[Malaria prophylaxis for long-term travellers and expatriates].
Long-term travellers and expatriates are often non-compliant with malaria chemoprophylaxis due to a gradual neglect of the malaria risk combined with an unwillingness to take drugs for prolonged periods. The available regimes either have limited efficacy or are hampered by side effects, fears, cost and lack of data on long-term use. In order to prevent the dire consequences of malaria, we suggest tailoring the antimalarial strategy to the individual traveller. This requires balancing the risk of getting malaria, based on local transmission patterns, mosquito control and other factors, with the traveller's access to medical care and the options for chemoprophylaxis, the use of which in some cases may be limited to the rainy season or periods of travel to high-risk areas.


Anti-ADAMTS13 Antibodies and a Novel Heterozygous p.R1177Q Mutation in a Case of Pregnancy-Onset Immune-Mediated Thrombotic Thrombocytopenic Purpura.
In this study, we investigated a case of pregnancy-onset thrombotic thrombocytopenic purpura (TTP). The patient had severely decreased ADAMTS13 ( a d isintegrin a nd m etalloprotease with t hrombo s pondin type 1 motif, member 13) activity levels during acute phase and the presence of inhibitory anti-ADAMTS13 autoantibodies was demonstrated, which led to the diagnosis of immune-mediated TTP. However, ADAMTS13 activity was only mildly restored during remission, although inhibitory anti-ADAMTS13 antibodies were no longer detected. We hypothesized that genetic abnormalities could account for this discrepancy between ADAMTS13 activity and antigen. Genetic analysis revealed the presence of two heterozygous substitutions on the same allele: a single nucleotide polymorphism (SNP) c.2699C > T (p.A900V), located in the beginning of the T5 domain, and a mutation c.3530G > A (p.R1177Q) located in the third linker region of ADAMTS13. In vitro testing of those substitutions by expression of recombinant proteins revealed a normal secretion but a reduced ADAMTS13 activity by the novel p.R1177Q mutation, which could partially explain the subnormal activity levels found during remission. Although changes in the linker region might induce conformational changes in ADAMTS13, the p.R1177Q mutation in the third linker region of ADAMTS13 did not expose a cryptic epitope in the metalloprotease domain. In conclusion, we report on an immune-mediated pregnancy-onset TTP patient who had inhibitory anti-ADAMTS13 autoantibodies during acute phase, but not during remission. Genetic analysis confirmed the diagnosis of immune-mediated TTP and revealed the novel p.R1177Q mutation which mildly impaired ADAMTS13 activity.


Force sensor based tool condition monitoring using a heterogeneous ensemble learning model.
Tool condition monitoring (TCM) plays an important role in improving machining efficiency and guaranteeing workpiece quality. In order to realize reliable recognition of the tool condition, a robust classifier needs to be constructed to depict the relationship between tool wear states and sensory information. However, because of the complexity of the machining process and the uncertainty of the tool wear evolution, it is hard for a single classifier to fit all the collected samples without sacrificing generalization ability. In this paper, heterogeneous ensemble learning is proposed to realize tool condition monitoring in which the support vector machine (SVM), hidden Markov model (HMM) and radius basis function (RBF) are selected as base classifiers and a stacking ensemble strategy is further used to reflect the relationship between the outputs of these base classifiers and tool wear states. Based on the heterogeneous ensemble learning classifier, an online monitoring system is constructed in which the harmonic features are extracted from force signals and a minimal redundancy and maximal relevance (mRMR) algorithm is utilized to select the most prominent features. To verify the effectiveness of the proposed method, a titanium alloy milling experiment was carried out and samples with different tool wear states were collected to build the proposed heterogeneous ensemble learning classifier. Moreover, the homogeneous ensemble learning model and majority voting strategy are also adopted to make a comparison. The analysis and comparison results show that the proposed heterogeneous ensemble learning classifier performs better in both classification accuracy and stability.


Müllerian inhibiting substance production associated with loss of oocytes and testicular differentiation in the transplanted mouse XX gonadal primordium.
The mouse XX gonadal primordium develops seminiferous-like tubules after transplantation into the renal subcapsular site of the adult male or female mouse. We examined the ontogeny of Sertoli cell differentiation in XX gonadal grafts by immunocytochemical staining and organ culture bioassay for Müllerian Inhibiting Substance (MIS). During normal in situ development of the XY gonad, MIS staining was first detected in fetal Sertoli cells at 12 days of gestation (d.g.) and remained intense until 4 days postpartum (d.pp.), after which it gradually diminished with progressive testicular development. In the normal in situ XX gonad, MIS was detected in granulosa cells of growing follicles at 7 d.pp. and thereafter. When the XX gonad at 12 d.g. was grafted beneath the renal capsule, a few testicular cords composed of MIS-positive cells appeared on Day 7 post-transplantation (equivalent to 19 d.g.), much earlier than the normal appearance of MIS production in the intact XX ovary. The ovarian region containing germ cells at the meiotic prophase was unstained for MIS in the same sections. The incidence of XX gonadal grafts containing MIS-positive testicular cords and the number of such cords per gonadal graft steadily increased from Day 7 to Day 14 post-transplantation. Germ cells were absent or scarce inside the MIS-positive testicular cords. The MIS bioactivity in both control gonads and gonadal grafts coincided with the immunocytochemical staining for MIS. These results support the hypothesis that XX cells differentiate into Sertoli cells as a consequence of oocyte loss in the gonadal graft.


Monoterpenes Support Systemic Acquired Resistance within and between Plants.
This study investigates the role of volatile organic compounds in systemic acquired resistance (SAR), a salicylic acid (SA)-associated, broad-spectrum immune response in systemic, healthy tissues of locally infected plants. Gas chromatography coupled to mass spectrometry analyses of SAR-related emissions of wild-type and non-SAR-signal-producing mutant plants associated SAR with monoterpene emissions. Headspace exposure of Arabidopsis thaliana to a mixture of the bicyclic monoterpenes α-pinene and β-pinene induced defense, accumulation of reactive oxygen species, and expression of SA- and SAR-related genes, including the SAR regulatory AZELAIC ACID INDUCED1 (AZI1) gene and three of its paralogs. Pinene-induced resistance was dependent on SA biosynthesis and signaling and on AZI1 Arabidopsis geranylgeranyl reductase1 mutants with reduced monoterpene biosynthesis were SAR-defective but mounted normal local resistance and methyl salicylate-induced defense responses, suggesting that monoterpenes act in parallel with SA The volatile emissions from SAR signal-emitting plants induced defense in neighboring plants, and this was associated with the presence of α-pinene, β-pinene, and camphene in the emissions of the "sender" plants. Our data suggest that monoterpenes, particularly pinenes, promote SAR, acting through ROS and AZI1, and likely function as infochemicals in plant-to-plant signaling, thus allowing defense signal propagation between neighboring plants.


Fine-tuning the regulation of Cas9 expression levels for efficient CRISPR-Cas9 mediated recombination in Streptomyces.
CRISPR-Cas9 has proven as a very powerful gene editing tool for Actinomyces, allowing scarless and precise genome editing in selected strains of these biotechnologically relevant microorganisms. However, its general application in actinomycetes has been limited due to its inefficacy when applying the system in an untested strain. Here, we provide evidence of how Cas9 levels are toxic for the model actinomycetes Streptomyces coelicolor M145 and Streptomyces lividans TK24, which show delayed or absence of growth. We overcame this toxicity by lowering Cas9 levels and have generated a set of plasmids in which Cas9 expression is either controlled by theophylline-inducible or constitutive promoters. We validated the targeting of these CRISPR-Cas9 system using the glycerol uptake operon and the actinorhodin biosynthesis gene cluster. Our results highlight the importance of adjusting Cas9 expression levels specifically in strains to gain optimum and efficient gene editing in Actinomyces.


Application of CE-MS to a metabonomics study of human urine from cigarette smokers and non-smokers.
Novel biomarkers of exposure and early adverse effects are needed for comparative studies of combustible and non-combustible tobacco products for regulatory authority evaluation. Metabolic biomarkers reflect both gene and environmental effects. CE-MS has been applied to human urine samples from non-smokers and smokers of cigarettes at two tar levels. Validated chemometric models were able to separate smokers from non-smokers, with discrimination mainly based on the presence of nicotine metabolites. With these removed, it still proved possible to discriminate smokers from non-smokers with models now based on endogenous metabolites. The biochemical relevance of these biomarkers is discussed. This proof-of-principle metabonomics study illustrates the potential of CE-MS to discover novel biomarkers in urine from tobacco users.


Vital working hour schemes: The dynamic balance between various interests.
"Balancing Interests", the theme of the 17th International Symposium on Shift Work and Working Time held in Hoofddorp, The Netherlands (September 2005), refers to the ambition to reach an optimal balance between the various aspects of shift work. Economic, ergonomic, physical, and psychosocial factors all interact in determining the impact of shift work at the individual, organizational, and societal level. It is the challenge of this multidisciplinary field of research to model all relevant factors in such a way that it will allow us to optimize the dynamic trade-off between the yield and the risk of shift work. The organizers of the 17th International Symposium and the co-editors of these proceedings are convinced that the high quality of the contributions will bring us closer to this ultimate goal.


[Sensitivity test of anticancer agents by subrenal capsule assay (SRC assay). II--Determination of tumor sensitivity by percentage inhibition of DNA protein].
Subrenal capsule assay(SRC assay) has been reported to be an effective and rapid method for predicting the tumor sensitivity of individual patients to anti-cancer agents. In order to establish a more objective method of determining sensitivity in SRC assay the DNA content was measured by the schmidt-Thannhauser-Schneider method and the protein content was estimated using Bio-Rad protein assay, after removal of a tumor implanted in the subrenal capsular space of ddY mice. Percentage inhibition of DNA/protein had a high correlation with that of relative increase of tumor weight, although three groups treated with mitomycin-C, 5-fluorouracil and cyclophosphamide indicated different values of tumor sensitivity. From these results, the percentage inhibition of DNA/protein seems to be more objective than microscopic measurement for predicting tumor sensitivity.


Effect of Substituent Groups on the Strength of Intramolecular Hydrogen Bonds in 2,4-Dihydroxybenzophenone UV Absorbers.
2,4-Dihydroxybenzophenone is the most widely used molecule in the benzophenone group of UV absorbers. It is known that the UV absorption ability is dependent on the substituents. Numerous studies have shown that the strength of intramolecular hydrogen bonds is the main factor affecting this type of UV absorber. However, the effect of substituents on the formation and nature of the hydrogen bonds has not been well studied. In this work, the effect of the type of substituent and the substitution position on the absorption intensity of 2,4-dihydroxybenzophenone molecules is verified both experimentally and theoretically. The effect of substituents on the intramolecular hydrogen bonding of 2,4-dihydroxybenzophenone was investigated by DFT calculations. The results indicate that the addition of different substituents leads to various changes in the strength of the hydrogen bonding in 2,4-dihydroxybenzophenone. On the X-substitution site or the Y-substitution site, halogen groups and electron-absorbing groups such as -CN and -NO2 increase the strength of the hydrogen bond, while electron-giving groups such as -N(CH3)2 and -OCH3 decrease the strength of the bond. For the same substituent, the one at the Y site has a higher effect on hydrogen bonding than that at the X site. By NBO analysis, it was found that the substituents would cause charge redistribution of the individual atoms of 2,4-dihydroxybenzophenones, thus affecting the formation and strength of the hydrogen bonds. Moreover, when the substituent is at the Y substitution site, the oxygen atom of the carbonyl group is less able to absorb electrons and more charge is attracted to the oxygen atom of the hydroxyl group, resulting in a larger charge difference between the two oxygen atoms and an increase of bond energy. Finally, a multiple linear regression analysis of the NPA charge number of the atoms involved in the formation of the hydrogen-bonded chelated six-membered ring was performed with the energy of the hydrogen bond and the percentage of influencing factors estimated, which were found to jointly affect the strength of hydrogen bonding. The aim of this study is to provide theoretical guidance for the design of benzophenone-based UV absorbers that absorb UV light of specific wavelength bands.


Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.
Sympathetic excitation characterizes heart failure, but the underlying mechanisms remain unknown. Abnormal baroreflex restraint of sympathetic neural outflow has been proposed, since baroreflexes are known to be abnormal in heart failure. The purpose of this study was to determine if sympathetic activation in humans with heart failure is limited to regions governed by the baroreflexes or is generalized to other regions free from baroreflex control. We report the first direct recordings of skin sympathetic nerve activity (free from baroreflex control) in humans with heart failure and compare simultaneous skin and muscle (baroreflex-dependent) sympathetic peroneal nerve activity in six patients with severe heart failure (mean left ventricular ejection fraction, 0.19 +/- 0.06) and in six age-matched normal control subjects. Although muscle sympathetic nerve activity was markedly increased in heart failure patients (heart failure versus controls, 69 +/- 3 versus 21 +/- 2 bursts per minute; P < .001), skin sympathetic nerve activity was not increased (heart failure versus controls, 12 +/- 1 versus 15 +/- 1 bursts per minute; P = NS). The finding that skin sympathetic nerve activity in contrast to muscle sympathetic nerve activity is not increased in heart failure supports the concept that an altered reflex system, such as the baroreflexes, with nonuniform effects on muscle and skin sympathetic nerve activity, underlies sympatho-excitation in heart failure.


Gut Microbiome Alterations Affect Glioma Development and Foxp3 Expression in Tumor Microenvironment in Mice.
Glioma is the most common malignant tumor of the central nervous system (CNS), with high degree of malignancy and poor prognosis. The gut microbiome (GM) is composed of microorganisms with different properties and functions, which play an important role in human physiology and biological activities. It has been proved that GM can affect the development of glioma through natural immunity, but whether GM can affect glioma through adaptive immunity and whether there are some microorganisms in the GM that may affect glioma growth still remain unclear. In our study, we evaluated the relationship between GM and glioma. We proved that (I) glioma growth can induce structural changes of mouse GM, including the decreased abundance of Bacteroidia and increased abundance of Firmicutes. (II) GM dysbiosis can downregulate Foxp3 expression in the brain and promote glioma growth. A balanced environment of GM can upregulate the expression of Foxp3 in the brain and delay the development of glioma. (III) The increased abundance of Bacteroidia is associated with accelerated glioma progression, while its decreased abundance is associated with delayed glioma progression, which may be one of the key microorganisms affecting glioma growth. This study is helpful to reveal the relationship between GM and glioma development and provide new ideas for adjuvant therapy of glioma.


Evaluation of corneal staining and patient preference with use of three multi-purpose solutions and two brands of soft contact lenses.
Clinical signs and symptoms vary depending on contact lens brand, lens care products, or a combination of the two. Studies evaluated corneal staining and subject preference associated with three multipurpose solutions (MPS) and two soft contact lens brands. Two sites conducted the randomized, investigator-masked, 2-month crossover studies. Forty-five subjects used regimen 1 (No Rub Opti-Free Express MPS [Alcon, Fort Worth, TX]) and regimen 2 (Complete MPS [Allergan, Irvine, CA]) for 1 month each (study 1). In study 2, 44 subjects used regimen 1 and regimen 3 (ReNu MultiPlus MPS [Bausch & Lomb, Rochester, NY]). ACUVUE 2 (Johnson & Johnson Vision Care, Jacksonville, FL) or SofLens 66 (Bausch & Lomb) lenses were randomly assigned to subjects for the duration of the study. Corneal staining was evaluated on days 0 (baseline), 7, 14, and 28 of each month. Corneal staining was significantly worse with regimen 3 for both lens brands at day 28 compared with baseline (P < 0.01). Significant differences in staining were noted between regimens 1 and 3 throughout the study, primarily with SofLens 66 lenses (P </= 0.0002). No consistent changes in staining were noted with regimens 1 and 2. Also, significantly more subjects preferred the comfort of regimen 1 (61.8%) to that of regimen 3 (11.8%). More subjects preferred the comfort of regimen 1 (57.1%) to that of regimen 3 (10.7%) compared with their prestudy regimen. These studies showed that chemical variations between lens care systems and their interaction with contact lens materials create significant clinical, physiologic, and subjective preference differences.


Substrate Specific Metal-Ligand Cooperative Binding: Considerations for Weak Intramolecular Lewis Acid/Base Pairs.
Metal-ligand cooperative binding modes were interrogated in a series of zinc bis(thiophenoxide) complexes. A weak B-S binding interaction is observed in solution between the weakly Lewis basic thiophenoxide ligands and an appended trialkylborane. The energy of this binding event is dependent upon the strength of the Lewis acid and its proximity to the zinc thiophenoxide.


Chaotic spreading of epidemics in complex networks of excitable units.
We explore the dynamics of an epidemiological disease spreading within a complex network of individuals. The local behavior of the epidemics is modelled by means of an excitable dynamics, and the individuals are connected in the network through a weighted small-world wiring. The global behavior of the epidemics can have stationary as well as chaotic states, depending upon the probability of substituting short-range with long-range interactions. We describe the bifurcation scenario leading to such latter states, and discuss the relevance of the observed chaotic dynamics for the description of the spreading mechanisms of epidemics inside complex networks.


Melatonin added to freezing diluent improves canine (Bulldog) sperm cryosurvival.
Cryopreservation compromises the capacity of sperm fertilizing due to a series of alterations in the structure and physiology of the sperm. The use of antioxidants, such as melatonin, added to freezing media, may help to reduce sperm cryoinjury. To test the effect of melatonin on Bulldog (Canis lupus familiaris) sperm cryosurvival, spermatozoa were diluted in a standard freezing medium and cooled to 5°C. Then, more freezing medium was added to obtain 200 × 106 cells/mL, and 5% glycerol. Diluted spermatozoa were treated with melatonin (0.0, 0.0005, 0.002, and 0.0035 mol/L), and packaged in 0.25 mL straws, which were further cooled to -5°C before freezing in liquid nitrogen. Thawing was carried out at 70°C for 5 s, and the progressive motility, viability, plasma membrane integrity, acrosome integrity, capacitation status, and plasma membrane fluidity of the spermatozoa (at 37°C) were assessed. Data were analyzed using ANOVA to detect differences between the melatonin doses. There were statistical differences (P < 0.05) in the percentage of sperm having hyper-fluid membranes, intact acrosome, capacitated acrosome-intact, and acrosome-reacted. The values for the high melatonin doses (0.002 and 0.0035 mol/L) were better than for the low melatonin doses (0.0 and 0.0005 mol/L). In conclusion, 0.002 and 0.0035 mol/L of melatonin improved the cryosurvival of sperm from male bulldogs. Preservation of sperm by freezing enables breeding of individuals geographically separated; protocols for the dog may be used to preserve the semen from threatened wild canids. To improve fertility of female dogs that become pregnant with frozen and then defrosted sperm, these cells must survive that process which can be damaging whilst keeping their ability to fertilize. Antioxidants are substances capable of retarding or preventing the oxidation of any oxidizing substrate such as lipids, proteins, and DNA, which are structural compounds of the sperm. The use of antioxidants, added to freezing media, may provide the sperm the capacity to neutralize oxidative compounds, such as reactive oxygen species, produced during the freezing and thawing process. In this work we tested different levels of melatonin, a natural antioxidant, on dog (English Bulldog) sperm survival and quality after freezing. We found that adding melatonin to the freezing media improved sperm quality after thawing.


Injuries from construction falls. Functional limitations and return to work.
Finding a measure that distinguishes well between the severity levels of less serious injuries such as those found in occupational settings has been problematic. In this study of 255 construction workers who sustained nonfatal falls at work, two measures of injury severity were used--the Injury Severity Score (ISS) and the disability index of the Stanford Health Assessment Questionnaire (HAQ), a functional limitation measure. The HAQ scores were more normally distributed than the ISS and provided useful information about the degree to which workers were disabled from falls during their first week of recovery. The mean HAQ score was 1.46 (SD = 0.75) on a scale of 0 to 3, with higher numbers representing more limited functioning. With regard to individual tasks, participants reported having the most difficulty performing heavy chores (mean = 1.89; SD = 1.02), dressing themselves (mean = 1.54; SD = 1.05), and bending to pick up clothing from the floor (mean = 1.40; SD = 1.02). The HAQ scores were significantly and moderately correlated with days lost from work (r = .52; p < .001). Unexpectedly, 97 workers reported that they were able to return to light or modified duty following their falls.


Views of the process and content of ethical reviews of HIV vaccine trials among members of US institutional review boards and South African research ethics committees.
Given the ethical controversies concerning HIV vaccine trials (HVTs), we aimed to understand through an exploratory study how members of institutional review boards (IRBs) in the United States (US) and research ethics committees (RECs) in South Africa (SA) view issues concerning the process and content of reviews of these studies. We mailed packets of 20 questionnaires to 12 US IRB chairs and administrators and seven REC chairs to distribute to their members. We received 113 questionnaires (76 from the US and 37 from SA). In both countries, members tended to be white males with advanced academic degrees. Compared to the US, SA members called for 'major changes' in HVT protocols more frequently (p = 0.004), and were less likely to think that HVT participants understood risks and benefits (p = 0.033) or informed consent forms (p = 0.000). In both countries, members were divided on several critical issues (e.g. the minimum standard for treatment for HVT participants who became infected during the HVT), but agreed that they needed more training. Of the SA respondents, 40% reported that they were 'self-taught' in ethics. This study, the first we know of to offer quantitative data comparing US vs. non-US IRBs/RECs, thus suggests key similarities and differences (e.g. compared to SA respondents, US respondents appeared to overestimate participants' understanding of informed consent), along with needs for education. These initial exploratory data in this area have important implications for IRBs, RECs, policy-makers and scholars concerning future practice, training, policy, and investigations in research ethics, and prevention and treatment of HIV and other diseases in the developing world and elsewhere.


Regulation of expression and role of peroxisome proliferator-activated receptors (PPARs) in luminal epithelial and stromal cells of the porcine endometrium.
Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of ligand-dependent transcription factors. PPARs are important regulators of glucose and fatty acid metabolism, apoptosis, angiogenesis, cell proliferation and differentiation, and immune response. Their possible role in the female reproductive tract was demonstrated. In the present study, cultured luminal epithelial (LE) and stromal (ST) cells of the porcine endometrium were used to examine (1) the effect of conceptus exposed medium (CEM) on mRNA and protein expression and DNA binding activity of PPARA, PPARD, and PPARG isoforms, and (2) the effect of PPARA, PPARD, and PPARG agonists on the expression of selected genes, apoptosis, and cell proliferation. The addition of CEM stimulated PPARA expression and DNA binding activity of this isoform in LE and ST cells (P < 0.05). Increased expression of PPARD mRNA in the presence of CEM was detected in ST cells (P < 0.05), while the concentration of PPARG transcripts decreased in response to CEM in both cell types (P < 0.05). LE and ST cells of the pig endometrium possess PPARA, PPARD, and PPARG proteins, with clear nuclear staining visible predominately in ST cells. In LE cells, activation of PPARG with 15-deoxy-Δ12,14-prostaglandin(PG)J2 down-regulated the expression of genes encoding amino acid transporter 1 (SLC38A1), leukemia inhibitory factor (LIF) and enzymes involved in PG synthesis (P < 0.05). In ST cells, activation of PPARD isoform with both agonists used (L-165,041 and cPGI2) and PPARG isoform with 15-deoxy-Δ12,14-PGJ2 increased vascular endothelial growth factor A (VEGFA) mRNA expression (P < 0.05). Moreover, GW9578 (PPARA agonist) and 15-deoxy-Δ12,14-PGJ2 stimulated glucose transporter 1 (SLC2A1) gene expression in ST cells. 15-deoxy-Δ12,14-PGJ2 was also effective in up-regulation of the ratio of BAX/BCL2 mRNA expression and active caspase-3 concentration in ST cells (P < 0.05). Finally, GW9578 stimulated LE and ST cell proliferation, while rosiglitazone (PPARG agonist) increased the number of viable ST but not LE cells. In conclusion, this study demonstrated that conceptus products differentially modulate PPARs expression and activity in the porcine endometrium. Activation of PPARs may in turn affect nutrient transport, PG synthesis, angiogenesis, apoptosis, or cell proliferation in this tissue. Therefore, PPAR isoforms seem to play an important role in development and function of the porcine uterus.


[Unenhanced spiral CT in the diagnosis of acute appendicitis].
To evaluate the role of unenhanced spiral computed tomography (CT) in the work-up of patients with suspicious symptoms of acute appendicitis. Sixty-five patients with suspected acute appendicitis (34 (52%) women and 31 (48%) men), were studied with spiral CT without administration of IV or oral contrast. From the upper L1 vertebral plate to the superior border of the iliac wings, slices of 10 mm collimation with 8 mm/sec table speed were taken, and from that level to the acetabular roof level, 5 mm thick slices were obtained with a table speed of 5 mm/sec and tube rotation time of 1.5 sec. The diagnosis of acute appendicitis was made by seeing a dilated appendix vermiformis greater than 6 mm in diameter and/or an appendicolith accompanied by periappendiceal inflammatory changes. The findings were compared with surgical and pathological results. Those patients who were not operated on were followed-up for 3 months. Acute appendicitis was diagnosed in 28 (43%) of the 65 patients. Of the 28 patients with a CT diagnosis of acute appendicitis, 25 (38%) had acute appendicitis proven by surgery and pathology. Twenty-one (32%) patients had a normal CT study and 16 (25%) patients had non-appendiceal pathologies. There were 25 true-positives, 35 true negatives, 3 false positives and 2 false negatives. Non-contrast helical CT had a sensitivity of 93%, specificity of 92%, accuracy of 95%, positive predictive value of 89% and negative predictive value of 95% in the diagnosis of acute appendicitis. Non-contrast CT is an accurate, reliable and efficacious method in the diagnosis of acute appendicitis. It also has the advantage of showing other pathologies mimicking the symptoms of acute appendicitis.


The use of carbohydrate binding modules (CBMs) to monitor changes in fragmentation and cellulose fiber surface morphology during cellulase- and Swollenin-induced deconstruction of lignocellulosic substrates.
Although the actions of many of the hydrolytic enzymes involved in cellulose hydrolysis are relatively well understood, the contributions that amorphogenesis-inducing proteins might contribute to cellulose deconstruction are still relatively undefined. Earlier work has shown that disruptive proteins, such as the non-hydrolytic non-oxidative protein Swollenin, can open up and disaggregate the less-ordered regions of lignocellulosic substrates. Within the cellulosic fraction, relatively disordered, amorphous regions known as dislocations are known to occur along the length of the fibers. It was postulated that Swollenin might act synergistically with hydrolytic enzymes to initiate biomass deconstruction within these dislocation regions. Carbohydrate binding modules (CBMs) that preferentially bind to cellulosic substructures were fluorescently labeled. They were imaged, using confocal microscopy, to assess the distribution of crystalline and amorphous cellulose at the fiber surface, as well as to track changes in surface morphology over the course of enzymatic hydrolysis and fiber fragmentation. Swollenin was shown to promote targeted disruption of the cellulosic structure at fiber dislocations.


Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer's Disease.
We have demonstrated in multiple studies that daily, long-term electromagnetic field (EMF) treatment in the ultra-high frequency range not only protects Alzheimer's disease (AD) transgenic mice from cognitive impairment, but also reverses such impairment in aged AD mice. Moreover, these beneficial cognitive effects appear to be through direct actions on the AD process. Based on a large array of pre-clinical data, we have initiated a pilot clinical trial to determine the safety and efficacy of EMF treatment to mild-moderate AD subjects. Since it is important to establish the safety of this new neuromodulatory approach, the main purpose of this review is to provide a comprehensive assessment of evidence supporting the safety of EMFs, particularly through transcranial electromagnetic treatment (TEMT). In addition to our own pre-clinical studies, a rich variety of both animal and cell culture studies performed by others have underscored the anticipated safety of TEMT in clinical AD trials. Moreover, numerous clinical studies have determined that short- or long-term human exposure to EMFs similar to those to be provided clinically by TEMT do not have deleterious effects on general health, cognitive function, or a variety of physiologic measures-to the contrary, beneficial effects on brain function/activity have been reported. Importantly, such EMF exposure has not been shown to increase the risk of any type of cancer in human epidemiologic studies, as well as animal and cell culture studies. In view of all the above, clinical trials of safety/efficacy with TEMT to AD subjects are clearly warranted and now in progress.


Interaural attention modulates outer hair cell function.
Mounting evidence suggests that auditory attention tasks may modulate the sensitivity of the cochlea by way of the corticofugal and the medial olivocochlear (MOC) efferent pathways. Here, we studied the extent to which a separate efferent tract, the 'uncrossed' MOC, which functionally connects the two ears, mediates inter-aural selective attention. We compared distortion product otoacoustic emissions (DPOAEs) in one ear with binaurally presented primaries, using an intermodal target detection task in which participants were instructed to report the occurrence of brief target events (visual changes, tones). Three tasks were compared under identical physical stimulation: (i) report brief tones in the ear in which DPOAE responses were recorded; (ii) report brief tones presented to the contralateral, non-recorded ear; and (iii) report brief phase shifts of a visual grating at fixation. Effects of attention were observed as parallel shifts in overall DPOAE contour level, with DPOAEs relatively higher in overall level when subjects ignored the auditory stimuli and attended to the visual stimulus, compared with both of the auditory-attending conditions. Importantly, DPOAE levels were statistically lowest when attention was directed to the ipsilateral ear in which the DPOAE recordings were made. These data corroborate notions that top-down mechanisms, via the corticofugal and medial efferent pathways, mediate cochlear responses during intermodal attention. New findings show attending to one ear can significantly alter the physiological response of the contralateral, unattended ear, probably through the uncrossed-medial olivocochlear efferent fibers connecting the two ears.


Long scleral tunnel technique for prevention of drainage tube-related complications during Ahmed glaucoma valve implantation.
To evaluate the safety and efficacy of modified Ahmed glaucoma valve (AGV) implantation (long scleral tunnel technique) in the treatment of neovascularization glaucoma (NVG). This retrospective observational case series included 23 patients (23 eyes) diagnosed with NVG secondary to proliferative diabetic retinopathy from January 2020 to June 2021. All 23 cases received anti-vascular endothelial growth factor treatment. Then, after 3 to 7 days, these cases were treated with modified AGV implantation (long scleral tunnel technique) and were followed up for at least 6 months. The best corrected visual acuity, intraocular pressure, numbers of antiglaucoma medications used, and postoperative complications were observed at 1 week and 1, 3, and 6 months after treatment. With treatment, the mean best corrected visual acuity improved significantly (P < .001) from 1.62 ± 0.52 logMAR preoperatively to 1.29 ± 0.36 logMAR at the 6-month follow-up. The mean postoperative intraocular pressure was significantly lower than that before modified AGV implantation during follow-up period, decreasing from 45.48 ± 7.86 mm Hg preoperatively to 14.87 ± 1.96 mm Hg at 1 week, 18.39 ± 2.25 mm Hg at 1 month, 16.61 ± 1.47 mm Hg at 3 months, and 17.48 ± 1.38 mm Hg at 6 months (F = 256.646, P < .001). The median number of antiglaucoma medications used by patients also significantly decreased from 3 (3-4) preoperatively to 0 (0-1) at the 6-month follow-up after surgery (Z = -4.248, P < .001). Postoperative complications included hyphema in 2 cases and vitreous hemorrhage in 1 case, and all 3 patients achieved satisfactory recovery with treatment. No drainage tube-related complications occurred among our patients. Long scleral tunnel technique is a safe and effective surgical treatment for NVG with fewer drainage tube-related complications.


First report of autologous cord blood transplantation in the treatment of a child with leukemia.
We present the case of a 3-year-old girl with acute lymphoblastic leukemia who developed isolated central nervous system relapse while receiving chemotherapy 10 months after diagnosis. The child achieved a second remission on retreatment with systemic and intrathecal chemotherapy. She then underwent myeloablative chemotherapy and radiation therapy followed by infusion of her own umbilical cord blood, which the parents had saved after her delivery. She is now doing well and is in complete remission 20 months after cord blood transplantation. In this first report of autologous cord blood transplantation for treatment of childhood leukemia, we discuss the safety and feasibility of this procedure as well as some of the uncertainties surrounding autologous cord blood collection and usage.


Detecting Rating Scale Malfunctioning With the Partial Credit Model and Generalized Partial Credit Model.
Rating scale analysis techniques provide researchers with practical tools for examining the degree to which ordinal rating scales (e.g., Likert-type scales or performance assessment rating scales) function in psychometrically useful ways. When rating scales function as expected, researchers can interpret ratings in the intended direction (i.e., lower ratings mean "less" of a construct than higher ratings), distinguish between categories in the scale (i.e., each category reflects a unique level of the construct), and compare ratings across elements of the measurement instrument, such as individual items. Although researchers have used these techniques in a variety of contexts, studies are limited that systematically explore their sensitivity to problematic rating scale characteristics (i.e., "rating scale malfunctioning"). I used a real data analysis and a simulation study to systematically explore the sensitivity of rating scale analysis techniques based on two popular polytomous item response theory (IRT) models: the partial credit model (PCM) and the generalized partial credit model (GPCM). Overall, results indicated that both models provide valuable information about rating scale threshold ordering and precision that can help researchers understand how their rating scales are functioning and identify areas for further investigation or revision. However, there were some differences between models in their sensitivity to rating scale malfunctioning in certain conditions. Implications for research and practice are discussed.


[Utilization of theta/alpha spectral range as an indicator of vigilance: pharmacological applications during repeated sleep latency tests].
Three successive double-blind, cross-over vs placebo trials with amphetamine 10 mg, amineptine 200 mg, clonidine 150 mcg were made in 12 x 3 healthy volunteers by means of a multiple sleep latency test (MSLT) associated with quantitative EEG. Data were evaluated by a 3-way ANOVA for repeated measurement. The aim of the study was to find out the most efficient parameters from theta/alpha ratio to exhibit a "time effect", i.e. the physiological variation of vigilance during the daytime and a "drug effect", i.e. a stimulant or sedative effect. The best parameter was the difference between the maximum and the minimum values of the theta/alpha ratio during the recording session. The time after which the theta/alpha doubled and the time after which the subject was the most relaxed (theta/alpha minimum) exhibited significant variations due to time effect and only sedative drug effect. The results of the other classical parameters from MSLT, visual analogue scales and sleep questionnaires were discussed as was the use of parameters from quantified EEG in order to make up homogeneous groups of healthy volunteers.


BODIPY-Based Fluorescent Sensor for the Recognization of Phosgene in Solutions and in Gas Phase.
As a highly toxic and widely used chemical, phosgene has become a serious threat to humankind and public security because of its potential use by terrorists and unexpected release during industrial accidents. For this reason, it is an urgent need to develop facile, fast, and selective detection methods of phosgene. In this Article, we have constructed a highly selective fluorescent sensor o-Pab for phosgene with a BODIPY unit as a fluorophore and o-phenylenediamine as a reactive site. The sensor o-Pab exhibits rapid response (∼15 s) in both colorimetric and turn-on fluorescence modes, high selectivity for phosgene over nerve agent mimics and various acyl chlorides and a low detection limit (2.7 nM) in solutions. In contrast to most undistinguishable sensors reported, o-Pab can react with phosgene but not with its substitutes, triphosgene and biphosgene. The excellent discrimination of o-Pab has been demonstrated to be due to the difference in highly reactive and bifunctional phosgene relative to its substitutes. Furthermore, a facile testing paper has been fabricated with poly(ethylene oxide) immobilizing o-Pab on a filter paper for real-time selective monitoring of phosgene in gaseous phase.


Lipid radicals: properties and detection by spin trapping.
Unsaturated lipids are rapidly oxidized to toxic products such as lipid hydroperoxides, especially when transition metals such as iron or copper are present. In a Fenton-type reaction Fe2+ converts lipid hydroperoxides to the very short-lived lipid alkoxyl radicals. The reaction was started upon the addition of Fe2+ to an aqueous linoleic acid hydroperoxide (LOOH) emulsion and the spin trap in the absence of oxygen. Even when high concentrations of spin traps were added to the incubation mixture, only secondary radical adducts were detected, probably due to the rapid re-arrangement of the primary alkoxyl radicals. With the commercially available nitroso spin trap MNP we observed a slightly immobilized ESR spectrum with only one hydrogen splitting, indicating the trapping of a methinyl fragment of a lipid radical. With DMPO or 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO) adducts were detected with carbon-centered lipid radical, with acyl radical, and with the hydroxyl radical. We also synthesized lipophilic derivatives of the spin trap DEPMPO in order to detect lipid radical species generated in the lipid phase. With all spin traps studied a lipid-derived carbon-centered radical was obtained in the anaerobic incubation system Fe2+/LOOH indicating the trapping of a lipid radical, possibly generated as a secondary reaction product of the primary lipid alkoxyl radical formed. Under aerobic conditions an SOD-insensitive oxygen-centered radical adduct was formed with DEPMPO and its lipophilic derivatives. The observed ESR parameters were similar to those of alkoxyl radical adducts, which were independently synthesized in model experiments using Fe3+-catalyzed nucleophilic addition of methanol or t-butanol to the respective spin trap.


Oral tolerance and inflammatory bowel disease.
Oral tolerance refers to the ability of the mucosal immune system to actively inhibit systemic immune responses to fed antigens. Recently, clinical trials have used oral tolerance as a therapy for certain chronic inflammatory and autoimmune diseases such as multiple sclerosis and type I diabetes. Inflammatory bowel disease is now widely thought to be caused by the breakdown of oral tolerance through a combination of genetic and environmental factors. Therefore, it seems incongruous that clinicians would try to use oral tolerance therapy to alleviate the symptoms of inflammatory bowel disease. Yet, armed with the results of select animal models, trials have begun for oral tolerance therapy for Crohn's disease. This review will outline the recent advances in understanding oral tolerance, explore the relation between oral tolerance and inflammatory bowel disease, and comment on the likelihood of successful oral tolerance therapy for inflammatory bowel disease. The results of an oral tolerance trial in Crohn's disease patients in Israel have shown some promising results, whereas the results of studies of experimentally induced oral tolerance in patients with inflammatory bowel disease from the authors' laboratory have shown that feeding a neoantigen in an attempt to induce oral tolerance is not successful in patients with inflammatory bowel disease. The fundamental difference in the mechanisms of oral tolerance in mice and humans requires a more focused effort to understand the human mucosal immune system before oral tolerance therapy for autoimmune and chronic inflammatory disorders reaches its full potential.


Endomyocardial Fibrosis With Bilateral Ventricular Thrombus: A Case Report and Literature Review.
Endomyocardial fibrosis (EMF) is a rare restrictive cardiomyopathy in non-tropical areas. It is seen in most of the patients living in or coming from tropical areas, and is rarely seen in patients who have never visited these areas. It is characterized by fibrotic thickening of the endocardium, predominantly affecting the ventricular apices and inflow tracts. Although thrombus formation is a known complication in various cardiac conditions such as atrial fibrillation, atrial flutter, ventricular heart disease, and patent foramen ovale, the occurrence of bilateral thrombus in EMF is exceptionally rare. We present a case report describing a unique finding of bilateral ventricular thrombus in a patient diagnosed with EMF, highlighting the clinical presentation, diagnostic approach, and management challenges associated with this rare phenomenon.


The Association Between Hospital Finances and Complications After Complex Abdominal Surgery: Deficiencies in the Current Health Care Reimbursement System and Implications for the Future.
To determine the relationship between complications after 3 common general surgery procedures and per-episode hospital finances. With impending changes in health care reimbursement, maximizing the value of care delivered is paramount. Data on the relative clinical and financial impact of postoperative complications are necessary for directing surgical quality improvement efforts. We reviewed the medical records of patients enrolled in the American College of Surgeons' National Surgical Quality Improvement Program who underwent pancreaticoduodenectomy, hepatectomy, and colectomy at a single academic institution between September 2009 and August 2012. Clinical outcomes data were subsequently linked with hospital billing data to determine hospital finances associated with each episode. We describe the association between postoperative complications, hospital length of stay, and different financial metrics. Multivariable linear regression modeling tested linear association between postoperative outcomes and cost data. There was a positive association between the number of surgical complications, payments, length of stay, total charges, total costs, and contribution margin for the three procedures. Multivariable models indicated that complications were independently associated with total cost among the selected procedures. Payments increased with complications, offsetting increased costs. In the current fee-for-service environment, the financial incentives are misaligned with quality improvement efforts. As we move to a value-driven method of reimbursement, administrators and health care providers alike will need to focus on improving the quality of patient care while remaining conscious of the cost of care delivered. Reducing complications effectively improves value.


Primary cholesteatoma in the congenitally atretic ear.
A developmental aberration significant enough to cause a congenital auricular atresia may well entrap ectodermal keratinous elements medial to an atresia plate, resulting in a primary cholesteatoma. We report such a case and discuss the proposed pathogenesis and pertinent embryology. A two-stage surgical procedure is offered as a reasonable management alternative when the cholesteatoma is well encapsulated.


IP3 type 1 receptors in the heart: their predominance in atrial walls with ganglion cells.
Previously we have shown that inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are abundantly expressed in the atria of rat hearts. Since arrangement of atria is very heterogeneous, in this work we focused on the precise localization of IP3 receptors in the left atrium, where the gene expression of the type 1 IP3R was the highest. The mRNA levels of the IP3 type 1 receptors in the left atrium, left ventricle and myocytes were determined using real-time polymerase chain reaction and Taqman probe. For precise localization, immunohistochemistry with the antibody against type 1 IP3Rs was performed. The mRNA of type 1 IP3 receptor was more than three times higher in the left atrium than in the left ventricle, as determined by real-time PCR. Expression of the type 1 IP3 receptor mRNA was higher in the atria, especially in parts containing cardiac ganglion cells. The atrial auricles, which are particularly free of ganglion cells, and the ventricles (wall of the right and left ventricle and ventricular septum) contained four to five times less IP3 receptors than atrial samples with ganglia. IP3R type 1 immunoreactivity detected by a confocal microscope attributed the most condensed signal on ganglionic cells, although light immunoreactivity was also seen in cardiomyocytes. These results show that type 1IP3 receptors predominate in intrinsic neuronal ganglia of cardiac atria.


Application of a liquid chromatography-tandem mass spectrometric method to multi-mycotoxin determination in raw cereals and evaluation of matrix effects.
A multi-analyte method for the liquid chromatography-tandem mass spectrometric determination of mycotoxins in crude grain extracts without clean-up has been applied to the analysis of spelt, rice and barley. Method performance characteristics were determined after spiking blank samples at multiple levels and were found to be comparable for all investigated matrices as regards linearity (linear calibration functions were obtained for all analyte/matrix combinations except for moniliformin), precision (coefficient of variations <6%) and sensitivity. Matrix-induced signal suppression/enhancement was studied in detail and varied significantly between the investigated matrices, as well as between individual samples (relative standard deviation was as high as 40% within three rice varieties) and individual toxins. It was concluded that a reliable quantitative analysis using matrix-matched calibration requires careful consideration of the model matrix, which should match the investigated samples as close as possible.


[Squamous cell carcinoma in neovagina at Mayer-Rokitansky-Küster-Hauser-syndrome].
Carcinoma of the vagina is a rare entity of cancer, also a primary carcinoma of the neovagina in patients with vaginal agenesia is of rare occurrence. We report on a 48-year-old female patient with a squamous cell carcinoma in neovagina after Mayer-Rokitansky-Kuester-Hauser-syndrome. Neovagina was constructed by method of Vecchietti 28 years before. Operative treatment consisted of anterior exenteration with construction of a modified Mainz-1-pouch. There were no complications intra- or postoperative. Microscopic findings showed a G2-differentiated invasive squamous cell carcinoma of the neovagina at stage FIGO III with an infiltration of urethra and the bladder neck. The tumor could be resected completely, no infestation of lymph nodes was observed. In the further process the aftercare is planned. In a systematic literature review 19 female patients with a primary carcinoma of neovagina after agenesia of vagina could be identified. Female patients with a neovagina require a regular gynaecologic examination in order not to survey a malignant transformation although a malignoma in neovagina is rare. A possible therapy option is the radical operation, there are no data of long-term prognosis at present.


Effects of reduced food intake on toxicity study parameters in rats.
This study comprehensively describes the effects of various levels of food reduction on a wide range of toxicological parameters in dietary-optimized rats (fed with approximately 75% of ad libitum food consumption daily; 16 g and 22 g/day for females and males, respectively) that has been established as a nutritionally appropriate and well-controlled animal model in conducting toxicity studies. Toxicological parameters, including general condition, ophthalmology, clinical pathology and anatomic pathology, were examined in dietary-optimized Crl:CD(SD) female and male rats fed 16 g and 22 g/day (control), 12 g and 17 g/day (75% group), 8 g and 11 g/day (50% group), or 4 g and 6 g/day (25% group), respectively for 2 weeks. There was mortality and morbidity including reddish urine in 25% group females. The reddish urine was identified as "hemoglobinuria" that resulted from extra/intra-vascular hemolysis induced by severe food reduction. Hemoconcentration, decreased leukocytes and platelets, decreases in nutritional elements (serum glucose, protein, and lipids), increased aspartate aminotransferase and alanine aminotransferase, imbalanced electrolytes, and/or decreased urinary pH were observed in all restriction groups. Histopathologically remarkable changes included erythrophagocytosis in the spleen/liver and renal tubular necrosis with hyaline cast/droplets in 25% group; in addition to bone marrow depletion, lymphoid depletion in thymus/spleen/lymph node, and/or decreased secretion in the prostate/seminal vesicle in all restriction groups. Most of these changes were considered attributable to nutritional deficiency, dehydration, accelerated protein catabolism, stress and/or hemolysis secondary to severe food reduction. These results will enable toxicologists to help distinguish primary drug-induced effects from secondary changes associated with decreases in food consumption.


How do older adults understand and manage distress? A qualitative study.
Distress is an expected emotional response to a negative life event. Experiences common in later life may trigger distress such as bereavement or loss of physical mobility. Distress is considered to be distinct to anxiety and/or depression and is not diagnostically labelled as a mental health problem. Older adults will often manage their own distress. Previous literature has focused on how younger adults self-manage mental health problems, however little research has explored the self-management strategies used by older people. There is a need to clarify the role of primary care in the context of distressed older adults who may consult healthcare services. This study seeks to address these gaps through qualitative methods. Keele University's ethical review panel approved this study. We recruited older adults who self-identified as distressed from community groups in North Staffordshire, England. Data were generated through semi-structured interviews and analysed thematically using constant comparison methods. A patient and public involvement and engagement group contributed to development of the research questions and methods, and offered their perspectives on the findings. After 18 interviews data saturation was achieved. Key themes were: experiences of distress, actions taken, help-seeking from healthcare services and perceptions of treatments offered in primary care. Various forms of loss contributed to participants' distress. Participants initiated their own self-management strategies which included: pursuing independent activities, seeking social support and attending community groups and church. Five participants reported having consulted a GP when distressed but described a lack of acceptable treatments offered. To support older adults who are distressed, healthcare professionals in primary care should consider exploring how patients currently manage their mood problems, provide a broad range of information about potential management options and consider sign-posting older adults to community resources.


Three-Dimensional Evaluation of the Accuracy of Zygomatic Implant Placement Through an In-House Fully Guided Approach.
Purpose: To validate guided surgery for zygomatic implants (ZIs) by analyzing the final position of the implants relative to the preoperatively planned position. Material and Methods: Five patients with fully edentulous atrophic maxillae treated with four ZIs through a fully guided implant surgical approach were evaluated. The preoperative phase included digital planning, through which the surgical guide was designed and created. Analysis of the guided surgery accuracy was carried out by superimposing the digital planning over the final position of the implants using preoperative and postoperative CBCT. The radiologic evaluation included implant angular deviation, entrance deviation, exit deviation, platform deviation, and apex apicocoronal and mesiodistal deviation. Results: All five patients (two men and three women; mean age: 61.8 ± 3 years) were each treated with four ZIs using a fully guided approach with an extrasinusal path, obtaining ideal emergence of the implants. Superimposition comparison found a mean axial angular implant deviation of 0.79 ± 0.41 degrees and a mean implant entrance deviation of 0.95 ± 0.26 degrees. The platform deviation was 0.62 ± 0.19 mm buccopalatally and 0.76 ± 0.14 mm mesiodistally, while the apical deviation was 0.42 ± 0.13 mm buccopalatally and 1.06 ± 0.37 mm mesiodistally. Conclusions: Guided surgery in zygomatic implants appears to be sufficiently accurate to make it a safe and predictable technique.


Eccentricity dependence of the curveball illusion.
When the Gaussian envelope of a Gabor patch moves straight down while its sine wave component drifts to the left, the Gabor is seen to move down to the left when viewed with peripheral vision (exhibiting the so-called curveball illusion) but straight down when viewed foveally. We used a nulling procedure to quantify the strength of the curveball illusion at a range of stimulus sizes and eccentricities to determine if the illusion is size dependent and whether size scaling can equate the strength of the illusion across the visual field. We find that the illusion is size dependent (illusion strength decreases with increasing stimulus size) but that size scaling is not sufficient to elicit an illusion at fixation that matches the strength of the illusion at 10°. These results suggest that certain changes in motion processing across the visual field differ in more than just the local scale of the mechanisms involved.


[Cyclophilins – proteins with many functions].
Cyclophilins together with FK-506-binding proteins and parvulins, belong to a group of proteins that have peptidyl-prolyl cis-trans isomerase activity. They also belong to proteins that are collectively known as immunophilins. Cyclophilins are found in all cells of all organisms studied, in both prokaryotes and eukaryotes. The first member of the cyclophilins to be identified in mammals, cyclophilin A, is the major cellular target for the immunosuppressive drug cyclosporin A. This review discusses recently available data about proteins with cyclophilin domain (CBD). Recent studies have implicated a diverse array of additional cellular functions for cyclophilins, including roles as chaperones and in cell signalling as well as in several human diseases.


Epidemiology of hepatitis B and hepatitis B virus infection in United States children.
Before the era of routine hepatitis B vaccination, an estimated 24,000 children acquired hepatitis B virus (HBV) infection each year in the United States. Childhood hepatitis B immunization has led to significant declines in the incidence and prevalence of HBV infection in U.S. children. Because the greatest burden of hepatitis B is caused by complications of hepatocellular carcinoma and cirrhosis in adults who were infected with HBV as children, most of the benefits of vaccination have yet to be realized. Reaching the goal of eliminating HBV transmission to children likely will require increasing vaccination coverage, ensuring timely administration of postexposure immunoprophylaxis to prevent more perinatal infections, and continued evaluation of the impact of immunization recommendations.


Mode of action of coronary arterial relaxation by prostacyclin.
Subsequent to previous observations suggesting a close association between the relaxing actions of PGI2 and its increasing effects on cyclic AMP levels in bovine coronary smooth muscle, evidence indicative of a transmitter function of cAMP in PGI2-induced relaxation is presented, by showing that a) in time course experiments in circular strips of bovine coronary arteries the increase in cAMP-levels caused by PGI2 preceded the mechanical response, b) the relaxant as well as cAMP-increasing effects produced by PGI2 were significantly potentiated by the PDE-inhibitor MIX, and c) in a particulate preparation of bovine coronary arteries PGI2 concentration dependently stimulated adenylate cyclase in the presence of GTP.


Isolation of KPC 3-producing Enterobacter aerogenes in a patient colonized by MDR Klebsiella pneumoniae.
We describe the interspecies transmission of the plasmid-mediated blaKPC-3 gene, which confers carbapenem resistance, between clinically relevant gram-negative bacteria in a single patient. A KPC-3 producing Enterobacter aerogenes was isolated from a hospitalized patient previously colonized and then infected by a Klebsiella pneumoniae ST101 carrying the blaKPC-3 gene. The strains showed identical plasmids. Since intense horizontal exchanges among bacteria can occur in the gut, clinicians should be aware that patients colonized by carbapenem-resistant K. pneumoniae could become carriers of other carbapenem-resistant Enterobacteriaceae.


Characteristics of flavonol glycosides in bean (Phaseolus vulgaris L.) seed coats.
Seed coats of coloured dry beans contain biologically active compounds. Flavonol glycosides were identified from acetone extracts of seed coats of black beans, pinto beans, and red kidney beans and evaluated for antioxidant activity. High Performance Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (HPLC-MS/MS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity were used to measure flavonols and antioxidant capacity, respectively. The main flavonol glycosides in black beans were the 3-O-glycosides of kaempferol, quercetin and myricetin; pinto beans contained kaempferol 3-O-glycosides, while red kidney beans contained quercetin 3-O-glycoside and quercetin 3-O-rutinoside (rutin). A flavonol triglycoside was identified in dark red kidney bean. Despite differences in total flavonol content, extracts from Eclipse, (black bean) and Windbreaker (pinto bean) had the significantly higher antioxidant activities than other bean seed coats. Results suggest seed coats of Windbreaker and Eclipse may have potential as functional food ingredients, though benefits may not be simply due to flavonols.


[Research Progress of Event-related Potential in Mild Cognitive Impairment].
Mild cognitive impairment caused by craniocerebral trauma is the key points and difficulties in judicial authentication. This article has comparative analysis of each mode of event-related potential (classical Oddball, Eriksen flanker task and so on), which can provide a more objective method for such craniocerebral trauma cases in clinical forensic judicial authentication.


Preserved corneal lamellar transplantation for infectious and noninfectious scleral defects: Three case reports and literature review.
: Reinforcement of thinned or necrotizing sclera has been conducted using various materials, including allogeneic sclera, allogenic cornea, amniotic membrane, fascia lata, pericardium, periosteum, and perichondrium. Among them, good outcomes have traditionally been obtained using preserved scleral grafts. However, scleral patch grafts have complications such as graft retraction, thinning, dehiscence, and necrosis. Furthermore, to promote epithelial healing, scleral patch grafting must be accompanied by procedures such as amniotic membrane transplantation (AMT) or grafting using conjunctival flaps or autografts. Recently, acellular preserved human corneas have been used in various ophthalmic surgeries, with emerging evidence supporting its use for treating scleral defects as an option that does not require AMT or conjunctival autografting. We investigated whether corneal patch grafting would show wound healing and tectonic success rate outcomes comparable to those of existing techniques. : Three patients presented with intractable ocular pain. Slit-lamp examination showed marked scleral thinning at the nasal side. : Scleral thinning progressed with conservative treatment; microbial staining and culturing were performed. Infectious or non-infectious scleritis was diagnosed according to slit-lamp examination and microbial culture results. : A preserved corneal lamellar patch was grafted at the scleral thinning area. All patients achieved tectonic success with reduction of inflammation following corneal patch grafting. Two patients achieved complete re-epithelialization within 7 days, while 25 days were required for the third patient. No patients experienced graft thinning, rejection, or infection. : Our report suggests the feasibility of using acellular preserved human cornea patch grafts to reinforce inflammatory scleral defects and obtain successful outcomes in terms of wound healing. This technique shows a comparable tectonic success rate and superior effect on scleral defect healing without the need for adjunctive AMT or conjunctival autografting.


Updates to the carnivore fauna from the Sima de los Huesos.
The Sima de los Huesos site in the Sierra de Atapuerca (Burgos, northern Spain) is a Middle Pleistocene locality with the most important accumulation of humans in the European record for this age. In addition to the hominin collection, the Sima has provided numerous faunal remains. Here, we update the carnivoran mammal fauna from the Sima de los Huesos. The analyzed carnivoran fauna is taxonomically diverse consisting of 11 species from 9 genera and four families. The high taxonomic diversity of carnivorans at the site is interpreted as corresponding to high overall ecosystem productivity. A synthetic description of the carnivoran remains is presented adding new information on the biochronology of the carnivoran species assemblage and its paleoecological association with European Middle Pleistocene hominins. Because of their similarity in taphonomic setting and diets-that the carnivoran fauna and humans were found in the same place and had similar protein-rich diets-clarifying the paleontological and paleoecological context of these carnivorans permits a better understanding of the humans also found at this site.


Management of Malignant Bowel Obstruction Associated With GI Cancers.
For many patients with GI malignancies, the seeding of the abdominal cavity with tumor cells, called peritoneal carcinomatosis, is a common mode of metastases and disease progression. Prognosis for patients with this aspect of their disease remains poor, with high disease-related morbidity and complications. Uniform and proven practices that provide optimal palliative care and quality of life for these patients are needed. The objective of this review is to critically assess the current literature regarding palliative strategies in the management of peritoneal carcinomatosis and associated symptoms in patients with advanced GI cancers. Despite encouraging results in the select population where cytoreductive surgery and intraperitoneal chemotherapy are indicated, the majority of patients who develop peritoneal carcinomatosis in the setting of GI cancers have poor prognosis, with malignant bowel obstruction representing a common terminal phase of their disease process. For all patients with peritoneal carcinomatosis, aggressive symptom control and early multimodality palliative care as further outlined should be sought.


Covert operations: cancer's many subversive tactics in overcoming host defenses.
In an effort to use the patient's T cells to fight his or her own cancer, we inadvertently discovered a distinctive form of tumor-induced immune suppression. T cells from tumor-bearing patients are often defective in signaling. They lack the zeta chain of the T-cell receptor and the src kinases crucial for its downstream effects including lck. They truncate the carboxy terminal of the p50 NF-kappaB transcription factor. At the population level, CD4 T cells are polarized toward the Th2 subtype and inhibitory Tregs expand. These T cells can recover after several days of culture outside of the tumor-bearing host environment. The effect is mediated by one or more factors made by the tumor given that the same T-cell defects occur in mice with tumors implanted in hollow fibers that never directly contact cells of the host. Several promising strategies may overcome these immunosuppressive effects.


Nitric oxide synthase expression after human brain contusion.
Nitric oxide is a universal mediator of biological effects in the brain, and it has been implicated in the pathophysiological processes of traumatic brain injury. Experimental studies have indicated posttraumatic up-regulation of the three different isoforms of nitric oxide synthase (NOS) (i.e., inducible NOS [iNOS], endothelial NOS, and neuronal NOS) after brain trauma. This study was undertaken to investigate the cellular sources and tissue compartments of nitric oxide produced by human patients undergoing surgical treatment for contusional brain injuries. Contused brain tissue specimens from eight consecutive patients who underwent surgical treatment for brain contusions 3 hours to 5 days after trauma were evaluated in immunohistochemical analyses. Double-staining assays were used to define which cells produced the different isoforms. Increases in iNOS-positive cells were detectable within 6 hours after trauma, with a peak at 8 to 23 hours. Expression of iNOS after trauma was detected in neurons, macrophages, neutrophils, astrocytes, and oligodendrocytes. The cellular sources of iNOS differed at different times after trauma. No detectable difference in the expression of the neuronal or endothelial isoforms was observed for trauma patients, compared with control subjects. iNOS expression was up-regulated in a time-dependent manner in human brain tissue obtained from patients undergoing surgical treatment for contusional trauma. Our human data largely parallel experimental findings in rats, indicating that such trauma models are relevant for experimental studies and treatment trials.


The Cost-Effectiveness of Tocilizumab (Actemra) Therapy in Giant Cell Arteritis.
Tocilizumab (Actemra) is a humanized anti-interleukin-6 receptor antibody that has been used as a steroid-sparing agent in giant cell arteritis (GCA). Although the clinical effects are well described in GCA, the cost-effectiveness of the use of tocilizumab in GCA is ill defined. The purpose of this study was to determine the cost-effectiveness of tocilizumab in GCA compared with prednisone alone. A retrospective study of 32 patients with biopsy-proven GCA comparing prednisone alone (16 patients) and prednisone with tocilizumab (16 patients) was performed. The cost for tocilizumab therapy for 26 weeks with mild and severe side effects (Groups 1 and 2, respectively) and for 52 weeks with mild and severe side effects (Group 3 and 4, respectively) was compared with estimated costs of mild and severe steroid-induced side effects (Groups 5 and 6, respectively). Statistical analysis between groups was conducted using independent sample t tests. Three out of the 4 group combinations of tocilizumab with prednisone demonstrated a statistically significant (P < 0.05) difference in cost compared with prednisone alone for GCA. Group 2 (26-week tocilizumab therapy with severe steroid-induced side effects), with no statically significant difference in price when compared with steroid therapy alone and far fewer side effects, demonstrated the potential use of tocilizumab in GCA therapy. As expected, longer treatment duration with tocilizumab was associated with greater cost. With respect to side effect severity, the number of side effects of steroid therapy was inversely associated with difference in cost between tocilizumab therapy and steroid side effect treatment. This study demonstrates that combination therapy of tocilizumab and prednisone is significantly more expensive than steroids alone with or without accounting for the cost of steroid-induced side effects in treated GCA. The difference in cost between the 2 therapy types is directly related to tocilizumab therapy duration and inversely related to the number or severity of steroid side effects. Patients with GCA who require a shorter duration of steroid therapy and are at risk for a high number of side effects from steroid use may be potential candidates for tocilizumab therapy, from an economic perspective.


Changes to the cytokine microenvironment in the genital tract mucosa of HIV+ women.
As previous studies have indicated that genital tract mucosal T cell function may be impaired in HIV infection, we investigated the T cell cytokine mRNA in the genital tract mucosa of HIV-infected women to determine if there are alterations in the cytokine profile which may explain the T cell impairment. The in situ hybridization technique was used to investigate the T helper-1 (Th1: IL-2, interferon-gamma (IFN-gamma)) and Th2 cytokine (IL-4, IL-5, IL-10) mRNA profile in cervical biopsies from 10 HIV+ and 10 HIV- subjects. Cervical intraepithelial neoplasia (CIN) and genital infection had previously been excluded and the distribution of immunocompetent cells within the cervical mucosa was known for each subject. Non-parametric tests were used to compare the optical density (OD) of cytokine mRNA in the HIV+ and HIV- groups. Comparisons were also made between peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA OD for the Th2 cytokines IL-4, IL-5 and IL-10 than HIV women. There was also significantly lower IL-2 mRNA OD in the former group. HIV+ women had lower IFN-gamma mRNA than HIV- women, but the difference was not statistically significant. There was no correlation between cytokine mRNA OD and peripheral CD4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno-inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the susceptibility of HIV-infected women to recurrent genital tract infections and cervical neoplasia.


Risk of Stress Fracture Varies by Race/Ethnic Origin in a Cohort Study of 1.3 Million US Army Soldiers.
Stress fractures (SF) are common and costly injuries in military personnel. Risk for SF has been shown to vary with race/ethnicity. Previous studies report increased SF risk in white and Hispanic Soldiers compared with black Soldiers. However, these studies did not account for the large ethnic diversity in the US military. We aimed to identify differences in SF risk among racial/ethnic groups within the US Army. A retrospective cohort study was conducted using data from the Total Army Injury and Health Outcomes Database from 2001 until 2011. SF diagnoses were identified from ICD-9 codes. We used Cox-proportional hazard models to calculate time to SF by racial/ethnic group after adjusting for age, education, and body mass index. We performed a sex-stratified analysis to determine whether the ethnic variation in SF risk depends on sex. We identified 21,549 SF cases in 1,299,332 Soldiers (more than 5,228,525 person-years of risk), revealing an overall incidence rate of 4.12 per 1000 person-years (7.47 and 2.05 per 1000 person-years in women and men, respectively). Using non-Hispanic blacks as the referent group, non-Hispanic white women had the highest risk of SF, with a 92% higher risk of SF than non-Hispanic black women (1.92 [1.81-2.03]), followed by American Indian/Native Alaskan women (1.72 [1.44-1.79]), Hispanic women (1.65 [1.53-1.79]), and Asian women (1.32 [1.16-1.49]). Similarly, non-Hispanic white men had the highest risk of SF, with a 59% higher risk of SF than non-Hispanic black men (1.59 [1.50-1.68]), followed by Hispanic men (1.19 [1.10-1.29]). When examining the total US Army population, we found substantial differences in the risk of stress fracture among racial/ethnic groups, with non-Hispanic white Soldiers at greatest risk and Hispanic, American Indian/Native Alaskan, and Asian Soldiers at an intermediate risk. Additional studies are needed to determine the factors underlying these race- and ethnic-related differences in stress fracture risk. © 2017 American Society for Bone and Mineral Research.


Planning focus group interviews with asylum seekers: Factors related to the researcher, interpreter and asylum seekers.
The aim of this article was to discuss factors related to the researcher, interpreter and asylum seekers when planning focus group interviews with asylum seekers. Focus group interview is one of the basic data collection methods in descriptive nursing and health research. It has been used in multicultural research, allowing an opportunity to participate without literacy and to have linguistic and cultural support from other participants. Asylum seekers form a specific, vulnerable group, and the growing number of asylum seekers increases the need for research related to them. A culturally, methodologically and ethically high-quality focus group interview is based on the researcher's special knowledge and skills, acknowledgement of asylum seekers as both individuals and part of cultural and communal groups, and careful planning of the interpreter's role during the interviews.


Computerized assessment of sustained attention: a review of factors affecting vigilance performance.
Results of empirical studies using computerized tests of sustained attention are summarized. Factors that affect vigilance performance fall into three broad categories: task parameters, environmental or situational factors, and subject characteristics. Complex interactions of factors from each category affect performance further. Such interactions may help to explain inconsistencies in the literature regarding effects on vigilance. Implications for both research and clinical practice are discussed.


Epidemiologic trend of severe sepsis in Taiwan from 1997 through 2006.
The epidemiologic data of severe sepsis are limited in developing countries. Among patients, the contribution of subsequent severe sepsis episodes to the disease burden is unclear. We analyzed the hospitalization claims data of a nationally representative sample of 200,000 people, approximately 1% of the population, enrolled in the Taiwan National Health Insurance program. We identified first and subsequent episodes of severe sepsis hospital admissions from 1997 to 2006 based on International Classification of Diseases, 9th ed., Clinical Modification codes for infections and acute organ dysfunction. During the 10-year period, we identified 5,258 patients having 7,531 hospitalizations for severe sepsis in the study cohort. The age-standardized annual incidence rates of first episodes increased by 1.6-fold from 135 per 100,000 in 1997 to 217 per 100,000 in 2006, with an annual percent change of 3.9% (95% CI, 2.3%-5.5%). Although the proportion of patients with multiorgan (>or= 2) dysfunctions increased from 11.7% in 1997 to 27.6% in 2006, the hospital mortality changed little, averaging 30.8%. Among survivors, 34.4% developed at least one subsequent severe sepsis episode, which contributed 30.2% to the disease burden in 10 years. The incidence and disease severity of severe sepsis in Taiwan are increasing. One-third of the survivors developed at least one subsequent episode, which contributed substantially to the disease burden over time.


Unilateral symptomatic palatal myoclonus: MRI evidence of contralateral inferior olivary lesion.
Symptomatic palatal myoclonus is a rare syndrome of segmental myoclonus which is thought to occur after damage to certain brainstem or cerebellar structures. We report two patients with unilateral PM, who showed hypertrophy of the inferior olivary nucleus on magnetic resonance imaging. In the first patient this was due to a left pontine tegmental hemorrhage, and a right-sided oculo-palato-facial myoclonus developed one month after the episode. The second one had a basilar artery occlusion with ischemic infarcts at the basis pontis, dorso-lateral aspects of the left pons, and left cerebellar dentate nucleus, as well as the occipital lobe. A delayed left oculopalatal myoclonus was recognized 3 months later. Interruption of the "dentato-rubro-olivary pathway" by the lesion with ensuing neuronal loss, cytoplasmic vacuolation, and astrocytic proliferation in the inferior olive, together with an increase of water content as mobile proton may cause the MR signal abnormalities in patients with unilateral symptomatic palatal myoclonus.


The correlation between gray matter volume and perceived social support: a voxel-based morphometry study.
Social support refers to interpersonal exchanges that include the combinations of aid, affirmation and affection. Perceived social support is a kind of subjective judgment of one's availability of social support. In spite of the importance of perceived social support to health, however, its neural substrate remains unknown. To address this question, voxel-based morphometry was employed to investigate the neural bases of individual differences in responses to the Perceived Social Support Scale (PSSS) in healthy volunteers (144 men and 203 women; mean age = 19.9; SD = 1.33, age range : 17-27). As a result, multiple regression analysis revealed that the PSSS scores were significantly and positively correlated with gray matter volume in a cluster that mainly included areas in posterior parts of posterior cingulate cortex, bilateral lingual cortex, left occipital lobe and cuneus. Highly-supported individuals had larger gray matter volume in these brain regions, implying a relatively high level of ability to engage in self-referential processes and social cognition. Our results provide a biological basis for exploring perceived social support particularly in relationship to various health parameters and outcomes.


Exploring the evidence of Middle Amazonian aquifer sedimentary outburst residues in a Martian chaotic terrain.
The quest for past Martian life hinges on locating surface formations linked to ancient habitability. While Mars' surface is considered to have become cryogenic ~3.7 Ga, stable subsurface aquifers persisted long after this transition. Their extensive collapse triggered megafloods ~3.4 Ga, and the resulting outflow channel excavation generated voluminous sediment eroded from the highlands. These materials are considered to have extensively covered the northern lowlands. Here, we show evidence that a lacustrine sedimentary residue within Hydraotes Chaos formed due to regional aquifer upwelling and ponding into an interior basin. Unlike the northern lowland counterparts, its sedimentary makeup likely consists of aquifer-expelled materials, offering a potential window into the nature of Mars' subsurface habitability. Furthermore, the lake's residue's estimated age is ~1.1 Ga (~3.2 Ga post-peak aquifer drainage during the Late Hesperian), enhancing the prospects for organic matter preservation. This deposit's inferred fine-grained composition, coupled with the presence of coexisting mud volcanoes and diapirs, suggest that its source aquifer existed within abundant subsurface mudstones, water ice, and evaporites, forming part of the region's extremely ancient (~ 4 Ga) highland stratigraphy. Our numerical models suggest that magmatically induced phase segregation within these materials generated enormous water-filled chambers. The meltwater, originating from varying thermally affected mudstone depths, could have potentially harbored diverse biosignatures, which could have become concentrated within the lake's sedimentary residue. Thus, we propose that Hydraotes Chaos merits priority consideration in future missions aiming to detect Martian biosignatures.


repDNA: a Python package to generate various modes of feature vectors for DNA sequences by incorporating user-defined physicochemical properties and sequence-order effects.
In order to develop powerful computational predictors for identifying the biological features or attributes of DNAs, one of the most challenging problems is to find a suitable approach to effectively represent the DNA sequences. To facilitate the studies of DNAs and nucleotides, we developed a Python package called representations of DNAs (repDNA) for generating the widely used features reflecting the physicochemical properties and sequence-order effects of DNAs and nucleotides. There are three feature groups composed of 15 features. The first group calculates three nucleic acid composition features describing the local sequence information by means of kmers; the second group calculates six autocorrelation features describing the level of correlation between two oligonucleotides along a DNA sequence in terms of their specific physicochemical properties; the third group calculates six pseudo nucleotide composition features, which can be used to represent a DNA sequence with a discrete model or vector yet still keep considerable sequence-order information via the physicochemical properties of its constituent oligonucleotides. In addition, these features can be easily calculated based on both the built-in and user-defined properties via using repDNA. The repDNA Python package is freely accessible to the public at http://bioinformatics.hitsz.edu.cn/repDNA/. email@example.com or firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Influence of Peripheral Arterial Disease on Wound Healing in Heel Pressure Ulcers.
There are cases of heel pressure ulcer with peripheral arterial disease (PAD). The influence of ischemia on wound healing was investigated. We retrospectively studied 253 patients with heel ulcers treated between January 2003 and March 2018. The patients were classified into PAD and non-PAD groups. The wound healing rate, wound healing time and the factors that influenced wound healing were examined. There were 186 patients with PAD (73.5%). There were 41 (22.0%) and 35 (52.2%) wound healing cases with PAD and non-PAD, respectively (P < 0.001). In the non-PAD group, the deeper the ulcer, the lower the wound healing rate. However, in the PAD group, the increase in blood flow owing to revascularization affected the wound healing rate. The wound healing rate in the endovascular therapy (EVT) and bypass groups were 26.7% and 65.0%, respectively (P = 0.003). The wound healing time was 128 (interquartile range [IQR] 88-196) and 79 (IQR 35.5-187) days, with PAD and non-PAD, respectively (P = 0.0268). The wound healing time in the PAD group was 128 (IQR 93-174.5) days with bypass and 155.5 (IQR 86-237.5) days with EVT (P = 0.459). Heel pressure ulcers with PAD are difficult to treat. The wound healing rate was lower in the PAD than in the non-PAD group and the wound healing time also tended to be long. Successful revascularization is important for wound healing and bypass surgery had a shorter wound healing time and a higher wound healing rate than EVT.


Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.
Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients. We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25). D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients. Clinicaltrials.gov NCT01175798.


Perceptions of support among Swedish parents of children on cancer treatment: a prospective, longitudinal study.
Given the important role of parents in ensuring the well-being of their children, their perceived support is crucial for their own, as well as their child's well-being. Perceptions of support were investigated among 214 Swedish parents of 115 children on cancer treatment. Parents answered questions about their satisfaction with their child's care (The Comprehensive Satisfaction with Care, Short Form, Version 4.0 (CASC SF 4.0)) and about their need, opportunity and benefit to talk to health professionals, significant others and other people. Data were collected over telephone at 1 week (T1), 2 (T2) and 4 (T3) months after the child's diagnosis. Parents reported at least moderate satisfaction with all aspects of their child's care, and highest satisfaction with the technical care. Less than half of the parents who reported a need to talk with a psychologist at T1-T3 reported having had the opportunity to do so. The care organization, doctors' interpersonal skills, information provision and availability, nurses' information provision and the availability of psychologists are areas within Swedish paediatric oncology care for which improvement most obviously is needed.


The performance of a risk score in predicting undiagnosed hyperglycemia.
Type 2 diabetes is a serious disease that is commonly undetected and for which screening is sometimes advocated. A number of risk factors are associated with prevalent undiagnosed diabetes. The use of routinely available information on these factors has been proposed as a simple and effective way of identifying individuals at high risk for having the disease. The objective of this study was to assess the effectiveness of the Cambridge risk score in a large and representative population. A risk score derived from data in a previous study was tested for its ability to detect prevalent undiagnosed hyperglycemia as measured by a GHb > or = 6.0, 6.5, or 7% in 6,567 subjects aged 39-78 years in the European Prospective Investigation of Cancer-Norfolk cohort. For a specificity of 78%, the risk score predicted a GHb of > or = 7.0% in subjects aged 39-78 years, with a sensitivity of 51% (95% CI 40-62). The areas under the receiver-operating characteristic (ROC) curve for GHb > or = 6.0, 6.5, and 7% were 65.7% (63.8-67.6), 71.2% (68.4-75.2), and 74.2% (69.5-79.0), respectively. The area under the ROC curve was not significantly reduced if data on family and smoking history were unavailable for any of the cut-offs for GHb. The risk score performed as well as other previously reported models in all age groups. We concluded that a simple risk score using data routinely available in primary care can identify people with an elevated GHb with reasonable sensitivity and specificity, and it could therefore form part of a strategy for early detection of type 2 diabetes.


[Effect of acupuncture at pericardium points of amplitude of low frequency fluctuations of healthy people in resting state functional magnetic resonance imaging].
To observe the effect of acupuncture at the whole points of Hand Jueyin pericardium meridian on the amplitude of low frequency fluctuations (ALFF) of healthy people in resting state (R1) functional magnetic resonance imaging (fMRI). Totally 16 healthy subjects received structure scan of T1 and T2. Then two fMRI scans were conducted for each participant. fMRI included the resting-state scan (R1; the scanning time was 8 min 6 s), the stimulating-acupoint scan (AP; the scanning time was 8 min 6 s). fMRI data acquisition from structure scanning and function scanning were processed with format conversion and statistical analysis. Under R1 state, brain regions with activated ALFF signals included bilateral superior frontal gyrus, medial frontal gyrus, middle occipital gyrus, precuneus, superior temporal gyrus, and cingulate gyrus. Under the AP state, brain regions with activated ALFF signals were bilateral superior frontal gyrus, medial frontal gyrus, middle temporal gyrus, left fusiform gyrus, precuneus, posterior cingulate, and declivis. Compared with R1 state, obvious difference of ALFF signal areas of the brain caused by acupuncture at pericardium were: bilateral cuneus, precuneus, left posterior cingulate gyrus, right middle occipital gyrus, and right occipital lingual gyrus. Acupuncture at the whole points of Hand Jueyin pericardium meridian could significantly change inherent activity states of the cerebral cortex, especially in bilateral superior frontal gyrus, medial frontal gyrus, and precuneus.


Adaptable Optical Fiber Displacement-Curvature Sensor Based on a Modal Michelson Interferometer with a Tapered Single Mode Fiber.
A compact, highly sensitive optical fiber displacement and curvature radius sensor is presented. The device consists of an adiabatic bi-conical fused fiber taper spliced to a single-mode fiber (SMF) segment with a flat face end. The bi-conical taper structure acts as a modal coupling device between core and cladding modes for the SMF segment. When the bi-conical taper is bent by an axial displacement, the symmetrical bi-conical shape of the tapered structure is stressed, causing a change in the refractive index profile which becomes asymmetric. As a result, the taper adiabaticity is lost, and interference between modes appears. As the bending increases, a small change in the fringe visibility and a wavelength shift on the periodical reflection spectrum of the in-fiber interferometer is produced. The displacement sensitivity and the spectral periodicity of the device can be adjusted by the proper selection of the SMF length. Sensitivities from around 1.93 to 3.4 nm/mm were obtained for SMF length between 7.5 and 12.5 cm. Both sensor interrogations, wavelength shift and visibility contrast, can be used to measure displacement and curvature radius magnitudes.


A novel eco-friendly approach for textile sludge.
Solid waste management is a very serious problem in both human settlements and industrial establishments. In such cirumstances, management of sludge in textile industry has now become a burning issue due to its surplus volume and undesired characteristics. In such grim scenario, an attempt has been made to effectively dispose of the sludge generated in the treatment units of the textile sectors of Tirupur (India). The main objective of this research work was to study the suitability of utilizing sludge in the manufacture of bricks. It thus serves two important purposes, namely - efficient management of textile sludge and production of useful by-product, which fetches cash to the industry and a low cost construction material to the public. The sludge was collected from the effluent treatment plant and it was analyzed to explore its characteristics. Then the bricks, made up of this sludge, were tested for water absorption, compressive strength, presence of soluble salts and drop test, and the results were compared with those of ordinary bricks.