Cross-linked cellulose nanocrystal aerogels as viable bone tissue scaffolds.
Chemically cross-linked cellulose nanocrystal (CNC) aerogels possess many properties beneficial for bone tissue scaffolding applications. CNCs were extracted using sulfuric acid or phosphoric acid, to produce CNCs with sulfate and phosphate half-ester surface groups, respectively. Hydrazone cross-linked aerogels fabricated from the two types of CNCs were investigated using scanning electron microscopy, X-ray micro-computed tomography, X-ray photoelectron spectroscopy, nitrogen sorption isotherms, and compression testing. CNC aerogels were evaluatedin vitrowith osteoblast-like Saos-2 cells and showed an increase in cell metabolism up to 7 days while alkaline phosphatase assays revealed that cells maintained their phenotype. All aerogels demonstrated hydroxyapatite growth over 14 days while submerged in simulated body fluid solution with a 0.1 M CaCl2 pre-treatment. Sulfated CNC aerogels slightly outperformed phosphated CNC aerogels in terms of compressive strength and long-term stability in liquid environments, and were implanted into the calvarian bone of adult male Long Evans rats. Compared to controls at 3 and 12 week time points, sulfated CNC aerogels showed increased bone volume fraction of 33% and 50%, respectively, compared to controls, and evidence of osteoconductivity. These results demonstrate that cross-linked CNC aerogels are flexible, porous and effectively facilitate bone growth after they are implanted in bone defects. STATEMENT OF SIGNIFICANCE: Due to the potential complications associated with autografts, there is a need for synthetic bone tissue scaffolds. Here, we report a new naturally-based aerogel material for bone regeneration made solely from chemically cross-linked cellulose nanocrystals (CNC). These highly porous CNC aerogels were shown to promote the proliferation of bone-like cells and support the growth of hydroxyapatite on their surface in vitro. The first in vivo study on these materials was conducted in rats and showed their osteconductive properties and an increase in bone volume up to 50% compared to sham sites. This study demonstrates the potential of using functionalized cellulose nanocrystals as the basis for aerogel scaffolds for bone tissue engineering.


MA 160 and EB33 cell lines: HeLa cell contaminants, hybrids or prostatic epithelial cells?
Studies of acid phosphates produced by cell lines MA 160 and EB 33 demonstrated immunochemically their prostatic origin. MA 160 and EB 33, rather than being HeLa contaminants, may be hybrids of prostatic epithelial and HeLa cells or true prostatic cell lines with chromosomal changes common to all long-term cultivated cell lines.


Developmental selection of var gene expression in Plasmodium falciparum.
The protozoan Plasmodium falciparum causes lethal malaria. Adhesion of erythrocytes infected with P. falciparum to vascular endothelium and to uninfected red blood cells (rosetting) may be involved in the pathogenesis of severe malaria. The binding is mediated by the antigenically variant erythrocyte-membrane-protein-1 (PfEMP-1), which is encoded by members of the P. falciparum var gene family. The control of expression and switching of var genes seems to lack resemblance to mechanisms operating in variant gene families of other microbial pathogens. Here we show that multiple, distinct var gene transcripts (about 24 or more) can be detected by reverse transcription and polymerase chain reaction in bulk cultures of the rosetting parasite FCR3S1.2, despite the adhesive homogeneity of the cultures. We also detected several var transcripts in single erythrocytes infected with a ring-stage parasite of FCR3S1.2, and found that different var genes are transcribed simultaneously from several chromosomes in the same cell. In contrast, we detected only one var transcript, FCR3S1.2 var-1, which encodes the rosetting PfEMP-1 protein, in individual rosette-adhesive trophozoite-infected cells, and we found only one PfEMP-1 type at the erythrocyte surface by labelling with 125iodine and immunoprecipitation. We conclude that a single P. falciparum parasite simultaneously transcribes multiple var genes but, through a developmentally regulated process, selects only one PfEMP-1 to reach the surface of the host cell.


Quantification of near-field heating during volumetric MR-HIFU ablation.
High-intensity focused ultrasound guided by magnetic resonance imaging has been extensively evaluated during the past decade as a clinical alternative for thermal ablation of tumor tissue. However, the maximal ablation volume is limited by the extensive treatment duration resulting from the small size of the focal point as compared to the average tumor size. Volumetric sonication has been shown to efficiently enlarge the ablated volume per sonication, but remains limited by the temperature increase induced in the skin and fat layers. In this study, multiplane MR thermometry is proposed for monitoring the near-field temperature rise in order to prevent related unintended thermal damage. The method was evaluated by performing sonications in the thigh muscle of 11 pigs maintained under general anesthesia. Volumetric ablations were performed by steering the focal point along trajectories consisting of multiple outward-moving concentric circles. Near-field heating was characterized with MR temperature maps and thermal dose maps. The results from the MR measurements were compared to simulations. In this study, the measured maximum temperature rise was found to correlate linearly with the surface energy density within the near field of the beam path with a slope of 4.2 K mm2/J. This simple linear model appears to be almost independent of the trajectory pattern and the sonication depth. The safety limit to avoid lethal damage of the subcutaneous tissues of the porcine thigh was identified to be an absolute temperature of 50 degrees C, corresponding to a surface energy density of 2.5 J/mm2 at 1.2 MHz. A linear relationship can be established to estimate the temperature increase based on the chosen power prior to ablation, thereby providing an a priori safety check for possible excessive near-field heating using a known surface energy density threshold. This method would also give the clinician the possibility to abort the sonication should excessive near-field temperature rise be seen before fat layer damage or skin burns are inflicted.


Modeling the epidemiological impact of a preventive behavioral group.
Concerning health, experience indicates that in all human groups a percentage of individuals behave conscientiously when facing contagious diseases. This aware group responds with activities to prevent disease transmission and to minimize risk. In contrast, other individuals tend to behave with less engagement except in catastrophic cases. Assuming the theoretical and methodological framework provided by mathematical epidemiology, and based on a Susceptible  Infectious - Recovered (SIR) model, we evaluated the factors of size and intensity of the behaviours in the aware group to determine the basic reproduction number. This number is the reduction in the number of secondary cases that would be produced by a first infectious individual. Additionally, we calculated the total and individual prevented prevalence for each aware individual for different parametric scenarios. Lastly, we suggest that distance and interpersonal contact should be included as factors associated to the potential of transmission.


Exercise increases the proportion of fat utilization during short-term consumption of a high-fat diet.
Increases in energy substrate oxidation occur at different rates after an increase in either fat or carbohydrate intake. Adaptations to increased fat intake are relatively slow and are influenced by activity level. We tested the hypothesis that increased levels of daily activity, as influenced by added exercise, would have a graded effect on the rate of compensatory adjustment to a short-term high-fat diet. Daily total energy expenditure and macronutrient oxidation were measured at 3 physical activity levels (PALs) by using a whole-room indirect calorimeter in 10 adult women as they transitioned from a 1-d low-fat (30% of energy) control diet to a 4-d high-fat (50% of energy) diet. The 3 PALs (1.4, 1.6, and 1.8) were provided daily by increases in bicycle ergometer exercise time. An increase in physical activity led to a greater increase in the nonprotein respiratory exchange ratio (-0.047 +/- 0.02, -0.064 +/- 0.02, and -0.071 +/- 0.02; P < 0.0001) and 24-h fat oxidation (113 +/- 24, 125 +/- 19, and 147 +/- 20 g/d; P < 0.0001) for PALs of 1.4, 1.6, and 1.8, respectively, after the transition from the low-fat control diet to the high-fat diet. Random-effects analysis found a significant (P = 0.003) relation between PAL and the compensatory fat oxidation response to a high-fat diet. Amounts of exercise consistent with the Institute of Medicine's recommendations reduce the time required to match fat oxidation to a change in the percentage of fat in the diet. Because short-term consumption of high-fat diets is thought to contribute to excess fat accumulation, regular exercise should be protective and should help maintain a healthy body composition.


The effect of trimethoprim and sulfamethoxazole on Toxoplasma gondii in vitro and in vivo.
Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination to determine their effect in vitro on intracellular Toxoplasma gondii and in vivo against murine toxoplasmosis. In the in vitro experiments, whereas 1 and 2 microgram/ml TMP had no demonstrable effect on intracellular T. gondii, 10-20 microgram/ml TMP resulted in death of the intracellular organisms; concentrations as high as 100 microgram/ml SMZ had no demonstrable effect against the intracellular organisms. When used in combination, a significant synergistic effect was noted with 2 microgram/ml TMP-50 microgram/ml SMZ. Studies on the kinetics of inhibition and/or killing of Toxoplasma revealed that 18 hours of treatment with 2 microgram/ml TMP-50 microgram/ml SMZ resulted in irreversible inhibition of the intracellular organisms. When used in vivo against a 50,000 LD100 dose of Toxoplasma, TMP fed by gavage or mixed in the diet had no effect in murine toxoplasmosis at doses as high as 200 mg/kg a day. SMZ administered by gavage had no effect at doses up to 200 mg/kg a day; but at 300 and 400 mg/kg SMZ, protection was 47% and 83%, respectively. Treatment of infected mice was continued for 14 consecutive days, whether the drugs were administered alone or in combination. The combination 200 mg/kg TMP-200 mg/kg SMZ, when administered by gavage, protected 87% of mice. Survival after 14 days of SMZ mixed in the diet was 0% at 100 mg/kg, 47% at 200 mg/kg, and 100% at 300 mg/kg. Survival with the combination was 40% for 200 mg/kg TMP-100 mg/kg SMZ and 100% for 100 mg/kg TMP-200 mg/kg SMZ. The half-life of TMP in serum of Swiss Webster mice was calculated to be 24 min. The results obtained in vivo were inferior to those obtainable with the combination of pyrimethamine plus sulfadiazine. The problems of interpretation of results obtained in the murine model using TMP-SMZ and in their extrapolation to the treatment of the infection in man are discussed.


Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans.
Interest in the health-promoting properties of berry anthocyanins is intensifying; however, findings are primarily based on in vitro characteristics, leaving mechanisms associated with absorption, metabolism and pharmacokinetics largely unexplored. The present review integrates the available anthocyanin literature with that of similar flavonoids or polyphenols in order to form hypotheses regarding absorption, metabolism and clearance in humans. Of the limited available literature regarding the absorption and clearance kinetics of anthocyanins, maximum plasma concentrations are reported anywhere between 1.4 and 592 nmol/l and occur at 0.5-4 h post-consumption (doses; 68-1300 mg). Average urinary excretion is reported between 0.03 and 4 % of the ingested dose, having elimination half-lives of 1.5-3 h. In addition, much is unknown regarding the metabolism of anthocyanins. The most commonly cited conjugation reactions involved in the metabolism of other flavonoids include glucuronidation, methylation and sulfation. It is reasonable to suspect that anthocyanins are metabolised in much the same manner; however, until recently, there was little evidence to suggest that anthocyanins were metabolised to any significant extent. New evidence now suggests that anthocyanins are absorbed and transported in human serum and urine primarily as metabolites, with recent studies documenting as much as 68-80 % of anthocyanins as metabolised derivatives in human urine. Further research is required to resolve mechanisms associated with the absorption, metabolism and clearance of anthocyanins in order to establish their true biological activities and health effects. The presented evidence will hopefully focus future research, refining study design and propagating a more complete understanding of anthocyanins' biological significance in humans.


T cells within germinal centers are specific for the immunizing antigen.
A normal antibody response to T cell-dependent Ag requires physical contact between Ag-specific B and T cells. Because such Ag-specific cells are rare in vivo, we sought to identify an in vivo site where they physically contact each other. We examined the Ag specificity of T cells in germinal centers (GC) in lymph nodes, where it is known that Ag-specific B cells proliferate and mature. We investigated the Ag specificity of GC T cells in situ by examining two characteristics: 1) expression of certain V alpha and V beta TCR families; and 2) incorporation of bromodeoxyuridine into T cell DNA after exposure to Ag as an index of Ag-induced proliferation. When GC were induced in mice with cytochrome c and myelin basic protein, the GC T cells were found to preferentially express V alpha 11 and V beta 8 TCR families, which are, respectively, the dominant TCR families in these two responses. Furthermore, GC T cells have proliferated upon exposure to the Ag that induced GC formation. Taken together, these results demonstrate that GC must recruit and retain Ag-specific T cells, thus implicating the GC as an in vivo site where Ag-specific T and B cells interact.


Studies on the polysaccharide B and native haptene of Brucella and Yersinia enterocolitica serotype 9.
Trichloroacetic (TCA) extraction of B. melitensis 115, or hot saline extraction of B. melitensis 16M yields a polysaccharide component that can be purified free of protein and lipopolysaccharide by gel filtration and TCA precipitation. Antibodies to this polysaccharide can be detected in sera of rabbits infected with virulent Brucella but not with B. abortus 19. Similarly, cattle with active brucellosis and humans with acute brucellosis develop antibodies against this polysaccharide. After extraction and purification, this polysaccharide does not elicit antibody response in rabbits or mice. It does not fix the complement, does not bind to red cells or to polystyrene plates.


Combination of histidine, lysine, methionine, and leucine promotes β-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells.
The ratio of different AA in the diets of cows is vital to improve milk protein yield. β-Casein is one of the important milk proteins with high nutritive value. However, the suitable ratio of essential amino acids (EAA) for the expression of β-casein in the immortalized bovine mammary epithelial cell line is not fully characterized. This study employed response surface methodology to determine the optimal ratio of His, Lys, Met, and Leu on β-casein expression level in vitro and clarified the effect of the 4 EAA on β-casein via the mechanistic target of rapamycin (mTOR) signaling pathway. A central composite design containing 5 axial points per EAA and 28 combinations of the 4 EAA was used in our study. The results of response surface methodology and the changes of the mTOR-related signaling proteins were determined by western blot. The results showed that β-casein level was significantly affected by all 4 EAA (R2 = 0.71). The optimum conditions for β-casein expression are found to be 5.47 mM of His, 7.48 mM of Lys, 1.17 mM of Met, and 8.21 mM of Leu (His:Lys:Met:Leu = 5:6:1:7) in the designed scope of concentration. The interaction of Leu and Met significantly affected β-casein expression (P < 0.01). The phosphorylation of mTOR (Ser2481), regulatory associated protein of target of rapamycin (Ser792), ribosomal protein S6 kinase 1 (Thr389), ribosomal protein S6 (Ser235/236), and eukaryotic elongation factor 2 (Thr56) was increased with the supplementation of either single EAA or an optimal combination of EAA. However, the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (Thr37) was decreased with the addition of Lys, Met, or Leu alone. Furthermore, the phosphorylation (P) of eIF2α (Ser51) was decreased when Met was supplemented alone. Under the optimal mixture of 4 EAA, the phosphorylation of mechanistic target of rapamycin complex 1 signaling proteins was significantly greater than the single EAA supplementations and the expression of β-casein was 98% as high as the positive control (i.e., medium with all AA). A similar trend was found with P-ribosomal protein S6 kinase 1 and P-ribosomal protein S6. In conclusion, the extracellular concentrations of His, Lys, Met, and Leu at a ratio of 5:6:1:7 maximized β-casein expression in the immortalized bovine mammary epithelial cell line may occur via activation of the mechanistic target of rapamycin complex 1 signaling pathway.


[Efficiency of prognostic scores for the assessment of patients with severe influenza pneumonias].
To compare the efficiency of some prognostic scores in patients with severe influenza pneumonias. The study was performed on a cohort of 75 cases of 2009 AH1N1 influenza associated pneumonias. Clinical and laboratory features at admission were used to calculate retrospectively the following prognostic scores: SCAP (Severe Community Acquired Pneumonia), CAP-PIRO (Community Acquired Pneumonia--Predisposition Infection Reaction, Organ failure), SMRT-CO (Systolic blood pressure, Multilobar infiltrates, Respiration rate, Tachycardia, Confusion, Oxygen), IDSA/ATS (Infectious Diseases Society of America/American Thoracic Society). The scores were used to assess two different outcomes--death and need for invasive mechanical ventilation (IMV). The performance of the prognostic tools were assessed using the area under receiver operating characteristic (AUC), and the sensitivity and specificity for identifying high risk patients for severe course of pneumonia. IMV was applied in 29 (38.7%) of studied cases, in 15 (20%) the diseases had a fatal outcome. Despite the fact that all scores had a very good discriminatory power in predicting both outcomes (AUC > 0,8), some of them have a very low sensitivity, in classes corresponding to sever pneumonias, in predicting mortality (IDSA/ATS-0%; 95% CI, 0-21.8%), as well as the need for IMV (IDSA/ATS-0%; 95% CI, 0-11.9%); SCAP-58.6% (95% CI, 38.9-76.5%); CAP-PIRO-58,6% (95% CI, 38.9-76.5%). The CAP-PIRO and SMRT-CO scores were found to have the best performances to predict death from influenza associated severe pneumonias and the last, also in predicting the need for IVM. Other analyzed scores underestimate the risk of occurrence of both assessed outcomes.


CYP3A catalyses schizandrin biotransformation in human, minipig and rat liver microsomes.
Schizandrin is recognized as the major absorbed effective constituent of Fructus schisandrae, which is extensively applied in Chinese medicinal formula. The present study aimed to profile the phase I metabolites of schizandrin and identify the cytochrome P450 (CYP) isoforms involved. After schizandrin was incubated with human liver microsomes, three metabolites were isolated by high-performance liquid chromatography (HPLC) and their structures were identified to be 8(R)-hydroxyl-schizandrin, 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, by liquid chromatography-mass spectrometry (LC-MS), (1)H-nuclear magnetic resonance (NMR), and (13)C-NMR, respectively. A combination of correlation analysis, chemical inhibition studies, assays with recombinant CYPs, and enzyme kinetics indicated that CYP3A4 was the main hepatic isoform that cleared schizandrin. Rat and minipig liver microsomes were included when evaluating species differences, and the results showed little difference among the species. In conclusion, CYP3A4 plays a major role in the biotransformation of schizandrin in human liver microsomes. Minipig and rat could be surrogate models for man in schizandrin pharmacokinetic studies. Better knowledge of schizandrin's metabolic pathway could provide the vital information for understanding the pharmacokinetic behaviours of schizandrin contained in Chinese medicinal formula.


Map of fluid flow in fractal porous medium into fractal continuum flow.
This paper is devoted to fractal continuum hydrodynamics and its application to model fluid flows in fractally permeable reservoirs. Hydrodynamics of fractal continuum flow is developed on the basis of a self-consistent model of fractal continuum employing vector local fractional differential operators allied with the Hausdorff derivative. The generalized forms of Green-Gauss and Kelvin-Stokes theorems for fractional calculus are proved. The Hausdorff material derivative is defined and the form of Reynolds transport theorem for fractal continuum flow is obtained. The fundamental conservation laws for a fractal continuum flow are established. The Stokes law and the analog of Darcy's law for fractal continuum flow are suggested. The pressure-transient equation accounting the fractal metric of fractal continuum flow is derived. The generalization of the pressure-transient equation accounting the fractal topology of fractal continuum flow is proposed. The mapping of fluid flow in a fractally permeable medium into a fractal continuum flow is discussed. It is stated that the spectral dimension of the fractal continuum flow d(s) is equal to its mass fractal dimension D, even when the spectral dimension of the fractally porous or fissured medium is less than D. A comparison of the fractal continuum flow approach with other models of fluid flow in fractally permeable media and the experimental field data for reservoir tests are provided.


The differentially spliced mouse tagL gene, homolog of tag7/PGRP gene family in mammals and Drosophila, can recognize Gram-positive and Gram-negative bacterial cell wall independently of T phage lysozyme homology domain.
Tag7/PGRP, a recently characterized antimicrobial protein, is conserved from insects to mammals. Recently its involvement in Toll signalling in Drosophila was demonstrated. A number of genes representing a new family homologous to PGRP were identified in Drosophila and human. Here we describe a splicing pattern of the tagL gene, mouse member of tag7/PGRP family. Some of the identified splice variants lacked characteristics for the family T phage lysozyme homology domain (also known as PGRP domain). Accordingly to the predicted transmembrane domains, mouse TagL may be secreted as inducible proteins or retained on intracellular membranes. All detected splice variant isoforms of TagL bound Gram-positive, Gram-negative bacteria and peptidoglycan. This binding did not depend on the presence of T phage lysozyme homology domain but was associated with the C-terminal portion of the polypeptides. Thus, this variety of isoforms of a single gene may play a role in circulating bacteria recognition in mammals.


Interhemispheric and intrahemispheric connectivity and manual skills in children with unilateral cerebral palsy.
This study investigated patterns of motor brain activation, white matter (WM) integrity of inter- and intrahemispheric connectivity and their associations with hand function in children with unilateral cerebral palsy (CP-U). Fourteen CP-U (mean age 10.6 ± 2.7 years) and 14 typically developing children (TDC) underwent magnetic resonance imaging. CP-U underwent extensive motor evaluation. Pattern of brain activation during a motor task was studied in 12 CP-U and six TDC, by calculating laterality index (LI) and percent activation in the sensorimotor areas (around the central sulcus), and quantifying the activation in the supplementary motor area (SMA). Diffusivity parameters were measured in CP-U and eight other TDC for the corpus callosum (CC), affected and less affected cortico-spinal tracts (CST), and posterior limb of the internal capsule (PLIC). Abnormal patterns of brain activation were detected in areas around the central sulcus in 9/12 CP-U, with bilateral activation and/or reduced percent activation. More activation in areas around the central sulcus of the affected hemisphere was associated with better hand function. CP-U demonstrated more activation in the SMA when moving the affected hand compared to the less affected hand. CP-U displayed reduced WM integrity compared to TDC, in the midbody and splenium of the CC, affected CST and affected PLIC. WM integrity in these tracts was correlated with hand function. While abnormal pattern of brain activation was detected mainly when moving the affected hand, the integrity of the CC was correlated with function of both hands and bimanual skills. This study highlights the importance of interhemispheric connectivity for hand function in CP-U, which may have clinical implications regarding prognosis and management.


Nutrition and lifestyle in relation to bone health and body weight in Croatian postmenopausal women.
The objective was to investigate the association of nutrients and lifestyle modifiers with bone mineral density (BMD) and weight and/or body mass index (BMI) in 120 healthy Croatian postmenopausal women. The hip and spine BMD was assessed by Lunar Prodigy (GE Medical Systems). Nutrient assessment from 3-day records was analyzed using the US Department of Agriculture Food Composition Tables and the Croatian National Institute of Public Health database. Subjects were asked to record the consumption of alcohol, coffee, tea and mineral waters, the amount of salt added to foods and smoking habits, as well as involvement in recreational activities, walking and heavy housework. Spot urine samples were analyzed for calcium, magnesium, sodium, potassium and zinc and were normalized by creatinine. Alcohol showed statistically significant positive association with femur and spine BMD and its consumption was higher in subjects without osteoporosis. Urinary sodium/creatinine was significantly positively associated with femoral neck and trochanter BMD, while urinary calcium/creatinine was significantly negatively associated with trochanter, total femur and spine BMD. Consumption of mineral waters was inversely associated with weight/BMI and so were dietary fiber and magnesium. In conclusion, moderate alcohol consumption and urinary sodium were positively associated while urinary calcium was negatively associated with either hip and/or spine BMD. Mineral waters, higher fiber and magnesium intake were beneficial for weight/BMI in this population of apparently healthy Croatian women.


Opioid-free Analgesia for Posterior Spinal Fusion Surgery Using Erector Spinae Plane (ESP) Blocks in a Multimodal Anesthetic Regimen.
A case report. The aim of this study was to report the use of erector spinae plane (ESP) blocks as part of an opioid-free multimodal anesthetic regimen and its impact on postoperative pain and opioid requirements following spine surgery. Posterior spinal fusion surgery is highly painful and usually requires significant amounts of opioids for adequate perioperative analgesia; this is commonly associated with adverse effects, including opioid-induced hyperalgesia, nausea, and ileus. The ESP block is a novel ultrasound-guided regional anesthetic technique involving local anesthetic injection into the musculofascial plane between erector spinae muscle and transverse processes. This safe and simple technique blocks dorsal rami of spinal nerves and can thus provide opioid-sparing analgesia for spine surgery. A 35-year-old woman with a previous T3-pelvis fusion for neuromuscular scoliosis underwent revision surgery involving T2-T8 decompression and fusion. She refused the use of perioperative opioids due to intolerable adverse effects during previous surgeries. Analgesia was provided by preoperative bilateral ESP blocks at T4 with 20 mL 0.25% bupivacaine and epinephrine 5 μg/mL on each side, and intraoperative infusion of ketamine and dexmedetomidine. Oral acetaminophen 1 g 6-hourly was administered postoperatively, together with baclofen 10 mg 8-hourly to treat muscle spasms. The patient had adequate analgesia without use of any opioids during her anesthetic or hospital stay. A multimodal intraoperative anesthetic regimen incorporating ESP blocks was able to eliminate the need for postoperative opioid analgesia following posterior spinal fusion. This case report serves as proof-of-concept that this regimen may significantly improve pain trajectories and reduce opioid use in this patient population. 4.


Global warming and Australian public health: reasons to be concerned.
Studies in global warming and climate change indicate that human populations will be deleteriously affected in the future. Studies forecast that Australia will experience increasing heat waves and droughts. Heat stress caused by frequent heat waves will have a marked effect on older Australians due to physiological and pharmacological factors. In this paper we present an overview of some of the foreseeable issues which older Australians will face from a public health perspective.


Azopolymer photopatterning for directional control of angiogenesis.
Understanding cellular behavior in response to microenvironmental stimuli is central to tissue engineering. An increasing number of reports emphasize the high sensitivity of cells to the physical characteristics of the surrounding milieu and in particular, topographical cues. In this work, we investigated the influence of dynamic topographic signal presentation on sprout formation and the possibility to obtain a space-time control over sprouting directionality without growth factors, in order to investigate the contribution of just topography in the angiogenic process. To test our hypothesis, we employed a 3D angiogenesis assay based on the use of spheroids derived from human umbilical vein endothelial cells (HUVECs). We then modulated the in situ presentation of topographical cues during early-stage angiogenesis through real-time photopatterning of an azobenzene-containing polymer, poly (Disperse Red 1 methacrylate) (pDR1m). Pattern inscription on the polymer surface was made using the focused laser of a confocal microscope. We demonstrate that during early-stage angiogenesis, sprouts followed the pattern direction, while spheroid cores acquired a polarized shape. These findings confirmed that sprout directionality was influenced by the photo-inscribed pattern, probably through contact guidance of leader cells, thus validating the proposed platform as a valuable tool for understanding complex processes involved in cell-topography interactions in multicellular systems. The complex relationship between endothelial cells and the surrounding environment that leads to formation of a newly formed vascular network during tissue repair is currently unknown. We have developed an innovative in vitro platform to study these mechanisms in a space and time controlled fashion simulating what happens during regeneration. In particular, we combine a "smart" surface, namely a polymer film, with a three-dimensional living cell aggregate. The polymer is activated by light through which we can design a path to guide cells toward the formation of a new vessel. Our work lies at the intersection of stimuli-responsive biointerfaces and cell biology and may be particularly inspiring for those interested in designing biomaterial surface related to angiogenesis.


Transcriptomics and metabolomics reveal the cardioprotective effect of Compound Danshen tablet on isoproterenol-induced myocardial injury in high-fat-diet fed mice.
Compound Danshen tablet, an herbal preparation consisting of salviae miltiorrhizae, notoginseng and borneolum, is extensively employed clinically to treat angina pectoris, coronary arteriosclerosis and significantly improve microcirculation. To reveal the potential underlying cardioprotective mechanism(s) in isoproterenol-induced myocardial injury in high-fat-diet fed mice. Cardiac transcriptomics was analyzed by Illumina mRNA-Seq sequencing. The restored cardiovascular diseases (CVD)-related genes by Compound Danshen tablet were validated by quantitative real time polymerase chain reaction (qRT-PCR). Furthermore, Cardiac metabolomics were also performed using gas chromatography-mass spectrometry. From the transcriptomics study, we found the levels of 24 up-regulated and 44 down-regulated genes in the control compared to model groups. Among them, seven gene levels were restored by treatment of Compound Danshen tablet. Four CVD-related genes at the mRNA level (Sprr1a, Ppp1r3c, Bmp10 and Hspa1b) were validated successfully by qRT-PCR. From the metabolomics study, 37 differentially expressed metabolites were identified between the control and model groups. Among them, 21 metabolites were restored by treatment of Compound Danshen tablet. These altered metabolites are involved in glucose metabolism, fatty acid metabolism and amino acid metabolism. These genes and metabolites might provide clues for further molecular mechanistic study of Compound Danshen tablet.


[Asthma and pregnancy].
Asthma is among the diseases that may complicate pregnancy. Asthma affects up to 4% of the pregnant women. Uncontrolled asthma may impair the proper oxygenation of both mother and child. According to asthma severity clinical manifestations may be unapparent or apparent requiring hospital treatment. It is necessary that pregnant asthmatic woman check daily the peak-flow by portable peak-flow meters. The asthma pharmacological treatment should consider the changes in the physiology of the pregnancy, such as low albumin and carrier proteins for the drugs inducing high levels of free active drugs. This point is important for theophylline, besides the low drug clearance. Bronchodilator should be used as they are required, using the inhaled forms, as well as short term corticoid courses. The goal of the treatment is to control the symptoms, avoid relapse and keep the ventilatory function close to the normal, in order to achieve a satisfactory state of the mother and the children.


Changing practice patterns of school-based occupational therapists in Israel.
Following the enactment of the Special Education Law in Israel in 1988, school-based occupational therapists (OTs) were expected to modify their practice patterns by, providing services within the classroom or other educational settings, increasing collaboration with other team members, and implementing indirect intervention models such as monitoring and consultation. The purpose of this study was to examine the intervention patterns of school-based OTs in Israel. The study sample included 77 school-based OTs. The survey was carried out through a questionnaire which included: (1) background information, (2) implementation and perceptions towards intervention models, and (3) team-work practices of the OTs. The findings indicated that most of the time (76.9%) OTs still implement the 'direct therapy' model, working outside the classroom and focusing on improving performance components. These findings imply that school-based OTs in Israel are still in the process of changing their practice patterns, and are mostly applying the medical model. However, due to the relatively small sample, it is important to repeat this survey using a larger sample of OTs who work in different settings and with various age groups.


Immunologic markers in non-Hodgkin's lymphoma.
The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.


Uptake of combination antiretroviral therapy and HIV disease progression according to geographical origin in seroconverters in Europe, Canada, and Australia.
We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART). Data from HIV seroconverter cohorts in Europe, Australia and Canada (CASCADE) was used; GO was classified as: western countries (WE), North Africa and Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), and Asia (ASIA). Differences by GO were assessed using Cox models. Administrative censoring date was 30 June 2008. Of 16 941 seroconverters, 15 548 were from WE, 158 NAME, 762 SSA, 349 LA, and 124 ASIA. We found no differences by GO in risks of AIDS (P = .99) and death (P = .12), although seroconverters from NAME (adjusted hazard ratio [aHR]: 0.57; 95% CI: 0.33-.94) and SSA (aHR: 0.74; 95% CI: 0.50-1.10) appeared to have lower mortality than WE. Chances of initiating cART differed by GO (P < .001): seroconverters from SSA were more likely to initiate cART than WE (aHR: 1.48; 95% CI: 1.26-1.74), but not after adjustment for CD4 at SC (aHR: 1.11; 95% CI: 0.88-1.40). In settings with universal access to healthcare, GO does not play a major role in HIV disease progression.


Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic study of 277 patients.
Unlike the case with acute myeloid leukemia, there is limited information on the prognostic impact of isocitrate dehydrogenase (IDH) mutations in myelodysplastic syndromes (MDS). In the current study of 277 patients with MDS, IDH mutations were detected in 34 (12%) cases: 26 IDH2 (all R140Q) and 8 IDH1 (6 R132S and 2 R132C). Mutational frequency was 4% (2 of 56) in refractory anemia with ring sideroblasts, 12% (16 of 130) in refractory cytopenia with multilineage dysplasia, 14% (2 of 14) in MDS-unclassifiable, 14% (6 of 42) in refractory anemia with excess blasts (RAEB)-1 and 23% (8 of 35) in RAEB-2. Normal karyotype was noted in all but one IDH1-mutated cases and 13 IDH2-mutated cases. Multivariable analysis identified presence of mutant IDH1 (P=0.0004; hazard ration 4.0, 95% confidence interval 1.9-8.8), revised International Prognostic Scoring System risk category (P<0.0001), and red cell transfusion need (P=0.002) as independent predictors of inferior survival. In a similar multivariable analysis, mutant IDH1 was the only variable associated with shortened leukemia-free survival (P=0.001; hazard ration 7.0, 95% confidence interval 2.3-20.8). The presence of IDH2R140Q did not affect the overall (P=0.54) or leukemia-free (P=0.81) survival. The current study suggests a powerful adverse prognostic effect for mutant IDH1 in MDS.


Severe gastrointestinal haemorrhage and ischaemic necrosis of the small bowel in a child with 70% full-thickness burns: a case report.
Splanchnic ischaemia is an important problem in patients with large burns. This reports the case of an 11-year-old boy with 70% full-thickness TBSA burns who sustained multiple episodes of severe gastrointestinal haemorrhage due to both extensive ischaemic enterocolitis and severe gastric ulceration which required surgical intervention on several occasions. Causative mechanisms of splanchnic ischaemia in this patient including increased mesenteric vascular resistance, abdominal compartment syndrome and enteric feeding, are considered.


Effect of progressive reduction in crude protein and lysine of heavy pigs diets on some technological properties of green hams destined for PDO dry-cured ham production.
In order to investigate the effects of dietary crude protein (CP) and lysine (Lys) content on some technological properties of green hams destined for Protected Designation of Origin (PDO) dry-cured ham, green hams visual appraisal scores, thickness, iodine number and fatty acid composition of subcutaneous fat, and ham weight losses during seasoning (SL) were assessed. The green hams were obtained from 233 pigs fed four diets containing 140 to 110g/kg CP and 6.5 to 5.3g/kg total Lys from 90 to 165kg body weight. A reduction in dietary CP and Lys of up to 20% compared with conventional feeds led to a 15% increase in the thickness of the subcutaneous fat, a 5% decrease in linoleic and polyunsaturated fatty acids in subcutaneous fat and a 7% decrease in SL. A 20% reduction of CP and Lys in diets for finishing pigs has positive effects on the technological properties of green hams destined for PDO dry-cured ham production.


Does lymphadenectomy improve survival in patients with intermediate risk endometrial cancer? A multicentric study from the FRANCOGYN Research Group.
The role of lymphadenectomy in intermediate risk endometrial cancer remains uncertain. We evaluated the impact of lymphadenectomy on overall survival and relapse-free survival for patients with intermediate risk endometrial cancer. We retrospectively reviewed patients from the FRANCOGYN database with intermediate risk endometrial cancer, based on pre-operative and post-operative criteria (type 1, grade 1-2 tumors with deep (> 50%) myometrial invasion and no lymphovascular space invasion), who received primary surgical treatment between November 2002 and August 2013. We compared overall survival and relapse-free survival between staged and unstaged patients. From 1235 screened patients, we selected 108 patients with intermediate risk endometrial cancer. Eighty-two (75.9%) patients underwent nodal staging (consisting of pelvic +/- para-aortic lymphadenectomy). Among them, 35 (32.4%) had lymph node disease. The median follow-up was 25 months (range 0.4 to 155.0). The overall survival rates were 82.5% for patients staged (CI 64.2 to 91.9) vs 77.9 % for unstaged patients (CI 35.4 to 94.2) (P = 0.73). The relapse-free survival rates were 68.9% for staged patients (CI 51.2 to 81.3) vs 68.8% for unstaged patients (CI 29.1 to 89.3) (P=0.67). Systematic nodal staging does not appear to improve overall survival and relapse-free survival for patients with IR EC but could provide information to tailor adjuvant therapy. Sentinel lymph node dissection may be an effective and less invasive alternative staging technique and should provide a future alternative for this population.


Cervical spine assessment in the unconscious trauma patient: a major trauma service's experience with passive flexion-extension radiography.
There is no consensus on the most appropriate method of cervical spine assessment in unconscious trauma patients. Passive flexion-extension imaging is one option for further investigating unconscious patients whose plain cervical radiographs are normal. This study examines the usefulness of this passive imaging in investigating for occult cervical injury. All unconscious patients admitted to The Alfred Trauma Intensive Care Unit over 1 year (January 1-December 31, 1998), who could not be clinically assessed within 48 hours in regard to their cervical spine, were identified. Results of passive flexion-extension radiography were compared with final injury status and clinical outcome as determined by retrospective review of the imaging reports, radiographic films, and case notes. One hundred twenty-three patients with normal three-view plain radiographs proceeded to passive functional investigation. These were false-negative in four of the seven patients with cervical spine injuries at presentation. No patients suffered any adverse neurologic events from their delayed diagnoses or from the flexion-extension procedure. Passive flexion-extension imaging has inadequate sensitivity for detecting occult cervical spine injuries. Although no patients suffered adverse neurologic complications, the potential for devastating consequences from missed cervical injury has resulted in the removal of passive flexion-extension imaging from the screening protocol.


Kinetic analysis of antibody-dependent cellular cytotoxicity: evidence for noncompetitive inhibition by autologous lymphoid cells.
Inhibition of antibody-dependent cellular cytotoxicity (ADCC) by autologous lymphocytes was analyzed by using classical techniques for enzyme-substrate interactions. We determined empirically that the interaction of murine spleen cells with antibody-coated targets to produce lysis was analogous to the interactions that have been described for an enzyme with its substrate. Varying numbers of antibody-coated target cells ("substrate") were mixed with a constant number of spleen cells ("enzyme") and the number of target cells killed ("product") was measured as a function of time. By analogy with Michaelis-Menten enzyme kinetics, two parameters of the reaction were determined: Vmax, the maximum velocity of lysis that is proportional to the number of killer cells present, and K1/2, an intrinsic property of the killer cells. These parameters were found to be independent variables. Addition of autologous lymph node cells produced a dose-dependent decrease in Vmax whereas K1/2 was not significantly changed. By analogy with enzyme kinetics, this inhibition is noncompetitive, suggesting that the autologous lymphocytes inactivate the killer cells rather than competing for the cell-cell binding sites.


Orientation to nutrition care process standards improves nutrition care documentation by nutrition practitioners.
To compare documentation of two groups of clinical nutrition practitioners for evidence of the nutrition care process. This study used a comparative descriptive design. A retrospective chart review was conducted on all nutrition documentation in closed patient records. Documentation of two groups of nutrition practitioners (institution A=practitioners who received initial orientation and routine reinforcement in use of nutrition care process standards; institution B=practitioners who received orientation in use of a further assessment and medical nutrition therapy intervention procedure) was compared for evidence of a six-step nutrition care process. The sample consisted of randomly selected patient records (N=60). A total of 15 oncology and 15 chronic renal failure patient records from each of two Midwestern tertiary-care hospitals were reviewed. Outcome measures were number of nutrition care process steps documented, appropriate relationships among documented steps in the nutrition care process, and the number of complete, incomplete, and interrupted chains. Two-sample t tests and chi(2) analyses were used. Nutrition practitioners at institution A documented approximately three times as many nutrition care process steps per patient per chain that demonstrated appropriate relationships as did nutrition practitioners at institution B (2.69+/-1.15 and 0.80+/-0.62, respectively [mean+/-standard deviation]) (P<.001). There were no outcome judgments related to goals documented in chains at either institution and because of this there were no completed nutrition care process chains at either institution. Nutrition practitioners with orientation to nutrition care process standards documented more related nutrition care process steps than practitioners without this orientation. Providing nutrition practitioners with ongoing education and clinical experiences in use and documentation of the nutrition care process and a standardized language may be indicated to increase the number of completed nutrition care process chains and improve documentation of nutrition care and patient outcomes.


Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia.
Individuals diagnosed as having mild cognitive impairment (MCI) have a high likelihood of progressing to dementia within 3 to 5 years, but not all individuals with MCI progress to dementia. Prognostic uncertainty suggests the need for additional measures to assist the clinician. To assess the added value of qualitative measures of medial temporal atrophy (MTA) to estimate the relative risk of progressing from MCI to dementia. A 3-year, double-blind, placebo-controlled Alzheimer's Disease Cooperative Study initially designed to evaluate the efficacy of donepezil hydrochloride or vitamin E vs placebo to delay progression of MCI to dementia. Memory assessment centers. A total of 190 individuals with MCI. Ratings of MTA performed using magnetic resonance images obtained at baseline. Log-rank tests and Cox proportional hazards ratios examining the significance of MTA estimates in predicting progression of MCI to dementia. A mean MTA score greater than 2.0 was associated with a greater than 2-fold increased likelihood of progression to dementia during the observation period (hazards ratio, 2.30; 95% confidence interval, 1.09-4.92; P = .03) after controlling for age, education, sex, and baseline Mini-Mental State Examination score. Adjusted estimates of MTA were associated with significantly increased risk of developing dementia within 3 years, suggesting that obtaining a magnetic resonance image during the evaluation of MCI may offer additional independent information about the risk of progression to dementia. Given the relatively high prevalence of MCI in the general population, use of this method as part of routine clinical evaluation may help identify individuals who might benefit from increased surveillance and future treatment. clinicaltrials.gov Identifier: NCT00000173.


Methylation of the serum albumin gene as compared to the Kirsten-ras oncogene in hepatocytes and non-parenchymal cells of rat liver.
The extent of methylation of a gene, i.e. percent of cytosine present as 5-methylcytosine, is correlated with its activity. Hypermethylation is associated with non-expression, whereas hypomethylation is a necessary but not sufficient condition for expression. In this study, the methylation state of the serum albumin gene as compared to the Kirsten-ras (Ki-ras) oncogene was assessed in hepatocytes and non-parenchymal cells (NPC) isolated from rat liver. The results of this investigation indicate that the serum albumin gene is hypomethylated in hepatocytes and hypermethylated in NPC. This is consistent with expression of the gene in the former cell type, and non-expression in the latter. In contrast, the Ki-ras oncogene is hypermethylated in both hepatocytes and NPC, suggesting that it is, at most, minimally expressed in normal rat liver.


First strains of the genus Kluyvera in Czechoslovakia.
Fourteen of 21 strains isolated from stools, urine specimens and the hospital environment were identified as Kluyvera. All of these 14 strains corresponded with the literary description of the genus Kluyvera and were identical with two reference strains except that one of them failed to utilize sodium acetate within 7 days. One strain (No. 23441) produced massive growth on Jordan's tartrate, which some Kluyvera do. Important in differentiating indole- and Simmons' citrate-negative Kluyvera strains from Escherichia vulneris (two other of our 21 strains) is negative ornithin decarboxylase and negative Christensen citrate in the latter. Three strains were identified as Citrobacter, where especially indole-positive and urease-negative strains may be reminiscent of Kluyvera. An aberrant strain, No. 25115, which alone failed to grow at 42 degrees C and by some characters differed from Kluyvera, E. vulneris and Enteric Group 10, was identified as E. coli.


Folate deficiency in chicks fed diets containing practical ingredients.
Development of folate deficiency was evaluated in young chicks fed diets containing corn and soybean meal as major constituents. Folic acid deficiency, as indicated by retarded growth and feed efficiency, could be produced in 18-day-old chicks. Chicks fed the basal diet had increased growth when given supplements of either folic acid, choline Cl, or DL-methionine, but not vitamin B12. Relative liver size (grams per 100 g of body weight) was reduced by a methionine or methionine plus choline supplement in two experiments but by folic acid in only one of two experiments. Plasma hemoglobin was reduced by folic acid or a methionine and choline supplement after 42 days on the diets. Folic acid deficiency can be produced in young chicks with a diet based on practical ingredients. Purified diets or very high levels of antibiotic feeding are not necessary to produce folic acid deficiency as long as low levels of methionine and choline are present in the basal diet.


Enhancing fraction in glioma and its relationship to the tumoral vascular microenvironment: A dynamic contrast-enhanced MR imaging study.
EnF is a newly described measure of proportional tumor enhancement derived from DCE-MR imaging. The aim of this study was to assess the relationship between EnF and the more established DCE-MR imaging parameters: K(trans), v(e), and v(p). Forty-two patients with 43 gliomas (16 grade II, 3 grade III, and 24 grade IV) were studied. Imaging included pre- and postcontrast T1-weighted sequences through the lesion and T1-weighted DCE-MR imaging. Parametric maps of EnF, K(trans), v(e), and v(p) were generated. Voxels were classified as enhancing if the IAUC was positive (EnF(IAUC)(60>0)). A threshold of IAUC > 2.5 mmol.s was used to generate EnF(IAUC)(60>2.5). Both measures of EnF were compared with the DCE-MR imaging parameters (K(trans), v(e), and v(p)). In grade II gliomas, EnF(IAUC60>0) and EnF(IAUC60>2.5) correlated with v(p) (R(2) = 0.6245, P < .0005; and R(2) = 0.4727, P = .003) but not with K(trans) or v(e). In grade IV tumors, both EnF(IAUC60>0) and EnF(IAUC60>2.5) correlated with K(trans) (R(2) = 0.3501, P = .001; and R(2) = 0.4699, P < .0005) and v(p) (R(2) = 0.1564, P = .01; and R(2) = 0.2429, P = .007), but not with v(e). Multiple regression analysis showed K(trans) as the only independent correlate of both EnF(IAUC60>0) and EnF(IAUC60>2.5) for grade IV tumors. This study suggests that in grade II tumors, EnF reflects v(p) and varies due to changes in vascular density. In grade IV gliomas, EnF is affected by K(trans) with secondary associated changes in v(p).


Comparison of selection based on yield of half sib progenies and of I1 lines Per Se in rye (Secale cereale L.).
Using the relation of genotype-location and error variances between half-sib families and I1 lines in rye, the efficiency of selection based on I1 lines per se in comparison with half sib family selection is investigated. It is concluded that selection on the performance of I1 lines could be advantageous especially in cases of higher degrees of dominance and gene frequencies of the favourable genes higher than 0,5. The difficulties caused by the strong self-incompatibility in rye and possible ways of overcoming them are discussed.


Recurrent acute pancreatitis in a child with primary hyperparathyroidism.
Hypercalcemia is an important etiology to consider in the evaluation of acute pancreatitis. Not only is it a treatable cause, but understanding the basis for this etiology may provide new insight into the common biochemical mechanisms involved in the pathogenesis of pancreatitis. We report a case of an 11-year-old girl with hypercalcemia due to primary hyperparathyroidism who developed recurrent pancreatitis. We review clinical and experimental data that implicate hypercalcemia as the cause and discuss mechanisms for the association.


Guilt, shame, and religious and spiritual pain.
Hospice care is dedicated to alleviating the pain of dying people. In addition to physical, social, and psychological pain, religious or spiritual pain can add to the struggles of many patients. Religious pain is rooted in guilt leading toward punishment and experienced as fear. It is resourced through the positive teachings of the patient's religious legacy. Spiritual pain is rooted in shame leading a patient to abandon hope in God's love. It is resourced through bringing unconditional love to the patient's sense of self-hatred and inner criticism.


Immunohistochemical localization of growth factors after cryopreservation and 3 weeks' xenotransplantation of human ovarian tissue.
To compare early follicular growth after fresh and frozen-thawed human ovarian tissue xenografting and to investigate whether expression of c-kit, kit ligand (KL), and growth differentiation factor-9 (GDF-9) is maintained after freezing and xenografting of human ovarian tissue. Prospective experimental study. Gynecology research unit in a university hospital. Ten nude (Swiss nu/nu) 6-week-old female mice. The ovarian biopsy samples were obtained from six women, aged 20 to 30 years. Fresh and frozen-thawed ovarian fragments intraperitoneally grafted into nude mice for 3 weeks. Histologic analysis and immunohistochemical evaluation of c-kit, KL, and GDF-9 expression before and after grafting. The integrity and proportion of growing follicles increased similarly in both fresh (64%) and frozen-thawed (59%) xenografts compared with non-grafted tissue (fresh: 40%; frozen-thawed: 21%). Both C-kit and KL staining were detected in the oocytes and granulosa cells of preantral follicles, and GDF-9 expression was observed in the oocytes of preantral follicles in all groups. Freezing does not appear to have a major impact on early follicular growth after transplantation. This study shows, for the first time, expression of c-kit, KL, and GDF-9 in human preantral follicles after ovarian tissue cryopreservation and xenotransplantation.


Induction of anti-GM1 ganglioside antibodies by Campylobacter jejuni lipopolysaccharides.
A frequent association exists between acute motor neuropathy, antecedent Campylobacter jejuni (CJ) and anti-GM ganglioside antibodies. Despite the chemical and immunological similarity between CJ lipopolysaccharides (LPS) and GM1, the mechanism of induction of anti-GM1 antibodies is still unclear. We used CJ LPS to immunize rats, mice and immunodeficient mice lacking in NK, CD8+ or T-cell populations. None of these animals developed significant anti-GM1 titers. However, rats immunized with keyhole limpet hemocyanin which contains the cross-reactive sugar epitope Gal(beta1-3)GalNAc developed high titers of IgM anti-GM1 antibodies. This occurred only after these rats were given an intraperitoneal injection of CJ LPS. These results suggest that a glycoprotein antigenic stimulus can induce B-cells which are autoreactive to ganglioside but which remain anergic. A second stimulus with a cross-reactive LPS can then overcome the anergy to induce autoantibody production. A similar mechanism may explain the occurrence of GM1 antibodies in patients after CJ enteritis.


Xenogenous fertilization of goat ova in the rabbit oviduct.
Eggs from superovulated goats were surgically placed in the oviducts of pseudopregnant rabbits previously inseminated with goat semen. Out of 81 eggs, 30 (37%) exhibited two pronuclei or two blastomeres when recovered 24-36 h later. Transplantation of these embryos into foster nanny goats resulted in the birth of kids.


Chronic kidney disease, anemia, and incident stroke in a middle-aged, community-based population: the ARIC Study.
Chronic kidney disease (CKD) has been linked to higher stroke risk. Anemia is a common consequence of CKD, and recent evidence suggests anemia may increase risk of cardiovascular events. The combined effect of CKD and anemia on stroke risk, however, has not been investigated thoroughly. We analyzed data from a middle-aged, community-based cohort to determine if CKD and anemia interacted to affect stroke risk. Data on 13,716 participants in the prospective Atherosclerosis Risk in Communities (ARIC) Study were analyzed to assess the joint effect of CKD and anemia on risk of incident stroke during a 9-year follow-up period. CKD was defined as a creatinine clearance of <60 mL/min. Anemia was defined as hemoglobin levels of <13 g/dL for men or <12 g/dL for women. Overall, CKD was associated with an increase in stroke risk after adjustment for other factors [hazard ratio HR) 1.81; 95% CI 1.26 to 2.02]. However, this association was modified substantially by anemia. In the presence of anemia, CKD was associated with a substantially higher risk of stroke compared to no CKD (HR 5.43; 95% CI 2.04 to 14.41). In contrast, when anemia was not present, CKD was associated with only a modest, nonsignificant elevation in stroke risk (HR 1.41; 95% CI 0.93 to 2.14). The interaction between CKD and anemia on risk of stroke was statistically significant (P < 0.01). Among middle-aged, community-based persons, the combination of CKD and anemia was associated with a substantial increase in stroke risk, independent of other known risk factors for stroke.


Retinol-binding protein and beta 2-microglobulin in urine of cadmium-fed rhesus monkeys.
Retinol-binding protein (RBP) in the Rhesus monkey had the same electrophoretic mobility, molecular weight, and common antigens as human RBP; beta 2-microglobulin protein (MG) had similar electrophoretic mobility and partial common antigens to human MG. After a prolonged oral administration of cadmium chloride to 10 monkeys over a period of 55 weeks, one monkey of the 30 mg Cd/day group indicated RBPuria and MGuria with the use of anti-human RBP and MG sera when proteinuria appeared. The immunological assay of low-molecular-weight proteins in urine was not applicable for the early detection of cadmium health effects in monkeys.


Immunohistochemistry in ocular carcinomas.
The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.


Gallbladder cancer: surgical results after cholecystectomy in 25 patients with lamina propria invasion and 26 patients with muscular layer invasion.
It has been stated that simple cholecystectomy is sufficient treatment for all patients with pT1 gallbladder cancer. However, other authors note the necessity of carrying out extended surgery when there is muscular-layer involvement. A consecutive series of gallbladder carcinomas with lamina propria or muscular layer invasion were analyzed. Between July 1982 and December 2000, 51 patients with pT1 gallbladder carcinomas were treated with simple cholecystectomy (group A, 25 patients with lamina propria-invasion; group B, 26 patients with muscular-layer invasion). Patients with intraepithelial carcinomas were excluded from the study. There were no differences between the groups in average age, sex ratios, association with other tumors, histologic type, malignancy grade, cholecystitis type, macroscopic aspects, lymph node status, or treatment applied. After an average of 6 years' follow-up, no patients in group A and nine patients (34.6%) in group B died due to gallbladder carcinoma. Cystic lymph nodes could be studied in five of these nine patients who relapsed, and the results were negative for metastasis. Lymphatic or venous invasion was observed in five of these nine patients. According to these results, cholecystectomy is not sufficient treatment for gallbladder carcinoma with muscular-layer invasion.


Transformation of 15-hydroperoxide of eicosapentaenoic acid to lipoxins and trihydroxyeicosatetraenoic acids by 5-lipoxygenase partially purified from potato tubers.
Incubation of 15-hydroperoxide of 5,8,11,14,17-eicosapentaenoic acid (15-HPEPE) with 5-lipoxygenase enzyme, partially purified from potato tubers, resulted in the generation of 6 isomers of lipoxin A5. These compounds were identified by GC/MS analysis of their methyl ester and trimethylsilyl ether derivatives with C-values: 23.3, 24.5, 24.6, 24.9, 25 and 25.2 respectively. The major products of the enzymatic reaction on 15-HPEPE are 5,15-DiHEPE and 13,14,15-trihydroxy eicosatetraenoic acid as identified by RP-HPLC and GC/MS analysis. There are also two new trihydroxyl compounds of eicosapentaenoic acid identified as 11,12,15-trihydroxy and 11,14,15-trihydroxy eicosatetraenoic acid respectively. The transformation of these two trihydroxyl compounds may be due to non-enzymatic rearrangement of 15-HPEPE.


Effects of in vivo and in vitro lindane treatment on rat ventral prostate lipids.
The rat ventral prostate accumulated lindane (gamma-hexachlorocyclohexane) (0.59 +/- 0.07 ppm) when this liposoluble toxicant was injected subcutaneously at a concentration of 1 mg of 100 g body weight for 12 days. Total lipids and phospholipids (especially phosphatidylcholine) amounts were augmented in treated rats. Lindane had no significant influence upon cholesterol mass content in the ventral prostate. Using [1-14C]acetate as radioactive precursor, it was possible to conclude that the mass lipid variations caused by lindane treatment were due, at least in part, to a modification of the endogenous biosynthesis of these lipids. No changes were found in the acetate oxidation to CO2 when control rats and lindane-treated rats were compared.


Common pediatric epilepsy syndromes.
Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as "fifth-day fits," are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as "benign" idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term "benign" may not be appropriate.


Postmortem 3-D reconstruction of skull gunshot injuries.
In cases of severe decomposition or skeletonization of a corpse after cerebral gun shot injury it is difficult to exactly reconstruct the bullet path in the brain. However, in case of murder or homicide this might become necessary to answer forensic questions such as the ability to move or other actions of the victim. Therefore a method in terms of three dimensional reconstruction technique was developed by fusing computed tomography scans (CT) of the original skull and magnetic resonance images (MRI) of a normal brain of adequate size. Hereby five cases were investigated. In three cases an excellent concordance between the reconstructed bullet trajectory and the autopsy reports was achieved. In one case the original brain was not available for CT-scanning due to previous autopsy. However, the findings were in line with the pathology report. In one case there was a difference of about 1-2 cm between the original autopsy description and the reconstructed bullet path. This was due to only a part of the skull being available for image reconstruction. The findings suggest that this method can successfully be applied to adequately reconstruct bullet paths in cases of completely skeletonized skulls, but should carefully be used in cases of incomplete skulls.


The impact of severe exacerbations on quality of life and the clinical course of chronic obstructive pulmonary disease.
Severe exacerbations of chronic obstructive pulmonary disease (COPD) are morbid events with slow recovery periods. They consume substantial healthcare resources, and they may cause a more rapid reduction in lung function over time. Quality of life (QOL) deteriorates in patients who experience exacerbations, and the more frequent the exacerbations, the more rapid the decline in QOL. Hospitalizations due to exacerbations account for up to 70% of the cost of medical care for patients with COPD. Patients with more severe COPD have more hospitalizations compared with those with less severe disease. A number of therapeutic interventions reduce the number of exacerbations and hospitalizations due to respiratory disease. The long-acting anticholinergic bronchodilator tiotropium, influenza vaccination, and possibly case management appear to reduce need for hospitalization substantially. COPD management should include drugs and other interventions that reduce the frequency of exacerbations and minimize their negative impact on the clinical course of the disease.


Portaprival collaterals following distal splenorenal shunt. Incidence, magnitude and associated portal perfusion changes.
Collateral venous pathways develop between the high pressure portal vein and low pressure splenic vein following distal splenorenal shunt. This review of angiography in 50 patients with cirrhosis prior to and 1 year after DSRS shows that 98% developed collaterals: 72% transpancreatic, 48% transgastric, and 46% colonic. Multiple pathways developed in 64% of patients. Grading of the size of these collaterals showed that in 74% these exceeded the size of the portal and/or superior mesenteric vein. The effect of these collaterals on portal perfusion showed that 32% lost perfusion at 1 year, but significantly (P less than 0.05) more alcoholics (48%) lost perfusion than nonalcoholics (16%). The size, site and number of collaterals was not different between etiologies. Late follow-up in a subset of 32 of the patients showed no change in the site, and minimal increase in size of the collaterals at 3-11 years, with no further loss of portal perfusion. We conclude that virtually all patients develop collaterals after DSRS, these are along predictable pathways and are of significant size in the majority. However, development of collaterals per se does not equate to loss of portal venous flow, and a stable pattern is set in the first year after shunt. Characterization of these pathways will permit new approaches to minimizing their development.


Streptomycin and tetracycline resistance plasmids in Staphylococcus hyicus and other staphylococci.
Plasmids associated with resistance to streptomycin, to streptomycin plus chloramphenicol or to tetracycline in Staphylococcus hyicus isolated from the skin of pigs have been compared, by restriction endonuclease digest patterns, with similar staphylococci from human sources and with published DNA base sequences. Several plasmids from Staph. hyicus have proved to have a very similar structure to those described from Staph. aureus but others appeared very dissimilar. This confirms the opinion that staphylococci from animal skin share a pool of plasmids with those from human skin but may also possess some of quite different structure.


Antibody responses and protection in mice immunized with herpes simplex virus type 1 antigen immune-stimulating complex preparations.
The formation of immune-stimulating complexes (iscoms) obtained by mixing the glycoside Quil A with an antigen preparation derived from herpes simplex virus type 1 (HSV-1)-infected cell cultures using a zwitterionic detergent is described. The HSV-1 antigen preparation incorporated into iscoms elicited significantly greater antibody responses in mice than the same preparation administered together with aluminium hydroxide gel, and provided complete protection against HSV-1 or HSV-2 lethal, systemic challenge infection in animals given a single dose containing 5 micrograms of protein. The HSV-1 iscom preparation also provided significant protection in mice against local reactions following challenge with HSV-1 by skin scarification.


The effects of poor sleep on cognitive, affective, and physiological responses to a laboratory stressor.
Recent research suggests that poor sleep may be associated with altered stress regulation. This study aims to examine the associations between prior-night and prior-month sleep measures and affective, cognitive, and physiological responses to a laboratory stressor. Ninety-eight (50 % female) young adults completed measures of sleep quality in the context of a laboratory stress study. Measures included positive (PA) and negative affects (NA) and blood pressure (BP) reactivity, as well as change in pre-sleep arousal. Prior-month poor sleep quality and sleep disturbances predicted dampened BP reactivity. Both prior-night and prior-month sleep quality predicted greater decrease in PA. Sleep-associated monitoring predicted NA reactivity and prolonged cognitive and affective activation. Prior-month sleep continuity predicted greater cognitive pre-sleep arousal change, and prior-month sleep quality, daytime dysfunction, and disturbances predicted prolonged cognitive and affective activation. Findings suggest that inadequate sleep confers vulnerability to poor cognitive, affective, and physiological responses to stress.


Telephone-administered cognitive behavior therapy for obsessive-compulsive disorder.
Exposure with response prevention and cognitive behavior therapy are widely recognized as effective treatments for obsessive-compulsive disorder. Unfortunately, many people with obsessive-compulsive disorder--particularly those living in rural areas--do not have access to therapists providing these treatments. Accordingly, we investigated the efficacy of telephone-administered cognitive behavior therapy for obsessive-compulsive disorder. Two open trials are reported, for a total of 33 people with obsessive-compulsive disorder (without major depression). The first trial consisted of 12 weeks on a waiting list followed by 12 weeks of treatment (delayed treatment). The second trial consisted of 12 weeks of immediate treatment. Obsessive-compulsive symptoms did not change during the waiting period. Symptoms declined from pre- to post-treatment, with gains maintained at 12-week follow-up. For the pooled sample our pre-to-post-treatment effect size was as large or larger than those obtained in other studies of reduced contact treatment, and similar to those of face-to-face exposure with response prevention. Our proportion of treatment dropouts tended to be lower than those of other reduced contact interventions. The results suggest that telephone-administered cognitive behavior therapy is effective and well-tolerated, at least for people with obsessive-compulsive disorder without major depression. It remains to be seen whether this treatment is safe and effective when comorbid major depression is present.


Crystallization of glycosylated and nonglycosylated phytohemagglutinin-L.
In the seeds of legume plants a class of sugar-binding proteins can be found, generally called legume lectins. In this paper we present the crystallization of phytohemagglutinin-L (PHA-L), a glycosylated lectin from the seeds of the common bean (Phaseolus vulgaris). Single PHA-L crystals were grown by vapor diffusion, using PEG as precipitant. The protein crystallizes in the monoclinic space group C2, and diffracts to a resolution of 2.7 angstroms. The unit cell parameters are a=106.3 angstroms, 121.2 angstroms, c=90.8 angstroms, and beta=93.7 degrees. The asymmetric unit probably contains one PHA-L tetramer. Crystals of a recombinant nonglycosylated form of PHA-L, grown under identical conditions, and crystals of the native PHA-L, grown in the presence of isopropanol, did not survive the mounting process.


A monolithic drug-in-adhesive patch of methoxyflavones from Kaempferia parviflora: in vitro and in vivo evaluation.
The aim of this study was to design and develop a suitable monolithic drug-in-adhesive type patch of methoxyflavones from Kaempferia parviflora (K. parviflora) using acrylic polymer Durotak(®) 87-2852. The absence of interaction between components in K. parviflora extract and the adhesive polymer was confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Thirteen K. parviflora patches with different extract loading and permeation enhancers were prepared by the solvent evaporation technique. All formulations showed good physicochemical properties, good stability and satisfactory adhesive properties. The effect of K. parviflora loading and permeation enhancers on methoxyflavones transport across porcine ear skin was also evaluated. The permeation of methoxyflavones increased with the amount of K. parviflora. Among the permeation enhancers investigated, oleic acid increased permeation flux of total methoxyflavones by 1.25 fold compared to the control; whereas menthol shortened the lag time. When oleic acid and menthol were combined, the maximum flux of methoxyflavones and shortest lag time were observed, suggesting a synergistic effect of menthol with oleic acid. The optimal patch formulation contained 15% K. parviflora, 3% oleic acid and 3% of menthol, and this was evaluated via an in vivo pharmacokinetic study using rats. The maximum plasma drug concentration (Cmax) of total methoxyflavones was 218.08ng/ml with Tmax at 8h. The concentrations of methoxyflavones in plasma continued to increase until the end of the experiment, indicating a sustained release into the systemic circulation.


[Malignant struma ovarii: a case report].
Malignant transformation of struma ovarii is exceptional (less than 1%). The histolological diagnosis of malignancy is difficult especially in the well differentiated forms. Immunohistochemistry is highly contributive in the anaplastic forms. The prognosis is relatively favorable except for the metastatic and undifferentiated forms. We report a case of malignant struma ovarii with metastasis observed in a 65-year-old woman who died rapidly from her disease. In light of this observation, we discuss the diagnositic, management and outcome features of these particular tumors.


Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is a slowly progressive abnormal glandular enlargement with heterogeneous morphology. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in this common and significantly morbid disease. Prostatic tissue from 20 patients with BPH and no prior or subsequent prostatic carcinoma was obtained by transurethral prostatectomy (TURP) at the University of California Davis. Apoptotic regulatory proteins: BCL2, BAX and p27 were analyzed by immunohistochemistry and evaluated for expression in four distinct histologic patterns: hyperplastic epithelium, nodules, dilated glands and atrophic/inflammatory glands. Particularly striking was the decreased expression of BAX and an abnormal BCL2 : BAX ratio within all nodules relative to expression in other epithelial patterns. p27 expression was decreased in 35% of the hyperplastic epithelial areas and 10% of the nodules. Overall, abnormal expression of BCL2, BAX and/or p27 was identified in the hyperplastic epithelium of 19 (90%) of specimens and all 12 (100%) of the hyperplastic nodules. The high frequency of abnormalities in apoptosis regulatory genes, suggests that alteration of apoptotic pathways is important for the development of this condition.


Does mesh location matter in abdominal wall reconstruction? A systematic review of the literature and a summary of recommendations.
Mesh implantation during abdominal wall reconstruction decreases rates of ventral hernia recurrence and has become the dominant method of repair. The authors provide a comprehensive comparison of surgical outcomes and complications by location of mesh placement following ventral hernia repair with onlay, interposition, retrorectus, or underlay mesh. A systematic search of the English literature published from 1996 to 2012 in the PubMed, MEDLINE, and Cochrane library databases was conducted to identify patients who underwent abdominal wall reconstruction using either prosthetic or biological mesh for ventral hernia repair. Demographic information was obtained from each study. Sixty-two relevant articles were included with 5824 patients treated with mesh repair of a ventral hernia between 1996 and 2012. Mesh position included onlay (19.6 percent), underlay (60.7 percent), interposition (6.4 percent), and retrorectus (12.4 percent). Prosthetic mesh was used in 80 percent of repairs and biological mesh in 20 percent. The weighted mean incidences of early events were as follows: wound complications, 19 percent; wound infections, 8 percent; seroma or hematoma formation, 11 percent; and reoperation, 10 percent. The weighted mean incidences of late complications included 8 percent for hernia recurrence and 2 percent for mesh explantation. Recurrence rates were highest for onlay (17 percent) or interposition (17 percent) reinforcement. The infection rate was also highest in the interposition cohort (25 percent). Seroma rates were lowest following a retrorectus repair (4 percent). Mesh reinforcement of a ventral hernia repair is safe and efficacious, but the location of the reinforcement appears to influence outcomes. Underlay or retrorectus mesh placement is associated with lower recurrence rates.


Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review.
Selective eligibility criteria of randomized controlled trials (RCTs) are vital to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalizability of results. To determine the nature and extent of exclusion criteria among RCTs published in major medical journals and the contribution of exclusion criteria to the representation of certain patient populations. The MEDLINE database was searched for RCTs published between 1994 and 2006 in certain general medical journals with a high impact factor. Of 4827 articles, 283 were selected using a series technique. Trial characteristics and the details regarding exclusions were extracted independently. All exclusion criteria were graded independently and in duplicate as either strongly justified, potentially justified, or poorly justified according to previously developed and pilot-tested guidelines. Common medical conditions formed the basis for exclusion in 81.3% of trials. Patients were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and 38.5% in older adults). Individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Conditions related to female sex were grounds for exclusion in 39.2% of trials. Of all exclusion criteria, only 47.2% were graded as strongly justified in the context of the specific RCT. Exclusion criteria were not reported in 12.0% of trials. Multivariable analyses revealed independent associations between the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35; 95% confidence interval, 1.11-1.65; P = .003) and between the total number of exclusion criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06-1.52; P = .009). Industry-sponsored trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, and age. Drug intervention trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, female sex, and socioeconomic status. Among such trials, justification for exclusions related to concomitant medication use and comorbidities were more likely to be poorly justified. The RCTs published in major medical journals do not always clearly report exclusion criteria. Women, children, the elderly, and those with common medical conditions are frequently excluded from RCTs. Trials with multiple centers and those involving drug interventions are most likely to have extensive exclusions. Such exclusions may impair the generalizability of RCT results. These findings highlight a need for careful consideration and transparent reporting and justification of exclusion criteria in clinical trials.


A novel method of self-pulling and latter transected delta-shaped Billroth-I anastomosis in totally laparoscopic distal gastrectomy.
We developed a modified delta-shaped gastroduodenostomy technique in totally laparoscopic distal gastrectomy. This novel technique, which effectively reduces the required quantity of linear stapler [1-3], was named as self-pulling and latter transected delta-shaped anastomosis (Delta SPLT) [4]. Delta SPLT was performed on 15 patients with stage cT1-2 antral cancer. We ligated the duodenum with a rope instead of transecting it and used the ligature rope to pull the duodenum during the whole progress of gastroduodenostomy. When closing the entry hole, the duodenum was transected at the same time, which saved one linear stapler. Data of clinicopathologic characteristics, surgical and postoperative outcomes were collected and expressed as means ± standard deviations. All the operations were successfully performed by using no more than four 60-mm linear staplers. The mean BMI of the patients is 23.0 ± 2.5 kg/m2 (range 17.0-26.0 kg/m2), and duration of the operation was 115.0 ± 33.4 min (range 75-215 min), including 22.3 ± 6.7 min (range 15-35 min) of reconstruction. Mean blood loss was 82.7 ± 71.3 mL (range 10-300 mL), and mean times to first flatus was 2.3 ± 1.1 days (range 1-5 days). A mean number of 27.5 ± 5.4 (range 18-38) lymph nodes was retrieved. Overall postoperative morbidity rate was 6.7% (1/15). There was no anastomosis-related complication, but one case of pneumonia developed on postoperative day (POD) 2 which was successfully managed by conservative methods. Patients were discharged (POD mean 5.8 ± 1.3, range 4-9) when their bowel movements recovered and no discomfort with soft diet was claimed. Delta SPLT is a safe and feasible technique and requires less clinical costs.


Preparation of an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine-silica hybrid monolithic column for the enantioseparation of amino acids by nano-liquid chromatography.
An O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine (MQD)-silica hybrid monolithic column was prepared by a facile "one-step" strategy within a 100 μm I.D. capillary. The influence of the methanol, ethylene glycol and water volume ratio, reaction temperature and time, cetyltrimethylammonium bromide and MQD monomers content and volume ratio of tetramethoxysilane and vinyltrimethoxysilane was investigated to obtain a satisfactory morphology of monolithic columns. The optimized MQD-silica hybrid monolithic column was evaluated in terms of permeability, stability, efficiency, reproducibility, and was characterized by scanning electron microscopy and nano-liquid chromatography. Among the 52 N-derivatized protein and non-protein amino acids, a total of 44 analytes could be baseline enantioseparated using the optimized conditions in either reversed phase mode (RPM) or polar organic phase mode (POM). The results showed that POM (ACN/MeOH/HAc/TEA (60/40/0.055/0.005, v/v/v/v)) offered better performance than RPM (10 mM ammonium acetate/ACN (30/70, v/v) (apparent pH=5.3)) in terms of enantioresolution and efficiency with shorter analysis times.


Uncommon causes of acute abdominal pain: multidetector computed tomography pearls and pitfalls for the radiologist on call.
We review uncommon causes of acute abdominal pain in which inconclusive multidetector computed tomography (MDCT) studies were followed by emergency surgery and unexpected diagnoses. Despite dedicated protocols and technical advances, MDCT of uncommon causes of acute abdominal pain still represents a significant challenge for the radiologist on call. We emphasize diagnostic pearls and pitfalls that may help the radiologist on call identify or suspect these uncommon causes of acute abdominal pain on MDCT.


Drug delivery of oligonucleotides by peptides.
Oligonucleotides are promising tools for in vitro studies where specific downregulation of proteins is required. In addition, antisense oligonucleotides have been studied in vivo and have entered clinical trials as new chemical entities with various therapeutic targets such as antiviral drugs or for tumour treatments. The formulation of these substances were widely studied in the past. With this review we will focus on peptides used as drug delivery vehicles for oligonucleotides. Different strategies are summarised. Cationically charged peptides from different origins were used e.g. as cellular penetration enhancers or nuclear localisation tool. Examples are given for Poly-L-lysine alone or in combination with receptor specific targeting ligands such as asialoglycoprotein, galactose, growth factors or transferrin. Another large group of peptides are those with membrane translocating properties. Fusogenic peptides rich in lysine or arginine are reviewed. They have been used for DNA complexation and condensation to form transport vehicles. Some of them, additionally, have so called nuclear localisation properties. Here, DNA sequences, which facilitate intracellular trafficking of macromolecules to the nucleus were explored. Summarizing the present literature, peptides are interesting pharmaceutical excipients and it seems to be feasible to combine the specific properties of peptides to improve drug delivery devices for oligonucleotides in the future.


Chemical sympatholysis: indications, technique and complications.
Chemical sympatholysis is commonly performed for palmar or plantar hyperhidrosis, Buerger's disease, critical lower limb ischaemia where there is no revascularization option available and palliation of pain. The outcome varies from symptomatic improvement to failure, which may result in limb loss in the case of ischaemic limbs.


Diagnostic accuracy of controlled attenuation parameter measured by transient elastography for the non-invasive assessment of liver steatosis: a prospective study.
A novel non-invasive tool based on the evaluation of ultrasound attenuation using transient elastography (TE) has been developed, called controlled attenuation parameter (CAP). We aim to establish the histopathological parameters that significantly influence CAP, the cutoff values and their performance in predicting each steatosis grade on a group of biopsied patients with chronic liver diseases (CLD) from Romania. We prospectively analyzed 201 consecutive CLD patients who underwent CAP measurements using TE. Steatosis, liver fibrosis and necroinflammatory activity were staged and graded during the pathological analysis of bioptic specimens. Univariate and multivariate regression analyses were applied to identify the variables correlated with CAP values. The diagnostic performance of CAP for steatosis prediction was assessed using an AUC analysis. Among the histopathological factors correlating with CAP, the multivariate analysis found steatosis as the only factor independently influencing CAP values (p < 0.001). Maximal diagnostic accuracy (DA) was obtained for the prediction of ≥ 34-66% (S2) fatty load and of 67-100% (S3) fatty load (82.06%, respectively 81.59%) while, for the prediction of ≥ 11-33% (S1) fatty load, DA reached only 76.11%. The negative predictive value for the exclusion of ≥ S2 and S3 was 93.5% and 98.7%, respectively. AUCs calculated between each two steatosis grades were: 0.772 (S0 vs S1), 0.874 (S0 vs S2), 0.904 (S0 vs S3), 0.659 (S1 vs S2), 0.777 (S1 vs S3), and 0.665 (S2 vs S3). Steatosis is the only histopathological factor independently influencing CAP. Maximal DA could be obtained for the prediction of ≥ S2 and S3 (82.06% and 81.59%), while for the prediction of S1, the accuracy reached only 76.11%.


Duplicated coronary sinus with a connecting branch.
A 48-year-old woman with class III heart failure and left bundle branch block underwent an implantation for cardiac resynchronization therapy. Right anterior oblique (RAO) view coronary sinus (CS) venography suggested the antero- and postero-lateral branches appeared to arise from the same vessel of a duplicated CS, but the antero-lateral branch arising from a different vessel was visualized via a connecting branch by the contrast injected into the vessel with the postero-lateral branch, and the distal parts of the two vessels were superimposed in the RAO view. This unusual anomaly may have the potential risk for complications such as perforations.


Clustering of chemisorbed H(D) atoms on the graphite (0001) surface due to preferential sticking.
We present scanning tunneling microscopy experiments and density functional theory calculations which reveal a unique mechanism for the formation of hydrogen adsorbate clusters on graphite surfaces. Our results show that diffusion of hydrogen atoms is largely inactive and that clustering is a consequence of preferential sticking into specific adsorbate structures. These surprising findings are caused by reduced or even vanishing adsorption barriers for hydrogen in the vicinity of already adsorbed H atoms on the surface and point to a possible novel route to interstellar H2 formation.


Influenza viruses in children attending major referral center in Saudi Arabia.
Full text is available as a scanned copy of the original print version.


Ultrasound contrast agents can influence the respiratory burst activity of human neutrophil granulocytes.
Activated leucocytes can bind and, subsequently, phagocytose microbubbles that are used as ultrasound (US) contrast agents. The purpose of this study was to investigate whether or not microbubbles can influence the inflammatory response of human neutrophil granulocytes. Granulocytes isolated from healthy volunteers were activated with various stimuli, for example, the bacterial peptide N-formyl-methyonyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, the protein kinase C activator phorbol myristate acetate (PMA) and the cytokine tumor necrosis factor alpha (TNF-alpha), and incubated with albumin or phospholipid microbubbles. Neutrophil respiratory burst activity and elastase release were quantified. Albumin (Optison) and phospholipid (SonoVue) contrast agents induced an extensive oxidative response of human granulocytes to all the stimuli used, and these effects could be significantly impaired by preincubation of the cells with cytochalasin B. Left heart contrast agents used for contrast-enhanced US assessment can activate human neutrophil granulocytes, inducing an extensive respiratory burst to secondary stimuli. The potential clinical relevance of this effect needs to be elucidated.