Modelling the effect of temperature and water activity of Aspergillus flavus isolates from corn.
The aim of this study was to model the effects of temperature (10-40 °C) and a(w) (0.80-0.98), in two media (Czapek yeast agar: CYA; corn extract medium: CEM) on the growth rates and growth boundaries (growth-no growth interface) of three strains of A. flavus isolated from corn in Argentina. Both kinetic and probability models were applied to colony growth data. The growth rates obtained in CYA were significantly (p<0.05) greater than those obtained in CEM medium. No significant differences (p<0.05) were observed among the three isolates. The growth rate data showed a good fit to the Rosso cardinal models combined with the gamma-concept with R(2)=0.98-0.99 and RMSE=0.60-0.78, depending on media and isolates. The probability model allowed prediction of safe storage (p of growth <0.01) for one month for moist maize (e.g. 0.90 a(w)) provided temperature is under 15 °C, or for dry maize (e.g. 0.80 a(w)) provided temperature is under 27 °C. Storage at <0.77 a(w) would be safe regardless of the storage temperature. Probability models allow evaluation of the risk of fungal contamination in the process of storage, so the results obtained in this study may be useful for application in systems of food safety management.


Two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cells for primary marrow alloengraftment failure: case report.
We describe herein a case of bone marrow failure in a 53-year-old patient affected by Ph1-positive chronic myeloid leukemia who received an HLA-identical AB0-mismatched bone marrow transplant from a 56-year-old sibling donor. Hematopoietic recovery after marrow failure was obtained following two consecutive courses of rh-G-CSF-mobilized peripheral blood stem cell infusions. No potential risk factors associated with graft failure, excluding recipient and donor age, were documented, whereas a relatively high number of progenitor cells were necessary to overcome the host-versus-graft barrier in our patient. Therefore we suggest that growth factor-stimulated peripheral blood should be considered as the first choice for allogeneic stem cells in order to avoid primary graft failure with donors over 50 years of age.


Coherent correlator and equalizer using a reconfigurable all-optical tapped delay line.
We experimentally demonstrate a reconfigurable optical tapped delay line in conjunction with coherent detection to search multiple patterns among quadrature phase shift keying (QPSK) symbols in 20 Gbaud data channel and also to equalize 20 and 31 Gbaud QPSK, 20 Gbaud 8 phase shift keying (PSK), and 16 QAM signals. Multiple patterns are searched successfully on QPSK signals, and correlation peaks are obtained at the matched patterns. QPSK, 8 PSK, and 16 QAM signals are also successfully recovered after 25 km of SMF-28 with average EVMs of 8.3%, 8.9%, and 7.8%. A penalty of <1 dB optical signal to noise penalty is achieved for a 20 Gbaud QPSK signal distorted by up to 400 ps/nm dispersion.


Transcriptome-guided amyloid imaging genetic analysis via a novel structured sparse learning algorithm.
Imaging genetics is an emerging field that studies the influence of genetic variation on brain structure and function. The major task is to examine the association between genetic markers such as single-nucleotide polymorphisms (SNPs) and quantitative traits (QTs) extracted from neuroimaging data. The complexity of these datasets has presented critical bioinformatics challenges that require new enabling tools. Sparse canonical correlation analysis (SCCA) is a bi-multivariate technique used in imaging genetics to identify complex multi-SNP-multi-QT associations. However, most of the existing SCCA algorithms are designed using the soft thresholding method, which assumes that the input features are independent from one another. This assumption clearly does not hold for the imaging genetic data. In this article, we propose a new knowledge-guided SCCA algorithm (KG-SCCA) to overcome this limitation as well as improve learning results by incorporating valuable prior knowledge. The proposed KG-SCCA method is able to model two types of prior knowledge: one as a group structure (e.g. linkage disequilibrium blocks among SNPs) and the other as a network structure (e.g. gene co-expression network among brain regions). The new model incorporates these prior structures by introducing new regularization terms to encourage weight similarity between grouped or connected features. A new algorithm is designed to solve the KG-SCCA model without imposing the independence constraint on the input features. We demonstrate the effectiveness of our algorithm with both synthetic and real data. For real data, using an Alzheimer's disease (AD) cohort, we examine the imaging genetic associations between all SNPs in the APOE gene (i.e. top AD gene) and amyloid deposition measures among cortical regions (i.e. a major AD hallmark). In comparison with a widely used SCCA implementation, our KG-SCCA algorithm produces not only improved cross-validation performances but also biologically meaningful results. Software is freely available on request.


Minding the gap: discovering the phenomenon of chemical transmission in the nervous system.
The neuron doctrine, according to which nerves consist of discontinuous neurons, presented investigators with the challenge of determining what activities occurred between them or between them and muscles. One group of researchers, dubbed the sparks, viewed the electrical current in one neuron as inducing a current in the next neuron or in muscles. For them there was no gap between the activities of neurons or neurons and muscles that required filling with a new type of activity. A competing group, the soups, came to argue for chemicals, subsequently referred to neurotransmitters, as carrying out the activities between neurons or between neurons and muscles. But even for them the conclusion that chemicals performed this activity was only arrived over time. I examine the prolonged period in which proponents of chemical transmission developed their account and challenged the sparks. My goal is to illuminate the epistemic processes that led to the discovery of a new scientific phenomenon-chemical transmission between neurons.


Electrically induced blink reflex and facial motor nerve stimulation in beagles.
Electrophysiologic assessment of the blink reflex test and the muscle-evoked potentials evoked by stimulation of the facial nerve were performed in 15 healthy adult Beagles before and after supraorbital (trigeminal) and facial anesthetic nerve blocks performed by lidocaine injections. Unilateral electrical stimulation of the supraorbital nerve elicited 2 ipsilateral (R1 and R2) and a contralateral (Rc) reflex muscle potential in orbicularis oculi muscles. Electrical stimulation of the facial nerve elicited 2 muscle potentials (a direct response [D] and a reflex faciofacial response [RF]) in the ipsilateral orbicularis oculi muscle. Anesthetic block of the left supraorbital nerve resulted in bilateral lack of responses upon left supraorbital nerve stimulation, but normal responses in right and left orbicularis oculi muscles upon right supraorbital stimulation. Right facial anesthetic block produced lack of responses in the right orbicularis oculi muscle regardless the side of supraorbital nerve stimulation. Results of this study demonstrate that the blink reflex can be electrically elicited and assessed in dogs. Reference values for the blink reflex responses and for the muscle potentials evoked by direct facial nerve stimulation in dogs are provided. The potential usefulness of the electrically elicited blink reflex test in the diagnosis of peripheral facial and trigeminal dysfunction in dogs was demonstrated.


Revisiting intensity-based image registration applied to mammography.
The detection of architectural distortions and abnormal structures in mammographic images can be based on the analysis of bilateral and temporal cases using image registration. This paper presents a quantitative evaluation of state-of-the art intensity based image registration methods applied to mammographic images. These methods range from a global and rigid transformation to local deformable paradigms using various metrics and multiresolution approaches. The aim of this study is to assess the suitability of these methods for mammographic image analysis. Evaluation using temporal cases based on quantitative analysis and a multiobserver study is presented which gives an indication of the accuracy and robustness of the different algorithms. Although previous studies suggested that local deformable methods were not suitable due to the generation of unrealistic distortions, in this work we show that local deformable paradigms (multiresolution B-Spline deformations) obtain the most accurate registration results.


Designing a nearly perfect infrared absorber in monolayer black phosphorus.
Black phosphorus (BP) is a type of 2D layered material with a direct bandgap that displays high carrier mobility and strong in-plane anisotropy; it also exhibits potential as a promising optoelectronic material for IR applications. In this paper, we propose a nearly perfect IR absorber composed of a metal film, a spacer with a monolayer BP inside, and a distributed Bragg reflector (DBR). The electric field is confined inside the resonator generated by the metal film and DBR, and the absorption can be enhanced up to nearly 100%, owing to the strong interaction of BP with the confined field. Our results show that the absorption performance of the proposed structure is not only critically dependent on the electron density but also relies on the position of the BP within the spacer. This dependence can be mitigated because the absorption peak wavelength can be tuned by adjusting the angle of the light and the parameters of the DBR. Moreover, the absorber can be served as a reflective linear polarizer based on the anisotropic absorption properties. Our work can be helpful in designing a narrow perfect absorber and polarization-sensitive devices for IR waves.


In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin.
Current treatments for Clostridium difficile infection include vancomycin, metronidazole and fidaxomicin. LFF571 is an experimental agent undergoing evaluation in humans for the treatment of moderate C. difficile infection. Reduced susceptibility of C. difficile to fidaxomicin or LFF571 in vitro can be mediated by single point mutations in genes encoding the targets, whereas the mechanism(s) mediating reduced susceptibility to vancomycin in vitro remains elusive. To further characterize mechanisms reducing susceptibility of C. difficile to vancomycin, fidaxomicin or LFF571 in vitro, selections via serial passage at low cell density were performed, followed by whole-genome sequencing. C. difficile strain ATCC 43255 and three clinical isolates were subjected to 10 passages on medium containing a range of concentrations of fidaxomicin, LFF571 or vancomycin. Genomic DNA from isolates with reduced susceptibility was sequenced using Illumina Whole Genome Sequencing. Clones exhibiting decreased susceptibility to fidaxomicin harboured mutations in rpoB and CD22120 (marR homologue). Clones exhibiting decreased susceptibility to vancomycin harboured mutations in rpoC and also in CD2725, CD3659 and sdaB, which encode a putative N-acetylglucosamine transferase, exonuclease and l-serine deaminase, respectively. All mutations resulted in non-synonymous substitutions. No clones with reduced susceptibility to LFF571 were selected in this study. Reduced susceptibility to fidaxomicin and vancomycin was associated with mutations mediating target modifications (RNA polymerase and cell wall, respectively), as well as with mutations that may contribute to reduced susceptibility via other mechanisms. The MIC of LFF571 was unaffected for those mutants with reduced susceptibility to fidaxomicin or vancomycin.


[The opinions of Belgian physicians about their practice].
Considering the numerous changes in the health system, do medical doctors (MDs) feel difficulties in practising their profession? Are there complaints regarding the fact that the "medical chart" is in danger? Is Herzberg's theory about factors of satisfaction confirmed? Qualitative analysis of MDs' spontaneous comments, stated at the end of a postal survey (MDs of the French speaking universities of Belgium, settled since 5 to 10 years or 15 to 20 years): 5 546 were contacted in 1999 and 2040 answered; 862 provided comments about their career and/or about their feelings regarding their profession (the latter theme had not been specifically addressed by the main survey). Most comments were issued by practitioners providing care: 296 general practitioners and 396 specialists; the remaining physicians perform other types of activities in the health system (prevention, teaching, research, management, ...): they number 170. A large diversity of careers; a few typical patterns are noticeable. Several satisfactions, which are largely outnumbered by the amount of complaints: onerousness, lack of collaboration, patients' requirements, bureaucracy, political interference, insufficient fees, lack of family- and private life and, mainly for specialists, shortcomings of training and problems with the hospital administration. Complaints about the medical chart are absent. Herzberg's theory holds true partially: among positive comments, "hygiene factors" are as frequent as aspects related to the content of work. 1) The evolution of relations with the patients is probably not only due to the changes within the health sector; other factors are also to be scented, e.g the difficulty of a) bearing uncomfortable working conditions within an hedonistic culture and b) meeting the various challenges proposed by diverse paradigms regarding the norms of good practice. 2) The previous importance of the medical chart enters in conflict with worries more down to earth. 3) All the positive comments do not reflect a large satisfaction: some are rather relative, regarding an improvement compared with a worse situation in the past or with difficulties endured by colleagues.


[About the "double" radioprotecting mechanism of some sulfur-containing substances].
The hypothesis about the double-acting mechanism of some radioprotectors during the irradiation of the DNA solutions is expressed in literature: the water radicals interception and the formation up to the irradiation of the additional intermolecular bonds "protector-DNA" (stabilization of the double helix). The realization conditions of this hypothesis were obtained by the molecular mechanics methods and the free radical mechanism appearance of the intrastrand cross-links "protector-DNA" during the irradiation of the polymer is given.


Personality disturbances in amyotrophic lateral sclerosis: a case study demonstrating changes in personality without cognitive deficits.
Patients with amyotrophic lateral sclerosis (ALS) often show deficits on neuropsychological tests that tap functions related to the integrity of the prefrontal lobes. Various aspects of personality are also known to be mediated by prefrontal regions, particularly ventromedial prefrontal cortex (vmPFC). Other than apathy, personality changes have not been widely reported in patients with ALS, although clinical observations indicate such changes might be relatively common. Here, we report on a middle-aged woman with bulbar onset ALS (diagnosed 06/2011, examined in Spring, 2012) whose neuropsychological exam did not reveal cognitive deficits. She performed normally on tests of executive functioning. Self-report measures of mood and personality were unremarkable. However, significant personality changes subsequent to disease onset were reported by her husband and two daughters, and these changes were quantified with the Iowa Scales of Personality Change. Results show that personality disturbance may manifest in the absence of notable cognitive changes in ALS, and careful assessment of personality may be important for documenting early neurobehavioral changes in some ALS patients. Findings also show that patients with ALS may not have good insight into personality changes, underscoring the importance of acquiring collateral information. More generally, the results provide further evidence that ALS may compromise the integrity of ventromedial prefrontal regions.


A nationwide analysis of successful litigation claims in neurological practice.
Neurological practice has previously been highlighted as a high-risk speciality with regard to malpractice claims. We set out to study the nature of these claims in order to inform physicians about hazardous areas within their speciality and potentially alter clinical practice. Nationwide retrospective analysis of successful neurology and neurosurgery claims over a 17-year period. We studied all successful claims occurring between 1995 and 2012 using the NHS Litigation Authority database, which collects data on claims made against clinicians practising in England and Wales. Four hundred and twenty-three successful claims were identified during the study period. The errors involved, the patient groups affected, the resulting mortality and the litigation payments. 63.1% of claims were due to negligence in neurosurgical care, whilst 36.9% were due to negligence in neurological care. Litigation payments were significantly higher in neurosurgery compared to neurology cases. Diagnostic error was the most common cause of litigation. The disease categories with the highest numbers of successful litigation claims were spinal pathology, cerebrovascular disease including subarachnoid haemorrhage, intracranial tumours, hydrocephalus and neuropathy/neuromuscular disease. This is the first study of successful litigation claims against the NHS for negligent neurological or neurosurgical care and provides data to help reduce risk and improve patient safety.


Large isotope effect on the pseudogap in the high-temperature superconductor HoBa2Cu4O8
The oxygen isotope effect on the relaxation rate of crystal-field excitations in the slightly underdoped high-temperature superconductor HoBa2Cu4O8 has been investigated by means of inelastic neutron scattering. For the 16O compound there is clear evidence for the opening of an electronic gap in the normal state at T(*) approximately 170 K far above T(c) = 79 K. Upon oxygen isotope substitution ( 16O vs 18O) T(c) decreases marginally to 78.5 K, whereas T(*) is shifted to about 220 K. This huge isotope shift observed for T(*) which is absent in NMR and NQR experiments suggests that the mechanism leading to an isotope effect on the pseudogap has to involve a time scale in the range 10(-8)>>tau>10(-13) s.


A Monte Carlo approach to the microdosimetric kinetic model to account for dose rate time structure effects in ion beam therapy with application in treatment planning simulations.
Advanced ion beam therapeutic techniques, such as hypofractionation, respiratory gating, or laser-based pulsed beams, have dose rate time structures which are substantially different from those found in conventional approaches. The biological impact of the time structure is mediated through the β parameter in the linear quadratic (LQ) model. The aim of this study was to assess the impact of changes in the value of the β parameter on the treatment outcomes, also accounting for noninstantaneous intrafraction dose delivery or fractionation and comparing the effects of using different primary ions. An original formulation of the microdosimetric kinetic model (MKM) is used (named MCt-MKM), in which a Monte Carlo (MC) approach was introduced to account for the stochastic spatio-temporal correlations characteristic of the irradiations and the cellular repair kinetics. A modified version of the kinetic equations, validated on experimental cell survival in vitro data, was also introduced. The model, trained on the HSG cells, was used to evaluate the relative biological effectiveness (RBE) for treatments with acute and protracted fractions. Exemplary cases of prostate cancer irradiated with different ion beams were evaluated to assess the impact of the temporal effects. The LQ parameters for a range of cell lines (V79, HSG, and T1) and ion species (H, He, C, and Ne) were evaluated and compared with the experimental data available in the literature, with good results. Notably, in contrast to the original MKM formulation, the MCt-MKM explicitly predicts an ion and LET-dependent β compatible with observations. The data from a split-dose experiment were used to experimentally determine the value of the parameter related to the cellular repair kinetics. Concerning the clinical case considered, an RBE decrease was observed, depending on the dose, ion, and LET, exceeding up to 3% of the acute value in the case of a protraction in the delivery of 10 min. The intercomparison between different ions shows that the clinical optimality is strongly dependent on a complex interplay between the different physical and biological quantities considered. The present study provides a framework for exploiting the temporal effects of dose delivery. The results show the possibility of optimizing the treatment outcomes accounting for the correlation between the specific dose rate time structure and the spatial characteristic of the LET distribution, depending on the ion type used.


De-novo designed library of benzoylureas as inhibitors of BCL-XL: synthesis, structural and biochemical characterization.
The prosurvival BCL-2 proteins are attractive yet challenging targets for medicinal chemists. Their involvement in the initiation and progression of many, if not all, tumors makes them prime targets for developing new anticancer therapies. We present our approach based on de novo structure-based drug design. Using known structural information from complexes engaging opposing members of the BCL-2 family of proteins, we designed peptidomimetic compounds using a benzoylurea scaffold to reproduce key interactions between these proteins. A library stemming from the initial de novo designed scaffold led to the discovery of ligands with low micromolar potency (KD = 4 μM) and selectivity for BCL-XL. These compounds bind in the canonical BH3 binding groove in a binding mode distinct from previously known BCL-2 inhibitors. The results of our study provide insight into the design of a new class of antagonists targeting a challenging class of protein-protein interactions.


Oritavancin--an investigational glycopeptide antibiotic.
Antibiotics save countless lives each year; however, increasing rates of drug-resistant bacteria have limited antibiotic selection. Currently, there are few available options for treating resistant Gram-positive organisms. Oritavancin, a novel glycopeptide antibiotic with bactericidal activity, has been developed and recently completed the first round of Phase III clinical trials for the treatment of complicated skin and skin structure infections. Investigations into oritavancin's efficacy will be explored in catheter-related bacteraemia and nosocomial pneumonia. Oritavancin demonstrates similar activity to vancomycin but possesses extended activity against vancomycin-resistant Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential. Further development of oritavancin is necessary to determine clinical efficacy.


Selective and direct immobilization of cysteinyl biomolecules by electrochemical cleavage of azo linkage.
Controlled orientation and reserved activity of biomolecules, when site-selectively immobilized in a highly integrated manner on a minimal time scale, are crucial in designing biosensors for the multiplex detection. Here, we describe a novel method for the orientation-controlled immobilization of biomolecules based on site-selective electrochemical activation of p-hydroxyazobenzene self-assembled monolayer (SAM) followed by one-step coupling of cysteinyl biomolecules. The p-aminophenol, a product of reductive cleavage of p-hydroxyazobenzene, was subsequently oxidized to yield p-quinoneimine which then conjugated with cysteinyl biomolecules through 1,4-Michael addition, thus obviating additional linker agents and the related time consumption. Using this method, we selectively activated the electrode surface and immobilized laminin peptide IKVAV, a neurite promoting motif. When we cultured hippocampal neurons on the electrode, the extended neurites were found only within the electrochemically activated area. Hence, the proposed method represents a new promising platform for the patterning of functional peptides, active proteins, and live cells.


Study of genes polymorphisms in RANK/RANKL/OPG and WNT signaling pathways and their associations with bone parameters in broiler chicken.
Limb problems are one of the most common problems with fast-growing meat-type chickens. Various bone abnormalities, which can lead to limping, bone weakness, or even fractures, bring overall discomfort to birds and a loss of production. Genetic aspects are often associated with these side effects on bone stability and are also cited as the dominant cause. These points to a close negative relationship of genetic selection for rapid growth with traits involved in bone integrity. Due to the assumption of an additive genetic background, improvements through genetic tools can be used. Our study is focused on selected genes of important signaling pathways for bone metabolism. We tried to detect polymorphisms that would show associations with selected bone parameters in a total of 48 broilers. Those were fast-growing Ross 308 hybrids and slow-growing Hubbard M22BxJA87A hybrids. The TNFRSF11A and WISP1 genes were tested. A total of fourteen polymorphisms were found, three of them were synonymous and five in the intron. In the case of four polymorphisms found in exons of the TNFRSF11A gene (c.11G > T, c.31G > A, c.37C > G, c.514G > A), associations with the observed bone parameters (bone strength, bone dimensions and bone mass) were demonstrated. The genetic architecture of bone traits is not fully understood, therefore the present study and the knowledge gained can help to increase the potential in poultry breeding processes and thus reduce the death of individuals.


Preoperative predictors of survival after resection of small hepatocellular carcinomas.
To determine preoperative predictors of survival that can guide the choice of treatment for patients with small hepatocellular cancers (HCCs). The treatment of patients with small (</=5 cm in diameter) HCCs is controversial. A cohort of 249 patients (69 women, 180 men; median age 62 years) who underwent resection with curative intent for small HCC was identified from a multiinstitutional database. For each patient, the clinical data and pathology slides were reviewed. Six clinical factors (age, gender, preoperative alpha-fetoprotein level, hepatitis serology, number of tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade) that can be determined before surgery were correlated with survival. Log-rank tests and Cox proportional hazards modeling were used to determine factors influencing survival. The median overall survival for the entire cohort was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and 19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score, Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant predictors of survival after resection. A prognostic scoring system based on these covariates was derived and applied to the entire cohort. Patients lacking all three risk factors were assigned a score of 1, patients with one risk factor were assigned a score of 2, and patients with two or three risk factors were assigned a score of 3. Pairwise log-rank tests indicated significant differences in survival between scores 1 and 2, scores 2 and 3, and scores 1 and 3. This scoring system retained its prognostic significance when a subset of 98 patients with positive hepatitis C serology was analyzed separately. Patients with small HCCs who will derive the least benefit from resection can be identified before surgery using a score based on tumor grade and the severity of underlying liver disease. In these patients, transplantation and/or ablation should be considered as possible alternative therapies.


The 1997 list. Proposed new bacterial taxa and proposed changes of bacterial names published during 1997 and considered to be of interest to medical or veterinary bacteriology (an informational note).
A list of names published or validated in 1997 is presented. We also comment on the tendency to base names of new taxa on a single bacterial strain, and the consequences for reliable descriptions that this tendency implies.


Acetyl-11-keto-β-boswellic Acid Inhibits Precancerous Breast Lesion MCF-10AT Cells via Regulation of LINC00707/miR-206 that Reduces Estrogen Receptor-α.
Acetyl-11-keto-β-boswellic acid (AKBA) has therapeutic effects on a range of diseases, including tumours. lncRNAs, as competing endogenous RNAs (ceRNAs), can interact with miRNAs to regulate the expression of target genes, which can affect the development of tumors. Here, we examined the effects of AKBA on breast precancerous lesions MCF-10AT cells. The expression profiles of breast cancer (BC) tissue were collated from The Cancer Genome Atlas (TCGA), and the lncRNA-miRNA-mRNA ceRNA network was constructed. AKBA targets were predicted by network pharmacology. The expression of long intergenic nonprotein-coding RNA 707 (LINC00707), miR-206 and ER-α was determined by qRT-PCR. Cell viability, apoptosis and cycle were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting. A total of 3205 differentially expressed mRNAs, 104 miRNAs, and 605 lncRNAs were identified. The ceRNA network consisting of 9 lncRNAs, 15 miRNAs and 82 mRNAs was constructed. We found that LINC00707 was up-regulated and miR-206 was down-regulated in MCF-10AT cells. Transfected si-LINC00707 could inhibit cell proliferation, induce cell apoptosis and cycle arrest of MCF-10AT cells. In addition, network pharmacology predicted that AKBA may regulate the ESR1 in the treatment of BC. Our research demonstrated that AKBA could induce cell apoptosis and G1-phase arrest and inhibit ER-α expression via LINC00707/miR-206 in MCF-10AT cells. AKBA inhibited MCF-10AT cells via regulation of LINC00707/miR-206 that reduces ER-α.


Casparian strip diffusion barrier in Arabidopsis is made of a lignin polymer without suberin.
Casparian strips are ring-like cell-wall modifications in the root endodermis of vascular plants. Their presence generates a paracellular barrier, analogous to animal tight junctions, that is thought to be crucial for selective nutrient uptake, exclusion of pathogens, and many other processes. Despite their importance, the chemical nature of Casparian strips has remained a matter of debate, confounding further molecular analysis. Suberin, lignin, lignin-like polymers, or both, have been claimed to make up Casparian strips. Here we show that, in Arabidopsis, suberin is produced much too late to take part in Casparian strip formation. In addition, we have generated plants devoid of any detectable suberin, which still establish functional Casparian strips. In contrast, manipulating lignin biosynthesis abrogates Casparian strip formation. Finally, monolignol feeding and lignin-specific chemical analysis indicates the presence of archetypal lignin in Casparian strips. Our findings establish the chemical nature of the primary root-diffusion barrier in Arabidopsis and enable a mechanistic dissection of the formation of Casparian strips, which are an independent way of generating tight junctions in eukaryotes.


Alignment influences wear in the knee after medial unicompartmental arthroplasty.
Failure of a medial unicompartmental arthroplasty may be related to wear of the cartilage in the opposite compartment or to wear in the polyethylene tibial implant. Limb alignment influences both of these factors in the long term. Fifty-eight knees with medial unicompartmental arthroplasties in patients alive at least 10 years postoperatively were evaluated for radiographic changes at their most recent followup. The average duration of clinical and radiographic followups for these patients was 15 years (range, 10-20 years). Alignment was measured preoperatively and postoperatively as the hip-knee-ankle angle on radiographs of the entire limb. An overcorrection in valgus of the preoperative deformity (hip-knee-ankle angle > 180 degrees was associated with an increased risk of degenerative changes in the opposite compartment. Severe undercorrection in varus of the deformity (hip-knee-ankle angle < 170 degrees) was associated with increased wear in the tibial component and recurrence of the deformity which was indicative of polyethylene wear. For medial implants that were implanted in moderate varus (hip-knee-ankle angle of 171 degrees to 179 degrees) the rate of wear of the polyethylene was less than in knees with severe undercorrection and the risk of degenerative changes in the opposite compartment was low.


Guillain-Barré Syndrome as a paraneoplastic neurological disease of pulmonary adenocarcinoma and squamous cell carcinoma: A case report.
We present the case of a 69-year-old male who presented with profound weakness in the extremities. Remarkably, he lacked any identifiable precipitating factors preceding the onset of his illness. However, a diagnosis of Guillain-Barré syndrome (GBS) was established based on typical clinical symptoms, cerebrospinal fluid analysis, and neurological examination. During his hospitalization, an incidental discovery of lung cancer was made. Subsequent pathology confirmed adenocarcinoma and squamous cell carcinoma in the lungs. This case report serves to underscore the exceptional rarity of the simultaneous occurrence of lung cancer and GBS, renewing interest in investigating GBS as a potential paraneoplastic neurological syndrome. Keywords: Guillain-Barré syndrome, paraneoplastic neurological disease, pulmonary adenocarcinoma, squamous cell carcinoma.


Role of corneal nerves in ocular surface homeostasis and disease.
Corneal nerves are key components of the physiological system that controls ocular surface homeostasis. The cornea is primarily innervated by the ophthalmic branch of the trigeminal nerves (cranial nerve V), which distend bilaterally from the pons. The nasociliary branch (afferent) of the ophthalmic nerve is sensory for cornea, eyelid and conjunctiva. These nerve fibres play a role in sensing temperature, chemical and mechanical stimuli, and pain, whereas, branches of the facial nerve (cranial nerve VII) contain motor nerves that control blinking and autonomic (sympathetic and a paucity of parasympathetic) fibres that stimulate tear production and secretion via feedback loops between the ocular surface, lacrimal glands and brain. Disruption of these nerves with interruption of neural feedback loops between the ocular surface and lacrimal glands can lead to corneal diseases such as dry eye disease (DED) and neurotrophic keratopathy (NK). Inversely, hypersensitivity of the nerve fibres and/or dysregulation of pain-controlling nervous centres may lead to neuropathic pain. Recently, medications that specifically target regeneration of corneal nerves have started to become available - and considering the high prevalence of diseases associated with corneal nerve dysfunction, these agents promise to fulfil a hitherto important unmet need. In this review, we explore the physiology of corneal nerves, the pathology of corneal nerve diseases and how these relate to neuropathic pain, NK and DED. We also discuss what novel treatments may be useful against diseases involving corneal nerves.


Exploitation of marine algae: biogenic compounds for potential antifouling applications.
Marine algae are one of the largest producers of biomass in the marine environment. They produce a wide variety of chemically active metabolites in their surroundings, potentially as an aid to protect themselves against other settling organisms. These active metabolites, also known as biogenic compounds, produced by several species of marine macro- and micro-algae, have antibacterial, antialgal, antimacrofouling and antifungal properties, which are effective in the prevention of biofouling, and have other likely uses, e.g. in therapeutics. The isolated substances with potent antifouling activity belong to groups of fatty acids, lipopeptides, amides, alkaloids, terpenoids, lactones, pyrroles and steroids. These biogenic compounds have the potential to be produced commercially using metabolic engineering techniques. Therefore, isolation of biogenic compounds and determination of their structure could provide leads for future development of, for example, environmentally friendly antifouling paints. This paper mainly discusses the successes of such research, and the future applications in the context of understanding the systems biology of micro-algae and cyanobacteria.


Dyslipidaemia in type 2 diabetes mellitus: bad for the heart.
Type 2 diabetes mellitus (T2DM) is associated with increased coronary heart disease (CHD) morbidity and mortality. These patients are also more prone to heart failure, arrhythmias and sudden cardiac death. Furthermore, coronary interventions performed in such high-risk patients have worse outcomes. In this narrative review, we discuss the role of diabetic dyslipidaemia on the risk of CHD in patients with T2DM. The effects of hypolipidaemic, antihypertensive and antidiabetic drugs on lipid and glucose metabolism in T2DM are also considered. Among CHD risk factors, diabetic dyslipidaemia characterized by moderately elevated low-density lipoprotein (LDL) cholesterol, increased triglycerides and small, dense LDL particles as well as decreased high-density lipoprotein cholesterol levels may contribute to the increased CHD risk associated with T2DM. Hypolipidaemic, antihypertensive and antidiabetic drugs can affect lipid and glucose parameters thus potentially influencing CHD risk. Such drugs may improve not only the quantity, but also the quality of LDL as well as postprandial lipaemia. Current data highlight the importance of treating diabetic dyslipidaemia in order to minimize CHD risk. Both fasting and postprandial lipids are influenced by drugs in patients with T2DM; physicians should take this into consideration in clinical decision making.


[Profile of primary care physicians in a health area: a cluster analysis].
To discover characteristics of primary care doctors. To find homogeneous groups of doctors. A basically descriptive crossover observational study. Primary care doctors from a health area. The following variables were recorded on the 99 doctors who worked in Castellon Area 03 during 1992: age, gender, fixed or temporary post, rural or urban area, MIR training, primary care model, patient load, sole employment, drugs expenditure, number of pensioners and total number of patients registered. We found a first group of older doctors, working mainly in the old model, for whom PC was not their sole employment; another younger group without MIR training and with an average patient load; the third group was women in temporary posts with a somewhat higher drugs expenditure; the fourth was doctors working in rural areas with a very low patient load; the fifth, final and youngest group was family doctors, with an average patient load, low expenditure and a high number of patients registered. We observed highly significant differences between groups. Doctors' age and gender divide them into different groupings; family doctors form one group. Multivariable, descriptive methods proved useful in finding, describing and classifying doctors and centres, etc., and could be of use in resource and action planning.


Maintenance of genetic variation in plants and pathogens involves complex networks of gene-for-gene interactions.
The RPP13 [recognition of Hyaloperonospora arabidopsidis (previously known as Peronospora parasitica)] resistance (R) gene in Arabidopsis thaliana exhibits the highest reported level of sequence diversity among known R genes. Consistent with a co-evolutionary model, the matching effector protein ATR13 (A. thaliana-recognized) from H. arabidopsidis reveals extreme levels of allelic diversity. We isolated 23 new RPP13 sequences from a UK metapopulation, giving a total of 47 when combined with previous studies. We used these in functional studies of the A. thaliana accessions for their resistance response to 16 isolates of H. arabidopsidis. We characterized the molecular basis of recognition by the expression of the corresponding ATR13 genes from these 16 isolates in these host accessions. This allowed the determination of which alleles of RPP13 were responsible for pathogen recognition and whether recognition was dependent on the RPP13/ATR13 combination. Linking our functional studies with phylogenetic analysis, we determined that: (i) the recognition of ATR13 is mediated by alleles in just a single RPP13 clade; (ii) RPP13 alleles in other clades have evolved the ability to detect other pathogen ATR protein(s); and (iii) at least one gene, unlinked to RPP13 in A. thaliana, detects a different subgroup of ATR13 alleles.


Comparison of temporalis fascia and cartilage graft over-under myringoplasty for repairing large perforations.
The objective of this study was to compare the operation time, graft success, audiometric outcomes and complications of over-under technique using a temporalis fascia (TMF) and cartilage grafts for the repair of large perforations. Randomized controlled trial. 80 large perforations >2 quadrants of eardrum were prospectively randomized to undergo TMF over-under technique group (TFON, n = 40) or cartilage-perichondrium over-under technique group (CPON, n = 40). The graft success rate, audiometric outcomes, and complications were compared among two groups at 12 months. The mean operation time was 56.8 ± 4.2 (range:52-71) min in the TFON group and 37.9 ± 2.8 (range: 31-47) min in the CPON group (P < 0.001). The lost follow-up rate was 3 (7.5 %) patients in the TFON group and 2 (5.0 %) patient in the CPON group (P = 0.644). Finally, 37 patients in the TFON group and 38 patients in the CPON group were included in this study. The graft infection rate was 2 (5.4 %) patients in the TFON group and 2 (5.3 %) patient in the CPON group (P = 0.626), all the graft infection resulted in the residual perforation. The remaining residual perforation was 2 (5.4 %) patients in the TFON group and 1 (2.6 %) patient in the CPON group; the re-perforation was 3 (8.1 %) patients in the TFON group and 0 (0.0 %) patient in the CPON group. The graft success rate was 81.1 % (30/37) patients in the TFON group and 92.1 % (35/38) patient in the CPON group. The mean preoperative and 12-month postoperative ABGs were significantly different in any group (P < 0.01). However, there were no significant difference among two groups regardless of pre-or post-ABGs or ABG closure. No lateralization of the graft or blunting was noted in any group. Four (10.8 %)patients developed atelectasis and one (2.7 %) developed the EAC scarring in the TFON group. Graft cholesteatomas was found in 2 (5.4 %) patients in the TFON group and in 5 (13.2 %) patients in the CPON group (P = 0.449). Three (8.1 %) patients had temporary hypogeusia in the TFON group. Although temporalis fascia graft over-under technique obtained similar graft success rates and hearing outcomes for large chronic perforations to the cartilage-perichondrium over-under technique, temporalis fascia graft technique prolonged the operation time and increased the re-perforation and graft atelectasis. Nevertheless, the graft cholesteatomas were comparable among two techniques.


Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability.
The p53 tumor suppressor protein is activated in cells in response to DNA damage and prevents the replication of cells sustaining genetic damage by inducing a cell cycle arrest or apoptosis. Activation of p53 is accompanied by stabilization of the protein, resulting in accumulation to high levels within the cell. p53 is normally degraded through the proteasome following ubiquitination, although the mechanisms which regulate this proteolysis in normal cells and how the p53 protein becomes stabilized following DNA damage are not well understood. We show here that p53 can also be a substrate for cleavage by the calcium-activated neutral protease, calpain, and that a preferential site for calpain cleavage exists within the N terminus of the p53 protein. Treatment of cells expressing wild-type p53 with an inhibitor of calpain resulted in the stabilization of the p53 protein. By contrast, in vitro or in vivo degradation mediated by human papillomavirus E6 protein was unaffected by the calpain inhibitor, indicating that the stabilization did not result from inhibition of the proteasome. These results suggest that calpain cleavage plays a role in regulating p53 stability.


A genome-wide search for genes that relate to a low level of response to alcohol.
The low level of response (LR) to alcohol is genetically influenced in both humans and animals, and a low LR is a characteristic of offspring of alcoholics that has been reported to predict alcoholism 10 and 15 years later. The genes that contribute to a low LR have not yet been identified. A 12-item questionnaire that measures LR, the Self Rating of the Effects of Alcohol (SRE) instrument, was filled out by 745 individuals from the Collaborative Study on the Genetics of Alcoholism (COGA) for whom genetic material was available. These subjects were genotyped by using 336 markers with an average heterozygosity of 0.74 and an average intermarker distance of 10.5 cM. Both quantitative and qualitative nonparametric, sib-pair analyses were carried out for the SRE measure related to early drinking experiences. Correlations of SRE scores across related individuals were significant and between 0.16 and 0.22 for most values, compared with nonsignificant correlations of 0.03 or less among unrelated individuals. Linkage analyses performed by using the FIRST 5 variables (first five times alcohol is consumed) identified four chromosomal regions with lod scores > or = 2.0 whose maximum was also near a marker. One of these chromosomal regions previously was linked to alcohol dependence in the COGA sample. These data document the familial nature of a low LR to alcohol as measured by the SRE and suggest several chromosomal regions that might contribute to the phenomenon.


An Incidental Finding of a Double-Lumen Trachea.
The aim of this case report is to present an incidental finding of a firm tracheal septum in a 61-year-old woman. The patient was admitted to the hospital with mild dyspnea and a preliminary diagnosis of a tracheal subglottic stenosis. During microlaryngoscopy, just below the subglottic stenosis, a firm, vertical symphysis (septum), forming a double-lumen trachea was found. There was no record of any previous difficulties with intubation. A computed tomography scan performed after the microlaryngoscopy revealed an airway branch arising from the trachea at the level of thyroid gland and joining its lumen below. The radiological and endoscopic findings in the presented case hardly resemble the conditions described in the literature, as the discovered septum does not have a pseudomembranous nature, nor does it form a tracheal bronchus. Therefore, the finding is thought to be an unusual complication of multiple intubations in the past. This is an extremely rare finding and it is important to share our experience in managing a patient with the aforementioned post-intubation complications.


Infusion of a lipid emulsion to treat lidocaine intoxication in a cat.
A 5-year-old castrated male domestic shorthair cat was examined because of presumptive lidocaine intoxication. Thirty minutes earlier, the cat had received an SC injection of approximately 140 mg of lidocaine hydrochloride (20 mg/kg [9.1 mg/lb]) to facilitate closure of a wound on the left pelvic limb. Initial physical examination revealed severe lethargy and respiratory distress; erratic, poor-quality pulses with severe hypotension; and pulmonary edema. Initial supportive treatment included administration of oxygen and IV administration of lactated Ringer's solution. Additional treatment with a 20% lipid emulsion (1.5 mL/kg [0.68 mL/lb], IV) delivered over a 30-minute period resulted in dramatic improvement in cardiovascular and behavioral variables. No adverse effects from lipid emulsion were detected on routine hematologic evaluation, thoracic radiography, or computed tomography. IV administration of a lipid emulsion was used in the treatment of lidocaine intoxication in a cat. Rapid infusion of a lipid emulsion may be a therapeutic option for veterinary patients with toxicosis attributable to local anesthetics or other lipid-soluble drugs.


Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes.
Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array. TN molecular subtypes were defined based on gene expression data associated with histopathologic features of TN tumors. Gene expression analysis yielded signatures for four TN subtypes (basal-like, androgen receptor positive, immune, and stromal) consistent with previous studies. Expression analysis also identified genes significantly associated with the 12 histological features of TN tumors. Development of signatures using these markers of histopathological features resulted in six distinct TN subtype signatures, including an additional basal-like and stromal signature. The additional basal-like subtype was distinguished by elevated expression of cell motility and glucose metabolism genes and reduced expression of immune signaling genes, whereas the additional stromal subtype was distinguished by elevated expression of immunomodulatory pathway genes. Histopathologic features that reflect heterogeneity in tumor architecture, cell structure, and tumor microenvironment are related to TN subtype. Accounting for histopathologic features in the development of gene expression signatures, six major subtypes of TN breast cancer were identified.


Picture archiving and communication systems in digital cytology.
The paper describes a fundamental feature of digital cytology relevant to the implementation of the technology in the hospital net services: the electronic recording of the virtual slides (VS) in the hospital information system (HIS) through a picture archiving and communication system (PACS). Starting from the digital cytology (D-CYT) state of art and considering the most important products in the field, particular attention has been devoted in this review to the comparison with the digital radiology (D-RAD). Two main indications emerged from the study: 1. there is not a standard in the digital files relevant to the virtual slides in D-CYT, while in D-RAD the standard digital imaging and communications in medicine (DICOM), introduced by the National Electrical Manufacturers Association (NEMA), has been adopted from several years; 2. the PACS in D-CYT are not standardized from manufacturers. The study makes a proposal of a useful software architecture to improve the PACS integration for D-CYT applications, with potentialities in the HIS.


Soldier-relevant body borne load impacts minimum foot clearance during obstacle negotiation.
Soldiers often trip and fall on duty, resulting in injury. This study examined ten male soldiers' ability to negotiate an obstacle. Participants had lead and trail foot minimum foot clearance (MFC) parameters quantified while crossing a low (305 mm) and high (457 mm) obstacle with (19.4 kg) and without (6 kg) body borne load. To minimize tripping risk, participants increased lead foot MFC (p = 0.028) and reduced lead (p = 0.044) and trail (p = 0.035) foot variability when negotiating an obstacle with body borne load. While obstacle height had no effect on MFC (p = 0.273 and p = 0.126), placing the trail foot closer to the high obstacle when crossing with body borne load, resulted in greater lead (R = 0.640, b = 0.241, p = 0.046) and trail (R = 0.636, b = 0.287, p = 0.048) MFC. Soldiers, when carrying typical military loads, may be able to minimize their risk of tripping over an obstacle by creating a safety margin via greater foot clearance with reduced variability.


Effect of earthworm powder on antioxidant enzymes in alcohol induced hepatotoxic rats.
Earthworms have been widely used in traditional medicine for thousands of years. However, it is only during the past few decades, with the development of biochemical technologies, that research on the pharmaceutical effects has been initiated. The present study was carried out to investigate the hepatoprotective and antioxidant properties of indigenous earthworm powder (Perionyx excavatus), using alcohol induction as a model of hepatotoxic and oxidative damage. Alcohol-hepatotoxic rats exhibited elevation in the lipid-peroxidative marker thiobarbituric acid reactive substance (TBARS). A decrease in the activities of enzymatic antioxidant enzymes: Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and non-enzymatic antioxidant vitamin C, vitamin E and reduced glutathione (GSH) was observed. Oral administration of dried earthworm powder (500 mg/kg body weight) for 42 days reversed these parameters towards normalcy. These results suggest that the indigenous earthworm Perionyx excavatus could afford a significant hepatoprotective and antioxidant effect against alcohol induced rats.


SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.
SHP2 phosphatase promotes full activation of the RTK-dependent Ras/MAPK pathway. Its mutations can drive cancer and RASopathies, a group of neurodevelopmental disorders (NDDs). Here we ask how same residue mutations in SHP2 can lead to both cancer and NDD phenotypes, and whether we can predict what the outcome will be. We collected and analyzed mutation data from the literature and cancer databases and performed molecular dynamics simulations of SHP2 mutants. We show that both cancer and Noonan syndrome (NS, a RASopathy) mutations favor catalysis-prone conformations. As to cancer versus RASopathies, we demonstrate that cancer mutations are more likely to accelerate SHP2 activation than the NS mutations at the same genomic loci, in line with NMR data for K-Ras4B more aggressive mutations. The compiled experimental data and dynamic features of SHP2 mutants lead us to propose that different from strong oncogenic mutations, SHP2 activation by NS mutations is less likely to induce a transition of the ensemble from the SHP2 inactive state to the active state. Strong signaling promotes cell proliferation, a hallmark of cancer. Weak, or moderate signals are associated with differentiation. In embryonic neural cells, dysregulated differentiation is connected to NDDs. Our innovative work offers structural guidelines for identifying and correlating mutations with clinical outcomes, and an explanation for why bearers of RASopathy mutations may have a higher probability of cancer. Finally, we propose a drug strategy against SHP2 variants-promoting cancer and RASopathies.


Quantum efficiency and antenna size of photosystems II alpha, II beta and I in tobacco chloroplasts.
Reaction center concentrations were determined in chloroplasts of tobacco, cv John William's Broadleaf, and its mutants Su/su and Su/su var. Aurea. Quantum yields of the primary reactions of Photosystems I, II alpha and II beta (Melis, A. and Homann, P.H. (1975) Photochem. Photobiol. 21, 431--437) were obtained by measurement of their rate constants and the absorbed energy, under conditions where all three photosystems operated simultaneously and produced almost irreversibly a single charge separation. The concentrations and reaction rates of the photosystems were different in chloroplasts from the wild type and the mutants, but in chloroplasts of each type of plant used essentially all quanta absorbed by chlorophyll caused a charge separation in PS I, PS II alpha or PS II beta. since the quantum efficiency of each photosystem was close to one, kinetic differences between the photosystems and between different kinds of chloroplasts were only due to differences in antenna size. From the rate constants the number of chlorophyll molecules in the antenna of each photosystem could be calculated. It is argued that PS II alpha and PS II beta must be different, independent structures.


Curvature sensor for ocular wavefront measurement.
We describe a new wavefront sensor for ocular aberration determination, based on the curvature sensing principle, which adapts the classical system used in astronomy for the living eye's measurements. The actual experimental setup is presented and designed following a process guided by computer simulations to adjust the design parameters for optimal performance. We present results for artificial and real young eyes, compared with the Hartmann-Shack estimations. Both methods show a similar performance for these cases. This system will allow for the measurement of higher order aberrations than the currently used wavefront sensors in situations in which they are supposed to be significant, such as postsurgery eyes.


Assessment of patients' and caregivers' informational and decisional needs for left ventricular assist device placement: Implications for informed consent and shared decision-making.
Several organizations have underscored the crucial need for patient-centered decision tools to enhance shared decision-making in advanced heart failure. The purpose of this study was to investigate the decision-making process and informational and decisional needs of patients and their caregivers regarding left ventricular assist device (LVAD) placement. In-depth, structured interviews with LVAD patients, candidates and caregivers (spouse, family members) (n = 45) were conducted. We also administered a Decisional Regret Scale. Participants reported LVAD decision-making to be quick and reflexive (n = 30), and deferred heavily to clinicians (n = 22). They did not perceive themselves as having a real choice (n = 28). The 2 most prevalent informational domains that participants identified were lifestyle issues (23 items), followed by technical (drive-line, battery) issues (14 items). Participants easily and clearly identified their values: life extension; family; and mobility. Participants reported the need to meet other patients and caregivers before device placement (n = 31), and to have an involved caregiver (n = 28) to synthesize information. Some participants demonstrated a lack of clarity regarding transplant probability: 9 of 15 patients described themselves as on a transplant trajectory, yet 7 of these were destination therapy patients. Finally, we found that decisional regret scores were low (1.307). Informed consent and shared-decision making should: (a) help patients offered highly invasive technologies for life-threatening disease get past the initial "anything to avoid thinking about death" reaction and make a more informed decision; (b) clarify transplant status; and (c) focus on lifestyle and technical issues, as patients have the most informational needs in these domains.


Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo.
Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)y1. Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.


Experiments on the application of IOHMMs to model financial returns series.
Input-output hidden Markov models (IOHMM) are conditional hidden Markov models in which the emission (and possibly the transition) probabilities can be conditioned on an input sequence. For example, these conditional distributions can be linear, logistic, or nonlinear (using for example multilayer neural networks). We compare the generalization performance of several models which are special cases of input-output hidden Markov models on financial time-series prediction tasks: an unconditional Gaussian, a conditional linear Gaussian, a mixture of Gaussians, a mixture of conditional linear Gaussians, a hidden Markov model, and various IOHMMs. The experiments compare these models on predicting the conditional density of returns of market and sector indices. Note that the unconditional Gaussian estimates the first moment with the historical average. The results show that, although for the first moment the historical average gives the best results, for the higher moments, the IOHMMs yielded significantly better performance, as estimated by the out-of-sample likelihood.


The relationships among pain, nonpain symptoms, and quality of life measures in older adults with cancer receiving hospice care.
Gathering firsthand or reported information about patients in the final stages of terminal cancer is difficult due to patient frailty, cognitive impairment, excessive fatigue, and severity of illness, as well as gatekeeping by hospice providers and caregivers, and highly variable documentation practices. We sought to further understand and elucidate end-of-life experiences in older cancer patients through the application of validated tools employed in the hospice setting. This article summarizes data collected about pain, non-pain symptoms, and other aspects of quality of life (QOL) as reported by older hospice patients or by their caregivers during the 2 weeks of hospice care. Data was collected from an ongoing Institutional Human Subjects Review Board-approved research project with 94 older adults with cancer or their caregivers receiving service in a home setting from 14 Midwestern hospices. Participants completed one or two telephone interviews. Instruments used to gather information include the Brief Pain Inventory and the Brief Hospice Inventory. Data analysis showed mean "worst pain" ratings significantly decreased from Interview 1 to Interview 2, and pain reports were significantly correlated with fatigue, anxiety, appetite, comfort, symptom control, and overall QOL. Our findings reinforce previously held views that older patients with cancer experience pain and non-pain symptoms. And both pain and non-pain symptoms can impact and confound the treatment of other symptoms and interfere with the patient's overall QOL. The results of this study support the assertion that hospice care can have a positive impact on pain severity and related suffering, as well as patient QOL as death approaches.


Is a single definition of the metabolic syndrome appropriate?--A comparative study of the USA and Asia.
The metabolic syndrome has been identified as an increasingly important precursor to cardiovascular diseases in many Asian populations. Our objective was to compare the contribution of component risk factors to the diagnosis of the metabolic syndrome, as defined by the Third report of the National Cholesterol Education Program Expert Panel Adult Treatment Panel (NCEP-ATPIII), in the US and selected Asian populations. Nationally representative survey data from Hong Kong, Taiwan, Thailand and the US were used. Analyses were restricted to men and women aged > or = 35 years. The age-standardized prevalence of the NCEP-ATPIII defined metabolic syndrome was highest in the US (31% in men, 35% in women), and lowest in Taiwan (11% in men, 12% in women). The component risk factors that defined the presence of the metabolic syndrome varied between countries. As expected, abnormal waist circumference was considerably more prevalent among individuals with the metabolic syndrome in the US (72% in men, 94% in women) compared with their Asian counterparts, but substantial variation was also observed between the Asian populations (13-22% in men, 38-63% in women). Furthermore, the relative contribution of other risk factors to the metabolic syndrome was also substantially different between countries. The NCEP-ATPIII definition identifies a heterogeneous group of individuals with the metabolic syndrome in different populations.


SREBP-1 transcription factors regulate skeletal muscle cell size by controlling protein synthesis through myogenic regulatory factors.
SREBP-1 are ubiquitously expressed transcription factors, strongly expressed in lipogenic tissues where they regulate several metabolic processes like fatty acid synthesis. In skeletal muscle, SREBP-1 proteins regulate the expression of hundreds of genes, and we previously showed that their overexpression induced muscle atrophy together with a combined lack of expression of myogenic regulatory factors. Here we present evidences that SREBP-1 regulate muscle protein synthesis through the downregulation of the expression of MYOD1, MYOG and MEF2C factors. In myotubes overexpressing SREBP-1, restoring the expression of myogenic factors prevented atrophy and rescued protein synthesis, without affecting SREBP-1 action on atrogenes and proteolysis. Our results point out the roles of MRFs in the maintenance of the protein content and cell size in adult muscle fibre, and contribute to decipher the mechanisms by which SREBP-1 regulate muscle mass.


The protein and neutral lipid composition of lipid droplets isolated from the fission yeast, Schizosaccharomyces pombe.
Lipid droplets consist of a core of neutral lipids surrounded by a phospholipid monolayer with bound proteins. Much of the information on lipid droplet function comes from proteomic and lipodomic studies that identify the components of droplets isolated from organisms throughout the phylogenetic tree. Here, we add to that important inventory by reporting lipid droplet factors from the fission yeast, Schizosaccharomyces pombe. Unique to this study was the fact that cells were cultured in three different environments: 1) late log growth phase in glucose-based media, 2) stationary phase in glucosebased media, and 3) late log growth phase in media containing oleic acid. We confirmed colocalization of major factors with lipid droplets using live-cell fluorescent microscopy. We also analyzed droplets from each of the three conditions for sterol ester (SE) and triacylglycerol (TAG) content, along with their respective fatty acid compositions. We identified a previously undiscovered lipid droplet protein, Vip1p, which affects droplet size distribution. The results provide further insight into the workings of these ubiquitous organelles.


Familial respiratory tract cancer. Opportunities for research and prevention.
Case studies of two families with lung and other respiratory tract cancers were investigated. Consenting family members underwent comprehensive evaluation, including physical examination, routine laboratory studies, pulmonary function testing, sputum cytology analysis, and lymphocyte karyotyping. In both families, the environmental influence of smoking and, to a lesser extent, occupational exposures were evident risks. Both families had members with multiple primary malignant neoplasms and probably radiogenic cancers, suggestive of inherent predisposition to environmentally induced neoplasia. Furthermore, one family had a newly recognized syndrome of limb and dental anomalies, and, independently, two members were carriers of a balanced translocation between chromosomes 13 and 14. Efforts were made to prevent further respiratory cancer deaths, to search for laboratory markers of risk, and to store blood and tissue specimens for assays in development.


The Relationship Between Arthroplasty Surgeons' Experience Level and Optimal Cable Tensioning in the Fixation of Extended Trochanteric Osteotomy.
In this study, our aim was to examine the relationship between the arthroplasty surgeons' experience level and their aptitude to adjust the cable tension to the value recommended by the manufacturer when asked to provide fixation with cables in artificial bones that underwent extended trochanteric osteotomy (ETO). A custom-made cable tensioning device with a microvoltmeter was used to measure the tension values in Newtons (N). An ETO was performed on 4 artificial femur bones. Surgeons at various levels of experience attending the IXth National Arthroplasty Congress were asked to fix the osteotomized fragment using 1.7-mm cables and the tensioning device. The participants' demographic and experience data were investigated and recorded. The surgeons with different level of experience repeated the tensioning test 3 times and the average of these measurements were recorded. In 19 (35.2%) of the 54 participants, the force applied to the cable was found to be greater than the 490.33 N (50 kg) value recommended by the manufacturer. No statistically significant difference was determined between the surgeon's years of experience, the number of cases, and the number of cables used and the tension applied over the recommended maximum value (P = .475, P = .312, and P = .691, respectively). No significant relationship was found between the arthroplasty surgeon's level of experience and the adjustment of the cable with the correct tension level. For this reason, we believe that the use of tensioning devices with calibrated tension gauges by orthopedic surgeons would help in reducing the number of complications that may occur due to the cable.


[Indication for laparoscopic resection of colorectal cancer].
Whether a laparoscopic resection for colorectal cancer is indicated depends on the technical feasibility as well as on the potential advantages of the laparoscopic approach compared to conventional surgery. Short-term results from 11 randomized studies are available showing potential advantages. Long term results from 2 randomized trials do not suggest disadvantages but more likely some survival benefits.


Measuring the T-cell down-regulation of TCR-zeta, ZAP-70 and CD28 in arthritis patients: An old tool for new biomarkers.
Low T-cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down-expression of TCR-related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR-ZETA, ZAP-70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)-derived T cells. In PB, ZETA-downregulation in CD4+ CD28+ and consequent CD4+ CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA-downregulation extends to CD8+ CD28null and/or CD8+ CD28+ cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA-downregulation in CD4+ CD28+ may also lead to CD4+ CD28+ ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA-downregulation in CD8+ CD28null and consequent CD8+ CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP-downregulation in CD8+ CD28+ and consequent CD8+ CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETA-downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down-regulation in CD8+ CD28null, and non-rheumatoid arthritides showing significant down-regulation in CD4+ CD28+ . Altogether, we identified new molecular and cellular biomarkers of arthritis-related T-cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.


Hemocyte-targeted gene expression in the female malaria mosquito using the hemolectin promoter from Drosophila.
Hemocytes, the immune cells in mosquitoes, participate in immune defenses against pathogens including malaria parasites. Mosquito hemocytes can also be infected by arthropod-borne viruses but the pro- or anti-viral nature of this interaction is unknown. Although there has been progress on hemocyte characterization during pathogen infection in mosquitoes, the specific contribution of hemocytes to immune responses and the hemocyte-specific functions of immune genes and pathways remain unresolved due to the lack of genetic tools to manipulate gene expression in these cells specifically. Here, we used the Gal4-UAS system to characterize the activity of the Drosophila hemocyte-specific hemolectin promoter in the adults of Anopheles gambiae, the malaria mosquito. We established an hml-Gal4 driver line that we further crossed to a fluorescent UAS responder line, and examined the expression pattern in the adult progeny driven by the hml promoter. We show that the hml regulatory region drives hemocyte-specific transgene expression in a subset of hemocytes, and that transgene expression is triggered after a blood meal. The hml promoter drives transgene expression in differentiating prohemocytes as well as in differentiated granulocytes. Analysis of different immune markers in hemocytes in which the hml promoter drives transgene expression revealed that this regulatory region could be used to study phagocytosis as well as melanization. Finally, the hml promoter drives transgene expression in hemocytes in which o'nyong-nyong virus replicates. Altogether, the Drosophila hml promoter constitutes a good tool to drive transgene expression in hemocyte only and to analyze the function of these cells and the genes they express during pathogen infection in Anopheles gambiae.


Complete genome sequence of an H5N2 avian influenza virus isolated from a parrot in southern China.
We report the complete genome sequence of an H5N2 avian influenza virus (AIV) that was first isolated from a parrot in Guangdong in southern China in 2004. Genomic sequence and phylogenetic analyses showed that it was highly homologous with the North American H5N2 viruses and all eight genes of this virus belonged to the North American gene lineage. These data will help in the investigation of the epidemiology and host range of AIVs in southern China.


[Hughes-Stovin Syndrome, a case report].
The Hughes-Stovin syndrome is a rare entity characterized by deep vein thrombosis and pulmonary artery aneurysms of unknown etiology and pathogenesis. Some authors considered a variant of Behcet's disease. Its natural course is usually fatal. The symptoms are cough, dyspnea, hemoptysis, chest pain and fever. The treatment goes from steroids and cytotoxic agents to surgery. We present the case of a 41 year old man who shows dyspnea, hemoptysis, and chest pain leading to the diagnosis of deep venous thrombosis of the right leg, lung thromboembolism and pulmonary artery aneurysms. He was treated with high-dose corticosteroids and 6 cyclophosphamide pulses of 1 gram each per 6 months with complete regression of aneurysms and symptomatology.


[Value of digital subtraction angiography in cerebrovascular diseases].
Digital Angiography was done on 1 000 patients with cerebral vascular diseases at the cervical or cerebral level. This was done by intravenous injection in 800 cases and by intra-arterial injection in 200 cases. The study of the cervical carotid bifurcation is favorably compared to the one obtained by the conventional arteriography. The intracranial aneurysms of 1 centimeter are well visualized and this method is valid to eliminate a giant aneurysm before transsphenoidal surgery. The digital angiography also allows the study of venous and sinus malformations. The postoperative controls of the aneurysms, carotid endarterectomies and extra-intracranial bypass are perfectly shown and can be repeated. The comparative study between the intravenous digital angiography and the conventional angiography have shown a good correlation between both tests in 80% of the cases. This rate can be risen by intra-arterial injection. It is a non-invasive method, reliable and economical with very little complications. This test can be done on an external basis and repeated if necessary. The disadvantages are the overlapping of the vessels, the necessity of the strict immobilisation of the head and the difficulty of evaluating the vessels whose diameter is inferior to 1 mm.


Polypharmacy and hospitalization among older home care patients.
One of the major goals of home care is the prevention of hospitalization. The objective of this study was to examine the relation between medication use (number, type, and inappropriateness) and hospitalization among home care patients older than 65 years. A retrospective chart review of 833 discharged older home care patients was performed. These patients were consecutive discharges from a single home care agency who either (a) returned to independent self-care or care of the family (S/F Care group) or (b) were admitted to the hospital (Hospitalized group). Medication assessment within these two groups included total number of medications (prescription and nonprescription); degree of polypharmacy (percentage of patients taking 5 or more, 7 or more, and 10 or more medications); and prevalence for different types of medications, including different types of inappropriate medications. Inappropriate medications were designated according to a list that was previously developed through a modified Delphi consensus technique by a panel of 13 experts in geriatric pharmacology and has been utilized in other studies. Student's t test was used for continuous variables and chi-square test was used for categorical variables to evaluate for differences between the S/F Care group and the Hospitalized group (p <.05). For comparisons of types of medications, p < .01 was used for significant differences, because of the high number of comparisons made. Of 833 discharges, 644 (77.3%) returned to self-care or care of the Family (S/F Care group) and 189 (22.7%) were hospitalized. The Hospitalized group, compared with the S/F Care group, was taking a higher number of medications (mean +/- SD: 6.6+/-3.9 vs 5.7+/-3.4, p = .004), and had a higher percentage of patients taking 7 or more medications (46% vs 26%, p = .002) and 10 or more medications (21% vs 10%, p = .005), but not 5 or more medications. Only three types of medications were more commonly used among patients in the Hospitalized group than among patients in the S/F Care group: clonidine (4.2% vs 1.1%, p = .004); mineral supplements (23.8% vs 14.8%, p = .003); and metoclopramide (5.8% vs 2.0%, p = .006). The Hospitalized group had a lower percentage of patients taking inappropriate medications than did the S/F Care group (20% vs 27%, p = .040), but none of the types of inappropriate medications was used more often in either group. This study shows a relationship between high levels of polypharmacy and hospitalization. Although it cannot be determined from this study whether a higher number of medications was an indicator of sicker patients at risk for hospitalization, or whether a higher number of medications might have directly led to hospitalization, polypharmacy should still be considered a marker for older home care patients for whom prevention of hospitalization is the goal.


The use of direct-fed microbials for mitigation of ruminant methane emissions: a review.
Concerns about the environmental effect and the economic burden of methane (CH4) emissions from ruminants are driving the search for ways to mitigate rumen methanogenesis. The use of direct-fed microbials (DFM) is one possible option to decrease CH4 emission from ruminants. Direct-fed microbials are already used in ruminants mainly to increase productivity and to improve health, and are readily accepted by producers and consumers alike. However, studies on the use of DFM as rumen CH4 mitigants are scarce. A few studies using Saccharomyces cerevisiae have shown a CH4-decreasing effect but, to date, there has not been a systematic exploration of DFM as modulators of rumen methanogenesis. In this review, we explored biochemical pathways competing with methanogenesis that, potentially, could be modulated by the use of DFM. Pathways involving the redirection of H2 away from methanogenesis and pathways producing less H2 during feed fermentation are the preferred options. Propionate formation is an example of the latter option that in addition to decrease CH4 formation increases the retention of energy from the diet. Homoacetogenesis is a pathway using H2 to produce acetate, however up to now no acetogen has been shown to efficiently compete with methanogens in the rumen. Nitrate and sulphate reduction are pathways competing with methanogenesis, but the availability of these substances in the rumen is limited. Although there were studies using nitrate and sulphate as chemical additives, use of DFM for improving these processes and decrease the accumulation of toxic metabolites needs to be explored more. There are some other pathways such as methanotrophy and capnophily or modes of action such as inhibition of methanogens that theoretically could be provided by DFM and affect methanogenesis. We conclude that DFM is a promising alternative for rumen methane mitigation that should be further explored for their practical usage.


Diagnostic and therapeutic application of noncoding RNAs for hepatocellular carcinoma.
MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate gene expression posttranscriptionally, targeting thousands of messenger RNAs. Long noncoding RNAs (lncRNAs), another class of noncoding RNAs, have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miRNAs and lncRNAs in hepatocellular carcinoma (HCC) are frequently observed, clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently expected. Here, we summarize recent findings regarding deregulated miRNAs and lncRNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically, we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers, a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics, we further summarize clinical and preclinical trials using oligonucleotides involving the use of miRNAs and small interfering RNAs against HCC as novel therapeutics. Finally, we discuss current open questions, which must be clarified in the near future for realistic clinical applications of these new strategies.


Cognitive Fatigability Interventions in Neurological Conditions: A Systematic Review.
Although fatigue is a well-studied concept in neurological disease, cognitive fatigability (CF) is less understood. While most studies measure fatigue using subjective self-report, fewer have measured CF objectively. Given the negative impact of CF on quality-of-life, there is a need for targeted interventions. The objective of this review was to determine which procedural, behavioural and pharmacological treatments for objectively measured CF are available to people living with neurological conditions. In accordance with the PRISMA guidelines, systematic searches for randomized control trials (RCTs), case-controlled studies and case reports/series were conducted across the Ovid Medline, PsycInfo, EMBASE and Cochrane Library databases. English-language articles published between 1980 and February 2019 were considered for eligibility. Included were those that objectively measured CF in individuals with neurological disease/disorder/dysfunction between the ages of 18 and 65 years. Studies were reviewed using a modified Cochrane Data Extraction Template. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review process was facilitated using Covidence software (www.covidence.org). Two authors reviewed articles independently, with a third resolving conflicts regarding article inclusion. The search identified 450 records. After duplicates were removed and remaining titles/abstracts were screened for eligibility, 28 full-text articles were assessed, and two studies were included in the qualitative synthesis. Studies were a priori divided into those with pharmacological, procedural or behavioural interventions. Two studies met eligibility criteria; both of these included participants with multiple sclerosis. One study utilized a procedural intervention (i.e. transcranial direct current stimulation), while the other utilized a pharmacological intervention (i.e. fampridine-SR). Studies were evaluated for risk of bias, and evidence from both eligible studies was discussed. Despite the positive results of the procedural intervention, the paucity of eligible studies and the nascent nature of the field suggests that more studies are required before firm conclusions can be drawn regarding the amenability of CF to treatment. The review was registered with PROSPERO (CRD42019118706).


Genetic Interaction Score (S-Score) Calculation, Clustering, and Visualization of Genetic Interaction Profiles for Yeast.
This protocol describes computational analysis of genetic interaction screens, ranging from data capture (plate imaging) to downstream analyses. Plate imaging approaches using both digital camera and office flatbed scanners are included, along with a protocol for the extraction of colony size measurements from the resulting images. A commonly used genetic interaction scoring method, calculation of the S-score, is discussed. These methods require minimal computer skills, but some familiarity with MATLAB and Linux/Unix is a plus. Finally, an outline for using clustering and visualization software for analysis of resulting data sets is provided.


Characterization of monophenolase activity of polyphenol oxidase from iceberg lettuce.
Polyphenol oxidase (EC 18.104.22.168), a thylakoid membrane-bound enzyme, was isolated by sonication of osmotically shocked chloroplasts from iceberg lettuce (Lactuca sativa). The enzyme showed monophenolase activity when assayed on (p-hydroxyphenyl)propionic acid with 3-methyl-2-benzothiazolinone hydrazone in a reliable continuous spectrophotometric method, with high sensitivity, accuracy, and precision. The monophenolase activity showed a lag period before the steady-state rate (V(ss)) was reached. Both kinetic parameters, the lag period and the steady-state rate, depended on the pH, the enzyme and substrate concentrations, and the presence of catalytic amounts of o-diphenol. This activity shows inhibition by high substrate concentration. The experimental results correspond with the mechanism previously described for PPO from other sources. Kinetic constants K(m), V(max), and K(i) were determined.


Vascular casting and scanning electron microscopy in diabetes.
Scanning electron microscopic (SEM) studies of the vascular casts of human eyes removed at autopsy from subjects with a long-standing history of Diabetes Type I were performed. Changes in the choroidal vasculature include: Venal focal dilations and narrowings, increased tortuosity, hypercellularity, increased formation of vascular loops and microaneurysms in choriocapillaries and formation of sinus-like structures between choroidal lobules. This study strongly supports earlier light microscopic and transmission electron microscopy observations on changes in the choroid. The retinal vascular changes shown by SEM are microaneurysm formation, drop-out of capillaries and neovascularization. Changes in the choroid, especially in diabetic choriocapillaries can be suspected to be a supporting factor in diabetic retinopathy by a decrease of oxygenation of the outer layers of the retina.


Fibronectin binding by Salmonella strains: evaluation of a particle agglutination assay.
Thirty-five Salmonella strains isolated from human cases of salmonellosis were tested and compared for their fibronectin (fn) binding capacities by using two fn-particle agglutination assays (fn-PAAs) prepared by coating with human fn either (i) latex beads (Difco; 0.81-micron diameter) (L-fn-PAA) or (ii) heat-killed formalin-treated Staphylococcus aureus Cowan 1 cells (C-fn-PAA). Six S. aureus strains were also included in this study as controls. The strains were cultured on colonization factor antigen agar and blood agar and in tryptic soy broth and brain heart infusion broth. The Salmonella and S. aureus strains were cultured at 33 and 37 degrees C, respectively, for optimal expression of fn-binding proteins. Bacterial cells (approximately 10(10) cells per ml) harvested from growth in various culture media and suspended in 0.02 M potassium phosphate buffer (pH 6.8) agglutinated the fn-PAA reagents. These reactions were scored semiquantitatively from + to + depending on the speed or intensity of the reactions within 2 min. Maximum agglutination in fn-PAA systems was observed when the cells were grown in brain heart infusion broth, while tryptic soy broth proved to be least suitable media for culturing cells for fn-PAAS. Although a statistically highly significant correlation was obtained between results of assays of radiolabeled fn and 29-kDa fragment binding, no significant correlation was observed (i) between the results of strains cultured in different media or (ii) when semiquantitative score results of the two fn-PAA systems were compared with those of the conventional radiolabeled fn assay. To enhance the efficiency of the test system, the C-fn-PAA reagent was stained with methylene blue (2% in 0.17 M glycine-NaOH buffer [pH 6.8]). This facilitated easy interpretation of results, which could be performed on hydrophobic paper instead of glass slides. The results obtained with both unstained C-fn-PAA and stained C-fn-PAA were comparable to each other and reproducible. Although the fn-PAAs are simple and easy to perform, the results did not differentiate between negative, low, moderate, and high binding abilities when Salmonella strains were evaluated for fn binding, and the results were not comparable to those obtained by the conventional radiolabeling method.


Developmental trajectories of physical activity and television viewing during adolescence among girls: National Growth and Health Cohort Study.
Analytic methodology for investigating physical activity patterns over time has been limited. The aim of this study was to demonstrate the group-based trajectory analysis process for identifying developmental physical activity (PA) and television (TV) viewing trajectories and the risk factor of PA trajectories, and for examining a relationship between PA and TV viewing trajectories among adolescent girls. Secondary analysis was conducted using the National Growth and Health Study (NGHS) dataset. The NGHS administered the Habitual Activity Questionnaire and TV viewing questionnaire to White and Black girls at age 10, 12, 14, 16, 17, 18, and 19 years. Group-based trajectory analyses were conducted to identify distinct PA trajectories. Race was chosen to present an example of the risk factor analysis and was added as a predictor in the trajectory model. Dual-trajectory analysis was conducted to estimate probabilities of TV viewing trajectory groups conditional on the PA trajectory groups. A total of 2,155 girls (52% Black) were included in the data analysis. We identified four PA trajectories: substantially decreasing from high PA (PA group 1, 9.4%), maintaining moderate PA (PA group 2, 31.6%), maintaining high PA (PA group 3, 5.8%), and decreasing from moderate PA (PA group 4, 53.2%). A significantly lower proportion of Black girls had high PA levels at baseline and maintained their baseline PA than White girls. Most girls who were classified as maintaining high PA (88%) were also classified as decreasing TV viewing. A group-based trajectory approach provides new insights about the patterns of maintaining moderate or high levels of PA that exist among adolescent girls. However, a lower proportion of Black girls followed the maintenance patterns than White girls. The behavioral development of PA and TV viewing may be intertwined among adolescent girls.


Deletion of histo-blood group A and B antigens and expression of incompatible A antigen in ovarian cancer.
Expression of histo-blood group ABH antigens in 53 cases of ovarian cancer was examined by immunoperoxidase staining of Formalin-fixed as well as frozen histological sections with various monoclonal antibodies, including those defining type 1, 2, 3, and 4 chain A. Findings of major interest were (a) deletion of A and B determinants in tumors from histo-blood group A and B individuals, and a high incidence of H antigen deletion in tumors from group O individuals were observed and (b) strong expression of incompatible A antigen in two of 10 samples from group B patients and in two of nine samples from group O patients was demonstrated. A antigen expression was defined by monoclonal antibody AH21, which reacts with monofucosyl type 1 chain A (ALed), but not by other types of anti-A antibodies directed to difucosyl type 1 chain A (ALeb), mono- or difucosyl type 2 chain A, or type 3 or type 4 chain A. The reactivity of monoclonal antibody AH21 was abolished by alpha-N-acetylgalactosaminidase from chicken liver. These findings clearly identified the specific expression of incompatible A antigen with the structure monofucosyl type 1 chain A (ALed) in tumors from histo-blood group B and O individuals.


Fluid flow assays.
Mechanical signals are major regulators of skeletal homeostasis as the addition of exogenous load is followed by enhanced bone formation and the removal of normal loads is followed by net bone loss. The mechanism by which bone cells perceive and respond to changes in their biophysical environment are still poorly understood, but it is widely accepted that the detection of interstitial fluid flow is an initiating cue. In this chapter, we describe two in vitro systems designed to examine the effects of fluid flow on bone cell behavior and to elucidate the signaling cascades activated by this stimulus. The first utilizes a parallel plate flow chamber designed to stimulate a single bone cell type grown on glass slides. The second employs a rotating disk fluid flow apparatus. Commercially-available cell culture inserts allow one type of bone cell to be exposed to fluid flow and signals to be communicated to a second bone cell model not exposed to fluid flow.


Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis.
Rapid and point-of-care (POC) tests for syphilis are an invaluable screening tool, yet inadequate evaluation of their diagnostic accuracy against best reference standards limits their widespread global uptake. To fill this gap, a systematic review and meta-analysis was conducted to evaluate the sensitivity and specificity of rapid and POC tests in blood and serum samples against Treponema pallidum (TP) specific reference standards. Five electronic databases (1980-2012) were searched, data was extracted from 33 articles, and Bayesian hierarchical models were fit. In serum samples, against a TP specific reference standard point estimates with 95% credible intervals (CrI) for the sensitivities of popular tests were: i) Determine, 90.04% (80.45, 95.21), ii) SD Bioline, 87.06% (75.67, 94.50), iii) VisiTect, 85.13% (72.83, 92.57), and iv) Syphicheck, 74.48% (56.85, 88.44), while specificities were: i) Syphicheck, 99.14% (96.37, 100), ii) Visitect, 96.45% (91.92, 99.29), iii) SD Bioline, 95.85% (89.89, 99.53), and iv) Determine, 94.15% (89.26, 97.66). In whole blood samples, sensitivities were: i) Determine, 86.32% (77.26, 91.70), ii) SD Bioline, 84.50% (78.81, 92.61), iii) Syphicheck, 74.47% (63.94, 82.13), and iv) VisiTect, 74.26% (53.62, 83.68), while specificities were: i) Syphicheck, 99.58% (98.91, 99.96), ii) VisiTect, 99.43% (98.22, 99.98), iii) SD Bioline, 97.95%(92.54, 99.33), and iv) Determine, 95.85% (92.42, 97.74). Rapid and POC treponemal tests reported sensitivity and specificity estimates comparable to laboratory-based treponemal tests. In resource limited settings, where access to screening is limited and where risk of patients lost to follow up is high, the introduction of these tests has already been shown to improve access to screening and treatment to prevent stillbirths and neonatal mortality due to congenital syphilis. Based on the evidence, it is concluded that rapid and POC tests are useful in resource limited settings with poor access to laboratories or screening for syphilis.