One last round of chemo? Insights from conversations between oncologists and lung cancer patients about prognosis and treatment decisions.
One more chemo or one too many? The increasing use of expensive cancer treatments close to the patient's death is often explained by oncologists' failure to communicate to patients how close to dying they are, implying that patients are often both ill-prepared and over-treated when they die. This article aims at interrogating the politically charged task of prognosticating. Drawing on an ethnographic study of conversations between oncologists and patients with metastatic lung cancer in a Danish oncology clinic, I show that oncologists utilize, rather than avoid, prognostication in their negotiations with patients about treatment withdrawal. The study informs the emerging sociology of prognosis in three ways: First, prognostication is not only about foreseeing and foretelling, but also about shaping the patient's process of dying. Second, oncologists prognosticate differently depending on the level of certainty about the patient's trajectory. To unfold these differences, the article provides a terminology that distinguishes between four 'modes of prognostication', namely hinting, informing, calibrating and organizing. Third, prognosticating can unfold over time through multiple consultations, emphasizing the relevance of adopting methodologies enabling the study of prognosticating over time.


Cost-effective frozen master mix modification of a commercial methicillin-resistant Staphylococcus aureus PCR assay.
The expense inherent to molecular diagnostics may be an overriding concern for a variety of clinical laboratories in the development of PCR-based methicillin-resistant Staphylococcus aureus (MRSA) active surveillance programs. BD GeneOhm MRSA assay master mix was reconstituted, aliquoted into SmartCycler tubes in 25-microl volumes, and frozen at -70 degrees C. One hundred percent of archival nasal swab lysates yielded the expected PCR results when incubated in master mix frozen for 1, 2, 3, and 4 weeks. A 98.8% concordance of the final result was observed upon prospective PCR analysis of 320 clinical lysates utilizing freshly reconstituted master mix and 2-week-frozen master mix. Initial unresolved rates generated by frozen master mix and freshly reconstituted master mix differed by 1.6% (P = 0.16). Of 50 MRSA-positive lysates, the titers of 32 (64%) were determined to the same value upon initial tandem frozen master mix and freshly reconstituted master mix utilization; the titers of an additional 14 were determined to the same value upon repeat testing. Frozen master mix maintains potency for at least 4 weeks, facilitating detection of MRSA from nasal swab lysates, and may decrease the amount of unused reagent up to an average of 33%.


[Treatment of severe cholestatic hepatitis by integrated traditional Chinese and Western medicine].
To study the curative effect of Chinese medicine in treating severe cholestatic-hepatitis (SCH). Three hundred and fifty patients of SCH with total bilirubin level > or = 171 mumol/L were treated with Chinese medicines. For those with Blood Stasis Syndrome, treated with the recipe mainly consisted of Radix Paeoniae Rubra, and for which accompanied with blood Heat, fluid retention in epigastric region. Dampness dissenubated in Sanjiao ([symbol: see text]) or both Spleen and Kidney Yang-Deficiency Syndrome, the recipe was used in modification according to the Syndrome. Treatment was markedly effective in 288 cases and effective in 26 cases, the total effective rate being 89.7%. It is difficult in treating severe cholestatic hepatitis, especially the chronic cholestatic hepatitis, which could develop to severe chronic hepatitis if the jaundice lasted for a long time. This study showed a good effect of Chinese herbal medicine in eliminating jaundice.


[Dubreuilh melanoma: and epidemiologic and prognostic study].
Lentigo maligna melanoma is a specific histoclinical type of melanoma. We studied the epidemiologic features of lentigo maligna melanoma (Dubreuilh's melanoma) and compared prognosis with other types of melanoma. A retrospective review of 516 cases of cutaneous melanomas, seen from 1985 to 1997, identified 29 cases of lentigo maligna melanoma. Epidemiologic, clinical and prognostic data were collected using a common scoring system for all patients. The chi-squared test, univariate log rank analysis, Cox multiple regression model for multivariate analysis, and actuarial survival curves were applied. The 29 cases of lentigo maligna melanoma (16 women, 13 men) accounted for 5.9 p. 100 of all melanomas. Mean age at diagnosis was 73 years compared with 54 years for others melanomas. Predominant localization was head and neck. There was no prior history of nevi compared with 50 p. 100. Mean delay to diagnosis was 4 years versus 1 year. All patients have had an occupation with to sun exposure. Mean tumoral thickness was 2 mm. Survival was the same as for extensive superficial melanomas and better than for nodular melanomas. Multivariate analysis showed that prognosis was not better in case of lentigo maligna melanoma. Tumoral thickness was the main prognosis factor. Our findings confirmed the specific nature of lentigo maligna melanoma and suggested that sun exposure plays an important role. Multivariate analysis did not show that prognosis was any better in case of lentigo maligna melanoma than in other types of melanoma. The thickness of the tumor must be taken into account as for other melanomas.


Structure of the caspase-recruitment domain from a zebrafish guanylate-binding protein.
The caspase-recruitment domain (CARD) mediates homotypic protein-protein interactions that assemble large oligomeric signaling complexes such as the inflammasomes during innate immune responses. Structural studies of the mammalian CARDs demonstrate that their six-helix bundle folds belong to the death-domain superfamily, whereas such studies have not been reported for other organisms. Here, the zebrafish interferon-induced guanylate-binding protein 1 (zIGBP1) was identified that contains an N-terminal GTPase domain and a helical domain typical of the mammalian guanylate-binding proteins, followed by a FIIND domain and a C-terminal CARD similar to the mammalian inflammasome proteins NLRP1 and CARD8. The structure of the zIGBP1 CARD as a fusion with maltose-binding protein was determined at 1.47 Å resolution. This revealed a six-helix bundle fold similar to the NLRP1 CARD structure with the bent α1 helix typical of all known CARD structures. The zIGBP1 CARD surface contains a positively charged patch near its α1 and α4 helices and a negatively charged patch near its α2, α3 and α5 helices, which may mediate its interaction with partner domains. Further studies using binding assays and other analyses will be required in order to address the physiological function(s) of this zebrafish protein.


Clinical evidence that the human monoclonal anti-idiotypic antibody 105AD7, delays tumor growth by stimulating anti-tumor T-cell responses.
A human monoclonal anti-idiotypic antibody, 105AD7, which mimics a colorectal tumor associated antigen, 791Tgp72, has been developed. A Phase I trial in advanced colorectal cancer patients showed that 105AD7 therapy was nontoxic and that immunised patients had prolonged survival when compared to a contemporary group of patients treated in the same center. There is accumulating clinical evidence that 105AD7 delays tumor growth by stimulating anti-tumor T-cell responses. Stimulation of helper T-cells was exemplified in the phase I study as 105AD7 immunized patients showed antigen specific T-cell blastogenesis responses and enhanced IL-2 production. Further evidence was obtained from a new clinical study in which colorectal cancer patients were immunized prior to tumor resection. Immune infiltrating cells were analysed by immunohistochemistry and effector cell function was studied in immune cells from peripheral blood and tumor draining lymph nodes. Both activated CD4 and natural killer (NK) cells were observed at the tumor site, which is of interest as NK cells are rarely found in colorectal tumors. Effector studies confirmed that NK activity was enhanced in 3/6 patients. Increased autologous tumor killing was also found in 3/4 patients and accumulation of CD8RO cells following 105AD7 immunization also suggested that CD8 T cells were being stimulated.


Direct measurement flow resistance of cochlear aqueduct in guinea pigs.
The cochlear aqueduct connects the scala tympani to the subarachnoid space and is the main pressure equalization canal for the inner ear. Increases in inner ear volume and pressure are thought to cause clinical symptoms such as vertigo, tinnitus and fluctuating hearing loss. In this study the flow resistance of the cochlear aqueduct was determined and its relation with inner ear pressure was studied. Inner ear pressure was measured in the scala tympani through the round window using a micropipette. Through a second micropipette, artificial perilymph was infused into, or withdrawn from, the scala tympani at various constant rates. From the infusion rate and the change in perilymphatic pressure during infusion the flow resistance of the cochlear aqueduct was calculated. The flow resistance was found not to be constant but to depend on the position of the round window membrane and possibly on the magnitude and direction of fluid flow through the aqueduct. Measured flow resistance values were in the range 11-45 Pa s/nl. For very small flow values the flow resistance averaged over 6 animals was 21 Pa s/nl. The flow resistance of the cochlear aqueduct is not a constant value. The cochlear aqueduct is a canal with dynamic properties and may play a role in the complicated process of inner ear pressure regulation.


Emerging therapeutic targets for cerebral edema.
Cerebral edema is a key contributor to death and disability in several forms of brain injury. Current treatment options are limited, reactive, and associated with significant morbidity. Targeted therapies are emerging based on a growing understanding of the molecular underpinnings of cerebral edema. We review the pathophysiology and relationships between different cerebral edema subtypes to provide a foundation for emerging therapies. Mechanisms for promising molecular targets are discussed, with an emphasis on those advancing in clinical trials, including ion and water channels (AQP4, SUR1-TRPM4) and other proteins/lipids involved in edema signaling pathways (AVP, COX2, VEGF, and S1P). Research on novel treatment modalities for cerebral edema [including recombinant proteins and gene therapies] is presented and finally, insights on reducing secondary injury and improving clinical outcome are offered. Targeted molecular strategies to minimize or prevent cerebral edema are promising. Inhibition of SUR1-TRPM4 (glyburide/glibenclamide) and VEGF (bevacizumab) are currently closest to translation based on advances in clinical trials. However, the latter, tested in glioblastoma multiforme, has not demonstrated survival benefit. Research on recombinant proteins and gene therapies for cerebral edema is in its infancy, but early results are encouraging. These newer modalities may facilitate our understanding of the pathobiology underlying cerebral edema.


A new mutation in the proteolipid protein (PLP) gene in a German family with Pelizaeus-Merzbacher disease.
A C-to-T transition in exon 4 of the PLP gene was found in 2 affected males and two obligate carriers in a German family with Pelizaeus-Merzbacher disease. The mutation, which causes loss of an HphI site and changes amino acid 155 from threonine to isoleucine, was absent from 108 normal chromosomes. There are 5 concordances and 1 discrepancy between these results and those obtained by magnetic resonance imaging in this family.


Hera from Thermus thermophilus: the first thermostable DEAD-box helicase with an RNase P protein motif.
DEAD-box proteins have been implicated in a wide array of cellular processes ranging from initiation of protein synthesis and ribosome biogenesis to mRNA splicing. Here, we report the isolation, biochemical characterization and crystallization of the first thermophilic DEAD box protein, Hera (heat-resistant RNA-dependent ATPase) from Thermus thermophilus HB8. The molecular mass of the deduced Hera protein sequence (510 amino acid residues) is 55.95 kDa. Hera possesses all of the conserved motifs found among the, DEAD-box RNA helicases. In addition, it also has a motif characteristic of the protein component of ribonuclease P at its C-terminal region (residues 372-386). Hera appears to be non-specific with respect to the RNA species that triggers ATPase activity. Nevertheless, at high temperature, ATPase activity is at a maximum when bacterial 16 S rRNA or 23 S rRNA are used as the substrates. Moreover, a deletion of the RNase P protein motif significantly reduces the ability of Hera to hydrolyze ATP in the presence of RNase P RNA. Hera has a specific ATPase activity of 480 units/microg and therefore, displays the highest ATPase specific activity reported for a protein of the RNA helicase family. We determined that Hera shows helix-destabilizing activity, and that the RNA-unwinding or helix-destabilizing activity of Hera is coupled to ATP hydrolysis. Since Hera is a stable thermophilic protein and we have obtained crystals of it diffracting beyond 2.6 A, the possibilities for structure determination of a full-length RNA-helicase are open.


A method for the analysis of tabun in multisol using gas chromatographic flame photometric detection.
Preparation and analysis of tabun (GA) solutions are necessary for the continued development of countermeasures to this nerve agent. GA solutions must be stable and compatible for use in the test systems chosen for study; however, GA is very unstable in saline solutions. In the past we have found GA in saline at 2 mg/mL to be stable for a month or less at -70 degrees C, whereas saline solutions of sarin (GB), soman (GD), and cyclosarin (GF) were stable for many months. Previous studies have shown that Multisol (48.5% H(2)O, 40% propylene glycol, 10% ethanol, and 1.5% benzyl alcohol) provides stable solutions of GA. We confirmed the stability of GA in Multisol with phosphorus nuclear magnetic resonance (P horizontal line NMR) and developed a method for the analysis of GA in Multisol using gas chromatographic flame photometric detection (GCFPD) in the phosphorus mode. The GC method used acetonitrile (CH(3)CN) for a dilution solvent because of its miscibility with GA in chloroform (CHCl(3)) standards and GA in Multisol samples at 1% (v/v). Furthermore, the dilutions with CH(3)CN made the phosphorus mode interference peak present in CHCl(3) analytically manageable, reduced the interferences of Multisol in the GC separation, and contributed to a safe and reliable analysis of GA at 20 mug/mL. We demonstrated the stability of GA in Multisol stored for more than a year at 70 degrees C. This method contributes a suitable technique for the preparation and analysis of reliable solutions of GA in nerve agent medical research and demonstrates the extended stability of GA in Multisol.


[Clonality and stem cell defects in the molecular pathology of chronic myeloproliferative disorders].
The chronic myeloproliferative disorders (CMD) are characterized by sustained or progressive proliferations of bone marrow cells, affecting one or more lineages in varying combinations. They are classified in 4 subgroups but transitional forms and transformations among the different entities are common. Analysing RFLPs and methylation patterns of X-chromosomal genes we could show, that in each entity granulocytes as well as bone marrow cells are of monoclonal origin. These findings support the view that all forms of CMD have in common that they arise from a multipotent hematopoietic stem cell. CML can be differentiated from all other forms of CMD by the Philadelphia-chromosome which on the molecular level has been revealed as bcr-abl gene junction. We investigated 258 cases of CMD for rearrangement of the bcr gene and found that it selectively occurred in CML. The methods applied can be of diagnostic value in differentiating reactive from neoplastic proliferations by analysis of clonality, and in differentiation of CML from other types of CMD by detection of the bcr-rearrangement.


Tapentadol, but not morphine, selectively inhibits disease-related thermal hyperalgesia in a mouse model of diabetic neuropathic pain.
Neuropathic pain in diabetic patients is a common distressing symptom and remains a challenge for analgesic treatment. Selective inhibition of pathological pain sensation without modification of normal sensory function is a primary aim of analgesic treatment in chronic neuropathic pain. Tapentadol is a novel analgesic with two modes of action, mu-opioid receptor (MOR) agonism and noradrenaline (NA) reuptake inhibition. Mice were rendered diabetic by means of streptozotocin, and neuropathic hyperalgesia was assessed in a 50 degrees C hot plate test. Normal nociception was determined in control mice. Tapentadol (0.1-1mg/kg i.v.) and morphine (0.1-3.16 mg/kg i.v.) dose-dependently attenuated heat-induced nociception in diabetic animals with full efficacy, reaching >80% at the highest doses tested. Tapentadol was more potent than morphine against heat hyperalgesia, with ED(50) (minimal effective dose) values of 0.32 (0.316) and 0.65 (1)mg/kg, respectively. Non-diabetic controls did not show significant anti-nociception with tapentadol up to the highest dose tested (1mg/kg). In contrast, 3.16 mg/kg morphine, the dose that resulted in full anti-hyperalgesic efficacy under diabetic conditions, produced significant anti-nociception in non-diabetic controls. Selective inhibition of disease-related hyperalgesia by tapentadol suggests a possible advantage in the treatment of chronic neuropathic pain when compared with classical opioids, such as morphine. It is hypothesized that this superior efficacy profile of tapentadol is due to simultaneous activation of MOR and inhibition of NA reuptake.


Is an elevated serum transferrin saturation associated with the development of diabetes?
Diabetes mellitus is a common comorbid condition of hemochromatosis and is often identified as a complication of untreated hemochromatosis. However, there are few primary data examining the development of diabetes secondary to hemochromatosis. Our objective was to determine the likelihood of developing diabetes in a nationally representative cohort of patients who have an elevated serum transferrin saturation rate but no current diagnosis of diabetes. This is a retrospective cohort study based on merging the National Health and Nutrition Examination Survey I (1971-1974; NHANES I) with the NHANES I Epidemiologic Followup Study (1992). Individuals aged 25 to 74 years at the time of the NHANES I without diabetes (n = 9274). The outcome was development of diabetes according to patient report, proxy report, or death certificate by the time of the follow-up interview. The incidence of diagnosed diabetes in the cohort was 10.2%. Among individuals with serum transferrin saturation levels above 55%, 7.5% developed diagnosed diabetes compared with 10.2% with a serum transferrin saturation of no more than 45% (P =.38). The relation remained nonsignificant in models adjusted for risk factors of diabetes and in analyses that assumed 10% of patients had received treatment for hemochromatosis. In this nationally representative cohort of adults, elevated serum transferrin saturation was not significantly associated with the development of diabetes.


Challenges in synthetically designing mammalian circadian clocks.
Synthetic biology, in which complex, dynamic biological systems are designed or reconstructed from basic biological components, can help elucidate the design principles of such systems. However, this engineering approach has only been applied to a few simple biological systems. The circadian clock is appropriate for this approach, since it is a dynamic system with complex transcriptional and post-transcriptional circuits that have been comprehensively described. Rational synthesis of the properties of the suprachiasmatic nucleus, the central clock tissue of the circadian system that controls many dynamic behaviors, will be important for understanding the neural-circuit systems that control physiological behaviors. These approaches will provide a deeper understanding of the biological clock, and of clinical problems associated with it, such as sleep disorders.


Short- and Long-Range Connections Differentially Modulate the Dynamics and State of Small-World Networks.
The human brain contains billions of neurons that flexibly interconnect to support local and global computational spans. As neuronal activity propagates through the neural medium, it approaches a critical state hedged between ordered and disordered system regimes. Recent work demonstrates that this criticality coincides with the small-world topology, a network arrangement that accommodates both local (subcritical) and global (supercritical) system properties. On one hand, operating near criticality is thought to offer several neurocomputational advantages, e.g., high-dynamic range, efficient information capacity, and information transfer fidelity. On the other hand, aberrations from the critical state have been linked to diverse pathologies of the brain, such as post-traumatic epileptiform seizures and disorders of consciousness. Modulation of brain activity, through neuromodulation, presents an attractive mode of treatment to alleviate such neurological disorders, but a tractable neural framework is needed to facilitate clinical progress. Using a variation on the generative small-world model of Watts and Strogatz and Kuramoto's model of coupled oscillators, we show that the topological and dynamical properties of the small-world network are divided into two functional domains based on the range of connectivity, and that these domains play distinct roles in shaping the behavior of the critical state. We demonstrate that short-range network connections shape the dynamics of the system, e.g., its volatility and metastability, whereas long-range connections drive the system state, e.g., a seizure. Together, these findings lend support to combinatorial neuromodulation approaches that synergistically normalize the system dynamic while mobilizing the system state.


Single-step elongation of oligodeoxynucleotides using terminal deoxynucleotidyl transferase.
Procedures for the stepwise addition of one or more deoxyribonucleotide residues to the 3' end of an oligodeoxyribonucleoside phosphate acceptor using commercially available terminal deoxynucleotidyl transferase is described. 2-80 nmol of acceptors with a chain length of four, five or nine monomer units were elongated with a single 2'-deoxyribonucleoside 5'-triphosphate in yields of 20-30%. The monomers carried no protecting groups and were used both radioactively labelled and unlabelled. The elongated oligodeoxynucleoside phosphates were isolated by reverse-phase (Nucleosil C18) high-performance liquid chromatography or paper chromatography. The isolated products were sequenced by the fingerprint method. Advantages and disadvantages of this new methodology for the enzymatic synthesis of defined oligodeoxynucleotides are discussed.


Peptide-vector strategy bypasses P-glycoprotein efflux, and enhances brain transport and solubility of paclitaxel.
We present the results obtained with paclitaxel coupled to a peptide-vector SynB3 (PAX-OSUC-SynB3), showing that this peptide-vector enhances the solubility of paclitaxel and its brain uptake in mice using the in situ brain perfusion model. We also show by the in situ brain perfusion in P-glycoprotein (P-gp)-deficient and wild-type mice that vectorized paclitaxel bypasses the P-gp present at the luminal side of the blood-brain barrier. The effect of the vectorized paclitaxel on various cancer cells was not significantly different from that of free paclitaxel. These results indicate that vectorization of paclitaxel may have significant potential for the treatment of brain tumors.


Scalable processes for fabricating non-volatile memory devices using self-assembled 2D arrays of gold nanoparticles as charge storage nodes.
We propose robust and scalable processes for the fabrication of floating gate devices using ordered arrays of 7 nm size gold nanoparticles as charge storage nodes. The proposed strategy can be readily adapted for fabricating next generation (sub-20 nm node) non-volatile memory devices.


Note: Generation of Raman laser beams based on a sideband injection-locking technique using a fiber electro-optical modulator.
Two phase-coherent Raman laser beams with a frequency offset of 6.835 GHz were generated by sideband injection-locking technique. A master diode laser was phase-modulated at 6.835 GHz by a fiber electro-optic modulator. A slave diode was injection-locked to the -1 sideband of the phase-modulated beam, and another diode was locked to the master laser carrier. This method produced stable and spatially separated Raman lasers with a large frequency shift range (>180 MHz). The relative linewidth of these two beams was ∼1 Hz, and the unwanted carrier mode was suppressed down to -24 dB. Stimulated Raman transitions and Ramsey fringes were driven by Raman lasers in a cold atomic beam.


A novel 3D-printed mechanical actuator using centrifugal force for magnetic resonance elastography.
Magnetic resonance elastography (MRE) is a technique for the quantification of tissue stiffness during MR examinations. It requires consistent methods for mechanical shear wave induction to the region of interest in the human body to reliably quantify elastic properties of soft tissues. This work proposes a novel 3D-printed mechanical actuator using the principle of centrifugal force for wave induction. The driver consists of a 3D-printed turbine vibrator powered by compressed air (located inside the scanner room) and an active driver controlling the pressure of inflowing air (placed outside the scanner room). The generated force of the proposed actuator increases for higher actuation frequencies as opposed to conventionally used air cushions. There, the displacement amplitude decreases with increasing actuation frequency resulting in a smaller signal-to-noise ratio. An initial phantom study is presented which demonstrates the feasibility of the actuator for MRE. The wave-actuation frequency was regulated in a range between 15 Hz and 60 Hz for force measurements and proved sufficiently stable (± 0.3 Hz) for any given nominal frequency. The generated forces depend on the weight of the eccentric unbalance within the turbine and ranged between 0.67 N to 2.70 N (for 15 Hz) and 3.09 N to 7.77 N (for 60 Hz). Therefore, the generated force of the presented actuator increases with rotational speed of the turbine and offers an elegant solution for sufficiently large wave actuation at higher frequencies. In future work, we will investigate an optimal ratio of the weight of unbalance to the size of turbine for appropriately large but tolerable wave actuation for a given nominal frequency.


Digital networks for laboratory data: potentials, barriers and current initiatives.
Medical care is increasingly delivered by multiple providers across healthcare sectors and specialties, leading to a fragmentation of the electronic patient record across organizations and vendor IT systems. The rapid uptake of wearables and connected diagnostic devices adds another source of densely collected data by the patients themselves. Integration of these data sources opens up several potentials: a longitudinal view of laboratory findings would close the gaps between individual provider visits and allow to more closely follow disease progression. Adding non-laboratory data (e.g. diagnoses, procedures) would add context and support clinical interpretation of findings. Case-based reasoning and disease-modelling approaches would allow to identify similar patient groups and classify endotypes. Realization of these potentials is, however, subject to several barriers, including legal and ethical prerequisites of data access, syntactic and semantic integration, comparability of items and user-centered presentation. The German Medical Informatics Initiative is presented as a current undertaking that strives to address these issues by establishing a national infrastructure for the secondary use of routine clinical data.


Satisfied carers of persons with enduring mental illness: who and why?
This secondary mixed-methods analysis was based on the interview data collected for an exploratory study of the experiences and needs of carers of persons with enduring mental illness. The aims were to identify and describe socio-demographic and contextual factors associated with the satisfaction of carers with family support. Content analysis and non-parametric tests were used for the exploration of qualitative and quantitative data collected from 38 carers. The majority of the satisfied carers were male and from a higher socio-economic group than other carers. The ill relatives of all satisfied participants resided outside their family homes. Carer satisfaction was associated with such categories as: a caring service; supportive and unintrusive family relationships; being accepted as partners; supportive community; and suitable family services. All the identified categories were interrelated. The identified categories and socio-demographic factors should be considered for inclusion in the planning and evaluation of family support services.


Kinetics of Ordering and Deformation in Photosensitive Azobenzene LC Networks.
Azobenzene-containing polymer networks are unique compounds that are able to change their shape in response to light, which makes them prospective materials for photocontrollable nano-templates, sensors, microrobots, artificial muscles, etc. In present work, we study the kinetics of light-induced ordering and deformation in two-component polymer networks containing optically inert liquid crystalline (LC) mesogens and azobenzene chromophores. By this, we generalize our previous theory [J. Phys. Chem. Lett. 2017, 8, 1094⁻1098] devoted to the kinetics of photoizomerization in one-component azo-polymers without mesogenic inclusions. The kinetic equations of photoisomerization are used, taking into account the angular selectivity of the photoisomerization with respect to the polarization direction of the light E. After multiple trans-cis-trans photoisomerization cycles, the azobenzenes are reoriented preferably perpendicular to the vector E. This changes the ordering of the mesogens due to the orientational LC interactions between the components. The light-induced reordering is accompanied by network deformation. Time evolution of ordering and deformation is found as a function of the intensity of light and structural parameters of the LC azo-networks, which define the viscosity, the strength of the LC interactions between the components, the volume fraction of the azobenzene moieties, and the angular distribution of azobenzenes in polymer chains. Established structure-property relationships are in agreement with a number of experimental data.


Rhizobium leguminosarum Glutathione Peroxidase Is Essential for Oxidative Stress Resistance and Efficient Nodulation.
Glutathione (GSH) plays a key role in regulating the cellular Redox Homeostasis, and appears to be essential for initiation and development of root nodules. Glutathione peroxidase (Gpx) catalyzes the reduction of H2O2 and organic hydroperoxides by oxidation of GSH to oxidized GSH (GSSG), which in turn is reduced by glutathione reductase (GR). However, it has not been determined whether the Rhizobium leguminosarum Gpx or GR is required during symbiotic interactions with pea. To characterize the role of glutathione-dependent enzymes in the symbiotic process, single and double mutants were made in gpxA (encoding glutathione peroxidase) and gshR (encoding glutathione reductase) genes. All the mutations did not affect the rhizobial growth, but they increased the sensitivity of R. leguminosarum strains to H2O2. Mutant in GpxA had no effect on intracellular GSH levels, but can increase the expression of the catalase genes. The gshR mutant can induce the formation of normal nodules, while the gpxA single and double mutants exhibited a nodulation phenotype coupled to more than 50% reduction in the nitrogen fixation capacity, these defects in nodulation were characterized by the formation of ineffective nodules. In addition, the gpxA and gshR double mutant was severely impaired in rhizosphere colonization and competition. Quantitative proteomics using the TMT labeling method was applied to study the differential expression of proteins in bacteroids isolated from pea root nodules. A total of 27 differentially expressed proteins were identified in these root bacteroids including twenty down-regulated and seven up-regulated proteins. By sorting the down-regulated proteins, eight are transporter proteins, seven are dehydrogenase, deoxygenase, oxidase, and hydrolase. Moreover, three down-regulating proteins are directly involved in nodule process.


No differences in emotion recognition strategies in children with autism spectrum disorder: evidence from hybrid faces.
Emotion recognition problems are frequently reported in individuals with an autism spectrum disorder (ASD). However, this research area is characterized by inconsistent findings, with atypical emotion processing strategies possibly contributing to existing contradictions. In addition, an attenuated saliency of the eyes region is often demonstrated in ASD during face identity processing. We wanted to compare reliance on mouth versus eyes information in children with and without ASD, using hybrid facial expressions. A group of six-to-eight-year-old boys with ASD and an age- and intelligence-matched typically developing (TD) group without intellectual disability performed an emotion labelling task with hybrid facial expressions. Five static expressions were used: one neutral expression and four emotional expressions, namely, anger, fear, happiness, and sadness. Hybrid faces were created, consisting of an emotional face half (upper or lower face region) with the other face half showing a neutral expression. Results showed no emotion recognition problem in ASD. Moreover, we provided evidence for the existence of top- and bottom-emotions in children: correct identification of expressions mainly depends on information in the eyes (so-called top-emotions: happiness) or in the mouth region (so-called bottom-emotions: sadness, anger, and fear). No stronger reliance on mouth information was found in children with ASD.


Concomitant Interstitial Lung Disease with Psoriasis.
We encounter interstitial lung disease (ILD) patients with psoriasis. The aim of this case series was to examine clinical and radiographic characteristics of patients with concomitant psoriasis and ILD. This is a retrospective review of our institutional experience of ILD concomitant with psoriasis, from the database in the Advanced Lung/Interstitial Lung Disease Program at the Mount Sinai Hospital. Out of 447 ILD patients, we identified 21 (4.7%) with antecedent or concomitant diagnosis of psoriasis. Clinical, radiographic, pathological, and outcome data were abstracted from our medical records. Median age was 66 years (range, 46-86) and 14 (66.7%) were male. Thirteen (61.9%) had not previously or concomitantly been exposed to immunosuppressive therapy directed against psoriasis. Two (9.5%) ultimately died. Clinical diagnosis of ILD included idiopathic pulmonary fibrosis, 11 (52.4%); nonspecific interstitial pneumonia (NSIP), 2 (9.5%); cryptogenic organizing pneumonia, 2 (9.5%); chronic hypersensitivity pneumonitis, 2 (9.5%); and the others, while radiographic diagnosis included usual interstitial pneumonia pattern, 9 (42.9%); NSIP pattern, 6 (28.6%); organizing pneumonia pattern, 4 (19.0%); hypersensitivity pneumonitis pattern, 2 (9.5%); and the others. We report 21 ILD cases with antecedent or concomitant diagnosis of psoriasis. Further prospective studies are required to determine the association between ILD and psoriasis.


Photoaffinity labeling of the DDT1 MF-2 cell alpha 1-adrenergic receptor.
In this study, we have used an alpha 1-adrenergic receptor photoaffinity ligand, 2-[4-(4-azido-3-iodo-benzoyl)-piperazin-1-yl]-4-amino-6, 7-dimethoxyquinazoline (125I-APD), to label covalently the alpha 1-adrenergic receptor in a smooth muscle cell line. Our results indicate that in the absence of light, (125I)APD binds reversibly to a site in the DDT1 MF-2 cell membranes having pharmacological characteristics of an alpha 1-adrenergic receptor. Following incorporation of (125I)APD into partially purified membranes a single labeled band of protein with a Mr of 81 000 was visualized by autoradiography following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Incorporation of (125I)-APD into this band was affected by adrenergic agonists and antagonists in a manner consistent with an alpha 1-adrenergic interaction. Prazosin (alpha 1-selective) blocked incorporation of the label into the Mr = 81 000 protein while yohimbine (alpha 2-selective) did not. Of the adrenergic agonists, (-)-epinephrine and (-)-norepinephrine but not (-)-isoproterenol blocked labeling of the Mr = 81 000 protein. We conclude that the ligand binding site of the DDT1 MF-2 cell alpha 1-adrenergic receptor resides in a Mr = 81 000 protein.


Orbital Apex Syndrome: A Clinico-anatomical Diagnosis.
An 8-month-old girl presented with fever, restricted left eye movements and increasing proptosis for 8 days. On examination she had left orbital cellulitis, relative afferent pupillary defect and ophthalmoplegia. Contrast-enhanced magnetic resonance imaging (MRI) brain with orbits revealed orbital apex syndrome (OAS) with cavernous sinus thrombosis. Orbital apex is located posteriorly in the orbit and characterised by involvement of cranial nerves II, III, IV, VI and ophthalmic division of Vth nerve. The close clinico-anatomical differentials of OAS are cavernous sinus and superior orbital fissure syndrome. The current case was treated successfully with intravenous antibiotics and anticoagulation therapy.


Hereditary genes and SNPs associated with breast cancer.
Breast cancer is the most common cancer among women affecting up to one third of tehm during their lifespans. Increased expression of some genes due to polymorphisms increases the risk of breast cancer incidence. Since mutations that are recognized to increase breast cancer risk within families are quite rare, identification of these SNPs is very important. The most important loci which include mutations are; BRCA1, BRCA2, PTEN, ATM, TP53, CHEK2, PPM1D, CDH1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, BRIP1, RAD50, RAD51C, STK11 and BARD1. Presence of SNPs in these genes increases the risk of breast cancer and associated diagnostic markers are among the most reliable for assessing prognosis of breast cancer. In this article we reviewed the hereditary genes of breast cancer and SNPs associated with increasing the risk of breast cancer that were recently were reported from candidate gene, meta-analysis and GWAS studies. SNPs of genes associated with breast cancer can be used as a potential tool for improving cancer diagnosis and treatment planning.


Association between malocclusion and articulation of phonemes in early childhood.
To evaluate the relationship between dental malocclusion and speech to understand the etiology of speech sound disorders (SSD) in schoolchildren and to make a correct diagnosis and treatment plan. Articulation and dental occlusion, oromyofunctional evaluation with orofacial praxis and musculature, resting tongue position, and swallowing pattern were analyzed in 290 schoolchildren between the ages of 4 and 7 years. Statistical tests were considered significant for P < .05. A significant association between dental malocclusions (Angle Class II and III, anterior open bite, edge-to-edge bite, overjet and anterior crossbite) and phonetic alterations (P = .008) was observed. Sigmatisms and rhotacisms were the most frequent disorders. Malocclusions also showed a significant association with oral habits and with orofacial praxis and muscle activity. The presence of malocclusion can cause imbalances in the functions involved in the stomatognathic system. Awareness of this relationship in young children would help professionals to implement preventive measures for the optimum development of children's oral health.


An external urine collection device for incontinent women. Evaluation of long-term use.
Urinary incontinence is common in aged women, may precipitate nursing home admission, and may prompt use of a urine collection device, usually an indwelling urethral catheter. The safety and efficacy of a new external urine collection device for women that is affixed to the perineum by an adhesive developed for ostomy bags was evaluated. Applied to 26 aged women, 78% of 2,264 devices were leak-free for 24 hours and 49% for 48 hours. The incidence of new bacteriuria was less than half that found in our earlier studies of long-term urethral catheters in the same institution. Perineal erythema was infrequent and preexisting decubitus ulcers improved or did not change. Four patients were withdrawn, one each because of periurethral itching, diminished urine output, recurrent wetness, and fracture of the proximal femur associated with severe osteoporosis. This device may offer an alternative to urethral catheters for management of urinary incontinence but should not be used on women with urine retention and should be used with care on women with severe osteoporosis. Controlled trials must determine effects upon bacteriologic complications and health-care costs.


Efficient and Rapid Mechanochemical Assembly of Platinum(II) Squares for Guanine Quadruplex Targeting.
We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt4(en)4(N∩N)4][CF3SO3]8 (en= ethylenediamine, N∩N = 4,4'-bipyridine derivatives) from commercially available precursor K2PtCl4 in good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and telomere-associated DNA and RNA sequences. Sub-micromolar binding affinities were obtained by fluorescence displacement assays (FID) and isothermal titration calorimetry (ITC), with binding preference to telomere RNA (TERRA) sequences. ITC showed a 1:1 binding stoichiometry of the metallosquare to TERRA, while the stoichiometry was more complex for telomeric quadruplex DNA and a double-stranded DNA control.


Serum class I and II alcohol dehydrogenase activity during the course of viral hepatitis.
We examined the activities of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with viral hepatitis using the fluorogenic substrates 4-methoxy-1-naphthaldehyde for class I and 6-methoxy-2-naphthaldehyde for class II. It was found that serum activities of class I and II alcohol dehydrogenase isoenzymes over the course of five weeks of hospitalisation were higher than those of controls. The greatest increase in activities was found at the onset of disease, exceeding the mean control value by about 30 fold for class I and 4 fold for class II. These activities were lower than that of aminotransferase but higher than those for lactate dehydrogenase, alkaline phosphatase and gamma-glutamyltransferase. Thereafter, the activity of alcohol dehydrogenase isoenzymes gradually decreased, but did not reach the values of the control groups in the last period of the study. Activities of class I and II alcohol dehydrogenase isoenzymes correlated well with those of alanine and aspartate aminotransferase and lactate dehydrogenase in the first weeks of illness. These results clearly demonstrate that especially the activity of class I alcohol dehydrogenase isoenzyme measured by a fluorimetric method can be a useful marker of liver cell damage in the course of viral hepatitis.


Posturographic Findings in Patients With Psychological Dizziness.
The diagnosis and treatment of patients with psychogenic vertigo (PSY) is difficult because of the lack of reliable objective findings for this condition. We examined the characteristics of foam posturography in patients with peripheral vestibular disorders (PVD) and those with PSY. In particular, we focused on the objective findings of foam posturography in PSY. Between January 2010 and December 2011, 2-legged stance tasks were conducted in patients with vertigo/dizziness under 4 conditions: eyes opened with/without foam rubber and eyes closed with/without foam rubber. In terms of the velocity of movement of the center of pressure, we examined Romberg ratios, that is, the ratios of changes in visual conditions under the fixed foam rubber conditions, and foam rubber ratios, that is, the ratios of changes in foam rubber conditions under fixed visual conditions. These ratios were compared among 3 groups: healthy controls (CONT) (n=195), PVD (n=178), and PSY (n=32). Romberg ratios using foam rubber in the PVD group were significantly higher than those in the CONT group. Those in the PSY group were significantly lower. Likewise, the foam rubber ratios in the PVD group were significantly higher than those in the CONT group when the eyes were closed. Those in the PSY group were significantly lower. Judging from scores in Romberg ratios using foam rubber and foam rubber ratios when eyes were closed, foam posturography might have the potential to differentiate PSY from PVD.


Intraesophageal manganese superoxide dismutase-plasmid liposomes ameliorates novel total-body and thoracic radiation sensitivity of NOS1-/- mice.
The effect of deletion of the nitric oxide synthase 1 gene (NOS1(-/-)) on radiosensitivity was determined. In vitro, long-term cultures of bone marrow stromal cells derived from NOS1(-/-) were more radioresistant than cells from C57BL/6NHsd (wild-type), NOS2(-/-) or NOS3(-/-) mice. Mice from each strain received 20 Gy thoracic irradiation or 9.5 Gy total-body irradiation (TBI), and NOS1(-/-) mice were more sensitive to both. To determine the etiology of radiosensitivity, studies of histopathology, lower esophageal contractility, gastrointestinal transit, blood counts, electrolytes and inflammatory markers were performed; no significant differences between irradiated NOS1(-/-) and control mice were found. Video camera surveillance revealed the cause of death in NOS1(-/-) mice to be grand mal seizures; control mice died with fatigue and listlessness associated with low blood counts after TBI. NOS1(-/-) mice were not sensitive to brain-only irradiation. MnSOD-PL therapy delivered to the esophagus of wild-type and NOS1(-/-) mice resulted in equivalent biochemical levels in both; however, in NOS1(-/-) mice, MnSOD-PL significantly increased survival after both thoracic and total-body irradiation. The mechanism of radiosensitivity of NOS1(-/-) mice and its reversal by MnSOD-PL may be related to the developmental esophageal enteric neuronal innervation abnormalities described in these mice.


Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.
High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM. We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint. Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients. This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.


Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam.
The anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (etifoxine), a non-benzodiazepine tranquilizer, was evaluated in mice in comparison to valproate, phenytoin and clobazam. Maximal seizures were induced by electroshock (MES) and the chemical convulsants pentetrazol (PTZ), picrotoxin (PTX), bicuculline (BIC), isoniazid (INH), nicotine (NIC) and strychnine (STR). Tonic extensor convulsions were prevented by etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (BIC), and greater than 800 mg/kg p.o. (STR). Clonic seizures were induced by threshold doses of PTZ, PTX and pilocarpine (PIL) and antagonized by etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence, etifoxine blocked both tonic and clonic seizures but was more potent against the tonic component. The anticonvulsant profile of etifoxine appeared similar to that of valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test) etifoxine was on an average 3.7, 12 and 14 times superior to valproate, respectively. It is concluded that etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type.


The complete mitochondrial genome of the crocodile shark, Pseudocarcharias kamoharai (Chondrichthyes, Lamnidae).
The complete mitochondrial genome of the crocodile shark consists of 16,688 bp and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, 1 replication origin region, and 1 control region. The mitochondrial gene arrangement of the crocodile shark is the same as that of most vertebrates. Base composition of the genome is A (32.0%), T (31.0%), C (23.7%) and G (13.3%).


Zellweger syndrome: first reported case in Thailand and literature review.
We describe an infant boy with facial dysmorphism, profound hypotonia, psychomotor retardation, seizure and hepatomegaly. Biochemical study revealed elevation of very long chain fatty acids and pipecolic acid, consistent with peroxisomal disorder. He died at the age of 4 months. Electron microscopic study demonstrated decreased amounts of peroxisomes in liver and kidneys. The clinical characteristic, accompanied the biochemical and microscopic findings led to the diagnosis of Zellweger syndrome. The recognition of this syndrome is important since it is a fatal disease. The pattern of inheritance is autosomal recessive, hence genetic counseling is necessary. We emphasize that peroxisomal disorder should be included in the differential diagnosis in patients with infantile hypotonia. This patient is the first reported case of Zellweger syndrome in Thailand.


Meiotic inhibition with different cyclin-dependent kinase inhibitors in bovine oocytes and its effects on maturation and embryo development.
Cyclin-dependent kinase inhibitors (CDKIs) such as butyrolactone I (BL-I) and roscovitine (ROS) maintain bovine oocytes blocked at the germinal vesicle (GV) stage. Bohemine (BOH), another CDKI, has been used for oocyte activation. The objective of this study was to determine whether BOH blocks meiosis and to compare its efficiency with other CDKIs (ROS and BL-I). Oocytes were cultured for 24 h in 0, 50, 100 and 150 microM BOH to determine the best concentration for blocking meiosis (experiment 1). GV rates were 3.3%, 64.5%, 83.3% and 88.9% (0,50, 100 and 150 microM, respectively). Experiment 2 compared meiotic inhibition efficiency of BOH (100 microM), ROS (25 microM) and BL-I (100 microM). BL-I presented the highest GV rates (97.5%). BOH and ROS were similar to each other (85.4% and 79.9%, respectively). To assess the reversibility of meiotic inhibition (experiment 3), oocytes underwent in vitro maturation (IVM) for 18 h after the 24 h inhibition. Control oocytes were submitted to IVM for 18 h (C18) or 24 h (C24). Maturation rates were either similar to (ROS and BL-I: 96.0% and 93.6%, respectively) or superior to (BOH, 96.9%) C24 (91.0%). All groups were superior to C18 (82.5%). In experiment 4, oocytes were treated as in experiment 3 and then in vitro fertilized and cultured for 8 days. Blastocyst rates for BL-I (32.3%) were similar to C24 (35.0%), while those for BOH (20.2%) and ROS (24.2%) were inferior. All groups were inferior to C18 (43.4%). The results show that: (a) BOH inhibits meiosis resumption; (b) BL-I is the most effective of the CDKIs tested for blocking meiosis; (c) culture of oocytes with meiosis inhibitors is fully reversible in terms of nuclear maturation but they may either decrease (BOH and ROS) or maintain (BL-I) embryo development rates.


Role of GABA receptor subtypes in inhibition of primate spinothalamic tract neurons: difference between spinal and periaqueductal gray inhibition.
1. gamma-Aminobutyric acid (GABA) is thought to inhibit both pre- and postsynaptically the transfer of nociceptive signals from primary afferent fibers to spinal dorsal horn sensory cells, including spinothalamic tract (STT) neurons. The inhibition can be mediated by both GABAA and GABAB receptors. We now attempt to characterize the synaptic inhibition of STT cells by spinal GABAA and GABAB receptors in anesthetized monkeys and to analyze the roles of these two receptor subtypes in the inhibition of STT cellular activity produced by stimulation in the periaqueductal gray (PAG). 2. Iontophoretic release of GABA or muscimol (a selective GABAA receptor agonist) onto STT cells elicited a profound and dose-related inhibition of the responses of all cells tested to noxious cutaneous stimuli. Only four cells (16.7%) were found to be inhibited when baclofen (a selective GABAB receptor agonist) was applied iontophoretically. However, a strong and dose-dependent inhibition of the responses to cutaneous mechanical and thermal stimuli was obtained in all cells examined when baclofen was administered into the dorsal horn through a microdialysis fiber. The inhibitory effects were mainly on nociceptive inputs. 3. The inhibition of cellular activity by GABAA and GABAB agonists could be selectively antagonized by specific antagonists applied through a microdialysis fiber. 4. The excitatory responses evoked by pulsed release of glutamic acid (GLUT) were also inhibited in a dose-related manner by iontophoretic application of GABA and muscimol, but not by baclofen. A high dose of baclofen administered by microdialysis resulted in only a small decrease in GLUT-evoked excitatory responses. 5. Infusion of GABAA and GABAB antagonists into the dorsal horn by microdialysis caused an increase in both background activity and responses to cutaneous stimuli, suggesting that there is a tonic GABAergic inhibition of STT cells. 6. The inhibition of responses to mechanical and thermal stimulation of the cutaneous excitatory receptive field resulting from stimulation in PAG was significantly antagonized in most of the STT cells tested when the GABAA antagonist bicuculline was infused into the spinal dorsal horn through a microdialysis fiber. In contrast, the inhibition produced by PAG stimulation in most of the cells examined was not significantly antagonized by the GABAB antagonists phaclofen or 3-amino-propyl(diethoxymethyl)phophinic acid (CGP35348) administered into the spinal dorsal horn by microdialysis. 7. Our results support the contention that GABAergic mechanisms in the spinal dorsal horn normally exert a tonic modulation of nociceptive inputs through both GABAA and GABAB receptors. The evidence provided here indicates that GABAA receptors located on primate STT neurons contribute to a postsynaptic inhibitory effect on the transmission of peripheral nociceptive inputs. A possible presynaptic GABAA action was not investigated. Our finding of a GABAB-receptor-mediated inhibition is consistent with the view that both pre- and postsynaptic GABAB receptors are involved in inhibitory modulation of spinal nociceptive transmission. Finally, it is suggested from this study that primate spinal GABAA, but not GABAB receptors, are involved in mediating the descending inhibition induced by PAG stimulation.


[Treatment of infectious osteoarthritis in children].
Treatment of septic arthritis is an emergency; therefore antibiotherapy must be started rapidly following the bacteriological sampling. The risk for the articles justifies that treatment be started with two antibiotics given intravenously, the choice of the antibiotics being dependent upon the clinical history. If the bacteria is isolated, an adopted monotherapy is then maintained. A drainage of the joint can be performed by needle aspiration or by a percutaneous catheter, and in case of difficulty to control the sepsis, by surgical debridment. Intravenous antibiotherapy is maintained for 7 to 15 days. Whenever a good response is observed the treatment is continued orally for a total duration of 4 to 6 weeks.


[Stability of the tetramine in blood samples under different temperatures].
To study the stability of tetramine in blood samples under different environment temperatures. The tetramine samples in 0.5 microg/mL concentration were stored in the environment temperature at 45 degrees C, 25 degrees C and 4 degrees C. The tetramine concentration were measured by GC-MS in 1, 3, 12, 18 and 39 days, respectively. And then the results of measurement were analyzed by SPSS software. At 45 degrees C and 25 degrees C, the concentration of tetramine changed without distinctly in first 3 days and declined significantly from 4 days to 12 days. Thereafter it declined more slowly. At 4 degrees C, the concentration of tetramine changed without distinctly in 12 days and declined significantly from 13 days to 18 days. Thereafter it declined more slowly. The concentration of tetra mine in blood samples is stable in 3 days. Thereafter it declined gradually. Temperature also influences the concentration of tetra mine.


Improved prediction formula for total body water assessment in obese women.
To validate an improved formula for the calculation of total body water (TBW) from impedance values in obese women. A sample of 37 overweight females BMI ranging from 29.5 to 44.1 kg/m2. The reference measurements for TBW were obtained by deuterium oxide dilution. Body height (h), hip circumference (C) as well as body impedance at 100 kHz (Z100) were also measured. The values obtained for h, C and Z100 were introduced in the calculations and the following developed formula for total body water was determined: TBW = 0.069 [hC2/(4 pi .Z100)]+19.671. The validity of this formula was assessed through the statistical test of Bland and Altman which we also performed for other formulas containing the weight and/or the height. We found that the accuracy of the prediction of TBW by our formula, although lower than those formulas using body weight, is higher than that which takes into account only body height. We conclude that body volume, expressed through body height and hip circumference, is a good choice of parameter in bioelectrical impedance measurements. The new approach can be useful in clinical settings for repeated monitoring of obese women, during diet-restricted treatment.


The sperm donor programme over 11 years at Newcastle Fertility Centre.
The UK national sperm donor shortage is well known. We aimed to analyse the trends in various aspects of the sperm donor programme at Newcastle Fertility Centre (NFC) between 2000 and 2010. A retrospective review of the assisted conception treatments with donor sperm was performed. A decline in the numbers of donors recruited alongside a declining trend in the number of patients treated with donor sperm and donor insemination (DI) treatment cycles carried out was apparent. There was an accompanying rising trend in donor IVF cycles and in same-sex couples and single women coming for treatment. The transfer of sperm to local peripheral centres ceased during this time and an increasing number of patients imported sperm from overseas commercial sperm banks. A waiting list for treatment was set up in 2007 with a gradual increase in waiting time to 18 months in 2010. Overall, there was a significant change in the sperm donor programme at NFC with fewer donors recruited, fewer patients receiving treatment, increasing sperm import and longer waiting times for treatment over the study period.


trans-4-Acetylcyclohexanecarboxylic acid and (+/-)-trans-2-acetylcyclohexanecarboxylic acid: hydrogen-bonding patterns in two isomeric keto acids.
Both title compounds, C(9)H(14)O(3), display carboxyl-dimer hydrogen-bonding patterns. The 4-acetyl isomer adopts a chiral conformation with negligible disordering of the methyl and carboxyl groups and forms centrosymmetric dimers across the b and c edges of the chosen cell [O.O = 2.667 (3) A and O-H.O = 175 degrees ]. Intermolecular C-H.O close contacts were found for both carbonyl groups. In the 2-acetyl isomer, there is no intramolecular interaction between the carboxyl and acetyl groups and the hydrogen bonding involves centrosymmetric carboxyl dimerization across the ab and ac faces of the chosen cell [O.O = 2.668 (2) A and O-H.O = 173 degrees ]. The carboxyl group is negligibly disordered, but significant rotational disordering was found for the acetyl methyl group. An intermolecular C-H.O close contact was found involving the ketone group.


Encouraging underscreened women to have cervical cancer screening: the effectiveness of a computer strategy.
Computers that collect data from patients and provide both patients and practitioners with printed feedback on a range of health risks are a tool for assisting general practitioners with preventive care. This study assessed the impact of computer-generated printed feedback on cervical screening among women who were underscreened for cervical cancer. Female attenders at two Australian general practices were randomly allocated to Experimental or Control groups. Women in both groups completed a health risk survey on a touch screen computer prior to their consultation. Those in the Experimental group received printed pages summarizing their results, including their eligibility for cervical screening and last Pap test, for themselves and their doctor. The number and proportion of underscreened women who had a Pap test in the 6 months after completing the computer survey, as determined by pathology records, were examined. Of the 679 participants, 139 were classified as underscreened on the basis of self-report (74 Experimental, 65 Control) and 272 on the basis of their pathology records (148 Experimental, 124 Control). Overall about one-third of women had a test in the 6-month period, and the differences between the groups were not significant for women overall (18-70 years) or for women 18-49 years. Among women 50-70 who were underscreened based on self-report, those receiving the printout were more likely to have a Pap test in the next 6 months (P < 0.05). This pattern was also evident, but did not reach statistical significance, for older women who were underscreened based on pathology records. We are unable to draw conclusions regarding the effectiveness of the computer system due to the modest proportions of women screened, the small numbers, and the fact that the computer survey may have created an intervention effect in the Control group. As the study suggests the computer system is acceptable to women and may be effective for encouraging screening among older women, further exploration of the system is desirable.


Africa: rapid population increase retards development.
The Organization of African Unity (OAU), the African Development Bank (ADB) and the UN Economic Commission for Africa (ECA) have criticized African governments for not taking the problem of unchecked population growth seriously enough. "Until recently most African governments did not view rapid population growth as a matter for concern," said the OAU assistant secretary-general for political affairs, Machivenyika Mapuranga, at a seminar on 'population and development'. The OAU estimates that an annual average population increase of 3.1% far outstrips Africa's economic growth, which in 1992 was less than 1%. Mapuranga acknowledged that cutting the population increase is an uphill struggle, especially among rural communities. African agriculture is largely labor intensive, sustained by smallholders, which encourages farmers to have more children. Like other wage earners, African farmers look to support from their family when they grow old and, for that reason, the number of children also counts. But with agricultural production growing at an average annual rate of 2.5%, self-sufficiency in food remains an elusive goal. Cities in sub-Saharan Africa are growing much faster than the overall rate of population increase of 3.1% per year. Between 1980 and 1988 the region's urban population increased at the rate of 6.9% a year. Urban areas now account for nearly 30% of the sub-Saharan Africa population, currently put at 680 million. By 2025, approximately 700 million people are expected to live in urban areas. Despite migration to towns, the rural population is expected to rise more than 68%, reaching over 590 million.


Electronic structure and spin coupling of the manganese dimer: The state of the art of ab initio approach.
A thorough ab initio study of the Mn(2) dimer in its lowest electronic states that correlate to the ground Mn((6)S)+Mn((6)S) dissociation limit is reported. Performance of multireference methods is examined in calculations of the fully spin-polarized S=5((11) summation operator(+) (u)) state against the recent accurate single-reference coupled cluster CCSD(T) results [A. A. Buchachenko, Chem. Phys. Lett. 459, 73 (2008)]. The detailed comparison reveals a serious disagreement between the multireference configuration interaction (MRCI) and related nonperturbative results on the one hand and the complete active space perturbation theory (CASPT) calculations on the other. A striking difference found in the CASPT results of the second and third orders indicates poor perturbation expansion convergence. It is shown that a similar problem has affected most of the previous calculations performed using CASPT2 and similar perturbative approximations. The composition of the active space in the reference multiconfigurational self-consistent field calculations, the core correlation contribution, and basis set saturation effects are also analyzed. The lower spin states, S=0-4, are investigated using the MRCI method. The results indicate a similar dispersion binding for all the spin states within the manifold related to the closed 4s shells, which appears to screen and suppress the spin coupling between the half-filled 3d atomic shells. On this premise, the full set of model potentials is built by combining the accurate reference CCSD(T) interaction potential for S=5 and the MRCI spin-exchange energies for the S<5 states. This approach leads to the value of 550 cm(-1) as a lower bound for the (1) summation (+) (g) ground-state dissociation energy. The spin-exchange energies themselves are found to comply with the simple Heisenberg model. The effective spin-coupling parameter J is estimated as -3.9 cm(-1), a value roughly 2.5 times smaller in magnitude than those measured in the inert gas cryogenic matrices. Compressing of the Mn(2) dimer in the matrix cage is suggested as the prime cause of this disagreement.


Transmission risk of respiratory viruses in natural and mechanical ventilation environments: implications for SARS-CoV-2 transmission in Africa.
Respiratory viruses can be transmitted through contact, droplet and airborne routes. Viruses that are not naturally airborne may be aerosolised during medical procedures and transmitted to healthcare workers. Most resource-limited healthcare settings lack complex air handling systems to filter air and create pressure gradients that are necessary for minimising viral transmission. This review explores the association between ventilation and the transmission of respiratory viruses like SAR-CoV-2. When used appropriately, both natural and mechanical ventilation can decrease the concentration of viral aerosols, thereby reducing transmission. Although mechanical ventilation systems are more efficient, installation and maintenance costs limit their use in resource-limited settings, whereas the prevailing climate conditions make natural ventilation less desirable. Cost-effective hybrid systems of natural and mechanical ventilation may overcome these limitations.


Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression.
The potential tumor suppressor protein prohibitin can prevent cell proliferation and this required its binding to the Rb protein. Prohibitin could repress the transcriptional activity of E2F family members and this required a part of the marked box region of E2F. The sub-cellular localization of prohibitin has been variously attributed to the mitochondria as well as the inner cell membrane. Here we show that a subset of prohibitin molecules are present in the nucleus where it co-localizes with the Rb protein. Deletion of a putative amino-terminal membrane-docking domain of prohibitin had no effect on its ability to suppress cell proliferation or inhibit E2F activity. Our experiments show that a 53 amino-acid stretch of E2F1 is sufficient for being targeted by prohibitin; fusion of this region to GAL4-VP16 construct could make it susceptible to prohibitin-mediated, but not Rb-mediated repression. Prohibitin, like Rb, could repress transcription from SV40 and major late promoters when recruited directly to DNA. Prohibitin mediated transcriptional repression required histone-deacetylase activity, but unlike Rb, additional co-repressors like N-CoR are also involved. Repression by prohibitin correlates with histone deacetylation on promoters and this was reversed by IgM stimulation of cells; IgM did not affect Rb-mediated repression or deacetylation of the promoters. Prohibitin thus appears to repress E2F-mediated transcription utilizing different molecular mediators and facilitate channeling of specific signaling pathways to the cell cycle machinery.


Effects of ciliary neurotrophic factor on excitotoxicity and calcium-ionophore A23187-induced cell death in cultured embryonic striatal neurons.
Ciliary neurotrophic factor (CNTF) has a protective effect on the striatum in animal models of Huntington's disease. However, the mechanism through which it exerts its effect is not clear. In this study, we show that there is a concentration-dependent direct protective effect of CNTF against N-methyl-D-aspartate-mediated excitotoxicity on striatal neurons in vitro. The CNTF has to be added more than half an hour before the insult for the effect to occur and its effect is eliminated by the presence of the protein synthesis inhibitor cycloheximide. This suggests that the protective mechanism of CNTF does not involve acute interference with the glutamate receptors, but probably requires gene/protein expression. We have also shown that the effect of CNTF against glutamate-induced excitotoxicity is dependent on the concentration of glutamate with a protective effect more evident at a low grade excitotoxic insult. Finally, we saw no effect of CNTF on calcium ionophore A23187-induced toxicity in striatal cultures, indicating that the growth factor does not promote survival by enhancing general defenses against raised intracellular levels of calcium.


[The ciliary apparatus of the lingual mucosa in the frog].
By means of scanning and transmission microscopy it has been examined the ciliary system of the tongue mucosa. The scanning electronmicrographs of the fungiform papillae have revealed three ciliary apparatuses allocated respectively: at the papillary summit (corona ciliata and a narrow but separated paracoronal ciliary system) and on the peduncolar papillary stem. The cilia of both paracoronal and peduncolar groups have not been yet described. Also the filiform papillae are supplied with cilia but as irregularly distributed groups. The border of the tongue is a continuous and normal ciliary epithelium and finally groups of cilia are scattered also on the whole sublingual epithelium. At the transmission microscopy the cells of all the examined mucosal ciliary groups are showing a normal ultrastructural aspect.


Limiting vancomycin use to combat vancomycin-resistant Enterococcus faecium.
The implementation, monitoring, and impact of a program to restrict vancomycin use are described. A vancomycin restriction program was implemented in February 1995 at an acute care teaching hospital after guidelines for vancomycin use were established by a multidisciplinary group. Pharmacists reviewed each vancomycin order, suggested alternative treatments when vancomycin use did not comply with the guidelines, and set duration limits for all orders. Orders requiring greater clinical experience for review were referred to a pharmacist or a physician in the division of infectious diseases. The program was monitored by an infectious diseases pharmacist. Data collected after the program was established showed that the volume of vancomycin use decreased substantially. Problems in enforcing the restriction program included administration of vancomycin for surgical prophylaxis before the order reached the pharmacy, continuing use of vancomycin for initial empirical treatment of febrile neutropenic and immunocompromised patients, inadequate tracking of the evaluations, and deficiencies in the evaluations related to a need for continuing education of the pharmacists about the program. Use of vancomycin decreased after a pharmacy-enforced restriction program was implemented.


Two different mechanisms for omission and substitution errors in neglect dyslexia.
Neglect dyslexia is a reading disorder often associated with right-sided brain lesions. In reading single words, errors are mostly substitutions or omissions of letters that occupy the left-sided positions. Typically, these errors have been thought to depend on a single mechanism. Conversely, we propose that they are due to different mechanisms. In particular, a visuo-spatial mechanism is responsible for omissions and a perceptual integration process for substitution errors. We measured the performance of six patients with both neglect and neglect dyslexia, analyzing their reading errors as a function of letter spacing. According to our conjecture, letter spacing should increase omissions by moving part of the string further in the unattended space, while it should reduce substitutions by restoring the integration processes. Furthermore, we predict that letter spacing should be more effective with pseudowords compared to words, in that in this latter case lexical effects are supposed to influence attentional and perceptual processes. Accordingly, we found that for pseudowords only the two types of errors are differently affected by this manipulation and only omissions correlate with the severity of the disorder in visuo-spatial tasks.


Coronary artery stenting in acute myocardial infarction.
Little information is available on the use of coronary stents to treat suboptimal results during direct angioplasty in acute myocardial infarction (AMI). In this study, we report 16 cases of AMI who underwent stent implantation in infarct-related artery for suboptimal results and their 6 months angiographic follow-up. Immediate angiographic success was achieved in all patients. The minimal luminal diameter increased from 0.06 +/- 0.12 mm to 2.89 +/- 0.12 mm (p < 0.001). One patient died in the hospital on day 8 due to subacute stent thrombosis. No patient required emergency bypass surgery. Two patients required blood transfusion for groin haematoma and one required intracoronary thrombolysis. All patients underwent exercise stress test at 1 month and at 3 months and coronary angiography at 4 months or earlier it indicated. At the end of 6 months follow-up, 4 patients had a positive exercise test and coronary angiography revealed angiographic restenosis in 3 and progression of disease in other vessels in 1 patient. We conclude that stent deployment is a viable option to treat suboptimal results after direct angioplasty in AMI.


Dietary vegetable oil suppressed non-specific immunity and liver antioxidant capacity but induced inflammatory response in Japanese sea bass (Lateolabrax japonicus).
High percentage of dietary vegetable oil (VO) induced negative effects on immunity in numerous fish species. The present study was conducted to investigate whether VO could exert anti-immunological effects by regulating non-specific immunity, liver antioxidant capacity and nuclear factor kappa beta (NF-κB) signaling in Japanese sea bass (Lateolabrax japonicus). Three iso-nitrogenous and iso-lipid diets were formulated by replacing 0% (FO, the control), 50% (FV) and 100% (VO) of fish oil with vegetable oil. Each diet was randomly fed to triplicate groups of fish for 10 weeks. Results showed that the alternative complement pathway (ACP) activity and the disease resistance were significantly lower in fish fed VO diets compared with the control group (P < 0.05). Liver superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx) enzyme activities, as well as total antioxidant capacity (T-AOC) significantly decreased in fish fed VO diets (P < 0.05). Meanwhile, significantly low level of liver SOD1 and CAT mRNA, nuclear factor erythroid 2-related factor 2 (Nrf2) of both mRNA and protein were observed in fish fed VO diets when compared with fish fed FO diets (P < 0.05). However, the transcription level of TNFα and IL1β was significantly higher in the liver of fish fed VO diets, which might be attributed to the activation of NF-κB signaling pathway since the protein expression of p65, one of the key members of NF-κB family, was significantly increased (P < 0.05). These results suggested that dietary VO could lower the ACP activity, disease resistance and liver antioxidant capacity, but it could also exacerbate inflammatory response by activating NF-κB signaling pathway in Japanese sea bass.


[The efficacy and safety of two schemes of desensitization to trimethoprim-sulfamethoxazole in HIV-positive patients].
Trimethoprim with sulfamethoxazole (TMP-SMX) is the drug of choice for the prophylaxis of AIDS-associated comorbidities. To compare the efficacy and safety of two schemes of desensitization to TMP-SMX in HIV-positive patients. A study was conducted from March 2018 to October 2019; it included HIV-positive patients who presented an adverse skin reaction to TMP-SMX; fifteen of them received desensitization scheme 1, which lasted ten days, and five patients received scheme 2, which lasted six hours. The average age of the patients who received scheme 1 was of 27.4 ± 5.7 years, while the average age of patients who received scheme 2 was of 33.6 ± 8 years. At baseline, the demographic, clinical, and immunological variables did not show significant differences between both groups (p> 0.05). In both groups, an efficacy of 100% was obtained and, in terms of safety, only three patients in group 1 presented rash and pruritus, however, the procedure was not suspended; the previous tolerated dose was resumed and, subsequently, the desensitization procedure continued. Both schemes of desensitization to TMP-SMX showed efficacy and safety in HIV-positive patients, who frequently present adverse reactions to these medications.


Chondroid syringoma in the hypothenar region.
A case of chondroid syringoma in the palm, probably the fourth to be reported, is presented. There was a large cystic cavity in the center of the tumor. The peculiar findings of hyaline, myxoid, or chondroid degeneration of the abundant stroma were observed histologically. This tumor should be considered in the differential diagnosis of painless, slow-growing palm tumors.


125I-F56 Peptide as Radioanalysis Agent Targeting VEGFR1 in Mice Xenografted with Human Gastric Tumor.
125I-Radiolabeled F56 peptide was designed as a radioactive analogue of F56 (peptide WHSDMEWWYLLG) to bind with VEGFR1 receptor. It was synthesized in high radiochemical yield and specific activity. The in vitro stability of 125I-F56 was tested, and the bioactivity of 125I-F56 was confirmed by both cell uptake and binding affinity measurement in VEGFR1 positive BGC-823 cells. The time-radioactivity relationship and biodistribution of 125I-F56 tracer were conducted using nude mice bearing human gastric carcinoma BGC-823, by noninvasive micro-SPECT/CT imaging. The tracer's tumor uptake was further confirmed by autoradiography and HE stain of 125I-F56 in tumor tissues ex vivo. Those results demonstrated that 125I-F56 holds great potential as a diagnostic agent in both molecular imaging and radioanalysis probe for gastric cancer.


Recent trends in Namibian urbanization.
"The theoretical debates on urbanization and spatial inequalities in development are sketched in relation to the Namibian (South West African) situation. 1951, 1960 and 1970 Population Census data as well as 1976 estimates for urban centres are analysed and interpreted, revealing growth trends in the urban hierarchy and in the three main racial groups in each town."


Allogeneic hematopoietic cell transplantation for primary refractory acute lymphoblastic leukemia: A report from the Acute Leukemia Working Party of the EBMT.
Patients with primary refractory acute lymphoblastic leukemia (PREF ALL) who fail to achieve a complete remission (CR) after ≥2 courses of chemotherapy have a dismal prognosis without undergoing allogeneic hematopoietic cell transplantation (HCT). To the authors' knowledge, there currently are no data regarding factors influencing transplantation outcomes. The authors retrospectively studied outcomes of transplantation for cases of PREF ALL reported to European Society for Blood and Marrow Transplantation registry. Eligibility criteria for the current analysis included adult patients who underwent their first HCT for PREF ALL between 2000 and 2012. PREF disease was defined as the failure to achieve a morphological CR after ≥2 courses of induction chemotherapy. Data regarding 86 adult patients were analyzed. With a median follow-up of 106 months, the probability of survival was 36% at 2 years and 23% at 5 years. The probability of leukemia-free survival was 28% and 17%, respectively, and the probability of nonrecurrence mortality was 20% and 29%, respectively, at 2 years and 5 years. For 66 patients who achieved a CR (77%), the survival at 2 years and 5 years was 36% and 29%, respectively. In multivariate analysis, use of total body irradiation was found to be associated with improved survival. Total body irradiation and infusion of female hematopoietic cells into male recipients was associated with improved leukemia-free survival. These findings were incorporated into a scoring system that identified 3 groups (those with 2, 1, or no prognostic factors) with survival rates of 57%, 22%, and 8%, respectively. Although overall these patients would clearly benefit from the introduction of novel antileukemic therapies, the data from the current study support the use of allogeneic HCT in selected patients with PREF ALL. Cancer 2017;123:1965-1970. © 2017 American Cancer Society.


Presentation of tumour antigens by dendritic cells and challenges faced.
The use of dendritic cells (DCs) for the generation of anti-tumour immunity has been the focus of a vast array of scientific and clinical studies. The ability of DCs to present protein tumour antigens (T-Ags) to CD4(+) and CD8(+) T cells is pivotal to the success of therapeutic cancer vaccines. DC's specialised capacity to cross-present exogenous Ags onto major histocompatibility (MHC) class I molecules for the generation of T-Ag-specific cytotoxic T lymphocytes (CTLs) has made these cells the focal point of vaccine-based immunotherapy of cancer. However, although DC-based strategies can induce T cell responses in cancer patients, recent reviews of clinical studies demonstrate that DC-based approaches have essentially failed to meet their clinical end points. These findings highlight the need to re-evaluate the DC-based vaccine strategies and incorporate recent advancements in DC biology and tumour immunology. The current review considers the issues related to how best to target the Ag-processing pathway of DCs, the role of adjuvants, the appropriate conditioning of the DCs and strategies to overcome tumour-mediated immune escape.


A novel mutant p53 binding partner BAG5 stabilizes mutant p53 and promotes mutant p53 GOFs in tumorigenesis.
Tumor suppressor p53 is the most frequently mutated gene in human tumors. Many tumor-associated mutant p53 (mutp53) proteins gain new tumor-promoting activities, including increased proliferation, metastasis and chemoresistance of tumor cells, which are defined as gain-of-functions (GOFs). Mutp53 proteins often accumulate at high levels in human tumors, which is important for mutp53 to exert their GOFs. The mechanism underlying mutp53 proteins accumulation in tumors is not fully understood. Here, we report that BAG5, a member of Bcl-2-associated athanogene (BAG) family proteins, promotes mutp53 accumulation in tumors, which in turn enhances mutp53 GOFs. Mechanistically, BAG5 interacts with mutp53 proteins to protect mutp53 from ubiquitination and degradation by E3 ubiquitin ligases MDM2 and CHIP, which in turn promotes mutp53 protein accumulation and therefore GOFs in promoting cell proliferation, tumor growth, cell migration and chemoresistance. BAG5 is frequently overexpressed in many human tumors and the overexpression of BAG5 is associated with poor prognosis of cancer patients. Altogether, this study revealed that inhibition of mutp53 degradation by BAG5 is a novel and critical mechanism underlying mutp53 protein accumulation and GOFs in cancer. Furthermore, our results also uncovered that promoting mutp53 accumulation and GOFs is a novel mechanism of BAG5 in tumorigenesis.


The Angiogenic Potential of DPSCs and SCAPs in an In Vivo Model of Dental Pulp Regeneration.
Adequate vascularization, a restricting factor for the survival of engineered tissues, is often promoted by the addition of stem cells or the appropriate angiogenic growth factors. In this study, human dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAPs) were applied in an in vivo model of dental pulp regeneration in order to compare their regenerative potential and confirm their previously demonstrated paracrine angiogenic properties. 3D-printed hydroxyapatite scaffolds containing DPSCs and/or SCAPs were subcutaneously transplanted into immunocompromised mice. After twelve weeks, histological and ultrastructural analysis demonstrated the regeneration of vascularized pulp-like tissue as well as mineralized tissue formation in all stem cell constructs. Despite the secretion of vascular endothelial growth factor in vitro, the stem cell constructs did not display a higher vascularization rate in comparison to control conditions. Similar results were found after eight weeks, which suggests both osteogenic/odontogenic differentiation of the transplanted stem cells and the promotion of angiogenesis in this particular setting. In conclusion, this is the first study to demonstrate the successful formation of vascularized pulp-like tissue in 3D-printed scaffolds containing dental stem cells, emphasizing the promising role of this approach in dental tissue engineering.


[Prokaryotic soluble expression, purification and function study of LEDGF/p75 protein].
HIV-1 integrase (IN) is a key enzyme for the viral replication. The protein-protein interaction (PPI) between HIV-1 IN and a cellular cofactor lens epithelium-derived growth factor (LEDGF/p75) is a validated target for anti-HIV drug discovery. In order to build the platform for screening inhibitor against PPI between IN and LEDGF/p75, the vector containing the LEDGF/p75 protein cDNA was constructed and expressed in Escherichia coli and the function of the LEDGF/p75 protein was assayed. The LGDGF/p75 encoding gene optimized according to the preference codon usage of E. coli, was synthesized and cloned into the expression vector pGEX-4T-1 to form a recombined plasmid, then transformed into host cell E. coli BL21 (DE3). The recombined clones were identified and confirmed by BamH I/Sal I digestion and sequencing, the successfully recombined plasmid in the host cell was induced by IPTG and the condition of the expression was optimized. The expressed protein was purified by the Ni2+ affinity chromatography column and SDS-PAGE was used to analyze the molecular weight and specificity. In addition, ELISA assay was used to analyze the function of the recombinant protein. The recombinant LGDGF/p75 was soluble, and expressed highly and stably in E. coli. The protein was proved to enhance HIV-1 IN strand transfer activity in vitro by ELISA. It will be helpful to build the platform of screening inhibitors against PPI between IN and LEDGF/p75.


Precepting in 2002.
Preceptorships have been used to bridge the gap between nursing education and the reality of the workplace. The role of preceptors to prepare new or transitioning nurses to function more efficiently and earlier has become increasingly important in recent years. To foster positive attitudes in the experienced nurses toward accepting and functioning in the roles of preceptors, nursing administration and nursing education must collaborate. Preceptors have the ability to shape, nurture, influence, and support novice nurses. Experienced nurses hold the responsibility to encourage this commitment.


Extracellular ATP: a modulator of cell death and pathogen defense in plants.
Living organisms acquire or synthesize high energy molecules, which they frugally conserve and use to meet their cellular metabolic demands. Therefore, it is surprising that ATP, the most accessible and commonly utilized chemical energy carrier, is actively secreted to the extracellular matrix of cells. It is now becoming clear that in plants this extracellular ATP (eATP) is not wasted, but harnessed at the cell surface to signal across the plasma membrane of the secreting cell and neighboring cells to control gene expression and influence plant development. Identification of the gene/protein networks regulated by eATP-mediated signaling should provide insight into the physiological roles of eATP in plants. By disrupting eATP-mediated signaling, we have identified pathogen defense genes as part of the eATP-regulated gene circuitry, leading us to the discovery that eATP is a negative regulator of pathogen defense in plants.(1) Previously, we reported that eATP is a key signal molecule that modulates programmed cell death in plants.(2) A complex picture is now emerging, in which eATP-mediated signaling cross-talks with signaling mediated by the major plant defense hormone, salicylic acid, in the regulation of pathogen defense and cell death.


Limited systemic sclerosis patients with pulmonary arterial hypertension show biomarkers of inflammation and vascular injury.
Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment. Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects. The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.


Sensitive antigenic determinations of high molecular weight kininogen performed by covalent coupling of capture antibody.
Knowledge of the role of high-molecular-weight kininogen (HK) in disease states has been limited by the lack of easy, reliable, and rapid assays for HK antigen. We have developed two immunochemical determinations, which use covalent coupling of the capture antibody, that will greatly facilitate the measurement of HK in plasma and cells. The first is an enzyme-linked immunosorbent assay (ELISA) that is performed in 96-well microplates and can be prepared up to 5 months in advance; it can, therefore, be available when needed. The second is a very rapid method that uses the technique known as particle concentration fluorescence immunoassay (PCFIA) and can be performed on 96 samples in less than 30 minutes. The HK-ELISA correlated well with HK coagulant activity in 22 normal donors (r = 0.88). The interassay coefficient of variation (CV) of 22 samples assayed on 5 separate days was 12%, whereas the interassay CV was 4%. The HK-PCFIA demonstrated an excellent correlation (r = 0.97) with HK coagulant activity in 22 normal donors, with an interassay CV of 7% and an intraassay CV of 1.5%. The HK ELISA was linear between 6 and 80 ng/ml, whereas the HK-PCFIA was linear between 5 and 800 ng/ml. Using the HK-PCFIA, we found a difference in HK antigen levels between two groups of patients with sepsis. The mean of those who survived (n = 10) was 70 micrograms/ml, whereas the mean of those who died (n = 6) was 48 micrograms/ml. Both HK-ELISA and HK-PCFIA were able to detect HK antigen in baboon plasma, enabling the monitoring of HK during experimental protocols. The HK-PCFIA was sensitive enough to detect HK antigen in the supernatant of hepatoma G2 at levels of 1 to 4 ng/ml. These assays should enable convenient and frequent measurement of HK antigen in various physiologic and pathophysiologic states, as well as in cell fractions.


Diffuse cerebral angiomatosis associated to basilar apex aneurysm.
Diffuse cerebral angiomatosis (DCA) is a diffuse infiltration of normal brain by complex vascular structures. It differs from arteriovenous malformations (AVMs) that are composed of a nidus of vessels through which arteriovenous shunting occurs without interposed functional brain parenchyma. A rare subgroup of AVMs is diffuse with no recognizable nidus with functional neuronal tissue interspersed within the malformed vessels. We present a rare association of DCA and cerebral arterial aneurysm, which dramatically influenced the patient's prognosis. A 43-year-old male patient with right hemispheric diffuse cerebral angiomatosis presented with a ruptured basilar tip aneurysm that was successfully embolised. Unfortunately, the patient developed a locked-in syndrome. The present report shows a possible association between diffuse cerebral angiomatosis and cerebral aneurysms, but this association appears to be less strong than it is with other AVMs.


Supramolecular Organization in Confined Nanospaces.
Empty spaces are abhorred by nature, which immediately rushes in to fill the void. Humans have learnt pretty well how to make ordered empty nanocontainers, and to get useful products out of them. When such an order is imparted to molecules, new properties may appear, often yielding advanced applications. This review illustrates how the organized void space inherently present in various materials: zeolites, clathrates, mesoporous silica/organosilica, and metal organic frameworks (MOF), for example, can be exploited to create confined, organized, and self-assembled supramolecular structures of low dimensionality. Features of the confining matrices relevant to organization are presented with special focus on molecular-level aspects. Selected examples of confined supramolecular assemblies - from small molecules to quantum dots or luminescent species - are aimed to show the complexity and potential of this approach. Natural confinement (minerals) and hyperconfinement (high pressure) provide further opportunities to understand and master the atomistic-level interactions governing supramolecular organization under nanospace restrictions.