Quantitative nonradioactive CAT assays using fluorescent BODIPY 1-deoxychloramphenicol substrates.
We report the development of fluorescent BODIPY 1-deoxychloramphenicol substrates for chloramphenicol acetyltransferase (CAT). These substrates not only simplify and improve quantitation of CAT activity but also extend the linear range of detection. Because the 1-deoxychloramphenicol derivatives have only one acetylation site, the enzyme reaction creates only one product, whereas chloramphenicol and its fluorescent derivatives produce three acetylated products, each of which accumulates at a different rate. Thus, 1-deoxychloramphenicol substrates eliminate the need to account for multiple products and provide a method in which product formation corresponds directly to enzyme activity. These nonradioactive substrates also allow researchers to streamline the standard thin-layer chromatography separation procedure: visible results can be obtained within minutes and quantitative results in a few hours. The sensitivity of CAT assays using fluorescent 1-deoxychloramphenicol substrates is comparable to that achieved using [14C]chloramphenicol--between 10(-5) and 10(-6) units of activity in a 1-h reaction--and the linear range extends through 3.6 or more orders of magnitude. We expect that CAT assays employing BODIPY 1-deoxychloramphenicol CAT substrates will be a valuable improvement over other methods currently in use.


[Management of fetal abnormalities].
Appropriate management of fetal malformations needs confirmation by a tertiary center and search for associated abnormalities and further investigations oriented to causal and prognostic factors. Therapeutic decisions are taken by a multidisciplinary term: pregnancy termination, maternal transfer to a tertiary center, premature delivery or cesarean extraction. Some malformations require immediate surgical treatments, others can be followed up and later corrected. Intrauterine treatments are nowadays evaluated, such as chronic derivations, operative fetoscopy or open fetal surgery. In case of fetal death, a post mortem examination must be performed in order to improve genetic counseling.


Pure populations of Dictyostelium discoideum prespore and prestalk cells obtained by flow cytometry have different redevelopment characteristics at their cell surfaces.
The multicellular slug stage of Dictyostelium discoideum consists of two major differentiated cell types: prespore and prestalk cells, which become, respectively, the spores and the stalk of the fruiting body. It is known that these cells, although expressing cell-type-specific proteins, remain totipotent, and experimental disruption of slugs results in redifferentiation taking place. We looked at what happens to cell-type-specific surface molecules when a cell changes from one type of another. Using monoclonal antibodies and flow cytometry we were able for the first time to obtain pure populations of single cells of each cell type. These were analysed during redevelopment. The initial hypothesis was that a proportion of each cell type would redifferentiate to reestablish the original proportions. However, it was found that the two cell types responded quite differently. Whereas almost all prestalk cells retained their prestalk surface antigen, in contrast, all prespore cells redifferentiated. During this process redifferentiating prespore cells simultaneously expressed surface determinants of both cell types, an event not seen in normal development.


Identification of NEO1 as a prognostic biomarker and its effects on the progression of colorectal cancer.
Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.


Respiratory Failure in a Child With Pulmonary Metastatic Osteosarcoma and COVID-19.
The novel coronavirus, SARS-CoV-2, causes much more severe disease in adults than in children. Although it is anticipated that immune compromised children and children with cancer may be at higher risk of developing severe or fatal COVID-19, there are no currently published reports of fatal disease in a child with cancer. Because of the discrepancy in disease severity between adult and pediatric patients, we report the case of an adolescent with pulmonary metastatic osteosarcoma who died of COVID-19 early in the course of the pandemic in New York City in the hope that heightening awareness that pulmonary metastatic disease may predispose to a more severe outcome will increase surveillance in this vulnerable population.


Why do G-quadruplexes dimerize through the 5'-ends? Driving forces for G4 DNA dimerization examined in atomic detail.
G-quadruplexes (G4) are secondary structures formed by guanine-rich nucleic acid sequences and shown to exist in living cells where they participate in regulation of gene expression and chromosome maintenance. G-quadruplexes with solvent-exposed guanine tetrads show the tendency to associate together through cofacial stacking, which may be important for packaging of G4-forming sequences and allows for the design of higher-order G4 DNA structures. To understand the molecular driving forces for G4 association, here, we study the binding interaction between two parallel-stranded G-quadruplexes using all-atom molecular dynamics simulations. The predicted dimerization free energies show that direct binding through the 5'-G-tetrads is the most preferred of all possible end-to-end stacking orientations, consistently with all available experimental data. Decomposition of dimerization enthalpies in combination with simulations at varying ionic strength further indicate that the observed orientational preferences arise from a fine balance between the electrostatic repulsion of the sugar-phosphate backbones and favorable counterion binding at the dimeric interface. We also demonstrate how these molecular-scale findings can be used to devise means of controlling G4 dimerization equilibrium, e.g., by altering salt concentration and using G4-targeted ligands.


Restoration of synaptic plasticity in the host striatum: can transplants make it?
Intrastriatal transplantation of dopamine (DA) neurons can restore DA levels in the striatum and improve parkinsonian deficits in experimental studies. However, the mechanisms underlying these effects are poorly understood. Corticostriatal synaptic plasticity represents an important cellular mechanism for information storage and behavioural learning in the brain. This mechanism is defective in Parkinson's disease (PD). Indeed, the lack of endogenous DA innervation to the striatum causes morphological and functional rearrangements that are associated with altered synaptic plasticity in the corticostriatal pathway. In turn, malfunctioning synaptic plasticity is associated with motor deficits that resemble features of PD. It is yet unknown whether or not transplanted dopaminergic neurons can restore these striatal deficits in PD. Could this be the mechanism underlying the therapeutic effects of transplants? Recent studies have begun to shed light on this matter using different approaches.


Use of a novel herbal medicine in a 75-year-old woman with multi-metastatic pancreatic cancer: A case report and review of the literature.
Pancreatic cancer is one of the most aggressive types of malignant tumors and is associated with an extremely poor prognosis. Despite numerous research efforts over the last few years, little progress has been made in the understanding and treatment of the disease. Gemcitabine-based regimens are considered as the first-line treatment for pancreatic cancer, but the effects of chemotherapy on the disease are limited. Natural products extracted from herbs represent a valuable resource for novel bioactive anticancer agents and could benefit multi-metastasis pancreatic adenocarcinoma patients with an Eastern Cooperative Oncology Group status of 3. Biological intra-control cancer treatment (BICT) is a novel systemic therapy involving palliative care and herbal extract combinations [including ginseng (Panax ginseng C.A. Mey.), Herba Agrimonia (Agrimonia pilosa Ledeb.), White Flower Patrinia Herb (Thlaspi arvense Linn.) and arginine], which has been approved by the State Food and Drug Association. The treatment is intended to regulate and inhibit blood vessel generation and tumor growth by inhibiting epidermal growth factor receptor and vascular endothelial growth factor receptor expression, and to manage symptoms to improve the quality of the treatment. The present study discusses the case of a 75-year-old female diagnosed with pancreatic cancer with multiple metastases in the liver and lymph nodes. The patient was administered BICT and achieved survival for 11 months without side-effects of a severity greater than grade 1 according to the Common Terminology Criteria for Adverse Events. The study also describes a possible approach to providing palliative care and treating late-stage, metastatic pancreatic adenocarcinomas in elderly patients.


Electronegativity under Confinement.
The electronegativity concept was first formulated by Pauling in the first half of the 20th century to explain quantitatively the properties of chemical bonds between different types of atoms. Today, it is widely known that, in high-pressure regimes, the reactivity properties of atoms can change, and, thus, the bond patterns in molecules and solids are affected. In this work, we studied the effects of high pressure modeled by a confining potential on different definitions of electronegativity and, additionally, tested the accuracy of first-order perturbation theory in the context of density functional theory for confined atoms of the second row at the Hartree-Fock level. As expected, the electronegativity of atoms at high confinement is very different than that of their free counterparts since it depends on the electronic configuration of the atom, and, thus, its periodicity is modified at higher pressures.


Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro.
An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1-3 mg ml-1, large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124+/-4 nm) and rP172 (126+/-7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of approximately 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250-1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean approximately 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral.


Synergistic switching of plasmonic resonances and molecular spin states.
Plasmonic resonance properties of a series of lithographically patterned gold nanorod arrays, spin coated by thin films of an iron(II)-triazole type spin crossover complex, were investigated upon heating/cooling and also under 633 nm laser irradiation. In both cases a reversible shift of the localised surface plasmon resonance wavelength was observed and quantitatively linked to the refractive index change accompanying the spin transition. These results show that molecular spin state switching can be very efficiently triggered by the photo-thermal effect, which - in turn - allows for an active tuning of the plasmon resonance.


Executive function and short-term remission of geriatric depression: the role of semantic strategy.
This study tested the hypothesis that use of semantic organizational strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal initiation/perseveration (CV I/P) task, a test of semantic fluency, is the function specifically associated with remission of late-life depression. Seventy elders with major depression participated in a 12-week escitalopram treatment trial. Neuropsychologic performance was assessed at baseline after a 2-week drug washout period. Patients with a Hamilton Depression Rating Scale Score ≤7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were considered to be remitted. Cox's proportional hazards survival analysis was used to examine the relationship between subtests of the I/P, other neuropsychologic domains, and remission rate. Participants' performance on the CV I/P subscale was coded for perseverations, and use of semantic strategy. The relationship between the performance on the CV I/P subscale and remission rate was significant. No other subtest of the MDRS I/P evidenced this association. There was no significant relationship between speed, confrontation naming, verbal memory, or perseveration with remission rate. Remitters' use of verbal strategy was significantly greater than nonremitters. Geriatric depressed patients who showed decrements in performance on a semantic fluency task showed poorer remission rates than those who showed adequate performance on this measure. Executive impairment in verbal strategy explained performance. This finding supports the concept that executive functioning exerts a "top down" effect on other basic cognitive processes, perhaps as a result of frontostriatal network dysfunction implicated in geriatric depression.


Can medical savings accounts for the nonelderly reduce health care costs?
To understand how medical savings account (MSA) legislation for the nonelderly would affect health care costs. Economic policy evaluation based on the RAND Health Expenditures Simulation Model. National probability sample of nonelderly noninstitutionalized households. Persons in 23 157 sampled households from the 1993 Current Population Survey. Medical savings account legislation would allow all Americans who are covered only by a catastrophic health care plan to set up a tax-exempt account that they can use to pay medical bills not covered by their health insurance. The interventions we evaluate differ in the deductibles of the catastrophic plan and in whether the employee or employer funds the MSA. Changes in national health expenditures and net societal benefits of health care. If all insured nonelderly Americans switched to MSAs, their health care expenditures would decline by between 0% and 13%, depending on how the MSAs are designed. However, not all nonelderly Americans would choose MSAs; taking into account selection patterns, health spending would change by + 1% to -2%. Medical savings account legislation would have little impact on health care costs of Americans with employer-provided insurance. However, depending on the size of the catastrophic limit, waste from the excessive use of generously insured care could be reduced, and MSAs would be attractive to both sick and healthy people.


Comparison of In Vitro Efficacy of Six Disinfectants on the Hatching of Larval Eggs of Toxocara canis.
The environmental contamination with Toxocara canis eggs increases the risk of dissemination and transmission of the parasite in dogs and paratenic hosts such as humans. We aimed to evaluate different disinfectants to compare their effect on T. canis eggs. For its realization, 850 embryonated eggs were obtained, which were suspended in a solution of 5% formaldehyde and distilled water in Eppendorf tubes. In the tubes containing the 850 embryonated eggs, researchers was added 0.5 mL of each solution (enzymatic solution, sodium hypochlorite, iodopovidone, quaternary of ammonium, benzalkonium chloride, and super oxidation solution). After mixing, an aliquot was taken, observed under the microscope, and the number of broken eggs counted at different times to find the most effective ovicidal moment. The enzymatic disinfectant present a significant difference (P = 0.05) with 276.06 broken eggs followed by ammonium with 105.20 broken eggs. After 10 min, the ammonium solution was the one that showed a significant difference of 50.50 hatched eggs, followed by the enzymatic 26.80 and hypochlorite 25.00 treatments. After 20 min, the enzymatic solution treatment showed a significant difference with the other solutions showing an increase of 98.80 broken eggs. In the 30 and 40-min times, only the enzymatic treatment showed a significant difference of 334.10 and 381.70 of broken eggs respectively. The enzymatic solution has the greatest ovicidal effect against the eggs of T. canis to present a greater number of broken eggs in a given time between 20 and 40 minutes.


Enhanced production of antifungal lipopeptide iturin A by Bacillus amyloliquefaciens LL3 through metabolic engineering and culture conditions optimization.
Iturins, which belong to antibiotic cyclic lipopeptides mainly produced by Bacillus sp., have the potential for application in biomedicine and biocontrol because of their hemolytic and antifungal properties. Bacillus amyloliquefaciens LL3, isolated previously by our lab, possesses a complete iturin A biosynthetic pathway as shown by genomic analysis. Nevertheless, iturin A could not be synthesized by strain LL3, possibly resulting from low transcription level of the itu operon. In this work, enhanced transcription of the iturin A biosynthetic genes was implemented by inserting a strong constitutive promoter C2up into upstream of the itu operon, leading to the production of iturin A with a titer of 37.35 mg l-1. Liquid chromatography-mass spectrometry analyses demonstrated that the strain produced four iturin A homologs with molecular ion peaks at m/z 1044, 1058, 1072 and 1086 corresponding to [C14 + 2H]2+, [C15 + 2H]2+, [C16 + 2H]2+ and [C17 + 2H]2+. The iturin A extract exhibited strong inhibitory activity against several common plant pathogens. The yield of iturin A was improved to 99.73 mg l-1 by the optimization of the fermentation conditions using a response surface methodology. Furthermore, the yield of iturin A was increased to 113.1 mg l-1 by overexpression of a pleiotropic regulator DegQ. To our knowledge, this is the first report on simultaneous production of four iturin A homologs (C14-C17) by a Bacillus strain. In addition, this study suggests that metabolic engineering in combination with culture conditions optimization may be a feasible method for enhanced production of bacterial secondary metabolites.


Long-term follow up in patients receiving a small aortic valve prosthesis.
Concern persists regarding the long-term effects of aortic valve replacement (AVR) in the small aortic root. Twenty-eight patients (21 females, seven males; mean age 54.1+/-11.7 years; mean body surface area (BSA) 1.39+/-0.07 m2) who underwent AVR with a 19 mm mechanical valve more than 10 years previously at the authors' institute, were followed up. Long-term echocardiographic evaluations were performed in 18 of 21 survivors. Follow up in the 28 patients was complete for up to 19.2 years (mean 11.4 years); cumulative follow up was 318.1 patient-years. Actuarial survival rates at 5, 10 and 15 years were 88.5+/-6.3%, 72.0+/-9.0% and 72.0+/-9.0%, respectively. In general, NYHA class showed satisfactory improvement. Long-term echocardiography showed significant reductions in left ventricular (LV) wall thickness and mass index compared with preoperative values, despite the existence of pressure gradients. A negative correlation was found between the rate of reduction of LV wall thickness and BSA. Implantation of the 19 mm aortic mechanical prosthesis was viable in patients with a small aortic annulus, especially if their BSA was <1.45 m2.


Comparison of oral and computerized versions of the word memory test.
A computer-administered version of the Word Memory Test (WMT) was compared with the orally administered version in two clinical samples to assess equivalency of the two versions. The two samples included inpatients at an epilepsy center (n = 67) and forensic and clinical referrals to a private practice (n = 58). A randomized procedure was used to assign participants to either version of the WMT. Only the results of the WMT primary effort measures were analyzed. Between-group comparisons of the WMT effort measures were conducted using Mann-Whitney nonparametric analysis. No significant differences were found between versions for several diagnostic subgroups. The data generally support equivalency of the orally administered version and the computerized version of the WMT effort measures in a mixed outpatient sample.


Synthesis and structure of preorganized, C(3)-symmetric trilactam scaffolds with convergently oriented (S)-acetylthiomethyl appendages.
[reaction: see text] Efficient modular synthesis of conformationally preorganized, C(3)-symmetric trilactams is reported. The allyl acetate cyclization substrate was synthesized in five steps from Garner's L-serine-derived aldehyde. After chiral ligand-mediated palladium cyclization, the resulting vinyl hydropyran was transformed into the orthogonally protected amino acids for iterative coupling. The final macrolactamization was accomplished using EDCI/HOBt or HATU/HOAt under high dilution conditions.


[Association between thyroid nodule diameter measured by ultrasound and thyroid papillocarcinoma].
Objective: To investigate the association between thyroid nodule diameter measured by ultrasound and thyroid papillocarcinoma. Methods: A total of 389 cases undergoing thyroidectomy because of thyroid nodule between January 2016 and June 2017 in Beijing Anzhen Hospital were retrospectively reviewed. Of these patients, 170 cases had thyroid papillocarcinoma, and 219 cases had benign nodule. The nodules were divided into five groups according to their diameters: ≤1.0 cm, 1.1-2.0 cm, 2.1-3.0 cm, 3.1-4.0 cm, >4.0 cm. The prevalence of papillocarcinoma and lymphatic metastasis in each group were compared. Results: There were significant differences in age [(45.4±12.8) years vs (51.7±13.4) years, P<0.001], thyroid stimulating hormone (TSH) [1.75(1.28, 2.65) mU/L vs 1.48(0.99, 2.23) mU/L, P=0.003], thyroid-peroxidase antibody (TPOAb) [1.65(0.60, 8.40) kU/L vs 0.90(0.50, 2.40) kU/L, P=0.001], and C-reactive protein (CRP)[0.60(0.31, 1.37) mg/L vs 0.85(0.42, 1.66) mg/L, P=0.023] between thyroid papillocarcinoma and benign nodule. Of those(≤1.0 cm, 1.1-2.0 cm, 2.1-3.0 cm, 3.1-4.0 cm, >4.0 cm) five groups, the prevalence of papillocarcinoma was 72.5%, 52.5%, 29.7%, 16.1%, 2.4%, respectively(P<0.05). For papillocarcinoma patients, in diameter ≤1.0 cm and >1.0 cm groups, the prevalence of lymphatic metastasis was 29.9% and 45.8%, respectively (P=0.032). Binary logistic regression analysis showed that TSH (OR=1.350, 95%CI: 1.057-1.660, P=0.009), age(OR=0.960, 95%CI: 0.937-0.983, P=0.001) and nodule diameter (OR=0.359, 95%CI: 0.269-0.480, P=0.001) were independent associated factors of papillocarcinoma. Conclusion: As nodule diameter increased, the proportion of papillocarcinoma decreased, while the risk of lymphatic metastasis increased.


Secret of the major birch pollen allergen Bet v 1: identification of the physiological ligand.
The major birch pollen allergen Bet v 1 is the main elicitor of airborne type I allergies and belongs to the PR-10 family (pathogenesis-related proteins 10). Bet v 1 is the most extensively studied allergen, and is well characterized at a biochemical and immunological level; however, its physiological function remains elusive. In the present study, we identify Q3OS (quercetin-3-O-sophoroside) as the natural ligand of Bet v 1. We isolated Q3OS bound to Bet v 1 from mature birch pollen and confirmed its binding by reconstitution of the Bet v 1-Q3OS complex. Fluorescence and UV-visible spectroscopy experiments, as well as HSQC (heteronuclear single-quantum coherence) titration, and the comparison with model compounds, such as quercetin, indicated the specificity of Q3OS binding. Elucidation of the binding site by NMR combined with a computational model resulted in a more detailed understanding and shed light on the physiological function of Bet v 1. We postulate that the binding of Q3OS to Bet v 1 plays an important, but as yet unclear, role during the inflammation response and Bet v 1 recognition by IgE.


Gender differences in posttraumatic stress symptoms and the level of posttraumatic growth among a Polish sample of HIV-positive individuals.
The main goal of the current study was to investigate gender differences in the relationship between the level of posttraumatic stress symptoms (PTSSs) and the intensity of posttraumatic growth (PTG), treated as the explained variable, among a Polish sample of HIV-positive individuals (n = 250) while controlling for participants' ages and time since HIV diagnosis. The level of PTG was measured using the Polish adaptation of the Posttraumatic Growth Inventory. The level of PTSSs was assessed using the PTSD Factorial Version Inventory. HIV-positive women scored higher for some PTSSs (intrusion/arousal) and for a particular PTG dimension (spiritual change). In addition, the PTSSs that occurred were negatively related to the PTG level but only among HIV-positive women. Given the important health-related benefits associated with PTG among HIV-positive people, it is vital to shape competencies for effective growth promotion among these individuals, taking into account gender differences within this phenomenon.


Drosophila tribbles antagonizes insulin signaling-mediated growth and metabolism via interactions with Akt kinase.
Drosophila Tribbles (Trbl) is the founding member of the Trib family of kinase-like docking proteins that modulate cell signaling during proliferation, migration and growth. In a wing misexpression screen for Trbl interacting proteins, we identified the Ser/Thr protein kinase Akt1. Given the central role of Akt1 in insulin signaling, we tested the function of Trbl in larval fat body, a tissue where rapid increases in size are exquisitely sensitive to insulin/insulin-like growth factor levels. Consistent with a role in antagonizing insulin-mediated growth, trbl RNAi knockdown in the fat body increased cell size, advanced the timing of pupation and increased levels of circulating triglyceride. Complementarily, overexpression of Trbl reduced fat body cell size, decreased overall larval size, delayed maturation and lowered levels of triglycerides, while circulating glucose levels increased. The conserved Trbl kinase domain is required for function in vivo and for interaction with Akt in a yeast two-hybrid assay. Consistent with direct regulation of Akt, overexpression of Trbl in the fat body decreased levels of activated Akt (pSer505-Akt) while misexpression of trbl RNAi increased phospho-Akt levels, and neither treatment affected total Akt levels. Trbl misexpression effectively suppressed Akt-mediated wing and muscle cell size increases and reduced phosphorylation of the Akt target FoxO (pSer256-FoxO). Taken together, these data show that Drosophila Trbl has a conserved role to bind Akt and block Akt-mediated insulin signaling, and implicate Trib proteins as novel sites of signaling pathway integration that link nutrient availability with cell growth and proliferation.


Religious Characteristics of Romanian Physicians: Towards an Integrative Support of Religious Psychiatric Patients.
The growing closeness between psychiatry and theology may impact positively the healthcare of the religious psychiatric patients. However, some significant divergences regarding the health care religious methods and the concept and believe in the demonic possession of psychiatric patients continue to shape the relationships between these professionals. While the religions generally admit the demonic or spirit possession as real, the current views of physicians and psychiatric patients are just taken for granted and therefore demands new investigations. In this study, we have performed a targeted survey on this subject. The survey was based on a questionnaire addressed to 216 psychiatrists and 201 non-psychiatrists, and 408 psychiatric patients. For physicians, the questionnaire was randomized sent to hospitals in Romania. The patients received the questionnaire on paper. Except for patients with dementia and those in the acute phase of a psychiatric illness, all psychiatric disorders available at the time of the investigation were randomized included in the study. The results showed that about 20% of physicians and 60% of psychiatric patients considered that demonic possession might be associated to a psychiatric illness, while the later would like a priest in the therapeutic team (89.4%, CI: 0.86-0.92). In addition, the psychiatrists declared a lower attendance of religious services, although the majority would accept a priest in the therapeutic team (p>0.05, CI: 0.61-0.70). These findings invite to a more practical collaboration between psychiatrists, clinical psychologists, and theologians/priests with training in psychiatry for a more integrative mental care of the religious psychiatric patients. The results call as well for more efficient practical solutions for psychiatric patients, raise awareness towards the personal religious needs and critical beliefs of such patients, and finally might narrow the gap of the controversy between psychiatrists, non-psychiatrists, psychologists and theologians/priests on the addressed issues.


Changes of cytokeratin filament organization in human and murine Mallory body-containing livers as revealed by a panel of monoclonal antibodies.
Mallory bodies (MBs) are characteristics morphologic features of alcoholic hepatitis and can be produced in mouse hepatocytes by chronic griseofulvin (GF) intoxication. The formation of MBs, which share some immunological, biochemical, and ultrastructural features with cytokeratin (CK) filaments of normal liver, is accompanied by derangement and even loss of the CK cytoskeleton of hepatocytes ("empty cells") as revealed by immunofluorescence microscopy. To clarify whether this diminution or lack of CK-related staining of MB-containing hepatocytes was due to loss of CK filaments or changes in antigenicity or accessibility of antigenic determinants immunohistochemical studies using a battery of monoclonal and polyclonal CK antibodies were performed. It could be shown that all these antibodies directed against different CK polypeptide components and antigenic determinants of CKs revealed a highly reduced or even undetectable cytoplasmic CK meshwork in most cells with fully developed large MBs. In the light of our present knowledge of the organization of CK intermediate filaments, these results indicate that the phenomenon of the "empty cells" reflects a diminution of CK meshwork rather than altered antigenic determinants.


One-tube and one-buffer system of RT-PCR amplification of 1D gene of foot-and-mouth disease virus field isolates.
A method of reverse transcription (RT) and polymerase chain reaction (PCR) amplification of 1D (VP1) gene of foot-and-mouth disease (FMD) virus using one reaction mixture containing both avian myeloblastosis virus (AMV) reverse transcriptase (RTase) and Tfl DNA polymerase is described. The procedure was time saving, made use of a single buffer for both RT and subsequent amplification and performed better than the two-step procedure usually conducted with Moloney murine leukemia virus (MMLV) RTase and Taq DNA polymerase for amplification of the VP1 gene of field isolates of FMD virus serotypes O,-A, C and Asia 1. The failure to amplify the VP1 gene of many type O and Asia 1 viruses using MMLV RTase-Taq polymerase enzyme system could be overcome by performing RT of the viral genome at a higher temperature (48 degrees C) with AMV RTase which is not possible with MMLV RTase.


Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals.
Visceral leishmaniasis is the most acute form of leishmaniasis and vaccination is the best approach to control it. One of the major groups of virulence factors in Leishmania belongs to cysteine proteinase family. In this study, for the first time, the protective potential of Leishmania infantum cysteine proteinase type III (CPC) by using a prime-boost strategy is evaluated in BALB/c mice. The experiment was carried out in three groups of mice. Vaccinated group was primed with pcDNA-cpc and boosted with rCPC-DHFR in combination with CpG motif and Montanide 720 as adjuvant. Control groups received pcDNA and rDHFR or PBS. The ratio of IgG2a/IgG1, nitric oxide concentration and IFN-gamma induction in vaccinated group is significantly higher than controls. Furthermore, the parasite load of vaccinated group is significantly lower than controls. In addition, sera reactivity of visceral leishmaniasis individuals was examined and showed considerable reactivities toward rCPC in comparison with cutaneous leishmaniasis. The achieved result is highly encouraging the use of cysteine proteinases types I, II and III as vaccine candidate against visceral leishmaniasis.


Cryopreservation-Altered Expression of RNA and Protein Markers in Biological Specimens.
The preservation of DNA, RNA, and protein markers in biological specimens is essential for initial diagnosis, subsequent verification, and comparison, as well as for archival retention of pathological materials in modern molecular diagnostics and precision medicine. Considerable attention has been paid to the methods of collection, handling, and preparation of specimens for initial testing, but insufficient attention to the long-term specimen preservation for later verification, comparison, and archival retention. In the present study, we have investigated the changes of expressions of RNAs and proteins in Hep-G2 cell specimens after cryopreservation at -80°C and in liquid nitrogen. Storage temperature and different cryoprotective agent (CPA) solutions not only affect cell viability but also more importantly the retention of various molecular markers after storage as detected by western blot and real-time fluorescent quantitative polymerase chain reaction. While the presence of CPAs increased the survival rates of cells after cryopreservation as expected, there was no consistent trend observed with regard to the RNA expression measurements. The data have significant implications with regard to the accuracy and interpretation of acquired data from specimens that have been cryopreserved without RNA and protein stabilization and point to the need for rethinking the assumptions, strategies, and criteria of optimizing biological specimen cryopreservation in molecular diagnostics.


Biphenotypic sinonasal sarcoma-A recently described entity with many mimics: A case report.
Biphenotypic sinonasal sarcoma (BSNS) is a recently described, low-grade, slow-growing sarcoma with neural and myogenic features with exclusive location in sinonasal track and characteristic PAX3- MAML3 gene fusion. Differentiating this tumor from its commoner mimics needs knowledge of this entity to avoid over treatment. This tumor has unique morphology, clinical course, and genetics. We report this in a 47-year-old female who was diagnosed with such a rare, solitary fibrous tumor-hemangiopericytoma (HPC-SFT) on limited initial biopsy. On subsequent excision, typical morphology and immunohistochemistry helped to clinch the diagnosis.


Indium-111 antimyosin antibody imaging and thallium-201 imaging--a comparative myocardial scintigraphic study using single-photon emission computed tomography in patients with myocarditis and dilated cardiomyopathy.
Indium-111 antimyosin antibody imaging (a tracer of myocardial necrosis) and thallium-201 imaging (a tracer of myocardial perfusion) were compared in patients with myocarditis and dilated cardiomyopathy. The distribution of each tracer and antimyosin/thallium-201 overlapping were evaluated with single-photon emission computed tomography (SPECT). Scintigraphic data were classified into 5 patterns according to the distribution of both images and were compared with histologic findings of endomyocardial biopsy: AM-D, intense and diffuse antimyosin uptake and no perfusion abnormality (active myocarditis); AM-L, localized antimyosin uptake and no perfusion abnormality (active myocarditis); HM, no antimyosin uptake with or without perfusion abnormality (healed myocarditis); DCM-NH, diffuse antimyosin uptake and inhomogeneous thallium-201 uptake (dilated cardiomyopathy); DCM-PD, diffuse or localized antimyosin uptake and myocardial perfusion defect(s) (dilated cardiomyopathy). Patients with dilated-phase hypertrophic cardiomyopathy were frequently found in the DCM-PD group. Taken together, comparative antimyosin/thallium-201 SPECT images are useful for evaluating the activity of myocarditis and ongoing myocardial damage even in areas with no perfusion in patients with dilated cardiomyopathy.


Cyclic AMP opposes IP3-induced calcium release from permeabilized human platelets.
Platelets permeabilized by means of a high voltage electric field demonstrated time- and ATP-dependent uptake of 45Ca++. Submicromolar concentrations of inositol-1,4,5-trisphosphate (IP3) caused a rapid release of 45Ca++ which was followed by a slower reuptake. Adenosine 3':5'-cyclic monophosphate (cAMP) did not affect 45Ca++ uptake but did reduce IP3-mediated calcium release in a concentration-dependent manner over the range of 1-100 microM. Because cAMP concentrations in this range occur following exposure of platelets to prostacyclin and other agents which interfere with platelet function, it is proposed that cAMP-mediated inhibition of the action of IP3 may play a role in the antithrombotic activity of compounds believed to elevate levels of this cyclic nucleotide.


The cotton tipped applicator - a scratch for the itch and more during dermatologic surgery.
An itch during surgery can be distracting. Sterile cotton tipped applicators are inexpensive and multipurpose tools that may be used for a variety of simple surgical tasks such as scratching an itch on the surgeon or patient's face. They may also be used to adjust glasses and turn on surgical lights or the electrocautery machine.


[Role of androgen in the elderly. The role of androgen on metabolic parameters].
Low concentrations of endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, dyslipidemia or hypertension. Androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease. On the other hand, administration of testosterone to hypogonadal men improved insulin sensitivity and glucose homeostasis. Men with diabetes have been reported to have lower serum testosterone concentrations than non-diabetic men, which lead to insulin resistance, depression, cognitive dysfunction, sexual dysfunction and cardiovascular disease. Further basic and clinical studies investigating the role for androgen on metabolic parameters and atherosclerosis are needed.


Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of Helicobacter pylori Morphology, Cell Wall Integrity, and Resistance to Antibiotics.
Infection of the human stomach caused by Helicobacter pylori is very common, as the pathogen colonizes more than half of the world's population. It is associated with varied outcomes of infection, such as peptic ulcer disease, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma, and is generally considered a risk factor for the development of gastric adenocarcinoma. Cholesteryl glucosides (CGs) constitute a vital component of the cell wall of H. pylori and contribute to its pathogenicity and virulence. The hp0421 gene, which encodes cholesteryl-α-glucoside transferase (CGT), appears critical for the enzymatic function of integrating unique CGs into the cell wall of H. pylori, and deletion of this gene leads to depletion of CGs and their variants. Herein, we report that the deletion of hp0421 and consequent deficiency of cholesterol alter the morphology, shape, and cell wall composition of H. pylori cells, as demonstrated by high-resolution confocal microscopy and flow cytometry analyses of two different type strains of H. pylori, their isogenic knockouts as well as a reconstituted strain. Moreover, measurement of ethidium bromide (EtBr) influx by flow cytometry showed that lack of CGs increased cell wall permeability. Antimicrobial susceptibility testing revealed that the hp0421 isogenic knockout strains (Hp26695Δ421 and Hp76Δ421) were sensitive to antibiotics, such as fosfomycin, polymyxin B, colistin, tetracycline, and ciprofloxacin, in contrast to the wild-type strains that were resistant to the above antibiotics and tended to form denser biofilms. Lipid profile analysis of both Hp76 and Hp76Δ421 strains showed an aberrant profile of lipopolysaccharides (LPS) in the Hp76Δ421 strain. Taken together, we herein provide a set of mechanistic evidences to demonstrate that CGs play critical roles in the maintenance of the typical spiral morphology of H. pylori and its cell wall integrity, and any alteration in CG content affects the characteristic morphological features and renders the H. pylori susceptible to various antibiotics.IMPORTANCEHelicobacter pylori is an important cause of chronic gastritis leading to peptic ulcer and is a major risk factor for gastric malignancies. Failure in the eradication of H. pylori infection and increasing antibiotic resistance are two major problems in preventing H. pylori colonization. Hence, a deeper understanding of the bacterial survival strategies is needed to tackle the increasing burden of H. pylori infection by an appropriate intervention. Our study demonstrated that the lack of cholesteryl glucosides (CGs) remarkably altered the morphology of H. pylori and increased permeability of the bacterial cell wall. Further, this study highlighted the substantial role of CGs in maintaining the typical H. pylori morphology that is essential for retaining its pathogenic potential. We also demonstrated that the loss of CGs in H. pylori renders the bacterium susceptible to different antibiotics.


Discovery and development of a new class of drugs: GH antagonists.
In attempting to understand the structure of the GH molecule and its function(s), we found that 1 amino acid, glycine, in the third alpha-helix of GH (Gly119 of bovine GH and Gly120 of human GH) was important for biologic activity. Substitution of this glycine residue with a variety of amino acids resulted in GH analogs that lacked growth-promoting activity. More important, these analogs inhibited the actions of GH in vitro and in vivo and were classic antagonists. In this regard, the in vivo expression of GH-antagonist genes in transgenic mice results in dwarf animals that are fertile and have no abnormal phenotypes. The mechanism by which the GH antagonists appear to operate is to inhibit proper or functional GH-receptor dimerization. GH antagonists may have clinical applications when endogenous GH levels are elevated (e.g. acromegaly), or when GH action has been implicated in disease states (e.g., cancer- or diabetes-induced end-organ damage). A GH-receptor antagonist, pegvisomant, has been developed for these clinical situations.


Observations on the motility of rabbit spermatozoa in dilute suspension.
1. Rabbit spermatozoa suspended in Baker's solution rapidly lose motility at relatively high dilutions. At a concentration of 0.4 million per ml., the spermatozoa from most ejaculates are completely immotile within 2 or 3 hours. The same phenomenon occurs with chloride-free diluents and is therefore not due to the toxic action of chlorides. 2. This rapid immobilisation may be prevented by suspension in cell-free supernatants from other more concentrated suspensions of rabbit semen and by the accessory secretions from a vasectomised buck. The most effective supernatants are those prepared from suspensions of spermatozoa which have been left overnight before centrifuging. Immobilisation may also be prevented by many other agents, the most effective of which are gum arabic, starch, glycogen, and serum proteins (carbohydrate-containing or carbohydrate-free). Yet, in no case is the action of these substances as effective as more concentrated suspension in Baker's solution. 3. The immobilisation is not prevented by catalase, gelatin, agar, or sodium silicate. It is almost certainly not due to the toxic action of traces of heavy metals and is not affected by the use of water doubly distilled over glass in the preparation of the diluent, or by treating the diluent with activated charcoal. 4. Washing with Baker's solution does not cause immobilisation of spermatozoa suspended at 20 million per ml. at a stage at which the concentration of seminal plasma has been reduced to that equivalent to dilution to 0.4 million per ml. Further washing (six repeated centrifugings of 0.2 ml. semen in 4 ml. of Baker's solution) immobilises them. This confirms the opinion that loss of intracellular, or perhaps rather paracellular, material is a responsible agent in the dilution phenomenon.


Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.
HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.


Comparison of the number of supervisors on medical student satisfaction during a child and adolescent psychiatry rotation.
Traditionally, third-year medical students are assigned to one supervisor during their 1-week rotation in child and adolescent psychiatry. However, the majority of supervisory staff in the Division of Child and Adolescent Psychiatry opted to switch the supervision schedule to one in which some medical students are assigned to two primary supervisors. The aim of the study was to determine if students assigned to two primary supervisors had greater rotation satisfaction compared with students assigned to one primary supervisor during a 1-week clerkship rotation in child and adolescent psychiatry. A satisfaction questionnaire was sent to 110 third-year medical students who completed their child and adolescent clerkship rotation. Based on the responses, students were divided into groups depending on their number of supervisors. Questionnaire responses were compared between the groups using independent t-tests. When students who had one primary supervisor were compared to students who had two primary supervisors, the lone item showing a statistically significant difference was regarding improvement of assessment reports/progress notes. The number of supervisors does not significantly affect the satisfaction of students during a 1-week clerkship rotation in child and adolescent psychiatry. Other factors are important in rotation satisfaction.


Risk behaviors for eating disorder in adolescents and adults with type 1 diabetes.
To evaluate the frequency of risk behaviors for eating disorder (ED) in patients with type 1 diabetes (T1D) and their association with gender, nutritional status, variables related to T1D, and body satisfaction. 189 individuals with T1D (12-56 years old) answered the Bulimic Investigation Test (BITE), the Eating Attitude Test (EAT), the Binge Eating Scale (BES), Stunkard's Figure Rating Scale, and questions regarding control of T1D. Association between ED risk behaviors and the selected variables was assessed with the chi-square test and Student's t-test; factors that influenced the risk of ED were identified by means of logistic regression. Of the patients with T1D, 58.7% were at risk of ED (45, 40, and 16% according to the EAT, BITE and BES, respectively). There were significant differences between groups with and without risk for ED related to BMI (p = 0.009), gender (p = 0.001), insulin omission (p = 0.003), use of the carbohydrate counting method (p = 0.019), and body dissatisfaction (p = 0.001). The risk of ED was nine times higher in patients who reduced or omitted insulin (p = 0.036). Patients with T1D demonstrated a high frequency of body dissatisfaction and ED risk behaviors; the omission or reduction of insulin was an important risk factor.


Integration of metabolism and virulence by Clostridium difficile CodY.
CodY, a global regulatory protein that monitors the nutrient sufficiency of the environment by responding to the intracellular levels of GTP and the branched-chain amino acids, was previously shown to be a potent repressor of toxin gene expression in Clostridium difficile during growth in rich medium. In the intestinal tract, such derepression of toxin synthesis would lead to destruction of epithelial cells and the liberation of potential nutrients for the bacterium. CodY is likely to play an important role in regulating overall cellular physiology as well. In this study, DNA microarray analysis and affinity purification of CodY-DNA complexes were used to identify and distinguish the direct and indirect effects of CodY on global gene transcription. A codY null mutation resulted in >4-fold overexpression of 146 genes (organized in 82 apparent transcription units) and underexpression of 19 genes. In addition to the toxin genes, genes for amino acid biosynthesis, nutrient transport, fermentation pathways, membrane components, and surface proteins were overexpressed in the codY mutant. Genome-wide analysis identified more than 350 CodY binding regions, many of which are likely to correspond to sites of direct CodY-mediated regulation. About 60% of the CodY-repressed transcription units were associated with binding regions. Several of these genes were confirmed to be direct targets of CodY by gel mobility shift and DNase I footprinting assays.


Size-Controllable Enzymatic Synthesis of Short Hairpin RNA Nanoparticles by Controlling the Rate of RNA Polymerization.
Thanks to a wide range of biological functions of RNA, and advancements in nanotechnology, RNA nanotechnology has developed in multiple ways for RNA-based therapeutics. In particular, among RNA engineering techniques, enzymatic self-assembly of RNA structures has gained great attention for its high packing density of RNA, with a low cost and one-pot synthetic process. However, manipulation of the overall size of particles, especially a reduction in size, has not been studied in depth. Here, we reported the enzymatic self-assembly of short hairpin RNA particles for the downregulation of target genes, and a rational approach to the manipulation of the resultant particle size. This is the first report of the size-controllable enzymatic self-assembly of short hairpin RNA nanoparticles. While keeping all the benefits of an enzymatic approach, the overall size of the RNA particles was controlled on a scale of 2 μm to 100 nm, falling within the therapeutically applicable size range.


Selective pharmacological inhibition of distinct nitric oxide synthase isoforms.
Nitric oxide (NO) is produced in physiological and pathophysiological conditions by three distinct isoforms of NO synthase (NOS): endothelial NOS (ecNOS), inducible NOS (iNOS), and brain NOS (bNOS). Selective inhibition of iNOS may be beneficial in various forms of shock and inflammation, whereas inhibition of bNOS may protect against neuroinjury. This article surveys the enzymatic mechanism of NO production, lists the strategies and pharmacological tools for selective inhibition of distinct NOS isoforms, and considers the side-effects of the various approaches. Selective inhibition of NOS isoforms is achieved by: (a) targeting the differential co-factor (calmodulin or tetrahydrobiopterin) requirement of various NOS isoforms, and NOS; (b) targeting the differential substrate requirements of cells expressing various isoforms of NOS (L-arginine uptake blockers or arginase); (c) the use of pharmacological agents that are selectively taken up by cells expressing various isoforms of NOS (7-nitroindazole); or (d) developing pharmacological NOS inhibitors with isoform specificity. The amino acid-based NOS inhibitor, NG-nitro-L-arginine, shows a preference for ecNOS and bNOS over iNOS, whereas L-N6-(1-iminoethyl)lysine is selective for iNOS over bNOS. Certain non-amino acid-based small molecules, such as aminoguanidine and certain S-alkylated isothioureas, also express selectivity towards iNOS and have anti-inflammatory and anti-shock properties. 7-nitroindazole, a bNOS-selective inhibitor, protects in central nervous system injury. Clearly, there are a number of distinct approaches that are worthy of further research efforts in order to achieve even more selective targeting of various NOS isoforms


The effects of relative food item size on optimal tooth cusp sharpness during brittle food item processing.
Teeth are often assumed to be optimal for their function, which allows researchers to derive dietary signatures from tooth shape. Most tooth shape analyses normalize for tooth size, potentially masking the relationship between relative food item size and tooth shape. Here, we model how relative food item size may affect optimal tooth cusp radius of curvature (RoC) during the fracture of brittle food items using a parametric finite-element (FE) model of a four-cusped molar. Morphospaces were created for four different food item sizes by altering cusp RoCs to determine whether optimal tooth shape changed as food item size changed. The morphospaces were also used to investigate whether variation in efficiency metrics (i.e. stresses, energy and optimality) changed as food item size changed. We found that optimal tooth shape changed as food item size changed, but that all optimal morphologies were similar, with one dull cusp that promoted high stresses in the food item and three cusps that acted to stabilize the food item. There were also positive relationships between food item size and the coefficients of variation for stresses in food item and optimality, and negative relationships between food item size and the coefficients of variation for stresses in the enamel and strain energy absorbed by the food item. These results suggest that relative food item size may play a role in selecting for optimal tooth shape, and the magnitude of these selective forces may change depending on food item size and which efficiency metric is being selected.


Inpatient Biophysical Profiles and the Effect on Clinical Decision Making.
Objective Our primary objective was to determine whether biophysical profiles (BPP) performed on the antepartum unit result in changes in clinical decision making. Study Design A retrospective cohort chart review was performed among women who had a BPP during hospital admission. BPP status was categorized as normal (8/8 points) and abnormal (6/8 or less points). The primary outcome, clinical decision making, was the need for prolonged external fetal monitoring (defined as > 2 hours) or decision to proceed with delivery. Secondary outcomes included mode of delivery, indicated preterm delivery, birth weight, 5-minute Apgar's score <7, and neonatal intensive care unit (NICU) admission. Results Among our cohort ( n = 186), 85.5% ( n = 159) had a normal BPP. Delivery management was altered in one case (0.54%) by the BPP findings, and there were no BPPs that resulted in need for prolonged monitoring. Compared with women with normal BPP, women with abnormal BPPs were more likely to deliver at <37 weeks, to be admitted to the NICU, or have a 5-minute Apgar's score <7. Conclusion In-hospital BPPs alter clinical decision making in less than 1% of cases.


Hydroxylamine-doping effect on the Tg of 160 K for water confined in silica-gel nanopores.
The glass transition behavior of hydroxylamine (HA) aqueous solutions in bulk and confined in silica-gel nanopores with average width of 1.1 nm was studied by means of differential scanning calorimetry measurements and adiabatic calorimetry. The glass transition temperature (Tg) of the confined solution with high HA mole-fraction (xHA) was essentially the same as the value of the bulk. This suggests that the nano-size confinement affects the Tg of HA aqueous solution little. Meanwhile, the bulk solution with xHA < 0.3 revealed partial crystallization on cooling and, on the other hand, the confined solution with the same xHA did not crystallize. The Tg of the xHA = 0.076 confined solution was 174 K which is higher than the value of 160 K for pure water confined in the same silica-gel pores. This demonstrates that HA doping leads to no abrupt Tg-decrease, unlike doping of all the other second components reported so far, suggesting that HA is set neatly in a hydrogen-bond network formed by water molecules. We discuss the xHA dependence of Tg for the HA aqueous solutions from a viewpoint related to peculiar phase-behavior of pure water. Considering that the xHA = 0.076 aqueous solution revealed no anomaly compared with pure water, it was recognized as corresponding to the high-temperature phase of pure water.


How does fear of COVID-19 affect the mental well-being of waiters in Turkey.
Empirical findings are needed to determine how the fear of COVID-19 might change in the context of different individuals. This study aims to determine the moderating role of fatalism and psychological resilience on the effect of fear of COVID-19 on general mental health. This study makes use of qualitative research methods that involved collecting data from 355 full-time waiters via questionnaires on online platforms. The collected data suggests that the fear of COVID-19 has a significant negative impact on mental well-being. Morever, the data gathered for this study also indicates that the fear of COVID-19 infection differs significantly according to the fatalistic belief and psychological resilience levels of the waiters. Findings of this study indicate that the psychological effects of infectious diseases on individuals are not universal, but rather depend on the personal characteristics of individuals. It is hoped that the results of this study will contribute to the reduction of negative effects associated with the general anxiety of pandemic that individuals experience.


Neuronal population activity dynamics reveal a low-dimensional signature of operant learning in Aplysia.
Learning engages a high-dimensional neuronal population space spanning multiple brain regions. However, it remains unknown whether it is possible to identify a low-dimensional signature associated with operant conditioning, a ubiquitous form of learning in which animals learn from the consequences of behavior. Using single-neuron resolution voltage imaging, here we identify two low-dimensional motor modules in the neuronal population underlying Aplysia feeding. Our findings point to a temporal shift in module recruitment as the primary signature of operant learning. Our findings can help guide characterization of learning signatures in systems in which only a smaller fraction of the relevant neuronal population can be monitored.


Reappraisal of the new UICC staging system for gastric cancer: problem in lymph node stage.
The International Union Against Cancer (UICC) TNM staging system defined a new system for classifying gastric cancer, based on the number of metastatic nodes (1997). However, the advantage of the new system is still a matter of debate. The aim of the present study is to compare the new system with the old one (1987), which is based on the location of positive lymph nodes. We analyzed the survival of 608 patients with curative resection of their gastric cancer. The average number of resected and involved lymph nodes for each resected patient was 31.4 and 7.7. Comparison of these two systems was carried out to determine which classification was more effective. The prognostic value of different lymph node staging systems was also analyzed. One hundred and thirty-five patients (22.2%) had different N classification and 109 (17.9%) had different TNM staging. There was a significant stepwise decrease of slope of survival curve for each stage, but the new system did not cleanly separate stage II with IIIa at 3 years and stage IIIb with IV at 5 years. Although different lymph node staging systems were able to predict survival, the ratio rather than the number of involved nodes had a more cleanly separated stepwise decrease of slope of survival curve. The new UICC staging system is not better than the old system for the staging of gastric cancer. The reason is that the category of node number seems not to be appropriate and will be influenced by the extent of lymph node dissection. To overcome this problem, the frequency of involved nodes can be adopted instead of the number.


Psychometric analysis of the Chinese version of the Posttraumatic Growth Inventory with cancer patients in Hong Kong and Taiwan.
Cancer patients in Hong Kong and Taiwan share traditional Chinese as a written form of language, but each region has its own sociocultural background. This study examined if the four-factor model (self, spiritual, life orientation, and interpersonal) of the Chinese version of the Posttraumatic Growth Inventory (PTGI-C), developed for Hong Kong cancer survivors, could be applied to cancer survivors in Taiwan. Multisample confirmatory factor analyses (MS-CFA) were used to examine the factorial invariance of the PTGI-C among cancer survivors in Taiwan (n = 217) and Hong Kong (n = 223). The goodness-of-fit of the four-factor model was satisfactory, χ²(180) = 372.36 (χ²/df = 2.07), goodness-of-fit index (GFI) = 0.90, adjusted GFI (AGFI) = 0.87, comparative fit index (CFI) = 0.92, Tucker-Lewis index (TLI) = 0.91, root mean square error of approximation (RMSEA) = 0.05, Akaike information criterion (AIC) = 492.36. This result suggests that the factor structure of the PTGI-C developed in Hong Kong could be applied to cancer survivors in Taiwan. The internal reliabilities of the 15-item whole scale, as well as all the subscales, were good and similar to those reported previously. Interregion comparison revealed that the Taiwan sample had higher mean 'spiritual' and 'interpersonal' posttraumatic growth subscale scores than the Hong Kong sample. The four-factor model of the PTGI-C is invariant among cancer survivors using traditional Chinese as a written form of the language. The differences in the degree of some posttraumatic growth dimensions may be because of differences in cultural factors and in psychosocial support for cancer patients between the two regions.


Pharmacodynamics of benzodiazepines.
Twenty benzodiazepines (BDZs) are at present registered in the RSA. They are anxiolytic, sedative, hypnotic, anticonvulsant and possibly muscle relaxant. Structure-activity relationships are important in modelling BDZ molecules for optimum binding to receptors. Electrophysiological, behavioural and neurochemical effects of BDZs are good indicators of therapeutic potential, and help to elucidate mechanism(s) of action. Specific BDZ receptors on neurons (gamma-aminobutyric acid (GABA)-receptor-associated) and on astrocytes (not associated with GABA receptors) exist in the mammalian central nervous system. BDZs enhance GABA neurotransmission. Selective BDZ antagonists (e.g. Ro 15-1788) are important as research tools, and potentially as diagnostic aids and therapeutic agents. Other possible mechanisms for BDZ action include the roles of adenosine and serotonin. Endogenous BDZ-receptor ligands (e.g. inosine, hypoxanthine, nicotinamide) may be important, but the physiological role of BDZ receptors remains speculative.


Graphene/AlGaN/GaN RF Switch.
RF switches, which use a combination of graphene and two-dimensional high-density electron gas (2DEG) in the AlGaN/GaN system, were proposed and studied in the frequency band from 10 MHz to 114.5 GHz. The switches were integrated into the coplanar waveguide, which allows them to be used in any system without the use of, e.g., bonding, flip-chip and other technologies and avoiding the matching problems. The on-state insertion losses for the designed switches were measured to range from 7.4 to 19.4 dB, depending on the frequency and switch design. Although, at frequencies above 70 GHz, the switches were less effective, the switching effect was still evident with an approximately 4 dB on-off ratio. The best switches exhibited rise and fall switching times of ~25 ns and ~17 ns, respectively. The use of such a switch can provide up to 20 MHz of bandwidth in time-modulated systems, which is an outstanding result for such systems. The proposed equivalent circuit describes well the switching characteristics and can be used to design switches with required parameters.


Unconventional indicators of drug dependence among elderly long-term users of benzodiazepines.
A quarter of the elderly population is prescribed benzodiazepines (BZD). This has led to growing concerns about drug dependence and the validity of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for dependence to a substance. This study aimed to understand how dependence was experienced by long-term BZD users. Interviews were conducted with 45 elderly persons who had been using BZDs for an average of nine years. These users' comments suggest six indicators of dependence: self-identifying as a dependent user, invoking multiple stressors to justify BZD use, using BZD to cope with anticipated stressors, trivializing the dangers of BZDs, keeping a supply in reserve, having previously tried and failed to stop, and reducing the dosage. Our results stress the need to take a more elaborate, person-centered view of dependence.


Low redundancy in seed dispersal within an island frugivore community.
The low species diversity that often characterizes island ecosystems could result in low functional redundancy within communities. Flying foxes (large fruit bats) are important seed dispersers of large-seeded species, but their redundancy within island communities has never been explicitly tested. In a Pacific archipelago, we found that flying foxes were the sole effective disperser of 57 % of the plant species whose fruits they consume. They were essential for the dispersal of these species either because they handled >90 % of consumed fruit, or were the only animal depositing seeds away from the parent canopy, or both. Flying foxes were especially important for larger-seeded fruit (>13 mm wide), with 76 % of consumed species dependent on them for dispersal, compared with 31 % of small-seeded species. As flying foxes decrease in abundance, they cease to function as dispersers long before they become rare. We compared the seed dispersal effectiveness (measured as the proportion of diaspores dispersed beyond parent crowns) of all frugivores for four plant species in sites where flying foxes were, and were not, functionally extinct. At both low and high abundance, flying foxes consumed most available fruit of these species, but the proportion of handled diaspores dispersed away from parent crowns (quality) was significantly reduced at low abundance. Since alternative consumers (birds, rodents and land crabs) were unable to compensate as dispersers when flying foxes were functionally extinct, we conclude that there is almost no redundancy in the seed dispersal function of flying foxes in this island system, and potentially on other islands where they occur. Given that oceanic island communities are often simpler than continental communities, evaluating the extent of redundancy across different ecological functions on islands is extremely important.


Abated microRNA-195 expression protected mesangial cells from apoptosis in early diabetic renal injury in mice.
MicroRNAs are a class of highly conserved, small, noncoding RNAs that tailor gene expression mainly at the posttranscriptional level. The aim of the present study was to investigate the renal expression profiles of microRNAs and their potential involvement in early diabetic nephropathy. Diabetic models were induced with streptozotocin in DBA/2 mice. MicroRNAs were detected by microarray and subjected to bioinformatics analyses. Real-time PCR and Western blots were performed. The relationships between pathological changes and microRNA expression were evaluated by linear regression analysis. Apoptosis and proliferation of cultured mesangial cells treated with microRNA inhibitor were determined by flow cytometry and MTT assay, respectively. Nine microRNAs, including miR-1187, miR-320, miR-214, miR-34a, miR-762, miR-466f, miR-720, miR-744 and miR-1937b, were increased significantly. Another 9 microRNAs, including miR-1907, miR-195, miR-568, miR-26b, miR-703, miR-1196, miR-194, miR-805 and miR-192, were decreased remarkably in diabetic mice. The levels of microRNA repressing BCL2 decreased. Accordingly, BCL2 levels were found elevated and caspase-3 and caspase-8 levels decreased in the diabetic group. MicroRNA-195 expression was negatively related to glomeruli diameter, mesangial score and extracellular matrix (ECM) accumulation. Moreover, the microRNA-195 inhibitor protected mesangial cells from apoptosis and promoted the cellular proliferation in vitro. These results demonstrated that the abated microRNA-195 expression protected mesangial cells from apoptosis, suggesting that the antiapoptosis in a microRNA-regulated manner may play an important role in the early stages of diabetic nephropathy.


Nickel-Catalyzed Reductive C(sp2 )-Si Coupling of Chlorohydrosilanes via Si-Cl Cleavage.
We report here a new method for the synthesis of organohydrosilanes from phenols and ketones. This method is established through reductive C-Si coupling of chlorohydrosilanes via unconventional Si-Cl cleavage. The reaction offers access to aryl- and alkenylhydrosilanes with a scope that is complementary to those of the established methods. Electron-rich, electron-poor, and ortho-/meta-/para-substituted (hetero)aryl electrophiles, as well as cyclic and acyclic alkenyl electrophiles, were coupled successfully. Functionalities, including Grignard-sensitive groups (e.g., primary amine, amide, phenol, ketone, ester, and free indole), acid-sensitive groups (e.g., ketal and THP protection), alkyl-Cl, pyridine, furan, thiophene, Ar-Bpin, and Ar-SiMe3 , were tolerated. Gram-scale reaction, incorporation of -Si(H)R2 into complex biologically active molecules, and derivatization of formed organohydrosilanes are demonstrated.


Modulation of opioid antinociception by CCK at the supraspinal level: evidence of regulatory mechanisms between CCK and enkephalin systems in the control of pain.
1. Much evidence in the literature supports the idea that cholecystokinin (CCK) interacts with opioids in pain mechanisms. In this work, we have investigated the supraspinal interactions between enkephalins and CCK, using the hot plate test in mice. 2. Intracerebroventricular (i.c.v.) administration of BDNL (a mixed CCKA/CCKB agonist) induced dose-dependent antinociceptive responses on both paw lick and jump responses. In contrast, using the same test, the i.c.v. injection of BC 264 (a selective CCKB agonist) induced a hyperalgesic effect, which was restricted to paw licking and occurred only at a high dose of 2.5 nmol. 3. In addition, i.c.v. administration of BDNL potentiated the antinociceptive effects of the mixed inhibitor of enkephalin degrading enzymes, RB 101 and of the mu-agonist, DAMGO, while BC 264 reduced these effects. 4. Furthermore, at a dose where it interacts selectively with delta-opioid receptors, the opioid agonist BUBU reversed the hyperalgesic responses of BC 264 (2.5 nmol) but was unable to modify the effects induced by BDNL. 5. Taken together, these results suggest the existence of regulatory mechanisms between CCK and enkephalin systems in the control of pain. These regulatory loops could enhance the antinociceptive effects of morphine allowing the opiate doses used to be reduced and thus, possibly, the side-effects to be minimized.


[Encephalopathy associated with severe bacterial infections: "presuppurative encephalitis" or "toxi-infectious disorder"?].
Three children are reported, exhibiting encephalopathic symptoms in the course of a severe bacterial infection, though they had no sign of intracranial purulent collection nor metabolic disturbances: the first was associated with a appendicular peritonitis, the second with a purulent knee arthritis, the third with a pneumoccus septicemia. The elements are reviewed that favor either a true septic encephalitis, i.e. microscopic presuppurative foci, versus a toxiinfectious process, either by direct action of toxins or through intracerebral activation of pre-inflammatory cytokines. Whatever the mechanism involved in individual cases, the treatment is mainly based on prompt administration of the convenient antibiotics.


Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection.
Infection with the liver fluke, Opisthorchis viverrini, is a causative agent of cholangiocarcinoma. One possible contributing factor in this carcinogenesis is the chronic, local generation of nitric oxide by inflammatory cells expressing inducible nitric oxide synthase and the production of N-nitroso compounds via the reaction between amines and nitrosating agents derived from nitric oxide. Our previous studies provided evidence that nitric oxide synthesis is elevated during human liver fluke infection. Here we present data on the same sample of men which definitively demonstrates increased nitrosation of proline and thioproline (thiazolidine-4-carboxylic acid) among infected men compared to uninfected control subjects on a low nitrate diet. This difference was specifically abolished by co-administration of ascorbic acid with proline and by elimination of parasites by praziquantel treatment. Multivariate statistical models demonstrate the importance of salivary thiocyanate levels to variation in the nitrosation of proline among uninfected individuals, but not among those with current fluke infection. This suggests that considerable generation of nitrosating agents (N203/N204) in infected people may be occurring via oxidation of arginine by nitric oxide synthase in inflamed tissue which is thiocyanate insensitive. Analyses revealed positive associations between N-nitrosoproline excretion and nitrate/nitrite levels in urine, plasma and saliva and with usual alcohol intake; with variation in these trends between groups. In conclusion, we have confirmed the relationship between O.viverrini infection and enhanced endogenous nitrosation, showing evidence of its extragastric site. New information is also provided on the determinants of N-nitrosamino acid excretion in men on a controlled low nitrate diet without smoking, conditions which reduce exogenous sources of nitrosating agents.


Interactions between bone cells and biomaterials: An update.
As the populations of the Western world become older, they will suffer more and more from bone defects related to osteoporosis (non-union fractures, vertebral damages), cancers (malignant osteolysis) and infections (osteomyelitis). Autografts are usually used to fill these defects, but they have several drawbacks such as morbidity at the donor site and the amount and quality of bone that can be harvested. Recent scientific milestones made in biomaterials development were shown to be promising to overcome these limitations. Cell interactions with biomaterials can be improved by adding at their surface functional groups such as adhesive peptides and/or growth factors. The development of such biomimetic materials able to control bone cell responses can only proceed if it is based on a sound understanding of bone cell behavior and regulation. This review focuses on bone physiology and the regulation of bone cell differentiation and function, and how the latest advances in biomimetic materials can be translated within promising clinical outcomes.


Esophageal Gastrointestinal Stromal Tumor with Rare Intracranial Metastasis.
Introduction. Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and constitute the largest group of nonepithelial digestive neoplasms. However, they do not represent more than 1% of primary digestive tumors. They commonly metastasize to the liver and peritoneum, but brain metastases are extremely rare. Clinical Case. A 76-year-old woman with a diagnosis of esophageal GIST with liver and lung metastases for 13 years, medicated with imatinib, is presented. She was brought to the emergency department after falling and due to changes in behavior and vertigo with 24 hours of evolution. On physical examination, she presented changes in behavior, dysarthria, dysmetria on the right, gait imbalance, and no motor or sensory deficits. On brain computed tomography and posteriorly on magnetic resonance, 2 lesions were observed, left frontal and right cerebellar, compatible with metastatic lesions. After contribution of neurosurgery, histology was obtained that confirmed the lesions were GIST metastases. Imatinib was maintained, and whole brain radiotherapy was performed. After 6 months, she died. Discussion. The rarity of GIST brain metastases is noteworthy, and because of that, there is not enough experience to be certain of the best treatment. Our patient lived for 13 years with excellent disease control with imatinib, but the fact that it does not cross the blood-brain barrier makes it not useful in preventing or treating brain lesions. New tyrosine kinase inhibitors that may cross the blood-brain barrier could be the answer to these cases.


The factor structure of the macaque social responsiveness scale-revised predicts social behavior and personality dimensions.
Most primate species are highly social. Yet, within species, pronounced individual differences in social functioning are evident. In humans, the Social Responsiveness Scale (SRS) measures variation in social functioning. The SRS provides a quantitative measure of social functioning in natural social settings and can be used as a screening tool for autistic traits. The SRS was previously adapted for use in chimpanzees and recently refined for rhesus macaques, resulting in the macaque Social Responsiveness Scale-Revised (mSRS-R). Here, we performed an exploratory factor analysis on the mSRS-R in a large sample of male rhesus macaques (N = 233). We investigated the relationships of the resulting mSRS-R factors to quantitative social behavior (alone, proximity, contact, groom, and play) and to previously-established personality dimensions (Sociability, Confidence, Irritability, and Equability). Factor analysis yielded three mSRS-R factors: Poor Social Motivation, Poor Social Attractiveness, and Inappropriate Behavior. mSRS-R factors mapped closely to social behavior and personality dimensions in rhesus macaques, providing support for this instrument's convergent and discriminant validity. Animals with higher Poor Social Motivation were more likely to be observed alone and less likely to be observed in contact and grooming with conspecifics. Animals with higher Poor Social Attractiveness were less likely to be observed playing but more likely to be observed grooming with conspecifics. Inappropriate Behavior did not predict any behavioral measure. Finally, animals with higher Poor Social Motivation and higher Poor Social Attractiveness had less sociable personalities, whereas animals with more Inappropriate Behavior were more confident and more irritable. These findings suggest that the mSRS-R is a promising, psychometrically robust tool that can be deployed to better understand the psychological factors contributing to individual differences in macaque social functioning and, with relevant species-specific modification, the SRS may hold promise for investigating variation in social functioning across diverse primate taxa.


Risk Assessment of the Cardiac Pregnant Patient.
Women with heart disease are at increased risk for maternal and fetal complications in pregnancy. Therefore, all women with heart disease should undergo evaluation and counseling, ideally before conception, or as early in pregnancy as possible. In this article we will review the role of risk assessment, the history of development of the cardiac risk prediction tools, and the role of current cardiac risk prediction tools.


Molecular characterization of Theileria species associated with mortality in four species of African antelopes.
Pathogen DNA was isolated from roan antelope (Hippotragus equinus), sable antelope (Hippotragus niger), greater kudu (Tragelaphus strepsiceros), and common gray duiker (Sylvicapra grimmia) in South Africa whose deaths were attributed to either theileriosis or cytauxzoonosis. We developed Theileria species-specific probes used in combination with reverse line blot hybridization assays and identified three different species of Theileria in four African antelope species. The close phylogenetic relationship between members of the genera Theileria and Cytauxzoon, similarities in the morphologies of developmental stages, and confusion in the literature regarding theileriosis or cytauxzoonosis are discussed.


Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A.
Blood coagulation factor XIII (FXIII) is a protransglutaminase circulating as a tetramer formed by two types of subunits (A2B2). The intracellular dimeric form of FXIII (A2) is present in platelets, megakaryocytes, monocytes and macrophages and has been detected in mono- and megakaryocytic leukemias. The aim of our study was to investigate FXIII-A expression in newly diagnosed B cell acute lymphoblastic leukemia (ALL) samples. We examined 47 de novo ALL cases of B cell origin by triple color labeling with flow cytometry. FXIII-A was detected by a FITC conjugated monoclonal antibody combined with CD34 and CD45 staining. In selected cases FXIII-A was investigated on slides prepared from blasts and visualized with a fluorescent microscope. In addition, blasts were studied by Western blot analysis and FXIII-A was measured by a highly sensitive ELISA method. By flow cytometry 19 samples of the 47 cases were found to be FXIII-A positive. Antigen concentration was 3.11 +/- 1.19 fg/blast, while normal lymphoid precursors and mature lymphocytes from B-CLL did not contain FXIII-A. In the lysate of lymphoblasts that were positive by flow cytometry, a single band (82 kDa) corresponding to FXIII-A was detected on Western blots. Confocal laser scanning microscopic examination revealed the presence of FXIII-A in the cytoplasm of these lymphoblasts. This novel expression site of FXIII-A in leukemic lymphoblasts can be utilized as a diagnostic tool and may also gain functional significance in B-lineage ALL.


Multigenerational hybridisation and its consequences for maternal effects in Atlantic salmon.
Outbreeding between segregating populations can be important from an evolutionary, conservation and economical-agricultural perspective. Whether and how outbreeding influences maternal effects in wild populations has rarely been studied, despite both the prominent maternal influence on early offspring survival and the known presence of fitness effects resulting from outbreeding in many taxa. We studied several traits during the yolk-feeding stage in multigenerational crosses between a wild and a domesticated Atlantic salmon (Salmo salar) population up to their third-generation hybrid in a common laboratory environment. Using cross-means analysis, we inferred that maternal additive outbreeding effects underlie most offspring traits but that yolk mass also underlies maternal dominant effects. As a consequence of the interplay between additive and dominant maternally controlled traits, offspring from first-generation hybrid mothers expressed an excessive proportion of residual yolk mass, relative to total mass, at the time of first feeding. Their residual yolk mass was 23-97% greater than those of other crosses and 31% more than that predicted by a purely additive model. Offspring additive, epistatic and epistatic offspring-by-maternal outbreeding effects appeared to further modify this largely maternally controlled cross-means pattern, resulting in an increase in offspring size with the percentage of domesticated alleles. Fitness implications remain elusive because of unknown phenotype-by-environment interactions. However, these results suggest how mechanistically co-adapted genetic maternal control on early offspring development can be disrupted by the effects of combining alleles from divergent populations. Complex outbreeding effects at both the maternal and offspring levels make the prediction of hybrid phenotypes difficult.


The distinct roles of calmodulin and calmodulin kinase II in the reversal of run-down of L-type Ca(2+) channels in guinea-pig ventricular myocytes.
In this study, we investigated the roles of calmodulin kinase II (CaMKII) and calmodulin (CaM) in the reversal of run-down of L-type Ca(2+) channels. Single Ca(2+)-channel activities in guinea-pig ventricular myocytes were recorded using the patch-clamp technique, and run-down of the channel activities was induced by inside-out patch formation in the basic internal solution. At 1 min after patch excision, 1 - 30 muM CaMKII mutant T286D (CaMKIIT286D), a constitutively active type of CaMKII, induced the Ca(2+)-channel activities to only 2% - 10% of that recorded in the cell-attached mode. However, in the presence of CaMKIIT286D, the time-dependent attenuation of CaM's effects in the reversal of run-down was abolished. A GST-fusion protein containing amino acids 1509 - 1789 of the C-terminal region of guinea-pig Cav1.2 (CT1) was prepared. In pull-down assays, CT1 treated with CaMKIIT286D showed a higher affinity for CaM compared with CT1 treated with phosphatase. We propose a model in which CaMKII-mediated phosphorylation of the channels regulates the binding of CaM to the channels in the reversal of run-down of L-type Ca(2+) channels.


Decellularized Alstroemeria flower stem modified with chitosan for tissue engineering purposes: A cellulose/chitosan scaffold.
Utilizing plant-based scaffolds has pulled in the consideration of tissue engineers. Plant tissues own different structures with particular porosity and structure. In this study, the stem of the Alstroemeria flower was designated for decellularization to fabricate a new scaffold. The stems were decellularized and called AFSP and then modified by chitosan and named AFSPC. Osteoblast precursor cell line was employed to assess the biological potential of the final scaffolds. The results uncovered that AFSP owns linear microchannels with a smooth surface. AFSPC delineated uniform chitosan coating on the walls with appropriate roughness. AFSPC showed higher potential in swelling, degradation, diffusion, and having a porous structure than AFSP. Modification with chitosan improved mechanical behavior. Biological assays depicted no cytotoxicity for AFSP and AFSPC. AFSPC showed good cell attachment, proliferation, and migration. In conclusion, modified tissue plants can be a good candidate for tissue engineering of both soft and hard tissues.


Investigation of the effect of acute to chronic glycemic ratio on major amputation development after surgical thromboembolectomy in patients with acute lower extremity ischemia.
Acute limb ischemia (ALI) is an emergency vascular pathology in which perfusion is disrupted in the lower extremity and threatens extremity viability. The admission blood glucose (ABG)/estimated average glucose (eAG) value has recently been shown as a prognostic marker in acute cardiovascular events. In this study, we aimed to investigate the predictive role of an ABG/eAG value in predicting development of early postoperative major amputation after emergency thromboembolectomy operations in patients presenting with ALI. Patients who admitted to our hospital with ALI between November 01, 2016 and September 01, 2021 and underwent surgical thromboembolectomy were retrospectively included in the study. Patients who did not undergo postoperative limb amputation were recorded as Group 1, and patients who underwent major amputation in the early postoperative period (in-hospital), were recorded as Group 2. The median age of the 226 patients included in Group 1 and 72 patients in Group 2 were 58 (34-86) years and 69 (33-91) years, respectively (p<0.001). In univariate analysis, in-hospital amputation was found to significantly correlate with age>70 years (odds ratio [OR]: 1.914, 95% confidence interval [CI]: 1.351-2.319, p<0.001), PAD (OR: 1.698, 95% CI: 1.270-1.992, p = 0.002 re-embolectomy (OR: 2.184, 95% CI: 1.663-3.085, p < 0.001), admission Rutherford class (OR: 0.762, 95% CI: 0.591-0.859, p = 0.032), admission time>6 h (OR: 1.770, 95% CI: 1.480-1.152, p = 0.009), ABG (OR: 1.275, 95% CI: 1.050-1.790, p < 0.001), and ABG/eAG (OR: 1.669, 95% CI: 1.315-2.239, p < 0.001). According to our study, we can predict patient groups with a high risk of major amputation with the ABG/eAG value calculated from the blood values of the patients at the time of admission.


A therapeutic approach to tardive dyskinesia.
An approach to treating tardive dyskinesia and tardive akathisia was tested in 33 patients. The common denominator was the elimination of antipsychotic drugs. In 7 of 8 patients with mild tardive dyskinesia and no akathisia who were treated by drug abstinence, gradual lessening of tardive dyskinesia occurred. Complete remission was seen after 2-4 years in 5 of these 8. Treatment with reserpine and discontinuance of antipsychotic drugs was useful for patients with severe symptoms of tardive dyskinesia or akathisia; complete remission with elimination of all drugs was achieved in 4 of 19 treated patients, without recurrence of symptoms. Although tetrabenazine masked symptoms in 5 of 7 patients to whom it was administered, none was able to achieve remission of tardive dyskinesia when taken off the drug. Seven of the total 33 patients received a course of levodopa; 2 of these 7 developed recurrence of their underlying psychosis. This agent should be used with caution.


Phenanthroline Derivative Fluorescent Probe for Rapid and Sensitive Detection of Silver(I).
In the present work, a phenanthroline derivative (2-(2-methoxyphenyl)-4-phenyl-1,10-phenanthroline, MPP), as a fluorescent probe, was synthesized to realize a rapid, simple and sensitive detection of silver(I). The detection conditions of Ag+ were optimized. This fluorescent probe has the advantages of a fast reaction time, a wide pH applicable range, and a low detection limit, exhibiting a good linear response between the fluorescence intensity and the concentration in the range of 0.05 - 1.5 μmol/L for Ag+. The detection limit is as low as 3.38 × 10-8 mol/L (S/N = 3). This probe had been used to detect Ag+ in real samples, and the recovery efficiency of spiked Ag+ had been also tested. The recovery efficiency is satisfactory, ranging from 92.0 to 105.4%. Therefore, this fluorescent probe should provide a new choice for the quantitative detection of silver ions in environmental water samples.


Surface-Enhanced Raman Spectroscopy Sensors From Nanobiosilica With Self-Assembled Plasmonic Nanoparticles.
We present an innovative surface-enhanced Raman spectroscopy (SERS) sensor based on a biological-plasmonic hybrid nanostructure by self-assembling silver (Ag) nanoparticles into diatom frustules. The photonic-crystal-like diatom frustules provide a spatially confined electric field with enhanced intensity that can form hybrid photonic-plasmonic modes through the optical coupling with Ag nanoparticles. The experimental results demonstrate 4-6× and 9-12× improvement of sensitivities to detect the Raman dye for resonance and nonresonance SERS sensing, respectively. Such low-cost and high-sensitivity SERS sensors have significant potentials for label-free biosensing.


Effect of the neuraminidase mutation H274Y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza A(H1N1) viruses.
The viral fitness of neuraminidase inhibitor (NAI)-resistant influenza viruses is believed to be impaired. Unexpectedly, an oseltamivir-resistant A(H1N1) variant containing the H274Y neuraminidase (NA) mutation recently disseminated worldwide, suggesting that the replication and virulence properties of this mutant virus were not compromised. In vitro replicative capacities were determined for old (A/WSN/33, A/Mississipi/3/01, A/New Caledonia/20/99, and A/Solomon Islands/03/06) and recent (A/Brisbane/59/2007-like) influenza A(H1N1) viruses either harboring or not harboring the H274Y NA mutation. Ferrets were infected with the A/Brisbane/59/2007-like wild-type (WT) isolate and its H274Y NA variant. Old A(H1N1) WT viruses grew at higher titers than did the A/Brisbane/59/2007-like viruses in vitro. The H274Y mutation was associated with reduced viral plaque areas in cells infected with A/WSN/33 and A/Mississippi/3/01, whereas the 2 A/Brisbane/59/2007-like isolates showed similar plaque sizes. In ferrets, the pyrexic response induced by the A/Brisbane/59/2007-like H274Y mutant was significantly higher than that induced by the WT isolate. Nasal wash viral titers were significantly greater for the mutant isolate on day 2 after inoculation, whereas the 2 viruses showed similar titers between days 3 and 7 after inoculation. The viral fitness of the recent A/Brisbane/59/2007-like H274Y variant is not impaired, consistent with its global dissemination. These results reinforce the need for new antiviral strategies.


The impact of physical, nutritional, and mental preparation on triathlon performance.
There are numerous variables that can impact a triathletes' performance. Research with this population has primarily focused on physical training habits to determine performance predictors, thus the purpose of this study was to explore the impact of nutritional and mental preparation strategies in addition to physical training on race times of Olympic-distance triathletes. Triathletes were asked to complete an online survey that focused on physical conditioning, nutritional habits, mental training, and educational experience related to triathlon training. Participants included 272 age-group triathletes (146 males, 126 females). ANOVAs and MANOVAs were conducted to identify variables that significantly related to race time, while a logistic regression was used to determine variables that predicted performance. Race time was predicted by competitive motivation to participate, participation in strength training, and use of intervals during run and swim training. Mental strategies that predicted faster race times included pre-competition routines, use of energizing strategies before a race, and setting outcome goals for races. Nutritional habits did not have an impact on race time. The results support the need to go beyond investigating physical training preparation.