Correlation between the behavior of magnetic iron oxide particles in the lungs of rabbits and phagocytosis.
Five New Zealand white male rabbits were exposed (30 min; 300 mg/m3) to a submicrometric magnetic iron oxide aerosol (gamma-Fe2O3) produced by burning iron pentacarbonyl in a reducing atmosphere. After aerosol inhalation, an external magnetic field was applied to the rabbits to magnetize and align the ferrimagnetic particles within their lungs. After removal of the external field, a remanent magnetic field was detectable at the body surface. Using a flux-gate magnetometer probe in an enclosure shielded against external magnetic noise, the peak remanent field after magnetization was measured periodically during the next 6 weeks. After each magnetization, the strength of the remanent field decayed rapidly with time (relaxation). The mechanism responsible is particle rotation caused by tissue, cell, organelle, or Brownian movement. The rate of relaxation changed with time after particle inhalation, especially during the first day; changes in the relaxation rate correlated with an estimate of in situ particle phagocytosis during that time. Analysis of pulmonary lavage fluid from 15 rabbits into which radioactive gold-198 had been intratracheally instilled showed that, at 1 hr after instillation, 27% of the gold had been phagocytized, whereas at 16 hr 91% had been ingested. The strength of the magnetic field immediately after each magnetization (that is, before relaxation) was used to estimate the amount of iron oxide in the lungs. At 1 day after exposure, 96.8 +/- 8.8% (mean +/- standard error) of the initial dust was still present; at 10 days, 67.9 +/- 16.2%; and at 40 days, 16.0 +/- 4.6%. It is concluded that ferrimagnetic particles can serve as an easily measured, long-lasting marker that can be used for noninvasive studies of clearance and of particle phagocytosis and as a probe for intracellular processes such as organelle motion.


Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology.
Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory endogenous TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients' plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients' plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and progression of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression in the blood and aorta. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.


The long-term sealing ability of an epoxy resin root canal sealer used with five gutta percha obturation techniques.
The aim of the present study was to evaluate the long-term sealing ability (both apical and coronal) of an epoxy resin root canal sealer (AH26) when used with different gutta-percha obturation techniques. Straight single-rooted teeth with mature apices were divided into 10 groups of 75 teeth and one group of 40 control teeth. Root canals were prepared according to the crown-down/step-back technique and using both 2.5% sodium hypochlorite and an EDTA paste. Root canals were obturated using cold lateral condensation, warm vertical condensation and hybrid condensation of gutta-percha; and with Thermafil and Soft-Core obturators. AH26 was used as the sealer in all cases. After root canal filling, each group was divided into five individual groups of 15 teeth. The first group of 15 teeth was kept for 1 day, the second for 1 week, the third for 4 months, the fourth for 6 months and the fifth for 12 months at 37 degrees C in vacutainers in 80% relative humidity. The teeth were immersed in India ink for 90 h, each root was split and sectioned longitudinally, and the maximum extent of leakage was measured using a stereomicroscope at x6 magnification. Leakage occurred whatever filling technique was combined with AH26. The number of teeth with gross leakage increased with time up to 4 months, but did not appear to increase between 6 and 12 months storage. The degree of apical leakage and the number of leaking teeth in the Soft-Core obturator groups was significantly higher than all four other gutta-percha obturation techniques. Up to 4 months the degree of coronal leakage and the number of leaking teeth in the Thermafil groups was significantly higher than the other gutta-percha obturation techniques, except for Soft-Core. In the Soft-Core obturator groups the degree of coronal leakage and the number of leaking teeth was significantly higher than the other gutta-percha obturation techniques, except for Thermafil at all evaluation times. The hybrid gutta-percha condensation technique was superior to the other four obturation techniques in respect of apical leakage. Coronal leakage was significantly greater during the first 4 months for the Thermafil system as compared to the three condensation techniques; coronal leakage was significantly greater at all time periods for the Soft-Core system. There were no significant differences between the Thermafil and the Soft-core system.


Combined effect of 2-5A-linked antisense against telomerase RNA and conventional therapies on human malignant glioma cells in vitro and in vivo.
We recently showed that therapy with 2'-5'-oligoadenylate (2-5A)-linked antisense against human telomerase RNA component (2-5A-anti-hTR) is a novel telomerase-targeting strategy against malignant gliomas. In this study, we investigated conventional chemotherapeutic agents and gamma-irradiation (IR) to determine whether they could augment the efficacy of 2-5A-anti-hTR against these tumors in vitro and in vivo. Treatment with 2-5A-anti-hTR inhibited the viability of U373-MG and U87-MG malignant glioma cells in a dose-dependent manner; the antitumor effect resulted from induction of apoptosis. Also, telomerase-positive astrocytes with oncogenic Ras were more sensitive to 2-5A-anti-hTR than were those without oncogenic Ras. In addition, we sought to determine the combined effect of 2-5A-anti-hTR with N, N'-bis (2-chloroethyl)-N-nitrosourea (BCNU), cisplatin (CDDP), paclitaxel (PTX), temozolomide (TMZ), or IR. When we administered the combination treatments on the same day, PTX and IR showed a greater combined effect with 2-5A-anti-hTR on both tumor cell lines than did BCNU, CDDP and TMZ. However, all of the combination regimens were synergistic when we first treated tumor cells with 2-5A-anti-hTR for 24 h and then exposed them to the conventional treatments. Apoptosis-inducing agents (CDDP and PTX) but not autophagy-inducing therapies (TMZ and IR) enhanced the incidence of apoptosis caused by 2-5A-anti-hTR. Lastly, we observed a combinatorial effect of 2-5A-anti-hTR and TMZ in vivo in subcutaneous U87-MG tumors in nude mice. Interestingly, treatment with TMZ increased the incidence of apoptosis in subcutaneous tumor cells treated with 2-5A-anti-hTR. These results suggest that 2-5A-anti-hTR is preferable in combination with established cancer therapies.


Porokeratosis of Mibelli in an HIV-positive patient.
Porokeratosis represents a group of disorders of epidermal keratinization that are characterized by one or more annular plaques surrounded by a histologically distinctive hyperkeratotic ridge-like border called the cornoid lamella. Many studies showed that organ transplantation and immunosuppression were associated in a significant number of cases. Furthermore, an association with squamous cell carcinoma and basal cell carcinoma has been noted in all variants of porokeratosis. The rarity of this disorder and its atypical clinical presentation - a single lesion on the thumb of an HIV-positive male patient - motivated this report.


In vitro biocompatibility between mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG).
Mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG) intravesical instillations are widely and effectively used as adjuvant treatment for superficial bladder cancer. In an attempt to improve the efficacy of intravesical therapy, MMC and BCG have also been used in a sequential or an alternating mode. The aim of this study was to assess the in vitro biocompatibility between these agents. The effect of MMC on BCG clumping tendency was assessed by estimating the number of colony forming units (CFU) of BCG in suspension, during incubation at 37 degrees C for 3 h, with repeated recordings of the suspension optical density (OD). Preparations containing either BCG plus MMC or BCG plus an equivalent amount of sterile water were cultivated using the non-radiometric system BACTEC MGIT 960. The final concentrations of the agents, following transfer of the preparations into the tubes of the system, were 1.25 mg/ml for BCG and 1 mg/ml for MMC. During the cultivation process, the tubes of the system were automatically checked every 60 min for fluorescence emission, which is an indication of mycobacteria growth. A comparative cultivation of the same preparations on Lowenstein-Jensen solid medium was also performed. The OD of the BCG preparation remained almost unaffected for 3 h and was minimally altered by inclusion of MMC. After 34-38 h of cultivation in the BACTEC MGIT 960 system, all 7 cultures of the BCG+sterile water preparations became positive. In contrast, no BCG+MMC specimen became positive after an incubation period of 42 days. Following re-cultivation of the 7 negative BCG+MMC specimens, 6 remained negative, whereas 1 specimen became positive after an incubation period of 22 days. On Löwenstein-Jensen medium, growth of mycobacteria was noted only in the BCG+sterile water specimens and not in the BCG+MMC specimens. The results of this study indicate that, although MMC has no apparent effect on BCG tendency to form clumps in suspension, it may inhibit its growth in vitro. However, this does not necessarily compromise BCG anti-tumour activity. As the in vivo interaction of the drugs may be different, the efficacy of the combined BCG+MMC treatment should be defined in clinical trials.


Transformation of MALT lymphoma to pure plasma cell histology following treatment with the anti-CD20 antibody rituximab.
Mucosa associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma arising from marginal-zone B-cells which are closely related to plasma cells. As opposed to the large majority of plasma cells, MALT lymphoma cells express CD20, and the anti-CD20 antibody rituximab has been reported as active treatment in patients with MALT lymphoma. We present a patient with MALT lymphoma involving stomach and lung which transformed to a pure plasma cell tumor after therapy with rituximab. This observation again supports the close association between the cell of origin of MALT lymphoma and plasma cells, suggesting that "plasmacytoma of the GI-tract" as anecdotally reported may in fact be a MALT lymphoma with extreme plasmacytic differentiation. In addition, our findings suggest that MALT lymphomas with plasmacytic differentiation might have a different 18F-FDG uptake as compared to classical MALT lymphoma.


The prevalence and topographic distribution of penile calcification in a large cohort: a retrospective cross-sectional study.
The prevalence of penile calcification in the population remains uncertain. This retrospective multicenter study aimed to determine the prevalence and characteristics of penile calcification in a large cohort of male patients undergoing non-contrast pelvic tomography. A total of 14 545 scans obtained from 19 participating centers between 2016 and 2022 were retrospectively analyzed within a 3-months period. Eligible scans (n = 12 709) were included in the analysis. Patient age, penile imaging status, presence of calcified plaque, and plaque measurements were recorded. Statistical analysis was performed to assess the relationships between calcified plaque, patient age, plaque characteristics, and plaque location. Among the analyzed scans, 767 (6.04%) patients were found to have at least one calcified plaque. Patients with calcified plaque had a significantly higher median age (64 years (IQR 56-72)) compared to those with normal penile evaluation (49 years (IQR 36-60) (p < 0.001). Of the patients with calcified plaque, 46.4% had only one plaque, while 53.6% had multiple plaques. There was a positive correlation between age and the number of plaques (r = 0.31, p < 0.001). The average dimensions of the calcified plaques were as follows: width: 3.9 ± 5 mm, length: 5.3 ± 5.2 mm, height: 3.5 ± 3.2 mm, with an average plaque area of 29 ± 165 mm² and mean plaque volume of 269 ± 3187 mm³. Plaques were predominantly located in the proximal and mid-penile regions (44.1% and 40.5%, respectively), with 77.7% located on the dorsal side of the penis. The hardness level of plaques, assessed by Hounsfield units, median of 362 (IQR 250-487) (range: 100-1400). Patients with multiple plaques had significantly higher Hounsfield unit values compared to those with a single plaque (p = 0.003). Our study revealed that patients with calcified plaques are older and have multiple plaques predominantly located on the dorsal and proximal side of the penis.


Prolactin-secreting adenomas in women. VII. Dopamine regulation of prolactin secretion.
Previous studies demonstrated that high doses of dopamine administered as a constant infusion were capable of suppressing PRL secretion in both normal and hyperprolactinemic individuals. The present study was designed to examine the dose-response relationship of PRL suppression to low doses of dopamine (between 0.06 and 4 micrograms/kg X min) infused in a step-wise fashion. Ten hyperprolactinemic patients with PRL-secreting pituitary adenomas and 10 normally menstruating women in the early follicular phase of a cycle were studied. For hyperprolactinemic women, the mean (+/- SD) serum PRL level (by RIA) was 112 +/- 101 ng/ml, with a range of 26-386 ng/ml, the mean estradiol level (by RIA) was 28 +/- 8 pg/ml, and the mean baseline dopamine level by carboxy-o-methyl transferase assay (COMT) was 357 +/- 237 pg/ml (2.33 +/- 1.54 X 10(-9) M). The normal women had a mean PRL of 8.1 +/- 3.5 ng/ml, a mean estradiol level of 42 +/- 12 pg/ml, and a mean baseline dopamine level of 317 +/- 223 pg/ml (2.07 +/- 1.45 X 10(-9) M). Concentrations of dopamine achieved at the lowest doses infused were less than 10 times baseline levels and were in the nanomolar range. The measured IC50 (the concentration of dopamine required to achieve 50% of maximal suppression) was 6 +/- 3 X 10(-9) M for normal women and 14 +/- 4 X 10(-9) M for hyperprolactinemic patients. The apparent inhibition constant determined by a nonlinear least squares procedure, was 3 +/- 3 X 10(-9) M for normal women and 11 +/- 12 X 10(-9) M for women with hyperprolactinemia. Both groups exhibited dose-dependent suppression of PRL to about 80% of initial values. Under these experimental conditions, the data do not support the hypothesis that there is a marked loss in sensitivity to dopamine in patients with PRL-secreting adenomas.


Crystal structure of human complement protein C8gamma at 1.2 A resolution reveals a lipocalin fold and a distinct ligand binding site.
C8gamma is a 22-kDa subunit of human C8, which is one of five components of the cytolytic membrane attack complex of complement (MAC). C8gamma is disulfide-linked to a C8alpha subunit that is noncovalently associated with a C8beta chain. In the present study, the three-dimensional structure of recombinant C8gamma was determined by X-ray diffraction to 1.2 A resolution. The structure displays a typical lipocalin fold forming a calyx with a distinct binding pocket that is indicative of a ligand-binding function for C8gamma. When compared to other lipocalins, the overall structure is most similar to neutrophil gelatinase associated lipocalin (NGAL), a protein released from granules of activated neutrophils. Notable differences include a much deeper binding pocket in C8gamma as well as variation in the identity and position of residues lining the pocket. In C8gamma, these residues allow ligand access to a large hydrophobic cavity at the base of the calyx, whereas corresponding residues in NGAL restrict access. This suggests the natural ligands for C8gamma and NGAL are significantly different in size. Cys40 in C8gamma, which forms the disulfide bond to C8alpha, is located in a partially disordered loop (loop 1, residues 38-52) near the opening of the calyx. Access to the calyx may be regulated by movement of this loop in response to conformational changes in C8alpha during MAC formation.


Outcomes in Valve-in-Valve Transcatheter Aortic Valve Implantation.
The use of valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) is increasing, but studies evaluating clinical outcomes in these patients are scarce. Also, there are limited data to guide the choice of valve type in ViV-TAVI. Therefore, this CENTER-study evaluated clinical outcomes in patients with ViV-TAVI compared to patients with native valve TAVI (NV-TAVI). In addition, we compared outcomes in patients with ViV-TAVI treated with self-expandable versus balloon-expandable valves. A total of 256 patients with ViV-TAVI and 11333 patients with NV-TAVI were matched 1:2 using propensity score matching, resulting in 256 patients with ViV-TAVI and 512 patients with NV-TAVI. Mean age was 81±7 years, 58% were female, and the Society of Thoracic Surgeons Predicted Risk of Mortality was 6.3% (4.0% to 12.8%). Mortality rates were comparable between ViV-TAVI and NV-TAVI patients at 30 days (4.1% vs 5.9%, p = 0.30) and 1 year (14.2% vs 17.3%, p = 0.34). Stroke rates were also similar at 30 days (2.8% vs 1.8%, p = 0.38) and 1 year (4.9% vs 4.3%, p = 0.74). Permanent pacemakers were less frequently implanted in patients with ViV-TAVI (8.8% vs 15.0%, relative risk 0.59, 95% confidence interval [CI] 0.37 to 0.92, p = 0.02). Patients with ViV-TAVI were treated with self-expandable valves (n = 162) and balloon-expandable valves (n = 94). Thirty-day major bleeding was less frequent in patients with self-expandable valves (3% vs 13%, odds ratio 5.12, 95% CI 1.42 to 18.52, p = 0.01). Thirty-day mortality was numerically lower in patients with self-expandable valves (3% vs 7%, odds ratio 3.35, 95% CI 0.77 to 14.51, p = 0.11). In conclusion, ViV-TAVI seems a safe and effective treatment for failing bioprosthetic valves with low mortality and stroke rates comparable to NV-TAVI for both valve types.


Amyotrophic Lateral Sclerosis: What Nurses Need to Know.
A MOTHER OF THREE teenage children, Mrs. S, 49, presented to her healthcare provider with bilateral leg twitching and weakness, difficulty swallowing, and fatigue that's worsened over the past few weeks. While she was on her daily morning walk, she tripped and fell. She experienced a small laceration to her leg, prompting her visit to the healthcare facility. Her husband said that she'd had periods of slurred speech over the past few months as well. She was alert and oriented, and her vital signs were all within normal limits.After an exam, her healthcare provider referred her to a neurologist who ordered magnetic resonance imaging (MRI), an electromyogram, and a full bloodwork panel. After multiple visits to rule out other causes, Mrs. S received the devastating diagnosis of amyotrophic lateral sclerosis (ALS).


New insights into cellular cholesterol acquisition: promoter analysis of human HMGCR and SQLE, two key control enzymes in cholesterol synthesis.
The two control points of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) are known targets of the transcription factor sterol-regulatory element binding protein-2 (SREBP-2). Yet the location of the sterol-regulatory elements (SREs) and cofactor binding sites, nuclear factor-Y (NF-Y) and specificity protein 1 (Sp1), have not been satisfactorily mapped in the human SQLE promoter, or at all in the human HMGCR promoter. We used luciferase reporter assays to screen the sterol-responsiveness of a library of predicted SRE, Sp1 and NF-Y site mutants and hence identify bone fide binding sites. We confirmed SREs via an electrophoretic mobility shift assay (EMSA) and ChIP-PCR. We identified two SREs in close proximity in both the human HMGCR and SQLE promoters, as well as one NF-Y site in HMGCR and two in SQLE. In addition, we found that HMGCR expression is highly activated only when SREBP-2 levels are very high, in contrast to the low density lipoprotein receptor (LDLR), a result reflected in mouse models used in other studies. Both HMGCR and SQLE promoters have two SREs that may act as a homing region to attract a single SREBP-2 homodimer, with HMGCR being activated only when there is absolute need for cholesterol synthesis. This ensures preferential uptake of exogenous cholesterol via LDLR, thereby conserving energy. We provide the first comprehensive investigation of SREs and NF-Ys in the human HMGCR and SQLE promoters, increasing our fundamental understanding of the transcriptional regulation of cholesterol synthesis.


Reduced threshold for store overload-induced Ca2+ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.
Mutations in the skeletal muscle ryanodine receptor (RyR1) cause malignant hyperthermia (MH) and central core disease (CCD), whereas mutations in the cardiac ryanodine receptor (RyR2) lead to catecholaminergic polymorphic ventricular tachycardia (CPVT). Most disease-associated RyR1 and RyR2 mutations are located in the N-terminal, central, and C-terminal regions of the corresponding ryanodine receptor (RyR) isoform. An increasing body of evidence demonstrates that CPVT-associated RyR2 mutations enhance the propensity for spontaneous Ca2+ release during store Ca2+ overload, a process known as store overload-induced Ca2+ release (SOICR). Considering the similar locations of disease-associated RyR1 and RyR2 mutations in the RyR structure, we hypothesize that like CPVT-associated RyR2 mutations, MH/CCD-associated RyR1 mutations also enhance SOICR. To test this hypothesis, we determined the impact on SOICR of 12 MH/CCD-associated RyR1 mutations E2347-del, R2163H, G2434R, R2435L, R2435H, and R2454H located in the central region, and Y4796C, T4826I, L4838V, A4940T, G4943V, and P4973L located in the C-terminal region of the channel. We found that all these RyR1 mutations reduced the threshold for SOICR. Dantrolene, an acute treatment for MH, suppressed SOICR in HEK293 cells expressing the RyR1 mutants R164C, Y523S, R2136H, R2435H, and Y4796C. Interestingly, carvedilol, a commonly used β-blocker that suppresses RyR2-mediated SOICR, also inhibits SOICR in these RyR1 mutant HEK293 cells. Therefore, these results indicate that a reduced SOICR threshold is a common defect of MH/CCD-associated RyR1 mutations, and that carvedilol, like dantrolene, can suppress RyR1-mediated SOICR. Clinical studies of the effectiveness of carvedilol as a long-term treatment for MH/CCD or other RyR1-associated disorders may be warranted.


Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains.
Catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamine neurotransmitters within the brain. A functional polymorphism COMT Val158Met has been associated with psychiatric disorders including suicidal behavior. In the present study we examined whether this polymorphism was related to COMT mRNA expression in frontal cortical regions, and whether the expression of COMT differed between depressed suicide victims and psychiatric healthy controls. The Val158Met polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. The levels of COMT mRNA expression in the frontopolar cortex (FPC; 29 suicides vs. 27 controls) and orbital frontal cortex (OFC; 19 suicides vs. 15 controls) were significantly increased among depressed individuals that died by suicide relative to those of controls, being up-regulated by approximately 60% and 65% in the FPC and OFC, respectively. Furthermore, among individuals with the Met allele (Met/Met and Met/Val genotypes) who died by suicide COMT mRNA expression was elevated relative to that of the nondepressed Met allele carriers. However, significant differences were not detected between suicides (n=49) and controls (n=72) with respect to the Val158Met genotypic distribution and allelic frequencies. These results are consistent with the perspective that altered COMT mRNA expression in frontal cortical brain regions might contribute to suicide and/or depression, further supporting the role of dysregulation of catecholaminergic pathway genes in the pathophysiology of suicide behaviors.


Understanding the process of social network evolution: Online-offline integrated analysis of social tie formation.
It is important to consider the interweaving nature of online and offline social networks when we examine social network evolution. However, it is difficult to find any research that examines the process of social tie formation from an integrated perspective. In our study, we quantitatively measure offline interactions and examine the corresponding evolution of online social network in order to understand the significance of interrelationship between online and offline social factors in generating social ties. We analyze the radio signal strength indicator sensor data from a series of social events to understand offline interactions among the participants and measure the structural attributes of their existing online Facebook social networks. By monitoring the changes in their online social networks before and after offline interactions in a series of social events, we verify that the ability to develop an offline interaction into an online friendship is tied to the number of social connections that participants previously had, while the presence of shared mutual friends between a pair of participants disrupts potential new connections within the pre-designed offline social events. Thus, while our integrative approach enables us to confirm the theory of preferential attachment in the process of network formation, the common neighbor theory is not supported. Our dual-dimensional network analysis allows us to observe the actual process of social network evolution rather than to make predictions based on the assumption of self-organizing networks.


Characterization of a highly glycosylated form of the human cytomegalovirus HLA class I homologue gpUL18.
Human cytomegalovirus (HCMV) gpUL18 is a HLA class I (HLA-I) homologue with high affinity for the inhibitory receptor LIR-1/ILT2. The previously described 67 kDa form of gpUL18 is shown here to be sensitive to endoglycosidase-H (EndoH). A novel form of gpUL18 with a molecular mass of approximately 160 kDa and resistance to EndoH was identified in cells infected with HCMV strain AD169 or the low passage HCMV isolates Merlin and Toledo. The 67 kDa EndoH-sensitive gpUL18 glycoform was detected earlier in a productive infection (from 24 h post-infection) than the slower-migrating EndoH-resistant glycoform (from 72 h post-infection). Deletion of the US2-US11 region from the HCMV genome was associated with a substantial up-regulation of endogenous HLA-I in infected cells, but had no obvious effect on the gpUL18 expression pattern. Vaccinia virus and adenovirus vectors were used to further analyse gpUL18 expression. Depending on the delivery vector system, differences in the electrophoretic motility of the EndoH-resistant >105 kDa form of gpUL18, but not the EndoH-sensitive 67 kDa form, were observed; post-translational modification of the higher molecular mass glycoform appears to be influenced by active virus infection and vector delivery. The EndoH-sensitive 67 kDa gpUL18 had a rapid turnover, while the maturation to the EndoH-resistant >105 kDa form was relatively slow and inefficient. However, synthesis of the EndoH-resistant >105 kDa form was enhanced with elevated levels of beta2-microglobulin. When expressed by using an adenovirus vector, both the EndoH-sensitive 67 kDa and the EndoH-resistant >105 kDa gpUL18 forms could be detected on the cell surface.


Epstein-Barr virus-associated malignancies.
The infectious aspects of cancer in humans were epidemiologically pioneered by Dr. David Burkitt through his observations of lymphomatous tumors seen in children in equatorial Africa. Years, later, the Epstein-Barr virus (EBV) was shown to be intimately associated with such tumors and is now recognized as a component of some B-cell lymphomas and nasopharyngeal carcinoma. Still the questions of an active, passive, or accessory role persist. The ability of this virus to cause immunosuppressive hemopoietic disturbances in individuals infected with EBV but not developing cancer raise questions about host susceptibility, host immune response, and possible coconspiring, infectious, oncogenic agents. Recent associations of EBV antibody found in diseases, such as squamous cell carcinoma of the head and neck and acquired immunodeficiency syndromes, point to its possible accessory role as an immunosuppressive agent. The ability of EBV to spread by extracellular and intracellular mechanisms demonstrates its variable infectious potential. Numerous EBV-transformed human cell lines attest to its ability to confer "immortality" with uncontrolled growth patterns. This review critically examines the association of EBV with various malignancies, the type of evidence which links it there, and the implications for further investigations and therapy.


[Electronic sheet in the management of difficult wounds].
Nowadays, the treatment of the difficult wounds represents an emergent socio-sanitary problem, due to the increase of the average duration of life, with consequent increasing costs by the National Sanitary System. The term 'difficult wounds' refers to all losses of cutaneous substances with multifactorial pathogenesis that do not spontaneously recover. Today it is possible to use advanced dressings, representing a valid tool to speed-up the healing process that--as a consequence--improves quality of life for the patient. These patients need to be followed by medical teams composed by different specialists sometimes working in different hospitals. As a consequence it is has been necessary to create an electronic document containing the clinical history of the patient and reporting the different treatments. The electronic sheet allows: a) to evaluate in detail the evolution of patient conditions, thanks to an always available iconographic documentation, even when the patient is not followed by the same physician; b) and to test the effectiveness of the new advanced dressings available on the market.


Lower Somatic Mutation Levels in the λ Light-Chain Repertoires with Chronic HBV Infection.
To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals.


Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of isocitrate dehydrogenase 2 (Rv0066c) from Mycobacterium tuberculosis.
Isocitrate dehydrogenase 2 (Icd-2, Rv0066c) from Mycobacterium tuberculosis was cloned and heterologously expressed in Escherichia coli. The protein was purified by affinity and size-exclusion chromatography and crystallized. A complete data set has been collected and reduced to 3.25 A resolution in space group C2. Preliminary diffraction data analysis suggests a complex packing with at least six molecules in the asymmetric unit.


Rapid monitoring of grape withering using visible near-infrared spectroscopy.
Wineries need new practical and quick instruments, non-destructive and able to quantitatively evaluate during withering the parameters that impact product quality. The aim of the work was to test an optical portable system (visible near-infrared (NIR) spectrophotometer) in a wavelength range of 400-1000 nm for the prediction of quality parameters of grape berries during withering. A total of 300 red grape samples (Vitis vinifera L., Corvina cultivar) harvested in vintage year 2012 from the Valpolicella area (Verona, Italy) were analyzed. Qualitative (principal component analysis, PCA) and quantitative (partial least squares regression algorithm, PLS) evaluations were performed on grape spectra. PCA showed a clear sample grouping for the different withering stages. PLS models gave encouraging predictive capabilities for soluble solids content (R(2) val = 0.62 and ratio performance deviation, RPD = 1.87) and firmness (R(2) val = 0.56 and RPD = 1.79). The work demonstrated the applicability of visible NIR spectroscopy as a rapid technique for the analysis of grape quality directly in barns, during withering. The sector could be provided with simple and inexpensive optical systems that could be used to monitor the withering degree of grape for better management of the wine production process.


Improving the Efficiency and Orthogonality of Genetic Code Expansion.
The site-specific incorporation of the noncanonical amino acid (ncAA) into proteins via genetic code expansion (GCE) has enabled the development of new and powerful ways to learn, regulate, and evolve biological functions in vivo. However, cellular biosynthesis of ncAA-containing proteins with high efficiency and fidelity is a formidable challenge. In this review, we summarize up-to-date progress towards improving the efficiency and orthogonality of GCE and enhancing intracellular compatibility of introduced translation machinery in the living cells by creation and optimization of orthogonal translation components, constructing genomically recoded organism (GRO), utilization of unnatural base pairs (UBP) and quadruplet codons (four-base codons), and spatial separation of orthogonal translation.


Malignant cystosarcoma phyllodes with lymph node metastasis--a case report.
A case of malignant cystosarcoma phyllodes with metastasis in the interpectoral lymph node (Rotter's) is presented in this paper. To the author's best knowledge, this is the first case in Japan on this disease, with lymph node metastasis. Although the surgical management of the disease has not yet been standardized, radical or modified radical mastectomy is thought to be the appropriate procedure.


Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology.
Read-across (RAx) translates available information from well-characterized chemicals to a substance for which there is a toxicological data gap. The OECD is working on case studies to probe general applicability of RAx, and several regulations (e.g., EU-REACH) already allow this procedure to be used to waive new in vivo tests. The decision to prepare a review on the state of the art of RAx as a tool for risk assessment for regulatory purposes was taken during a workshop with international experts in Ranco, Italy in July 2018. Three major issues were identified that need optimization to allow a higher regulatory acceptance rate of the RAx procedure: (i) the definition of similarity of source and target, (ii) the translation of biological/toxicological activity of source to target in the RAx procedure, and (iii) how to deal with issues of ADME that may differ between source and target. The use of new approach methodologies (NAM) was discussed as one of the most important innovations to improve the acceptability of RAx. At present, NAM data may be used to confirm chemical and toxicological similarity. In the future, the use of NAM may be broadened to fully characterize the hazard and toxicokinetic properties of RAx compounds. Concerning available guidance, documents on Good Read-Across Practice (GRAP) and on best practices to perform and evaluate the RAx process were identified. Here, in particular, the RAx guidance, being worked out by the European Commission's H2020 project EU-ToxRisk together with many external partners with regulatory experience, is given.


Hemodynamic and metabolic effects of cerebral arteriovenous malformations studied by positron emission tomography.
Seventeen patients with an intracranial arteriovenous malformation were studied with positron emission tomography. Cerebral blood flow, cerebral blood volume, oxygen extraction fraction, and glucose and oxygen metabolism were evaluated in both hemispheres, excluding the area of the malformation itself. Patients were divided into three groups according to the size of their malformation, and results obtained were compared with studies in healthy volunteers. The glucose metabolism was significantly (p less than 0.01) decreased in the ipsilateral hemisphere in all patients. The cerebral blood volume was significantly increased (p less than 0.001) ipsilaterally in the three groups, and contralaterally in patients with medium- and large-sized arteriovenous malformations. The cerebral blood volume to cerebral blood flow ration, an index of vascular mean transit time, was significantly increased (p less than 0.005) ipsilaterally in patients with medium- and large-sized malformations and contralaterally in patients with large ones. Cerebral blood flow, oxygen extraction fraction, and oxygen metabolism were within the normal range bilaterally in all three groups, but oxygen extraction fraction tended to be higher in patients with larger lesions. The lack of significant change in oxygen metabolism suggests that oxygen metabolism in cortical areas remote from the arteriovenous malformation has been maintained by compensatory hemodynamic mechanisms. These data reveal widespread metabolic and hemodynamic consequences of arteriovenous malformations and suggest that they are associated with impairment of glucose metabolism, both in ipsilateral regions remote from the lesion and in the contralateral hemisphere in patients with large lesions.


Pulmonary Kaposi's sarcoma in two recipients of renal transplants.
Among 350 recipients of renal transplants seen at the Riyadh Military Hospital, 12 developed Kaposi's sarcoma. Two of these sarcomas presented primarily as a problem of diffuse lung infiltrates in an immunocompromised host. In one the diagnosis was established by transbronchial lung biopsy. Withdrawal of immunosuppression led to satisfactory radiological resolution in both patients.


Atypical Lung Carcinoid With EML4/ALK Fusion Detected With Circulating Tumor DNA.
Atypical carcinoids are a rare subset of neuroendocrine tumors that originate from cells within the bronchopulmonary tree. Compared to typical carcinoids, atypical carcinoids are associated with a worse prognosis. EML4-ALK fusions are reported in 5% of non-small cell lung carcinoma, but are rare in atypical carcinoids with only five previously reported cases. We report a case of a 70-year-old female with atypical carcinoid with metastasis to the liver and axial skeleton. She did not respond to standard of care chemotherapy with carboplatin and etoposide and was elected to enroll in hospice because of worsening clinical status. However, a circulating tumor DNA (ctDNA) sample was obtained the same day which revealed an EML4-ALK fusion gene. She immediately began therapy with the second-generation ALK inhibitor alectinib, with a remarkable symptomatic and radiographic response. Seven months later, the disease progression was demonstrated in the liver and the patient was switched to the third-generation ALK inhibitor lorlatinib. At the time of writing, the patient has continued to demonstrate sustained clinical, radiographic, and biochemical responses while on lorlatnib for two years. The dramatic treatment results highlighted in this case make the argument to consider ctDNA after the diagnosis of locally advanced or metastatic atypical carcinoid.


MILDLY DELETERIOUS MUTATIONS IN AVIAN MITOCHONDRIAL DNA: EVIDENCE FROM NEUTRALITY TESTS.
To determine whether mildly deleterious mutations (MDMs) are present in nonrecombining genomes such as avian mitochondrial DNA (mtDNA), I analyzed molecular data from 14 studies using the neutrality tests of Tajima (1989a) and McDonald and Kreitman (1991). The presence of MDMs in mtDNA is inferred from trends observed across species in estimates of heterozygosity (θ and π) and by comparisons of polymorphism and divergence using the neutrality index (NI). Assuming neutrality, θ equals π and NI equals one. In this study, however, θ is greater than π more often than expected by chance, which reflects an excess of low-frequency alleles, and NI values presented here and elsewhere are consistently greater than one, which suggests an excess of nonsynonymous mutations within species (polymorphism) relative to between species (divergence). These observations suggest that, within species, there is an excess of rare haplotypes and that these haplotypes are carrying MDMs. The excess rare haplotypes may need to be accounted for when estimating population genetic parameters that assume strict neutrality.


Acute respiratory distress in cattle.
The term "fog fever" was originally used identify a disease of adult cattle grazing lush pastures in the autumn. Unfortunately, the name has subsequently been applied to other respiratory disorders which occurred under different epidemiological circumstances, so that the name "fog fever" has lost much of its original specificity and become almost synonymous with "acute respiratory distress". The pulmonary lesions in 151 cattle, of all ages, with acute respiratory distress are described in this report. While most of the animals were referred as examples of "fog fever", in only 43 of the 151 cases were the clinical signs, epidemiology and post mortem findings consistent with that disease. Twelve other pulmonary disturbances were encountered in the other animals and the pathology of these conditions has bee described.


Occurrence of the ectoparasite Isocyamus deltobranchium (Amphipoda: Cyamidae) on cetaceans from Atlantic waters.
The cyamids collected from a True's beaked whale (Mesoplodon mirus), a common dolphin (Delphinus delphis), and a harbour porpoise (Phocoena phocoena) stranded in Galicia (NW Spain) were identified as Isocyamus deltobranchium, extending the range of this species to the Atlantic Ocean. The three cetacean species examined are new hosts for this parasite. The microscopic examination of female specimens reveals that certain important taxonomic characters can be present or absent depending on the maturation stage, an aspect which should be considered in future studies describing cyamid species.


Membrane-anchored heparin-binding epidermal growth factor-like growth factor acts as a tumor survival factor in a hepatoma cell line.
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family, is produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (sHB-EGF). It is known that high expression of pro-HB-EGF occurs in hepatoma tissues, although its biological meaning remains unknown. We established two types of hepatoma cell lines (AH66tc), which stably produce pro-HB-EGF and sHB-EGF, respectively. While sHB-EGF-producing cells (sHB-AH) showed rapid growth, pro-HB-EGF-producing cells (pHB-AH) showed markedly suppressed cell growth as compared with the parental cells. Transforming growth factor beta or serum-starved conditions induced apoptosis of mock and sHB-AH as well as the parental cells, but not of pHB-AH. The resistance to apoptosis upon serum-starved treatment was correlated with an increase in the rate of the G1 phase in the cell cycle due to up-regulation of the cyclin-dependent kinase inhibitor p21. The mechanism underlying this resistance of pHB-AH to apoptosis was thought to be related to the prolonged half-life of the EGF receptor followed by continuous phosphorylation of the tyrosine residues. These observations demonstrate a unique function of pro-HB-EGF that is not observed for the mature form and show that pro-HB-EGF may act as a tumor survival factor in hepatoma cells.


Origin of Mechanoluminescence from Cu-Doped ZnS Particles Embedded in an Elastomer Film and Its Application in Flexible Electro-mechanoluminescent Lighting Devices.
Mechanically driven light emission from particles embedded in elastomer films has recently attracted interest as a strong candidate for next-generation light sources on display devices because it is nondestructive, reproducible, real-time, environmentally friendly, and reliable. The origin of mechanoluminescence (ML) obtained from particles embedded in elastomer films have been proposed as the trapping of drifting charge carriers in the presence of a piezoelectric field. However, in this study, we propose a new origin of ML through the study of the microstructure of a Cu-doped ZnS particles embedded in an elastomer composite film with high brightness using transmission electron microscopy (TEM) to clearly demonstrate the origin of ML with respect to the microstructure of ML composite films. The TEM characterization of the ML composite film demonstrated that the Cu-doped ZnS particles were fully encapsulated by a 500 nm thick Al layer, which acts as an electron source for ML emission. Furthermore, we fabricated a flexible electro-mechanoluminescence (EML) device using a Cu-doped ZnS particles embedded in a flexible elastomer composite film. Our research results on a new emission mechanism for ML and its application in flexible light generating elastomer films represent an important step toward environmentally benign and ecofriendly flexible electro-mechanoluminescent lighting devices.


Intestinal Farnesoid X Receptor and Takeda G Protein Couple Receptor 5 Signaling in Metabolic Regulation.
Bile acids play a critical role in the regulation of glucose, lipid and energy metabolisms by activating the nuclear bile acid receptor farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (aka takeda G protein couple receptor 5, TGR5) signaling. Paradoxical roles of FXR in the regulation of glucose and lipid metabolism and metabolic disorder have been reported recently. The activation or inhibition of intestinal FXR signaling has been shown to improve insulin and glucose sensitivity and energy metabolism to prevent diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). TGR5 has an anti-inflammatory function in the intestine and stimulates glucagon-like peptide-1 (GLP-1) secretion in the intestine to stimulate insulin secretion from the pancreas. The role of TGR5 in metabolism and metabolic regulation is not clear and warrants further study. FXR and TGR5 are co-expressed in the ileum and colon. These 2 bile acid-activated receptors may cooperate to stimulate GLP-1 secretion and improve hepatic metabolism. FXR and TGR5 dual agonists may have therapeutic potential for treating diabetes and NAFLD.


Problems in developing functional handwriting.
The development of handwriting quality and speed of 407 primary school children was followed from Grade 1 to Grade 5 in a longitudinal experiment. Performance was analyzed to enquire into the extent and bases for handwriting dysfunction. 27% of the children were classified as dysfunctional at the end of Grade 1. At the end of Grade 5 only 13% were so classified. Most children have adequate perception and motor abilities to develop functional handwriting. Dysfunction of handwriting speed can usually be traced to dysfunction of its quality. Dysfunction of quality can be traced to insufficient individualization in the primary instruction in handwriting which leads to a mismatch between the time allocated to teach certain letters to certain children and the time required for these children to learn the form of these letters.


Unusual centrosymmetric structure of [M(18-crown-6)](+) (M = Rb, Cs and NH4) complexes stabilized in an environment of hexachloridoantimonate(V) anions.
In (1,4,7,10,13,16-hexaoxacyclooctadecane)rubidium hexachloridoantimonate(V), [Rb(C12H24O6)][SbCl6], (1), and its isomorphous caesium {(1,4,7,10,13,16-hexaoxacyclooctadecane)caesium hexachloridoantimonate(V), [Cs(C12H24O6)][SbCl6]}, (2), and ammonium {ammonium hexachloridoantimonate(V)-1,4,7,10,13,16-hexaoxacyclooctadecane (1/1), (NH4)[SbCl6]·C12H24O6}, (3), analogues, the hexachloridoantimonate(V) anions and 18-crown-6 molecules reside across -3 axes passing through the Sb atoms and the centroids of the 18-crown-6 groups, both of which coincide with centres of inversion. The Rb(+) [in (1)], Cs(+) [in (2)] and NH4(+) [in (3)] cations are situated inside the cavity of the 18-crown-6 ring; they are situated on -3 axes and are equally disordered about centres of inversion, deviating from the centroid of the 18-crown-6 molecule by 0.4808 (13), 0.9344 (7) and 0.515 (8) Å, respectively. Interaction of the ammonium cation and the 18-crown-6 group is supported by three equivalent hydrogen bonds [N...O = 2.928 (3) Å and N-H...O = 162°]. The centrosymmetric structure of [Cs(18-crown-6)](+), with the large Cs(+) cation approaching the centre of the ligand cavity, is unprecedented and accompanied by unusually short Cs-O bonds [2.939 (2) and 3.091 (2) Å]. For all three compounds, the [M(18-crown-6)](+) cations and [SbCl6](-) anions afford linear stacks along the c axis, with the cationic complexes embedded between pairs of inversion-related anions.


[Clinical studies of the specificity of detecting viral DNA in non-A, non-B hepatitis in liver tissue and lymphocytes].
The clinical specifity of an intraparticular virus-DNA of 5001 Bp associated with non-A, non-B hepatitis (HNANB) was evaluated. Investigations were done in liver biopsies and lymphocytes in 173 patients having acute or chronic HNANB (n = 107) or liver diseases of other etiology (n = 66). The sensitivity of the test system (polymerase chain reaction, southern-transfer, DNA-hybridisation with synthetic oligonucleotides) was less than 100 virus particles per probe. In all patients with acute HNANB (n = 5) (parenteral mode of infection) the DNA was found in 100% in liver and lymphocytes, and in 22 of 27 patients with acute sporadic HNANB. HNANB associated substance (HNANB-AS) (1.3 g/ml CsCl) excreted with feces was found in 50%, and 29.6%, respectively. In chronic HNANB the DNA was found in 83.3% in the liver (n = 42) and in 56.7% in lymphocytes (n = 30). The HNANB-AS was found in 45.6% (n = 68). In liver diseases with other etiologies as HNANB-infection (e.g. HBV, HAV, cholestasis, HBsAg pos.-liver cirrhosis) (n = 33) the DNA was found neither in liver biopsies nor in lymphocytes. In liver diseases of uncertain etiology, but with NANB-infection under discussion (e.g. nonspecific reactive hepatitis, fatty liver, HBV neg liver cirrhosis) the DNA was found in the liver in 24% (n = 25) and in lymphocytes in 40% (n = 5). In patients with clinically resolved HNANB no DNA was found in liver and lymphocytes (n = 5). All stools were negative for HNANB-AS in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)


A quasi-free-field transducer system for high-frequency audiometry.
Previous attempts to measure human hearing capacity in the high frequencies (8 to 20 kHz) have only been met with rather limited success. Based on the results of Shaw and co-workers we have developed a free-field transducer system where the stimuli are delivered from a point source and meet the ear as plane progressive waves at a carefully chosen angle of incidence. The system can be calibrated in a precise manner by means of a specially designed coupler. Preliminary results indicate that the procedure is easily applicable also in a group of inexperienced test subjects and the test-retest variability was within such limits that are acceptable for subjective audiometric testing. These results require validation in a large group of subjects and we hope it will be possible to establish normative values for various age groups.


Evaluation of the Impacts of Long-Term Enriched Artemia with Bacillus subtilis on Growth Performance, Reproduction, Intestinal Microflora, and Resistance to Aeromonas hydrophila of Ornamental Fish Poecilia latipinna.
The present study investigated the effect of enriched Artemia with Bacillus subtilis on growth performance, reproductive factors, proximate composition, intestinal microflora, and resistance to Aeromonas hydrophila of ornamental fish, Poecilia latipinna. Using a completely randomized design, the experiment included three groups. The first group was fed with commercial food without any probiotic. The second group was fed with unenriched Artemia, and the last group consumed long-time enriched Artemia with Bacillus subtilis. The bacteria B. subtilis with a density of 1 × 105 CFU mL-1 was added daily to Artemia culture medium. The total microflora and Bacillus subtilis counts were significantly increased in enriched Artemia compared to the unenriched group (P < 0.05). In fish fed groups, growth factors did not show any significant difference (P > 0.05). The maximum relative fecundity (28.65 ± 2.52 egg number g-1), fry production (62.93 ± 4.6 individual per female), and fry survival (70.97 ± 1.56%) obtained in the third group were found to be significantly more than those in the first and the second groups. Moreover, intestinal bacterial count for Bacillus revealed that the higher concentration of bacteria was significantly related to the third group (6.24 ± 0.11 log CFU g-1) (P < 0.05). Maximum protein and fat contents were observed in fish fed with Bacillus-enriched Artemia; however, no significant difference was found between control and unenriched Artemia groups (P > 0.05). The highest amount of ash was observed in fish fed with commercial food without any probiotic (P < 0.05). At the end of the feeding period, each of the three groups along with positive group (oxytetracycline 100 mg kg-1 of commercial food) was exposed to A. hydrophila (BCCM5/LMG3770) bacteria intraperitoneally. Based on the results, the lowest cumulative mortality was significantly found in group three (68.75 ± 3.6%) and positive group (62.5 ± 7.0%) compared to control and unenriched Artemia groups (P < 0.05). Hence, B. subtilis with a concentration of 1 × 105 CFU mL-1 during the period of Artemia culturing can improve the reproductive parameters, intestinal microflora, and resistance to pathogenic bacteria of Poecilia latipinna.


Spiroplasma as a candidate agent for the transmissible spongiform encephalopathies.
The recovery of a novel Spiroplasma sp. from brain tissues from sheep with scrapie, cervids with chronic wasting disease, and from patients with Creutzfeldt-Jakob disease through passage through embryonated eggs has raised the issue of the role of Spiroplasma in the transmissible spongiform encephalopathies (TSE). In this review, we have inserted into an epidemiologic infection model evidence accumulated over the past 30 years showing involvement of Spiroplasma infection in TSE. These data support our hypothesis that a Spiroplasma sp. is the causal agent of TSE, although Koch's postulates must be fulfilled to definitively answer that question.


Lipoic acid stimulates bone formation in ovariectomized rats in a dose-dependent manner.
This study was undertaken to determine the osteotropic effect of different doses of lipoic acid (LA) on the mineralization of bone tissue in female Wistar rats with experimental osteopenia induced by bilateral ovariectomy. Fifty-six rats were randomly selected and submitted to either a sham operation (n = 8) or an ovariectomy (n = 48). The ovariectomized rats were randomly placed into two control groups, treated subcutaneously with either physiological saline or 17β-estradiol in the dose of 4 μg/kg body mass per day, and four experimental groups that received LA subcutaneously in the doses of 12.5, 25, 50, and 100 mg/kg body mass per day (n = 8 in each group). After 28 days of experimental treatment, the rats were sacrificed, and body mass, total skeletal density, and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that the osteoprotective effect of LA was dose-dependent and was observed in rats treated with 50 and 100 mg/kg of LA. Moreover, the LA applied to the ovariectomized rats in the dose of 50 mg/kg not only stopped the bone resorption, but stimulated its formation.


Synergistic inhibition of platelet activation by plasmin and prostaglandin I2.
Endothelial cell prostacyclin (PGI2) inhibits platelet activation by raising platelet cyclic AMP. Previously, platelet activation was also shown to be blocked by plasmin formed by endothelium-derived tissue plasminogen activator (TPA). We have now studied interactions between PGI2 and plasmin in the control of platelet function. PGI2 and plasmin cause synergistic inhibition of thrombin- and ADP-induced aggregation of washed platelets. Inhibition by PGI2 is similarly potentiated by TPA added to platelet-rich plasma to generate plasmin. Thrombin-stimulated rise in platelet cytosolic Ca2+, measured by fura2 fluorescence, and thromboxane A2 formation, measured by radioimmunoassay (RIA), are likewise synergistically inhibited by PGI2 and plasmin. Plasmin neither increases nor potentiates PGI2-stimulated increases in platelet cyclic AMP. Thus, PGI2 and plasmin cause synergistic inhibition of platelet activation by both cyclic AMP-dependent and independent mechanisms. This interaction between two different endothelium-derived products may play an important role in localizing the hemostatic plug to a site of vascular injury by preventing further thrombin-mediated accrual of platelets.


Managing radiation use in medical imaging: a multifaceted challenge.
This special report aims to inform the medical community about the many challenges involved in managing radiation exposure in a way that maximizes the benefit-risk ratio. The report discusses the state of current knowledge and key questions in regard to sources of medical imaging radiation exposure, radiation risk estimation, dose reduction strategies, and regulatory options.


[Lung transplantation].
Three different ways of pulmonary transplants are feasible: heart and lungs together, one single lung or both lungs. While concerning the primitive or secondary pulmonary arterial hypertension, only the cardio-pulmonary transplant is possible, concerning the respiratory deficiency; the respective indications of each of these transplants are not yet clearly defined. During the postoperative period, rejection and bacteriological, viral, fungal or parasitical infections are responsible for a mortality of about 30%. In the long term, the transplant patients are in danger of respiratory insufficiency by obliterating bronchiolitis due to untreated chronic rejection. The development of these transplants is considerably limited by the rarity of donors whose lungs are usable and by the frequency of isolated heart removals to the prejudice of the cardiopulmonary bloc transplants.


Remineralizing Agents: The Next Frontier.
Remineralizing agents represent a new frontier in dentistry. They may be classified as fluoride agents, calcium and phosphate based agents, herbal agents or combinations. The modes of delivery of remineralizing agents may be as dentifrices, mouth rinses, lozenges or chewing gums. The applications of remineralizing agents may be extrapolated to virtually every branch of dentistry ranging from pediatric to geriatric dentistry.


Salivary Levels of Interleukin-1β in Temporomandibular Disorders and Fibromyalgia.
To evaluate salivary levels of the proinflammatory cytokine interleukin-1β (IL-1β) in patients with temporomandibular disorders (TMD), fibromyalgia, or both conditions in comparison to healthy individuals. A total of 69 females (18 to 84 years of age) were assigned to one of four groups: (A) healthy controls (n = 27); (B) TMD only (n = 18); (C) fibromyalgia only (n = 15); and (D) fibromyalgia plus TMD (n = 9). Clinical data and salivary IL-1β levels were evaluated. Statistical analysis was performed by using Fischer exact test, unpaired Student t test, or one-way analysis of variance plus multiple comparisons Tukey test, depending on the variable. The correlation between age and IL-1β levels was assessed by using Pearson correlation coefficient. Most patients in groups B and D displayed clinical features of Group I (muscle disorders) and Group II (disc displacements) of the Axis I Research Diagnostic Criteria for Temporomandibular Disorders. The subjects in groups C and D presented values of > 7 on the Widespread Pain Index (WPI) and > 5 for Symptom Severity Score (SS) according to the Fibromyalgia Survey Diagnostic Criteria and Severity Scale. There were no significant differences when SS and WPI levels were compared between groups C and D. The patients with TMD showed significantly higher salivary IL-1β levels irrespective of a fibromyalgia diagnosis (groups B and D), whereas the fibromyalgia-only patients (group C) did not show any significant difference in relation to controls. This study provides novel evidence indicating that salivary IL-1β may be a biomarker for TMD.


Frontoparietal activity with minimal decision and control.
In the human brain, a well known frontoparietal circuit, including lateral prefrontal cortex (LPFC), presupplementary motor area/anterior cingulate cortex (pre-SMA/ACC), and both the superior and inferior parietal cortex, is involved in cognitive control. One proposal is that the frontoparietal cortex holds a flexible description of attended or task-relevant information, biasing processing in favor of this information in many different parts of the brain. Here, we separate frontoparietal coding of attended information from its active use in behavior. In two experiments, subjects watch a stream of visual stimuli in a fixed location. In the first experiment, there is no task to perform; in the second, decisions are orthogonal to the occurrence of new stimulus events. Even in these simple circumstances, we find that attended stimulus changes give extensive activation of LPFC, pre-SMA/ACC and parietal cortex, whereas unattended changes do not. Even without behavior to control, these classical "control" regions are active in simple update of attended information.


La-related protein 6 controls ciliated cell differentiation.
La-related protein 6 (LARP6) is an evolutionally conserved RNA-binding protein. Vertebrate LARP6 binds the 5' stem-loop found in mRNAs encoding type I collagen to regulate their translation, but other target mRNAs and additional functions for LARP6 are unknown. The aim of this study was to elucidate an additional function of LARP6 and to evaluate the importance of its function during development. To uncover the role of LARP6 in development, we utilized Morpholino Oligos to deplete LARP6 protein in Xenopus embryos. Then, embryonic phenotypes and ciliary structures of LAPR6 morphants were examined. To identify the molecular mechanism underlying ciliogenesis regulated by LARP6, we tested the expression level of cilia-related genes, which play important roles in ciliogenesis, by RT-PCR or whole mount in situ hybridization (WISH). We knocked down LARP6 in Xenopus embryos and found neural tube closure defects. LARP6 mutant, which compromises the collagen synthesis, could rescue these defects. Neural tube closure defects are coincident with lack of cilia, antenna-like cellular organelles with motility- or sensory-related functions, in the neural tube. The absence of cilia at the epidermis was also observed in LARP6 morphants, and this defect was due to the absence of basal bodies which are formed from centrioles and required for ciliary assembly. In the process of multi-ciliated cell (MCC) differentiation, mcidas, which activates the transcription of genes required for centriole formation during ciliogenesis, could partially restore MCCs in LARP6 morphants. In addition, LARP6 likely controls the expression of mcidas in a Notch-independent manner. La-related protein 6 is involved in ciliated cell differentiation during development by controlling the expression of cilia-related genes including mcidas. This LARP6 function involves a mechanism that is distinct from its established role in binding to collagen mRNAs and regulating their translation.


Gradient Descent-Barzilai Borwein-Based Neural Network Tracking Control for Nonlinear Systems With Unknown Dynamics.
In this article, a combined gradient descent-Barzilai Borwein (GD-BB) algorithm and radial basis function neural network (RBFNN) output tracking control strategy was proposed for a family of nonlinear systems with unknown drift function and control input gain function. In such a method, a neural network (NN) is used to approximate the controller directly. The main merits of the proposed strategy are given as follows: first, not only the NN parameters, such as weights, centers, and widths but also the learning rates of NN parameter updating laws are updated online via the proposed learning algorithm based on Barzilai-Borwein technique; and second, the controller design process can be further simplified, the controller parameters that should be tuned can be greatly reduced. Theoretical analysis about the stability of the closed-loop system is manifested. In addition, simulations were conducted on a numerical discrete time system and an inverted pendulum system to validate the presented control strategy.


Off-axis wave front measurements for optical correction in eccentric viewing.
In a previous study we have shown that correction of peripheral refractive errors can improve the remaining vision of subjects with large central visual field loss. Measuring peripheral refractive errors with traditional methods is often difficult due to low visual acuity and large aberrations. Therefore a Hartmann-Shack sensor has been designed to measure peripheral wave front aberrations in subjects using eccentric viewing. The sensor incorporates an eye tracker and analyzing software designed to handle large wave front aberrations and elliptic pupils. To ensure that the measurement axis is aligned with the direction of the subject's preferred retinal location, a special fixation target has been developed. It consists of concentric rings surrounding the aperture of the sensor together with a central fixation mark along the measurement axis. Some initial measurements on subjects using eccentric viewing have been performed successfully. As a first step in improving the peripheral optics of the eye, the wave front has been used to calculate the eccentric refraction. This refraction has been compared to the refraction found with the PowerRefractor instrument. Measuring the off-axis wave front is a fast way to assess the optical errors in the subject's eccentric viewing angle and to better understand the problems of eccentric correction.


Call to Action for Advancing Equitable Genomic Newborn Screening.
Newborn screening (NBS) facilitates early detection and treatment of infants with rare, treatable conditions, improving their health and well-being. Integrating genomic sequencing into NBS (genomic newborn screening, or gNBS) is an approach being considered by an increasing number of jurisdictions worldwide. Despite the potential benefits of gNBS, there remain substantial challenges to its global implementation. The purpose of this perspective paper is to discuss four pressing challenges to the equitable implementation of gNBS at a population level, and to present calls to action for each challenge. The four pressing challenges are selecting conditions for gNBS, respecting self-determination through informed consent and parent education, protecting privacy and confidentiality, and mitigating adverse psychosocial sequelae. All of these topics highlight significant disparities between high-income and low- and middle-income countries in implementing gNBS, which will make its equitable implementation even more challenging. The proposed calls to action acknowledge and provide recommendations for addressing these disparities. Across all of the challenges, the impact of local and community resources, priorities, policies, and infrastructure on implementation of gNBS is an especially important consideration. Differences between jurisdictions will influence whether, when, and how gNBS is implemented. Substantial gaps in empirical knowledge of gNBS remain, underscoring opportunities for innovative research. The pressing challenges discussed in this perspective paper must be addressed for the equitable and just implementation of gNBS and advancement of global health equity.


Academic Difficulties in Children with Prenatal Alcohol Exposure: Presence, Profile, and Neural Correlates.
Academic achievement was evaluated in children with heavy prenatal alcohol exposure to determine potential strengths and weaknesses, evaluate the utility of different definitions for identifying low academic performance, and explore the neural correlates that may underlie academic performance. Children (8 to 16 years) were assessed using the WIAT-II. Patterns of performance were examined in 2 subject groups: children with heavy prenatal alcohol exposure (n = 67) and controls (n = 61). A repeated-measures MANCOVA examining group differences on academic domain (reading, spelling, math) scores was conducted. Post hoc comparisons examined within-group profiles. Numbers and percentage of children with low achievement were calculated using several criteria. In a subsample (n = 42), neural correlates were analyzed using FreeSurfer v5.3 to examine relations between cortical structure (thickness and surface area) and performance. The alcohol-exposed group performed worse than controls on all domains and had a unique academic profile, supported by a significant group × academic domain interaction (p < 0.001). For the alcohol-exposed group, math reasoning was significantly lower than numerical operations, which was significantly lower than spelling and word reading. Over half of the alcohol-exposed group (58.2%) demonstrated low achievement on 1 or more academic domains. The number and percentage of children meeting criteria for low achievement varied based on the domain and definition used. The imaging analysis identified several surface area clusters that were differentially related to math (L superior parietal and R lateral/middle occipital) and spelling (bilateral inferior and medial temporal) performance by group, with no relations for the other academic domains. Generally, scores improved as surface area decreased in controls, whereas no relation or a positive relation was observed in the alcohol-exposed group. Alcohol-exposed children demonstrated deficits in academic performance across domains and definitions, with a relative weakness in math functioning. Atypical brain development may contribute to these impairments in academic achievement. Understanding academic difficulties can assist in advocating effectively for alcohol-exposed children.


Measurement of local magnetic fields in actinide tetrafluorides.
Fluorine-19 magnetic shielding tensors have been measured in a series of actinide tetrafluorides (AnF4) by solid state nuclear magnetic resonance spectroscopy. Tetravalent actinide centers with 0-8 valence electrons can form tetrafluorides with the same monoclinic structure type, making these compounds an attractive choice for a systematic study of the variation in the electronic structure across the 5f row of the Periodic Table. Pronounced deviations from predictions based on localized valence electron models have been detected by these experiments, which suggests that this approach may be used as a quantitative probe of electronic correlations.


Social determinants of intra-urban differentials of admissions by respiratory diseases in Salvador (BA), Brazil.
Respiratory diseases (RD) represent a significant cause of hospitalization in Brazil, occupying the first position in the rank by group of diseases. To identify social determinants (SD) of intra-urban differentials of hospitalizations by RD and their main types (asthma and pneumonia) a study of spatial aggregation was carried out in Salvador (BA), between 2001 and 2007, taking Information Zones (IZ) as unit of analysis. Data on hospitalizations were provided by the Health Department of Bahia State. Socioeconomic indicators were obtained from the Demographic Census carried out in 2000, and the number of health centers was acquired from the National Register of Health Services. Multiple linear regression analysis indicated association between spatial variation of the rates of hospitalization due to RD and income (β = 0.54, p < 0.001) and rate of health facilities per 10,000 inhabitants (β = 2.91, p < 0.001). Crowding was not associated. The identification of variation in SD in hospitalizations by RD in the IZ of Salvador will help in the decision-making process by public managers in defining goals and effective measures to reduce inequities in health.


Improved cerebral microbleeds detection using their magnetic signature on T2*-phase-contrast: A comparison study in a clinical setting.
In vivo detection of cerebral microbleeds (CMBs) from T2* gradient recalled echo (GRE) magnitude image suffers from low specificity, modest inter-rater reproducibility and is biased by its sensitivity to acquisition parameters. New methods were proposed for improving this identification, but they mostly rely on 3D acquisitions, not always feasible in clinical practice. A fast 2D phase processing technique for computing internal field maps (IFM) has been shown to make it possible to characterize CMBs through their magnetic signature in routine clinical setting, based on 2D multi-slice acquisitions. However, its clinical interest for CMBs identification with respect to more common images remained to be assessed. To do so, systematic experiments were undertaken to compare the ratings obtained by trained observers with several image types, T2* magnitude, Susceptibility Weighted Imaging reconstructions (SWI) and IFM built from the same T2*-weighted acquisition. 15 participants from the MEMENTO multi-center cohort were selected: six subjects with numerous CMBs (20 ± 6 CMBs), five subjects with a few CMBs (2 ± 1 CMBs) and four subjects without CMB. 2D multi-slice T2* GRE sequences were acquired on Philips and Siemens 3T systems. After pilot experiments, T2* magnitude, Susceptibility Weighted Imaging (SWI) minimum intensity projection (mIP) on three slices and IFM were considered for the rating experiments. A graphical user interface (GUI) was designed in order to consistently display images in random order. Six raters of various background and expertise independently selected "definite" or "possible" CMBs. Rating results were compared with respect to a specific consensus reference, on both lesion and subject type points of view. IFM yielded increased sensitivity and decreased false positives rate (FPR) for CMBs identification compared to T2* magnitude and SWI-mIP images. Inter-rater variability was decreased with IFM when identifying subjects with numerous lesions, with only a limited increase in rating time. IFM thus appears as an interesting candidate to improve CMBs identification in clinical setting.


Utility of Orchidometric Parameters for Assessing Sexual Maturation in Male Cynomolgus Macaques (Macaca fascicularis).
Testicular volume is one of several parameters that have been used in preclinical toxicology to facilitate the identification of sexually mature male cynomolgus macaques when semen evaluation is unavailable. Furthermore, testicular volume provides additional information to pathologists to aid in the interpretation of microscopic findings. Orchidometry has been proposed as a useful tool for assessing testicular volume. To assess its utility for this purpose, we used orchidometry to measure testicular volume in untreated control male cynomolgus macaques during preclinical toxicology studies. Additional parameters including age, body weight, testicular weight, serum testosterone, and testicular histology were also evaluated. Serum inhibin B and the diameter of histologic testicular sections were assessed to determine whether they might provide any additional corroborative evidence for differentiating stages of sexual maturity in males. Orchidometry was easy to use in sedated or awake macaques and, in combination with testicular histology, enabled the establishment of cut-off values by which sexually mature male cynomolgus macaques can be identified with a high degree of confidence. The relative utility of the parameters examined for discriminating sexually mature and immature males was testicular volume ≥ serum testosterone > body weight > age; for differentiation of sexually mature and peripubertal males the order was testicular volume ≥ body weight > serum testosterone > age. Testicular weight and the diameter of histologic testicular sections provided corroborative information for discriminating stages of sexual maturity. Serum inhibin B was of little value in helping to differentiate the different stages of sexual maturation evaluated in this study.


Preparation and properties of metallic, superhard rhenium diboride crystals.
Single crystals of ReB(2) have been prepared from an aluminum flux under inert gas flow. The crystals are typically 1-3 mm in diameter and 500 microm thick, growing along the [002] direction with a distinct hexagonal morphology. Vickers microhardness and nanoindentation testing indicate that the (002) plane possesses the highest hardness with measured values of 40.5 and 36.4 GPa, respectively. The elastic anisotropy was examined and the indentation moduli of the basal plane and an (hk0) plane of unknown indices are 675 and 510 GPa, respectively. Four-probe electrical resistivity measurements demonstrate that ReB(2) is the hardest material known to exhibit metallic behavior. Thermogravimetric analysis indicates that the crystals are stable in air up to 1000 degrees C due to the formation of a protective boron oxide coating.


Prevalence, Perceived Benefits, and Perceived Barriers Regarding Breast Cancer Screening Among Three Arab American Women Subgroups.
Introduction: Mammography screening (MS) has been identified as a valuable tool to decrease mortality rates from breast cancer (BC). Arab American women (AAW) have been recognized as an ethnic group that needs further research to promote their participation in BC screening. This study aims to explore MS rates, and investigate differences in attitudes and beliefs about BC screening in AAW. Method: This comparative, cross-sectional study investigated 316 American Muslim and Christian women from three Arab countries. The Arab Culture-Specific Barriers instrument was employed. Results: The results revealed lower MS rates in AAW compared with national screening rates. Cultural and religious benefits and barriers were identified. Discussion: This study was able to provide a better understanding of AAW beliefs, attitudes, and behaviors regarding BC screening based on their unique ethnic identity and religion. Implications of such findings include increasing efforts to improve MS rates and providing cultural training for health care professionals.


Advertised sustainability practices among suppliers to a university hospital operating room.
The present study aimed to identify firms supplying products to our university operating room (OR) that promote sustainable manufacturing methods. Results show that 72% of our suppliers, or 152 of 211 companies, do not promote sustainability practices in a salient manner. Multi-national firms document sustainability methods significantly more than U.S. divisions of multi-nationals or U.S. firms with chi-square = 157.93 (p < 0.001). Although the current study did not evaluate real manufacturing methods, sustainability promotion is an important marketing tool through which purchasers may begin the process of due diligence for product selection. Lack of sustainability information among suppliers in this study suggests that hospital procurement departments likely focus solely on issues like price or quality when making purchase decisions. These results also suggest an opportunity for healthcare administrators to evaluate more fully the products involved in the healthcare supply chain; the intrinsic, intangible value added to hospital products through sustainable manufacturing is consistent with responsible patient care and has the potential to create marketing and public relations value.


Femoral condylar fractures in four continental giant breed rabbits.
Four male neutered continental giant rabbits aged between 10 and 30 months were presented with femoral condylar fractures, which developed without an observed traumatic injury. Stabilisation of the condylar fracture was achieved with screw fixation in all cases, which was supplemented with additional fixation in three cases. Complications consequent to the surgical intervention occurred in two cases: a femoral fracture and loss of fixation. Three rabbits were reported to have recovered normal limb function, and the rabbit that developed a femoral fracture as a consequence of its surgical intervention was treated with amputation.


Transgenic mice secreting coronavirus neutralizing antibodies into the milk.
Ten lines of transgenic mice secreting transmissible gastroenteritis coronavirus (TGEV) neutralizing recombinant monoclonal antibodies (rMAbs) into the milk were generated. The rMAb light- and heavy-chain genes were assembled by fusing the genes encoding the variable modules of the murine MAb 6A.C3, which binds an interspecies conserved coronavirus epitope essential for virus infectivity, and a constant module from a porcine myeloma with the immunoglobulin A (IgA) isotype. The chimeric antibody led to dimer formation in the presence of J chain. The neutralization specific activity of the recombinant antibody produced in transiently or stably transformed cells was 50-fold higher than that of a monomeric rMAb with the IgG1 isotype and an identical binding site. This rMAb had titers of up to 10(4) by radioimmunoassay (RIA) and neutralized virus infectivity up to 10(4)-fold. Of 23 transgenic mice, 17 integrated both light and heavy chains, and at least 10 of them transmitted both genes to the progeny, leading to 100% of animals secreting functional TGEV neutralizing antibody during lactation. Selected mice produced milk with TGEV-specific antibody titers higher than 10(6) as determined by RIA, neutralized virus infectivity by 10(6)-fold, and produced up to 6 mg of antibody per ml. Antibody expression levels were transgene copy number independent and integration site dependent. Comicroinjection of the genomic beta-lactoglobulin gene with rMAb light- and heavy-chain genes led to the generation of transgenic mice carrying the three transgenes. The highest antibody titers were produced by transgenic mice that had integrated the antibody and beta-lactoglobulin genes, although the number of transgenic animals generated does not allow a definitive conclusion on the enhancing effect of beta-lactoglobulin cointegration. This approach may lead to the generation of transgenic animals providing lactogenic immunity to their progeny against enteric pathogens.


Evaluation of Debrisan in the treatment of chronic leg ulcers.
Seventeen patients with chronic leg ulcers of a 14-week mean duration were treated with daily application of Debrisan (hydrophilic microspheres of crosslinked dextran). Clean granulation tissue was present in the ulcer floor after a mean period of three weeks of treatment, and healing (with or without skin grafting) was achieved in a mean period of 9.5 weeks in 15 patients, including eight patients whose chronic leg ulcers had been refractory to all previous treatment measures. Debrisan effectively desloughs moist exudative ulcers, and allows early skin grafting.


A functional role of RB-dependent pathway in the control of quiescence in adult epidermal stem cells revealed by genomic profiling.
Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis.


A novel adaptive-weighted-average framework for blood glucose prediction.
Blood glucose (BG) prediction plays a very important role in daily BG management of patients with diabetes mellitus. Several algorithms, such as autoregressive (AR) models and artificial neural networks, have been proposed for BG prediction. However, every algorithm has its own subject range (i.e., one algorithm might work well for one diabetes patient but poorly for another patient). Even for one individual patient, this algorithm might perform well during the preprandial period but poorly during the postprandial period. A novel framework was proposed to combine several BG prediction algorithms. The main idea of the novel framework is that an adaptive weight is given to each algorithm where one algorithm's weight is inversely proportional to the sum of the squared prediction errors. In general, this framework can be applied to combine any BG prediction algorithms. As an example, the proposed framework was used to combine an AR model, extreme learning machine, and support vector regression. The new algorithm was compared with these three prediction algorithms on the continuous glucose monitoring system (CGMS) readings of 10 type 1 diabetes mellitus patients; the CGMS readings of each patient included 860 CGMS data points. For each patient, the algorithms were evaluated in terms of root-mean-square error, relative error, Clarke error-grid analysis, and J index. Of the 40 evaluations, the new adaptive-weighted algorithm achieved the best prediction performance in 37 (92.5%). Thus, we conclude that the adaptive-weighted-average framework proposed in this study can give satisfactory predictions and should be used in BG prediction. The new algorithm has great robustness with respect to variations in data characteristics, patients, and prediction horizons. At the same time, it is universal.


The immunohistochemical profile of the adenocarcinoma of upper gastric pole.
Although gastric adenocarcinoma continue to be the second continues to be the second cause of death worldwide, its incidence and mortality appear to have decreased in recent decades. Despite this decline, adenocarcinomas from proximal stomach tend to be more frequent during the last three decade. Adenocarcinomas with this location it seems that are a different, specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences between gastric adenocarcinomas from upper and distal gastric pole using the immunohistochemistry. For this reason, we investigate histopathological and immunohistochemically 77 cases of upper gastric pole adenocarcinoma selected from a number of 472 gastric tumors. The immunohistochemistry was performing only in 32 cases by ABC technique with the following primary antibodies: Cytokeratin 7, Cytokeratin 19, Epithelial Membrane Antigen (EMA), Carcinoembryonic Antigen (CEA), Lysozyme, Vimentin, p53 protein, CD34 and Ki67 antigen. The acquired results do not distinguish a peculiar immunohistochemically profile unlike distal gastric adenocarcinomas. Nevertheless, we pointed out the predominance of diffuse adenocarcinomas type according to Laurens classification, which immunohistochemically were strong positive to cytokeratins, EMA, CEA and lysozyme. Moreover, investigation of some antigens likes lysozyme, p53, Ki67 and CD34 seems to be useful for prognostic estimation of carcinoma with this topography.


Junctional communication and cellular differentiation.
Gap junctions provide pathways of direct cell to cell communication in the tissues of metazoan animals. Cells joined by gap junctions share their small ions and molecules but can maintain distinctive activities through expression of different macromolecules which are too large to pass through the junctions. The junctional channels are made of a tissue invariant, evolutionarily conserved 16-18 k protein but the formation and maintenance of active coupling also requires one or more connexins, a family of tissue-specific proteins ranging in size from 21 k to 70 k. Junctions can be isolated as complexes containing both types of protein by mild procedures using high pH but the connexins can be removed by detergent, urea and protease treatment without destroying the characteristic junctional-morphology of hexagonally packed channels in the double membrane structures. There is also some evidence for the participation in the complex of tissue-specific proteoglycans which perhaps interact with the tissue-specific connexins and account for specificity of junction formation. Such specificity in mixed cultures leads to the production of communication compartments, groups of cells joined by junctions but separated by reduced trans-boundary coupling from cells in adjacent compartments. Compartmentation also occurs in vivo resulting in specific patterns of junctional communication which have been mapped in most detail in mouse skin. These mapping data and the changes which are associated with abnormal proliferation have lead to new ideas on intercellular control.(ABSTRACT TRUNCATED AT 250 WORDS)


Examining problem solving skills of physical education and sport students from several factors.
In this research, problem solving skills of university students are examined in the factors of sex and class. In this research problem solving inventory that is improved by Heppner and Petersen (1982) is applied to the students that are training 1. and 4. class 58 female 86 male at Selcuk University Konya, Turkey Physical Education and Sport Collage. In statistical analysis of research for the factors sex and class, variance analysis and t test are used. In the research while meaningful difference is found in the above dimension of the factors sex and there is not found meaningful difference in the factors of class. In conclusion, female students have more positive problem solving skills than male students.


Cell volume regulation in the nervous system.
There is good evidence that the three main compartments of the brain, i.e. extracellular space, neurones and glial cells, change their volume during physiological and pathophysiological neuronal activity. However, there is strikingly little knowledge about the mechanisms underlying such alterations in cell volume. For this purpose, a better understanding of the electrophysiological behavior of the neurones and glial cells during volume changes is necessary. Examples are discussed for which changes in cell volume can be derived from the underlying changes in membrane permeabilities. Volume regulatory mechanisms in the brain have not been described under isotonic conditions. However, a rapid volume regulatory decrease is occurring in cultured glial cells during exposure to hypotonic solutions. In contrast, in these cells no volume regulatory increase was found during superfusion with hypertonic media. On the other hand, the entire brain is able to compensate chronic hypertonic perturbations within hours to days. Interestingly, not only ion fluxes induce cellular volume changes but, in turn, water movements can also influence ion fluxes in both neurones and glial cells. With respect to this it should be considered that volume regulatory membrane processes might not exclusively be activated by changes in transmembranal ion gradient, but also by changes of membrane surface shape. Future studies on cellular mechanisms of volume regulation in the brain should imply a combined use of recent techniques such as computerized video-imaging, radiotracer flux measurements and ion-sensitive microelectrodes in defined cell cultures. Optical monitoring and ion-sensitive microelectrodes should enable measurements of volume changes in identified cellular elements of intact nervous structures such as brain slices.


Protective effects of inosine on mice subjected to lethal total-body ionizing irradiation.
Mammals can barely survive total-body ionizing irradiation greater than 10 Gy. To date, there are few drugs available for radioprotective therapy under such circumstances. Inosine, a natural derivative of adenosine, has been known to provide powerful protection for many kinds of cells and tissues against various insults both in vitro and in vivo. In the present study, we examined whether inosine was also beneficial for mammals subjected to an absolutely lethal total-body ionizing irradiation. Immediately after adult Balb/c mice were exposed to (60)Co gamma-rays at a single dose of 12 Gy, a moiety of them were administered daily with inosine or adenosine, either at doses of 375 or 750 micromol/kg up to death, and their body weight and survival time were recorded. Some irradiated mice were administered inosine or adenosine daily at doses of 750 micromol/kg and assessed for spatial memory abilities using the Morris water maze. The results demonstrated that, although inosine could not prevent body weight loss in irradiated mice, it was able to significantly prolong their survival time at doses of 750 micromol/kg. Moreover, inosine but not adenosine could suppress spatial memory deficit in irradiated mice. The data suggested that inosine had protective effects on mammals suffering from total-body ionizing irradiation at a single lethal dose.


Treatment of nonuniting osteotomies with pulsating electromagnetic fields. A controlled animal experiment.
To evaluate treatment of nonunions or pseudarthrosis in humans by pulsating electromagnetic fields (PEMF), the authors tested the method in four- to six-year-old beagle dogs with midshaft osteotomies of both ulnae. This type of osteotomy in dogs leads to nonunion. After surgery one foreleg of each dog was stimulated for an average of 25 days; the second foreleg served as a control. Subsequently all ulnae were harvested, radiographs were obtained, and the stiffness of the callus was mechanically tested. Thus, the reputed efficiency is not confirmed by controlled experiments on dogs. The stimulated bones were neither radiologically nor mechanically superior to the controls.


Improvement of left ventricular function after starting insulin treatment in patients with non-insulin-dependent diabetes.
Left ventricular function was evaluated noninvasively before and three months after starting insulin treatment in nine patients (mean age 61.8 years, range 51-68 years) with non-insulin dependent diabetes showing an impaired insulin secretion capacity. After starting insulin treatment, fasting blood glucose decreased from 12.9 +/- 0.5 mmol/l (mean +/- SEM) to 9.8 +/- 1.2 mmol/l (p = 0.03), but the decrease of glycosylated haemoglobin Alc was not significant (9.0 +/- 0.4% vs. 8.3 +/- 0.6%). On systolic time intervals, PEP/LVET ratio improved from 0.44 +/- 0.03 to 0.37 +/- 0.02 (p = 0.03). On M-mode echocardiography, E-F slope became steeper (89 +/- 6 mm/sec vs. 103 +/- 8 mm/sec; p = 0.01) but no significant changes were observed in other variables reflecting diastolic or systolic function. On equilibrium radionuclide angiocardiography, the left ventricular ejection fraction at rest was similar before and after starting insulin treatment (48.6 +/- 3.2% vs. 49.2 +/- 2.8%) but during peak exercise the left ventricular ejection fraction improved significantly (51.0 +/- 5.3% vs. 59.9 +/- 4.7%; p = 0.02). The change of PEP/LVET ratio correlated significantly with the changes of blood glucose and glycosylated haemoglobin Alc levels, but the correlation between these metabolic variables and the change of left ventricular ejection fraction during exercise did not reach statistical significance. In conclusion, the left ventricular function improved concomitantly with improved metabolic control after starting insulin treatment in middle-aged patients with non-insulin-dependent diabetes having an impairment in insulin secretion capacity. This finding suggests that metabolic factors are involved in the left ventricular dysfunction observed in diabetes.