Interleukin-21 effectively induces apoptosis in mantle cell lymphoma through a STAT1-dependent mechanism.
Interleukin-21 (IL-21) has been recently shown to modulate the growth of specific types of B-cell neoplasm. Here, we studied the biological effects of IL-21 in mantle cell lymphoma (MCL). All MCL cell lines and tumors examined expressed the IL-21 receptor. Addition of recombinant IL-21 (rIL-21) in vitro effectively induced STAT1 activation and apoptosis in MCL cells. As STAT1 is known to have tumor-suppressor functions, we hypothesized that STAT1 is important in mediating IL-21-induced apoptosis in MCL cells. In support of this hypothesis, inhibition of STAT1 expression using siRNA significantly decreased the apoptotic responses induced by IL-21. To further investigate the mechanism of IL-21-mediated apoptosis, we employed oligonucleotide arrays to evaluate changes in the expression of apoptosis-related genes induced by rIL-21; rIL-21 significantly upregulated three proapoptotic proteins (BIK, NIP3 and HARAKIRI) and downregulated two antiapoptotic proteins (BCL-2 and BCL-XL/S) as well as tumor necrosis factor-alpha. Using an ELISA-based assay, we demonstrated that rIL-21 significantly decreased the DNA binding of nuclear factor-kappaB, a transcriptional factor known to be a survival signal for MCL cells. To conclude, IL-21 can effectively induce apoptosis in MCL via a STAT1-dependent pathway. Further understanding of IL-21-mediated apoptosis in MCL may be useful in designing novel therapeutic approaches for this disease.


Prospective validation of two mathematical models to calculate the risk of endometrial malignancy in patients with postmenopausal bleeding and sonographic endometrial thickness ≥4.5 mm.
To prospectively validate two mathematical models for calculating the likelihood of endometrial malignancy in patients with postmenopausal bleeding (PMPB), sonographic endometrial thickness (ET) ≥4.5 mm and no fluid in the uterine cavity. This is a prospective observational diagnostic validation study performed in a PMPB clinic in a university hospital. Of 860 consecutive patients, 350 fulfilled our inclusion criteria. A standardized history was taken, clinical and transvaginal grey scale and power Doppler ultrasound examinations were performed following a research protocol. The percentage vascularized area of the endometrium at power Doppler examination (VI) was calculated using computer software. The colour content of the endometrial scan was estimated subjectively on a visual analogue scale (VAS). Gold standard was the histological diagnosis of the endometrium. Main outcome measures were area under the receiver operating characteristic curve (AUC), sensitivity and specificity when using the cut-offs suggested in the original study, and calibration curves. Eighty (23%) patients had malignant endometrium. The performance of the models was similar to that in the original study. The model including patient's age, use of hormone therapy, ET and VAS performed best (AUC 0.91; 95% confidence interval [CI] 0.87-0.95; sensitivity 70%, specificity 93%). The model including ET, VI, patient's age and hormone therapy use had AUC 0.89 (95% CI 0.84-0.93; sensitivity 79%; specificity 81%). ET had AUC 0.83 (95% CI 0.78-0.88). The models were reasonably well calibrated. On prospective validation both models retained their diagnostic performance. This suggests that they are robust and potentially clinically useful for individualized patient management.


The physical attractiveness of facially deformed patients before and after craniofacial surgery.
The present experiment investigated whether the physical attractiveness of craniofacially deformed children and adolescents could be improved by surgical procedures. Twenty patients between the ages of 5 months and 17 years were randomly selected from patient files. Patient diagnoses included facial clefts, hypertelorism, Treacher Collins syndrome, and craniofacial dysostosis (Crouzon's and Apert's syndromes). Rigorously standardized photographs of patients taken before and after surgery were shown to 40 "naive" raters ranging in age from 17 to 52 years. Raters analyzed the photographs with regard to global physical attractiveness. These ratings indicated that the patients' physical attractiveness was reliably (62 percent) improved following surgery. The results are discussed in light of recent evidence that untreated craniofacial patients may be at risk for psychosocial disorders and in terms of the growing evidence of the importance of physical appearance for the development of cognitive and social-emotional competence. In addition, a standardized assessment system is described that can be used to facilitate the compilation of actuarial data predicting surgical outcomes. Finally, the importance of empirically evaluating the effectiveness of surgical procedures and practitioners on a continuing basis is emphasized.


Immunologic mechanisms in the pathogenesis of virus-induced murine leukemia. III. Target cell specificity of autoreactive thymocytes.
Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infected with nononcogenic lymphocytic choriomeningitis virus (LCMV), or transformed by the chemical carcinogen 3-methylcholanthrene were not similarly spared. This phenomenon, apparently induced by MuLV-M, is not associated with all persistent virus carrier states. Thymocytes from mice persistently infected with LCMV or with the lactic dehydrogenase virus (LDHV) failed to demonstrate an autoaggressive behavior. That transplantable lymphoma cells (derived from MuLV-M-carriers) were autoreactive in a pattern similar to thymocytes from preleukemic mice suggests a unique role for MuLV in the events leading from altered recognition of "self" to lymphoma.


Molecular analysis of four cases of chronic granulomatous disease caused by defects in NCF-2: the gene encoding the p67-phox.
Chronic granulomatous disease (CGD), a rare inherited primary immunodeficiency disorder, is caused by mutation in any one of the genes encoding components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. NCF2 gene (encoding P67-phox component) is one of them and its mutation is less common to cause CGD (around 5-6%). Here, we assessed mutation analysis of NCF2 in 4 CGD patients with p67-phox defect in Iran. These patients showed classical CGD symptoms. NCF2 sequence analyses revealed two different homozygous mutations including a nonsense mutation in exon 4, c.304C>T (Arg 102X) in one case and a CA deletion in exon 13 (Leu346fsX380) in one brother and sister; the latter is a new mutation which has not been reported in previous studies. In another patient in whom the attempts to amplify exon 2 individually from genomic DNA were unsuccessful, PCR amplification of exon 2 revealed no band of this exon on agarose gel. A PCR amplification mix of exon 2 and exon 7, with an internal control, confirmed the lack of exon 2 in this patient. Although a gross deletion in other exons of NCF2 has been previously reported, a large deletion encompassing exon 2 has been not reported yet. This abstract was also presented in ESID 2012, Florence, Italy.


Optimization of podophyllotoxin extraction method from Linum album cell cultures.
Suspension cultures of Linum album Kotschy ex Boiss. (Linaceae) accumulate podophyllotoxin (an anticancer agent) and could therefore serve as an alternative source of this important aryltetralin lactone lignan. The present work compared four podophyllotoxin extraction methods and optimization of the best one by using single factor experiments. Linum album cell cultures were established from in vitro plantlets and subcultured in MS medium with hormones every 7-8 days. Four podophyllotoxin extraction methods were assayed and the best one was optimized by single factor experiments, studying the effect of methanol concentration, extraction time, and sonication time. Cell cultures accumulated enough podophyllotoxin to be analyzed by HPLC. The methanol/dichloromethane and buffer extraction methods were found to be the best. Methanol alone and hot ethanol were not effective for extracting podophyllotoxin. The optimized method based on methanol/dichloromethane extraction combined with HPLC quantification was able to determine small amounts of podophyllotoxin in Linum album cell cultures, showing that this system could constitute a possible alternative source of podophyllotoxin to Podophyllum (Berberidaceae).


Human intronless genes: functional groups, associated diseases, evolution, and mRNA processing in absence of splicing.
Intronless genes (IGs) constitute approximately 3% of the human genome. Human IGs are essentially different in evolution and functionality from the IGs of unicellular eukaryotes, which represent the majority in their genomes. Functional analysis of IGs has revealed a massive over-representation of signal transduction genes and genes encoding regulatory proteins important for growth, proliferation, and development. IGs also often display tissue-specific expression, usually in the nervous system and testis. These characteristics translate into IG-associated diseases, mainly neuropathies, developmental disorders, and cancer. IGs represent recent additions to the genome, created mostly by retroposition of processed mRNAs with retained functionality. Processing, nuclear export, and translation of these mRNAs should be hampered dramatically by the lack of splice factors, which normally tightly cover mature transcripts and govern their fate. However, natural IGs manage to maintain satisfactory expression levels. Different mechanisms by which IGs solve the problem of mRNA processing and nuclear export are discussed here, along with their possible impact on reporter studies.


The effect of glycemic control on plasma prealbumin levels in type-1 diabetic children.
Plasma prealbumin levels have been used as a sensitive biochemical index in the assessment of nutritional status. The present study was undertaken to determine if diabetic children with uncontrolled diabetes are at greater nutritional risk than those with controlled glycemia. Plasma prealbumin was determined using a radial immunoassay in 42 diabetics and 20 age-matched normal volunteers. Results (mean +/- SE) show that prealbumin levels are significantly (p < 0.02) lower in diabetics (21.5 +/- 1.0) than in normals (25.8 +/- 1.3). Compared with normals, prealbumin levels in controlled diabetics are similar; whereas uncontrolled diabetics have significantly lower (p < 0.05) prealbumin levels. Prealbumin levels were 20.4 +/- 1.7 in uncontrolled diabetics (GHb > 9.00), 21.8 +/- 2.3 in intermediately controlled diabetics (GHb 7.0-9.0), and 22.2 +/- 1.5 in controlled diabetics (GHb < 7.0). The data suggest that diabetics in good control are nutritionally similar to the normal population and that patients in poor control have significantly lower prealbumin than the normal population indicating that metabolic derangement may result in malnutrition.


Rainforests as concert halls for birds: are reverberations improving sound transmission of long song elements?
In forests reverberations have probably detrimental and beneficial effects on avian communication. They constrain signal discrimination by masking fast repetitive sounds and they improve signal detection by elongating sounds. This ambivalence of reflections for animal signals in forests is similar to the influence of reverberations on speech or music in indoor sound transmission. Since comparisons of sound fields of forests and concert halls have demonstrated that reflections can contribute in both environments a considerable part to the energy of a received sound, it is here assumed that reverberations enforce also birdsong in forests. Song elements have to be long enough to be superimposed by reflections and therefore longer signals should be louder than shorter ones. An analysis of the influence of signal length on pure tones and on song elements of two sympatric rainforest thrush species demonstrates that longer sounds are less attenuated. The results indicate that higher sound pressure level is caused by superimposing reflections. It is suggested that this beneficial effect of reverberations explains interspecific birdsong differences in element length. Transmission paths with stronger reverberations in relation to direct sound should favor the use of longer signals for better propagation.


Weight training injuries: part 2: diagnosing and managing chronic conditions.
The repetitive nature of weight training and the often heavy loads involved provide fertile ground for chronic injuries. Common chronic injuries include rotator cuff tendinopathy and stress injuries to the vertebrae, clavicles, and upper extremities. In addition, muscle hypertrophy, poor technique, or overuse can contribute to nerve injuries such as thoracic outlet syndrome or suprascapular neuropathy. Chronic medical conditions that are known to occur in weight trainers include vascular stenosis and weight lifter's cephalgia. Management of chronic problems will vary by condition, but relative rest and correction of poor technique are important for many.


NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia.
Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. We have previously reported that lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons is mediated by the release of proinflammatory factors from activated microglia. Here, we report the pivotal role of NADPH oxidase in inflammation-mediated neurotoxicity, where the LPS-induced loss of nigral dopaminergic neurons in vivo was significantly less pronounced in NADPH oxidase-deficient (PHOX-/-) mice when compared with control (PHOX+/+) mice. Dopaminergic neurons in primary mensencephalic neuron-glia cultures from PHOX+/+ mice were significantly more sensitive to LPS-induced neurotoxicity in vitro when compared with PHOX-/- mice. Further, PHOX+/+ neuron-glia cultures chemically depleted of microglia failed to show dopaminergic neurotoxicity with the addition of LPS. Neuron-enriched cultures from both PHOX+/+ mice and PHOX-/- mice also failed to show any direct LPS-induced dopaminergic neurotoxicity. However, the addition of PHOX+/+ microglia to neuron-enriched cultures from either strain resulted in reinstatement of LPS-induced dopaminergic neurotoxicity, supporting the role of microglia as the primary source of NADPH oxidase-generated insult and neurotoxicity. Immunostaining for F4/80 in mensencephalic neuron-glia cultures revealed that PHOX-/- microglia failed to show activated morphology at 10 h, suggesting an important role of reactive oxygen species (ROS) generated from NADPH oxidase in the early activation of microglia. LPS also failed to elicit extracellular superoxide and produced low levels of intracellular ROS in microglia-enriched cultures from PHOX-/- mice. Gene expression and release of tumor necrosis factor alpha was much lower in PHOX-/- mice than in control PHOX+/+ mice. Together, these results demonstrate the dual neurotoxic functions of microglial NADPH oxidase: 1) the production of extracellular ROS that is toxic to dopamine neurons and 2) the amplification of proinflammatory gene expression and associated neurotoxicity.


Supernumerary marker chromosome 7 and maternal uniparental disomy 7 in a boy with growth retardation and triangular face.
We report on a 12-month-old boy with pre and post-natal growth retardation, triangular face and mild psychomotor retardation. Karyotyping revealed a supernumerary marker chromosome (SMC) in 36% of cells. Using fluorescence in situ hybridization and BAC clones, the supernumerary marker chromosome was found to be a highly deleted chromosome 7 with breakpoints within the pericentric euchromatin (partial trisomy 7). Microsatellite typing indicated maternal uniparental disomy of chromosome 7 (matUPD7). The patient showed only few signs of the Silver-Russell syndrome. He therefore reflects the mild end of the phenotypic spectrum in patients with matUPD7. The case supports the argument that karyotyping is warranted in patients with short stature and only few additional features, and that UPD studies are required in patients with a SMC(7). Considering that the SMC(7) contributed very little, if any, to the phenotype of this boy, we propose that UPD7 studies should be carried out in children with pre- and postnatal growth retardation of unknown cause even in the absence of a SMC.


Induction and decay of thermotolerance in rainbow trout fibroblasts.
Thermotolerance was studied in the rainbow trout fibroblast cell line RTG-2. RTG-2 cultures that had been incubated at 28 degrees C for 24 h were better able to withstand ultimately lethal temperatures above 28 degrees C than RTG-2 cultures that had been maintained at the routine growth temperature of 22 degrees C. This thermotolerance developed rapidly between 3 and 6 h and was fully developed by 24 h at 28 degrees C. After development for 24 hr at 28 degrees C, thermotolerance showed little change over 72 h at 0 and 5 degrees C but approximately a 40 and 60% reduction at 10 and 22 degrees C, respectively. This is the first demonstration of heat-induced thermal resistance in the cells of a poikilothermic vertebrate.


Effects of levodopa on pulmonary function in Parkinson's disease.
Upper-airway obstruction (UAO) may be present in patients with Parkinson's disease (PD), and its reversibility after levodopa therapy has been suggested. To investigate the effects of oral intake of levodopa on pulmonary function and UAO criteria in patients with PD, we studied 22 patients with PD. Pulmonary function tests were performed after a 12-h withdrawal of levodopa therapy, and 1 h after oral intake of placebo or levodopa, according to a double-blind, placebo-controlled, crossover study. Six UAO criteria were recorded to detect UAO in patients. UAO was found in 5 of 21 patients on baseline conditions (1 patient could not perform all tests). Among the patients with UAO, after levodopa therapy three of five patients did not meet the four of six required criteria for defining UAO. Levodopa produced its effects on UAO criteria by means of a saw-tooth pattern improvement and/or a decrease below the defined thresholds of the peak inspiratory flow and the FEV(1)/peak expiratory flow (PEF) and FEV(1)/forced expiratory flow after 50% of the FVC (FEV(0.5)) ratios. Levodopa PEF increased by 0.85 L/s in patients with UAO and by 0.24 L/s in patients without UAO, while after placebo it increased by 0.03 L/s in patients with UAO and decreased by 0.16 L/s in patients without UAO (p = 0.02). Whereas in patients without UAO an increase of the FEV(1)/PEF and FEV(1)/FEV(0.5) ratios was observed after placebo and levodopa intake, these ratios decreased after levodopa and increased after placebo in patients with UAO. These results show that levodopa administration in patients with PD induces significant variations in PEF and UAO ratios (FEV(1)/PEF and FEV(1)/FEV(0.5)).


Promoter sequences from two different Brassica napus tapetal oleosin-like genes direct tapetal expression of beta-glucuronidase in transgenic Brassica plants.
To investigate the sequences responsible for the regulated expression of tapetal-specific oleosin-like genes, ca. 2 kb of the 5'-upstream regions from two divergent genes, OlnB;4 and OlnB;13, were isolated, sequenced and fused to the reporter gene beta-glucuronidase for study in transgenic Brassica napus plants. Although the proteins encoded by these two genes are highly divergent, except for the conserved oleosin-like domain, the first 250 bp of their 5'-upstream regions was 86% identical, including a region of 150 bp upstream from the TATA box. Analysis of 42 independent transformants by histochemical and fluorometric methods showed that both promoters directed tapetal-specific expression that peaked at the 4 mm flower bud stage.


Rational drug design, synthesis and biological evaluation of dihydrofolate reductase inhibitors as antituberculosis agents.
A series of 2,4-diamino-s-triazines was designed, with potential for activity against Mycobacterium tuberculosis (Mtb) dihydrofolate reductase enzyme, on the basis of virtual screening results and structure-based drug design. The compounds were evaluated against Mtb (H37Rv) and their cytotoxicity was assessed using VERO cell lines. Of particular note, two compounds were found to have the most promising antituberculosis activity (6b minimum inhibitory concentration: 1.76 μM and 6i minimum inhibitory concentration: 1.57 μM) along with low cytotoxicity (CC50: >300 μM). The enzyme assay results of these two indicated significant inhibition of Mtb dihydrofolate reductase along with selectivity. Selected derivatives were tested against dormant tubercle bacilli in vivo and ex vivo indicating potential inhibition. This study provides promising antituberculosis dihydrofolate reductase inhibitors that can act as potential leads for further development.


Peroxiredoxin 5 prevents iron overload-induced neuronal death by inhibiting mitochondrial fragmentation and endoplasmic reticulum stress in mouse hippocampal HT-22 cells.
Iron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca2+, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood. In this study, we demonstrated that iron overload induces ROS production earlier in the ER than in the mitochondria, and peroxiredoxin 5 (Prx5), which is a kind of antioxidant induced by iron overload, prevents iron overload-induced mitochondrial fragmentation mediated by contact with ER and translocation of Drp1, by inhibiting ROS production and calcium/calcineurin pathway in HT-22 mouse hippocampal neuronal cells. Moreover, Prx5 also prevented iron overload-induced ER-stress and cleavage of caspase-3, which consequently attenuated neuronal cell death. Therefore, we suggested that iron overload induces oxidative stress in the ER earlier than in the mitochondria, thereby increasing ER stress and calcium levels, and consequently causing mitochondrial fragmentation and neuronal cell death. So we thought that this study is essential for understanding iron toxicity in neurons, and Prx5 may serve as a new therapeutic target to prevent iron overload-induced diseases and neurodegenerative disorders.


Long-term follow-up after pulmonary valve replacement in repaired tetralogy of Fallot.
Surgical pulmonary valve replacement (PVR) in previously repaired tetralogy of Fallot (TOF) is frequently required. There are few data in large series of patients with long-term follow-up. Our aim was to review our 40-year experience with PVR after TOF repair and to evaluate prognostic factors for reintervention and death. Between 1973 and 2012, 278 patients with repaired TOF (53% men; 31.4 ± 16.4 years) underwent first PVR 24 ± 13 years after TOF repair. Three or more previous operations were performed in 17% of the patients, and 42% were in New York Heart Association (NYHA) class III/IV. PVR types included porcine (n = 211), pericardial (n = 37), homograft (n = 27), and mechanical (n = 3). Early mortality was 1.4%. Mean follow-up was 7.3 ± 6.8 years (maximum, 34 years). Overall survival at 5, 10, and 15 years was 93%, 83%, and 80% compared with 99%, 97%, and 95% in a gender- and age-matched US population, p <0.001. Independent risk factors for death were older age at complete repair (hazards ratio [HR] 1.2, p = 0.012), ≥ 3 previous cardiac operations (HR 1.9, p = 0.019), NYHA class III/IV at PVR (HR 2.7, p = 0.019), and large body surface area at PVR (HR 1.9, p <0.001). Reintervention after initial PVR occurred in 25 patients. Overall 5, 10, and 15 years freedom from pulmonary valve reintervention was 97%, 85%, and 75%, respectively. Multivariate analysis demonstrated older age at PVR to be protective from reintervention (HR 0.7, p <0.001). In conclusion, PVR is a safe operation with a low rate of reintervention in repaired TOF. The total number of cardiac operations, surgical timing, and the NYHA classification before PVR are important prognostic factors.


Intermittent applications of continuous ultrasound on the viability, proliferation, morphology, and matrix production of chondrocytes in 3D matrices.
Chondrocytes, the cellular component of the articular cartilage, have long been recognized as strain-sensitive cells, and have the ability to sense mechanical stimulation through surface receptors and intracellular signaling pathways. This strain-induced biological response of chondrocytes has been exploited to facilitate chondrocyte culture in in vitro systems; examples include the application of hydrostatic pressure, dynamic compression, hydrodynamic shear (i.e., rotating bioreactors), and low-intensity pulsed ultrasound (US). While the ability of US to influence chondrogenesis has been documented, the precise mechanisms of US-induced stimulation continue to be investigated. There remains a critical need to evaluate the impact of US on chondrocytes in 3D culture, which is a necessary microenvironment for maintaining the chondrocyte phenotype. In this study, a continuous US wave for predetermined time intervals was employed, as opposed to pulsed US used in previous studies, to stimulate chondrocytes seeded in 3D scaffolds. The chondrocytes (n = 6) were subjected to US stimulation as follows: 1.5 MHz for 161 seconds, 5.0 MHz for 51 seconds, and 8.5 MHz for 24 seconds, and the US signal was applied twice in a 24-hour period. Scaffolds that are not stimulated by US served as the control. Both the control and the US-stimulated groups were maintained in culture for 10 days, and at the conclusion of the culture period, chondrocytes were assayed for total DNA content, morphology, and cartilage-specific gene expression by reverse transcriptase polymerase chain reaction. Our results show that chondrocytes when stimulated with continuous US for predetermined time intervals possessed higher cellular viability (1.2 to 1.4 times) and higher levels of type II collagen and aggrecan mRNA expression when compared to controls.


Bedside methods versus dual energy X-ray absorptiometry for body composition measurement in COPD.
The measurement of body composition is of value in the nutritional assessment of patients with chronic obstructive pulmonary disease (COPD). The purpose of the present study was to compare two bedside methods for the measurement of body composition using dual energy X-ray absorptiometry (DEXA) as a reference method. Fat-free mass (FFM) was measured using DEXA, bioelectric impedance analysis (BIA) and skinfold anthropometry (SFA) in a cohort of 85 COPD patients accepted for pulmonary rehabilitation. Patients whose body mass index was >30 were excluded. Relative to DEXA, BIA underestimated FFM, whereas it was overestimated by SFA. There was a systematic increase in bias with mean FFM for both DEXA versus BIA and DEXA versus SFA, but this was almost eliminated when results were expressed as FFM index. Significant sex differences in the bias of BIA and SFA measurements of FFM were found. Forty-two (49.4%) patients were identified as nutritionally depleted using DEXA. Compared to DEXA, the sensitivity for detecting nutritional depletion was 86 and 74% for BIA and SFA, respectively, and the specificity 88 and 98%, respectively. There are significant intermethod differences in the measurement of body composition in chronic obstructive pulmonary disease patients. The choice of measurement method will have implications for nutritional assessment in chronic obstructive pulmonary disease.


Neuropathogenicity and sensitivity to antibody neutralization of lactate dehydrogenase-elevating virus are determined by polylactosaminoglycan chains on the primary envelope glycoprotein.
Common strains of lactate dehydrogenase-elevating virus (LDV, an arterivirus), such as LDV-P and LDV-vx, are highly resistant to antibody neutralization and invariably establish a viremic, persistent, yet asymptomatic, infection in mice. Other LDV strains, LDV-C and LDV-v, have been identified that, in contrast, are highly susceptible to antibody neutralization and are incapable of a high viremic persistent infection, but at the same time have gained the ability to cause paralytic disease in immunosuppressed C58 and AKR mice. Our present results further indicate that these phenotypic differences represent linked properties that correlate with the number of N-glycosylation sites associated with the single neutralization epitope on the short ectodomain of the primary envelope glycoprotein, VP-3P. The VP-3P ectodomains of LDV-P/vx possess three N-glycosylation sites, whereas those of LDV-C/v lack the two N-terminal sites. We have now isolated four independent neutralization escape variants of neuropathogenic LDV-C and LDV-v on the basis of their ability to establish a high viremic persistent infection in mice. The VP-3P ectodomains of all four variants had specifically regained two N-glycosylation sites concomitant with decreased immunogenicity of the neutralization eptitope and decreased sensitivity to antibody neutralization as well as loss of neuropathogenicity.


The physiologic role and therapeutic potential of the Mpl-ligand in thrombopoiesis.
The constant and appropriate production of megakaryocytes, and subsequently platelets, is critical for maintenance of hemostasis. Inadequate megakaryopoiesis and/or thrombopoiesis can lead to serious bleeding disorders. The humoral factors regulating these processes have been the subject of study for several decades. Although many cytokines have been shown to influence megakaryocyte development and platelet production, none appeared to do so in a lineage-dominant fashion analogous to the situation with erythrocyte and neutrophil production. More recently, a ligand for the hematopoietic cytokine receptor encoded by the c-mpl gene (Mpl ligand) has been shown to have profound effects on megakaryocyte growth and development. These effects appear to include the expansion of megakaryocyte progenitors (i.e. megakaryocyte-colony stimulating activity), and induction of megakaryocyte maturation to the point of platelet production (i.e. thrombopoietin). Administration of recombinant Mpl-ligand to rodents or primates treated with myelosuppressive agents abrogates or alleviates the severity and the duration of the resultant thrombocytopenias. The in vitro and in vivo data to date indicate that this new cytokine holds tremendous promise as a therapeutic agent for the treatment of thrombocytopenia associated with cancer therapies.


Drug and vehicle deposition from topical applications: localization of minoxidil within skin strata of the hairless mouse.
The cutaneous bioavailability of topical 2% minoxidil solution was verified in live hairless mice. Minoxidil and propylene glycol deposition on the skin surface, epidermis and dermis from the single-dose in vivo study were compared with the results from previous in vitro studies. A distinct difference is apparent in the epidermis where the in vitro values are 11-22 times higher than the in vivo values for minoxidil and 8-16 times higher for propylene glycol. The differences were not as great in the dermis. Percutaneous absorption of the drug appeared to be a very small fraction of the applied dose. Similarly shaped stratum corneum and plasma concentration profiles and the relatively constant dermal profiles of minoxidil and propylene glycol open the possibility of transappendageal routes being involved in percutaneous absorption. The greater amount of drug and vehicle found in the dermis from in vitro studies can be explained by the absence of dermal clearance. The overestimation in the amount of drug found in the epidermis in vitro may also be attributable to poor dermal clearance. On the whole, the study raises questions about the use of in vitro tissue dispositions for bioavailability assessment and bioequivalence demonstration.


Large volume injection in gas chromatography using the through oven transfer adsorption desorption interface operating under vacuum.
The present work describes a modification of the Through Oven Transfer Adsorption Desorption (TOTAD) interface, consisting of coupling a vacuum system to reduce the consumption of the helium needed to totally remove the eluent for large volume injection (LVI) in gas chromatography (GC). Two different retention materials in the liner of the TOTAD interface were evaluated: Tenax TA, which was seen to be unsuitable for working under vacuum conditions, and polydimethylsiloxane (PDMS), which provided satisfactory repeatability as well as a good sensitivity. No variability was observed in the retention times in either case. Solutions containing organophosphorous pesticides in two different solvents, a polar (methanol/water) and a non-polar (hexane) solvent, were used to evaluate the modification. The vacuum system coupled to the TOTAD interface allowed up to 90% helium to be saved without affecting the performance.


Pregnant diabetic rats fed the antioxidant butylated hydroxytoluene show decreased occurrence of malformations in offspring.
The increased incidence of congenital malformations in diabetic pregnancy may be associated with an excess of free oxygen radicals in the embryo. We have previously blocked the dysmorphogenesis of rat embryos exposed to high glucose and beta-hydroxybutyrate concentrations in vitro by increasing the antioxidant capacity of the conceptus. In the present study, we attempted to diminish the teratogenic process in vivo in a rat model of diabetic pregnancy. Thus, pregnant diabetic and normal rats were fed either a standard diet or a diet enriched with 1% of the antioxidant butylated hydroxytoluene (BHT). The fetuses of the diabetic rats were smaller than the fetuses of the normal rats (body weight 2.70 g vs. 3.68 g) when the mothers were fed a standard diet. The BHT diet increased the fetal weight in the offspring of diabetic rats (3.17 g), with no change in fetuses of the normal rats (3.65 g). The placentas of diabetic rats were heavier than the placentas of normal rats; this difference was not present in the BHT-fed rats. The BHT treatment had no effect on the rate of resorptions, which was increased in the diabetic rats compared with the normal rats. In contrast, the increased rate of congenital malformations in the offspring of diabetic rats (19%), compared with that in the normal rats (0%), was markedly decreased by the BHT diet (2.3%). No malformations were found in the normal rats treated with BHT. These data support the notion that an excess of free oxygen radicals in the embryo contributes to the teratogenic process of diabetic pregnancy and, thus, suggest an area for future preventive therapeutic treatment.


Nanostructures for pH-sensitive Drug Delivery and Magnetic Resonance Contrast Enhancement Systems.
According to the differences of microenvironments between tumors and healthy tissues, if the anticancer drugs or magnetic resonance contrast agents (MRCAs) can be controlled to precisely match physiological needs at targeted tumor sites, it is expected to acquire better therapeutic efficacy and more accurate diagnosis. Over the decade, stimuli-responsive nanomaterials have been a research hotspot for cancer treatment and diagnosis because they show many excellent functions, such as in vivo imaging, combined targeting drug delivery and systemic controlled release, extended circulation time, etc. Among the various stimuli nanosystems, pH-stimuli mode is regarded as the most general strategy because of solid tumors acidosis. When exposed to weakly acidic tumor microenvironment, pH-responsive nanoplatforms can generate physicochemical changes for their structure and surface characteristics, causing drug release or contrast enhancement. In this review, we focused on the designs of various pH-responsive nanoplatforms and discussed the mechanisms of controlled drug release or switch on-off in MRCAs. This review also discussed the efficacy of cellular internalization for these nanoplatforms via endocytosis of acidic tumor cell. Meanwhile, nanoplatforms response to acidic intracellular pH (such as endosome, lysosome) are discussed, along with approaches for improving drug release performance and magnetic resonance contrast enhancement. A greater understanding of these pH-responsive nanoplatforms will help design more efficient nanomedicine to address the challenges encountered in conventional diagnosis and chemotherapy.


Long-term weight loss: the effect of pharmacologic agents.
We reviewed 20 English-language weight-reduction studies, reported between 1967 and March 1993, of the effect of > or = 6 mo of pharmacologic therapy on weight loss and its maintenance to determine the clinical benefits of extended treatment, propose treatment guidelines, and identify future research needs. Pharmacologic agents included phentermine, mazindol, fenfluramine, dexfenfluramine, and fluoxetine. Study designs varied with respect to blinding, use of a single agent vs a combination, dosing, length of therapy, patient selection, adjunctive therapy, and visit frequency. At endpoint, weight loss varied from study to study but a plateauing of weight loss or weight regain was observed after approximately 6 mo. The benefits of extended treatment appear to outweigh the risks for those patients who are unable to lose sufficient weight without pharmacologic therapy but who maintain adequate weight loss with long-term pharmacologic therapy. Future studies should define and evaluate pharmacologically responsive and unresponsive subgroups.


Understanding the contemporary role of the intellectual disability nurse: A review of the literature.
To identify the specialist role/s that nurses perform and the specialist skills that nurses use when caring for people with intellectual disability. Adhering to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," various subject headings were used to systematically search six electronic databases for articles published in English between 2000 and 2017. A total of 27 articles were reviewed. The literature demonstrates that similarities exist between the physical care delivered to people with intellectual disability and that delivered to people without intellectual disability. However, skills in the areas of communication, advocacy and person-centred care differ between these two groups. Our findings suggest that the skill set of the specialist intellectual disability nurse is not uniquely technical but it is uniquely relational that incorporate increased patience and resilience when developing relationships with the people they care for. This review has provided insights into the main differences in the skills required when working with people with intellectual disability compared to working with those without. However, minimal literature was identified that adequately describes what is unique about the performance of the role of specialised intellectual disability nurses-especially in Australia. Understanding the skills required of nurses caring for people with intellectual disability provides the opportunity for more nurses to develop these specialised relational skills and for this branch of nursing to attract professional recognition that is currently limited.


Investigating the post-chemiluminescence behavior of phenothiazine medications in the luminol-potassium ferricyanide system: molecular imprinting-post-chemiluminescence method for the determination of chlorpromazine hydrochloride.
A new post-chemiluminescence (PCL) phenomenon was observed when phenothiazine medications were injected into the reaction mixture after the chemiluminescence (CL) reaction of luminol and potassium ferricyanide had finished. A possible reaction mechanism was proposed based on studies of the kinetic characteristics of the CL, CL spectra, fluorescence spectra, and on other experiments. The feasibility of determining various phenothiazine medications by utilizing these PCL reactions was examined. A molecular imprinting-post-chemiluminescence (MI-PCL) method was established for the determination of chlorpromazine hydrochloride using a chlorpromazine hydrochloride-imprinted polymer (MIP) as the recognition material. The method displayed high selectivity and high sensitivity. The linear range of the method was 1.0 x 10(-8) approximately 1.0 x 10(-6), with a linear correlation coefficient of 0.9985. The detection limit was 3 x 10(-9) g/ml chlorpromazine hydrochloride, and the relative standard deviation for a 1.0 x 10(-7) g/ml chlorpromazine hydrochloride solution was 4.0% (n = 11). The method has been applied to the determination of chlorpromazine hydrochloride in urine and animal drinking water with satisfactory results.


Comparison of sensitivity to ultraviolet B irradiation between human lymphocytes and hematopoietic stem cells.
To investigate the clinical applicability of prophylaxis of post-transplant graft-versus-host disease by UV-B irradiation of stem cell preparations, the UV-B sensitivities of human lymphocytes and primitive hematopoietic progenitors were compared. The mononuclear cell fractions (MNC) derived from human cord blood and granulocyte-colony-stimulating factor-mobilized peripheral blood were used. After UV-B irradiation, lymphocyte proliferation ability, hematopoietic colony-forming cells, and apoptotic cells were analyzed. At a dose of 33 J/m(2), significant differences were observed in the residual percentages of hematopoietic progenitors and lymphocyte functions [ANOVA, F (5,46) = 19.4; P <.0001], and the difference between CFU-C (85.2% + 24.0%; n = 8) and MLR (12.7% + 12. 6%; n = 10) was significant (P <.0001). There were no significant differences in the residual percentages of CFU-C, HPP-CFC, and LTC-IC. Percentages of annexin V-positive cells in the total MNC and the CD34(+) cell population in MNC after UV-B irradiation were 69.8% and 18.7%, respectively. In conclusion, there was a range of UV-B doses over which T lymphocytes were inactivated but hematopoietic progenitors, including HPP-CFC and LTC-IC, were preserved.


Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.
A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI).


[Determination of 15 trace rare earth elements in rice by microwave digestion ICP-MS].
An ICP-MS method for direct determination of 15 trace rare earth elements in rice was developed. Rapid and complete dissolution of rice was achieved by a microwave digestion procedure with concentrated nitric acid and hydrogen peroxide. The detection limits are 7.0-25.8 pg/mL, the recoveries for spiked samples are 95-105%, RSDs are 2.3-4.2%. This method is rapid, sensitive and accurate.


Cesarean rates and severe maternal and neonatal outcomes according to the Robson 10-Group Classification System in Khon Kaen Province, Thailand.
To assess cesarean rates and maternal and neonatal outcomes in each group in the Robson 10-Group Classification System (TGCS). In a cross-sectional study, data were reviewed from all pregnant women who delivered at 24 government hospitals in Khon Kaen Province, Thailand, in 2014. Delivery and perinatal outcomes were recorded. Of 18 043 deliveries, 5666 (31.4%) were by cesarean. Women in group 5 (previous cesarean) accounted for the most cesareans (1472, 26.0%). Groups 1 and 2 (nulliparous women) accounted for 2355 (41.6%) of procedures; the rate of cesarean within these two groups was 19.4% (1162/5981) and 71.2% (1193/1675), respectively. As compared with group 1, women in groups 2, 4, 6, 7, and 10 had significantly increased risk of severe maternal outcomes, and those in groups 6, 7, 8, 9, and 10 had an increased risk of severe neonatal outcomes. The rate of cesarean in the study setting was high, and three out of four procedures were performed for women in groups 5, 1, and 2. Interventions should be focused on these groups to reduce the overall cesarean rates.


Standardized propolis extract and calcium hydroxide as pulpotomy agents in primary pig teeth.
The purpose of this study was to evaluate the histological features of the pulp tissue in primary pig teeth submitted to pulpotomy and capped with calcium hydroxide-based and standardized propolis extract-based pastes, and the combination of these pastes. Nine 4-month-old male pigs were used in this study, which were distributed into 4 groups, according to the studied pastes: Group 1-calcium hydroxide; Group2-standardized propolis extract; Group 3-combination of pastes 1 and 2 in the proportion 1:1; and Group 4-control. The teeth used for the pulpotomy were the 4 mandibular primary incisors. After 7, 21, and 42 days, the animals were killed and the teeth were re-moved for histological analysis. At 42 days, all teeth in Groups 1 to 3 presented a complete hardtissue barrier and the pulp tissue beneath was without inflammation. According to these findings, calcium hydroxide and standardized propolis extract favored the formation of a hard tissue barrier in primary pig teeth submitted to pulpotomy.


[Characteristics of the G-loads in sports stunt flying].
Thirty well-qualified flying sportsmen, aged 22-42, who performer 210 aerobatic flights onboard a sporting airplane Yak-50, were examined, using an automatic monitoring system. The flyers were exposed to +9 Gz and -6 Gz as a maximum the duration of which was 10 s and 5 s, respectively. The onset rate varied from 0.5 to 2.5 G/s (with the mean rate 1 G/s), reaching 4.2 G/s as a maximum. On the average, the training flight lasts 25 min, 45-50% of which the pilot experiences acceleration of various values and different sign. The most common acceleration values are: +6 and +7 Gz or -4 and -5 Gz.


Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration.
Exudative age-related macular degeneration (AMD) is a common cause for a severe central visual loss. The complement system has been implicated in the pathogenesis of drusen. Recently, a complement factor H (CFH) polymorphism, which is characterized by a tyrosine (Y)-to-histidine (H) exchange at position 402 of the CFH gene, has been suggested as a major risk factor for AMD in a North American population. The aim of the present study was to investigate a hypothesized association between the CFH Y402H polymorphism and the presence of exudative AMD in a Central European population of Caucasoid descent as well as to determine the genotype distribution among different types of exudative AMD. Retrospective case-control study. The study cohort consisted of 179 patients with exudative AMD and 163 controls. Determination of genotypes was carried out by allele-specific digestion of polymerase chain reaction products. Genotypes of CFH Y402H polymorphism. The prevalence of the CFH 402HH genotype was significantly higher in patients with exudative AMD than among controls (35.2% vs. 8.6%; P<0.001). Homozygosity for the CFH Y402H polymorphism was associated with an odds ratio of 5.78 (95% confidence interval, 3.09-10.83) for exudative AMD. Subgroup analysis revealed that the CFH 402HH genotype was significantly more prevalent in eyes with predominantly classic with no occult choroidal neovascularization (CNV) than in those with either retinal angiomatous proliferation, occult with no classic CNV, or predominantly classic with occult CNV. Our data suggest that the CFH Y402H polymorphism is a major risk factor for exudative AMD in a Central European population.


Modifications of glucose storage and oxidation in nonobese diabetics, measured by continuous indirect calorimetry.
A new application of continuous indirect calorimetry is described for measuring the disposal of a glucose load. In a group of 10 normal subjects, 3 h after a 100 g oral glucose load, 20 g glucose was oxidized at basal rate, 19 g in response to the load and 63 g stored, while a decrease of 2 g was observed in the glucose space (GS). In a group of four type I, insulin-dependent diabetics, both glucose oxidation (9 g at the basal rate and 4 g in response to the load) and glucose storage (9 g) were markedly decreased, with the remainder either being lost in the urine (36 g) or remaining in the glucose space (42 g). In a group of eight nonobese type II, non-insulin-dependent diabetics, glucose oxidation both in the basal rate and in response to the load was slightly decreased (13 and 14 g, respectively) and glucose storage decreased to 40 g. These results suggest that, in type I diabetics, complete insulin deficiency seriously impairs two major mechanisms regulating glucose homeostasis, i.e., glucose storage and oxidation, while, in type II diabetics, the remaining insulin secretion attentuates these disturbances.


Properties of two calcium transport systems of isolated rat ileal epithelial cells: effects of Ca2+ channel modulators and membrane potential examined with fluorescent dye, fura-2.
Calcium transport systems of isolated ileal epithelial cells were investigated. The concentration of cytosolic free calcium ions, [Ca2+]i, was monitored with a fluorescent Ca2+ dye, fura-2. The fluorescence intensity ratio (I340/I380) was used as an index of [Ca2+]i. [Ca2+]i of the cells suspended in the nominally Ca(2+)-free solution was estimated at 52 +/- 3 nM. Ca2+ uptake was followed for as long as 5 min in the presence of 100-1000 microM added CaCl2. Most of the experiments were performed at 200 microM CaCl2. The Ca2+ uptake was abolished by 0.8 mM Ni2+ and 50 microM Mn2+ and partitally antagonized by 50 microM verapamil and 50 microM diltiazem but not affected by 20 microM nifedipine. The Ca2+ entry was reduced by increasing concentrations of extracellular K+ in the presence of valinomycin, suggesting a voltage-dependent nature of the uptake. On the other hand, the Ca2+ transport doubled in the presence of Bay K8644 (8 microM), a Ca2+ channel agonist. The Bay-K-8644-induced uptake was inhibited by either 10 microM nifedipine, 10 microM verapamil or 10 microM diltiazem and was relatively independent of extracellular K+ concentration. These results suggest that there are at least two distinct Ca2+ transport systems in the rat ileal epithelial cells, one resistant to organic Ca2+ channel blockers but relatively sensitive to membrane potential (basal uptake) and another inducible by Bay K 8644 and sensitive to the channel blockers but relatively independent of membrane potential.


[The impact of the case of definition in public health surveillance. Assessment of the number of hepatitis C cases].
Hepatitis C cases in Poland are notified based on symptoms of hepatic disease and anti-HCV and/or PCR for HCV RNA test results. The purpose of this study was to make an effort to define hepatitis C for public health surveillance and assessment of the number of acute hepatitis C cases reported from Warsaw Voivodeship during 1998. The 1998 hepatitis C infection case reports were analyzed. Additional data were collected through medical charts and laboratory reports review. The definition for an acute case of hepatitis C included: positive anti-HCV or PCR for HCV RNA, symptoms of acute hepatic disease, negative IgM anti-HAV, and negative IgM anti-HBc or HBsAg. Of the 268 (99.3% of 270) available case reports, 15 (5.6%) were identified as acute cases of hepatitis C. Currently used hepatitis C case criteria do not allowed for a proper assessment of the burden of disease. It is necessary to create explicit definition of acute and chronic hepatitis C cases for public health surveillance.


Correlation of global electrophilicity with the activation energy in single-step concerted reactions.
The experimental energy of activation (Ea) of the single-step concerted oxidation process of aliphatic primary alcohols by quinolinium bromochromate (QBC) are correlated with the theoretically evaluated global electrophilicity values (w) [as proposed by Parr et al. (J. Am. Chem. Soc. 1999, 121, 1922)]. Conceptual justification in favor of correlating w of the substrate with Ea involved in a single-step concerted reaction is also discussed. The evaluated w values at HF/cc-pVTZ and MP2/6-31G(d,p) methods are found to be as expected (when we consider structural aspects), although there are some inconsistencies in other methods [e.g., HF/6-31G(d,p), B3LYP/cc-pVTZ, BLYP/dnp, PW91/dnp, PWC/dnp, VWN/dnp]. The reasons for the inconsistencies, even with a superior B3LYP/cc-pVTZ method, are discussed thoroughly. It is observed that the higher the value of w, the more the value of Ea involved in the process of oxidation of primary alcohols by QBC. The present study also reveals that the apparent success of insignificant (i.e., much smaller) local electrophilicity values (S+O(OH)), evaluated using Hirshfeld population analysis (HPA), in explaining observed trend of experimental Ea values turns out to be ambiguous when more significant (i.e., much larger) local nucleophilicity values (S-O(OH)) are also compared. This is evident from the corresponding correlation coefficient values.


Anion binding to monotopic and ditopic macrocyclic amides.
[Structure: see text] Binding of fluoride anion as well as carboxylic acid tetraalkylammonium salts by macrocyclic compounds of different size was studied by NMR in DMSO-d6. It has been found that at least a 15-membered ring is necessary for successful recognition of fluoride. Larger macrocycles obtained in a [2+2] cyclization were shown to bind dicarboxylic acid salts. Effects of binding topicity are discussed.


Beta-adrenoceptors in the transplanted human heart: unaltered beta-adrenoceptor density, but increased proportion of beta 2-adrenoceptors with increasing posttransplant time.
To study whether in the (denervated) transplanted human heart beta-adrenoceptors are up-regulated we determined in right ventricular endomyocardial biopsies (weighing 2-7 mg) of 8 heart transplant recipients beta-adrenoceptor density and beta 1:beta 2-adrenoceptor ratio in weekly, later monthly intervals for 6-18 posttransplant months. beta-adrenoceptor density was assessed by 1-2 concentration (-)-[125I]-iodocyanopindolol (ICYP, 200 and 150 pmol/l) binding, the beta 1:beta 2-adrenoceptor ratio by a beta 1-adrenoceptor saturating concentration of the selective beta 1-adrenoceptor antagonist CGP 20712 A (500 nmol/l). In biopsies taken from the donor hearts immediately before transplantation beta-adrenoceptor density was 64.5 +/- 6.3 fmol ICYP bound/mg protein (n = 5), the beta 1:beta 2-adrenoceptor ratio 81.2 +/- 2.2:18.8 +/- 2.2%. beta-Adrenoceptor density did not change during the whole period investigated; it was in the first 9 posttransplant weeks 73.1 +/- 8.3 (n = 22) and after 4-18 months 74.2 +/- 7.6 fmol/mg protein (n = 16). In contrast, with increasing posttransplant time beta 1:beta 2-adrenoceptor ratio was shifted towards beta 2-adrenoceptors: in the first 9 weeks it was 80:20% (n = 17), after 16 weeks 75:25% (n = 10) and after 25-80 weeks 65:35% (n = 7). We conclude that in the first 18 posttransplant months beta-adrenoceptors in the transplanted human heart are not up-regulated. There is, however, a gradual decline in beta 1- and increase in beta 2-adrenoceptors with increasing posttransplant time. As noradrenaline acts in the human heart solely at beta 1-adrenoceptors, while adrenaline activates both beta 1- and beta 2-adrenoceptors with about the same potency, with increasing posttransplant time (and increasing proportion of beta 2-adrenoceptors) adrenaline may play an important role for regulation of contractility and/or heart rate in heart transplant recipients.


Transconjunctival approach to the zygomatico-frontal limb of orbitozygomatic complex fractures.
Fractures of the orbitozygomatic complex represent one of the most common injuries of the facial skeleton. Repair of the fractures often requires multiple surgical access points and the necessity for skin incisions. As surgeons attuned to aesthetics, we strive to minimize the signs of injury and treatment. We propose an approach designed to treat orbitozygomatic fractures without the use of skin incisions. The objective of this article is to outline the surgical technique designed by the senior author (PRL) to address the zygomatico-frontal fracture component of orbitozygomatic complex fractures through an upper lid lateral transconjunctival approach. Relevant anatomy and technique is described. The combination of previously described lower lid transconjunctival and gingivobuccal sulcus incisions with this new upper lid lateral transconjunctival approach provides adequate access for rigid fixation of all major components of orbitozygomatic fractures without skin incisions.


Review of In Vivo Bone Strain Studies and Finite Element Models of the Zygomatic Complex in Humans and Nonhuman Primates: Implications for Clinical Research and Practice.
The craniofacial skeleton is often described in the clinical literature as being comprised of vertical bony pillars, which transmit forces from the toothrow to the neurocranium as axial compressive stresses, reinforced transversely by buttresses. Here, we review the literature on bony microarchitecture, in vivo bone strain, and finite-element modeling of the facial skeleton of humans and nonhuman primates to address questions regarding the structural and functional existence of facial pillars and buttresses. Available bone material properties data do not support the existence of pillars and buttresses in humans or Sapajus apella. Deformation regimes in the zygomatic complex emphasize bending and shear, therefore conceptualizing the zygomatic complex of humans or nonhuman primates as a pillar obscures its patterns of stress, strain, and deformation. Human fossil relatives and chimpanzees exhibit strain regimes corroborating the existence of a canine-frontal pillar, but the notion of a zygomatic pillar has no support. The emerging consensus on patterns of strain and deformation in finite element models (FEMs) of the human facial skeleton corroborates hypotheses in the clinical literature regarding zygomatic complex function, and provide new insights into patterns of failure of titanium and resorbable plates in experimental studies. It is suggested that the "pillar and buttress" model of human craniofacial skeleton function be replaced with FEMs that more accurately and precisely represent in vivo function, and which can serve as the basis for future research into implants used in restoration of occlusal function and fracture repair. Anat Rec, 299:1753-1778, 2016. © 2016 Wiley Periodicals, Inc.


[Angiolipoma of the cecum].
The paper reports a case of angiolipoma localised on the ileocecal valve. No cases of intestinal angiolipoma have been reported in the literature. The authors analyse the anatomopathological diagnostic criteria used, together with the clinical characteristics of a pathology which, even when examined macroscopically, resembles a malignant neoplasia of the colon. The authors conclude by underlining the importance of histological diagnosis for a correct surgical choice.


The histopathology and prevalence of Henneguya sebasta and Kudoa clupeidae in the rockfish, Sebastes paucispinis of southern California.
The pathogenesis of two histozoic myxosporidans, Henneguya sebasta and Kudoa clupeidae, was studied from the Pacific rockfish, Sebastes paucispinis. Infection of the bulbus and truncus arteriosus with H. sebasta was observed in 30 of 100 fish. The parasite metastasized throughout the tissue causing necrosis, hyperplasia and hypertrophy of the connective tissue and smooth muscle. K. clupeidae, found in 37 of 100 fish, caused necrosis and atrophy of host skeletal muscle. The unattractive appearance of Kudoa cysts in rockfish filets detracted from their commercial value.


Reduction of HLA-DR+ lymphocytes after treatment with enzastaurin in patients with metastatic thyroid cancer.
Cytotoxic anti-tumor agents like methotrexate or cyclophosphamide have been used in the treatment of autoimmune diseases although the exact mechanism of their immunomodulatory function is unclear. By contrast, molecularly targeted anti-tumor agents, such as the serine/threonine kinase inhibitor enzastaurin, have not been evaluated for treatments other than cancer. Blood was sampled from patients with metastatic thyroid cancer treated with enzastaurin followed by the combination treatment of enzastaurin and the anti-folate pemetrexed. During this sequential treatment, blood was drawn every 14 days to monitor changes in the lymphocyte population. We observed that enzastaurin monotherapy reduced the number of HLA-DR-expressing lymphocytes. No signs of infection were observed in any patient. Our findings suggest an immunomodulatory effect of enzastaurin in addition to the anti-tumor effect.


Intra-individual patterns of hormonal and affective adaptation to work demands: an n = 2 study of junior doctors.
This paper examines the detailed pattern of hormonal and affective response to natural variations in work demands, in relation to a taxonomy of adaptive response based on Frankenhaeuser's (1986) psychobiological analysis of coping modes and Hockey's (1993) regulatory control model. Two junior doctors were monitored every day over a 7-week period of work on a cardio-thoracic surgery ward. Measurements were made for each morning and afternoon work period of self-rated workload, effort and affective state, and the level of urinary catecholamines and cortisol. The de-trended data were analysed separately for the two individuals, using multivariate methods. Following reduction of work variables by principal components analysis, canonical correlation analyses were carried out for each individual. These revealed differences in the patterns of adaptation to two distinctive work contexts (enabling and demanding work) across the two doctors, as identified through loadings on two significant pairs of canonical variates. As expected, enabling work (high medical demands, with high personal resources) was associated with active coping in both subjects (low fatigue, high effort/adrenaline and low cortisol). However, demanding work (high general demands) was associated with marked differences between them in the pattern of loadings. One subject showed the strain pattern normally associated with effortful engagement in difficult tasks (high anxiety and fatigue, high effort/adrenaline), though without the anticipated reduction in cortisol. The response pattern of the other individual was indicative of passive coping (high anxiety and cortisol, with no effort/adrenaline component). The findings are interpreted in terms of the role of personal coping styles on the adaptive response to work demands. The use of canonical correlation methods with intra-individual data sets, although relatively unusual, appears to provide potentially valuable evidence on the nature of individual differences in the process of psychobiological response to stress underlying work-health relationships.


Expression and function of lysophosphatidic acid LPA1 receptor in prostate cancer cells.
The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell proliferation, survival, and migration by acting on cognate G protein-coupled receptors named LPA(1), LPA(2), and LPA(3). We profiled gene expression of LPA receptors in androgen-dependent and androgen-insensitive prostate cancer cells and found that LPA(1) gene is differentially expressed in androgen-insensitive and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human prostate specimens, expression of LPA(1) gene was significantly higher in the cancer compared with the benign tissues. The androgen-dependent LNCaP cells do not express LPA(1) and do not proliferate in response to LPA stimulation, implying LPA(1) transduces cell growth signals. Accordingly, stable expression of LPA(1) in LNCaP cells rendered them responsive to LPA-induced cell proliferation and decreased their doubling time in serum. Implantation of LNCaP-LPA(1) cells resulted in increased rate of tumor growth in animals compared with those tumors that developed from the wild-type cells. Growth of LNCaP cells depends on androgen receptor activation, and we show that LPA(1) transduces Galphai-dependent signals to promote nuclear localization of androgen receptor and cell proliferation. In addition, treatment with bicalutamide inhibited LPA-induced cell cycle progression and proliferation of LNCaP-LPA(1) cells. These results suggest the possible utility of LPA(1) as a drug target to interfere with progression of prostate cancer.


Occurrence detection and selection procedures in healthcare facilities: a comparison across Canada and Brazil.
Healthcare institutions face high levels of risk on a daily basis. Efforts have been made to address these risks and turn this complex environment into a safer environment for patients, staff, and visitors. However, healthcare institutions need more advanced risk management tools to achieve the safety levels currently seen in other industries. One of these potential tools is occurrence investigation systems. In order to be investigated, occurrences must be detected and selected for investigation, since not all institutions have enough resources to investigate all occurrences. A survey was conducted in healthcare institutions in Canada and Brazil to evaluate currently used risk management tools, the difficulties faced, and the possibilities for improvement. The findings include detectability difficulties, lack of resources, lack of support, and insufficient staff involvement.


Regulatory mechanisms controlling hematopoiesis: principles and problems.
Hematopoiesis is regulated by the combined action of specialized stromal cells and a consortium of hematopoietic regulatory factors. The multiplicity of these regulatory controls does result in overlapping regulator action, but multiple regulators are required to stimulate stem cell proliferation and are more efficient than single regulators when stimulation of progenitor cells is required. Gene inactivation studies have indicated that despite overlapping actions each hematopoietic regulator does have unique functions. Delayed elevations of stem and progenitor cells in the blood are a feature of enhanced hematopoiesis induced by the injection of regulators. These cells are not a random sample of marrow cells in such situations and may well be selected to rapidly amplify hematopoiesis by seeding previously inactive hematopoietic regions.


Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep.
We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 micrograms/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 micrograms.kg-1.min-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 +/- 0.7 to 8.9 +/- 0.51.min-1.m-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7. Other indexes of the LV contractility (+dP/dtmax) were also reduced. OKY-046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also attenuated the increased lung lymph flow changes seen with LPS.


Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity.
The glycosylation pattern of chCE7, an antineuroblastoma chimeric IgG1, was engineered in Chinese hamster ovary cells with tetracycline-regulated expression of beta(1,4)-N-acetylglucosaminyltransferase III (GnTIII), a glycosyltransferase catalyzing formation of bisected oligosaccharides that have been implicated in antibody-dependent cellular cytotoxicity (ADCC). Measurement of the ADCC activity of chCE7 produced at different tetracycline levels showed an optimal range of GnTIII expression for maximal chCE7 in vitro ADCC activity, and this activity correlated with the level of constant region-associated, bisected complex oligosaccharides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The new optimized variants of chCE7 exhibit substantial ADCC activity and, hence, may be useful for treatment of neuroblastoma. The strategy presented here should be applicable to optimize the ADCC activity of other therapeutic IgGs.


Relationship Between a Standardized Tackling Proficiency Test and Match-Play Tackle Performance in Semiprofessional Rugby League Players.
This study examined the relationships between tackling ability, playing position, muscle strength and power qualities, and match-play tackling performance in semiprofessional rugby league players. Sixteen semiprofessional rugby league players (mean ± SD age 23.8 ± 1.9 y) underwent tests for muscle strength and power. Tackling ability of the players was tested using video analysis of a standardized 1-on-1 tackling drill. After controlling for playing position, players were divided into "good tackler" or "poor tackler" groups based on the median split of the results of the 1-on-1 tackling drill. A total of 4547 tackles were analyzed from video recordings of 23 matches played throughout the season. Maximal squat was significantly associated with tackling ability (rS = .71, P < .05) and with the proportion of dominant tackles (rS = .63, P < .01). Forwards performed more tackles (P = .013, ES = 1.49), with a lower proportion of missed tackles (P = .03, ES = 1.38) than backs. Good tacklers were involved in a larger proportion of dominant tackles and smaller proportion of missed tackles than poor tacklers. These findings demonstrate that lower-body strength contributes to more effective tackling performance during both a standardized tackling assessment and match play. Furthermore, players with good tackling ability in a proficiency test were involved in a higher proportion of dominant tackles and missed a smaller proportion of tackles during match play. These results provide further evidence of the practical utility of an off-field tackling assessment in supplying information predictive of tackling performance in competition.


[A new non-invasive method for assessing steatosis in chronic liver diseases].
To assess the diagnostic accuracy of the controlled attenuation parameter (CAP) to determine the grade of hepatic steatosis (HS) in patients with chronic liver diseases (CLD) of different etiologies and to compare the obtained results with morphological findings. A total of 45 patients (18 men and 27 women) aged 25 to 73 years with CLD were examined. All the patients underwent liver puncture biopsy for assessing the HS index and fibrosis stage, as well as determination of hepatic elasticity (F, kPa) for estimating the stage of fibrosis and the grade of HS by CAP (S, dB/m) using a FibroScan device. When assessing HS, the CAP values of <229, 230-249, 250-276, and more than 277 dB/m correspond to HS grade 0 (S0), S1, S2, and S3, respectively. This is a pilot study in Russia. CAP is a rather high effective method in determining the absence of steatosis (S0) (the area under the receiver operating characteristics curve (AUROC) was 0.78) and severe steatosis (S3) (AUROC 0.90). AUROC was 0.64 and 0.59 for HS S1 and S2, which is regarded as satisfactory and poor respectively. Only 3 out of the 45 patients had HS, as evidenced by morphological examination; and the results of CAP showed another result; all the other cases had a HS grade corresponding to S1. In the entire cohort of the examinees, the sensitivity, specificity, and accuracy of CAP was 86, 69.5, and 78%, respectively; AUROC was 0.77 (95% CI, 0.6587-0.9006; p=0.40). CAP is a promising method for the rapid and non-invasive diagnosis of HS in patients with CLD. At the same time, our findings show that it is necessary to clarify the quantitative indicators of the compliance of CAP and morphological evaluation of HS.


Frictional drag and electrical manipulation of recombinant proteins in polymer-supported membranes.
We establish a lipid monolayer supported by a polymer interface that offers advantages over conventional solid-supported membranes for determining the frictional drag at the membrane-protein interface as well as for electric field manipulation of membrane-anchored proteins. Polymer-supported monolayers with functional lipid anchors allow for the specific docking of His-tagged green fluorescent protein variants (His-EGFP and His-DsRed tetramer) onto the membrane surface at a defined surface density. In the first part, we measure the lateral diffusion coefficients of lipids and proteins and calculate the frictional drag at the protein-membrane interface. The second part deals with the electric field-induced accumulation of recombinant proteins on a patterned surface. The mean drift velocity of proteins, which can be obtained analytically from the shape of the steady-state concentration gradient, can be controlled by tuning the interplay of electrophoresis and electroosmosis. The results demonstrate the potential of such molecular constructs for the local functionalization of solid substrates with membrane-associated proteins.


Catalytic sp3 -sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules.
A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3 -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.


The Stroke Patient: A Team Approach The Stroke Patient: A Team Approach Johnstone M Published by Churchill Livingstone 108pp £5.95 0-443-03397-8 [Formula: see text].
Adherents of part:cular schools of physiotherapy tend to emphasise their differences, while having similar philosophies in aiming to restore optimum functional performance by specific treatment stimuli and careful positioning of the patient. Margaret Johnstone uses the proprioceptive neuromuscular facilitation (PNF) system. The Bobath technique, however, is more generally used and regarded as the most effective method in neurophysiotherapy.


Usefulness of standard EEG in predicting the outcome of patients with disorders of consciousness after anoxic coma.
Although standard EEG is performed routinely in patients with disorders of consciousness after coma, its prognostic value is still debated. The aim of the present study was to evaluate the role of standard EEG in predicting the recovery of cognitive functioning in patients affected by severe disturbances of consciousness after coma caused by cerebral anoxia. A standard EEG was recorded at admission to our Rehabilitation Department in 15 patients experiencing impaired consciousness because of cerebral anoxia. We quantified EEG abnormalities using the Synek scale (1988). Cognitive functioning was measured with the levels of cognitive functioning scale at the time of admission and after 3 months of recovery. EEG scores were significantly correlated with both levels of cognitive functioning scores at admission (P = 0.004) and change in levels of cognitive functioning score after 3 months (P < 0.001). The first correlation confirms the relationship between EEG and cognitive functioning, while the second correlation indicates the prognostic value of EEG in cognitive outcome. In conclusion, standard EEG is a simple and readily available tool with significant prognostic value in patients with disorders of consciousness after coma caused by cerebral anoxia.


The Role of Transcutaneous Electrical Nerve Stimulation in the Management of Temporomandibular Joint Disorder.
Temporomandibular joint disorders (TMD) constitutes of a group of diseases that functionally affect the masticatory system, including the muscles of mastication and temporomandibular joint (TMJ). A number of etiologies with specific treatment have been identified, including the transcutaneous electrical nerve stimulation (TENS). The current paper presents a literature review on the use of TENS in the management of TMD patients. Temporomandibular joint disorder is very common disorder with approximately 75% of people showing some signs, while more than quarter (33%) having at least one symptom. An attempt to treat the pain should be made whenever possible. However, in cases with no defined etiology, starting with less intrusive and reversible techniques is prescribed. Transcutaneous electrical nerve stimulation is one such treatment modality, i.e. useful in the management of TMD. It comprises of controlled exposure of electrical current to the surface of skin, causing hyperactive muscles relaxation and decrease pain. Although the value of TENS to manage chronic pain in TMD patients is still controversial, its role in utilization for masticatory muscle pain is significant. However, an accurate diagnosis is essential to minimize its insufficient use. Well-controlled randomized trials are needed to determine the utilization of TENS in the management of TMD patients.


Experimental setup for characterization of self-actuated microcantilevers with piezoresistive readout for chemical recognition of volatile substances.
This paper summarizes our achievements in the development of an advanced microcantilever-based platform for the detection and recognition of various volatile analytes. The implemented microcantilevers include integrated piezoresistive readout, integrated thermally driven bimorph actuator, and a gold pad at the cantilever apex for functionalization toward the detection of specific substances. Up to eight single microcantilevers can be installed and investigated quasisimultaneously in either gas flow or gas/vapor single injection mode. The experimental setup enables the detection of the microcantilever bending via surface stress changes, characterization of either amplitude or phase spectra of the microcantilever, and also calibration of its sensitivity.


Hay fever: an update on current treatments.
Most hay fever sufferers can help themselves by taking steps to avoid high levels of pollen. Where eye symptoms are severe, sodium cromoglycate eye drops are recommended. Oral antihistamines are suitable for mild to moderate symptoms. For severe nasal symptoms, corticosteroid nasal sprays are useful. As with many medicines, use by expectant and breast-feeding mothers is best avoided. If symptoms are particularly troublesome, referral to a doctor is advisable.


Illuminating the Gap: Neuronal Cross-Talk within Sensory Ganglia and Persistent Pain.
How primary sensory neurons contribute to persistent pain remains unclear. A novel imaging technique introduced here by Kim et al. (2016) in this issue of Neuron to view the activities of large numbers of ganglion neurons simultaneously analyzes the importance of neuronal cross-talk in pain transmission.


IL-15 has innate anti-tumor activity independent of NK and CD8 T cells.
The innate immune system is crucial for host defense and immunosurveillance against pathogens and tumor cells. IL-15 is a pleiotropic cytokine with important effects on cells of the innate and adaptive immune systems. The NK cell- and CD8(+) T cell-mediated functions of IL-15 against tumor cells have been well documented. However, it has not been established whether IL-15 has innate anti-tumor functions independent of these cells. Here, we explored the innate anti-tumor potential of IL-15 using a B16F10 melanoma tumor model. IL-15tg mice exhibited significantly more resistance to tumor growth and metastasis compared to B6 mice, and to IL-15(-/-) mice, which exhibited increased susceptibility to B16F10 challenge. In vivo depletion of NK cells and CD8(+) T cells abrogated the innate resistance to B16F10 cells in B6 but not in IL-15tg mice. In addition, lung macrophages from IL-15tg mice produced significantly higher levels of NO and IL-12 compared with macrophages from B6 or IL-15(-/-) mice. To examine whether IL-15 has innate anti-tumor activity independent of NK cells and CD8(+) T cells, we developed Ad-Op-hIL-15; this resulted in significantly higher levels of biologically active hIL-15. Delivery of Ad-Op-hIL-15 into RAG-2(-/-)/gamma(c)(-/-) mice significantly suppressed tumor burden in the lungs compared with the control adenovirus vector. Our results show that IL-15 can have innate anti-tumor activity independent of NK cells and CD8(+) T cells and the common gamma(c)R.


Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders.
Although there is a growing body of research concerning the prevalence and correlates of chronic pain conditions and their association with mental disorders, cross-national research on age and gender differences is limited. The present study reports the prevalence by age and gender of common chronic pain conditions (headache, back or neck pain, arthritis or joint pain, and other chronic pain) in 10 developed and 7 developing countries and their association with the spectrum of both depressive and anxiety disorders. It draws on data from 18 general adult population surveys using a common survey questionnaire (N = 42,249). Results show that age-standardized prevalence of chronic pain conditions in the previous 12 months was 37.3% in developed countries and 41.1% in developing countries, with back pain and headache being somewhat more common in developing than developed countries. After controlling for comorbid chronic physical diseases, several findings were consistent across developing and developed countries. There was a higher prevalence of chronic pain conditions among females and older persons; and chronic pain was similarly associated with depression-anxiety spectrum disorders in developed and developing countries. However, the large majority of persons reporting chronic pain did not meet criteria for depression or anxiety disorder. We conclude that common pain conditions affect a large percentage of persons in both developed and developing countries. Chronic pain conditions are common in both developed and developing countries. Overall, the prevalence of pain is greater among females and among older persons. Although most persons reporting pain do not meet criteria for a depressive or anxiety disorder, depression/anxiety spectrum disorders are associated with pain in both developed and developing countries.


Fatalities in the construction industry in the United States, 1992 and 1993.
To improve the estimates of occupational fatality rates for persons employed in the construction industry, several sources of data on the number of fatalities (the numerator) and the number of persons engaged in construction work (the denominator) were examined. Based on this examination, the Census of Fatal Occupational Injuries (CFOI), complied by the Bureau of Labor Statistics (BLS), was used to obtain numerators and the Current Population Survey, conducted by the Bureau of the census for the BLS, was used to obtain denominators. Adjustments were made in the numerator to include only occupations that were included in the denominator. Occupations were divided into two groups-those in the construction trades and those in other occupations within construction (e.g., clerical, sales). The analysis found fatality rates of 14.2 and 13.3 per 100,000 person-years, respectively, for 1992 and 1993, with wide variation in rates among the different trades. There were also major differences among the trades in the types of fatal injuries. Self-employed workers had much lower death rates overall than wage workers, but this is largely due to much lower proportions of high hazard trades among the self-employed. There have been wide variations in the occupational fatality rates reported for construction workers each year due to the differing methods of estimating the number of fatalities by the different data sources. This study provides a baseline of fatality rates using the best available current data. It compares the results from these data sources with those from other sources that have been used and discusses some of the problems inherent in the data from other sources. This study provides a significantly improved protocol for the calculation of fatality rates against which later rates can be compared consistently. Nevertheless, many deficiencies in the data sources used are identified. There remains ample room for continued improvement.


Effect of heat shock treatment on stress tolerance and biocontrol efficacy of Metschnikowia fructicola.
The effect of high temperature and oxidative stress on the cell viability of the yeast antagonist, Metschnikowia fructicola was determined. A mild heat shock (HS) pretreatment (30 min at 40 °C) improved the tolerance of M. fructicola to subsequent high temperature (45 °C, 20-30 min) and oxidative stress (0.4 mol L⁻¹ hydrogen peroxide, 20-60 min). HS-treated yeast cells showed less accumulation of reactive oxygen species (ROS) than nontreated cells in response to both stresses. Additionally, HS-treated yeast exhibited significantly greater (P<0.0001) biocontrol activity against Penicillium expansum and a significantly faster (P<0.0001) growth rate in wounds of apple fruits stored at 25 °C compared with the performance of untreated yeast cells. Transcription of a trehalose-6-phosphate synthase gene (TPS1) was upregulated in response to HS and trehalose content also increased. Results indicate that the higher levels of trehalose induced by the HS may contribute to an improvement in ROS scavenging, stress tolerance, population growth in apple wounds and biocontrol activity of M. fructicola.


Image quality in low-dose multidetector computed tomography: a pilot study to assess feasibility and dose optimization in whole-body bone imaging.
To study the impact of dose parameters on image quality at whole-body low-dose multidetector computed tomography (CT) in an attempt to derive parameters that allow diagnostic quality images of the skeletal system without incurring significant radiation dose in patients referred for investigation of plasma cell dyscrasias. By using a single cadaver, 14 different whole-body low-dose CT protocols were individually assessed by 2 radiologists, blinded to acquisition parameters (kVp and mAs, reconstruction algorithm, dose reduction software). Combinations of kVps that range from 80-140 kVp, and tube current time product from 14-125 mAs were individually scored by using a Likert scale from 1-5 in 4 separate anatomical areas (skull base, thoracic spine, pelvis, and distal femora). Correlation between readers scores and effective doses were obtained by using correlation coefficient statistical analysis, statistical significance was considered P < .01. Interobserver agreement was assessed by using a Bland and Altman plot. Interobserver agreement in each of the 4 anatomical areas was assessed by using kappa statistics. A single set of parameters was then selected for use in future clinical trials in a cohort of patients referred for investigation of monoclonal gammopathy, including multiple myeloma. Several sets of exposure parameters allowed low-dose whole-body CT to be performed with effective doses similar to skeletal survey while preserving diagnostic image quality. Individual reader's and average combined scores showed a strong inverse correlation with effective dose (reader 1, r = -0.78, P = .0001; reader 2, r = -0.75, P = .0003); average combined scores r = -0.81, P < .0001). Bland and Altman plot of overall scores shows reasonable interobserver agreement, with a mean difference of 1.055. Whole-body low-dose CT can be used to obtain adequate CT image quality to assess normal osseous detail while delivering effective doses similar to those associated with conventional radiographic skeletal survey.


A process to address disparities in rates of sudden infant death syndrome.
Fetal and Infant Mortality Review (FIMR) is a continuous quality improvement program that leads to improvements in services and resources for families and, ultimately, a decrease in infant mortality. It is an action-oriented process that combines medical data with the mother's report of experiences during the life and death of her infant. The FIMR has proven to be especially important in addressing community issues associated with infant deaths related to sudden infant death syndrome.


A rare case of primary anaplastic large cell lymphoma of the central nervous system.
Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin's lymphoma, confined to the central nervous system (CNS) and is usually seen in immunocompromised patients. The vast majority of cases are of the B-cell type and T-cell PCNSL is rare. Here, we report an 18-year-old male who presented with fever, headache, and history of seizures. On evaluation, he was found to have a left parieto-occipital mass which was completely excised. Histopathology was suggestive of a T-cell neoplasm and immunohistochemistry showed tumor cells positive for leukocyte common antigen, anaplastic lymphoma kinase (ALK), CD30, and CD4 which confirmed the diagnosis of ALK-positive anaplastic large cell PCNSL. There was no evidence of disease outside the CNS. He was started on the DeAngelis protocol for PCNSL. To the best of our knowledge, only 27 cases of anaplastic large cell PCNSL have been previously reported in literature.


Sediment Profile and Fluxes of Mercury and Methyl Mercury in Weihe Watershed in Henan, China.
Sediment core samples were collected from the Weihe River in February and August 2013. Cores were sectioned and analyzed for total Hg (THg) and methyl mercury (MeHg). THg in sediment cores ranged from 156 to 282 ng g(-1) in February, and from 172 to 300 ng g(-1) in August. MeHg concentrations ranged from 0.80 to 3.11 ng g(-1) in both seasons. Results showed that the diffusive fluxes were up to two orders of magnitude lower than the in situ benthic fluxes. Fluxes of MeHg measured in in situ experiments in August were positively correlated with [Formula: see text] (r = 0.930). THg and MeHg release were not strongly correlated with TOC in February. Patterns of MeHg flux differed greatly depending on oxidation-reduction potential (Eh) (r > 0.70) conditions in the two seasons.


[Analysis on the temperature-time curve in warm needling manipulation with acupuncture needles of different materials].
To analyze the characteristics of the temperature-time curve in warm needling manipulation with the acupuncture needles made of copper, silver, gold and stainless steel and explore the applicable temperature range and most suitable needle materials of warm needling manipulation in clinical practice. A total of 10 healthy subjects were included. Using the digital thermometer, with different moxibustion dose (1.2 g or 1.5 g, moxa), the temperature was measured at the site where the skin contacts with the needle body during the warm needling manipulation with stainless steel needle, copper needle, gold needle and sliver needle separately. The initial heat pain threshold (the temperature when hot feeling started) and the burning pain threshold (feeling very hot but tolerable) were recorded when using the different needles mentioned above. Through the subject questionnaire, the comfort degree, the heat sensation, the adverse reaction and the acceptability to warm needling manipulation with the different needles were investigated. During the warm needling manipulation, the initial heat pain threshold was (42.8±2.7) ℃ and the burning pain threshold was (46.7±2.9) ℃. The strongest warm stimulation was presented in the warm needling manipulation with 1.5 g moxa and silver needle and the highest temperature was (55.5±6.3) ℃, followed by (52.9±4.2) ℃ with 1.2 g moxa and silver needle, (46.6±3.7) ℃ with 1.5 g moxa and gold needle, (46.6±1.9) ℃ with 1.5 g moxa and copper needle, (43.1±1.5) ℃ with 1.2 g moxa and copper needle and (41.7±0.9) ℃ with 1.5 g moxa and stainless steel needle. The sequence of the maintaining time of the initial heat pain threshold over 43℃ was 480 s with silver needle and 1.5 moxa, 325 s with silver needle and 1.2 g moxa, 270 s with gold needle and 1.5 g moxa, 185 s with copper needle and 1.5 g moxa, 42 s with copper needle and 1.2 g moxa and 0 s with stainless steel needle and 1.5 g moxa successively. The heat score graded by the subjects to the warm needling manipulation with different needles, from high to low, was presented in the manipulation with 1.5 g moxa and silver needle, 1.2 g moxa and silver needle, 1.5 g moxa and copper needle, 1.5 g moxa and gold needle, 1.2 g moxa and copper needle and 1.5 g moxa and stainless steel needle. The VAS score was different significantly in comparison among the six needles in warm needling manipulation (P<0.001). The comfort degree of the subjects in the warm needling manipulation with silver needle and 1.5 g moxa was significantly lower than the warm needling manipulation with the other 5 materials (P<0.05). Three subjects complained that the warm needling manipulation with silver needle and 1.5 g moxa was too hot to be tolerable and the most of subjects were willing to accept warm needling manipulation with these 6 materials (acceptability 70.0% to 100.0%). Except blisters presented in 9 subjects after warm needling manipulation with silver needle and 1.5 g moxa, no severe adverse reaction occurred in warm needling manipulation with 6 materials. In the warm needling manipulation in the human body, the initial heat pain and the burning pain threshold were 43 ℃ and 47 ℃ respectively, which is the applicable temperature range of moxibustion in clinical practice. The warm needling manipulation with silver needle induces a quite strong heat stimulation and the discomfort may be caused when the temperature is exceeded to some threshold. The warm needling manipulation with copper needle generates the onset temperature, without inducing adverse reactions, e.g. discomfort and burning in the subjects.


A simplified gamma-ray self-attenuation correction in bulk samples.
Gamma-ray spectrometry is a very powerful tool for radioactivity measurements. For accurate gamma-ray spectrometry, certain correction measures should be considered, for instance, systematic uncertainty in the photo-peak efficiency due to the differences between the matrix (density and chemical composition) of the reference and the other bulk samples. Therefore, gamma-ray attenuation correction factors are of major concern for precise gamma-ray spectrometry. Simple practical correction for the photo-peak efficiency, due to discrepancies in both the samples' matrices and densities (self-attenuation), is performed in this study. This study suggests a brief measurement of relative photons transmission through both reference and unknown bulk samples where the variations of photon transmissions are assumed to be linearly correlated to the samples' densities. Specific correction factors would be produced for each analyzed sample to be considered when their activities are calculated. Practically, the suggested method was verified and succeeded in improving the obtained results.


Mitochondrial K+ transport and cardiac protection during ischemia/reperfusion.
Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK(ATP)) are strongly cardioprotective under these conditions. Furthermore, mitoK(ATP) are physiologically activated during ischemic preconditioning, a procedure which protects against ischemic damage. In this review, we discuss mechanisms by which mitoK(ATP) may be activated during preconditioning and the mitochondrial and cellular consequences of this activation, focusing on end-effects which may promote ischemic protection. These effects include decreased loss of tissue ATP through reverse activity of ATP synthase due to increased mitochondrial matrix volumes and lower transport of adenine nucleotides into the matrix. MitoK(ATP) also decreases the release of mitochondrial reactive oxygen species by promoting mild uncoupling in concert with K+/H+ exchange. Finally, mitoK(ATP) activity may inhibit mitochondrial Ca2+ uptake during ischemia, which, together with decreased reactive oxygen release, can prevent mitochondrial permeability transition, loss of organelle function, and loss of physical integrity. We discuss how mitochondrial redox status, K+ transport, Ca2+ transport, and permeability transitions are interrelated during ischemia/reperfusion and are determinant factors regarding the extent of tissue damage.