Large scale depletion of the high-abundance proteins and analysis of middle- and low-abundance proteins in human liver proteome by multidimensional liquid chromatography.
An unbiased method for large-scale depletion of high-abundance proteins and identification of middle- or low-abundance proteins by multidimensional LC (MDLC) was demonstrated in this paper. At the protein level, the MDLC system, coupling the first dimensional strong cation exchange (SCX) chromatography with the second dimensional RP-HPLC, instead of immunoaffinity technology, was used to deplete high-abundance proteins. Sixty-two fractions from SCX were separated further by RPLC. UV absorption spectra were observed to differentiate high-abundance proteins from middle- or low-abundance proteins. After the depletion of high-abundance proteins, middle- or low-abundance proteins were enriched, digested, and separated by online 2D-micro-SCX/cRPLC. The eluted peptides were deposited on the MALDI target and detected by MALDI-TOF/TOF MS. This depletion strategy was applied to the proteome of the normal human liver (NHL) provided by the China Human Liver Proteome Project (CHLPP). In total, 58 high-abundance proteins were depleted in one experiment. The strategy increases greatly the number of identified proteins and around 1213 proteins were identified, which was about 2.7 times as that of the nondepletion method.


(N-Benzoyl-N-phenyl-hydroxy-laminato)carbon-yl(tri-phenyl-arsine)rhodium(I).
The mol-ecule of the title compound, [Rh(C13H10NO2){As(C6H5)3}(CO)] or [Rh(BPHA)(AsPh3)(CO)] (BPHA is the N-benzoyl-N-phenyl-hydroxy-laminate anion), comprises a bidentate N-benzoyl-N-phenyl-hydroxy-laminate anion coordinating through the O atoms to the soft Lewis acid, rhodium(I), and two monodentate ligands, viz. tri-phenyl-arsine and carbonyl. The resulting CO2As coordination environment around the central RhI atom is distorted square planar.=.


Health-related quality of life in older people with osteoporotic vertebral fractures: a systematic review and meta-analysis.
Health-related quality of life in osteoporotic patients with vertebral fracture is of increasing interest, but relevant studies have yielded debatable results. This systematic review and meta-analysis of 16 observational studies demonstrate a clear association between physical health status and presence of vertebral fracture after accounting for age. This meta-analysis was conducted to identify if there are any differences between physical and/or mental health-related quality of life (HRQoL) in older people with osteoporosis based on conventional T-score definitions and the presence or absence of vertebral fracture. A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the "grey" literature from 1950 to the end of April 2015. Search terms for vertebral fracture (VF) included VF, osteoporotic fracture, fragility fracture, and spinal fracture. Quality of life was searched using the following terms: quality of life, health-related quality of life, HRQoL, and QoL. Strict inclusion and exclusion criteria were used. The standardized mean difference (SMD) was calculated for each HRQoL domain by the difference in means between case and control groups divided by the pooled SD of participants. Sixteen eligible studies were identified involving 3131 men and women. There was evidence of publication bias and heterogeneity. The meta-analysis showed worse physical (SMD = 0.53, 95 % confidence interval (CI) 0.38 to 0.68; P < 0.001) and mental (SMD = 0.19, 95 % CI 0.05 to 0.33; P = 0.009) HRQoL in osteoporotic older people with vertebral fracture compared to those without fracture. Similar differences were observed for physical HRQoL in further analyses accounting for possible confounding effects of age. Sub-analysis to assess associations between number/severity of fractures and time since fracture was not possible due to small numbers of studies that accounted for age. Osteoporotic older people with vertebral fracture have worse physical HRQoL than osteoporotic older people without vertebral fracture, even after accounting for age differences.


Correction: A novel therapeutic approach to colorectal cancer in diabetes: role of metformin and rapamycin.
[This corrects the article DOI: 10.18632/oncotarget.26641.].


Metabolic liver disease in diabetes - From mechanisms to clinical trials.
Non-alcoholic fatty liver disease (NAFLD) comprises fatty liver (steatosis), non-alcoholic steatohepatitis (NASH) and fibrosis/cirrhosis and may lead to end-stage liver failure or hepatocellular carcinoma. NAFLD is tightly associated with the most frequent metabolic disorders, such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Both multisystem diseases share several common mechanisms. Alterations of tissue communications include excessive lipid and later cytokine release by dysfunctional adipose tissue, intestinal dysbiosis and ectopic fat deposition in skeletal muscle. On the hepatocellular level, this leads to insulin resistance due to abnormal lipid handling and mitochondrial function. Over time, cellular oxidative stress and activation of inflammatory pathways, again supported by multiorgan crosstalk, determine NAFLD progression. Recent studies show that particularly the severe insulin resistant diabetes (SIRD) subgroup (cluster) associates with NAFLD and its accelerated progression and increases the risk of diabetes-related cardiovascular and kidney diseases, underpinning the critical role of insulin resistance. Consequently, lifestyle modification and certain drug classes used to treat T2DM have demonstrated effectiveness for treating NAFLD, but also some novel therapeutic concepts may be beneficial for both NAFLD and T2DM. This review addresses the bidirectional relationship between mechanisms underlying T2DM and NAFLD, the relevance of novel biomarkers for improving the diagnostic modalities and the identification of subgroups at specific risk of disease progression. Also, the role of metabolism-related drugs in NAFLD is discussed in light of the recent clinical trials. Finally, this review highlights some challenges to be addressed by future studies on NAFLD in the context of T2DM.


A metabolic force for gene clustering.
Bacterial chromosomes frequently contain arrays of contiguous genes that group according to related metabolic roles. We propose that clustering of genes for metabolically related functions confers thermodynamic advantage to the organism based upon our protein immobility model (PIM) of intracellular diffusion. This thermodynamic effect provides the selection force argument that is missing from previous models of gene clustering. The PIM posits that clustered genes produce local clusters of enzymes in bacteria owing to the co-linearity of transcription and translation, and to the relative immobility of large proteins released into the cytosol. We maintain that the resulting physical proximity of enzymes for related pathway steps minimizes the steady state level of reaction step intermediates and thus conserves the energy and material required for rapid growth and maintenance. Support for this idea comes from in silico experiments using the PIM applied to a model metabolic pathway A --> B --> C. The metabolites A, B, and C are small molecules that diffuse freely in a cytosol crowded with macromolecules, whereas the large enzyme molecules, E1 and E2, tend to remain in the vicinity of their point of release. Modeling E1 as a source of B from A, and E2 as a sink for B, numerical experiments suggest that the steady state concentration of B in the cytosol increases approximately in proportion to the square of the distance of the E1 and E2 separation. A further model prediction is that the steady state concentration of B is influenced by the geometric effects of the spatial location and orientation of E1 relative to E2. These results suggest that: (i) gene clustering reduces the energy and material costs of enzyme reactions linked by metabolic intermediates; (ii) gene clusters near ori, the origin of replication, utilize the geometric effect to conserve free energy by further reducing the steady state concentration of the intermediate; (iii) gene organization on a chromosome influences the organism's capacity to accelerate into steady state growth and is, in turn, influenced by the abundance and frequency of access to nutrients.


Simulating of the measurement-device independent quantum key distribution with phase randomized general sources.
We present a model on the simulation of the measurement-device independent quantum key distribution (MDI-QKD) with phase randomized general sources. It can be used to predict experimental observations of a MDI-QKD with linear channel loss, simulating corresponding values for the gains, the error rates in different basis, and also the final key rates. Our model can be applicable to the MDI-QKDs with arbitrary probabilistic mixture of different photon states or using any coding schemes. Therefore, it is useful in characterizing and evaluating the performance of the MDI-QKD protocol, making it a valuable tool in studying the quantum key distributions.


Gene therapy access: Global challenges, opportunities, and views from Brazil, South Africa, and India.
Gene and cell therapies for a variety of life-limiting illnesses are under investigation, and a small number of commercial products have successfully obtained regulatory approval. The cost of treatment is high, and clinical studies evaluating safety and efficacy are performed predominately in high-income countries. We reviewed the current status of gene and cell therapies in low- and middle-income countries and highlighted the need and current barriers to access. The state of product development in Brazil, South Africa, and India is discussed, including lessons learned from American Society of Gene and Cell Therapy (ASGCT)-sponsored virtual symposia in each of these countries.


Monitoring of blood pressure among children and adolescents in a coastal province in China: results of a 2010 survey.
Several studies have provided ample evidence that hypertension in adults has its onset in childhood; children and adolescents with elevated blood pressure (BP) are more likely to become hypertensive adults. The present study examined the prevalence of relatively high BP among children and adolescents in Shandong, China. Data for this study were obtained from a large cross-sectional survey of schoolchildren carried out in 2010. A total of 38 860 students (19 481 boys and 19 379 girls) aged 7 to 17 years participated in this study. Relatively high BP status was defined as systolic blood pressure and/or diastolic blood pressure ≥95th percentile for age and gender. Shandong children had a high BP level, with the 50th percentiles of systolic and diastolic blood pressure of children and adolescents aged 7 to 17 years in Shandong being above the reference values for Chinese children and adolescents by 3 to 12 mm Hg and 3 to 7 mm Hg for boys, and by 3 to 6 mm Hg and 3 to 5 mmHg for girls, respectively. The overall prevalence of relatively high BP was 26.22% for boys and 20.27% for girls. There is a high prevalence of relatively high BP among children and adolescents in Shandong, China. It has become a threatening hazard to children and adolescents and should arouse special attention.


Characterization of the promoter region of the bovine SIX1 gene: Roles of MyoD, PAX7, CREB and MyoG.
The SIX1 gene belongs to the family of six homeodomain transcription factors (TFs), that regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and mediate skeletal muscle growth and regeneration. Previous studies have demonstrated that SIX1 is positively correlated with body measurement traits (BMTs). However, the transcriptional regulation of SIX1 remains unclear. In the present study, we determined that bovine SIX1 was highly expressed in the longissimus thoracis. To elucidate the molecular mechanisms involved in bovine SIX1 regulation, 2-kb of the 5' regulatory region were obtained. Sequence analysis identified neither a consensus TATA box nor a CCAAT box in the 5' flanking region of bovine SIX1. However, a CpG island was predicted in the region -235 to +658 relative to the transcriptional start site (TSS). An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with serial deletion constructs of the 5' flanking region, site-directed mutation and siRNA interference demonstrated that MyoD, PAX7 and CREB binding occur in region -689/-40 and play important roles in bovine SIX1 transcription. In addition, MyoG drives SIX1 transcription indirectly via the MEF3 motif. Taken together these interactions suggest a key functional role for SIX1 in mediating skeletal muscle growth in cattle.


Prognostic significance of tumor markers in T4a gastric cancer.
The clinical importance of preoperative tumor markers remain elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of AFP, CEA, CA19-9, and CA50 in T4a stage gastric cancer. Two hundred and seventy-three T4a gastric cancer patients who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. The correlation between tumor markers and clinicopathologic characteristics and prognostic value of preoperative tumor markers were investigated. Correlation analysis showed that AFP was associated with Borrmann type (P = 0.010); CEA with sex (P = 0.029), tumors site (P = 0.014), and N stage (P = 0.001); CA19-9 with age (P = 0.047), tumor site (P = 0.011), lymphovascular invasion (P = 0.004), and N stage (P = 0.000); CA50 with age (P = 0.017), tumor site (P = 0.004), tumor size (P = 0.014), and N stage (P = 0.000). Multivariate analysis showed that the positivity of preoperative CEA, CA19-9, and CA50 were major independent poor prognostic factors of patients with T4a stage gastric cancer. Preoperative serum tumor marker might be a candidate for the staging system in addition to conventional factors.


Activation of RNA polymerase II transcription by the specific DNA-binding protein LSF. Increased rate of binding of the basal promoter factor TFIIB.
While the components of the initiation complex at an RNA polymerase II basal promoter have been well characterized, few mechanistic studies have focused on how upstream DNA-binding, transcriptional activators influence protein assembly at the initiation site. Our analysis of basal transcription on both the simian virus 40 and adenovirus major late promoters demonstrates that two slow steps in initiation of transcription are the assembly of the general transcription factors TFIID and TFIIB onto the template DNA. On the simian virus 40 major late promoter, the rate of initiation complex formation is dramatically increased in the presence of the cellular transcriptional activator LSF. Direct analysis by band mobility shift assays demonstrates that LSF has no effect on the rate of binding, or the stability of TFIID on the promoter, predicting that LSF would not affect the template commitment step. Rather, kinetic analyses demonstrate that LSF reduces the lag in the rate of initiation complex formation attributable to the slow addition of TFIIB and suggest that LSF increases the rate of association of TFIIB with the committed template. In addition, LSF increases the total number of transcription complexes in long term assays, which is also consistent with LSF increasing the rate of association of TFIIB, where TFIIB is not saturating. These results indicate a mechanism for the activation of the initiation of RNA polymerase II transcription by one upstream activating protein, LSF. This mechanism may also be applicable to other activators that function in cases where limiting concentrations of TFIIB in the cell dictate slow binding of TFIIB.


Association between HLA class II locus and the susceptibility to Artemisia pollen-induced allergic rhinitis in Chinese population.
The aim of the study was to determine whether susceptibility or resistance to Artemisia pollen-induced allergic rhinitis was associated with HLA class II DQA1, DQB1 loci. Study design and setting Forty-one subjects with allergic rhinitis and 41 healthy controls from Beijing were genotyped at HLA class II DQA1, DQB1 alleles by polymerase chain reaction amplification with sequence-specific primers-based technique. The allele frequencies of HLA-DQA1*0201, DQB1*0602 were lower in patients with allergic rhinitis compared with the controls (24.39% versus 46.34%, P = 0.038; 4.88% versus 26.83%, P = 0.007), and the frequency of DQA1*0302 was higher among patients than the controls (58.54% versus 14.63%, P = 0.00004, Pc = 0.0004). HLA-DQA1 and -DQB1 genes may be involved in the development of Artemisia pollen-induced allergic rhinitis. HLA-DQA1*0201, DQB1*0602 alleles may be a protective factor and DQA1*0302 may be a susceptible factor for Artemisia pollen-induced allergic rhinitis.


Collagen type 1 retards tube formation by human microvascular endothelial cells in a fibrin matrix.
Angiogenesis, or the formation of new microvessels, is often encountered in pathological situations. A fibrinous exudate can often act as a temporary matrix for the ingrowth of these new microvessels. This matrix consists mainly of fibrin, but is mingled with other plasma components and interstitial collagen fibres. In vitro, capillary-like tube formation can be mimicked by exposing human microvascular endothelial cells (hMVECs), seeded on top of a three-dimensional fibrin matrix, to an angiogenic growth factor (e.g. fibroblast growth factor (FGF)-2) and the cytokine tumour necrosis factor (TNF)-alpha. Plasmin activity is required in this process. We investigated whether the angiogenic potential of hMVECs was altered by the presence of collagen. The addition of type I collagen to fibrin matrices dose-dependently inhibited tube-formation. Tube-formation in these fibrin/collagen matrices by hMVECs required matrix metalloprotease (MMP) activity, as well as plasmin activity. On a pure collagen type I matrix, hMVECs were not able to form tube-like structures in the matrix but formed sprouts. This sprouting required MMP activity and was, in contrast to the tube-like structures in a fibrin matrix, not influenced by hypoxia. These data indicate that the interaction between endothelial cells and different matrix components is of importance for the angiogenic potential of these cells.


Co-chairman's remarks: reverse genetics: directed modification of DNA for functional analysis.
The classic paradigm for identifying the genetic basis of a particular organism's properties proceeds from the phenotype to the gene, and thence to the molecular structures of the corresponding DNA, RNA and protein. 'Positional cloning' of disease genes and the molecular characterization of the responsible mutations (inappropriately referred to as reverse genetics, initially) exemplifies this approach. Now, the ability to clone, modify and test the biological activities of DNA segments provides a new approach, referred to as 'reverse genetics'. This paradigm begins with a segment of DNA whose molecular structure is known, and proceeds to explore the gene's contribution to the organism's phenotype; thus, the experimental path is from the gene as a nucleotide sequence to the corresponding phenotypic characteristic. Such a strategy follows from the ability to modify these sequences in highly directed and nearly unlimited ways, and to assess the phenotypic relevance of such alterations either in vitro, in cultured cells, or even in whole organisms. This approach permits the full panoply of molecular techniques to be used for creating uniquely altered structures and obviates the reliance on chance events as the source of mutations. As a consequence, the range of questions that can be studied is greatly expanded, and the information that is obtained is all the richer.


Two ligands may bind simultaneously to the muscarine receptor.
Competition between 3H-3-quinuclidinyl benzilate (2 and 18 nM) and varying concentrations of antagonists (4-N-methyl piperidinyl benzilate (4-NMPB), atropine, scopolamine and pirenzepine (0-1000 nM) and agonists (acetylcholine, carbamylcholine, oxotremorine and pilocarpine (0.10(-10) to 10(-2) M)) was studied. Inhibition of specific 3H-3-quinuclidinyl benzilate binding was evaluated by Dixon plots which for both competing agonists and antagonists showed deviations from linearity. The best nonlinear least square fit to the Dixon plots was offered by a hyperbola, parabola or a straight line, depending on the ligand used. The data support a model of equilibrium binding which assumes that 3H-3-quinuclidinyl benzilate and one competing ligand molecule may simultaneously bind to the receptor at high concentrations of the competing ligand.


Leveraging telemedicine to preserve pediatric global health missions in the era of COVID-19.
This paper outlines the use of a global telehealth program to leverage the potential of telehealth to not only 1) preserve the previous progress of our pediatric surgical airway global teaching mission, but also: 2) to provide rapid, international dissemination of information related to care of pediatric COVID-19 patients; 3) to virtually support the attainment of self-sufficiency of our host countries in relation to our teaching mission; and 4) to inspire host countries to be local champions for each other during the COVID-19 crisis.


The effect of the humoral immune system-derived bursal anti-steroidogenic peptide (BASP) on corticosteroid biosynthesis in avian, porcine and canine adrenal cortical cells.
Utilizing avian, porcine and canine adrenocortical cells, we have examined the effect of bursal anti-steroidogenic peptide (BASP) on adrenocorticotropin (ACTH) and dibutyryl cyclic AMP (DB-cAMP)-stimulated corticosteroid and cAMP formation. BASP significantly (P < 0.05) suppressed corticosteroid production from adrenocortical cells derived from chickens, pigs and dogs. BASP significantly increased cAMP formation (up to 10-fold) in a dose-related manner. These findings suggest that BASP structure and activity may be conserved between chicken, porcine and canine species.


Surface modification of PAMAM dendrimer improves its biocompatibility.
Modification of dendrimer surface groups is one of the methods available to obtain compounds characterized by reduced toxicity. This article reports results of preliminary biocompatibility studies of a modified polyamidoamine dendrimer of the fourth generation. Reaction with dimethyl itaconate resulted in transformation of surface amine groups into pyrrolidone derivatives. Interaction of the modified dendrimer with human serum albumin (HSA) was analyzed. The influence of the dendrimer on mouse neuroblastoma cell line viability and its hemolytic properties were also investigated. The binding constant between analyzed dendrimer and HSA was found to be equal to 1.2 × 10(5) ± 0.2 × 10(5) M(-1). Small changes in HSA secondary structure were observed. The analyzed dendrimer revealed minor toxic activity, as diminishment in cell viability was observed only for dendrimer concentrations higher than 2 mg/mL. Moreover, under the applied experimental conditions, no hemolytic activity was observed. Those observations point to the potential of the analyzed compound for further studies toward its applicability in nanomedicine.


Motion perception deficits in glaucomatous optic neuropathy.
The mechanisms mediating impaired motion perception in glaucoma were investigated. Direction discrimination thresholds for low (4.2 deg/sec) and high (12.5 deg/sec) velocity random-dot kinematograms were measured in controls and patients with glaucoma or ocular hypertension. Thresholds were elevated significantly in glaucoma patients and individual ocular hypertensives. Threshold elevations were not due to blur or pupil size. After compensating for motion reversals, high but not low velocity thresholds remained elevated. Only high velocity thresholds correlated with differential luminance sensitivity. A hypothesis that different mechanisms mediate glaucoma-induced deficits at high and low velocities is presented.


Usage patterns and 1-year outcomes with the TAXUS Liberté stent: results of the TAXUS OLYMPIA registry.
The TAXUS OLYMPIA registry is a prospective, global, post-approval program designed to collect clinical outcome data through 1 year from patients receiving the TAXUS Liberté paclitaxel-eluting stent in routine interventional cardiology practice. The thin-strut TAXUS Liberté stent has been studied in ongoing clinical trials with specific inclusion/exclusion criteria. Between September 2005 and April 2007, a total of 21,954 patients from 365 sites in 57 countries eligible to receive a TAXUS Liberté stent were enrolled in the TAXUS OLYMPIA registry. Baseline characteristics and procedure patterns were collected and clinical follow-up is available for 1 year. The primary endpoint was the composite cardiac event (cardiac death, MI, and reintervention of the target vessel) rate related to the TAXUS Liberté stent at 1 year. All cardiac events were monitored and all endpoints were independently adjudicated. Complex patients and lesions were prevalent, including: 27% medically-treated diabetes, 58% ACC/AHA type B2/C lesions, 32% multiple stenting, 13% long lesions (>28 mm), and 10% small vessels (<2.5 mm). At 1 year, the composite cardiac event rate was 4.4%, including 1.4% cardiac death, 1.0% MI, and 3.2% TVR. Stent thrombosis (ST, angiographically confirmed) occurred in 0.8% of patients, with 0.4% ST occurring >30 days postprocedure. The composite cardiac event rate related to the TAXUS Liberté stent was 3.8% at 1 year. Low 1-year cardiac event rates were reported with TAXUS Liberté in a broad spectrum of patients, thereby confirming the technical and clinical performance of this stent in a "real-world" setting.


Effects of shrimp shell powder on antibiotic resistance genes and the bacterial community during swine manure composting.
The present study compared the effects of adding shrimp shell powder (SSP) at four levels comprising 0% (CK), 5% (L), 10% (M), and 15% (H) on the abundance of antibiotic resistance genes (ARGs) and the bacterial community succession during swine manure composting. The relative abundances of 5/11 ARGs were reduced in CK, and 7/11 in H. Moreover, the removal rate was enhanced by adding SSP. Thus, H decreased the total abundance of ARGs by 32.68%, whereas CK increased it by 6.31%. Redundancy analysis indicated that mobile genetic elements (MGEs) (46.6%) and the bacterial community (31.1%) mainly explained the changes in ARGs. H enhanced the removal of MGEs, prolonged the thermophilic phase, stabilized copper and zinc, and retained nitrogen. LEfSe analysis and non-metric multidimensional scaling indicated that the bacterial community changed in the composting process, and it was optimized by H. The abundances of the potential bacterial co-hosts (such as Lactobacillus, Corynebacterium_1, and Ornithinicoccus) of ARGs and MGEs were lower and the decomposition of organic matter was higher in H compared with CK. Thus, composting with 15% SSP can reduce the risk of ARGs and improve the practical value for agronomic application.


[Quality of life of young patients with haemophilia in Europe].
Haemophilia, an inherited x-linked bleeding disorder, is a rare disease with comparable prevalence worldwide, which leads to early disability if untreated, and which, if treated via substitution of blood clotting factor, is associated with high treatment costs. Recent research has focused on bio-psychosocial consequences of treatment from the patient's perspective, in order to identify new treatment approaches, to quantify the patient benefit, and to compare haemophilia care across countries. For this, generic and disease-specific instruments have been developed and are currently being used in studies. The present paper describes clinical aspects of haemophilia as well as the assessment of quality of life and proceeds to introduce two recent studies on quality of life of children and adolescents with haemophilia in Europe. The HAEMO-QoL study investigated the quality of life of 339 children with haemophilia age 4 and above from six European countries. A total of 1,424 patients from 21 European countries participated in the ESCHQoL study, among these were 444 children aged 4 and above years. In both studies clinical data, information about health care and psychosocial determinants such as coping, life satisfaction and social support were assessed. Significant differences in quality of life between countries were found. Psychosocial determinants were associated with quality of life. Current analyses suggest that important determinants for quality of life are availability of factor concentrate from the clinical side and social support from the psychosocial side. The difference in quality of life across countries is a future major health-political challenge.


Imaging of Subdural Hematomas.
The imaging of subdural hematoma has evolved significantly. Computed tomography and MRI have supplanted other procedures and rendered most obsolete for the evaluation of intracranial pathology because of ease of use, tremendous soft tissue resolution, safety, and availability. Noncontrast computed tomography has become the accepted standard of care for the initial evaluation of patients with suspected subdural hematoma because of widespread availability, rapid acquisition time, and noninvasive nature. MRI offers important features in determining potential secondary causes of subdural hematoma, such as dural-based neoplasms.


Ultrafast giant magnetic cooling effect in ferromagnetic Co/Pt multilayers.
The magnetic cooling effect originates from a large change in entropy by the forced magnetization alignment, which has long been considered to be utilized as an alternative environment-friendly cooling technology compared to conventional refrigeration. However, an ultimate timescale of the magnetic cooling effect has never been studied yet. Here, we report that a giant magnetic cooling (up to 200 K) phenomenon exists in the Co/Pt nano-multilayers on a femtosecond timescale during the photoinduced demagnetization and remagnetization, where the disordered spins are more rapidly aligned, and thus magnetically cooled, by the external magnetic field via the lattice-spin interaction in the multilayer system. These findings were obtained by the extensive analysis of time-resolved magneto-optical responses with systematic variation of laser fluence as well as external field strength and direction. Ultrafast giant magnetic cooling observed in the present study can enable a new avenue to the realization of ultrafast magnetic devices.The forced alignment of magnetic moments leads to a large change in entropy, which can be used to reduce the temperature of a material. Here, the authors show that this magnetic cooling effect occurs on a femtosecond time scale in cobalt-platinum nano-multilayers.


IκBζ is a key driver in the development of psoriasis.
Psoriasis is a common immune-mediated, chronic, inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. Although TNFα- and IL-17A-targeting drugs have recently proven to be highly effective, the molecular mechanism underlying the pathogenesis of psoriasis remains poorly understood. We found that expression of the atypical IκB member IκB (inhibitor of NF-κB) ζ, a selective coactivator of particular NF-κB target genes, was strongly increased in skin of patients with psoriasis. Moreover, in human keratinocytes IκBζ was identified as a direct transcriptional activator of TNFα/IL-17A-inducible psoriasis-associated proteins. Using genetically modified mice, we found that imiquimod-induced psoriasis-like skin inflammation was completely absent in IκBζ-deficient mice, whereas skin inflammation was still inducible in IL-17A- and TNFα-deficient mice. IκBζ deficiency also conferred resistance against IL-23-induced psoriasis. In addition, local abrogation of IκBζ function by intradermal injection of IκBζ siRNA abolished psoriasis-like skin inflammation. Taken together, we identify IκBζ as a hitherto unknown key regulator of IL-17A-driven effects in psoriasis. Thus, targeting IκBζ could be a future strategy for treatment of psoriasis, and other inflammatory diseases for which IL-17 antagonists are currently tested in clinical trials.


Tectal plate gliomas: a review.
Tectal plate gliomas are generally benign neoplastic lesions arising in the brainstem which can, with local extension, obstruct the aqueduct of Sylvius and lead to hydrocephalus. Diagnosis is based on initial suspicion fostered by the presentation of an obstructive hydrocephalus followed by physical exam which may potentially reveal indications of pyramidal tract dysfunction or cranial nerve palsies. MRI studies reveal a characteristic well-circumscribed, isodense or hypodense mass on T1-weighted images, with hyperdensity on T2 imaging. Yet current radiological methods insufficiently distinguish tectal plate gliomas from brainstem tumors or gliomas in the neighboring structures, and a definitive diagnosis requires biopsy and histopathological analysis. Management is planned according to the degree of associated signs and symptoms, and may range from diligent observation and periodic screening for advancing tumor development, to cerebrospinal fluid shunting in an effort to resolve obstructive hydrocephalus, to radio- and chemotherapy. A wide range of minimally invasive approaches using endoscopy is available for the neurosurgeon, including endoscopic third ventriculostomy and endoscopic aqueductoplasty.


Telemedicine in the treatment of gestational diabetes: An observational cohort study on pregnancy outcomes and maternal satisfaction.
Gestational diabetes treatment requires several outpatient consultations from diagnosis until delivery in order to prevent hyperglycaemia, which is associated with maternal and fetal complications. There is limited evidence in the literature about telemedicine superiority in improving pregnancy outcomes for women with gestational diabetes. The primary aim of the study was to evaluate maternal and fetal outcomes, while the secondary aim was to estimate the degree of satisfaction with gestational diabetes treatment, comparing telemedicine versus outpatient care. This observational cohort study involved 60 consecutive women with gestational diabetes treated at the Diabetology Unit of Ferrara: 27 were followed up through a weekly remote control method (telemedicine group) and 33 in ambulatory clinics every 2 or 3 weeks (conventional group). After giving birth, 56 women responded to the modified Oxford Maternity Diabetes Treatment Satisfaction Questionnaire to assess their satisfaction with diabetes care. No statistically significant differences were found in most of the maternal and neonatal parameters evaluated in both groups. The questionnaire scores were positive in all areas investigated. Telemedicine follow-up made women feel more controlled (p = 0.045) and fit better with their lifestyle (p = 0.005). It also emerged that almost all women treated with telemedicine would recommend this method to a relative or a friend. Telemedicine follow-up proved to be safe both in terms of metabolic control and pregnancy outcomes; furthermore, it significantly decreased the need for outpatient consultations and increased women's satisfaction. Studying the impact of telemedicine is also necessary, considering the current difficulties associated with the Sars-COV-2 pandemic.


Early pregnancy triglycerides and not fructosamine are associated with birth weight (with foetal sexual dimorphism).
We evaluated whether maternal triglycerides (TGs) or fructosamine (measured in early pregnancy) predominantly contribute to birth weight (BW), in a foetal sexual dimorphism. Analysis of data from the Amsterdam Born Children and their Development cohort study (total n = 3514). Maternal nonfasting TGs and fructosamine were determined in early gestation (median 13 weeks). Multivariable linear regression analysis was used to determine whether maternal TGs or fructosamine was associated with BW-small for gestational age (SGA)-large for gestational age (LGA) and whether it was sex-dependent. With each 1 mmol/L increase in TGs, BW increased significantly by 81.7 g. This increase was larger with boys (107.3 g; 95% CI 66-148) than girls (60.5 g; 95% CI 23.6-97.4). No association was found with fructosamine. When including different covariates (gestational age at blood sampling, total duration of pregnancy, maternal height, age, parity, ethnicity, educational level, smoking, alcohol, and pre-pregnancy BMI), 29% of the variance in BW can be explained. Adding fructosamine to this model gave no added value in predicting BW, in contrast to adding TGs (R2 raised from 0.292 to 0.299, p < .001). The odds of a newborn LGA with higher maternal TG were increased (OR 1.6, 95% CI 1.3-2.0), in contrast to fructosamine. Maternal TGs were more dominant (compared to fructosamine) in its association with BW (measured in early physiological pregnancy) and more prominently present when carrying a male foetus. These remarkable observations warrant more future research, especially in obese patients at risk for gestational diabetes.


A phenol amine molecule from Salinivenus iranica acts as the inhibitor of cancer stem cells in breast cancer cell lines.
In recent years, the anticancer properties of metabolites from halophilic microorganisms have received a lot of attention. Twenty-nine halophilic bacterial strains were selected from a culture collection to test the effects of their supernatant metabolites on stem cell-like properties of six human cancer cell lines. Human fibroblasts were used as normal control. Sphere and colony formation assay were done to assess the stem cell-like properties. invasion and migration assay, and tumor development in mice model were done to assess the anti-tumorigenesis effect in vitro and in vivo. The metabolites from Salinivenus iranica demonstrated the most potent cytotoxic effect on breast cancer cell lines (IC50 = 100 µg/mL) among all strains, with no effect on normal cells. In MDA-MB-231 cells, the supernatant metabolites enhanced both early and late apoptosis (approximately 9.5% and 48.8%, respectively) and decreased the sphere and colony formation ability of breast cancer cells. Furthermore, after intratumor injection of metabolites, tumors developed in the mice models reduced dramatically, associated with increased pro-apoptotic caspase-3 expression. The purified cytotoxic molecule, a phenol amine with a molecular weight of 1961.73 Dalton (IC50 = 1 µg/mL), downregulated pluripotency gene SRY-Box Transcription Factor 2 (SOX-2) expression in breast cancer cells which is associated with resistance to conventional anticancer treatment. In conclusion, we suggested that the phenol amine molecule from Salinivenus iranica could be a potential anti-breast cancer component.


The Trauma and Injury Severity Score (TRISS) revised.
The Trauma and Injury Severity Score (TRISS) remains the most commonly used tool for benchmarking trauma fatality outcome. Recently, it was demonstrated that the predictive power of TRISS could be substantially improved by re-classifying the component variables and treating the variable categories nominally. This study aims to develop revised TRISS models using re-classified variables, to assess these models' predictive performances against existing TRISS models, and to identify and recommend a preferred TRISS model. Revised TRISS models for blunt and penetrating injury mechanism were developed on an adult (aged 15 years) sample from the National Trauma Data Bank National Sample Project (NSP), using 5-category variable classifications and weighted logistic regression. Their predictive performances were then assessed against existing TRISS models on the unweighted NSP, National Trauma Data Bank (NTDB), and New Zealand Database (NZDB) samples using area under the Receiver Operating Characteristic curve (AUC) and Bayesian Information Criterion (BIC) statistics. The weighted NSP sample included 1,124,001 adults with blunt or penetrating injury mechanism events and known discharge status, of whom 1,061,709 (94.5%) survived to discharge. Complete information for all TRISS variables was available for 896,212 (79.7%). Revised TRISS models that included main-effects and two-factor interaction terms had superior AUC and BIC statistics to main effects models and existing TRISS models for patients with complete data in NSP, NTDB and NZDB samples. Predictive performance decreased as the number of variables with missing values included within revised TRISS models increased, but model performances generally remained superior to existing TRISS models. Revised TRISS models had importantly improved predictive capacities over existing TRISS models. Additionally, they were easily computed, utilised only those variables already collected for existing TRISS models, and could be applied and produce meaningful survival probabilities when one or more of the predictor variables contained missing values. The preferred revised TRISS model included main-effects and two-factor interaction terms and allowed for missing values in all predictor variables. A strong case exists for replacing existing TRISS models in trauma scoring systems benchmarking software with this preferred revised TRISS model.


An analysis of the origin of an early medieval group of individuals from Gródek based on the analysis of stable oxygen isotopes.
In the early Middle Ages, the region of the Cherven Towns, which is now located on both sides of the Polish-Ukrainian border, was fiercely contested by Slavs in the process of forming their early states. The main objective of the present study was to investigate the homogeneity of an early medieval population uncovered in that region, in the town of Gródek on the Bug River, by screening for non-local individuals. The origin of the studied skeletons was ascertained using analysis of oxygen isotopes in the phosphates isolated from bone tissue. In this paper, the isotope ratios obtained for samples collected from 62 human skeletons were compared to the background δ(18)O (in precipitation water) from the regions of Kraków (south-eastern Poland), Lviv (western Ukraine), Brest (western Belarus), and Gródek, as well as to the ratios determined for the animals coexisting with the studied population. Proportions of oxygen isotopes obtained for all the studied individuals were found to be similar to those for the precipitation water and animals, which indicates the absence of bone fragments of individuals originating in other regions.


Tuberous sclerosis complex with multiple intracranial aneurysms in an infant.
Tuberous sclerosis complex is a protean, genetically determined disease that may involve any organ or tissue and lead to a great number of signs and clinical features. Occlusive vascular disease and aneurysms of the cerebral and visceral arteries were described in these patients. We report on an 8-month-old boy who manifested tuberous sclerosis complex with multiple intracranial aneurysms involving the internal carotid artery and middle cerebral artery. The unusual features of our case favor the concepts of the presence of an arterial dysplasia in tuberous sclerosis complex, and of developmental defects as the cause of intracranial aneurysms.


Soil depth exerts a stronger impact on microbial communities and the sulfur biological cycle than salinity in salinized soils.
The distribution of microbial communities along salinity gradients in the surface layer of salinized soils has been widely studied. However, it is unknown whether microbial communities exhibit similar distribution patterns in surface and deep soils. Additionally, the relationship between soil depth, salinity, and sulfur metabolism remains unclear. Herein, bulk soils in the surface (S, 5-10 cm) and deep (D, 20-25 cm) layers from high- and low-salinity soils were analyzed using metagenomic and physicochemical analyses. Soil depth was significantly correlated to the concentration of sulfur compounds in the soil and exerted a stronger effect than salinity. Non-metric multidimensional scaling analysis revealed significant differences in microbial community structure with varying soil depths and salinities. However, soil depth clearly influenced microbial community abundance, homogeneity, and diversity, while salinity had a limited effect on microbial abundance. Archaea and bacteria were enriched in the surface and deep soils, respectively. Gene abundance analysis revealed significant differences in the abundance of sulfur-related genes at different soil depths. The abundance of sulfur oxidation genes was lower in deep soil than in surface soil, whereas the abundance of other sulfur-related genes showed the opposite trend. Redundancy analysis (RDA) showed that environmental factors and sulfur compounds have a significant impact on sulfur metabolism genes, with sulfide significantly affecting low-salinity soils in the surface and deep layers, whereas salinity and sulfane sulfur had a greater correlation with high-salinity soils. Correlation analysis further showed that Euryarchaeota clustered with Bacteroidetes and Balneolaeota, while Proteobacteria clustered with many phyla, such as Acidobacteria. Various sulfur metabolism genes were widely distributed in both clusters. Our results indicate that microorganisms actively participate in the sulfur cycle in saline soils and that soil depth can affect these processes and the structure of microbial communities to a greater extent than soil salinity.


The metabolic and cardiovascular effects of intravenous infusion of glucose or intralipid in normal humans.
This study was performed to determine whether the administration of intravenous fluids, isosmolar with plasma, activated the sympathetic nervous system, thereby causing changes in cardiovascular variables. On four separate occasions, six young, healthy men were studied for 30 min before and, for 40 min after a 60 min period of either (a) intravenous infusion of 500 ml of 5% dextrose, (b) intravenous infusion of 500 ml of a mixture of 10% Intralipid and saline (154 mmol NaCl 1(-1)), (c) intravenous infusion of 500 ml of saline (154 mmol NaCl 1(-1)) or (d) no intravenous infusion. Venous plasma noradrenaline and adrenaline concentrations did not change significantly during any of these interventions. The venous plasma insulin level rose during infusion of 5% dextrose (p<0.001). The respiratory exchange ratio rose during the dextrose infusion and fell during the infusion of the Intralipid and saline mixture (p<0.01). Hand and calf blood flows and vascular resistances were not significantly affected by any procedure. Similar, small, changes in heart rate, arterial blood pressure, metabolic rate, core temperature and mean skin temperature were observed during the four protocols. The provision of small amounts of metabolic substrate, as either glucose or fat, led to rapid changes in fuel utilisation. However, under the conditions of the present experiments, there was no evidence of activation of the sympathetic nervous system.


Colorectal adenoma characteristics as predictors of recurrence.
The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians. This study was designed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence. The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial. At both baseline and three-year examinations, the characteristics of adenomas were recorded according to a standardized protocol. The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size > or = 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia), and proximal and distal recurrence. A three-year recurrence was observed in 122 patients (22.1 percent), and more than one-half of them had recurrent adenomas on the proximal colon. After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence. In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence (5.3; 95 percent confidence interval, 2.7-10.3), proximal recurrence (8.5; 95 percent confidence interval, 4.1-18), and advanced adenoma recurrence (5.5; 95 percent confidence interval, 2.4-12.6). Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon. The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas.


Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development.
Members of the Lef/Tcf family of HMG-box transcription factors mediate the response to Wnt as part of the canonical Wnt signaling cascade. Positive and negative cofactors, including beta-catenin, CtBP, and Smad3, regulate the activity of Lef/Tcf transcription complexes. Interaction of Lef/Tcfs with beta-catenin results in target gene activation or repression, depending on the context. Here, we report the cloning of a novel chick Tcf-1 splice variant and of a partial cDNA for chick Tcf-3. We describe their expression patterns during early development and have compared them with the expression profiles of Lef-1 and beta-catenin. We found restricted patterns during gastrulation, neurulation, somitogenesis, and early limb development. beta-catenin and Lef/Tcf expression did not always coincide, indicating developmental contexts in which Lef/Tcf proteins may interact with other cofactors and conversely, the areas in which beta-catenin may interact with other coregulators, or be involved in regulating adhesive properties of cells.


Location specificity of plantar cutaneous reflexes involving lower limb muscles in humans.
It is known that cutaneous reflexes in human hand muscles show strong location-specificity dependent on the digit stimulated. We hypothesized that in lower leg muscles the cutaneous reflex following tactile sensation of the plantar surface of the foot is also organized in a location-specific manner. The purpose of the present study was to test this hypothesis. Middle latency reflexes (approximately 70-110 ms, MLR) following non-noxious electrical stimulation to different locations on the plantar foot were recorded from 16 neurologically intact volunteers (15 males, 1 female). Electrical stimulation was given to the fore-medial (f-M), fore-lateral (f-L) and heel (HL) regions of the plantar surface of the right foot while the subjects performed isometric dorsiflexion (tibialis anterior, TA), plantarflexion (soleus, Sol and medial gastrocnemius, MG), eversion (peroneus longus, PL) and knee extension (vastus lateralis, VL) while sitting and standing. In the Sol and MG, an excitatory response was observed following HL stimulation, which was switched to an inhibitory response following f-M or f-L stimulation (P < 0.001). A reciprocal pattern in contrast to Sol was observed in the TA. In the PL, MLR exhibited significant excitation following both f-L and HL stimulation, which, however, was switched to an inhibitory response following f-M stimulation (P < 0.001). Moderate inhibition of the MLR was seen in the VL for all stimulated positions. Systematic stimulation along the lateral side of the plantar foot demonstrated that the reflex reversal occurred around the middle of the plantar foot in the Sol and TA. In all muscles tested, the slope of the regression line between the magnitude of the MLR and background electromyographic activity significantly decreased during standing compared with sitting except for the PL following f-L simulation. These results suggest that reflex effects from cutaneous nerves in the plantar foot onto the motoneurons innervating the lower leg muscles are organized in a highly topographic manner in humans. The organization of these reflexes may play an important role in the alteration of limb loading and/or ground contact in response to tactile sensation of the plantar foot while sitting and standing.


ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose-results after 3 months' follow-up.
Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.


Gammaproteobacterial diazotrophs and nifH gene expression in surface waters of the South Pacific Ocean.
In addition to the cyanobacterial N2-fixers (diazotrophs), there is a high nifH gene diversity of non-cyanobacterial groups present in marine environments, yet quantitative information about these groups is scarce. N2 fixation potential (nifH gene expression), diversity and distributions of the uncultivated diazotroph phylotype γ-24774A11, a putative gammaproteobacterium, were investigated in the western South Pacific Ocean. γ-24774A11 gene copies correlated positively with diazotrophic cyanobacteria, temperature, dissolved organic carbon and ambient O2 saturation, and negatively with depth, chlorophyll a and nutrients, suggesting that carbon supply, access to light or inhibitory effects of DIN may control γ-24774A11 abundances. Maximum nifH gene-copy abundance was 2 × 10(4) l(-1), two orders of magnitude less than that for diazotrophic cyanobacteria, while the median γ-24774A11 abundance, 8 × 10(2) l(-1), was greater than that for the UCYN-A cyanobacteria, suggesting a more homogeneous distribution in surface waters. The abundance of nifH transcripts by γ-24774A11 was greater during the night than during the day, and the transcripts generally ranged from 0-7%, but were up to 26% of all nifH transcripts at each station. The ubiquitous presence and low variability of γ-24774A11 abundances across tropical and subtropical oceans, combined with the consistent nifH expression reported in this study, suggest that γ-24774A11 could be one of the most important heterotrophic (or photoheterotrophic) diazotrophs and may need to be considered in future N budget estimates and models.


Choroidal vascular changes after encircling scleral buckling for rhegmatogenous retinal detachment.
There is an ongoing debate on whether encircling scleral buckling (SB) procedure for the treatment of rhegmatogenous retinal detachment (RRD) may cause an impairment in choroidal blood flow. The aim of this study was to compare choroidal vascularity index (CVI) and subfoveal choroidal thickness (CT) between eyes that had undergone encircling SB with unoperated fellow eyes (FEs). Thirty patients treated with encircling SB for unilateral RRD were included. Demographic and clinical characteristics as well as enhanced depth imaging-optical coherence tomography scans were retrospectively collected. Images were binarised using ImageJ software, total choroidal area along with luminal and stromal area (respectively, TCA, LA and SA) were segmented and the CVI was computed as the ratio of LA/TCA. In addition, CT was evaluated. The mean follow-up interval between surgery and examination was 25.5 ± 16.8 months. Choroidal thickness, TCA, LA and SA were significantly increased in the operated eyes compared to FEs (respectively, 271.7 ± 78.0 µm vs. 238.5 ± 83.4, P = 0.001; 1.804 ± 0.491 mm2 vs. 1.616 ± 0.496, P = 0.001; 1.199 ± 0.333 mm2 vs. 1.067 ± 0.337, P < 0.001 and 0.605 ± 0.171 mm2 vs. 0.550 ± 0.171, P = 0.001). Conversely, CVI did not significantly differ between the two groups (66.4 ± 3.6 vs. 65.9 ± 3.2, P = 0.490). In conclusion, eyes treated with encircling SB for RRD presented increased LA, SA and CT compared with FEs, but showed no difference in CVI.


Strong Bonds Made Weak: Towards the General Utility of Amides as Synthetic Modules.
Breaking good: The amide bond is widely recognized as the strongest bond among the carboxylic acid derivatives. Therefore, the potential of amides to serve as synthetic building blocks has remained mostly untapped thus far. This Highlight describes a recent breakthrough that enables the catalytic conversion of amides into esters for the first time.


Predicting adjuvant endocrine therapy initiation and adherence among older women with early-stage breast cancer.
The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, estrogen receptor positive (ER +) breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast conserving surgery followed by adjuvant endocrine therapy (AET) alone. However, most patients in this population still undergo RT in part because AET adherence is low. We sought to develop a predictive model for AET initiation and adherence in order to improve decision-making with respect to RT omission. Women ages 70 and older with early-stage, ER + BC were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidities, socioeconomic measures, prescription medications, and demographics were collected as potential predictors. Bivariate analysis was performed to identify factors associated with AET initiation and adherence. Stepwise selection of significant predictors was used to develop logistic regression classifiers for initiation and adherence. Model performance was evaluated using the c-statistic and other measures. 11,037 patients met inclusion criteria. Within the cohort, 8703 (78.9%) patients initiated AET and 6685 (60.6%) were adherent to AET over 1 year. Bivariate predictors of AET initiation were similar to predictors of adherence. The best AET initiation and adherence classifiers were poorly predictive with c-statistics of 0.65 and 0.60, respectively. The best models in the present study were poorly predictive, demonstrating that the reasons for initiation and adherence to AET are complex and individual to the patient, and therefore difficult to predict. Initiation and adherence to AET are important factors in decision-making regarding whether or not to forgo adjuvant RT. In order to better formulate treatment plans for this population, future work should focus on improving individual prediction of AET initiation and adherence.


Experimental study on microstructure characteristics of saturated remolded cohesive soil during consolidation.
In this paper, drained consolidation tests of saturated remolded cohesive soil were carried out at different loading rates, and the samples at different loading stages were measured by nuclear magnetic resonance (NMR) testing. Through qualitative analysis of the relationship between the transverse relaxation time T2, peak area and porosity, the deformation micro-response of the saturated remolded cohesive soil was studied. The results showed that the transverse relaxation time T2 of the saturated remolded cohesive soil samples during the initial stage consisted of two spectral peaks, representing pores with large and small pore diameters, respectively. As loading progressed, the pore diameters in each sample group gradually shifted to smaller sizes, and the final form of the T2 spectrum was unimodal, in which the pores became denser and more uniform. In the initial stage of loading, the T2 spectrum of the soil sample with faster loading showed no obvious change trend due to the influence of drainage lag. After a sufficiently long dead load time, the final shape of the T2 spectrum was very similar regardless of loading rate, indicating that the loading rate only affected the intermediate state of the soil sample, and the final state was determined by the initial state of the sample. At the same time, after a certain dead load time, the changes in pore diameter were no longer obvious, indicating that the flowing fluid in the pore was drained and that drainage consolidation was complete. According to the positive correlation between the loading rate and maximum pore pressure, a boundary rate was obtained. We could reasonably infer that if the controlled loading rate was less than this value, drainage consolidation was complete in the main consolidation stage.


Small conductance calcium-activated potassium channels and nitric oxide/cGMP pathway mediate cardioprotective effects of Croton urucurana Baill. In hypertensive rats.
Croton urucurana Baill. (Euphorbiaceae), popularly known as 'sangue de dragão' is a Brazilian species widely used in traditional medicine for cardiovascular ailments. To investigate the cardiovascular effects of the C. urucurana extract in spontaneously hypertensive rats (SHRs). Leaves from C. urucurana were collected and morphoanatomically characterized. The ethanol-soluble fraction (ESCU) was obtained and analyzed by LC-DAD-MS. Using female Wistar rats we investigated the acute toxicity of ESCU. Then, SHRs (six months old) received vehicle, hydrochlorothiazide (25 mg/kg), or ESCU (30, 100, 300 mg/kg) for 28 days. At the beginning and at the end of treatments, urine samples were obtained to assess renal function. At the end of the trial period, the blood pressure, mesenteric vascular beds (MVBs) reactivity, and electrocardiographic profile were evaluated. Serum angiotensin-converting enzyme activity, as well as urea, creatinine, sodium, potassium, nitrite, malondialdehyde, nitrotyrosine, and aldosterone levels were determined. Relative organ weights and histopathological analysis were performed. Finally, the cardiac function on a Langendorff system, as well as the molecular mechanisms involved in the vasodilator effects of ESCU in MVBs were also investigated. The compounds annotated from ESCU by LC-DAD-MS included mainly phenylpropanoid derivatives, alkaloids, O-glycosylated megastigmanes, glycosylated flavonoids, flavan-3-ols, and others, such as quercetin O-deoxyhexosyl-hexoside, magnoflorine, reticuline, and taspine. None of the animals showed any signs of toxicity. Male SHRs treated only with the vehicle showed important cardiovascular changes, including a reduction in renal function, increase in serum oxidative stress, and hemodynamic, electrocardiographic, and morphological changes typical of hypertensive disease. Moreover, parameters of cardiac function, including left ventricular developed pressure, peak rate of contraction, peak rate of relaxation, and the rate pressure product were significantly altered, showing a significant impairment of ventricular function. All ESCU-doses presented a significant cardioprotective effect in SHRs rats. The 28-day treatment normalized the hemodynamic, electrocardiographic, morphological, and renal impairments, as well as reversed the changes in ventricular function induced by hypertension. In MVBs with an intact endothelium, ESCU (0.1, 0.3, and 1 mg) dose-dependently induced vasodilation. Endothelium removal or the inhibition of nitric oxide synthase prevented the vasodilatory effect of ESCU. Perfusion with a physiological saline solution that contained KCl, tetraethylammonium, or apamin also abolished the vasodilatory effect of ESCU. Prolonged ESCU-treatment showed significant cardioprotective effects in SHRs. Moreover, the data showed the role of nitric oxide and calcium-activated small conductance potassium channels in the cardiovascular effects of ESCU.


Biochemical studies on Francisella tularensis RelA in (p)ppGpp biosynthesis.
The bacterial stringent response is induced by nutrient deprivation and is mediated by enzymes of the RSH (RelA/SpoT homologue; RelA, (p)ppGpp synthetase I; SpoT, (p)ppGpp synthetase II) superfamily that control concentrations of the 'alarmones' (p)ppGpp (guanosine penta- or tetra-phosphate). This regulatory pathway is present in the vast majority of pathogens and has been proposed as a potential anti-bacterial target. Current understanding of RelA-mediated responses is based on biochemical studies using Escherichia coli as a model. In comparison, the Francisella tularensis RelA sequence contains a truncated regulatory C-terminal region and an unusual synthetase motif (EXSD). Biochemical analysis of F. tularensis RelA showed the similarities and differences of this enzyme compared with the model RelA from Escherichia coli. Purification of the enzyme yielded a stable dimer capable of reaching concentrations of 10 mg/ml. In contrast with other enzymes from the RelA/SpoT homologue superfamily, activity assays with F. tularensis RelA demonstrate a high degree of specificity for GTP as a pyrophosphate acceptor, with no measurable turnover for GDP. Steady state kinetic analysis of F. tularensis RelA gave saturation activity curves that best fitted a sigmoidal function. This kinetic profile can result from allosteric regulation and further measurements with potential allosteric regulators demonstrated activation by ppGpp (5',3'-dibisphosphate guanosine) with an EC50 of 60±1.9 μM. Activation of F. tularensis RelA by stalled ribosomal complexes formed with ribosomes purified from E. coli MRE600 was observed, but interestingly, significantly weaker activation with ribosomes isolated from Francisella philomiragia.


Transcriptome profiling of grass carp (Ctenopharyngodon idellus) infected with Aeromonas hydrophila.
Aeromonas hydrophila is the causative pathogen of intestinal hemorrhage which has caused great economic loss in grass carp aquaculture. In order to understand the immunological response of grass carp to infection by A. hydrophila, the transcriptomic profiles of the spleens from infected and non-infected grass carp groups were obtained using HiSeq™ 2500 (Illumina). An average of 63 million clean reads per library was obtained, and approximately 80% of these genes were successfully mapped to the reference genome. A total of 1591 up-regulated and 530 down-regulated genes were identified. Eight immune-related categories involving 105 differently expressed genes were scrutinized. 16 of the differently expressed genes involving immune response were further validated by qRT-PCR. Our results provide valuable information for further analysis of the mechanisms of grass carp defense against A. hydrophila invasion.


New method for the determination of metolachlor and buprofezin in natural water using orthophthalaldehyde by thermochemically-induced fluorescence derivatization (TIFD).
Herbicide metolachlor (MET) and insecticide buprofezin (BUP) were determined in natural waters by means of a newly-developed, simple and sensitive thermochemically-induced fluorescence derivatization (TIFD) method. The TIFD approach is based on the thermolysis transformation of naturally non-fluorescent pesticides into fluorescent complex O-phthalaldehyde-thermoproduct(s) in water at 70°C for MET and at 80°C for BUP. The TIFD method was optimized with respect to the temperature, pH, complex formation kinetic and pesticides concentrations. The limit of detection (LOD=0.8ngmL(-1) for MET and 3.0ngmL(-1) for BUP) and quantification (LOQ=2.6ngmL(-1) for MET and 9.5 ngmL(-1) for BUP) values were low, and the relative standard deviation (RSD) values were small (between 1.2% and 1.8%), which indicates a good analytical sensitivity and a great repeatability of TIFD method. Recovery studies were performed on spiked well, sea and draining waters samples collected in the Niayes area by using the solid phase extraction (SPE) procedure. Satisfactory recovery results (84-118%) were obtained for the determination of MET and BUP in these natural waters.


Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients.
Maturation and differentiation of B-cells are driven by T-cells' help through IL-21/STAT3 axis in GC centers or through extrafollicular pathways, in a T-independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27(-) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID.


Ratiometric visualization of lysosomal pH fluctuations during autophagy by two-photon carbonized polymer dots-based probe.
Monitoring the pH variation in lysosomes is very conducive to studying the autophagy process, and fluorescent ratiometric pH nanoprobes with inherent lysosome targeting ability are highly desirable. Here, a carbonized polymer dots-based pH probe (oAB-CPDs) was developed by self-condensation of o-aminobenzaldehyde and further carbonization at low temperature. The obtained oAB-CPDs display improved performance in pH sensing, including robust photostability, intrinsic lysosome-targeting ability, self-referenced ratiometric response, desirable two-photon-sensitized fluorescence property, and high selectivity. With the suitable pKa value of 5.89, the as-prepared nanoprobe was successfully applied to monitor the variation of lysosomal pH in HeLa cells. Moreover, the occurrence that lysosomal pH decreased during both starvation-induced and rapamycin-induced autophagy was observed by using oAB-CPDs as fluorescence probe. We believe that nanoprobe oAB-CPDs can work as a useful tool for visualizing autophagy in living cells.


Visual receptive field properties in the posterior suprasylvian cortex of the cat: a comparison between the areas PMLS and PLLS.
Receptive field (RF) properties of single units were examined in two visual areas in the cat's postero-medial and postero-lateral suprasylvian cortex (PMLS/PLLS). Electrophysiological recordings were made in the paralyzed and anesthetized preparation in corresponding regions of the medial and lateral banks of the lateral suprasylvian sulcus (LS). In both areas, cell samples were obtained from within the same range of A/P co-ordinates. In both samples, cells responded best to moving stimuli, had large RF's, and did not differ with respect to the distributions of their ocular dominance. Binocularity was equally high, but units in PLLS showed significantly less binocular summation. Cells in both areas preferred high velocities, and a high percentage was direction selective, with directions up and away from the vertical meridian being most common. While in PMLS the preferred direction of a unit usually could be classified into a "radial" vs a "circular" category when RF position was taken into account, this was not possible in PLLS. Units in PLLS also had significantly higher spontaneous activity, higher optimal velocity, and larger RF sizes. In PLLS the investigation of background-foreground interactions revealed a large variety of phase-dependent responses. This is in contrast to the clear preponderance of in-phase inhibition and antiphase facilitation effects in PMLS. The results indicate important differences of RF properties for the two areas, but do not yet suggest a clear functional differentiation. These differences reflect in some respects the RF properties of cells in the structures that provide the main afferents to the two areas.


Brief Report: Predictors of Relapse for Patients With Dextromethorphan Dependence.
The recreational use of dextromethorphan (DXM) triggers dependence. The pattern and clinical predictors of relapse are unclear. Here, we retrospectively analyzed the clinical information of 28 patients with DXM dependence (20 males and 8 females). The mean age at admission was 25.89 years (standard deviation [SD] = 7.84), and the average duration of DXM abuse was 24.96 months (SD = 17.40). The relapse rates at 1 month, 3 months, 6 months, and 1 year were 7.14%, 25%, 71.43%, and 89.29%, respectively. Depression and anxiety status at baseline were positive predictors of relapse (r = -.539, P = .006, R2 = 0.290; r = -.449, P = .024, R2 = 0.202, respectively). Our results suggest that patients with DXM dependence are at high risk of relapse and that measuring affective disturbance is important for predicting the outcomes of their treatment. This study first identified a high relapse rate among patients with DXM dependence and found that the baseline depression and anxiety status was correlated with the time length of relapse. These findings not only warn us of the vulnerability of DXM-dependent relapse but also reveal the importance of measuring affective disturbance in relapse prevention. (Am J Addict 2020;00:00-00).


Hysterical symptoms in ophthalmology.
Ophthalmologic symptoms are often not sufficiently accounted for by organic pathology. The complaints of these patients have been labeled hysterical, psychogenic, non-organic, or functional. The psychiatric nosology in this area may be the most confusing in the whole field of clinical medicine. The Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) offers a classification designed to reduce non-empirical concepts and ideology to a minimum. On this background, we discuss the hysterical symptoms encountered in clinical ophthalmology with special emphasis on psychogenic amblyopia and blepharospasm. Motor symptoms are commonly not of psychogenic origin. It is suggested that ophthalmologists are most likely to treat patients with psychogenic symptoms, using suggestion, patience, and reassurance. Few patients require psychiatric consultation and a specific psychiatric therapy. The association of hysteria with organic brain disease and the issue of symptom lateralization are briefly discussed. Eventually, we reject the psychoanalytic approach and suggest that the concept of abnormal illness behavior and the neurobiological models involving corticofugal inhibition, primitive reflex mechanisms, and an attention disturbance, serve best to understand the nature of the phenomenon hysteria.


Endoplasmic reticulum stress promotes endometrial fibrosis through the TGF-β/SMAD pathway.
Intrauterine adhesion (IUA) is one of the main causes of female infertility. This study reveals that endoplasmic reticulum stress activation upregulates the TGF-β/SMAD pathway to induce epithelial-mesenchymal transition and promote endometrial fibrosis in an IUA model. IUA is a common gynecological disease and is a leading cause of female infertility. Mechanical or infectious damage to the endometrial basal layer can lead to endometrial fibrosis, which is the most common cause of IUA. Endoplasmic reticulum stress (ERS), the transforming growth factor beta signaling pathway (TGF-β/SMAD) and epithelial-mesenchymal transition (EMT) are important factors promoting endometrial fibrosis. The purpose of this study was to determine the up- and downstream regulatory relationships of the above three in the process of endometrial fibrosis. The rat IUA model was induced by double injury method and prophylactic injection of the ERS inhibitor 4-phenylbutyric acid (4-PBA) was given in vivo. The ERS activator tunicamycin and the TGF-β/SMAD pathway inhibitor A 83-01 were used in human endometrial epithelial cells (HEECs) in vitro. Masson's trichrome, Sirius red staining, immunohistochemistry, immunofluorescence and Western blot analyses were used to determine ERS, TGF-β/SMAD pathway, EMT and fibrosis markers in the uterine tissue and HEECs of the different treatment groups. In animal experiments, ERS and the TGF-β/SMAD pathway had been activated and EMT occurred in an in vivo model of IUA but was suppressed in animals treated with prophylactic 4-PBA. In in vitro experiments, tunicamycin-treated HEECs had increased the activation of ERS, the abundance of TGF-β/SMAD pathway and fibrosis markers while EMT occurred, but the TGF-β/SMAD pathway and EMT were significantly inhibited in the tunicamycin+A 83-01 group. Our data suggest that increased ERS can induce EMT and promote endometrial fibrosis through the TGF-β/SMAD pathway.


Opening of the closed water area and consequent changes of ²²⁸Ra/²²⁶Ra activity ratios in coastal lagoon Nakaumi, southwest Japan.
In Lake Nakaumi, the second largest coastal lagoon in Japan, artificially closed (Honjyo) area, which was left untouched for 28 years, was partly opened in May, 2009. (228)Ra/(226)Ra ratio of waters in Honjyo area and Lake Nakaumi showed a well-tuned seasonal variation exhibiting high value in summer. After the opening event, however, the (228)Ra/(226)Ra ratios in the Honjyo water showed an unclear seasonal variation in both surface and deep water. This opening event caused the change of active movement of lake and marine water.


GABA, glutamate and excitatory-inhibitory ratios measured using short-TE STEAM MRS at 7-Tesla: Effects of macromolecule basis sets and baseline parameters.
Macromolecules (MMs) affect the precision and accuracy of neurochemical quantification in magnetic resonance spectroscopy. A measured MM basis is increasingly used in LCModel analysis combined with a spline baseline, whose stiffness is controlled by a parameter named DKNTMN. The effects of measured MM basis and DKNTMN were investigated. Twenty-six healthy subjects were prospectively enrolled and scanned twice using a short echo-time Stimulated Echo Acquisition Mode (STEAM) at 7-T. Using LCModel, analyses were conducted using the simulated MM basis (MMsim) with DKNTMN 0.15 and an MM basis measured inhouse (MMmeas) with DKNTMN of 0.15, 0.30, 0.60 and 1.00. Cramér-Rao lower bound (CRLB) and the concentrations of gamma-aminobutyric acid (GABA), glutamate and excitatory-inhibitory ratio (EIR), in addition to MMs were statistically analyzed. Measurement stability was evaluated using coefficient of variation (CV). CRLBs of GABA were significantly lower when using MMsim than MMmeas; those of glutamate were 2-3. GABA concentrations were significantly higher in the analysis using MMsim than MMmeas where concentrations were significantly higher with DKNTMN of 0.15 or 0.30 than 0.60 or 1.00. Difference in glutamate concentration was not significant. EIRs showed the same difference as in GABA depending on the DKNTMN values. CVs between test-retest scans were relatively stable for glutamate but became larger as DKNTMN increased for GABA and EIR. Neurochemical quantification depends on the parameters of the basis sets used for fitting. Analysis using MMmeas with DKNTMN of 0.30 conformed best to previous studies and is recommended.


Sex-based differences in outcomes after lower extremity bypass for chronic limb-threatening ischemia.
Lower extremity bypass surgery is an effective treatment option for patients with chronic limb-threatening ischemia (CLTI). Recent studies have suggested that sex-based differences may impact patient outcomes following lower extremity revascularization, however, results have been inconsistent. In this multicenter analysis, we retrospectively identified all infrainguinal bypass procedures performed for CLTI from 2002 to 2021. Patients were separated into two groups based on sex. Primary outcomes were major limb amputation and reintervention for graft patency. Of 843 bypasses performed over the study period, 347 (41.2%) patients were female. Racial/ethnic distribution and medical comorbidities were similar across sex groups. Surgical indications and operative details were also similar between groups, including conduit type (49.9% autogenous), bypass target (65.4% infrageniculate), and concurrent endarterectomy (38.9%). Female and male patients had similar hospital length of stay (6 days [4-9] vs 6 days [4-9]), hospital readmission (25.6% vs 25.0%), and postoperative complications (p=NS each). Female patients had higher major amputation rates (10.1% vs 6.3%, p=0.04) after one year, whereas reintervention rates were similar between groups (26.2% vs 24.6%, p=NS). After accounting for patient factors, female sex (odds ratio [OR] 1.02 [1.00-1.04]), infrageniculate target (OR 1.02 [1.00-1.04]), and bypass for tissue loss (OR 1.02 [1.00-1.04]) were associated with major amputation after bypass (p<0.05 each). Female sex is associated with a small but significant increase major amputation after lower extremity bypass surgery for CLTI, despite similar clinical presentation, medical comorbidities, and operative details. These data support the increasingly recognized sex disparities in peripheral arterial disease.


Litters of Various-Sized Mummies (LVSM) and Stillborns after Porcine Reproductive and Respiratory Syndrome Virus Type 1 Infection-A Case Report.
Diverse origins and causes are described for papyraceous mummifications of porcine foetuses, but the porcine reproductive and respiratory syndrome virus (PRRSV) is not one of them. In contrast, PRRSV is unlikely to cause mid-term placental transmission but may cause late-term abortions and weakness of piglets. This case report describes a sudden occurrence of mummified foetuses of various sizes and stillborns and delayed birth (>115 days) in more than 50% of sows from one farrowing batch, while newborn piglets were mostly vital. Neither increased embryonic death nor infertility was reported. Three litters with mummies, autolysed piglets and stillborn piglets were investigated, and infections with porcine parvoviruses, porcine teschoviruses, porcine circoviruses, encephalomyocarditis virus, Leptospira spp. and Chlamydia spp. were excluded. Instead, high viral loads of PRRSV were detected in the thymus pools of piglets at all developmental stages, even in piglets with a crown-rump length between 80 and 150 mm, suggesting a potential mid-term in utero transmission of the virus. Genomic regions encoding structural proteins (ORF2-7) of the virus were sequenced and identified the virulent PRRSV-1 strain AUT15-33 as the closest relative. This case report confirms the diversity of PRRSV and its potential involvement in foetal death in mid-gestation.


Preparation of two types of silver-doped fluorescent carbon dots and determination of their antibacterial properties.
The preparation and performance of doped antibacterial carbon dots (CDs) have been the research hotspot. In this paper, we report the preparation of two blue light-emitting silver-doped CDs, CD-1 and CD-2, through one- and two-step routes, respectively, by using polyethyleneimine, citric acid, and AgNO3 as raw materials. Both CDs exhibited excellent and broad-spectrum activity against gram-positive bacteria, gram-negative bacteria, and fungi. We compared the emission wavelength, surface group, particle size, chargeability, and element content of the two CDs through various characterization methods. CD-2 exhibiting longer emission wavelength, larger particle size, and higher silver content displayed higher antibacterial activity against microorganisms than CD-1. On the other hand, CDs exhibited varying antibacterial properties against different microorganisms because of differences in the cell wall structure of gram-positive bacteria (peptidoglycan), gram-negative bacteria (lipopolysaccharides), and fungi (chitin). Based on scanning electron microscopy observations, circular dichroism spectroscopy and agarose gel electrophoresis, we speculate that CDs exert antibacterial activity mainly through membrane disruption and their effect on intracellular DNA and proteins. At the same time, CDs have multicolor imaging capabilities of Staphylococcus aureus. The antibacterial activity and versatility of bioimaging make them more potential antibacterial agents than traditional agents.


The moderating effect of cultural intelligence between nurses' relationship conflict and teamwork.
To determine if there is a moderating effect of cultural intelligence between the conflict of nursing relationships and teamwork. Relationship conflicts that exist in the nursing teamwork cannot be ignored. It would lead to poor teamwork and impact on patients' poor outcomes. In the meantime, cultural intelligence has been proven that people who have a higher cultural intelligence can do better at the work. The sample included 550 clinic nurses from five different hospitals in Shanghai. The Cultural Intelligence Scale, the Relationship Conflict Scale, and the Nursing Teamwork Survey Scale were used to investigate. Through the Johnson-Neyman method and SPSS Process Macro, the moderating effect of cultural intelligence was analysed. The findings showed that cultural intelligence was founded to be significant (b = 2.03, p < 0.01). When the cultural intelligence score is greater than or equal to 90.8, the relationship conflict between nurses will not affect teamwork. The findings of this study may provide data to improve nurses' performance in team cooperation. Nursing managers should pay attention to the construction of the nurse's cultural intelligence. Nursing managers should guide nurses in daily work to continuously develop their own cultural intelligence. Enable nurses to effectively transfer social skills from one culture to another, and improve teamwork skills.


Ornithophily in the subtribe Maxillariinae (Orchidaceae) proven with a case study of Ornithidium fulgens in Guatemala.
Ornithophily has been long speculated to occur in the subtribe Maxillariinae (Orchidaceae), relying either solely on micromorphological analyses or scarce field observations of undefined species. In Guatemala we were able to observe regular visits of the azure-crowned hummingbirds feeding on flowers of Ornithidium fulgens. These observations have led us to investigation of floral attractants by means of scanning and transmission microscopy, histochemical and chemical analyses (GC-MS). Conducted investigation revealed that the epidermis of basal protuberance of column-foot has features proving the secretory activity and that secreted nectar is sucrose-dominant. Slight secretion on the middle part of the lip is puzzling. The presence of other potential pollinators has not been reported. Based on the results of this study, we confirmed that the flowers of O. fulgens meet all criteria of ornithophily and thus that the hypothesis about bird pollination in the subtribe Maxillariinae is proven. The presented results confirm that the previously described floral features predicting the bird pollination in this group are justified. This strengthens the theory about floral adaptations to different pollinators and gives valid reasons to consider species with flowers with a certain set of traits as ornithophilous, even in the absence of the pollination observation.


Attitudes of patients to randomised clinical trials of cancer therapy.
The aim of this study was to test an instrument which might be useful for doctors in explaining the randomisation procedure to an individual patient. The sample comprised 323 patients with cancer attending for out-patient appointments and/or chemotherapy treatment in two major cancer centres in the U.K. 315 patients completed a self-report questionnaire--The Attitudes to Randomised Trials Questionnaire (ARTQ). The results show that the majority of subjects 287 (91.1%) believe that patients should be asked to take part in medical research, but only 242 (76.8%) would be prepared to take part in a study comparing two treatments. If treatment was randomised, only 141 (44.8%) would agree to participate. When given further information about the randomisation procedure, 119 (68.4%) of the 174 (55.2%) who initially said 'no' to randomisation or who were unsure, would change their minds and take part in a trial. The ARTQ discriminated between three categories of patient with the following prevailing attitudes: (a) those who seem comfortable with the concept of randomisation; (b) those with some concerns, who with fuller explanation are prepared to consider randomisation; and (c) those firmly against randomisation and participation in trials whatever information is provided. Prior knowledge of patients' attitudes might assist communication about trials and encourage more doctors to approach eligible patients.


Autorenal transplantation in the treatment of renovascular hypertension.
Autorenal transplantation was performed on 32 renal units including three bilateral transplants, in 29 renovascular hypertensive patients. Aortoarteritis in 18, fibromuscular dysplasia in six, and atherosclerosis in five were the causative renal arterial lesions. Young patients with severe or uncontrolled hypertension but with functioning kidneys were selected for this procedure. Follow-up varied from one to seven years. Twenty-two patients were cured of hypertension, four showed improvement and in three the transplanted kidneys failed to function due to vascular thrombosis postoperatively. There was no death in the series.


Sulfated proteoglycans and sulfated proteins in guinea pig megakaryocytes and platelets in vivo. Relevance to megakaryocyte maturation and platelet activation.
This study has examined changes in proteoglycan synthesis during megakaryocyte maturation in vivo. Guinea pigs were injected with Na235SO4, and megakaryocytes and platelets were isolated from 3 h to 5 days later. The proteoglycans and other sulfated molecules in both cells were characterized at each time point by gel filtration, ion-exchange chromatography, gel electrophoresis, and chemical and enzymatic digestions. Two populations of chondroitin 6-sulfate proteoglycans were found by DEAE-Sephacel chromatography. The major fraction was eluted with 4 M guanidine hydrochloride and the minor fraction with 4 M guanidine HCl, 2% Triton X-100. The Kav of the major proteoglycan peak in the platelets at 1 day after injection was 0.18-0.20 on Sepharose CL-6B and decreased gradually to 0.12 by 3 days, when proteoglycan radioactivity per cell was maximal. The peak for megakaryocyte proteoglycans at 3 h was broad, with Kav = 0.1-0.2. The appearance of different portions of the proteoglycan peak in platelets coincided with their disappearance from megakaryocytes. Proteoglycan size was a function of glycosaminoglycan chain length. The proteoglycans eluted with Triton X-100 from DEAE-Sephacel (Kav = 0.04-0.07 on Sepharose CL-6B) were not labeled in platelets until 2 days after injection. Our data suggest that megakaryocytes synthesize different-sized chondroitin sulfate proteoglycans at different stages of development. The proteoglycans of the major fraction were released from platelets in response to thrombin, and a small amount was released by ADP. The proteoglycans of the Triton X-100 eluate were not released by thrombin or ADP. About 20% of the sulfate radioactivity was incorporated into molecules that appear to be sulfated proteins and were not released by thrombin or ADP.


Sonochemical preparation of SbSI gel.
A novel sonochemical method for direct preparation of nanocrystalline antimony sulfoiodide (SbSI) has been established. The SbSI gel was synthesized using elemental Sb, S and I in the presence of ethanol under ultrasonic irradiation (35 kHz, 2 W/cm2) at 50 degrees C for 2 h. The products were characterized by using techniques such as powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED), and optical diffuse reflection spectroscopy (DRS). The SEM and HRTEM investigations exhibit that the as-prepared samples are made up of large quantity nanowires with diameters of about 10-50 nm and lengths reaching up to several micrometers and single-crystalline in nature.


The Purification and Characterization of Exosomes from Macrophages.
Macrophages play an essential role in diverse biological processes, from the immune response to inflammatory and neurodegenerative disorders, to various cancers. A macrophage subpopulation, known as tumor-associated macrophages (TAMs), has been shown to promote tumorigenesis, metastasis, and immune escape of cancer cells. Some of the pro-tumorigenic effects of TAMs are mediated via the secretion of nano-vesicles (exosomes) from macrophages to neighboring cells. In this chapter, we describe peritoneal macrophage isolation methods, polarization of TAMs, and purification and characterization of macrophage-derived exosomes.


Evidence for a juvenile hormone receptor involved in protein synthesis in Drosophila melanogaster.
The larval fat body of newly eclosed adults of Drosophila melanogaster was found to contain a single major binding protein specific for juvenile hormone (JH). Binding to this protein was saturable, of high affinity, and specific for JH III. The protein has a subunit molecular weight (Mr) of 85,000, as determined by photoaffinity labeling. The same or similar JH-binding protein was found in larval fat body and cuticle of third instar larvae and in male accessory glands and heads of newly eclosed adults. It was not found in several other tissues in adults. Male accessory gland cytosol from wild-type flies was found to contain a single binder with a dissociation constant (KD) of 6.7 nM for JH III; a binder in similar preparations from the methoprene-tolerant (Met) mutant had a KD value 6-fold higher. JH III stimulated protein synthesis in glands cultured in vitro, but this effect was reduced in Met flies as compared to wild-type flies, establishing a correlation between JH binding and biological activity of the hormone. In addition, glandular protein accumulation during the first 2 days of adult development was less in Met flies than in wild-type flies. These results strongly suggest that the binding protein we have identified mediates this JH effect in male accessory glands and thus is acting as a JH receptor.


Properties of growth and molecular profiles of rat progenitor cells from ciliary epithelium.
Recent studies have demonstrated that multipotent retinal stem or progenitor cells can be isolated from the ciliary epithelium (CE) of the eye using a neurosphere culture. In this study, we investigated the properties of growth and differentiation, and molecular profiles of rat adult ciliary epithelium (CE)-derived retinal progenitors and forebrain (FB) derived neurospheres. Under clonogenic culture conditions, we found that the CE-derived neurospheres contained fewer undifferentiated cells compared with the FB-derived neurospheres, and that CE-derived neurospheres initially expressed the set of Notch pathway molecules genes including Notch 1 and Delta 1, HES-1 and HES-5, but partially lose their expression after passaging. Furthermore, we found that the CE-derived neurospheres did not express several markers for in vivo embryonic retinal progenitors. Additionally, when the eye was divided into four subregions along its dorsoventral and nasotemporal axes and progenitor cells were obtained from the subregions, the progenitor cells did not express the subregion specific transcription factors, suggesting that subregional specificity is not maintained in vitro. Together, our results demonstrate that CE-derived progenitor cells may have intrinsic limitations in the production of cell types.


Lyme disease associated with unilateral interstitial keratitis.
To report a case of Lyme disease that presented with a single nummular unilateral interstitial keratitis. Case report and review of the literature. A 57-year-old black man who had contact with freshly killed deer had a chief complaint of foreign-body sensation in his right eye (OD) that had been diagnosed and treated for herpes simplex stromal keratitis. The patient underwent a systemic workup for interstitial keratitis. All results including RPR and MHA-TP were negative except for Lyme antibody titer (enzyme-linked immunosorbent assay [ELISA]) 178 U/ml (normal, <159 U/ml). Interstitial keratitis from Lyme disease has been regarded as a bilateral disease in the literature. We present this infrequent ocular manifestation of Lyme disease as a rare single nummular unilateral presentation.