Proton beam irradiation using a light-field technique for the treatment of choroidal hemangiomas.
To describe the clinical outcomes of patients with circumscribed and diffuse choroidal hemangiomas treated by proton beam irradiation using a nonsurgical light-field technique. A retrospective chart review was performed on a series of 19 patients (19 eyes) with choroidal hemangiomas treated with proton beam therapy between July 1988 and August 2005. Choroidal hemangiomas were treated with proton beam irradiation using a light-field technique and doses ranging from 15 to 30 cobalt Gray equivalents (CGE; CGE = proton Gy x relative biological effectiveness 1.1) in 4 fractions. Patients with at least 6 months' follow-up were included in the study. Tumor regression, visual acuity, absorption of subretinal fluid, and treatment-associated complications were evaluated by clinical examination and ultrasonography. Visual acuity improved or remained stable in 14 of 18 eyes (78%). Subretinal fluid was initially present in 16 of 19 eyes (84%), and completely resolved in all 16 eyes. Tumor height, as measured by B-scan ultrasonography, decreased in 18 of 19 eyes and remained stable in 1 of 19, as of the last examination. Complications of radiation developed in 9 of 19 eyes (47%) with the total applied dose ranging from 15 to 30 CGE for these 9 eyes. Proton beam irradiation using a light-field technique without surgical tumor localization is an effective treatment option in managing both circumscribed choroidal hemangiomas and diffuse hemangiomas associated with Sturge-Weber syndrome. A total proton dose as low as 15 CGE applied in 4 fractions appears to be sufficient to reduce tumor size, promote absorption of subretinal fluid, and improve or stabilize vision in most patients.


Investigating protein patterns in human leukemia cell line experiments: A Bayesian approach for extremely small sample sizes.
Human cancer cell line experiments are valuable for investigating drug sensitivity biomarkers. The number of biomarkers measured in these experiments is typically on the order of several thousand, whereas the number of samples is often limited to one or at most three replicates for each experimental condition. We have developed an innovative Bayesian approach that efficiently identifies clusters of proteins that exhibit similar patterns of expression. Motivated by the availability of ion mobility mass spectrometry data on cell line experiments in myelodysplastic syndrome and acute myeloid leukemia, our methodology can identify proteins that follow biologically meaningful trends of expression. Extensive simulation studies demonstrate good performance of the proposed method even in the presence of relatively small effects and sample sizes.


Development of a method for the determination of pulsatile growth hormone secretion in mice.
Measures of pulsatile GH secretion require frequent collection and analysis of blood samples at regular intervals. Due to blood volume constraints, repeat measures of circulating levels of GH in mice remain challenging. Consequently, few observations exist in which the pulsatile pattern of GH secretion in mice have been characterized. To address this, we developed a technique for the collection and analysis of circulating levels of GH at regular and frequent intervals in freely moving mice. This was achieved through the development of a sensitive assay for the detection of GH in small (2 μl) quantities of whole blood. The specificity and accuracy of this assay was validated following guidelines established for single-laboratory validation as specified by the International Union of Pure and Applied Chemistry. We incorporated an established method for tail-clip blood sample collection to determine circulating levels of GH secretion in 36 whole blood samples collected consecutively over a period of 6 h. Resulting measures were characterized by peak secretion periods and interpulse stable baseline secretion periods. Periods characterized by elevated whole blood GH levels consisted of multicomponent peaks. Deconvolution analysis of resulting measures confirmed key parameters associated with pulsatile GH secretion. We show a striking decrease in pulsatile GH secretion in mice after 12-18 h of fasting. This model is necessary to characterize the pulsatile profile of GH secretion in mice and will significantly contribute to current attempts to clarify mechanisms that contribute to the regulation of GH secretion.


[Chronic delusional psychosis].
The current Anglo-Saxon trend is to consider that schizophrenia includes all psychoses. However, far from being a uniform set, there is a lot of different clinical presentations of patients with psychosis. Chronic delusional psychosis, as a paradigm, show that subtyping psychosis on a clinical basis is useful for therapeutic and prognosis purposes.


An investigation of the endoplasmic reticulum stress in obesity exposure in the prenatal period.
Exposure to maternal obesity has been shown to make offspring more prone to cognitive and metabolic disorders later in life. Although the underlying mechanisms are unclear, the role of endoplasmic reticulum (ER) stress in the fetal programming process is remarkable. ER stress can be activated by many chronic diseases, including obesity and diabetes. Therefore, our study aimed to investigate the role of ER stress caused by maternal diet-induced obesity in the offspring hippocampus. We also evaluated the protective effect of N-acetylcysteine (NAC) against ER stress. A rat obesity model was created by providing a high-fat (60 % kcal) diet. N-acetylcysteine (NAC) was administered at a dosage of 150 mg/kg via the intragastric route. The animals were mated at the age of 12 weeks. The same diet was maintained during pregnancy and lactation. The experiment was terminated on the postnatal 28th day, and the offspring's brain tissues were examined. Immunohistochemical staining for ER stress markers was performed on sections taken from tissues after routine histological procedures. The results revealed increased GRP78, PERK, and eIF2α immunoreactivities in the hippocampal dentate gyrus (DG) and cornu ammonis 1 (CA1) regions in the obese group offspring, while the expression of those markers in those regions normalized with NAC supplementation (p < 0.01). Statistical analysis of XBP1 immunoreactivity H-scores revealed no difference between the study groups (p > 0.05). These results suggest that exposure to obesity during the prenatal period may cause increased ER stress in hippocampal neurons, which have an important role in the regulation of learning, memory and behavior, and this may contribute to decreased cognitive performance. On the other hand, NAC stands out as an effective agent that can counteract hippocampal ER stress.


Internal Jugular Phlebectasia: Diagnosis by Ultrasonography, Doppler and Contrast CT.
Jugular phlebectasia is an isolated saccular or fusiform dilation of a vein without tortuosity. Its aetiology remains controversial. It is infradiagnosed, as it is generally asymptomatic. However, it has been increasingly recognized in recent years due to the better imaging techniques which are available. Phlebectasia of the Internal Jugular Vein (IJV) is a rare disease. It is mostly unilateral and it involves only the right side. It is usually a childhood disease which is diagnosed during the study of an intermittent neck mass. Its treatment is controversial. Presently, a conservative approach to unilateral or bilateral asymptomatic phlebectasia is recommended. Symptomatic phlebectasia requires surgery. The diagnosis is suggested by clinical features which can be confirmed by noninvasive radiology. This paper is reporting a case of unilateral right internal jugular phlebectasia in a 12 year old female patient who complained of an intermittent, right sided neck swelling, where we used UltraSonoGraphy(USG) with Doppler and Contrast enhanced CT(CECT) to evaluate the lesion.


On the use of fast blue, fluoro-gold and diamidino yellow for retrograde tracing after peripheral nerve injury: uptake, fading, dye interactions, and toxicity.
The usefulness of three retrograde fluorescent dyes for tracing injured peripheral axons was investigated. The rat sciatic was transected bilaterally and the proximal end briefly exposed to either Fast Blue (FB), Fluoro-Gold (FG) or to Diamidino Yellow (DY) on the right side, and to saline on the left side, respectively. The nerves were then resutured and allowed to regenerate. Electrophysiological tests 3 months later showed similar latencies and amplitudes of evoked muscle and nerve action potentials between tracer groups. The nerves were then cut distal to the original injury and exposed to a second (different) dye. Five days later, retrogradely labelled neurones were counted in the dorsal root ganglia (DRGs) and spinal cord ventral horn. The number of neurones labelled by the first tracer was similar for all three dyes in the DRG and ventral horn except for FG, which labelled fewer motoneurones. When used as second tracer, DY labelled fewer neurones than FG and FB in some experimental situations. The total number of neurones labelled by the first and/or second tracer was reduced by about 30% compared with controls. The contributions of cell death as well as different optional tracer combinations for studies of nerve regeneration are discussed.


Functional consequences of animal community changes in managed grasslands: An application of the CAFE approach.
In the midst of an ongoing biodiversity crisis, much research has focused on species losses and their impacts on ecosystem functioning. The functional consequences (ecosystem response) of shifts in communities are shaped not only by changes in species richness, but also by compositional shifts that result from species losses and gains. Species differ in their contribution to ecosystem functioning, so species identity underlies the consequences of species losses and gains on ecosystem functions. Such research is critical to better predict the impact of disturbances on communities and ecosystems. We used the "Community Assembly and the Functioning of Ecosystems" (CAFE) approach, a modification of the Price equation to understand the functional consequences and relative effects of richness and composition changes in small nonvolant mammal and dung beetle communities as a result of two common disturbances in North American prairie restorations, prescribed fire and the reintroduction of large grazing mammals. Previous research in this system has shown dung beetles are critically important decomposers, while small mammals modulate much energy in prairie food webs. We found that dung beetle communities were more responsive to bison reintroduction and prescribed fires than small nonvolant mammals. Dung beetle richness increased after bison reintroduction, with higher dung beetle community biomass resulting from changes in remaining species (context-dependent component) rather than species turnover (richness components); prescribed fire caused a minor increase in dung beetle biomass for the same reason. For small mammals, bison reintroduction reduced energy transfer through the loss of species, while prescribed fire had little impact on either small mammal richness or energy transfer. The CAFE approach demonstrates how bison reintroduction controls small nonvolant mammal communities by increasing prairie food web complexity, and increases dung beetle populations with possible benefits for soil health through dung mineralization and soil bioturbation. Prescribed fires, however, have little effect on small mammals and dung beetles, suggesting a resilience to fire. These findings illustrate the key role of re-establishing historical disturbance regimes when restoring endangered prairie ecosystems and their ecological function.


Shear stress-initiated signaling and its regulation of endothelial function.
Atherosclerosis develops preferentially at branches and curvatures of the arterial tree, where blood flow pattern is disturbed rather than being laminar, and wall shear stress has an irregular distribution without defined directions. The endothelium in the atherosusceptible regions, in comparison to that in atheroresistant regions, shows activation of proproliferative and proinflammatory gene expressions, reduced production of nitric oxide (NO), increased leukocyte adhesion, and permeability, as well as other atheroprone phenotypes. Differences in gene expressions and cell phenotypes have been detected in endothelia residing in native atherosusceptible and atheroresistant regions of the arteries, or in arteries from animal models with artificial creation of disturbed flow. Similar results have also been shown in in vitro systems that apply controlled shear stresses with or without clear directions to cultured endothelial cells in fluid-dynamically designed flow-loading devices. The available evidence indicates that the coordination of multiple signaling networks, rather than individual separate pathways, links the mechanical signals to specific genetic circuitries in orchestrating the mechanoresponsive networks to evoke comprehensive genetic and functional responses.


Water quality, availability, and acute gastroenteritis on the Navajo Nation - a pilot case-control study.
The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited. Data on demographics and water use practices were collected using a standard questionnaire. Household drinking water was tested for presence of pathogens, coliforms, and residual chlorine. Sixty-one subjects (32 cases and 29 controls) participated in the study. Cases and controls were not significantly different with respect to water sources, quality, or patterns of use. Twenty-one percent (n = 12) of study participants resided in dwellings not connected to a community water system. Eleven percent (n = 7) of subjects reported drinking hauled water from unregulated sources. Coliform bacteria were present in 44% (n = 27) of household water samples, and 68% (n = 40) of samples contained residual chlorine concentrations of <0.2 mg/L. This study highlights issues with water availability, quality, and use patterns within the Navajo Nation, including sub-optimal access to community water systems, and use of water hauled from unregulated sources.


Injectable, Antibacterial, and Hemostatic Tissue Sealant Hydrogels.
Hemorrhage and bacterial infections are major hurdles in the management of life-threatening surgical wounds. Most bioadhesives for wound closure lack sufficient hemostatic and antibacterial properties. Furthermore, they suffer from weak sealing efficacy, particularly for stretchable organs, such as the lung and bladder. Accordingly, there is an unmet need for mechanically robust hemostatic sealants with simultaneous antibacterial effects. Here, an injectable, photocrosslinkable, and stretchable hydrogel sealant based on gelatin methacryloyl (GelMA), supplemented with antibacterial zinc ferrite (ZF) nanoparticles and hemostatic silicate nanoplatelets (SNs) for rapid blood coagulation is nanoengineered. The hydrogel reduces the in vitro viability of Staphylococcus aureus by more than 90%. The addition of SNs (2% w/v) and ZF nanoparticles (1.5 mg mL-1 ) to GelMA (20% w/v) improves the burst pressure of perforated ex vivo porcine lungs by more than 40%. Such enhancement translated to ≈250% improvement in the tissue sealing capability compared with a commercial hemostatic sealant, Evicel. Furthermore, the hydrogels reduce bleeding by ≈50% in rat bleeding models. The nanoengineered hydrogel may open new translational opportunities for the effective sealing of complex wounds that require mechanical flexibility, infection management, and hemostasis.


ATP serves two distinct roles in protein degradation in reticulocytes, one requiring and one independent of ubiquitin.
Protein degradation in rabbit reticulocytes is a nonlysosomal process requiring ATP. Recently, appreciable evidence has been presented that ATP is required for the covalent binding of the polypeptide ubiquitin to epsilon-amino groups on protein substrates. To test whether linkage of ubiquitin to substrates is required for ATP-dependent proteolysis, the amino groups of 3H-methyl-casein and denatured 125I-bovine serum albumin (BSA) were completely (93-99%) blocked by methylation, acetylation, carbamylation, or succinylation. In each case, the proteins lacking amino groups were still degraded by an ATP-stimulated process, although these various treatments altered absolute rates of proteolysis and reduced the magnitude of the ATP stimulation (two- to fourfold) below that seen measured with the unmodified substrates. When ubiquitin was removed by ion exchange chromatography, ATP still stimulated breakdown of casein and carbamylated casein twofold. The addition of ubiquitin in the presence of ATP caused a further twofold increase in the hydrolysis of unmodified casein but did not affect the degradation of casein lacking amino groups. Thus ubiquitin conjugation to substrates appears important in the breakdown of certain substrates (especially of BSA), but this reaction is not essential for ATP-stimulated proteolysis. The ATP-activated step that is independent of ubiquitin probably is also involved in the degradation of unblocked proteins, since both processes require Mg++ and ATP hydrolysis and are inhibited by hemin but not by protoporphyrin IX. These results suggest that ATP has distinct roles at different steps in the degradative pathway.


Racial variation of cephalometric measurements in Hawaii.
To establish the race-specific norms and investigate the underlying etiological basis of racial differences in malocclusion, cephalometric measurements of Steiner were analyzed for five major racial groups in Hawaii: Caucasians, Japanese, Chinese, Filipinos, and Hawaiians. Subjects consisted of 210 healthy and orthodontically normal individuals of both sexes aged 15 years or older. Analysis of age- and sex-adjusted cephalometric values showed that bone-to-bone relationships are largely comparable among races with an exception of GoGn/SN. Significant racial differences are incisal inclinations in relation to the maxilla, the mandible, or the opposite incisors, with the least inclination for Caucasians and the greatest for Chinese. The result is general tendency of bimaxillary protrusion of non-Caucasians. No significant differences were detected in arch lengths of both jaws among these groups. It is suggested that the observed higher prevalence of mesioclusion in non-Caucasians--especially Orientals--is due to an imbalance of tooth dimension to the alveolar bone.


An improved physical and genetic map of Campylobacter jejuni NCTC 11168 (UA580).
Campylobacter jejuni is recognized as the major cause of food-borne gastrointestinal disease in the developed world. To facilitate the molecular genetic analysis of this pathogen, an approximately 18-fold redundant Tropist3 cosmid library was constructed from C. jejuni NCTC 11168 genomic DNA. The cosmid library was partially ordered by hybridization to 15 pulsed-field electrophoresis (PFGE) restriction fragments. This analysis confirmed the estimated size of the genome to be 1730 kb, but suggested discrepancies in some regions of the published physical map. The precise locations of two of the three rRNA gene clusters were mapped using a combination of restriction fingerprinting, sample sequencing and riboprobing. Additionally, 15 further genes were located on the revised map. A more detailed physical and genetic map of C. jejuni NCTC 11168 is presented.


New Potential Role of European Mouflon (Ovis aries musimon) in the Epidemiology of Border Disease in the Pyrenees.
Since 2001, high-mortality outbreaks of border disease (BD) have negatively affected populations of Pyrenean chamois (Rupicapra pyrenaica pyrenaica). Studies in the affected areas determined that sympatric wild ruminants did not seem to have an epidemiologic role in the circulation of border disease virus (BDV). However, the recent increase in European mouflon (Ovis aries musimon) densities might enhance the risk of pathogen transmission among chamois and mouflons. We conducted a serologic and virologic investigation of BDV in European mouflon from the Spanish Pyrenees, with the aim of determining potential changes in the role of this species in BDV epidemiology. From 2018 to 2022, we detected antibodies against BDV in 31/185 (16.7%) animals but did not detect BDV RNA in any spleen sample (0/65). These results indicate that BDV infection is occurring in these mouflon populations to a greater extent than previously described, which could shift the current understanding of BD epidemiology in the Pyrenees and cause an unpredictable effect on both chamois and mouflon populations. Further studies on the molecular identification of BDV in mouflon and chamois are required to better understand the contribution of mouflon in the epidemiology of BD.


Genomic organization of the S locus: Identification and characterization of genes in SLG/SRK region of S(9) haplotype of Brassica campestris (syn. rapa).
In Brassica, two self-incompatibility genes, encoding SLG (S locus glycoprotein) and SRK (S-receptor kinase), are located at the S locus and expressed in the stigma. Recent molecular analysis has revealed that the S locus is highly polymorphic and contains several genes, i.e., SLG, SRK, the as-yet-unidentified pollen S gene(s), and other linked genes. In the present study, we searched for expressed sequences in a 76-kb SLG/SRK region of the S(9) haplotype of Brassica campestris (syn. rapa) and identified 10 genes in addition to the four previously identified (SLG(9), SRK(9), SAE1, and SLL2) in this haplotype. This gene density (1 gene/5.4 kb) suggests that the S locus is embedded in a gene-rich region of the genome. The average G + C content in this region is 32.6%. An En/Spm-type transposon-like element was found downstream of SLG(9). Among the genes we identified that had not previously been found to be linked to the S locus were genes encoding a small cysteine-rich protein, a J-domain protein, and an antisilencing protein (ASF1) homologue. The small cysteine-rich protein was similar to a pollen coat protein, named PCP-A1, which had previously been shown to bind SLG.


Microbial conversion of indene to indandiol: a key intermediate in the synthesis of CRIXIVAN.
Indene is oxidized to mixtures of cis- and trans-indandiols and related metabolites by Pseudomonas putida and Rhodococcus sp. isolates. Indene metabolism is consistent with monooxygenase and dioxygenase activity. P. putida resolves enantiomeric mixtures of cis-1,2-indandiol by further selective oxidation of the 1R, 2S-enantiomer yielding high enantiomeric purity of cis-(1S, 2R)-indandiol, a potential intermediate in the synthesis of indinavir sulfate (CRIXIVAN), a protease inhibitor used in the treatment of AIDS. Molecular cloning of P. putida toluene dioxygenase in Escherichia coli confirmed the requirement for the dihydrodiol dehydrogenase in resolving racemic mixtures of cis-indandiol. Rhodococcus sp. isolates convert indene to cis-(1S, 2R)-indandiol at high initial enantiomeric excess and one isolate also produces trans-(1R, 2R)-indandiol, suggesting the presence of monooxygenase activity. Scale up and optimization of the bioconversions to these key synthons for chiral synthesis of potential intermediates for commercial manufacture of indinavir sulfate are described.


Economic analysis of Royalactin production under uncertainty: Evaluating the effect of parameter optimization.
Royalactin is a protein with several different potential uses in humans. Research, in insects and in mammalian cells, has shown that it can accelerate cell division and prevent apoptosis. The method of action is through the use of the epidermal growth factor receptor, which is present in humans. Potential use in humans could be to lower cholesterolemic levels in blood, and to elicit similar effects to those seen in bees, e.g., increased lifespan. Mass production of Royalactin has not been accomplished, though a recent article presented a Pichia pastoris fermentation and recovery by aqueous two-phase systems at laboratory scale as a possible basis for production. Economic modelling is a useful tool with which compare possible outcomes for the production of such a molecule and in particular, to locate areas where additional research is needed and optimization may be required. This study uses the BioSolve software to perform an economic analysis on the scale-up of the putative process for Royalactin. The key parameters affecting the cost of production were located via a sensitivity analysis and then evaluated by Monte Carlo analysis. Results show that if titer is not optimized the strategy to maintain a low cost of goods is process oriented. After optimization of this parameter the strategy changes to a product-oriented and the target output becomes the critical parameter determining the cost of goods. This study serves to provide a framework for the evaluation of strategies for future production of Royalactin, by analyzing the factors that influence its cost of manufacture.


Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain.
The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.


Peripheral metabolism of intact parathyroid hormone. Role of liver and kidney and the effect of chronic renal failure.
The plasma disappearance rate (metabolic clearance rate) of administered intact parathyroid hormone (intact PTH) was analyzed in awake dogs with indwelling hepatic and renal vein catheters. The metabolic clearance rate (MCR) of intact PTH was found to be very rapid, 21.6 +/- 3.1 ml/min per kg in 11 normal dogs. The liver accounted for the greatest fraction of the MCR of intact PTH (61 +/- 4%) by virtue of an arterial minus venous (a - v) difference across the liver of 45 +/- 3%. The renal uptake of intact PTH accounted for 31 +/- 3% of the MCR of intact PTH. The renal a - v difference for intact PTH of 29 +/- 2% was significantly greater than the filtration fraction indicating renal uptake of intact PTH at sites independent of glomerular filtration. Together, the hepatic and renal clearances of intact PTH accounted for all but a small fraction of the MCR of intact PTH. The MCR of intact PTH, rendered biologically inactive by oxidation, was markedly decreased to 8.8 +/- 1 ml/min per kg. The a - v difference of oxidized intact PTH was reduced both in the liver and kidney. These data suggested that the high uptake rates of intact PTH are dependent, at least in part, upon sites recognizing only biologically active PTH. Chronic renal failure (CRF) decreased the MCR of intact PTH to 11.3 +/- 1.3 ml/min per kg (n = 10). Both the hepatic and renal a - v differences of intact PTH were reduced in dogs with CRF. This resulted in reductions in the hepatic and renal clearances of intact PTH. These studies identify the liver as a major extrarenal site of PTH metabolism affected by CRF. They suggest that CRF impairs the function of the major uptake sites involved in intact PTH metabolism.


Successful aging. How increased life expectancy and medical advances are changing geriatric care.
If the unprecedented increase in life expectancy has a downside, it is the exposure of risk to chronic age-related disorders. As clinicians work to foster healthy aging, we must also seek ways to prevent the disabling disorders that keep many older persons from enjoying their longevity. The high prevalence of chronic illness and functional limitation among older persons underscores the need for strategically directed health and social services. Successful patient management must extend beyond diagnosis and disease treatment and include promotion of function and prevention of decline. Achieving this goal requires a seamless continuum of management and interdisciplinary caregiving. There also must be a focus on improving the understanding of the science of aging. New treatment approaches for managing aging may one day include cognitive enhancers, designer hormones, telomerase, antioxidants, and gene therapy.


Mixing in Langmuir Monolayers: Perfluorotetradecanoic Acid and a Gemini Surfactant without a Linker.
A recently reported anionic gemini surfactant, a member of the so-called "gemini without a linker" family, has recently been reported to form closely packed crystalline monolayers at the air-water interface. In this work, the impact on monolayer properties of the compound, C18-0-C18, that result from its mixing with a benchmark perfluorinated surfactant, perfluorotetradecanoic acid (PF), is explored. The films exhibit nonideal mixing, as determined by surface pressure-area (π-A) isotherms and surface potential measurements, and phase-separation between the two components was observed by the direct visualization of the monolayers, and grazing-incident X-ray diffraction at the air-water interface. The pure and mixed films follow similar trends in the order of C18-0-C18 < PF < χPF = 0.50 mixed films for both their extent of hysteresis and their stability at the air-water interface. Further, crystallographic data for the mixed film emerge as a simple combination of distinct diffraction patterns characteristic of both the individual components, consistent with the other findings reported here and thus clarify the intermolecular behavior of the binary mixture at the surface.


Sonographic screening for thyroid cancer in females undergoing breast sonography.
The purpose of our prospective study was to evaluate incidental thyroid cancer diagnosed by screening sonography in a population who underwent breast sonography and the differences in the incidences of thyroid cancer between those with and those without breast cancer. Between January 2003 and March 2004, we examined thyroid glands during routine diagnostic or follow-up breast sonography. A total of 5,549 females underwent breast and thyroid screening sonography (n = 4,864) or sonography for diagnosis or follow-up of breast cancer (n = 685). When a thyroid lesion was suspicious for malignancy, sonographically guided fine-needle aspiration was performed. We compared the cases of pathologically proven thyroid cancer in two groups: a cancer group, including patients with breast cancer, and a noncancer group, including patients with negative or benign breast disease. Among the 5,549 cases, 42 (0.76%) were diagnosed as thyroid cancer; all were papillary carcinomas. Pathologically proven thyroid cancers were identified in 13 (1.9%) of the 685 breast cancer patients and in 29 (0.6%) of the 4,864 non-breast-cancer patients. The diameters of the 13 thyroid masses were 0.1-3.0 cm; the mean diameters in the cancer and noncancer groups were 9.9 and 8.6 mm, respectively. The incidence of thyroid cancer was significantly higher in the group with breast cancer than in the group who did not have breast cancer. The results of routine concurrent sonographic breast and thyroid examinations were helpful in detecting small thyroid tumors in both patient groups.


Synthesis of an O-glycosylated cell surface protein induced in yeast by alpha factor.
A number of cell surface glycoproteins can be specifically and completely released from intact cells of Saccharomyces cerevisiae with 0.5% mercaptoethanol. Among these proteins is one with a molecular mass of 22 kDa, which is synthesized only in haploid a cells treated with the peptide mating pheromone alpha factor. This protein could be radiolabeled in vivo with [2-(3)H]mannose, [(14)C]phenylalanine, and [(35)S]sulfate. Its synthesis and export to the cell surface were not inhibited by tunicamycin. beta-Elimination released almost all radioactivity from the [2-(3)H]mannose-labeled protein, 36% of its radioactivity being recovered subsequently as mannose and 43% as a dimannoside. Evidence is presented that the 22-kDa O-glycosylated protein is a mating-type specific a cell agglutinin.


Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.
Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.


Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.
Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies.


Sequence analysis of cfxA2-like beta-lactamases in Prevotella species.
Sixty-two strains of oral (32) and non-oral (30) Prevotella producing beta-lactamases were screened for cfxA by PCR, using an intragenic primer pair. All 62 were cfxA/cfxA2 positive. Fourteen of these strains, representing seven pigmented and seven non-pigmented Prevotella species were submitted to further PCR with specific primers that amplified the whole beta-lactamase structural gene (966 bp). After cloning and sequencing, the deduced amino acid sequences were compared with that of Bacteroides vulgatus CfxA beta-lactamase. All 14 sequences possessed the E272K substitution characteristic of CfxA2. CfxA sensu stricto was not observed in the present series. G83D, F/V189L, W193L and D239Y substitutions were observed more than once, without species specificity. This sequence analysis indicates that most oral and non-oral beta-lactamase-producing Prevotella isolates from French patients produce variants of the CfxA enzyme.


Age- and sex-dependent disparity in physical fitness between obese and normal weight children and adolescents.
Aim of the present study was to determine whether the association between obesity and physical fitness in children and adolescents is age- and sex-specific. A total of 4519 children and adolescents aged 4-17 years grouped by age (4-5, 6-10, 11-13 and 14-17 years), sex and BMI (normal-weight: BMI≤90th percentile; overweight: BMI>90th percentile; adipose: BMI>97th percentile) participated in this large-scale representative cross-sectional study. Endurance, strength, flexibility and fine and gross motor coordination was measured using the following physical fitness tests: PWC170, push-ups test, standing long-jumps, side-to-side jumps, one-minute single leg stance on the dominant leg, balancing backwards on three beams of different width, lowest point reached by the fingertips while standing on a box with legs extended, reaction to colour changes of traffic light, tracing lines without touching the rim and sorting 25 pens. Overweight and obese boys and girls had lower physical fitness values describing endurance, strength and gross motor coordination than normal-weight boys and girls, respectively (P<0.001 for all; boys: -12% and -19%, respectively; girls: -9% and -19%, respectively). Differences in physical fitness between weight groups were greater in older groups (P<0.001). Fine motor skills and flexibility values did not differ between weight groups. The disparity in physical fitness, in particular in endurance, strength and gross motor coordination, between obese and normalweight is greater in adolescents than in children. Physical fitness programs are warranted for all overweight and obese children and adolescents but especially for overweight and obese adolescents.


Vasoactive components of dialysis solution.
Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions. Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution. All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H(+) concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA). (1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H(+)]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H(+)], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.


Grading amino acid properties increased accuracies of single point mutation on protein stability prediction.
Protein stabilities can be affected sometimes by point mutations introduced to the protein. Current sequence-information-based protein stability prediction encoding schemes of machine learning approaches include sparse encoding and amino acid property encoding. Property encoding schemes employ physical-chemical information of the mutated protein environments, however, they produce complexity in the mean time when many properties joined in the scheme. The complexity introduces noises that affect machine learning algorithm accuracies. In order to overcome the problem we described a new encoding scheme that graded twenty amino acids into groups according to their specific property values. We employed three predefined values, 0.1, 0.5, and 0.9 to represent 'weak', 'middle', and 'strong' groups for each amino acid property, and introduced two thresholds for each property to split twenty amino acids into one of the three groups according to their property values. Each amino acid can take only one out of three predefined values rather than twenty different values for each property. The complexity and noises in the encoding schemes were reduced in this way. More than 7% average accuracy improvement was found in the graded amino acid property encoding schemes by 20-fold cross validation. The overall accuracy of our method is more than 72% when performed on the independent test sets starting from sequence information with three-state prediction definitions. Grading numeric values of amino acid property can reduce the noises and complexity of input information. It is in accordance with biochemical concepts for amino acid properties and makes the input data simplified in the mean time. The idea of graded property encoding schemes may be applied to protein related predictions with machine learning approaches.


Caffeine supplementation and multiple sprint running performance.
The aim of this study was to examine the effects of caffeine supplementation on multiple sprint running performance. Using a randomized double-blind research design, 21 physically active men ingested a gelatin capsule containing either caffeine (5 mg x kg(-1) body mass) or placebo (maltodextrin) 1 h before completing an indoor multiple sprint running trial (12 x 30 m; repeated at 35-s intervals). Venous blood samples were drawn to evaluate plasma caffeine and primary metabolite concentrations. Sprint times were recorded via twin-beam photocells, and earlobe blood samples were drawn to evaluate pretest and posttest lactate concentrations. Heart rate was monitored continuously throughout the tests, with RPE recorded after every third sprint. Relative to placebo, caffeine supplementation resulted in a 0.06-s (1.4%) reduction in fastest sprint time (95% likely range = 0.04-0.09 s), which corresponded with a 1.2% increase in fatigue (95% likely range = 0.3-2.2%). Caffeine supplementation also resulted in a 3.4-bpm increase in mean heart rate (95% likely range = 0.1-6.6 bpm) and elevations in pretest (+0.7 mmol x L(-1); 95% likely range = 0.1-1.3 mmol x L(-1)) and posttest (+1.8 mmol x L(-1); 95% likely range = 0.3-3.2 mmol x L(-1)) blood lactate concentrations. In contrast, there was no significant effect of caffeine supplementation on RPE. Although the effect of recovery duration on caffeine-induced responses to multiple sprint work requires further investigation, the results of the present study show that caffeine has ergogenic properties with the potential to benefit performance in both single and multiple sprint sports.


Alcohol, suppressed anger and violence.
Is alcohol related causally to violence, and if so, is the effect of drinking contingent on suppressed anger such that it is strongest among individuals who are highly inclined to withhold angry feelings? We addressed these questions by analysing panel data using a method that diminishes the effects of confounding factors. We analysed data on heavy episodic drinking and violent behaviour from the second (1994) and third (1999) waves of the Young in Norway Longitudinal Study (n = 2697; response rate: 67%). The first difference method was applied to estimate the association between these behaviours, implying that changes in the frequency of violence were regressed on changes in the frequency of drinking. Hence, the effects of time-invariant confounders were eliminated. Analyses were conducted for the whole sample, and for groups scoring low, medium and high on a short version of the STAXI anger suppression scale. Changes in drinking were related positively and significantly to changes in violent behaviour, but the alcohol effect varied with the level of suppressed anger: it was strongest in the high-anger group (elasticity estimate = 0.053, P = 0.011) and weakest (and insignificant) in the low-anger group (elasticity estimate = 0.004, P = 0.806). Alcohol use may be related causally to violence, but the effect of drinking is confined to individuals who are inclined to suppress their angry feelings.


Challenges faced by blind patients using chronic medication at a tertiary hospital in South Africa.
Difficulties faced by blind patients in using medicines are largely unknown and underexplored. This limits the ability of health providers and health policy makers to plan and provide for medicine related needs of this special group. To describe the challenges faced by blind patients around Mankweng Hospital when taking chronic medications and to identify methods used to overcome the challenges. Quantitative cross-sectional descriptive study, where questionnaires were administered to 82 blind patients, 18 years and older, and who were on chronic medications. Data was analysed using the Statistical Package for the Social Sciences (SPSS) software. Majority of participants were elderly (59%) and had partial blindness (78%). Challenges faced by participants included inability to locate and identify medication (60%), missing doses (64%), inaccurate dosing and spilling medicines (33%). A staggering 68.3% of the participants did not have specific methods to overcome challenges. Challenges faced by the blind and visually impaired are similar across the world. However, participants are unaware of other simple, feasible methods available in the market. Current methods used by the participants to overcome the challenges encountered are minimal or caregiver dependent. Programs may be set up at clinics, hospitals and health care centers to teach the visually impaired simple and inexpensive methods to help administer medications. Results obtained may be used to raise awareness in health care policy makers of the under-explored challenges faced by the partially blind or completely blind patients in the use of medicines.


[Public-private relations in the Colombian health system from 1991 to 2015].
The case of Colombia's health system exemplifies the neoliberal reforms conducted in Latin America, characterized by the private sector's broad participation in the administration of resources and provision of health services. The system includes a set of benefits for persons that can afford to pay and a package of basic services with state financing for poor persons. This study aimed to analyze the public-private arrangements in the Colombian health system from 1991 and 2015, including the dimensions of insurance and financing. A case study was performed that included a literature review and analysis of documents and secondary data. The results suggest that the 1993 reform conceived of health as a public service to be provided by the market. There were changes in the state's role, delegating health care functions to the private sector through regulatory and contractual measures. Beginning in 2000, incremental reforms included instrumental changes in the system, while other initiatives aimed to expand the state's responsibilities in guaranteeing the right to health. In terms of health insurance, the main advances were the expansion of insurance coverage and harmonization of baskets of benefits between different insurance systems (although late). As for financing, there are important inequities in per capita spending between the different insurance systems and inefficiency in the financial intermediation. The Colombian case underscores the limits of structuring health systems with heavy market participation, and the study contributes to the debate on the challenges for social protection in health in Latin American countries.


An elastic contour matching model for tropical cyclone pattern recognition.
In this paper, an elastic graph dynamic link model (EGDLM) based on elastic contour matching is proposed to automate the Dvorak technique for tropical cyclone (TC) pattern interpretation from satellite images. This method integrates traditional dynamic link architecture (DLA) for neural dynamics and the active contour model (ACM) for contour extraction of TC patterns. Using satellite pictures provided by National Oceanic and Atmospheric Administration (NOAA), 120 tropical cyclone cases that appeared in the period from 1990 to 1998 were extracted for the study. An overall correct rate for TC classification was found to be above 95%. For hurricanes with distinct "eye" formation, the model reported a deviation within 3 km from the "actual eye" location, which was obtained from the aircraft measurement of minimum surface pressure by reconnaissance. Compared with the classical DLA model, the proposed model has simplified the feature representation, the network initialization, and the training process. This leads to a tremendous improvement of recognition performance by more than 1000 times.


B-cell fate decisions following influenza virus infection.
Rapidly induced, specific Ab generated in extrafollicular foci are important components of early immune protection to influenza virus. The signal(s) that prompt B cells to participate in extrafollicular rather than germinal center responses are incompletely understood. To study the regulation of early B-cell differentiation events following influenza infection, we exploited earlier findings of a strong contribution of C12 idiotype-expressing B cells to the primary HA-specific response against influenza A/PR/8/34. Using an idiotype-specific mAb to C12 and labeled HA, in conjunction with multicolor flow cytometry, we followed the fate of C12Id-expressing influenza HA-specific B cells in WT BALB/c mice, requiring neither genetic manipulation nor adoptive cell transfer. Our studies demonstrate that HA-specific C12Id(+) B cells are phenotypically indistinguishable from follicular B cells. While they induced both extrafollicular and germinal center responses, extrafollicular responses were strongly predominant. Provision of increased HA-specific T-cell help increased the magnitude of the extrafollicular response, but did not shift the C12Id(+) response toward germinal center formation. Collectively the data are consistent with the hypothesis that B-cell fate determination following activation is a stochastic process in which infection-induced innate signals might drive the preferential expansion of the early extrafollicular response.


Decision making in pediatric spinal deformity.
To review the concepts involved in the decision-making process for management of pediatric patients with spinal deformity. The literature was reviewed in reference to pediatric deformity evaluation and management. Pediatric spinal deformity includes a broad range of disorders with differing causes, natural histories, and treatments. Appropriate categorization of pediatric deformities is an important first step in the clinical decision-making process. An understanding of both nonoperative and operative treatment modalities and their indications is requisite to providing treatment for pediatric patients with spinal deformity. The primary nonoperative treatment modalities include bracing and casting, and the primary operative treatments include nonfusion instrumentation and fusion with or without instrumentation. In this article, we provide a review of pediatric spinal deformity classification and an overview of general treatment principles. The decision-making process in pediatric deformity begins with appropriate diagnosis and classification of the deformity. Treatment decisions, both nonoperative and operative, are often predicated on the basis of the age of the patient and the natural history of the disorder.


Effect that the relative abundance of copper oxide and zinc oxide corrosion has on the visualization of fingerprints formed from fingerprint sweat corrosion of brass.
From an examination of the fingerprint sweat corrosion of 40 different individuals on α phase brass, we show that an increase in visualization can be achieved by applying a negative potential to the brass followed by the introduction of a conducting powder. Previously, this technique has been demonstrated only for a positive applied potential and a corrosion product that was dominated by p-type copper (I) oxide. X-ray photoelectron and Auger electron spectroscopic analyses of the surface of the corroded brass show that an increase in visualization with a negative applied potential corresponds with an increase in the concentration of n-type zinc oxide relative to p-type copper (I) oxide with the Cu:Zn ratio <0.8:1. Work function conditions for the formation of an n-type zinc oxide/brass rectifying Schottky barrier are fulfilled.


The effect of chronic kidney disease on CYP2B expression and activity in male Wistar rats.
Chronic kidney disease (CKD) is characterized by progressive reduction in kidney function over time. CKD affects greater than 10% of the population and its incidence is on the rise due to the growing prevalence of its risk factors. Previous studies demonstrated CKD alters nonrenal clearance of drugs in addition to reducing renal clearance. We assessed the function and expression of hepatic CYP2B enzymes using a rat model of CKD. CKD was induced in Wistar rats by supplementing their chow with adenine and confirmed through the detection of elevated uremic toxins in plasma. Liver enzymes AST and ALT were unchanged by the adenine diet. Bupropion was used as a probe substrate for hepatic CYP2B function using rat liver microsomes. The resulting metabolite, hydroxy-bupropion, and bupropion were quantified by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Level of mRNA and protein were determined by RT-PCR and Western blot, respectively. The results of our study demonstrate that CYP2B1 is downregulated in a rat model of CKD. CYP2B1 mRNA level was significantly decreased (88%, P < 0.001) in CKD relative to control. Similarly, maximal enzymatic velocity (Vmax) for CYP2B was decreased by 46% in CKD relative to control (P < 0.0001). Previous studies involving patients with CKD demonstrated altered bupropion pharmacokinetics compared to control. Hence, our results suggest that these alterations may be mediated by attenuated CYP2B hepatic metabolism. This finding may partially explain the alterations in pharmacokinetics and nonrenal drug clearance frequently observed in patients with CKD.


Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure.
The importance and priority of specific micro-structural and mechanical design parameters must be established to effectively engineer scaffolds (biomaterials) that mimic the extracellular matrix (ECM) environment of cells and have clinical applications as tissue substitutes. In this study, three-dimensional (3-D) matrices were prepared from type I collagen, the predominant compositional and structural component of connective tissue ECMs, and structural-mechanical relationships were studied. Polymerization conditions, including collagen concentration (0.3-3 mg/mL) and pH (6-9), were varied to obtain matrices of collagen fibrils with different microstructures. Confocal reflection microscopy was used to assess specific micro-structural features (e.g., diameter and length) and organization of component fibrils in 3-D. Microstructural analyses revealed that changes in collagen concentration affected fibril density while maintaining a relatively constant fibril diameter. On the other hand, both fibril length and diameter were affected by the pH of the polymerization reaction. Mechanically, all matrices exhibited a similar stress-strain curve with identifiable "toe," "linear," and "failure" regions. However the linear modulus and failure stress increased with collagen concentration and were correlated with an increase in fibril density. Additionally, both the linear modulus and failure stress showed an increase with pH, which was related to an increasedfibril length and a decreasedfibril diameter. The tensile mechanical properties of the collagen matrices also showed strain rate dependence. Such fundamental information regarding the 3-D microstructural-mechanical properties of the ECM and its component molecules are important to our overall understanding of cell-ECM interactions (e.g., mechanotransduction) and the development of novel strategies for tissue repair and replacement.


Integrating biogeochemistry with multiomic sequence information in a model oxygen minimum zone.
Microorganisms are the most abundant lifeform on Earth, mediating global fluxes of matter and energy. Over the past decade, high-throughput molecular techniques generating multiomic sequence information (DNA, mRNA, and protein) have transformed our perception of this microcosmos, conceptually linking microorganisms at the individual, population, and community levels to a wide range of ecosystem functions and services. Here, we develop a biogeochemical model that describes metabolic coupling along the redox gradient in Saanich Inlet-a seasonally anoxic fjord with biogeochemistry analogous to oxygen minimum zones (OMZs). The model reproduces measured biogeochemical process rates as well as DNA, mRNA, and protein concentration profiles across the redox gradient. Simulations make predictions about the role of ubiquitous OMZ microorganisms in mediating carbon, nitrogen, and sulfur cycling. For example, nitrite "leakage" during incomplete sulfide-driven denitrification by SUP05 Gammaproteobacteria is predicted to support inorganic carbon fixation and intense nitrogen loss via anaerobic ammonium oxidation. This coupling creates a metabolic niche for nitrous oxide reduction that completes denitrification by currently unidentified community members. These results quantitatively improve previous conceptual models describing microbial metabolic networks in OMZs. Beyond OMZ-specific predictions, model results indicate that geochemical fluxes are robust indicators of microbial community structure and reciprocally, that gene abundances and geochemical conditions largely determine gene expression patterns. The integration of real observational data, including geochemical profiles and process rate measurements as well as metagenomic, metatranscriptomic and metaproteomic sequence data, into a biogeochemical model, as shown here, enables holistic insight into the microbial metabolic network driving nutrient and energy flow at ecosystem scales.


Cryptococcus neoformans and cryptococcal glucuronoxylomannan, galactoxylomannan, and mannoprotein induce different levels of tumor necrosis factor alpha in human peripheral blood mononuclear cells.
Tumor necrosis factor alpha (TNF-alpha) release by peripheral blood mononuclear cells (PBMC) during disseminated infection by Cryptococcus neoformans may initiate and amplify the immune response of the host, leading to elimination of the fungus. The ability to induce TNF-alpha in PBMC by four clinical strains of C. neoformans, a laboratory strain (NIH 37), and the purified cryptococcal components glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins (MP1 and MP2) were investigated under different opsonic conditions. In the absence of serum, the levels of TNF-alpha induced by all strains and cryptococcal components were not above background levels. Normal human serum (NHS) enhanced TNF-alpha induction by whole cryptococci and the different cryptococcal components, with MP2 being the most potent TNF-alpha inducer. Inactivation of complement (HI NHS) almost abrogated the ability of whole cryptococci and the GXMs to induce TNF-alpha. In contrast, when MP1, MP2, and GalXM were incubated with HI NHS, 48, 71, and 44%, respectively, of the original TNF-alpha levels remained. MPs incubated with heat-inactivated immunoglobulin G (IgG)-depleted serum still induced 50% of the levels of TNF-alpha induced by components incubated with HI NHS. Both these sera contained the same very low levels of anti-MP IgG antibodies, indicating the opsonic effect of a heat-stable factor other than antibody. Two anti-CD14 monoclonal antibodies (60BCA and 3C10) inhibited the production of TNF-alpha induced by MP2. The results indicate that (i) induction of TNF-alpha by C. neoformans and GXMs strongly depends on complement, (ii) MP1 and MP2 induction of TNF-alpha is facilitated by a heat-stable serum factor other than Ig, and (iii) CD14 may be involved in the induction of TNF-alpha by MP2.


Effects of estradiol on glycemic and CNS neuronal activational responses to recurrent insulin-induced hypoglycemia in the ovariectomized female rat.
Recurrent insulin-induced hypoglycemia (RIIH) results in glucose counterregulatory dysfunction in men and male rodents. Intensified hypoglycemia in the latter coincides with diminished neuronal Fos expression in central metabolic regulatory structures, evidence that supports habituation of CNS-mediated compensatory motor outflow during re-exposure to this metabolic stress. In light of the evidence for counterregulatory resistance to precedent hypoglycemia in women, we utilized estradiol-treated ovariectomized (OVX) female rats to examine the hypothesis that this hormone regulates neural adaptability to recurring hypoglycemia. Groups of OVX rats were implanted with subcutaneous silastic capsules containing estradiol benzoate (E) or oil alone, and injected subcutaneously with one or four doses of the intermediate-acting insulin, Humulin NPH, one dose daily, or with diluent alone. Blood glucose levels were not altered by RIIH in E-implanted OVX animals, but were significantly decreased after four versus one insulin injection in the OVX+oil group. Mean numbers of Fos-immunoreactive (ir) neurons in the paraventricular nucleus hypothalamus (PVH), dorsomedial nucleus hypothalamus (DMH), and lateral hypothalamic area (LHA) were higher in both E- versus oil-implanted OVX rats injected with diluent only. Acute hypoglycemia significantly increased mean counts of Fos-ir-positive neurons in the PVH, DMH, and LHA, as well as the nucleus of the solitary tract (NTS) and area postrema (AP) in E- and oil-treated animals to an equivalent extent. OVX+E rats exhibited comparable numbers of Fos-positive neurons in the PVH, DMH, and LHA after one versus four insulin injections, whereas the numbers of labeled neurons in NTS and AP were increased or decreased, respectively, by RIIH. Oil-implanted OVX rats showed significantly diminished numbers of Fos-ir-positive neurons in each neural structure after repeated hypoglycemia. The present data demonstrate that estradiol sustains or enhances neuronal reactivity to recurring hypoglycemia in central metabolic structures, whereas hypoglycemic patterns of Fos expression in each site become habituated during RIIH in the absence of this steroid. The brain sites characterized here by estrogen-dependent maintenance of neuronal genomic reactivity to this substrate fuel imbalance may contain direct and/or indirect cellular targets for hormonal actions that prevent adaptation of CNS-controlled motor responses to this metabolic stress.


Immunoenzymometric assay for a small molecule,11-deoxycortisol, with attomole-range sensitivity employing an scFv-enzyme fusion protein and anti-idiotype antibodies.
To overcome the sensitivity limit in immunoassays for small molecules (haptens), we established a noncompetitive immunoenzymometric assay (IEMA) format that can detect attomole-range hapten molecules. We selected 11-deoxycortisol (11-DC; Mr 346.5), a corticosteroid serving a diagnostic index for pituitary-adrenal function, as a model target hapten. A fusion of a single-chain Fv fragment (scFv) specific for 11-DC and alkaline phosphatase (ALP) was generated for use as an enzyme-labeled antibody, instead of the conventional chemically linked enzyme-antibody conjugates. After binding reaction of 11-DC and fixed amounts of the fusion protein (scFv-ALP), the unbound fusion protein was removed by incubation with a mouse beta-type anti-idiotype antibody recognizing the scFv paratope. These complexes were captured by magnetic separation using anti-mouse IgG antibody-coated magnetic beads. Following magnetic sedimentation of the beads, immune complexes of scFv-ALP and 11-DC remained in the supernatant were further purified by capture on microtiter plates with immobilized alpha-type anti-idiotype antibody. As measured fluorometrically, ALP activity from bound immune complexes on the plates increased with increasing 11-DC, which is characteristic of a noncompetitive relationship. This IEMA afforded an extremely low detection limit (20 amol/assay), a very wide measurable range, and practical specificity. The plasma 11-DC levels determined for healthy subjects were validated as reliable.


Central hypoadrenocorticism associated with Rathke's cleft cyst.
Rathke's cleft cysts (RCCs) are non-neoplastic, sellar or suprasellar epithelium-lined cysts originating from Rathke's pouch in the pituitary gland. Patients with RCCs are usually asymptomatic, but some have only been identified when symptoms manifested in middle age. The characteristics of these patients during childhood or adolescence remains unknown. We describe an 18-year-old girl who had occasionally suffered from malicious fatigue in the morning since her early teens. Brain magnetic resonance imaging (MRI) revealed T1 hyperintense/T2 hypointense signals between the anterior and posterior pituitary glands, indicating the presence of RCC. Based on an authentic endocrinological evaluation, her adrenal function seemed normal; nevertheless, her serum cortisol level strangely dropped around noon. Furthermore, daily supplementation of oral hydrocortisone bizarrely suppressed ACTH secretion to below the detection range in the morning. These data appeared compatible with the presence of central adrenal dysfunction. We also review the literature for previously reported cases. In conclusion, the symptoms and endocrinological data for dysfunction of the hypothalamic pituitary system might be non-specific and vary among patients, especially in teenagers. Brain MRI and daily cortisol profiling in blood are key to obtaining a diagnosis of an impaired hypothalamic adrenal function due to RCC.


Perturbation of parentally biased gene expression during interspecific hybridization.
Interspecific hybridization often induces epigenetic remodeling that leads to transposon activation, gene expression changes, and loss of imprinting. These genomic changes can be deleterious and contribute to postzygotic hybrid incompatibility. In Arabidopsis, loss of genomic imprinting of PHERES1 and presumed failure of Polycomb Repressive Complex contributes to seed inviability observed in A. thaliana X A. arenosa interspecific hybrids. We used this species pair to further analyze the relationship between parentally biased gene expression and postzygotic hybrid incompatibility using two A. thaliana accessions, Col-0 and C24, with differential seed survival. We found that parentally biased expression was perturbed to a similar degree in both A. thaliana hybrids for PHERES1, HDG3, and six other normally paternally expressed genes. We propose that early genome remodeling and loss of imprinting of seed development genes induces lethality in both compatible and incompatible hybrids.


Ethnobotanical, Ethnopharmacological, and Phytochemical Studies of Myrtus communis Linn: A Popular Herb in Unani System of Medicine.
Myrtus communis L (Myrtaceae) is one of the popular drugs being used in the Unani system of phytomedicine since ancient Greece period. From time immemorial, different parts of this plant and essential oil have been used for a variety of purposes such as cosmetics (hair fall control), flavoring of food and drinks as well as extensive therapeutic purposes. Ethnobotanical information revealed that M communis L has been a folkloric repute for the treatment of several diseases like gastric ulcer, diarrhea, dysentery, cancer, rheumatism, hemorrhage, deep sinuses, leucorrhoea, hemorrhoid, inflammation, dyspepsia, anxiety, insomnia, diabetes, hypertension, pulmonary disorders, and skin diseases. Moreover, ethnopharmacological studies revealed that the plant is endowed with extensive pharmacological activities, including antimicrobial, antidiarrheal, antidiabetic, antispasmodic, vasodilator, antiulcer, antioxidant, anticancer, anxiolytic, sedative-hypnotic, and anti-inflammatory activities, among others. The plant has been known to contain phenolic acids, tannins, flavonoids, glycosides, and terpenes. The myrtle oil was also found to be rich in a variety of bioactive monoterpenes and sesquiterpenes with their derivatives. Most of these studies validate the aforementioned traditional claims of this medicinal plant. Further studies are needed to unravel other pharmacological activities of this plant in the long run.


Conservative surgery for adnexal abscess.
Twenty-eight women were treated with conservative surgery for adnexal abscesses over a six-year period (1968-74). The mean age was 29.9 +/- 8.9 years (SD) and mean parity 1.2 +/- 1.1. Indications for surgery included failure to respond to medical therapy (16 cases) and exploration of a pelvic mass of uncertain etiology (12). The mean admission-operation interval was 8.7 +/- 9.9 days. The mean total hospital stay was 23.1 +/- 14.7 days. The most common procedures were unilateral adnexectomy (13 cases), simple drainage (6) and bilateral medial ligation (4). The intraoperative complications (one fatal cardiac arrest, two bladder lacerations and one bowel laceration) did not appear to be related to the conservative nature of the surgery. The postoperative complications, wound sepsis (six cases) and fecal fistula (one case), might have occurred equally with more radical operations. Menstrual function was retained in all the surviving patients and the potential for pregnancy in 18 (62%). Extrapolating these data from unselected cases in a developing nation, it seems likely that conservative procedures would afford an acceptable option in well-selected, fully informed women undergoing surgery for adnexal abscess in developed countries.


Dopamine precursor depletion affects performance and confidence judgements when events are timed from an explicit, but not an implicit onset.
Dopamine affects processing of temporal information, but most previous work has tested its role in prospective tasks, where participants know in advance when the event to be timed starts. However, we are often exposed to events whose onset we do not know in advance. We can evaluate their duration after they have elapsed, but mechanisms underlying this ability are still elusive. Here we contrasted effects of acute phenylalanine and tyrosine depletion (APTD) on both forms of timing in healthy volunteers, in a within-subject, placebo-controlled design. Participants were presented with a disc moving around a circular path and asked to reproduce the duration of one full revolution and to judge their confidence in performance. The onset of the revolution was either known in advance (explicit onset) or revealed only at the end of the trial (implicit onset). We found that APTD shortened reproduced durations in the explicit onset task but had no effect on temporal performance in the implicit onset task. This dissociation is corroborated by effects of APTD on confidence judgements in the explicit task only. Our findings suggest that dopamine has a specific role in prospective encoding of temporal intervals, rather than the processing of temporal information in general.


Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes.
Inhibition of the iron-mediated generation of toxic oxygen species by polymorphonuclear leukocytes (PMN) might prevent oxidative damage and thus enhance phagocytic function of PMN. To investigate this point, we studied the effect of the specific iron chelator, deferoxamine, on the antibacterial function of PMN. PMN were incubated for 20 hr with various concentrations of deferoxamine at 37 degrees C in medium containing 0.54 microM endogenous iron. The cells were then washed, and the phagocytic cell function was assessed. The results were compared with those for control PMN preincubated for 20 hr without deferoxamine, and those of nonincubated PMN. Compared with that of control PMN, the uptake of radiolabeled Staphylococcus aureus by PMN treated with 1 microM-1 mM deferoxamine was, on average, 10%-20% higher. This effect was not observed when iron-saturated deferoxamine (DFO) was used. Bacterial uptake was similarly increased in nonpreincubated PMN or PMN preincubated for 20 hr at 4 degrees C instead of 37 degrees C. The intracellular killing capacity of both deferoxamine-treated and control PMN exceeded 90%. PMN incubated for 20 hr at 37 degrees C with DFO not only phagocytosed more bacteria than control cells, but were also capable of killing the greater number of bacteria ingested. This increased activity of deferoxamine-treated PMN was accompanied by enhanced generation of chemiluminescence and production of superoxide during phagocytosis of S. aureus. These findings indicate that deferoxamine may enhance the antibacterial activity of PMN by protecting the cells against damage by iron-mediated generation of toxic oxygen metabolites in resting PMN.


Statins inhibit iNOS-mediated microbicidal potential of activated monocyte-derived dendritic cells by an IFN-β-dependent mechanism.
Statins are prescribed to 25 million people worldwide for treating hypercholesterolemia and reducing the risk of cardiovascular diseases. However, the side effects of statins on immunity, and particularly on DC immunobiology, have not been analyzed in-depth. Here, we have investigated the impact of lovastatin treatment during monocyte differentiation into DCs on the responsiveness of the resulting monocyte-derived DCs (moDCs) to TLR-mediated activation. Lovastatin positively regulated TLR4 signaling in LPS-stimulated moDCs, leading to strong activation of p38 MAP-kinase paralleled by increased proinflammatory cytokine and IFN-β production. In contrast, lovastatin promoted negative regulation of IFN-β-mediated autocrine signaling through the IFN-αβ receptor, paralleled by low expression of the transcription factor IRF-1, leading to the inhibition of the enzymes iNOS and HO-1. Defective activation of iNOS/HO-1 resulted in limited cytoprotective capacity against ROS and reduced microbicidal potential. These data were validated using an in vivo model of Listeria monocytogenes infection, which revealed that iNOS activation by splenic inflammatory moDCs, specialized in NO and TNF-α production, was strongly reduced in lovastatin-treated, Listeria-infected mice. Statin treatment could have severe implications in immunity against pathogens due to defective iNOS/HO-1 metabolism activation in inflammatory moDCs that might lead to immune failure.


fs3.1: a major fruit shape QTL conserved in Capsicum.
fs3.1 is a major fruit shape (defined as the ratio of fruit length to fruit width) quantitative trait locus (QTL) originally detected in an intraspecific cross of Capsicum annuum between the blocky and elongated-fruited inbreds 'Maor' and 'Perennial', respectively. In addition to increasing fruit shape index, the 'Perennial' allele at fs3.1 increased fruit elongation and decreased fruit width and pericarp thickness. We verified the effect of fs3.1 in backcross inbred lines (BILs) derived from crossing 'Perennial' with 'Maor' and with a second blocky-type inbred line of C. annuum. To determine the effect of the fs3.1 region in additional Capsicum species, we constructed an advanced backcross population from the cross of 'Maor' and the oval-fruited Capsicum frutescens BG 2816 and an F2 of the introgression line IL 152 that contains an introgression of the fs3.1 region from Capsicum chinense PI 152225. QTLs for fruit shape, fruit width, and pericarp thickness, but not for fruit length, were detected in both crosses, indicating the conservation of the fs3.1 region as a QTL affecting fruit shape in pepper. We also tested tomato (Lycopersicon spp.) introgression lines containing the corresponding fs3.1 region from L. pennellii and L. hirsutum, but we did not detect a significant fruit shape QTL in these lines. The effect of fs3.1 on the growth of fruit dimensions varied with the genetic background. By measuring the length and width of ovaries and fruits of near-isogenic C. annuum lines that differ in fs3.1 during fruit development, we determined that fs3.1 controls shape predominantly by increasing the growth rate of the longitudinal axis in the first 2 weeks after pollination. However, in the crosses of C. annuum with C. frutescens and C. chinense, fs3.1 predominantly exerted its effect on the width dimension.


Evaluation of circulating CD4+CD25+ and liver-infiltrating Foxp3+ cells in HCV-associated liver disease.
In hepatitis C virus (HCV)-associated liver disease, the immune system is unable to clear the viral infection. Previous studies have raised the possibility of an involvement of regulatory T cells (Tregs). In this study, we analysed the peripheral blood from 30 patients with HCV-associated chronic liver disease and 20 healthy controls by flow cytometry for the evaluation of the Treg population [CD4⁺CD25hi forkhead box protein 3 (Foxp3)⁺], as well as the activated/effector CD4⁺ T cells (CD4⁺CD25low) and IFN-γ-secreting cells. We also analysed liver biopsies of the patients by immunohistochemical evaluation of Foxp3⁺ cells. Our results showed higher proportions of CD4⁺CD25low and IFN-γ⁺ cells in the patients than in the controls. By contrast, the proportions of peripheral CD4⁺CD25hi cells did not significantly differ. The 11 patients displaying Foxp3⁺ cells in the liver infiltrates showed significantly higher proportions of peripheral CD4⁺CD25low cells. Moreover, we found lower serum transaminase levels in the patients than in the controls, as shown by Foxp3⁺ immunohistochemistry, although these results were only statistically significant as regards alanine transaminase (ALT). In conclusion, these data suggest that the presence of Tregs infiltrating the liver is associated with high levels of activated/effector T cells in the peripheral blood and lower activity of hepatitis. Therefore, liver-infiltrating Tregs may play a role in limiting tissue damage and may thus support an effective immune response against HCV.


[Muscle carnitine deficiency: report of 8 cases with clinical, electromyographic, histochemical and biochemical studies].
We describe 8 patients with muscle carnitine deficiency, 7 males and 1 female, varying in age from 5 days to 64 years. Seven had decreased muscle strength and all had increased lipids droplets in the muscle biopsy. The symptoms began in the first days of life in three cases, in childhood in two, in adult life in two, while one case was free of symptoms at age 64 (heterozygote?). Some patients had difficulty chewing, dysphagia, hypotonia and splenomegaly; one patient had a fluctuating clinical course. All had elevated serum enzymes, mainly creatine-kinase. The electromyogram showed primary muscle involvement in one case, denervation in two, "mixed" features in two and was not done in three. The muscle biopsy, beside lipid storage, showed denervation in four, chronic myopathy in four and type II fiber atrophy in one. In two cases, histological findings suggested infantile spinal muscle atrophy. One patient appeared to have a systemic form of carnitine deficiency, with severe myocardial involvement and died of heart failure before treatment was initiated. A discussion about clinical findings, metabolism and therapeutic aspects of muscle carnitine deficiency is made.


Effect of Gut Microbiota Biotransformation on Dietary Tannins and Human Health Implications.
Tannins represent a heterogeneous group of high-molecular-weight polyphenols that are ubiquitous among plant families, especially in cereals, as well as in many fruits and vegetables. Hydrolysable and condensed tannins, in addition to phlorotannins from marine algae, are the main classes of these bioactive compounds. Despite their low bioavailability, tannins have many beneficial pharmacological effects, such as anti-inflammatory, antioxidant, antidiabetic, anticancer, and cardioprotective effects. Microbiota-mediated hydrolysis of tannins produces highly bioaccessible metabolites, which have been extensively studied and account for most of the health effects attributed to tannins. This review article summarises the effect of the human microbiota on the metabolism of different tannin groups and the expected health benefits that may be induced by such mutual interactions. Microbial metabolism of tannins yields highly bioaccessible microbial metabolites that account for most of the systemic effects of tannins. This article also uses explainable artificial intelligence to define the molecular signatures of gut-biotransformed tannin metabolites that are correlated with chemical and biological activity. An understanding of microbiota-tannin interactions, tannin metabolism-related phenotypes (metabotypes) and chemical tannin-metabolites motifs is of great importance for harnessing the biological effects of tannins for drug discovery and other health benefits.


Centrifugal dewatering of acid casein curd: effect of casein manufacturing and centrifugation variables on curd compression in a laboratory centrifuge.
Data relevant to curd compression in a horizontal, solid bowl decanter centrifuge have been obtained by studying the dewatering of acid casein curd in a batch laboratory centrifuge. Analysis of curd compression under centrifugal force predicts a moisture content gradient in the dewatered curd from a maximum at the curd-liquid interface to a minimum at the centrifuge bowl wall. This moisture content gradient was also measured experimentally, and its practical implications are discussed. Increases in centrifugal force, centrifugation time, and centrifugation temperature all caused a marked de crease in dewatered curd moisture content, whereas in creases in precipitation pH and maximum washing temperature caused a smaller decrease in dewatered curd moisture content.


The identification of a lipid-mobilizing factor from sheep midbrain.
The mass spectrum of a lipolytic substance from purified sheep midbrain extract indicated that it was isoprenaline, not N-n-propylnoradrenaline, noradrenaline or adrenaline. The identification of the lipid-mobilizing factor as isoprenaline was confirmed qualitatively by t.l.c. and g.l.c. and quantitatively by determination of its lipolytic activity and u.v. absorption and by fluorimetric determination of its catecholamine content.


Severity of foraminal lumbar stenosis and the relation to clinical symptoms and response to periradicular infiltration-introduction of the "melting sign".
Nerve root compression causing symptomatic radiculopathy can occur within the intervertebral foramen. Sagittal magnetic resonance imaging (MRI) sequences are reliable in detection of nerve root contact to intraforaminal disc material, but a clinically relevant classification of degree of contact is lacking. This study aimed to investigate a potential relation of amount of contact between intraforaminal disc material and nerve root to clinical findings and response after periradicular corticosteroid infiltration. A post hoc analysis of a prospective cohort was carried out. Patients who underwent computed tomography (CT)-guided periradicular corticosteroid infiltration (L1-L5) at our institution (January 2014 to May 2016) were included. The medical records and radiographic imaging were reviewed. T2-weighted MRI of the lumbar spine of patients with single-level symptomatic radiculopathy with (responders, n=28) or without (non-responders, n=14) pain relief after periradicular infiltration with corticosteroids were measured and compared by two independent readers to determine the amount of intraforaminal nerve root contact with the intervertebral disc ("melting" of the T2-hypointense signal). Pain relief was defined with a pain level decrease of >50% on a visual analogue scale and lack of pain relief with a pain level decrease of <25%, respectively. The amount of T2-hypointensity melting of disc and nerve root was categorized to 0%, 1%-25%, and over 25%. Reader one identified 0% T2-melting in none of the responders, 1%-25% melting in 13 patients (46.4%), 26%-50% in 15 of the 28 patients (53.6%) with pain relief after periradicular corticosteroid infiltration (responders), with a mean amount of T2-melting of 5.9±2.1 mm, whereas the non-responder group had 0% T2-melting in 2 patients (14.3%), 1%-25% T2-melting in 11 patients (78.6%), and 26%-50% in 1 patient (7.1%), with a mean amount of T2-melting of 2.6±1.9 mm (p<.05). Reader two identified 0% T2-melting in none, 1%-25% T2-melting in 15 (53.6%) patients, and 26%-50% in 13 of the 28 responders (46.4%), with mean amount of 6.3±1.9 mm. In the non-responder group 0% T2-melting was seen in 3 patients (21.4%), 1%-25% T2-melting in 10 patients (71.4%), and 26%-50% in 1 patient (7.1%), with a mean amount of T2-melting of 2.7±1.9 mm (p<.05). None of the MRI showed T2-melting in over 50% of the circumference of the intraforaminal nerve root. A T2-melting of >25% had a high specificity of 93% but a sensitivity of 50%, thus a positive likelihood ratio of 7.5, to identify those with a pain relief of more than 50% after infiltration. The amount of T2-melting of disc material and nerve root on sagittal MRI (>25%) predicts the amount of pain relief by periradicular infiltration in patients with intraforaminal nerve root irritation.


Rapid cardiothoracic ultrasound protocol for diagnosis of acute heart failure in the emergency department.
The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED). We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B-lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography.CaTUS had a sensitivity of 100% (95% confidence interval: 91.4-100%), a specificity of 95.8% (95% confidence interval: 84.6-99.3%), and an area under the curve of 0.979 for diagnosing AHF (P<0.001). The diagnostic accuracy of CaTUS was higher than of either E/e' or LUS alone. Adding the inferior vena cava index to CaTUS did not improve diagnostic accuracy. CaTUS seemed helpful also for differential diagnostics of dyspnea, mainly regarding pneumonias and pulmonary embolisms. CaTUS, combining E/e' and LUS, provided excellent accuracy for diagnosing AHF.


Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the dorsomedial pallium.
It has been suggested that cerebral cortex arealization relies on positional values imparted to early cortical neuroblasts by transcription factor genes expressed within the pallial field in graded ways. Foxg1, encoding for one of these factors, previously was reported to be necessary for basal ganglia morphogenesis, proper tuning of cortical neuronal differentiation rates, and the switching of cortical neuroblasts from early generation of primordial plexiform layer to late production of cortical plate. Being expressed along a rostral/lateral(high)- to-caudal/medial(low) gradient, Foxg1, moreover, could contribute to shaping the cortical areal profile as a repressor of caudomedial fates. We tested this prediction by a variety of approaches and found that it was correct. We found that overproduction of Cajal-Retzius neurons characterizing Foxg1-/- mutants does not arise specifically from blockage of laminar histogenetic progression of neocortical neuroblasts, as reported previously, but rather reflects lateral-to-medial repatterning of their cortical primordium. Even if lacking a neocortical plate, Foxg1-/- embryos give rise to structures, which, for molecular properties and birthdating profile, are highly reminiscent of hippocampal plate and dentate blade. Remarkably, in the absence of Foxg1, additional inactivation of the medial fates promoter Emx2, although not suppressing cortical specification, conversely rescues overproduction of Reelin(on) neurons.


Approximations for the arctangent function in efficient fringe pattern analysis.
In fringe pattern analyses, the computational burden of implementing the arctangent function over an entire phase map is not trivial, hindering it from being used in real-time measurements. For overcoming this problem, this paper presents a general method for approximating the arctangent function. The domain of the arctangent function is split into a sequence of intervals. For each interval, approximation polynomials are determined in the maximum-norm sense. By applying these polynomials instead of the standard arctangent function to the fringe analyses, the efficiencies of phase evaluations are improved significantly. The accuracies and simplicities of the approximations have been analyzed numerically, and their validities have also been verified by using experimental results.


Time Spent Walking and Risk of Diabetes in Japanese Adults: The Japan Public Health Center-Based Prospective Diabetes Study.
The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (<30 minutes, 30 minutes to <1 hour, 1 to <2 hours, or ≥2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined. In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of <30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of ≥2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02-1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed. Increased risk of diabetes was implied in those with time spent walking of <30 minutes per day, although the longitudinal analysis failed to show a significant result.


Chondromyxoid Fibroma of the Pelvis: Institutional Case Series With a Focus on Distinctive Features.
Chondromyxoid fibroma (CMF) is a relatively uncommon benign bone tumor of cartilaginous differentiation. The primary pitfall in the histopathologic diagnosis of CMF is confusion with a high-grade chondrosarcoma, owing to the atypical stellate and spindled cells set within a chondromyxoid background. CMF is particularly challenging to diagnose within the pelvis, where clinical suspicion for chondrosarcoma is high and benign lesions may grow to a large size to occupy the pelvic bones. In our practice, we noted this difficulty in several consecutive cases, especially when older patients presented with CMF within the pelvis. This prompted an institutional retrospective case review of all CMF within the pelvis. In 10 cases, we found overall that CMF of pelvis occurred in an older age range (mean age = 48.6 years), was larger in size (mean size = 6.0 cm), and showed a higher rate of soft tissue extension (50%) as compared with prior reports of nonpelvic CMF. Typical histologic features of CMF were seen in all cases; however, a high frequency of dystrophic calcification (50%) and necrosis (30%) was observed. Of interest, these aggregate demographic, radiologic, and histologic findings are all consistent with a benign neoplasm that has grown undetected within the pelvis over a long period of time. Recognition of these differences between pelvic CMF and tumors involving other sites will aid in avoiding misdiagnosis of this uncommon entity.


[Reliability of sonography in diagnosing liver metastases in breast and bronchial cancer. A retrospective comparison of physical examination, laboratory tests and liver scintigraphy].
To determine the accuracy of liver sonography in the diagnosis of liver metastases, the results of 99 patients with breast or lung cancer were compared with liver scintigraphy, physical examination, laboratory tests, histological examination and clinical follow-up. Liver sonography proved to be an accurate method to demonstrate or exclude liver metastases, with a sensitivity of 78.6% and a specificity of 90.0%. The highest accuracy was achieved if the sonographic examination of the liver was performed while there was a clinical suspicion of liver metastases and if compoundscan sonography was supplemented by real-time sonography.


The use of herpes virus induced dTk as a marker for serological and direct identification of herpes virus infection in man.
This report summarizes the essential features of a sensitive deoxythymidine kinase (dTk) assay, which can be used for the diagnosis of Herpes virus infections. A type specific antibody response towards the different Herpes virus dTk isozymes, the Herpes simplex virus (HSV) type 1, type 2, and Varicella Zoster virus (VZV), was found in human sera. The occurrence of dTk antibody in relation to complement fixing (cf) antibody and the state of infection, was found to differ between HSV and VZV. The VZV dTk antibody was only found in patients with Herpes Zoster, while most HSV cf positive individuals had HSV dTk antibody. Absence of dTk in HSV cf positive individuals was related to a "recent primary infection". The type specificity of the dTk isozymes makes these antigens suitable for typing of isolates, and this in combination with the sensitivity of the assay, made it possible to verify and type HSV infection by direct analysis of blister secrete without previous virus isolation. Such results can be obtained within five hours. Combined with conventional isolation procedures the dTk typing assay also detects dTk negative "therapy resistant" strains. The use of the dTk assay for diagnostic purposes is discussed.