[Case of Heerfordt's syndrome presenting polyneuropathy].
Acute presentation of sarcoidosis with the combination of uveitis, parotid gland enlargement, facial nerve palsy, and fever is called Heerfordt's syndrome. Clinically recognizable involvement of the nervous system occurs in < 10% of patients with sarcoidosis, and polyneuropathy in 24% with neurosarcoidosis. A 28-year-old woman diagnosed with Guillain-Barré syndrome was admitted and treated for a month in the Department of Neurology, Mie University hospital. Her visual acuity decreased 2 weeks after discharge. She was admitted to the Department of Ophthalmology, Mie University Hospital. She presented typical optic sarcoidosis. As she had uveitis, facial nerve palsy, parotid gland enlargement and fever in the clinical course, we diagnosed her condition as Heerfordt's syndrome. On rare occasions a Heerfordt's syndrome patient may present with Guillain-Barré-like symptoms.


The Synergistic Effect of Triterpenoids and Flavonoids-New Approaches for Treating Bacterial Infections?
Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.


Immunostimulatory Effects Triggered by Enterococcus faecalis CECT7121 Probiotic Strain Involve Activation of Dendritic Cells and Interferon-Gamma Production.
Probiotics can modulate the immune system, conferring beneficial effects on the host. Understanding how these microorganisms contribute to improve the health status is still a challenge. Previously, we have demonstrated that Enterococcus faecalis CECT7121 implants itself and persists in the murine gastrointestinal tract, and enhances and skews the profile of cytokines towards the Th1 phenotype in several biological models. Given the importance of dendritic cells (DCs) in the orchestration of immunity, the aim of this work was to elucidate the influence of E. faecalis CECT7121 on DCs and the outcome of the immune responses. In this work we show that E. faecalis CECT7121 induces a strong dose-dependent activation of DCs and secretion of high levels of IL-12, IL-6, TNFα, and IL-10. This stimulation is dependent on TLR signaling, and skews the activation of T cells towards the production of IFNγ. The influence of this activation in the establishment of Th responses in vivo shows the accumulation of specific IFNγ-producing cells. Our findings indicate that the activation exerted by E. faecalis CECT7121 on DCs and its consequence on the cellular adaptive immune response may have broad therapeutic implications in immunomodulation.


Cellulitis in Grade III ankle sprain requiring treatment for antibiotic-resistant bacteria.
This case report describes a novel occurrence of a Grade III ankle sprain complicated by cellulitis. The patient ultimately required aspiration of an extra-articular fluid collection and treatment with parenteral antibiotics due to worsening of the infection despite treatment with second-generation cephalosporins. This individual's infection was consistent with MRSA-cellulitis. Cellulitis, in the context of a preceding ankle sprain, has not been reported in the literature; the resultant edema from the injury may have served as the nidus for infection. MRSA comprises a significant proportion of soft-tissue infections in the ambulatory setting, and physicians should incorporate this trend into therapeutic strategies for their infected patients.


Microarray Analysis and Detection of MicroRNAs Associated with Chronic Thromboembolic Pulmonary Hypertension.
The aim of this study was to understand the importance of chronic thromboembolic pulmonary hypertension- (CTEPH-) associated microRNAs (miRNAs). miRNAs differentially expressed in CTEPH samples compared with control samples were identified, and the target genes were predicted. The target genes of the key differentially expressed miRNAs were analyzed, and functional enrichment analyses were carried out. Finally, the miRNAs were detected using RT-PCR. Among the downregulated miRNAs, MiR-3148 regulated the most target genes and was significantly enriched in pathways in cancer, glioma, and ErbB signaling pathway. Furthermore, the number of target genes coregulated by miR-3148 and other miRNAs was the most. AR (androgen receptor), a target gene of hsa-miR-3148, was enriched in pathways in cancer. PRKCA (Protein Kinase C Alpha), also a target gene of hsa-miR-3148, was enriched in 15 of 16 KEGG pathways, such as pathways in cancer, glioma, and ErbB signaling pathway. In addition, the RT-PCR results showed that the expression of hsa-miR-3148 in CTEPH samples was significantly lower than that in control samples (P < 0.01). MiR-3148 may play an important role in the development of CTEPH. The key mechanisms for this miRNA may be hsa-miR-3148-AR-pathways in cancer or hsa-miR-3148-PRKCA-pathways in cancer/glioma/ErbB signaling pathway.


Off-plane anastigmatic imaging in Offner spectrometers.
In this paper, the imaging performance of an Offner concentric imaging spectrometer is analyzed when the spectrometer entrance slit is disposed arbitrarily on the plane that is parallel to the grating grooves and contains the common center of curvature. Astigmatism-corrected designs are obtained for off-plane incidence on the grating if one point on the slit is located on the Rowland circle of the primary mirror. In this case, the combined system of primary mirror plus diffraction grating provides two astigmatic line images oriented parallel and orthogonal to the plane of diffraction, with the former located on the same plane as the slit. Consequently, these images can be brought to a single focus on this plane by the tertiary mirror if its radius of curvature is chosen properly. In addition, coma aberration is simultaneously removed. These results can be applied to the design of two-mirror or three-mirror spectrometers, generalizing the concept of the best imaging circle and providing solutions to get anastigmatic imaging for two object points and two wavelengths.


[Case-report. Malignant nerve sheath tumor in a cow with symptoms of suspected BSE].
We report here on a 3 1/2-year-old mother cow with a malignant perineural tumour near the pontine angle of the cerebellum, but which first drew attention because of clinical signs of BSE. Neurological symptoms that manifested during the course of the disease included disturbances in behaviour, movement and aesthesia, as described by BRAUN et al. (2001) in cases of BSE. Inconsistent with a diagnosis of BSE were focal neurological disturbances (head held aslant to the right, tendency to fall to the right, right-sided facial weakness, left-sided nystagmus and ventral strabismus). Following euthanasia, magnetic resonance imaging (MRI) revealed a tumour in the cerebellopontine angle. Histological findings describe a malignant peripheral nerve tumour of the vagal nerve with rhabdoid differentiation (a so-called Triton tumour) with an intracranial and an extracranial part.


Anti-Inflammatory Activity of AF-13, an Antioxidant Compound Isolated from the Polar Fraction of Allomyrina dichotoma Larva, in Palmitate-Induced INS-1 Cells.
This study was conducted to evaluate the fractions isolated from Allomyrina dichotoma larva extract (ADLE) that exhibited anti-apoptotic and anti-inflammatory effects. A total of 13 fractions were eluted from ADLE by centrifugal chromatography (CPC), and the polar AF-13 fraction was selected, which exerted a relatively protective effect against fat-induced toxicity in INS-1 cells. AF-13 treatment of palmitate-treated INS-1 cells decreased the expression level of apoptosis-related proteins and DNA fragmentation. AF-13 also significantly inhibited the production of nitric oxide and reactive oxygen species and the triglyceride content induced by palmitate, and the effect was found to be similar to that with ADLE treatment. Palmitate upregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) through the activation of NF-κB p65; however, this effect was significantly attenuated by AF-13 treatment. In conclusion, AF-13 is one of the major components of ADLE responsible for anti-apoptotic and anti-inflammatory activities.


The effect of coat clipping on thermoregulation during intense exercise in trotters.
The aim of this study was to study the physiological, especially thermoregulatory, responses during intense exercise in the clipped horse compared to the horse with winter coat. Six Standardbred trotters were studied before and after clipping. They performed an inclined incremental high intensity treadmill exercise test and were monitored during recovery. The clipped horse differed significantly (ANOVA) during exercise as compare to coated: less increase in central venous blood temperature, higher skin surface temperature, greater difference skin to ambient temperature and higher rate of nonevaporative heat loss. The clipped horse had significantly lower total cutaneous evaporative heat loss from walk to end of peak exercise and a shorter time for recovery for the respiratory rate using a paired t test. The clipped horse showed a tendency (P = 0.059) to decreased oxygen uptake during the stepwise increase in workload. We concluded that the clipped horse experienced less strain on the thermoregulatory system due to an enhanced heat loss. Some clipped horses in the study showed a more efficient power output; future studies with emphasis on respiration and oxygen demand are needed to explain this.


CsSWEET2, a Hexose Transporter from Cucumber (Cucumis sativus L.), Affects Sugar Metabolism and Improves Cold Tolerance in Arabidopsis.
Sugars, which are critical osmotic compounds and signalling molecules in plants, and Sugars Will Eventually be Exported Transporters (SWEETs), which constitute a novel family of sugar transporters, play central roles in plant responses to multiple abiotic stresses. In the present study, a member of the SWEET gene family from cucumber (Cucumis sativus L.), CsSWEET2, was identified and characterized. Histochemical analysis of β-glucuronidase expression in transgenic Arabidopsis plants showed that CsSWEET2 is highly expressed in the leaves; subcellular localization indicated that CsSWEET2 proteins are localized in the plasma membrane and endoplasmic reticulum. Heterologous expression assays in yeast demonstrated that CsSWEET2 encodes an energy-independent hexose/H+ uniporter that can complement both glucose and fructose transport deficiencies. Compared with wild-type Arabidopsis plants, transgenic Arabidopsis plants overexpressing CsSWEET2 had much lower relative electrolyte leakage levels and were much more resistant to cold stress. Sugar content analysis showed that glucose and fructose levels in the transgenic Arabidopsis plants were significantly higher than those in the wild-type plants. Taken together, our results suggest that, by mediating sugar metabolism and compartmentation, CsSWEET2 plays a vital role in improving plant cold tolerance.


The mechanism of ion selectivity of OmpF-porin pores of Escherichia coli.
The OmpF porin from the outer membrane of Escherichia coli acts as a lightly cation-selective pore, allowing the diffusion of small cations and cationic molecules, whose Mr are a little larger than the threshold exclusion limit. To ascertain the mechanism of this cation selectivity, we have examined a possible influence of cationic solutes on the fluorescence emission and the circular dichroic spectrum of tryptophan residues of the porin trimer, searching for conformational change(s). The diffusion of cationic solutes was determined with the native and the amidated porins in the presence or the absence of the effector cations. The following results were obtained. (a) Cations, e.g. spermidine, caused fluorescence quenching in the native trimer, with a half-maximum fluorescence quenching at 11-18 microM. A change in the circular dichroic spectrum was also recorded at around 280 nm. (b) The dissociation constant of spermidine to the native trimer was calculated to be 16 microM as determined by the method of equilibrium dialysis. (c) The cation-caused fluorescence quenching was reversed when the carboxyl groups of the trimer were modified by the amidation reaction, though amidation of the trimer resulted in no significant change in the fluorescence intensity. (d) The diffusion rate of N-benzyloxycarbonyl-glycyl-L-prolyl-L-arginine p-nitroanilide through the native and the amidated porins was lowered in the presence and the absence, respectively, of cations. Both the extent of fluorescence quenching in the presence of cation and the rate of cation diffusion were inversely proportional to the number of amidated carboxyl residues. The relative fluorescence quenching of the porin trimer (the amidated versus the native) in the presence of cations was linearly related to the relative solute diffusion via the porin (the amidated versus the native). These results suggested that cations caused a conformational change in the trimer, resulting in an easier diffusion of the solutes. The results suggested further that a limited number of carboxyl groups in the pore interior are involved in the cation selectivity of OmpF-porin pores.


[Comparison of Cmac vs Vivasight devices in terms of time and effectiveness of intubation among medical students].
While analysing the use of the new videolaryngoscopes in the hands of the well experienced anaesthesiologists it is difficult to get answers to all intriguing questions and gain insights that might arise only from the untrained users. We can form a thesis that if a manikin, with the use of a particular device, is intubated quickly and effectively by the novices, it is probable that the more experienced operators will be even more satisfied with its use. The aim of our study was to evaluate the effectiveness of the use of these devices in the hands of the users untrained in intubation. We also wanted to find out what are the subjective perceptions of using the devices by unsuccessful users. We investigated intubation times, effectiveness as well as parameters such as tooth damage. The aim of the secondary and obvious benefit to students was familiarity Them with new advanced methods of clearing the upper respiratory tract with which they will probably meet in the future. The study included 104 medical students. Every participant took three attempts to intubate the manikin using each device. The technical parameters of the devices have been studied by the experts from the Lodz University of Technology. The average time of intubation in the case of the Cmac was 28,3±10,1, while as regards the Vivasight the average time of intubation was 30,9±9,0. In order to check the statistical significance, the Mann - Whitney U test was used (p <0,005). A larger proportion of successful attempts that amounted to 60% were observed while using the CMAC. According to the subjective opinion of the students, the Cmac is easier to operate than the Vivasight. This study proved that videolaryngocopes can be a great tool for training new methods of intubation even during studies.


Injectable cell-laden hydrogels fabricated with cellulose and chitosan nanofibers for bioprinted liver tissues.
Bio-based hydrogels as three-dimensional (3D) constructs have attracted attention in advanced tissue engineering. Compared with conventional two-dimensional (2D) cell culture, cells grown in 3D scaffolds are expected to demonstrate the inherent behavior of living organisms of cellular spheroids. Herein, we constructed cell-laden nanofiber-based hydrogels in combination with 2,2,6,6-tetramethylpiperidine 1-oxyl-oxidized cellulose nanofiber (TOCNF) and chitosan nanofiber (CsNF) for bioadaptive liver tissue engineering. The carboxylates of TOCNF and amines of CsNF were directly crosslinked via EDC/NHS chemistry. The rheological properties of the solutions for the nanofibers and hydrogels revealed sufficient physical properties for the injection, printing, and plotting process, as well as significant encapsulation of living cells. As-designed hydrogels exhibited excellent viscoelastic properties with typical shear-thinning behavior, and had a storage modulus of 1234 Pa ± 68 Pa, suitable for cell culture. Non-cytotoxicity was confirmed using a live/dead assay with mouse-derived fibroblast NIH/3T3 cells. Human hepatocellular carcinoma HepG2 cells could be cultured on a gel surface (2D environment) and encapsulated in the gel structure (3D environment), which enabled 10 d growth with high gene expression level of albumin of HepG2 spheroids in the 3D gels. The biodegradable cell-laden hydrogels are expected to mimic the cellular microenvironment and provide potential for bioadaptive 3D cell cultures in biomedical applications.


Iranian hospital efficiency: a systematic review and meta-analysis.
The purpose of this paper (systematic review and meta-analysis) is to synthesize and analyze studies that assessed Iranian hospital efficiency. A systematic literature search was conducted using both international (the Institute for Scientific Information, Scopus and PubMed) and Iranian scientific (Magiran, IranMedex and Scientific Information Database) databases. The review included original studies that used the Pabon Lasso Model to examine Iranian hospital performance, published in Persian or English. A self-administered checklist was used to collect data. In total, 12 questions were used for quality assessment. In total, 34 studies met our inclusion criteria. The fixed-effects meta-analysis indicated that 19.2 percent (95% confidence interval (CI): 15.6-23.2 percent) of hospitals were in Zone 1 (poor performance: low bed turnover rate (BTR) and bed occupancy rate (BOR) and high average hospital stay (ALoS)), 23.7 percent (95% CI: 20.1-27.8 percent) were in Zone 2, 31.7 percent (95% CI: 27.7-36 percent) in Zone 3 (good performance: high BTR and BOR and low ALoS) and 25.4 percent (95% CI: 21.7-29.5 percent) in Zone 4. Results help Iranian health policymakers to understand hospital performance, which, in turn, may lead to promoting greater awareness and policy attention to improve Iranian hospital efficiency. This study indicated that most Iranian hospitals had sub-optimal performance. Further studies are required to understand factors that explain the country's hospital inefficiency.


Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.
The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin α/β heterodimer, and that G-actin competes with importin α/β for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-α, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-α- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-α recognition.


Adenosine deaminase prefers a distinct sugar ring conformation for binding and catalysis: kinetic and structural studies.
Several recent X-ray crystal structures of adenosine deaminase (ADA) in complex with various adenosine surrogates have illustrated the preferred mode of substrate binding for this enzyme. To define more specific structural details of substrate preferences for binding and catalysis, we have studied the ADA binding efficiencies and deamination kinetics of several synthetic adenosine analogues in which the furanosyl ring is biased toward a particular conformation. NMR solution studies and pseudorotational analyses were used to ascertain the preferred furanose ring puckers (P, nu(MAX)) and rotamer distributions (chi and gamma) of the nucleoside analogues. It was shown that derivatives which are biased toward a "Northern" (3'-endo, N) sugar ring pucker were deaminated up to 65-fold faster and bound more tightly to the enzyme than those that preferred a "Southern" (2'-endo, S) conformation. This behavior, however, could be modulated by other structural factors. Similarly, purine riboside inhibitors of ADA that prefer the N hemisphere were more potent inhibitors than S analogues. These binding propensities were corroborated by detailed molecular modeling studies. Docking of both N- and S-type analogues into the ADA crystal structure coordinates showed that N-type substrates formed a stable complex with ADA, whereas for S-type substrates, it was necessary for the sugar pucker to adjust to a 3'-endo (N-type) conformation to remain in the ADA substrate binding site. These data outline the intricate structural details for optimum binding in the catalytic cleft of ADA.


The ecarin clotting time, a universal method to quantify direct thrombin inhibitors.
The ecarin clotting time (ECT) is a meizothrombin generation test that allows for precise quantification of direct thrombin inhibitors. The ECT has demonstrated its usefulness for more than 10 years in biochemical-pharmacological investigations as well as in clinical research and in the clinical routine. It has proved valuable especially as a drug-monitoring method in r-hirudin therapy. This test has been adjusted to clinical requirements by numerous modifications. Following the description of the biochemical background and the measuring principle of the ECT, this article gives a short survey of several modifications of the ECT for both preclinical and clinical use, e.g., for biochemical investigations, as a point-of-care method and for cardiac surgery. Advantages and disadvantages of these methods are discussed.


Double-enzyme conjugates, producing an intermediate color, for simultaneous and direct detection of three different intracellular immunoglobulin determinants with only two enzymes.
A new double-enzyme conjugate was synthesized by coupling alkaline phosphatase (AP) to horseradish peroxidase (HRP). After AP (blue) and subsequent HRP (red) cytochemistry, this new conjugate produced a stable intermediate-colored (violet) product. By coupling this double-enzyme conjugate to an antigen (trinitrophenyl, TNP) or an antibody (anti-mouse immunoglobulin G2a), anti-TNP or -IgG2a-producing cells could be demonstrated as violet cells in spleen sections. This led to the development of a rapid one-step incubation--two-step cytochemical procedure for simultaneous detection of three different determinants in a single tissue section. To demonstrate this novel triple staining method, we coupled three different antigens to, respectively, AP, HRP, and AP-HRP. When spleen sections of immunized animals were incubated with a mixture of these three antigen-enzyme conjugates, we could distinguish antibody-forming cells against each of these three antigens simultaneously as red (HRP), blue (AP), and violet (AP-HRP) cells. The simultaneous detection of three different classes of intracellular antibodies in a single section also proved to be possible with this method. With this study we provide a new direct method for detection of three different intracellular immunoglobulins after a one-step incubation and a two-step standard cytochemical procedure.


Intramuscular transplantation of bone marrow cells prolongs the lifespan of SOD1G93A mice and modulates expression of prognosis biomarkers of the disease.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There is no effective treatment for ALS and stem cell therapy has arisen as a potential therapeutic approach. SOD1 mutant mice were used to study the potential neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle. Bone marrow intramuscular transplants resulted in increased longevity with improved motor function and decreased motoneuron degeneration in the spinal cord. Moreover, the increment of the glial-derived neurotrophic factor and neurotrophin 4 observed in the grafted muscles suggests that this partial neuroprotective effect is mediated by neurotrophic factor release at the neuromuscular junction level. Finally, certain neurodegeneration and muscle disease-specific markers, which are altered in the SOD1G93A mutant mouse and may serve as molecular biomarkers for the early detection of ALS in patients, have been studied with encouraging results. This work demonstrates that stem cell transplantation in the muscle prolonged the lifespan, increased motoneuron survival and slowed disease progression, which was also assessed by genetic expression analysis.


Fabrication of a thin PDMS film with complex liquid metal electrodes embedded and its application as skin sensors.
This research work reports an approach for the fabrication of liquid metal patterned thin films. By using this method, very complex liquid metal electrodes can be successfully integrated into a thin PDMS film with a thickness as low as 119 μm. The high resolution of the microelectrode channel is achieved by soft lithography technology. The relatively-thin electrode structure is developed with the assistance of the reversible PC membrane bonding technique that we reported earlier. Femtosecond laser drilling is applied in this work to drill small holes at the channel ends, allowing the air to escape during the filling of liquid metal and making the blind-end liquid metal electrode structure possible. In this work, the fabrication process with some key procedures involved is introduced for developing a microelectrode. Further, a wearable strain sensor is designed with the fabricated microelectrode to show its potential to be used in flexible electronics.


Monoclonal antibodies to human intermediate filament proteins. III. Analysis of tumors.
A panel of monoclonal antibodies to human intermediate filament proteins was tested on an unselected series of 246 neoplasms. The antibody panel includes two different anti-cytokeratin antibodies, an anti-vimentin antibody, and an anti-neurofilament antibody (Gown and Vogel, Am J Pathol 114:309, 1984). The studies were done on Carnoy's or methacarn-fixed, paraffin-embedded tissue. When used as a panel, they can unequivocally distinguish carcinomas, melanomas, and lymphomas. All carcinomas react with at least one of the anti-cytokeratin antibodies, and carcinomas can be subtyped based upon the pattern of reactivity with the two anti-cytokeratin antibodies. Melanomas react only with the anti-vimentin antibody, and lymphomas react with none of the antibodies. Neural and neuroendocrine tumors can be identified with the anti-neurofilament antibody. A minority of neoplasms, including lymphomas, seminomas, and some sarcomas, do not react with any of the antibodies. These antibodies are reliable diagnostic reagents that are useful in distinguishing different categories of human tumors.


Rapid response teams in hospitals: improving quality of care for patients and quality of the work environment for nursing staff.
As the healthcare delivery system continues to evolve in the new millennium, initiatives such as the Institute for HealthCare Improvement's 100,000 Lives Campaign include the development of rapid response teams in hospitals. Introduction of rapid response teams provides nurses assistance in difficult clinical situations and provides early clinical intervention to mitigate negative patient outcomes and save lives. Development, implementation strategies, and benefits of rapid response teams are described.


Topoisomerase 2α status in invasive breast carcinoma - comparison of its clinical value according to immunohistochemical and fluorescence in situ hybridization methods of evaluation.
The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a combination chemotherapy treatment for breast cancer, namely AC [cyclophosphamide, doxorubicin]). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical [IHC] and fluorescence in situ hybridization [FISH]). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.


Fesselin, a synaptopodin-like protein, stimulates actin nucleation and polymerization.
Fesselin is a proline-rich actin binding protein that has recently been isolated from smooth muscle [Leinweber, B. D., Fredricksen, R. S., Hoffman, D. R., and Chalovich, J. M. (1999) J. Muscle Res. Cell Motil. 20, 539-545]. Fesselin is similar to synaptopodin [Mundel, P., Heid, H. W., Mundel, T. M., Krüger, M., Reiser, J., and Kriz, W. (1997) J. Cell Biol. 139, 193-204] in terms of its size, isoelectric point, and sequence although synaptopodin is not present in smooth muscle. The function of fesselin is unknown. Evidence is presented here that fesselin accelerates the polymerization of actin. Fesselin was effective on actin isolated from either smooth or skeletal muscle at low ionic strength and in the presence of 100 mM KCl. At low ionic strength, fesselin decreased the time for 50% polymerization to about 1% of that in the absence of fesselin. The lag phase characteristic of the slow nucleation process of polymerization was eliminated as the fesselin concentration was increased from very low levels. Fesselin did not alter the critical concentration for actin but did increase the rate of elongation by approximately 3-fold. The increase in elongation rate constant is insufficient to account for the total increase in polymerization rate. It is likely that fesselin stabilizes the formation of actin nuclei. Time courses of actin polymerization at varied fesselin concentrations and varied actin concentrations were simulated by increasing the rate of nucleation and both the forward and reverse rate constants for elongation.


High pressure liquid chromatographic separation of furocoumarins in Heracleum laciniatum.
Furocoumarins from chloroform extraction of Heracleum laciniatum were separated by high pressure liquid chromatography (HPLC) with microparticulate silica gel column investigating different concentrations of acetonitrile and water, acetonitrile and methanol and acetonitrile, methanol and water for mobile phase. With a mixture of 42:43:15 of the latter for mobile phase optimal separation was obtained of the 6 furocoumarins from the plant. Removal of lipid fractions of plant extractions with hexane is recommended to avoid damage to the HPLC column.


Vocabulary as a Central Link between Phonological Working Memory and Narrative Competence: Evidence from Monolingual and Bilingual Four-Year-Olds from Different Socioeconomic Backgrounds.
Phonological working memory capacity, vocabulary size, and narrative competence are important skills in children's L1 and L2 acquisition, which may vary as a function of their language background and socioeconomic status (SES). We investigated test data of 56 typically developing 4-year-old kindergarten children from two SES and two language backgrounds: 29 children (15 higher SES, 14 lower SES) were monolingual German-speaking, and 27 children (14 higher SES, 13 lower SES) were successive Turkish-German bilinguals. The tests comprised a non-word repetition task testing phonological working memory, receptive vocabulary tests (in L1 and L2), and a narrative task. We investigated the effects of SES and language background on children's test performance. Results indicate that SES was a highly significant factor for phonological working memory and vocabulary in the monolingual children, but not in the bilingual children. Although the items of the non-word repetition task followed German phonotactic structure, lower SES (LSES) L2 children did not differ significantly from their monolingual LSES peers, demonstrating that there was no bilingual working memory disadvantage in the LSES group. A significant effect of language background was found for German vocabulary and for all categories of narrative competence, but only two slight SES effects on narrative competence. Significant correlations were found between phonological working memory and vocabulary as well as between vocabulary and narrative competence, but not between phonological working memory and narrative competence. Results suggest that phonological working memory and narrative competence are different domains of language awareness, and that vocabulary may act as the central variable mediating between them.


Prevalence and morphological characterisation of Cysticercus tenuicollis (Taenia hydatigena cysts) in sheep and goat from north India.
Taenia hydatigena is an adult parasite of dogs with the metacestode (Cysticercus tenuicollis) stage residing in ruminants and pigs. Documentation and surveillance data concerning to the prevalence and risk factors associated with the disease in India is largely lacking. In this experiment, 3,199 carcasses, including 760 sheep and 2,439 goat were examined for the presence of C. tenuicollis (T. hydatigena cysts) on post-mortem inspection at different slaughter houses/shops in northern India. Morphological analysis was also conducted on five samples from each species. Out of 3199 carcasses examined, 135 were found containing cysts of T. hydatigena indicating a prevalence of 4.22 %. Most of the cysts were present in abdominal cavity, except few which were embedded in the liver. The high prevalence of 4.83 was recorded in goats as compared to 2.23 % in sheep. Principal component analysis was applied for statistical analysis. The results of morphological analysis indicated its usefulness as a valid criterion for differentiation of T. hydatigena cysts and that there might be possibility of two different strains infecting sheep and goat.


Tumor necrosis factor induces contraction of mesangial cells and alters their cytoskeletons.
Cultures of human mesangial cells (MC) were established from the renal cortex of surgical specimen. The characteristic spindle-shaped or stellate appearance of MC was altered after treatment with tumor necrosis factor (TNF). After two hours, the MC retracted and lost reciprocal contacts. Furthermore, this treatment altered the cytoskeletal organization of MC, since a peripheral band of actin and stress fibers disappeared while the streaks of vinculin at focal contacts decreased. These changes were reversible when the MC were cultured in fresh medium. After five minutes of treatment with platelet activating factor (PAF), changes similar to those induced by TNF were observed. Inhibitors of PAF synthesis, such as plasma alpha 1-proteinase inhibitor and an anti-inflammatory peptide, blocked changes induced by TNF, PAF receptor antagonists inhibited changes induced by PAF and also by TNF. These results and the finding that MC are stimulated to produce PAF by TNF suggest that PAF is a secondary mediator of the changes in cell shape and cytoskeletal organization induced by this cytokine.


[Immunomediation or hyperviscosity in rapidly progressive sensorineural hearing loss. A therapeutic approach].
To evaluate the therapeutic response and the rheologic and immunological characteristics in subjects bearing of rapidly progressive sensorineural hearing loss (RPSHL). A comparative prospective study on three groups of damaged ears treated with piracetam (n=29), corticosteroids (n=32) and plabcebo (n=25). Hearing loss and recovery level, whole blood filterability (WBF) and a Western-blot (WB) to anticochlear antibodies were evaluated. Recovery average was 20,8 +/- 55,9% in the first group, with progressive of deafness in the rest (p<0,01). WB did not show differences among groups. The higher WBF at the end of therapy was detected on group 1 (20,36 +/- 2,54 Vs 18,42 +/- 3,42 microl/seg on group 3; p<0,05). Moreover, it impaired only on those treated with piracetam, with statistically significative differences over the other two groups. We detected alterations on WBF in patients with RPSHL that justify the use of rheoactive measures as a pathophysiological therapy.


Reduction of Selenate and Selenite to Elemental Selenium by a Pseudomonas stutzeri Isolate.
A Pseudomonas stutzeri isolate rapidly reduced both selenite and selenate ions to elemental selenium at initial concentrations of both anions of up to 48.1 mM. Optimal selenium reduction occurred under aerobic conditions between pH 7.0 and 9.0 and at temperatures of 25 to 35 degrees C. Reduction of both selenite and selenate was unaffected by a number of anions except for sulfite, chromate, and tungstate ions, which inhibited both growth and reduction.


Comparative study of modified-release clarithromycin and immediate-release clarithromycin in the treatment of Helicobacter pylori-associated peptic ulcer disease.
Proton pump inhibitor-based triple therapy containing immediate-release clarithromycin is an important regimen for the eradication of Helicobacter pylori (H. pylori). However, the efficacy of modified-release clarithromycin for the treatment of H. pylori-associated peptic ulcer disease is still unknown. The aims of the study were to compare the efficacy of modified-release clarithromycin and immediate-release clarithromycin on the rates of ulcer healing and eradication of H. pylori. One hundred and sixty-one patients with Helicobacter pylori-associated peptic ulcer were randomized to receive one-week triple therapy with either modified-release clarithromycin 1000mg once daily (AECMR) or immediate-release clarithromycin 500mg twice daily (AECIR) in combination with amoxicillin 1,000mg twice daily (A) and esomeprazole 40mg once daily (E). Post-treatment ulcer healing status and Helicobacter pylori status was determined by endoscopy and 13C urea-breath test at 16 weeks and 8 weeks after completion of triple therapy, respectively. Helicobacter pylori eradication rates were 87.5% and 87.7% for AECMR and AECIR, respectively, in the intent-to-treat analysis. Eradication rates in the per-protocol groups were 90.3% and 91.4% for AECMR and AECIR, respectively. In both the intent-to-treat and per-protocol analyses, the eradication rates were comparable in the AECMR and AECIR groups (p= 1.0 and 1.0, respectively). Ulcer healing rates in the intention-to-treat analysis were 81.3% and 77.8% for AECMR and AECIR, respectively. Ulcer healing rates in the per-protocol analysis were 90.3% and 90.0% for AECMR and AECIR groups, respectively. In both the intention-to-treat and per-protocol analyses, the ulcer healing rates were comparable in the AECMR and AECIR groups (p=0.645 and 0.584, respectively). Modified-release clarithromycin 1000mg once daily can be used as an alternative to immediate-release clarithromycin 500mg twice daily for the treatment of Helicobacter pylori-associated peptic ulcer disease.


Human Bone Marrow Plasma Cell Atlas: Maturation and Survival Pathways Unraveled by Single Cell Analyses.
Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASC) to long-lived plasma cells (LLPC). We provide single cell transcriptional resolution of 17,347 BM ASC from 5 healthy adults. Fifteen clusters were identified ranging from newly minted ASC (cluster 1) expressing MKI67 and high MHC Class II that progressed to late clusters 5-8 through intermediate clusters 2-4. Additional clusters included early and late IgM-predominant ASC of likely extra-follicular origin; IFN-responsive; and high mitochondrial activity ASC. Late ASCs were distinguished by differences in G2M checkpoints, MTOR signaling, distinct metabolic pathways, CD38 expression, and utilization of TNF-receptor superfamily members. They mature through two distinct paths differentiated by the degree of TNF signaling through NFKB. This study provides the first single cell resolution atlas and molecular roadmap of LLPC maturation, thereby providing insight into differentiation trajectories and molecular regulation of these essential processes in the human BM microniche. This information enables investigation of the origin of protective and pathogenic antibodies in multiple diseases and development of new strategies targeted to the enhancement or depletion of the corresponding ASC. One Sentence Summary: The single cell transcriptomic atlas of human bone marrow plasma cell heterogeneity shows maturation of class-switched early and late subsets, specific IgM and Interferon-driven clusters, and unique heterogeneity of the late subsets which encompass the long-lived plasma cells.


Inflammatory epilepsy (FIRES) and haemophagocytic lymphohistiocytosis (HLH): an adult case.
We describe a man in his 30s with haemophagocytic lymphohistiocytosis (HLH), secondary to an upper respiratory tract infection, with subsequent febrile infection-related epilepsy syndrome. He had a prolonged hospital admission, during which he was treated with chemotherapy for HLH and antiepileptic medications for refractory seizures. He was discharged fully dependent to a care facility and died from aspiration pneumonia 11 months later. This case report highlights his management and discusses these conditions' pathophysiology and future management.


Assessing the professional development needs of public health professionals.
This article describes the major activities associated with designing and implementing a comprehensive, professional development needs assessment of public health professionals in four states of the South Central region of the United States. The instrumentation, research design, and summary results of the needs assessment described in this article may facilitate similar efforts by interested researchers and program developers to assess the public health professional workforce training needs. Results of needs assessments can be useful in designing and evaluating professional development curricula and activities to strengthen public health services in the United States.


Psychometric Support for a Japanese Version of the Sport Imagery Ability Questionnaire.
In this two-part study, we addressed psychometric properties of the Japanese version of the Sport Imagery Ability Questionnaire (SIAQ-J). We analyzed the SIAQ-J factor structure, assessed gender, competitive level, sport type and years of experience differences on the SIAQ-J, and we investigated whether the SIAQ-J was predicted by goal clarity. In Study 1, we translated the original SIAQ (15 items) into Japanese and performed an exploratory factor analysis (n = 366). In Study 2 (n = 422), we verified the measurement model established in Study 1 with exploratory factor analysis (EFA). Study 1 found five exploratory factors-skill, strategy, goal, affect and mastery imagery-and these were confirmed through the confirmatory factor analysis (CFA) conducted in Study 2. Structural equation modelling supported a model wherein goal clarity positively predicted all SIAQ-J subscales. This study provided additional validation of the original SIAQ. Overall, the SIAQ-J demonstrated good factorial validity, temporal reliability and gender invariance and discriminated among athletes of different competitive levels and years of experience.


Impaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistance.
Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance. We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting. At the end of each treatment period, participants had a frequently sampled iv glucose tolerance test and ramp clamp, in which insulin secretion rates (ISR) were determined in response to a matched 5-10 mm glucose stimulus. Insulin sensitivity (S(I)), acute insulin response to iv glucose (AIRg), and disposition index (AIRg x S(I), or beta-cell compensation for insulin resistance) from frequently sampled iv glucose tolerance testing, and ISR area under the curve (or beta-cell sensitivity to glucose) from ramp clamp were determined. Progressive impairments in insulin secretion as assessed by AIRg, disposition index, and ISR area under the curve were identified in older people with NGT, with more marked defects in older people with IGT. Nicotinic acid treatment significantly reduced S(I) in all groups. beta-Cell compensation for nicotinic acid-induced insulin resistance was incomplete in all three groups, with greater defects in the two older groups. Human aging is associated with impaired beta-cell sensitivity to glucose and impaired beta-cell compensation to insulin resistance.


Gas phase photo-formation and vacuum UV photofragmentation spectroscopy of tryptophan and tyrosine radical-containing peptides.
Tryptophan (Trp(•)) and tyrosyl (Tyr(•)) radical containing peptides were produced by UV laser-induced electron detachment from a suitable precursor. Vacuum ultraviolet (VUV) action spectra of these radical peptides were recorded with synchrotron radiation in the 4.5-16 eV range, from which fragmentation pathways and yields are measured as a function of the VUV photon energy. An enhancement in photofragmentation yields of radical species by 1 order of magnitude with respect to nonradical peptides is demonstrated here for the first time. Photofragmentation spectra are compared with absorption spectra for model chromophores calculated in the frame of the time-dependent density functional theory (TDDFT). A qualitative agreement in the position of bands in the 6-8 eV region is observed between experimental photofragmentation and calculated absorption spectra. Photofragmentation spectra of peptide radicals can be useful to better assess the complex deactivation pathways that occur following the absorption of a VUV photon in biomolecular radical anions.


Highly efficient [Ni{iPrHNC(S)NP(S)(OiPr)2-1,3-N,S'}2]/PR3 (R3 = Me3, Me2Ph) complexes for the generation of Ni(0) for catalysis.
We have developed new complexes of the type [Ni{iPrHNC(S)NP(S)(OiPr)(2)-1,3-N,S'}(2)]/PR(3) (R(3) = Me(3), Me(2)Ph) for the generation of Ni(0) catalysts which can be used for the catalytic addition of Ph(2)S(2) to 1-, 2- and 3-hexynes. A detailed study of the catalytic reaction mechanism suggests two possible pathways for the in situ formation of Ni(0) species, depending on the presence or absence of water.


Ethylene Activates the EIN2-EIN3/EIL1 Signaling Pathway in Tapetum and Disturbs Anther Development in Arabidopsis.
Ethylene was previously reported to repress stamen development in both cucumber and Arabidopsis. Here, we performed a detailed analysis of the effect of ethylene on anther development. After ethylene treatment, stamens but not pistils display obvious developmental defects which lead to sterility. Both tapetum and microspores (or microsporocytes) degenerated after ethylene treatment. In ein2-1 and ein3-1 eil1-1 mutants, ethylene treatment did not affect their fertility, indicating the effects of ethylene on anther development are mediated by EIN2 and EIN3/EIL1 in vivo. The transcription of EIN2 and EIN3 are activated by ethylene in the tapetum layer. However, ectopic expression of EIN3 in tapetum did not induce significant anther defects, implying that the expression of EIN3 are regulated post transcriptional level. Consistently, ethylene treatment induced the accumulation of EIN3 in the tapetal cells. Thus, ethylene not only activates the transcription of EIN2 and EIN3, but also stabilizes of EIN3 in the tapetum to disturb its development. The expression of several ethylene related genes was significantly increased, and the expression of the five key transcription factors required for tapetum development was decreased after ethylene treatment. Our results thus point out that ethylene inhibits anther development through the EIN2-EIN3/EIL1 signaling pathway. The activation of this signaling pathway in anther wall, especially in the tapetum, induces the degeneration of the tapetum and leads to pollen abortion.


Scientific Development of HTA-A Proposal by the Health Technology Assessment International Scientific Development and Capacity Building Committee.
To report from the Scientific Development and Capacity Building Committee of Health Technology Assessment International (HTAi) on activities that are being undertaken within HTAi regarding the promotion of scientific rigor in the field of health technology assessment (HTA). Retrieval of definitions of HTA that the SDCB committee considered reflective of the current practice of HTA, followed by a narrative synthesis of the core components of HTA. Several definitions of HTA have been provided, all sharing the notion that HTA is the formal, systematic, and transparent inquiry into the meaning and value, broadly defined, of health technologies, when used in specific patient populations.Many frameworks and tools have been developed for assessing the quality of specific tasks that may be conducted in the context of HTA. Collating such frameworks and tools is likely to be helpful in developing standards and in providing guidance as to how the scientific quality of HTA may be secured. Two current trends in HTA were noted: a stronger health systems focus, and the need to involve stakeholders throughout the HTA process. A wider systems' perspective requires that plausible alternative scenarios are being developed, and wide consultation of various stakeholders is a prerequisite to the development of such scenarios with data from various sources. Current trends in HTA will lead to different demands on the HTA expert. The task of this emerging policy professional would be not just to provide technical information for problem-solving, but also to combine it with a new function of facilitating public deliberation and learning.


The urea cycle disorders.
The urea cycle is the primary nitrogen-disposal pathway in humans. It requires the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea. Whereas ammonia is toxic, urea is relatively inert, soluble in water, and readily excreted by the kidney in the urine. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life. Patients are at risk for metabolic decompensation throughout life, often triggered by illness, fasting, surgery and postoperative states, peripartum, stress, and increased exogenous protein load. Here the authors address neurologic presentations of ornithine transcarbamylase deficiency in detail, the most common of the urea cycle disorders, neuropathology, neurophysiology, and our studies in neuroimaging. Special attention to late-onset presentations is given.


Inelastic neutron scattering and Raman spectroscopic investigation of L-alanine alaninium nitrate, a homologue of a ferroelectric material.
The 2 : 1 amino acid salt of L-alanine with nitric acid was crystallized and the vibrational spectrum measured at 25 K by incoherent inelastic neutron scattering (INS) spectroscopy. The spectrum was simulated using solid-state density functional theory based on a new 90 K structure determination. A feature observed at approximately 450 cm(-1) in the INS spectrum of L-alanine alaninium nitrate is noticeably absent in the calculation. Raman spectroscopy reveals spectral differences between the spectra at 77 and 293 K with a 450 cm(-1) feature appearing at low temperature. The nature of these spectral changes and the disagreement between the INS spectrum and its simulation are discussed in relation to an apparent structural change involving motion of a proton at low (<90 K) temperature.


Functionalization of atomic force microscope tips by dielectrophoretic assembly of Gd(2)O(3):Eu(3+) nanorods.
An atomic force microscopy (AFM) tip has been coated with photoluminescent Eu(3+)-doped Gd(2)O(3) nanorods using a dielectrophoresis technique, which preserves the red emission of the nanorods (quantum yield 0.47). The performance of the modified tips has been tested by using them for regular topography imaging in tapping and contact modes. Both a regular AFM standard grid and a patterned surface (of an organic-inorganic methacrylate Zr-based oxo-cluster and poly(oxyethylene)/siloxane hybrid) have been used. Similar depth values have been measured using a conventional silicon tip and the nanorod-modified tip. The tips before and after use exhibit similar SEM images and photoluminescence spectra and, thus, seem to be stable under working conditions. These tips should find applications in scanning near-field optical microscopy and other scanning techniques.


Imaging the Distribution of Gastrin-Releasing Peptide Receptors in Cancer.
Targeting tumor-expressed receptors using selective molecules for diagnostic, therapeutic, or both diagnostic and therapeutic (theragnostic) purposes is a promising approach in oncologic applications. Such approaches have increased significantly over the past decade. Peptides such as gastrin-releasing peptide receptors targeting radiopharmaceuticals are small molecules with fast blood clearance and urinary excretion. They demonstrate good tissue diffusion, low immunogenicity, and highly selective binding to their target cell-surface receptors. They are also easily produced. Gastrin-releasing peptide receptors, part of the bombesin family, are overexpressed in many tumors, including breast and prostate cancer, and therefore represent an attractive target for future development.


One-step modification of fabrics with bioinspired polydopamine@octadecylamine nanocapsules for robust and healable self-cleaning performance.
An in-situ polymerization to coat fabrics with polydopamine-encapsulated octadecylamine endows the fabrics with self-cleaning and self-healing abilities. The treated fabric exhibits self-healing after losing its hydrophobicity. It is durable against washing and mechanical abrasion without changing the hydrophobicity. Thanks to the versatile adhesive property of polydopamine, the approach is compatibile with a variety of substrates, such as fabrics, glass, sponge, paper, and polymeric materials.


Indicator-focussed technical assistance in South Africa's HIV programme: A stepped-wedge evaluation.
There is a lack of research on technical assistance (TA) interventions in low- and middle-income countries. Variation in local contexts requires tailor-made approaches to TA that are structured and replicable across intervention sites whilst retaining the flexibility to adapt to local contexts. We developed a systematic process of TA using multidisciplinary roving teams to provide support across the various elements comprising local HIV services. To examine the effectiveness of targeting specific HIV and TB programme indicators for improvement using roving teams. We conducted a cluster-randomised stepped-wedge evaluation of a TA support package focussing on clinical, managerial and pharmacy services in the Mopani district of the Limpopo province, South Africa (SA). Three roving teams delivered the intervention. Seventeen primary and community healthcare centres that had 400-600 patients on antiretroviral therapy (ART) were selected for inclusion. The TA package was implemented for six consecutive months across facilities until all had received the same level of support. Data were collected from the relevant health management information systems for 11 routine indicators. The mean proportion of PLWH screened for tuberculosis (TB) at ART initiation increased from 85.2% to 87.2% (P = 0.65). Rates of retention in care improved, with the mean proportion of patients retained in care at three months post-ART initiation increasing from 79.9% to 87.4% (P < 0.001) and from 70.3% to 77.7% (P < 0.01) after six months. Finally, the mean proportion of patients with TB who completed their treatment increased from 80.6% to 82.1% (P = 0.75). Tailored TA interventions in SA using a standardised structure and process led to a significant improvement in retention-in-care rates and to non-significant improvements in the proportion of PLWH screened for TB and of those who completed their treatment.


Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma.
Long non-coding RNAs (lncRNAs) have been recognized as a regulator of gene expression, and the deregulation of lncRNAs have been reported to be correlated with carcinogenesis and cancer progression. To explore the function of lncRNA in endometrial carcinoma, we analyzed the expression profiles of lncRNAs and coding genes in 3 paired endometrial carcinoma and adjacent non-tumor tissues, using a microarray. The results of microarray analysis indicated a significant difference in lncRNA and coding gene expression between endometrial carcinoma and their paired adjacent non-tumor tissues. A total of 53 lncRNAs (fold change >2.0, p-value <0.05) were found to be differently expressed in endometrial carcinoma compared to the normal controls. Among these ASLNC04080 was the most significantly upregulated lncRNA in microarray data, highly expressed in 22 out of 24 endometrial carcinoma tissues and HEC-1-B cell line. ASLNC04080 is 1867nt in length, consist of 6 exons, and locates at 1 p35.3(chr1: -28905061 - -28909492). In addition, 46 coding gene transcripts were differentially expressed (fold change >2.0, p-value <0.05) between endometrial carcinoma and adjacent non-tumor tissues. Pathway and gene ontology analysis demonstrated that these deregulated transcripts were involved in multiple signal pathways, biological processes, cellular components and molecular functions. Moreover, the ASLNC04080 lncRNA expression was correlated with 19 coding genes, and may contribute to endometrial carcinoma genesis and progression by co-regulating with coding gene. Expression inhibition of lncRNA ASLNC04080 in HEC-1-B cells caused repression of cell proliferation, increased cell apoptosis, and G1 phase arrest. These results suggested a potential function of ASLNC04080 in endometrial carcinoma genesis and progression.


Does Decreasing Below-Knee Prosthesis Pylon Longitudinal Stiffness Increase Prosthetic Limb Collision and Push-Off Work During Gait?
Investigations have begun to connect leg prosthesis mechanical properties and user outcomes to optimize prosthesis designs for maximizing mobility. To date, parametric studies have focused on prosthetic foot properties, but not explicitly longitudinal stiffness that is uniquely modified through shock-absorbing pylons. The linear spring function of these devices might affect work performed on the body center-of-mass during walking. This study observed the effects of different levels of pylon stiffness on individual limb work of unilateral below-knee prosthesis users walking at customary and fast speeds. Longitudinal stiffness reductions were associated with minimal increase in prosthetic limb collision and push-off work, but inconsistent changes in sound limb work. These small and variable changes in limb work did not suggest an improvement in mechanical economy due to reductions in stiffness. Fast walking generated greater overall center-of-mass work demands across stiffness conditions. Results indicate limb work asymmetry as the prosthetic limb experienced on average 61% and 36% of collision and push-off work, respectively, relative to the sound limb. A series spring model to estimate residuum and pylon stiffness effects on prosthesis energy storage suggested that minimal changes to limb work may be due to influences of the residual limb which dominate the system response.


Seasonal changes in sleep and behavioral problems in a pubescent case with autism.
This study reports on the seasonal changes in sleep problems and behavioral problems in a pubescent case with autism. His care diary, kept for 1 year, showed seasonal changes of sleep and behavioral problems, and that his behavioral problems preceded his sleep problems.


An LL-diaminopimelate aminotransferase defines a novel variant of the lysine biosynthesis pathway in plants.
Although lysine (Lys) biosynthesis in plants is known to occur by way of a pathway that utilizes diaminopimelic acid (DAP) as a central intermediate, the available evidence suggests that none of the known DAP-pathway variants found in nature occur in plants. A new Lys biosynthesis pathway has been identified in Arabidopsis (Arabidopsis thaliana) that utilizes a novel transaminase that specifically catalyzes the interconversion of tetrahydrodipicolinate and LL-diaminopimelate, a reaction requiring three enzymes in the DAP-pathway variant found in Escherichia coli. The LL-DAP aminotransferase encoded by locus At4g33680 was able to complement the dapD and dapE mutants of E. coli. This result, in conjunction with the kinetic properties and substrate specificity of the enzyme, indicated that LL-DAP aminotransferase functions in the Lys biosynthetic direction under in vivo conditions. Orthologs of At4g33680 were identified in all the cyanobacterial species whose genomes have been sequenced. The Synechocystis sp. ortholog encoded by locus sll0480 showed the same functional properties as At4g33680. These results demonstrate that the Lys biosynthesis pathway in plants and cyanobacteria is distinct from the pathways that have so far been defined in microorganisms.


Designing diffractive optical elements for shaping partially coherent beams by proximity correction.
We propose a new method to design diffractive optical elements (DOE) for shaping partially coherent beams. The diffraction patterns of a DOE under a certain partially coherent beam can be modeled by the convolution of the coherent diffraction pattern and the inherent degree of coherent function. Two basic types of diffraction anomalies induced by partially coherent beams are discussed, including line-end shortening and corner rounding. A proximity correction (PC) method similar to the optical proximity correction (OPC) technique in lithography is used to compensate for these anomalies. The designed DOE exhibits good performance in partially coherent beam shaping and noise suppression.


Progestogens for preterm birth prevention: a systematic review and meta-analysis.
We systematically reviewed the effectiveness of progestogens for prevention of preterm birth among women with prior spontaneous preterm birth, multiple gestations, preterm labor, short cervix, or other indications. We searched MEDLINE and EMBASE databases for English language articles published from January 1966 to October 2011. We excluded publications that were not randomized controlled trials or had fewer than 20 participants, identifying 34 publications, of which 19 contained data for Bayesian meta-analysis. Two reviewers independently extracted data and assigned overall quality ratings based on predetermined criteria. Among women with prior preterm birth and a singleton pregnancy (five randomized controlled trials), progestogen treatment decreased the median risk of preterm birth by 22% (relative risk [RR] 0.78, 95% Bayesian credible interval 0.68-0.88) and neonatal death by 42% (RR 0.58, 95% Bayesian credible interval 0.27-0.98). The evidence suggests progestogen treatment does not prevent prematurity (RR 1.02, 95% Bayesian credible interval 0.87-1.17) or neonatal death (RR 1.44, 95% Bayesian credible interval 0.46-3.18) in multiple gestations. Limited evidence suggests progestogen treatment may prevent prematurity in women with preterm labor (RR 0.62, 95% Bayesian credible interval 0.47-0.79) and short cervix (RR 0.52, 95% Bayesian credible interval 0.36-0.70). Across indications, evidence about maternal, fetal, or neonatal health outcomes, other than reducing preterm birth and neonatal mortality, is inconsistent, insufficient, or absent. Progestogens prevent preterm birth when used in singleton pregnancies for women with a prior preterm birth. In contrast, evidence suggests lack of effectiveness for multiple gestations. Evidence supporting all other uses is insufficient to guide clinical care. Overall, clinicians and patients lack longer-term information to understand whether intervention has the ultimately desired outcome of preventing morbidity and promoting normal childhood development.


Isoflurane post-conditioning influences myocardial infarct healing in rats.
Isoflurane post-conditioning causes an early increase in cardiac progenitor cells; however, during the chronic phase of infarct healing, the number was smaller compared to control, which suggests a positive effect on infarct scar maturity. Myofibroblasts participate in early phase infarct contraction, but their number is small in a mature scar. We investigated whether isoflurane post-conditioning stimulates differentiation of progenitor cells to myofibroblasts and to verify our hypothesis that isoflurane post-conditioning improves maturation of a myocardial scar. Ischemia was induced for 30 min in female rats. From the last 5 min of ischemia until 10 min into reperfusion, the isoflurane group received 1.5% isoflurane, while the control group received only an air-oxygen mixture. Infarct area was analyzed using immunohistochemistry. During the subacute phase of infarct healing, the number of myofibroblasts was greater in isoflurane-treated animals than in the control group. During the chronic phase of infarct healing, post-conditioned animals exhibited fewer myofibroblasts compared to control animals, even those derived from progenitor cells, i.e., α-smooth actin-nestin positive cells. In addition, isoflurane post-conditioning resulted in higher percentage of mature blood vessels compared to control animals. The myocardium of the isoflurane treated animals exhibited more myofibroblasts in granulation tissue compared to control animals. The smaller number of myofibroblasts together with the greater number of mature blood vessels during the chronic phase of healing demonstrated faster healing of the infarct area of isoflurane-treated animals compared to control animals.


miR-3168 promotes hepatocellular carcinoma progression via downregulating p53.
Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis, which is partly due to the presence of liver cancer stem cells (CSCs). CSCs participate in tumor recurrence, metastasis, and chemoresistance. However, the mechanisms underlying liver CSC regulation are unknown. In this study, we found that miR-3168 expression is increased in HCC and that it predicts poor prognosis. Functional assays showed that miR-3168 promotes HCC cells' proliferation and facilitates liver CSC self-renewal and tumorigenicity. Mechanistically, bioinformatics and the luciferase reporter assay demonstrated that miR-3168 targets the 3'UTR of the p53 mRNA. MiR-3168 expression was negatively correlated with p53 mRNA in HCC tissue samples. Rescue assays demonstrated that p53 knockdown abrogates the discrepancies in proliferation, self-renewal, and tumorigenicity between miR-3168 knockdown HCC cells and control HCC cells. Furthermore, miR-3168 expression was negatively correlated with p53 in HCC tissues. The combined HCC panels exhibited a worse prognostic value for HCC patients than any of these components alone. Moreover, miR-3168 expression was increased in cisplatin-resistant HCC cells and patient-derived xenografts. Clinical cohort analysis revealed that HCC patients with low miR-3168 levels have a superior survival rate when treated with postoperative transcatheter arterial chemoembolization compared with that of patients with high miR-3168 levels. In conclusion, our study uncovered a novel mechanism of liver CSC regulation and provided a potential therapeutic target for liver CSCs.


Eosinophilic cellulitis - A case study and management with griseofulvin.
A 47 year old hypertensive and diabetic male patient suffering from eosinophilic cellulitis (Wells syndrome) is being reported. The patient responded very well to oral griseofulvin at the time of first presentation and subsequent three recurrences in a period of three years.


Dynamics of surface-plasmon lasing in planar metal gratings on semiconductor.
We investigate the dynamics of surface plasmon (SP) lasing in Au gratings fabricated on InGaAs with a period of around 400 nm, which locates the SP resonance near the semiconductor energy gap and facilitates efficient energy transfer. By optically pumping the InGaAs to reach the population inversion required for the amplification and the lasing, we observe SP lasing at specific wavelengths that satisfy the SPR condition depending on the grating period. The carrier dynamics in semiconductor and the photon density in the SP cavity was investigated from the time-resolved pump-probe measurement and the time resolved photoluminescence spectroscopy, respectively. Our results reveal that the photon dynamics is strongly correlated with the carrier dynamics and the lasing build-up is accelerated as the initial gain proportional to the pumping power increases, and this trend is satisfactorily explained using the rate equation model.


Surgical Biopsy of Pathologically Enlarged Lymph Nodes: A Reappraisal.
Enlarged lymph nodes (ELN) pose a great diagnostic challenge. They may represent the first clinical finding of a hematologic disease or other malignancy and may be an indication of a wide range of infectious and non-infectious diseases. Because many patients undergo percutaneous biopsy, surgical excisional biopsy is not often considered. To analyze indications for a patient's referral for surgical biopsy of ELN and diagnostic steps to follow until referral, and to determine the number of ELN. A retrospective study was conducted of prospectively collected data of patients who underwent surgical biopsy of ELN from January 2004 to December 2013. Of 118 patients who underwent surgical biopsy of ELN, only 52 (44%) had needle biopsy (NB) before referral. Lymphoma was diagnosed by NB in 24 (46%) of the referred patients. In patients with a previous diagnosis of lymphoma, NB of ELN yielded a sensitivity of 67% and specificity of 79%. In patients with lymphadenopathy but with no previous history of malignancy, sensitivity for lymphoma was 68% and specificity was 71%. The investigative time period until final diagnosis was 3 months in patients who had NB but only 1.25 months in patients who were referred directly for surgery (P < 0.0001). Surgical biopsy of ELN still has a place in the clinical evaluation of patients with ELN. Surgery may significantly reduce the length of investigation and prevent unnecessary diagnostics, especially in patients with suspected lymphoma recurrence.


Properties of Desulfovibrio carbinolicus sp. nov. and Other Sulfate-Reducing Bacteria Isolated from an Anaerobic-Purification Plant.
Several sulfate-reducing microorganisms were isolated from an anaerobic-purification plant. Four strains were classified as Desulfovibrio desulfuricans, Desulfovibrio sapovorans, Desulfobulbus propionicus, and Desulfovibrio sp. The D. sapovorans strain contained poly-beta-hydroxybutyrate granules and seemed to form extracellular vesicles. A fifth isolate, Desulfovibrio sp. strain EDK82, was a gram-negative, non-spore-forming, nonmotile, curved organism. It was able to oxidize several substrates, including methanol. Sulfate, sulfite, thiosulfate, and sulfur were utilized as electron acceptors. Pyruvate, fumarate, malate, and glycerol could be fermented. Because strain EDK82 could not be ascribed to any of the existing species, a new species, Desulfovibrio carbinolicus, is proposed. The doubling times of the isolates were determined on several substrates. Molecular hydrogen, lactate, propionate, and ethanol yielded the shortest doubling times (3.0 to 6.3 h). Due to the presence of support material in an anaerobic filter system, these species were able to convert sulfate to sulfide very effectively at a hydraulic retention time as short as 0.5 h.


Acromioclavicular Joint Injuries: Evidence-based Treatment.
Injuries to the acromioclavicular (AC) joint are common in the athletic patient population. Most AC joint injuries occur in young males, typically from a direct fall onto the superior aspect of the shoulder when the arm is adducted. Numerous publications describing joint anatomy and biomechanics, surgical techniques for reconstruction, and rehabilitation protocols are available to guide treatment strategies for injuries to the AC joint. Treatment is typically nonsurgical for type I and II injuries and surgical for type IV and VI injuries. Controversy surrounds the indications for nonsurgical versus surgical treatment of type III and V injuries. Multiple surgical techniques have been described, including coracoclavicular (CC) screw fixation, coracoacromial ligament transfer, and numerous methods of CC ligament reconstruction. Anatomic CC ligament reconstruction can be performed either open or arthroscopically, with and without graft augmentation. This article will discuss clinically relevant anatomy and biomechanical properties of the AC joint and will review decision-making principles and treatment options for common AC joint injuries. An updated summary of clinical outcomes after AC joint treatment will also be presented.


A Bcl6 Intronic Element Regulates T Follicular Helper Cell Differentiation.
In response to an intracellular infectious agent, the immune system produces a specific cellular response as well as a T cell-dependent Ab response. Precursor T cells differentiate into effector T cells, including Th1 cells, and T follicular helper (TFH) cells. The latter cooperate with B cells to form germinal centers and induce the formation of Ab-forming plasmacytes. One major focal point for control of T cell differentiation is the transcription factor BCL6. In this study, we demonstrated that the Bcl6 gene is regulated by FOXO1-binding, cis-acting sequences located in a highly conserved region of the first Bcl6 intron. In both mouse and human T cells, deletion of the tandem FOXO1 binding sites increased the expression of BCL6 and enhanced the proportion of TFH cells. These results reveal a fundamental control point for cellular versus humoral immunity.


Atopic diseases and related risk factors among Dutch adolescents.
The aim of the present study was to gain insight into the prevalence of asthma, allergic rhinitis, and eczema among Dutch early adolescents, and to study the impact of several social demographic and individual risk factors. Cross-sectional survey study using the self-report questionnaires of the International Study of Asthma and Allergies in Childhood (ISAAC). In January 2003, 10 087 12- to 14-year-old students from 33 secondary schools in four regions of the Netherlands participated in this study. Of all participants, 52.6% reported that they had an allergic disease at least once in their lifetime. The 12 months prevalence of wheezing, rhinitis, and itchy rash was 12.3%, 28.3%, and 13.5%, respectively. Several social demographic and individual factors (gender, age, education levels, ethnicity, body mass index, and residential area) were significantly associated with the atopic symptoms and diseases. This study showed that allergic conditions are common in the Netherlands. Several social demographic and individual risk factors were related to the atopic diseases and symptoms.


Agonists interaction with radiolabeled alpha-adrenoceptor antagonists binding sites in rat mesenteric artery.
The nature of the postsynaptic alpha-adrenoceptors in vasculature has been a matter of debate with the differences in the observations from in vivo and in vitro experiments. These studies were done on the basis of the selectivity of the alpha-adrenoceptor agonists. In the present study, we investigated the nature of these agonists interaction with the [3H]prazosin and [3H]yohimbine binding sites in the plasma membrane vesicles of rat mesenteric artery. Phenylephrine and methoxamine were used as the putative alpha 1-adrenoceptor agonists. Clonidine, naphazoline, B-HT 920, and UK-14,304 were used as the putative alpha 2-adrenoceptor agonists. All these agonists except B-HT 920 competed with similar affinity for the specific binding sites of [3H]prazosin and [3H]yohimbine. The order of the potency for the agonists in competing for [3H]prazosin binding sites was clonidine greater than naphazoline greater than UK-14,304 greater than phenylephrine much greater than B-HT 920 greater than or equal to methoxamine, and for the [3H]yohimbine binding sites, the order was clonidine greater than naphazoline greater than B-HT 920 greater than UK-14,304 greater than phenylephrine much greater than methoxamine. Similar pA2 values for prazosin and yohimbine were calculated regardless of whether alpha 1-selective agonist, methoxamine, or alpha 2-selective agonist, B-HT 920 were used. Putative alpha 2-adrenoceptor-selective agonists behave as partial agonists in functional studies inhibiting just maximal responses to alpha 1-adrenoceptor agonists and norepinephrine in a dose-dependent fashion. It is therefore concluded that in rat mesenteric artery, there are two distinct sites of interaction for the antagonists, prazosin and yohimbine, but the alpha-adrenoceptor agonists interact nonselectively with a single site in such a way that they are capable of affecting binding of either antagonist. A model for the postsynaptic alpha-adrenoceptor as a macromolecule has been proposed.


A Subpopulation of Synovial Fibroblasts Leads to Osteochondrogenesis in a Mouse Model of Chronic Inflammatory Rheumatoid Arthritis.
Specific major histocompatibility complex (MHC) class II genes result in a high susceptibility to rheumatoid arthritis (RA), with co-stimulatory molecules working together with MHC class II during the progression of the disease. To elucidate the involvement of the B7.1 co-stimulatory molecule in RA, we analyzed the phenotype of B7.1 transgenic (named D1BC) mice and the sequential differentiation of synovial fibroblasts (SFs) by studying the expression of chondrogenic and osteogenic lineage markers together with lineage tracing experiment using B7.1 transgene in vivo. The B7.1 transgene was driven by a collagen type II (CII) promoter and enhancer in the D1BC mouse. A low-dose of bovine CII (bCII) was used to induce chronic articular inflammation with interstitial pneumonitis. Joint damage was analyzed by histopathological examination and computed tomography. B7.1 was expressed in articular cartilage and SFs of D1BC mice. Chronic inflammatory arthritis in the bCII-D1BC mouse shared common features with those found in patients with RA, such as pannus formation, bone destruction, osteoporosis, and joint ankylosis. A subpopulation of SFs (Runx2 +, Sox9 +, Col10a1 +, Osx+, and CX-) in the pannus was classified as osteochondrogenic lineage rather than mesenchymal stromal lineage. These cells underwent differentiation into osteogenic lineage via hypertrophic chondrocytes at the end of the chronic phase. The ectopic expression of B7.1 in chondrocytes and SFs leads to an increased susceptibility to chronic inflammatory arthritis and subsequent new bone formation, reminiscent of ankylosis. The regulation of cartilage remodeling in pannus tissue is an important consideration in the treatment of RA.


Caffeine induction of sulfotransferases in rat liver and intestine.
Sulfotransferases (SULTs) are important phase II drug-metabolizing enzymes. Regulation of SULTs by hormones and other endogenous molecules is relatively well understood, while xenobiotic induction of SULTs is not well studied. Caffeine is one of the most widely consumed psychoactive substances. However, SULT regulation by caffeine has not been reported. In this report, male and female rats were treated with different oral doses of caffeine (2, 10, 50 mg kg⁻¹ per day) for 7 days. Western blot and real-time RT-PCR were used to investigate the changes in SULT protein and mRNA expression following the caffeine treatment. Caffeine induced both rat aryl sulfotransferase (rSULT1A1, AST-IV) and rat hydroxysteroid sulfotransferase (rSULT2A1, STa) in the liver and intestine of female rats in a dose-dependent manner. Caffeine induction of rSULT1A1 and rSULT2A1 in the female rat intestine was much stronger than that in the liver. Although caffeine induced rSULT1A1 significantly in the male rat liver, it did not significantly induce rSULT2A1. In male rat intestine, caffeine significantly induced rSULT2A1. The different SULTs induction patterns in male and female rats suggest that the regulation of rat SULTs by caffeine may be affected by different hormone secretion patterns and levels. Our results suggest that consumption of caffeine can induce drug metabolizing SULTs in drug detoxification tissues.


An excellent enzymatic lactic acid biosensor with ZnO nanowires-gated AlGaAs/GaAs high electron mobility transistor.
An excellent biosensor with ZnO nanowires-gated AlGaAs/GaAs high electron mobility transistor (HEMT) was used to detect lactic acid. Due to the new structure, addition of the Si-doped GaAs cap layer, the HEMT biosensor could detect a wide range of lactic acid concentrations from 0.03 nM to 300 mM. The novel biosensor exhibiting good performance along with fast response, high sensitivity, wide detection range, and long-term stability, can be integrated with a commercially available transmitter to realize lactic acid detection.


Phosphatidylserine synthesis in Saccharomyces cerevisiae. Purification and characterization of membrane-associated phosphatidylserine synthase.
Membrane-associated phosphatidylserine synthase (CDP-diacylglycerol:L-serine O-phosphatidyltransferase, EC 188.8.131.52) was purified from the microsomal fraction of Saccharomyces cerevisiae strains S288C and VAL2C(YEpCHO1). VAL2C(YEpCHO1) contains a hybrid plasmid bearing the structural gene for phosphatidylserine synthase and overproduces the enzyme 6-7 fold (Letts, V. A., Klig, L. S., Bae-Lee, M., Carman, G. M., and Henry, S. A. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 7279-7283) compared to wild-type S288C. The purification procedure included Triton X-100 extraction of the microsomal membranes, CDP-diacylglycerol-Sepharose affinity chromatography, and DE-53 chromatography. The procedure yielded a preparation from each strain containing a major peptide band (Mr = 23,000) upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phosphatidylserine synthase was dependent on manganese and Triton X-100 for maximum activity at pH 8.0. The apparent Km values for serine and CDP-diacylglycerol were 0.58 mM and 60 microM, respectively. Thioreactive agents inhibited enzyme activity. The enzyme was thermally labile above 40 degrees C. Results of isotopic exchange reactions between substrates and products suggest that the enzyme catalyzes a sequential Bi Bi reaction.


Physical Activity Intensity and Suspected Dementia in Older Japanese Adults: A Dose-Response Analysis Based on an 8-Year Longitudinal Study.
Moderate- to vigorous-intensity physical activity (PA) may reduce the risk of dementia; however, few studies have examined the effects of PA intensity on dementia risk. To prospectively examine the dose-response relationship of PA intensity with the incidence of suspected dementia in community-dwelling older adults. We conducted a baseline mail survey with an 8-year follow-up of 3,722 older adults in Japan. We assessed PA levels using the International Physical Activity Questionnaire short form and calculated the amount of time per week spent performing moderate- and vigorous-intensity PA (VPA). Information regarding suspected dementia was obtained from the city database during the follow-up period. Cox proportional-hazard models with age as time scale, and delayed entry and restricted cubic spline regression as variables were used to estimate risk of developing suspected dementia, excluding cases occurring < 1 year after baseline evaluation. The cumulative incidence of suspected dementia during the follow-up period was 12.7%. Compared with those who did not practice moderate-intensity PA (MPA), those who practiced≥300 min (hazard ratio, 0.73; 95% confidence interval 0.56-0.95) of MPA showed a lower risk of developing suspected dementia. Furthermore, when the dose-response relationship was examined, the hazard of developing suspected dementia decreased almost linearly with MPA. A significantly lower hazard was observed from 815 minutes/week. There was no significant association between VPA and suspected dementia. This study suggested that MPA is often practiced in older adults and this PA intensity has a sufficiently favorable effect on dementia prevention.


Choanal atresia. Clinical considerations for management.
Taking cognizance of the embryology and newer diagnostic techniques, the transpalatal route is strongly recommended as the optimal surgical procedure for the management of choanal atresia. It should be performed as soon as general anesthesia can be safely administered. In selected instances, but particularly when a patient is at increased surgical risk, necessitating surgical brevity, the endonasal puncture technique should be considered as the initial procedure. Parents must be appraised of the potential for subsequent growth deficiencies, mental retardation, and crossbite.


Measurement of D0-D0 mixing parameters in D0 --> Ks pi+ pi- decays.
We report a measurement of D0-D(0) mixing parameters in D(0) --> K(s)(0) pi(+) pi(-) decays using a time-dependent Dalitz-plot analysis. We first assume CP conservation and subsequently allow for CP violation. The results are based on 540 fb(-1) of data accumulated with the Belle detector at the KEKB e(+)e(-) collider. Assuming negligible CP violation, we measure the mixing parameters x = (0.80 +/- 0.29(-0.07-0.14)(+0.09+0.10))% and y = (0.33+/-0.24(-0.12-0.08)(+0.08+0.06))%, where the errors are statistical, experimental systematic, and systematic due to the Dalitz decay model, respectively. Allowing for CP violation, we obtain the CP-violating parameters |q / p| = 0.86(-0.29-0.03)(+0.30+0.06) +/- 0.08 and arg(q/p) = (-14(-18-3-4)(+16+5+2)) degrees .


Eosinophilic inflammation in lymph nodes of dogs with visceral leishmaniasis.
Eosinophils are traditionally associated with the immune response against helminth parasites. However, several studies have demonstrated that these cells have a role regarding protective immunity in leishmaniasis. Here, we examined the relationship between the presence of eosinophils and parasite load in biopsy samples from dogs, obtained through fine needle puncture and aspiration of lymph nodes. Histological slides containing biopsy material from lymph nodes of dogs with canine visceral leishmaniasis and healthy dogs were used to obtain baseline eosinophil counts. Subsequently, scrapings were taken from slides for DNA extraction and determination of parasite load, using real-time PCR (qRT-PCR). Additionally, production of nitric oxide (NO) and reactive oxygen species (ROS) levels by eosinophils in the peripheral blood of dogs with canine visceral leishmaniasis and healthy dogs was measured. The eosinophil percentage were higher in lymph nodes of infected group, and the parasite load showed a significant negative correlation with the eosinophil count. The production of NO and ROS by eosinophils in the peripheral blood was higher in the dogs with canine visceral leishmaniasis. All the results together suggest that eosinophils may participate in antileishmanial immunity in canine visceral leishmaniasis.


Patient characteristics and treatment variables associated with apical root resorption during orthodontic treatment.
Multivariate analysis of patient characteristics and clinical variables was carried out with the maximum single maxillary incisor apical root resorption for each patient as the dependent variable. Root lengths were measured in standardized intraoral radiographs from 485 consecutively treated patients, 11.5 to 25 years of age. The correlation matrix revealed a complex pattern of positive and negative associations between the six pretreatment and seven treatment variables. Variables found to contribute significantly to apical root resorption were overjet, history of trauma to maxillary incisors before initiation of treatment, time of treatment with rectangular arch wires, time of treatment with Class II elastics, lip/tongue dysfunction, and/or history of finger-sucking habits persisting beyond the age of 7 years, and impacted maxillary canines to be corrected orthodontically. Clinical application of an open activator was significantly correlated with overjet but negatively correlated with apical root resorption, with the use of rectangular arch wires and/or Class II elastics, and with total banding time.


Inspiratory resistance training in severe chronic obstructive pulmonary disease.
Twenty-eight patients with stable chronic obstructive pulmonary disease (COPD) undertook a training program with a simple respiratory apparatus for 15 min three times daily for 6 weeks. Fourteen patients were allocated to an inspiratory resistance training program and 14 to a control group. In all subjects the median FEV1 was 0.72 and the median FEV1/FVC was 39%. There was no difference in FEV1 or FEV1/FVC between the control and the test groups. In both groups of patients FEV1 FVC and the corresponding values during inspiration, FIV1 and FIVC, as well as MVV, were found unchanged following the training period. Inspiratory resistance tolerance increased in both groups but no significant difference in the improvement could be observed between the two groups. Both groups also showed a similar increase, 23 (76-10) %, in stair-climbing ability. There was no correlation between increases in inspiratory load tolerance and stair-climbing ability. It is suggested that both inspiratory load tolerance and work ability can be improved in COPD patients, but that inspiratory resistance training does not contribute to these improvements.


Effect of the initial structure on the electrical property of crystalline silicon films deposited on glass by hot-wire chemical vapor deposition.
Crystalline silicon films on an inexpensive glass substrate are currently prepared by depositing an amorphous silicon film and then crystallizing it by excimer laser annealing, rapid thermal annealing, or metal-induced crystallization because crystalline silicon films cannot be directly deposited on glass at a low temperature. It was recently shown that by adding HCI gas in the hot-wire chemical vapor deposition (HWCVD) process, the crystalline silicon film can be directly deposited on a glass substrate without additional annealing. The electrical properties of silicon films prepared using a gas mixture of SiH4 and HCl in the HWCVD process could be further improved by controlling the initial structure, which was achieved by adjusting the delay time in deposition. The size of the silicon particles in the initial structure increased with increasing delay time, which increased the mobility and decreased the resistivity of the deposited films. The 0 and 5 min delay times produced the silicon particle sizes of approximately 10 and approximately 28 nm, respectively, in the initial microstructure, which produced the final films, after deposition for 300 sec, of resistivities of 0.32 and 0.13 Omega-cm, mobilities of 1.06 and 1.48 cm2 V(-1) S(-1), and relative densities of 0.87 and 0.92, respectively.


Front-line use of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: Practice considerations.
The development of BCR-ABL-targeting tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia (CP CML) from a disease with a terminal prognosis to a treatable chronic illness. Long-term treatment with tyrosine kinase inhibitors means that patients have to be clinically managed and monitored over extended periods of time, thus a patient-centered, medically integrated, and multidisciplinary oncology healthcare team is required to support patients through their journey. Pharmacists work with patients, physicians, and the wider support team to select the optimum therapy plan for a given patient. These decisions are based on risk factors, comorbidities, concomitant medications, and personal circumstances and pharmacists advise on the efficacy and safety of different treatment options. Additionally, pharmacists are a key point-of-contact and resource for monitoring patient response to treatment, identifying and managing adverse events and drug-drug interactions, any subsequent therapy plan modifications, and, potentially, treatment-free remission. Pharmacists also assist with patient education, medication adherence, and financial discussions with patients throughout the long course of the disease. This review provides an overview of BCR-ABL tyrosine kinase inhibitors, discusses the role of the medically integrated pharmacy team, and suggests strategies that pharmacists can use in patient management and clinical decision-making to optimize the treatment of CP CML.


FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities.
Fibroblast growth factor 1 (FGF1) is a prototypic member of the FGFs family overexpressed in various tumors. Contrarily to most FGFs, FGF1 lacks a secretion peptide signal and acts mainly in an intracellular and nuclear manner. Intracellular FGF1 induces cell proliferation, differentiation and survival. We previously showed that intracellular FGF1 induces neuronal differentiation and inhibits both p53- and serum-free-medium-induced apoptosis in PC12 cells. FGF1 nuclear localization is required for these intracellular activities, suggesting that FGF1 regulates p53-dependent apoptosis and neuronal differentiation by new nuclear pathways. To better characterize intracellular FGF1 pathways, we studied the effect of three mutations localized in the C-terminal domain of FGF1 (i.e., FGF1(K132E), FGF1(S130A) and FGF1(S130D)) on FGF1 neurotrophic and anti-apoptotic activities in PC12 cells. The change of the serine 130 to alanine precludes FGF1 phosphorylation, while its mutation to aspartic acid mimics phosphorylation. These FGF1 mutants kept both a nuclear and cytosolic localization in PC12 cells. Our study highlights for the first time the role of FGF1 phosphorylation and the implication of FGF1 C-terminal domain on its intracellular activities. Indeed, we show that the K132E mutation inhibits both the neurotrophic and anti-apoptotic activities of FGF1, suggesting a regulatory activity for FGF1 C terminus. Furthermore, we observed that both FGF1(S130A) and FGF1(S130D) mutant forms induced PC12 cells neuronal differentiation. Therefore, FGF1 phosphorylation does not regulate FGF1-induced differentiation of PC12 cells. Then, we showed that only FGF1(S130A) protects PC12 cells against p53-dependent apoptosis, thus phosphorylation appears to inhibit FGF1 anti-apoptotic activity in PC12 cells. Altogether, our results show that phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after p53-dependent apoptosis induction, giving new insight into the poorly described FGF1 intracrine/nuclear pathway. The study of nuclear pathways could be crucial to identify key regulators involved in neuronal differentiation, tumor progression and resistances to radio- and chemo-therapy.