Cognitive Dissonance of Self-Standards: A Negative Interaction of Green Compensation and Green Training on Employee Pro-Environmental Behavior in China.
Studies of GHRM practices number in thousands; however, they have failed to provide Chinese contextual evidence for their interactive effects on employee pro-environmental behavior (EPEB). To bridge this research gap as well as to address organizational practitioners' concern in GHRM practices, our study explores the possible interactive effect of green compensation (GC) and green training (GT), which are two core practices of GHRM and are widely employed by Chinese organizations simultaneously, on EPEB drawing on self-determination theory, and unravels the underlying mechanism by introducing employee green self-accountability (EGSA) as a mediator based on the cognitive dissonance theory of self-standards. Using on-line survey and five-point Likert rating method, employees (N=847) working in Chinese organizations were requested to self-rate GC, GT, and EGSA; their direct supervisors were invited to evaluate EPEB. The mediated moderation testing procedures with SPSS and the bootstrapping approach with MPLUS were adopted to test the mediated moderation. When being used separately, GC and GT are positively related to EPEB (β=0.426, p < 0.001; β=0.368, p < 0.001). When being adopted simultaneously, a negative relationship (the simple slope=-0.454, t=3.671, p=0.000) exists between GC and EPEB at higher-level GT. EGSA partially mediates the negative interaction with 95% bias-corrected confidence intervals [-0.054, -0.018]. In the Chinese context, when being used simultaneously with high-high combination, GC and GT negatively interact with each other to engender the squeezed effect of intrinsic motivation by extrinsic motivation, which directly impairs EPEB, and cause employee cognitive dissonance of self-standards, which indirectly weakens EPEB through reducing EGSA. This paper is an attempt to show novelty in identifying negative interactions between GC and GT in EPEB in China and a mediating role of EGSA. Additionally, it addresses organizational practitioners' concern well and provides important implications for decision-making in GHRM practices and EPEB enhancement.


Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging the MicroRNA 15a/16 cluster.
Hepatitis B virus (HBV) causes chronic hepatitis in hundreds of millions of people worldwide, which can eventually lead to hepatocellular carcinoma (HCC). The molecular mechanisms underlying HBV persistence are not well understood. In this study, we found that HBV inhibited the chemotherapy drug etoposide-induced apoptosis of hepatoma cells. Further analysis revealed that HBV mRNAs possess a microRNA 15a/16 (miR-15a/16)-complementary site (HBV nucleotides [nt] 1362 to 1383) that acts as a sponge to bind and sequester endogenous miR-15a/16. Consequently, Bcl-2, known as the target of miR-15a/16, was upregulated in HBV-infected cells. The data from HBV-transgenic mice further confirmed that HBV transcripts cause the reduction of miR-15a/16 and increase of Bcl-2. More importantly, we examined the levels of HBV transcripts and miR-15a/16 in HBV-infected HCC from patients and found that the amount of HBV mRNA and the level of miR-15a/16 were negatively correlated. Consistently, the level of Bcl-2 mRNA was upregulated in HBV-infected patients. In conclusion, we identified a novel HBV mRNA-miR-15a/16-Bcl-2 regulatory pathway that is involved in inhibiting etoposide-induced apoptosis of hepatoma cells, which may contribute to facilitating chronic HBV infection and hepatoma development.


Rothmund-Thomson syndrome: a case series from a tertiary pediatric hospital in Mexico.
Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a multisystem level. Case 1. A 4-year-old male patient, consanguineous parents, 26-year-old brother with a probable diagnosis of Rothmund-Thompson syndrome. He presented with adactyly of the right thumb, hypoplasia of the left thumb, delayed growth and psychomotor development. At 3 months, he presented rough, dry, sparse hair and erythematous lesions on the face, leaving hyperpigmented and hypopigmented spots with a reticulated pattern. We detected hypoacusis, skeletal alterations, narrow chin, short stature, severe malnutrition, and chronic and asymptomatic hypodontia. Genetic sequencing showed a mutation for the RECQL4 gene, for which a multidisciplinary follow-up was provided by the genetics, gastroenterology, nutrition, endocrinology, stomatology, audiology, orthopedics, rehabilitation, ophthalmology and oncology services. Case 2. A 2-year-old female patient presented facial erythema that spread to the arms and legs at 3 months; skin biopsy showed poikiloderma. She was evaluated by the endocrinology service and followed up for short stature and hypogonadism. A genetic study was not performed. Rothmund-Thomson syndrome is characterized by atrophy. Only a few cases are reported in the literature. We present two cases of Rothmund-Thomson syndrome, emphasizing its clinical and dermatological characteristics.


Improving platelet supply chains through collaborations between blood centers and transfusion services.
Blood centers and hospital transfusion services are challenged with maintaining an adequate platelet (PLT) inventory to minimize the number of outdated units without risking a major shortage. A novel approach to inventory management was established at our institution through a collaboration between the Stanford University Medical Center (SUMC) Transfusion Service, the Stanford Blood Center (SBC), and the Department of Management Science and Engineering. An analysis of the supply chain performance between SBC and SUMC Transfusion Service was performed. First, the interaction between processes, such as blood collection, rotation, and inventory management, was studied. Second, changes were implemented based on the recommendations from the analysis team. Finally, a postanalysis was performed reflecting on the improvement of the operations between SUMC and SBC. A comprehensive data analysis of the PLT supply chain allowed the identification of three series of improvements to be implemented: 1) on SBC's PLT collection, 2) on SBC's rotation process, and 3) on the PLT inventory management policy at SUMC. A postimplementation analysis showed a reduction in the overall PLT outdate rate from 19% in the first quarter of 2006, down to 9% in the third quarter of 2008. A multidisciplinary effort among SUMC Transfusion Service, SBC, and experts in supply chain management resulted in a process improvement, which reduced the rate of PLT outdate at both SBC and SUMC Transfusion Service down to 9%, with a significant cost reduction of more than half a million dollars per year.


Explicit analytic equations for multimolecular thermal melting curves.
The analysis of thermal melting curves requires the knowledge of equations for the temperature dependence of the relative fraction of folded and unfolded components. To implement these equations as standard tools for curve fitting, they should be as explicit as possible. From the van't Hoff formalism it is known that the equilibrium constant and hence the folded fraction is a function of the absolute temperature, the van't Hoff transition enthalpy, and the melting temperature. The work presented here is devoted to the mathematically self-contained derivation and the listing of explicit equations for the folded fraction as a function of the thermodynamic parameters in the case of arbitrary molecularities. Part of the results are known, others are new. It is in particular shown for the first time that the folded fraction is the composition of a universal function which depends solely on the molecularity and a dimensionless function which is governed by the concrete thermodynamic regime but is independent of the molecularity. The results will prove useful for extracting the thermodynamic parameters from experimental data on the basis of regression analysis. As supporting information, open-source Matlab scripts for the computer implementation of the equations are provided.


[The coordination of care for tuberculosis control].
This descriptive epidemiological study analyzed the coordination of tuberculosis (TB) patient care in primary healthcare services according to 23 patients, 16 professionals, and 17 administrators from Ribeirão Preto, Sao Paulo, using an instrument adapted to evaluate TB. According to the informants, the coordination of healthcare provided to patients under the treatment of the Tuberculosis Control Program team was considered satisfactory; however, when there is a need to refer the patient to other care units there are weak points in the coordination of healthcare, which include: interruption of communication flow; and patients' incipient participation in the care process, with a need to increase the sense of responsibility for patient care and encourage patients to become active agents in the process.


Cyclic nucleotides modulate the release of [3H] adenosine cyclic 3',5'-phosphate bound to the regulatory moiety of protein kinase I by the catalytic subunit of the kinase.
The rate of release of bound c[3H]AMP from the two types (A and B) of cAMP binding sites on the regulatory subunit dimer (R2I) of rabbit muscle protein kinase I was studied in the presence of the catalytic (C) subunit of protein kinase. Rebinding of released c[3H]AMP was avoided by using highly diluted reactants or adding unlabeled cAMP or its analogues. No significant C-induced dissociation of R2I-(c[3H]AMP)4 occurred in the absence of Mg2+-ATP. Of the two options that one or two molecules of C are required to induce the release of c[3H]AMP bound to R2I, only the first one was compatible with the first-order dependence on [C] of the rate of release of c[3H]AMP observed over a wide range of C concentrations. In the absence of added unlabeled cyclic nucleotide, the rate of the C-induced release of c[3H]AMP was the same from site A and site B. The apparent second-order rate constant for the association of C to R2I(c[3H]AMP)4 was 6 X 10(6) M-1 s-1 (37 degrees C, 0.15 M KCl). Raising the concentration of unlabeled cAMP in the medium up to 1 microM decreased by up to 50% the rate of the C-induced release of bound c[3H]AMP from both sites. This is explained by assuming that the association of one molecule of C to R2I(c-[3H]AMP)4 leads to the release of c[3H]AMP first from one R subunit and subsequently, by a process that can be blocked by about 1 microM cAMP, from the other R subunit. A further rise of the cAMP concentration decreased the rate of release from site B only, so that the C-induced release of c[3H]AMP occurred almost exclusively from site A at very high concentrations of cAMP. This suggests that c[3H]AMP is released first from site A and that this vacant site by interacting with cAMP inhibits the release of c[3H]AMP from site B of the same R subunit. The role of site A in controlling the C-induced release was further supported by the finding that several cAMP analogues inhibited the release with potencies correlating with their affinities for site A. The C-induced release of c[3H]AMP from aged R2I was about 10 times slower than that from fresh R2I. No significant C-induced release of c[3H]AMP was observed from the monomeric fragment obtained by limited trypsin treatment of R2(1).


Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab.
We evaluated the influence of HER2 gene amplification, as determined by fluorescence in situ hybridization (FISH), on clinical outcomes (objective response rates, time to disease progression, and overall survival time) in women with metastatic breast cancer treated with trastuzumab in 3 clinical trials. Breast cancer tissue specimens were evaluated using a direct labeled, dual-probe FISH assay. Specimens with a HER2:CEP17 ratio of > or = 2:0 were considered positive for gene amplification. All specimens had previously demonstrated overexpression of HER2 protein at the 2+ or 3+ level by immunohistochemistry using the Clinical Trials Assay. Response rate, time to disease progression, and survival times were then compared between the FISH-positive and FISH-negative cohorts in each of the 3 clinical trials. Informative FISH results were obtained in 765 (96%) of the 799 patients enrolled in the 3 clinical trials. Overall, 596 (78%) were FISH-positive and 169 (22%) were FISH-negative. The proportion of FISH-positive patients was comparable in all 3 trials. Clinical benefit from trastuzumab therapy appeared to be restricted to patients with FISH-positive metastatic breast cancer. In each clinical trial, the cohort of FISH-positive patients had higher overall response rates and longer durations of survival compared with FISH-negative patients. These data indicate that assessment of HER2 amplification by FISH is the preferred method to select patients for trastuzumab therapy.


Semi-automated generation of pictures for the Mouse Grimace Scale: A multi-laboratory analysis (Part 2).
The Mouse Grimace Scale (MGS) is an established method for estimating pain in mice during animal studies. Recently, an improved and standardized MGS set-up and an algorithm for automated and blinded output of images for MGS evaluation were introduced. The present study evaluated the application of this standardized set-up and the robustness of the associated algorithm at four facilities in different locations and as part of varied experimental projects. Experiments using the MGS performed at four facilities (F1-F4) were included in the study; 200 pictures per facility (100 pictures each rated as positive and negative by the algorithm) were evaluated by three raters for image quality and reliability of the algorithm. In three of the four facilities, sufficient image quality and consistency were demonstrated. Intraclass correlation coefficient, calculated to demonstrate the correlation among raters at the three facilities (F1-F3), showed excellent correlation. The specificity and sensitivity of the results obtained by different raters and the algorithm were analysed using Fisher's exact test (p < 0.05). The analysis indicated a sensitivity of 77% and a specificity of 64%. The results of our study showed that the algorithm demonstrated robust performance at facilities in different locations in accordance with the strict application of our MGS setup.


Digital Hardware Implementation of ReSuMe Learning Algorithm for Spiking Neural Networks.
Within this paper, we demonstrate the feasibility of the FPGA implementation as well as the 180nm CMOS circuit design of a particular biologically plausible supervised learning algorithm (ReSuMe). Based on the Spike-Timing-Dependent Plasticity (STDP) learning phenomenon, this design proposes a fully configurable implementation of STDP learning window function to adjust the learning process for different applications, optimizing results for each use case. The CMOS implementation in 180nm technology node supplied with 1.8V shows a core area of 0.78mm2 and verifies the suitability of an on-chip ReSuMe learning algorithm implementation and its capability of integration with a multitude of external and already designed structures of Spiking Neural Networks (SNNs).


Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.
Malignant peripheral nerve sheath tumors (MPNSTs) are the leading cause of death in neurofibromatosis type 1 (NF1) patients. Current treatment modalities have been largely unsuccessful in improving MPNST patient survival, making the identification of new therapeutic targets urgent. In this study, we found that interference with Usp9X, a deubiquitinating enzyme which is overexpressed in nervous system tumors, or Mcl-1, an anti-apoptotic member of the Bcl-2 family whose degradation is regulated by Usp9X, causes rapid death in human MPNST cell lines. Although both Usp9X and Mcl-1 knockdown elicited some features of apoptosis, broad spectrum caspase inhibition was ineffective in preventing knockdown-induced MPNST cell death suggesting that caspase-independent death pathways were also activated. Ultrastructural examination of MPNST cells following either Usp9X interference or pharmacological inhibition showed extensive cytoplasmic vacuolization and swelling of endoplasmic reticulum (ER) and mitochondria most consistent with paraptotic cell death. Finally, the Usp9X pharmacological inhibitor WP1130 significantly reduced human MPNST growth and induced tumor cell death in an in vivo xenograft model. In total, these findings indicate that Usp9X and Mcl-1 play significant roles in maintaining human MPNST cell viability and that pharmacological inhibition of Usp9X deubiquitinase activity could be a therapeutic target for MPNST treatment.


Prognostic significance of allelic imbalance of chromosome arms 7q, 8p, 16q, and 18q in stage T3N0M0 prostate cancer.
Frequent allelic imbalance of polymorphic markers mapped to regions of the 7q, 8p, 16q, and 18q arms has been reported in prostate cancer. To better define the clinical significance of these genetic alterations, we undertook a retrospective analysis of systemic progression and survival in patients with a single stage of prostate cancer. We ascertained all 227 patients from the Mayo Clinic Radical Prostatectomy Registry who had a histologic high-grade, pathologic stage C (pT3N0M0) tumor surgically removed between 1966 and 1987. The mean follow-up of this population of patients was 7.7 years. DNAs were extracted from cancer lesions identified in 5-micron paraffin-embedded tumor sections. Control DNAs were obtained from surgically removed lymph nodes. Paired DNA samples of 153 patients were available for analysis using 16 polymorphic microsatellite markers mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22. The frequencies of allelic imbalance for at least one marker mapped to 7q31, 8p22-p21, 16q23-qter, and 18q21-q22 were 30, 58, 53, and 45% of all informative cases, respectively. Allelic imbalance at 7q31 strongly correlated with systemic cancer progression and to a slightly lesser extent with cancer-specific death. Eight-year systemic cancer progression-free rates were 58 and 81% for cases with and without 7q31 allelic imbalance, respectively (P < 0.001). Eight-year prostate cancer-specific survival rates were 70 and 85% with and without 7q31 allelic imbalance, respectively (P = 0.019). Multivariate analysis indicated that allelic imbalance at 7q31 is a significant independent predictor of systemic progression (P < 0.001) and possibly prostate cancer death (P = 0.029). In addition, allelic imbalance of the specific loci D7S522 (7q31.1) and D8S258 (8p22-p21.3) was strongly associated with systemic progression (P < 0.001 and P = 0.010, respectively) and with prostate cancer death (P < 0.001 and P = 0.009, respectively). The results suggest that a gene or genes mapped to 7q31.1 and possibly 8p22-p21.3 play an important role in tumor progression, and that allelic imbalances at these regions are markers for poor prognosis in prostate carcinoma.


Seat cushion design for elderly wheelchair users based on minimization of soft tissue deformation using stiffness and pressure measurements.
A method for designing seat support surfaces using interface pressure and soft tissue stiffness criteria was evaluated. An algorithm designed to drive a rigid support surface on a programmable seating system to a shape for which the externally applied pressure is inversely related to the measured stiffness of adjacent soft tissue was evaluated on 30 elderly subjects (age 65 years or older). The resulting support surface shapes were transferred to compliant foam cushions and evaluated using interface pressure measurements. Pressure and stiffness measurements on the seating system indicated the surface shape control algorithm met the desired programmed criteria by achieving an inverse relationship between pressure and stiffness, as it converged to an "optimal" support surface shape. Evaluation of interface pressures on the compliant foam cushions showed that the pressure distributions on the cushions contoured to the optimal surface shapes were more uniform and had lower values than distributions on flat foam cushions and foam cushions contoured to shapes measured using state-of-the-art load-deflection devices. The results suggest that support surfaces designed using tissue stiffness as a criteria can provide loading conditions intended to minimize relative deformation and, thus, stress in load-bearing soft tissue.


Drag reduction using lubricant-impregnated surfaces in viscous laminar flow.
Lubricant-impregnated surfaces (LIS), where micro/nanotextured surfaces are impregnated with lubricating liquids, have received significant attention for their robust, superslippery properties. In this study, we systematically demonstrate the potential for LIS to reduce drag in laminar flows. We present a scaling model that incorporates the viscosity of the lubricant and elucidates the dependence of drag reduction on the ratio of the viscosity of the working fluid to that of the lubricant. We experimentally validate this dependence in a cone and plate rheometer and demonstrate a drag reduction of 16% and slip length of 18 μm in the case where the ratio of working fluid viscosity to lubricant viscosity is 260.


[Selective microproteinuria as a marker of incipient renal impairment in patients with hypertension].
Incidence of chronic renal failure has a worldwide tendency to growth. Hypertension occupies an important place among causes of this upward trend. That is why in patients with hypertension and incipient changes of the kidneys it seems most appropriate to use antihypertensive drugs with renoprotective properties. Early treatment with these drugs enables most effective lowering of risk of renal failure development and thus has a potential to prolong life of a patient. Selective microproteinuria is considered to be a marker of incipient renal impairement. Among groups of antihypertensive agents angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, beta-blockers, and diuretics have proven renoprotective properties.


Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-β (Aβ) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative Aβ-binding receptors that mediate Aβ neurotoxicity in cells and models of AD. Once Aβ interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, Aβ can also be internalized into neurons through unidentified Aβ receptors and induces malfunction of subcellular organelles, which explains some part of Aβ neurotoxicity. Understanding the neurotoxic signaling initiated by Aβ-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on Aβ-binding receptors and the neurotoxicity of oligomeric Aβ.


Surgical wound mucormycosis necessitating hand amputation: a case report.
We report an unusual case of cutaneous mucormycosis in a 17-year-old man who had no risk factors for fungal infection. The aggressive nature of cutaneous mucormycosis is illustrated. A high index of suspicion is crucial for identifying and preventing progression of this disease, which can lead to limb amputation, even death. Extra vigilance should be given to those who are immunocompromised, including those receiving short courses of steroids. Early recognition, prompt surgical intervention and initiation of an appropriate antifungal treatment are crucial in the management of this rare but potentially limb- and life-threatening infection.


The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.
Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.


Prior expectations bias sensory representations in visual cortex.
Perception is strongly influenced by expectations. Accordingly, perception has sometimes been cast as a process of inference, whereby sensory inputs are combined with prior knowledge. However, despite a wealth of behavioral literature supporting an account of perception as probabilistic inference, the neural mechanisms underlying this process remain largely unknown. One important question is whether top-down expectation biases stimulus representations in early sensory cortex, i.e., whether the integration of prior knowledge and bottom-up inputs is already observable at the earliest levels of sensory processing. Alternatively, early sensory processing may be unaffected by top-down expectations, and integration of prior knowledge and bottom-up input may take place in downstream association areas that are proposed to be involved in perceptual decision-making. Here, we implicitly manipulated human subjects' prior expectations about visual motion stimuli, and probed the effects on both perception and sensory representations in visual cortex. To this end, we measured neural activity noninvasively using functional magnetic resonance imaging, and applied a forward modeling approach to reconstruct the motion direction of the perceived stimuli from the signal in visual cortex. Our results show that top-down expectations bias representations in visual cortex, demonstrating that the integration of prior information and sensory input is reflected at the earliest stages of sensory processing.


Europium luminescent polymeric microspheres fabricated by spray drying process.
The spray drying method was used to prepare luminescent microspheres. These microspheres were prepared by spraying an aqueous solution of dextrin and an europium(III) complex with subsequent drying in a hot medium. The spray dried powder was characterized by scanning electron microscopy (SEM) and photoluminescence spectroscopy (PL). Particle size distribution was estimated from SEM images. The ultrasonic spray drying technique was successfully applied to yield a microparticulated and red luminescent powder composed by the [Eu(dpa)(3)](3-) (dpa = dipicolinic acid) complex incorporated in dextrin microspheres.


The tumor necrosis factor-inducing potency of lipopolysaccharide and uronic acid polymers is increased when they are covalently linked to particles.
Lipopolysaccharide (LPS) and polymers of the uronic acid family stimulate monocytes to produce tumor necrosis factor (TNF). The TNF-inducing potency of these polysaccharides may depend on their supramolecular configuration. In this study detoxified LPS and uronic acid polymers have been covalently linked to particles which have been added to monocytes under serum-free conditions. Reducing the size of mannuronan from 350,000 to 5,500 Da (M-blocks) led to a 10- to 100-fold reduction in TNF-inducing potency. However, covalently linking the M-blocks to monodisperse suspensions of magnetic particles increased the TNF-inducing potency by up to 60,000-fold. Also, the TNF-inducing potency of glucuronic acid polymers was increased when they were linked to particles, but no potentiation was observed with guluronic acid blocks covalently attached to particles. Furthermore, O chains of LPS (detoxified LPS) became potent TNF inducers when they were presented to monocytes on a particle surface. No activation of the LPS-responsive SW480 adenocarcinoma cells was found with detoxified LPS or M-block particles, suggesting a preference for cells expressing CD14 and/or other membrane molecules. The potentiating effects were not restricted to polymers attached to aminated magnetic particles. Of particular interest, we found that short blocks of mannuronan induced TNF production also when covalently linked to biodegradable, bovine serum albumin particles.


[Isolation and characteristics of fragments from the cyanogen bromide splitting of inclusion body proteins of Bombyx mori nuclear polyhedrosis virus].
The cyanogen bromide cleavage of "acetic" polyhedral protein from nuclear polyhedrosis virus of B. mori was performed. Two peptides BrCN-II and BrCN-II' which consist of 29 and 34 amino acid residue were isolated from a mixture of cyanogen bromide fragments. The amino acid composition and N-terminal amino acids were established. The tryptic proteolysis of these fragments was conducted and the tryptic peptides were separated. The amino acid composition of tryptic peptides was determined. The data obtained make it possible to consider these fragments to be internal areas of polypeptide chain of the protein under investigation.


Overview of benign and malignant prostatic disease in Pakistani patients: a clinical and histopathological perspective.
To present the overall clinical and histological perspective of benign and malignant prostatic disease as seen in our practice in the Section of Histopathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, Pakistan. All consecutive prostate specimens (transurethral resection or TUR, enucleation, needle biopsies) received between July 1, 2012 and December 31, 2012 were included in the study. Of the total of 785 cases, 621 (79.1%) were TUR specimens, 80 (10.2%) enucleation specimens, and 84 (10.7%) needle biopsies. Some 595 (75.8%) were benign, while 190 (24.2%) were malignant. Mean weight of BPH specimens was 19 grams and 43 grams for TUR and enucleation specimens respectively. Almost 67% of adenocarcinomas were detected on TUR or enucleation specimens. Of the above cases, 41.7% were clinically benign while 58.3% were clinically malignant. The average volume of carcinoma in all cases ranged between 60 to 65%. The average number of cores involved in needle biopsies was 5. In general, higher Gleason scores were seen in TUR/enucleation specimens than in needle biopsies. Overall, in all types of specimens, commonest Gleason score was 7, seen in 74 (38.9%) cases, followed by Gleason score 9 seen in 47 (24.7%) cases. Out of the 63 needle biopsies with carcinoma, radical prostatectomy was performed in 16 cases (25.4%). Benign prostatic hyperplasia (BPH) is extremely common and constitutes the bulk of prostate specimens. TMajority of prostatic carcinomas are still diagnosed on TUR or enucleation specimens. These included both clinically benign and clinically malignant cases. The volume of carcinoma in these specimens was quite high indicating extensive disease. Gleason scores were also generally high compared with scores from needle biopsies. Commonest Gleason score in all type of specimens was 7. Pathologic staging was possible in very few cases since radical prostatectomies are rarely performed.


Reduced Expression of Cerebral Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome.
Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) in fmr1 knockout (KO) mouse models have not been confirmed in humans with FXS. Measurement of cerebral mGluR5 expression in humans with FXS exposed to NAMs might help in that effort. We used positron emission tomography (PET) to measure the mGluR5 density as a proxy of mGluR5 expression in cortical and subcortical brain regions to confirm target engagement of NAMs for mGluR5s. The density and the distribution of mGluR5 were measured in two independent samples of men with FXS (N = 9) and typical development (TD) (N = 8). We showed the feasibility of this complex study including MRI and PET, meaning that this challenging protocol can be accomplished in men with FXS with an adequate preparation. Analysis of variance of estimated mGluR5 expression showed that mGluR5 expression was significantly reduced in cortical and subcortical regions of men with FXS in contrast to age-matched men with TD.


Forecasting of breathing events during nocturnal sleep using encoder-decoder recurrent neural network based on a sensors data of consumer smartwatches.
Respiratory disorders during nocturnal sleep are the states of abnormal and difficult breathing, including snoring, hypopnea and different apnea types. Some of them have a negligible effect on health, while others can lead to a serious consequences. Therefore, the development of low-cost, portable, user-friendly devices and corresponding algorithms for diagnosis and forecasting of such events is of particular importance. In the current paper, an encoder-decoder recurrent neural network was developed for respiratory pattern forecasting. The system is based on a physiological sensors (accelerometer and photoplethysmography) data gathered from the consumer smartwatches during nocturnal sleep. The influence of the length of time series in the encoder part (available history for forecasting), and the length of time series at the output of decoder (forecasting length) is studied. The average achieved f1 score and Cohen's Kappa agreement of the proposed model varies in the range from 0.35 to 0.5 and from 0.25 to 0.4, respectively, depending on forecasting length. The efficiency of the forecasting largely depends on the model complexity, presence or absence of respiration events in the encoder part, and forecasting length.Clinical Relevance- Results of the current paper may be used for the development of the respiration events screening tool based on a wearable devices sensors data.


Circulating endotoxin, tumour necrosis factor-alpha, and their natural antagonists in the pathophysiology of acute pancreatitis.
Inflammatory mediators, such as endotoxin and tumour necrosis factor-alpha (TNF-alpha) have been implicated in the pathogenesis of acute pancreatitis. However, serum levels of these mediators in patients with acute pancreatitis are often not detectable on hospital admission. In contrast, their circulating antagonists (antiendotoxin antibodies and soluble TNF-alpha receptors) are detectable in all patients. With increasing severity of disease, patients are more likely to manifest a fall in antiendotoxin levels, suggesting exposure to endotoxin. Similarly, there is a stepwise increase in soluble TNF-alpha receptors with increasing severity of disease. This suggests that the degree of TNF-alpha-induced inflammation correlates with disease severity. The role of endotoxin, TNF-alpha and their relevant antagonists as markers or mediators of the systemic complications of acute pancreatitis remains under investigation.


Three-dimensional spectral domain optical coherence tomography of a clear corneal cataract incision.
A prototype 1,310-nm wavelength spectral domain optical coherence tomography (SD-OCT) instrument was constructed and mounted onto a conventional slit lamp for imaging of the anterior segment. The device had an axial resolution of 8 microm and was able to acquire real-time two-dimensional images at 14 frames/second and full three-dimensional datasets in approximately 7 seconds. An SD-OCT dataset of 100 B-scans, each consisting of 512 A-scans, was acquired from the left eye ofa patient who had undergone phacoemulsification with a clear corneal incision. The resulting dataset could be manipulated in three-dimensional space to analyze the geometry of the wound. Additionally, stromal edema and iris features were clearly imaged with the device. SD-OCT can be used to analyze clear corneal incisions to determine optimal wound construction technique and geometry as they relate to the prevention of complications such as postoperative wound leak, infection, and epithelial ingrowth.


Mobilization of dendritic cell precursors in patients with cancer by flt3 ligand allows the generation of higher yields of cultured dendritic cells.
Flt3 ligand (Flt3L) stimulates the proliferation and differentiation of hematopoietic cells. Subcutaneous Flt3L administration has been shown to effectively manage some murine cancers and in humans, to lead to an increase in peripheral blood monocyte and dendritic cell (DC) counts. In the current study, we determined the effects of Flt3L therapy on patients with melanoma and renal cancer, and in particular, if Flt3L could be used either by enhancing the immunization of patients with melanoma to tumor antigen peptides in vivo, or by mobilizing DC precursors to allow the production of larger numbers of cultured DC. Flt3 ligand administration resulted in a 19-fold increase in DC counts in the peripheral blood of patients. The DC generated in vivo appeared only partially activated, expressing increased levels of CD86, CD33, and major histocompatibility complex class II, but no or low levels of CD80 and CD83. This partial activation may account for the lack of enhanced immune responses to melanoma antigens and absence of clinical responses in the patients even in combination with antigen immunization. Flt3 ligand administration did result, however, in a 7-fold increased yield of monocytes per liter of blood from leukapheresed patients. Dendritic cells were as readily generated from monocytes collected before and after Flt3L therapy, and they stimulated allogeneic T-cell proliferation in a mixed leukocyte reaction to a similar magnitude. Thus, the use of Flt3L may be an important method to mobilize DC precursors to allow patient therapy with larger numbers of cultured DC.


Application of an Intensive Rehabilitation Program After Very Late Recovery of Consciousness: A Single-Case Neurorehabilitation and Neuroimaging Study.
Late recovery of consciousness in vegetative state is considered as an exceptional outcome and has been reported prevalently in patients who suffered a traumatic brain injury. In these patients, the benefits of prolonging the rehabilitation, aimed at the recovery of autonomy in basic everyday activities, has been demonstrated. Here, we describe the application of an intensive multi-professional rehabilitation program carried out on a young female patient, with exceptionally late recovery of consciousness, specifically, after 7 years of vegetative state due to severe brain hemorrhage. Neuropsychological and functional assessment was conducted before and after the end of the rehabilitation program. In addition, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)-based probabilistic tractography were performed. Two follow-up neuropsychological and functional assessments were also conducted 6 and 29 months after the conclusion of the program. Functional results showed an improvement, maintained over time, in walking with assistance, cognitive efficiency, visual acuity and visual field, dysarthria, and execution of activities of daily living. Moreover, functional and structural magnetic resonance imaging (MRI) data documented the existence of preserved neural networks involved in sensory, motor, and linguistic tasks, which in all likelihood support the recovery process. This report suggests the possibility of undertaking an intensive rehabilitation program in patients who remain for long periods in altered states of consciousness, in spite of early negative prognosis.


Improving Patient Involvement in Medicines Research and Development:: A Practical Roadmap.
The value of patient involvement (PI) in medicines research and development (R&D) is increasingly recognized by all health stakeholders. Despite numerous ongoing PI initiatives, PI so far lacks structure and consistency in approach. Limited formal documentation of PI activities further hampers the sharing of experience and learnings, preventing timely and systematic implementation. This article summarizes the outcomes of several multistakeholder discussions during 2013-2016 in a practical roadmap for PI in medicines R&D. The roadmap highlights specific opportunities for PI along the 4 key stages of the medicines R&D life cycle and is illustrated with concrete examples. This roadmap's aim is to provide a tool to facilitate PI during medicines research and development and is being shared to encourage implementation and further refinement.


Quantity and Reporting Quality of Kidney Research.
In 2004, researchers reported that the number of nephrology clinical trials was low and that the reporting quality of such trials was suboptimal. Furthermore, the number or quality of preclinical kidney-related studies has not been systematically evaluated. We performed a systematic review of randomized clinical trials published in 1966-2017 (listed in the Cochrane Library) and preclinical studies published in 1945-2017 (listed in PubMed). For reporting quality analysis, we evaluated the final main paper of 118 clinical trial reports and 135 preclinical studies published in leading journals in 1996, 2006, and 2016 on the basis of criteria from the widely used CONSORT and ARRIVE guidelines. The annual number of reports of clinical kidney-related trials more than doubled between 2004 and 2014 along with reports in other medical disciplines. Hypertension remains the dominant focus of study, but ongoing trials also center on CKD, ESRD, and AKI. The reporting quality analysis revealed improvements, but deficits in reporting of clinical trial design, mode of randomization, and intention-to-treat analysis remain. Annual numbers of kidney-related preclinical studies remained low between 1945 and 2017 compared with other disciplines. Reporting quality analysis of preclinical studies revealed substantial reporting deficits across all leading journals, with little improvement over the last 20 years, especially for group size calculations, defining primary versus secondary outcomes, and blinded analysis. Nephrology studies keep increasing in number but still lag behind other medical disciplines, and the quality of data reporting in kidney research can be further improved.


Tidal volume expandability and ventilatory efficiency as predictors of mortality in Taiwanese male patients with chronic obstructive pulmonary disease: A 10-year follow-up study - Is V̇O2peak or FEV1% the gold standard?
Despite our knowledge of the risk factors for mortality associated with chronic obstructive pulmonary disease (COPD), the mortality rate for this condition continues to increase. This study aimed to investigate the predictive power of physiological variables on all-cause mortality in COPD patients compared to peak oxygen uptake (V˙O2peak) and forced expired volume in one second (FEV1). We conducted a retrospective study of 182 COPD patients with complete lung function tests, cardiopulmonary exercise testing (CPET), and survival data. Cox regression analysis was used to estimate the hazard ratios for all-cause mortality. The median follow-up period was 6.8 (IQR 3.9-9.2) years. Out of the 182 patients in our study, sixty-two (34.1%) succumbed to various causes. Of these, 27.4% (n = 17) experienced acute exacerbations, 24.2% (n = 15) had advanced cancer, and 12.9% (n = 8) had cardiovascular disease as the primary cause of death. Another 25.8% (n = 16) passed away due to other underlying conditions, while 6.5% (n = 4) had an unknown cause of death. One patient's demise was attributed to a benign tumor, and another's to a connective tissue disease. The ratio of tidal volume to total lung capacity (VTpeak/TLC) and the ratio of minute ventilation and V˙O2 at nadir (V˙E/V˙O2nadir) (AUR 0.83, 95% CI 0.76-0.91) were superior predictors of all-cause mortality compared to V˙O2peak and FEV1%. A mortality prediction formula was derived using these variables. This study highlights the potential of VTpeak/TLC and V˙E/V˙O2nadir as predictive markers for COPD all-cause mortality in COPD. CPET is an effective tool for evaluating COPD mortality; however, the predictive equation requires further validation.


Micromolar calcium stimulates proteolysis and glutamate binding in rat brain synaptic membranes.
Incubation of cortical synaptic membranes with low concentrations of calcium resulted in a decrease in the amount of a high-molecular-weight doublet protein and an increase in the sodium-independent binding of glutamate. Both effects were blocked by the thiol protease inhibitor leupeptin. These results suggest that calcium-induced proteolysis of membrane components regulates the number of glutamate receptors in neuronal membranes.


What physicians from diverse specialties know and support in health care reform.
The United States is in an unprecedented era of health care reform that is pushing medical professionals and medical educators to evaluate the future of their patients, careers, and the field of medicine. Our objectives were to describe physician familiarity and knowledge with the Patient Protection and Affordable Care Act (ACA) and to determine if knowledge is associated with support and endorsement of the ACA. We used a cross-sectional Internet-based survey of 559 physicians practicing in California. Primary outcomes were physician support and endorsement of ACA: (1) overall impact on the country (one item) and (2) perceived impact on physician's medical practice (one item). The primary predictor was knowledge of the ACA as measured with 10 questions. Other measures included age, gender, race-ethnicity, specialty, political views, provision of direct care, satisfaction with the practice of medicine, and compensation type. Descriptive statistics and multiple variable regression models were calculated. Respondents were 65% females, and the mean age was 54 years (+/- 9.7). Seventy-seven percent of physicians understood the ACA somewhat well/very well, and 59% endorsed the ACA, but 36% of physicians believed that health care reform will most likely hurt their practice. Primary care physicians were more likely to perceive that the new law will help their practice, compared to procedural specialties. Satisfaction with the practice of medicine, political affiliation, compensation type, and more knowledge of the health care law were independently associated with endorsement of the ACA. Endorsement of the ACA varied by specialty, knowledge, and satisfaction with the practice of medicine.


Crispness, the Key for the Palatability of "Kakinotane": A Sensory Study with Onomatopoeic Words.
Crispness is among the most important food textures that contribute significantly to palatability. This study investigated the association between the perceived crispness and palatability of five types of Japanese rice crackers known as "kakinotane." Two experiments were conducted using the temporal dominance of sensations (TDS) and temporal drivers of liking (TDL) methods. As descriptors for the TDS evaluation, we used 10 Japanese onomatopoeias to indicate various attributes of crispness. We also measured the mastication sounds and electromyography (EMG) activity during mastication. Principal component analysis data revealed that principal component 1, representing moisture characteristics, contributed more than 60% in both experiments. The palatability of the stimulus, which was described as having a very soft, moist, and sticky texture, BETA-BETA, was significantly lower than the others. However, there was no significant relationship between the amplitude of mastication sound or EMG activity and palatability. We demonstrated that naïve university students can discriminate the fine nuances of the crispness of "kakinotane" using the TDS and TDL methods. Our findings also suggested that the onomatopoeias used as descriptors in the TDS method had a greater influence on describing the nuances of food texture than the physiological data.


Importance of the conserved aromatic residues in the scorpion alpha-like toxin BmK M1: the hydrophobic surface region revisited.
About one-third of the amino acid residues conserved in all scorpion long chain Na+ channel toxins are aromatic residues, some of which constitute the so-called "conserved hydrophobic surface." At present, in-depth structure-function studies of these aromatic residues using site-directed mutagenesis are still rare. In this study, an effective yeast expression system was used to study the role of seven conserved aromatic residues (Tyr5, Tyr14, Tyr21, Tyr35, Trp38, Tyr42, and Trp47) from the scorpion toxin BmK M1. Using site-directed mutagenesis, all of these aromatic residues were individually substituted with Gly in association with a more conservative substitution of Phe for Tyr5, Tyr14, Tyr35, or Trp47. The mutants, which were expressed in Saccharomyces cerevisiae S-78 cells, were then subjected to a bioassay in mice, electrophysiological characterization on cloned Na+ channels (Nav1.5), and CD analysis. Our results show an eye-catching correlation between the LD50 values in mice and the EC50 values on Nav1.5 channels in oocytes, indicating large mutant-dependent differences that emphasize important specific roles for the conserved aromatic residues in BmK M1. The aromatic side chains of the Tyr5, Tyr35, and Trp47 cluster protruding from the three-stranded beta-sheet seem to be essential for the structure and function of the toxin. Trp38 and Tyr42 (located in the beta2-sheet and in the loop between the beta2- and beta3-sheets, respectively) are most likely involved in the pharmacological function of the toxin.


Assembly structures and dynamics of active colloidal cells.
Many types of active matter are deformable, such as epithelial cells and bacteria. To mimic the feature of deformability, we built a model called an active colloidal cell (ACC), i.e. a vesicle enclosed with self-propelled particles (SPPs), which as a whole can move actively. Based on the model, we then study the role of deformability in the assembly structures and dynamics of ACCs by Langevin dynamics simulation. We find that deformability weakens the self-trapping effect and hence suppresses the clustering and phase separation of the deformable soft ACCs (sACCs). Instead of forming a large compact cluster like ordinary SPPs, sACCs pack into a loose network or porous structure in the phase-separation region. The condensed phase is liquid-like, in which sACCs are strongly compressed and deformed but still keep high motility. The interface between the gas and the condensed phases is blurry and unstable, and the effective interfacial energy is very low. Our work gives new insights into the role of deformability in the assembly of active matter and also provides a reference for further studies on different types of deformable active matter.


A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings.
The inappropriate expression of the c-MET cell surface receptor in many human solid tumors necessitates the development of companion diagnostics to identify those patients who could benefit from c-MET targeted therapies. Tumor tissues are formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation, making the development of an antibody against c-MET that accurately and reproducibly detects the protein in FFPE samples an urgent need. We have developed a monoclonal antibody (mAb), designated MET4, from a panel of MET-avid mAbs, based on its specific staining pattern in FFPE preparations. The accuracy of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in FFPE cell pellets with immunoblotting analysis. The technical reproducibility of MET4-IHC possessed a percentage coefficient of variability of 6.25% in intra-assay and interassay testing. Comparison with other commercial c-MET antibody detection reagents demonstrated equal specificity and increased sensitivity for c-MET detection in prostate tissues. In cohorts of ovarian cancers and gliomas, MET4 reacted with ovarian cancers of all histologic subtypes (strong staining in 25%) and with 63% of gliomas. In addition, MET4 bound c-MET on the surfaces of cultured human cancer cells and tumor xenografts. In summary, the MET4 mAb accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and can be used for molecular imaging in vivo. These properties encourage further development of MET4 as a multipurpose molecular diagnostics reagent to help to guide appropriate selection of patients being considered for treatment with c-MET-antagonistic drugs.


Epigallocatechin-3-gallate protects against cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis.
Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.


Determination of effects of internal countershock by direct cardiac recordings during normal rhythm.
Recording cardiac electrical activity after a countershock has been limited by amplifier saturation. Modifications to our computer-assisted mapping system allowed us to record electrical activity from 56 epicardial electrodes within 5 ms of the end of a countershock. Modifications included the use of solid-state switches to disconnect the filter section of the amplifiers during the shock and changing the low-frequency response of the amplifiers from 0.1 to 10 Hz to filter out large, low-frequency potentials after the shock. Six-millisecond truncated exponential shocks were delivered between the superior vena cava and right ventricular apex through a quadripolar catheter during normal rhythm in seven dogs. As shocks of increasing voltage were delivered during the T-Q interval, progressively more of the epicardium was directly depolarized. A shock of 109 +/- 17 (SD) V directly depolarized the entire epicardium. Shocks of constant voltage were then delivered with increasing prematurity during diastole. As the ventricles became more refractory with increasing shock prematurity, the amount of epicardium depolarized became progressively less. Thus computer-assisted mapping techniques are capable of measuring the area depolarized by a shock during normal rhythm and may be useful during arrhythmias to improve our understanding of defibrillation and cardioversion.


[Ageing rate in workers of mechanic workshops of machinery construction industry in Armenia].
Studies of biologic age formation and ageing rate in workers of mechanic workshops revealed that able-bodied population grew old demographically. That is proved by absent age group of 20-29 years and increased share of able-bodied workers older than 50. Young workers aged 30-39 appeared the most vulnerable for occupational hazards--they demonstrated increased ageing rate and maximal excess of biologic age over chronological age and due biologic age.


[Treatment for children and adolescents with pain in Spain: data from a survey on current specialized programs].
The treatment of children and adolescents with pain has improved considerably in the last 30 years. In Spain, progress is also evident, and specialized units or programs have emerged as part of the care provided for this population. However, there are no studies on the characteristics or activities of these specialized units or programs. This lack of information prevents an adequate evaluation of the current procedures, and hinders an adequate administration and management of these resources. The objective of this work was to study the characteristics of these units and programs for the treatment of children and adolescents with pain in Spain. A total of 10 specialized units or specific treatment programs for pediatric pain in Spain were identified, and the person responsible was contacted. Through a self-administered online survey, information was collected on the organization of the program, the involvement in relevant fields such as research, training of professionals and the raising of awareness and visibility of the problem, the specialties involved, the type of treatments offered, the evaluation of results and the services provided. Of the ten units or programs contacted, eight answered the survey (80%). Pain programs for children and adolescents proved to be primarily pharmacological, also for chronic pain. They reported to promote awareness about the problem (88%), to contribute to the training of specialists (88%) and to a lesser extent to research and knowledge generation (75%). This survey provides valuable information on the current characteristics of specialized programs and units for the treatment of children and adolescents with pain in Spain, and can be used to propose actions that improve its current management and administration.


Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol.
Kaempferol is a natural flavonol that possesses various pharmacological activities, including anti-arthritis effects, yet the underlying mechanisms remain controversial. To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol, collagen-induced arthritis (CIA) mice were treated with kaempferol intragastrically (200 mg · kg-1 · d-1) and intraperitoneally (20 mg · kg-1 · d-1). Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index, arthritis index, paw thickness, and inflammatory factors; the bioavailability (1.5%, relative to that of the intraperitoneal injection) and circulatory exposure of kaempferol (Cmax = 0.23 ± 0.06 ng/mL) and its primary metabolite kaempferol-3-O-glucuronide (Cmax = 233.29 ± 89.64 ng/mL) were rather low. In contrast, the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects, although it achieved a much higher in vivo exposure. The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut. Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level, whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice. A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan, fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice. In conclusion, we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism, which are potentially responsible for the anti-arthritis activities of kaempferol.


Patients Age 40 Years and Younger With Multiple Myeloma Have the Same Prognosis as Older Patients: An Analysis of Real-World Patients' Evidence From Latin America.
Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.


Surgical management of vulvar lymphangioma circumscriptum: two case reports.
To evaluate the efficacy of major labiaectomy as a surgical management of vulvar lymphangioma circumscriptum, we report two cases of this rare clinical entity. Two female patients, aged 56 and 68 years, presented with persistent edema of the lower limbs, papule-like condyloma of the labia majora, and lymph oozing from these papules of the vulva, which had developed 24 and 10 years, respectively, after radical hysterectomy with adjuvant pelvic radiation therapy for cervical cancer. After major labiaectomy was performed, symptoms in the first case, of extensive resected skin margin, improved clearly, in the second case, vulvar lymphangioma circumscriptum was more severe than in the first case, and a small amount of lymph oozing occurred from residual papules of the labia majora. In both cases, histology revealed lymphangioma circumscriptum of the vulva. Major labiaectomy is an effective therapy for vulvar lymphangioma circumscriptum. Particularly, in the case which was extensive and deep resected skin margin, symptoms such as papules of the labia majora and lymph oozing from these papules of the vulva associated with lymphangioma seemed to be clearly improved.


Pain tolerance and threshold in suicide attempters: A systematic review and meta-analysis.
It has been hypothesized that individuals less sensitive to pain could be at higher risk of suicide. However, data on pain sensitivity in suicide attempters (SA) obtained using experimental procedures are heterogeneous. The aim of this systematic review and meta-analysis was to investigate and compare pain tolerance and threshold in SA (patients with lifetime history of suicide attempt), non-attempters (psychiatric controls, PC), and healthy controls (HC). A random effects meta-analysis was used to estimate the standardized mean differences using data from 16 studies that compared physical pain tolerance and threshold in SA and PC or HC. Pain tolerance and threshold were not significantly different in SA and PC. However, pain tolerance, but not threshold, was higher in SA than HC. Our findings do not support the hypothesis of an altered pain perception related as a trait for suicidal vulnerability, but rather suggest altered pain perception related to psychiatric vulnerability.


Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments.
Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes. To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI. Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80°C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS). Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (≤50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (r = 0.153; 0.220, P < 0.001). In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.


Transcutaneous neuromuscular electrical stimulation (VitalStim) curative therapy for severe dysphagia: myth or reality?
VitalStim therapy was approved by the US Food and Drug Administration in 2001 for the treatment of dysphagia through the application of neuromuscular electrical stimulation to cervical swallowing muscles. This approval was based upon submission of data on more than 800 patients who received this therapy collected by the principal developer and patent-holder of the device. The therapy is marketed as successful in restoring long-term swallowing function in 97.5% of dysphagic patients past the point of requiring a feeding tube and as significantly better than existing therapies. More than 2,500 speech-language pathologists have taken the certification course, and thousands of devices have been sold. To date, however, aside from the developer's own studies, there are no peer-reviewed publications supporting these claims. We sought to evaluate the effectiveness of VitalStim therapy in a heterogeneous group of dysphagic patients. We performed a retrospective analysis of 18 patients who received this therapy at an urban tertiary referral center. All patients underwent pretherapy evaluation by speech-language pathologists, including modified barium swallow and/or functional endoscopic evaluation of swallowing and clinical evaluation of swallowing that included assessment of laryngeal elevation, diet tolerance, and swallowing delay, and were then assigned an overall dysphagia severity score. After therapy, all patients underwent the same assessments. Twelve of the 18 also underwent a functional swallowing telephone survey months (range, 1 to 21 months) after their therapy to assess whether the improvement was worthwhile and sustained. Eleven of the 18 patients (61%) demonstrated some improvement in their swallowing. Six of the 18 patients (33%) were improved enough to no longer require a feeding tube. However, of the 5 patients categorized as having "severe dysphagia" before therapy, only 2 showed any improvement, and these patients still required a feeding tube for adequate nutrition. Telephone surveys did confirm that those who improved with their therapy seemed to maintain their progress and that most patients were satisfied with their therapy. VitalStim therapy seems to help those with mild to moderate dysphagia. However, the patients with the most severe dysphagia in our study did not gain independence from their feeding tubes. The authors conclude that VitalStim therapy clearly has a place in the management of dysphagia, but that the most severely afflicted are unlikely to gain dramatic improvement.


Resilient Sensor Networks with Spatiotemporal Interpolation of Missing Sensors: An Example of Space Weather Forecasting by Multiple Satellites.
This paper attempts to construct a resilient sensor network model with an example of space weather forecasting. The proposed model is based on a dynamic relational network. Space weather forecasting is vital for a satellite operation because an operational team needs to make a decision for providing its satellite service. The proposed model is resilient to failures of sensors or missing data due to the satellite operation. In the proposed model, the missing data of a sensor is interpolated by other sensors associated. This paper demonstrates two examples of space weather forecasting that involves the missing observations in some test cases. In these examples, the sensor network for space weather forecasting continues a diagnosis by replacing faulted sensors with virtual ones. The demonstrations showed that the proposed model is resilient against sensor failures due to suspension of hardware failures or technical reasons.


Applications of Graphene Quantum Dots in Biomedical Sensors.
Due to the proliferative cancer rates, cardiovascular diseases, neurodegenerative disorders, autoimmune diseases and a plethora of infections across the globe, it is essential to introduce strategies that can rapidly and specifically detect the ultralow concentrations of relevant biomarkers, pathogens, toxins and pharmaceuticals in biological matrices. Considering these pathophysiologies, various research works have become necessary to fabricate biosensors for their early diagnosis and treatment, using nanomaterials like quantum dots (QDs). These nanomaterials effectively ameliorate the sensor performance with respect to their reproducibility, selectivity as well as sensitivity. In particular, graphene quantum dots (GQDs), which are ideally graphene fragments of nanometer size, constitute discrete features such as acting as attractive fluorophores and excellent electro-catalysts owing to their photo-stability, water-solubility, biocompatibility, non-toxicity and lucrativeness that make them favorable candidates for a wide range of novel biomedical applications. Herein, we reviewed about 300 biomedical studies reported over the last five years which entail the state of art as well as some pioneering ideas with respect to the prominent role of GQDs, especially in the development of optical, electrochemical and photoelectrochemical biosensors. Additionally, we outline the ideal properties of GQDs, their eclectic methods of synthesis, and the general principle behind several biosensing techniques.


Specificity of effect of osmolality on aldosterone secretion.
Small (3-7 mM) changes in [NaCl] have a marked inverse effect on angiotensin II- or K-stimulated aldosterone secretion by the isolated, perfused canine adrenal gland. The effect is due to the accompanying changes in osmolality rather than to the changes in [Na] or [Cl]. The present study was undertaken to determine whether osmolality is a specific and discrete signal that modulates the secretion of aldosterone only or is simply a nonspecific physical factor that alters the secretion of other adrenocortical hormones as well. The study also determined whether small changes in osmolality affect the conversion of corticosterone to aldosterone. The secretion of both cortisol and aldosterone by isolated canine adrenal glands responded in a dose-dependent fashion to adrenocorticotropin (ACTH), but in contrast to the rapid and potent modulating action of osmolality reported previously for angiotensin II- or K-stimulated aldosterone secretion, changes in osmolality at the midpoint of ACTH infusion had no detectable effect on either cortisol secretion or, unexpectedly, aldosterone secretion. This indicates that osmolality is a highly specific signal that modulates responsiveness of the zona glomerulosa to the factors, angiotensin II and K, which are considered to be most important in the acute regulation of aldosterone secretion, but does not influence secretion of cortisol by inner zones of the adrenal cortex. In glands treated with agents that block aldosterone production from endogenous precursors, small changes in osmolality had no detectable effect on the conversion of exogenous corticosterone to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)


Developing a national salt reduction strategy for Mongolia.
The increase in prevalence of risk factors such as hypertension has contributed to an incremental rise in non-communicable diseases (NCDs) in Mongolia over recent decades, such that they now account for 80% of all deaths in the country. Salt reduction is one of the most cost-effective interventions to reduce the burden of NCDs. In 2011, the Ministry of Health (MOH) instigated the development of a national salt reduction strategy for Mongolia. As part of a 2-week national consultation and training program on salt reduction, it established an inter-sectoral working party and organized a series of bilateral meetings and visits to factories. Actions arising included a baseline survey of population salt consumption patterns and the implementation of a series of pilot salt reduction initiatives. The results of the baseline assessment revealed that average daily intake of salt, based on 24 hour urine samples from a representative national sample (n=1,027), was 11.06±5.99 g in 2011, more than double the World Health Organization (WHO) five grams recommendation. Moreover, while most participants knew that salt was bad for health, few were taking efforts to reduce intake, and many were consuming highly salty meals and tea; salt in tea alone was estimated to contribute 30% of daily salt intake. A pilot Pinch Salt intervention to reduce salt consumption of factory workers was undertaken in Ulaanbaatar (UB) city between 2012 and 2013, and was associated with a reduction of 2.8 g of salt intake. Ongoing food industry initiatives have led to significant reductions in salt levels in bread, and companies producing processed meat have indicated a willingness to reduce salt. Relevant stakeholders have also supported the campaign by participating in annual World Salt Awareness Week events. The activities to date have demonstrated the potential for action and there is now a need scale these up to a national level to ensure that Mongolia is in a strong position to achieve a 30% reduction in population salt intake by 2025. The main goal of the Mongolian national salt reduction strategy is to create a social, economic and legal environment that supports salt reduction, including by influencing food supply, increasing partnerships between government and relevant stakeholders, and creating an enabling environment to support improved consumer choices. The strategy will be implemented from 2015 to 2025, with an interim review of progress in 2020. Given that Mongolia has one of the highest rates of stroke in the world, which is strongly associated with population-wide blood pressure (BP) levels, the addition of a population-based stroke surveillance program would provide a reliable direct assessment of the impact of these salt reduction initiatives on the health of the Mongolian people. The results from this research would likely be widely generalizable to other populations experiencing similar lifestyle transitional changes.


[Serotonin simulates the neuronal effects of nociceptive sensitization in the snail].
Serotonin (5-HT) application (10 mcM) onto L-PPl1 neurons of the pleural ganglia of land snail Helix lucorum produced the synaptic facilitation of the neuronal response evoked by sensory stimulation. At the same time, it did not change the parameters of the neuronal membrane (resting potential and membrane excitability). In addition to synaptic facilitation, the higher 5-HT concentration (100 mcM) produced an increase in membrane excitability and a slight membrane depolarization. The 5-HT effects were modality-dependent: the duration of facilitation of the response evoked by tactile stimulation of the snail head was about 1 h while that of the response evoked by quinine application (0.3% solution) onto the snail lip was 2-3 h. The 5-HT effects were site-specific: its application facilitated only the neuronal responses evoked by tactile stimulation of the snail head but not other body sites. The dynamics of the electrophysiological effects and the level of bound calcium were similar in L-PPl1 neurons. The described neuronal effects resemble those observed after the nociceptive sensitization of these neurons. The data obtained suggest the 5-HT involvement in the mechanisms of short-term changes and consolidation of long-term plasticity underlying the sensitization in Helix L-PPl1 neurons.


CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein Survivin.
Survivin is a member of the inhibitor of apoptosis (IAP) family of negative regulators of programmed cell death that is frequently overexpressed in human tumors. Survivin is not only involved in the regulation of apoptosis, but is also known to play a role in the control of cell cycle progression at the G2/M phase. Survivin is a predominantly cytoplasmic protein expressed in a cell cycle-dependent manner, but the mechanism(s) that determine its nuclear-cytoplasmic localization have not been described. In this study, we report that Survivin is a nuclear shuttling protein that is actively exported from the nucleus via the CRM1-dependent pathway. Nuclear export of Survivin is independent of the export of other shuttling proteins that control the G2/M phase transition, such as cyclin B1 and cdc25. The carboxy-terminal domain of Survivin is both necessary and sufficient for its nuclear export, although this region does not contain a functional leucine-rich nuclear export signal. Differences in the amino acid sequence of this region determine the dramatically different localization of Survivin (in the cytoplasm) and its splicing variant Survivin-DeltaEx3 (in the nucleus). The carboxy-terminal end of Survivin-DeltaEx3 contains a bipartite nuclear localization signal, not present in Survivin, which mediates its strong nuclear accumulation. These data suggest that active transport between the nucleus and cytoplasm may constitute an important regulatory mechanism for Survivin function.


Management of dyslipidemia in adults.
The importance of treating dyslipidemias based on cardiovascular risk factors is highlighted by the National Cholesterol Education Program guidelines. The first step in evaluation is to exclude secondary causes of hyperlipidemia. Assessment of the patient's risk for coronary heart disease helps determine which treatment should be initiated and how often lipid analysis should be performed. For primary prevention of coronary heart disease, the treatment goal is to achieve a low-density lipoprotein (LDL) cholesterol level of less than 160 mg per dL (4.15 mmol per L) in patients with only one risk factor. The target LDL level in patients with two or more risk factors is 130 mg per dL (3.35 mmol per L) or less. For patients with documented coronary heart disease, the LDL cholesterol level should be reduced to less than 100 mg per dL (2.60 mmol per L). A step II diet, in which the total fat content is less than 30 percent of total calories and saturated fat is 8 to 10 percent of total calories, may help reduce LDL cholesterol levels to the target range in some patients. A high-fiber diet is also therapeutic. The most commonly used options for pharmacologic treatment of dyslipidemia include bile acid-binding resins, HMG-CoA reductase inhibitors, nicotinic acid and fibric acid derivatives. Other possibilities in selected cases are estrogen replacement therapy, plasmapheresis and even surgery in severe, refractory cases.


Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form.
The proliferating cell nuclear antigen, PCNA, has recently been identified as the polymerase delta accessory protein. PCNA is essential for cellular DNA synthesis and is also required for the in vitro replication of simian virus 40 (SV40) DNA where it acts to coordinate leading and lagging strand synthesis at the replication fork. The cDNA for rat PCNA was cloned into a series of bacterial expression vectors and the resulting protein used to immunize mice. Eleven new monoclonal antibodies to PCNA have been isolated and characterized. Some of the antibodies recognize epitopes conserved from man to fission yeast. Immunocytochemical analysis of primate epithelial cell lines showed that the antibodies recognized antigenically distinct forms of PCNA and that these forms were localized to different compartments of the nucleus. One antibody reacted exclusively with PCNA in the nucleolus. These results suggest that the PCNA protein may fulfil several separate roles in the cell nucleus associated with changes in its antigenic structure.


Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study.
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients. Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2-19) years. Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied. Patients varied widely in their age of presentation [3.5 (0.1-17) years] and number of clinical manifestations [5 (2-11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3-23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians. Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.


Cylindrical optimized nonmagnetic concentrator with minimized scattering.
By using optimized transformation function, we research on a minimized scattering nonmagnetic concentrator, which can realize impedance matching at the inner and the outer boundaries. It has been demonstrated that the optimized transformation function method can improve the concentrating performance remarkably. The cylindrical anisotropic shell can be mimicked by radial symmetrical sectors which alternate in composition between two profiles of isotropic dielectrics, and the permittivity in each sector can be properly determined by the effective medium theory. The nonmagnetic concentrator has been validated by full-wave finite element simulations. We can believe that this work will improve the flexibilities for the EM concentrator design.


Occurrence of polyamines in coliphages T5, phiX174 and in phage-infected bacteria.
The polyamine spermidine and the diamine putrescine have been detected in coliphages T5 and phiX174. Polyamines were identified by thin-layer chromatography and mass-spectrometry of dansyl derivatives, as well as by ion-exchange chromatography. In phiX174 phages, polyamines were sufficient to neutralize 0.5% of DNA phosphates. The polyamine content of T5 phages depended on growth media and purification procedures, but at least 1% of DNA phosphates were neutralized by polyamines. After infection, an increase in cellular polyamine was noticed. This increase paralleled variations in ornithine decarboxylase activity.


Tracking of body mass index from childhood to adolescence: a 6-y follow-up study in China.
Although extensive descriptive research shows that childhood obesity predisposes a person to adult obesity, little is understood about the dynamics of weight during childhood and the predictors of weight tracking. Our objective was to examine tracking patterns of body mass index (BMI) as well as their predictors between childhood and adolescence. A cohort of 975 Chinese children aged 6-13 y was followed for 6 y (1991-1997). Tracking of BMI was defined as an individual maintaining a certain status (overweight or underweight) or relative position (relative BMI quartile) over time. Relative BMI related BMI to age- and sex-specific BMI cutoffs. After 6 y, approximately 40% of the subjects had maintained their relative positions, but 30% had moved into a lower or higher quartile. The BMIs of thin and fat children were more likely to track: 51% and 46% remained in the bottom and upper quartiles, respectively. Nearly one-third of the underweight children remained underweight in 1997. Overweight children were 2.8 times as likely as all other children to become overweight adolescents; underweight children were 3.6 times as likely to remain underweight as adolescents. Parental obesity and underweight, individuals' initial BMIs, dietary fat intake, and family income helped predict tracking and changes in BMI. In a society undergoing enormous changes in diet and activity, BMI tracking is still very important between childhood and adolescence in China.


Exploring effects of social information on talker-independent accent adaptation.
The present study examined whether race information about speakers can promote rapid and generalizable perceptual adaptation to second-language accent. First-language English listeners were presented with Cantonese-accented English sentences in speech-shaped noise during a training session with three intermixed talkers, followed by a test session with a novel (i.e., fourth) talker. Participants were assigned to view either three East Asian or three White faces during training, corresponding to each speaker. Results indicated no effect of the social priming manipulation on the training or test sessions, although both groups performed better at test than a control group.


Obesity in pregnancy: what's next? Long-term cardiovascular morbidity in a follow-up period of more than a decade.
To investigate whether obesity during pregnancy poses a risk for subsequent maternal long-term cardiovascular morbidity, after controlling for diabetes and hypertensive disorders. Data were analyzed from consecutive pregnant women who delivered between 1988 and 1999, and were followed-up until 2010. Long-term cardiovascular morbidity was compared among women with and without obesity in pregnancy (maternal pre-pregnancy body mass index (BMI) of 30 kg/m(2) or more). Kaplan-Meier survival curves were used to compare cumulative incidence of cardiovascular hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for long-term cardiovascular hospitalizations. During the study period 46 688 women met the inclusion criteria, 1221 (2.6%) had a BMI ≥30 kg/m(2). During a follow-up period of more than 10 years, patients with obesity had higher rates of simple cardiovascular events and total number of cardiovascular hospitalizations. These complications tended to occur at a shorter interval (mean 4871 days ± 950 versus 5060 days ± 1140; p = 0.001). In a Cox proportional hazards model that adjusted for diabetes mellitus, preeclampsia and maternal age, obesity was independently associated with cardiovascular hospitalizations (adjusted HR 2.6, 95% CI 2.0-3.4). Obesity during pregnancy is an independent risk factor for long-term cardiovascular morbidity, and these complications tend to occur earlier. Pregnancy should be considered as a window of opportunity to predict future health problems and as an opportunity to promote women's health. Obese parturients might benefit from cardiovascular risk screening that could lead to early detection and secondary prevention of cardiovascular morbidity.


[The neuronal activity of the caudate nucleus in monkeys during the realization of delayed behavior].
A greater part (64%) of recorded neurones of the caudate nucleus head changed its activity at various stages of fulfillment by the monkey of the task of delayed spatial choice. Most of them (46.5% of all studied) reacted at key depressing and/or taking food from the feeder. During signal presentation and with delay the frequency of impulse activity changed respectively in 17% and 14% of the studied neurones. Besides, 2 neurones had spatially-selective activity in the instructive period of the program. It can be suggested that caudate neurones participate in realization of the delayed behaviour not only during motor response fulfillment but in the instructive period as well--at the stage of perception and processing of the visual information and its storing in short-term memory.


The new dioxolane, (-)-2'-deoxy-3'-oxacytidine (BCH-4556, troxacitabine), has activity against pancreatic human tumor xenografts.
There is a great need for new therapeutic agents for patients with advanced pancreatic cancer. The new dioxolane analogue troxacitabine was evaluated in two human pancreatic cancer xenograft models. The models used included the Panc-01 and MiaPaCa pancreatic cancer cell lines. Whereas there is certainly no absolute evidence that either of the in vivo models is predictive for clinical activity, there is at least some evidence that they may be helpful in selecting agents for clinical trials in patients with pancreatic cancer. Troxacitabine was administered i.v. to the animals at doses of 10 and 25 mg/kg on a daily x 5 regimen. Gemcitabine was used as a positive control. The end points for the study included tumor growth inhibition (TGI), final weight, and the number of partial and complete tumor responses in the animals. Troxacitabine was highly active against the Panc-01 model (n = 8), with TGI levels of 88.5% and 84.3% at the 10 and 25 mg/kg doses, respectively. The mean final tumor weights for animals given troxacitabine were also significantly smaller (P < 0.001) compared with vehicle controls. At the 10 mg/kg dose, there were three partial tumor shrinkages and one complete tumor shrinkage, whereas at the 25 mg/kg dose, there were three partial tumor shrinkages. Troxacitabine had less activity against the MiaPaCa model (n = 10) and, by traditional response criteria, would be considered inactive, with TGIs of 4% and 22.7% at the 10 and 25 mg/kg dose level, respectively. Of note is that in comparison with gemcitabine, troxacitabine was more efficacious against Panc-01 and was equally active against MiaPaCa. These in vivo results are encouraging and support the prospect of performing Phase II and perhaps Phase III trials with troxacitabine in patients with advanced pancreatic cancer.


The FACAM study: protocol for a randomized controlled study of an early interdisciplinary intervention to support women in vulnerable positions through pregnancy and the first 5 years of motherhood.
Inequality in health can have profound short- and long-term effects on a child's life. Infants develop in a responsive environment, and the relationship between mother and infant begins to develop during pregnancy. The mother's ability to bond with the fetus and newborn child may be challenged by mental health issues which can cause impaired functioning and poorer health outcomes. Families with complex problems need interdisciplinary interventions starting in early pregnancy to be prepared for motherhood and to ensure healthy child development. This study aims to examine the effects of an early and coordinated intervention (the Family Clinic and Municipality (FACAM) intervention) offered to vulnerable pregnant women during pregnancy and the child's first year of life on the mother-child relationship, maternal social functioning, mental health, reflective functioning, well-being, parental stress, and the development and well-being of the child. The study is a prospective randomized controlled trial where we will randomize 320 pregnant women enrolled to receive antenatal care at the family clinic at Odense University Hospital, to either FACAM intervention or usual care. The FACAM intervention consists of extra support by a health nurse or family therapist during pregnancy and until the child starts school. The intervention is most intensive in the first 12 months and also includes attachment-based support provided either individually or in groups. The participants are assessed at baseline, and when the infant is 3 and 12 months old. The primary outcome is maternal sensitivity measured by the Coding Interactive Behavior (CIB) instrument. Secondary outcomes include prenatal parental reflective functioning, mental well-being, depressive symptoms, breastfeeding duration, maternal satisfaction, child development, parent competence, parental stress, and activities with the child. The trial is expected to contribute knowledge about the effect of early coordinated support in antenatal and postnatal care for vulnerable pregnant women and their families. ClinicalTrials.gov NCT03659721 . Registered on September 6, 2018.


[Biology of mosquito Aedes impiger (Culicidae) and its possible role as a phenological indicator].
The biology of Aedes impiger Walk. from the polar region of the European part of the USSR has been studied and literary data have been summarized. Its biological peculiarities such as rapid and simultaneous development of larvae and pupae, a short period of seasonal activity, long daily activity, the presence of autogeny and long obligate diapause provide a distinct localization of the active period of the life cycle within a season. A. impiger develops quicker than other spring species of mosquitoes, emerges the first and can serve as phenoindicator for specification of developmental periods and mass emergence of bloodsucking mosquitoes.


Composite small lymphocytic lymphoma and extra-medullary myeloid tumor: a potential diagnostic pitfall.
Reported herein is a case of composite small lymphocytic lymphoma (SLL) and extramedullary myeloid tumor (EMT) occurring in the same lymph node. Routine morphologic examination revealed a diffuse proliferation of small mature lymphocytes with numerous irregularly dispersed nodules, closely resembling SLL with prominent proliferation centers or Richter's transformation. Flow cytometric immunophenotyping and immunohistochemical stains demonstrated the presence of SLL cells as well as myeloblasts, confirming the diagnosis of a composite SLL and EMT. Conventional cytogenetics and fluorescence in situ hybridization studies revealed inversion 16 chromosome involving the core binding factor beta and myosin heavy chain 11 genes, characteristic of acute myeloid leukemia with abnormal bone marrow eosinophils and inv(16) or t(16;16) [CBFbeta/MYH11]. In conclusion, the occurrence of SLL and EMT in the same lymph node is rare and multiparameter approach is essential for a definitive diagnosis.


A stacked regression ensemble approach for the quantitative determination of biomass feedstock compositions using near infrared spectroscopy.
Rapid, robust, and accurate biomass compositional analyses are required in the bioenergy industry to accurately determine the chemical composition of biomass feedstocks. A stacked regression ensemble approach using near infrared spectroscopic method was developed for the quantitative determination of glucan, xylan, lignin, ash, and extract in biomass feedstocks. A comprehensive comparison of the performance of various machine learning techniques including support vector regression (linear and radial), least absolute shrinkage and selection operator (LASSO), ridge regression, elastic net, partial least squares, random forests, recursive partitioning and regression trees, gradient boosting, and gaussian process regression was assessed in the training set data (n = 188). The predictive performance of the aforementioned machine learning approaches was then compared with stacked regression, an ensemble learning algorithm which collates the performance of the abovementioned machine learning regression techniques. Results show that the stacked regression primarily outperformed other machine learning techniques (Root mean square error of prediction (RMSEP)average=1.660%wt,R2=0.907) across all five constituents in the validation set data (n = 81). Further results also show that the RMSEP of the stacked ensemble technique is significantly different than that of the partial least squares (PLS) approach in predicting glucan, ash, lignin, and extract components in biomass samples. The stacked ensemble learning approach offers an alternative method for a more accurate prediction of biomass compositions than the traditional PLS technique.