Emergency and elective surgery for small bowel Crohn's disease.
Advancements in the medical treatment of Crohn's disease have reduced the need for surgery. The indications for surgery include the failure of medical management, especially the persistence or worsening of symptoms in spite of proper treatment and complications of the disease process. These complications include intestinal obstruction, intestinal perforation with fistula formation or abscess, free perforation, gastrointestinal bleeding, urologic complications, cancer, and perianal disease. In these cases, operative therapy should be directed to the specific indication for surgery, resecting only the segment of bowel involved in the complicating process while preserving as much bowel length as possible in order to prevent short-bowel syndrome. Laparoscopic surgery has been gaining acceptance as an alternative surgical approach for properly selected patients with Crohn's disease. In conclusion, identifying the need for surgery and determining the timing of operation are the cornerstones to successful surgical management of patients with Crohn's disease.


Comment arising from a paper by Wolda and Dennis: using and interpreting the results of tests for density dependence.
We argue that tests for density dependence are useful in analyses of population dynamics and suggest guide lines for their use and interpretation of results which avoid many of the problems discussed by Wolda and Dennis (1993). Processes other than density dependence per se can cause statistical tests to indicate the presence of density dependence (Wolda and Dennis 1993 and unpublished simulations). Tests for density dependence cannot reveal the mechanism of regulation, but they do indicate the nature of long-term population dynamics. Tests for density dependence give misleading results if sampling is not at generation intervals; however, this problem is avoided if we only use tests on data collected in each generation (Holyoak 1993a). Similarly, species should be semelparous. Non-delayed density dependence should not be considered without looking for delayed density dependence, since the presence of delayed density dependence can lead to over-detection of non-delayed density dependence (Woiwod and Hanski 1992; Holyoak 1993b). The partial autocorrelation function and knowledge of life-history are more useful than tests for density dependence for indicating whether any density dependence is delayed or not (Royama 1992; Holyoak 1993b). Estimation error with a constant upper size limit causes tests for density dependence to overestimate the frequency of delayed density dependence; however we do not know whether estimation error is bounded in real populations. Work in progress suggests that 20-40 generations (depending on the nature of population dynamics) gives a moderate level of accuracy with tests for density dependence, and >40 generations are necessary for tests to be accurate in their assessment of the strength of density dependence. We conclude that tests are useful indicators of whether density dependence, or other feedback mechanisms are likely to be acting.


Conformational dynamics of supramolecular protein assemblies.
Supramolecular protein assemblies including molecular motors, cytoskeletal filaments, chaperones, and ribosomes play a central role in a broad array of cellular functions ranging from cell division and motility to RNA and protein synthesis and folding. Single-particle reconstructions of such assemblies have been growing rapidly in recent years, providing increasingly high resolution structural information under native conditions. While the static structure of these assemblies provides essential insight into their mechanism of biological function, their dynamical motions provide additional important information that cannot be inferred from structure alone. Here we present an unsupervised computational framework for the analysis of high molecular weight protein assemblies and use it to analyze the conformational dynamics of structures deposited in the Electron Microscopy Data Bank. Protein assemblies are modeled using a recently introduced coarse-grained modeling framework based on the finite element method, which is used to compute equilibrium thermal fluctuations, elastic strain energy distributions associated with specific conformational transitions, and dynamical correlations in distant molecular domains. Results are presented in detail for the ribosome-bound termination factor RF2 from Escherichia coli, the nuclear pore complex from Dictyostelium discoideum, and the chaperonin GroEL from E. coli. Elastic strain energy distributions reveal hinge-regions associated with specific conformational change pathways, and correlations in collective molecular motions reveal dynamical coupling between distant molecular domains that suggest new, as well as confirm existing, allosteric mechanisms. Results are publically available for use in further investigation and interpretation of biological function including cooperative transitions, allosteric communication, and molecular mechanics, as well as in further classification and refinement of electron microscopy based structures.


Minimal amounts of dipalmitoylphosphatidylcholine improve aerosol performance of spray-dried temocillin powders for inhalation.
Administration of antibiotics by inhalation can greatly improve drug targeting to the site of respiratory infections. In addition, dry powder inhalers are particularly convenient for the patients. The purposes of this study were to demonstrate the interest of pulmonary temocillin delivery to reach high temocillin concentrations locally in the lungs as well as to prepare a spray-dried temocillin powder for inhalation using a minimal amount of generally recognized as safe excipients. Intratracheal instillation of a temocillin solution allowed to reach higher and more sustained drug concentrations in the lungs than intravenous injection in mice, although a 10-fold lower temocillin dose was delivered intratracheally than systemically. A spray-dried powder of pure temocillin presented a fine particle fraction of 9% of the dose loaded in the inhaler. However, the incorporation of 0.5% to 20% of dipalmitoylphosphatidylcholine (DPPC) in the powder increased the fine particle fraction 4- to 5-fold. X-ray photoelectron spectroscopy and X-ray diffraction revealed that DPPC concentrated at the particle surface with its aliphatic chains laterally packed. The minimal amount of DPPC needed to improve the aerosol performance of temocillin supports the use of this excipient in the formulation of cohesive antibiotic powders for inhalation.


Functional and phenotypic properties of subpopulations of murine thymocytes. I. The bulk of peanut agglutinin-positive Lyt-1,2,3 thymocytes lacks precursors of cytotoxic T lymphocytes responsive to interleukin 2 (T cell growth factor).
Thymocytes were separate according to their surface phenotype and tested for cytotoxic T lymphocyte (CTL) precursor function by stimulation with allogeneic or hapten-coupled cells, with or without addition of T cell growth factor (interleukin 2). The data show that only a minor subpopulation of thymocytes agglutinated by peanut agglutinin, expressing relatively high amounts of H-2K antigen, contained CTL precursors. The remaining population, approximately 80%, could not be induced to generate CTL, even in the presence of interleukin 2.


Economies of scale, physician volume for urology patients, and DRG prospective hospital payment system.
Diagnosis Related Group (DRG) hospital payment has begun to squeeze hospitals financially and is likely to do so in the future. This study analyzed the relationship between the volume of urologic procedures by an individual urologist, hospital costs per patient, and outcome. We used a three-year DRG database of urology patients (N = 2,980) at an academic medical center to analyze these. Low-volume urologists (arbitrarily defined by us) had higher hospital costs per patient, financial losses versus profits under DRGs, and a poorer outcome when compared with high-volume urologists. Pearson correlation showed a positive relationship between cost per patient and physician volume for nonemergency patients (-0.129, p less than 0.0001) and emergency patients (-0.368, p less than 0.0001). This may have been explained (in part) by a greater severity of illness for patients of low-volume urologists. These findings suggest, however, that the volume of urologic procedures per urologist may be related to hospital resource consumption. The health care financing environment of the future should provide substantial interest in this finding for those involved in the consumption of urologic services.


Dynamics of Preferential Solvation of 5-Aminoquinoline in Hexane-Alcohol Solvent Mixtures.
Dynamics of preferential solvation of 5-aminoquinoline (5AQ) has been studied in hexane-alcohol solvent mixtures. Significant spectral red shift and fluorescence quenching are observed, even for miniscule amounts of alcohols. A nonlinear variation of these parameters, with alcohol mole fraction, indicates dipolar enrichment around 5AQ in its excited state. A nanosecond rise at the red end of emission spectra is ascribed to translational diffusion of alcohol molecules and consequent preferential solvation of 5AQ. Electrostatic stabilization and hydrogen bonding between the dipolar excited state of the fluorophore and polar alcohol molecules are major driving factors here. Time evolution of emission spectra, from those in a predominantly hexane-like environment to those in a predominantly alcohol-like environment, takes place in nanosecond time scale and depends on the alcohol concentration in the mixture. This in agreement with calculations using an existing model. Hence, 5AQ is found to be a suitable fluorescent probe for the study of dynamics in complex systems.


Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes.
Vitamin E, an antioxidant, improves insulin sensitivity through the suppression of conventional PKC in vascular smooth muscle cells. It has been reported that vitamin E reduces platelet aggregation through the suppression of PKC alpha and beta (Diabetes 47 (1998) 1494). On the other hand, 1 alpha,25-dihydroxy vitamin D3 (1,25D3) activates conventional PKC and may subsequently cause insulin resistance. Against this background, we examined the effect of vitamin E and 1,25D3 on PKC beta and PKC zeta/lambda activities in vitro and 10 nM insulin-induced glucose uptake in rat adipocytes. In vitro PKC beta activity of adipocytes was slightly decreased by the addition of 1 microM vitamin E, but not PKC zeta/lambda activity. In contrast, a 10-1000 nM 1,25D3 dose responsively activated PKC beta activity of adipocytes (ED 50%, 10 nM), but not PKC zeta/lambda activity. Pretreatment with 1 microM vitamin E for 60 min did not improve the insulin-induced glucose uptake. On the other hand, pretreatment with a 10-1000 nM 1,25D3 dose responsively suppressed insulin-induced glucose uptake. Moreover, 1,25D3 increased membrane-associated PKC beta immunoreactivity for 60 min, but no additional increase in membrane-associated PKC beta immunoreactivity during treatment with insulin was observed. These results suggest that 1,25D3 reduces insulin-induced glucose uptake via activation of PKC beta, but not vitamin E in rat adipocytes.


Production of human-mouse chimeric antibody by high cell density perfusion culture.
Two mouse myeloma cell lines which were transfected with chimeric mouse variable-human constant immunoglobulin heavy and light chain genes have been cultured at high cell density in a settling perfusion culture vessel to produce chimeric antibody specific for human common acute lymphocytic leukemia antigen (cALLA).J558L transfectant proliferated well in a serum-free medium (ITES-eRDF) to a viable cell density of 3.7×10(7) cells/ml and produced chimeric antibody to a maximum value of 60 μg/ml in 120 ml scale vessel. X63Ag8.653 transfectant reached a density of 1.9×10(7) cells/ml in 1.2 I scale vessel in serum supplemented medium (10% FCS-eRDF) and produced chimeric antibody which consisted of chimeric gamma and chimeric kappa chains to a maximum value of 5.8 μg/ml.


A specific and reversible macromolecular inhibitor of phenylalanine ammonia-lyase and cinnamic acid-4-hydroxylase in gherkins.
A non-dialysable inhibitor of phenylalanine ammonia-lyase (L-phenylalanine ammonia-lyase, EC 220.127.116.11) has been partially purified from dark-grown gherkin hypocotyls. On extraction of tissue it is found both in the soluble (106 000 X g supernatant) and microsomal (106 000 X g pellet) fractions and can be extracted from the microsomal membranes with 10 mM sodium cholate and 1 M KCl. The soluble and microsomal fractions have similar properties, suggesting the presence of the same active component. The inhibitor is small (Mr less than 20 000), thermolabile, sensitive to proteolytic digestion, and apparently hydrophobic. Purification of the inhibitor was achieved by chromatography on DEAE-cellulose by gel filtration on Sephadex G-50. The inhibitor preparations inhibit phenylalanine ammonia-lyase isolated from a number of plant tissues and also cinnamic acid-4-hydroxylase (trans-cinnamate, NADPH:oxygen oxidoreductase (4-hydroxylating), EC 188.8.131.52) from gherkins and peas, but not a wide range of other enzymes. The evidence suggests that inhibition of the two enzymes is due to the same substance, but this has not yet been confirmed. Kinetic experiments show that the inhibitor is competitive with phenylalanine for the lyase and that its association with the lyase is reversible. Further, a mixture of inhibitor and lyase can be separated on non-denaturing polyacrylamide gels without loss of lyase activity. The activities of phenylalanine ammonia-lyase and cinnamic acid 4-hydroxylase are often concurrently regulated and both have regulatory roles in phenol metabolism; it is suggested that the inhibitor may be specifically involved in controlling their activities in vivo.


Structure and partial genomic sequence of the human retinoblastoma susceptibility gene.
This report describes the genomic organization of the human retinoblastoma susceptibility locus. This gene spans approximately 200 kb of DNA within human chromosome 13, band q14. The previously determined cDNA sequence comprises 27 exons, ranging in size from 31 bp to 1873 bp, and 26 introns, ranging in size from 80 bp to 70,500 bp. We have mapped the positions of the exons and the positions of the recognition sites for six restriction endonucleases. We also present the sequence of 9.2% of the locus (18,335 bp), including approximately 200 bp of intron sequence immediately flanking each exon. This map of a wild-type allele will form the foundation for future studies of mutant, oncogenic alleles at this locus.


The bactericidal activity of ampicillin, amoxicillin, tetracycline, and doxycycline against H. influenzae under various conditions of culture.
The bactericidal activities of ampicillin, amoxicillin, tetracycline, and doxycycline at a concentration of 1 mg/l were compared for 13 strains of H. influenzae with a typical minimal inhibitory concentration of these drugs. Conditions of culture used were: liquid medium in shaken flasks, stationary flasks and stationary tubes, with and without the addition of 30% human serum. Ampicillin and amoxicillin exerted the same bactericidal activity. Survival rates at 5 h were on the average near 1%, however, with large variations. At 24 h survival rate was uniformly below 0.12%. The bactericidal activity of the tetracyclines depended more on the cultural conditions. A marked reduction of the bacterial population below 1% was found at 24 h between 12 of 12 and 5 of 13 strains according to the experimental circumstances. Tetracycline was more bactericidal than doxycycline, especially in the presence of serum.


Interleukin 6 and tumour necrosis factor alpha serum levels in monoclonal gammopathy of undetermined significance.
The objectives of the present study were to compare the interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) serum levels of individuals with monoclonal gammopathy of undetermined significance (MGUS) with those of healthy controls, and to ascertain the predictor value of these cytokines in the evolution from MGUS to multiple myeloma. After a median follow-up of 7 years from the initial cytokine measurements, nine patients with MGUS have evolved to a malignant condition. The actuarial probability of malignant transformation in patients with increased IL-6 and TNF-alpha was not significantly higher than in those with normal values.


Basic principles of cellular organization.
The hypothesis is put forward that the division of the animal body into three germ layers represents not only histological, but also functional specialization, the ectoderm taking over functions through which the animal is in contact with, acted upon or reacts to the external world, the entoderm metabolism and the mesoderm architectural and mechanical organization. This is assumed to mean that the tasks of life have been divided into three large function domains at an early stage of multicellular evolution, each germ layer taking over one domain and developing largely independently of the other two in the further course of phylogeny. The germ layers are autonomous in their own spheres, giving the body, in effect, a tripartite government. The potentiality of conceptual thought is inherent in all germ layers, reaching a high state of development in the entoderm and mesoderm at a much earlier stage of development than in the ectoderm. The animal body, as a whole, is in control of all its biologic activities; it is a self-designing, self-developing and self-perpetuating entity. The control of cellular organization is a mesodermal task.


Intracorneal hematoma after canaloplasty and clear cornea phacoemulsification: surgical management.
This is a case report of intracorneal hematoma after canaloplasty and clear cornea phacoemulsification. A 75-year-old woman presented with primary open angle glaucoma and visually significant cataract. Canaloplasty and clear corneal phacoemulsification were performed. Postoperatively she had an intracorneal hematoma, which was removed through a clear corneal tunnel. Preoperative best-corrected visual acuity (BCVA) was 20/40 in the right eye and mean intraocular pressure (IOP) was 20 mmHg. Uneventful canaloplasty, clear corneal phacoemulsification, and implantation of a posterior chamber intraocular lens were performed. One day after the operation, BCVA was 20/400 in the right eye. The IOP was 8 mmHg. Anterior segment examination revealed a nasally located intrastromal hematoma between corneal stroma and Descemet membrane. The intracorneal hematoma was removed through a clear corneal tunnel. Six months postoperatively, BCVA was 20/25 in the right eye. The IOP with one medication was 17 mmHg. This operation was a minimally invasive technique to remove intrastromal hematocornea after viscocanaloplasty.


Acute effects of exergaming on young adults' energy expenditure, enjoyment, and self-efficacy.
This study investigated the effects of a dance-based exergaming on Chinese college students' energy expenditure, self-efficacy, and enjoyment in comparison with the traditional aerobic dance exercise. Forty young adults (33 females; Mage = 21.55 years, SD = 2.06) completed two separate 20 min exercise sessions with 10 min intervals on the same day: (1) Xbox 360 Kinect Just Dance exergaming session; and (2) a traditional instructor-led aerobic dance exercise session. Participants' energy expenditure (Kcal/session) was measured by the ActiGraph GT9X Link accelerometers, and their perceived self-efficacy and enjoyment were assessed via validated surveys following each session. Dependent t-test indicated significant differences in participants' enjoyment (t = -1.83, p = 0.04). Specifically, participants in the dance-based exergaming session reported a higher level of enjoyment (M = 3.96, SD = 0.65) as compared to the aerobic dance session (M = 3.61, SD = 0.54). However, there was no significant difference in energy expenditure and self-efficacy between the two sessions. Findings suggest that college students had comparable energy expenditure as the traditional aerobic dance session while experiencing more fun and enjoyment. This suggests that exergaming can be a fun exercise alternative for promoting physical activity among young adults.


Understanding the effects of building block rings of π electron-rich organic photocatalysts in CO2 transformation to amino acids.
Understanding the effective factors in the performance of some Oligo (p-phenylenes) (OPPs) and Polycyclic Aromatic Hydrocarbons (PAHs), as efficient organocatalysts in photocatalytic CO2 transformations are the main goals of this investigation. The studies are based on density functional theory (DFT) calculations on the mechanistic aspects of C-C bond formation through a coupling reaction between CO2•- and amine radical. The reaction is performed through two successive single electron transfer steps. After careful kinetic investigations by Marcus' theory rules, powerful descriptors are used to describe the behavior of observed barrier energies of electron transfer steps. The studied PAHs and OPPs consist of different numbers of rings. Thus, it can be considered different charge densities, afforded from π electrons, of PAHs and OPPs that cause distinguished efficiency in kinetic aspects of electron transfer steps. Electrostatic Surface Potential (ESP) analyses reveal a good relationship between the charge density of the studied organocatalysts in single electron transfer (SET) steps and the kinetic parameters of the steps. Moreover, the contribution of rings in the framework of PAHs and OPPs would be another effective factor in the barrier energies of SET steps. Aromatic properties of the rings, studied by the Anisotropy of the Current-Induced Density (ACID), Nucleus-Independent Chemical Shift (NICS), the multi-center bond order (MCBO), and AV1245 Indexes, are the other impressive factors in the role of rings in SET steps. The results show that the aromatic properties of the rings are not similar to each other. Higher aromaticity affords remarkable reluctance of the corresponding ring to participate in SET steps.


Synthesis and chirality analysis of carbocyclic 5'-nor nucleosides.
Achiral carbocyclic "DL-like" 5'-nor nucleosides have been synthesized and analyzed by the chiral capillary electrophoresis to elucidate the "D-like" monomers.


Nuclear phosphatase PPM1G in cellular survival and neural development.
PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown. Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g(-/-) mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g(-/-) embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g(-/-) embryos failed to grow without immortalization while immortalized ppm1g(-/-) fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts. Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival.


A differential pulse polarographic serum protein assay.
Human serum and albumin show a differential pulse polarographic band near -0.6 V. For sufficiently dilute solutions (less than 7 micrograms/ml) at pH 7.0, the polarographic response is linearly related to the solution concentration. At pH 12.6 a near-linear response to 70 micrograms/ml is obtained, but sample equilibration time is slow. The polarographic assay for total serum protein using bovine serum albumin (BSA) to generate a standard curve gave a correlation coefficient of 0.89. The cellular constituents of whole blood do not interfere. The correlation with BSA does not hold for protease-digested serum or albumin.


Modulation of Cancer-Associated Fibrotic Stroma by An Integrin αvβ3 Targeting Protein for Pancreatic Cancer Treatment.
Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapeutics owing to dense fibrotic stroma orchestrated by cancer-associated pancreatic stellate cells (CAPaSC). CAPaSC also support cancer cell growth, metastasis, and resistance to apoptosis. Currently, there is no effective therapy for PDAC that specifically targets CAPaSC. We previously reported a rationally designed protein, ProAgio, that targets integrin αvβ3 at a novel site and induces apoptosis in integrin αvβ3-expressing cells. Because both CAPaSC and angiogenic endothelial cells express high levels of integrin αvβ3, we aimed to analyze the effects of ProAgio in PDAC tumor. Expression of integrin αvβ3 was examined in both patient tissue and cultured cells. The effects of ProAgio on CAPaSC were analyzed using an apoptosis assay kit. The effects of ProAgio in PDAC tumor were studied in 3 murine tumor models: subcutaneous xenograft, genetic engineered (KrasG12D; p53R172H; Pdx1-Cre, GEM-KPC) mice, and an orthotopic KrasG12D; p53R172H; Pdx1-Cre (KPC) model. ProAgio induces apoptosis in CAPaSC. ProAgio treatment significantly prolonged survival of a genetically engineered mouse-KPC and orthotopic KPC mice alone or in combination with gemcitabine (Gem). ProAgio specifically induced apoptosis in CAPaSC, resorbed collagen, and opened collapsed tumor vessels without an increase in angiogenesis in PDAC tumor, enabling drug delivery into the tumor. ProAgio decreased intratumoral insulin-like growth factor 1 levels as a result of depletion of CAPaSC and consequently decreased cytidine deaminase, a Gem metabolism enzyme in cancer cells, and thereby reduced resistance to Gem-induced apoptosis. Our study suggests that ProAgio is an effective PDAC treatment agent because it specifically depletes CAPaSC and eliminates tumor angiogenesis, thereby enhancing drug delivery and Gem efficacy in PDAC tumors.


Accumulation of mtDNA with a mutation at position 3271 in tRNA(Leu)(UUR) gene introduced from a MELAS patient to HeLa cells lacking mtDNA results in progressive inhibition of mitochondrial respiratory function.
A new mitochondrial DNA (mtDNA) mutation of tRNA(Leu)(UUR) at nucleotide position 3271 (MELAS3271) was determined to be involved in the pathogenic process of mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) using intercellular transfer of patient-derived mtDNA to mtDNA-less HeLa cells (rho 0 HeLa cells). Cybrid clones containing imported mtDNA exclusively from a MELAS patient with MELAS3271 mtDNA were isolated, and the influence of MELAS3271 mtDNA on mitochondrial translation activity and mitochondrial respiratory complex I enzyme activity were examined. Accumulation of more than 87% MELAS3271 mutant mtDNA in the cybrid clones induced both low complex I activity and abnormal mtDNA-encoded polypeptide synthesis including at least complex I subunit ND6. suggesting involvement of the new MELAS-associated mutation in the pathogenesis.


Treatment of patients with extreme maxillary atrophy using sinus floor augmentation and implants: preliminary results.
Twenty consecutive patients with extreme maxillary atrophy underwent bilateral sinus floor augmentation, either with autogenous bone from the iliac crest or with a combination of autogenous bone and hydroxyapatite. One patient was treated using autogenous bone from the chin region. After a period of three to eight months, three to four implants were placed in each posterior maxilla. Only 10 out of 155 inserted implants were located in the anterior non-augmented maxilla. During the observation period of one to six years, four implants (one of them located in the anterior maxilla) had to be removed prior to prosthetic treatment. Another three implants were lost during the follow up period. This corresponds to a Kaplan-Meier survival probability of 95.4% after 70 months. No statistically significant difference in implant success was observed between women and men (P=0.16). All prosthetic suprastructures are still in function despite these implant losses. Mean peri-implant bone resorption was 1.34 mm with no statistically significant difference between implants placed more mesially and those placed more distally in the augmented area, though a trend could be observed (P=0.058) for a more pronounced bone resorption around implants placed in the premolar region. When a mean mesial and distal bone resorption of >2 mm was considered in the calculation of the success prognosis, the survival probability dropped to 74.7% after 70 months.


Everyday life experiences of spouses of patients who suffer from pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.
Spouses play a crucial role, both physically and psychologically, for patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Our aim was to investigate the spouse's experiences when living with a partner diagnosed with PAH or CTEPH. We used a qualitative interview study design based on open-ended questions analysed using qualitative content analysis. 14 spouses were interviewed. Two categories that describe spouses' experiences of dealing with everyday life were identified: "Living in an insecure life situation" and "Providing and receiving information and support". The experiences reported by the spouses were that their life situation was insecure, and that they had challenges in providing and receiving information and support. Most spouses also wanted and felt a need to be more involved in the care. The spouses were only partly satisfied with their life situation. To support the spouse's participation, the PAH/CTEPH team should encourage the patient to bring their spouse along, and offer them the opportunity to participate in the contacts with healthcare and provide information on an individual family perspective.


Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis.
Structure analysis and ensemble refinement of the apo-structure of thymidine diphosphate (TDP)-rhamnose 3'-O-methyltransferase reveal a gate for substrate entry and product release. TDP-rhamnose 3'-O-methyltransferase (CalS11) catalyses a 3'-O-methylation of TDP-rhamnose, an intermediate in the biosynthesis of enediyne antitumor antibiotic calicheamicin. CalS11 operates at the sugar nucleotide stage prior to glycosylation step. Here, we present the crystal structure of the apo form of CalS11 at 1.89 Å resolution. We propose that the L2 loop functions as a gate facilitating and/or providing specificity for substrate entry or promoting product release. Ensemble refinement analysis slightly improves the crystallographic refinement statistics and furthermore provides a compelling way to visualize the dynamic model of loop L2, supporting the understanding of its proposed role in catalysis.


Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection.
The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV infection. We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <18 years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 in subjects receiving all doses of treatment and proportion of adverse events in subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses. Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among children with cirrhosis (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.


Zinc binding stabilizes mitochondrial Tim10 in a reduced and import-competent state kinetically.
Tim10 and all the small Tim proteins of the mitochondrial intermembrane space contain a consensus twin CX3C Zn2+-finger motif. While disulphide bond formation between the Cys residues of this motif is essential for complex formation by the small Tim proteins, the specific role of Zn2+-binding during the import and assembly of these proteins is not clear. In this study, we investigated the effects of the biologically relevant thiol-disulphide redox molecule, glutathione, and Zn2+-binding on the oxidative folding of yeast mitochondrial Tim10 using both biochemical and biophysical methods in vitro. We show that, whilst oxidized Tim10 cannot be reduced by reduced glutathione, reduced Tim10 is effectively oxidized at levels of glutathione comparable to those found in the cytosol. The oxidized Tim10 generated in the presence of glutathione is competent for complex formation with its partner protein Tim9, confirming it has a native fold. The standard redox potential of Tim10 at pH 7.4 was determined to be -0.32 V, confirming that Tim10 is a much stronger reductant than glutathione (-0.26 V, at pH 7.4) and could therefore be oxidized rapidly by oxidized glutathione in the cytosol. However, we found that Zn2+-binding can stabilize the reduced Tim10, decreasing the rate of the oxidative folding more than tenfold. In addition, we show that protein disulphide isomerase can catalyse the oxidative folding of Tim10 provided that Zn2+ was removed. We propose that Zn2+-binding is essential to maintain the protein in a reduced and import-competent state in the cytosol, and that zinc has to be removed after the protein is imported into mitochondria to initiate protein oxidative folding and assembly.


Cell-mediated immune response in human hepatic echinococcosis. Analysis of antigen-induced lymphoproliferation and NK activity.
In vitro cellular immune responsiveness was studied in 25 patients undergoing surgery for hepatic hydatid disease and in 22 matched healthy controls. Proliferation of peripheral blood mononuclear cells (PBMC) induced by phytohaemagglutinin (PHA) was not statistically different in the two groups, while proliferation induced by antigenic preparations obtained from the human commensal microorganism Candida albicans was depressed in patients as compared to healthy subjects. Confirming previous data, antigen specific proliferative response to hydatid cyst fluids was greatly enhanced in patients as compared to controls (P less than 0.01). On the other hand, natural killer (NK) activity was significantly reduced (P less than 0.005). Both impairment of NK activity and lymphoproliferation induced by commensal microorganisms suggest that patients following the parasitic infection present a condition of relevant hyporesponsiveness in cell-mediated defence.


Rapid ascents of Mt Everest: normobaric hypoxic preacclimatization.
Acclimatization to high altitude is time consuming. An expedition to Mt Everest (8848 m) requires roughly 8 weeks. Therefore it seems very attractive to reach the summit within 3 weeks from home, which is currently promised by some expedition tour operators. These rapid ascent expeditions are based on two main components, normobaric hypoxic training (NHT) prior to the expedition and the use of high flow supplemental oxygen (HFSO2). We attempted to assess the relative importance of these two elements. We evaluated the effect of NHT on the basis of the available information of these rapid ascent expeditions and our experiences made during an expedition to Manaslu (8163 m) where we used NHT for preacclimatization. To evaluate the effect of an increased O2 flow rate we calculated its effect at various activity levels at altitudes of 8000 m and above. So far rapid ascents to Mt Everest have been successful. The participants carried out 8 weeks of NHT, reaching sleeping altitudes = 7100 m and spent at least 300 h in NH. At rest a flow rate of 2 l O2/min is sufficient to keep the partial pressure of inspired oxygen (PIO2) close to 50 mm Hg even at the summit. For ativities of ~80% of the maximum rate of oxygen consumption (VO2max) at the summit 6 l O2/min are required to maintain a PIO2 above 50 mm Hg. NHT for preacclimatization seems to be the decisive element of the offered rapid ascent expeditions. An increased O2 flow rate of 8 l/min is not mandatory for climbing Mt Everest. Preacclimatization using normobaric hypoxica (NH) is far more important than the use of HFSO2. We think that NHT will be widely used in the future. The most effective regimen of preacclimatization in NH, the duration of each session and the optimal FIO2 are still unclear and require further study.


Isosorbide-5-mononitrate treatment prevents cyclosporin A-induced platelet hyperactivation and the underlying nitric oxide-cyclic guanosine-3',5'-monophosphate disturbances.
The clinical use of cyclosporin A (CsA) is commonly associated with the development of hypertension and increased risk of thromboembolic events. Decreased endothelium-dependent relaxation and increased platelet activation seems to be involved on those side effects, but the underlying mechanisms are not yet elucidated. The present study aimed to evaluate the CsA effect on the platelet NO-cyclic guanosine-3',5'-monophosphate (cGMP) pathway and the putative benefits of concomitant isosorbide-5-mononitrate (IS-5-MN) administration on CsA-induced hypertension and on platelet hyperactivation. Blood pressures, platelet NO synthase activity and cGMP content, intracellular free calcium concentration ([Ca2+]i) and whole blood platelet aggregation were assessed in three rat groups orally treated, during 7 weeks, with the following diets: orange juice (control group), 5 mg/kg/day of CsA (CsA group) and 150 mg/kg/day, b.i.d., of IS-5-MN for 2 weeks and IS-5-MN plus 5 mg/kg/day of CsA for 7 weeks (IS-5-MN+CsA group). IS-5-MN treatment has prevented hypertension development obtained in the solely CsA-treated rats. CsA treatment has inhibited NOS activity, which was reverted by the concomitant IS-5-MN and CsA administration. On the contrary, platelets from CsA-treated rats had cGMP content increased when compared with the control rats. The variation obtained when ISMN was present was less predominant. Therefore, the organic nitrate treatment has prevented platelet hyperactivation, namely, by decreasing thrombin-evoked [Ca2+]i and collagen-evoked platelet aggregation, when compared with the solely CsA-treated group. The preventive effect of IS-5-MN was reinforced by electron microscopy studies of platelet activation. By increasing [Ca2+]i and aggregation, CsA induces platelet hyperactivation and simultaneously increases cGMP content, which might represent a compensatory inhibitory mechanism. The concomitant IS-5-MN treatment prevents the above-mentioned platelet hyperreactivity and tends to normalize the NO-cGMP pathway as well as the development of hypertension.


On derivation of spectral sensitivities of the human cones from trichromatic colour matching functions.
Despite the recent advance made by using the direct methods of retinal densitometry, microspectrophotometry and suction electrophysiology, the psychophysical approach based on colour matching data still remains an important source of accurate information about the spectral sensitivity of the cone photoreceptors in the human visual system. However, the commonly used technique of estimating cone sensitivities, based on the assumption that dichromacy is caused by the lack of one of the three types of the cone photoreceptors, requires the colour matching functions not only from trichromatic observers but from dichromats as well. Here we evaluate an alternative approach, originally put forward by Bongard and Smimov, that derives cone spectral sensitivities from colour matching functions only; without resorting to colour deficiency or any other data. When applied to CIE standard colour matching functions, this method yields curves of spectral sensitivities that are close to the classical Smith-Pokorny fundamentals, though the long-wave cone is shifted towards the short-wave region of the spectrum by 5 nm, as compared with Smith and Pokorny's results.


Inadequacy of diagnosis related group (DRG) reimbursements for limb salvage lower extremity arterial reconstructions. Ad hoc committee of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery.
Prospective cost and reimbursement data were collected from 10 centers in various parts of the United States on 566 patients undergoing lower extremity arterial reconstructions for limb salvage and nonlimb salvage indications. Information for each patient was available on indication and type of procedure, length of stay, the type of hospital insurance, and hospital costs/charges. Diagnosis related group payments from each center were used to determine net gain or loss for each patient. Patients were classified as having claudication or critical ischemia (limb salvage). Reimbursements matched costs/charges for the claudication group; overall mean loss in this group was only $915 per patient. However, all centers had important losses in the limb salvage group. Reimbursements averaged 60% of costs/charges, with a mean loss of $8158 per patient and an overall loss for all 10 centers of $3,653,918. An effort to remedy this inequity is progressing via a dialogue between representatives of the Society for Vascular Surgery, the North American Chapter of the International Society for Cardiovascular Surgery, and the federal government.


Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis.
Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient.


Ganglioside-induced acceleration of axonal transport following nerve crush injury in the rat.
The role of gangliosides in the re-establishment of neuronal continuity was examined in rats whose peroneal nerve had been crushed by a standardized procedure. Neuronal continuity was determined by the ability of the nerve to transport horseradish peroxidase retrogradely back to the spinal cord. The number of retrogradely labeled neurons provided an index of the degree of axonal transport that was re-established. Comparison of ganglioside-treated animals with saline-treated controls showed that ganglioside treatment advanced the re-establishment of retrograde axonal transport by 3 days.


PSYCHIATRIC COMORBIDITY DOES NOT ONLY DEPEND ON DIAGNOSTIC THRESHOLDS: AN ILLUSTRATION WITH MAJOR DEPRESSIVE DISORDER AND GENERALIZED ANXIETY DISORDER.
High rates of psychiatric comorbidity are subject of debate: To what extent do they depend on classification choices such as diagnostic thresholds? This paper investigates the influence of different thresholds on rates of comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD). Point prevalence of comorbidity between MDD and GAD was measured in 74,092 subjects from the general population (LifeLines) according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria. Comorbidity rates were compared for different thresholds by varying the number of necessary criteria from ≥ 1 to all nine symptoms for MDD, and from ≥ 1 to all seven symptoms for GAD. According to DSM thresholds, 0.86% had MDD only, 2.96% GAD only, and 1.14% both MDD and GAD (odds ratio (OR) 42.6). Lower thresholds for MDD led to higher rates of comorbidity (1.44% for ≥ 4 of nine MDD symptoms, OR 34.4), whereas lower thresholds for GAD hardly influenced comorbidity (1.16% for ≥ 3 of seven GAD symptoms, OR 38.8). Specific patterns in the distribution of symptoms within the population explained this finding: 37.3% of subjects with core criteria of MDD and GAD reported subthreshold MDD symptoms, whereas only 7.6% reported subthreshold GAD symptoms. Lower thresholds for MDD increased comorbidity with GAD, but not vice versa, owing to specific symptom patterns in the population. Generally, comorbidity rates result from both empirical symptom distributions and classification choices and cannot be reduced to either of these exclusively. This insight invites further research into the formation of disease concepts that allow for reliable predictions and targeted therapeutic interventions.


Pacing induced mitral regurgitation following radiofrequency ablation of the atrioventricular conduction system: case report and potential mechanism.
We describe a patient with hemodynamic deterioration and worsening mitral regurgitation related to right ventricular apex pacing. Time-dependent changes in papillary muscle contraction as well as ventricular remodeling by right ventricular apex pacing might be responsible for this rare but serious complication.


Psychotic symptoms and violent behaviors: probing the components of "threat/control-override" symptoms.
Evidence for an association between mental illness and violence has grown in recent years, leading many to ask why such an association exists. One hypothesis links elevated rates of violence among people with mental illness to a small set of psychotic symptoms--so called threat/control-override (TCO) symptoms. Several studies have supported this hypothesis, but none has examined which of the components, threat or control-override--if either--predominates in explaining violence. To explore this issue we used data from a two-stage epidemiological study (n = 2741) conducted in Israel. Data on TCO symptoms were collected using two methods--fixed-format self-report questions from the first stage and psychiatrists' ratings based on interviews using the Schedule for Affective Disorders and Schizophrenia (SADS) from the second. Results show that both a measure of threat and a measure of control-override are independently associated with violent behaviors. Results also show that neither method--neither fixed-format questions nor psychiatrist rating--predominates in explaining violence. In sum, these results indicate that both the threat and the control-override components of the TCO concept are useful in predicting violent behaviors and that a better measurement of the TCO concept is achieved using a multimethod approach.


Extrarenal transplant artery pseudoaneurysm: a combined therapeutic approach.
Extrarenal transplant pseudoaneurysms are rare, and treatment usually involves sacrificing of the transplant kidney. We report a case where combined use of a thrombotic agent and covered stents successfully excluded a pseudoaneurysm while preserving renal function.


HRSA's PEPFAR-Supported Resilient and Responsive Health Systems Initiative in Liberia.
During the 2014-16 Ebola outbreak, Liberia suffered 2,544 deaths, including 8% of its doctors, nurses and midwives. The Government responded in 2016 with a seven-year Health Workforce Program (HWP), the goal of which was "the creation of a fit-for-purpose, motivated, and highly-skilled workforce." The US Health Resources and Services Administration (HRSA) with the support from the US President's Emergency Plan for AIDS Relief (PEPFAR), established Resilient and Responsive Health Systems project to assist Liberia in strengthening health workforce and health systems. As the HWP approaches its final year, progress the numbers and skills of physicians, nurses and midwives have improved, through national and global support, and there have been some improvements in the overall health system. Improving health for everyone in Liberia is an ongoing process that requires continuing support and collaboration from national and global partners including US government agencies, UN agencies, academic and training institutions, private foundations, regional networks, and especially the people of Liberia.


Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability.
Vessel growth is often associated with ischemia. VEGF, a potent angiogenic factor, has been shown to be induced by low oxygen concentrations. These studies were conducted to investigate the molecular basis of the hypoxia-induced increase in VEGF mRNA. Run-on analysis of VEGF revealed a minimal increase in the rate of gene transcription in a human retinal epithelial cell line grown under hypoxic conditions. Examination of VEGF mRNA stability revealed that the half-life of VEGF transcripts under normoxia was short, 30-45 min, but was dramatically increased to 6-8 h in cells grown under hypoxia. Cobalt chloride, which elevates VEGF and has been suggested to be similar to hypoxia in its mechanism of action, had only a slight effect on decay rate. We postulate that hypoxia-induced increases in mRNA stability provide the sustained increases in VEGF mRNA levels necessary to support a neovascular response.


The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.
Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P < .0001). A radiation dose of >45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age < or = 70 years, absence of dyspnea or dysphagia at presentation, a tumor size < or = 5 cm, and any surgical resection improved survival (P < .05). Candidates for surgery with curative intent for ATC are patients < or = 70 years, tumors < or = 5 cm, and no distant disease. Radiotherapy >45 Gy improves outcome.


Carotid sinus syndrome in parapharyngeal tumours.
We describe three cases of metastatic carcinoma in the parapharyngeal space associated with the Carotid Sinus Syndrome. This has not been previously described.


Primary intracranial haemangiopericytoma: comparison of survival outcomes and metastatic potential in WHO grade II and III variants.
Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours with a high propensity for local recurrence and distant metastasis. Optimal treatment includes maximal surgical resection followed by adjuvant radiotherapy. In 2007, new histopathological grading criteria were introduced to differentiate between high grade (World Health Organization [WHO] grade III) and low grade (WHO grade II) tumours. Given the rarity of this tumour, there is a paucity of information regarding the prognostic significance of histological grade. We conducted a retrospective review of our 20 year experience in treating 27 patients with HPC at our institution. Statistical analysis to compare overall survival, local recurrence rate and metastatic potential between the two grades were conducted using Kaplan-Meier analysis. The estimated median survival for grade II HPC was 216 months and for grade III tumours was 142 months. On multivariate analysis, grade II tumours were associated with better survival than grade III lesions (hazard ratio=0.16, 95% confidence interval 0.26-0.95; p=0.044). During the study period, 33% of grade III tumours developed local recurrence compared to 21% of grade II tumours. Metastases were found in 36% of grade II patients and 25% of grade III patients. There was no significant statistical difference in local recurrence rate and metastasis between the two grades. Higher histological grading in HPC is associated with worse overall survival. However based on our series higher histological grading is not associated with higher local recurrence or distant metastatic rates.


Surgical resection of an epileptogenic cortical dysplasia in the deep foot sensorimotor area.
Epileptogenic foci in the foot/leg motor area of cortex are rarely resected, due to the risks of the surgical procedures. A 31-year-old right-handed man with cortical dysplasia deep in the central sulcus suffered from disturbances in walking due to frequent daily seizures. Following subdural electrode implantation to define the epileptogenic area and assess cortical function, limited regions of cortex were removed from the foot/leg primary motor and sensory areas under local anesthesia until the epileptiform discharges disappeared. Postoperative motor weakness and sensory disturbances completely resolved within 2 weeks and 2 months, respectively; the patient has been free from seizures for more than a year and a half postsurgery. Intraoperative examination demonstrated that small and moderate cortical dysplasia in the depths of the central sulcus exhibits both intrinsic epileptogenicity and function. Focused resection of the lower extremity of the sensorimotor area may be a surgical strategy for intractable epilepsy if resolution of clinical symptoms with minimal dysfunction due to the limited size of the resection is expected to follow surgery.


Evaluation of the psychometric properties and clinical applications of the Timed Up and Go test in Parkinson disease: a systematic review.
To review and systematically summarize the psychometric and clinical properties (reliability, validity, responsiveness) of the Timed Up and Go test applied to persons diagnosed with Parkinson disease. A systematic review was performed by screening four scientific databases (MED-LINE, CINAHL, and PubMed). Independent reviewers selected and extracted data from articles that assessed the reliability, validity, sensitivity to change, and/or clinical properties of the Timed Up and Go test in persons with Parkinson disease. Twenty-four studies were selected. Nine analyzed reliability and yielded "good" to "moderate" scores. Seventeen used a range of different contrast tests to assess validity of the Timed Up and Go test and found "good" quality scores in those that assessed balance. Only two studies analyzed sensitivity to change and they reported "poor" quality scores. The use of Timed Up and Go in Parkinson disease patients presents good reliability and validity (when compared to tests that assess balance).


In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.
Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes.


Inhaled beta2-agonists for treating non-specific chronic cough in children.
The pathophysiology of so called 'cough variant asthma' has not received a great deal of research interest and opinion lies divided as to whether it is really asthma or not. The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma To determine the effectiveness of inhaled ss2 agonists in non-specific chronic cough in children over the age of 2 years. The Cochrane Airways Group database (including MEDLINE, EMBASE and CINAHL) and the Cochrane Controlled Trials Register (CCRT) were searched. Additional searching included hand searching of medical journals through the Cochrane Collaboration, references, references of references listed in primary sources and personal communication with authors. In addition "Grey literature" including theses, internal reports, non-peer reviewed journals were sought. All randomised (randomised and quasi-randomised) controlled clinical trials in which inhaled ss2 agonists were given for chronic cough in children over 2 years of age were included. Two reviewers independently assessed articles for inclusion and methodological quality. Data for trials of salbutamol versus placebo were extracted by both reviewers and entered into the Cochrane Collaboration software program Review Manager, version 4.2 In children presenting with isolated chronic cough there was no significant difference between salbutamol treated group and placebo group. Salbutamol was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively.


7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease.
Increasing evidence suggests that reductions in brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) may have a role in the pathogenesis of Alzheimer's disease (AD). However, the efficacy and safety profile of BDNF therapy (eg, gene delivery) remains to be established toward clinical trials. Here, we evaluated the effects of 7,8-dihydroxyflavone (7,8-DHF), a recently identified small-molecule TrkB agonist that can pass the blood-brain barrier, in the 5XFAD transgenic mouse model of AD. 5XFAD mice at 12-15 months of age and non-transgenic littermate controls received systemic administration of 7,8-DHF (5 mg/kg, i.p.) once daily for 10 consecutive days. We found that 7,8-DHF rescued memory deficits of 5XFAD mice in the spontaneous alternation Y-maze task. 5XFAD mice showed impairments in the hippocampal BDNF-TrkB pathway, as evidenced by significant reductions in BDNF, TrkB receptors, and phosphorylated TrkB. 7,8-DHF restored deficient TrkB signaling in 5XFAD mice without affecting endogenous BDNF levels. Meanwhile, 5XFAD mice exhibited elevations in the β-secretase enzyme (BACE1) that initiates amyloid-β (Aβ) generation, as observed in sporadic AD. Interestingly, 7,8-DHF blocked BACE1 elevations and lowered levels of the β-secretase-cleaved C-terminal fragment of amyloid precursor protein (C99), Aβ40, and Aβ42 in 5XFAD mouse brains. Furthermore, BACE1 expression was decreased by 7,8-DHF in wild-type mice, suggesting that BDNF-TrkB signaling is also important for downregulating baseline levels of BACE1. Together, our findings indicate that TrkB activation with systemic 7,8-DHF can ameliorate AD-associated memory deficits, which may be, at least in part, attributable to reductions in BACE1 expression and β-amyloidogenesis.


Weight outcomes for adolescents with atypical anorexia nervosa in family-based treatment.
Although over one-third of adolescents presenting with restrictive eating disorders have a history of being overweight, there is no evidence-based treatment for atypical anorexia nervosa (AAN). Family-Based Treatment (FBT) is a feasible treatment and is routinely applied to treat atypical anorexia nervosa in adolescents; however, identifying a treatment target weight within FBT for these patients is a challenge. This study aimed to 1) increase understanding regarding recommendations for weight gain versus weight stabilization in FBT for adolescents with AAN and 2) examine treatment outcomes in FBT for adolescents with AAN. Using a retrospective design, we reviewed the files of 41 patients with AAN who were referred for FBT at a pediatric eating disorder program located within a tertiary care health centre. We found variability in recommendations for weight gain, with 56% of the sample recommended to gain weight and 44% recommended to stabilize weight. Baseline BMI for age appeared to be a key factor in establishing recommendations for weight gain. AAN patients in our sample gained a significant amount of weight across treatment, with those recommended to gain weight showing more weight gain during treatment. Forty-nine percent of the sample completed FBT; those patients displayed a mean of 10kg of weight gain during treatment. Findings suggest that many patients gained weight during the course of FBT for AAN. Further study on weight changes during FBT for adolescents with AAN and increased diagnostic consistency for AAN will be important for this field.


The effect of progestin on rabbit endometrial aromatase activity.
The ability of rabbit endometrium to synthesize estrogen was investigated. Aromatase activity was measured by incubating the viable tissue fragments with [3H] testosterone at 37 degrees C and quantitated the [3H]estrogens at the end of 6 h incubation. The activity was not detectable in endometrium and myometrium of non-pregnant rabbits. In pregnant rabbit, the activity increased from 2 to 12 fmol/h/g of tissue in endometrium obtained from both gravid and nongravid uterine horns 4-8 days after mating. Aromatase activity in endometrium at implanted sites on the 8th day after mating reached up to 550 fmol/h/g of tissue. Hormonal regulation of the aromatase activity was studied directly in cultured rabbit endometrial stromal cells. Both progesterone and medroxyprogesterone acetate stimulated the activity with 2- to 25-fold increase over the control values (0.2-1 fmol/h/mg protein). The stimulation of aromatase activity by progestin was found to be both time- and dose-dependent. Estrogen, Bu2cAMP, forskolin, HCG or relaxin had no effect on the activity. Aromatase activity in glandular epithelial cells was neither detectable nor affected by progestin. These results indicate that aromatase activity in rabbit endometrium is concentrated in stromal cells and progestin stimulates the activity. However, estrogen, forskolin and relaxin which enhanced the stimulation of the activity by progestin in human endometrium had no effect on aromatase in rabbit endometrium. The increase of aromatase activity observed after the onset of conception may be physiologically important to increase the local estrogen content for decidualization of the endometrium.


Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen.
To compare standard nurse-based pain therapy with a patient-controlled analgesia (PCA) regimen. Prospective, randomized study. Single-institutional, clinical investigation in an urban, university-affiliated hospital. Sixty patients undergoing elective first-time cardiac surgery were included. In 30 patients, a standard analgesic regimen was used, and in 30 patients, a PCA regimen was used. The perioperative and postoperative management was similar for all patients. Degree of sedation, satisfaction, and pain (by visual analog scale [VAS]) was assessed within the first 3 postoperative days. Vital capacity (VC) and forced expiratory volume in 1 second (FEV1) were measured using a portable spirometry system. Cortisol and troponin T (TnT) plasma levels were also measured. The expectation of pain was similar in both groups, and the postoperative pain score was significantly lower in the PCA than in the standard group throughout the study period. Significantly more piritramid was used in the PCA (total, 75.6 +/- 33.4 mg) than in the standard group (total, 20.1 +/- 31.9 mg). VC and FEV1 were significantly lower in the standard group compared with the PCA patients. Cortisol and TnT plasma levels were similar in both groups. Frequency of side effects were similar for both groups. Because of the beneficial effects with regard to degree of pain and satisfaction, pain management using PCA systems can be recommended for cardiac surgery patients. It appears to be superior to standard nurse-based pain therapy.


Adverse Effects of Glycemia-Lowering Medications in Type 2 Diabetes.
Treatment of patients with type 2 diabetes mellitus is focused on preventing the occurrence and delaying the development of macro- and micro-vascular complications. Glycemic control can help prevent these complications, but there is concern about the adverse effects of glycemia-lowering medications. A rational approach is to balance the desired low risk of adverse events against the unwanted higher risk of major complications resulting from suboptimal glucose control. Using the above approach, approved glucose-lowering agents have favorable benefit-to-risk profiles for use in most patients with type 2 diabetes. We first briefly review the mechanism of actions and benefits of the different commonly used classes of glycemia-lowering medications and then discuss adverse effects and safety concern associated with their use. Our overall assessment is that if used appropriately, the different classes of glycemia-lowering medications offer beneficial outcomes with relatively modest and, in some instances, preventable adverse events.


Periodontal parameters and BANA test in patients with chronic renal failure undergoing hemodialysis.
The aim of this study was to analyze the periodontal parameters of patients with chronic renal failure. The periodontal status of 16 Brazilian patients aged 29 to 53 (41.7 ± 7.2) years with chronic renal failure (CRF) and another matched group of 14 healthy controls with periodontitis was assessed clinically and microbiologically. Probing pocket depth (PPD), gingival recession (GR), dental plaque index (PLI), gingival index (GI), and dental calculus index (CI) were the clinical parameters recorded for the entire dentition (at least 19 teeth), while the anaerobic periodontopathogen colonization in four sites with the highest PPD was evaluated using the BANA test ("PerioScan"; Oral B). The results for the CRF group and control group, respectively were: PPD: 1.77 ± 0.32 and 2.65 ± 0.53; GR: 0.58 ± 0.56 and 0.51 ± 0.36; PLI: 1.64 ± 0.56 and 1.24 ± 0.67; GI: 0.64 ± 0.42 and 0.93 ± 0.50; CI: 1.17 ± 0.54 and 0.87 ± 0.52. Comparison between groups using the "t" test revealed a significantly increased PPD (p<0.001) in the control group. Comparison of the other clinicial parameters by the Mann-Whitney test showed differences only for PLI, which was significantly higher (p<0.05) in the CRF group. Spearman's test applied to each group showed a positive correlation among all clinical parameters, except for GR (p<0.05). None of the groups showed any correlation between GR and GI, while a significant negative correlation between GR and PPD was observed for the CRF group. The percentage of BANA-positive sites was 35.9% for the CRF group and 35.7% for the control group. The BANA test correlated positively with PPD only in the control group and with GR only in the CRF group. In spite of a higher PLI and dense anaerobic microbial population even in shallow PPD, patients with CRF exhibited better periodontal conditions than periodontitis patients, which is an evidence of altered response to local irritants.


Technology outcome measures in neuromuscular disorders: A systematic review.
Portable and wearable devices can monitor a number of physical performances and lately have been applied to patients with neuromuscular disorders (NMDs). We performed a systematic search of literature databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) principles, including all studies reporting the use of technological devices for motor function assessment in NMDs from 2000 to 2021. We also summarized the evidence on measurement properties (validity, reliability, responsiveness) of the analyzed technological outcome measures. One hundred studies fulfilled the selection criteria, most of them published in the past 10 years. We defined four categories that gathered similar technologies: gait analysis tools, for clinical assessment of pace and posture; continuous monitoring of physical activity with inertial sensors, which allow "unsupervised" activity assessment; upper limb evaluation tools, including Kinect-based outcome measures to assess the reachable workspace; and new muscle strength assessment tools, such as Myotools. Inertial sensors have the evident advantage of being applied in the "in-home" setting, which has become especially appealing during the COVID-19 pandemic, although poor evidence from psychometric property assessment and results of the analyzed studies may limit their research application. Both Kinect-based outcome measures and Myotools have already been validated in multicenter studies and different NMDs, showing excellent characteristics for application in clinical trials. This overview is intended to raise awareness on the potential of the different technology outcome measures in the neuromuscular field and to be an informative source for the design of future clinical trials, particularly in the era of telemedicine.


Context effects in recognition memory: the role of familiarity and recollection.
A variant of the process dissociation procedure was coupled with a manipulation of response signal lag to assess whether manipulations of context affect one or both of the familiarity and search processes described by the dual process model of recognition. Participants studied a list of word pairs (context+target) followed by a recognition test with target words presented in the same or different context, and in the same or different form as study (singular/plural). Participants were asked to recognize any target word regardless of changes to form (inclusion), or to only recognise words that were presented in the same form (exclusion). The standard context reinstatement effect was evident even at the short response lags. Analyses of the estimates of the contributions of familiarity and search processes suggest that the context effect demonstrated here can be attributed in part to the influence of familiarity on recognition, whereas the effect on recollection was less clear.


Is post-trabeculectomy serous choroidal detachment a risk factor for failure in the long term.
To investigate the long-term effect of serous choroidal detachment on the success of trabeculectomy in glaucoma patients. In this case-control study, 17 patients who underwent trabeculectomy and developed choroidal detachment, and completed at least 3 years of follow-up were included. The controls were matched based on age, sex, preoperative intraocular pressure, and glaucoma type, and lack of choroidal detachment. Surgical success was defined based on two definitions of 5 < IOP < 16 and 20% reduction from the baseline and no need for further glaucoma surgery and all the same but 5 < IOP < 22. The mean estimated duration of survival ±SD was 2.73 ± 0.35 years (CI 95% 2.1, 3.4), which was significantly shorter than 3.98 ± 0.38 years (CI 95% 3.3, 4.7) in the control group. (LogRank = 5.03 p = 0.02). Cumulative probability of success was 76.5%, 52.9%, 29.4%, 17.6%, and 11.8% in year 1, 2, 3, 4, and 5 in the case group, respectively. Corresponding values were 88.2%, 82.4%, 68.6%, 58.8%, and 47.1%. In the control group, respectively. At baseline, average IOP was 22.3 ± 2.7 and 23.8 ± 8.3 mmHg in the case and control groups, respectively (p = 0.17). Mean IOP was significantly higher in the case group than in the control group in years 2, 3, 4, and 5. Serous choroidal detachment affects the long-term surgical success of trabeculectomy, especially in patients with advanced glaucoma when lower target pressure is required.


[Training program for vitreoretinal surgery in Nairobi, Kenya from 2000 - 2006].
After the U. S. Embassy bombing in 1998 in Nairobi, Kenya, a relief operation was immediately initiated by the Department of Ophthalmology of the Ludwig Maximilians University (LMU) Munich, Germany. Surgical devices and material (such as a vitrectomy unit, silicon oil, perfluorodecalin, intraocular lenses, sutures) were supplied to operate on 42 ocular-injured victims of this bombing attack. Apart from these specific operations in Kenya, there is a big need for vitreoretinal surgery in East Africa, as in all other developing countries. Therefore, a vitreoretinal training program was started in 2000 in Nairobi, Kenya. We report about the first 7 years of collaboration between the Ludwig Maximilians University of Munich, Germany and the University of Nairobi in cooperation with the Kenyatta National Hospital, Kenya. The training program was based on an annual project week in which the author (CLS) carried out vitreoretinal surgery himself and assisted and supervised surgery done by the local Kenyan colleagues at the Kenyatta National Hospital. Within the observation period of the present work (2000 - 2006) the following data were collected: number and kind of surgery, indications, surgeons, grading of eye pathology and the surgical procedure, time to prepare for surgery and duration of surgery. In total, 293 vitreoretinal surgeries were performed during the observation period. Surgeries carried out by the local Kenyan colleagues independently, without intervention of the author, increased from 29.4 % (2000) to 78.6 % (2006). Due to a constant development in the learning process during the project week more severe cases were treated and preparation time for surgery from the nursing side has shortened. By initiating a project week with high frequency surgery, supported by a highly experienced visiting surgeon, vitreoretinal surgery can be successfully set up in an ophthalmic clinic of a developing country. This approach has some advantages when compared to long-period projects, especially for the purposes of sustainability. However, to be successful it requires systematic planning which is described in this article.


Persistence of host Langerhans cells following allogeneic bone marrow transplantation: possible relationship with acute graft-versus-host disease.
Langerhans cells (LC) are bone marrow-derived dendritic antigen-presenting cells found in the epidermis. In an effort to determine the origin (host versus donor) of LC at different intervals following bone marrow transplantation, we performed skin biopsies in 16 recipients of sex-mismatched marrow. LC were identified using monoclonal antibody OKT6 in an indirect immunoperoxidase assay and their donor or host origin determined according to the presence or absence of Y body. The presence of Y-positive (donor) LC could be demonstrated in all (6/6) skin biopsies of female recipients of male marrow tested between days 39 and 730 post-transplant. Persistence of host LC in male recipients of female marrow was documented in all (6/6) recipients studied on day 39 and in two out of seven patients tested on day 120 post-transplant. From day 365 onward, no residual host LC could be detected, suggesting that by this time all epidermal LC are donor-derived. Our study demonstrates that host LC usually persist for 39 and up to 120 d following bone marrow transplantation. The relevance of this observation to the possible role of LC and other host dendritic antigen-presenting cells in the graft-versus-host reaction is discussed.


Non-canonical odor coding in the mosquito.
Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demonstrates that the broad ligand-sensitivity of mosquito olfactory neurons depends on this non-canonical co-expression. The redundancy afforded by an olfactory system in which neurons co-express multiple chemosensory receptors may increase the robustness of the mosquito olfactory system and explain our long-standing inability to disrupt the detection of humans by mosquitoes.


Ceramic coating improves tibial component fixation in total knee arthroplasty.
Forty uncemented total knee arthroplasties (36 patients) were randomly allocated to a Miller-Galante II prosthesis with or without hydroxyapatite/tricalcium phosphate (HA/TCP) coating on the titanium fiber mesh on the undersurface of the tibial component. The patients were followed for 2 years with repeated radiostereometric examinations. After 2 years, the HA/TCP tibial components displayed smaller anterior-posterior tilt and less subsidence. The mean value of maximal total point motion was small: 0.5 mm in both groups. At 24 months, there were more radiolucent lines under the tibial tray and around the stem in the uncoated group, but the clinical results did not differ. HA/TCP coating on the undersurface of the tibial component improved the stability and seemed to improve the quality of the interface between the tibial component and the bone.


Phosphate administration increases both size and number of parathyroid cells in adult rats.
Phosphate administration increases both parathyroid hormone (PTH) secretion and parathyroid size in rats, but the relative contribution of hypertrophy and hyperplasia is unknown. Accordingly, we reexamined parathyroid histology in a previously published experiment [6], quantitatively rather than qualitatively. Ninety female Long-Evans rats were divided into six groups; three were given a normal diet, and three a high phosphate diet (Ca/P 1:7). One group from each arm was killed after 1, 2, and 3 months. Quantitative microscopy was performed on the parathyroid section with the largest area from each animal, without knowledge of its experimental status. Total gland area and total number of cell profiles did not change significantly in the control rats, but increased progressively in the phosphate-loaded rats. At 3 months, the difference was +194% for gland area and+151% for profile number (P < 0.0001), much more than could be accounted for by suppression of apoptosis. Mean nuclear profile area and mean cell profile area (including associated connective tissue as well as cytoplasm) were both significantly increased at 1 month (P < 0.0001). The differences persisted, but their magnitudes (about +16%) did not change further. This time course was consistent with the morphologic expression of increased PTH secretory activity. We conclude that phosphate administration to adult rats increases both size and number of parathyroid cells, the latter due to increased cell proliferation. Phosphate-stimulated parathyroid growth could be due to either hypocalcemia or decreased calcitriol production; increased cell division may also be linked to increased hormone secretion, regardless of its cause. The relative importance of these different mechanisms remains to be determined.


Helix-helix packing angle preferences for finite helix axes.
Recently, James Bowie addressed the question of how to normalize correctly the distribution of observed helix-helix packing angles in proteins (Bowie, Nature Struct. Biol. 4:915-917, 1997). A hitherto unrealized yet significant bias toward crossed packing angles was revealed. However, the derived random reference distribution of packing angles requires that helices have to be assumed as infinite in length. Here, we complement Bowie's analysis by consideration of the more realistic case where helices are of finite length. As a result, the statistical bias toward near perpendicular packings appears to be even stronger.


Primary ovarian pregnancy two years after bilateral tubal ligation. A case report.
This is the first documented case of intrafollicular ovarian pregnancy following bilateral tubal ligation. The patency of the previously ligated tube was demonstrated by hysterosalpinography. It appears that the incidence of ovarian pregnancy is not related to the rising incidence of tubal pregnancy.


Bionic effects of nano hydroxyapatite dentifrice on demineralised surface of enamel post orthodontic debonding: in-vivo split mouth study.
Orthodontic debonding procedure produces inevitable enamel surface alterations, sequelae to which are enamel demineralization, sensitivity and retention of pigments. Several agents have been employed to counterbalance the same. The purpose of this study was (1) To evaluate the hypothesis that no significant difference exists in the remineralising potential of nano hydroxyapatite (NanoHAP) dentifrice and fluoridated dentifrice after orthodontic debonding, (2) To estimate the enamel topographic parameters following use of nano HAP dentifrice, post orthodontic debonding. Sixty upper first bi-cuspids (30 subjects) planned for therapeutic extraction for the orthodontic treatment were bonded with a light cured adhesive. Envelope method of randomisation was followed in this prospective in-vivo study. In each subject, one of the first premolar brackets was debonded using a debonding plier and polished following standard protocols. Envelope method of randomisation was used to determine the side of the premolar to be debonded first. Patient was advised to use fluoridated (Group I) dentifrice for the first 15 days, then the first premolar was covered with a heavy-bodied putty cap, extracted and subjected to atomic force microscopy (AFM). Contralateral first premolar was then debonded and polished using similar protocol, and patient was advised to use nano hydroxyapatite dentifrice (Group II) for next 15 days. The premolar was then extracted and analyzed for surface roughness using AFM. The remineralizing potential of dentifrices was assessed by evaluating surface roughness parameters of the two groups and were compared using a two-sample t test. A significant difference was found amongst Group I (Fluoridated dentifrice) and Group II (NanoHAP dentifrice) (p > 0.001***) for enamel surface roughness variables which reflect remineralising potential of dentifrices. Group II showed significantly lesser value of surface roughness characteristics. NanoHAP dentifrice was shown, after 15 days, to be superior to fluoridated dentifrice in remineralising enamel post orthodontic debonding.


Right- and left-sided carcinoid heart disease without intracardiac shunting.
We present a case of a 54-year-old man with carcinoid heart disease and mitral valve involvement. He had hepatic carcinoid with an extremely elevated urinary excretion of 5-hydroxyindole acetic acid and was referred to our division for shortness of breath and leg edema. Transthoracic echocardiography showed the thickened and retracted tricuspid valve leaflets and severe tricuspid regurgitation. Moderate mitral regurgitation was observed, with the involvement of mitral valve leaflets. A patent foramen ovale was not detected on transesophageal echocardiography. The extremely high concentration of circulating serotonin and/or other vasoactive substances may have contributed to left- as well as right-sided carcinoid heart disease.


Density compensation in island avifaunas.
This paper analyzes factors which determine the extent of density compensation on islands; i.e., is the summed population density of all species on an island equal to the summed mainland density? A graphical analysis allows quantitative comparisons of density compensation studies. Two hypotheses which are generally applicable predict the extent of density compensation on islands: (1) Niche theory predicts that summed population densities should be low if island species number is low. (2) The "habitat appropriateness" hypothesis predicts that summed population densities should be low if island populations occupy unfamiliar habitat. Both hypotheses successfully explain variability in the extent of density compensation on islands. Relative to the mainland, summed population densities on islands are high when islands support a large number of species and those species occupy familiar habitats. Summed population densities on islands are low when islands support few species and those species occupy novel habitats.


A new nucleoside derivative, AJP117510, as an inhibitor of integrin alpha2beta1-collagen binding.
A new nucleoside derivative, AJP117510 (1) was isolated from unidentified fungus AJ117510. The structure of 1 was elucidated by spectroscopic analyses. Nucleoside 1 inhibited the binding of integrin alpha2beta1 to collagen in a dose dependent manner with an IC50 value of 5.9 microM.


A Novel Device for Closed Reduction and Percutaneous Fixation of Thoracolumbar Fractures.
Open surgical reduction/fixation of thoracolumbar fractures results in significant soft-tissue trauma and related complications. Minimally-invasive technical developments could deliver similar radiological outcomes, while avoiding the related complications. We evaluated radiological and perioperative outcomes in thoracolumbar fractures by using a novel minimally-invasive device. Twenty-six patients with 29 thoracolumbar fractures using the NForce device were analyzed. Postoperative reduction and alignment were assessed by radiographic measurement of the local kyphosis angle (LKA) up until a follow-up period of 9 months. Postoperative imaging revealed an average reduction of traumatic kyphosis of 8.25° (±7.72°) with an average postoperative LKA of 3.24° (±8.97°). The highest degree of reduction was 27.39°. The mean LKA had increased to 5.08° (±5.17°) at 3 months postoperative, 5.43° (±4.32°) at 6 months and 6.21° (±3.82°) at 9 months. The minimally invasive NForce system is effective in performing anatomic percutaneous reduction/fixation.


Mechanistic insights into the inhibition of human placental glutathione S-transferase P1-1 by abscisic and gibberellic acids: An integrated experimental and computational study.
The interactions of the classic phytohormones gibberellic acid (gibberellin A3 , GA3 ) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S-transferase P1-1 (hpGSTP1-1), an enzyme that plays a role in endo- or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA3 against hpGSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hpGSTP1-1 and phytohormones was predicted with the aid of molecular docking simulations. The IC50 values of ABA and GA3 were 5.3 and 5.0 mM, respectively. Both phytohormones inhibited hpGSTP1-1 in competitive manner with respect to the cosubstrates GSH and CDNB. When ABA was the inhibitor at [CDNB]f -[GSH]v and at [GSH]f -[CDNB]v , Vm , Km , and Ki values were statistically estimated to be 205 ± 16 μmol/min-mg protein, 1.32 ± 0.18 mM, 1.95 ± 0.25 mM and 175 ± 6 μmol/min-mg protein, 0.85 ± 0.06 mM, 1.85 ± 0.16 mM, respectively. On the other hand, the kinetic parameters Vm , Km , and Ki obtained with GA3 at [CDNB]f -[GSH]v and at [GSH]f -[CDNB]v were found to be 303 ± 14 μmol/min-mg protein, 1.77 ± 0.13 mM, 3.38 ± 0.26 mM and 249 ± 7 μmol/min-mg protein, 1.43 ± 0.07 mM, 2.89 ± 0.19 mM, respectively. Both phytohormones had the potential to engage in hydrogen-bonding and electrostatic interactions with the key residues that line the G- and H-sites of the enzyme's catalytic center. Inhibitory actions of ABA/GA3 on hpGSTP1-1 may guide medicinal chemists through the structure-based design of novel antineoplastic agents. It should be noted, however, that the same interactions may also render fetuses vulnerable to the potentially toxic effects of xenobiotics and noxious endobiotics.


MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.
We have cloned cDNA encoding a human transcription factor that belongs to the MEF2 (myocyte-specific enhancer-binding factor 2) subfamily of the MADS (MCM1-agamous-deficiens-serum response factor) gene family. This factor, which we have named MEF2C, binds specifically to the MEF2 element and activates transcription via this element. Specific isoforms of this factor are found exclusively in brain and are robustly expressed by neurons in cerebral cortex. In situ hybridization indicates that the factor is expressed preferentially in certain neuronal layers of cortex and that expression declines during postnatal development. The unusual pattern of expression in brain suggests that this transcription factor may be important in the development of cortical architecture.


Stress and immune function in diabetes mellitus.
Type I diabetic men were found to have a greater number of stresses, more perceived stress per episode, greater anxiety, poorer immune function, and less metabolic control than Type II diabetic men. Degree of family support and compliance with the medical regimen did not differ. Correlation of perceived stress with immune function and metabolic control showed that Type I had more correlates than Type II, with more perceived stress associated with more depressed immune responses.


Ischemic stroke functional outcomes are independently associated with C-reactive protein concentrations and cognitive outcomes with triiodothyronine concentrations: a pilot study.
Elevated concentrations of C-reactive protein (CRP) and decreased concentrations of triiodothyronine (T3) were shown to predict poor outcomes in patients with stroke. However, the prognostic value of CRP and T3 has not been studied simultaneously in relation to stroke functional and cognitive outcomes despite of close interaction between inflammatory markers and thyroid function. We evaluated the association of thyroid hormone and CRP concentrations with immediate outcomes after ischemic stroke. Eighty-eight ischemic stroke patients on admission to the stroke unit were evaluated for clinical stroke severity (Scandinavian stroke scale or SSS) and concentrations of thyroid-stimulating hormone, free thyroxin, free T3, and CRP. Functional outcome (modified Rankin scale) and cognitive outcome (Mini mental state examination) were evaluated at discharge. Greater ln CRP concentrations (r = -0.35, p = 0.001), but not thyroid hormone concentrations, correlated with score on the SSS. In univariate analyses lower free T3 concentrations and higher CRP concentrations were associated with poor functional and poor cognitive outcomes. After adjustment for clinical stroke severity, higher CRP concentrations (β = 0.18, p = 0.04) remained associated with worse functional outcome and lower free T3 concentrations with worse cognitive outcome (β = 0.23, p = 0.03). In sum, clinical stroke severity is associated with elevated CRP concentration. Higher CRP concentration is independently associated with worse functional outcomes and lower free T3 concentration with worse cognitive outcomes at discharge. T3 and CRP can be important biomarkers in patients with acute ischemic stroke.


Age Difference of the Relationship Between Cerebral Oxygen Saturation and Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.
Recently, monitoring of cerebral oxygen saturation (ScO2) has become widespread in pediatric cardiac surgery. Our previous study reported that mean blood pressure (mBP) was the major contributor to ScO2 throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg. We speculated that this result might be attributable to incomplete cerebral autoregulation in such young children. Accordingly, our hypothesis is that the relationship between ScO2 and the physiological parameters may change according to the growth of the children. ScO2 was measured with an INVOS 5100C (Somanetics, Troy, MI). Random-effects analysis was employed with ScO2 as a dependent variable, and seven physiological parameters (mBP, central venous pressure, nasopharyngeal temperature, SaO2, hematocrit, PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods by dividing the patients into two groups: infants (Infant Group) and children who were more than 1 year old (Child Group). The Infant and Child Groups consisted of 28 and 21 patients. In the random-effects analysis, mBP was the major contributor to ScO2 during CPB in both groups. During the pre-CPB period, the effect of mBP was strongest in the Infant group. However, its effect was second to that of SaO2 in the Child Group. During the post-CPB period, SaO2 and mBP still affected ScO2 in the Infant group. However, the dominant contributors were unclear in the Child Group. Cerebral autoregulation may be immature in infants. In addition, it may be impaired during CPB even after 1 year of age.


Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses.
Type I interferons (IFNs) are critical for antiviral responses. Here we generated a knockin mouse in which green fluorescence protein (GFP) was expressed under the control of the Ifna6 promoter. Virus-induced expression of GFP recapitulated various IFN-alpha subtypes. Systemic infection of the mice with Newcastle disease virus (NDV) increased GFP(+) plasmacytoid dendritic cells (pDCs) via the Toll-like receptor system, and GFP(+) conventional dendritic cells (cDCs) and macrophages via the RIG-I-like helicase system. By contrast, lung infection with NDV led to IFN-alpha production in alveolar macrophages (AMs) and cDCs, but not in pDCs. Specific depletion of AMs caused a marked defect in the initial viral elimination in the lung. pDCs produced IFN-alpha in the absence of AM-mediated viral recognition, suggesting that pDCs function when the first defense line is broken. Thus, AMs act as a type I IFN producer that is important for the initial responses to viral infection in the lung.