Prediction accuracy for a simulated maternally affected trait of beef cattle using different genomic evaluation models.
Different methods for genomic evaluation were compared for accuracy and feasibility of evaluation using phenotypic, pedigree, and genomic information for a trait influenced by a maternal effect. A simulated population was constructed that included 15,800 animals in 5 generations. Genotypes from 45,000 SNP were available for 1,500 animals in the last 3 generations. Genotyped animals in the last generation had no phenotypes. Weaning weight data were simulated using an animal model with direct and maternal effects. Additive direct and maternal effects were considered either noncorrelated (formula in text) or negatively correlated (formula in text). Methods of analysis were traditional BLUP, BayesC using phenotypes and ignoring maternal effects (BayesCPR), BayesC using deregressed EBV (BayesCDEBV), and single-step genomic BLUP (ssGBLUP). Whereas BayesCPR can be used when phenotypes of only genotyped animals are available, BayesCDEBV can be used when BLUP EBV of genotyped animals are available, and ssGBLUP is suitable when genotypes, phenotypes, and pedigrees are jointly available. For all genotyped and young genotyped animals, mean accuracies from BayesCPR and BayesCDEBV were lower than accuracies from BLUP for direct and maternal effects. The differences in mean accuracy were greater when genetic correlation was negative. Gains in accuracy were observed when ssGBLUP was compared with BLUP; for the direct (maternal) effect the average gain was 0.01 (0.02) for all genotyped animals and 0.03 (0.02) for young genotyped animals without phenotypes. Similar gains were observed for 0 and negative genetic correlation. Accuracy with BayesCPR was affected by ignoring phenotypes of nongenotyped animals and maternal effect and by not accounting for parent average. Accuracy with BayesCDEBV was affected by approximations needed for deregression, not accounting for parent average, and sequential rather than simultaneous fitting of genomic and nongenomic information. Whereas BayesCDEBV presented a considerable bias, especially for maternal effect, ssGBLUP was unbiased for both effects. The computing time was 1 s for BLUP, 44 s for ssGBLUP, and over 2,000 s for BayesC. Greatest computational efficiency and accuracy of genomic prediction for a maternally affected trait was obtained when information from all nongenotyped but related individuals was included and phenotypes, pedigree, and genotypes were available and considered jointly. Increasing the gain in accuracy of genomic predictions obtained by ssGBLUP over BLUP may require an increase in the number of genotyped animals.


Venous Thromboembolism in Patients Discharged From the Emergency Department With Ankle Fractures: A Population-Based Cohort Study.
Temporary lower limb immobilization may be a risk for venous thromboembolism. The purpose of this study was to examine the 90-day incidence of venous thromboembolism among patients discharged from an emergency department (ED) with ankle fractures requiring temporary immobilization. Secondary objectives were to examine individual factors associated with venous thromboembolism in this population and to compare the risk of venous thromboembolism in patients with ankle fractures against a priori-selected control groups. This was a retrospective cohort study using province-wide health datasets from Ontario, Canada. We included patients aged 16 years and older discharged from an ED between 2013 and 2018 with closed ankle fractures requiring temporary immobilization. We estimated 90-day incidence of venous thromboembolism after ankle fracture. A Cox proportional hazards model was used to evaluate risk factors associated with venous thromboembolism, censoring at 90 days or death. Patients with ankle fractures were then propensity score matched to 2 control groups: patients discharged with injuries not requiring lower limb immobilization (ie, finger wounds and wrist fractures) to compare relative hazard of venous thromboembolism. There were 86,081 eligible patients with ankle fractures. Incidence of venous thromboembolism within 90 days was 1.3%. Factors associated with venous thromboembolism were older age (hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 1.00 to 1.39), venous thromboembolism or superficial venous thrombosis history (HR: 5.18; 95% CI: 4.33 to 6.20), recent hospital admission (HR: 1.33; 95% CI: 1.05 to 1.68), recent nonankle fracture surgery (HR: 1.58; 95% CI: 1.30 to 1.93), and subsequent surgery for ankle fracture (HR: 1.80; 95% CI: 1.48 to 2.20). In the matched cohort, patients with ankle fractures had an increased hazard of venous thromboembolism compared to matched controls with finger wounds (HR: 6.31; 95% CI: 5.30 to 7.52) and wrist fractures (HR: 5.68; 95% CI: 4.71 to 6.85). The 90-day incidence of venous thromboembolism among patients discharged from the ED with ankle fractures requiring immobilization was 1.3%. These patients had a 5.7- to 6.3-fold increased hazard compared to matched controls. Certain patients immobilized for ankle fractures are at higher risk of venous thromboembolism, and this should be recognized by emergency physicians.


Pressure evolution of the potential barriers of phase transition of MoS2, MoSe2 and MoTe2.
Two-dimensional crystals with weak layer interactions, such as twisted graphene, have been a focus of research recently. As a representative example, transitional metal dichalcogenides show a lot of fascinating properties due to stacking orders and spin-orbit coupling. We analyzed the dynamic energy barrier of possible phase transitions in MoX2 (X = S, Se and Te) with first-principles methods. In the structural transition from 2Hc to 2Ha, the energy barrier is found to be increased following an increase of pressure which is different from the phase transition in usual semiconductors. Among MoS2, MoSe2 and MoTe2, the energy barrier of MoS2 is the lowest and the stability of both 2Hc and 2Ha is reversed under pressure for MoS2. It is found that the absence of a phase transition in MoSe2 and MoTe2 is due to the competition between van der Waals interaction of layers and the coulomb interaction of Mo and X in nearest-neighbor layer of Mo in both phases.


Somatoform dissociative symptoms as related to animal defensive reactions to predatory imminence and injury.
The authors hypothesized that there would be a similarity between animal defensive responses to variable predatory imminence and injury and certain somatoform dissociative symptoms of trauma-reporting patients who have dissociative disorder. As a first test of this hypothesis, 12 somatoform symptom clusters consisting of clinically observed somatoform dissociative phenomena were constructed. All clusters discriminated between patients with dissociative disorders (n = 50) and patients with other psychiatric diagnoses (n = 50). Those expressive of the hypothesized similarity--freezing, anesthesia-analgesia, and disturbed eating--belonged to the 5 most characteristic symptoms of dissociative disorder patients. Anesthesia-analgesia, urogenital pain, and freezing symptom clusters independently contributed to predicted presence of dissociative disorder. Using an independent sample, it appeared that anesthesia-analgesia best predicted presence of dissociative disorder after controlling for symptom severity. The results were largely consistent with the hypothesized similarity.


Effect of prebonding procedures on shear bond strength of resin composite to pressable ceramic.
Low bond strength between tooth structure and restorative ceramic material is a major cause of ceramic fractures or failures. Prebonding measures performed on pressable ceramic material were evaluated and the different shear bond strengths obtained by each method were tabulated. The three individual groups were subjected to 9% hydrofluoric (HF) acid gel for 0, 1, and 5 minutes. The different acid-etched time groups were chemically treated with silane coupler alone, silane coupling agent with bonding agent, and bonding agent alone. The silane coupling agent produced the highest bond strength between the composite structure and the pressable ceramic restorative material. High bond values were achieved by etching the porcelain for one minute. The use of the silane coupling agent with a one minute 9% HF acid etch yielded the greatest bond strength.


Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study.
Conversion of living-donor kidney transplant patients from calcineurin inhibitor therapy to an mTOR inhibitor is poorly documented. In the prospective, multicentre ZEUS study, 300 kidney transplant recipients without prior rejection (Banff grade >1) and serum creatinine ≤265 μmol/l were randomized to continue cyclosporine or convert to everolimus at 4.5 months post-transplant. In a post hoc analysis of 80 living-donor recipients, adjusted estimated GFR (Nankivell) at month 12 (the primary endpoint) was 74.3 (95% CI [70.7, 77.9]) ml/min/1.73 m(2) with everolimus versus 63.8 (95% CI [60.0, 67.7]) ml/min/1.73 m(2) ) with cyclosporine, a difference of 10.5 ml/min/1.73 m(2) in favour of everolimus (P < 0.001). From randomization to month 12, adjusted estimated GFR increased by a mean of 9.8 (95% CI [6.2, 13.4]) ml/min/1.73 m(2) with everolimus versus -0.7 (95% CI [-4.6, 3.1]) ml/min/1.73 m(2) ) (P < 0.001) with cyclosporine. There were six biopsy-proven acute rejection episodes in everolimus-treated patients (five Banff grade I) and one episode in cyclosporine-treated patients (Banff grade 1). Overall safety profile was similar between groups. Discontinuation due to adverse events occurred in three everolimus patients (7.1%) and five cyclosporine patients (13.2%) between randomization and month 12. Initiation of everolimus with early elimination of calcineurin therapy is associated with a significant renal benefit at 12 months post-transplant that is observed in both living and deceased-donor recipients. (clinicaltrials.gov NCT00154310).


[Autism Spectrum Disorder in Infancy and Early Childhood: The Model of the Centro de Estudos do Bebé e da Criança for Diagnosis and Therapeutic Intervention].
The Centro de Estudos do Bebé e da Criança in Hospital Dona Estefânia has organized a multidisciplinary model for children under three with suspected autism spectrum disorder, thus implementing the recent guidelines established by the Directorate General for Health. The aim of this study is to describe this model and case series. A retrospective descriptive study of observed children with suspected ASD. They were observed according to the model of the Centro de Estudos do Bebé e da Criança and DC:0-5TM classification, between January 2018 and September 2019. The study included 178 children. The average age at the initial assessment was 27 months. From the total sample, 116 children concluded the diagnostic sessions (axis I): Autism Spectrum Disorder/Early Atypical (36%), Developmental Language Disorder (18%), Other (19%). Factors of axes II, III, IV and V of DC:0-5TM were determinant for clinical diagnosis in 26%. Of 116 children, 36% were diagnosed with Autism Spectrum Disorder. This highlights the diagnostic challenge posed by neurodevelopmental disorders in early infancy. The sample shows that the characteristics of the relationship with the caregiver (axis II), presence of physical conditions (axis III), psycho-social stressors (axis IV) and developmental trajectory (axis V) have a significant clinical impact. In the future, the initial assessment should take place well before the age of 27 months because of the impact on prognosis. This model is a pioneering approach in Portugal. It promotes a common approach of Child and Adolescent Psychiatry and Neuropediatrics/Developmental Pediatrics in early infancy. Moreover, it increases the diagnostic acuity of Autism Spectrum Disorders and early therapeutic intervention.


Effects of ebselen on ischemia/reperfusion injury in rat brain.
Interruption of blood flow may result in considerable tissue damage via ischemia/reperfusion (I/R) injury-induced oxidative stress in brain tissues. The aim of the present study was to investigate the effects of Ebselen treatment in short-term global brain I/R injury in rats. The study was carried out on 27 Wistar-albino rats, divided into three groups including Sham group (n = 11), I/R group (n = 8) and I/R+Ebselen group (n = 8). Malondialdehyde (MDA) levels were significantly increased in I/R group in comparison with the Sham group and I/R+Ebselen group (p < 0.001 and p < 0.01). Superoxide dismutase (SOD) activity was significantly lower in I/R group in comparison to both Sham (p < 0.001) and I/R+Ebselen (p < 0.01) groups. Similarly, SOD activity was decreased in I/R+Ebselen group when compared with Sham group (p < 0.001). Sham and I/R groups were similar in terms of nitric oxide (NO) levels. In contrast, the NO level was lower in I/R+Ebselen group when compared with Sham (p < 0.001) and I/R (p < 0.01) groups. There was no significant difference among the groups in terms of glutathione peroxidase and catalase activities. In histopathological examination, the brain tissues of rats that received Ebselen showed morphological improvement. Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.


Explosion of Burning Zirconium Droplets Caused by Nitrogen.
Single droplets of zirconium were photographed as they burned luminously in free fall. When the oxidizer was oxygen containing small amounts of nitrogen (less than 5 percent), the burning droplets exploded only when a threshold concentration of nitrogen was exceeded. Explosions also occurred when the zirconium was partially nitrided before being burned in pure oxygen. These experiments prove that the presence of nitrogen can cause the explosion of zirconium droplets burning in oxygen-rich atmospheres.


Inactivation of RASSF1A, the tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma.
To evaluate the genetic and epigenetic inactivation mechanism of the RASSF1A tumor suppressor gene at 3p21.3 in extrahepatic cholangiocarcinoma. RT-PCR was used to investigate the transcriptional expressing and re-expression of RASSF1A. RASSF1A mutation was analyzed with SSCP and selective sequencing. PCR was performed to detect the loss of heterozygosity (LOH) at the region of chromosome 3p21.3. Genomic DNA were modificated bisulfite and the frequency of methylation of CpG islands in RASSF1A promoter were evaluated by methylation specific PCR (MS-PCR). In all 48 samples and one cell lines of extrahepatic cholangiocarcinoma, the RASSF1A mutation is rare (6.12%, 3/49), 33 samples (68.75%) and QBC-939 cell lines (chi2 = 14.270, P = 0.001 > 0.01) showed RASSF1A express inactivation with LOH at microsatellite loci D3S4604. Among these 33 samples and QBC-939, 28 of 33 (84.85%) tumor samples and 1 cell lines were methylated for majority of 16 CpGs, the average frequency is 73.42%. The data we present suggest that RASSF1A which we have been searching for at 3p21.3 may be one of the key tumor suppressor gene and play an important role in the pathogenesis of extrahepatic cholangiocarcinoma, and the promoter methylation and allelic loss are the major mechanism for inactivation of RASSF1A.


Development of a new HPLC method with precolumn fluorescent derivatization for rapid, selective and sensitive detection of triterpenic acids in fruits.
Triterpenic acids are widespread in plants and have multiplicity of biological properties. Unfortunately the method for accurate analysis of these compounds remains poorly investigated. This study proposed a highly sensitive and selective precolumn derivatization method for accurate determination of five triterpenic acids (betulinic acid, betulonic acid, maslinic acid, ursolic acid and oleanolic acid) in fruits using acridone-9-ethyl-p-toluenesulfonate (AETS) as fluorescent labeling reagent by HPLC with fluorescence detection (FLD). Response surface methodology was employed to optimize the derivatization reaction, ensuring the sufficient labeling of the analyzed components. The rapid separation of five triterpenic acids could be achieved in as little as 16 min. This developed method offered the exciting detection limits of 1.68-2.04 ng/mL. When applied to several popular fruits in China, it revealed satisfactory applicability and reproducibility. This developed method also exhibits powerful potential for accurate detection of triterpenic acids from other foodstuffs and nature products.


TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.
With recent progress in understanding the pathogenesis of adrenocortical tumors (ACTs), identification of molecular markers to predict their prognosis has become possible. Transcription factor 21 (TCF21)/podocyte-expressed 1 (POD1) is a transcriptional regulatory protein expressed in mesenchymal cells at sites of epithelial-mesenchymal transition during the development of different systems. Adult carcinomas express less TCF21 than adenomas, in addition, the KEGG pathway analysis has shown that BUB1B, among others genes, is negatively correlated with TCF21 expression. The difference between BUB1B and PTEN-induced putative kinase 1 (PINK1) expression has been described previously to be associated with survival in adult but not in pediatric carcinomas. Here, we analyzed the gene expression of TCF21, BUB1B, PINK1, and NR5A1 in adult and pediatric ACTs. We found a negative correlation between the relative expression levels of TCF21 and BUB1B in adult ACTs, but the relative expression levels of TCF21, BUB1B, PINK1, and NR5A1 were similar in childhood ACTs. In addition, we propose using the subtracted expression levels of the TCF21/POD-1 genes as a predictor of overall survival (OS) in adult carcinomas and TCF21-NR5A1 as a predictor of malignancy for pediatric tumors in patients aged <5 years. These results require further validation in different cohorts of both adult and pediatric samples. Finally, we observed that the OS for patients aged <5 years was markedly favorable compared with that for patients >5 years as well as adult patients with carcinoma. In summary, we propose TCF21/POD-1 as a new prognostic marker in adult and pediatric ACTs.


Apical maxi K channels in intercalated cells of CCT.
High-conductance (maxi) K channels in the apical membrane of rat and rabbit cortical collecting tubules (CCT) were studied using the patch-clamp technique. Principal cells (PC) and intercalated cells (IC) were distinguished with Hoffman modulation optics in split-open tubules. IC were further identified by staining tubules with the fluorescent mitochondrial dye, rhodamine 123. Maxi-K channels were distinguished by their high conductance (greater than 80 pS) and voltage-dependent kinetics. In CCT of rats on a low-Na diet, maxi K channels were observed in 11% of the cell-attached patches on PC and 79% of patches on IC. In rats on a normal diet, the channels were seen in 23 and 79% of patches on PC and IC, respectively. In the rabbit CCT, maxi K channels were observed in 12% (4 of 32) of the patches on PC and 82% (122 of 148) of the patches on IC. The greater abundance of channels in IC was confirmed in rat CCT using the whole-cell clamp technique. Current through the maxi K channels (IK) was measured as the tetraethylammonium (TEA)-sensitive (2.5 mM) outward current in cells equilibrated with 115 mM K and 10(-5) M Ca2+ in the pipette solution. When the cell was clamped to an internal potential of +40 mV, the average IK per cell was -4 +/- 5 pA in PC and 290 +/- 90 pA in IC. Lowering cytoplasmic Ca2+ from 10(-5) M to 10(-7) M reduced IK to 32 +/- 21 pA. Neither single Na channels nor amiloride-sensitive whole-cell currents were seen in IC. Finally, maxi K channels could be activated by pipette suction (10-40 cm H2O) in either cell-attached or inside-out patches on IC from rabbit CCT. This mechanosensitivity was observed even after chelation of free Ca2+ with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the pipette or the bath solutions, implying that stretch activation of these channels was not mediated by increased Ca2+ entry into the cell. The IC maxi K channel may play a role in cell volume regulation or in K secretion during elevation of luminal hydrostatic pressure.


Synthesis, structure, and reactivity of new tetranuclear Ru-Hbpp-based water-oxidation catalysts.
The preparation of three new octadentate tetranucleating ligands made out of two Ru-Hbpp-based units [where Hbpp is 3,5(bispyridyl)pyrazole], linked by a xylyl group attached at the pyrazolate moiety, of general formula (Hbpp)(2)-u-xyl (u = p, m, or o) is reported, together with its dinucleating counterpart substituted at the same position with a benzyl group, Hbpp-bz. All of these ligands have been characterized with the usual analytical and spectroscopic techniques. The corresponding tetranuclear ruthenium complexes of general formula {[Ru(2)(trpy)(2)(L)](2)(μ-(bpp)(2)-u-xyl)}(n+) [L = Cl or OAc, n = 4; L = (H(2)O)(2), n = 6] and their dinuclear homologues {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(n+) [L = Cl or OAc, n = 2; L = (H(2)O)(2), n = 3] have also been prepared and thoroughly characterized both in solution and in the solid state. In solution, all of the complexes have been characterized spectroscopically by UV-vis and NMR and their redox properties investigated by means of cyclic voltammetry techniques. In the solid state, monocrystal X-ray diffraction analysis has been carried out for two dinuclear complexes {[Ru(2)(trpy)(2)(L)](μ-bpp-bz)}(2+) (L = Cl and OAc) and for the tetranuclear complex {[Ru(2)(trpy)(2)(μ-OAc)](2)(μ-(bpp)(2)-m-xyl)}(4+). The capacity of the tetranuclear aqua complexes {[Ru(2)(trpy)(2)(H(2)O)(2)](2)(μ-(bpp)(2)-u-xyl)}(6+) and the dinuclear homologue {[Ru(2)(trpy)(2)(H(2)O)(2)](μ-bpp-bz)}(3+) to act as water-oxidation catalysts has been evaluated using cerium(IV) as the chemical oxidant in pH = 1.0 triflic acid solutions. It is found that these complexes, besides generating significant amounts of dioxygen, also generate carbon dioxide. The relative ratio of [O(2)]/[CO(2)] is dependent not only on para, meta, or ortho substitution of the xylylic group but also on the concentration of the starting materials. With regard to the tetranuclear complexes, the one that contains the more sterically constrained ortho-substituted ligand generates the highest [O(2)]/[CO(2)] ratio.


Towards a personalized health care using a divisive hierarchical clustering approach for comorbidity and the prediction of conditioned group risks.
The objective was to assess risk of hospitalization and mortality of comorbidities using divisive hierarchical risk clustering to advice clinical interventions. Subjects and Methods: Data from the EHR of a general population, 3799885 adults, followed by 5 years. Model were performed using Spark and Scikit-learn and accuracy for the models was analyzed. Results: The number of models generated depends in part on the number of chronic diseases included (ex testing a sample of six diseases, a total number of 397 models for all-cause mortality and 431 models for hospitalization). The estimated models offered an ordered selection for the relevant clinical variables and their estimated risk as a group and for the individual patient in the group. Accuracy was assessed according to age, sex and the cardinality of the comorbid groups. A mobile version and dashboard were developed. Conclusion: The software developed stratified hospital admission and mortality risk in clusters of chronic diseases, and for a given patient, it could advise intensifying treatment or reallocating the patient risk.


Fetal puncture during midtrimester amniocentesis.
Four cases of fetal puncture during midtrimester amniocentesis are reported; in one instance the baby apparently sustained temporary neurologic damage. None of the lesions was detected at the initial neonatal examination. From our data and a review of the literature, we estimate that fetal puncture occurs in 1-3% of midtrimester amniotic taps. The implications of the accident are not clear. We conclude that midtrimester amniocentesis should not be considered a routine benigh procedure; and whenever the use of this diagnostic modality is being considered, the prospective parents should be informed of its hazards.


Heterogeneous nucleation-controlled particulate formation of recombinant human platelet-activating factor acetylhydrolase in pharmaceutical formulation.
Clinical lots of recombinant human platelet-activating factor acetylhydrolase (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with sterile water for injection to form an aqueous solution (10 mM sodium citrate, 7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly growing particles formed consistently within hours at room temperature. To investigate the mechanism of this phenomenon, immediately after reconstitution, all protein aggregates and exogenous particles were removed by filtration. During 20 days incubation at room temperature, no visible aggregates formed in these filtered samples. In contrast, when nano-sized hydrophilic silica particles were added, they seeded rapid and extensive aggregation of rhPAF-AH. This effect was exacerbated in solutions containing a lower Pluronic-F68 concentration at 0.01%. Aggregation occurred even under conditions where rhPAF-AH adsorption was reversible, and induced no detectable changes to protein secondary and tertiary structures. Decreasing the extent (e.g., adding Pluronic-F68) or affinity (e.g., increasing solution pH) of rhPAF-AH adsorption on nano-sized silica particles was found to be effective at reducing aggregation. Accelerated aggregation was not observed when rhPAF-AH formulation was seeded with aggregated rhPAF-AH. These results show that rhPAF-AH aggregation proceeds through a heterogeneous nucleation-controlled mechanism, where exogenous particles present in solution serve as seeds on which rhPAF-AH adsorb, nucleate, and grow into large aggregates.


Visual workflows for 13C-metabolic flux analysis.
The precise quantification of intracellular metabolic flow rates is of fundamental importance in bio(techno)logy and medical research. The gold standard in the field is metabolic flux analysis (MFA) with 13C-labeling experiments. 13C-MFA workflows orchestrate several, mainly human-in-the-loop, software applications, integrating them with plenty of heterogeneous information. In practice, this had posed a major practical barrier for evaluating, interpreting and understanding isotopic data from carbon labeling experiments. Graphical modeling, interactive model exploration and visual data analysis are the key to overcome this limitation. We have developed a first-of-its-kind graphical tool suite providing scientists with an integrated software framework for all aspects of 13C-MFA. Almost 30 modules (plug-ins) have been implemented for the Omix visualization software. Several advanced graphical workflows and ergonomic user interfaces support major domain-specific modeling and proofreading tasks. With that, the graphical suite is a productivity enhancing tool and an original educational training instrument supporting the adoption of 13C-MFA applications in all life science fields. The Omix Light Edition is freely available at http://www.omix-visualization.com email@example.com, email@example.com Supplementary data are available at Bioinformatics online.


[Perforating monolateral autokeratoplasty (author's transl)].
The author describes his own techniques of perforating monolateral autokeratoplasty, using two trephines of the same diameter, one of them turning with the right, the other with the left hand. To prevent loss of aqueous humor at first the one and then the other trephine is used up to half the thickness of the cornea. Then the central disc is excised, but to close the hole the trephine left in place until after the finishing of trephining the peripheral disc. The peripheral clear graft is sutured into the central hole, and the central clouded graft is sutured into the peripheral hole. The cornea is overlapped with a conjunctival flap. The diameter of the trephine may be 3 or 4 mm. In total we performed 24 perforating monolateral autokeratoplasties. In 13 the graft remained clear, in 9 they became semitransparent and in two cases they became clouded. In 20 patients the visual acuity improved, in 4 patients no change could be attained. In case of a clear healing the picture of the cornea is characteristic: in the dim center a clear disc and in the periphery - at most in the upper part - the dim graft from the leukoma.


Severity of anabolic steroid dependence, executive function, and personality traits in substance use disorder patients in Norway.
Anabolic androgenic steroids (AAS), including testosterone and synthetic derivatives, are typically used to increase muscle mass. Many users develop a dependence on these substances, contributing to worsened physical and mental health outcomes. Aspects of personality and executive dysfunction may represent underlying vulnerabilities for developing dependence. To identify levels of AAS dependence within substance use disorder (SUD) treatment patients and assess the relationship between dependence severity and personality traits and executive function (EF). Data were collected from patients at 38 SUD treatment facilities in Norway. Questionnaires were completed for measures of personality and EF. Measures of symptoms of AAS dependence were used in latent class analysis to identify sub-groups of patients, which were evaluated for association with EF and personality traits, and compared with a group of non-AAS using SUD patients. Three classes were identified; largely reflecting low, moderate, and high symptoms of dependence. Multinomial regression analyses indicated that moderate and high symptoms were associated with several measures of EF and personality traits, particularly self-monitoring, antagonism, disinhibition, and rigid perfectionism while users with low symptoms exhibited higher capacities for emotional control and shift, and lower negative affectivity, relative to non-AAS using SUD patients. Backward stepwise regressions indicated antagonism, and decreased self-monitoring as key personality and cognitive characteristics of SUD patients with severe AAS dependence. Our findings indicate that specific executive dysfunctions and personality features, particularly those associated with poor emotional control, reduced empathy, and impulsivity are associated with more severe AAS dependence in the SUD population.


Did Early Pleistocene hominins control hammer strike angles when making stone tools?
In the study of Early Pleistocene stone artifacts, researchers have made considerable progress in reconstructing the technical decisions of hominins by examining various aspects of lithic technology, such as reduction sequences, hammer selection, platform preparation, core management, and raw material selection. By comparison, our understanding of the ways in which Early Pleistocene hominins controlled the delivery and application of percussive force during flaking remains limited. In this study, we focus on a key aspect of force delivery in stone knapping, namely the hammerstone striking angle (or the angle of blow), which has been shown to play a significant role in determining the knapping outcome. Using a dataset consists of 12 Early Pleistocene flake assemblages dated from 1.95 Ma to 1.4 Ma, we examined temporal patterns of the hammer striking angle by quantifying the bulb angle, a property of the flake's Hertzian cone that reflects the hammer striking angle used in flake production. We further included a Middle Paleolithic flake assemblage as a point of comparison from a later time period. In the Early Pleistocene dataset, we observed an increased association between the bulb angle and other flake variables related to flake size over time, a pattern similarly found in the Middle Paleolithic assemblage. These findings suggest that, towards the Oldowan-Acheulean transition, hominins began to systematically adjust the hammer striking angle in accordance with platform variables to detach flakes of different sizes more effectively, implying the development of a more comprehensive understanding of the role of the angle of blow in flake formation by ∼1.5 Ma.


Multi-Channel Interactive Reinforcement Learning for Sequential Tasks.
The ability to learn new tasks by sequencing already known skills is an important requirement for future robots. Reinforcement learning is a powerful tool for this as it allows for a robot to learn and improve on how to combine skills for sequential tasks. However, in real robotic applications, the cost of sample collection and exploration prevent the application of reinforcement learning for a variety of tasks. To overcome these limitations, human input during reinforcement can be beneficial to speed up learning, guide the exploration and prevent the choice of disastrous actions. Nevertheless, there is a lack of experimental evaluations of multi-channel interactive reinforcement learning systems solving robotic tasks with input from inexperienced human users, in particular for cases where human input might be partially wrong. Therefore, in this paper, we present an approach that incorporates multiple human input channels for interactive reinforcement learning in a unified framework and evaluate it on two robotic tasks with 20 inexperienced human subjects. To enable the robot to also handle potentially incorrect human input we incorporate a novel concept for self-confidence, which allows the robot to question human input after an initial learning phase. The second robotic task is specifically designed to investigate if this self-confidence can enable the robot to achieve learning progress even if the human input is partially incorrect. Further, we evaluate how humans react to suggestions of the robot, once the robot notices human input might be wrong. Our experimental evaluations show that our approach can successfully incorporate human input to accelerate the learning process in both robotic tasks even if it is partially wrong. However, not all humans were willing to accept the robot's suggestions or its questioning of their input, particularly if they do not understand the learning process and the reasons behind the robot's suggestions. We believe that the findings from this experimental evaluation can be beneficial for the future design of algorithms and interfaces of interactive reinforcement learning systems used by inexperienced users.


What is the nature of peer interactions in children with language disorders? A qualitative study of parent and practitioner views.
Children with Language Disorders (LDs) can exhibit increased levels of social withdrawal, aggression and problems managing social conflicts. The reasons underlying this pattern of social interaction profiles remain unclear. This qualitative study aimed to document the nature of social interactions between children with LDs and their peers, and to evaluate explanations for their social behaviour, as understood by parents and practitioners. This study focused on children with LDs who spend school hours with other children with LDs. Three parent focus groups (n = 8) and three practitioner focus groups (n = 10) were conducted with parents of children aged 4-12 attending specialist language schools and practitioners working at these schools. This was a mixed clinical sample. All children of participating parents had LD as their primary area of need, which was the reason they required specialist schooling. Focus groups were conducted across two specialist schools in the UK between March and June 2018. An inductive reflective thematic analysis of the data identified three themes; social knowledge, coping strategies, and emotional competence. Parents and school staff reported that children with LDs experience difficulties managing peer interactions due to a combination of challenges including difficulties with understanding and regulating emotions, and difficulties understanding social situations. Some of the children with LDs were described as having developed strategies to cope with their challenges, for example imposing structure on their social interactions to manage uncertainty, which has implications for their social interactions with peers. Children with LDs have difficulties understanding emotions, difficulties understanding their peer's intentions and difficulties resolving conflict situations independently according to their parents and practitioners working with these children. Participants proposed a novel explanation that social withdrawal may be used adaptively by children with LDs to process information. This study demonstrates the complexity of the relationship between Language Disorders and peer interaction profiles.Implications: Suggestions are offered regarding future research directions, such as investigating the specific contribution language skills make to children's emotion understanding, to better understand the reasons for peer interaction difficulties in children with Language Disorders.


[X-ray-induced breaks in the X chromosomes in Drosophila lines of various radiosensitivities].
The frequency of X-ray induced X-chromosome breaks has been studied in females of the line rad (2) 201G1 hypersensitive to radiation and in females of the control line selected from the same population. The frequency of X-chromosome breaks was judged based on the frequency of X0 males occurrence. Synergism of the effects of X-rays (at doses 0.1, 0.5 and 1.0 kr) and of hyperthermia (+37 degrees C, 5.5 hours) applied after irradiation served as an indirect evidence for the functioning of DNA repair systems. It is demonstrated that radiosensitivity of mature oocytes of the lines compared was equal and that hyperthermia applied after irradiation increased the latter effect in both lines. Young oocytes of the control line were radioresistant, and hyperthermia applied after irradiation enhanced its effect. Opposite to them, young oocytes of the rad line females were radiosensitive. They did not differ from mature oocytes in the frequency of X-chromosome losses. Synergism of the two factors (irradiation and hyperthermia) was not registered in young oocytes. On the basis of the results obtained, it may be concluded that radiosensitivity of young oocytes in the hypersensitive line is conditioned by the failure of DNA repair systems and that the rad (2) 201G1 gene may be considered, in relation to the genes controlling DNA repair, as a suppressor functioning selectively at a certain stage of oogenesis.


Chlorogenic Acid, the Main Antioxidant in Coffee, Reduces Radiation-Induced Apoptosis and DNA Damage via NF-E2-Related Factor 2 (Nrf2) Activation in Hepatocellular Carcinoma.
Radiotherapy produces excessive reactive oxygen species (ROS), which can lead to DNA damage and apoptosis in tumor cells, thereby killing malignant cells. Chlorogenic acid (CGA) is a well-known antioxidant in coffee due to its strong ability to remove ROS. However, the effect of CGA on radiotherapeutic efficacy remains unclear. In this study, we showed that CGA could hinder the therapeutic effect of radiotherapy by inhibiting radiation-induced apoptosis and DNA damage via scavenging excessive ROS and activating the NF-E2-related factor 2 (Nrf2) antioxidant system in hepatocellular carcinoma (HCC) cells and a murine model. The knockdown of Nrf2 reversed CGA-mediated radiation resistance in HCC cells. In conclusion, CGA might be a potential tumor-protective compound upon irradiation and reduce the efficacy of radiotherapy via ROS scavenging and Nrf2 activation.


Activation of mitogen-activated protein kinase in xenografts and cells during prolonged treatment with aromatase inhibitor letrozole.
Ovariectomized mice bearing tumor xenografts grown from aromatase-transfected estrogen receptor (ER)-positive human breast cancer cells (MCF-7Ca) were injected s.c. with 10 microg/d letrozole for up to 56 weeks. Western blot analysis of the tumors revealed that ERs (ERalpha) were increased at 4 weeks but decreased at weeks 28 and 56. Expression of erbB-2 and p-Shc increased throughout treatment, whereas growth factor receptor binding protein 2 (Grb2) increased only in tumors proliferating on letrozole (weeks 28 and 56). In cells isolated from tumors after 56 weeks and maintained as a cell line (LTLT-Ca) in 1 micromol/L letrozole, ERalpha was also decreased whereas erbB-2, adapter proteins (p-Shc and Grb2), and the signaling proteins in the mitogen-activated protein kinase (MAPK) cascade were increased compared with MCF-7Ca cells. Growth was inhibited in LTLT-Ca cells but not in MCF-7Ca cells treated with MAPK kinase 1/2 inhibitors U0126, and PD98059 (IC(50) approximately 25 micromol/L). PD98059 (5 micromol/L) also reduced MAPK activity and increased ERalpha to the levels in MCF-7Ca cells. Epidermal growth factor receptor kinase inhibitor, gefitinib (ZD1839) inhibited growth of LTLT-Ca cells (IC(50) approximately 10 micromol/L) and restored their sensitivity to tamoxifen and anastrozole. In xenografts, combined treatment with ER down-regulator fulvestrant and letrozole, prevented increases in erbB-2 and activation of MAPK and was highly effective in inhibiting tumor growth throughout 29 weeks of treatment. These results indicate that blocking both ER- and growth factor-mediated transcription resulted in the most effective inhibition of growth of ER-positive breast cancer cells.


Chloroplast genome sequencing analysis of Heterosigma akashiwo CCMP452 (West Atlantic) and NIES293 (West Pacific) strains.
Heterokont algae form a monophyletic group within the stramenopile branch of the tree of life. These organisms display wide morphological diversity, ranging from minute unicells to massive, bladed forms. Surprisingly, chloroplast genome sequences are available only for diatoms, representing two (Coscinodiscophyceae and Bacillariophyceae) of approximately 18 classes of algae that comprise this taxonomic cluster. A universal challenge to chloroplast genome sequencing studies is the retrieval of highly purified DNA in quantities sufficient for analytical processing. To circumvent this problem, we have developed a simplified method for sequencing chloroplast genomes, using fosmids selected from a total cellular DNA library. The technique has been used to sequence chloroplast DNA of two Heterosigma akashiwo strains. This raphidophyte has served as a model system for studies of stramenopile chloroplast biogenesis and evolution. H. akashiwo strain CCMP452 (West Atlantic) chloroplast DNA is 160,149 bp in size with a 21,822-bp inverted repeat, whereas NIES293 (West Pacific) chloroplast DNA is 159,370 bp in size and has an inverted repeat of 21,665 bp. The fosmid cloning technique reveals that both strains contain an isomeric chloroplast DNA population resulting from an inversion of their single copy domains. Both strains contain multiple small inverted and tandem repeats, non-randomly distributed within the genomes. Although both CCMP452 and NIES293 chloroplast DNAs contains 197 genes, multiple nucleotide polymorphisms are present in both coding and intergenic regions. Several protein-coding genes contain large, in-frame inserts relative to orthologous genes in other plastids. These inserts are maintained in mRNA products. Two genes of interest in H. akashiwo, not previously reported in any chloroplast genome, include tyrC, a tyrosine recombinase, which we hypothesize may be a result of a lateral gene transfer event, and an unidentified 456 amino acid protein, which we hypothesize serves as a G-protein-coupled receptor. The H. akashiwo chloroplast genomes share little synteny with other algal chloroplast genomes sequenced to date. The fosmid cloning technique eliminates chloroplast isolation, does not require chloroplast DNA purification, and reduces sequencing processing time. Application of this method has provided new insights into chloroplast genome architecture, gene content and evolution within the stramenopile cluster.


[Osteoplastic materials in the treatment of parodontosis].
Efficiency of bioactive osteoplastic composition HA-phage at a surgical stage of combined treatment of chronic generalized periodontitis was examined. The results obtained in the control and experimental groups proved that HA-phage allows reducing the time of treatment and to achieve remission of the disease. Out of 92 patients with chronic generalized periodontitis 52 undertook microplasmic scalpel-irradiator in complex treatment. The treatment course comprises 3-5 procedures. The quantity of manipulations is determined by the pathological process. Before and after the treatment the radiographic investigations were carried out in persons of both groups. 18 months later after the operation a bone regeneration was shown in 87,8% cases in the investigated group and 60,1%--in the control group patients. The therapy has shown positive results. So, the new method of treatment of chronic generalized periodontitis may prove to be more practical in clinical dentistry. Currently, it is possible to isolate highly purified BMSSCs from bone marrow using STRO-1. The management of periodontal defects has been an ongoing challenge in clinical periodontics. This is mainly a result of the fact that the tissues which comprise the periodontium, the periodontal ligament, and the cementum and alveolar bone represent three unique tissues in their own right. Thus, reconstruction of the periodontium is not just a simple matter of regenerating one tissue but involves at least three quite diverse and unique tissues. Taking into account the results of recent studies we hypothesize that mesenchymal stem cells transplantation should be a perspective approach in the treatment of periodontal defects. For this purpose we plan to perform an experimental investigations which will include an induction of periodontitis, purification of the bone marrow stem cells and their transplantation.


Exotic nuclear spin behavior in dendritic macromolecules.
Dendrimers are a class of branched, highly symmetric macromolecules that have been shown to be useful for a vast number of different applications. Potential uses as fluorescence sensors, in catalysis and perhaps most importantly in medical applications as drug delivery systems or cytotoxica have been proposed. Herein we report on an exotic behaviour of the nuclear spins in a dendritic macromolecule in the presence of different paramagnetic ions. We show that the stability of the long lived nuclear singlet state, is affected by the presence of Cu(II), whereas other ions did not have any influence at all. This effect could not be observed in the case of a simple tripeptide, in which the nuclear singlet stability was influenced by all investigated paramagnetic ions, a potentially useful effect in the development of Cu(II) selective probes. By adding a fluorescent marker to our molecule we could show that the nuclear singlet multimer (NUSIMER) is taken up by living cells. Furthermore we were able to show that nuclear singlet state NMR can be used to investigate the NUSIMER in the presence of living cells, showing that an application in in vivo NMR can be feasible.


Effect of varying fixture width on stress and strain distribution associated with an implant stack system.
The purpose of this investigation was to evaluate the dissipation of a force applied to an assembled stack of implant components. The stack consisted of a 10-mm threaded implant, a screw-retained abutment and a screw-retained gold crown. The dissipation of force was analyzed in relation to varying the implant diameter with and without a concomitant change in abutment diameter. Two experimental groups were evaluated. The first group consisted of 25 titanium screw-form implants (Implant Innovations, Inc.). These implants measured 10 mm in length and 3.25 mm, 3.75 mm, 4.0 mm, 5.0 mm, and 6.0 mm in diameter. The second group included 15 titanium screw-form implants (Nobel Biocare, Inc.) measuring 10 mm in length and 3.75 mm, 4.0 mm, and 5.0 mm in diameter. All implants were embedded in standardized photoelastic resin blocks. Points of interest were marked on each block using standardized templates to ensure consistency. Implants were restored using system-specific conical abutments and standardized single-unit restorations. A strain gauge was affixed to each abutment, and an eccentric load of 176 N was applied to the restoration. Periimplant stresses were measured using photoelastic analysis. Abutment strain was determined using an electronic strain indicator. Data were collated and compared using ANOVA and the Duncan multiple range statistical tests. When stress was analyzed at points on the resin-implant interface or a fixed distance from the interface, stress tended to decrease from the 5-mm-wide implant to the 6-mm-wide implant. Stress in relation to the 3.25-mm, 3.75-mm, and 4.0-mm implant was not as well defined, indicating the possibility that some deformation of implants was occurring. Increased abutment width resulted in decreased abutment strain. Therefore, using a wider abutment may be helpful in preventing preload reduction in clinical applications. This may reduce the incidence of loosening and fracture of abutment and restoration screws.


Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome.
Reactivation of varicella zoster virus (VZV) can manifest with facial palsy diagnosed as Ramsay Hunt Syndrome (RHS) or Ramsay Hunt Syndrome zoster sine herpete (RHS-ZSH). These syndromes are associated with poor prognosis despite treatment with antivirals and corticosteroids. Concentrations of biomarkers such as neurofilament protein (NFL), S-100β protein and glial fibrillary acidic protein (GFAp) have previously been measured in cerebrospinal fluid (CSF) to assess neuronal damage and glial pathology. We employed immunochemical methods to measure concentrations of NFL, S-100β protein and GFAp in CSF from patients with RHS (n = 15) and RHS-ZSH (n = 13) diagnosed by detection of VZV DNA in the CSF by quantitative PCR, and compared with a control group (n = 52). The biomarker concentrations were correlated with CSF viral load and outcome measured by House-Brackmann score. NFL and GFAp concentrations were increased compared with controls (P = 0.008 and P = 0.04), while S-100β levels were decreased. This pattern was more pronounced in patients with RHS compared to the patients with RHS-ZSH (NS and P = 0.028). The amount of viral DNA in CSF correlated with increased GFAp (P = 0.003) and NFL (P = 0.006). No correlations were found between biomarker concentrations and patient outcome. Patients with facial palsy caused by VZV had biochemical signs of neuronal damage and astrogliosis. High amounts of viral DNA may be associated with the degree of damage on neuronal and astroglial cells. Prospective studies are warranted to elucidate the association of elevated biomarkers in the CSF and outcome assessed by more sensitive tests.


Optimal scaling of weight and waist circumference to height for adiposity and cardiovascular disease risk in individuals with spinal cord injury.
Observational cross-sectional study. Body mass index (BMI), measured as a ratio of weight (Wt) to the square of height (Wt/Ht(2)), waist circumference (WC) and waist-to-height ratio (WHtR) are common surrogate measures of adiposity. It is not known whether alternate scaling powers for height might improve the relationships between these measures and indices of obesity or cardiovascular disease (CVD) risk in individuals with spinal cord injury (SCI). We aimed to estimate the values of 'x' that render Wt/Ht(x) and WC/Ht(x) maximally correlated with dual energy x-ray absorptiometry (DEXA) total and abdominal body fat and Framingham Cardiovascular Risk Scores. Canadian public research institution. We studied 27 subjects with traumatic SCI. Height, Wt and body fat measurements were determined from DEXA whole-body scans. WC measurements were also obtained, and individual Framingham Risk Scores were calculated. For values of 'x' ranging from 0.0 to 4.0, in increments of 0.1, correlations between Wt/Ht(x) and WC/Ht(x) with total and abdominal body fat (kg and percentages) and Framingham Risk Scores were computed. We found that BMI was a poor predictor of CVD risk, regardless of the scaling factor. Moreover, BMI was strongly correlated with measures of obesity, and modification of the scaling factor from the standard (Wt/Ht(2)) is not recommended. WC was strongly correlated with both CVD risk and obesity, and standard measures (WC and WHtR) are of equal predictive power. On the basis of our findings from this sample, alterations in scaling powers may not be necessary in individuals with SCI; however, these findings should be validated in a larger cohort.


Azathioprine in rheumatoid arthritis: a long-term follow-up study.
In 1973 we reported the beneficial effects of azathioprine in a double blind, cross-over study in 17 patients with classic rheumatoid arthritis. During subsequent follow-up over a mean period of 40 months, 4 patients had discontinued therapy because of poor therapeutic response and 1 because of nausea. Eleven of the 12 patients still taking azathioprine had maintained their initial beneficial response or showed further improvement. Adverse side effects during the follow-up period were minor. They included nausea in 1 patient and leukopenia with thrombocytopenia in another. An increased incidence of chromosomal abnormalities was detected in those patients still receiving azathioprine.


Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases.
The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure. We conducted a systematic review of this issue. Studies published from January 1, 1977, until August 11, 2008, were identified by use of MEDLINE, EMBASE, and the Cochrane Library. A total of 58 studies (total number of patients = 297,533) were included and divided into three categories according to the method for pathological assessment of the lymph nodes: cohort studies with single-section pathological examination of axillary lymph nodes (n = 285,638 patients), occult metastases studies with retrospective examination of negative lymph nodes by step sectioning and/or immunohistochemistry (n = 7740 patients), and sentinel lymph node biopsy studies with intensified work-up of the sentinel but not of the nonsentinel lymph nodes (n = 4155 patients). We used random-effects meta-analyses to calculate pooled estimates of the relative risks (RRs) of 5- and 10-year disease recurrence and death and the multivariably corrected pooled hazard ratio (HR) of overall survival of the cohort studies. In the cohort studies, the presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes was associated with poorer overall survival (pooled HR of death = 1.44, 95% confidence interval [CI] = 1.29 to 1.62). In the occult metastases studies, the presence (vs the absence) of occult metastases was associated with poorer 5-year disease-free survival (pooled RR = 1.55, 95% CI = 1.32 to 1.82) and overall survival (pooled RR = 1.45, 95% CI = 1.11 to 1.88), although these endpoints were not consistently assessed in multivariable analyses. Sentinel lymph node biopsy studies were limited by small patient groups and short follow-up. The presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival.


Selective borane reduction of phosphinoferrocene carbaldehydes to phosphinoalcohol-borane adducts. The coordination behaviour of 1-(diphenylphosphino)-1'-(methoxymethyl)ferrocene, a new ferrocene O,P-hybrid donor prepared from such an adduct.
The reduction of ferrocene phosphino-aldehydes, R(2)PfcCHO (R = Ph, 2; Cy, 3; fc = ferrocene-1,1'-diyl, Cy = cyclohexyl) and (S(p))-[Fe(η(5)-C(5)H(3)-1-CHO-2-PPh(2))(η(5)-C(5)H(5))] ((S(p))-4), with BH(3)·THF or BH(3)·SMe(2) in THF at 0 °C selectively afforded the corresponding phosphinoalcohol-borane adducts, R(2)PfcCH(2)OH·BH(3) (R = Ph, 5; Cy, 6) and (S(p))-[Fe(η(5)-C(5)H(3)-1-CH(2)OH-2-PPh(2))(η(5)-C(5)H(5))]·BH(3) ((S(p))-7), in quantitative yields. In contrast, the reactions performed at elevated temperatures favoured the formation of methyl derivatives (e.g., Ph(2)PfcCH(3)·BH(3) (8)) resulting from overreduction (deoxygenation). The crystal structures of 3, 5, (S(p))-7, 8 and Cy(2)PfcBr (9) have been determined by single-crystal X-ray diffraction analysis. The crystal assemblies of adducts 5 and (S(p))-7 are built up by means of C-H...O contacts, O-H...HB dihydrogen bonds and other soft interactions but, surprisingly, not via the conventional O-H...O hydrogen bonds. Adduct 5 was smoothly deprotected to give the corresponding free phosphine, Ph(2)PfcCH(2)OH (1), and was further used for the preparation of a hybrid phosphinoether ligand, Ph(2)PfcCH(2)OMe (11). The latter compound was studied as a donor for Group 8-10 metal ions and for Cu(i), whereupon the following complexes were isolated and structurally characterised: [(η(6)-p-cymene)RuCl(2)(11-κP)] (12*), [(η(6)-p-cymene)RuCl(11-κP)(MeCN)][SbF(6)] (13*), [RhCl(cod)(11-κP)] (cod = η(2):η(2)-cycloocta-1,5-diene; 14), trans-[PdCl(2)(11-κP)(2)] (trans-15*), [PdCl(μ-Cl)(11-κP)](2) (16*), cis- and trans-[PtCl(2)(11-κP)(2)] (cis-17 and trans-17*), and [Cu(CF(3)SO(3)-κO)(11-κP)(H(2)O)] (18) (the asterisk indicates that the crystal structure was determined). In all these compounds, ligand 11 behaves as a P-monodentate donor while its ether group remains uncoordinated. This probably reflects structural flexibility of 11 resulting from the presence of the methylene linker and also distinguishes 11 from its known, non-spaced analogue Ph(2)PfcOMe.


Mucoglycoprotein hypersecretion in allergic rhinitis and cystic fibrosis.
There is little information about specific changes in submucosal gland exocytosis in diseases such as allergic rhinitis (AR), nonallergic rhinitis (NAR), and cystic fibrosis (CF). Nasal lavage fluids were collected from normal, AR, NAR, and CF subjects. Concentrations of lysozyme, Alcian blue-staining mucoglycoconjugate material (AB + m), and human high-molecular-weight mucoglycoconjugates recognized by the 7F10 murine monoclonal antibody [7F10-immunoreactive mucoglycoconjugates (7F10-irm)] were measured. AB + m and 7F10-irm were characterized by Sepharose-2B column chromatography and glycosidase digestion. 7F10-irm was increased in CF (2.4-fold; P = 0.001) and AR (12.7-fold; P = 0.00007) subjects. AB + m was increased in CF (1.8-fold; P = 0.049) and AR (1.2-fold; P = 0.07) subjects. There were no changes in NAR subjects. On Sepharose-2B columns, AB + m peaks were at 1.3-3.0 x 10(6) and 0.36-0.65 x 10(6) Da. 7F10-irm showed four distinct peaks at 1.5, 1.2, 0.85, and 0.53 x 10(6) Da that were nearly identical in both normal and CF samples. Sialic acid was present in both 7F10-irm and AB + m. 7F10-irm and AB + m are mutually exclusive sialylated mucoglycoproteins that are significantly induced in AR and CF but not in NAR.


Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.
Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.


Gram-negative bacterial endocarditis in adults: state-of-the-heart.
Gram-negative endocarditis due to HACEK bacteria (Haemophilus species, Actinobacillus, Cardiobacterium, Eikenella and Kingella species) and non-HACEK organisms is an infrequent occurrence but is associated with significant morbidity and mortality. Traditionally, non-HACEK Gram-negative endocarditis has been associated with injection drug use. However, emerging data from more contemporary cohorts suggest changing epidemiology and risk factors for Gram-negative endocarditis, necessitating an updated review of this subject. Moreover, optimal management, including the need for surgical intervention, and strategies for the prevention of Gram-negative endocarditis need to be revisited.


The gap junction blockers carbenoxolone and 18beta-glycyrrhetinic acid antagonize cone-driven light responses in the mouse retina.
Gap junctions are widely expressed throughout the retina, and play an important role in the processing of visual information. It has been proposed that horizontal cells express unpaired gap junctions, or hemichannels, in their dendrites, and that current flowing through hemichannels reduces transmembrane voltage at cone terminals, promoting the opening of Ca2+ channels near sites of transmitter release. This model predicts that pharmacological block of gap junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby decreasing the postsynaptic light response. To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18beta-glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the light response to about 30% of control. Cells that were physiologically identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or glutamate receptors, as they did not affect responses to direct activation of these receptors. Under control conditions, spots larger than 200 microm in diameter activated ganglion cell receptive-field surrounds. Comparing responses to small and large spots before and during carbenoxolone treatment, we found that carbenoxolone did not preferentially inhibit surround antagonism at the ganglion cell level, but instead scaled the responses to all spot sizes. Our results extend the findings of studies in lower vertebrates which showed that light responses in horizontal cells are decreased by carbenoxolone treatment, and support the idea that hemichannels in the outer retina, most likely on horizontal cells, constitute important gates that are critical for allowing light responses to move forward into the retinal circuit. Furthermore, it suggests that ganglion cell surrounds are generated in the inner retina.


Preventing the progression of chronic kidney disease: two case reports and review of the literature.
A variety of therapeutic modalities are available to alter the abnormalities seen in patients with chronic kidney disease (CKD). A comprehensive plan can now be developed to slow the progression of CKD. Two clinical cases of delay in the need for renal replacement therapy are described. This delay was achieved by using recognized recommendations for optimal diabetes therapy (HbA1c target 7 %), goals for blood pressure levels, reduction of proteinuria, and the proper use of ACEI/ARB therapies. Recent recommendations include BP <140/90 mmHg for patients <60 years old and <150/90 mmHg for older patients unless they have CKD or diabetes. Limits on dietary sodium and protein intake and body weight reduction will decrease proteinuria. Proper treatment for elevated serum phosphorous and parathyroid hormone levels is now appreciated as well as the benefits of therapy for dyslipidemias and anemia. Concerns regarding unfavorable outcomes with excess ESA therapy have led to hemoglobin goals in the 10-12 g/dL range. Finally, new therapeutic considerations for the treatment of acidosis and hyperuricemia are presented with data available to suggest that increasing serum bicarbonate to >22 mmol/L is beneficial, while serum uric acid therapeutic goals are still uncertain. Also, two as yet insufficiently understood approaches to altering the course of CKD (FGF-23 level reduction and balancing gut microbiota) are noted.


Sensitive and specific detection of ligands using engineered riboswitches.
Riboswitches are RNA elements found in non-coding regions of messenger RNAs that regulate gene expression through a ligand-triggered conformational change. Riboswitches typically bind tightly and specifically to their ligands, so they have the potential to serve as highly effective sensors in vitro. In B. subtilis and other gram-positive bacteria, purine nucleotide synthesis is regulated by riboswitches that bind to guanine. We modified the xpt-pbuX guanine riboswitch for use in a fluorescence quenching assay that allowed us to specifically detect and quantify guanine in vitro. Using this assay, we reproducibly detected as little as 5 nM guanine. We then produced sensors for 2'-deoxyguanosine and cyclic diguanylate (c-diGMP) by appending the P1 stem of the guanine riboswitch to the ligand-binding domains of a 2'-deoxyguanosine riboswitch and a c-diGMP riboswitch. These hybrid sensors could detect 15 nM 2'-deoxyguanosine and 3 nM c-diGMP, respectively. Each sensor retained the ligand specificity of its corresponding natural riboswitch. In order to extend the utility of our approach, we developed a strategy for the in vitro selection of sensors with novel ligand specificity. Here we report a proof-of-principle experiment that demonstrated the feasibility of our selection strategy.


Quantitative measurement of precipitating antibodies in streptococcal grouping antisera by the single radial immunodiffusion technique.
A comparative study was made of the single radial immunodiffusion test and the classical quantitative precipitin test for determining the amount of precipitable antibodies present in streptococcal groups A and C antisera. The potency of 21 group A and 54 group C antisera was determined by both methods; purified group-specific carbohydrates were used as antigens. The coefficient of correlation between the results from the two methods was 0.976 for group A antisera and 0.946 for group C antisera. When the concentration of antigen, the volume of antiserum used, and the depth of the antigen-agar mixture are kept constant, the diameter of the precipitin disc is directly related to the concentration of precipitable antibodies present in the antiserum. The use of the radial immunodiffusion test for evaluating and standardizing streptococcal grouping antisera is discussed as well as the advantages and disadvantages of using a concentrated vaccine for producing these antisera.


Cross-sectional study of food insecurity and medical expenditures by race and ethnicity.
Food insecurity is a risk factor for morbidity and mortality leading to high medical expenditures, but race/ethnicity was used as adjustments in the literature. The study sought to use race/ethnicity as a key predictor to compare racial differences in associations between food insecurity and expenditures of seven health services among non-institutionalized adults. This cross-sectional study used Medical Expenditure Panel Survey that collects information on food insecurity in 2016 (n=24,179) and 2017 (n=22,539). We examined the association between race/ethnicity and food insecurity status and documented the extent to which impacts of food insecurity on medical expenditures varied by race/ethnicity. We fit multivariable models for each racial group, adjusting for states, age, gender, insurance, and education. Adults older than 18 years were included. The results show that blacks experienced an inter-racial disparity in food insecurity whereas Hispanics experienced intra-racial disparity. A higher percentage of blacks (28.7%) reported at least one type of food insecurity (11.2% of whites). Around 20% of blacks reported being worried about running out of food and the corresponding number is 8.4% among whites. Hispanics reported more food insecurity issues than whites. Moreover, food insecurity is positively associated with expenditures on emergency room utilization (99% increase for other races vs. 51% increase for whites) but is negatively associated with dental care utilization (43% decrease for blacks and 44% for whites). Except for Hispanics, prescription expenditure has the most positive association with food insecurity, and food insecure blacks are the only group that did not significantly use home health. The study expanded our understanding of food insecurity by investigating how it affected seven types of medical expenditures for each of four racial populations. An interdisciplinary effort is needed to enhance the food supply for minorities. Policy interventions to address intra-racial disparities among Hispanics and inter-racial disparities among African Americans are imperative to close the gap.


Why do residents leave general surgery? The hidden problem in today's programs.
Much has been written and discussed about the reasons for reduced interest in surgery, but few institutions have chosen to examine the loss or attrition of general surgery residents from their own programs. In preparation for an upcoming Residency Review Committee analysis of our program, we took the opportunity to examine the reasons for attrition in our own institution. During the years 1990 to 2003, 120 categorical residents were admitted into our general surgery residency program. Residents who matched into preliminary positions or non-5-year categorical positions were not included in this study. During this period of time, 20 residents (9 female and 11 male) left the program for a variety of reasons. The folders of those 20 residents along with all of the correspondence pertaining to each resident were reviewed in detail. Our overall attrition rate during this 13-year period of time was 20 of 120 residents or 17%. This is comparable with the often-quoted figure of approximately 20% attrition in other general surgery programs. The reasons for leaving could be divided into 4 categories: (1) lifestyle, (2) opportunity for early specialization, (3) asked to leave the program because of emotional or performance difficulties, or (4) decided to leave medicine entirely. The largest group was related to lifestyle issues and comprised 13 of the total of 20 residents who left the program. Of this group of 13, 3 went into plastic surgery, 4 went into anesthesiology, 2 went into radiology, and the remaining 4 went into public health, internal medicine, pathology, and emergency medicine. Seven of these 13 individuals were women. Two individuals entered residency with the goal of specializing in plastic surgery. They both left their 5-year categorical general surgery positions after the third year when they were offered the opportunity to enter three-year plastic surgery fellowship positions. The third category was composed of 4 individuals who were asked to leave the program during this 13-year period because of performance or emotional problems, with 3 of these 4 being men. Only 1 person left medicine entirely, and he is now the vice-president of a successful software company. Of the total of 20 residents who left our program, 9 (45%) were female. Given that there were 33 females in our program during the subject period of time, these 9 females represent an attrition rate of 27%. The 11 males who left during this period represent, however, an attrition rate of only 13%. Although much concern has been expressed over the declining numbers of medical students interested in surgery, loss of residents after matching in general surgery is an equally significant problem. In our program over a 13-year period, 20 out 120 residents, or 17% dropped out or were released. The attrition rate for females (27%) was approximately twice that of males (13%), with 7 out of 9 females (78%) leaving for lifestyle reasons.


Detection of high-risk human papillomavirus infected cervical biopsies samples by immunohistochemical expression of the p16 tumor marker.
Cervical cancer is the fourth most common type of cancer in women worldwide. It is widely accepted that the main cause of cervical cancer, especially in underdeveloped countries like Pakistan, is the infection caused by the human papillomavirus (HPV). The current screening and diagnostic methods face several challenges in accurately detecting the various types of lesions caused by HPV. Therefore, the present study was conducted to assess the effectiveness of p16 immunohistochemistry (IHC) analysis as a diagnostic method in samples of cervical biopsies. One hundred cervical biopsy samples were obtained from female patients across various age groups (> 20- ≤ 30, > 31- ≤ 40, > 41- ≤ 50, > 51- ≤ 60 years). These samples were subsequently prepared for subsequent examination. All samples were analyzed using automated tissue processing followed by Hematoxylin and Eosin (H & E) staining, and p16 IHC tumour marker staining. The H & E slides showed changes in normal cervical tissues, while four cervical abnormalities were identified statistically significant using p16 marker including chronic cervicitis, nabothian cyst formation, cervical intraepithelial neoplasia, and cervical cancers (P value 0.014). Furthermore, among females of different age groups (> 31- ≤ 40, > 41- ≤ 50, > 51- ≤ 60 years) were found statistically significant suffering from cervical cancer (P value 0.04), HPV with cervical cancer (P value 0.01), HPV with cervical intraepithelial neoplasia (P value 0.01). Based on the available data, it can be inferred that the incorporation of the p16 tumor marker may be a valuable method for detecting high-risk HPV in cervical biopsies samples.


[Structure and functional organization of integrated cardiac intensive care].
The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.


Timing for implant placement in patients treated with radiotherapy of head and neck.
Aim of this retrospective study was to evaluate the most appropriate timing for the implant placement in oral cancer patients treated with radiation therapy. We collected data for 17 subjects (10 females, 7 males; mean age: 51 ± 19) with malignant oral tumors who had been treated with ablative surgery and radiation therapy of head and neck. The radiotherapy was set in accordance with the NCCN guidelines. Every patient received dental implant rehabilitation between 2014 and 2016. A total of 84 titanium implants were placed, at a minimum interval of 12 months, in irradiated residual bone. Every patient underwent a minimum follow-up of 12 months. Implant loss was dependent on the position and location of the implants (P = 0.05-0.1). Moreover, implant survival was dependent on the total dose of radiation and, mostly, on the timing of implant insertion after the end of the radiation therapy. This result was highly statistically significant (P < 0.01). Whether the implant was loaded is another highly significant (P < 0.01) factor determining survival. We observed significantly better outcomes when the implant was placed at least after 14 months and not loaded until at least 6 months after placement. Although the retrospective design of this study could be affected by selection and information biases, we conclude that a delayed implant placement after the end of the radiation therapy and a delayed loading protocol will give the best chance of implant osseointegration, stability and, ultimately, effective dental rehabilitation.


[A stock of infected snails for the mass breeding of cercariae and schistosomules].
A routine to maintain infected snails Biomphalaria glabrata able to produce 1-2 million cercariae per week and a mean shedding of about 3,500 cercariae per snail was quantitatively described. To a monthly production of about 5.3 and 6.5 million cercariae during the years of 1982 and 1983 it was necessary to expose an average of 1,557 and 1,957 snails, respectively. The efficiency described was maintained by infecting 2,000 snails per month (infectivity index of about 60%). A maximal production of 6,000 cercariae/snail was obtained in the period between 56-70 days after the snail infection by miracidia. By this period, however, 90% of the infected snails were dead. In the summer of 1982-1983 it was observed an impairment on the daily cercarial harvests which was related to ambient temperature increase, and the presence of rotifers in the aquaria water. When the cercariae were transformed into schistosomula in vitro, a yield of 55% schistosomula was obtained, with 7% of tail contamination. Lyophilization of cercariae produced 50.9 +/- 63 g dry weight per 1,000 cercariae.


A role for dopamine in the peripheral sensory processing of a gastropod mollusc.
Histological evidence points to the presence of dopamine (DA) in the cephalic sensory organs of multiple gastropod molluscs, suggesting a possible sensory role for the neurotransmitter. We investigated the sensory function of DA in the nudipleuran Pleurobranchaea californica, in which the central neural correlates of sensation and foraging behavior have been well characterized. Tyrosine hydroxylase-like immunoreactivity (THli), a signature of the dopamine synthetic pathway, was similar to that found in two other opisthobranchs and two pulmonates previously studied: 1) relatively few (<100) THli neuronal somata were observed in the central ganglia, with those observed found in locations similar to those documented in the other snails but varying in number, and 2) the vast majority of THli somata were located in the peripheral nervous system, were associated with ciliated, putative primary sensory cells, and were highly concentrated in chemotactile sensory organs, giving rise to afferent axons projecting to the central nervous system. We extended these findings by observing that applying a selective D2/D3 receptor antagonist to the chemo- and mechanosensory oral veil-tentacle complex of behaving animals significantly delayed feeding behavior in response to an appetitive stimulus. A D1 blocker had no effect. Recordings of the two major cephalic sensory nerves, the tentacle and large oral veil nerves, in a deganglionated head preparation revealed a decrease of stimulus-evoked activity in the former nerve following application of the same D2/D3 antagonist. Broadly, our results implicate DA in sensation and engender speculation regarding the foraging-based decisions the neurotransmitter may serve in the nervous system of Pleurobranchaea and, by extension, other gastropods.


A genetic map of Dictyostelium discoideum based on mitotic recombination.
A genetic map of the cellular slime mold Dictyostelium discoideum is presented in which 42 loci are ordered on five of the seven linkage groups. Although most of the loci were ordered using standing mitotic crossing-over techniques in which recessive selective markers were employed, use was also made of unselected recombined haploid strains. Consistent with cytological studies in which the chromosomes appear to be acrocentric, only a single arm has been found for each of the five linkage groups studied. The mating-type locus, matA, has been located in the tsgE-sprA interval on linkage group I on the basis of studies on diploids formed between strains of opposite mating type that have escaped from vegetative incompatibility.


Microbial functional structure of Montastraea faveolata, an important Caribbean reef-building coral, differs between healthy and yellow-band diseased colonies.
A functional gene array (FGA), GeoChip 2.0, was used to assess the biogeochemical cycling potential of microbial communities associated with healthy and Caribbean yellow band diseased (YBD) Montastraea faveolata. Over 6700 genes were detected, providing evidence that the coral microbiome contains a diverse community of archaea, bacteria and fungi capable of fulfilling numerous functional niches. These included carbon, nitrogen and sulfur cycling, metal homeostasis and resistance, and xenobiotic contaminant degradation. A significant difference in functional structure was found between healthy and YBD M. faveolata colonies and those differences were specific to the physical niche examined. In the surface mucopolysaccharide layer (SML), only two of 31 functional categories investigated, cellulose degradation and nitrification, revealed significant differences, implying a very specific change in microbial functional potential. Coral tissue slurry, on the other hand, revealed significant changes in 10 of the 31 categories, suggesting a more generalized shift in functional potential involving various aspects of nutrient cycling, metal transformations and contaminant degradation. This study is the first broad screening of functional genes in coral-associated microbial communities and provides insights regarding their biogeochemical cycling capacity in healthy and diseased states.


The bone and joint decade. strategies to reduce the burden of disease: the Bone and Joint Monitor Project.
Musculoskeletal conditions are the major cause of morbidity and substantially influence health and quality of life, with enormous costs to health systems. This article describes the Bone and Joint Monitor Project, whose objective is to provide evidence to enable development of policies and strategies to improve the prevention and treatment of musculoskeletal conditions, relevant to their geographic and socioeconomic settings. By identifying the burden of disease and establishing strategies that can be implemented in routine clinical practice, musculoskeletal conditions can be managed more effectively and progress can be demonstrated through the establishment of routine health monitoring. With the interventions currently available, it is feasible that all people will be afforded the right to pain control, mobility, and independence.


Cytomegalovirus assembly protein nested gene family: four 3'-coterminal transcripts encode four in-frame, overlapping proteins.
The genomic region encoding the assembly protein of simian cytomegalovirus (CMV) strain Colburn has been cloned, sequenced, and found to be organized as a nested set of four in-frame, 3'-coterminal genes, each with its own TATA promoter element and translational start codon, and all using a single 3' polyadenylation signal. The 3' end of the longest open reading frame (1.770 bp) was identical to the 930-bp sequence coding for the assembly protein precursor, as determined from a cDNA clone. The assembly protein coding region of human CMV strain AD169 was similarly organized, suggesting that both viral genomes could give rise to four independently transcribed 3'-coterminal RNAs coding for four overlapping, in-frame, carboxy-coterminal proteins. These predictions were tested and confirmed. Four mRNAs corresponding in size and sequence to those predicted were identified in both human and simian CMV-infected cells by using transcript-specific antisense oligonucleotide probes in Northern (RNA blot) assays. The 5' ends of the three largest of these Colburn transcripts were determined by S1 nuclease protection assays and found to map between the anticipated TATA sequences and corresponding translational start codons. The four predicted overlapping proteins were identified by immunoassays in lysates of simian and human CMV-infected cells by using an antiserum specific for the carboxyl end of the assembly protein precursor. The structural relationship of both sets of proteins was verified by comparing their peptide patterns following protein cleavage at tryptophan residues by N-chlorosuccinimide. The similar organization of the homologous coding regions in other herpesviruses into at least two nested, in-frame, 3'-coterminal genes is discussed.


Internet addiction is associated with social anxiety in young adults.
Problematic Internet use or excessive Internet use is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding computer use, and Internet access that leads to impairment or distress. Cross-sectional studies on samples of patients reported high comorbidity of Internet addiction with psychiatric disorders, especially affective disorders (including depression), anxiety disorders (generalized anxiety disorder, social anxiety disorder), and attention-deficit/hyperactivity disorder. We have investigated the association between Internet addiction and social anxiety in 2 samples of 120 university students (60 males and 60 females in each sample). We found a correlation between Internet addiction and social anxiety in the 2 samples (r=0.411, P<.001; r=0.342, P<.01) respectively. Secondly, we found no difference between males and females on the level of Internet addiction. Thirdly, we did not find a preference for social networks among participants with high levels of social anxiety. The results of the study support previous evidence for co-occurrence of Internet addiction and social anxiety, but further studies need to clarify this association.


Pramipexole Modulates Interregional Connectivity Within the Sensorimotor Network.
Pramipexole is widely prescribed to treat Parkinson's disease but has been reported to cause impulse control disorders such as pathological gambling. Recent neurocomputational models suggested that D2 agonists may distort functional connections between the striatum and the motor cortex, resulting in impaired reinforcement learning and pathological gambling. To examine how D2 agonists modulate the striatal-motor connectivity, we carried out a pharmacological resting-state functional magnetic resonance imaging study with a double-blind randomized within-subject crossover design. We analyzed the medication-induced changes of network connectivity and topology with two approaches, an independent component analysis (ICA) and a graph theoretical analysis (GTA). The ICA identified the sensorimotor network (SMN) as well as other classical resting-state networks. Within the SMN, the connectivity between the right caudate nucleus and other cortical regions was weaker under pramipexole than under placebo. The GTA measured the topological properties of the whole-brain network at global and regional levels. Both the whole-brain network under placebo and that under pramipexole were identified as small-world networks. The two whole-brain networks were similar in global efficiency, clustering coefficient, small-world index, and modularity. However, the degree of the right caudate nucleus decreased under pramipexole mainly due to the loss of the connectivity with the supplementary motor area, paracentral lobule, and precentral and postcentral gyrus of the SMN. The two network analyses consistently revealed that pramipexole weakened the functional connectivity between the caudate nucleus and the SMN regions.


Electric and Magnetic Dipole Strength at Low Energy.
A low-energy enhancement of radiative strength functions was deduced from recent experiments in several mass regions of nuclei, which is believed to impact considerably the calculated neutron capture rates. In this Letter we investigate the behavior of the low-energy γ-ray strength of the ^{44}Sc isotope, for the first time taking into account both electric and magnetic dipole contributions obtained coherently in the same theoretical approach. The calculations are performed using the large-scale shell-model framework in a full 1ℏω sd-pf-gds model space. Our results corroborate previous theoretical findings for the low-energy enhancement of the M1 strength but show quite different behavior for the E1 strength.


Evaluating the bio-economic performance of a Callo de hacha (Atrina maura, Atrina tuberculosa & Pinna rugosa) fishery restoration plan in La Paz, Mexico.
Small-scale fisheries are large contributors to regional economies and livelihoods in coastal communities of Latin America. While Mexico is one of the cases where small-scale fisheries play an important role, overfishing and poor management strategies have led to the collapse of many of its fisheries. The callo de hacha scallop fishery of the Ensenada de La Paz in Baja California Sur is an example of such a fishery which, after years of mismanagement, was closed by the Mexican authorities in 2009. The present study evaluated the recovery efforts in the cove and the potential outcomes of a collaboration between a non-governmental organization and a fishing community working towards the restoration of this pen-shell fishery. After more than four years of closure and active monitoring of the recovering process, the callo de hacha population has shown a significant population recovery, with potential solvency for reopening fishing activities. Four scenarios of uncertainty are evaluated with two of them providing positive net present values from reopening the fishery. We also document the involvement of a non-governmental organization with a fishing community, which created social capital and, in our opinion, was essential for a successful restoration. Having an actively involved community helped raise funds for the fishing closure so fishers were able to comply with Mexican legislation; it also fostered community building and self-organization that will be crucial to maintaining the sustainability of the fishery.


Regulated necrosis role in inflammation and repair in acute kidney injury.
Acute kidney injury (AKI) frequently occurs in patients with chronic kidney disease (CKD) and in turn, may cause or accelerate CKD. Therapeutic options in AKI are limited and mostly relate to replacement of kidney function until the kidneys recover spontaneously. Furthermore, there is no treatment that prevents the AKI-to-CKD transition. Regulated necrosis has recently emerged as key player in kidney injury. Specifically, there is functional evidence for a role of necroptosis, ferroptosis or pyroptosis in AKI and the AKI-to-CKD progression. Regulated necrosis may be proinflammatory and immunogenic, triggering subsequent waves of regulated necrosis. In a paradigmatic murine nephrotoxic AKI model, a first wave of ferroptosis was followed by recruitment of inflammatory cytokines such as TWEAK that, in turn, triggered a secondary wave of necroptosis which led to persistent kidney injury and decreased kidney function. A correct understanding of the specific forms of regulated necrosis, their timing and intracellular molecular pathways may help design novel therapeutic strategies to prevent or treat AKI at different stages of the condition, thus improving patient survival and the AKI-to-CKD transition. We now review key regulated necrosis pathways and their role in AKI and the AKI-to-CKD transition both at the time of the initial insult and during the repair phase following AKI.


Nanostructures in diatom frustules: functional morphology of valvocopulae in Cocconeidacean monoraphid taxa.
Nanopositioning is one of the most intriguing challenges in nanoelectronics and photonics. As the optoelectronic circuit components become more and more complex, the importance of nanopositioning becomes critical. For example, in single-mode fiber telecommunications it is easy to show that an alignment deviation as small as a few tens of nanometers can yield to 50 percent of loss performance. Diatoms are unicellular plants occurring in almost every aquatic environment. Their main morphological character is the frustule, a silica cell wall that consists of two valves, encasing the protoplasm, joined together by a girdle. The girdle is composed of a series of silica bands (copulae) linked together along their margins. In several diatom species, the first girdle bands (valvocopulae), which associate the valves with the rest of the girdle, appear different in shape and bring specific nanostructures devoted to facilitate this linkage. The species of the diatom family Cocconeidaceae show elaborate linkage systems between the valves in which functionally complex valvocopulae are involved. Different levels of complexity and functional efficiency are recognizable in the valve-valvocopula and valvocopula-valvocopula linkages of different cocconeidacean taxa. This work briefly reviews the morphological characteristics and the functional role of the nanostructures involved in the linkages; in fact, we firmly believe that they are stimulating models for design and manufacturing engineers working in the technological nanoworld.


Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.
This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded firstname.lastname@example.com NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.


Polar plot representation of time-resolved fluorescence.
Measuring changes in a molecule's fluorescence emission is a common technique to study complex biological systems such as cells and tissues. Although the steady-state fluorescence intensity is frequently used, measuring the average amount of time that a molecule spends in the excited state (the fluorescence lifetime) reveals more detailed information about its local environment. The lifetime is measured in the time domain by detecting directly the decay of fluorescence following excitation by short pulse of light. The lifetime can also be measured in the frequency domain by recording the phase and amplitude of oscillation in the emitted fluorescence of the sample in response to repetitively modulated excitation light. In either the time or frequency domain, the analysis of data to extract lifetimes can be computationally intensive. For example, a variety of iterative fitting algorithms already exist to determine lifetimes from samples that contain multiple fluorescing species. However, recently a method of analysis referred to as the polar plot (or phasor plot) is a graphical tool that projects the time-dependent features of the sample's fluorescence in either the time or frequency domain into the Cartesian plane to characterize the sample's lifetime. The coordinate transformations of the polar plot require only the raw data, and hence, there are no uncertainties from extensive corrections or time-consuming fitting in this analysis. In this chapter, the history and mathematical background of the polar plot will be presented along with examples that highlight how it can be used in both cuvette-based and imaging applications.


Fitting accuracy and fracture resistance of crowns using a hybrid zirconia frame made of both porous and dense zirconia.
The purpose of this study is to evaluate the fitting accuracy and fracture resistance of crowns using a hybrid zirconia frame made of both porous and dense zirconia. Commercial semi-sintered zirconia, sintered dense zirconia and sintered hybrid zirconia were used. Sintered zirconia was milled using the CAD/CAM system, and semi-sintered zirconia was milled and sintered to fabricate molar crown frames. Completed frames were veneered with tooth-colored porcelain. The marginal and internal gaps between frames/crowns and abutments were measured. Each crown specimen was subjected to a fracture test. There were no significant differences in marginal and internal gap among all the frames and crowns. The crown with the hybrid zirconia frame had a 31-35% greater fracture load than that with the commercial or dense zirconia frame (p<0.01). This suggests that the all-ceramic crowns with a hybrid zirconia frame have a high fracture resistance.