The ovalbumin gene. Partial purification of the coding strand.
Purified ovalbumin messenger RNA was employed to selectively enrich the concentration of the gene coding for ovalbumin from total chick DNA by molecular hybridization. The coding strand of the ovalbumin gene was partially purified from sheared chick DNA by affinity column chromatography using ovalbumin mRNA immobilized on phosphocellulose. The concentrations of the ovalbumin DNA sequence in various DNA fractions were quantitated by measuring their rates of hybridization with 125I-labeled ovalbumin mRNA. When apparent Cot1/2 values of these reactions were compared to the apparent Cot1/2 value obtained from the hybridization reaction between 125I-ovalbumin mRNA and complementary DNA synthesized against ovalbumin mRNA using the enzyme reverse transcriptase, purification of the coding ovalbumin DNA strand over total chick DNA was estimated to be approximately 9,600-fold. There was no apparent degradation of the 4,000 nucleotide strands of chick DNA throughout the purification procedure. Since ovalbumin mRNA has a complexity of 1890 nucleotides, the resulting DNA was more than twice the length of ovalbumin mRNA and thus should contain DNA sequences adjacent to the structural portion of the ovalbumin gene.


Pertussis toxin-insensitive phosphoinositide hydrolysis, membrane depolarization, and positive inotropic effect of carbachol in chick atria.
Muscarinic agonists can stimulate rather than inhibit cardiac muscle in some preparations. In left atria from hatched chicks, treatment with pertussis toxin reversed the membrane action of carbachol from hyperpolarization to depolarization and reversed the inotropic effect of carbachol from negative to positive. Acetylcholine also depolarized the membrane and increased the force of contraction in atria from pertussis-toxin-treated chicks although oxotremorine did not. These cholinergic responses were blocked by atropine but not by adrenoceptor antagonists, suggesting that they are mediated via muscarinic receptors and are not due to actions of endogenously released catecholamines. Muscarinic receptor stimulation leads to two distinct biochemical responses in chick atria: inhibition of adenylate cyclase and activation of phosphoinositide (PI) hydrolysis. The former is lost in atria from pertussis-toxin-treated chicks, whereas the PI response persists. The pharmacologic characteristics of the PI response resemble those of the depolarization and positive inotropic response. Both are insensitive to blockade by pertussis toxin, require high concentrations of carbachol, and are elicited by acetylcholine but not by oxotremorine. The present study suggests that muscarinic agonist-induced PI turnover may be responsible for the membrane depolarization and positive inotropic effects of carbachol and acetylcholine; that an increase in Na+ conductance underlies these responses; and that it is stimulated either by an increase of intracellular calcium mobilized by inositol triphosphate and/or by activation by protein kinase C.


[Mechanism of cellular cholesterol removal: a communication system between extracellular cholesterol transport and intracellular cholesterol homeostasis].
Cholesterol efflux is one of the essential events in cellular cholesterol homeostasis since peripheral cells do not catabolize the cholesterol molecule. There are two distinct mechanisms for the efflux. One is the non-specific classical pathway mediated by physicochemical diffusion of cholesterol through the aqueous phase and its esterification on high density lipoprotein (HDL) by lecithin: cholesterol acyltransferase (LCAT). The other is the specific and biological pathway in which new HDL particles are generated from cellular lipid by the direct interaction of cell membrane and amphiphilic apolipoproteins that have dissociated from HDL. The latter reaction consists of binding of apolipoprotein to the specific binding site of the cellular surface and subsequent mobilization of intracellular cholesterol for the HDL generation mediated by intracellular signal transduction. This reaction seems to be a major source of plasma HDL.


Overview of Target Enrichment Strategies.
Target enrichment is commonly used in next generation sequencing (NGS) workflows to eliminate genomic DNA regions that are not of interest for a particular experiment. By only targeting specific regions such as exons, one can obtain greater depth of DNA sequencing coverage for regions of interest or increase the sampling numbers of individuals, thereby saving both time and cost. This overview of target enrichment strategies provides a high-level review of distinct approaches to capture specific sequences: (a) hybridization-based strategies, (b) transposon-mediated fragmentation (tagmentation), (c) molecular inversion probes (MIPs), and (d) singleplex and multiplex polymerase chain reaction (PCR) target enrichment. Strategies for assay design and performance criteria are also discussed. Other platforms currently in development are also briefly described.


Fatigue in women with breast cancer receiving radiation therapy.
Fatigue is a common complaint of individuals receiving treatment for cancer. There is a dearth of rigorous research investigating the clinical course and prognosis of fatigue over the course of radiation therapy. Seventy six patients with breast cancer receiving external radiation therapy were followed longitudinally from the onset of treatment to 6 months post-treatment. Fatigue significantly increased over the course of treatment, was highest at the last week of treatment, and returned to pretreatment levels by 3 months after treatment. Fatigue was not influenced by the patient's age, stage of disease, time since surgery, weight, and length of time since diagnosis. Fatigue was significantly related to symptom distress, psychologic distress, and self-reported fatigue relief strategies. The most frequently reported self-relief strategies were "sit" and "sleep." Fatigue had a negative impact on the patient's quality of life. Impairment in quality of life was evident by the end of treatment, with improvement by 3 and 6 months after treatment. The second week through to the last week of radiation therapy are critical times to target interventions for the management of fatigue. The amelioration of concomitant symptoms is a supportive approach that might be helpful. Self-help strategies focusing on the cessation of activity and increasing rest were reported as successful by patients.


Socioeconomic and ethnic inequalities in screen-detected breast cancer in London.
We investigated socioeconomic and ethnic inequalities in screen-detected breast cancer in London-a city with relatively low breast cancer screening uptake and a diverse population. Data on 11 957 breast cancers in London women aged 50-64 between 1998 and 2005 were extracted from the Thames Cancer Registry. We investigated the relationship between socioeconomic deprivation and the incidence and 5-year relative survival of screen-detected and non screen-detected cancers. Using logistic regression analysis we explored whether differences in screen-detected cancers between White, Asian and Black women were influenced by age and socioeconomic deprivation. The incidence of screen-detected breast cancer was lower in deprived women and their 5-year relative survival was worse than affluent women. However, survival differences were smaller for screen-detected disease. Among women with breast cancer the odds ratios (OR) for screen-detected disease differed between ethnic groups and these differences were not influenced by adjustment for age and deprivation. Compared with White women, Indian women had higher odds (OR 1.50, 95% confidence interval (1.23-1.84)], and Black Caribbean [0.68 (0.54-0.87)] and Black African women [0.53 (0.38-0.76)] significantly lower odds. A sustained focus on increasing screening uptake among deprived women and in Black communities could decrease inequalities in early diagnosis.


Relation between serum N-terminal pro-brain natriuretic peptide and prognosis in patients with hypertrophic cardiomyopathy.
To determine the relation between serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognosis in patients with hypertrophic cardiomyopathy (HCM). In total, 847 patients (53 ± 15 years; 67% male) with HCM (28% with left ventricular outflow tract obstruction ≥ 30 mmHg at rest) were followed for 3.5 years (IQR 2.5-4.5 years). The median NT-proBNP concentration was 78 pmol/L (range < 5-1817 pmol/L and IQR 31-183 pmol/L). Sixty-eight patients (8%) reached the primary endpoint of all-cause mortality or cardiac transplantation. NT-proBNP concentration predicted long-term survival from the primary endpoint [area under the receiver operating characteristic curve of 0.78 (95% confidence interval 0.73-0.84)]. A serum concentration of ≥ 135 pmol/L was associated with an annual event rate of 6.1% (95% CI 4.4-7.7). Three independent predictors of primary outcome were identified in a multivariable Cox model: New York Heart Association class III/IV (HR 2.10, 95% CI 1.21-3.65, P = 0.008), ejection fraction (HR 0.98, 95% CI 0.96-1.00, P = 0.035), log NT-proBNP (HR 2.04, 95% CI 1.56-2.66, P < 0.001). Log NT-proBNP was a significant predictor of heart failure (HF) and transplant-related deaths (n = 23; HR 3.03, 95% CI 1.99-4.60, P < 0.001) but not sudden death or appropriate implantable cardioverter defibrillator shock (n = 11; HR 1.54, 95% CI 0.91-2.60, P = 0.111). In patients with ejection fraction ≥ 50% (n = 673), log NT-proBNP remained an independent predictor of the primary outcome (HR 2.11, 95% CI 1.54-2.90, P < 0.001). In patients with HCM, elevated NT-proBNP concentration is a strong predictor of overall prognosis, particularly HF-related death and transplantation.


Does the Genetic Cause of Prader-Willi Syndrome Explain the Highly Variable Phenotype?
Prader-Willi syndrome (PWS) is characterized by extensive clinical and genetic variability caused by lack of expression of imprinted genes of the chromosomal region 15q11.2-q13. The genotye-phenotype correlation has not been yet fully elucidated. To analyze these correlations in order to determine the role of specifi c geneic alterations in the development of clinical symptoms in PWS. We retrospectively analyzed data routinely collected as part of the clinical care of 52 patients with clinical suspicion of PWS. FISH test was performed in all patients; in case of negative results, methylation test was performed. PWS was confi rmed in 35 patients that were divided in two groups according to the genetic cause of PWS: group A-21 patients with 15q11-q13 region deletion, mean age at evaluation 8.1 years (SD= 5.6) and mean of clinical score 9.4 ± 1.8; group B-14 patients with positive methylation test, with mean age at evaluation 6.7 years (SD= 4.6) and mean of clinical score 10.1 ± 1.9. Facial dysmorphism and neonatal hypotonia were present in all evaluated patients; while, higher frequency of major and minor PWS criteria were noted in the group A. Onset of hyperphagia, was around the age of 2 years in most patients, however one patient from group B had normal eating behavior and normal weight beyond age 5 years. In our study, the various genotypes did not seem to explain the diff erence in phenotype in PWS patients. We found a delayed time until diagnosis in these patients, although all had neonatal hypotonia and other suggestive phenotypic features, underlining once more the need for increased awareness of this syndrome, as well as easier accessibility to genetic counseling.


Anti-Mycobacterium leprae monoclonal antibodies cross-react with human skin: an alternative explanation for the immune responses in leprosy.
A panel of 17 mouse monoclonal antibodies (MoAb) raised against Mycobacterium leprae (M. leprae) antigens was used to detect antigenic determinants in normal human skin. An indirect immunoperoxidase technique was used. Eight of the MoAb detected epidermal antigens similar to patterns well known for human sera. Five of these MoAb detected determinants in the dermis, too. These observations may indicate a certain degree of similarity between the antigenic determinants occurring in M. leprae and in the human host. We propose that such a similarity on the one hand may facilitate the survival of M. leprae in the human host when the antigens are not recognized as "non-self," a situation which seems to occur in lepromatous leprosy, when the patients' tissues are loaded with bacteria virtually without any immune response. On the other hand, M. leprae antigens which mimic host antigens may induce an auto-immune reaction against the host's own antigens, which could explain the immune reaction in tuberculoid leprosy and during a "reversal reaction" when M. leprae is not observed in the host tissues, but extensive granuloma formation occurs.


18F-FDG PET/CT and Whole-Body Bone Scan Findings in Gorlin-Goltz Syndrome.
Gorlin-Goltz syndrome (basal cell nevus syndromes) is an uncommon, autosomal dominant inherited disorder characterized by developing basal cell carcinomas from a young age. Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and 18F-FDG PET/CT findings in a 32-year-old man with odontogenic keratocyst, early-onset basal cell carcinoma, multiple ectopic calcifications in extremities, calcified falx cerebri, spinal scoliosis, macrocephaly, and ocular hypertelorism.


The impact of close surveillance on pregnancy outcome among women with a prior history of antepartum complications attributed to thrombosis: a cohort study.
There is limited evidence, so far, as to the optimal management of women with a prior obstetric history of antepartum complications attributed to thrombosis. We aimed to investigate the contribution of close antepartum surveillance on pregnancy outcome among women with prior antepartum complications attributed to thrombosis. The study was conducted on all women who were delivered, conceived and delivered again between January 2000 and January 2006 at a university teaching hospital. Women included were managed in previous pregnancy at a low risk setting and had unpredicted antepartum complications occurring at a gestational age of 23 weeks or more. Antepartum complications considered were intrauterine fetal death, neonates who were small for gestational age, severe pre-eclampsia and placental abruption. All women were tested for the presence of thrombophilia after delivery. In the following pregnancy, only women found to have any thrombophilia (thrombophilic group) were treated with enoxaparin. Both the thrombophilic group and the non-thrombophilic group (tested negatively for thrombophilia) were managed and observed closely at our high-risk pregnancy clinic. Ninety-seven women, who conceived at least once after the diagnosis of the relevant antepartum complications, were included in this study. Forty-nine had any thrombophilia and 48 tested negatively. Composite antepartum complications (all antepartum complications considered) were reduced significantly after close antepartum surveillance in both groups. Mean birth weight and mean gestational age improved significantly and were comparable between the groups. Close antepartum surveillance may contribute to improvement in the perinatal outcomes of women with prior antepartum complications attributed to thrombosis.


An Atypical Clinical Presentation of Post-traumatic Syringomyelia: A Case Report and Brief Review of the Literature.
Syringomyelia classically presents as a bilateral sensory loss of the dissociated type which includes the loss of pain and temperature with the preservation of fine touch, vibratory sensation, and proprioception in the shoulder, arm, and hand. Eventually, weakness of the legs, muscle wasting, and ataxia can also be seen due to the involvement of the corticospinal tracts and the posterior columns of the spinal cord. We present the case of a 64-year-old patient with an atypical presentation of post-traumatic syringomyelia. This atypical presentation included a unilateral sensory loss of fine touch, pain, and temperature in the shoulder, arm, and hand which was of the non-dissociated type with no weakness, muscular atrophy, loss of vibratory sensation, or proprioception.


Action of Ants on Vertebrate Carcasses and Blow Flies (Calliphoridae).
Forensic entomology is a science that uses insect fauna as a tool to assist in criminal investigations and civil proceedings. Although the most researched insects are the Diptera and Coleoptera, ants may be present in all stages of decomposition. The aim of this study was to evaluate the role of ants and their action on blow flies during the decomposition process. Experiments were performed in which four pig carcasses were exposed in the cold and dry season (November/2012 and March/2013) and four in the hot and wet season (May/2013 and August/2013). Flies were the first insects to detect and interact with the carcasses, and six species of the Calliphoridae family were identified. Ants (Hymenoptera: Formicidae) were the second group, with six subfamilies identified. Myrmycinae represented 42% of the species, followed by Formicinae (28%), Ectatominae and Ponerinae (both 10%), and Ecitoninae and Dolichoderinae (both 5%). The ants acted on the carcasses as predators of visiting species, omnivores, and necrophagous, in all cases significantly affecting the decomposition time, slowing it down when the ants preyed on adult and immature insects consuming the carcass, or accelerating it by consuming the carcass and creating holes that could serve as gateways for the action of other organisms. The ants also generated artifacts that could lead to forensic misinterpretation.


Improvement of the beam quality of a high-pulse-energy mid-infrared fractional-image-rotation-enhancement ZnGeP2 optical parametric oscillator.
The beam quality of a high-energy mid-infrared ZnGeP2 (ZGP) optical parametric oscillator has been improved by use of a negative lens inside the nonplanar fractional-image-rotation enhancement (FIRE) resonator compensating for the thermal lensing and gain guiding effects. With an f=-0.9 m CaF2 lens, the beam quality is 1.5 and ∼2 for the resonant signal beam and the non-resonant idler beam, respectively. Up to 33 mJ of mid-infrared pulse energy in the 3-5 μm wavelength range is obtained with 94 mJ of pump energy on the crystal. This is an improvement of the beam quality by a factor of 3 for the signal beam and ∼2 for the idler beam compared without using a lens inside the FIRE resonator.


Approximate but accurate quantum dynamics from the Mori formalism. II. Equilibrium time correlation functions.
The ability to efficiently and accurately calculate equilibrium time correlation functions of many-body condensed phase quantum systems is one of the outstanding problems in theoretical chemistry. The Nakajima-Zwanzig-Mori formalism coupled to the self-consistent solution of the memory kernel has recently proven to be highly successful for the computation of nonequilibrium dynamical averages. Here, we extend this formalism to treat symmetrized equilibrium time correlation functions for the spin-boson model. Following the first paper in this series [A. Montoya-Castillo and D. R. Reichman, J. Chem. Phys. 144, 184104 (2016)], we use a Dyson-type expansion of the projected propagator to obtain a self-consistent solution for the memory kernel that requires only the calculation of normally evolved auxiliary kernels. We employ the approximate mean-field Ehrenfest method to demonstrate the feasibility of this approach. Via comparison with numerically exact results for the correlation function Czz(t)=Re⟨σz(0)σz(t)⟩, we show that the current scheme affords remarkable boosts in accuracy and efficiency over bare Ehrenfest dynamics. We further explore the sensitivity of the resulting dynamics to the choice of kernel closures and the accuracy of the initial canonical density operator.


Retail food environments research: Promising future with more work to be done.
As members of the scientific committee for the Food Environments in Canada conference, we reflect on the current state of food environments research in Canada. We are very encouraged that the field is growing and there have been many collaborative efforts to link researchers in Canada, including the 2015 Food Environments in Canada Symposium and Workshop. We believe there are 5 key challenges the field will need to collectively address: theory and causality; replication and extension; consideration of rural, northern and vulnerable populations; policy analysis; and intervention research. In addressing the challenges, we look forward to working together to conduct more sophisticated, complex and community-driven food environments research in the future.


Doubly robust estimation of attributable fractions in survival analysis.
The attributable fraction is a commonly used measure that quantifies the public health impact of an exposure on an outcome. It was originally defined for binary outcomes, but an extension has recently been proposed for right-censored survival time outcomes; the so-called attributable fraction function. A maximum likelihood estimator of the attributable fraction function has been developed, which requires a model for the outcome. In this paper, we derive a doubly robust estimator of the attributable fraction function. This estimator requires one model for the outcome, and one joint model for the exposure and censoring. The estimator is consistent if either model is correct, not necessarily both.


A 5-Year Survival Prediction Model for Chronic Heart Failure Patients Induced by Coronary Heart Disease with Traditional Chinese Medicine Intervention.
This study aimed to construct a 5-year survival prediction model of coronary heart disease (CHD) induced chronic heart failure (CHF), which is supported by the traditional Chinese medicine (TCM) factor, and to verify the model. Inpatients from January 1, 2012, to December 31, 2017, in seven hospitals in Shandong Province were studied. The random number table was used to randomly divide the seven hospitals into two groups (training set and verification set). In the training set, the least absolute shrinkage selection operator regression was first used to screen the independent variables. Logistic regression was then applied to construct a survival prediction model. The following nomogram visualizes the prediction model results. Finally, C-indices, calibration curves, and decision curves were used to discriminate and calibrate the established model and evaluate its practicability in the clinic. Bootstrap resampling and the verification set were used for internal and external verification, respectively. A total of 424 eligible patients were included in the model construction and verification. In this 5-year survival prediction model of patients with CHF induced by CHD, eight independent predictors were included. The series of C-indices for the training set, bootstrap resamples, and verification set was 0.885, 0.867, and 0.835, respectively, demonstrating the credibility of our model. Additionally, the receiver operating characteristic curve, calibration curve, and clinical decision curve analysis of the training and verification sets showed that this 5-year survival prediction model was good in discrimination, calibration, and clinical practicability. This work highlights eight independent factors affecting 5-year mortality in patients with CHF induced by CHD after discharge and further helps reallocate medical resources rationally by precisely identifying high-risk groups. The constructed prediction model not only plays a credible role in prediction but also demonstrates TCM intervention as a protective factor for the 5-year death of patients with CHF induced by CHD, thereby advancing the use of TCM in CHF.


Characterization of polyvalent and safe Bacillus thuringiensis strains with potential use for biocontrol.
Sixteen Bacillus thuringiensis (Bt) strains were screened for their anti-insect, antibacterial and antifungal determinants by phenotypic tests and PCR targeting major insecticidal proteins and complements, chitinases, lactonases, beta-1,3-glucanases and zwittermicinA. Six strains had genes of at least two major insecticidal toxins and of insecticidal complements. With regard to fungal biocontrol, all the strains inhibited Fusarium oxysporum and Aspergillus flavus growth and four strains had all or most of the antifungal determinants examined, with strain Bt HD932 showing the widest antifungal activity spectrum. Autolysins, bacteriocin and AHL-lactonases were produced by all or most of the tested strains with different activity spectra including pathogens like Listeria monocytogenes. Safety evaluation was carried out via PCR by screening the B. cereus psychrotolerance-related genes, toxin genes and the virulence pleiotropic regulator plcR. Diarrheal enterotoxins and other toxin genes were widespread among the collection with strains Bt HD9 and H45 lacking psychrotolerance-related genes, while five strains were positive. Only three strains (BMG1.7, H172, H156) resulted positive with primer sets targeting partial or complete plcR gene. By Vero Cell Assays, Bt HD868 followed by Bt HD9 were shown to be the safest strains. These polyvalent and safe Bt strains could be very promising in field application.


Genetically Defined Subtypes of Somatostatin-Containing Cortical Interneurons.
Inhibitory interneurons play a crucial role in proper development and function of the mammalian cerebral cortex. Of the different inhibitory subclasses, dendritic-targeting, somatostatin-containing (SOM) interneurons may be the most diverse. Earlier studies used GFP-expressing and recombinase-expressing mouse lines to characterize genetically defined subtypes of SOM interneurons by morphologic, electrophysiological, and neurochemical properties. More recently, large-scale studies classified SOM interneurons into 13 morpho-electric transcriptomic (MET) types. It remains unclear, however, how these various classification schemes relate to each other, and experimental access to MET types has been limited by the scarcity of specific mouse driver lines. To address these issues, we crossed Flp and Cre driver lines with a dual-color intersectional reporter, allowing experimental access to several combinatorially defined SOM subsets. Brains from adult mice of both sexes were retrogradely dye labeled from the pial surface to identify layer 1-projecting neurons and immunostained against several marker proteins, revealing correlations between genetic label, axonal target, and marker protein expression in the same neurons. Lastly, using whole-cell recordings ex vivo, we analyzed and compared electrophysiological properties between different intersectional subsets. We identified two layer 1-targeting subtypes with nonoverlapping marker protein expression and electrophysiological properties, which, together with a previously characterized layer 4-targeting subtype, account for >50% of all layer 5 SOM cells and >40% of all SOM cells, and appear to map onto 5 of the 13 MET types. Genetic access to these subtypes will allow researchers to determine their synaptic inputs and outputs and uncover their roles in cortical computations and animal behavior.


The evolution of medical uncertainty.
Modern developments of scientific medicine have uncovered and created uncertainties and risks that were previously not known or experienced; the stakes have become very much higher. The rise in public expectation, however, is paralleled by a lowered tolerance of uncertainty. Metaphors of "deliverance" and "disaster" abound in discussions of scientific discovery, reflecting differing conceptions and philosophies about errors and mistakes, and the role they play in the physical universe, the biosphere, and human affairs. These concerns highlight the difficulties and dilemmas of finding scientifically adequate, culturally appropriate, and socially effective ways of appraising and controlling risk.


Surface Hybridization Chain Reaction of Binary Mixture DNA-PEG Corona Nanostructures Produced by Low-Volume RAFT-Mediated Photopolymerization-Induced Self-Assembly.
DNA-polymer hybrids have been attracting interest as adaptable functional materials by combining the stability of polymers with DNA nanotechnology. Both research fields have in common the capacity to be precise, versatile, and tunable, a prerequisite for creating powerful tools which can be easily tailored and adapted for bio-related applications. However, the conjugation of hydrophilic DNA with hydrophobic polymers remains challenging. In recent years, polymerization-induced self-assembly (PISA) has attracted significant attention for constructing nano-objects of various morphologies owing to the one-step nature of the process, creating a beneficial method for the creation of amphiphilic DNA-polymer nanostructures. This process not only allows pure DNA-polymer-based systems to be produced but also enables the mixture of other polymeric species with DNA conjugates. Here, we present the first report of a DNA-PEG corona nano-object's synthesis without the addition of an external photoinitiator or photocatalyst via photo-PISA. Furthermore, this work shows the use of DNA-macroCTA, which was first synthesized using a solid-support method resulting in high yields, easy upscaling, and no need for HPLC purification. In addition, to the formation of DNA-polymer structures, increasing the nucleic acid loading of assemblies is of great importance. One of the most intriguing phenomena of DNA is the hybridization of single-stranded DNA with a second strand, increasing the nucleic acid content. However, hybridization of DNA in a particle corona may destabilize the nanomaterial due to the electrostatic repulsive force on the DNA corona. Here, we have investigated how changing the DNA volume fraction in hybrid DNA-polymer self-assembled material affects the morphology. Moreover, the effect of the corona composition on the stability of the system during the hybridization was studied. Additionally, the hybridization chain reaction was successfully applied as a new method to increase the amount of DNA on a DNA-based nano-object without disturbing the morphology achieving a fluorescence signal amplification.


Hyrtiazepine, an azepino-indole-type alkaloid from the Red Sea marine sponge Hyrtios erectus.
Biological and chemical investigations of the methanolic crude extract of the Red Sea marine sponge Hyrtios erectus led to the isolation of a novel azepino-indole-type alkaloid named hyrtiazepine (2) and 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), together with the known metabolites hyrtiosulawesine (1), 5-hydroxyindole-3-carbaldehyde (4), hyrtiosin A (5), and hyrtiosin B (6). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosulawesine (1) displayed a significant antiphospholipase A2 activity with an IC50 value of 14 microM in a fluorometric assay using Crotalus adamanteus venom phospholipase A2.


Halogen Bonded Chiral Emitters: Generation of Chiral Fractal Architecture with Amplified Circularly Polarized Luminescence.
Self-assembled chiroptical materials have attracted considerable attention due to their great applications in wide fields. During the chiral self-assembly, it remains unknown how achiral molecules can affect the assembly process and their final chiroptical performance. Herein, we report an achiral molecule directed chiral self-assembly via halogen bonds, exhibiting not only an unprecedented chiral fractal architecture but also significantly amplified circularly polarized luminescence (CPL). Two axially chiral emitters with halogen bond sites co-assemble with an achiral 1,4-diiodotetrafluorobenzene (F4 DIB) and well-ordered chiral fractal structures with asymmetry amplification are obtained. The enhancement of the dissymmetry factors of the assemblies was up to 0.051 and 0.011, which was approximately 100 folds than those of the corresponding molecules. It was found that both the design of the chiral emitter and the highly directional halogen bond played an important role in hierarchically chirality transfer from chiral emitters to the micrometer scale chiral fractal morphology and amplified dissymmetry factors. We hope that this strategy can give a further insight into the fabrication of structurally unique featured highly efficient chiroptical materials.


Serving the poorest of the poor: the story of Jeremiah J. Lowney.
Since 1966, Dr Jerry Lowney has practiced orthodontics in Norwich, Connecticut, where he has been active in both community and professional organizations, including the University of Connecticut Board of Trustees and the Board of Governors for Higher Education. Since his first volunteer trip to Haiti in the mid-1980s, during which he provided dental services for the poor, he has returned to that country at least three times each year. Over time the nature of his activities has changed. Through grant writing, personal influence, liaison with a religious order, a huge investment of time, successful fundraising, the seizing of every opportunity, and the expenditure of large amounts of his own money, he has created a multimillion-dollar general health facility in one of the poorest areas in Haiti. Besides dental treatment, the scope of his activities has ranged from creating centers for high-risk pregnancy and malnutrition to the hiring of physicians, the training of local nurse practitioners, and an Adopt-a-Family program run by his wife, Virginia. His actions have been influenced by Virginia's caring attitudes and by his conviction that much is expected from those who have received life's bounties.


Molecular docking based screening of Listeriolysin-O for improved inhibitors.
Listeriolysine-O (LLO) is a 50KDa protein responsible for Listeria monocytogenes pathogenicity. The structure of LLO (PDB ID: 4CDB) with domains D1 to D4 is known. Therefore, it is of interest to identify conserved regions among LLO variants for destabilizing oligomerization (50 mer complex) of its monomers using appropriate inhibitors. Therefore, it is of interest to identify suitable inhibitors for inhibiting LLO. Previous reports suggest the use of flavanoids like compounds for inhibiting LLO. Our interest is to identify improved compounds to destabilize LLO oligomerization. We used a library (Zinc database) containing 200,000 drug-like compounds against LLO using molecular docking based screening. This resulted in five hits that were further analyzed for pharmacological properties. The hit #1 (2-methyloctadecane- 1, 3, 4-triol) was further refined using appropriate modifications for creating a suitable pharmacophore model LLO inhibition. The modified compound (1-(4-Cyclopent-3-enyl-6, 7-dihydroxy-8-hydroxymethyl-nona-2, 8-dienylideneamino)-penta-1,4-dien-3-one) shows fitting binding properties with LLO with no undesirable pharmacological properties such as toxicity.


Nuclear factor-κB modulates osteogenesis of periodontal ligament stem cells through competition with β-catenin signaling in inflammatory microenvironments.
Inflammation can influence multipotency and self-renewal of mesenchymal stem cells (MSCs), resulting in their awakened bone-regeneration ability. Human periodontal ligament tissue-derived MSCs (PDLSCs) have been isolated, and their differentiation potential was found to be defective due to β-catenin signaling indirectly regulated by inflammatory microenvironments. Nuclear factor-κB (NF-κB) is well studied in inflammation by many different groups. The role of NF-κB needs to be studied in PDLSCs, although genetic evidences have recently shown that NF-κB inhibits osteoblastic bone formation in mice. However, the mechanism as to how inflammation leads to the modulation of β-catenin and NF-κB signaling remains unclear. In this study, we investigated β-catenin and NF-κB signaling through regulation of glycogen synthase kinase 3β activity (GSK-3β, which modulates β-catenin and NF-κB signaling) using a specific inhibitor LiCl and a phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002. We identified that NF-κB signaling might be more important for the regulation of osteogenesis in PDLSCs from periodontitis compared with β-catenin. BAY 11-7082 (an inhibitor of NF-κB) could inhibit phosphorylation of p65 and partly rescue the differentiation potential of PDLSCs in inflammation. Our data indicate that NF-κB has a central role in regulating osteogenic differentiation of PDLSCs in inflammatory microenvironments. Given the molecular mechanisms of NF-κB in osteogenic differentiation governed by inflammation, it can be said that NF-κB helps in improving stem cell-mediated inflammatory bone disease therapy.


Involvement of long noncoding RNAs in diseases affecting the central nervous system.
DNA sequences associated with protein-coding genes have been the primary focus of most genetic analyses of complex human diseases. Although we are rapidly gaining a comprehensive view of the etiology of certain central nervous system disorders, major gaps in our understanding persist. Recent studies have uncovered that many human genomic sequences are transcribed but not translated, generating an astounding diversity of noncoding RNAs (ncRNAs). This awareness should be taken into account when studying human diseases and may have profound implications on the development of novel biomarkers as well as therapies.


Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin.
Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0×10-8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10-14, beta = -0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2 = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations.


Gene duplication and paleopolyploidy in soybean and the implications for whole genome sequencing.
Soybean, Glycine max (L.) Merr., is a well documented paleopolyploid. What remains relatively under characterized is the level of sequence identity in retained homeologous regions of the genome. Recently, the Department of Energy Joint Genome Institute and United States Department of Agriculture jointly announced the sequencing of the soybean genome. One of the initial concerns is to what extent sequence identity in homeologous regions would have on whole genome shotgun sequence assembly. Seventeen BACs representing approximately 2.03 Mb were sequenced as representative potential homeologous regions from the soybean genome. Genetic mapping of each BAC shows that 11 of the 20 chromosomes are represented. Sequence comparisons between homeologous BACs shows that the soybean genome is a mosaic of retained paleopolyploid regions. Some regions appear to be highly conserved while other regions have diverged significantly. Large-scale "batch" reassembly of all 17 BACs combined showed that even the most homeologous BACs with upwards of 95% sequence identity resolve into their respective homeologous sequences. Potential assembly errors were generated by tandemly duplicated pentatricopeptide repeat containing genes and long simple sequence repeats. Analysis of a whole-genome shotgun assembly of 80,000 randomly chosen JGI-DOE sequence traces reveals some new soybean-specific repeat sequences. This analysis investigated both the structure of the paleopolyploid soybean genome and the potential effects retained homeology will have on assembling the whole genome shotgun sequence. Based upon these results, homeologous regions similar to those characterized here will not cause major assembly issues.


Adjuvant chemoradiation for patients with adenocarcinoma of the pancreas: an expirence of single institute.
Only a small percentage of patients with pancreatic cancer have limited disease suitable for curative resection. Even with surgery, patients often have poor long-term survival due to relapse of the disease. There are controversies about the adjuvant treatment of these patients. We reported the survival of resected pancreatic cancer from a single institute. About 128 consecutive patients who had complete resection of the pancreatic ductal adenocarcinoma were evaluated, retrospectively. Chemoradiotherapy (45 Gy plus 5-fluorouracil) was given to 63 patients. Fifty-five patients declined to take chemoradiotherapy or with poor performance status were observed without additional treatment. Eight patients took only chemotherapy and two patients took only radiotherapy. The median survival of chemoradiotherapy group was significantly higher than the observation group (13 months vs. 4 months, respectively; P < 0.001). In multivariate analyses the most important factors improving survival were the application of chemoradiation (P < 0.001), low-level serum LDH (P = 0.026), good performance status (P = 0.033) and low serum CA19-9 (P = 0.037). Although adjuvant chemoradiotherapy has a significant survival benefit when compared with the observation group, the survival data are still poor for pancreatic cancer. Therefore, we need more effective additional or adjuvant treatment modalities.


Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast.
We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions.


Lymphoepithelioma-Like Carcinoma of the Breast: A Case Report of a Rare Type of Invasive Carcinoma.
Lymphoepithelioma carcinoma (LELC) is an extremely rare type of mammary cancer. Based on the histology, it can be misdiagnosed with inflammatory lesions like mastitis and medullary carcinoma or other hematopoietic neoplasms like lymphoma in the breast. Since LELC has a good response to chemotherapy with a good prognosis, t is prognostically important to recognize LELC. We report a rare case of LELC in a 51-year-old pre-menopausal female with a left breast mass, diagnosed with invasive ductal carcinoma (IDC), LELC type, treated with mastectomy, followed by adjuvant chemotherapy and radiotherapy, with a disease-free interval of 10 months. Herein, we present the case with its clinical presentation, radiologic imaging, histopathological features, and immunohistochemistry (IHC) findings. The rarity of this type of breast tumor warrants studying the behavior of these uncommon tumors to avoid misdiagnosis and establish well-defined criteria for diagnosis.


Encephalitis and antibodies to synaptic and neuronal cell surface proteins.
The identification of encephalitis associated with antibodies against cell surface and synaptic proteins, although recent, has already had a substantial impact in clinical neurology and neuroscience. The target antigens are receptors and proteins that have critical roles in synaptic transmission and plasticity, including the NMDA receptor, the AMPA receptor, the GABA(B) receptor, and the glycine receptor. Other autoantigens, such as leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2, form part of trans-synaptic complexes and neuronal cell adhesion molecules involved in fine-tuning synaptic transmission and nerve excitability. Syndromes resulting from these immune responses resemble those of pharmacologic or genetic models in which the antigens are disrupted. For some immune responses, there is evidence that the antibodies alter the structure and function of the antigen, suggesting a direct pathogenic effect. These disorders are important because they can affect children and young adults, are severe and protracted, occur with or without tumor association, and respond to treatment but may relapse. This review provides an update on these syndromes and autoantigens with special emphasis on clinical diagnosis and treatment.


Conductive carbon nanofibers incorporated into collagen bio-scaffold assists myocardial injury repair.
Currently, treatment of myocardial infarction considered as unmet clinical need. Nanomaterials have been used in the regeneration of tissues such as bone, dental and neural tissue in the body and have increased hope for revitalizing of damaged tissues. Conductive carbon base nanomaterials with its superior physicochemical properties have emerged as promising materials for cardiovascular application. In this study, we applied a biosynthetic collagen scaffold containing carbon nanofiber for regenerating of damaged heart tissue. The collagen-carbon nanofiber scaffold was fabricated and fully characterised. The scaffold was grafted on the affected area of myocardial ischemia, immediately after ligation of the left anterior descending artery in the wistar rat's model. After 4 weeks, histological analyses were performed for investigation of formation of immature cardio-myocytes, epicardial cells, and angiogenesis. Compared to untreated hearts, this scaffold significantly protects heart tissue against injury. This improvement is accompanied by a reduction in fibrosis and the increased formation of a blood vessel network and immature cardio-myocytes in the infarction heart. No toxicity detected with apoptotic and TUNEL assays. In conclusion, the mechanical support of the collagen scaffold with carbon nanofiber enhanced the regeneration of myocardial tissue.


Primary multi-drug resistant tubercular lymphadenitis in an HIV infected patient.
Cervical lymphadenitis is a common extra-pulmonary manifestation of tuberculosis in HIV patient; nevertheless, it seems that the primary Multi Drug Resistant (MDR) involving extra-pulmonary site is uncommon. We report a case of tubercular lymphadenitis by multi-drug resistant strain of Mycobacterium tuberculosis in an HIV seropositive male, which has not been reported so far in literature.


[Sero-negative tsutsugamushi disease (scrub typhus) diagnosed by polymerase chain reaction].
We report a case of sero-negative tsutsugamushi disease diagnosed by polymerase chain reaction (PCR). A 54-year-old man who worked in Nagano prefecture presented with flu-like symptoms that did not respond to cephalosporin therapy. On admission to another hospital, chest roentgenography revealed abnormal shadows; liver dysfunction was also present. Despite therapy, the patient's condition gradually worsened and he was transferred to our intensive care unit. Erythema on all extremities and scabs on the right medial femoral region and the dorsum of the left foot suggested a diagnosis of tsutsugamushi disease. We administered minocycline and gave percutaneous cardiopulmonary support for adult respiratory distress syndrome. Despite all efforts, the patient died. Although serologic tests were not positive, Karp strains of R. tsutsugamuschi were identified on PCR amplification. Autopsy revealed evidence of acute hemorrhagic pancreatitis, which has not been reported previously in tsutsugamushi disease. We conclude that PCR techniques may be useful in confirming a diagnosis of early tsutsugamushi disease.


Effective Interaction between Homo- and Heteropolymer Block of Poly(n-butyl acrylate)-b-poly(methyl methacrylate-r-styrene) Diblock Copolymers.
We investigated the segregation behavior of a molten diblock copolymer, poly(n-butyl acrylate)-b-poly(methyl methacrylate-r-styrene) (PBA-b-P(MMA-r-S)), wherein styrene (S) is incorporated as a comonomer in the second block to modulate the effective interaction between homopolymer and a random copolymer block. The temperature dependence of the effective interaction parameter χeff between n-butyl acrylate (BA) and the average monomer of the MMA-r-S random block was evaluated from small-angle X-ray scattering (SAXS) analysis using the random phase approximation (RPA) approach. The calculated χeff, as a function of the styrene fraction in the random copolymer block, shows a good agreement with the mean-field binary interaction model. This consistency indicates that the effective interaction between component BA and the average monomer of the random copolymer block is smaller than the interactions between pure components (χBA,MMA,χBA,S). The present study suggests that the introduction of a random copolymer block to a block copolymer can effectively reduce the degree of incompatibility of the block copolymer system without altering the constituent species, which may serve as a viable methodology in designing novel thermoplastic elastomers based on triblock or multiblock copolymers.


Outlet syndrome: is there a surgical option?
Of 46 patients investigated for constipation, 21 were found to have some other primary abnormality, leaving 25 patients for study: 6 had evidence of the outlet syndrome alone, 5 had slow transit constipation, 8 had both abnormalities and 6 had no apparent physiological disorder in the colon or rectum. Although colectomy and ileorectal anastomosis gave good results for slow transit constipation, partial pelvic floor division provided satisfactory long-term improvement in only one of the 7 patients with the outlet syndrome.


Recurrent exercise-induced rhabdomyolysis due to low intensity fitness exercise in a healthy young patient.
Rhabdomyolysis is an uncommon but life threatening condition that develops due to breakdown of muscle and release of intracellular components into the circulation. A 24-year-old man otherwise healthy was admitted to our hospital because of muscle aches and weakness as well as cola coloured urine developed 3 days after carrying out the low intensity exercise. Diagnosis of rhabdomyolysis was made with creatine kinase (CK) levels of 214 356 U/l. He was treated for a similar condition at age 21. A muscle biopsy was done and the findings were normal. Rhabdomyolysis can develop with low intensity exercise; thus, it be considered in healthy young people. Young people with recurrent rhabdomyolysis due to low intensity exercise, in the absence of obvious medical and physical causes, should be evaluated further to rule out uncommon metabolic diseases. Our case demonstrates that complications especially renal failure in patients with rhabdomyolysis do not correspond to CK levels.


The purification of large numbers of antigen presenting dendritic cells from mouse spleen.
Dendritic cells (DC) are found at low frequency in lymphoid and non-lymphoid tissues. Different DC subsets are adept at different roles in immunity in diverse scenarios of attack by infectious agents, as well as in the maintenance of self-tolerance. A key element in the ability of DC to initiate adaptive immune responses is their capacity to capture and process antigen, whether from pathogens, vaccines or self-components, and present it to T cells. Our typical procedure for isolation of the different DC types from murine spleen involves their digestion from the tissue using collagenase, selection of cells of light density, and negative selection for DC. DC may then be separated into their functionally distinct subpopulations using immunofluorescent labeling and flow cytometric cell sorting. If the availability of mice is limiting, our protocol can cater for DC numbers boosted by the administration of fms-like tyrosine kinase 3 ligand (Flt3L), directly via subcutaneous injection or via the introduction of a Flt3L secreting melanoma cell line. Large numbers of in vitro equivalents of the spleen DC subsets may also be produced by culturing bone marrow with Flt3L. If flow cytometric sorting time is a limitation splenic DC subpopulations may instead be separated using a combination of fluorescent antibody labeling and anti-fluorochrome magnetic beads. Careful segregation of these functionally distinct subpopulations of DC will enable a thorough examination of their antigen processing and presenting capabilities.


Factors affecting A-aDo2 after open-heart surgery.
Intrapulmonary shunt, cardiac output, and O2 consumption as factors contributing to alveolar-arterial O2 tension difference (A-aDo2) were tested in 11 patients after open-heart surgery. A-aDo2 was well correlated with intrapulmonary shunt, as expected, but no correlation was found between cardiac index (CI) and intrapulmonary shunt. When total shunt (venous admixture) was above 11%, there was an inverse correlation between A-aDo2 and CI, and it was observed that CI falling below 2.5 L/min/sq m contributed significantly to the enlargement of A-aDo2. Low Pao2 (less than 65 torr, breathing air) was characterized by larger arterial-mixed venous O2 content difference than high Pao2 (is greater than 65 torr, on room air), indicating that A-aDo2 was influenced by cardiac output relative to metabolic demand. Intrapulmonary shunt played a main role in increasing A-aDo2 after open-heart surgery, and systemic factors, including changes in cardiac output and O2 consumption, also contributed to development of hypoxia.


Experience with fosfomycin in the treatment of complicated urinary tract infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.
The aim of this study was to evaluate the efficacy of fosfomycin in the treatment of complicated urinary tract infections (cUTIs) caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We retrospectively evaluated 42 ambulatory patients with cUTIs caused by ESBL-producing Enterobacteriaceae at the Outpatient Internal Medicine Clinic of the University Clinical Hospital Centre Zagreb in the period from June 2012 to June 2014. ESBL production was confirmed by double disk synergy test according to Jarlier. In vitro susceptibility to fosfomycin of ESBL-producing Escherichia coli, Klebsiella pneumoniae and Citrobacter freundii isolates was tested according to the European Committee on Antimicrobial Susceptibility Testing methodology. In 42 patients with cUTIs, 43 urinary pathogens susceptible to fosfomycin were isolated in the urine cultures, including 34 E. coli ESBL, seven K. pneumoniae ESBL and two C. freundii ESBL isolates. On average, patients had 2.2 complicating factors (CFs) and received 3.6 fosfomycin doses per treatment course. The overall microbiological cure was 50%, clinical cure was 71% and ESBL eradication rate was 74%. Patients with between zero and one CFs received significantly fewer fosfomycin doses than patients with two or more CFs (p = 0.022). Three kidney transplant patients achieved microbiological cure following prolonged fosfomycin administration. No statistically significant correlation was found between the presence of individual CFs and treatment outcome. Fosfomycin may be a valid option for oral treatment of cUTIs caused by ESBL-producing pathogens. The optimal duration of fosfomycin treatment for cUTIs remains to be determined.


Turbulence in continuous flow surface aeration systems.
Turbulence characteristics in an optimal continuous surface aeration system were investigated in this study. The experimental system consists of a rectangular tank, where flow is driven by equally spaced aerators placed on the liquid surface. The mass-transfer coefficient and turbulent parameters at the tank's inlet and outlet were measured to enable analysis of their interdependent relationships. The turbulence parameters are linked closely to the system's mass-transfer process. Turbulent bursting analysis has shown that ejection and sweep events govern the hydrodynamics of the systems. Turbulent intensity increases with increasing speed of rotation, and consequently the mass-transfer coefficient also increases. The universal probability distribution functions of the velocity fluctuations in continuous flow surface aeration systems follow the Gram-Charlier series, based on exponential distribution, and the theoretical and experimental curves match.


Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung.
During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas, and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells, and cells of the immune system. Detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as pre-eclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health.


Tissue Washing Improves Native Ambient Mass Spectrometry Detection of Membrane Proteins Directly from Tissue.
Native ambient mass spectrometry enables the in situ analysis of proteins and their complexes directly from tissue, providing both structural and spatial information. Until recently, the approach was applied exclusively to the analysis of soluble proteins; however, there is a drive for new techniques that enable analysis of membrane proteins. Here we demonstrate native ambient mass spectrometry of membrane proteins, including β-barrel and α-helical (single and multipass) integral membrane proteins and membrane-associated proteins incorporating lipid anchors, by integration of a simple washing protocol to remove soluble proteins. Mass spectrometry imaging revealed that washing did not disrupt the spatial distributions of the membrane and membrane-associated proteins. Some delocalization of the remaining soluble proteins was observed.


"A Good Guy" Again: Biosociality in a Cancer Self-help Organization.
The notion of biosociality has been employed in the understanding of forging new forms of social groupings and other forms of social solidarity, with its feasibility and basis challenged in non-Western contexts. According to our study of a Chinese cancer self-help organization, an emergent biosociality occurs through an increasingly common diagnostic biomedical category, cancer. But what truly binds these people tighter is the pre-modern local knowledge of qi, as well as state ideology about living a useful life. A new form of biosocial citizenship, "a good guy (haoren yige)," linked to cancer, is thus endowed.


CLN3L, a novel protein related to the Batten disease protein, is overexpressed in Cln3-/- mice and in Batten disease.
Batten disease is a severe autosomal recessive neurodegenerative disease which results from mutations in CLN3. Although the gene was cloned in 1995, the tissue distribution and subcellular localization of the CLN3 protein (CLN3P) remains inconclusive. We have demonstrated the presence of a novel 33 kDa protein in both normal human and wild-type mouse brain. This 33 kDa protein, which is overexpressed in brains of patients with Batten disease and in Cln3-/- mouse brain, binds to the antibody raised against the peptide sequence of CLN3P and results in aberrant CLN3P localization studies. We expressed a novel 33 kDa protein that is highly similar to CLN3P. We showed that the 33 kDa protein is identical to that recognized in Batten disease and Cln3-/- brain. These studies strongly suggest the presence of an alternative CLN3-like (CLN3L) product in Batten disease. Previous studies of CLN3P tissue distribution and intracellular localization will require extensive reanalysis in order to determine the true expression of CLN3P.


The effect of assigning dedicated general practitioners to nursing homes.
To determine whether assigning a dedicated general practitioner (GP) to a nursing home reduces hospitalizations and readmissions. Secondary data on hospitalizations and deaths by month for the universe of nursing home residents in Denmark from January 2011 through February 2014. In 2012, Denmark initiated a program in seven nursing homes that volunteered to participate. We used a difference-in-differences model to estimate the effect of assigning a dedicated GP to a nursing home on the likelihood that a nursing home resident will be hospitalized, will experience a preventable hospitalization, and will be readmitted. The unit of observation is a resident-month. Data were extracted from the Danish public administrative register dataset. We found that assigning a GP to a nursing home was associated with a 0.55 [95 percent CI, 0.08 to 1.02] percentage point reduction in the monthly probability of a preventable hospitalization, which was a 26 percent reduction from the preintervention level of 2.13 percentage points. The associated reduction in the monthly probability of a readmission was 0.68 [95 percent CI, -0.01 to 1.37] percentage points, which was a 25 percent reduction from the baseline level of 2.68 percentage points. Survey results indicated that the likely mechanism for the effect was more efficient and consistent communication between GPs and nursing home personnel. Assigning a dedicated physician in a nursing home can reduce medical spending and improve patients' health.


Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.
The prognosis of colorectal cancer (CRC) patients can be influenced by genetic mutations and nutritional status. The relationship between these variables is unclear. The objective of the study was to verify the variables involved in the nutritional status and genetic mutations, which correlate with survival of CRC patients. Patients with surgical intervention for tumor resection were evaluated using body mass index, nutritional screening, patient self-produced global subjective assessment, phase angle, and computed tomography to calculate the areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue, and muscle mass for the determination of sarcopenia. Ten gene mutations involved in CRC carcinogenesis were studied (PIK3CA, KRAS, BRAF, EGFR, NRAS, TP53, APC, PTEN, SMAD4, and FBXW7). DNA was extracted from fresh tumor or paraffin tissues. Of the 46 patients, 29 (64.4%) were at nutritional risk and 21 (45.7%) were moderately malnourished. However, there was a high percentage of VAT in 24 (61.5%) and sarcopenia in 19 (48.7%) patients. These variables were associated with a higher risk of mortality. Nutritional risk, moderate or severe malnutrition, phase angle < 5°, VAT < 163.8 cm2 in men and < 80.1 cm2 in women, and sarcopenia were associated with the relative risk of death, with respective hazard ratios/odds ratios and 95% confidence intervals of 8.77 (1.14-67.1), 3.95 (1.11-14.0), 3.79 (1.10-13.1), 3.43 (1.03-11.4), and 3.95 (1.06-14.6). Increased VAT was associated with a lower risk of death, even in patients older than 60 years or those harboring mutated KRAS. Patients with positive indicators for malnutrition or risk of malnutrition had an increased risk of death. No relationship was identified between the presence of mutations and survival.


Common Distribution of gad Operon in Lactobacillus brevis and its GadA Contributes to Efficient GABA Synthesis toward Cytosolic Near-Neutral pH.
Many strains of lactic acid bacteria (LAB) and bifidobacteria have exhibited strain-specific capacity to produce γ-aminobutyric acid (GABA) via their glutamic acid decarboxylase (GAD) system, which is one of amino acid-dependent acid resistance (AR) systems in bacteria. However, the linkage between bacterial AR and GABA production capacity has not been well established. Meanwhile, limited evidence has been provided to the global diversity of GABA-producing LAB and bifidobacteria, and their mechanisms of efficient GABA synthesis. In this study, genomic survey identified common distribution of gad operon-encoded GAD system in Lactobacillus brevis for its GABA production among varying species of LAB and bifidobacteria. Importantly, among four commonly distributed amino acid-dependent AR systems in Lb. brevis, its GAD system was a major contributor to maintain cytosolic pH homeostasis by consuming protons via GABA synthesis. This highlights that Lb. brevis applies GAD system as the main strategy against extracellular and intracellular acidification demonstrating its high capacity of GABA production. In addition, the abundant GadA retained its activity toward near-neutral pH (pH 5.5-6.5) of cytosolic acidity thus contributing to efficient GABA synthesis in Lb. brevis. This is the first global report illustrating species-specific characteristic and mechanism of efficient GABA synthesis in Lb. brevis.


Dr John Clarke: licentiate in midwifery of the Royal College of Physicians of London.
John Clarke was one of ten licentiates in midwifery created by the College of Physicians in the late eighteenth century to regularise the growing involvement of medical men in obstetrics. He was an excellent clinician and a popular teacher. His publications included original observations about puerperal fever, nausea and other complications of pregnancy and the management of labour. He opposed the attitude of the College that prevented its Fellows from practising midwifery and he stridently criticised the College's neglect of the diseases of children. Part one of his book on the diseases of children contained the first exact description of tetany. Part two was never published because of his early death.


Bias Adjustment Techniques Are Underutilized in HIV Sexual Risk Estimation: A Systematic Review.
Background: Valid measurement of determinants of HIV infection among men who have sex with men (MSM) is critical for intervention planning and resource allocation. However, sexual minority research concerning HIV risk often relies on proxy exposures of sexual behaviors such as sexual orientation and partner gender. Inferring high risk sexual behaviors (i.e., condomless anal intercourse) from these proxies inaccurately captures HIV risk, but few studies have attempted to correct for this bias. Methods: We performed a systematic review of methodological practices for estimating risk of HIV infection among MSM. Results: We identified 32 studies in which high risk sexual behavior was assessed: 82% (n = 26) measured and used sexual risk behaviors (e.g., condomless anal intercourse or sexual positioning) to assess risk of HIV infection; 9% (n = 3) used proxy measures; and 9% (n = 3) used both behavior and proxy variables. Various treatments of misclassification reported by investigators included the following: 82% (n = 26) discussed misclassification of sexual behavior as a potential limitation; however, among these studies, no attempts were made to correct misclassification; 12% (n = 4) did not report exposure misclassification, and 6% (n = 2) explicitly considered this information bias and conducted a Bayesian approach to correct for misclassification. Conclusions: Our systematic review indicates that a majority of studies engaging in collecting primary data have taken additional steps to acquire detailed information regarding sexual risk behaviors. However, reliance on population-based surveys may still lead to potentially biased estimates. Thus, bias analytic techniques are potential tools to control for any suspected biases.


Partition of energy for air-fluidized grains.
The dynamics of one and two identical spheres rolling in a nearly levitating upflow of air obey the Langevin equation and the fluctuation-dissipation relation [Ojha Nature (London) 427, 521 (2004); Phys. Rev. E 71, 016313 (2005)]. To probe the range of validity of this statistical mechanical description, we perturb the original experiments in four ways. First, we break the circular symmetry of the confining potential by using a stadium-shaped trap, and find that the velocity distributions remain circularly symmetric. Second, we fluidize multiple spheres of different density, and find that all have the same effective temperature. Third, we fluidize two spheres of different size, and find that the thermal analogy progressively fails according to the size ratio. Fourth, we fluidize individual grains of aspherical shape, and find that the applicability of statistical mechanics depends on whether or not the grain chatters along its length, in the direction of airflow.


Contrasting Foraging Patterns: Testing Resource-Concentration and Dilution Effects with Pollinators and Seed Predators.
Resource concentration effects occur when high resource density patches attract and support more foragers than low density patches. In contrast, resource dilution effects can occur if high density patches support fewer consumers. In this study, we examined the foraging rates of pollinators and seed predators on two perennial plant species (Rudbeckia triloba and Verbena stricta) as functions of resource density. Specifically, we examined whether resource-dense patches (densities of flower and seeds on individual plants) resulted in greater visitation and seed removal rates, respectively. We also examined whether foraging rates were context-dependent by conducting the study in two sites that varied in resource densities. For pollinators, we found negative relationships between the density of flowers per plant and visitation rates, suggesting dilution effects. For seed predators, we found positive relationships consistent with concentration effects. Saturation effects and differences in foraging behaviors might explain the opposite relationships; most of the seed predators were ants (recruitment-based foragers), and pollinators were mostly solitary foragers. We also found that foraging rates were site-dependent, possibly due to site-level differences in resource abundance and consumer densities. These results suggest that these two plant species may benefit from producing as many flowers as possible, given high levels of pollination and low seed predation.


Impact of Using a Precompleted Consent Form for Procedural Sedation in the Pediatric Emergency Department.
This study aimed to compare elements discussed during the consent process for procedural sedation in the pediatric emergency department to documentation and parental recall before and after implementation of a standardized consent form. This is a mixed-methods study combining retrospective electronic record review and cross-sectional surveys of providers and parents after consent for procedural sedation. Surveys were obtained before and after implementation of a precompleted consent form. Providers' survey responses were compared with consent documentation. Recall of consent elements discussed by linked parent-provider dyads were compared. Six hundred fifty-five encounters were reviewed. Pediatric emergency medicine fellows and pediatric emergency department-based pediatricians were more likely to document any benefit (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0-2.4) or alternative (OR, 2.7; 95% CI, 1.8-3.9) compared with PEM attendings. Providers were more likely to report discussion of failure to complete the procedure (OR, 7.3; 95% CI, 2.3-23.3) and parents were more likely to recall discussion of this risk (OR, 5.3; 95% CI, 1.0-27.8) in the postintervention group. Based on provider recall, using the precompleted consent form was associated with providers discussing at least 2 of the 3 benefits (84.0% vs 97.2%, P < 0.01), 5 of the 5 risks (31% vs 67.7%, P < 0.01), and improved parental recall of risks (5.7% vs 22.9%, P = 0.03). More providers reported taking less than 1 minute to complete the form in the postimplementation group (12.0% vs 43.7%, P < 0.01). Implementing a precompleted consent form for procedural sedation was associated with providers reporting decreased time spent completing the consent form and better alignment of key consent elements between reported provider discussion and parental recall.


Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light.
Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO₂) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm² (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%-67%) with 24 h PORTHE (40-80 µM)/40% PG treatment (pH 5). 28 J/cm² LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.


Structural probing of Zn(II), Cd(II) and Hg(II) binding to human ubiquitin.
A structural investigation performed on adducts of human ubiquitin with group-12 metal ions reveals common preferential anchoring sites, the most populated one being His68; at higher metal ion concentration a second and a third site, close to the N-terminus of the protein, become populated and promote a polymorphic transition from orthorhombic to cubic form; Glu16 and Glu18, involved in the latter metal binding, undergo a remarkable displacement from their position in native ubiquitin; the aggregate stereochemistry appears to be driven by the clustering of deshielded backbone hydrogen-bond patches, and metal ions foster this process.


The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.
The remarkable growth of genome-wide association studies (GWAS) has created a critical need to experimentally validate the disease-associated variants, 90% of which involve non-coding variants. To determine how the field is addressing this urgent need, we performed a comprehensive literature review identifying 36,676 articles. These were reduced to 1454 articles through a set of filters using natural language processing and ontology-based text-mining. This was followed by manual curation and cross-referencing against the GWAS catalog, yielding a final set of 286 articles. We identified 309 experimentally validated non-coding GWAS variants, regulating 252 genes across 130 human disease traits. These variants covered a variety of regulatory mechanisms. Interestingly, 70% (215/309) acted through cis-regulatory elements, with the remaining through promoters (22%, 70/309) or non-coding RNAs (8%, 24/309). Several validation approaches were utilized in these studies, including gene expression (n = 272), transcription factor binding (n = 175), reporter assays (n = 171), in vivo models (n = 104), genome editing (n = 96) and chromatin interaction (n = 33). This review of the literature is the first to systematically evaluate the status and the landscape of experimentation being used to validate non-coding GWAS-identified variants. Our results clearly underscore the multifaceted approach needed for experimental validation, have practical implications on variant prioritization and considerations of target gene nomination. While the field has a long way to go to validate the thousands of GWAS associations, we show that progress is being made and provide exemplars of validation studies covering a wide variety of mechanisms, target genes, and disease areas.


A trabecular metal tibial component in total knee replacement in patients younger than 60 years: a two-year radiostereophotogrammetric analysis.
We compared the performance of uncemented trabecular metal tibial components in total knee replacement with that of cemented tibial components in patients younger than 60 years over two years using radiostereophotogrammetric analysis (RSA). A total of 22 consecutive patients (mean age 53 years, 33 to 59, 26 knees) received an uncemented NexGen trabecular metal cruciate-retaining monobloc tibial component and 19 (mean 53 years, 44 to 59, 21 knees) a cemented NexGen Option cruciate-retaining modular tibial component. All the trabecular metal components migrated during the initial three months and then stabilised. The exception was external rotation, which did not stabilise until 12 months. Unlike conventional metal-backed implants which displayed a tilting migration comprising subsidence and lift-off from the tibial tray, most of the trabecular metal components showed subsidence only, probably due to the elasticity of the implant. This pattern of subsidence is regarded as being beneficial for uncemented fixation.


The utilization of dental emergency services during COVID-19 pandemic in a German university center: Do we lose vulnerable patients?
The COVID-19 pandemic poses a major challenge to health care worldwide. As a part of the virus containment strategy, health care services were limited to the treatment of essential emergencies. The aim was to evaluate the influence of COVID-19 pandemic on patients' utilization of dental emergency services, focusing on patients vulnerable to severe courses of COVID-19. Files of 1,299 patients of the Dental School of the University Hospital Wuerzburg between 3 February and 7 June 2020 were retrospectively analyzed. The observation period was divided into pre-lockdown (Pre-L), during lockdown (Dur-L), and post-lockdown (Post-L). Patients' demographics, diagnosis, and medical history including COVID-19 anamnesis were recorded. The number of dental emergency patients decreased by approximately 50% (Pre-L, n = 576; Dur-L, n = 309). Proportions of risk patients among them did not change. Stationary admissions increased by approximately 4% (Pre-L, 12.3% to Dur-L, 16.2%). The most frequent diagnosis was uncontrollable pain (45.6%), originating in 25.2% of endodontic and periodontal diseases. Abscesses (23.0%), dental trauma (16.5%), facial trauma (9.4%), and uncontrollable bleeding (5.5%) followed consecutively. Patients with an increased risk for severe courses of COVID-19 infection did not refrain from consulting dental emergency care. Dental emergencies should be treated early to avoid stationary admissions to preserve hospital bed capacities.


Combined aneurysms of the main renal and celiac arteries: an unusual association.
Celiac artery aneurysm (CAA) is a rare condition, which occasionally occurs in association with such visceral aneurysms as splenic, common hepatic, left hepatic, superior mesenteric and renal arteries. We describe our observation of a patient with CAA and bilateral main renal artery aneurysm. To the best of our knowledge, a combination of these visceral arterial aneurysms has not been reported previously. The available literature on this topic is briefly reviewed.


Early Onset of HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) and Adult T-cell Leukemia/Lymphoma (ATL): Systematic Search and Review.
Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in some regions and its vertical transmission occurs mainly through breastfeeding. About 10% of carriers develop associated diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T-cell leukemia/lymphoma (ATL) and infectious dermatitis associated with HTLV-1 (IDH). We searched for available case reports of early-onset HAM/TSP and ATL to evaluate demographic and disease aspects in infantile-juvenile patients. In the reviewed literature, 27 HAM/TSP and 31 ATL cases were found. In almost all of them, the most likely route of transmission was through breastfeeding. ATL is rarely reported, notwithstanding it may be underestimated because T-cell lymphomas are not investigated for HTLV-1 infection in this age group. IDH was frequently associated with HAM/TSP. The investigation of HTLV-1 infection in pregnant women is an important matter of public health and should be mandatory in endemic countries.


Cryoenzymic studies on yeast 3-phosphoglycerate kinase. Attempt to obtain the kinetics of the hinge-bending motion.
This is a continuation of a study on the 3-phosphoglycerate kinase (PGK) reaction in the direction of 1,3-bisphosphoglycerate (bPG) formation: ATP + 3-phosphoglycerate (PG) <==> ADP + bPG [Schmidt, P. P., Travers, F., & Barman, T. (1995) Biochemistry 34, 824-832]. We showed that species containing bPG accumulate in the steady state, but their low concentrations and rapid kinetics of formation precluded a full study, even under cryoenzymic conditions in 40% ethylene glycol. Here we studied the PGK reaction in 30% methanol. The transient kinetics of bPG formation were obtained by chemical sampling: PGK was mixed with PG and [gamma-32P]ATP in a rapid flow quench apparatus, the mixture aged 4 ms up and quenched in acid, and the [1-(32)P]bPG was determined. The time course consisted of a rapid rise of bPG (kinetics k(obs)) and a steady state phase. In methanol, the amplitude of the rise was large (>50% of the PGK in the steady state), and k(obs) was measurable. Fluorescence stopped flow was used to study the formation of the binary E x PG and E x ATP. The affinities of PGK for ATP and PG were high in methanol (Kd = 102 and 1.5 microM, respectively), but the kinetics of the formation of E x PG and E x ATP were too rapid to be measured. From these and the chemical sampling experiments, we propose a reaction scheme for PGK: a rapid formation of the collision complex E x PG x ATP (K1), a slow isomerisation to E* x PG x ATP (k2,k(-2)), a rapid phosphorylation transfer step to E x bPG x ADP (K3), and a slow release of the products (k4). In our scheme, k(obs) is the reflection mainly of k2 and k(-2) and the steady state of k4. Using a computer simulation procedure, k2/K1 = 0.37 microM(-1) s(-1), k(-2) = 33 s(-1), K3 = 4, and k4 = 7.1 s(-1). We propose that k(obs) measures the kinetics of the putative hinge-bending motion of PGK, i.e., the conformational change that is necessary for the substrates to line up for phosphoryl transfer.


Functional physiotherapy method results for the treatment of idiopathic clubfoot.
Idiopathic clubfoot is a congenital deformity of multifactorial etiology. The initial treatment is eminently conservative; one of the methods applied is the Functional physiotherapy method (FPM), which includes different approaches: Robert Debré (RD) and Saint-Vincent-de-Paul (SVP) among them. This method is based on manipulations of the foot, bandages, splints and exercises adapted to the motor development of the child aimed to achieve a plantigrade and functional foot. Our hypothesis was that the SVP method could be more efficient than the RD method in correcting deformities, and would decrease the rate of surgeries. To compare the RD and SVP methods, specifically regarding the improvement accomplished and the frequency of surgery needed to achieve a plantigrade foot. Retrospective study of 71 idiopathic clubfeet of 46 children born between February 2004 and January 2012, who were evaluated and classified in our hospital according to severity by the Dimeglio-Bensahel scale. We included moderate, severe and very severe feet. Thirty-four feet were treated with the RD method and 37 feet with the SVP method. The outcomes at a minimum of two years were considered as very good (by physiotherapy), good (by percutaneous heel-cord tenotomy), fair (by limited surgery), and poor (by complete surgery). Complete release was not required in any case; limited posterior release was done in 23 cases (74%) with the RD method and 9 (25%) with the SVP method (P < 0.001). The percutaneous heel-cord tenotomy was done in 2 feet treated with the RD method (7%) and 6 feet (17%) treated with the SVP method (P < 0.001). Six feet in the RD group (19%) and twenty-one feet (58%) in the SVP group did not require any surgery (P < 0.001). Our study provides evidence of the superiority of the SVP method over the RD method, as a variation of the FPM, for the treatment of idiopathic clubfoot.


Traumatic shock: the fifth shock.
Although, historically, shock associated with traumatic injury has been evaluated through knowledge of the 4 recognized shock patterns--cardiogenic, obstructive, distributive, and hypovolemic--many trauma practitioners view traumatic shock as a unique fifth shock pattern. Although secondary to a systemic inflammatory response syndrome triggered by endogenous danger signals, traumatic shock represents a unique pathological condition that begins with multiple, usually blunt, trauma and may conclude with multiple organ dysfunction syndrome and death. While varying mechanisms of injury may lead to different presentations of shock and cardiovascular decompensation, a unifying theme of traumatic shock is an overwhelming inflammatory response driven by proinflammatory cytokines, and the downstream results of this cytokine storm including, but not limited to, acute respiratory distress syndrome, coagulopathy, sepsis, and multiple organ dysfunction syndrome. Treatment is primarily supportive; however, research into novel therapeutics for traumatic shock is ongoing and promises some direction for future care.


Aorto-left renal vein fistula caused by a ruptured abdominal aortic aneurysm.
Retroaortic left renal vein is a malformation in which the left renal vein courses dorsal to the abdominal aorta. In patients with abdominal aortic aneurysm, an aorto-left renal vein fistula can form if the left renal vein is sandwiched between the aneurysm wall and lumbar vertebrae. The patient was an 84-year-old man with lower back pain. We performed a contrast-enhanced computed tomography (CT), although renal dysfunction was noted. The CT showed a ruptured juxta-renal abdominal aortic with aorto-left renal vein fistula. This clinical condition can cause severe renal dysfunction, in spite of which an enhanced contrasted CT scan would be extremely informative preoperatively.


Alternatives for solid waste management in Isfahan, Iran: a case study.
This articles presents the status of municipal solid waste (MSW) management practices in the city of Isfahan, Iran. It provides an overview of the generation, collection, separation, recycling and disposal of MSW. Field studies were carried out from 2009 to 2010. According to this study, the city generates about 399,000 metric tons of MSW per year, of which 72.5% is organic matter. In Isfahan more than 90% of the MSW is collected by official municipal forces and the other 10% is collected by informal collectors. About 70% of the MSW in Isfahan is composted to produce a humus material, 5% is rejected and 25% is stockpiled for future use as fuel in a waste-to-energy incineration plant. Non-compostable waste and other residues are landfilled. This investigation also includes an analysis of economic benefits that could be realized by implementing incineration and a discussion of the challenges confronted in Isfahan for implementing changes to the city's existing MSW management system. This article concludes with recommendations for improving the city's MSW management system.


Zinc oxide nanowire interphase for enhanced interfacial strength in lightweight polymer fiber composites.
A novel functionalization method for aramid fibers is developed to enhance the bonding of a ZnO nanowire interphase grown on the fiber surface for interfacial strength enhancement. The nanowire interphase functionally grades the typically discrete interface and reduces the stress concentration between the fiber and matrix. The functionalization process is developed to improve the bonding between the ZnO nanowires and the aramid fiber and is validated through Fourier transform IR and X-ray photoelectron spectroscopy studies. Mechanical testing shows significant improvement in the interfacial shear strength with no decrease in the base fiber strength. This is the only technique found in the literature for the growth of a nanowire interphase on polymer fibers for structural enhancement without degrading the in-plane properties of the bulk composite. Furthermore, it is firmly shown that the functionalization process is a necessary condition for enhanced interfacial strength, demonstrating that ZnO nanowires strongly interact with carboxylic acid functional groups.


Response of the subterranean termite Coptotermes formosanus (Isoptera: Rhinotermitidae) to soil treated with microencapsulated fenobucarb.
Treating soil with insecticides is thought to be an effective method for termite control. Speed of action and repellency of insecticides are important factors for discussing their barrier effects as soil-treatment termiticides. The chemical barrier effect of microencapsulated fenobucarb against Coptotermes formosanus Shiraki was examined in the laboratory. Fenobucarb had a significantly faster lethal effect when applied to the mouthparts than to the tergites of worker termites. Soil that had been treated with > or = 50 mg kg(-1) of microencapsulated fenobucarb had a barrier effect within a single day, and could stop or retard the penetration of termites for 7 days. Microencapsulated fenobucarb did not act as a repellent, as indicated by a gradual increase in mortality at > or = 50 mg kg(-1) with slight penetration into the treated soil during the 7 day test. The results suggest that microencapsulated fenobucarb is a fast-acting termiticide, with a good barrier effect as a soil treatment, that also acts as a reduced repellent, retarding entry of termites into treated soil.


Antiproteases and Down's syndrome in an Australian population.
alpha 1-Antitrypsin phenotypes and alpha 2-macroglobulin concentrations were determined for an Australian population of 286 Down's syndrome patients, 296 newborn babies, and 193 patients with non-specific mental retardation. There was no significant difference between the groups in the distribution of the phenotypes or level of heterozygosity. The phenotypic frequencies were 89.5% PiMM, 8.0% PiMS and 1.0% PiMZ among controls. The mean alpha 2-macroglobulin concentrations were investigated and it was shown that PiMZ phenotypes had a higher concentration, 2.67 +/- 0.27 g/l (newborns) and 2.74 +/- 0.32 g/l (Down's syndrome), in comparison with PiMS, PiSS, and PiMM.


Change in the number of occlusal contacts following splint therapy in patients with a temporomandibular disorder (TMD).
The mean number of occlusal contacts before and after occlusal appliance therapy were compared in three temporomandibular disorder groups and one control group. Only patients with a successful treatment outcome were considered in the statistical analysis. Statistically significant changes were seen in the disc displacement with reduction group, which was managed with anterior repositioning splint: the mean number of contacts increased 3 months after weaning off the splint. If the disc is out of position then the number of occlusal contacts appears to be reduced. It would therefore appear to be sound advice not to make permanent and irreversible adjustment to the occlusion in the presence of disc displacement as when the disc is repositioned occlusal contacts will change.


Preemptive caudal anesthesia on back pain after lumbar discectomy: a randomized and controlled study.
In this randomized and prospective research, we aimed to relieve surgical and muscle-related pain early after lumbar disc operations with caudal preemptive analgesia. A total of 120 patients with single-level lumbar disc herniation were included in this study. The caudal epidural injection was performed for all patients 20 min before surgery. The patients were divided into three groups. Non-steroidal anti-inflammatory drugs or tramadol use were recorded. Pre-operative and post-operative pain was interpreted through a visual analog scale. There was a difference between the groups in all post-operative measurements (p < 0.05), between Group 1 and Group 3, and between Group 2 and Group 3. A statistical significance has been achieved between the groups at the 1st h, 2nd h, 4th h, and 24th h (p < 0.05). The difference between the pain intensities of the patients at the 24th h and the 1st week was statistically significant in Groups 1 and 2 (p < 0.05). Evaluation of the effects of medical treatments reduced the severity of back pain and foot pain. The preemptive bupivacaine or in combination with methylprednisolone caudal injection is an effective and safe method to reduce post-operative pain and ameliorate functional capacity for the treatment of lumbar disc herniation.


Rho-mediated assembly of stress fibers is differentially regulated in corneal fibroblasts and myofibroblasts.
Corneal keratocytes (stromal cells) are activated to fibroblasts and myofibroblasts during wound healing. Myofibroblast transdifferentiation is accompanied by the expression of alpha-smooth muscle actin (alpha-SMA) and the assembly of a robust stress fiber network and larger focal adhesions (FAs). The regulation of the assembly of stress fibers was evaluated in cultured corneal fibroblast and myofibroblast phenotypes. In both cell types, the inhibition of Rho GTPase activity by microinjecting C3 transferase into the cells resulted in the disassembly of stress fibers and FAs. However, the inhibition of the Rho-associated kinases ROKalpha and ROKbeta with their inhibitor, Y27632, or by overexpression of their mutant kinase-dead forms resulted in only a partial loss of the stress fibers and FAs in myofibroblasts but a total loss in fibroblasts. ROK inhibitor-sensitive and -resistant stress fibers in myofibroblasts contained alpha-SMA, nonmuscle myosin II, tropomyosin, and calponin. The ROK inhibition-resistant stress fibers and FAs were lost upon the overexpression of the dominant-negative form of mDia1 (a mammalian homolog of Drosophila diaphanous protein). These findings indicated that while the assembly of stress fibers in fibroblasts critically involves both ROK and mDia1, in myofibroblasts, the assembly of alpha-SMA-containing stress fibers also occurs independently of ROK and involves Rho/mDia1.