Effect of adrenergic blockade on pressure-related ventricular arrhythmias.
This paper examines whether adrenergic blockade (B1) may prevent the arrhythmogenic effect of acute arterial pressure (AP) elevation. In 7 anesthetized dogs iv propranolol (0.2 mg/kg) was given and in another 2 dogs stellate ganglion excision was performed. Before and after these B1 manoeuvres the AP was repeatedly increased by either elevating an open-air arterial pressure reservoir or administering iv metaraminol and decreased by abating the pressure reservoir. In a continuous recording of AP and ECG the systolic (S) AP and the presence (or absence) of ventricular arrhythmia (A) was noted. Before B1 A was noted in 652/1715 (38.0%) 5-sec periods at a SAP of 160.3 +/- 69.9 mm Hg which was significantly higher than in the 1063 5-sec periods without A (104.2 +/- 54.3) in all experiments. Following B1 it was impossible to cause A in 3 experiments. In the remaining experiments the A incidence was reduced (significantly in 5/9 experiments) to a total of 253/983 (25.7%) periods (P less than 0.001). In the 5/9 experiments with post-B1 A, the mean SAP was higher with (185.0 +/- 97.9 mm Hg) than without A (113.7 +/- 59.9 mm Hg) (significantly in 2/9 experiments). Following fitting of the SAP distributions before and after B1 to their common distribution (i.e. the same AP), the incidence of A was higher before than after B1 in all experiments (significantly in 7/9). It is concluded that B1 has an antiarrhythmic action on AP-related A. This antiarrhythmic effect seems to be due partly to an antihypertensive effect of B1 and partly to an antiarrhythmic effect of B1 for a given AP.


The Dead Sea needs salt water… massively bleeding patients need whole blood: The evolution of blood product resuscitation.
Whole blood, that is blood that is not manufactured into its component red blood cells (RBC) plasma, and platelets (PLT) units, was the mainstay of transfusion for many years until it was discovered that the component parts of a blood donation could be stored under different conditions thereby optimizing the storage length of each product. The use of low anti-A and -B titer group O whole blood (LTOWB) has recently been rediscovered for use in massively bleeding trauma patients. Whole blood has several advantages over conventional component therapy for these patients, including simplifying the logistics of the resuscitation, being more concentrated than whole blood that is reconstituted from conventional components, and providing cold-stored PLTs, amongst other benefits. While randomized controlled trials to determine the efficacy of using LTOWB in the resuscitation of massively bleeding trauma patients are currently underway, retrospective data has shown that massively bleeding recipients of LTOWB with traumatic injury do not have worse outcomes compared to patients who received conventional components and, in some cases, recipients of LTOWB have more favourable outcomes. This paper will describe some of the advantages of using LTOWB and will discuss the emerging evidence for its use in massively bleeding patients.


Interferon induction by poly(inosinic acid).poly(cytidylic acid) segmented by spin-labels.
Poly(inosinic acid).poly(cytidylic acid) [(I)n.(C)n] duplexes of which the (C)n strand was modified to various degrees chemically or enzymatically with nitroxide radicals (spin-labels) were evaluated for interferon-inducing activity. Upon annealing of the chemically modified (C)n, (1C,Cx)n (X = 1000 or 16), with (I)n, the interferon-inducing activity was similar to that of (I)n.(C)n in PRK cell cultures. However, to overcome hydrolysis of the spin-label linkage in (1C,Cx)n, and enzymatic approach was taken to synthesize (1S(4)U,Cx)n copolymers with x = 100, 38, 16, and 8. The (1s(4)U,Cx)n copolymers were chemically stable, and upon annealing with (I)n the correlation time of the nitroxide moiety in (I)n. (1s(4)U,Cx)n was determined. A comparison of this correlation time with that measured for (RUGT,U100)n.(A)n, which contains the nitroxide moiety in position 5 of the U moiety, suggests that the 1s(4)U residue is in a nonintrahelical conformation and partitions the duplex into double-helical segments of varying size. The interferon-inducing activity of (I)n. (1s(4)U,Cx)n was evaluated in primary rabbit kidney, human skin fibroblast (strain VGS), and mouse L-929 cell cultures as well as in rabbits. The 1s(4)U residue did not cause a significant change in the interferon induction as compared to (I)n.(C)n in most systems tested unless x less than 16. These findings indicate that double-helical segments of approximately 16 base pairs partitioned by nonintrahelical 1s(4)U residues suffice to trigger the interferon response in all systems studied.


Use of virulence determinants and seropathotypes to distinguish high- and low-risk Escherichia coli O157 and non-O157 isolates from Europe.
The presence of 10 virulence genes was examined using polymerase chain reaction (PCR) in 365 European O157 and non-O157 Escherichia coli isolates associated with verotoxin production. Strain-specific PCR data were analysed using hierarchical clustering. The resulting dendrogram clearly separated O157 from non-O157 strains. The former clustered typical high-risk seropathotype (SPT) A strains from all regions, including Sweden and Spain, which were homogenous by Cramer's V statistic, and strains with less typical O157 features mostly from Hungary. The non-O157 strains divided into a high-risk SPTB harbouring O26, O111 and O103 strains, a group pathogenic to pigs, and a group with few virulence genes other than for verotoxin. The data demonstrate SPT designation and selected PCR separated verotoxigenic E. coli of high and low risk to humans; although more virulence genes or pulsed-field gel electrophoresis will need to be included to separate high-risk strains further for epidemiological tracing.


Naturally occurring human antiglobulins with specificity for E.
Human sera have been examined for antibodies with specific reactivity for gammaE using the tanned cell hemagglutination test. Cells tanned with three different gammaE myeloma proteins provided a reproducible test system. Inhibition of agglutination reactions by gammaE proteins, but not by gammaG, gammaA, gammaM, or gammaD confirmed the specificity of these reactions. 8.5% of 304 serial serum samples obtained from miscellaneous hospitalized patients showed clear-cut anti-gamma-globulins with specificity for gammaE. In most of these instances no definite clinical history of concomitant allergic disorders could be obtained. 53% of 73 patients with well-established allergic disorders (hay fever, extrinsic asthma) showed serum anti-gamma-globulins with reactivity for gammaE. Some patients studied before and after desensitization to Bermuda grass allergen showed an increase in titer or a conversion from negative to positive reactions for anti-gammaE antibodies following several month courses of progressive desensitization. Gradient and gel filtration studies indicated that anti-gammaE globulins were 19S gammaM in all instances. No clear correlation was noted between quantitative serum gammaE levels and titer of anti-gammaE antibodies.19S serum fractions with anti-gammaE antibody activity did not release histamine from normal human peripheral blood leukocytes, whereas specific rabbit anti-gammaE antisera consistently induced leukocytic histamine release. Moreover, macroglobulin fractions with anti-gammaE activity did not block allergen-specific leukocyte histamine release induced by in vitro leukocyte challenge with allergens such as Bermuda grass and leukocytes from allergic donors. In some instances 19S human serum fractions with anti-gammaE activity appeared to potentiate histamine release when incubated concomitantly with specific allergen and leukocytes from allergic individuals.


Genetic harm: bitten by the body that keeps you?
... We must attempt to explain, how, if ever, our existence may harm us. To address this and the other questions raised, I propose to examine what constitutes harm and whether it makes sense to say that our genetic makeup may harm us. To do this I will describe three approaches to the problem of describing the status of negative effects our genes have upon us, which I have named the "technical harm" view, the "constitutive" view, and the "harmful conditions" view. On the technical harm view, the standard definitions of harm are applied to genetic disposition in an attempt to couch genetic defects or flaws in terms of harming. The constitutive view rejects applying the concept of harm to genetic disposition on the grounds that it is impossible to separate genetic disposition from individual identity. Lastly, the harmful conditions view, which I conclude is the most successful of the three, focuses on the tendency of certain genetic dispositions to cause harm in the future and thus avoids what I will argue are the "context" shortcomings of the other two approaches. To conclude the discussion I will very briefly analyze the ramifications of a harmful conditions view for the concept of genetic disease and the prospects for genetic counseling, gene therapy, and reproductive decision making.


Protein tyrosine kinases and TNF alpha secretion in human monocytes.
The role of protein tyrosine kinases (PTK) in TNF alpha secretion by human monocytes was investigated in this report. We showed that an immunomodulator such as Nocardia lysozyme digest (NLD) and a particulate agonist, zymosan, stimulated an increase in tyrosine phosphorylation of several endogenous substrates including 53-56 kDa protein which was the predominant phosphoprotein. In addition, NLD and zymosan induced TNF alpha secretion which was impaired by a PTK inhibitor, tyrphostin. We suggest that a cascade of kinases including PTK is involved in NLD and zymosan signalling.


Heme-dependent activation of neuronal nitric oxide synthase by cytosol is due to an Hsp70-dependent, thioredoxin-mediated thiol-disulfide interchange in the heme/substrate binding cleft.
We have reported that heme-dependent activation of apo-neuronal nitric oxide synthase (apo-nNOS) to the active holo-enzyme dimer is dependent upon factors present in reticulocyte lysate and other cytosols. Here, we find that both Hsp70 and thioredoxin are components of the activation system. The apo-nNOS activating activity of reticulocyte lysate is retained in a pool of fractions containing Hsp70 that elute from DE52 prior to Hsp90. All of the activating activity and 20-30% of the Hsp70 elute in the flow-through fraction upon subsequent ATP-agarose chromatography. Apo-nNOS activation by this flow-through fraction is inhibited by pifithrin-μ, a small molecule inhibitor of Hsp70, suggesting that a non-ATP-binding form of Hsp70 is involved in heme-dependent apo-nNOS activation. Previous work has shown that apo-nNOS can be activated by thiol-disulfide exchange, and we show substantial activation with a small molecule dithiol modeled on the active motifs of thioredoxin and protein disulfide isomerase. Further fractionation of the ATP-agarose flow-through on Sephacryl S-300 separates free thioredoxin from apo-nNOS activating activity, Hsp70, and a small amount of thioredoxin, all of which are eluted throughout the macromolecular peak. Incubation of apo-nNOS with the macromolecular fraction in combination either with the thioredoxin-containing fraction or with purified recombinant human thioredoxin restores full heme-dependent activating activity. This supports a model in which Hsp70 binding to apo-nNOS stabilizes an open state of the heme/substrate binding cleft to facilitate thioredoxin access to the active site cysteine that coordinates with heme iron, permitting heme binding and dimerization to the active enzyme.


COMT genetic variation confers risk for psychotic and affective disorders: a case control study.
Variation in the COMT gene has been implicated in a number of psychiatric disorders, including psychotic, affective and anxiety disorders. The majority of these studies have focused on the functional Val108/158Met polymorphism and yielded conflicting results, with limited studies examining the relationship between other polymorphisms, or haplotypes, and psychiatric illness. We hypothesized that COMT variation may confer a general risk for psychiatric disorders and have genotyped four COMT variants (Val158Met, rs737865, rs165599, and a SNP in the P2 promoter [-278A/G; rs2097603]) in 394 Caucasian cases and 467 controls. Cases included patients with schizophrenia (n = 196), schizoaffective disorder (n = 62), bipolar disorder (n = 82), major depression (n = 30), and patients diagnosed with either psychotic disorder NOS or depressive disorder NOS (n = 24). SNP rs2097603, the Val/Met variant and SNP rs165599 were significantly associated (p = 0.004; p = 0.05; p = 0.035) with a broad "all affected" diagnosis. Haplotype analysis revealed a potentially protective G-A-A-A haplotype haplotype (-278A/G; rs737865; Val108/158Met; rs165599), which was significantly underrepresented in this group (p = 0.0033) and contained the opposite alleles of the risk haplotype previously described by Shifman et al. Analysis of diagnostic subgroups within the "all affecteds group" showed an association of COMT in patients with psychotic disorders as well as in cases with affective illness although the associated variants differed. The protective haplotype remained significantly underrepresented in most of these subgroups. Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.


Chemical leukoderma induced by dimethyl sulfate.
Chemical leukoderma occurs due to the toxic effect of a variety of chemical agents. Mechanisms include either destruction or inhibition of melanocytes. We report two male patients (36 and 51 years old) who presented with multiple hypopigmented macules and patches on the neck, wrist, and legs after exposure to dimethyl sulfate in a chemical industry. Physical examination revealed irregular depigmentation macules with sharp edges and clear hyperpigmentation around the lesions. History of repeated exposure to a chemical agent can help the clinical diagnosis of chemical leukoderma. This diagnosis is very important for prognosis and therapeutic management of the disease.


Controlling the sign of magnetoconductance in Andreev quantum dots.
We construct a theory of coherent transport through a ballistic quantum dot coupled to a superconductor. We show that the leading-order quantum correction to the two-terminal conductance of these Andreev quantum dots may change sign depending on (i) the number of channels carried by the normal leads or (ii) the magnetic flux threading the dot. In contrast, spin-orbit interaction may affect the magnitude of the correction, but not always its sign. Experimental signatures of the effect include a nonmonotonic magnetoconductance curve and a transition from an insulator-like to a metal-like temperature dependence of the conductance. Our results are applicable to ballistic or disordered dots.


β-1,4-Galactosyltransferase III enhances invasive phenotypes via β1-integrin and predicts poor prognosis in neuroblastoma.
Neuroblastoma (NB) is a neural crest-derived tumor that commonly occurs in childhood. β-1,4-Galactosyltransferase III (B4GALT3) is highly expressed in human fetal brain and is responsible for the generation of poly-N-acetyllactosamine, which plays a critical role in tumor progression. We therefore investigated the expression and role of B4GALT3 in NB. We examined B4GALT3 expression in tumor specimens from 101 NB patients by immunohistochemistry and analyzed the correlation between B4GALT3 expression and clinicopathologic factors or survival. The functional role of B4GALT3 expression was investigated by overexpression or knockdown of B4GALT3 in NB cells for in vitro and in vivo studies. We found that B4GALT3 expression correlated with advanced clinical stages (P = 0.040), unfavorable Shimada histology (P < 0.001), and lower survival rate (P < 0.001). Multivariate analysis showed that B4GALT3 expression is an independent prognostic factor for poor survival of NB patients. B4GALT3 overexpression increased migration, invasion, and tumor growth of NB cells, whereas B4GALT3 knockdown suppressed the malignant phenotypes of NB cells. Mechanistic investigation showed that B4GALT3-enhanced migration and invasion were significantly suppressed by β1-integrin blocking antibody. Furthermore, B4GALT3 overexpression increased lactosamine glycans on β1-integrin, increased expression of mature β1-integrin via delayed degradation, and enhanced phosphorylation of focal adhesion kinase. Conversely, these properties were decreased by knockdown of B4GALT3 in NB cells. Our findings suggest that B4GALT3 predicts an unfavorable prognosis for NB and may regulate invasive phenotypes through modulating glycosylation, degradation, and signaling of β1-integrin in NB cells.


[Sex chromosome analysis and IGF-II expression on activated human unfertilized oocytes after ICSI with calcium ionophore A23187 and puromycin].
To investigate the sex chromosomes and the expression of insulin-like growth factor-II (IGF-II) on activated human unfertilized oocytes after intracytoplasmic sperm injection(ICSI) with calcium ionophore A23187 and puromycin. All 95 discarded oocyes that showed no evidence of fertilization at 16-18 h after in vitro maturation and intracytoplasmic sperm injection cycles (IVM-ICSI)/conventional ICSI were exposed to calcium ionophore A23187 (5 micromol/L) for 5 min and then were incubated with puromycin (10 microg/mL) for 4 h. After activation, the oocytes were cultured in vitro for 3-5 days. The sex chromosome analysis was performed by dual color fluorescence in situ hybridization. The expression of IGF-II on the activated embryos, normal embryos, and parthenotes was examined. The combination of calcium ionophore A23187 with puromycin could activate the unfertilized oocytes 22 h after ICSI. The activated rate, cleavage rate, and quality of activated embryos of the IVM-ICSI group were similar to those of ICSI group, respectively. Sex chromosome analysis indicated that 8 male and 5 female embryos had been derived from two pronucleus and a second polar body. The expression of IGF-II on activated embryos and normal embryos was high and similar, which was much stronger than that of parthenotes. The combination of calcium ionophore A23187 with puromycin could effectively activate unfertilized oocytes 22 h after ICSI. Moreover, the unfertilized oocytes activated by calcium ionophore A23187 and puromycin had normal sex chromosomes and expression of IGF-II like the normal embryos. These suggest that oocyte activation may be considered as a remedial measure in the presence of total or nearly total fertilization failure in ICSI.


[The Effect of Repeated Local Ischemia on the Temperature and Skin Microcirculation in Human Hand].
Thermal imaging and laser Doppler flowmetry were applied to study the effects of infrared (IR) radiation mediated by vascular response in healthy volunteers during regular unilateral arteriovenous occlusion of one of the fingers (4 times a day for 7 months with a gradual increase in exposure from 10 to 30 min). After repeated unilateral exposure, we observed consistent changes in temperature conditions and modes of thermoregulation of corresponding skin areas of both hands. We discovered a high level of positive correlation between the dynamics of IR emission from the experimental and control skin areas in the recovery phase after clamping, which indicates that systemic vascular response is involved. The possible mechanisms of post-occlusive changes in skin of the distal phalanges are discussed. These data suggest that multiple regular unilateral arteriovenous occlusions enhance the intradermal blood flow and can be used for the prevention of disorders of the peripheral microcirculation in various pathological conditions.


Interaction of actin with N-ethylmaleimide modified heavy meromyosin in the presence and absence of adenosine triphosphate.
N-Ethylmaleimide modified heavy meromyosin in only 3-fold activated by actin rather than 200-fold as is normal heavy meromyosin (Silverman, R., Eisenberg, E., and Kielley, W. W. (1972), Nature (London) 240, 207). Ultracentrifuge studies demonstrated that in the absence of ATP the N-ethylmaleimide modified heavy meromyosin binds to actin at a ratio of 2 actins to 1 N-ethylmaleimide modified heavy meromyosin. However, it was found that most of the N-ethylmaleimide modified heavy meromyosin was not bound to actin during ATP hydrolysis. Ultracentrifuge studies demonstrated that in the presence of 25 or 50 mM KCl under conditions where the ATPase is maximally activated by actin, less than 5% of the N-ethylmaleimide modified heavy meromyosin was bound to actin. In the absence of KCl there was limited binding but even this binding did not appear to correlate with the N-ethylmaleimide modified heavy meromyosin ATPase rate. Turbidity and viscosity studies also indicated that in the presence of ATP under conditions of maximal actin activation the N-ethylmaleimide modified heavy meromyosin and actin are almost completely dissociated, whereas there is a marked increase in turbidity and viscosity after all of the ATP is hydrolyzed. These results suggest that in the presence of ATP and actin N-ethylmaleimide modified heavy meromyosin exists most of the time in a refractory state unable to bind to actin and only a small part of the time in a nonrefractory state which can interact with actin. It follows that the major rate-limiting step during actin activation is the transition from the refractory to the nonrefractory state. Since the actin activation of N-ethylmaleimide modified heavy meromyosin is lower than that of normal heavy meromyosin this transition may be slower for N-ethylmaleimide modified heavy meromyosin than for normal heavy meromyosin.


Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex.
Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore-microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubule-binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex.


Two-Dimensional MXene with Controlled Interlayer Spacing for Electrochemical Energy Storage.
In this issue of ACS Nano, Luo et al. report the preparation of pillared two-dimensional (2D) Ti3C2 MXenes with controllable interlayer spacings between 1 and 2.708 nm. These materials were further intercalated by ion exchange with Sn(+IV) ions. The results show improved electrochemical performance due to improved ion accessibility into the 2D structure as well as the confinement effect, which limits volume expansion during the Li-alloying reaction. Beyond this specific example, the demonstration that the interlayer spacings of MXenes can be fine-tuned by creating pillared structures based on the spontaneous intercalation of surfactants opens new perspectives in the field of electrochemical energy storage.


Lipoteichoic acid as a target for antimicrobial action.
Daptomycin, a lipopeptide antibiotic active against gram-positive bacteria, has been found to inhibit lipoteichoic acid (LTA) synthesis as a consequence of membrane binding in the presence of Ca2+. The present study shows that among the bacterial-membrane components, daptomycin binds the protein fraction with a noncovalent bond, as suggested by the instability of the bond in the presence of an ionic detergent such as sodium dodecyl sulfate. Analysis of membrane proteins by isoelectric focusing electrophoresis reveals that 5 bands with isoelectric points ranging from 5.9 to 6.2 bind radioactive daptomycin. These proteins are therefore called daptomycin-binding proteins. In an attempt to correlate these proteins with the main inhibition observed in LTA synthesis, two-dimensional thin-layer chromatography of lipids synthesized during daptomycin treatment was performed. A 3-fold increase in diglucosyl diacylglycerol is demonstrated, while the compounds phosphatidyl-alpha-kojibiosyldiacylglycerol, glycerophosphophosphatidyl-alpha-kojibiosyldiacyl glycerol, and glycerophosphokojibiosyldiacylglycerol, which follow diglucosyl diacylglycerol in LTA synthesis, decrease progressively with time during the course of daptomycin treatment.


Revisiting the issue: can the reading for serologic reactivity following 37 degrees C incubation be omitted?
Omitting the 37 degrees C reading from screening tests for unexpected antibodies results in failure to detect some Rh, K, and Jk agglutinins of potential significance (wanted positives). However, this measure avoids unwanted positive tests due to cold agglutinins. Using data from prior publications, actual risk calculations (ARCs) were made to predict the risk of eliminating the 37 degrees C reading, pretransfusion direct antiglobulin test (DAT), and routine indirect antiglobulin crossmatch (IAT-XM). ARCs used the equation: wanted positives missed x 0.34 (or 0.80) x 5 x percent antigen-positive, where 0.34 = percent of patients transfused (ARCs for 37 degrees C reading and DAT); 0.80 = percent of crossmatched patients transfused (ARCs for IAT-XM); 5 = average number of units transfused. Following elimination of the 37 degrees C reading, the impact of this change on patient care was monitored. Antibody detection and identification data and transfusion reaction reports for 6 months after the change were reviewed. Recently transfused patients with new antibodies were evaluated for immune hemolysis by review of clinical and laboratory data. The findings were compared with those from the same dates of the preceding year. The risk of transfusing incompatible blood by eliminating the DAT, IAT-XM, and 37 degrees C reading is approximately 1:13,000, 1:2,000, and 1:2,400 units transfused, respectively. The cumulative risk from eliminating all three tests is approximately. 1 :1,000 units. With respect to the 37 degrees C reading, there were no differences between the pre-change and post-change study periods in the incidence of reported transfusion reactions or cases of immune hemolysis associated with newly formed antibodies. However, unwanted positive tests decreased from 162 to 61 following elimination of the 37 degrees C reading. This represents a decrease of 20 percent in the number of samples requiring antibody identification annually. Eliminating the 37 degrees C reading from pretransfusion antibody screening tests imposes less risk than omitting the routine IAT-XM, and it avoids the time and costs of evaluating unwanted positive tests, thus reducing expenditures and delays in patient care.


[Thrombocytopenia after autologous bone marrow transplantation in in acute lymphatic leukemia].
There is reported about the treatment of refractory thrombocytopenia in a 9 years old boy following the autologous bone marrow transplantation for acute lymphoblastic leukaemia. The megakaryocytes were found diminished in the bone marrow smears. Controls of the thrombocyte count and the kinetics with radioactively labeled platelets of a donor spoke in favour of immunothrombocytopenia. Threatening bleeding complications challenged the use of all treatment possibilities. The irradiation of the spleen was without any success. After the splenectomy the thrombocyte count increased slowly, but after a remarkable lag phase, however. A diminished reproduction capacity of the bone marrow graft for special cell sorts has to be taken into account in such cases. The usual cytodynamics after splenectomy cannot be expected at all.


LncRNA AATBC regulates Pinin to promote metastasis in nasopharyngeal carcinoma.
Long noncoding RNA (lncRNA) have emerged as crucial regulators for a myriad of biological processes, and perturbations in their cellular expression levels have often been associated with cancer pathogenesis. In this study, we identified AATBC (apoptosis-associated transcript in bladder cancer, LOC284837) as a novel lncRNA. AATBC was found to be highly expressed in nasopharyngeal carcinoma (NPC), and increased AATBC expression was associated with poor survival in patients with NPC. Furthermore, AATBC promoted migration and invasion of NPC cells in vitro, as well as metastasis in vivo. AATBC upregulated the expression of the desmosome-associated protein pinin (PNN) through miR-1237-3p sponging. In turn, PNN interacted with the epithelial-mesenchymal transition (EMT) activator ZEB1 and upregulated ZEB1 expression to promote EMT in NPC cells. Collectively, our results indicate that AATBC promotes NPC progression through the miR-1237-3p-PNN-ZEB1 axis. Our findings indicate AATBC as a potential prognostic biomarker or therapeutic target in NPC.


Hepatic gastrinoma.
A solitary hepatic tumor in a 50-year-old woman, which was observed as a hemangioma, ultimately was resected because it increased in size. The tumor volume doubling time was 28.8 months over the observed period of 30 months. The histologic diagnosis was carcinoid tumor. Immunohistochemical staining showed strong focal reactivity for gastrin and diffuse reactivity for pancreatic polypeptide, vasointestinal polypeptide, calcitonin, and parathormone. Preoperative gastric hyperacidity with diarrhea and a body weight loss of 7 kg, moderately controlled by cimetidine on admission, suggested high serum gastrin levels produced by the tumor. Her symptoms resolved after surgery, and she had a normal serum gastrin level with negative secretin stimulation test results. A review of six cases of hepatic gastrinoma suggests that surgical resection, if feasible, would be the treatment of choice.


miR-182-3p/Myadm contribute to pulmonary artery hypertension vascular remodeling via a KLF4/p21-dependent mechanism.
Rationale: There is a continued need for investigating the roles of microRNAs and their targets on the pathogenesis of pulmonary arterial hypertension (PAH) vascular remodeling. We recently identified the association of myeloid miR-182-3p and its new target, Myeloid-Associated Differentiation Marker (Myadm), with vascular remodeling. Here, we aimed to determine the role of miR-182-3p/Myadm on PAH vascular remodeling and the underlying molecular mechanism. Methods: The miR-182-3p/Myadm expression profiles were detected in PAH patients and experimental rodent models. Loss-of-function and gain-of-function studies using gene knock-in or gene knock-out and the combinations of the proteomic technology and genome-wide ChIP-Seq were employed to determine the downstream targets of miR-182-3p/Myadm in response to monocrotaline (MCT)-induced PAH. Results: The miR-182-3p/Myadm expression was altered in PAH patients and experimental rodent models. Both miR-182-3p inhibitor and overexpression of Myadm augmented the pathological progression in rats in response to MCT-induced PAH. In contrast, miR-182-3p mimic and Myadm gene knockout attenuated the changes in the hemodynamics and structure of the cardio-pulmonary system in MCT-induced PAH in rats. Myadm mediated the proliferation of pulmonary artery smooth muscle cells (PASMCs) by altering the cell cycle kinase inhibitor (p21/Cip1) expression through the transcription factor Krüppel-like factor 4 (KLF4) translocation into the cytoplasm. Conclusion: Our findings indicate the prognostic and therapeutic significance of miR-182-3p in PAH and provide a new regulatory model of the myeloid-derived miR-182-3p/Myadm/KLF4/p21 axis in PAH vascular remodeling.


Thaxterogaster revisited: A phylogenetic and taxonomic overview of sequestrate Cortinarius from Patagonia.
In the Patagonian region, Cortinarius is the most diverse and abundant genus of ectomycorrhizal fungi with at least 250 species. Sequestrate forms were until recently documented within the genus Thaxterogaster, a genus now known to be polyphyletic, and many were consequently transferred to Cortinarius. Original descriptions were mostly available in German and Spanish and interpretations of morphological structures outdated. Despite recent advances in Cortinarius systematics, the current classification, diversity, and ecology of sequestrate "cortinarioid" fungi in Patagonia remain unclear. The objective of this study was to provide an update on sequestrate Cortinarius of southern South America. We documented each species with morphological descriptions, photographs, basidiospore scanning electron microscopy (SEM) images, and molecular characterization using nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and nuc 28S rDNA (28S) sequence data. Original descriptions of taxa were also translated to English and revised based on fresh collections. We documented 24 species from Patagonia based on molecular data and conducted morphological and phylogenetic analysis for 18 previously described species based on type and reference specimens. In addition, we formally described two new species. Four additional taxa were provisionally determined as new but require further study. New ITS sequence data were produced from eight type specimens. We also provide a new name, Cortinarius gloiodes, nom. nov., for the taxon previously described as Thaxterogaster gliocyclus. In addition to the species treated in detail, we provided additional reference information and discussion on six described species that remained incompletely known or for which no recent collections were found. Of the 24 taxa documented from Patagonia, 15 species were assigned to 12 current sections in the genus Cortinarius. Analysis of spore ultrastructure showed that sequestrate forms of Patagonian Cortinarius lack a true perisporium.


An inferential approach to the knew-it-all-along phenomenon.
Two studies tested the hypothesis that the knew-it-all-along effect may be the result of an inferential process. Specifically, that individuals use their feelings and experiences (e.g., "This question seems so familiar to me, surely I would have known the answer!") to infer their judgement. Drawing on subjective feelings such as certainty or perceptual fluency, individuals can use a provided actual value as an informational cue and draw inferences from it. Thus, the occurrence of the knew-it-all-along effect is expected to depend on the experienced feeling of confidence with a question. This feeling may indicate to an individual that he or she did know the answer; a total lack of such a feeling may suggest that he or she never would have known the answer. In the reported studies we both measured feelings of confidence (Study 1) and induced them by manipulating perceptual fluency (Study 2) to show that the knew-it-all-along effect proves to be a phenomenon of inferences based on these experienced feelings. Participants experiencing high confidence or high perceptual fluency more strongly assimilated their judgements to the provided values, than did participants experiencing low confidence or low perceptual fluency.


Use of social media in the marketing of agricultural products and farmers' turnover in South-South Nigeria.
Background: The study investigated the use of social media in the marketing of agricultural products and farmers turnover in South-South Nigeria. The purpose of the study was to determine the extent to which the usage of social media in the marketing of agricultural products in Nigeria can enhance efficiency and farmers' sales turnover. Methods: It employed the survey research design and data were collected with the help of a structured questionnaire. Research data were analysed using a t-test and least squares method. Results: The use of social media (WhatsApp and Instagram) in the marketing of agricultural products was found to enhance efficiency and turnover of farmers through a significant reduction in the cost of marketing agricultural products as well as increased demand for agricultural products. Conclusions: The use of social media (WhatsApp and Instagram) in the marketing of agricultural products significantly influences cost reduction and hence efficiency in marketing as well as enhances turnover of farmers through increased demand for agricultural products. Contribution: The examination of the implications of the usage of social media usage in agricultural marketing on marketing efficiency and sales turnover in Nigeria.


Physicochemical properties of superfine grinding-microwave modified artichoke soluble dietary fiber and their alleviation of alcoholic fatty liver in mice.
The effects of superfine grinding (SG) and microwave treatment (MT) on the structure and physicochemical properties of artichoke soluble dietary fiber (ASDF) and its protective effects on mice with alcoholic fatty liver (AFL) were studied. We compared the changes in structural characteristics and physicochemical properties of ASDF, SG-ASDF (ASDF treated by SG), MT-ASDF (ASDF treated by MT), and CM-ASDF (ASDF treated by SG and MT). Moreover, we evaluated the effects of the obtained ASDF on the growth characteristics, blood lipid levels, and liver of mice with AFL. Our results of the study showed that CM-ASDF had a more concentrated and uniform particle size, a higher extraction rate of ASDF and significantly improved water-holding capacity (WHC), oil-holding capacity (OHC) and water swelling capacity (WSC) of ASDF (p < 0.05). After the ASDF intervention, mice with AFL exhibited a significant improvement in body lipid levels and reduce liver inflammation. Specifically, aspartate aminotransferase (AST), alanine aminotransferase (ALT), malonaldehyde (MDA), Tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly increased (p < 0.05). And the hematoxylin-eosin (HE) staining results showed significant improvement of hepatic steatosis in mice with AFL. In summary, our study found that both SG and MT could improve the structure and physicochemical properties of ASDF, with CM-ASDF being the most effective. Additionally, CM-ASDF was selected to continue the investigation and demonstrated an excellent protective effect on mice with AFL, with the high dose group (H-ASDF) showing the greatest benefit. These findings provided some new insights for future comprehensive utilization of ASDF and drug development for the treatment of AFL.


IDI2, a second isopentenyl diphosphate isomerase in mammals.
We recently described the identification of a novel isopentenyl diphosphate isomerase, IDI2 in humans and mice. Our current data indicate that, in humans, IDI2 is expressed only in skeletal muscle. Expression constructs of human IDI2 in Saccharomyces cerevisiae can complement isomerase function in an idi1-deficient yeast strain. Furthermore, IDI2 has the ability to catalyze the isomerization of [(14)C]IPP to [(14)C]DMAPP. Enzyme kinetic analysis of partially purified IDI2 demonstrate the novel isozyme has a maximal relative specific activity of 1.2 x 10(-1) +/- 0.3 micromol min(-1) mg(-1) at pH 8.0 with a K(IPP)(m) value of 22.8 microm IPP. Both isozymes, IDI1 and IDI2 are localized to the peroxisome by a PTS1-dependent pathway. Finally, our data suggest that IDI2 is regulated independently from IDI1, by a mechanism that may involve PPARalpha.


Radiotherapy and short-term androgen deprivation for localized prostate cancer.
It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).


Traumatic rupture of sternocleidomastoid muscle following an epileptic seizure.
A 29-year-old man, a known epileptic, presented to an accident and emergency department following a tonic-clonic seizure, suffering a second seizure in the department. Subsequently, he reported neck pain, swelling and stiffness. An otorhinolaryngology neck examination revealed a tender left side with two palpable masses and a reduced range of movement. Ultrasound confirmed a ruptured middle third of the left sternocleidomastoid muscle, which was successfully treated non-surgically with analgaesia and intensive physiotherapy. Uncommonly, sternocleidomastoid muscle rupture has been reported following high-velocity trauma, but to the best of our knowledge this is the first case described in the literature following an epileptic seizure.


Synthesis and Characterization of (89)Zr-Labeled Ultrasmall Nanoparticles.
The ultrasmall nanoparticle AGuIX is a versatile platform that tolerates a range of chemical diversity for theranostic applications. Our previous work showed that AGuIX clears rapidly from normal tissues, while durably accumulating within the tumor microenvironment. On this basis, AGuIX was used to detect tumor tissue with Gd(3+) enhanced MRI and can sensitize tumors to radiation therapy. As we begin the translation of AGuIX, we appreciated that coupling AGuIX to a long-lived radioisotope would help to more completely measure the magnitude and duration of its retention within the tumor microenvironment. Therefore, we developed (89)Zr-DFO-AGuIX. AGuIX was coupled to DFO and then to (89)Zr in ∼99% radiochemical yield. Stability studies showed that (89)Zr-DFO-AGuIX did not dissociate after 72 h. In animals bearing U87MG xenografts, it was detectable at levels above background for 72 h. Lastly, (89)Zr-DFO-AGuIX did not accumulate in inflammatory abscesses in vivo, highlighting its specificity for well vascularized tumors.


Human albumin solutions in intensive care: A review.
Albumin plays a key role in the critically ill patient acting as a prognostic marker and as a therapy in the form of human albumin solutions. However, the use of human albumin solution has varied over time with notable differences between health systems. Whilst its use is widely accepted for some clinical indications, its role has not always been clear in the critically ill and has been found to be harmful in some cohorts. Numerous studies have showed conflicting results and critical care clinicians have not always been guided by robust evidence. Nonetheless, at present the use of human albumin solution appears to be increasing again in the United Kingdom. Below, we discuss the latest evidence base for its use in critically ill patients.


Social recapitulation: moulting can restore social tolerance in aggressive spiderlings.
In many taxa, the subsocial route is considered the main pathway to permanent sociality, but the relative contribution of offspring interactions and parental care to the maintenance of cohesion and tolerance at advanced developmental stages remains poorly studied. Spiders are relevant models for this question because they all show a transient gregarious phase before dispersal, and the transition to permanent sociality, which concerns approximately 20 of the ∼50,000 species, is assumed to rely on the subsocial route. Using spiderlings of the solitary species Agelena labyrinthica, we manipulated the social context to demonstrate that tolerance in aggressive juveniles can be restored when exposed to siblings after moulting. We propose that moulting can reopen closed critical periods and renew the imprinting to social cues and thus lead to the reacquisition of tolerance. Our study highlights the critical role of contacts between juveniles in the expression of tolerance, which opens novel avenues for understanding social transitions.


On the Performance and Implementation of Parallax Free Video See-Through Displays.
In see-through systems an observer watches a (background) scene partially occluded by a display. In this display, usually positioned close to the observer, a region of the background scene is shown, yielding the sensation that the display is transparent. To achieve the transparency effect, it is very important to compensate the parallax error and other distortions caused by the image acquisition system. In this paper a detailed study of a video see-through methodology with parallax correction is performed. In a system composed by two cameras-one directed to the user and another to the background scene-and a display, the relative position between the user, the display and the scene is estimated using a feature detection algorithm and the parallax error is compensated assuming a planar scene model. The application of the proposed methodology on Driver Assistance Systems (DAS) is proposed. A theoretical assessment of the algorithm shows that although approximations are proposed to simplify the methodology and reduce the computational cost, such as the planar scene model and fixed working distance, on some practical situations their effects can be neglected without noticeable impact on the perceptual quality of the solution.


Direct access to poly(glycidyl azide) and its copolymers through anionic (co-)polymerization of glycidyl azide.
Glycidyl azide polymer or poly(glycidyl azide) which is considered as an excellent energetic binder or plasticizer in advanced solid propellants is generally obtained by post-modification or azidation of poly(epichlorohydrin). Here we report that glycidyl azide can be directly homopolymerized through anionic ring-opening polymerization to access poly(glycidyl azide) using onium salts as initiator and triethyl borane as activator. Molar masses of poly(glycidyl azide) up to 11.0 Kg/mol are achieved in a controlled manner with a narrow polydispersity index (PDI ≤ 1.2). Similarly, alternating poly(glycidyl azide carbonate) are also prepared through alternating copolymerization of glycidyl azide with carbon dioxide. Lastly, the copolymerization of glycidyl azide with other epoxide monomers is carried out; the azido functions carried by glycidyl azide which are successfully incorporated into the backbones of polyethers and polycarbonates based on cyclohexene oxide and propylene oxide subsequently served to introduce other functions by click chemistry.


[Radioadaptive response in vitro of unstimulated rat lymphocytes according to metallothionein test].
It was shown that 24 h after acute action of gamma-radiation in vitro on unstimulated rat lymphocytes the metallothionein (MT) level did not change for doses of 0.01; 0.5 and 1.0 Gy, while dosed of 1.75 and 2.5 Gy increased this parameter 2 and 2.6 times on the average. After exposure to 0.01 Gy of adaptive radiation 2 h before exposure to 1.75 Gy of the damaging dose reliably lower (1.5 times on the average) increase in MT content was found. The heterogeneity in display of the radioadaptive response by MT test for various lymphocyte preparations was found. Two possible mechanisms of the obtained changes were discussed. One of them is connected with the selection irradiation death of cells with the initially low MT level, and the other is caused by postradiation MT synthesis as a result of accumulation of the DNA damages and MT genes amplification.


Radiologic correlates of reaction time measurements in olivopontocerebellar atrophy.
We measured simple visual and auditory reaction time (RT) and movement time (MT) in 32 patients with olivopontocerebellar atrophy (OPCA) in comparison to 32 control subjects. In addition, we followed 2 approaches to radiologic assessment by computed tomographic scans: subjective (by inspection of films) and objective (by measurement of 4 radiologic ratios at the level of the posterior fossa and 1 ratio at the supratentorial level). All OPCA patients had various degrees of cerebellar atrophy and lengthened RT and MT in comparison to their controls. There were no significant differences in RT and MT performances in patients with mild-moderate versus those with severe cerebellar atrophy as assessed by inspection of their films. OPCA patients with severe versus mild-moderate atrophy evaluated by 3 measures, i.e., brainstem, brachium pontis and fourth ventricle ratios, presented few significantly lengthened RT and MT performances. In contrast, patients with severe atrophy revealed by the midbrain ratio had significantly lengthened RT and MT performances compared to those with mild-moderate atrophy assessed by this ratio on 7 of 8 measures; the 8th measure showed a borderline significant difference. This could be explained by the fact that atrophy at the midbrain level is the only one which involves dopaminergic, noradrenergic and glutamatergic structures and pathways.


Brazilian donkeys (Equus asinus) have a low exposure to Neospora spp.
Donkeys (Equus asinus) are closely related to horses and are known to be infected by several equine pathogens. Neospora caninum and Neospora hughesi are protozoan parasites that infect horses, but they were not confirmed in donkeys up to this date. The aim of this study was to evaluate the exposure of donkeys (Equus asinus) to Neospora spp. using tachyzoites of N. caninum as antigen and employing two common serologic methods, IFAT and immunoblot. Sera from 500 donkeys were obtained from 30 municipalities in Bahia state and tested by IFAT. Two of 500 sera were positive for Neospora spp. by IFAT with antibody titers of 100, and recognized a 37kDa antigen in immunoblot. Approximately 22% of the samples showed strong apical reactions and/or incomplete fluorescence, what may cause confusion in the interpretation of IFAT. We concluded that Neospora spp. are possibly of minor importance for Brazilian donkeys. Future studies are necessary to prove that Neospora spp. can naturally infect donkeys.


Modification of osteopontin and MMP-9 levels in patients with psoriasis on anti-TNF-α therapy.
Psoriasis is a chronic skin inflammatory disease in which a pleiotropic cytokine, tumor necrosis factor alpha (TNF-α), plays a central role, as demonstrated by the clinical success of anti-TNF-α therapy. Among the multiple effects of TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammation, might be one of the key mechanisms in psoriasis pathogenesis. Interestingly, MMP-9 expression can be enhanced also by osteopontin (OPN), a glycosylated protein whose levels are increased in skin and peripheral blood mononuclear cells (PBMC) of psoriasis patients. The aim of the current study is to investigate the relationship between OPN, MMP-9 and TNF-α in psoriasis. Our survey identified high levels of both OPN and MMP-9 in PBMC as well as skin of psoriatic patients with respect to healthy controls. Significant reduction of OPN and MMP-9 levels in PBMC, plasma and lesional skin of psoriasis patients was observed after 24 weeks of anti-TNF-α therapy. Moreover, OPN and MMP-9 were enhanced by TNF-α and down-regulated by anti-TNF-α treatment in healthy PBMC. These findings may suggest that OPN and MMP-9 may be regulated by TNF-α, indicating a possible role in the pathogenesis of psoriasis.


Metabolic state does not influence lymphocyte subsets in type 1 diabetic patients.
In most studies the distribution of peripheral lymphocyte subsets at diagnosis of type 1 diabetes has been found to be altered. Lymphocyte subpopulations were therefore studied during longitudinal changes in the glycaemic control of 11 type 1 diabetics to investigate whether poor metabolic status affects these results. To avoid any influence of the etiopathogenetic mechanisms, the patients studied had a disease duration of 10 +/- 2 (SEM) years and all but one had no residual beta-cell function. The patients were selected randomly amongst those with a long record of poor glycaemic control and at the first examination they had a mean fasting blood glucose of 15 +/- 1 mmol/l and a mean glucosuria of 67 +/- 11 g/24 h. They were then hospitalized and strictly regulated using pump treatment, resulting in a massive reduction in glucosuria (0 +/- 0 g/24 h) and fasting blood glucose (6 +/- 1 mmol/l) at a second examination a week later. Five of the patients were tested for a third time 35 +/- 4 days later and were still in very good glycaemic control. Peripheral lymphocytes were labelled with monoclonal antibodies and examined by flow cytometry (FACS). Neither CD3+ (pan) T-lymphocytes, CD4+ (helper) T-cells, CD8+ (suppressor/cytotoxic) T-cells, the relation between CD4+ and CD8+ T-cells, nor the total amount of lymphocytes, changed significantly between the first, second, and third examination. None of the results were significantly different from those of healthy controls. There was no correlation between any of the immunological and metabolic parameters. It is concluded that metabolic influence on the distribution of lymphocyte subsets is unlikely.


Lymphatic mapping and sentinel node harvesting in patients with recurrent breast cancer.
To evaluate the feasibility and consequences of lymphatic mapping and a ("repeat") sentinel lymph node (SLN) procedure in patients with breast cancer relapse after previous breast and axillary surgery. Review and presentation of a patient cohort. All SLN procedures included lymphoscintigraphy and blue dye injection technique. Twelve cases are described: two patients after a previous SLN procedure and ten after a previous complete axillary lymph node dissection (ALND). Ten patients (83%) had a successful repeat SLN biopsy. After previous ALND, lymphoscintigraphy revealed drainage towards the internal mammary chain in three patients, and contralateral axillary drainage in four. Based on the information from the "repeat" SLN biopsy further treatment strategy was altered in seven of the 12 patients. Lymphatic mapping and (repeat) SLN biopsy is possible and can be informative in patients who present with a relapse of breast cancer after previous surgery for primary breast cancer.


Deterministic Construction of Nodal Surfaces within Quantum Monte Carlo: The Case of FeS.
In diffusion Monte Carlo (DMC) methods, the nodes (or zeroes) of the trial wave function dictate the magnitude of the fixed-node (FN) error. In standard DMC implementations, the nodes are optimized by stochastically optimizing a short multideterminant expansion in the presence of an explicitly correlated Jastrow factor. Here, following a recent proposal, we pursue a different route and consider the nodes of selected configuration interaction (sCI) expansions built with the CIPSI (Configuration Interaction using a Perturbative Selection made Iteratively) algorithm. By increasing the size of the sCI expansion, these nodes can be systematically and deterministically improved. The present methodology is used to investigate the properties of the transition metal sulfide molecule FeS. This apparently simple molecule has been shown to be particularly challenging for electronic structure theory methods due to the proximity of two low-energy quintet electronic states of different spatial symmetry and the difficulty to treat them on equal footing from a one-electron basis set point of view. In particular, we show that, at the triple-ζ basis set level, all sCI results-including those extrapolated at the full CI (FCI) limit-disagree with experiment, yielding an electronic ground state of 5Σ+ symmetry. Performing FN-DMC simulation with sCI nodes, we show that the correct 5Δ ground state is obtained if sufficiently large expansions are used. Moreover, we show that one can systematically get accurate potential energy surfaces and reproduce the experimental dissociation energy as well as other spectroscopic constants.


Class II-restricted bifunctional T-cell hybridomas reactive to self- and foreign myelin basic protein.
To study the cross-reactivity and functional properties oF murine T cells specific for myelin basic protein (MBP), a panel of 15 interleukin-2(IL-2)-releasing T-cell hybridomas was produced from SJL/J mice immunized either with human MBP or alternatively with a peptide corresponding to the known encephalitogenic sequence for SJL/J mice at positions 89-106. Hybridomas were I-As-restricted and activated by an MBP challenge as low as 20 nM. Cross-reactivity to other MBP indicated at least three immunodominant specificities for xenogeneic determinants, which could be further subdivided on the basis of antigen-independent reactivity to allogeneic stimulator cells. In addition, two self-specificities were demonstrated, one of which was to a determinant outside the 89-106 region. Irrespective of specificity pattern (self or foreign), all hybridomas effected antigen-dependent cytotoxicity of an antigen-presenting B-cell hybridoma (LS-102.9), which was mediated by cell contact or at close range. These findings suggest an approach to identifying new autoantigenic epitopes on MBP, and to studying T-cell-mediated effector pathways in myelin autoimmunity.


Quantitative assessment of tracheal collapsibility in infants with tracheomalacia.
Infantile tracheomalacia is a potentially life-threatening disease requiring prolonged artificial respiratory support. Diagnosis and management of this disease may be further improved by establishing a suitable objective and quantitative assessment protocol for tracheal collapsibility. It is our hypothesis that tracheal collapsibility can be represented by the relationship between intraluminal pressure and the cross-sectional area of the trachea. To test this hypothesis, static pressure/area relationships of the trachea were obtained from anesthetized and paralyzed infants, who were diagnosed as having tracheomalacia by endoscopic observation. These relationships were fitted on a linear regression model, followed by calculation of the estimated closing pressure. The tracheal closing pressure ranged from -8 to -27 cm H(2)O, suggesting easy collapsibility of the trachea during crying or coughing and noncollapsibility during the spontaneous respiratory cycle, which coincided with the infants' symptoms. It is our conclusion that tracheal collapsibility of infants with tracheomalacia can be quantitatively assessed by the static pressure/area relationship of the trachea obtained under general anesthesia and paralysis.


Metabolic aromatization of N-alkyl-1,2,3,4-tetrahydroquinoline substructures to quinolinium by human liver microsomes and horseradish peroxidase.
Metabolic aromatization of xenobiotics is an unusual reaction with some documented examples. For instance, the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the neurotoxic pyridinium ion metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase (MAO) B in the brain has been of interest to a number of investigators. It has also been reported that although the aromatization of N-methyl-tetrahydroisoquinoline occurs with MAO B, the metabolism does not proceed for its isomer, N-methyl-tetrahydroquinoline, by the same enzyme. The aromatization of an N-alkyl-tetrahydroquinoline substructure was identified during in vitro metabolite profiling of compound A, which was designed as a potent renin inhibitor for the treatment of hypertension. The N-alkylquinolinium metabolite of compound A was identified by liquid chromatography-tandem mass spectrometry of human liver microsomal incubates and proton NMR of the isolated metabolite. Further in vitro metabolism studies with a commercially available chemical (compound B), containing the same substructure, also generated an N-alkylquinolinium metabolite. In vitro cytochrome P450 (P450) reaction phenotyping of compound A revealed that the metabolism was catalyzed exclusively by CYP3A4. Although compound B was a substrate for several P450 isoforms, its quinolinium metabolite was also generated predominantly by CYP3A4. Neither compound A nor compound B was a substrate of MAOs. The quinolinium metabolites were readily produced by horseradish peroxidase, suggesting that aromatization of the N-alkyltetrahydroquinoline could occur via a mechanism involving single electron transfer from nitrogen. Although dihydro intermediates from the tetrahydroquinoline substrates were not observed in the formation of quinolinium metabolites, cyanide trapping results indicated the occurrence of iminium intermediates.


Functional outcomes and height restoration for patients with multiple myeloma-related osteolytic vertebral compression fractures treated with kyphoplasty.
A retrospective review of pathologic vertebral fractures related to multiple myeloma. To report the functional status and height restoration of 32 patients treated with kyphoplasty for multiple myeloma-related vertebral compression fractures. Multiple myeloma can cause significant bony resorption, and vertebral involvement is extremely common. Compression fractures due to myelomatous vertebral metastases result in significant pain and can lead to kyphosis and sagittal imbalance. Nonoperative treatment can result in deformity and continued pain, and large surgical procedures have significant morbidity. Percutaneous cement augmentation (kyphoplasty and vertebroplasty) is a minimally invasive technique that can improve pain in these patients. Kyphoplasty also has the potential to provide mild deformity correction in addition to fracture stabilization. Study participants were patients with biopsy-proven multiple myeloma presenting with compression fracture treated with kyphoplasty. Data were compiled from patient charts and preoperative and postoperative radiographs. Patient self-reported functional status were obtained through the use of the Oswestry Disability Index. The degree of vertebral body collapse and deformity was evaluated using the method of Genant and analyzed using paired Student t test. Thirty-two consecutive patients who underwent kyphoplasty at a total of 76 levels for myelomatous vertebral compression fractures were identified. Sixteen fractures were at the thoracolumbar junction. The mean age was 64.3 years. The average Genant grade for the involved levels improved from 1.9 preoperative to 1.53 postoperative, which was statistically significant (P<0.0001). The postoperative Oswestry Disability Index score was obtained at a mean of 24 months, with a mean of 29.6%. Complications occurred in 12 (37.5%) patients, all consisting of minimal intraoperative cement extravasation without clinical sequelae. No changes in the neurological status were observed. The average hospital stay was 1.34 days postprocedure. Kyphoplasty for vertebral compression fractures due to multiple myeloma is a safe and effective procedure that can lead to pain relief and vertebral height restoration.


Use of maintenance intravesical bacillus Calmette-Guérin (BCG), with or without intradermal BCG, in patients with recurrent superficial bladder cancer. Long-term follow-up of a randomized phase 2 study.
To study maintenance Bacillus Calmette-Guérin (BCG) therapy we treated 49 patients with recurrent superficial bladder cancer pTa and/or carcinoma in situ, failing previous intravesical chemotherapy. They received 20 intravesical instillations in 1 year, with or without 6 intradermal inoculations. Side effects were frequent, causing treatment stop in 14 patients (29%). Drug-induced cystitis was the most frequent side effect, seen in 29 patients (59%). Forty-two patients were evaluable for response. During the first 2 years of the study 14 patients (33%) had one (n = 8) or more (n = 6) recurrences. A total of 18 patients (43%) remained recurrence free with a median follow-up of 47 months. Progression was seen in 2 patients from pTa to pT1, another patient died of metastatic bladder cancer after 47 months. PPD skin test conversion was of no prognostic value. The use of intradermal inoculations caused no significant increase of toxicity and had no effect on efficacy, however, both groups were small. It caused no local side effects. We conclude that maintenance BCG therapy can be useful for patients with recurrent superficial bladder cancer failing previous intravesical chemotherapy.


Bioenergetic profile of human coronary artery smooth muscle cells and effect of metabolic intervention.
Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown. Thus, we profiled cellular bioenergetics of human coronary artery smooth muscle cells and effects of metabolic intervention. Mitochondria and glycolysis stress tests utilizing Seahorse technology revealed that mitochondrial oxidative phosphorylation accounted for 54.5% of ATP production at rest with the remaining 45.5% due to glycolysis. Stress tests also showed that oxidative phosphorylation and glycolysis can increase to a maximum of 3.5 fold and 1.25 fold, respectively, indicating that the former has a high reserve capacity. Analysis of bioenergetic profile indicated that aging cells have lower resting oxidative phosphorylation and reduced reserve capacity. Intracellular ATP level of a single cell was estimated to be over 1.1 mM. Application of metabolic modulators caused significant changes in mitochondria membrane potential, intracellular ATP level and ATP:ADP ratio. The detailed breakdown of cellular bioenergetics showed that proliferating human coronary artery smooth muscle cells rely more or less equally on oxidative phosphorylation and glycolysis at rest. These cells have high respiratory reserve capacity and low glycolysis reserve capacity. Metabolic intervention influences both intracellular ATP concentration and ATP:ADP ratio, where subtler changes may be detected by the latter.


Phosphorylation-dependent interaction of SATB1 and PIAS1 directs SUMO-regulated caspase cleavage of SATB1.
Special AT-rich sequence-binding protein 1 (SATB1) is a tissue-restricted genome organizer that provides a key link between DNA loop organization, chromatin modification/remodeling, and transcription factor association at matrix attachment regions (MARs). The SUMO E3 ligase PIAS1 enhances SUMO conjugation to SATB1 lysine-744, and this modification regulates caspase-6 mediated cleavage of SATB1 at promyelocytic leukemia nuclear bodies (PML NBs). Since this regulated caspase cleavage occurs on only a subset of SATB1, and the products are relatively stable, proteolysis likely mediates cellular processes other than programmed cell death. However, the mechanism for the spatial and temporal regulation of SATB1 sumoylation and caspase cleavage is not known. Here we report that these processes are controlled by SATB1 phosphorylation; specifically, PIAS1 interaction with SATB1 is inhibited by phosphorylation. Mutagenesis studies identified interaction of the PIAS SAP (scaffold attachment factor-A/B/acinus/PIAS) motif with SATB1 N-terminal sequences. Notably, phosphorylation of SATB1 at threonine-188 regulates its interaction with PIAS1. Sequences near this phosphorylation site, LXXLL (residues 193 to 197), appear to be conserved among a subset of SUMO substrate proteins. Thus, this motif may be commonly involved in interaction with the PIAS SAP, and phosphorylation may similarly inhibit some of these substrates by preventing their interaction with the ligase.


High Tracheal Resection With Intralaryngeal Extension as an Alternative to Cricotracheal Resection for Treatment of Subglottic Stenosis.
Some patients with subglottic stenosis (SGS) require open airway reconstruction, which traditionally involves resection of the anterior cricoid cartilage. As an alternative, we present a novel technique: cricoid-sparing high tracheal resection with excision of subglottic stenotic tissue from below. A novel set of posterior circumferential cricoid sutures is used to reline the exposed cricoid plate. Retrospective chart review. Single tertiary care center. The surgical technique is described and illustrated. A chart review was performed for all patients who underwent surgery between January 1, 2016, and June 30, 2021. Fourteen patients (100% female) underwent this airway resection and reconstruction surgery during the study time period. After a mean follow-up of 12 months, no patients required tracheostomy. Twelve of 14 patients (86%) had durable airways. Two patients (14%) have required repeated endoscopic procedures for recurrent stenosis and are considered treatment failures. None exhibited postoperative dysfunction to suggest posterior cricoarytenoid muscle injury. Thirteen patients (93%) had a postoperative normal voice or only transient dysphonia. One patient had permanent unilateral vocal fold paralysis. Cricoid-sparing high tracheal resection is a safe and effective alternative to cricotracheal resection, especially for predominantly posterior SGS. The cricoid cartilage and cricothyroid muscles are left undisturbed, potentially decreasing the risk of postoperative dysphonia, namely lowered fundamental frequency. This is especially meaningful in the setting of a predominantly female patient population.


Snake venomics of the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei.
Venoms from the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei were analyzed by RP-HPLC, N-terminal sequencing, MALDI-TOF mass fingerprinting and CID-MS/MS. The venom proteins of M.l. obtusa and V. raddei belong to 9 and 11 families, respectively. The two mountain viper venoms share bradykinin-potentiating/C-natriuretic peptides, and proteins from the dimeric distegrin, DC-fragment, CRISP, PLA(2), serine proteinase, C-type lectin-like, L-amino acid oxidase, and Zn(2+)-dependent metalloproteinase families, albeit each species exhibits distinct relative abundances. M.l. obtusa and V. raddei venoms contain unique components, e.g. the short disintegrin obtustatin in M.l. obtusa, and Kunitz-type serine proteinase inhibitor and VEGF-like molecules in V. raddei. The toxin formulation of M.l. obtusa and V. raddei venoms may be related to their adaptation to rocky mountain ecosystems. On the other hand, the possibility that the VEGF-like proteins from V. raddei underlie the reported potential therapeutic value of V. raddei venom for regenerating damaged peripheral nerves deserves further investigations. Using a similarity coefficient, we estimate that the similarity of venom proteins between M. l. obtusa and M. l. transmediterranea is less than 4%. Although this result would support the classification of M.l. obtusa and M.l. transmediterranea as different species, additional detailed genomic analyses are also required.


Formula supplementation in hospital and subsequent feeding at discharge among women who intended to exclusively breastfeed: An administrative data retrospective cohort study.
Among women who intend to exclusively breastfeed, it is important to identify mothers and their infants who have a greater risk of formula supplementation in hospital, and are unlikely to recover exclusive breastfeeding at discharge. We investigated factors associated with in-hospital formula feeding among healthy term infants born to women who intended to exclusively breastfeed, and among this group, predictors of infant feeding at discharge. Retrospective cohort study utilizing routinely collected clinical data for women who intended to exclusively breastfeed and gave birth to healthy term infants in five hospitals in New South Wales, Australia, 2010-2013. Robust Poisson regression was used to obtain adjusted relative risks (aRR) for the associations between formula feeding in hospital, feeding at discharge, and associated factors. Of 24 713 mother-infant dyads in the study population, 16.5% received formula in hospital. After adjustment, the strongest predictors of formula supplementation were breastfeeding difficulties (aRR 2.90 [95% confidence interval {CI} 2.74-3.07]), Asian born mother (aRR 2.07 [95% CI 1.92-2.23]), and neonatal conditions (aRR 2.00 [95% CI 1.89-2.13]). Among infants who received formula (n=3998), 49.3% were fully breastfeeding at discharge, 33.1% partially breastfeeding, and 17.5% formula-only feeding. Compared with formula-only feeding, special care nursery admission (aRR 1.23 [95% CI 1.17-1.30]) and ≥1 neonatal conditions (compared with none) were most strongly associated with fully breastfeeding at discharge (aRR 1.21 [95% CI 1.16-2.16]). Women and their infants who receive formula in hospital need additional support to attain exclusive breastfeeding by hospital discharge. Such support is especially needed for younger women, smokers, and women with breastfeeding difficulties.


Carcinogen-induced immune depression: absence in mice resistant to chemical oncogenesis.
Administration of 3-methylcholanthrene 6 days before antigenic challenge depressed the immune response to sheep red cells in young adult mice (C3Hf/Bi strain) sensitive to the oncogenic effect of the drug (100 percent local tumors 240 days after carcinogen). The drug was not immunodepressant in the I strain, which is relatively resistant to its carcinogenic effect (11 percent local tumors 240 days after carcinogen).


Causal mediation analysis with multiple causally non-ordered and ordered mediators based on summarized genetic data.
Causal mediation analysis investigates the mechanism linking exposure and outcome. Dealing with the impact of unobserved confounders among exposure, mediator and outcome is an issue of great concern. Moreover, when multiple mediators exist, this causal pathway intertwines with other causal pathways, rendering it difficult to estimate the path-specific effects. In this study, we propose a method (PSE-MR) to identify and estimate path-specific effects of an exposure (e.g. education) on an outcome (e.g. osteoarthritis risk) through multiple causally ordered and non-ordered mediators (e.g. body mass index and pack-years of smoking) using summarized genetic data, when the sequential ignorability assumption is violated. Specifically, PSE-MR requires a specific rank condition in which the number of instrumental variables is larger than the number of mediators. Furthermore, we illustrate the utility of PSE-MR by providing guidance for practitioners and exploring the mediation effects of body mass index and pack-years of smoking in the causal pathways from education to osteoarthritis risk. Additionally, the results of simulation reveal that the causal estimates of path-specific effects are almost unbiased with good coverage and Type I error properties. Also, we summarize the least number of instrumental variables for the specific number of mediators to achieve 80% power.


[Ankle sprain during a volleyball game].
A 27-year old woman was admitted to the emergency room after her left ankle rolled inward during a volleyball game. On physical examination a bony prominence on the lateral side of the left foot was noticeable, without neurovascular injury. An X-ray (anterior-posterior view) showed a subtalar dislocation without associated fractures.


Assessment of right hepatic artery involvement in patients with biliary tract cancer using color Doppler ultrasonography.
The accuracy of color Doppler ultrasonography (CDUS) in diagnosing right hepatic artery (RHA) involvement was preoperatively evaluated in 28 patients with biliary tract cancer. When a tumor partially or completely surrounded the RHA, the circumferential involvement was diagnosed as positive. With B-mode ultrasonography imaging alone in the 10 nonsurgical patients, the correspondence rates with angiography for the presence of invasion, absence of invasion, and overall were 33%, 0%, and 10%, respectively. However, CDUS allowed clearer visualization of the RHA than did B-mode imaging, and the correspondence rates of CDUS with angiography were 100%, 43%, and 60%, respectively. In the 13 surgical patients, the accuracy levels of B-mode imaging, CDUS, computed tomography, and angiography for the detection of RHA involvement were 46%, 77%, 58%, and 92%, respectively, when compared with surgical and histopathologic findings. Although the accuracy of CDUS was lower than that of angiography, it can be performed repeatedly and noninvasively. CDUS is expected to be useful for the initial assessment of RHA involvement.


Premature rupture of membranes at 20 weeks: report of a successful outcome after transcervical application of fibrin glue.
A 30-year-old primigravida was admitted to hospital at 20 weeks of gestation because of premature rupture of membranes and oligohydramnios. The patient was maintained in bed rest and given intravenous ampicillin. Forty-eight hours later, after documenting the absence of infection and maintenance of the oligohydramnios, fibrin glue was applied transcervically under ultrasound control. There was subjective improvement in amniotic fluid volume after treatment, but always within the criteria of oligohydramnios. Fibrin glue application was repeated twice due to reported increase in fluid loss and diminished amniotic fluid volume on ultrasound. Amoxicillin per os was started at 23 weeks, and clavulanic acid was added at 26 weeks due to the isolation of an Escherichia coli on cervical-vaginal cultures. No signs of infection ensued until 34 weeks, when an axillary temperature of 39.5 degrees C was detected together with a non-reassuring cardiotocographic pattern, the latter leading to the performance of an urgent cesarean section. The newborn had an Apgar score of 9/10/10, umbilical artery pH of 7.32, and no external deformities. He showed no signs of lung hypoplasia and required no oxygen supplementation. Oropharyngeal and blood cultures revealed an E. coli infection and antibiotic treatment was started. No further complications occurred and he was discharged home on the 8th day of life. At 12 months, the child reveals a normal development. The mother had a mild and short-lasting wound infection and was discharged on the 8th postoperative day.


Biogenic amines in human brain in normal aging, senile dementia, and chronic alcoholism.
Postmortem examination of various brain regions of cases without known brain pathology showed an age-related decrease in the levels of dopamine in the nigrostriatal system, of norepinephrine in the hippocampus, and of 5-HT in the gyrus cinguli but an increase of 5-HT in the medulla oblongata and of MAO B in several brain regions.


Meibomian Gland Dropout in Hematological Patients Before Hematopoietic Stem Cell Transplantation.
To perform qualitative and quantitative analysis of meibomian gland (MG) dropout in hematological patients before hematopoietic stem cell transplantation (HSCT) and to correlate it with both ocular surface and hematological characteristics. This prospective study included 46 consecutive patients undergoing HSCT and 30 age- and sex-matched healthy controls. Noninvasive meibography of the lower eyelid, meiboscore (Pult scale), Schirmer test type I, tear film breakup time, and corneal and conjunctival staining were measured. Subjective symptoms were scored by the Ocular Surface Disease Index. The dry eye diagnosis was ascertained according to TFOS DEWS II Criteria. Hematological data included diagnosis (acute leukemias vs. other malignancies), stage of the disease, time from diagnosis to ophthalmological examination, and previous therapy (chemotherapy, radiotherapy, or autograft). Hematological patients presented a significantly lower tear film breakup time and a higher meiboscore compared with controls (respectively 4.8 ± 3.0 seconds vs. 11.0 ± 3.0 and 2.0 ± 1.1 vs. 0.9 ± 0.4; P < 0.001). Conversely, other parameters did not differ between both groups. Dry eye was diagnosed in 14 out 46 hematological patients (30.4%). MG loss was significantly higher in hematological patients than in controls (29.8% ± 15.0% vs. 21.2 ± 13.0; P = 0.007) and was higher in the nasal third compared with both central and temporal thirds (respectively, 39.8% ± 21.4% vs. 18.5 ± 15.6 and 25.1 ± 18.3; P < 0.0001). The diagnosis of acute leukemia (β = 0.449; P = 0.003) and the history of previous chemotherapy (β = 0.444; P = 0.003) were associated with lower MG loss. Hematological patients presented significantly reduced MG areas even before HSCT, particularly those affected by nonacute malignancies. The topographical pattern of MG dropout resembles that of conventional dry eye.


Occurrence of Eimeria species parasites on small-scale commercial chicken farms in Africa and indication of economic profitability.
Small-scale commercial poultry production is emerging as an important form of livestock production in Africa, providing sources of income and animal protein to many poor households, yet the occurrence and impact of coccidiosis on this relatively new production system remains unknown. The primary objective of this study was to examine Eimeria parasite occurrence on small-scale commercial poultry farms in Ghana, Tanzania and Zambia. Additionally, farm economic viability was measured by calculating the farm gross margin and enterprise budget. Using these economic measures as global assessments of farm productivity, encompassing the diversity present in regional husbandry systems with a measure of fundamental local relevance, we investigated the detection of specific Eimeria species as indicators of farm profitability. Faecal samples and data on production parameters were collected from small-scale (less than 2,000 birds per batch) intensive broiler and layer farms in peri-urban Ghana, Tanzania and Zambia. All seven Eimeria species recognised to infect the chicken were detected in each country. Furthermore, two of the three genetic variants (operational taxonomic units) identified previously in Australia have been described outside of Australia for the first time. Detection of the most pathogenic Eimeria species associated with decreased farm profitability and may be considered as an indicator of likely farm performance. While a causal link remains to be demonstrated, the presence of highly pathogenic enteric parasites may pose a threat to profitable, sustainable small-scale poultry enterprises in Africa.


Oogenesis in pig ovaries during the prenatal period: ultrastructure and morphometry.
Oogenesis in fetal pig ovaries comprises the successive changes from the primordial germ cells to the dictyotene oocytes in primordial ovarian follicles. In this study the observations were carried out with an electron microscope and stereological analysis was performed. At the ultrastructural level there are no differences between the primordial germ cells and oogonia, but oogonia are connected with the intercellular bridges. The onset of the dictyotene phase was accompanied by the changes in the cytoplasm of oocytes. Near the nucleus, the yolk nucleus is formed containing numerous Golgi bodies, endoplasmic reticulum (ER), mitochondria and granules. ER proliferates in contact with the external leaflet of the nuclear envelope forming the narrow ER cisterns. Between the nuclear envelope and ER cisterns, the vesicles with grey content are visible. The proliferating ER forms numerous concentric cisterns around the nucleus. Next, the most external cisterns fragment, detach, and then form the cup-like structures. These structures separate the distinct areas of cytoplasm-compartments, which contain mitochondria, ribosomes and lipid droplets. The cells of cortical sex cords of the ovary, which encloses the oocyte, form the follicles. The volume of oocytes in forming follicle increases due to the increase in the number of the cell inclusions: lipid droplets, vacuoles and yolk globules. In the oocytes of primordial ovarian follicles, the compartments are transformed into the yolk globules, which are encountered by a sheath of ER cisterns and the grey vesicles; they contain the mitochondria, lipid droplets and light vacuoles. The role of the compartments and yolk globules as metabolic units is discussed in comparison with similar structures of the mature eggs of pigs and other mammal species.


Disaster Exposure and Temperament as Predictors of Adolescent Substance Use.
Children who have been exposed to a natural disaster in their lifetime comprise a significant population with specific risks and vulnerabilities, particularly for at-risk youth. The goal of the current study was to examine the role that severity of disaster exposure plays in determining the timing of alcohol and marijuana use initiation and the frequency of use four years later in a sample of at-risk, aggressive youth exposed to a devastating tornado. Of further interest was the examination of the moderating effect of temperamental fear and inhibitory control. Three hundred and forty-six youth (Mage = 11.33; 65% boys; 77.5% African-Americans, 18.3% Caucasian, 1.7% Hispanic) initially recruited for a prevention program for at-risk youth were followed for 4 years after a tornado. Cox PH regressions were conducted to predict timing of alcohol and marijuana use initiation. Zero-inflated negative binomial regressions were used to predict frequency of alcohol and marijuana use 4 years after the tornado. Disaster exposure severity was predictive of frequency of marijuana use four years after the tornado, but exposure alone was not predictive of initiation. Exposure severity predicted increases in risk for alcohol use initiation only for youth high in fear. Additionally, greater levels of inhibitory control protected youth from earlier alcohol use initiation. Findings highlight a need to research the initiation and frequency of use for substances individually, while also assessing the needs of youth exposed to natural disasters with both their degree of disaster exposure and specific temperamental characteristics in mind.


Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer.
Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated. We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated. The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 μg/mL and 101.5 ng/mL in the benign group and 5.4 μg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively). Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.


Modeling the Reduction Kinetics of Munition Compounds by Humic Acids.
Dissolved organic matter (DOM) comprises a sizeable portion of the redox-active constituents in the environment and is an important reductant for the abiotic transformation of nitroaromatic compounds and munition constituents (NACs/MCs). Building a predictive kinetic model for these reactions would require the energies associated with both the reduction of the NACs/MCs and the oxidation of the DOM. The heterogeneous and unknown structure of DOM, however, has prohibited reliable determination of its oxidation energies. To overcome this limitation, humic acids (HAs) were used as model DOM, and their redox moieties were modeled as a collection of quinones of different redox potentials. The reduction and oxidation energies of the NACs/MCs and hydroquinones, respectively, via hydrogen atom transfer (HAT) reactions were then calculated quantum chemically. HAT energies have been used successfully in a linear free energy relationship (LFER) to predict second-order rate constants for NAC reduction by hydroquinones. Furthermore, a linear relationship between the HAT energies and the reduction potentials of quinones was established, which allows estimation of hydroquinone reactivity (i.e., rate constants) from HA redox titration data. A training set of three HAs and two NACs/MCs was used to generate a mean HA redox profile that successfully predicted reduction kinetics in multiple HA/MC systems.


MyD88 signaling in T regulatory cells by endogenous ligands dampens skin inflammation in filaggrin deficient mice.
Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient flaky tail (Flgft/ft) mice develop spontaneous inflammatory skin lesion that wax and wane. We show that loss of MyD88 promotes the persistence of skin lesions in Flgft/ft mice and exaggerates their expression of the Th17-associated cytokines Il7a and Il22. The development and persistence of skin lesions in Flgft/ft mice was independent of the microbiota. MyD88-mediated signals are shown to be important for the accumulation of T regulatory cells (Tregs) in lesional skin of Flgft/ft mice. Adoptive transfer of WT Tregs dampened the severity of skin lesions in MyD88-/-/Flgft/ft mice. These results suggest that MyD88 signaling in Treg cells by endogenous ligands attenuates skin inflammation in filaggrin deficiency.


Total synthesis of bi-magnolignan.
Bi-magnolignan, isolated from the leaves of Magnolia officinalis, has shown excellent physiological activity against tumor cells. An efficient strategy for the first total synthesis of bi-magnolignan is reported. The bi-dibenzofuran skeleton was constructed via functional group interconversions of commercially available materials 1,2,4-trimethoxybenzene and 4-allylanisole. Then, the dibenzofuran skeleton was afforded by subsequent Suzuki coupling and intramolecular dehydration. The total synthesis of natural product was accomplished through FeCl3 catalyzed oxidative coupling.


"I'm not going to walk, just for the sake of walking…": a qualitative, phenomenological study on physical activity during hospital stay.
Purpose: To understand beliefs, thoughts, attitudes, and experiences related to physical activity during hospital stay in patients and health care providers.Methods: A qualitative, interpretive, phenomenological study examined the common meaning and lived experiences of patients and health care providers related to inpatient physical activity. Data from semi-structured interviews were analysed using qualitative content analysis.Results: A total of 42 participants (18 patients and 24 health care providers) were interviewed. Patients and health care providers described physical activity as a purposeful activity to achieve a goal. In contrast, they talked about physical and mental rest to balance inpatient physical activity. Furthermore, the hospital environment was felt to discourage patients to be physically active with care centred around the hospital beds, frequent disturbances of rest on hospital rooms, and dependency of patients on health care providers as important sources. The ability of patients to perform physical activity was associated with feelings, such as freedom and autonomy.Conclusions: Physical activity during hospital stay is a purposeful activity to achieve a goal, and should be well-balanced with both physical and mental rest according to patients and health care providers. In addition, the hospital environment seems to be a source of low inpatient physical activity. Implications for rehabilitationHealth care providers should offer meaningful activities to engage patients' interest in being physically active during hospital stay.Tailored interventions aiming to increase inpatient physical activity should be balanced with phases of both physical and mental rest.A change of the hospital environment in both culture and the build environment is needed to elicit physical activity in patients during hospital stay.


The case for treating hypertension in the elderly.
Not so long ago it was fashionable to ignore a little bit of hypertension in an elderly person. The rationalizations for this position included the limited epidemiological data establishing the risk of elevated blood pressure in the age group over 65, particularly for women; and concern that lowering the blood pressure might not be desirable, from the standpoint of reduced blood flow to vital organs. There was also concern over the known greater responsiveness or sensitivity of older people to customary doses. It was also argued by some that even if the blood pressure could be safely controlled it was hardly worth it, since age itself is the most powerful predictor of mortality in the elderly. Moreover, it seemed unlikely to many that the risk of hypertension could be reduced--that is, that life expectancy could be extended; at the same time it seemed fairly certain that the quality of life would be compromised by therapy. However, since systolic blood pressure continues to be predictive of coronary heart disease mortality well into the ninth decade, and since considerable life expectancy remains for those who have survived to their senior years, it seems logical to attempt to reduce the risk and preserve life expectancy by controlling blood pressure. The question is, is the evidence that treatment helps really convincing, or are we simply extrapolating from studies carried out in younger subjects? Review of the early literature, which focused almost exclusively on stroke survivors and the influence of hypertension on stroke recurrence, provides inconsistent, conflicting, and not persuasive information.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of cortical and sub-cortical regions in autistic mr images using level set method and structure tensors.
Autism is a complex disease that causes micro structural changes in brain due to delayed growth. In this work, the cortical regions of brain are extracted from T1 -weighted magnetic resonance mid-sagittal view slices. The images are skull stripped using edge based Level Set (LS) which is regularized by a signed distance function. This skull stripping technique is validated with the Brain extraction tool (BET). The extracted cortical regions are then analyzed by calculating the structure tensor matrix from the gradient of the skull stripped images. The anisotropy index derived from the tensor matrix is correlated with the clinical features such as verbal, full scale and performance Intelligent Quotients (IQ). The results show that the level set method is able to extract the cortical brain boundaries correctly with distinct edges. The structure tensor features extracted from the skull stripped images discriminates the control and autistic images. Also, the anisotropy index is negatively correlated with the performance IQ values of autistic subjects.