K(V)7/KCNQ channels are functionally expressed in oligodendrocyte progenitor cells.
K(V)7/KCNQ channels are widely expressed in neurons and they have multiple important functions, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Mutations in KCNQ genes have been demonstrated to associate with human neurological pathologies. However, little is known about whether K(V)7/KCNQ channels are expressed in oligodendrocyte lineage cells (OLCs) and what their functions in OLCs. In this study, we characterized K(V)7/KCNQ channels expression in rat primary cultured OLCs by RT-PCR, immunostaining and electrophysiology. KCNQ2-5 mRNAs existed in all three developmental stages of rat primary cultured OLCs. K(V)7/KCNQ proteins were also detected in oligodendrocyte progenitor cells (OPCs, early developmental stages of OLCs) of rat primary cultures and cortex slices. Voltage-clamp recording revealed that the I(M) antagonist XE991 significantly reduced K(V)7/KCNQ channel current (I(K(Q))) in OPCs but not in differentiated oligodendrocytes. In addition, inhibition of K(V)7/KCNQ channels promoted OPCs motility in vitro. These findings showed that K(V)7/KCNQ channels were functionally expressed in rat primary cultured OLCs and might play an important role in OPCs functioning in physiological or pathological conditions.


[The cystic component in the renal cancer: conceptual overiew].
The renal cancer (RC) cystic component is on the radiological tests and could be consolidate with pathological analysis. The concepts "cystic renal cancer" or "cystic renal tumor" contain a group of entities range from cystic grown pattern RCs to pseudocystic tumors as well as cystic renal diseases coinciding with the RC. The CR and the cystic renal diseases have a great variety to sorts of presentations, giving different ways of radiological images, blending solid and cystic areas. Some papers use indiscriminately expression "cystic" without pathologic proof. Just cystic grown pattern RCs and multilocular cystic carcinoma could be named "cystic renal tumors". For de rest, especially over image study, is more suitable to use expressions as "renal tumor of cystic configuration", while pathologic report are available.


How the Porous Transport Layer Interface Affects Catalyst Utilization and Performance in Polymer Electrolyte Water Electrolysis.
Cost reduction and fast scale-up of electrolyzer technologies are essential for decarbonizing several crucial branches of industry. For polymer electrolyte water electrolysis, this requires a dramatic reduction of the expensive and scarce iridium-based catalyst, making its efficient utilization a key factor. The interfacial properties between the porous transport layer (PTL) and the catalyst layer (CL) are crucial for optimal catalyst utilization. Therefore, it is essential to understand the relationship between this interface and electrochemical performance. In this study, we fabricated a matrix of two-dimensional interface layers with a well-known model structure, integrating them as an additional layer between the PTL and the CL. By characterizing the performance and conducting an in-depth analysis of the overpotentials, we were able to estimate the catalyst utilization at different current densities, correlating them to the geometric properties of the model PTLs. We found that large areas of the CL become inactive at increasing current density either due to dry-out, oxygen saturation (under the PTL), or the high resistance of the CL away from the pore edges. We experimentally estimated the water penetration in the CL under the PTL to be ≈20 μm. Experimental results were corroborated using a 3D-multiphysics model to calculate the current distribution in the CL and estimate the impact of membrane dry-out. Finally, we observed a strong pressure dependency on performance and high-frequency resistance, which indicates that with the employed model PTLs, a significant gas phase accumulates in the CL under the lands, hindering the distribution of liquid water. The findings of this work can be extrapolated to improve and engineer PTLs with advanced interface properties, helping to reach the required target goals in cost and iridium loadings.


Cell surface alpha-D-galactopyranosyl end groups: use as markers in the isolation of murine tumor cell lines with different cancer-causing potentials.
Cell lines from 2 3-methylcholanthrene-induced murine tumors were established in culture and examined for reactivity with Griffonia simplicifolia isolectin B4 (GS I-B4), a lectin that has strict specificity for terminal alpha-D-galactopyranosyl residues. Virtually all of the cells in both populations were strongly reactive, indicating the presence of this carbohydrate on the cell surface. Both tumor lines were exposed to human serum with antibodies to the blood group B antigen. More than 99.99% of the exposed cells were killed by this treatment. This is not surprising, because terminal alpha-D-galactopyranosyl residues comprise the blood group B antigen. From the few surviving cells, it was possible to establish cell lines resistant to the cytotoxic effects of the anti-blood group B antibodies. A total of 4 cell lines were independently obtained in this way. The human serum-resistant lines showed no detectable reactivity with GS I-B4, indicating that alpha-D-galactopyranosyl-deficient cell lines had been obtained. The parent and variant cells were compared for reactivity with anti-laminin antibodies. Both parent lines showed strong reactivity by immunofluorescence in the viable state, whereas the alpha-D-galactopyranosyl-deficient lines showed no reactivity. The parent and variant lines were also compared with regard to in vitro and in vivo growth. The alpha-D-galactopyranosyl-deficient lines had reduced in vitro growth capacity relative to the parent lines. More importantly, in contrast to the parent lines, these lines were significantly less tumorigenic than the parent lines when injected into syngeneic mice and did not metastasize spontaneously.


Torulopsis glabrata in the neonate: an emerging fungal pathogen.
Fungi are becoming increasingly common nosocomial pathogens in the neonatal intensive care patient. The fungus Torulopsis glabrata, a common skin inhabitant, is a potential pathogen in the high-risk neonate. In this report we have reviewed the cases of two infants in which systemic T glabrata infection was diagnosed. One patient survived without apparent sequelae; the other died before diagnosis and initiation of therapy. Five other cases of systemic infection by T glabrata in neonates have been reported previously, with only one survivor. Early recognition and treatment of this nearly uniformly fatal infection is imperative.


V2-like receptors mediate cerebral blood flow increase following vasopressin administration in rats.
Experiments were performed on anesthetized (chloral hydrate) Wistar rats to determine the effect of vasopressin (VP) on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), cerebrovascular resistance (CVR), and mean arterial blood pressure (MAP) before and after V1 or V2 VP receptor blockade. Influence of synthetic V2 receptor agonist (dVDAVP) on these variables was also tested. Intracarotid administration of 5 mU VP (Pitressin, n = 15) significantly increased CBF by 28% and CMRO2 by 27% and reduced CVR by 20% of control value. Intravenous (i.v.) infusion of dEt2AVP (V1 antagonist, 15 micrograms kg-1 h-1, n = 7) did not influence the effect of VP on CBF, CMRO2, and CVR but abolished MAP increase after VP. Intravenous (i.v.) infusion of d(CH2)5[D-Ile2,Abu4] AVP (V2 antagonist, 15 micrograms kg-1 h-1, n = 8) abolished the effect of VP on CBF, CMRO2, and CVR without changing its influence on MAP. Intracarotid administration of 12.5 ng dVDAVP (n = 7) increased CBF by 43% and CMRO2 by 29% and decreased CVR by 29% of control value. MAP was not affected. The results suggest that VP-induced CBF increase is, at least partly, caused by the rise of CMRO2 and mediated by V2-like receptors.


Effects of vision and lumbar posture on trunk neuromuscular control.
The goal of this study was to determine the effects of vision and lumbar posture on trunk neuromuscular control. Torso perturbations were applied with a pushing device while the subjects were restrained at the pelvis in a kneeling-seated position. Torso kinematics and the muscle activity of the lumbar part of the M. Longissimus were recorded for 14 healthy subjects. Four conditions were included: a flexion, extension and neutral lumbar posture with eyes closed and the neutral posture with eyes open. Frequency response functions of the admittance and reflexes showed that there was no significant difference between the eyes open and eyes closed conditions, thereby confirming that vision does not play a role in the stabilization of the trunk during small-amplitude trunk perturbations. In contrast, manipulating posture did lead to significant differences. In particular, the flexed condition led to a lower admittance and lower reflex contribution compared to the neutral condition. Furthermore, the muscle pre-activation (prior to the onset of the perturbation) was significantly lower in the flexed posture compared to neutral. This confirms that flexing the lumbar spine increases the passive tissue stiffness and decreases the contribution of reflex activity to trunk control.


Phyto-relief CC: prevention of cold episodes. Control of signs/symptoms and complications.
The aim of this supplement, registry study was to evaluate the effects of the use of standardized, oral supplement (Phyto-Relief CC, Alchem). Phyto-Relief CC includes anti-inflammatory, anti-oxidant and anti- edema natural compounds. Increased salivation produced by ginger is useful in the prevention of cold episodes and on signs and symptoms associated to the episodes by increasing saliva and its content (i.e. lysozyme). Main targets of the study were the evaluation of the occurrence of episodes and the reduction of signs/symptoms, the reduction of days of disease, the reduction in the use of other treatments and the control of cold-related complications. The two resulting registry groups were comparable. There were 5 full episodes (lasting at least 3 days) of cold in 61 registry subjects (8.1%) in comparison with 17 cases in 63 subjects (26.98%) in controls. Phyto-Relief CC subjects - even in this time-limited and small study population registry - had 30.1% of the episodes of the control group with a reduction of 69.88% of the cold episodes (p<0.0221). Also in the following, continuation, third week only 3 episodes of cold were recorded in the Phyto- Relief CC group vs 6 (50% reduction) observed in controls. All the other chosen parameters were better in the supplement group (p<0.05). Affected days (2.9;1.1 vs 4.6; 1.2 in controls), lost working days (0.58;0.5 vs 1.02;0.43 in controls. The use of any other OTC product, nasal drops, aspirin, Vit C, antihistamines, aerosols, the number of complications after 4 days were better in the Phyto-Relief CC group. Disease 'extension' (to >4 days), particularly tracheal and bronchial extension were significantly less frequent (p<0.05) with the supplement. No safety or tolerability problem was observed. In conclusion this preliminary study shows that Phyto-Relief CC may help the evolution of cold if used early, when initial symptoms could be identified. More specific evaluations and larger prevention studies are needed.


P2X receptors: New players in cancer pain.
Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2X receptor are adenosine triphosphate (ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesis of cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.


Frequency of incomplete urolith removal, complications, and diagnostic imaging following cystotomy for removal of uroliths from the lower urinary tract in dogs: 128 cases (1994-2006).
To determine the effectiveness of cystotomy for complete removal of urocystoliths and urethroliths in dogs, the types and frequency of diagnostic imaging performed to verify complete urolith removal, the complications that develop as a result of cystotomy, and predictors of each of these variables. Retrospective case series. 128 dogs that underwent a cystotomy for removal of urocystoliths, urethroliths, or both from 1994 through 2006. The following data were obtained from medical records: sex, body weight, number and locations of lower urinary tract uroliths identified in preoperative and postoperative imaging reports, types of imaging used for urolith detection, number of uroliths recovered during cystotomy, quantitative urolith composition, and major complications attributable to cystotomy. Objective criteria were applied to determine whether a cystotomy failed or succeeded and whether appropriate imaging was performed. Associations between potential prognostic factors and outcomes were statistically assessed. Effectiveness of cystotomy could be determined in 44 (34%) dogs, of which 9 (20%) had incomplete removal of uroliths. Appropriate postoperative imaging was performed for only 19 (15%) dogs, of which 8 had incomplete removal. Dogs with both urethroliths and urocystoliths were more likely to have a failed cystotomy than dogs with only urethroliths or urocystoliths. Complications developed in 5 (4%) dogs. Cystotomy was a safe and effective surgical procedure for removal of lower urinary tract uroliths in most dogs. Failure to remove all uroliths occurred in a substantial percentage of patients.


A Biomechanical Comparison of Allograft Tendons for Ligament Reconstruction.
Allograft tendons are frequently used for ligament reconstruction about the knee, but they entail availability and cost challenges. The identification of other tissues that demonstrate equivalent performance to preferred tendons would improve limitations. Hypothesis/Purpose: We compared the biomechanical properties of 4 soft tissue allograft tendons: tibialis anterior (TA), tibialis posterior (TP), peroneus longus (PL), and semitendinosus (ST). We hypothesized that allograft properties would be similar when standardized by the looped diameter. Controlled laboratory study. This study consisted of 2 arms evaluating large and small looped-diameter grafts: experiment A consisted of TA, TP, and PL tendons (n = 47 each) with larger looped diameters of 9.0 to 9.5 mm, and experiment B consisted of TA, TP, PL, and ST tendons (n = 53 each) with smaller looped diameters of 7.0 to 7.5 mm. Each specimen underwent mechanical testing to measure the modulus of elasticity (E), ultimate tensile force (UTF), maximal elongation at failure, ultimate tensile stress (UTS), and ultimate tensile strain (UTε). Experiment A: No significant differences were noted among tendons for UTF, maximal elongation at failure, and UTϵ. UTS was significantly higher for the PL (54 MPa) compared with the TA (44 MPa) and TP (43 MPa) tendons. E was significantly higher for the PL (501 MPa) compared with the TP (416 MPa) tendons. Equivalence testing showed that the TP and PL tendon properties were equivalent or superior to those of the TA tendons for all outcomes. Experiment B: All groups exhibited a similar E. UTF was again highest in the PL tendons (2294 N) but was significantly different from only the ST tendons (1915 N). UTϵ was significantly higher for the ST (0.22) compared with the TA (0.19) and TP (0.19) tendons. Equivalence testing showed that the TA, TP, and PL tendon properties were equivalent or superior to those of the ST tendons. Compared with TA tendons, TP and PL tendons of a given looped diameter exhibited noninferior initial biomechanical strength and stiffness characteristics. ST tendons were mostly similar to TA tendons but exhibited a significantly higher elongation/UTϵ and smaller cross-sectional area. For smaller looped-diameter grafts, all tissues were noninferior to ST tendons. In contrast to previous findings, PL tendons proved to be equally strong. The results of this study should encourage surgeons to use these soft tissue allografts interchangeably, which is important as the number of ligament reconstructions performed with allografts continues to rise.


Comparative transcriptome analysis of the different tissues between the cultivated and wild tomato.
Although domesticated tomato is cultivated by wild tomato, there are a lot of differences between cultivated tomato and wild tomato, such as shape, physiological function and life history. Many studies show that wild tomato has better salt resistance and drought resistance. In addition to, domesticated tomato's fruit is bigger and has more nutritious than wild tomato. The different features are closely related to differentially expressed genes. We identified 126 up-regulated differentially expressed genes and 87 down-regulated differentially expressed genes in cultivated tomato and wild tomato by RNA-Seq. These differentially expressed genes may be associated with salt resistance, drought resistance and fruit nutrition. These differentially expressed genes also further highlight the large-scale reconstruction between wild and cultivated species. In this paper, we mainly study GO enrichment analysis and pathway analysis of the differentially expressed genes. After GO and pathway enrichment analysis, a set of significantly enriched GO annotations and pathways were identified for the differentially expressed genes. What's more, we also identified long non-coding RNAs and mRNAs in the two species and analyzed its essential features. In addition to, we construct a co-expression network of long non-coding RNAs and mRNAs, and annotate mRNAs associated with long non-coding RNAs as target genes, and speculate the regulation function of long non-coding RNAs. In total, our results reveal the effects of artificial and natural selection on tomato's transcript, providing scientific basis for tomato's research in the future.


Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis.
Recently we proposed inhibition of aldosterone synthase (CYP11B2) as a novel strategy for the treatment of congestive heart failure and myocardial fibrosis. In this study the synthesis and biological evaluation of heteroaryl-substituted naphthalenes and quinolines (1-31) is described. Key step for the preparation of the compounds was a Suzuki cross-coupling. Activity of the compounds was determined in vitro using human CYP11B2 and selectivity was evaluated toward the human steroidogenic enzymes CYP11B1, CYP19, and CYP17. A large number of highly active and selective inhibitors of CYP11B2 was identified. The most active inhibitor was the 6-cyano compound 8 (IC50 = 3 nM) showing a competitive type of inhibition (K(i) value = 1.9 nM). The 6-ethoxy derivative 5 was found to be the most selective CYP11B2 inhibitor (IC50 = 12 nM; K(i) value = 8 nM; CYP11B1 IC50 = 5419 nM; selectivity factor = 451), showing no inhibition of human CYP3A4 (50 nM) and CYP2D6 (20 nM). Docking and molecular dynamics studies using our homology modeled CYP11B2 structure with selected compounds were performed. Caco-2 cell experiments revealed a large number of medium and highly permeable compounds and metabolic studies with 2 using rat liver microsomes showed sufficient stability.


Vascular remodeling process in reversibility of pulmonary arterial hypertension secondary to congenital heart disease.
Pulmonary vascular remodeling process was analyzed using morphometry in lung biopsy specimens taken from 26 children, aged 6 to 160 months, who had congenital heart disease and significant pulmonary arterial hypertension. Reparative surgery was performed in 22 patients and palliative surgery was performed in four patients. One patient expired postoperatively and four others after hospital discharge. Vascular remodeling examination revealed a characteristic pathological picture: pronounced medial thickening with increased collagen content (fibrosis), without significant arterial intimal proliferation. At a mean follow-up of 44 months, 72% of the survivors were asymptomatic with no medication. Diagnosed by echocardiogram, 22% of these patients were shown to have pulmonary arterial hypertension. The characteristic pathological features described above occurred in 38% of the patients who either expired or had pulmonary hypertension postoperatively. These findings were an aid to identifying a high risk group in which the outcome does not meet expectations for the classical grade I and II changes. We concluded that the presence of isolated medial thickening does not ensure either survival or a normal postoperative pulmonary arterial pressure at late follow-up and that the collagen content can be a better reference for good outcome. Early intracardiac repair is recommended before the development of significant medial fibrosis.


The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1.
The toroidal damage checkpoint complex Rad9-Rad1-Hus1 (9-1-1) has been characterized as a sensor of DNA damage. Flap endonuclease 1 (FEN1) is a structure-specific nuclease involved both in removing initiator RNA from Okazaki fragments and in DNA repair pathways. FEN1 activity is stimulated by proliferating cell nuclear antigen (PCNA), a toroidal sliding clamp that acts as a platform for DNA replication and repair complexes. We show that 9-1-1 also binds and stimulates FEN1. Stimulation is observed on a variety of flap, nick, and gapped substrates simulating repair intermediates. Blocking 9-1-1 entry to the double strands prevents a portion of the stimulation. Like PCNA stimulation, 9-1-1 stimulation cannot circumvent the tracking mechanism by which FEN1 enters the substrate; however, 9-1-1 does not substitute for PCNA in the stimulation of DNA polymerase beta. This suggests that 9-1-1 is a damage-specific activator of FEN1.


Case vignette: premature surrender.
Three commentaries are offered on the following case: George, age 57, is a previously healthy man who recently underwent surgery for removal of a low-grade malignant thymoma. At the time of admission to the hospital, George stressed to the staff that he had long ago signed a "living will," which he renewed immediately after he learned of his cancer diagnosis. At the time of surgery, the tumor was found to extend into his mediastinum; although it was removable, this required revision of part of the sternum and grafting of the vessels feeding the heart chambers. Because of the resultant tissue damage and neuronal hyperactivity, George experienced postoperative episodes of cardiac arrhythmia and bronchospasm. Unanimous medical opinion was that this situation was a temporary problem that would resolve itself as the tissues healed. Until that time, however, it will be difficult to wean him from ventilatory support. When his stay in the intensive care unit became prolonged, George and his family began to insist that his status be changed to "do not resuscitate" and reminded the staff about his longstanding living will. All of this is happening despite the fact that the patient and family seemingly comprehend that although the short-term interventions are invasive, there is a high probability of a successful outcome. George's cancer prognosis is excellent, and, although he may well have an episode of life-threatening arrhythmia, he is likely to respond to resuscitation interventions. Once the immediate postoperative period is over, his potential for a long and productive life with full capacities is excellent. Consider the following questions: (a) Should George's expressed wishes be respected, or should the staff take additional steps to help him survive the postoperative period, even if that means violating his stated wishes? and (b) What steps might the staff follow in sorting through this problem?


When should cranial magnetic resonance imaging be used in girls with early sexual development?
To determine whether concise parameters can be established in girls who present with signs of early puberty before the age of 8 years, which would help to identify those in whom cranial magnetic resonance imaging (MRI) is indicated. A retrospective chart review was undertaken over a 10-year period from 1992-2002. The two requirements for inclusion in this study were girls who manifested pubertal changes before the age of 8.0 years and who underwent MRI of the brain. The records of 130 female patients with the presumptive diagnosis of precocious puberty (PP) were evaluated. Patients' medical records were reviewed for histories of any reported focal neurological complaint suspicious for intracranial lesions, such as headaches, seizures, or visual disturbances, as well as menses and advanced bone age (>2 SD) compared to chronological age. Seventy-five patients met these criteria and were divided into two groups. Group I consisted of nine patients with abnormal cranial MRI; Group II consisted of 66 patients with normal MRI. The patients in each group who had one or more of the central nervous system (CNS) signs and symptoms of early sexual development that were evaluated were markedly different. In Group I, 89% (CI 52-99.7%) had positive signs and symptoms that were suspicious for an intracranial lesion. In Group II, 94% (CI 85-98%), 63 of 66 girls, had no CNS signs or symptoms. The use of cranial MRI in the evaluation of girls with early sexual development is excessive. Girls with signs of pubertal development before age 8 years should be evaluated and followed. Those with specific CNS signs and symptoms, menses, and girls with a rapid advance in sexual development should undergo cranial MRI. Using this approach, far fewer patients in our study would have had cranial MRI.


Electrochemical sensing for the determination of activated cyclic AMP-dependent protein kinase.
A novel electrochemical system has been developed for monitoring the cyclic AMP-dependent protein kinase (PKA) activity. In this method, PKA activity was monitored as the change in the redox current of a ferrocene-pendant PKA substrate peptide (Fe-LRRASLG) on a gold electrode, which had been modified with thioctic acid, using cyclic voltammetry. The phosphrylation of the ferrocene-pendant substrate with PKA changed the net charge from +1 to -1. This caused a decrease in the redox current of the ferrocene unit due to an electrostatic repulsion between the substrate and the anionic surface of the electrode. We expect that this method is potentially useful for monitoring the enzyme activity in medical or pharmacological fields.


Outbreak of Salmonella enteritidis associated with nationally distributed ice cream products--Minnesota, South Dakota, and Wisconsin, 1994.
From September 19 through October 10, 1994, a total of 80 confirmed cases of Salmonella enteritidis (SE) infection were reported to the Minnesota Department of Health (MDH); in comparison, 96 cases were reported statewide during all of 1993. Cases were characterized by diarrhea, abdominal cramps, and fever. Recent increases in SE cases also were reported from South Dakota (14 cases during September 6-October 7, compared with 20 cases during all of 1993) and Wisconsin (48 cases during September 6-October 7, compared with 187 during all of 1993). This report summarizes preliminary findings from the outbreak investigation.


Mesodermal expression of Fgfr2S252W is necessary and sufficient to induce craniosynostosis in a mouse model of Apert syndrome.
Coordinated growth of the skull and brain are vital to normal human development. Craniosynostosis, the premature fusion of the calvarial bones of the skull, is a relatively common pediatric disease, occurring in 1 in 2500 births, and requires significant surgical management, especially in syndromic cases. Syndromic craniosynostosis is caused by a variety of genetic lesions, most commonly by activating mutations of FGFRs 1-3, and inactivating mutations of TWIST1. In a mouse model of TWIST1 haploinsufficiency, cell mixing between the neural crest-derived frontal bone and mesoderm-derived parietal bone accompanies coronal suture fusion during embryonic development. However, the relevance of lineage mixing in craniosynostosis induced by activating FGFR mutations is unknown. Here, we demonstrate a novel mechanism of suture fusion in the Apert Fgfr2(S252W) mouse model. Using Cre/lox recombination we simultaneously induce expression of Fgfr2(S252W) and β-galactosidase in either the neural crest or mesoderm of the skull. We show that mutation of the mesoderm alone is necessary and sufficient to cause craniosynostosis, while mutation of the neural crest is neither. The lineage border is not disrupted by aberrant cell migration during fusion. Instead, the suture mesenchyme itself remains intact and is induced to undergo osteogenesis. We eliminate postulated roles for dura mater or skull base changes in craniosynostosis. The viability of conditionally mutant mice also allows post-natal assessment of other aspects of Apert syndrome.


Urinary fructose-1,6-bisphosphatase activity as a marker of the damage to the renal proximal tubules in children with idiopathic nephrotic syndrome.
Disturbances in the function of renal proximal tubules increase the activity of several enzymes in urine. Among them is fructose-1,6-bisphosphatase (FBP-1), the key enzyme of gluconeogenesis normally present in the renal convoluted, and to smaller degree, proximal renal tubular cells cytosol. FBP-1 activity in urine and serum was used for evaluation of the degree of graft ischemia during human kidney transplantation. The aim of our present research was to determine FBP-1 activity in urine as an indicator of damage to renal proximal tubules in children with idiopathic nephrotic syndrome (INS). We evaluated the excretion of FBP-1 into urine of 21 children (10 girls and 11 boys) with INS, aged from 10 to 15 years and 30 healthy children (14 girls and 16 boys), aged from 2 to 15 years. FBP-1 activity was determined by the Latzko and Gibbs method. Creatinine (mg%) in urine and blood serum was measured by the Jaffe method in Larsen modification. Protein in blood serum was determined by the biuret method (g/L), and albumin (mg%) by the Young method. Proteinuria in the urine collected over 24 h was measured with the Exton turbidimetric method by Tomaszewski with modification and expressed in mg/kg body weight/24 h. In the urine of 30 healthy children, FBP-1 activity was in the range from 0-1.74 micromol FPB/h/mmol of creatinine. In 43% of the healthy children, FBP-1 activity in urine was not detectable. In the period of intensive proteinuria during the INS in children, FBP-1 activity and protein concentrations in urine were significantly higher than in the control group (p<0.0008 and p<0.0001, respectively). In the urine of children with active INS, we observed a very weak negative linear correlation between protein concentration and FBP-1 activity (r=-0.5018, p=0.067). After treatment with Encorton (prednisone), FBP-1 activity and protein concentration in urine dropped to values of the control group. "The overload" of proximal renal tubules by proteins in children with INS releases FBP-1 into urine. FBP-1 activity in urine may therefore be considered as a marker of damage to the proximal renal tubules in children with INS.


Non-linear dynamics of operant behavior: a new approach via the extended return map.
Previous efforts to apply non-linear dynamic tools to the analysis of operant behavior revealed some promise for this kind of approach, but also some doubts, since the complexity of animal behavior seemed to be beyond the analyzing ability of the available tools. We here outline a series of studies based on a novel approach. We modified the so-called 'return map' and developed a new method, the 'extended return map' (ERM) to extract information from the highly irregular time series data, the inter-response time (IRT) generated by Skinner-box experiments. We applied the ERM to operant lever pressing data from rats using the four fundamental reinforcement schedules: fixed interval (FI), fixed ratio (FR), variable interval (VI) and variable ratio (VR). Our results revealed interesting patterns in all experiment groups. In particular, the FI and VI groups exhibited well-organized clusters of data points. We calculated the fractal dimension out of these patterns and compared experimental data with surrogate data sets, that were generated by randomly shuffling the sequential order of original IRTs. This comparison supported the finding that patterns in ERM reflect the dynamics of the operant behaviors under study. We then built two models to simulate the functional mechanisms of the FI schedule. Both models can produce similar distributions of IRTs and the stereotypical 'scalloped' curve characteristic of FI responding. However, they differ in one important feature in their formulation: while one model uses a continuous function to describe the probability of occurrence of an operant behavior, the other one employs an abrupt switch of behavioral state. Comparison of ERMs showed that only the latter was able to produce patterns similar to the experimental results, indicative of the operation of an abrupt switch from one behavioral state to another over the course of the inter-reinforcement period. This example demonstrated the ERM to be a useful tool for the analysis of IRT accompanying intermittent reinforcement schedules and for the study of the non-linear dynamics of operant behavior.


Treatment of cytomegalovirus retinitis in a patient with AIDS with 9-(1,3-dihydroxy-2-propoxymethyl)guanine.
Asymptomatic retinal lesions were found on annual ophthalmic examination in a 38-year-old homosexual man with the acquired immune deficiency syndrome (AIDS). The lesions were compatible with cytomegalovirus retinitis and progressed. Treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) resulted in regression of the lesions and improvement in his overall clinical condition. The retinal lesions in AIDS are reviewed.


Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL.
Apoptosis is an integral aspect of B lymphocyte development and homeostasis and is regulated by the engagement of antigen costimulatory and cytokine receptors. Although it is well established that interleukin 4 (IL-4) is a potent anti-apoptotic cytokine for B lymphocytes, little is known about the IL-4-induced molecular events regulating cell survival. Stat6 is rapidly activated after IL-4 stimulation, but its role in B lymphocyte apoptosis has not been explored. In this report we demonstrate that Stat6 is a critical signaling molecule for IL-4 in protecting primary B cells from passive and Fas-induced cell death. We show that expression of the Bcl-2 family member, Bcl-xL, is induced maximally by IL-4 and anti-IgM/IL-4 in a Stat6-dependent manner. Additionally, we demonstrate that bcl-xL transcription is likely to be directly activated through a Stat6 binding site in the bcl-xL-flanking region. Finally, reconstitution of Stat6-deficient splenic B cells with Bcl-xL was able to protect those cells from Fas-induced cell death. These results suggest that the anti-apoptotic activity of IL-4 in B cells is mediated through the activation of Stat6 and subsequent transcription of Bcl-xL.


Obstructive sleep apnea during REM sleep and hypertension. results of the Wisconsin Sleep Cohort.
Obstructive sleep apnea (OSA) is associated with hypertension. We aimed to quantify the independent association of OSA during REM sleep with prevalent and incident hypertension. We included adults enrolled in the longitudinal community-based Wisconsin Sleep Cohort Study with at least 30 minutes of REM sleep obtained from overnight in-laboratory polysomnography. Studies were repeated at 4-year intervals to quantify OSA. Repeated measures logistic regression models were fitted to explore the association between REM sleep OSA and prevalent hypertension in the entire cohort (n = 4,385 sleep studies on 1,451 individuals) and additionally in a subset with ambulatory blood pressure data (n = 1,085 sleep studies on 742 individuals). Conditional logistic regression models were fitted to longitudinally explore the association between REM OSA and development of hypertension. All models controlled for OSA events during non-REM sleep, either by statistical adjustment or by stratification. Fully adjusted models demonstrated significant dose-relationships between REM apnea-hypopnea index (AHI) and prevalent hypertension. The higher relative odds of prevalent hypertension were most evident with REM AHI greater than or equal to 15. In individuals with non-REM AHI less than or equal to 5, a twofold increase in REM AHI was associated with 24% higher odds of hypertension (odds ratio, 1.24; 95% confidence interval, 1.08-1.41). Longitudinal analysis revealed a significant association between REM AHI categories and the development of hypertension (P trend = 0.017). Non-REM AHI was not a significant predictor of hypertension in any of the models. Our findings indicate that REM OSA is cross-sectionally and longitudinally associated with hypertension. This is clinically relevant because treatment of OSA is often limited to the first half of the sleep period leaving most of REM sleep untreated.


Histopathological diagnosis and its correlations with anatomoclinical features, surgical approach and postoperative prognosis in sacral tumors.
Sacral tumors encompass numerous histopathological types. They represent an uncommon pathology and, when diagnosed, they are often in advanced stage of the disease, becoming a therapeutic challenge. The correct treatment of a sacral tumor should be established by a multidisciplinary team that will assess the exact anatomical, imagistic and histopathological characteristic of the tumors thus choosing an optimal surgical approach while taking into consideration the risk of recurrence. We conducted a retrospective analysis of both primitive and metastatic sacral tumors in "Bagdasar-Arseni" Emergency Hospital, Bucharest, Romania, for a period of 10 years, studying demographic data, clinical signs, anatomical and histopathological features as well as surgical approach and postoperative prognosis. Sacral tumors were diagnosed with a peak incidence in the age group 60-69 years, being more frequent in women. Primitive sacral tumor was predominant and, in this subgroup, chordoma was the most frequent. Metastatic tumors appeared in older subjects. None of the histopathological types associated a preferred topography of the resection or increased resectability. Posterior surgical approach was chosen in most cases, total resection being a hard goal to accomplish due to the invasion of vascular and nervous structures. Bleeding was the most frequently reported incident, carcinomas recording the highest blood loss amongst primitive tumors. Overall prognosis was clearly favorable for subjects diagnosed with primitive sacral tumors. Interpreting imaging data in a clinical context, paying attention to histopathological examination and knowing each histological type characteristics is mandatory in choosing the surgical approach thus obtaining the best postoperative outcome possible.


THE PREGNANCY PENALTY.
Punishing pregnant women increasingly serves as a litmus test in political discourse, inviting more than a metaphor about state sanctioned violence targeted at women. In 2016, candidates for the United States presidency threatened to defund Planned Parenthood if elected and a leading candidate promised he would "punish" pregnant women who seek abortions. Other presidential candidates urged that even victims of rape and incest should be forced to carry their pregnancies to term, imposing yet another penalty or strike against sexually violated women and girls. Local legislatures and governors show equal contempt for and desire to penalize women in their states. In Utah, Gov. Gary Herbert took up the call to use a "very strong stick" in policing reproduction by signing into law the Criminal Homicide and Abortion Revisions Act, which applies only to pregnant women. The law seeks to punish pregnant women who "knowingly" commit acts that might result in miscarriages. In 2011, Texas Rep. Doug Miller authored and introduced a bill in his state legislature that would make it a felony to ingest any controlled substance during pregnancy. Wisconsin's legislature passed a law that forces pregnant women to receive vaginal probes as a pre-condition to receiving an abortion. To obtain an abortion without undergoing the vaginal probe is a punishable violation of law. Some women's groups compare vaginal ultrasound laws such as that in Wisconsin to state sanctioned rape with a rod. Other legislative efforts include establishing personhood in embryos and fetuses. Many of the laws seeking to punish pregnant women and regulate their pregnancies introduce criminal sanctions into gestational conduct, broadly criminalizing any behavior that could harm fetal health. All of these laws selectively target pregnant women.


Postembedding staining of Brunner's gland with lectin-ferritin conjugates.
Postembedding staining of intracellular carbohydrates of rat Brunner's gland cells embedded in Epon and acrylamide was carried out with Ricinus communis agglutinin-ferritin, concanavalin A-ferritin, and wheat germ agglutinin-ferritin conjugates. Th Golgi vacuoles and mucous granules were stained with these conjugates. In each staining, the tissues embedded in acrylamide were stained more strongly than those embedded in Epon. The staining intensity of wheat germ agglutinin-ferritin was the strongest among the three conjugates and the staining intensity of Ricinus communis agglutinin-ferritin was stronger than that of concanavalin A-ferritin in both embedding methods. Free ferritin showed almost no binding to these structures and staining with the conjugates was inhibited by the addition of appropriate competitive sugars to the staining solutions. Osmium-postfixed tissues were not stained well with the conjugates. Washing of the sections with bovine serum albumin solution after staining was an essential step in the present method to reduce the nonspecific adsorption of the conjugates. The present method was very simple and had good reproducibility.


Highly Effective Conductance Modulation in Planar Silicene Field Effect Devices Due to Buckling.
Silicene is an exciting two-dimensional material that shares many of graphene's electronic properties, but differs in its structural buckling. This buckling allows opening a bandgap in silicene through the application of a perpendicular electric field. Here we show that this buckling also enables highly effective modulation of silicene's conductance by means of an in-plane electric field applied through silicene side gates, which can be realized concurrently within the same silicene monolayer. We illustrate this by using silicene to implement Self-Switching Diodes (SSDs), which are two-dimensional field effect nanorectifiers realized within a single silicene monolayer. Our quantum simulation results show that the atomically-thin silicene SSDs, with sub-10 nm dimensions, achieve a current rectification ratio that exceeds 200, without the need for doping, representing a 30 fold enhancement over graphene SSDs. We attribute this enhancement to a bandgap opening due to the in-plane electric field, as a consequence of silicene's buckling. Our results suggest that silicene is a promising material for the realization of planar field effect devices.


Prognostic significance of microRNA-375 downregulation in solid tumors: a meta-analysis.
Recently, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. We performed a meta-analysis to evaluate the impact of miR-375 expression in solid tumors on patients' overall survival (OS). Studies were identified by searching PubMed, Embace, and Cochrane Library (last search update was in May 2014) and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between miR-375 expression and cancer patients OS. Our analysis results indicated that downregulation of miR-375 predicted poor OS (HR = 1.91, 95% CI 1.48-2.45, P < 0.001). Subgroup analyses showed that lower expression of miR-375 was significantly related with poor OS in patients with esophageal carcinoma (HR = 2.24, 95% CI 1.69-2.96, P < 0.001) and non-small-cell lung cancer (NSCLC) (HR = 1.71, 95% CI 1.31-2.24, P < 0.001). The findings from this meta-analysis suggest that miR-375 expression is associated with OS of patients with malignant tumors and could be a useful clinical prognostic biomarker.


Three-dimensional analysis of the movement of lumbar spinal nerve roots in nonsimulated and simulated adhesive conditions.
Biomechanical analysis of the movement of the lumbar spinal nerve roots (NRs). The characteristics of the movement of lumbar spinal NRs corresponding to the change of posture were three-dimensionally analyzed in nonsimulated and simulated adhesion conditions using a porcine model. There is a paucity of data on the movement of NRs. Thirty two NRs of four pig cadavers were investigated. (study 1) Two tantalum beads were sutured on respective NRs from L3 to L6. Five beads were put into each bony structure as reference points. The porcine body was put on the cage designed for three-dimensional radiostereometric analysis. Two oblique radiographs were simultaneously taken at flexion, neutral, and extension. (study 2) After study 1, either L4 NR was ligated onto the adjacent bone to mimic monoradicular adhesion. Radiographs were taken in the same manner. The movements of the beads on NRs relative to immobile standard points in each vertebra were analyzed. The movement of NRs was characterized as a combination of stretching/slackening and pendulum motion. The distance that NRs were stretched/slackened, the excursion, and the angles that NRs moved were: 0.39 +/- 0.29 mm, 1.81 +/- 0.63 mm, and 10.46 +/- 5.93 degrees (in nonadhesion), and 0.30 +/- 0.20 mm, 1.02 +/- 0.50 mm, and 7.13 +/- 3.79 degrees (in simulated adhesion), respectively. Adhesion might play a part in the pathogenesis of lumbar spinal disorders because mechanical irritation secondary to stretching/slackening and pendulum motion might be concentrated at the distal part of NRs, adjacent to adhesion site, which has less cerebrospinal fluid and is close to dorsal root ganglion.


How microsaccades relate to lateralized ERP components of spatial attention: A co-registration study.
Covert shifts of attention that follow the presentation of a cue are associated with lateralized components in the event-related potential (ERP): the "early directing attention negativity" (EDAN) and the "anterior directing attention negativity" (ADAN). Traditionally, these shifts are thought to take place while gaze is fixated and, thus, in the absence of saccades. However, microsaccades of small amplitude (<1°) occur frequently and involuntarily also during fixation and are closely correlated with spatial attention. To investigate potential links between microsaccades and lateralized ERP components, we simultaneously recorded eye movements and ERPs in a spatial cueing task. As a first major result, we show that both the posterior EDAN and the orientation of microsaccades align more strongly with the location of the task-relevant part of the cue stimulus than with the direction of the attention shift indicated by that cue. A coupling between microsaccades and EDAN was also present on the single-trial level: The EDAN was largest when microsaccades were oriented toward the relevant cue, but absent when microsaccades were oriented away from it, suggesting that EDAN and microsaccades are generated by the same neural network, which selects relevant stimuli and orients behavior toward them. As a second major result, we show that small corneoretinal artifacts from microsaccades, which fall below conventional EOG rejection thresholds, contaminate the measurement of the ADAN. After correcting the EEG for microsaccade-related artifacts with an optimized variant of independent component analysis, ADAN was abolished at frontal sites, but a genuine ADAN was still present at central sites. Thus, the combined measurement of microsaccades and lateralized ERPs sheds new light onto cue-elicited shifts of covert attention.


Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning.
The transcription factor encoded by the Pdx1 gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β-cell development, and adult islet β-cell function. Transgenic- and cell line-based experiments have identified 5'-flanking conserved sequences that control pancreatic and β-cell type-specific transcription, which are found within areas I (bp -2694 to -2561), II (bp -2139 to -1958), III (bp -1879 to -1799), and IV (bp -6200 to -5670). Because of the presence in area IV of binding sites for transcription factors associated with pancreas development and islet cell function, we analyzed how an endogenous deletion mutant affected Pdx1 expression embryonically and postnatally. The most striking result was observed in male Pdx1ΔIV mutant mice after 3 weeks of birth (i.e., the onset of weaning), with only a small effect on pancreas organogenesis and no deficiencies in their female counterparts. Compromised Pdx1 mRNA and protein levels in weaned male mutant β-cells were tightly linked with hyperglycemia, decreased β-cell proliferation, reduced β-cell area, and altered expression of Pdx1-bound genes that are important in β-cell replication, endoplasmic reticulum function, and mitochondrial activity. We discuss the impact of these novel findings to Pdx1 gene regulation and islet β-cell maturation postnatally.


Broadband cholesteric liquid crystal lens for chromatic aberration correction in catadioptric virtual reality optics.
A planar and broadband cholesteric liquid crystal (CLC) lens is designed, fabricated, and hybridized with a refractive lens to form a catadioptric pancake lens for virtual reality (VR) displays. Due to their opposite optical dispersion behaviors, the chromatic aberration of the assembled pancake lens is dramatically suppressed, as verified by both ray-tracing analysis and experimental results. The demonstrated catadioptric pancake lens has great potential for next-generation VR displays.


Therapeutic effects of β-elemene via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells.
Concurrent radio chemotherapy treatment prolongs the survival rate of patients with advanced cervical cancer; however, it has adverse side‑effects. β‑elemene, an active component of the traditional Chinese medicinal herb Curcuma zedoaria, is a promising alternative therapeutic drug for the treatment of advanced cervical cancer. The aim of the present study was to investigate the antitumor effects of β‑elemene in human cervical cancer SiHa cells and to determine its underlying therapeutic molecular mechanisms. Cell viability, cell cycle progression and apoptosis were detected using an MTT assay and flow cytometry analysis. Furthermore, the levels of cell migration and cell invasion were investigated using Transwell and wound healing assays. The expression levels of Cyclin‑dependent kinase inhibitor 2B (P15), Cyclin D1, cellular tumor antigen p53, apoptosis regulator Bcl‑2 (Bcl‑2), apoptosis regulator BAX (Bax), 72 kDa type IV collagenase (MMP‑2), matrix metalloproteinase‑9 (MMP‑9), β‑catenin, transcription factor 7 (TCF7), and Myc proto‑oncogene protein (c‑Myc) were analyzed via western blotting. The results revealed that β‑elemene inhibited the proliferation of SiHa cells in a dose and time‑dependent manner. Administration of β‑elemene induced G1 phase cell‑cycle arrest, as demonstrated by the upregulation of P15 expression and the downregulation of Cyclin D1 expression. Furthermore, the present study revealed that β‑elemene induced apoptosis in SiHa cells by enhancing the expression of p53 and Bax, and suppressing the expression of Bcl‑2. In addition, treatment with β‑elemene inhibited cell migration and invasion via downregulation of MMP‑2 and MMP‑9 expression levels. Western blotting demonstrated that β‑elemene reduced the expression levels of β‑catenin and its downstream target molecule TCF7, thus resulting in reduced levels of their target proteins, including c‑Myc, Cyclin D1, Bax and MMP‑2 in cervical cancer cells. The results of the present study suggested that β‑elemene may inhibit cell proliferation and invasion, in addition to inducing apoptosis, via attenuation of the Wnt/β‑catenin signaling pathway in cervical cancer cells.


The Contribution of Alexithymia to Obsessive-Compulsive Disorder Symptoms Dimensions: An Investigation in a Large Community Sample in Italy.
Poor attention has been dedicated to the relation between Alexithymia and specific OCD symptoms dimensions. Knowledge about which Alexithymia domains are the most affected ones in OCD dimensions could inform clinical practice, suggesting the need for the introduction of psychotherapeutic interventions targeting Alexithymia deficits. The current study aimed to investigate which OCD symptom dimension correlated with Alexithymia domains. A total of 425 community individuals (mean age = 27.80, SD = 9.89, 60% women) completed measures of Alexithymia, OCD symptoms dimensions, anxiety, and depression. Moderate correlations emerged between Difficulty Identifying Feelings and Hoarding (r = .36, p < .001) and Checking symptoms (r = .34, p < .001) and between Difficulty Describing Feelings and Pure Obsessing (r = .31, p < .001). Difficulty Identifying Feelings uniquely predicted OCD symptoms (β = 0.20, t = 3.96, and p < .001), after controlling for anxiety and depression. A main effect emerged of Alexithymia on Ordering (β = 0.70, t = 2.50, p < .05) and Pure Obsessing symptoms (β = 0.043, t = 2.08, and p < .05). Psychotherapeutic interventions specifically targeting Alexithymia should be integrated in the treatment of Ordering and Pure Obsessing symptoms. Difficulty Identifying Feelings and Difficulty Describing Feelings should be addressed in the psychotherapeutic treatment of Hoarding, Checking, and Pure Obsessing, respectively.


Treatment costs of adjuvant cytotoxic therapy in premenopausal breast cancer patients.
The interest in cost calculations of medical treatment programs has increased during the last decade. In the Danish Breast Cancer Cooperative Group's (DBCG) protocol 77B, 1,028 premenopausal patients were randomized after mastectomy to radiotherapy (RT) alone (control), RT + 12 cycles of cyclophosphamide (C) or to RT + 12 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). This study analyzes the costs associated with systemic treatment and follow-up programs in the 3 regimens. Costs connected with the primary mastectomy and the radiotherapy, which were identical in the 3 regimens, have not been included in the analysis. The analysis shows that the expenses for the postoperative treatment and follow-up program for 9 years in the control regimen are 8,250 DKK, whereas the costs for the C regimen are 11,000 DKK, and the costs for the CMF regimen are 18,000 DKK.


Comparison of normal and Bernard-Soulier platelet membrane glycoproteins: isoelectric characteristics and surface radiolabel.
The protein and glycoprotein compositions of platelets from normal individuals, patients with B-S disease, and subjects heterozygous for B-S were determined by two-dimensional gel electrophoretic analysis of platelets that had been radiolabeled on the surface by lactoperoxidase-catalyzed iodination or by the periodate-borohydride reaction. In normal platelets, five PAS-stained glycoproteins were found in the GP I region of the two-dimensional gels. B-S platelets contained four of the glycoproteins of the GP I complex but were deficient in one glycoprotein (Mr = 139,000 and pI 6.36) that, in normal platelets, was not stained by Coomassie blue but had a high affinity for both PAS stain and alcian blue stain and was heavily labeled on the surface of platelets by the periodate-borohydride reaction but only faintly with radioiodine. Platelets from three heterozygous B-S individuals did not differ from normal controls by these techniques. These results further define the glycoprotein composition of normal platelets and show a specific deficiency of a portion of the GP I complex in B-S platelets.


Electronic Structure of Few-Layer Black Phosphorus from μ-ARPES.
Black phosphorus (BP) stands out among two-dimensional (2D) semiconductors because of its high mobility and thickness dependent direct band gap. However, the quasiparticle band structure of ultrathin BP has remained inaccessible to experiment thus far. Here we use a recently developed laser-based microfocus angle resolved photoemission (μ-ARPES) system to establish the electronic structure of 2-9 layer BP from experiment. Our measurements unveil ladders of anisotropic, quantized subbands at energies that deviate from the scaling observed in conventional semiconductor quantum wells. We quantify the anisotropy of the effective masses and determine universal tight-binding parameters, which provide an accurate description of the electronic structure for all thicknesses.


Magnetic stimulation using a triple-stimulation technique in patients with multifocal neuropathy without conduction block.
It has been suggested previously that multifocal motor neuropathy (MMN) without conduction block (CB) or other features of demyelination is axonal in nature. Conventional transcranial magnetic stimulation (TMS) and the triple-stimulation technique (TST) performed on 10 MMN patients without CB revealed a proximal focal CB in 4 patients. In 3 other patients, the amplitude ratio obtained in response to conventional TMS was abnormally low, but the area ratio was normal. The TST amplitude ratio and area ratio were normal in these 3 patients. This pattern suggested the occurrence of temporal dispersion without CB. The occurrence of temporal dispersion or CB was associated with a relatively satisfactory response to intravenous immunoglobulins. These findings suggest that some forms of MMN previously thought to be axonal are in fact proximal variants of MMN with CB.


Two-dimensional ambipolar carriers of giant density at the diamond/cubic-BN(111) interfaces: toward complementary logic and quantum applications.
The extremely difficult ambipolar doping activation greatly hinders the outstanding performance of diamond for electronic devices. The main concern has been devoted to surface conduction by two-dimensional (2D) carriers. 2D hole gas (2DHG) in the diamond is induced by surface transfer doping dominated by the adsorbate's status and faces stability issues. Meanwhile, a feasible way to generate the other essential ambipolar carrier-2D electron gas (2DEG) is still lacking. We propose that the well-lattice-matched diamond/cBN(111) interfaces can spontaneously induce 2D ambipolar carriers with a giant density of 4.17 × 1014 cm-2, an order higher than other competitors. 2DEG and 2DHG can be separately achieved near the hetero-interfaces consisting of C-N and C-B bonds, respectively. Interestingly, the robust 2D charges are derived from a novel bulk-induced polarization-discontinuity at the interfaces, which can be attributed to an unexpected non-zero formal polarization of centrosymmetric cBN along the [111] direction. The existence of 2D ambipolar carriers at the diamond/cBN(111) interfaces has resolved the missing n-type conduction in diamond, thus opening up possibilities for complementary logic applications. Additionally, the high density of quantum-confined 2D ambipolar carriers provides an excellent platform for strongly correlated systems, which could lead to novel quantum information processing applications.


[Systemic complications and side effects of retrobulbar anesthesia in risk patients].
Serious systemic complications with possibly lethal exit after retrobulbar anesthesia have been reported. The present study was performed to evaluate the incidence of complications after anesthesia in risk patients with pre-existing diseases. 2.8% of 3000 cataract operations in our department during October 1991 to April 1993 were performed under general anesthesia, 97.2% under local anesthesia. 1000 anesthesia protocols of these cataract operations under retrobulbar anesthesia and facial block with anesthesia stand-by were analyzed retrospectively. After retrobulbar injection in Atkinson technique we performed a modified O'Brien facial block. The patients were assigned to five different risk groups on the basis of a special point system. The mean age of the patients increased with the risk group from 60.4 years in group 1 to 77.1 years in group 5. Cardiovascular, pulmonary and general risk factors appeared more frequently in the groups of higher risk. The frequency of cardiovascular complications was dependent on affiliation to risk group. The percentual frequency of cardiovascular complications increased from 1.7% in risk group 1 to 7.7% in risk group 5. Decrease of heart rate or blood pressure of more than 30%, or in combination, with the necessity of medical treatment occurred absolutely and relatively most frequently. The frequency of cardiovascular complications amounted 2.2% in the mean. Life-threatening complications with the need of endotracheal intubation or other occurred in 0.1%. The relatively high total frequency of systemic complications of 2.4% is related with age and preexisting diseases. The results underline the necessity of anesthesia stand-by in risk patients with the essential requirements for treatment of typical complications.


[Metabolic endoradiotherapy with P32 in skeletal metastases from breast neoplasms. Note I].
22 patients suffering from breast neoplasia with particularly painful bone metastasis were treated with radiophosphorus. Only occasionally was an evident recalcification condition encountered and survival, although exceptional in some cases, did not deviate from normal. On the basis, also, of clinical and experimental observations reported in the literature, it is held that the use of 32P in metabolic radiotherapy of bone metastases is worthwhile and is justified because of the encouraging successes obtained, especially in pain remission.


Blocking Babesia bovis vaccine reactions of dairy cattle in milk.
The use of 1.16 mg/kg (one third) of the recommended dose of diminazene aceturate, administered indiscriminately to cattle on day seven of the unfrozen Babesia bovis and Babesia bigemina bivalent live blood vaccine reaction, was an infection and block treatment method of immunisation used successfully with no known adverse effect on the parasites or the development of protective immunity. Continuing with this practice after replacement of the unfrozen vaccine with deep-frozen monovalent B. bovis and B. bigemina live blood vaccines resulted in reports of vaccine failure. Laboratory investigation indicated the harmful effect of block treatment in preventing the development of durable immunity against B. bigemina as opposed to the much lesser effect it had on B. bovis. Consequently the practice was no longer recommended. A B. bovis vaccination attempt aimed at controlling the disease of dairy cows in milk (n = 30) resulted in 20% fatalities during the expected vaccine reaction period. The practice of block treating B. bovis was therefore reinvestigated, this time in a field trial using dairy cattle in milk (n = 11). Using 0.88 mg/kg (one quarter) of the recommended dose of diminazene administered on day 12 of the B. bovis vaccine reaction resulted in only two animals (n = 5) testing ≥ 1/80 positive with the indirect fluorescent antibody test (IFAT) although parasites could be demonstrated in three. In the untreated control group, by contrast, five of the vaccinated animals (n = 6) tested ≥ 1/80 positive with IFAT and parasites could be demonstrated in all. The unsatisfactory outcome obtained in this study, combined with that of the earlier investigation, indicated that there are more factors that influence successful vaccination than previously considered. It is therefore concluded that block treatment of the live frozen South African cattle babesiosis vaccines reactions is not recommended.


Identification of three new genes involved in morphogenesis and antibiotic production in Streptomyces coelicolor.
We report the isolation and partial characterization of three new mutants of Streptomyces coelicolor that are defective in morphogenesis and antibiotic production. The genes identified by the mutations were located and cloned by using a combination of Tn5 in vitro mutagenesis, cotransformation, and genetic complementation. Mutant SE69 produces lower amounts of antibiotics than the wild type produces, produces spores only after prolonged incubation on rich media, and identifies a gene whose predicted protein product is similar to the GntR family of transcriptional regulators; also, production of aerial mycelia on both rich and poor media is significantly delayed in this mutant. Mutant SE293 is defective in morphogenesis, overproduces antibiotics on rich media, fails to grow on minimal media, and identifies a gene whose predicted protein product is similar to the TetR family of transcriptional regulators. Preliminary evidence suggests that the SE293 gene product may control a molybdopterin binding protein located immediately adjacent to it. Mutant SJ175 sporulates sooner and more abundantly than the wild type and overproduces antibiotics on rich media, and it identifies a gene whose predicted protein product contains regions of predominantly hydrophobic residues similar to those of integral membrane proteins.


What can be deduced about the structure of Shaker from available data?
Voltage-gated K+ channels are transmembrane proteins that control and regulate the flow of K+ ions across cell membranes in response to changes in membrane potential and are essential for the propagation of action potentials in the nervous system. One of the most studied voltage-gated channels is Shaker. Available experimental results clearly provide specific constraints on the structure of the channel, even though the direct translation of the available information into 3D structures is not trivial. The goal of this work is to develop a computational approach to construct and refine 3D models of Shaker by incorporating and integrating available experimental data. Our approach is based on comparative modelization and global conformational optimization using energy restraints extracted from experimental data.


Treatment decision for cancer patients with fever during the coronavirus disease 2019 (COVID-19) pandemic.
Cancer patients have been disproportionally affected by the coronavirus disease 2019 (COVID-19) pandemic, with high rates of severe outcomes and mortality. Fever is the most common symptom in COVID-19 patients. During the COVID-19 pandemic, physicians may have difficulty in determining the cause of fever (COVID-19, another infection, or cancer fever) in cancer patients. Furthermore, there are no specific guidelines for managing cancer patients with fever during the COVID-19 pandemic. Thus, this study evaluated the clinical characteristics and outcomes of cancer patients with fever during the COVID-19 pandemic. This study retrospectively reviewed the medical records of 328 cancer patients with COVID-19 symptoms (fever) admitted to five hospitals in Daegu, Korea from January to October 2020. We obtained data on demographics, clinical manifestations, laboratory test results, chest computed tomography images, cancer history, cancer treatment, and outcomes of all enrolled patients from electronic medical records. The most common COVID-19-like symptoms were fever (n=256, 78%). Among 256 patients with fever, only three (1.2%) were diagnosed with COVID-19. Most patients (253, 98.8%) with fever were not diagnosed with COVID-19. The most common solid malignancies were lung cancer (65, 19.8%) and hepatobiliary cancer (61, 18.6%). Twenty patients with fever experienced a delay in receiving cancer treatment. Eighteen patients discontinued active cancer treatment because of fever. Major events during the treatment delay period included death (2.7%), cancer progression (1.5%), and major organ dysfunction (2.7%). Considering that only 0.9% of patients tested for COVID-19 were positive, screening for COVID-19 in cancer patients with fever should be based on the physician's clinical decision, and patients might not be routinely tested.


Challenges in Interpreting the Ob/Gyn Literature: Studies of Screening.
Screening tests are critical to patient care. Screening tests must meet ten criteria established by the World Health Organization in order to be considered effective. Common types of studies on screening tests include those that establish test characteristics, such as sensitivity, specificity, positive predictive value, and negative predictive value, as well as cost-effective analyses. In this paper, we review the criteria for effective screening tests, and discuss the strengths and pitfalls of common study designs evaluating screening tests.


Lipid composition of nipple discharges of women with galactorrhea.
The biochemical nature of nipple discharge, including galactorrhea, and the physiology of lactation in patients with nipple discharge have not been studied extensively. Studies of the composition of nipple discharges may provide further insight into the complex processes involved in their secretion. In this study we compared the lipid composition of nipple discharges from patients with galactorrhea with that of human colostrum. The diagnosis of galactorrhea was confirmed by the presence of casein, detected by the anti-casein radial immunodiffusion test. Triglyceride, cholesterol and phospholipid levels in the nipple discharge samples were quite high compared with the colostrum samples. The proportion of 6:0 and 22:1 fatty acids was lower in the discharge samples and the proportion of 18:2 and 20:4 fatty acids was higher. Levels of phospholipid and neutral lipids, determined by quantitative densitometry in situ after separation by thin layer chromatography, also varied between discharge and colostrum, with a higher level of free fatty acids and triglyceride fractions in the nipple discharge. The lipoprotein electrophoretic bands of the nipple discharge samples resembled serum lipoprotein bands while colostrum samples gave no bands on electrophoresis.


[Corneal astigmatism among 2 085 age-related cataract patients before surgery].
Objective: To investigate the characteristics and distribution of corneal astigmatism before surgery among age-related cataract patients in the Hubei area. Methods: Retrospective study. From January 1, 2012 to July 31, 2016, IOL Master measurements of all qualified cataract surgery candidates were retrospectively collected. Descriptive statistical analysis was used to assess the degree, distribution and type of corneal astigmatism. Kolmogorov-Smirnov (K-S) test was used to evaluate the normal distribution of variables. One-way analysis of variance and Kruskal-Wallis test were applied for the comparison of variance for normally and non-normally distributed quantitative data among different age groups. Spearman's rank test was used to assess the relationship between age and corneal astigmatism. Results: The mean age of the 2 085 patients (3 586 eyes) involved was (73.1±9.43) years old, with more women (58.3%) than men. The mean value of corneal curvature was 44.33 D (95%CI: 44.28-44.39), and the mean corneal astigmatism was 1.06 D (range, 0.05 D to 6.74 D). K-S test indicated the distribution of corneal curvature was normal (P=0.18), while corneal astigmatism did not obey the normal distribution (P<0.01). Corneal astigmatism was between 0.25 D and 1.25 D in 67.7% of the eyes, >1.25 D in 29.7%, and<0.25 D in 4.2%. Corneal astigmatism degree increased with the age increase (P<0.01). There was no statistical difference in corneal astigmatism between women and men (P=0.075). However, women had steeper corneal curvatures than men with statistical difference (P<0.01). Corneal astigmatism with the rule was observed in 29.0% of the eyes, while astigmatism against the rule was found in 53.0%. And astigmatism against the rule increased with age. Conclusion: Corneal astigmatism mostly distributes between 0.25 D and 1.25 D in age-related cataract patients who lived in Hubei. Corneal astigmatism degree increased with age, and the dominant type was astigmatism against the rule. There was no difference in astigmatism between men and women patients aged 50 years and above, but in 70- to 79-year-old patients, women had a higher astigmatism degree than men. The corneal curvature of women was steeper than men in general and in each age group. (Chin J Ophthalmol, 2017, 53: 522-527).


Effect of cross-linking properties on the vibrational dynamics of cyclodextrins-based polymers: an experimental-numerical study.
The vibrational dynamics of cyclodextrin nanosponges (CDNS), a new class of nanostructured soft materials synthesized via cross-linking reaction of natural cyclic oligosaccharide β-cyclodextrin (β-CD) with suitable organic reagents, is investigated by means of the combined use of Raman and infrared spectroscopy, supported by numerical simulations. The vibrational spectra of the polymers show significant changes in the frequency ranges 3000-3700 and 1500-1800 cm(-1) correlated to the relative amount of cross-linker with respect to monomeric CD. By using band deconvolution and best-fit procedure of the experimental data and quantum chemical computations, a correlation between such changes and the degree of cross-linking of the polymeric network is proposed. This experimental-numerical approach, here applied to a model class of nanoporous polymeric systems, appears to be of general application for the study of polymeric matrixes of interest for biolife applications.


Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity.
Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin-angiotensin-aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47(phox) mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47(phox) mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47(phox). In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.


Na(+):aspartate coupling stoichiometry in the glutamate transporter homologue Glt(Ph).
The Na(+) aspartate symporter Glt(Ph) from Pyrococcus horikoshii is the only member of the glutamate transporter family for which crystal structures have been determined. The cation:aspartate coupling stoichiometry is unknown, thus hampering the elucidation of the ion coupling mechanism. Here we measure transport of (22)Na(+) and [(14)C]aspartate in proteoliposomes containing purified Glt(Ph) and demonstrate that three Na(+) ions are symported with aspartate.


Status of insecticide resistance in Culex pipiens field populations from north-eastern areas of Italy before the withdrawal of OP compounds.
Heavy and constant use of organophosphorus (OP) larvicides selected Culex pipiens L. resistant populations through two main mechanisms of genetic resistance, the increased activity of detoxifying esterase and the production of alterate acetylcholinesterase-1 (AChE1) by G119S mutation. The aim of this study was the assessment of the distribution of Cx. pipiens populations resistant to temephos and chlorpyrifos in the north-eastern regions of Italy and the occurrence of the insensitive AChE in these populations. Data describe the situation in the last years before European legislation prohibited the use of OP larvicides in mosquito control, up until 2007. For the first time a high level of OP resistance in the samples from Ravenna (182-fold, 80% A4/B4 or A5/B5 esterases and 38.3% Ester(5)), Emilia Romagna region, was detected; therefore, new data from the Veneto and Friuli Venezia Giulia regions were obtained and reinforced existing knowledge about resistance previously studied along the Adriatic coast. Nearby, in the Villa Verucchio locality, the highest (87.5%) AChE1R was found. Cx. pipiens resistance esterases A5/B5 and A4/B4 spread southward along the Adriatic coastal plain while OPs were being used in mosquito control, as confirmed by the first molecular screening of the AChE1 gene in these populations.


Inhibitory effects of Bcl-2 on mitochondrial respiration.
In contrast to the well-established anti-apoptotic effect of Bcl-2 protein, we have recently demonstrated that Bcl-2 overexpression by vaccinia virus causes apoptosis in BSC-40 cells, while it prevents apoptosis in HeLa G cells. Given the key role of mitochondria in the process of apoptosis, we focused on effects of Bcl-2 expression on mitochondrial energetics of these two cell lines. In this study we present data indicating that BSC-40 cells derive their ATP mainly from oxidative phosphorylation whereas HeLa G cells from glycolysis. More importantly, we show that in both cell lines, Bcl-2 inhibits mitochondrial respiration and causes a decrease of the ATP/ADP ratio. However, it appears that BSC-40 cells cannot sustain this decrease and die, while HeLa G cells survive, being adapted to the low ratio of ATP/ADP maintained by glycolysis. Based on this observation, we propose that the outcome of Bcl-2 expression is determined by the type of cellular ATP synthesis, namely that Bcl-2 causes apoptosis in cells relying on oxidative phosphorylation.


Combining Peyton's four-step approach and Gagne's instructional model in teaching slit-lamp examination.
Developing skills in performing basic slit-lamp biomicroscopy is an important element of the ophthalmology undergraduate curriculum. As a doctor working in an ophthalmology department, I often provide slit-lamp teaching for medical students. This paper describes a lesson plan for this technique using Gagne's nine events of instruction. The presented lesson plan is a combination of Gagne's nine events of instruction and Peyton's four-step approach. Gagne's nine events of instruction correlate with and address the mental conditions of learning when adult learners are presented with various stimuli. Peyton's four-step approach is a model for teaching practical skills that consists of demonstration, deconstruction, explanation, and performance. This article describes a slit-lamp biomicroscopy teaching session using Gagne's nine events of instruction. Each step is carefully elaborated with relevant activities to suit learners with various learning styles. Peyton's approach is used to teach the actual skill. This lesson plan is particularly relevant for tutors designing slit-lamp biomicroscopy teaching for undergraduate students, foundation doctors, general practitioners and emergency department staff. Ultimately, this lesson plan also serves as a model that is applicable for acquiring many other practical skills. The flexible adoption of Gagne's nine events of instruction in combination with other teaching models helps in the planning of effective teaching sessions.


Measuring and analysing quality of life in cancer clinical trials: a review.
After brief consideration of the definition of the term 'quality of life', methods previously adopted and problems encountered in assessing and evaluating quality of life in clinical studies of cancer are reviewed. Desirable properties of any such assessment methods and approaches to the analysis of quality of life data are discussed. Illustrations are provided by reference to the methods of assessment of quality of life incorporated in two recently-initiated studies of cancer treatment.


Differential expression of ABCF2 protein among different histologic types of epithelial ovarian cancer and in clear cell adenocarcinomas of different organs.
Previously, we reported that ABCF2 protein expression is higher in clear cell than serous histotype of ovarian adenocarcinomas and that its expression correlates with chemoresponse in patients with clear cell ovarian cancer. In this study, we examined ABCF2 protein expression in mucinous, endometrioid, and poorly differentiated type of ovarian adenocarcinomas. In addition, ABCF2 expression was evaluated in clear cell adenocarcinomas derived from different organs. A total of 335 epithelial ovarian cancers, 23 clear cell adenocarcinomas of uterine corpus, and 34 clear cell adenocarcinomas of kidney were included in this study. ABCF2 protein expression was determined by immunohistochemistry. The results showed that cytoplasmic ABCF2 expression was significantly higher in clear cell-type ovarian cancer specimens compared with other types (P < .0001). There was a close relationship between nuclear ABCF2 expression levels and age of patients with clear cell ovarian cancer. Multivariate logistic regression model also demonstrated that cytoplasmic ABCF2 expression was associated with clear cell histology (odds ratio, 5.557; 95% confidence interval, 2.694-11.462; P < .0001). In addition, both clear cell adenocarcinomas of the ovary and the uterine corpus showed significantly higher levels of ABCF2 expression, compared with those of the clear cell adenocarcinoma of the kidney (P < .0001). These data suggest that ABCF2 protein may be a candidate marker for clear cell adenocarcinomas of the ovary and the uterine corpus and may be important for the pathogenesis of these diseases.


Characterization of non-heme iron aliphatic halogenase WelO5* fromHapalosiphon welwitschiiIC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones.
The in vitro biochemical characterization revealed that iron/2-oxoglutarate (Fe/2OG)-dependent aliphatic halogenase WelO5* in Hapalosiphon welwitschii IC-52-3 has an enhanced substrate specificity towards 12-epi-hapalindole C (1) in comparison to WelO5 in H. welwitschii UTEX B1830. This allowed us to define the origin of the varied chlorinated versus dechlorinated alkaloid structural diversity between the two welwitindolinone producers. Furthermore, this study, along with the recent characterization of the AmbO5 protein, collectively confirmed the presence of a signature sequence motif in the C-terminus of this newly discovered halogenase enzyme family that confers substrate promiscuity and specificity. These observations may guide the rational engineering and evolution of these proteins for biocatalyst application.


Cardiac tamponade due to primary pericardial lymphoma in a patient with AIDS.
Cardiac tamponade due to lymphomatous involvement of the heart is a dramatic and unusual complication. Because of their nonspecific clinical presentation, these tumors are seldom diagnosed antemortem. We report the case of a patient with AIDS who presented with signs and symptoms of cardiac tamponade. Emergency pericardiocentesis followed by staging studies revealed large cell B-lymphocyte lymphoma confined to the pericardial space. With combination chemotherapy, a durable complete response was obtained. This case illustrates the potential benefit of aggressive treatment of extranodal non-Hodgkin's lymphoma in a patient with AIDS. The case is of particular interest because of the unusual development of isolated pericardial involvement as the sentinel sign of lymphoma.


Long-term leaf C:N ratio change under elevated CO2 and nitrogen deposition in China: Evidence from observations and process-based modeling.
Climate change, elevating atmosphere CO2 (eCO2) and increased nitrogen deposition (iNDEP) are altering the biogeochemical interactions between plants, microbes and soils, which further modify plant leaf carbon‑nitrogen (C:N) stoichiometry and their carbon assimilation capability. Many field experiments have observed large sensitivity of leaf C:N ratio to eCO2 and iNDEP. However, the large-scale pattern of this sensitivity is still unclear, because eCO2 and iNDEP drive leaf C:N ratio toward opposite directions, which are further compounded by the complex processes of nitrogen acquisition and plant-and-microbial nitrogen competition. Here, we attempt to map the leaf C:N ratio spatial variation in the past 5 decades in China with a combination of data-driven model and process-based modeling. These two approaches showed consistent results. Over different regions, we found that leaf C:N ratio had significant but uneven changes between 2 time periods (1960-1989 and 1990-2015): a 5% ± 8% increase for temperate grasslands in northern China, a 3% ± 6% increase for boreal grasslands in western China, and by contrast, a 7% ± 6% decrease for temperate forests in southern China, and a 3% ± 5% decrease for boreal forests in northeastern China. Additionally, the structural equation models indicated that the leaf C:N change was sensitive to ΔNDEP, ΔCO2 and ΔMAT rather than ΔMAP and ecosystem types. Process-based modeling suggested that iNDEP was the main source of soil mineral nitrogen change, dominating leaf C:N ratio change in most areas in China, while eCO2 led to leaf C:N ratio increase in low iNDEP area. This study also indicates that the long-term leaf C:N ratio acclimation was dominated by climate constraint, especially temperature, but was constrained by soil N availability over decade scale.


Odontogenic Infection and dental Pain negatively impact Schoolchildren's Quality of Life.
The aim of this study is to assess the prevalence of odontogenic infection in low-income Brazilian schoolchildren and evaluate its association with the subjective variables of oral health-related quality of life and dental pain. In this cross-sectional study, 230 schoolchildren aged eight to ten years old underwent a clinical oral survey in which the DMFT/dmft and PUFA/pufa indexes were measured. Afterward, children responded individually to the Child Perceptions Questionnaire (CPQ8-10) and self-reports of dental pain were collected. Data were statistically analyzed using MannWhitney or Kruskal-Wallis test with a post-test by Dunn's and Pearson correlation. Of the children evaluated, 42.6% had odontogenic infection and 80% reported experiencing dental pain. Children's age (p = 0.034) and past experience of dental pain (p < 0.002) were associated with odontogenic sepsis, in addition to impairment of their emotional well-being (p = 0.008), social welfare (p = 0.009) and overall impact on quality of life (p = 0.019). Toothache intensity (p < 0.001), frequency (p < 0.001) and duration (p < 0.001) were correlated to the overall impact on children's quality of life. The prevalence of odontogenic infection remains high among low-income Brazilian schoolchildren. Pediatric infection and its related pain induce not only various biological disorders but also impair children's self-perception of quality of life.


Total synthesis of the turrianes and evaluation of the DNA-cleaving properties.
The first total synthesis of three naturally occurring cyclophane derivatives belonging to the turriane family of natural products is described. Their sterically hindered biaryl entity is formed by reaction of the Grignard reagent derived from aryl bromide 10 with the oxazoline derivative 18, and the macrocyclic tether of the targets is efficiently forged by ring closing metathesis. While conventional RCM catalyzed by the ruthenium-carbene complexes 33 or 34 invariably leads to the formation of mixtures of both stereoisomers with the undesirable (E)-alkene prevailing, ring closing alkyne metathesis (RCAM) followed by Lindlar reduction of the resulting cycloalkynes 37 and 38 opens a convenient and stereoselective entry into this class of compounds. RCAM can either be accomplished by using the tungsten alkylidyne complex [(tBuO)3 [triple bond] WCCMe3] or by means of a catalyst formed in situ from [Mo(CO)6] and para-trifluoromethylphenol. The latter method is significantly accelerated when carried out under microwave heating. Furthermore, the judicious choice of the protecting groups for the phenolic -OH functions turned out to be crucial. PMB-ethers were found to be compatible with the diverse reaction conditions en route to 3-5; their cleavage, however, had to be carried out under carefully optimized conditions to minimize competing O-C PMB migration. Turrianes 3-5 are shown to be potent DNA cleaving agents under oxidative conditions when administered in the presence of copper ions.


Canine hepatic vein branches associated with subendothelial mast cells and an adventitial lymphatic plexus.
Branches of the hepatic veins in the dog are equipped with peculiar, periodically arranged sphincter muscles which are known to constrict in response to hematogenous shock agents, causing the severe hepatic congestion characteristic of this species. As was confirmed in this study, the sphincters are more strongly and effectively disposed in the peripheral portion of the veins, including the sublobular and central veins. Mast cells were numerous around the sublobular branches, being specifically gathered beneath the endothelium as recorded by Fujita (1964). The present observation light-microscopically extended his findings, particularly with regard to the distribution of the mast cells along the entire course of the hepatic vein branches--from the proximal trunks through the sublobular veins to the central veins. In addition, mast cell condensation was especially pronounced in the peripheral branches, apparently in accordance with the development of the sphincters. Electron microscope observation confirmed the subendothelial location of the mast cells and revealed that, through an endothelial gap, the cells may extend a microprocess into the venous lumen, thus enabling the direct detection of hematogenous agents. A suspension of a bacterium, Listeria monocytogenes, was injected into the dog livers to induce hepatitis, and the resulting pathologically altered parts of the organ were examined light-microscopically. A heavy infiltration of inflammatory cells was found around the peripheral branches of the hepatic veins. The lymphatics accompanying the veins often contained lymphocytes and macrophages at two days after the injection. At five days, the lymphatics were extremely distended and twisted. The subendothelial mast cells were not encountered at the sites of severe cell infiltration.(ABSTRACT TRUNCATED AT 250 WORDS)


Retrobulbar hydatid cyst: assessment of two cases.
A 54-year-old man with a unilocular hydatid cyst within the infero-posterior angle of the orbit and a 6-year-old male child with a unilocular hydatid cyst within the supero-medial angle of the orbit are presented. The retrobulbar cysts were diagnosed with computed tomography and ultrasonography and were treated after serologic confirmation.


Channel Selection in Uncoordinated IEEE 802.11 Networks Using Graph Coloring.
One of the big challenges in decentralized Wi-Fi networks is how to select channels for the different access points (APs) and their associated stations (STAs) in order to minimize interference and hence maximize throughput. Interestingly enough, de facto standards in terms of uncoordinated channel selection are quite simple, and in many cases result in fairly suboptimal channel allocations. Here, we explore how graph coloring can be used to evaluate and inform decisions on Wi-Fi channel selection in uncoordinated settings. Graph coloring, in its most basic form, is a classic mathematical problem where colors have to be assigned to nodes in a graph while avoiding assigning the same color to adjacent nodes. In this paper, we modeled Wi-Fi uncoordinated channel selection as a graph coloring problem and evaluated the performance of different uncoordinated channel selection techniques in a set of representative scenarios of residential buildings. The results confirm some of the widely accepted consensus regarding uncoordinated channel selection but also provide some new insights. For instance, in some settings, it would be better to delegate the decision on which channel to use to transmit the STAs, rather than having the AP make the decision on its own, which is the usual way.


Fluorescence-activated single cell sorting of human embryonic stem cells.
Human embryonic stem cells (hESC) are the subject of intense investigation for use in regenerative medicine, in toxicity testing, and as models for the study of human development. Automated cell sorting will enhance the isolation of homogenous pools of differentiated hESCs both for basic studies and for therapeutic applications. Sorting could also be used to deplete undifferentiated, potentially tumourigenic cells. However, hESCs are sensitive to single cell disaggregation and recover poorly when plated at clonal density. Here we report a method for successful semi-automated single cell sorting of hESCs. This method utilizes an ES-specific promoter-transgene construct and automated FACS-based single cell sorting and plating. Clonal recovery in physiologic oxygen (2%) was increased fourfold over room oxygen (21%; p < 0.01). This automated protocol will help to realize proposed hESC strategies that are hampered by low throughput and poor yields.


Identifying differential expression genes and single nucleotide variations using RNA-seq in metastatic melanoma.
Melanoma is a malignant tumor and one of the most frequent metastatic cancers. This study was conducted to identify differential expression genes (DEGs) and single nucleotide variations (SNVs) in metastatic melanoma. We analyzed microarray data of GSE23056 downloaded from the Gene Expression Omnibus, including two normal samples (skinN1 and skinN2) and 2 metastatic melanoma samples (skinT and lymphT). We not only compared DEGs in metastatic melanoma samples with normal samples (lymphT_skinN and skinT_skinN), but also compared DEGs between two metastatic melanoma types (lymphT_skinT). SNVs were identified by using Burrows-Wheeler Aligner and Cufflinks in metastatic melanoma samples using RNA-seq. Sequence Alignment/Map tools and the ANNOVAR software were used to analyze and annotate SNVs. We identified 18 significantly common DEGs in lymphT_skinN and skinT_skinN and one common gene, YBX1, in lymphT_skinN, skinT_skinN, and lymphT_skinT. We identified 49,534, 48,118, 63,812, and 33,096 SNVs in skinN1, skinN2, skinT, and lymphT, respectively. Twenty-nine SNVs were located in exonic regions of two DEGs, HLA-B and TSPAN10. SNVs that exist only in tumors were located in MARVELD1, SLC16A3, and VAV3. The DEGs screened in our study are potential biomarkers for metastatic melanoma therapy.


Diagnostic Value of Fine-Needle Aspiration Biopsies and Pathologic Methods for Benign and Malignant Breast Masses and Axillary Node Assessment
Bacground: The goal of this study was to evaluate the fine needle aspiration (FNA) preoperatively together with Touch Print, Crush Print, frozen section and pathologic methods to reach a diagnosis for patients with breast and axillary masses. Methods: This study was conducted on 107 patients, and included 111 samples of breast and 43 of axillary masses taken at surgery. Data on epidemiological and clinical features of the patients were collected using a questionnaire. The results of the methods of FNA, Touch Print, and Crush Print were compared with the results of pathology after operations. Results: Comparison between the diagnosis values of FNA with pathology for breast cancer showed sensitivity, sensitivity, positive predictive values, negative predictive values, positive mendacious percentages, and negative mendacious percentages of 80.4%, 98%, 97.3%, 87.6%, 2%, and 19.6% , respectively, and for metastatic axillary lymph nodes, 80%, 95.6%, 94.1%, 84.6%, 4.4%, and 20%. Comparison of diagnosis values of FNA with Touch Print and Crush Print for breast cancer gave values of 82.2%, 89%, 97.3%, 89%, 1.6%, and 17.8%, respectively, and for metastatic axillary lymph nodes 84.2%, 95.8%, 94.1%, 88.4%, 14.2%, and 15.8%. Conclusion: Use of these methods, compared with pathology, can decrease cost, time, and a need for a second surgery and related complications.