and an angle of 8.54 (15)° with the bridging planar ethyl-idene C atoms. These last atoms subtend an angle of 8.37 (16)° with the mean plane through the major cyclo-hexa-none configuration. The mol-ecules pack approximately parallel to the ([Formula: see text]01) plane via C-H⋯π and C-H⋯O inter-actions.


Rectovaginal fistula following colectomy with an end-to-end anastomosis stapler for a colorectal adenocarcinoma.
An 11-year-old, female neutered Labrador retriever was presented with a micro-invasive differentiated papillar adenocarcinoma at the colorectal junction. A colorectal end-to-end anastomosis stapler device was used to perform resection and anastomosis using a transanal technique. A rectovaginal fistula was diagnosed two days later. An exploratory laparotomy was conducted and the fistula was identified and closed. Early dehiscence of the colon was also suspected and another colorectal anastomosis was performed using a manual technique. Comparison to a conventional manual technique of intestinal surgery showed that the use of an automatic staple device was quicker and easier. To the authors' knowledge, this is the first report of a rectovaginal fistula occurring after end-to-end anastomosis stapler colorectal resection-anastomosis in the dog. To minimise the risk of this potential complication associated with the limited surgical visibility, adequate tissue retraction and inspection of the anastomosis site are essential.


Lives and limbs: company records as a source for the history of industrial injuries.
The paper demonstrates how much information can be extracted about the history of industrial injuries from company records. After some background on work processes in the mining industry, accident registers of the Wemyss Coal Company are examined for two three-year periods, 1906-9 and 1921-23. Discussion and statistics are provided for types of injuries, duration of absence for different kinds of injuries, parts of the body affected, and causes of injuries, with comparisons made between the two periods. After some background on the jute industry the accident register of the Bow Bridge works is examined over four five-year periods between 1897 and 1934 for number and severity of accidents, types of injuries, parts of the body affected, causes, and age and gender distribution of accident victims. Wherever possible comparison is made with national statistics. The study shows how much information - both quantitative and qualitative - can be extracted from company records and provides a framework for further local studies in a hitherto neglected field.


Cell cycle arrest and apoptosis responses of human breast epithelial cells to the synthetic organosulfur compound p-methoxyphenyl p-toluenesulfonate.
There are several studies documenting that organosulfur compounds show promise as anticancer agents. Although some mechanisms of the antiproliferative activity of naturally occurring organosulfur compounds have been elucidated, few studies have reported the differential response of human breast cells to these compounds. The effect of the synthetic sulfonate ester, p-methoxyphenyl p-toluenesulfonate on growth inhibitory activity depending upon the estrogen-receptor (ER), p53, bcl-2 and caspase-3 status of cells was investigated by comparing its effects on three distinct human breast cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-453) and on one normal human mammary epithelial cell line (MCF-10A). This sulfonate ester selectively killed cancer cells at doses of 100 microM. Flow cytometry analysis showed that treatment with p-methoxyphenyl p-toluenesulfonate caused different cell cycle responses in the four cell lines but no clear association with p53 status was observed. Apoptosis was also induced in cells harboring different levels of Bcl-2 expression, but again independently of the p53 or ER status of the cells. These results suggest that p-methoxyphenyl p-toluenesulfonate acts on multiple signaling pathways leading to growth inhibition and activation of mechanisms of cell death selectively affecting survival of breast cancer cells. Thus, p-methoxyphenyl p-toluenesulfonate is the first member of a new class of tumor-specific chemotherapeutic agents for the treatment of breast cancer.


Stochastic model of self-assembly of cell-laden hydrogels.
Recent progress in bottom-up tissue engineering has demonstrated that three-dimensional tissue constructs with predefined architectures may be obtained by assembling shape-controlled hydrogels in multiphase reactor systems. Driven by the hydrophobic force between gel unit and liquid media, highly ordered hydrogel clusters can be formed. Many complex factors occurring at microscale (i.e., gel unit collisions, hydrophobic forces, and gel unit movement) are involved in the self-assembly process. In this paper a two-dimensional off-lattice Monte Carlo model with Lennard-Jones-type potential describing unit-unit interactions is introduced for studying this process. Simulations are shown to agree well with the experimental results for hydrogel assembly in mineral oil. The simulation method is demonstrated for rectangular hydrogel units of different aspect ratios as well as extended to the case of more complex hydrogel unit geometries.


Pru p 3, a marker allergen for lipid transfer protein sensitization also in Central Europe.
In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant-food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract-based diagnosis is often complicated by co-sensitization to Bet v 1, the major birch pollen allergen, its cross-reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant-derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant-food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients.


Mouse biodiversity in the genomic era.
Comparative genomics has developed by comparison of distantly related genomes, for which the link between the reported evolutionary changes and species development/physiology/ecology is not obvious. It is argued that the mouse (genus Mus) is an optimal model for microevolutionary genomics in vertebrates. This is because the mouse genome sequence, physical and genetic map have been completed, because mouse genetics, morpho-anatomy, pathology, behavior and ecology are well-studied, and because the Mus genus is a diverse, well- documented taxon, allowing comparative studies at the level of individual, population, subspecies, and species. The potential of the interaction between mouse genome and mouse biodiversity is illustrated by recent studies of speciation in the house mouse Mus musculus, and studies about the evolution of isochores, the peculiar pattern of GC-content variation across mammalian genomes.


A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for Diagnosis and Research.
The article "Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A Critical Review of 2,200 Cases" by Zajicek et al. [Acta Cytol 1967;11:169-175] is composed of two separate parts as can be seen from the title. Both are, however, of great historical interest. The first describes the early days of fine-needle aspiration cytology diagnosis of breast lesions in particular carcinomas. The results are still impressive with a diagnostic accuracy close to 90%. The second deals with the effect of negative pressure on cell viability during the aspiration procedure. These studies were aimed at evaluating the usefulness of aspirated tumor cells to analyze the effects of therapy and the origin of tumor cells.


Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing.
Congenital cataract is one of the most frequent causes of visual impairment and childhood blindness. Approximately one quarter to one third of congenital cataract cases may have a genetic cause. However, phenotypic variability and genetic heterogeneity hamper correct genetic diagnosis. In this study, we used whole-exome sequencing (WES) to identify pathogenic mutations in two Korean families with congenital cataract. Two affected members from each family were pooled and processed for WES. The detected variants were confirmed with direct sequencing. WES readily identified a CRYAA mutation in family A and a CRYGC mutation in family B. The c.61C>T (p.R21W) mutation in CRYAA has been previously reported in a family with congenital cataract and microcornea. The novel mutation, c.124delT, in CRYGC may lead to a premature stop codon (p.C42Afs*60). This study clearly shows the efficacy of WES for rapid genetic diagnosis of congenital cataract with an unknown cause. WES will be the first choice for clinical services in the near future, providing useful information for genetic counseling and family planning.


The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients.
Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count. The aim of the study was to evaluate the efficacy of vinca alkaloids in preparing adult corticosteroid refractory chronic ITP patients for splenectomy as well as to compare the costs of this method with costs of applying intravenous immunoglobulins. The study included 12 chronic ITP patients refractory to corticosteroids applied for 3-144 months. The patients were prepared for splenectomy with average 3.0 (from 1 to 4) 2-h intravenous infusions of vinca alkaloids at 7 day intervals. In eight patients, vincristin was used in a total dose of 6 mg (2 mg per infusion), in two patients, vinblastin was used in total dose of 30 mg (10 mg per infusion), and in two patients, vincristin and vinblastin infusions were administered alternatively. In nine of the 12 treated patients (75%) the platelet count increased to > or = 80 x 10(9)/l, which allowed safe splenectomy. Three patients unreactive to VA treatment were prepared for splenectomy with intravenous gammaglobulin infusions. Splenectomy was performed in 12 patients, in eight with laparoscopic method, in four with classic method. No complications during surgical intervention were observed. In none of the VA treated patients was myelosupression or liver or/and kidney dysfunction observed. Splenectomy resulted in normalization of platelet count in all patients after operation and in six of nine patients followed up for 10 months (on the average). Matching of VA costs with treatment efficacy and comparison with similar costs for intravenous immunoglobulin treatment revealed many fold lower costs of the former method.


Qualitative and quantitative skeletal muscle ultrasound in late-onset acid maltase deficiency.
Acid maltase deficiency (AMD, or Pompe disease) is an inherited myopathic disorder of glycogen degradation. Diagnosis is often delayed. Muscle ultrasound could improve diagnosis. We compared skeletal muscle ultrasound images from adults with AMD (n = 10) to other myopathies (n = 81) and, in AMD, compared qualitative (Heckmatt) and quantitative (backscatter) ultrasound measurements with strength and function. Qualitative ultrasound was abnormal in at least one muscle in all AMD subjects. Ultrasound patterns specific for AMD were: normal triceps brachii despite abnormalities in elbow flexors (89% vs. 17%, P < 0.0001); focal abnormalities affecting deep more than superficial biceps brachii (40% vs. 4%, P = 0.002); and more severe involvement of vastus intermedius than rectus femoris (40 vs. 11%, P = 0.03). In AMD, both qualitative (Heckmatt) and quantitative (backscatter) ultrasound measures increased with decreasing strength and function. Muscle ultrasound identifies the presence and specific patterns of AMD pathology, measures disease severity, and can help in the diagnosis of AMD.


The reverse transcriptase gene of cauliflower mosaic virus is translated separately from the capsid gene.
Cauliflower mosaic virus (CaMV) possesses start codons at the beginning of its reverse transcriptase (RT) gene (ORF V) suggesting that, unlike in retroviruses and retrotransposons, it is translated independently from the capsid gene (ORF IV). To test this hypothesis a mutational analysis of the CaMV ORF IV/V overlapping region was performed. Mutants in which both ORFs are separated by stop codons in all three reading frames are viable and stable, while mutations affecting the first two AUG codons of ORF V are either lethal or unstable, giving rise to true and second site reversions. Mutants in which the AUG codons were replaced by ACG or AAG reverted only slowly and ACG could direct the synthesis of small amounts of reporter enzyme in transfected plant protoplasts, showing that this codon can act in plant cells as a weak start codon. CaMV has apparently developed a strategy for translation of the RT gene different from that in retroviruses and retrotransposons, but similar to that of hepadnaviruses, another group of pararetroviruses. The separate translation of the RT gene as a common feature of pararetroviruses might reflect the difference in their life cycle in comparison with retroviruses.


Structural insights into catalysis by βC-S lyase from Streptococcus anginosus.
Hydrogen sulfide (H(2)S) is a causative agent of oral malodor and may play an important role in the pathogenicity of oral bacteria such as Streptococcus anginosus. In this microorganism, H(2)S production is associated with βC-S lyase (Lcd) encoded by lcd gene, which is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the α,β-elimination of sulfur-containing amino acids. When Lcd acts on L-cysteine, H(2)S is produced along with pyruvate and ammonia. To understand the H(2)S-producing mechanism of Lcd in detail, we determined the crystal structures of substrate-free Lcd (internal aldimine form) and two reaction intermediate complexes (external aldimine and α-aminoacrylate forms). The formation of intermediates induced little changes in the overall structure of the enzyme and in the active site residues, with the exception of Lys234, a PLP-binding residue. Structural and mutational analyses highlighted the importance of the active site residues Tyr60, Tyr119, and Arg365. In particular, Tyr119 forms a hydrogen bond with the side chain oxygen atom of L-serine, a substrate analog, in the external aldimine form suggesting its role in the recognition of the sulfur atom of the true substrate (L-cysteine). Tyr119 also plays a role in fixing the PLP cofactor at the proper position during catalysis through binding with its side chain. Finally, we partly modified the catalytic mechanism known for cystalysin, a βC-S lyase from Treponema denticola, and proposed an improved mechanism, which seems to be common to the βC-S lyases from oral bacteria.


Attitudes Formation by Small but Meaningful Personal Information.
People often evaluate others using fragmentary but meaningful personal information in recent days through social media. It is not clear that whether this process is implicit or explicit and what kind of information is more important in such process.We examined the effects of several meaningful fragmentary information onattitude. Thirty three KAIST students were provided four fragmentary information about four virtual people that are meaningful in evaluating people and frequently seen in real life situations, and were asked to imagine that person during four follow-up sessions. Explicit and Implicit attitudes were measured using Likert scale and Implicit Association Test respectively. Also, eye tracking was done to find out the most important information. Strong explicit attitudes, were formed toward both men and women, and weak but significant implicit attitudes, were generated toward men only. Eyetracking results showed that people spent more time reading morality information. Our results indicate that explicit attitudes are made by propositional learning, which is the main component for evaluating others with several meaningful fragmentary information, and implicit attitudes are formed by top down process. And as well as those of previous studies, morality information was suggested as the most important factor in developing attitudes.


In a Class of Their Own - RXFP1 and RXFP2 are Unique Members of the LGR Family.
The leucine-rich repeat-containing G protein-coupled receptors (LGRs) family consists of three groups: types A, B, and C and all contain a large extracellular domain (ECD) made up of the structural motif - the leucine-rich repeat (LRR). In the LGRs, the ECD binds the hormone or ligand, usually through the LRRs, that ultimately results in activation and signaling. Structures are available for the ECD of type A and B LGRs, but not the type C LGRs. This review discusses the structural features of LRR proteins, and describes the known structures of the type A and B LGRs and predictions that can be made for the type C LGRs. The mechanism of activation of the LGRs is discussed with a focus on the role of the low-density lipoprotein class A (LDLa) module, a unique feature of the type C LGRs. While the LDLa module is essential for activation of the type C LGRs, the molecular mechanism for this process is unknown. Experimental data for the potential interactions of the type C LGR ligands with the LRR domain, the transmembrane domain, and the LDLa module are summarized.


In Vitro Anti-Inflammatory Activity of Morus alba L. Stem Extract in LPS-Stimulated RAW 264.7 Cells.
Morus alba L., also known as white mulberry or Mhon, has long been used in traditional medicines. This study was aimed to investigate anti-inflammatory activities of mulberry stem ethanolic extract (MSE) in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The MSE was first prepared and then investigated for cell viability using the MTT assay. The anti-inflammatory activities were investigated through the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2 mRNA expression, and iNOS protein expression using reverse transcription-polymerase chain reaction (RT-PCR) assay and immunoblotting analysis, respectively. The inhibition of nitric oxide production of the MSE was also investigated using the Griess reaction assay. The MSE concentration ranging from 10 to 40 µg/ml yielded cell viability higher than 80%. The MSE at concentrations of 20 and 40 µg/ml demonstrated anti-inflammatory activity through the inhibition of nitric oxide production via suppression of both the iNOS mRNA and protein. It was also found to inhibit the expression of COX-2 mRNA in LPS-induced RAW 264.7 cells. This study is the first to report the anti-inflammatory potential of the extract prepared from the stem of mulberry.


Quantum interference in acyclic systems: conductance of cross-conjugated molecules.
We calculate that significant quantum interference effects can be observed in elastic electron transport through acyclic molecules. Interference features are evident in the transmission characteristics calculated for cross-conjugated molecules; significantly, these effects dominate the experimentally observable conduction range. The unusual transport characteristics of these molecules are highlighted through comparison with linearly conjugated and nonconjugated systems. The cross-conjugated molecules presented here show a large dynamic range in conductance. These findings represent a new motif for electron transfer through molecules that exhibit both very high and very low tunneling conductance states accessible at low bias without nuclear motion. In designing single molecule electronic components, a large dynamic range allows a high on/off ratio, a parameter of fundamental importance for switches, transistors, and sensors.