A Phase II Study of Stereotactic Body Radiation Therapy for Low-Intermediate-High-Risk Prostate Cancer Using Helical Tomotherapy: Dose-Volumetric Parameters Predicting Early Toxicity.
Endpoint: To assess early urinary (GU) and rectal (GI) toxicities after helical tomotherapy Stereotactic body radiation therapy (SBRT), and to determine their predictive factors. Since May 2012, 45 prostate cancer patients were treated with eight fractions of 5.48 (low risk, 29%) or 5.65 Gy (intermediate-high risk, 71%) on alternative days over 2.5 weeks. The exclusion criteria were Gleason score 9-10, PSA >40 ng/mL, cT3b-4, IPSS ≥20, and history of acute urinary retention. During the follow-up, a set of potential prognostic factors was correlated with urinary or rectal toxicity. The median follow-up was 13.8 months (2-25 months). There were no grade ≥3 toxicities. Acute grade 2 GU complications were found in a 22.7% of men, but in 2.3% of patients at 1 month, 0% at 6 months, and 0% at 12 months. The correspondent figures for grade 2 GI toxicities were 20.4% (acute), 2.3% (1 month), 3.6% (6 months), and 5% (12 months). Acute GI toxicity was significantly correlated with the rectal volume (>15 cm(3)) receiving 28 Gy, only when expressed as absolute volume. The age (>72 years old) was a predictor of GI toxicity after 1 month of treatment. No correlation was found, however, between urinary toxicity and the other analyzed variables. IPSS increased significantly at the time of the last fraction and within the first month, returning to the baseline at sixth month. Urinary-related quality of life (IPSS question 8 score), it was not significantly worsen during radiotherapy returning to the baseline levels 1 month after the treatment. At 12 months follow-up patient's perception of their urinary function improved significantly in comparison with the baseline. Our scheme of eight fractions on alternative days delivered using helical tomotherapy is well tolerated. We recommend using actual volume instead of percentual volume in the treatment planning, and not to exceed 15 cm(3) of rectal volume receiving ≥25 Gy in order to diminish acute GI toxicity.


Tertiary structure formation in the propeptide of subtilisin BPN' by successive amino acid replacements and its close relation to function.
The propeptide of subtilisin BPN', located between a signal peptide and the mature region of the protease, is known to exhibit inhibitory activity toward subtilisin BPN', in addition to its activity as an intramolecular chaperone that facilitates folding of subtilisin BPN'. Another unique feature is that although the isolated propeptide is in a random-coil state, it forms a defined tertiary structure when it is bound to subtilisin BPN'. In this study, amino acid replacements likely to increase the hydrophobicity of the propeptide have been introduced so that the isolated propeptide forms a defined tertiary structure. By successive replacements of Ala47 by Phe, Gly13 by Ile and Val65 by Ile, the propeptide was found to form a tertiary structure in addition to an increase in its secondary structure content, which were identified by circular dichoism spectra measurements. Concurrently, the propeptide, which is a temporary inhibitor in its wild-type form, became resistant to proteolytic digestion by subtilisin BPN'. These results show not only the close relationship between tertiary structure formation in the propeptide and its function as a protease inhibitor but also the ability of a random-coil protein to form a tertiary structure after a limited number of well-designed amino acid replacements.


Current-induced Néel order switching facilitated by magnetic phase transition.
Terahertz (THz) spin dynamics and vanishing stray field make antiferromagnetic (AFM) materials the most promising candidate for the next-generation magnetic memory technology with revolutionary storage density and writing speed. However, owing to the extremely large exchange energy barriers, energy-efficient manipulation has been a fundamental challenge in AFM systems. Here, we report an electrical writing of antiferromagnetic orders through a record-low current density on the order of 106 A cm-2 facilitated by the unique AFM-ferromagnetic (FM) phase transition in FeRh. By introducing a transient FM state via current-induced Joule heating, the spin-orbit torque can switch the AFM order parameter by 90° with a reduced writing current density similar to ordinary FM materials. This mechanism is further verified by measuring the temperature and magnetic bias field dependences, where the X-ray magnetic linear dichroism (XMLD) results confirm the AFM switching besides the electrical transport measurement. Our findings demonstrate the exciting possibility of writing operations in AFM-based devices with a lower current density, opening a new pathway towards pure AFM memory applications.


Dissociation of chemotactic and inflammatory leukocyte responses.
Leukocyte accumulation at inflammatory sites probably involves chemotactic migration of the cells, and it is often presumed that abnormalities in cell accumulation derive from defective chemotaxis. The latter contention was examined by measuring the chemotactic response of leukocytes obtained from the circulation during conditions associated with depressed cellular inflammatory reactions. In two transplanted-tumor models induced by different chemical carcinogens in DA strain rats, monocyte chemotaxis was normal or enhanced while macrophage accumulation at inflammatory foci was severely curtailed. Late pregnancy in outbred Wistar rats depressed macrophage accumulation to peritoneal irritants while enhancing monocyte chemotaxis. Irritant-induced anti-inflammation (counterirritation) in Wistar rats decreased both polymorphonuclear leukocyte and macrophage accumulation during inflammation but enhanced the chemotactic activity of the corresponding cells obtained from the circulation. We concluded that in vitro chemotactic measurements were not predictive of cellular accumulation during inflammation in these conditions and that an intrinsic defect in chemotaxis was insufficient to explain anti-inflammation associated with cancer, pregnancy, or counterirritation.


The use of embryonic spinal cord grafts to replace identified motoneuron pools depleted by a neurotoxic lectin, volkensin.
The viability of solid pieces of embryonic spinal cord grafted into adult spinal cords that had been depleted of motoneurons by a neurotoxic lectin, volkensin, was investigated. The possibility that the grafted neurons will extend their axons via the degenerated ventral roots and reinnervate the denervated muscles was also studied. Cells in the embryonic spinal cord were prelabeled with bromodeoxyuridine and grafted into the host cord 2 or 3 weeks after volkensin treatment. Six to 24 weeks later the fluorescent dyes Fast Blue and Diamidino Yellow were applied to the peripheral nerve or muscles which were expected to be reinnervated by neurons from the graft. The grafted cells were visualized by bromodeoxyuridine immunocytochemistry. Although the transplants survived, no neurons of graft origin reinnervated the muscles via the ventral roots of the host spinal cord. Therefore, in another series of experiments axons from grafted and host neurons were guided toward an implanted extensor hallucis longus (EHL) muscle via its motor nerve. The EHL muscle was removed from either healthy or volkensin-affected hindlimb of the host, placed paravertebrally, and the proximal end of its motor nerve inserted into the spinal cord at the site of the graft. In these experiments, neurons of graft origin reinnervated the paravertebrally placed muscle implant via the muscle's own nerve. However, significantly fewer neurons were observed when volkensin-affected nerve-muscle implants were used. To establish whether grafted spinal cord neurons are necessary for reinnervation of skeletal muscles, in separate experiments embryonic neocortical tissue was transplanted into the motoneuron-depleted spinal cord. These grafts were connected to healthy nerve-muscle implants. In this case little reinnervation of the muscle occurred. These results suggest that, though volkensin-affected peripheral nerve is not a good conduit for regenerating axons, other inhibitory effects located in the CNS may be responsible for the failure of growing embryonic neurons to reach their peripheral targets via the existing anatomical routes. Experiments with grafted neocortical tissue indicate that good reinnervation of implanted muscles can only be achieved by using homologous embryonic tissue.


Obesity and Asthma: A Missing Link.
Obesity and asthma are two chronic conditions that affect millions of people. Genetic and lifestyle factors such as diet, physical activity, and early exposure to micro-organisms are important factors that may contribute to the escalating prevalence of both conditions. The prevalence of asthma is higher in obese individuals. Recently, two major phenotypes of asthma with obesity have been described: one phenotype of early-onset asthma that is aggravated by obesity, and a second phenotype of later-onset asthma that predominantly affects women. Systemic inflammation and mechanical effect, both due to the expansion of the adipose tissue, have been proposed as the main reasons for the association between obesity and asthma. However, the mechanisms involved are not yet fully understood. Moreover, it has also been suggested that insulin resistance syndrome can have a role in the association between these conditions. The intestinal microbiota is an important factor in the development of the immune system, and can be considered a link between obesity and asthma. In the obese state, higher lipopolysaccharide (LPS) serum levels as a consequence of a microbiota dysbiosis have been found. In addition, changes in microbiota composition result in a modification of carbohydrate fermentation capacity, therefore modifying short chain fatty acid (SCFA) levels. The main objective of this review is to summarize the principal findings that link obesity and asthma.


Disruption of the ifkA and ifkB genes results in altered cell adhesion, morphological defects and a propensity to form pre-stalk O cells during development of Dictyostelium.
IfkA and ifkB are two GCN2-like genes present in Dictyostelium. Disruption of either gene alone results in subtle developmental defects. However, disruption of ifkA and ifkB within the same strain results in severe morphological and patterning defects in the developing double null cells. The mutant cells aggregate in streams that give tightly clumped mounds. Fingers form from the mounds but remain attached to one another, especially at their bases. The fingers culminate to give fused and entangled structures lacking proper stalk but containing some spores. The morphological defects are consistent with an enhanced cell-cell and cell-substrate adhesiveness of the developing double null cells, which may result in inappropriate cell contacts and altered cell motility and sorting properties. In ifkA/ifkB nulls, cell type proportioning and patterning is altered in favor of ALC/pstO cell types. The bias toward the ALC/pstO cell types may be due, in part, to the nuclear localization of the transcription factor STATc in growing ifkA/ifkB null cells. STATc normally becomes localized to the nucleus during finger formation and only within the pre-stalk O zone. The precocious nuclear localization seen in the mutant cells may predispose the cells to a ALC/pstO cell fate. The findings indicate that IfkA and IfkB have redundant functions in Dictyostelium morphogenesis that involve maintaining proper cell-cell and cell-substrate adhesion and the equilibrium between different cell types for proper spatial patterning.


Ultrasound-enhanced protective effect of tetramethylpyrazine against cerebral ischemia/reperfusion injury.
In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong) and its bioactive ingredient, tetramethylpyrazine (TMP), have been used to treat cardiovascular diseases and to relieve various neurological symptoms, such as those associated with ischemic injury. In the present study, we investigated whether ultrasound (US) exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R) injury. Glutamate-induced toxicity to pheochromocytoma (PC12) cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate-induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosis-related proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of proinflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. Taken together, our findings suggest that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize ultrasound treatment parameters.


The Estonian study of Chernobyl cleanup workers: I. Design and questionnaire data.
Nearly 2% of the male population of Estonia aged 20-39 years were sent to Chernobyl to assist in the cleanup activities after the reactor accident. A cohort of 4,833 cleanup workers was assembled based on multiple and independent sources of information. Information obtained from 3,704 responses to a detailed questionnaire indicated that 63% of the workers were sent to Chernobyl in 1986; 54% were of Estonian and 35% of Russian ethnicity; 72% were married, and 1,164 of their 5,392 children were conceived after the Chernobyl disaster. The workers were less educated than their counterparts in the general population of Estonia, and only 8.5% had attended university. Based on doses entered in worker records, the mean dose was 11 cGy, with only 1.4% over 25 cGy. Nearly 85% of the workers were sent as part of military training activities, and more than half spent in excess of 3 months in the Chernobyl area. Thirty-six percent of the workers reported having worked within the immediate vicinity of the accident site; 11.5% worked on the roofs near the damaged reactor, clearing the highly radioactive debris. The most commonly performed task was the removal and burial of topsoil (55% of the workers). Potassium iodide was given to over 18% of the men. The study design also incorporates biological indicators of exposure based on the glycophorin A mutational assay of red blood cells and chromosome translocation analyses of lymphocytes; record linkage with national cancer registry and mortality registry files to determine cancer incidence and cause-specific mortality; thyroid screening examinations with ultrasound and fine-needle biopsy; and cryopreserved white blood cells and plasma for future molecular studies. Comprehensive studies of Chernobyl cleanup workers have potential to provide new information about cancer risks due to protracted exposures to ionizing radiation.


Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice.
The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2+/+ and Nrf2-/- C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2-/- mice than in Nrf2+/+ mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2+/+ mice than in Nrf2-/- mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.


Compound heterozygosity (G71R/R140H) in the lecithin:cholesterol acyltransferase (LCAT) gene results in an intermediate phenotype between LCAT-deficiency and fish-eye disease.
The esterification of free cholesterol (FC) in plasma, catalyzed by the enzyme lecithin:cholesterol acyltransferase (LCAT; EC 18.104.22.168), is a key process in lipoprotein metabolism. The resulting cholesteryl esters (CE) represent the main core lipids of low (LDL) and high density lipoproteins (HDL). Primary (familial) LCAT-deficiency (FLD) is a rare autosomal recessive genetic disease caused by the complete or near absence of LCAT activity. In fish-eye disease (FED), residual LCAT activity is still detectable. Here, we describe a 32-year-old patient with corneal opacity, very low LCAT activity, reduced amounts of CE (low HDL-cholesterol level), and elevated triglyceride (TG) values. The lipoprotein pattern was abnormal with regard to lipoprotein composition and concentration, but distinct lipoprotein classes were still present. Despite of typical features of glomerular proteinuria, creatinine clearance was normal. DNA sequencing and restiction fragment analyses revealed two separate mutations in the patient's LCAT gene: a previously described G to A transition in exon 4 converting Arg140 to His, inherited from his mother, and a novel G to C transversion in exon 2 converting Gly71 to Arg, inherited from his father, indicating that M.P. was a compound heterozygote. Determination of enzyme activities of recombinant LCAT proteins obtained upon transfection of COS-7 cells with plasmids containing G71R-LCAT or wild-type LCAT cDNA revealed very low alpha- and absence of beta-LCAT activity for the G71R mutant. The identification of the novel G71R LCAT mutation supports the proposed molecular model for the enzyme implying that the "lid" domain at residues 50-74 is involved in enzyme:substrate interaction. Our data are in line with the hypothesis that a key event in the etiology of FLD is the loss of distinct lipoprotein fractions.


Circadian pain assessment in neonates from a nurse's perspective.
Circadian rhythms modulate the activity of pain pathways. But there appears to be a lack of understanding of how the perception of pain varies in neonates during the day. To assess circadian variations in pain perception we analyzed intensities of pain at 3 h intervals in neonates (within 24 hours). We also followed up the nursing interventions practiced for pain reduction and their effectivity within a day. We have analyzed the clinical observations of pain in 16 neonates during 62 days of hospitalization (with Mean = 3.87, Min = 1, Max = 19). The pain was assessed by a modification of the Comfort scale supplemented with Wong-Baker scale. Procedure used for acute pain elimination was administration of 24% sucrose to the neonates. This procedure was centralized and performed in an incubator or neonatal bed. We confirmed statistically significant difference in pain scores in our group of neonates at 10:00 am, 4:00 pm, 4:00 am as compared to 10:00 pm (p values being 0.02603; 0.02885, 0.01673). The pain score was highest at 10:00 pm (Mean = 18.86, Max = 34) and at 1:00 am (Mean = 18.89, Max = 33). There was no significant difference in the pain score at 10:00 pm and 1:00 am (p = 0.2951). The results of our studies provided further evidence of circadian rhythm in the pain scores in neonates. A better understanding of circadian control of pain in neonates can help promote a more frequent use of time-contingent pain treatment strategies to help improve neonates care (Tab. 1, Fig. 2, Ref. 28) Keywords: circadian rhythm, neonate, nursing care, pain, the Comfort scale.


Non-viral VEGF(165) gene therapy--magnetofection of acoustically active magnetic lipospheres ('magnetobubbles') increases tissue survival in an oversized skin flap model.
Adenoviral transduction of the VEGF gene in an oversized skin flap increases flap survival and perfusion. In this study, we investigated the potential of magnetofection of magnetic lipospheres containing VEGF(165)-cDNA on survival and perfusion of ischemic skin flaps and evaluated the method with respect to the significance of applied magnetic field and ultrasound. We prepared perfluoropropane-filled magnetic lipospheres ('magnetobubbles') from Tween60-coated magnetic nanoparticles, Metafectene, soybean-oil and cDNA and studied the effect in an oversized random-pattern-flap model in the rats (n= 46). VEGF-cDNA-magnetobubbles were administered under a magnetic field with simultaneously applied ultrasound, under magnetic field alone and with applied ultrasound alone. Therapy was conducted 7 days pre-operative. Flap survival and necrosis were measured 7 days post-operatively. Flap perfusion, VEGF-protein concentration in target and surrounding tissue, formation and appearance of new vessels were analysed additionally. Magnetofection with VEGF-cDNA-magnetobubbles presented an increased flap survival of 50% and increased flap perfusion (P < 0.05). Without ultrasound and without magnetic field, the effect is weakened. VEGF concentration in target tissue was elevated (P < 0.05), while underlying muscle was not affected. Our results demonstrate the successful VEGF gene therapy by means of magnetobubble magnetofection. Here, the method of magnetofection of magnetic lipospheres is equally efficient as adenoviral transduction, but has a presumable superior safety profile.


Clinical impact of chronic renal insufficiency on endovascular aneurysm repair.
Endovascular aneurysm repair of abdominal aortic aneurysms has become a viable alternative to open repair. A significant proportion of this patient population has chronic renal insufficiency. The surgical outcomes associated with endovascular repair in 342 patients, with and without chronic renal insufficiency, are reported. Perioperative mortality, length of admission, length of intensive care unit admission, and rates of acute renal failure, congestive heart failure, myocardial infarction, conversion to open surgery, progression to hemodialysis, and incidence of endoleaks were retrospectively reviewed and analyzed. Endovascular repair demonstrated higher rates of acute renal failure, longer length of stay, and longer intensive care unit admissions in patients with chronic renal insufficiency. Patients with severe renal dysfunction demonstrated markedly elevated mortality and morbidity. These results indicate that chronic renal insufficiency is not an absolute contraindication to endovascular repair in patients with moderate renal dysfunction, but patients with severe renal dysfunction perform poorly after aortic reconstruction.


Discrete iridium pyridonate chains with variable metal valence: nature and energetics of the Ir-Ir bonding from DFT calculations.
The structure of the Ir(I) complex [Ir2(mu-OPy)2(CO)4] (Opy = 2-pyridonate) has been fully characterized in its head-to-head (A) configuration as a "dimer of dimers" AA in which two binuclear complexes are connected by means of a weak, but unsupported, iridium-iridium interaction (Ir(2)...Ir(2A) 2.9808(6) A). The head-to-tail isomer, referred to as B, was found in equilibrium with A in solution. It has been shown that this complex can be oxidized by diiodine to give iridium chains with highly selective configurations and general formula I-[Ir2(mu-OPy)2(CO)4]n-I (n = 1-3). The synthesis of IAI (1), of the isomers IAAI (2AA) and IABI (2AB), and of IABAI (3) is reported. DFT calculations have been carried out on A and B and on the known isomers of 1-3, as well as on two isomers of the hypothetic chain of eight Ir(1.25) atoms corresponding to n = 4. The stability of the metal chain is assigned to a 2-electron/2n-center sigma bond delocalized along the metal backbone and supplemented with a weak attractive interaction of the metallophilic type. Calculations confirm that further oxidation of the Ir chains corresponding to n > 1 by iodine, yielding the cleavage of one or two unsupported bond(s), is a highly exothermic process. The formation of the I-[Ir2(mu-OPy)2(CO)4]n-I chains is also computed to be exothermic, either highly for n = 1 or still significantly for n = 2 and 3. At variance with these results, the formation of an octanuclear chain is predicted to be no more than marginally exothermic (DeltaG = 1.7 kcal.mol(-1)), mainly because of interligand strain induced by the steric bulk of the amidate rings.


Primary leiomyosarcoma of the aorta: report of a case and review of the literature.
Leiomyosarcoma of vascular origin is an extremely rare lesion especially when it occurs in the arteries. In the present study, we report a case of such a neoplasm, originating in the wall of the descending aorta and give an ample review of world references on the subjects of primary aortic neoplasm. Wright classified aortic tumors into two categories concerning the site of origin in the aortic wall: the first involves the intima, the second group consists of tumors arising in the media or adventitia. The aspecific clinical findings that characterize these lesions explain the difficulty of a preoperative diagnosis. Very important, therefore, are sonography and CT which point out signs and symptoms which refer to a local and distal diffusion of the tumor. However, even in the cases in which the diagnosis is done before surgery, there is no codified therapeutic management. In fact both surgical and non-surgical methods (radiotherapy, chemotherapy) have poor results with an average survival. Due to the limited prognosis "quoad vitam", the elective therapy must preferably be of conservative type.


Comparison of the anesthetic effects of intrathecal levobupivacaine + fentanyl and bupivacaine + fentanyl during caesarean section.
Regional anesthesia techniques are increasingly preferred for caesarean section. The aim of the present study was to compare the anesthetic effects of levobupivacaine + fentanyl and bupivacaine + fentanyl on the mother and newborn during elective caesarean section under spinal anesthesia. In this prospective study, 50 gravidas, who were scheduled for cesarean section were enrolled after Ethics Committee approval had been obtained. The patients were randomized into one of the following two groups: bupivacaine + fentanyl group (group B; n = 25), 7.5 mg of 0.5% bupivacaine + 15 microg fentanyl intrathecally; levobupivacaine + fentanyl group (group L; n = 25), 7.5 mg of 0.5% levobupivacaine + 15 microg fentanyl intrathecally. The patients were immediately placed in supine position with 20-30 degrees head up-tilt. The level of sensory and motor blocks were evaluated by pin-prick test and Bromage scale, respectively. The time to sensory block at the T4 dermatome was shorter in group B (group B, 4.8 min; group L, 6.0 min; p < 0.05). The time to maximum motor block was also shorter in group B (group B, 3.4 min; group L, 4.7 min; p < 0.05). The duration of analgesia was longer in group L compared to group B (group B, 102 min; group L, 118 min; p < 0.05). Time to sensory and maximum motor block was shorter in the bupivacaine + fentanyl group. On the other hand, a longer duration of analgesia was achieved in the levobupivacaine + fentanyl group. Although levobupivacaine is a novel drug, it is a good alternative for bupivacaine.


Application of Spectral Crosstalk Correction for Improving Multiplexed MicroRNA Detection Using a Single Excitation Wavelength.
MicroRNAs (miRNAs) play crucial roles in the regulation of cellular activities and are next-generation biomarkers for early cancer detection. Simultaneous monitoring of multiplexed miRNA is very important for enhancing the accuracy of cancer diagnostics. Traditional fluorescence methods for multicomponent analysis were usually operated under multiple excitation wavelengths, because spectral crosstalk is very detrimental to detecting accuracy for multicomponent analysis. Herein, we present a fluorescence strategy for multi-miRNAs detection in plasma under a single excitation wavelength. Nucleic acid stain TOTO-1 and three labeled fluorescence dyes Cy3, Cy3.5, and Cy5 emit no fluorescence in their free state. Target miRNA hybridized the auxiliary and probe oligonucleotides into duplex nucleic acid. Intercalation interaction localized TOTO-1 and labeled dyes into the duplex nucleic acid. As a result, TOTO-1 emitted strong fluorescence and efficient Förster resonance energy transfer (FRET) happened. MicroRNAs miRNA-155, miRNA-182, and miRNA-197, which are significant for the early diagnosis of lung cancer, were simultaneously detected as models. Deviations from spectral crosstalk in the presence of other miRNAs were corrected by mathematical methods. Results demonstrated that, after spectra crosstalk corrections, every miRNA at high or low concentration in plasma was determined accurately in the presence of either high or low concentrations of the other two miRNAs. This new multiplexed assay for miRNAs is promising for clinical diagnosis, prognosis, and therapeutic monitoring of early-stage lung cancer.


Genome and Transcriptome Sequences Reveal the Specific Parasitism of the Nematophagous Purpureocillium lilacinum 36-1.
Purpureocillium lilacinum is a promising nematophagous ascomycete able to adapt diverse environments and it is also an opportunistic fungus that infects humans. A microbial inoculant of P. lilacinum has been registered to control plant parasitic nematodes. However, the molecular mechanism of the toxicological processes is still unclear because of the relatively few reports on the subject. In this study, using Illumina paired-end sequencing, the draft genome sequence and the transcriptome of P. lilacinum strain 36-1 infecting nematode-eggs were determined. Whole genome alignment indicated that P. lilacinum 36-1 possessed a more dynamic genome in comparison with P. lilacinum India strain. Moreover, a phylogenetic analysis showed that the P. lilacinum 36-1 had a closer relation to entomophagous fungi. The protein-coding genes in P. lilacinum 36-1 occurred much more frequently than they did in other fungi, which was a result of the depletion of repeat-induced point mutations (RIP). Comparative genome and transcriptome analyses revealed the genes that were involved in pathogenicity, particularly in the recognition, adhesion of nematode-eggs, downstream signal transduction pathways and hydrolase genes. By contrast, certain numbers of cellulose and xylan degradation genes and a lack of polysaccharide lyase genes showed the potential of P. lilacinum 36-1 as an endophyte. Notably, the expression of appressorium-formation and antioxidants-related genes exhibited similar infection patterns in P. lilacinum strain 36-1 to those of the model entomophagous fungi Metarhizium spp. These results uncovered the specific parasitism of P. lilacinum and presented the genes responsible for the infection of nematode-eggs.


Radioimmunotherapy of B-Cell Non-Hodgkin's Lymphoma.
This manuscript reviews current advances in the use of radioimmunotherapy (RIT) for the treatment of B-cell non-Hodgkin's lymphoma (NHL). RIT has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (MAbs), and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved: (131)I-tositumomab (Bexxar(®)), and (90)Y-ibritumomab tiuxetan (Zevalin(®)). (131)I-tositumomab is available in the United States, and (90)Y-ibritumumab tiuxetan in Europe, the United States, Asia, and Africa. RIT can be integrated in clinical practice using non-ablative activities for treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy in front-line treatment in FL patients. Despite the lack of phase III studies to clearly define the efficacy of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing refractory FL and transformed NHL, RIT as a monotherapy induces around 30% complete response with a possibility of durable remissions. RIT consolidation after induction therapy significantly improves the quality of the response. Dose-limiting toxicity of RIT is hematological, depending on bone marrow involvement and prior treatment. Non-hematological toxicity is generally low. Different studies have been published assessing innovative protocols of RIT or new indications, in particular treatment in patients with aggressive lymphomas. High-dose treatment, RIT as consolidation after different therapeutic induction modalities, RIT in first-line treatment or fractionated RIT showed promising results. New MAbs, in particular humanized MAbs, or combinations of naked and radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should be developed to determine injected activity.


[Data acquisition in clinical trials].
Methods of data acquisition in clinical trials are reviewed and their advantages and disadvantages are discussed. To avoid the effort of multiple data acquisition and to eliminate possible transcription errors the data of the patients should be collected and stored in a data bank only once also in case of a drug study. From the data bank the results can be used for the different clinical purposes as well as for the statistical evaluation when testing drugs.


Partial characterization of a subtilisin inhibitor from black bean seeds.
The subtilisin inhibitor (SI), isolated from black beans (Phaseolus vagaris) has a molecular weight of 8918 and it contains four half cystine residues. The N-terminal residue is arginine and the C-terminal is lysine. The subtilisin inhibiting site is composed of an Ala-Leu or Ile bond. This site interacts in addition to subtilisin (S) with elastase from human leukocytes (HLE), both of which compete for the inhibitor. Also, HLE-cleaved SI (SIHLE) is inactive against HLE as well as against S. It was shown that the inhibition of S by SI resembles a temporary inhibition, involving a very slow release of enzyme activity. The trypsin reactive site is a Lys-Val bond, and its interaction with bovine trypsin is very weak. No complexes of SI or trypsin-cleaved SI (SIT) with trypsin could be detected on cellulose-acetate membrane electrophoresis, while SIT forms a clearly visible complex with S.


Different Heterotrimeric G Protein Dynamics for Wide-Range Chemotaxis in Eukaryotic Cells.
Chemotaxis describes directional motility along ambient chemical gradients and has important roles in human physiology and pathology. Typical chemotactic cells, such as neutrophils and Dictyostelium cells, can detect spatial differences in chemical gradients over a background concentration of a 105 scale. Studies of Dictyostelium cells have elucidated the molecular mechanisms of gradient sensing involving G protein coupled receptor (GPCR) signaling. GPCR transduces spatial information through its cognate heterotrimeric G protein as a guanine nucleotide change factor (GEF). More recently, studies have revealed unconventional regulation of heterotrimeric G protein in the gradient sensing. In this review, we explain how multiple mechanisms of GPCR signaling ensure the broad range sensing of chemical gradients in Dictyostelium cells as a model for eukaryotic chemotaxis.


Development of a novel and highly efficient method of isolating bacteriophages from water.
Bacteriophages are widely used to the treatment of drug-resistant bacteria and the improvement of food safety through bacterial lysis. However, the limited investigations on bacteriophage restrict their further application. In this study, a novel and highly efficient method was developed for isolating bacteriophage from water based on the electropositive silica gel particles (ESPs) method. To optimize the ESPs method, we evaluated the eluent type, flow rate, pH, temperature, and inoculation concentration of bacteriophage using bacteriophage f2. The quantitative detection reported that the recovery of the ESPs method reached over 90%. The qualitative detection demonstrated that the ESPs method effectively isolated 70% of extremely low-concentration bacteriophage (100 PFU/100L). Based on the host bacteria composed of 33 standard strains and 10 isolated strains, the bacteriophages in 18 water samples collected from the three sites in the Tianjin Haihe River Basin were isolated by the ESPs and traditional methods. Results showed that the ESPs method was significantly superior to the traditional method. The ESPs method isolated 32 strains of bacteriophage, whereas the traditional method isolated 15 strains. The sample isolation efficiency and bacteriophage isolation efficiency of the ESPs method were 3.28 and 2.13 times higher than those of the traditional method. The developed ESPs method was characterized by high isolation efficiency, efficient handling of large water sample size and low requirement on water quality.


A(3) adenosine receptor deficiency does not influence atherogenesis.
Atherosclerosis is a multifactorial disease, the progression of which is modulated by several factors, including inflammation and hypercholesterolemia. The A(3) adenosine receptor (A(3)AR) has been reported to affect mast cell degranulation leading to inflammation, as well as to influence cardiovascular homeostasis. Here, we show that its deletion can also impact vascular smooth muscle cell (VSMC) proliferation in vitro. Based on these observations, we hypothesized that A(3)AR deficiency would affect atheromatous lesion development in vivo. Our results indicate that the expression of the matrix enzyme lysyl oxidase (LO) is increased while the proliferation potential of VSMC is decreased in A(3)AR-null aortas. This is in accordance with the previously reported inverse correlation between LO level and proliferation. Nevertheless, we found that A(3)-deficiency does not protect vessels against atherogenesis. This was demonstrated in mouse models of high fat diet-induced atherosclerosis and guidewire-induced femoral artery injury. We conclude that the contributions of the A(3)AR to inflammation and to modulating LO levels are not significant enough to control vascular response to injury.


Effect of the nonlocal exchange on the performance of the orbital-dependent correlation functionals from second-order perturbation theory.
Adding a fraction of the nonlocal exchange operator to the local orbital-dependent exchange potential improves the many-body perturbation expansion based on the Kohn-Sham determinant. The effect of such a hybrid scheme on the performance of the orbital-dependent correlation functional from the second-order perturbation theory (PT2H) is investigated numerically. A small fraction of the nonlocal exchange is often sufficient to ensure the existence of the self-consistent solution for the PT2H potential. In the He and Be atoms, including 37% of the nonlocal exchange leads to the correlation energies and electronic densities that are very close to the exact ones. In molecules, varying the fraction of the nonlocal exchange may result in the PT2H energy closely reproducing the CCSD(T) value; however such a fraction depends on the system and does not always result in an accurate electronic density. We also numerically verify that the "semicanonical" perturbation series includes most of the beneficial effects of the nonlocal exchange without sacrificing the locality of the exchange potential.


Soft salt-mannitol agar-cloxacillin test: a highly specific bedside screening test for detection of colonization with methicillin-resistant Staphylococcus aureus.
The early detection of colonization with methicillin-resistant Staphylococcus aureus (MRSA) of patients in intensive-care units is an essential step in the strategy for preventing MRSA epidemics. In this study, tubes containing soft salt-mannitol agar with cloxacillin (6 microg/ml) (SSMAC) were prepared for inoculation of clinical samples at patients' bedsides by personnel of an intensive-care unit. A total of 1,914 swabs from different sample sites of 81 patients were dipped into SSMAC tubes, and after 24 h of incubation (in an incubator located near the intensive-care unit), an evident color change was considered by the intensive-care-unit personnel to be an MRSA alarm. Sixty-three (3.3%) SSMAC tubes were considered positive for MRSA, 1,827 (95.4%) were considered negative, and 24 (1.2%) were considered intermediate. Compared with values for parallel conventional surveillance cultures for MRSA, excluding tubes with intermediate results, the SSMAC test had a sensitivity of 72.7%, a specificity of 99.2%, a positive predictive value of 76.2%, and a negative predictive value of 99.0%. When intermediate tubes were considered positive, the corresponding values were 75.3, 98.2, 63.2, and 99.0%, respectively. The sensitivity and specificity values of the test to identify MRSA-colonized patients were 89.4 and 100%, respectively. Oropharyngeal and naris specimens were the most reliable samples for MRSA detection. False-negative results were frequent in bronchial aspirates with low (< 10(3) to 10(6) CFU/ml) MRSA counts. False-positive results were mainly due to methicillin-resistant Staphylococcus haemolyticus. The SSMAC tube is a useful, rapid, and inexpensive tool for the early identification of MRSA-colonized patients and, consequently, for the implementation of measures to prevent the spread of MRSA.


A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor.
Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes). The response was found to be dependent on aryl hydrocarbon receptor (AhR) activation, although induction of the response was delayed compared to upregulation of CYP1A1, a classic AhR-responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inhibitor partially attenuated the PCB126-induced inflammatory response and partly, but not completely, ameliorated disruption of adipogenesis caused by PCB126. Our results indicate a role for PCB126 in mediating an inflammatory response through AhR in preadipocytes that interferes with adipogenesis.


Influence of Solvent Polarizability on the Keto-Enol Equilibrium in 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol.
This work presents spectroscopic studies of the keto-enol equilibrium induced by solvent polarizability in 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl]benzene-1,3-diol a strong antiproliferative and anticancer thiadiazol derivative. Electronic absorption, steady state and time resolved fluorescence, and infrared spectroscopies were applied to investigate the keto and enol forms of this compound in a series of polar and non-polar solvents. The enol form dominates in polar solvents while, surprisingly, the keto form dominates in non-polar solvents with high average electric dipole polarizability e.g. n-alkenes. The electronic absorption spectrum of this derivative is more dependent on spatially averaged electric dipole polarizability of the solvent than on Kirkwood's correlation or on Lorenz-Lorenz electric polarizability. By analogy of n-alkanes to the alkyl parts of lipids, one can expect that the transformation of 1,3,4-thiadiazoles to the keto form may be facilitated in the hydrophobic core of the lipid membrane. Such a transition may be of great practical importance for the design of biologically active pharmaceutics, which are able to interact with the hydrophobic regions of cell membranes in a specific manner.


Mechanism of Cu(II) and Cd(II) immobilization by extracellular polymeric substances (Escherichia coli) on variable charge soils.
Extracellular polymeric substances (EPS) found in soils can reduce the mobility of heavy metals through the use of both electrostatic and non-electrostatic mechanisms. Their effects vary from one soil type to another. The influence of EPS from Escherichia coli on the adsorption behaviors of Cu(II) and Cd(II) by two bulk variable charge soils, Oxisol and Ultisol, was studied at constant and varied pH, and the results were compared to a constant charge Alfisol. The maximum adsorption capacities of the soils were significantly (P < 0.05) enhanced in the presence of EPS, with Cu(II) adsorption being greater. Interaction of EPS with soils made the soil surface charge more negative by neutralizing positive charges and shifting the zeta potentials in a negative direction: from -18.6 to -26.4 mV for Alfisol, +5.1 to -22.2 mV for Oxisol, and +0.3 to -28.0 mV for Ultisol at pH 5.0. The adsorption data fitted both the Freundlich and Langmuir isotherms well. Preadsorbed Cd(II) was more easily desorbed by KNO3 than preadsorbed Cu(II) from both the control and EPS treated soils. The adsorption of both metals was governed by electrostatic and non-electrostatic mechanisms, although more Cu(II) was adsorbed through the non-electrostatic mechanism. The information obtained in this study will improve our understanding of the mechanisms involved in reducing heavy metals mobility in variable charge soils and hence, their bioavailability.


Numerical investigation into the effects of ordered particle packing and slip flow on the performance of chromatography.
The pressure drop and the plate height of chromatography columns packed with particles in the face-centered cubic, the body-centered cubic and the simple cubic configurations are calculated by a volume averaging method model. It is found that the Kozeny-Carman equation provides a reasonable prediction of the pressure drop when particles are in the face-centered cubic configuration, but overestimates the pressure drop when particles are in the body-centered cubic and the simple cubic configurations. The face-centered cubic configuration has the advantage to provide a smaller longitudinal dispersion coefficient than the body-centered cubic, the simple cubic, and the random configurations. The pressure drop and the plate height for slip flow through particles in the face-centered cubic configuration are lower than that for no-slip flow. The values of the smallest reduced plate height of columns packed with particles in the face-centered cubic configuration for no-slip flow and slip flow are about 0.084 and 0.059, respectively. The plate height of the ordered particle packing structures is smaller and the effect of slip flow on the plate height is less remarkable than results reported in literature.


Murine transfer factor. I. Description of the model and evidence for specificity.
A model for studying transfer of delayed-type sensitivity to mice with cellfree materials is described. The results with a particulate antigen (Candida) and 4 soluble protein antigens (PPD, ferritin, cytochrome c, and horseradish peroxidase) suggest that the phenomenon is antigen specific. Identical preparations from the spleens of insensitive donors were not active. This murine model should facilitate characterization of the immunologic and chemical properties of transfer factor.


Truncation of fibronectin-binding proteins in Staphylococcus aureus strain Newman leads to deficient adherence and host cell invasion due to loss of the cell wall anchor function.
Staphylococcus aureus fibronectin-binding proteins (FnBPs) play a critical role in S. aureus pathogenesis. FnBPs mediate adhesion to fibronectin and invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, by fibronectin bridging to the host cell fibronectin receptor integrin (alpha(5))beta(1). Strain Newman is a laboratory strain frequently used for genetic, functional, and in vivo studies. However, despite pronounced production of FnBPs, strain Newman is only weakly adherent to immobilized Fn and weakly invasive. We examined whether these effects are due to a structural difference of FnBPs. Here, we show that both fnbA(Newman) and fnbB(Newman) contain a centrally located point mutation resulting in a stop codon. This leads to a truncation of both FnBPs at the end of the C domain at identical positions. Most likely, the stop codon occurred first in fnbB(Newman) and was subsequently transferred to fnbA(Newman) by replacement of the entire region encompassing the C, D, and W domains with the respective sequence of fnbB(Newman). Using heterologous expression in Staphylococcus carnosus, we found that truncated FnBPs were completely secreted into the culture medium and not anchored to the cell wall, since they lack the sortase motif (LPETG). Consequently, this led to a loss of FnBP-dependent functions, such as strong adhesion to immobilized fibronectin, binding of fibrinogen, and host cell invasion. This mutation may explain some of the earlier reported conflicting data with strain Newman. Thus, care should be taken when drawing negative conclusions about the role of FnBPs as a virulence factor in a given model.


Middle ear disease in native Indian children in British Columbia--incidence of disease and an evaluation of screening methods.
A total of 1,109 Indian children in five British Columbia communities were surveyed for middle ear disease. Evaluation included a history, pure screening, impedance audiometry, and otolaryngological examination. Of these, 12.7 per cent had middle ear disease requiring treatment, namely serous otitis media, perforated tympanic membrane, or cholesteatoma. Serous otitis media was the commonest disease and it was most prevalent in the 0-4 years age group. Pure tone audiometry and impedance audiometry were both unsatisfactory screening methods in this study. The tests could not be performed in the majority of patients four years of age or younger, and they both showed a high incidence of false positive results as well as a significant incidence of false negative results. On the basis of this preliminary report a proposal is made for a screening and continuing evaluation program involving local health care personnel, audiologists, and otolaryngologists.


The pathogenesis of murine coronavirus infection of the central nervous system.
Mouse hepatitis virus (MHV) is a positive-strand RNA virus that causes an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. Cytokine production, chemokine secretion, and immune cell infiltration into the central nervous system are critical to control viral replication during acute infection. Despite potent antiviral T-lymphocyte activity, sterile immunity is not achieved, and MHV chronically persists within oligodendrocytes. Continued infiltration and activation of the immune system, a result of the lingering viral antigen and RNA within oligodendrocytes, lead directly to the development of an immune-mediated demyelination that bears remarkable similarities, both clinically and histologically, to the human demyelinating disease multiple sclerosis. MHV offers a unique model system for studying host defense during acute viral infection and immune-mediated demyelination during chronic infection.


Thymic stromal lymphopoietin (TSLP) secretion from human nasal epithelium is a function of TSLP genotype.
Recent candidate gene and genome-wide association studies have identified "protective" associations between the single-nucleotide polymorphism (SNP) rs1837253 in the TSLP gene and risk for allergy, asthma, and airway hyperresponsiveness. The absence of linkage disequilibrium of rs1837253 with other SNPs in the region suggests it is likely a causal polymorphism for these associations, having functional consequences. We hypothesized that rs1837253 genotype would influence TSLP secretion from mucosal surfaces. We therefore evaluated the secretion of TSLP protein from primary nasal epithelial cells (NECs) of atopic and nonatopic individuals and its association with rs1837253 genotype. We found that although atopic sensitization does not affect the secretion of TSLP from NECs, there was decreased TSLP secretion in NECs obtained from heterozygous (CT; 1.8-fold) and homozygous minor allele (TT; 2.5-fold) individuals, as compared with NECs from homozygous major allele individuals (CC; P<0.05), after double-stranded RNA (dsRNA) stimulation (50 μg ml(-1)). Our novel results show that rs1837253 polymorphism may be directly involved in the regulation of TSLP secretion. This may help explain the protective association of this genetic variant with asthma and related traits. Identifying functional consequences of SNPs in genes with previously reported clinical associations is critical in understanding and targeting allergic inflammation.


Knee Pain and Low Back Pain Additively Disturb Sleep in the General Population: A Cross-Sectional Analysis of the Nagahama Study.
Association of knee and low back pain with sleep disturbance is poorly understood. We aimed to clarify the independent and combined effects of these orthopedic symptoms on sleep in a large-scale general population. Cross-sectional data about sleep and knee/low back pain were collected for 9,611 community residents (53±14 years old) by a structured questionnaire. Sleep duration less than 6 h/d was defined as short sleep. Sleep quality and the presence of knee and low back pain were evaluated by dichotomous questions. Subjects who complained about knee or low back pains were graded by tertiles of a numerical response scale (NRS) score and a Roland-Morris disability questionnaire (RDQ) score respectively. Multivariate regression analyses were performed to determine the correlates of short sleep duration and poor sleep quality. Frequency of participants who complained of the orthopedic symptoms was as follows; knee pain, 29.0%; low back pain, 42.0% and both knee and low back pain 17.6%. Both knee and low back pain were significantly and independently associated with short sleep duration (knee pain: odds ratio (OR) = 1.19, p<0.01; low back pain: OR = 1.13, p = 0.01) and poor sleep quality (knee pain: OR = 1.22, p<0.01; low back pain; OR = 1.57, p<0.01). The group in the highest tertile of the NRS or RDQ score had the highest risk for short sleep duration and poor sleep quality except for the relationship between the highest tertile of the RDQ score and short sleep duration.(the highest tertile of the NRS: OR for short sleep duration = 1.31, p<0.01; OR for poor sleep quality = 1.47, p<0.01; the highest tertile of the RDQ: OR for short sleep duration = 1.11, p = 0.12; OR for poor sleep quality = 1.81, p<0.01) Further, coincident knee and low back pain raised the odds ratios for short sleep duration (either of knee or low back pain: OR = 1.10, p = 0.06; both knee and low back pain: OR = 1.40, p<0.01) and poor sleep quality (either of knee or low back pain: OR = 1.61, p<0.01; both knee and low back pain: OR = 2.17, p<0.01). Knee and low back pains were independently associated with short sleep duration and poor sleep quality. Further, they additively increased the correlation with these sleep problems in the general population.


Optics ellipticity performance of an unobscured off-axis space telescope.
With the development of astronomy, more and more attention is paid to the survey of dark matter. Dark matter cannot be seen directly but can be detected by weak gravitational lensing measurement. Ellipticity is an important parameter used to define the shape of a galaxy. Galaxy ellipticity changes with weak gravitational lensing and nonideal optics. With our design of an unobscured off-axis telescope, we implement the simulation and calculation of optics ellipticity. With an accurate model of optics PSF, the characteristic of ellipticity is modeled and analyzed. It is shown that with good optical design, the full field ellipticity can be quite small. The spatial ellipticity change can be modeled by cubic interpolation with very high accuracy. We also modeled the ellipticity variance with time and analyzed the tolerance. It is shown that the unobscured off-axis telescope has good ellipticity performance and fulfills the requirement of dark matter survey.


Poly(I:C)/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.
Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed. To improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C)], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA), ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C)/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1)-specific cellular immune response. HBSS1 immunisation with poly(I:C)/alum priming also generated high-level CD4(+) and CD8(+) T cell responses in terms of Th1 cytokines (IFN-γ and IL-2). The protein-vaccine HBSS1 with mixed poly(I:C)/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.


Design strategies and applications of nacre-based biomaterials.
The field of tissue engineering and regenerative medicine relies heavily on materials capable of implantation without significant foreign body reactions and with the ability to promote tissue differentiation and regeneration. The field of bone tissue engineering in particular requires materials capable of providing enhanced mechanical properties and promoting osteogenic cell lineage commitment. While bone repair has long relied almost exclusively on inorganic, calcium phosphate ceramics such as hydroxyapatite and their composites or on non-degradable metals, the organically derived shell and pearl nacre generated by mollusks has emerged as a promising alternative. Nacre is a naturally occurring composite material composed of inorganic, calcium carbonate plates connected by a framework of organic molecules. Similar to mammalian bone, the highly organized microstructure of nacre endows the composite with superior mechanical properties while the organic phase contributes to significant bioactivity. Studies, both in vitro and in vivo, have demonstrated nacre's biocompatibility, biodegradability, and osteogenic potential, which are superior to pure inorganic minerals such as hydroxyapatite or non-degradable metals. Nacre can be used directly as a bulk implant or as part of a composite material when combined with polymers or other ceramics. While nacre has demonstrated its effectiveness in multiple cell culture and animal models, it remains a relatively underexplored biomaterial. This review introduces the formation, structure, and characteristics of nacre, and discusses the present and future uses of this biologically-derived material as a novel biomaterial for orthopedic and other tissue engineering applications. Mussel derived nacre, a biological composite composed of mineralized calcium carbonate platelets and interplatelet protein components, has recently gained interest as a potential alternative ceramic material in orthopedic biomaterials, combining the integration and mechanical capabilities of calcium phosphates with increased bioactivity derived from proteins and biomolecules; however, there is limited awareness of this material's potential. Herein, we present, to our knowledge, the first comprehensive review of nacre as a biomaterial. Nacre is a highly promising yet overlooked biomaterial for orthopedic tissue engineering with great potential in a wide variety of material systems. It is our hope that publication of this article will lead to increased community awareness of the potential of nacre as a versatile, bioactive ceramic capable of improving bone tissue regeneration and will elicit increased research effort and innovation utilizing nacre.


NIH Director's Pioneer Awards: could the selection process be biased against women?
One of the first National Institutes of Health (NIH) Roadmap initiatives to be launched was the Director's Pioneer Award. This award was established to "identify and fund investigators of exceptionally creative abilities and diligence, for a sufficient term (five years) to allow them to develop and test far-ranging ideas." Nine excellent scientists were chosen as NIH Pioneers, but the selection of all men is at odds with the percentage of women receiving doctoral degrees for the past three decades, serving as principal investigators on NIH research grants, and achieving recognition as scientific innovators in non-NIH award competitions. The absence of women Pioneers provokes the following question: In the context of extant research on the impact of gender-based assumptions on evaluation of men and women in traditionally male fields, such as science, were there aspects about the process of nomination, evaluation, and selection that inadvertently favored men? We present evidence to suggest that women scientists would be disadvantaged by the following components of the NIH Director's Pioneer Award initiative: (1) time pressure placed on evaluators, (2) absence of face-to-face discussion about applicants, (3) ambiguity of performance criteria, given the novelty of the award, combined with an emphasis on subjective assessment of leadership, potential achievements rather than actual accomplishments, and risk taking, (4) emphasis on self-promotion, (5) weight given to letters of recommendation, and (6) the need for finalists to make a formal, in-person presentation in which the individual and not his or her science was the focus of evaluation. We offer an analysis of this process to encourage the NIH to embark on self-study and to educate all reviewers regarding an evidence-based approach to gender and evaluation.


Evaluation of three stone-scoring systems for predicting SFR and complications after percutaneous nephrolithotomy: a systematic review and meta-analysis.
Clinical studies assessing the feasibility and accuracy of three stone scoring systems's (SSSs: Guy's stone score, CROES nomogram and S.T.O.N.E nephrolithometry scoring system) have reported contradictory outcomes. This systematic evaluation was performed to obtain comprehensive evidence with regard to the feasibility and accuracy of three SSSs. A systematic search of Embase, Pubmed, Medline, and the Cochrane Library was conducted to identify studies that compared three SSSs up to Mar 2018. Patients were categorized according to stone free (SF) and no-stone free (NSF), Outcomes of interest included perioperative variables, stone-free rate (SFR), and complications. Ten studies estimating three SSSs were included for meta-analysis. The results showed that SF patients had a significantly lower proportion of male (OR = 1.48, P = 0.0007), lower stone burden (WMD = -504.28, P < 0.0001), fewer No of involved calyces (OR = -1.23, P = 0.0007) and lower proportion of staghorn stone (OR = 0.33, P < 0.0001). Moreover, SF patients had significantly lower score of Guy score (WMD = -0.64, P < 0.0001), but, S.T.O.N.E. score (WMD = -1.23, P < 0.0001) and a higher score of CROES nomogram (WMD = 29.48, P = 0.003). However, the comparison of area under curves (AUC) of predicting SFR indicated that there was no remarkable difference between three SSSs. Nonetheless, Guy score was the only stone scoring system that predicted complications after PCNL (WMD = -0.29, 95% CI: - 0.57 to - 0.02, P = 0.03). Our meta-analysis indicated that the three SSSs were equally, feasible and accurate for predicting SFR after PCNL. However, Guy score was the only stone scoring system that predicted complications after PCNL.


Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: The AGATA study.
Prevalence of vulvar-vaginal atrophy (VVA) has been always investigated by phone or web interview without any objective evaluation. Objective signs associated with symptoms of VVA are now termed genitourinary syndrome of menopause (GSM). This multi-centric study was performed in order to provide nation-wide data on the prevalence and management of GSM. Nine hundred thirteen females, 59.3 ± 7.4 years old asking for a routine gynecological examination were recruited. Diagnosis of GSM was based on patient sensation of vaginal dryness, any objective sign of VVA and a pH > 5. A 722/913 (79.1%) women were diagnosed with GSM with a prevalence ranging from 64.7% to 84.2%, starting from 1 to 6 years after menopause. Sedentary women were at higher risk of GSM (OR 1.8, 95% CI: 1.3-2.5; p = 0.0005). Recent vaginal infection was more likely in women with GSM (OR 2.48, 95% CI: 1.33-4.62; p = 0.0041). Symptoms reported by women with GSM were vaginal dryness (100%), dyspareunia (77.6%), burning (56.9%), itching (56.6%) and dysuria (36.1%). Signs detected by gynecologists were mucosal dryness (99%), thinning of vaginal rugae (92.1%), pallor of the mucosa (90.7%), mucosal fragility (71.9%) and petechiae (46.7%). Only 274 (30%) of women had had a previous diagnosis of VVA/GSM. These were treated either with no therapy (9.8%), systemic hormone (9.2%), local hormone (44.5%) or local non-hormonal (36.5%) therapy. At the time of our investigation 266 of them (97.1%) still had the disorder. GSM is a common, under-diagnosed and under-treated disorder. Measures to improve its early detection and its appropriate management are needed.


Nutrient-responsive promoter elements of the V4 gene of Dictyostelium discoideum.
Expression of the V4 gene of Dictyostelium discoideum is required for the transition from growth to development in response to an altered nutrient environment. In addition, the expression itself is sensitive to the types and amounts of nutrients supporting growth. We describe the structure of the two copies of the V4 gene and the relationship between these genes and the two V4 mRNA species produced during growth. In addition, three regions were identified within the upstream sequences of the V4b gene that are important for proper transcription. At least two of the regions can, independently of the others, confer deactivation of transcription upon initiation of development and thus serve as redundant regulatory sequences. However, the regions are differentially responsive to the types and amounts of nutrients present in the cell's environment and thus are distinct from one another.


A remedial intervention linked to a formative assessment is effective in terms of improving student performance in subsequent degree examinations.
Intervention may help weaker medical students improve their performance. However, the effectiveness of remedial intervention is inconclusive due to small sample sizes in previous studies. We asked: is remedial intervention linked to a formative assessment effective in terms of improving student performance in subsequent degree examinations? This was a retrospective, observational study of anonymous databases of student assessment outcomes. Data were analysed for students due to graduate in the years 2005-2009 (n = 909). Exam performance was compared for students who received remediation versus those who did not. The main outcome measure was summative degree examination marks. After adjusting for cohort, gender, overseas versus home funding, previous degree and previous performance in the corresponding baseline third year summative exam, students receiving a remedial intervention (after poor performance on a formative objective structured clinical examination and written exams mid-fourth year) were significantly more likely to obtain an improved mark on end-of-fourth year summative written (p = 0.005) and OSCE (p = 0.001) exams compared to those students who did not receive remediation. A remedial intervention linked to poor assessment performance predicted improved performance in later examination. There is a need for prospective studies in order to identify the effective components of remedial interventions.


Seminal plasma proteins as modulators of the sperm function and their application in sperm biotechnologies.
Seminal plasma (SP) is known to play an important role in mammalian fertilization. However, the variability found in its composition among species, males and even fractions of the same ejaculate has made difficult to completely understand its effect in sperm function. Proteins are one of the major SP components that modulate sperm functionality. During the last years, intensive work has been performed to characterize the role of these proteins. They have been found to influence sperm capacitation, formation of the oviductal sperm reservoir and sperm-oocyte interaction. Sperm biotechnologies, such as sperm cryopreservation and flow cytometric sex-sorting, that involve a substantial dilution of the SP are detrimental to sperm quality. Attempts to improve the outcome of these biotechnologies include the restoration of SP, which has produced contradictory results. To overcome this variability, different research groups have proposed the application of isolated SP proteins. Herein, we will review the current knowledge in the role of the major SP proteins as modulators of sperm functionality. Furthermore, we will discuss the possible applications of the SP proteins in sperm cryopreservation and flow cytometric sex-sorting.


MR body stereotaxis: an aid for MR-guided biopsies.
The use of a new body stereotactic system to facilitate magnetic resonance (MR) guided biopsies is described. A skin entry point is first found using a localizer MR scan. The articulating arm of the stereotactic unit is then used to aim the MR needle at the entry point and accurately maintain the needle at the correct angle to intersect the target area. Complex angles may be used to allow needle passes outside the scan plane. This is accomplished by angling the arm out of the plane of the section.


Loss of cyclin D1 and p16 expression correlates with local recurrence in nasopharyngeal carcinoma following radiotherapy.
The cyclin D1/p16/Rb pathway plays a critical role in tumorigenesis and each component of this pathway may be affected in various malignancies. The purpose of this study was to investigate the expression and prognostic significance of these proteins in nasopharyngeal carcinoma (NPC). Sixty-five patients undergoing radiotherapy for NPC were analyzed. The expression of cyclin D1, p16 and pRb was evaluated with immunohistochemical analysis of archived pretreatment tumor materials and expression of these proteins was correlated with clinicopathological parameters. Positive expression of cyclin D1 was observed in 43 of 65 NPCs (66%). p16 and pRb inactivation was identified in 42 of 65 (65%) and four of 65 (6%) tumors, respectively. All but seven tumors (58 of 65, 89%) contained at least one alternation in the cyclin D1/p16/Rb pathway. Loss of cyclin D1 as well as p16 was closely related to local recurrence after radiotherapy for NPC (P = 0.015 and 0.047). No association between pRb expression and clinicopathological outcome was apparent. The study's results suggest that the cyclin D1/p16/Rb pathway plays an important role in NPC tumorigenesis. We also find that cyclin D1 and p16 protein levels in NPC may be of use clinically as a predictor of local tumor control.


Acceleration of Greenland ice mass loss in spring 2004.
In 2001 the Intergovernmental Panel on Climate Change projected the contribution to sea level rise from the Greenland ice sheet to be between -0.02 and +0.09 m from 1990 to 2100 (ref. 1). However, recent work has suggested that the ice sheet responds more quickly to climate perturbations than previously thought, particularly near the coast. Here we use a satellite gravity survey by the Gravity Recovery and Climate Experiment (GRACE) conducted from April 2002 to April 2006 to provide an independent estimate of the contribution of Greenland ice mass loss to sea level change. We detect an ice mass loss of 248 +/- 36 km3 yr(-1), equivalent to a global sea level rise of 0.5 +/- 0.1 mm yr(-1). The rate of ice loss increased by 250 per cent between the periods April 2002 to April 2004 and May 2004 to April 2006, almost entirely due to accelerated rates of ice loss in southern Greenland; the rate of mass loss in north Greenland was almost constant. Continued monitoring will be needed to identify any future changes in the rate of ice loss in Greenland.


Changes in intracellular electrolyte concentrations during apoptosis induced by UV irradiation of human myeloblastic cells.
Decreases in the intracellular concentrations of both K(+) and Cl(-) have been implicated in playing a major role in the progression of apoptosis, but little is known about the temporal relationship between decreases in electrolyte concentration and the key events in apoptosis, and there is no information about how such decreases affect different intracellular compartments. Electron probe X-ray microanalysis was used to determine changes in element concentrations (Na, P, Cl, and K) in nucleus, cytoplasm, and mitochondria in U937 cells undergoing UV-induced apoptosis. In all compartments, the initial stages of apoptosis were characterized by decreases in [K] and [Cl]. The largest decreases in these elements were in the mitochondria and occurred before the release of cytochrome c. Initial decreases in [K] and [Cl] also preceded apoptotic changes in the nucleus. In the later stages of apoptosis, the [K] continued to decrease, whereas that of Cl began to increase toward control levels and was accompanied by an increase in [Na]. In the nucleus, these increases coincided with poly(ADP-ribose) polymerase cleavage, chromatin condensation, and DNA laddering. The cytoplasm was the compartment least affected and the pattern of change of Cl was similar to those in other compartments, but the decrease in [K] was not significant until after active caspase-3 was detected. Our results support the concept that normotonic cell shrinkage occurs early in apoptosis, and demonstrate that changes in the intracellular concentrations of K and Cl precede apoptotic changes in the cell compartments studied.


Airborne signals of communication in sagebrush: a pharmacological approach.
When plants receive volatiles from a damaged plant, the receivers become more resistant to herbivory. This phenomenon has been reported in many plant species and called plant-plant communication. Lab experiments have suggested that several compounds may be functioning as airborne signals. The objective of this study is to identify potential airborne signals used in communication between sagebrush (Artemisia tridentata) individuals in the field. We collected volatiles of one branch from each of 99 sagebrush individual plants. Eighteen different volatiles were detected by GC-MS analysis. Among these, 4 compounds; 1.8-cineol, β-caryophyllene, α-pinene and borneol, were investigated as signals of communication under natural conditions. The branches which received either 1,8-cineol or β-caryophyllene tended to get less damage than controls. These results suggested that 1,8-cineol and β-caryophyllene should be considered further as possible candidates for generalized airborne signals in sagebrush.


Double-outlet right ventricle with intact ventricular septum.
An infant with double-outlet right ventricle (DORV) with intact ventricular septum (VS) is described. Hypoplastic left ventricle and mitral valve atresia were also associated. To the authors' knowledge, this appears to be the first case in which this rare form has been demonstrated with magnetic resonance imaging (MRI). The patient required balloon atrial septostomy (BAS) three times until 4 months of age because of progressive cyanosis. In such a form of DORV, surgical atrial septectomy should be performed instead of repeating BAS because the tendency to functional closure of the restrictive secundum arterial septal defect caused by incompetent foramen ovale seems to be prominent.


Activation of bone morphogenetic protein-6 gene transcription in MCF-7 cells by estrogen.
Bone morphogenetic protein-6 (BMP-6) is closely correlated with tumor differentiation and skeletal metastasis. Estrogen is considered as a stimulant for the initiation and promotion of breast cancer. Previous studies demonstrated that 17beta-estadiol (E2) can selectively increase the expression of BMP-6. This experiment is designed to detect the molecular mechanism of estrogen activating BMP-6 gene transcription in human estrogen receptor positive (ER+) breast cancer cell line MCF-7. After the treatment of MCF-7 cells with E2 at different concentrations (10(-11) mol/L, 10(-9) mol/L, 10(-7) mol/L), the BMP-6 expression level was examined through real-time polymerase chain reaction. Through restriction enzyme digestion, human BMP-6 1.2 kb long promoter, BMP-6 0.7 kb long promoter was cloned into pGL-3 basic vector; after the treatment with 10(-7) mol/L E2, luciferase activities of the two promoters were detected. Site-directed mutagenesis was performed to obtain the mutant forms of estrogen response element half-site (1/2 ERE) element and Sp1 sites in the BMP-6 promoter, the activities of these mutant form promoters were detected following the methods mentioned above. Chromatin immunoprecipitation (ChIP) assay was also used to confirm the binding of estrogen receptor alpha (ERalpha) on BMP-6 promoter in the presence of E2. E2 dose dependently increased BMP-6 mRNA expression in human ER+ breast cancer cell line MCF-7. At a dose of 10(-7) mol/L E2, human BMP-6 1.2 kb promoter activity was increased by 90% compared with the control group treated with ethanol (P < 0.05). Both the 1/2 ERE response element mutant form and the Sp1 site mutant form of the BMP-6 promoter abolished the activation of the BMP-6 promoter's response to E2. Through ChIP assay, the binding of ERalpha on 1/2 ERE response element in BMP-6 promoter was further validated. Estrogen induces BMP-6 expression in human ER+ breast cancer cell line MCF-7 through its receptor ERalpha binding on 1/2 ERE element in the BMP-6 promoter.


Complications in pediatric interventional neuroradiology management. Reflections on a personal experience.
Pediatric interventional neuroradiology is a rewarding but demanding specialty. It cannot be classified as a miniaturized technical procedure simply because it deals with small vessels in small patients but remains a field requiring specific knowledge combining clinical, anatomical, physiologic, and technical features. Complications that occur remain terrible experiences in this population whose patients have not personally requested to be treated for their vascular malformations. The aim of this article is to evoke the various possible groups of complications that may occur during a pediatric endovascular procedure in order to make physicians aware of these problems and help them to avoid them.


Draping education to promote patient dignity: canadian physiotherapy student and instructor perceptions.
To determine the perceptions of educators and students in Canadian entry-level professional physiotherapy programmes with respect to the current draping curriculum and the methods of delivery of that content and to determine if there is a need for additional draping education time and resources in these programmes. Canadian university physiotherapy students (n=127) and educators (n=183) completed questionnaires designed by the authors. Data were collected via Survey Monkey, exported as Excel files, and analyzed using descriptive statistics and Pearson chi-square analysis. Students and educators agreed that dignity as a concept and draping as a skill to protect patient dignity are both important and should be included in Canadian physiotherapy curricula. Respondents also agreed that students often have difficulty with draping. Educators identified barriers to teaching draping while students identified components of an effective educational resource on draping. To enhance the development of effective draping skills among entry-level physiotherapists, draping education should be included in Canadian physiotherapy curricula. An effective draping educational resource should be developed for educators and students. Purpose: To determine the perceptions of educators and students in Canadian entry-level professional physiotherapy programmes with respect to the current draping curriculum and the methods of delivery of that content and to determine if there is a need for additional draping education time and resources in these programmes. Methods: Canadian university physiotherapy students (n=127) and educators (n=183) completed questionnaires designed by the authors. Data were collected via Survey Monkey, exported as Excel files, and analyzed using descriptive statistics and Pearson chi-square analysis. Results: Students and educators agreed that dignity as a concept and draping as a skill to protect patient dignity are both important and should be included in Canadian physiotherapy curricula. Respondents also agreed that students often have difficulty with draping. Educators identified barriers to teaching draping while students identified components of an effective educational resource on draping. Conclusions: To enhance the development of effective draping skills among entry-level physiotherapists, draping education should be included in Canadian physiotherapy curricula. An effective draping educational resource should be developed for educators and students.


Nicotine withdrawal and dependence among smokers with a history of childhood abuse.
Previous studies have found that those with a history of childhood abuse are more likely to smoke cigarettes than those without a history of abuse. Mechanisms underlying this greater prevalence are unclear. We examined whether current smokers with a history of childhood abuse reported greater levels of nicotine dependence and more severe nicotine withdrawal symptoms. We analyzed data from a 2-wave, national, random-digit-dial survey of adult cigarette smokers (n = 751). We examined whether childhood physical, emotional, and sexual abuse were associated with greater levels of nicotine dependence. Among those who made a quit attempt (n = 368), we examined whether abuse was associated with more severe withdrawal symptoms recalled during the 14 months between surveys. For both dependence and withdrawal, we tested a mediation pathway through current serious mental illness (SMI). All 3 types of childhood abuse were associated with more severe withdrawal symptoms. These associations were partially mediated by SMI. Sexual abuse and physical abuse were directly associated with dependence, whereas emotional abuse was indirectly associated with dependence through SMI. All 3 forms of childhood abuse were associated with both dependence and withdrawal. The greater prevalence of smoking found among those with a history of childhood abuse may be explained by heightened vulnerability to nicotine dependence and withdrawal and may be partially due to comorbid mental illness.


Pulmonary disease in patients with hematologic malignancies.
Patients with hematologic neoplasms frequently experience pulmonary disease. The possibility of a malignant involvement of the lung parenchyma is a well recognized and not unusual event, secondary spread due to lymphoproliferative disorders being the most common situation. Furthermore, the development and the advances in treatment options such as hematopoietic stem cell transplantation, radiation therapy and/or combined drug regimen use have significantly widened the spectrum of non-neoplastic pulmonary complications that can crop up in these patients. Infections, drug/radiation-induced toxicity, and graft-versus-host disease (GVHD)-related complications account by now for most pulmonary problems in hematologic patients and represent a difficult challenge both in diagnostic and in therapeutic terms for the clinician. The aim of this review is to highlight the clinicopathologic spectrum of lung diseases which can occur in the setting of hematologic malignancies. A particular emphasis is devoted to the diagnostic approach, high-resolution computed tomography (HRCT) assuming a key role since different patterns of CT abnormalities are associated with a different yield of the available diagnostic tools and may help in narrowing the differential diagnosis.


The influence of missing value imputation on detection of differentially expressed genes from microarray data.
Missing values are problematic for the analysis of microarray data. Imputation methods have been compared in terms of the similarity between imputed and true values in simulation experiments and not of their influence on the final analysis. The focus has been on missing at random, while entries are missing also not at random. We investigate the influence of imputation on the detection of differentially expressed genes from cDNA microarray data. We apply ANOVA for microarrays and SAM and look to the differentially expressed genes that are lost because of imputation. We show that this new measure provides useful information that the traditional root mean squared error cannot capture. We also show that the type of missingness matters: imputing 5% missing not at random has the same effect as imputing 10-30% missing at random. We propose a new method for imputation (LinImp), fitting a simple linear model for each channel separately, and compare it with the widely used KNNimpute method. For 10% missing at random, KNNimpute leads to twice as many lost differentially expressed genes as LinImp. The R package for LinImp is available at http://folk.uio.no/idasch/imp.


Focal hippocampal gain of NGF function elicits specific septal cholinergic reorganization.
The influence of NGF on the neuroanatomic substrate(s) subserving learning and memory was probed by somatic mosaic analysis. NGF XAT mice underwent unilateral hippocampal delivery of virus vector expressing cre recombinase to produce focal NGF gain of function mosaics. Activated mice expressing increased NGF, but not control mice transduced with the lacZ gene showed reorganization of the septohippocampal projection assessed by retrograde labeling with Fluorogold (FG). Mice mosaic for NGF function demonstrated in ipsilateral medial septum and diagonal band significant increases in FG-labeled cell bodies (94%), ChAT-labeled cells (55%), double-positive cells (190%) and increased somal size of double-positive cells (56%) than did non-activated mice. These results indicate that reorganization of the cholinergic septal input to a specific hippocampal region is promoted by gain of NGF function.


[The risk of nerve lesions in hip alloarthroplasty].
Repeated luxations, periprosthetic fractures, infections, and nerve palsies are the most frequent complications of hip alloarthroplasty. Paresis acquired during elective implantation entails considerable restrictions in the quality of life. The risk of sustaining a nerve injury depends upon the initial clinical situation, cases of planned leg lengthening in patients with hip dysplasia and high luxations being particularly at risk. A Medline search was conducted using the query "nerve palsies during hip prosthesis implantation", yielding 126 publications, of which 18 were used to predict the risk of nerve palsies in cases with simultaneous leg lengthening during total hip arthroplasties according to different preconditions. The risk for an acquired nerve lesion during hip alloarthroplasty in arthritis was 0.5 %. In cases of hip dysplasia (with no or moderate leg lengthening during the procedure), the risk was increased to 2.3 %. An even higher risk of 3.5 % was found in cases of revision surgery. According to the literature, the risk of nerve palsies in cases of continuous leg lengthening before THA is raised to 5.9 % with a linear correlation between the amount of leg lengthening and rate of nerve palsies. Neural lesions during single-stage leg lengthening of less than 3 cm in hip alloarthroplasty are uncommon. More extensive lengthening can be achieved with continuous procedures, which should be conducted under clinical monitoring of the peripheral nerves to avert possible nerve injury.


Flail Mandible and Immediate Airway Management: Traumatic Detachment of Mandibular Lingual Cortex Results in Obstructive Dyspnea and Severe Odynophagia.
Isolated mandibular fractures usually represent themselves as non-life-threatening injuries and are not treated in emergency setting. However, some rare patterns of them may result in airway obstruction as a result of displacement of bony fragments. The authors report a patient of an open comminuted fracture of mandibular symphysis which exhibited an uncommon split pattern with retrogression of lingual cortical plate, and thereby induced glossoptosis, painful deglutition, and obstruction of the upper airway within a few hours. The patient underwent immediate intubation for establishing a definitive airway, followed by open reduction and internal fixation of fracture. Surgical airway management was not needed. Anatomic reduction of the fracture was achieved, by reestablishing the patency of upper airway and resolving the painful deglutition. Patient's occlusion and mouth opening returned to the preinjury status. Timely osteosynthesis surgery offered early relief of patient's signs and symptoms, prevented airway complications and development of traumatic mandibular osteomyelitis, as well as obviated the potential need for surgical airway management. The appropriate management of mandibular fractures placing the airway at risk requires immediate diagnosis based on knowledge of specific clinical and radiographic findings. This case emphasizes that emergency clinicians should be able to distinguish those patients who will need airway securing techniques in emergent or prophylactic context, due to an uncommon fracture pattern of facial skeleton. Moreover, emergency clinicians should be conversant with wiring techniques to achieve stabilization of the mandibular framework and to control the pain, hemorrhage, and airway patency.


A novel approach to an old problem: tracking dispersed seeds.
Animals are the principal vectors of dispersal for a large number of plant species. Unfortunately it is not easy to discern their movement patterns or the fate of their dispersed seeds. Many animals transport seeds by consuming them and then, some time later, defecating them. Others gather seeds and then store them for later consumption. Both circumstances lead to a set of seeds that have been dispersed in a clumped pattern, which offers a unique opportunity to assess seed movements. We introduce a novel approach that uses maternally inherited seed tissue to quantify the genetic structure of dispersed seed pools. This direct approach measures the genetic variability within and among seed pools, and estimates the scale of seed movement, without requiring a highly polymorphic battery of markers or the location and genotypes of all possible seed parents. We demonstrate this approach with the specific case of seed transport of valley oak (Quercus lobata) acorns by acorn woodpeckers (Melanerpes formicivorus). These territorial birds store acorns in drilled holes in the bark of trees, called granaries. We sampled stored acorns from different granaries, extracted DNA from the maternally inherited pericarp, and then assessed individuals for three microsatellite markers. We found extremely high genetic structure among granaries, a low number of effective seed donors per granary, and restricted seed movement. A maternity analysis performed on the same sample with seven microsatellites confirms acorn transport is limited to approximately 100-m radius. Our findings provide insight into the foraging and seed-dispersal behaviour of acorn woodpeckers, with an approach that can be widely extended to other systems.


Value of serum immunoglobulins in the diagnosis of liver disease.
Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.


A Double-Blind, 12-Week Study to Evaluate the Antiaging Efficacy of a Cream Containing the NFκB Inhibitor 4-Hexyl-1, 3-Phenylenediol and Ascorbic Acid-2 Glucoside in Adult Females.
The 5 main physical manifestations of aged skin are wrinkles, uneven tone, brown spots, loss of elasticity, and dryness. One mechanism resulting in these physical manifestations is increased activity of the nuclear factor kappa B (NFκB) protein. This 12-week, double-blind, placebo-controlled, randomized split-face study compared the antiaging effect and safety of a face cream containing 4-Hexyl-1, 3-phenylenediol, an NFκB inhibitor, and ascorbic acid-2 glucoside versus placebo in adult females aged 45-70 years old. Subjects (n=42) applied active treatment or placebo to the same half face twice daily at home for 12 weeks. Clinical evaluation was carried out by a dermatologist. Subjects carried out similar self-grading assessments. Colorimetric measurements analyzed skin color, and biomechanical skin properties were evaluated. Clinical grading showed that most wrinkle parameters were significantly improved after 8 weeks of active treatment compared with baseline and placebo (P≤.05), with improvements maintained after 12 weeks. Only Marionette wrinkles did not show a significant improvement. Brown spots (color intensity/number), overall photodamage, and most complexion parameters improved significantly after 8 and 12 weeks compared with baseline and placebo (P≤.05). Self-grading yielded similar results compared with baseline. Self-grading did not demonstrate improvements with active treatment versus placebo, except for skin firmness at 8 and 12 weeks (P≤.05). A significant difference was seen with active treatment compared with placebo in all colorimetric parameters (L*, b*, and ITA°) after 8 weeks, and in spot coloration (b*) after 12 weeks (P<.05). Improvements in skin elasticity were not significantly different between treatments. Overall tolerability of active treatment was judged as good. In conclusion, a cream containing 4-Hexyl-1, 3-phenylenediol and ascorbic acid-2 glucoside improves the clinical appearance of aged skin, validating the potential use of NFκB inhibition as a novel, effective method of topical antiaging.

 J Drugs Dermatol. 2016;15(6):750-758.


Synthesis and characterization of nucleoside derivatives, n-(benzoyl)-n-(deoxyguanosin-8-yl)4-aminobiphenyl and n-(2'-deoxyguanosin-8-yl)4-aminobiphenyl via alpha-phenyl-n-(4-biphenyl)nitrone.
Lead tetraacetate (LTA) oxidation of alpha-Phenyl-N-(4-bipheny])nitrone (8) to give a new ultimate carcinogen, N-acetoxy-N-benzoyl-4-aminobiphenyl (9) which was reacted with deoxyguanosine (dG) at pH 6.9 to give nucleoside derivative, N-(benzoyl)-N-(deoxyguanosin-8-yl)-4-aminobiphenyl (10). Following debenzoylation with sodium carbonate-methanol leads to N-(2'-deoxyguanosin-8-yl)-4-aminobiphenyl (11).


On the accuracy of predicting shear viscosity of molecular liquids using the periodic perturbation method.
Non-equilibrium molecular dynamics simulations are performed to calculate shear viscosities of 16 representative molecular liquids using the periodic perturbation method (PPM). A perturbation index is defined to measure the strength of the perturbation. It is identified that the predictions are systematically underestimated using PPM. The origin of the underestimate is the acoustic wave in the liquid density, which is persistent in the simulation box unless the perturbation is completely removed. However, there is a linear correlation between the perturbation indexes and the apparent viscosities, which can be utilized to accurately predict the shear viscosities. Finally, it is demonstrated that general force fields derived based on equilibrium properties can be used to predict the shear viscosities of small molecular liquids with relative errors less than 10%.