[Protein patterns of Pasteurella multocida strains in relation to the animal host and the geographic site of isolation].
Protein patterns from 681 Pasteurella multocida strains of different animal species and distinct geographical regions were analyzed by PAGE. We found 9 protein types taking the most intense band as reference. This band represents a protein of the outer membrane (OMP). In assigning the strains to protein types a relation to animal hosts of the strains was established. The majority of isolates from rabbits (88%) belongs to type P6, which is not found in strains isolated from cattle or pigs. Strains from pigs did not include the protein types P2, P4 and P8, in cattle strains type P9 was absent. The distribution of protein types in bovine isolates was shown to be related to the geographical location. The results are discussed with particular emphasis on immuno-prophylaxis. It appears promising to develop P. m. vaccines specific for certain animal species.


Cloning and characterization of a full-length pronociceptin in zebrafish: evidence of the existence of two different nociceptin sequences in the same precursor.
We report the cloning and molecular characterization of a zebrafish pronociceptin gene, which is expressed in brain and intestine. This fish precursor codes for two different nociceptin peptides, one of which presents an opioid sequence in its N-terminus, being more similar to dynorphin A than its mammalian counterparts. Our results represent a new tool to investigate the function of nociceptin and its receptor in relation to pain and drug addiction.


Jack of all trades? The versatility of RNA in DNA double-strand break repair.
The mechanisms by which RNA acts in the DNA damage response (DDR), specifically in the repair of DNA double-strand breaks (DSBs), are emerging as multifaceted and complex. Different RNA species, including but not limited to; microRNA (miRNA), long non-coding RNA (lncRNA), RNA:DNA hybrid structures, the recently identified damage-induced lncRNA (dilncRNA), damage-responsive transcripts (DARTs), and DNA damage-dependent small RNAs (DDRNAs), have been shown to play integral roles in the DSB response. The diverse properties of these RNAs, such as sequence, structure, and binding partners, enable them to fulfil a variety of functions in different cellular contexts. Additionally, RNA can be modified post-transcriptionally, a process which is regulated in response to cellular stressors such as DNA damage. Many of these mechanisms are not yet understood and the literature contradictory, reflecting the complexity and expansive nature of the roles of RNA in the DDR. However, it is clear that RNA is pivotal in ensuring the maintenance of genome integrity. In this review, we will discuss and summarise recent evidence which highlights the roles of these various RNAs in preserving genomic integrity, with a particular focus on the emerging role of RNA in the DSB repair response.


Interleukin 7 receptor alpha-chain-mutation severe combined immunodeficiency without lymphopenia: correction with haploidentical T-cell-depleted bone marrow transplantation.
Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency characterized by abnormal lymphocyte development and lymphopenia. It often presents during the first year of life with recurrent, opportunistic infections, failure to thrive, and malabsorption. To advocate newborn screening for SCID. We reviewed the case histories of dizygotic twins with Pneumocystis carinii pneumonia (PCP) at the age of 6 months. Full-term fraternal twin girls were born to nonconsanguineous parents. Twin A developed recurrent oral candidiasis at 2 months, followed by pneumococcal bacteremia and PCP. At 5 months she had failure to thrive, but her absolute lymphocyte count was normal (5,887 cells/mm3). Subsequently, twin B presented with acute respiratory distress and was also diagnosed as having PCP; her absolute lymphocyte count was 5,852 cells/mm3. Flow cytometric analysis of peripheral blood lymphocytes from both girls demonstrated a T-B+NK+ phenotype consistent with interleukin 7 receptor alpha-chain-mutation SCID. Both girls received a haploidentical T-cell-depleted bone marrow transplant from their mother. In the interim, a homozygous point mutation in the interleukin 7 receptor alpha-chain gene was identified in twin B. Both parents were found to be carriers. Twin A died of chronic lung disease 8 months after transplantation; twin B is currently thriving. Early diagnosis and treatment of SCID are associated with an increased rate of survival and improved long-term outcome. Some patients with SCID can present without lymphopenia. Thus, we advocate that more sensitive screening tests be considered for inclusion in the newborn screening program currently used in most states.


The insulin-stimulated receptor kinase is a tyrosine-specific casein kinase.
Insulin stimulates a kinase that phosphorylates tyrosines in the insulin receptor; this kinase is tightly associated with the insulin receptor itself. We now show that the insulin-stimulated casein kinase, present in solubilized, lectin-purified receptor preparations from rat liver, is indistinguishable from the insulin receptor kinase. As with phosphorylation of the insulin receptor, insulin selectively enhanced by 2-3-fold the phosphorylation of tyrosines in casein. The insulin-stimulated activities of both kinases were inactivated at 37 degrees C with the same t0.5 of 5 min and were identically affected by alkylating agents. Both receptor and casein kinase activities were specifically coprecipitated by anti-receptor antibodies or by insulin and anti-insulin antibodies. When the latter type of immune complexes were incubated with an excess of insulin, both kinase activities were quantitatively recovered. We therefore conclude that insulin-stimulated receptor and casein phosphorylations are probably catalyzed by a single enzyme which is tightly associated with the receptor itself. Now, by replacing casein for receptor as substrate, it is possible to measure the enzymatic activity of this receptor-related kinase itself, i.e. independent of the receptor as substrate. Detection of this activity is improved in the presence of certain alkylating agents. Use of artificial substrates (in combination with alkylating agents) is particularly important to dissect the functional components of the receptor complex, to study mechanisms of enzyme regulation and especially in situations where the available receptor for study is limited, e.g. fresh or cultured cells from patients.


Effect of repeated use of an implant handpiece on an output torque: An in-vitro study.
This study aimed to evaluate the effect of repeated use of an implant handpiece under an implant placement torque (35 Ncm) and overloading torque condition (50 Ncm) on an output torque. Two types of implant handpiece systems (Surgicpro/X-DSG20L [NSK, Kanuma, Japan] and SIP20/CRB46LN [SAESHIN, Daegu, South Korea]) were used. The output torque was measured using a digital torque gauge. The height and angle (x, y, and z axes) of the digital torque gauge and implant handpiece were adjusted through a jig for passive connection. The experiment was conducted under the setting torque value of 35 Ncm (implant placement torque) and 50 Ncm (overloading torque condition) and 30 times per set; a total of 5 sets were performed (N = 150). For statistical analysis, the difference between the groups was analyzed using the Mann-Whitney U test and the Friedman test was used to confirm the change in output torque (α=.05). NSK and SAESHIN implant handpieces showed significant differences in output torque results at the setting torques of 35 Ncm and 50 Ncm (P<.001). The type of implant handpiece and repeated use influenced the output torque (P<.001). There may be a difference between the setting torque and actual output torque due to repeated use, and the implant handpiece should be managed and repaired during long-term use. In addition, for successful implant results in dental clinics, the output torque of the implant handpiece system should be checked before implant placement.


Sex differences in recall of real or nonsense words.
Women perform better than men on tests of verbal memory, but the nature of this advantage has not been precisely established. To examine whether phonemic memory is a factor in the female advantage, we presented, along with other verbal memory tasks, one containing nonsense words. Overall, there was the expected female advantage. However, an examination of the individual tests showed female superiority in recall of the real words but not the nonsense words.


Significance of Magnetic Resonance Imaging-Assessed Tumor Response for Locally Advanced Rectal Cancer Treated With Preoperative Long-Course Chemoradiation.
To study the predictive and prognostic value of magnetic resonance imaging (MRI)-assessed tumor response after long-course neoadjuvant therapy for locally advanced rectal cancer. This study included 79 patients who had T3 or T4 and/or N+ rectal cancer treated with long-course neoadjuvant chemoradiation. MRI-assessed tumor regression grade (mrTRG) was assessed in 64 patients. MRIs were reviewed by the study radiologist. Surgical and pathologic reports for those who underwent surgery were reviewed. Disease-free survival (DFS) was estimated. Progression during therapy, local relapse, metastasis, and death resulting from the tumor were classified as events. Statistical significance was calculated. In 11 patients, the tumor completely disappeared on MRI; that is, it had an mrTRG of 1. All but one patient, who chose deferred surgery, had a complete pathologic response (pCR), with a positive predictive value of nearly 100%. Of the 20 patients who had an mrTRG of 2 on MRI, six had a pCR. mrTRG 3, mrTRG 4, and mrTRG 5 were detected in 24, six, and three patients, respectively, of whom only one patient had a pCR. The 2-year DFS was 77%. The mrTRG was significant for DFS. The 2-year DFS was 88% for patients with a good response versus 66% for those with a poor response (P = .046). MRI-assessed complete tumor response was strongly correlated with pCR and, therefore, can be used as a surrogate marker to predict absence of viable tumor cells. Our results can be used to implement use of mrTRGs in larger prospective correlative studies as a tool to select patients for whom deferred surgery may be appropriate. Also, those with a poor response may be offered further treatment options before definitive surgery.


[Ultrasound in the emergency department as an extension of the practitioner's clinical examination].
Ultrasound in the emergency department and general practice can be used as an extension of the physical examination, answering simple questions. It requires a short basic training that is easily accessible. This article illustrates with a few examples (kidney, lung and fractures) the interest of this formidable tool becoming unavoidable in the emergency department and general practice.


Priming inhibits the right ear advantage in dichotic listening: implications for auditory laterality.
The typical finding in dichotic listening with verbal stimuli is the right ear advantage (REA), indicating a left hemisphere processing superiority, thus making this an effective tool in studying hemispheric asymmetry. It has been shown that the amplitude of the REA can be modulated by instructions to direct attention to left or right side. The current study attempted to modulate the REA by changing the dichotic listening stimulus situation. In Experiment 1, a consonant vowel (CV) syllable prime was presented binaurally briefly before the dichotic stimuli (consisting of two CVs). The prime could be the same as either the left or right ear dichotic stimulus, or it could be a different stimulus. Participants were instructed to report the CV they heard best from the dichotic syllable pair. The traditional REA was found when the prime was different from both dichotic stimuli. When the prime matched the CV in the left half of the subsequent dichotic pair, the REA was increased, while if the prime matched the right half, the REA was reduced. In order to see at which perceptual stage the modulation takes place, in Experiment 2 the prime was visual, presented on a PC screen. The same effect was seen, although the modulation of the REA was weaker. We propose that the memory trace of the prime is a source of interference, and causes cognitive control of attention to inhibit recognition of stimuli similar to recent distractors. Based on previous studies we propose that this inhibition of attention is performed by prefrontal cortical areas. Similarities to the mechanisms involved in negative priming and implications for auditory laterality studies are pointed out.


Nurse-led palliative care for HIV-positive patients taking antiretroviral therapy in Kenya: a randomised controlled trial.
People with HIV accessing antiretroviral therapy (ART) have persistent physical, psychological, social, and spiritual problems, which are associated with poor quality of life and treatment outcomes. We assessed the effectiveness of a nurse-led palliative care intervention on patient-reported outcomes. We did this randomised controlled trial at a clinic in Kenya for adults with HIV, established on ART, and reporting moderate-to-severe pain or symptoms. We randomly assigned participants (1:1) either to a palliative care intervention (including assessments of physical, emotional, and spiritual wellbeing and quality of life) given six times over 4 months, or to usual care. Participants and investigators were not masked to allocation. The primary outcome was pain (scored on the African Palliative Care Association's African Palliative Outcome Scale). This trial is registered with ClinicalTrials.gov, number NCT01608802. We screened 2070 patients, of whom we enrolled 120: 60 allocated to each group. In the control group, median pain score improved from 1·0 (IQR 0·0-2·0) at baseline to 5·0 (3·0-5·0) at 4 months; in the intervention group, it improved from 1·0 (0·0-2·0) at baseline to 4·5 (3·0-5·0) at 4 months. Compared with standard care, the intervention had no significant effect on pain (coefficient -0·01, 95% CI -0·36 to 0·34, p=0·95). A nurse-led palliative care intervention was not effective in reducing pain. However, person-centred assessment and care delivered by staff who have received additional training had positive effects on self-reported mental health related quality of life and psychosocial wellbeing. Diana Princess of Wales Memorial Fund.


Conversion coefficients for H'(3;Ω) for photons.
In this work, conversion coefficients for the operational quantity H'(3;Ω) have been calculated for both mono-energetic photons from 2 keV to 50 MeV for angles of incidence from 0° up to 180° in steps of 15° (to complement ICRU 57) as well as for photon reference radiation qualities (to complement ISO 4037). Finally, parameters necessary to determine the influence of the air density on the conversion coefficients have been determined.


Structural and Ultrastructural Analysis of the Cervical Discs of Young and Elderly Humans.
Several studies describing the ultrastructure and extracellular matrix (ECM) of intervertebral discs (IVDs) involve animal models and specimens obtained from symptomatic individuals during surgery for degenerative disease or scoliosis, which may not necessarily correlate to changes secondary to normal aging in humans. These changes may also be segment-specific based on different load patterns throughout life. Our objective was to describe the ECM and collagen profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years) presumably-asymptomatic individuals. Thirty cervical discs per group were obtained during autopsies of presumably-asymptomatic individuals. IVDs were analyzed with MRI, a morphological grading scale, light microscopy, scanning electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I, II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of annulus-nucleus distinction and fissures were found in both groups and significantly more severe in G2 as expected. MRI could not detect all morphological changes when compared even with simple morphological inspection. The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with predominantly cartilaginous characteristics, chondrocyte clusters and absent elastic fibers. SEM demonstrated persistence of an identifiable nucleus and Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2 specimens. All collagen types were detected in every disc sector except for collagen X, with the largest area stained by collagens II and IV. Collagen detection was significantly decreased in G2: although significant intradiscal differences were rare, changes may occur faster or earlier in the posterior annulus. These results demonstrate an extensive modification of the ECM with maintenance of basic ultrastructural features despite severe macroscopic degeneration. Collagen analysis supports there is not a "pathologic" collagen type and changes are generally similar throughout the disc. Understanding the collagen and ultrastructural substrate of degenerative changes in the human disc is an essential step in planning restorative therapies.


Factors associated with pain during vascular access intervention therapy.
The objective of this study is to investigate and compare factors associated with pain during vascular access intervention therapy. Fifty patients provided informed consent to participate in a survey of pain by questionnaire after receiving dialysis treatment at our hospital. Balloons for use during the procedure were chosen at random in this prospective randomized control study. A numeric rating scale (NRS) was used for pain assessment. A semi-compliant balloon caused significantly worse pain as compared with the other types of balloons (NRS, 7.67 ± 1.57 vs. 6.02 ± 1.89; p<0.05). There was no correlation between maximum inflation pressure and pain, or between age and pain, and no difference between diabetic and non-diabetic patients. A comparison among vascular dilation locations, as well as a comparison of AVF with AVG also revealed no significant differences. The reason for severe pain with use of the semi-compliant balloon as compared with the other types might have been due to its characteristics during inflation, as increased diameter leads to an increase in pressure. Mismatching of balloon diameter to vascular diameter may also increase pain.


Selective main portal vein clamping to minimize the risk of recurrence after curative liver resection for hepatocellular carcinoma.
Our aim was to compare the postoperative outcomes of partial hepatectomy using Pringle maneuver and selective main portal vein clamping. From January 2004 to December 2006, 169 consecutive patients received liver resection by the same surgical team. The surgical techniques were the same for all patients except for the hepatic vascular inflow occlusion techniques during liver parenchymal transection. Patients either received clamping of the portal triad (PTC group, n=118) or selective main portal vein clamping (PVC group, n=51). Operative time to carry out PVC was significantly longer than PTC (110.6±21.8 vs. 129.6±29.8min), however intraoperative blood loss was the same. There was no significant difference in operative mortality or morbidity rates, although the liver function recovered quicker in the PVC group. Significantly more patients in the PTC group developed HCC recurrence at postoperative one year than the PVC group (60.2% vs. 33.3%). There was no significant difference in overall survival between the 2 groups. Univariate analysis showed that clamping method, tumor size and BCLC grade were risk factors for disease-free survival (DFS) at one year, and multivariate analyses demonstrated clamping method and AFP level as independent risk factors for DFS. Patients subjected to selective portal vein clamping did better than those to Pringle maneuver in the postoperative outcomes. The underlying mechanism may be I/R injury of the liver remnant which might also contribute to an increase in tumor recurrence after liver resection.


Diuretic and natriuretic properties of prestegane B, a mammalian lignan.
The effect of increasing doses of prestegane B, a synthetic lignan, was examined in the anesthetized normal rat, using clearance methodology. Increasing doses of prestegane B 0.5, 1.0, 2.0, and 5.0 mg) were administered intravenously in our separate groups of hydropenic rats. Urine flow increased by 2.8 +/- 0.3, 4.5 +/- 0.5, 7.7 +/- 0.5, and 18.2 +/- 0.8 microliters/min, respectively, above control values. The rise of urinary sodium secretion was of similar magnitude and averaged 0.4 +/- 0.1, 0.8 +/- 0.2, 1.1 +/- 0.3, and 2.4 +/- 0.3 mu eq/min, respectively. No significant change in urinary phosphate excretion was obtained in all groups of rats, and glomerular filtration rate remained constant from control to experimental clearance periods. The natriuretic effect of prestegane B observed in this in vivo model could be related to the inhibition of the Na+-K+-adenosine triphosphate activity demonstrated in vitro in previous studies from our laboratory. The action of this substance is likely to be situated beyond the proximal tubule, since urinary phosphate was not altered. Prestegane B mimics the effects of other endogenous diuretic and natriuretic hormones, but its site of action and its effect on renal hemodynamics are obviously different.


Serological identification of oral Bacteroides spp. by enzyme-linked immunosorbent assay.
A rapid method for identifying black-pigmented oral Bacteroides spp. is described. Species-specific rabbit antisera to Bacteroides gingivalis, B. intermedius, and B. melaninogenicus were used in an enzyme-linked immunosorbent assay to identify clinical isolates of black-pigmented Bacteroides spp. from humans. The results showed excellent agreement with biochemical identification of B. gingivalis and B. intermedius. Only 36% of the B. melaninogenicus isolates were identified with the enzyme-linked immunosorbent assay, suggesting that this group of black-pigmented Bacteroides spp. is made up of more than one serotype. The serological enzyme-linked immunosorbent assay should enable rapid identification of black-pigmented Bacteroides spp. isolated from sites of oral diseases and may also be used to identify the presence of these organisms in complex bacterial mixtures from oral sites.


Functional Redundancy of Septin Homologs in Dendritic Branching.
Septins are cytoskeletal GTPases present in nonpolar heteromeric complexes that assemble in a palindromic fashion from two to eight subunits. Mammalian septins function in several fundamental cellular processes at the membrane-cytoskeleton interface including dendritic branching in neurons. Sequence homology divides the 13 mammalian septin genes into four homology groups. Experimental findings suggest that septin function is redundant among septins from one homology group. This is best understood for the isoforms of the SEPT2 group, which form a homodimer at the center of septin complexes. In vitro, all SEPT2-group septins form recombinant hexameric complexes with two copies of SEPT6 and SEPT7. However, it remains unclear to what extent homologs septins can substitute for each other in specific cellular processes. Here, we use the experimental paradigm of dendritic branching in hippocampal rat neurons to ask, to what extent septins of the SEPT2-group are functionally redundant. Dendritic branching is significantly reduced when SEPT5 is downregulated. In neurons expressing SEPT5-shRNA, simultaneously expressed SEPT2-GFP, and SEPT4-GFP colocalize with SEPT7 at dendritic spine necks and rescue dendritic branching. In contrast, SEPT1-GFP is diffusely distributed in the cytoplasm in SEPT5 downregulated neurons and cannot rescue dendritic branching. Our findings provide a basis for the study of septin-specific functions in cells.


The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine of rats are unchanged from birth to adulthood.
The ontogenetic development of PepT1, NBAT and EAAC1 along the vertical and horizontal axes of the rat small intestine was evaluated using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The proximodistal profiles of mRNA levels showed that PepT1 was evenly distributed, whereas NBAT had greater expression in the proximal part, and EAAC1 in the distal part. These regionalizations were the same from postnatal days 4 to 50. PepT1 and NBAT proteins were detected in the microvilli of enterocytes along the length of the villi. NBAT was also found in the cytoplasm. Surprisingly, EAAC1 was located exclusively in the microvilli of enterocytes in the crypt and the bases of the villi. These protein expression patterns were similar in all parts of the small intestine (proximal, median and distal), at all ages. We conclude that the expression of PepT1, NBAT or EAAC1 are differently regulated according to both the horizontal and vertical axes.


Metastatic Thymoma in a Scarlet Macaw ( Ara macao ).
A 49-year-old female scarlet macaw ( Ara macao ) was presented with a mass in the cervical region. The bird showed no evidence of pain or discomfort, it swallowed food normally, and its breathing pattern was unremarkable. Results of contrast radiographic imaging revealed a well-demarcated mass in the right cervical region not related to the crop. After surgical resection and histopathologic evaluation, a malignant nodular stage of an epithelioid cortical-type thymoma was diagnosed. One year later, metastasis of the thymoma to the lung was diagnosed and confirmed at postmortem examination. The final diagnosis was corrected to malignant nodular stage of an epithelioid cortical-type thymoma with metastasis to the lung. This is the first report in an avian species of a malignant thymoma with metastasis to the lung after complete resection of the initial cervical thymoma and a survival time of 1 year.


Cigarette smoking and risk of atrial fibrillation: the Rotterdam Study.
Cigarette smoking is an important risk factor for cardiovascular disease, but it is unknown whether it also contributes to the risk of atrial fibrillation. The study is part of the Rotterdam Study, a population-based cohort study among subjects aged > or =55 years. The association between cigarette smoking and the risk of atrial fibrillation was examined in 5,668 subjects without atrial fibrillation at baseline. During a median follow-up of 7.2 years, 371 cases of atrial fibrillation were identified. Relative risks (RR) were calculated with 95% CIs using the Cox proportional hazards model, adjusted for age, gender, body mass index, hypertension, systolic blood pressure, serum cholesterol level, diabetes mellitus, left ventricular hypertrophy on the electrocardiogram, prevalent and incident myocardial infarction, prevalent heart failure, and the use of pulmonary medication. After multivariate adjustment, current smokers and former smokers had increased risks of atrial fibrillation as compared to never smokers (RR 1.51, 95% CI 1.07-2.12; and RR 1.49, 95% CI 1.14-1.97, respectively). No differences were found between men and women. The results of this prospective, population-based study show that current and former smoking of cigarettes are associated with increased risk of atrial fibrillation.


Detection of Pesticide Residues in Food Using Surface-Enhanced Raman Spectroscopy: A Review.
Pesticides directly pollute the environment and contaminate foods ultimately being absorbed by the human body. Their residues contain highly toxic substances that have been found to cause serious problems to human health even at very low concentrations. The gold standard method, gas/liquid chromatography combined with mass spectroscopy, has been widely used for the detection of pesticide residues. However, these methods have some drawbacks such as complicated pretreatment and cleanup steps. Recent technological advancements of surface-enhanced Raman spectroscopy (SERS) have promoted the creation of alternative detection techniques. SERS is a useful detection tool with ultrasensitivity and simpler protocols. Present SERS-based pesticide residue detection often uses standard solutions of target analytes in conjunction with theoretical Raman spectra calculated by density functional theory (DFT) and actual Raman spectra detected by SERS. SERS is quite a promising technique for the direct detection of pesticides at trace levels in liquid samples or on the surface of solid samples following simple extraction to increase the concentration of analytes. In this review, we highlight recent studies on SERS-based pesticide detection, including SERS for pesticide standard solution detection and for pesticides in/on food samples. Moreover, in-depth analysis of pesticide chemical structures, structural alteration during food processing, interaction with SERS substrates, and selection of SERS-active substrates is involved.


Cytotoxic effect of hemolytic culture supernatant from Enterococcus faecalis on mouse polymorphonuclear neutrophils and macrophages.
We reconfirmed that the LD50s of hemolytic Enterococcus faecalis strains were significantly less than those of nonhemolytic E. faecalis strains in normal mice. Hemolysin produced by E. faecalis lysed human, horse, rabbit, and mouse erythrocytes, but not cow and sheep erythrocytes. Sphingomyelin comprises a part of the lipid composition of the erythrocyte membrane of all mammalian species tested. But phosphatidylcholine exists only in human, horse, rabbit, and mouse. These two lipids inhibited lysis of horse erythrocytes by hemolytic E. faecalis. Phosphatidylcholine is probably the binding component on the membrane of erythrocytes for E. faecalis hemolysin. The hemolytic culture supernatant lysed not only erythrocytes but also mouse polymorphonuclear neutrophils (PMNs) and macrophages.


Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine lung cancer. SCLC progression and treatment resistance involve epigenetic processes. However, links between SCLC DNA methylation and drug response remain unclear. We performed an epigenome-wide study of 66 human SCLC cell lines using the Illumina Infinium MethylationEPIC BeadChip array. Correlations of SCLC DNA methylation and gene expression with in vitro response to 526 antitumor agents were examined. We found multiple significant correlations between DNA methylation and chemosensitivity. A potentially important association was observed for TREX1, which encodes the 3' exonuclease I that serves as a STING antagonist in the regulation of a cytosolic DNA-sensing pathway. Increased methylation and low expression of TREX1 were associated with the sensitivity to Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901; the CDK inhibitor R-547; the Vertex ATR inhibitor Cpd 45; and the mitotic spindle disruptor vinorelbine. Compared with cell lines of other cancer types, TREX1 had low mRNA expression and increased upstream region methylation in SCLC, suggesting a possible relationship with SCLC sensitivity to Aurora kinase inhibitors. We also identified multiple additional correlations indicative of potential mechanisms of chemosensitivity. Methylation of the 3'UTR of CEP350 and MLPH, involved in centrosome machinery and microtubule tracking, respectively, was associated with response to Aurora kinase inhibitors and other agents. EPAS1 methylation was associated with response to Aurora kinase inhibitors, a PLK-1 inhibitor and a Bcl-2 inhibitor. KDM1A methylation was associated with PLK-1 inhibitors and a KSP inhibitor. Increased promoter methylation of SLFN11 was correlated with resistance to DNA damaging agents, as a result of low or no SLFN11 expression. The 5' UTR of the epigenetic modifier EZH2 was associated with response to Aurora kinase inhibitors and a FGFR inhibitor. Methylation and expression of YAP1 were correlated with response to an mTOR inhibitor. Among non-neuroendocrine markers, EPHA2 was associated with response to Aurora kinase inhibitors and a PLK-1 inhibitor and CD151 with Bcl-2 inhibitors. Multiple associations indicate potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggest targets for combination therapies. While many correlations were not specific to SCLC lineages, several lineage markers were associated with specific agents.


The ultrastructural organization of lamina VI of the spinal cord of the cat. Morphological characterization of the synaptic population.
The synaptic population of lamina VI of the cervical enlargement of the cat spinal cord has been studied analysing 9 different morphological features and determining the incidence of possible combinations. The most important factors to characterize the synaptic boutons were the shape and size of pre-synaptic vesicles and the size of the synaptic boutons. The incidence of features like the density of the synaptic vesicles, the characteristics of the synaptic junction, the occurrence of post-synaptic specializations, the fibrillar or glycogen content of the pre-synaptic bag and the presence of dense-core vesicles, was unimportant. Most of the boutons (69%) contain pleomorphic vesicles (P boutons), 22% round vesicles (R boutons) and 9% flattened vesicles (F boutons). These synaptic types were further subdivided on the basis of the size of their synaptic vesicles. Most of the synapses (84%) were symmetrical, without relation to the shape of the pre-synaptic vesicles. Dense-core vesicles were found in 15% of the synaptic boutons and occurred most frequently in R boutons. On the basis of the analysis performed, we propose to classify synaptic boutons of lamina VI in 13 different types.


Sponge-Inspired Dibromohemibastadin Prevents and Disrupts Bacterial Biofilms without Toxicity.
Since the banning of several families of compounds in antifouling (AF) coatings, the search for environmentally friendly AF compounds has intensified. Natural sources of AF compounds have been identified in marine organisms and can be used to create analogues in laboratory. In a previous study, we identified that dibromohemibastadin-1 (DBHB) is a promising AF molecule, leading to the inhibition of the activity of phenoloxidase, an enzyme involved in the attachment of mussels to surfaces. This paper describes the activity of the DBHB on biofilm formation and its detachment and on bacterial adhesion and communication: quorum sensing. DBHB has an anti-biofilm activity without affecting adhesion of marine and terrestrial bacteria at a dose of 10 µM. Moreover, DBHB activity on quorum sensing (QS) is demonstrated at doses of 8 and 16 µM. The activity of DBHB on QS is compared to kojic acid, a quorum sensing inhibitor already described. This compound is a promising environmentally friendly molecule potentially useful for the inhibition of microfouling.


Increased drop formation frequency via reduction of surfactant interactions in flow-focusing microfluidic devices.
Glass capillary based microfluidic devices are able to create extremely uniform droplets, when formed under the dripping regime, at low setup costs due to their ease of manufacture. However, as they are rarely parallelized, simple methods to increase droplet production from a single device are sought. Surfactants used to stabilize drops in such systems often limit the maximum flow rate that highly uniform drops can be produced due to the lowering interfacial tension causing jetting. In this paper we show that by simple design changes we can limit the interactions of surfactants and maximize uniform droplet production. Three flow-focused configurations are explored: a standard glass capillary device (consisting of a single round capillary inserted into a square capillary), a nozzle fed device, and a surfactant shielding device (both consisting of two round capillaries inserted into either end of a square capillary). In principle, the maximum productivity of uniform droplets is achieved if surfactants are not present. It was found that surfactants in the standard device greatly inhibit droplet production by means of interfacial tension lowering and tip-streaming phenomena. In the nozzle fed configuration, surfactant interactions were greatly limited, yielding flow rates comparable to, but lower than, a surfactant-free system. In the surfactant shielding configuration, flow rates were equal to that of a surfactant-free system and could make uniform droplets at rates an order of magnitude above the standard surfactant system.


Standardization of the Romanowsky staining procedure: an overview.
Commerically available Romanowsky blood stains are variable mixtures of thiazein dyes and brominated fluorescein derivatives with varying degrees of metallic salt contamination in a number of different solvent systems. There is a need for standardized Romanowsky stains of constant composition, which, when used in conjunction with a carefully controlled specimen preparation technique, should give consistent performance. Such a preparation system would be of great value to hematologists in general and would be essential to the validity of data obtained by the digital processing of blood cell images. It is possible to prepare standardized Romanowsky stains as mixtures of two or three dye components, namely, eosin Y, azure B and methylene blue, although azure B has only recently become commercially available at an acceptable degree of purity. The logistic problems of stain standardization are discussed.


Acid-based lignocellulosic biomass biorefinery for bioenergy production: Advantages, application constraints, and perspectives.
The production of chemicals and fuels from renewable biomass with the primary aim of reducing carbon footprints has recently become one of the central points of interest. The use of lignocellulosic biomass for energy production is believed to meet the main criteria of maximizing the available global energy source and minimizing pollutant emissions. However, before usage in bioenergy production, lignocellulosic biomass needs to undergo several processes, among which biomass pretreatment plays an important role in the yield, productivity, and quality of the products. Acid-based pretreatment, one of the existing methods applied for lignocellulosic biomass pretreatment, has several advantages, such as short operating time and high efficiency. A thorough analysis of the characteristics of acid-based biomass pretreatment is presented in this review. The environmental concerns and future challenges involved in using acid pretreatment methods are discussed in detail to achieve clean and sustainable bioenergy production. The application of acid to biomass pretreatment is considered an effective process for biorefineries that aim to optimize the production of desired products while minimizing the by-products.


Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates.
Immunity to autologous protein has not previously been described following nonhuman primate cardiac transplant. Native hearts and cardiac allografts from cynomolgus monkeys were assessed by immunohistology for vimentin, a highly conserved intermediate filament protein. IgM and IgG to vimentin were measured in serial sera from untreated (n = 4) or cyclosporine (CsA)-treated (n = 8, 2 with ATG) cardiac allograft recipients, and in groups treated with anti-CD154 antibody with (n = 6) or without ATG (n = 28). IgM or IgG reactive with vimentin was elaborated within 30 days with unmodified acute rejection (3/4) or in CsA-treated animals (5/6). CD154 blockade did not prevent anti-vimentin IgM (14/28) but tended to delay the IgG response during therapy (anti-CD154: 8/28, p = 0.10 vs. CsA; anti-CD154+ATG: 2/6). CAV and alloantibody were seen in 25 of 26 animals with grafts surviving over 30 days, including seven animals without increasing anti-vimentin antibody. Anti-vimentin antibodies and vascular complement deposition were found in rejected hearts. Acute and chronic alloimmunity disrupt modulation of autoreactivity to vimentin through pathways, which are resistant to CsA, but may be partially regulated by CD154.


Clinical, serologic and instrumental data of ten patients affected by sclerodermatous chronic graft versus host disease: similarities and differences in respect to systemic sclerosis.
Chronic graft versus host disease (cGVHD), the most common late complication of allogeneic haematopoietic stem cell transplantation (HSCT), may present with sclerodermatous lesions resembling in some cases the cutaneous involvement of systemic sclerosis (SSc). Certain pathogenetic findings connect the two diseases. In this report we describe ten subjects affected by cGVHD who underwent the examinations routinely carried out to stage SSc patients. Demographic, clinical, serologic and instrumental data were recorded. These patients showed differences in appearance, extent and progression of the sclerodermatous lesions with greater involvement of the trunk and proximal part of the limbs than the extremities. In seven subjects ANA test was positive; scleroderma-associated autoantibodies were not detected in any of the cases. Moreover, typical organ involvement of SSc was not found. Only one patient developed Raynauds phenomenon after HSCT and only one patient demonstrated a nailfold videocapillaroscopic scleroderma pattern. Except for cutaneous involvement of cGVHD, that may resemble SSc, the clinical features of the two diseases are quite different, suggesting that the fibrotic process characterizing cGVHD and SSc has different etiologies and different initial pathobiologic events.


[Ion channels and asthenospermia].
Asthenospermia is one of the familiar causes of male infertility. Recently, more and more studies have discovered that some diseases result from gene defect and functional variation of ion channels, known as ion channelopathies. Meanwhile, it has been found that even though many diseases do not fall into the category of the ion channelopathies, some links or passages during the disease development are closely related with the malfunction of ion channels, and many drugs can prevent and cure these diseases by acting on ion channels. The relationship of sperm physiology and pathophysiology with ion channels is gradually becoming one of the hot topics in the current researches. Recent progress in the researches on the relationship between sperm motility and ion channels ( including cation channel s and anion channels) is briefly reviewed in this article.


Does Sarcopenia Impact Complications and Overall Survival in Patients Undergoing Radical Nephrectomy for Stage III and IV Kidney Cancer?
To investigate the association of sarcopenia (muscle mass wasting) with complications and survival in patients undergoing radical nephrectomy for advanced kidney cancer. We identified 137 patients with stage III and IV kidney cancer who underwent radical nephrectomy between 2008 and 2012. Preoperative cross-sectional imaging was used to measure total psoas area (TPA) at the level of L3 and controlled for height (m(2)). Sarcopenia was identified as TPA in the lowest gender-specific quartile. Patient characteristics and postoperative complications were compared between sarcopenic and nonsarcopenic patients. Kaplan-Meier survival curve estimates were generated for overall and gender-specific survival. Preoperative cross-sectional imaging was available for 128 patients (93%, 85 men and 43 women). Mean TPA for men was 5.49 cm(2)/m(2) versus 4.27 cm(2)/m(2) for women (P < 0.05). Sarcopenia was associated with risk of Clavien grade III or higher complication (P = 0.03) and node-positive disease (P = 0.01). Median follow-up was 48.3 months. Kaplan-Meier estimates of overall and gender-specific survival were similar between sarcopenic and nonsarcopenic patients. Sarcopenia appears to be associated with risk of major complication after radical nephrectomy for advanced kidney cancer. It was not related to overall survival, however. This preoperative imaging tool may be helpful in preoperative counseling and preparation.


Reconstituted Newcastle disease virus envelopes as a split vaccine.
Isolated envelope proteins of Newcastle disease virus (NDV) were inserted into the lipid bilayer of artificial vesicles to create a viral envelope-like structure. The structure-containing viral antigens at high density elicited a strong immune response, in contrast to purified viral proteins. The artificial envelopes or immunosomes possessed several advantageous properties when used as vaccines. They elicited a faster response and the immunity lasted longer in animals treated with these vesicles than in controls vaccinated with envelope proteins in combination with traditional adjuvants. A further useful feature of the artificial envelopes is that no inflammatory lesions develop at the site of their injection.


An assessment of financial catastrophe and impoverishment from out-of-pocket health care payments in Swaziland.
As the drive towards universal coverage is gaining momentum globally, the need for assessing levels of financial health protection in countries, particularity the developing world, has increasingly become important. In Swaziland, the level of financial health protection is not clearly understood. To assess financial catastrophe and impoverishment from out-of-pocket payments for health services in Swaziland. The nationally representative Swaziland Household Income and Expenditure Survey (2009/2010) dataset is used for the analyses. Data are collected by the Central Statistics Office in Swaziland. The final dataset contains information on 3,167 households (i.e. about 14,145 individuals) out of the anticipated 3,750 households. Financial catastrophe is assessed using an initial threshold that is adjusted to increase with household income (i.e. rank-dependent). Payment for health services is considered catastrophic when they exceed the threshold. Impoverishment is assessed using a national poverty line and an international poverty line ($1.25/day). Using an initial threshold of 10.0% of household expenditure, 9.7% of Swazi households experience financial catastrophe while the proportion is estimated at 2.7% using an initial threshold of 40.0% of non-food expenditure. Between 1.0% and 1.6% of the Swazi population, representing between 10,000 and 16,000 people are pushed below the poverty line because of out-of-pocket payments. These findings indicate that financial health protection is not adequate in Swaziland. If Swaziland is to move towards achieving universal health coverage, there is a need to address the burden created by direct out-of-pocket payments. Among other things, this means that the country needs to consider financing mechanisms that guarantee equitable access to needed quality health services, which do not place undue hardship on the poor and vulnerable.


Improved synthesis and molecular modeling of 4beta,19-dihydroxyandrost-5-en-17-one, an excellent inhibitor of aromatase.
4Beta,19-dihydroxyandrost-5-en-17-one (6) is an excellent competitive inhibitor of estrogen synthetase (aromatase). Alternate, improved synthesis of this inhibitor was established. Treatment of 19-(tert-butyldimethylsilyloxy)androst-4-en-17-one (8) with m-chloroperbenzoic acid gave a 1.4:1 mixture of 4alpha,5alpha-epoxide 9 and its 4beta,5beta-isomer 10. The mixture was reacted with diI. HClO4 in dioxane to produce principally 4beta,5alpha-diol 11 (80%) of which acetylation followed by dehydration with SOCl2 yielded 4beta,19-diacetoxy-5-ene compound 14 in good yield. Alkaline hydrolysis of diacetate 14 gave 4beta,19-diol 6. The minimum energy conformation of the powerfull aromatase inhibitor 6 was obtained with the PM3 method and compared with that of the structurally related diol steroid, 4-ene-5beta,19-diol 3, a weak competitive inhibitor.


RosettaLigand docking with full ligand and receptor flexibility.
Computational docking of small-molecule ligands into protein receptors is an important tool for modern drug discovery. Although conformational adjustments are frequently observed between the free and ligand-bound states, the conformational flexibility of the protein is typically ignored in protein-small molecule docking programs. We previously described the program RosettaLigand, which leverages the Rosetta energy function and side-chain repacking algorithm to account for flexibility of all side chains in the binding site. Here we present extensions to RosettaLigand that incorporate full ligand flexibility as well as receptor backbone flexibility. Including receptor backbone flexibility is found to produce more correct docked complexes and to lower the average RMSD of the best-scoring docked poses relative to the rigid-backbone results. On a challenging set of retrospective and prospective cross-docking tests, we find that the top-scoring ligand pose is correctly positioned within 2 A RMSD for 64% (54/85) of cases overall.


Occupational exposure to airborne dust, respirable quartz and metals arising from refuse handling, burning and landfilling.
Industrial hygiene investigations were conducted in 1983 at a refuse derived fuel (RDF) burning plant, a refuse transfer station and three municipal landfill sites. The field surveys were conducted during the warmer and drier seasons of the year. The investigations included air sampling for total dust, respirable quartz and airborne metals. Bulk samples of soil cover, precipitator/boiler ash and transfer station baghouse fines were analyzed for quartz, elements, asbestos and polychlorinated biphenyls (PCBs) content. Asbestos and PCBs were not detected in any of the bulk samples taken. Quartz content of the bulk samples varied from 8% to 31%. Except for the boiler grate inspector and the precipitator cleaner at the RDF burning plant, exposure to airborne metals was not excessive at the sites tested. One personal sample (at landfill site A) for total dust exceeded 10 mg/m3 out of a total of eighteen personal and area samples. Significant exposure to respirable quartz was found at all the sites (up to 0.20 mg/m3). Respirable quartz exposures in excess of the NIOSH criteria concentration of 0.05 mg/m3 were found in three out of seven personal samples at the RDF burning plant, two out of three personal samples at the refuse transfer station and six out of nine personal samples taken at the three landfill sites.


Intestinal microbial translocation: immunologic consequences and effects of interleukin-4.
Administration of a chemically defined, liquid, elemental diet (CDD) results in intestinal microbial translocation, but the immunologic consequences of this process are unclear. This study evaluated the effects of CDD feeding and interleukin-4 (IL-4) administration on mesenteric lymphocyte, peritoneal macrophage (PMO), and hepatic Kupffer cell (KC) functions. BALB/C mice (n = 60) were randomized to receive a paired feeding of regular diet (RD) or a CDD for 14 days. Mesenteric lymph nodes (MLN) and cecum were cultured for bacteria. Mixed lymphocyte response and cytotoxic T-lymphocyte function of MLN lymphocytes were assayed. PMO and KC were harvested to measure tumor necrosis factor production, macrophage binding of fluorescent-labeled lipopolysaccharide, and Candida albicans phagocytosis (CAP) and killing (CAK); KC-hepatocyte interaction was assessed by hepatocyte protein synthesis. In a second study 75 BALB/c mice received RD, CDD, and CDD+IL-4 (30,000 units/mouse intraperitoneally). MLN lymphocyte and PMO functions were measured and intestinal immunoglobulin A levels were determined. Oral feeding of a CDD resulted in significant impairment of mesenteric lymphocyte mixed lymphocyte response and cytotoxic T-lymphocyte functions and decreased PMO tumor necrosis factor production, fluorescent-labeled lipopolysaccharide binding, CAP, and CAK. KC function was preserved in CDD-fed mice. Administration of IL-4 significantly reduced the incidence of bacteria positive MLN and increased PMO superoxide production, CAP, CAK, and MLN lymphocyte mitogenesis. Use of IL-4 may be beneficial in situations where intestinal microbial translocation contributes to sepsis.


A simple method for the treatment of the inverted nipple.
We introduce a simple method for correcting the inverted nipple in which there is preservation of the lactiferous duct, less surgical invasion, and negligible scar formation. Our method consists of two parts: releasing fibrous tissue around the lactiferous ducts, and keeping the nipple in the everted position with a bolster suture and milk suction pump.


Regulation of insulin gene expression by dexamethasone, Ca2+ and a phorbol ester.
The transcription of the insulin genes in rat pancreatic islets was determined in response to dexamethasone, cholera toxin and Ca2+. Furthermore, the contents of islet insulin mRNA after culture with the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (TPA) were assayed by dot-blot analysis. Dexamethasone and cholera toxin stimulated the rates of insulin gene transcription, whereas the withdrawal of Ca2+ and addition of TPA exerted no effects on insulin gene expression. It is concluded that islet cAMP may be one factor regulating the transcription of the insulin gene in response to nutrient secretagogues, whereas Ca2+ and activation of protein kinase C do not serve such a function.


Differential exposure of the major gangliosides in rabbit thymocytes to Vibrio cholerae neuraminidase.
Neuraminidase treatment of lymphocytes is known to cause changes of cellular responses in several biological phenomena, but the molecules modified on the cell surface by neuraminidase are not known in detail. Rabbit thymocytes, which contain tissue-characteristic gangliosides, were treated with Vibrio cholerae neuraminidase, and the susceptibility of the cell surface sialic acid residues was examined. The amount of sialic acid released from the thymocytes at the highest level was 42.4 nmol per 1 X 10(9) cells, among which 26.5% was from gangliosides. Ninety-three percent of the VI3NeuGc-nLc6Cer, 84% of the IV3NeuGc-nLc4Cer, and 50% of the II3NA2-LacCer in the thymocytes was hydrolyzed to nLc6Cer, nLc4Cer, and LacCer, respectively, but II3NA-LacCer was completely cryptic. Also, among the molecular species of II3NA2-LacCer, C20:0- to C24:0-containing, but not C16:0- to C18:0-containing molecules, were susceptible to neuraminidase. After neuraminidase treatment, nLc4Cer and nLc6Cer became the major glycosphingolipids, and a 15-fold increase of radioactivity incorporated into the glycosphingolipids was observed by the galactose oxidase-sodium borotritide procedure, suggesting that the beta-galactose of the glycosphingolipids produced by neuraminidase treatment is accessibly to the several ligands which are functionally associated with lymphocytes.


Looking ahead through lenses of justice: the relevance of just-world beliefs to intentions and confidence in the future.
Recent research distinguishes the belief in a just-world for the self (BJW-self) from that for others (BJW-others), showing BJW-self to be associated with subjective well-being and BJW-others to be associated with harsh social attitudes. The present research examines the implications of these two types of just-world belief for aspects of motivation and ideation about the future. A sample of 100 young British adults living in assisted accommodation completed measures of BJW-self, BJW-others, life satisfaction and intention to engage in delinquent behaviour. They also listed their personal goals and indicated their confidence that they would attain them. In partial correlation and hierarchical regression analyses, BJW-self predicted confidence in the realization of goals, but was inversely related to delinquent intentions. In contrast, BJW-others was directly related to delinquent intentions but inversely related to confidence in achieving socially legitimate personal goals. These results were not attributable to variations in life satisfaction or in the achievability of participants' goals.


Perceptions of Yoga Therapy Embedded in Two Inpatient Rehabilitation Hospitals: Agency Perspectives.
Inpatient medical rehabilitation has maintained a typical medical-model focus and structure for many years. However, as integrative therapies, such as yoga therapy, emerge as treatments which can enhance the physical and mental health of its participants, it is important to determine if they can be easily implemented into the traditional rehabilitation structure and milieu. Therefore, the purpose of this study was to examine the perceptions of key agency personnel on the feasibility and utility of yoga therapy implemented in inpatient rehabilitation. This study reports the results of focus groups and an individual interview with key stakeholders (administrators and rehabilitation therapists) from two rehabilitation hospitals following the implementation of yoga therapy. Results focused on several key themes: feasibility from the therapist and administrator perspectives, challenges to implementation, and utility and benefit. Overall, the implementation and integration of yoga therapy were positive; however, some programmatic and policy and organizational considerations remain. Implications for practice and future research are provided.


Nuclear-spin selection rules in the chemistry of interstellar nitrogen hydrides.
Nitrogen hydrides are at the root of the nitrogen chemistry in interstellar space. The detailed modeling of their gas phase formation, however, requires the knowledge of nuclear-spin branching ratios for chemical reactions involving multiprotonated species. We investigate in this work the nuclear-spin selection rules in both exothermic and near thermoneutral ion–molecule reactions involved in the synthesis of ammonia, assuming full scrambling of protons in the reaction complexes. The formalism of Oka [ J. Mol. Spectrosc. 2004, 228, 635] is employed for highly exothermic ion–molecule and dissociative recombination reactions. For thermoneutral reactions, a simple state-to-state statistical approach is suggested, which is in qualitative agreement with both quantum scattering and microcanonical statistical calculations. This model is applied to the seven atom reaction NH4(+) + H2, of possible importance in the nuclear-spin thermalization of ammonia.


Patient doses from noncardiac diagnostic and therapeutic interventional procedures.
To determine the patient doses during noncardiac diagnostic and therapeutic interventional procedures carried out in a dedicated angiographic unit. For 1,214 interventional procedures, the technique type, dose-area product (DAP), cumulative dose (CD), and fluoroscopy time were recorded. These procedures were classified into 23 categories (10 diagnostic and 13 therapeutic) that included nine to 259 patients each. For each category, descriptive statistical analysis was used to determine the characteristics of DAP, CD, and fluoroscopy time distributions. The statistical significance of the differences observed between categories in terms of DAP was assessed. For the 23 categories studied, the median DAP values ranged from 0.2 to 176.8 Gycm(2). In comparison with the literature, the mean and median DAP values in this study were within reported ranges for eight categories, greater for three, and less for six, whereas for the remaining six categories no relevant data were found in the literature. Overall, the results of this survey indicate that the techniques used by the interventionalists, the operation skills of radiation technologists, and the performance of the x-ray unit present no obvious deficiencies in terms of patient radiation protection. However, for those procedures in which lower DAP values were found in the literature, it should be further investigated whether patient doses could be reduced without degradation of the diagnostic and therapeutic outcomes.


Transcriptomics of different tissues of blueberry and diversity analysis of rhizosphere fungi under cadmium stress.
Blueberry (Vaccinium ssp.) is a perennial shrub belonging to the family Ericaceae, which is highly tolerant of acid soils and heavy metal pollution. In the present study, blueberry was subjected to cadmium (Cd) stress in simulated pot culture. The transcriptomics and rhizosphere fungal diversity of blueberry were analyzed, and the iron (Fe), manganese (Mn), copper (Cu), zinc (Zn) and cadmium (Cd) content of blueberry tissues, soil and DGT was determined. A correlation analysis was also performed. A total of 84 374 annotated genes were identified in the root, stem, leaf and fruit tissue of blueberry, of which 3370 were DEGs, and in stem tissue, of which 2521 were DEGs. The annotation data showed that these DEGs were mainly concentrated in a series of metabolic pathways related to signal transduction, defense and the plant-pathogen response. Blueberry transferred excess Cd from the root to the stem for storage, and the highest levels of Cd were found in stem tissue, consistent with the results of transcriptome analysis, while the lowest Cd concentration occurred in the fruit, Cd also inhibited the absorption of other metal elements by blueberry. A series of genes related to Cd regulation were screened by analyzing the correlation between heavy metal content and transcriptome results. The roots of blueberry rely on mycorrhiza to absorb nutrients from the soil. The presence of Cd has a significant effect on the microbial community composition of the blueberry rhizosphere. The fungal family Coniochaetaceae, which is extremely extremelytolerant, has gradually become the dominant population. The results of this study increase our understanding of the plant regulation mechanism for heavy metals, and suggest potential methods of soil remediation using blueberry.


Fetopathies associated with exposure to angiotensin converting enzyme inhibitor from Tropaeolum majus L.
The prevalence of the use of herbal medicines is on the rise across the world, especially amongst pregnant women. A fact that draws attention is that many species commonly used by pregnant women, including the Tropaeolum majus L. (Tropaeolaceae), also present inhibitory activity on the angiotensin-converting enzyme (ACE). Herein, we have investigated the effects of T. majus extract (HETM) on fetal development, evaluating its relationship with possible ACE inhibitory activity. Pregnant Wistar rats were treated with different HETM doses (3, 30 and 300 mg/kg/day) from gestational days 8-20. Rats were sacrificed on the day 20 of pregnancy and the following parameters were evaluated: clinical symptoms of maternal toxicity; maternal body weight; feed and water intake; maternal liver, kidney, and ovary weights, maternal ACE activity and aldosterone levels, live fetuses mean; dead fetuses percentage, fetus weight, and fetal malformation. All pregnant rats treated with high HETM doses showed significant reduction in plasma ACE activity accompanied by a decrease in serum aldosterone levels. Moreover, significant changes in fetal development were observed, including growth retardation and renal damage after 20 days of gestation. Thus, data presented demonstrate the significant effects of the use of HETM on fetal development during pregnancy.


[An experimental study of recombinant human erythropoietin on the treatment of acute myocardial infarction in rats].
To observe the treatment and it's mechanisms of rHu-EPO on acute myocardial infarction of SD rats in vitro and vivo. Cardiomyocytes were isolated from neonatal Sprague-Dawley rats. Hypoxia condition and oxidative stress were used to induce apoptosis. rHu-EPO was added to the culture system. Apoptosis was assessed by using Hoechst 33258 dyeing. Apoptosis index (AI) was then calculated. Thirty two rats were divided into three groups including sham operation group (Sham), acute myocardial infarction group (MI) and treated group (MI + EPO). Acute myocardial infarction model was made by ligating the anterior descending coronary artery. rHu-EPO was administered i.p. in MI + EPO group at the dose of 5000 units/kg of body weight immediately after the ligation and the next six days. At the fourteenth day all animals underwent hemodynamic measurements and then executed, the samples were examined with hematoxylin and eosin (HE) stain, immunohistochemistry technique (Bcl-2, Bax) and TdT-mediated dUTP nick end labeling (TUNEL) dyeing. rHu-EPO significantly down-regulated the apoptosis of cardiomyocytes which underwent hypoxia or oxidative stress. In vivo experiment rHu-EPO protected the hemodynamic function of the rats from myocardial infarction and down-regulated the ratio of the positive cells for TUNEL and Bax. The ratio of the positive cells for Bcl-2 was up-regulated by rHu-EPO. These findings suggested rHu-EPO improve myocardial infarction by attenuating apoptosis. Potential mechanism is to up-regulated Bcl-2 expression and down-regulated Bax expression.


The shared signal hypothesis: effects of emotion-gaze congruency in infant and adult visual preferences.
In this study, 4-month-old infants' and adults' spontaneous preferences for emotional and neutral displays with direct and averted gaze are investigated using visual preference paradigms. Specifically, by presenting two approach-oriented emotions (happiness and anger) and two avoidance-oriented emotions (fear and sadness), we asked whether the pattern of emotion-gaze interaction suggested by the shared signal hypothesis (SSH) would also be found with this paradigm. Both age groups demonstrated an ability to discern the approach- and avoidance-oriented emotions, matching them with direct and averted gaze, respectively. Nonetheless, infants showed a greater sensitivity for the congruent emotion-gaze combination in the approach-oriented emotions, while adults were equally sensitive to the gaze-expression congruence for both the approach- and avoidance-oriented emotions. In a follow-up experiment, infants showed no preference for direct or averted gaze in the context of neutral faces. We conclude that the SSH may have validity from infancy, gradually extending from approach-oriented emotions to avoidance-oriented emotions over the course of development.


Mammalian mitogenomic relationships and the root of the eutherian tree.
The strict orthology of mitochondrial (mt) coding sequences has promoted their use in phylogenetic analyses at different levels. Here we present the results of a mitogenomic study (i.e., analysis based on the set of protein-coding genes from complete mt genomes) of 60 mammalian species. This number includes 11 new mt genomes. The sampling comprises all but one of the traditional eutherian orders. The previously unrepresented order Dermoptera (flying lemurs) fell within Primates as the sister group of Anthropoidea, making Primates paraphyletic. This relationship was strongly supported. Lipotyphla ("insectivores") split into three distinct lineages: Erinaceomorpha, Tenrecomorpha, and Soricomorpha. Erinaceomorpha was the basal eutherian lineage. Sirenia (dugong) and Macroscelidea (elephant shrew) fell within the African clade. Pholidota (pangolin) joined the Cetferungulata as the sister group of Carnivora. The analyses identified monophyletic Pinnipedia with Otariidae (sea lions, fur seals) and Odobenidae (walruses) as sister groups to the exclusion of Phocidae (true seals).


Impact of highly active antiretroviral therapy on cognitive processing in HIV infection: cross-sectional and longitudinal studies of event-related potentials.
Patients with HIV infection often complain of cognitive disturbances, which can be related to AIDS dementia or HIV-associated encephalopathy (HIVE). We investigated the impact of highly active antiretroviral therapy (HAART) in comparison with other therapeutic regimens on the progression of these cognitive disturbances as measured by visual event-related potentials (ERP). In a cross-sectional study, 214 patients without secondary neuromanifestation of their infection were divided into four groups with respect to their treatment status for 1 year before examination: (1) without antiretroviral treatment, (2) zidovudine monotherapy, (3) zidovudine in combination with didanosine, zalcitabine, or lamivudine, and (4) HAART. In a prospective longitudinal study, we divided 54 patients into three groups: (1) without antiretroviral treatment, (2) zidovudine monotherapy, and (3) HAART. Latencies of the P2, N2, and P3 components and the amplitude of the P3 component were evaluated. A significant negative correlation between CD4(+) lymphocyte cell count and P3 latency was found in all patients (p < 0.004). In the cross-sectional study, P3 latency was significantly decreased in the HAART group as compared with patients with no antiretroviral treatment (p < 0.01). During the 1-year period of the prospective longitudinal study, the P3 latency significantly increased in patients with no antiretroviral treatment (p < 0.05) and significantly decreased in patients with HAART (p < 0.05). In summary, these results suggest that HAART has an improving therapeutic effect on cognitive processing in HIV-infected patients and is superior to zidovudine monotherapy or dual antiretroviral treatment. Because prolongation of ERP might in part reflect HIVE, we conclude that this condition represents an indication for HAART.


An Experimental Evaluation of Competing Age-Predictions of Future Time Perspective between Workplace and Retirement Domains.
Future time perspective (FTP) is defined as "perceptions of the future as being limited or open-ended" (Lang and Carstensen, 2002; p. 125). The construct figures prominently in both workplace and retirement domains, but the age-predictions are competing: Workplace research predicts decreasing FTP age-change, in contrast, retirement scholars predict increasing FTP age-change. For the first time, these competing predictions are pitted in an experimental manipulation of subjective life expectancy (SLE). A sample of N = 207 older adults (age 45-60) working full-time (>30-h/week) were randomly assigned to SLE questions framed as either 'Live-to' or 'Die-by' to evaluate competing predictions for FTP. Results indicate general support for decreasing age-change in FTP, indicated by independent-sample t-tests showing lower FTP in the 'Die-by' framing condition. Further general-linear model analyses were conducted to test for interaction effects of retirement planning with experimental framings on FTP and intended retirement; While retirement planning buffered FTP's decrease, simple-effects also revealed that retirement planning increased intentions for sooner retirement, but lack of planning increased intentions for later retirement. Discussion centers on practical implications of our findings and consequences validity evidence in future empirical research of FTP in both workplace and retirement domains.


Lifestyle for Brain Health (LIBRA): a new model for dementia prevention.
Modifiable risk factors for dementia were recently identified and compiled in a systematic review. The 'Lifestyle for Brain Health' (LIBRA) score, reflecting someone's potential for dementia prevention, was studied in a large longitudinal population-based sample with respect to predicting cognitive change over an observation period of up to 16 years. Lifestyle for Brain Health was calculated at baseline for 949 participants aged 50-81 years from the Maastricht Ageing Study. The predictive value of LIBRA for incident dementia and cognitive impairment was examined by using Cox proportional hazard models and by testing its relation with cognitive decline. Lifestyle for Brain Health predicted future risk of dementia, as well as risk of cognitive impairment. A one-point increase in LIBRA score related to 19% higher risk for dementia and 9% higher risk for cognitive impairment. LIBRA predicted rate of decline in processing speed, but not memory or executive functioning. Lifestyle for Brain Health (LIBRA) may help in identifying and monitoring risk status in dementia-prevention programmes, by targeting modifiable, lifestyle-related risk factors. Copyright © 2017 John Wiley & Sons, Ltd.


A case of trichogerminoma.
Trichogerminoma is a rare neoplasm which was first described in 1992 and there is still controversy over its inclusion into the spectrum of trichoblastoma. A 79-year-old woman presented with a 5-year history of an asymptomatic nodule on the left posterior neck. Histologically, the lesion revealed a well-demarcated deep dermal nodule surrounded by a pseudocapsule. The tumor was composed of lobules with basophilic cells and some of the lobules displayed a distinctive pattern of densely packed 'cell balls' with peripheral condensation. Immunohistochemically, the tumor cells showed zonal CK5/6 immunoactivity in contrast with the negatively stained 'cell balls'. These characteristics were compatible with the diagnosis of trichogerminoma. We report here on a rare case of a hair germ tumor called trichogerminoma.


Unusual Anatomic Variation: Intradural Conjugation of the Hypoplastic Left ICA and the Enlarged Accessory Meningeal Artery.
The precise definition of the accessory meningeal artery was not available until 1961. It can originate from the maxillary artery or middle meningeal artery and supplies the meatus and membranous portion of the auditory tube, the lateral pharyngeal muscle, and the medial pterygoid muscle; Laterally, it supplies the lateral pterygoid muscle, the extracranial part of the mandibular nerve, the pterygoid venous plexus, and the sphenoid periosteum. Here, we present a 70-year-old male patient who applied to the neurosurgery clinic with complaints of chronic headaches and dizziness. Magnetic resonance angiography and computed tomography angiography showed hypoplasic appearance of the left internal carotid artery and an enlarged accessory meningeal artery variant merging with its ophthalmic segment.


Using the case method to explore characteristics of the clinical reasoning process among ambulance nurse students and professionals.
Clinical reasoning is proposed to represent cognitive processes, skills and decision-making aspects of nursing practice and is important for quality care. It has been suggested that the reasoning processes should be practiced during education to develop decision-making competence among nurses. The aim of the study was to explore and describe clinical reasoning processes at different times during specialist ambulance nurse education and among specialist ambulance nurses. Nurses were invited to participate: at initiation of specialist education (n = 19) and during the final weeks of specialist education (n = 17). We also invited nurses employed in ambulance service (n = 13). At each session a written case was presented for small group discussions. Discussions were recorded and transcribed. A mapping sentence was used to analyse the meaning units of the text capturing different elements of clinical reasoning. For interpretation of data the results were then plotted in a three-dimensional diagram. Professional experiences and reflectivity seemed to influence both the content and the process of clinical reasoning. At initiation of specialist education, more analytical reasoning was used, while the specialist nurses mainly used a non-analytical approach. Specialist nurses incorporated a larger variety of content during their reasoning. Based on the findings here, the case-method might be useful for practicing various clinical reasoning skills and elaborating on decision-making processes.


Depression, dementia, and social supports.
Recent literature on the relationships among dementia, depression, and social support was reviewed, with particular emphasis on the diagnostic differentiation of dementia and depression, and the role of these three entities in elderly individuals with cognitive impairment. Dementia-like symptoms arising in depression and the coexistence of dementia and depression are discussed. Research is necessary to determine more objective criteria for depression and dementia, to provide cognitive and psychiatric testing for elderly individuals, to clarify the diagnostic or prognostic value of the term pseudodementia, and to further elucidate relationships between depression, dementia, and social support.


Assessment of healthcare professionals' perceptions and attitudes towards the COVID-19 pandemic in Turkey.
Determining the healthcare professionals' perceptions and attitudes towards the COVID-19 pandemic will contribute to managing and struggling their efforts against COVID-19. This study aimed to determine the perceptions and attitudes of healthcare professionals who are at the forefront in the fight against this pandemic. In the study, the survey technique used as the data collection method and 216 participants agreed to participate. The questionnaire consisted of three sections. Reliability analysis and descriptive statistical methods used to analyze the data obtained using the SPSS package program. According to the study results, 80.4%of the participants perceive the probability of being infected with the COVID-19 to be very high, and 64%of them consider that the conditions are very favorable for them to be infected. More than half of them are afraid of being infected and believe that if they contract COVID-19, adverse effects may continue for a long time. Furthermore, almost all participants (96.20%) consider personal protective equipment beneficial and will protect them from the COVID-19 as a wise preventive measure. However, 82.30%of the participants stated that using personal protective equipment is uncomfortable, and 76.60%said it is challenging to take care of patients while using personal protective equipment. The current study results show that healthcare professionals are aware of how serious COVID-19 is, understand the importance of protective equipment in protection from COVID-19, and are seriously afraid of COVID-19. Given that the fears of healthcare professionals may have adverse effects on them, it is recommended that healthcare administrators take measures to comfort healthcare workers and ensure that they maintain their positive attitude towards COVID-19.


Comparison of effects of dry versus wet swallowing on Eustachian tube function via a nine-step inflation/deflation test.
The aim of the present study is to evaluate the effect of swallowing type (dry versus wet) on the outcome of a nine-step inflation/deflation tympanometric Eustachian tube function (ETF) test in healthy adults. Fourteen normal healthy volunteers, between 19 and 28 years of age, were included in the study. The nine-step test was performed in two different test procedures: (1) test with dry swallows (dry test procedure) and (2) test with liquid swallows (wet test procedure). If the equilibration of middle-ear (ME) pressure was successful in all the steps of the nine-step test, ETF was considered 'Good'. Otherwise, the test was considered 'Poor', and the test was repeated at a second session. In the dry test procedure, ETF was 'Good' in 21 ears at the first session and in 24 ears after the second session (p > 0.05). However, in the wet test procedure, ETF was 'Good' in 13 ears at the first session and in 21 ears after the second session (p < 0.05). At the first session, ETF was 'Good' in 21 and 13 ears in the dry and wet test procedures, respectively. The difference was statistically significant (p < 0.05). However, after the second session, the overall number of ears with 'Good' tubal function was almost the same in both test procedures (24 ears at dry test procedures versus 21 ears at wet test procedures;p > 0.05). Dry swallowing seems to be more effective for the equilibration of ME pressure. Thus, a single-session dependent evaluation of ETF may be efficient for the dry test procedure of the nine-step test. Swallowing with water may be easier for subjects, but a repetition of the test at a second session may be necessary when the test result is 'Poor'.


DNA methylation at the mu-1 opioid receptor gene (OPRM1) promoter predicts preoperative, acute, and chronic postsurgical pain after spine fusion.
The perioperative pain experience shows great interindividual variability and is difficult to predict. The mu-1 opioid receptor gene (OPRM1) is known to play an important role in opioid-pain pathways. Since deoxyribonucleic acid (DNA) methylation is a potent repressor of gene expression, DNA methylation was evaluated at the OPRM1 promoter, as a predictor of preoperative, acute, and chronic postsurgical pain (CPSP). A prospective observational cohort study was conducted in 133 adolescents with idiopathic scoliosis undergoing spine fusion under standard protocols. Data regarding pain, opioid consumption, anxiety, and catastrophizing (using validated questionnaires) were collected before and 2-3 months postsurgery. Outcomes evaluated were preoperative pain, acute postoperative pain (area under curve [AUC] for pain scores over 48 hours), and CPSP (numerical rating scale >3/10 at 2-3 months postsurgery). Blood samples collected preoperatively were analyzed for DNA methylation by pyrosequencing of 22 CpG sites at the OPRM1 gene promoter. The association of each pain outcome with the methylation percentage of each CpG site was assessed using multivariable regression, adjusting for significant (P<0.05) nongenetic variables. Majority (83%) of the patients reported no pain preoperatively, while CPSP occurred in 36% of the subjects (44/121). Regression on dichotomized preoperative pain outcome showed association with methylation at six CpG sites (1, 3, 4, 9, 11, and 17) (P<0.05). Methylation at CpG sites 4, 17, and 18 was associated with higher AUC after adjusting for opioid consumption and preoperative pain score (P<0.05). After adjusting for postoperative opioid consumption and preoperative pain score, methylation at CpG sites 13 and 22 was associated with CPSP (P<0.05). Novel CPSP biomarkers were identified in an active regulatory region of the OPRM1 gene that binds multiple transcription factors. Inhibition of binding by DNA methylation potentially decreases the OPRM1 gene expression, leading to a decreased response to endogenous and exogenous opioids, and an increased pain experience.


[Role of calcineurin in the progression of cardiac hypertrophy in renovascular hypertensive rats].
The present study was to investigate the mRNA, protein expression and the activity of calcineurin in the hypertrophic heart, and to determine the effect of calcineurin inhibitor--cyclosporine A (CsA) on the regression of cardiac hypertrophy in renovascular hypertensive rats. Renovascular hypertension was induced by two kidney-one clip methods. Two months after the operation, cardiac hypertrophy was determined by histological analysis performed in some rats (2K1C-2M), then the rats were subdivided into 2 groups: (1) 3-month old two kidney-one clip group (2K1C-3M) with rats receiving 0.9% NaCl per day for one month, and (2) CsA-treated group with rats treated with CsA for one month. Sham-operated rats were used as control. The ratio of the left ventricular weight to tibial length (LVW/TL), the area of cardiac myocyte, mRNA and protein expression and the activity of calcineurin were determined. Both the LVW/TL and the cardiomyocyte area were significantly larger in 2K1C-2M and 2K1C-3M rats than in age-matched sham-operated rats. Treatment with CsA significantly attenuated the increase in the LVW/TL as well as the cardiomyocyte area. The mRNA, protein expression and the activity of calcineurin were significantly higher in 2K1C-2M and 2K1C-3M rats than those in the age-matched sham-operated rats, while the elevation of mRNA, protein expression and activity of calcineurin were significantly suppressed in the CsA-treated rats. In conclusion, calcineurin plays a role in the progression of cardiac hypertrophy in renovascular hypertensive rats. The inhibition of calcineurin can reverse cardiac hypertrophy.


Human heart transplantation. Rejection risk factors.
The present analysis of risk factors in human cardiac transplantation is based on a review of 682 endomyocardial biopsies from 52 grafts in 51 recipients. Acute rejection was diagnosed in 149 biopsies (21.8%). The cumulative 1-year graft survival was 91.5 4%. Four out of seven patients died of irreversible rejection. An univariate analysis using the linearized rate of total rejection showed significantly higher frequency of acute rejection when donor and recipient differed for two HLA-DR antigens compared to zero or one HLA antigen disparity (p less than 0.01), as well as in patients treated with low dose steroids, Cyclosporine (CyA) and Azathioprine (p less than 0.01), compared to treatment with CyA high dose steroids. Other risk factors were graft ischemia extending 60 minutes (p less than 0.05) and patient age exceeding 40 years (p less than 0.05). A multivariate analysis using the competing risk hazard model for irreversible (= lethal) rejection was performed. The presence of two HLA-DR mismatches between donor and recipient was found to be an independent risk factor (relative risk = 8.9), and immunosuppression with CyA and high dose steroids without Azathioprine another (relative risk = 15.3). Potential risk factors such as donor and recipient sex, donor age, prior surgery and time on extracorporeal circulation were not of significant prognostic value neither in regard to rejection nor irreversible rejection.


GA101 induces NK-cell activation and antibody-dependent cellular cytotoxicity more effectively than rituximab when complement is present.
Both complement and antibody-dependent cellular cytotoxicity (ADCC) contribute to the clinical efficacy of anti-CD20 monoclonal antibody (mAb) therapy. Paradoxically, the C3b component of complement can block interaction between mAb and natural killer (NK) cells. The present study compared the effect of complement on the ability of two anti-CD20 mAbs, rituximab and GA101, to activate NK cells and mediate ADCC. Complement blocked adherence of NK cells to rituximab, but had little effect on NK binding to GA101. Target cells coated with rituximab or GA101 were able to activate NK cells in the absence of serum. Complement in serum blocked NK activation induced by rituximab, but not GA101. Complement blocked rituximab-induced NK-cell mediated ADCC, but not GA101-induced ADCC. These results demonstrate that the decreased ability of GA101 to fix complement relative to rituximab results in an enhanced ability of GA101 to bind to NK cells, activate NK cells and induce ADCC when serum is present.


Association of congenital heart defects with season and population density.
Infants born in New England with congenital heart defects were examined for association with time of year or population density. Moderate seasonal peaks in births were noted for complex ventricular septal defect, malposition defects, and transposition of the great arteries. Positive associations with population density were found for pulmonary atresia with ventricular septal defect, ventricular septal defect with secondary anomalies, and tricuspid atresia.


Attention in post-lexical processes of utterance production: Dual-task cost in younger and older adults.
There is a general agreement that speaking requires attention at least for conceptual and lexical processes of utterance production. However, conflicting results have been obtained with dual-task paradigms using either repetition tasks or more generally tasks involving limited loading of lexical selection. This study aimed to investigate whether post-lexical processes recruit attentional resources. We used a new dual-task paradigm in a set of experiments where a continuous verbal production task involved either high or low demand on lexical selection processes. Experiment 1 evaluates lexical and post-lexical processes with a semantic verbal fluency task, whereas Experiments 2 and 3 focus on post-lexical processes with a non-propositional speech task. In each experiment, two types of non-verbal secondary tasks were used: processing speed (simple manual reaction times) or inhibition (Go/No-go). In Experiment 1, a dual-task cost was observed on the semantic verbal fluency task and each non-verbal task. In Experiment 2, a dual-task cost appeared on the non-verbal tasks but not on the speech task. The same paradigm was used with older adults (Experiment 3), as increased effort in post-lexical processes has been associated with ageing. For older adults, a dual-task cost was also observed on the non-propositional verbal task when speech was produced with the inhibition non-verbal task. The results suggest an attentional cost on post-lexical processes and strategic effects in the resolution of the dual-task.


Lichen Sclerosus: Incidence and Risk of Vulvar Squamous Cell Carcinoma.
The association between lichen sclerosus and vulvar squamous cell carcinoma (VSCC) has long been recognized, but large epidemiologic studies are lacking. Data of women diagnosed with vulvar pathology in the Netherlands were retrieved from the Dutch Pathology Registry. All vulvar pathology reports of this historical cohort were reviewed to construct a research database, including 3,038 women with lichen sclerosus diagnosed between 1991 and 2011. The incidence rate of lichen sclerosus and the cumulative incidence of VSCC among women with lichen sclerosus were estimated. Between 1991 and 2011, the incidence rate of lichen sclerosus increased from 7.4 to 14.6 per 100,000 woman-years. The median age at time of lichen sclerosus diagnosis was 59.8 years and the cumulative VSCC incidence was 6.7%. The 10-year VSCC incidence in women with lichen sclerosus was associated with concurrent vulvar intraepithelial neoplasia (VIN; 18.8% in women with VIN and 2.8% in women without VIN) and age at time of lichen sclerosus diagnosis (5.9% in women of ≥70 years, 3% in women between 50 and 70 years, and 1.8% in women <50 years). The effects of presence of VIN and age remained significant in adjusted Cox regression analysis. This historical cohort showed a nearly 100% increase in incidence of lichen sclerosus between 1991 and 2011. Concurrent VIN and age ≥70 years at time of lichen sclerosus diagnosis are important risk factors for vulvar cancer development. The incidence of lichen sclerosus is rising and special attention is needed in particular in women with concurrent VIN because of their high risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(8); 1224-30. ©2016 AACR.


The patella: A mechanical determinant of coordination during vertical jumping.
The patella is traditionally understood to be a "joint spacer" that increases the moment arm of the patellar tendon. This characterisation is unsatisfactory as it fails to explain the more interesting characteristics of the patella: 1) that the changing pivot point of the patella causes the ratio of quadriceps to patellar tendon force to almost double as the knee flexes; 2) that the patellar tendon exerts an anteriorly directed force on the tibia when the knee is extended but this switches to a posterior draw as the knee flexes; and 3) that the presence of the patella allows the quadriceps to exert different moments on the femur and tibia. Here, I use a simple, model of the geometry of the knee to calculate the changes in the effective moment arms of the quadriceps on the femur and tibia as the knee extends during vertical jumping. These effective moment arms are then contrasted with the actual changes in moments seen during a vertical jump. This analysis demonstrates that the changing geometry of the knee alone can explain 93% (p < 0.05) of the variance in the characteristic femoral to tibial pattern of moment production during jumping - suggesting that the mechanics of the patella have a crucial influence on the coordination of jumping. These results lend support to the contention that mechanical considerations play a pivotal role in the control of movement by creating a stronger imperative towards a particular movement solution than might be suggested by the large degree of redundancy in the neuromuscular system. This idea is consistent with dynamic systems theories of motor control, i.e. the mechanical structure of the musculoskeletal system itself is important in the organisation of movement (so called mechanical intelligence).


Design and characterization of antithrombotic ClEKnsTy-Au nanoparticles as diagnostic and therapeutic reagents.
Thrombosis can cause various cardiovascular diseases, which seriously endanger human life. Development of diagnostic and therapeutic reagents for thrombosis at an early stage would be helpful for the improvement of treatment and the reduction of mortality. In the present study, based on an antithrombotic peptide lEKnsTy (lowercase letters represent D-amino acid residues), a diagnostic and therapeutic reagent targeting collagen and the early stage of thrombosis was proposed, where cysteine was introduced into the amino terminus of lEKnsTy to prepare ClEKnsTy, followed by coupling with AuNPs to prepare nanoconjugate AuNP-Cl. The binding of AuNP-Cl on the collagen surface was then confirmed by the molecular dynamics simulations of the binding of ClEKnsTy on collagen, and the experimental results of the binding of AuNP-Cl on collagen. The inhibition of platelet adhesion on the collagen surface by AuNP-Cl was also confirmed. Moreover, the good imaging ability of AuNP-Cl was confirmed by dark-field microscopy. These results indicated that AuNP-Cl was a potential effective diagnostic and therapeutic reagent targeting collagen, which would be helpful for the research and development of multifunctional antithrombotic reagents.


Cysteine protease and cystatin expression and activity during soybean nodule development and senescence.
Nodules play an important role in fixing atmospheric nitrogen for soybean growth. Premature senescence of nodules can negatively impact on nitrogen availability for plant growth and, as such, we need a better understanding of nodule development and senescence. Cysteine proteases are known to play a role in nodule senescence, but knowledge is still fragmented regarding the function their inhibitors (cystatins) during the development and senescence of soybean nodules. This study provides the first data with regard to cystatin expression during nodule development combined with biochemical characterization of their inhibition strength. Seventy nine non-redundant cysteine protease gene sequences with homology to papain, belonging to different subfamilies, and several legumain-like cysteine proteases (vacuole processing enzymes) were identified from the soybean genome assembly with eighteen of these cysteine proteases actively transcribed during nodule development and senescence. In addition, nineteen non-redundant cystatins similar to oryzacystatin-I and belonging to cystatin subgroups A and C were identified from the soybean genome assembly with seven actively transcribed in nodules. Most cystatins had preferential affinity to cathepsin L-like cysteine proteases. Transcription of cystatins Glyma05g28250, Glyma15g12211, Glyma15g36180 particularly increased during onset of senescence, possibly regulating proteolysis when nodules senesce and undergo programmed cell death. Both actively transcribed and non-actively transcribed nodule cystatins inhibited cathepsin-L- and B-like activities in different age nodules and they also inhibited papain and cathepsin-L activity when expressed and purified from bacterial cells. Overlap in activities and specificities of actively and non-actively transcribed cystatins raises the question if non-transcribed cystatins provide a reservoir for response to particular environments. This data might be applicable to the development of strategies to extend the active life span of nodules or prevent environmentally induced senescence.


The effect of the beta2-adrenoceptor agonist prodrug BRL-47672 on cardiovascular function, skeletal muscle myosin heavy chain, and MyoD expression in the rat.
The intracellular mechanisms that regulate changes in postnatal myosin heavy chain (MHC) expression are not well established. The major objective of this study was to examine the acute and chronic effects of administration of BRL-47672, the prodrug of the beta2-adrenoceptor agonist clenbuterol on MHC and MyoD transcription factor expression to determine whether or not changes in MHC composition are preceded by changes in MyoD protein expression. To assess to what extent the use of BRL-47672 minimized cardiovascular effects, its hemodynamic actions were compared with those of clenbuterol. The effect of BRL-47672 on heart rate, mean arterial blood pressure, and hindquarters vascular conductance was significantly less than that of clenbuterol after a single i.p. injection (250 microg kg(-1) body mass). In the main study, 4-week old rats were given BRL-47672 (900 microg kg(-1) body mass) or an equivalent volume of saline (control) daily for 1, 28, or 56 days. Soleus muscle (SOL) was excised and MHC and MyoD expression analyzed. After 4 weeks, SOL from the BRL-47672-treated animals had significantly faster MHC composition (49 +/- 2% MHCIIA) compared with those from the control animal (39 +/- 3% MHCIIA, P <0.05). MyoD expression increased by 40% after 1 day of BRL-47672 administration (P <0.05) before a change in MHC composition. In conclusion, these data suggest that increased expression of fast-type MHCIIA expression in rat SOL induced by BRL-47672 administration is preceded by changes in the level of MyoD transcription factor expression.