Measuring safety culture: Application of the Hospital Survey on Patient Safety Culture to radiation therapy departments worldwide.
Minimizing errors and improving patient safety has gained prominence worldwide in high-risk disciplines such as radiation therapy. Patient safety culture has been identified as an important factor in reducing the incidence of adverse events and improving patient safety in the health care setting. The aim of distributing the Hospital Survey on Patient Safety Culture (HSPSC) to radiation therapy departments worldwide was to assess the current status of safety culture, identify areas for improvement and areas that excel, examine factors that influence safety culture, and raise staff awareness. The safety culture in radiation therapy departments worldwide was evaluated by distributing the HSPSC. A total of 266 participants were recruited from radiation therapy departments and included radiation oncologists, radiation therapists, physicists, and dosimetrists. The positive percent scores for the 12 dimensions of the HSPSC varied from 50% to 79%. The highest composite score among the 12 dimensions was teamwork within units; the lowest composite score was handoffs and transitions. The results indicated that health care professionals in radiation therapy departments felt positively toward patient safety. The HSPSC was successfully applied to radiation therapy departments and provided valuable insight into areas of potential improvement such as teamwork across units, staffing, and handoffs and transitions. Managers and policy makers in radiation therapy may use this assessment tool for focused improvement efforts toward patient safety culture.


Repetitive TMS over posterior STS disrupts perception of biological motion.
Biological motion perception, the recognition of human action depicted in sparse dot displays, is supported by a network of brain areas including the human posterior superior temporal sulcus (pSTS). We have used repetitive transcranial magnetic stimulation (rTMS) to temporarily disrupt cortical activity within the pSTS and subsequently measured sensitivity to biological motion. Sensitivity was measured for canonical (upright) point-light animations and for animations inverted 180 deg, a manipulation that renders biological motion more difficult to recognize. Observers were markedly less sensitive to upright biological motion following pSTS stimulation. In contrast, performance remained normal for inverted biological motion following pSTS stimulation, and normal for upright and inverted biological motion following stimulation over visual motion sensitive area MT+/V5. In connection with previous brain imaging results, our findings demonstrate that normal functioning of the posterior STS is required for intact perception of biological motion.


Characterization of subsets of bone marrow-derived macrophages by flow cytometry analysis.
Normal C3H bone marrow cells were grown 7 days in medium containing L cell-derived colony stimulating factor-1 (CSF-1). During the first 4 days of culture, erythroid and granulocytic cells decreased while macrophages increased exponentially with a doubling time of about 31 hr. Only 0.3% of all cells in the initial bone marrow suspension formed discrete colonies of mononuclear phagocytes, but by day 6 60% of the nonadherent cells were capable of forming macrophage colonies, representing a 200-fold enrichment of the original progenitor population. Using flow cytometry, mononuclear phagocytes obtained after 4 days of culture were separated into two distinct phenotypes based on their autofluorescence. Nonadherent cells were a discrete population of small cells exhibiting low autofluorescence, and the adherent cells were a broad heterogeneous population of large cells exhibiting high autofluorescence. A panel of currently available rat monoclonal antibodies (MABs) against murine hematopoietic cells were used to determine whether unique subsets of macrophages could be resolved. The MABs RA 31B6 and H-11 stained virtually all the nonadherent cells but not adherent cells. The MABs E-2 and 11-4.1 (anti-H-2Kk) stained almost all the adherent cells and demonstrated no significant staining of nonadherent cells. Nearly all the nonadherent and adherent cells were stained by the MABs DNL 4.4 and MAC-1. Additionally, the data suggest that the epitopes for MAC-2 and MAC-3 and gamma 2a Fc receptors develop late in nonadherent progenitor cells as they mature into adherent macrophages.


The influence of π-conjugated moieties on the thermodynamics of cooperatively self-assembling tricarboxamides.
A detailed investigation of the self-assembly behaviour of C3-symmetrical tricarboxamides reveals that a larger π-conjugated core does not increase the stability of assemblies in an apolar solvent but makes the system more sensitive to destabilization by addition of a good solvent.


Relationship between body mass index and outcomes of coronary artery disease in Asian population: Insight from the FOCUS registry.
Obesity is often considered as a risk factor of cardiovascular events, but recent researches showed conflicting results regarding to the effect of body weight on prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between body mass index (BMI) and clinical outcomes of CAD in Asian population. A total of 4315 patients from the FOCUS registry were enrolled into this analysis. Patients were divided into 4 groups according to BMI: lean group (BMI<18.5 kg/m2), normal group (BMI 18.5-24.9 kg/m2), overweight group (BMI 25-30 kg/m2) and obesity group (BMI>30 kg/m2). Follow-up was continued to 3 years to evaluate clinical outcomes, and the primary endpoint was a composite of all-cause death and myocardial infarction (MI). Patients with higher BMI were more likely to be associated with cardiovascular risk factors like hypertension, hypercholesterolemia and diabetes, but not smoking. At the end of the follow-up period, however, the incidence of a composite endpoint of all-cause death and MI was significantly lower in the higher BMI (overweight and obese) subsets, as compared with the lower BMI group (5.2% vs. 8.0%, p < 0.001). So did the cumulative rates of all-cause death (p < 0.001), cardiovascular death (p < 0.001), and a combined endpoint of cardiovascular death and MI (p = 0.001). In Asian patients with CAD, an inverse association between BMI and long-term prognosis was observed. Although overweight or obese patients were associated with more metabolism-associated comorbidities, they had significantly lower adverse events at 3-year follow up after percutaneous coronary intervention.


An insight into the emerging exopolysaccharide gellan gum as a novel polymer.
The microbial exopolysaccharides are water-soluble polymers secreted by microorganisms during fermentation. The biopolymer gellan gum is a relatively recent addition to the family of microbial polysaccharides that is gaining much importance in food, pharmaceutical and chemical industries due to its novel properties. It is commercially produced by C.P. Kelco in Japan and the USA. This article presents a critical review of the available information on the gum synthesized by Sphingomonas paucimobilis with special emphasis on its fermentative production. Factors affecting the fermentative production of gellan gum and problems associated with mass transfer have been addressed. Classification and trade names of gellan gum has been specified. Characteristics of gellan gum with respect to its structure, physicochemical properties are discussed. An attempt has also been made to review the current and potential applications of gellan gum in food, pharmaceutical and other industries.


"And let me see them damn papers!" The role of STI/AIDS screening among urban African American and Puerto Rican youth in the transition to sex without a condom.
Common strategies employed in preventing STI/AIDS transmission among young adults in America include abstinence, monogamy and safer sex. These strategies require a high level of vigilance and responsibility and, according to inner city participants in Project PHRESH.comm, neither option is always desirable, available, or rational in the context of their lived experiences. This article reports findings from Project PHRESH.comm, a mixed-method, ethnographic study incorporating data from focus group discussions, semi-structured interviews, coital diaries, systematic cultural assessments and a structured survey designed to explore concepts of risk and decision making about condom use among at risk African American and Puerto Rican young adults aged 18-25 years in Hartford, CT. We found that many young adults from our study population rely on a strategy of using clinic-sponsored STI/AIDS screening when wanting to discontinue condom use with a partner. While our data suggest that screening is a common strategy used by many couples to transition to having sex without a condom, the data also show that most youth do not maintain monogamy even in long-term, serious relationships. Thus, sharing test results may provide a false sense of security in the sexual culture of inner city, minority youth.


Interchain disulfide bond formation in types I and II procollagen. Evidence for a protein disulfide isomerase catalyzing bond formation.
The assembly of reduced pro-alpha chains of type I and type II procollagen into the native triple-helical molecule was examined in vitro in the presence and absence of pure protein disulfide isomerase. The data clearly indicates that protein disulfide isomerase is able to accelerate the formation of native interchain disulfide bonds in these procollagens. It takes about 6 min after disulfide bonding before triple-helical molecules exist, while the time required to produce triple-helical type I procollagen in the presence of protein disulfide isomerase is 9.4 min and that for type II procollagen 17.2 min. These values agree with those obtained for type I and II procollagen in vivo suggesting that protein disulfide isomerase is also an enzyme catalyzing interchain disulfide bond formation in procollagen in vivo. The formation of native disulfide bonds can proceed without any enzyme catalysis but then requires the presence of reduced and oxidized glutathione. Bonding is rather slow in such a case, however, resulting in a delay in the formation of the triple helix.


Biosynthesis of protein products by animal cells. Are growth and non-growth associated concepts valid or useful?
The application of simple growth and non-growth associated concepts from microbial systems describing substrate uptake and production formation is considered unlikely to assist in the understanding of antibody formation and, hence, in maximising antibody yield. Such concepts have many significant limitations - notably, their strict application only to products of catabolic pathways and their inability to include metabolisms which either have multiple catabolic pathways (eg, fermentation and respiration in yeast and animal cells) or in which the major product of interest is predominantly anabolic in nature (eg. amino acid production in bacteria and antibody formation in animal cells). In addition, products which undergo an assembly and secretion process or a secretion process which allows intracellular pools of product to exist are also not well described by such simple relationships. In this work, inadequacies in the current approach to the study of the kinetics of growth of hybridoma cells and antibody production are described and the examples of growth ofSaccharomyces cerevisiae andCandida utilis, amino acid production by bacteria and antibody production by animal cells are used to illustrate these limitations. Having identified these limitations, suggestions are made as to how studies might be undertaken to assist our future understanding of the process of antibody manufacture and, subsequently, maximizing antibody yield. The process of characterising the metabolism of anabolic products is subject to detailed computer simulation of the pathways involved. It is argued that such approaches will assist us in understanding more fully the nature of biosynthetic products and how they integrate with the major energy producing pathways of the cell and the cell cycle. This will assist in maximising the yield of such products.


Structure of Rb-III: novel modulated stacking structures in alkali metals.
The crystal structure of Rb-III, stable between 13 and 17 GPa, has been determined from quasi-single-crystal x-ray diffraction data. It is orthorhombic, space group C222(1), with 52 atoms in the unit cell, and has an 8-10-8-8-10-8 stacking of 8- and 10-atom layers. The recently reported 84-atom structure of Cs-III can be understood as an 8-8-10-8-8-8-8-10-8-8 stacking of the same layers. These represent a new class of modulated elemental structures.


Bringing genome tests into clinical practice.
To provide a review of recent progress in the use of genomic data in clinical contexts. Survey of key articles selected from the previous year (2012). Two major themes emerged as areas of focus in 2012: (1) integration of genomic data into electronic health records; and (2) determining the clinical utility of genomic tests. Significant advances are being made towards the integration of genomic data such that they may useful for clinical decision making. While the short term advances will likely still be seen in clinically valid genotype-phenotype research, there have been promising advances towards developing genomic tests that may be of clinical utility in the near future.


Retracted: Clinical Evaluation of the Medium-Term Efficacy of Laparoscopic Sleeve Gastrectomy against Obstructive Sleep Apnea-Hypopnea Syndrome in Obese Patients.
[This retracts the article DOI: 10.1155/2022/7682706.].


Physiological response to salinity stress and tolerance mechanics of Populus euphratica.
The salinity stress inhibits the growth of Populus euphratica (P. euphratica), and the extent of inhibition tends to increase with a rise of salt concentration while the net photosynthesis rate, stomatal conductance, transpiration rate, and internal CO2 concentration are seen to decline with increasing salt concentration. Compared with the control group, the percentage decline is found to be about 48.50, 15.72, 42.09, and 48.33%, respectively. Although all chlorophyll fluorescence of P. euphratica exhibits a typical O-J-I-P curve in differently concentrated salt solutions, salinity stress shows a significant influence on the value of J and I step (P < 0.05). However, salinity stress was seen to induce a decrease in variable fluorescence (Fv)/maximal fluorescence value by 2.32, 8.78, 12.80, 12.93, 16.46, and 19.63% treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution compared with the control group, respectively. Salinity stress appeared also to induce a decrease in Fv/minimal fluorescence values by a magnitude of 5.22, 16.02, 18.06, 22.95, 26.34, and 32.19% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution relative to the control group, respectively. An increase in the content of malondialdehyde amounted to 4.12, 25.59, 34.60, 68.11, 70.72, and 67.68% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution compared to the control group, respectively. In terms of the content of proline, the salinity stress induced an increase by 4.94, 29.49, 53.20, 77.65, 82.46, and 90.68% in P. euphratica treated by 50-, 100-, 150-, 200-, 250-, and 300-mM salt solution, respectively.


MicroRNA-182 regulates otocyst-derived cell differentiation and targets T-box1 gene.
Recently, in vitro and in vivo models have identified that microRNAs (miRNAs), which are extensively expressed in the inner ear, play important roles in inner ear development and function. However, the function of miRNA in vertebrate tissue is not well understood. The current study used an in vitro model of embryonic mouse inner ear in a stem/progenitor cell culture to demonstrate that: 1) miR-182 is expressed during differentiation of inner ear stem/progenitor cell into a hair cell-like fate, 2) ectopic miR-182 promotes inner ear stem/progenitor cell differentiation into a hair cell-like fate, and 3) the function of miR-182 may be associated with its putative target Tbx1, a transcription factors that have been implicated in inner ear development and hair cell fate. Our findings suggest that miR-182 could regulate inner ear progenitor cell differentiation and that miRNAs are important regulators of hair cell differentiation, providing new targets for hair cell repair.


Multifunctional deadenylase complexes diversify mRNA control.
Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse deadenylase enzymes. Modulating the length of the poly(A) tail of an mRNA is a widespread means of controlling protein production and mRNA stability. Recent insights illuminate the specialized activities, biological functions and regulation of deadenylases. We propose that the recruitment of multifunctional deadenylase complexes provides unique opportunities to control mRNAs and that the heterogeneity of the deadenylase complexes is exploited to control translation and mRNA stability.


High levels of anti-mitochondrial antibodies in MRL mice. Influence of anti-DNA antibodies on anti-mitochondrial antibodies measured by an enzyme-linked immunosorbent assay.
We developed an easy enzyme-linked immunosorbent assay (ELISA) for anti-mitochondrial antibodies, and detected high levels of anti-mitochondrial antibodies in MRL/Mp-lpr/lpr (MRL1/l) mice. The influence of the presence of anti-DNA antibodies in the tested sera on this assay was also evaluated. The monoclonal anti-DNA antibodies, which were made from non-immunized MRL1/l mice, did not react with the mitochondrial antigens adhering to polystyrene plates. Absorption with DNA had little effect on the levels of mitochondrial antibodies in MRL1/l sera. Our assay for mitochondria-binding antibody was very easy and sensitive, although it could not differentiate among heterogeneous anti-mitochondrial antibodies.


Biosynthesis of meso-lanthionine in Fusobacterium nucleatum.
The opportunistic oral pathogen, Fusobacterium nucleatum contains meso-lanthionine as the diaminodicarboxylic acid in the pentapeptide crosslink of the peptidoglycan layer. The diastereomer, l,l-lanthionine is formed by lanthionine synthase, a PLP-dependent enzyme that catalyzes the β-replacement of l-cysteine with a second equivalent of l-cysteine. In this study, we explored possible enzymatic mechanisms for the formation of meso-lanthionine. Our inhibition studies with lanthionine synthase, described herein, revealed that meso-diaminopimelate, a bioisostere of meso-lanthionine, is a more potent inhibitor of lanthionine synthase compared to the diastereomer, l,l-diaminopimelate. These results suggested that lanthionine synthase could also form meso-lanthionine by the β-replacement of l-cysteine with d-cysteine. Through steady-state and pre-steady state kinetic analysis, we confirm that d-cysteine reacts with the ⍺-aminoacylate intermediate with a kon that was 2-3-fold faster and Kd value that was 2-3fold lower compared to l-cysteine. However, given that intracellular levels of d-cysteine levels are assumed to be significantly lower than that of l-cysteine, we also determined if the gene product, FN1732, with low sequence identity to diaminopimelate epimerase could convert l,l-lanthionine to meso-lanthionine. Using diaminopimelate dehydrogenase in a coupled spectrophotometric assay, we show that FN1732 can convert l,l-lanthionine to meso-lanthionine with a kcat of 0.07 ± 0.001 s-1 and a KM of 1.9 ± 0.1 mM. In summary, our results provide two possible enzymatic mechanisms for the biosynthesis of meso-lanthionine in F. nucleatum.


Microheterogeneity in Aspergillus nidulans 5S rRNA genes.
We have determined the sequence of 4 Aspergillus nidulans 5S rRNA genes and compared it with 4 previously established sequences. No extensive homologies are found in 5' flanking sequences, but in the 3' flanks of two genes and two pseudogenes similar sequences are observed. In the coding sequences differences occur in 7 positions. Two 5S rRNA genes which are found in one plasmid 1.1 kb apart are located in opposite orientations.


Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?
Previous static and dynamical density functional theory studies of the 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts has led to an hypothesis that these cations exist in two families of conformers characterized as (2)S(O) and B(2,5), respectively. These families differ by ring inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl-3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the isopropylidene group allows more flexibility, but two families of conformers can be discerned with the monocyclic oxocarbenium ions in the E(3) conformation and the bicyclic dioxolenium ions in the (4)H(5) conformation. Attack on the beta-face of these monocyclic cations is favored by hydrogen bonding and the anomeric effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O-benzylidene protecting groups can be rationalized assuming that the trans-fused 1,3-dioxane ring allows population of only one family of conformers. The combination of hydrogen bonding and conformational changes of the pyranose ring in response to the C-5[bond]O-5[bond]C-1[bond]C-2 torsion angle changes are identified as key factors in stereoselectivity. Based on these observations a strategy to design face discriminated glycosyl donors that exist predominantly in only one family of conformers is proposed.


Steroid-protein interaction: from past to present.
In this review, the association between biologically active compounds and proteins is seen in the light of axioms expressed by Paracelsus and Paul Ehrlich long ago, and the physiological significance of the interactions is pointed out. Of the various types of proteins that form noncovalent complexes with steroid hormones, only the serum proteins will be discussed. Recent results, obtained in several laboratories, on the physicochemical properties of the human corticosteroid-binding globulin (CBG, transcortin) makes this glycoprotein perhaps the best known one among the steroid-binding serum proteins. Influence of pH on stability of the complexes, kinetics of the associations and their significance, as well as thermodynamic parameters of complex formation are being discussed. Characteristics of the binding sites are deduced from specificity studies. Influence of the entrance of hydrophilic or hydrophobic substituents into the steroid molecule illuminates the difference between typically hydrophobic binders such as the progesterone-binding globulin (PBG) of the pregnant guinea-pig and typically hydrophilic binders such as CBG. Complete elucidation of the steroid-binding proteins awaits the determination of the amino acid sequence and the X-ray crystallographic analysis of the steroid-protein complex.


Soil ingestion in children and adults in the same family.
Ingestion of soil may be a potentially important pathway of exposure to environmental pollutants. Although several studies have estimated soil ingestion in children, data on ingestion in adults are sparse. The purposes of this study were to estimate soil ingestion in children aged 3 to 8 years and their parents, identify factors associated with increased ingestion, and compare ingestion rates within the same family. Food/liquid, excreta, and soil/dust samples were collected for the mother, father, and participant child for 11 consecutive days in 19 families. Soil ingestion was estimated using a mass balance approach. Soil ingestion levels in children were similar to those reported previously, whereas adult estimates were somewhat higher than previous estimates. Children's eating of dirt and parents' occupational contact with soil were associated with increased ingestion. Within families, soil ingestion levels in children and adults were not correlated, although this analysis was based on fewer than 19 participant families. Children's mean soil ingestion rates ranged from 37 to 207 mg/day depending on the tracer, with the highest values based on titanium as a tracer. Adult mean soil ingestion rates ranged from 23 to 625 mg/day depending on the tracer, with the highest value based on titanium as a tracer. Soil ingestion rate estimates were more variable in adults than in children.


Methiothepin attenuates gastric secretion and motility effects of vagal stimulants at the dorsal vagal complex.
Methiothepin, a nonselective 5-HT receptor antagonist was utilized to explore the 5-HT modulation of dorsal vagal complex-TRH (thyrotropin releasing hormone) analogue stimulated gastric functional parameters. Intracisternal methiothepin pretreatment (200, 0.1 nmol) produced significant inhibition (70%, 44%, respectively) of the TRH analogue [p-Glu-His-(3,3'-dimethyl)-Pro NH2; RX 77368 (12 pmol)]-induced gastric acid output compared to vehicle pretreatment. Intracisternal pretreatment with methysergide (nonspecific 5-HT receptor antagonist) or combined cyanopindolol (5-HT(1A and 1B) receptor antagonist)+ritanserin (receptor antagonist of the 5-HT(2) family) did not alter the dorsal vagal complex-RX 77368 response. Unilateral dorsal vagal complex pretreatment with methiothepin (50 nmol/50 nl) attenuated ipsilateral dorsal vagal complex-TRH analog (12 pmol) induced gastric secretory response by 57%. The gastric secretagogue response to stimulation of the raphe obscurus (mediated by TRH release into the dorsal vagal complex) was inhibited 50% by pretreatment with intracisternal dorsal medullary methiothepin (0.1 nmol/10 microl). Intracisternal methiothepin (200 nmol/20 microl) also attenuated (a) dorsal vagal complex-glutamate (60 nmol/30 nl) stimulated gastric acid secretion and (b) gastric motility stimulated by dorsal vagal complex-RX 77368 (12 pmol/30 nl). The data suggest that other properties of methiothepin, alone or in addition to its 5-HT receptor antagonist effect, mediate its inhibitory actions at the dorsal vagal complex.


Quantitative phosphoproteomic analysis reveals chemoresistance-related proteins and signaling pathways induced by rhIL-6 in human osteosarcoma cells.
IL-6 plays a pivotal role in resistance to chemotherapeutics, including lobaplatin. However, the underlying mechanisms are still unclear. This study was to investigate the changes in phosphoproteins and their related signaling pathways in the process of IL-6-induced chemoresistance to lobaplain in osteosarcoma cells. We performed a quantitative phosphoproteomic analysis of the response of SaOS-2 osteosarcoma cells to recombinant human IL-6 (rhIL-6) intervention prior to lobaplatin treatment. The cells were divided into the control group (Con), the lobaplatin group (Lob), and the rhIL-6-and-lobaplatin group (IL-6). Three biological replicates of each group were included. The differentially expressed phosphoproteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Netphos 3.1 was used for the prediction of kinases, and STRING was used for the visualization of protein-protein interactions. The conserved motifs surrounding the phosphorylated residues were analyzed using the motif-x algorithm. Western blot analysis was performed to verify the differential expression of p-FLNC, its predicted kinase and the related signaling pathway. The results of the bioinformatic analysis were validated by immunohistochemical staining of clinical specimens. In total, 3373 proteins and 12,183 peptides, including 3232 phosphorylated proteins and 11,358 phosphorylated peptides, were identified and quantified. Twenty-three significantly differentially expressed phosphoproteins were identified in the comparison between the IL-6 and Lob groups, and p-FLNC ranked second among these phosphoproteins. GO and KEGG analyses revealed the pivotal role of mitogen-activated protein kinase signaling in drug resistance induced by rhIL-6. Four motifs, namely, -SPxxK-, -RxxSP-, -SP-, and -SPK-, demonstrated higher expression in the IL-6 group than in the Lob group. The western blot analysis results verified the higher expression of p-FLNC, AKT1, and p-ERK and the lower expression of p-JNK in the IL-6 group than in the Con and Lob groups. The immunohistochemical staining results showed that p-FLNC, AKT1 and p-ERK1/2 were highly expressed in platinum-resistant clinical specimens but weakly expressed in platinum-sensitive specimens, and platinum-resistant osteosarcoma specimens demonstrated weak expression of p-JNK. This phosphoproteomic study is the first to reveal the signature associated with rhIL-6 intervention before lobaplatin treatment in human osteosarcoma cells. p-FLNC, AKT1, and MAPK signaling contributes to resistance to lobaplatin in osteosarcoma SaOS-2 cells and may represent molecular targets to overcome osteosarcoma chemoresistance.


Evaluation of a robot-assisted testing system for multisegmental spine specimens.
Mono- and multi-segmental testing methods are required to identify segmental motion patterns and evaluate the biomechanical behaviour of the spine. This study aimed to evaluate a new testing system for multisegmental specimens using a robot combined with an optical motion analysis system. After validation of the robotic system for accuracy, two groups of calf specimens (six monosegmental vs. six multisegmental) were mounted and the functional unit L3-4 was observed. Using rigid body markers, range of motion (ROM), elastic zone (EZ) and neutral zone (NZ), as well as stiffness properties of each functional spine unit (FSU) was acquired by an optical motion capture system. Finite helical axes (FHA) were calculated to analyse segmental movements. Both groups were tested in flexion and extension. A pure torque of 7.5 Nm was applied. Statistical analyses were performed using the Mann-Whitney U-test. Repeatability of robot positioning was -0.001±0.018 mm and -0.025±0.023° for translations and rotations, respectively. The accuracy of the optical system for the proposed set-up was 0.001±0.034 mm for translations and 0.075±0.12° for rotations. No significant differences in mean values and standard deviations of ROM for L3-4 compared to literature data were found. A robot-based facility for testing multisegmental spine units combined with a motion analysis system was proposed and the reliability and reproducibility of all system components were evaluated and validated. The proposed set-up delivered ROM results for mono- and multi-segmental testing that agreed with those reported in the literature. Representing the FHA via piercing points determined from ROM was the first attempt showing a relationship between ROM and FHA, which could facilitate the interpretation of spine motion patterns in the future.


A microstructural study of sleep instability in drug-naive patients with schizophrenia and healthy controls: sleep spindles, rapid eye movements, and muscle atonia.
This study aimed at characterizing the functional stability of sleep in schizophrenia by quantifying dissociated stages of sleep (DSS), and to explore their correlation with psychopathology. The sleep of 10 first-break, drug-naive young adults with schizophrenia and 10 controls was recorded. Four basic DSS patterns were scored: 1) the transitional EEG-mixed intermediate stage (EMIS); 2) Rapid-eye-movement (REM) sleep without rapid eye movement (RSWR); 3) REM sleep without atonia (RSWA); and 4) non-REM sleep with rapid eye movements. An intermediate sleep (IS) score was calculated by summing EMIS and RSWR scores, and the durations of intra-REM sleep periods IS (IRSPIS) and IS scored "at the expense" of REM sleep (ISERS) were determined. Patients were administered the Brief Psychiatric Rating Scale (BPRS) at the time of recording. Proportions of each DSS variables over total sleep time and proportions of IRSPIS and ISERS over REM sleep duration were compared between patients and controls. Correlation coefficients between DSS variables and BPRS total scores were calculated. The proportion of total DSS did not differ between patients and controls. Among DSS subtypes, RSWA was significantly increased in patients while other comparisons showed no significant differences. Significant positive correlations were found between BPRS scores and proportions of DSS, IS, RSWR, IRSPIS and ISERS over total sleep and REM sleep durations. These results demonstrate the functional instability of REM sleep in first-break, drug naive young adults with schizophrenia and unveil a pattern reminiscent of REM sleep behavior disorder. The significant correlation suggests that schizophrenia and REM sleep share common neuronal control mechanisms.


High-performance thermoplastic starch/poly(butylene adipate-co-terephthalate) blends through synergistic plasticization of epoxidized soybean oil and glycerol.
Utilizing starch, an abundant polysaccharide, as the renewable filler to blend with poly(butylene adipate-co-terephthalate) (PBAT) is a feasible tactic to construct cost-effective and high-performance biodegradable materials. It's worth noting that the thermal processing properties of starch can be manipulated by its plasticized behavior. Herein, epoxidized soybean oil (ESO) and glycerol were used as the plasticizer for native corn starch and the plasticized starch was integrated with PBAT to manufacture starch-based biodegradable blend films. ESO breaks the hydrogen bonds between starch chains through the fatty chains grafting reaction and increases the distance between starch molecular chains due to the large molecular weight of ESO. Meanwhile, glycerol molecules are incorporated into the starch molecular chains, and fatty chains grafted starch chains, effectively reducing the intermolecular forces of molecular chains. On account of the synergistic plasticization of ESO and glycerol which possess good compatibility with PBAT, the PSG20E10 blend film achieved a tensile strength, an elongation at break of 16.11 MPa and 612.09 %, and the balanced water and oxygen permeability properties.


Coupled gyration modes in one-dimensional skyrmion arrays in thin-film nanostrips as new type of information carrier.
We report on a micromagnetic numerical simulation study of dynamic coupling between neighboring skyrmions periodically arranged in narrow-width nanostrips. We explored the coupled gyration modes and their characteristic dispersions in terms of the interdistance between the neighboring skyrmions. The application of perpendicular magnetic fields allows for the control and modification of the dispersion of the coupled gyration modes. The coupled gyration modes of individual skyrmions might provide a new type of information carrier in narrow-width straight and curved nanostrips, as driven by magnetic interactions in such continuous thin films.


Effects of the Methionine Hydroxyl Analogue Chelate Zinc on Antioxidant Capacity and Liver Metabolism Using 1H-NMR-Based Metabolomics in Aged Laying Hens.
This study aimed to investigate the effects of different levels of methionine hydroxyl analogue chelated zinc (MHA-Zn) on antioxidant capacity and liver metabolism of aged laying hens. A total of 960 57-week-old layers were fed a basal diet (Zn: 35.08 mg/kg) without extra zinc for two weeks, and then allocated to four treatments consisting of eight replicates of 30 birds each for 14 weeks. Four levels of Zn (zinc sulfate (ZnSO4): 80 mg/kg; MHA-Zn: 20, 40, 80 mg/kg) were added to the diet. The results indicated that compared with inorganic zinc, organic zinc of 80 mg/kg has a significant advantage in improving the antioxidant capacity of aged hens, which increased the level of Cu/Zn-superoxide dismutase (SOD) and the total antioxidant capacity (T-AOC) in the serum and liver, and reduced the concentration of malondialdehyde (MDA) of laying hens. The serum albumen composition was significantly modified, meanwhile, the level of total protein, globulin, and urea increased remarkably, whereas serum glutamic-oxaloacetic transaminase decreased notably in 80 mg/kg MHA-Zn groups. Compared with the 20 mg/kg MHA-Zn group, the metabolic profile of 40 and 80 mg/kg MHA-Zn groups was higher than that of the inorganic zinc group. Furthermore, integrated key metabolic pathway analysis showed that 40 and 80 mg/kg MHA-Zn groups participated in the regulation of glutathione metabolism, glycine, serine, and threonine metabolism. Therefore, this study suggests that 40 and 80 mg/kg supplementation of MHA-Zn can increase the activity of Cu/Zn-SOD and T-AOC and decrease MDA; additionally the 80 mg/kg MHA-Zn group has better antioxidant capacity. Meanwhile, the enhanced MHA-Zn promoted methionine (Met) synthesis and protein metabolism.


Atomistic simulation of the effect of porosity on shock response of nanoporous gold.
Nanoporous metals (NPMs) have a three-dimensional bicontinuous porous network structure that consists of interconnected nanoligaments. NPMs have the potential to effectively attenuate and dissipate the effects of impacts and blasts. Previous studies do not provide data on the possible effects of porosity at the nanoscale. Molecular dynamics simulations based on the embedded-atom method potential were performed using the open-source code LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator). Nanoporous gold (NPG) absorbs shock energy first through the elastic-plastic deformation of ligaments and then through the collapse of ligaments. After the shock loading is relaxed, NPG with lower porosity has a higher amount of springback, and new voids tend to nucleate and grow at collapsed ligaments where the packing is looser. NPG with higher porosity has a better ability to resist the propagation of a shock wave and is subjected to a smaller stress effect.


Stories to Take the Edge Off Pain During Immunization for Preschoolers: A Randomized Controlled Trial.
Fear and distress during immunization may lead to long-term preprocedural anxiety and nonadherence to immunization schedules. Pictorial stories provide a way of educating the parent and child about the procedure. To determine the efficacy of pictorial stories in reducing pain perception among children and anxiety among mothers during immunization. Three-arm randomized controlled trial Setting: Immunization clinic of a tertiary care hospital in South India. Fifty children ages 5 to 6 yr, who reported to the hospital for measles, mumps, and rubella and typhoid conjugate virus vaccines. Inclusion criteria were that the child was accompanied by the mother and maternal knowledge of either Tamil or English. Exclusion criteria were child hospitalization in the past year or neonatal intensive care unit admission in the neonatal period. Pictorial story regarding immunization before the procedure that contained information related to immunization, coping strategies, and distraction techniques. Pain perception was evaluated using the Sound, Eye, Motor Scale; the Observation Scale of Behavioral Distress; and the Wong-Baker FACES Pain Rating Scale (FACES). Maternal anxiety was measured using the General Anxiety-Visual Analog Scale. Of 50 children recruited, 17 were in the control group, 15 were in the placebo group, and 18 were in the intervention group. Children in the intervention group reported lower pain scores on the FACES (p = .04) compared with the placebo and control groups. A pictorial story is a simple and cost-effective intervention to reduce pain perception among children. What This Article Adds: Pictorial stories may be a feasible, simple, and cost-effective intervention to reduce pain perception during immunization.


Multi-scale NMR characterisation of mesostructured materials using 1H-->13C through-bond polarisation transfer, fast MAS, and 1H spin diffusion.
A NMR method for the characterisation of materials at different length scales, robust and simple to implement, is presented. It combines selection of 1H-13C pairs by a through-bond polarisation transfer (INEPT here) and exploration of larger distances by the introduction of 1H spin diffusion. This characterisation method is well adapted to the highest MAS rates and takes benefits of it. The effect of 1H dephasing on the efficiency of the 1H-->13C through-bond polarisation transfer is determined. This allows consecutively the quantification of signals. Mesostructured spherical silica-based particles containing CTA+ cations were studied by this multi-scale characterisation method. Contrasted spin diffusion curves were found and qualitatively explained by differences in terms of mobility and spatial distributions.


Mechanisms of cell volume regulation in hypo-osmolality.
Cells respond to a condition of hypo-osmolality by rapid swelling followed by an adaptive response that tends to recover the normal cell volume despite the persistence of the hypo-osmotic condition. This is an active process accomplished by the extrusion of intracellular osmolytes, essentially K+, Cl-, and small organic molecules. This regulatory process operates through a chain of events that essentially consists of a sensor or sensing mechanism to detect changes in cell volume, a signaling cascade to amplify the sensing signal and orient it to activate pathways for osmolyte extrusion, and a memory of the original cell volume, which sets the timing for inactivation of the volume-regulatory process. This article presents a brief overview of recent progress in these different aspects of the volume-regulatory process, including (1) the mechanisms and/or candidate molecules serving the role of volume sensors, (2) the osmosignaling network and the interplay and hierarchy of the different elements in this chain, and (3) the nature and properties of the osmolyte extrusion pathways. Emphasis is placed on some of the main unsolved questions concerning different aspects of the volume-regulatory process. Recent findings regarding the effect of hypo-osmolality on synaptic function are briefly discussed in terms of the possible molecular basis for the neurologic symptoms induced by hyponatremia.


Oral corticosteroids for post-infectious cough in adults: study protocol for a double-blind randomized placebo-controlled trial in Swiss family practices (OSPIC trial).
Cough is a common reason for patients to visit general practices. So-called post-infectious cough is defined as lasting 3 to 8 weeks after an upper respiratory tract infection. It can be disabling in daily activities, with substantial impact on physical and psychosocial health, leading to impaired quality of life and increased health care costs. Recommendations for the management of post-infectious cough in primary care are scarce and incoherent. A systematic review and meta-analysis of randomized clinical trials (RCT) assessing patient-relevant benefits and potential harms of available treatments identified six eligible RCTs assessing different treatment regimens (i.e. inhaled fluticasone propionate, inhaled budesonide, salbutamol plus ipratropium-bromide, montelukast, nociception-opioid-1-receptor agonist, codeine, gelatine). No RCT found clear patient-relevant benefits and most had an unclear or high risk of bias. Post-infectious cough is thought to be mediated by inflammatory processes that are also present in exacerbations of asthma or chronic obstructive pulmonary diseases for which there is strong evidence that oral corticosteroids provide patient-relevant benefit without relevant harm. We therefore plan to conduct the first RCT evaluating the effectiveness of oral corticosteroids for post-infectious cough. We are conducting a triple-blinded randomized-controlled and multicentred superiority trial in primary health care practices in Switzerland. We will include 204 adult patients who consult their general practitioner (GP) for a cough lasting 3 to 8 weeks following an upper respiratory tract infection. Participants will be randomly allocated to either the 5-day treatment with oral corticosteroids or placebo. The primary outcome is cough-related quality of life assessed by the Leicester Cough Questionnaire score 14 days after randomization. Secondary outcomes include cough-related quality of life at several time points, overall cessation of cough and adverse events. This RCT will provide evidence on whether oral corticosteroids are beneficial and safe in patients with post-infectious cough. Results can have a substantial impact on the well-being and management of these patients in Switzerland and beyond. An evidence-based treatment for this condition may reduce re-consultations with GPs and spending for antitussive drugs, thus possibly having an impact on health care spending. ClinicalTrials.gov NCT04232449 . Prospectively registered on 18 January 2020.


Assessment of oxidative stress responses and the cytotoxic and genotoxic potential of the herbicide tembotrione in HepG2 cells.
Tembotrione is a triketone herbicide, usually used for post-emergence weed control in corn. Currently, there is little or no published data on its genotoxicity to human cells either in vitro or in vivo. This study evaluated the impact of acute (4 and 24 h) exposure to low concentrations of tembotrione [corresponding to the acceptable daily intake (0.17 μg/mL), residential exposure level (0.002 μg/mL) and acceptable operator exposure level (0.0012 μg/mL)] on human hepatocellular carcinoma cell line HepG2, using biomarkers of oxidative stress, CCK-8 colorimetric assay for cell viability, alkaline comet assay, and cytokinesis-block micronucleus "cytome" assay. Tembotrione applied at concentrations likely to be encountered in occupational and residential exposures induced cytogenetic outcomes in non-target cells despite non-significant changes in the values of oxidative stress biomarkers. We assume that the observed effects were mainly the consequence of impaired metabolic pathways in HepG2 cells due to the inhibition of the enzyme 4-hydroxyphenyl-pyruvate-dioxygenase by tembotrione, which possibly caused a depletion of folate levels leading to excess formation of nuclear buds in the affected cells. Regardless of the fact that tembotrione was previously reported negative for mutations and chromosome aberrations in vitro, our findings call for more precaution in its use.


Synaptic transmission at retinal ribbon synapses.
The molecular organization of ribbon synapses in photoreceptors and ON bipolar cells is reviewed in relation to the process of neurotransmitter release. The interactions between ribbon synapse-associated proteins, synaptic vesicle fusion machinery and the voltage-gated calcium channels that gate transmitter release at ribbon synapses are discussed in relation to the process of synaptic vesicle exocytosis. We describe structural and mechanistic specializations that permit the ON bipolar cell to release transmitter at a much higher rate than the photoreceptor does, under in vivo conditions. We also consider the modulation of exocytosis at photoreceptor synapses, with an emphasis on the regulation of calcium channels.


Effects of 4-tert-octylphenol on the testes and seminal vesicles in adult male bank voles.
The present study was designed to evaluate the effects of 4-tert-octylphenol (OP) on male testes and seminal vesicles of bank vole. Adult males kept under long or short photoperiod were orally administered OP (200mg/kg bw) for 30 or 60 days. Treatment for 30 days had no discernible effect on the parameters examined. Treatment for 60 days adversely influenced weights and histological structure of the testes and seminal vesicles. In these tissues, expression of 3β-hydroxysteroid dehydrogenase and androgen receptor and testosterone levels were reduced, whereas expression of aromatase and estrogen receptor α and estradiol levels were increased. The alterations were more evident in voles kept in long photoperiod. Taken together, it is suggested that adverse changes in bank vole reproductive tissues induced by long-term OP-exposure result from disturbed androgen and estrogen synthesis and action. Moreover, there might be a subtle difference in the sensitivity to OP between voles kept in different light conditions.


Radio frequency analysis of partially grafted immediate dental implant with and without use of static magnetic field: An in vivo study.
Replacement of missing teeth with dental implants represents one of the most successful treatment modalities in modern dentistry. Patients desire for a shorter treatment time has made clinicians to attempt loading implants early or immediately after placement. The primary stability is determined by density and mechanical properties of the bone, the implant design, edentulous site complications, and the surgical technique. Various researchers have tried to achieve faster osseointegration static magnetic field is one of them. So the aim of this study was to investigate whether Static magnetic field created by using safer magnets was useful to promote osseointegration. Subjects were selected according to the predetermined inclusion and exclusion criteria in two groups (20 in each group). Conventional implant placement protocol was used and implant placement was performed and grafting was done. Magnetic healing cap was used in group I and conventional healing cap in group II. Implant stability assessment using radio frequency analyser was assessed at 2, 3 and 4 months on interval. Mann-Whitney U test revealed that there was significant difference was observed between the groups I and II at 2, 3 and 4 months of interval (P < 0.001). Static magnetic field improve osseointegration in group I as compared to group II. The present double-blinded RCT showed significantly improved implant stability and osseointegration in implants which were stimulated by static magnetic field by using magnetic healing cap as compared to implants with conventional healing cap.


Second malignancies in very-long-term survivors of childhood cancer.
Although most second malignancies are treatment related, their occurrence also may be due to an underlying systemic disease or chromosomal abnormalities shared by multiple organs in which they are tumorigenic. We attempted to identify unusual tumor pairs that might provide a clue to shared genetic etiologies. Medical records and tumor registry correspondence of 1,743 patients (0 to 18 years at diagnosis) were reviewed. For those said to have a second malignancy, biopsy and autopsy records and slides were reviewed to confirm initial and secondary diagnoses. Two hundred fifty-eight patients had follow-up of at least 10 years and 157 of at least 20 years. Second malignancies were identified in 14 patients. The estimated cumulative incidence of a second cancer was approximately 1% within 10 years. At 20 years after diagnosis, the actuarial estimate was 3%. Although most second cancers were likely treatment related, several tumor pairs could not clearly be explained on that basis, including thyroid carcinoma followed by an ovarian sarcoma, and acute lymphoblastic leukemia associated with renal leiomyosarcoma. Based on one case in this series and a review of the literature, associations between Wilms' tumor, abdominal radiation, and adenocarcinoma of the colon and hepatocellular carcinoma are suggested. We conclude that continued surveillance of very-long-term survivors of childhood cancer, which is usually accomplished by internists, family practitioners, and adult oncologists, may be one approach to defining the life-time incidence of second malignancies. In addition, although the yield is likely to be small, descriptions of unexpected tumor pairs may target families for studies of pleiotropic genetic abnormalities.


Treatment of systemic scleroderma with fucidine with regard to some free amino acids contents before and after therapy.
In 7 patients with systemic scleroderma and acroscleroderma improvement was observed after the administration of fucidine. In the same time 4 amino acids contents, which had been abnormal prior to the therapy, normalized.


Hermitian-Randić matrix and Hermitian-Randić energy of mixed graphs.
Let M be a mixed graph and [Formula: see text] be its Hermitian-adjacency matrix. If we add a Randić weight to every edge and arc in M, then we can get a new weighted Hermitian-adjacency matrix. What are the properties of this new matrix? Motivated by this, we define the Hermitian-Randić matrix [Formula: see text] of a mixed graph M, where [Formula: see text] ([Formula: see text]) if [Formula: see text] is an arc of M, [Formula: see text] if [Formula: see text] is an undirected edge of M, and [Formula: see text] otherwise. In this paper, firstly, we compute the characteristic polynomial of the Hermitian-Randić matrix of a mixed graph. Furthermore, we give bounds on the Hermitian-Randić energy of a general mixed graph. Finally, we give some results about the Hermitian-Randić energy of mixed trees.


A new solution structure of ATP synthase subunit c from thermophilic Bacillus PS3, suggesting a local conformational change for H+-translocation.
In F(o)F(1)-ATP synthase, an oligomer ring of F(o)c subunits acts as a rotary proton channel of the F(o)-proton motor. On the basis of the solution structure of the Escherichia coli F(o)c (EF(o)c) monomer, the rotation of the C-terminal helix coupled with the reorientation of the essential Asp61 side-chain on deprotonation was proposed to drive rotation of the whole c-ring. We have determined the NMR structure of F(o)c from thermophilic Bacillus PS3, TF(o)c, in an organic solvent mixture (chloroform/methanol (3:1, v/v)). Our results showed that, independent of pH, the carboxyl group of the essential Glu56 of TF(o)c protrudes toward the outside of the hairpin, a third orientation that differs from either of the two orientations in EF(o)c. Therefore, it would be inappropriate to draw conclusions about the mechanism of c-ring rotation on the basis of the conformations observed only for EF(o)c. The appearance of different hairpin structures shows that there are multiple energy minima for the hairpin structure in terms of helix rotation and axial displacement. The multiple energy minima may also provide a base for the different oligomeric states in the c-ring structure. A rotation mechanism of the F(o) motor coupled with H(+)-translocation is discussed on the basis of these results and the recently reported crystal structure of the c-ring from Ilyobacter tartaricus Na(+)-ATPase.


Degradation of p-nitrophenol in a BES-Fenton system based on limonite.
This study confirmed the feasibility of natural limonite working as the iron catalyst for the PNP wastewater treatment in the BES-Fenton system. After the start-up period of the BES-Fenton systems, air and limonite powder were injected into the cathode chamber as the original materials for manufacturing Fenton reagents of H₂O₂ and Fe(II) respectively. The experiment parameters like pH, external resistance, limonite dosage and initial PNP concentration were investigated in this research. The removal efficiency of PNP (0.25 mM) could achieve 96% in 6h under the optimal experimental conditions. A limonite dosage of 112 mg per 50 ml of PNP solution at 0.25 mM concentration each time could sustain 7 cycles of the BES-Fenton system operation with PNP removal efficiency >94%. This study suggests an efficiency and cost-effective approach for the PNP removal by using the natural limonite as the iron catalyst of the BES-Fenton system.


Reciprocating sliding wear behavior of alendronate sodium-loaded UHMWPE under different tribological conditions.
The aim of this study is to investigate the tribological behaviors and wear mechanisms of ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), a potential drug to treat osteolysis, under different normal loads and lubrication conditions. A mixture of UHMWPE powder and ALN (1.0 wt.%) solution was dried and hot pressed. The static and dynamic friction coefficients of UHMWPE-ALN were slightly higher than those of UHMWPE except under normal load as 10 N and in 25 v/v % calf serum. The specific wear rates of UHMWPE-ALN and UHMWPE were the lowest in 25 v/v % calf serum compared to those in deionized water or physiological saline. In particular, the specific wear rate of UHMWPE-ALN was lower than that of UHMWPE at 50 N in 25 v/v % calf serum. The main wear mechanisms of UHMWPE and UHMWPE-ALN in deionized water and UHMWPE in physiological saline were abrasive. The main wear mechanism of UHMWPE-ALN in physiological saline was micro-fatigue. In 25 v/v % calf serum, the main wear mechanism of UHMWPE and UHMWPE-ALN was abrasive wear accompanied with plastic deformation. The results of Micro-XRD indicated that the molecular deformation of UHMWPE-ALN and UHMWPE under the lower stress were in the amorphous region but in the crystalline region at the higher stress. These results showed that the wear of UHMWPE-ALN would be reduced under calf serum lubricated, which would be potentially applied to treat osteolysis.


Modeling prenatal opioid exposure in animals: Current findings and future directions.
The past decade has seen a drastic rise in the number of infants exposed to opioids in utero. It is unclear what lasting effect this exposure may have on these children. Animal models of prenatal opioid exposure may provide insight into potential areas of vulnerability. The present review summarizes the findings across animal models of prenatal opioid exposure, including exposure to morphine, methadone, buprenorphine, and oxycodone. Details regarding the drug, doses, and duration of treatment, as well as key findings, are summarized in tables with associated references. Finally, significant gaps in the current preclinical literature and future directions are discussed.


Preferences in medications for patients seeking treatment for opioid use disorder: A conjoint analysis.
The opioid epidemic continues to be a public health crisis that has worsened during the COVID-19 pandemic. Medications for opioid use disorder (MOUD) are the most effective way to reduce complications from opioid use disorder (OUD), but uptake is limited by both structural and individual factors. To inform strategies addressing individual factors, we evaluated patients' preferences and trade-offs in treatment decisions using conjoint analysis. We developed a conjoint analysis survey evaluating patients' preferences for FDA-approved MOUDs. We recruited patients with OUD presenting to initiate treatment. This survey included five attributes: induction, location and route of administration, impact on mortality, side effects, and withdrawal symptoms with cessation. Participants performed 12 choice sets, each with two hypothetical profiles and a "none" option. We used Hierarchical Bayes to identify relative importance of each attribute and part-worth utility scores of levels, which we compared using chi-squared analysis. We used the STROBE checklist to guide our reporting of this cross-sectional observational study. Five-hundred and thirty participants completed the study. Location with route of administration was the most important attribute. Symptom relief during induction and withdrawal was a second priority. Mortality followed by side effects had lowest relative importance. Attribute levels with highest part-worth utilities showed patients preferred monthly pick-up from a pharmacy rather than daily supervised dosing; and oral medications more than injection/implants, despite the latter's infrequency. We measured treatment preferences among patients seeking to initiate OUD treatment to inform strategies to scale MOUD treatment uptake. Patients prioritize the route of administration in treatment preference-less frequent pick up, but also injections and implants were less preferred despite their convenience. Second, patients prioritize symptom relief during the induction and withdrawal procedures of medication. These transition periods influence the sustainability of treatment. Although health professionals prioritize mortality, it did not drive decision-making for patients. To our knowledge, this is the largest study on patients' preferences for MOUD among treatment-seeking people with OUD to date. Future analysis will evaluate patient preference heterogeneity to further target program planning, counseling, and decision aid development.


Regional convergence analysis of sustainable innovation efficiency in European Union countries.
Sustainable innovation strategies have been taken very seriously by the European Union (EU), which aims to reduce energy consumption and environmental pollutants emissions. For the sake of testing the sustainable performance of EU countries empirically, this research evaluates the sustainable innovation efficiency (SIE) of EU countries through a DEA-SBM model and analyzes the convergence trends of the EU regions by convergence analysis. The results show that the EU has attached great importance to sustainable innovation efficiency, indicating that the EU makes a concerted effort in technological innovation, energy saving, and environmental protection. Significant differences exist in SIE among EU regions, even though the southern region has the highest efficiency. In addition, there are distinct convergence trends in regional sustainable innovation efficiency. Control variables have significant impacts on the convergence of SIE in the EU regions. Furthermore, policymakers are also provided with useful decision support for regional sustainable innovation, energy conservation, and emission reduction policies.


Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein.
Two-photon (2P) ratiometric redox fluorometry and microscopy of pyridine nucleotide (NAD(P)H) and flavoprotein (FP) fluorescence, at 800-nm excitation, has been demonstrated as a function of mitochondrial metabolic states in isolated adult dog cardiomyocytes. We have measured the 2P-excitation spectra of NAD(P)H, flavin adenine dinucleotide (FAD), and lipoamide dehydrogenase (LipDH) over the wavelength range of 720-1000 nm. The 2P-excitation action cross sections (sigma2P) increase rapidly at wavelengths below 800 nm, and the maximum sigma2P of LipDH is approximately 5 and 12 times larger than those of FAD and NAD(P)H, respectively. Only FAD and LipDH can be efficiently excited at wavelengths above 800 nm with a broad 2P-excitation band around 900 nm. Two autofluorescence spectral regions (i.e., approximately 410-490 nm and approximately 510-650 nm) of isolated cardiomyocytes were imaged using 2P-laser scanning microscopy. At 750-nm excitation, fluorescence of both regions is dominated by NAD(P)H emission, as indicated by fluorescence intensity changes induced by mitochondrial inhibitor NaCN and mitochondria uncoupler carbonyl cyanide p-(trifluoromethoxy) phenyl hydrazone (FCCP). In contrast, 2P-FP fluorescence dominates at 900-nm excitation, which is in agreement with the sigma2P measurements. Finally, 2P-autofluorescence emission spectra of single cardiac cells have been obtained, with results suggesting potential for substantial improvement of the proposed 2P-ratiometric technique.


Collegiality and careerism trump critical questions and bold new ideas: a student's perspective and solution. The structure of scientific funding limits bold new ideas.
Funding agencies (and journals) seem to be discriminating against ideas that are contrary to the mainstream, leading to leading to the preferential funding of predictable and safe research over radically new ideas. To remedy this problem a restructuring of the scientific funding system is needed, e.g. by utilizing laymen--together with scientists--to evaluate grant proposals.


Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2.
Lipid nanoparticle (LNP)-mRNA vaccines offer protection against COVID-19; however, multiple variant lineages caused widespread breakthrough infections. Here, we generate LNP-mRNAs specifically encoding wild-type (WT), B.1.351, and B.1.617 SARS-CoV-2 spikes, and systematically study their immune responses. All three LNP-mRNAs induced potent antibody and T cell responses in animal models; however, differences in neutralization activity have been observed between variants. All three vaccines offer potent protection against in vivo challenges of authentic viruses of WA-1, Beta, and Delta variants. Single-cell transcriptomics of WT- and variant-specific LNP-mRNA-vaccinated animals reveal a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induces a systemic increase of reactive CD8 T cells and altered gene expression programs in B and T lymphocytes. BCR-seq and TCR-seq unveil repertoire diversity and clonal expansions in vaccinated animals. These data provide assessment of efficacy and direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.


Death by splicing: tumor suppressor RBM5 freezes splice-site pairing.
In a recent issue of Molecular Cell, Bonnal et al. (2008) demonstrate that the tumor suppressor gene RBM5 regulates alternative splicing of Fas pre-mRNA by interfering with splice-site pairing.


Effects of delayed administration of (-)-epigallocatechin gallate, a green tea polyphenol on the changes in polyamine levels and neuronal damage after transient forebrain ischemia in gerbils.
(-)-Epigallocatechin gallate has a potent antioxidant property and can reduce free radical-induced lipid peroxidation as a green tea polyphenol. In previous study, systemic administration of (-)-epigallocatechin gallate immediately after ischemia has been shown to inhibit the hippocampal neuronal damage in the gerbil model of global ischemia. Polyamines are thought to be important in the generation of brain edema and neuronal cell damage associated with various types of excitatory neurotoxicity. We examined the effects of delayed administration of (-)-epigallocatechin gallate on the changes in polyamine levels and neuronal damage after transient global ischemia in gerbils. To produce transient global ischemia, both common carotid arteries were occluded for 3 min with micro-clips. The gerbils were treated with (-)-epigallocatechin gallate (50 mg/kg, i.p.) at 1 or 3 h after ischemia. The polyamines; putrescine, spermidine, and spermine levels were examined using high performance liquid chromatography in the cerebral cortex and hippocampus 24 h after ischemia. Putrescine levels in the cerebral cortex and hippocampus were increased significantly after ischemia and the delayed administrations of (-)-epigallocatechin gallate (1 or 3 h after ischemia) attenuated the increases. Only minor changes were noted in the spermidine and spermine levels after ischemia. In histology, neuronal injuries in the hippocampal CA1 regions were evaluated quantitatively 5 days after ischemia. (-)-Epigallocatechin gallate administered 1 h or 3 after ischemia significantly reduced hippocampal neuronal damage. The present results show that the delayed administrations of (-)-epigallocatechin gallate inhibit the transient global ischemia-induced increase of putrescine levels in the cerebral cortex and hippocampus. (-)-Epigallocatechin gallate is neuroprotective against neuronal damage even when administered up to 3 h after global ischemia. These findings suggest that (-)-epigallocatechin gallate may be promising in the acute treatment of stroke.


Cord Blood Manganese Concentrations in Relation to Birth Outcomes and Childhood Physical Growth: A Prospective Birth Cohort Study.
Gestational exposure to manganese (Mn), an essential trace element, is associated with fetal and childhood physical growth. However, it is unclear which period of growth is more significantly affected by prenatal Mn exposure. The current study was conducted to assess the associations of umbilical cord-blood Mn levels with birth outcomes and childhood continuous physical development. The umbilical cord-blood Mn concentrations of 1179 mother-infant pairs in the Sheyang mini birth cohort were measured by graphite furnace atomic absorption spectrometry (GFAAS). The association of cord-blood Mn concentrations with birth outcomes, and the BMI z-score at 1, 2, 3, 6, 7 and 8 years old, were estimated separately using generalized linear models. The relationship between prenatal Mn exposure and BMI z-score trajectory was assessed with generalized estimating equation models. The median of cord-blood Mn concentration was 29.25 μg/L. Significantly positive associations were observed between Mn exposure and ponderal index (β, regression coefficient = 0.065, 95% CI, confidence interval: 0.021, 0.109; p = 0.004). Mn exposure was negatively associated with the BMI z-score of children aged 1, 2, and 3 years (β = -0.383 to -0.249, p < 0.05), while no significant relationships were found between Mn exposure and the BMI z-score of children at the age of 6, 7, and 8 years. Prenatal Mn exposure was related to the childhood BMI z-score trajectory (β = -0.218, 95% CI: -0.416, -0.021; p = 0.030). These results indicated that prenatal Mn exposure was positively related to the ponderal index (PI), and negatively related to physical growth in childhood, which seemed most significant at an early stage.


Evidence that amylase is released from two distinct pools of secretory proteins in the pancreas.
Previous experiments demonstrated the existence of at least two pools of secretory proteins in the exocrine pancreas. We have measured the specific activities of amylase released under resting conditions and of amylase in the zymogen granules. Specific activity of resting secretion was twice that found under stimulated conditions or in zymogen granules. Secretory proteins were pulse-labeled and amylase was measured after precipitation of the enzyme with glycogen. Pancreatic juice collected at 45-50 min post-pulse contained 10-25-times the amylase activity found in zymogen granules. These results confirm the existence of at least two distinct pools of secretory proteins in the exocrine pancreas and suggest the existence of an intracellular route of secretory proteins which would bypass the zymogen granule compartment.


Intraperitoneal splenosis mimics peritoneal carcinomatosis of leiomyosarcoma and ovarian cancer.
Leiomyosarcoma and ovarian cancer are often diagnosed late due to the absence of initial symptoms. Patients seek help when abdominal distension occurs; this is associated with pelvic tumor and carcinomatosis. Initial imaging often reveals pelvic tumors with diffuse abdominal nodules; however, this imaging could be misleading, such as in the cases of splenosis. A female presented with vaginal bleeding at our outpatient department. Serum CA125 level was elevated. Abdominal and pelvic CT showed multiple uterine masses and left adnexal cysts with peritoneal nodules. Leiomyosarcoma or ovarian cancer with carcinomatosis was suspected. Exploratory laparotomy was performed. Multiple purple spots spreading over peritoneal cavity were noted during the surgery. Pathological examination revealed adenomyosis with multiple uterine myomas and left ovarian endometrioma. Splenic tissues peritoneal implants were observed. In patients with a history of spleen rupture or splenectomy, splenosis should be considered in the differential diagnosis, especially in young patients.


Herbaceous peony (Paeonia lactiflora Pall.) PlDELLA gene negatively regulates dormancy release and plant growth.
DELLA protein plays a significant role in plant growth and development. In this study, PlDELLA with the open reading frame of 1866 bp in length was isolated from Paeonia lactiflora. Overexpression of PlDELLA in Arabidopsis thaliana showed that seed germination was significantly repressed as it took 144∼192 h for the OEs to reach 100 % germination and it required only 60 h for the WT. The OEs were also inhibited in bolting time and in plant vegetative growth. When PlDELLA was silenced in peony by virus-induced gene silencing method, peony budbreak occurred earlier by 8∼10 d and the vegetative growth was significantly accelerated compared with the control group. These results collectively indicated that PlDELLA negatively regulated dormancy release and plant growth. During chilling process to release peony endodormancy, PlDELLA expression down-regulated, and the content of both endogenous active GAs and ABA decreased, indicating decreasing of PlDELLA expression under chilling was not caused by the known gibberellin signal transduction pathway. Besides, PlDELLA had no interaction with the four screened PlWRKYs, PlWRKY13, PlWRKY18, PlWRKY40 or PlWRKY50. These findings not only enrich the knowledge of DELLA protein family, but also provide insights into understanding the function of PlDELLA protein in endodormancy release in peony.


Sexual activity, contraceptive practice and abortion among adolescents in Lagos, Nigeria.
Nine hundred fifty randomly selected secondary school girls were surveyed. Sexual activity was claimed by 29%, the youngest age was 12 years and age had no influence on the frequency of sexual intercourse. Multiple sexual partners, a high risk behaviour for contracting STD including AIDS was demonstrated in 33.7% and only 20.3% used orthodox methods of contraception. Induced abortion was procured by 23.5% and most were procured from unskilled personnel and by dangerous methods.


[Viral acute diarrhea: clinical and evolutive aspects].
The molecular characterization of gastroenteritis viruses has led to advances both in our understanding of the pathogens themselves and in development of a new generation of diagnostics. In developing countries, gastroenteritis is a common cause of death in children under 5 years that can be linked to a wide variety of pathogens. In developed countries, while deaths from diarrhoea are less common, much illness leads to hospitalization or doctor visits. Much of the gastroenteritis in children is caused by viruses belonging to four distinct families: rotaviruses, caliciviruses, astroviruses and adenoviruses. Viral gastroenteritis occurs with two epidemiologic patterns, diarrhoea that is endemic in children and outbreaks that affect people of all ages. Rotavirus infection causes severe gastroenteritis, particularly in infants under six months of age.


Using modular connectome-based predictive modeling to reveal brain-behavior relationships of individual differences in working memory.
Working memory plays a crucial role in our daily lives, and brain imaging has been used to predict working memory performance. Here, we present an improved connectome-based predictive modeling approach for building a predictive model of individual working memory performance from whole-brain functional connectivity. The model was built using n-back task-based fMRI and resting-state fMRI data from the Human Connectome Project. Compared to prior models, our model was more interpretable, demonstrated a closer connection to the known anatomical and functional network. The model also demonstrates strong generalization on nine other cognitive behaviors from the HCP database and can well predict the working memory performance of healthy individuals in external datasets. By comparing the differences in prediction effects of different brain networks and anatomical feature analysis on n-back tasks, we found the essential role of some networks in differentiating between high and low working memory loads conditions.


Accelerating progress towards the elimination of mother-to-child transmission of HIV: a narrative review.
Findings from biomedical, behavioural and implementation studies provide a rich foundation to guide programmatic efforts for the prevention of mother-to-child HIV transmission (PMTCT). We summarized the current evidence base to support policy makers, programme managers, funding agencies and other stakeholders in designing and optimizing PMTCT programmes. We searched the scientific literature for PMTCT interventions in the era of universal antiretroviral therapy for pregnant and breastfeeding women (i.e. 2013 onward). Where evidence was sparse, relevant studies from the general HIV treatment literature or from prior eras of PMTCT programme implementation were also considered. Studies were organized into six categories: HIV prevention services for women, timely access to HIV testing, timely access to ART, programme retention and adherence support, timely engagement in antenatal care and services for infants at highest risk of HIV acquisition. These were mapped to specific missed opportunities identified by the UNAIDS Spectrum model and embedded in UNICEF operational guidance to optimize PMTCT services. From May to November 2019, we identified numerous promising, evidence-based strategies that, properly tailored and adopted, could contribute to population reductions in vertical HIV transmission. These spanned the HIV and maternal and child health literature, emphasizing the importance of continued alignment and integration of services. We observed overlap between several intervention domains, suggesting potential for synergies and increased downstream impact. Common themes included integration of facility-based healthcare; decentralization of health services from facilities to communities; and engagement of partners, peers and lay workers for social support. Approaches to ensure early HIV diagnosis and treatment prior to pregnancy would strengthen care across the maternal lifespan and should be promoted in the context of PMTCT. A wide range of effective strategies exist to improve PMTCT access, uptake and retention. Programmes should carefully consider, prioritize and plan those that are most appropriate for the local setting and best address existing gaps in PMTCT health services.


NPTX2 in Cerebrospinal Fluid Predicts the Progression From Normal Cognition to Mild Cognitive Impairment.
This study examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of mild cognitive impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels. Longitudinal NPTX2 levels were also examined. CSF was collected longitudinally from 269 cognitively normal BIOCARD Study participants (mean baseline age = 57.7 years; mean follow-up = 16.3 years; n = 77 progressed to MCI/dementia). NPTX2 levels were measured from 3 correlated peptides using quantitative parallel reaction monitoring mass spectrometry. Levels of Aβ42 /Aβ40 , p-tau181 , and t-tau were measured from the same CSF specimens using Lumipulse automated electrochemiluminescence assays. In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (hazard ratio [HR] = 0.76, SE = 0.09, p = 0.023). This association was significant for progression within 7 years (p = 0.036) and after 7 years from baseline (p = 0.001). Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline AD biomarker levels (p < 0.01), and NPTX2 did not interact with the CSF AD biomarkers or APOE-ε4 genetic status. In linear mixed effects models, higher baseline p-tau181 and t-tau levels were associated with higher baseline levels of NPTX2 (both p < 0.001) and greater rates of NPTX2 declines over time. NPTX2 may be a valuable prognostic biomarker during preclinical AD that provides additive and independent prediction of MCI onset among individuals who are cognitively normal. We hypothesize that NPTX2-mediated circuit homeostasis confers resilience during the early phase of AD. ANN NEUROL 2023;94:620-631.


A new avian brain nomenclature: why, how and what.
Many of the assumptions of homology on which the standard nomenclature for the cell groups and fiber tracts of the avian brain have been based are in error, and consequently that terminology promotes misunderstanding of the functional organization of avian brain and its evolutionary relationship to mammalian brain. Recognizing this problem, a number of avian brain researchers began an effort to revise the terminology, which culminated in the Avian Brain Nomenclature Forum, held at Duke University from 18 to 20 July 2002. In the new terminology approved at this Forum, the flawed conception that the telencephalon of birds consists nearly entirely of a hypertrophied basal ganglia has been purged, and the actual parts of the basal ganglia and its brainstem afferent cell groups given names reflecting their now-evident mammalian homologues. The pallial telencephalic regions that were erroneously named to reflect presumed homology to mammalian basal ganglia were renamed as parts of pallium, using prefixes in most cases that retained established abbreviations (for continuity with the replaced nomenclature). The new nomenclature should lead to better communication among neuroscientists, especially between avian brain specialists and those not specialized in avian neurobiology. More information is available at the Avian Brain Nomenclature Exchange website ().


Congenital hypoplastic anemia: Diamond-Blackfan syndrome. Historical and clinical aspects.
A summary of the historical developments associated with congenital anemias are discussed. The clinical status, the peripheral blood and bone marrow picture of these patients are reviewed. The effectiveness of treatment and prognosis for these patients is evaluated.


Alpha-melanocyte-stimulating hormone stimulates prolactin secretion through melanocortin-3 receptors expressed in mammotropes in the mouse pituitary.
The intermediate lobe of rodent pituitaries is involved in the regulation of prolactin (PRL) secretion from the anterior lobe. In a previous study, we demonstrated the stimulatory effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on PRL release and the expression of melanocortin-3 receptors (MC3-Rs) in cultured mouse pituitary cells. The aim of the present study was to clarify whether alpha-MSH directly stimulates PRL release through the MC3-Rs by determining the cell type of MC3-R-expressing cells in the mouse pituitary anterior lobe. Northern blot analysis revealed a 2.7-kb transcript for MC3-R mRNA in the anterior and neurointermediate lobes of pituitary glands of adult male and female mice. Dual cellular localization of MC3-R mRNA and PRL or growth hormone (GH) in the mouse pituitary glands was performed by in situ hybridization analysis of MC3-R mRNA followed by immunocytochemical detection of PRL or GH. MC3-R mRNA was detected in most mammotropes and some somatotropes. alpha-MSH increased PRL release and stimulated DNA replication in mammotropes, and these effects were blocked by SHU9119, an antagonist of MC3-R and MC4-R. These results indicate that alpha-MSH stimulates PRL release and proliferation of mammotropes through MC3-Rs, and suggest that alpha-MSH from intermediate lobes can regulate mammotrope functions in the mouse pituitary.


Multiplexed tyrosine kinase activity detection in cancer cells using a hydrogel immobilized substrate.
Kinases play a key role in cellular signaling, and the overactivation or overexpression of these kinases has been linked to a variety of cancers. Tyrosine kinase inhibitors treat the mechanism of these cancers by targeting the specific kinases that are overactive. Some patients, however, do not respond to these inhibitors or develop resistance to these inhibitors during treatment. Additionally, even within cancers of the same tissue type, different kinases may be overactive in different patients. For example, some lung cancers overexpress epidermal growth factor receptor (EGFR) and respond to EGFR inhibitors, whereas other lung cancers do not overexpress EGFR and receive no benefit from this treatment. Even among patients exhibiting EGFR overexpression, some do not respond to EGFR kinase inhibitors because other kinases, such as Met kinase, are also overactivated. Here we describe a quantitative and specific multiplexed microfluidic assay using a hydrogel immobilized substrate for measuring the kinase activity of Met and Abl kinase from cancer cells. We immobilized kinase-specific substrates on macroporous hydrogel micropillars in microchannels. These microchannels were incubated with 6 μl of a kinase reaction solution containing cancer cell lysate, and we measured kinase activity via fluorescence detection of a phosphotyrosine antibody. We showed that the assay can specifically measure the activity of both Met and Abl kinase within one microchannel and has the potential to measure the activity of as many as five kinases within one microchannel. The assay also detected Met kinase inhibition from lysates of cancer cells grown in the Met kinase inhibitor PHA665752.


A kinetic, chromatographic method for studying protein hydrodynamic behavior.
A chromatographic method based on "split-peak" behavior was described for the determination of the coefficient of mass transfer of proteins on small reversed-phase columns. The coefficient of mass transfer was found to be a linear function of the protein translational diffusion coefficient and inversely proportional to the square of the support particle diameter, as predicted by chromatographic theory. As an example of the practical application of this method for the measurement of protein diffusion coefficients, the denaturation of bovine serum albumin with decreasing solution pH was followed by measuring the change in the coefficient of mass transfer. A major advantage of this method was that the results were not affected by the interaction of the protein with the stationary phase.


The differentiation of anaemia in rheumatoid arthritis: parameters of iron-deficiency in an Indian rheumatoid arthritis population.
Iron deficiency anaemia (IDA) is common in Indian patients with rheumatoid arthritis (RA). We evaluated red blood cell indices, serum iron related and bone marrow iron stores measurements in diagnosing iron deficiency in patients with RA. Fifty consecutive anaemic patients with RA had their complete blood counts, red cell indices, serum iron, serum ferritin and serum total iron binding capacity (TIBC) measured and underwent posterior iliac crest bone marrow aspiration. Fixed smears were stained for iron with Perl's Prussian blue and patients who had no (grade 0) or minimal stainable iron (grade I) were regarded as iron deficient and rest iron replete (grade II-IV) and hence as having anaemia of chronic disease (ACD). To determine diagnostic power of tests used for diagnosing iron deficiency in addition to positive likelihood ratio, sensitivity, specificity and negative predictive values; receiver operating characteristics (ROC) curves were plotted and areas under the receiver-operating curves were compared. Eighteen patients (36%) had IDA and 32 (64%) had ACD. Correlation between the bone marrow iron stores and serum ferritin was poor in the IDA group (r = -0.09, P = 0.57) and significant in the ACD group (r = 0.79, P < 0.0001). Areas under the ROC curves for mean corpuscular haemoglobin (MCV), serum iron, TIBC and mean corpuscular haemoglobin concentration (MCHC) were relatively low (0.52, 0.71, 0.75 and 0.77, respectively) and these tests had low positive likelihood ratios (1.08, 2.13, 4.62 and 1.5, respectively). Both area under ROC curve [0.98, 95% confidence interval (0.94, 0.99)] and negative predictive value (97%) were highest when cut off serum ferritin was <82 microg/l. In patients with RA serum iron, TIBC, MCV and MCHC have limited value in diagnosing iron deficiency. In this study compared to American and European studies a much higher cut off value of serum ferritin had most diagnostic power for detecting iron deficiency. Bone marrow iron stores measurements appears to be the most reliable method for diagnosing IDA however, it needs to be taken in conjunction with other laboratory findings and the clinical scenario.


Activity of carboplatin in patients with advanced non-small cell lung cancer pre-treated with a non-platinum combination.
To assess the efficacy of carboplatin when used as a single agent in patients with advanced non small cell lung cancer (NSCLC) and who are refractory to chemotherapy with a non-platinum combination, we recruited patients (n=40) NSCLC patients, 36 of whom were males, with an overall median age of 59 years (range 39-79) and Karnofsky Performance Status of 70% (range 60-90%). At baseline, the patients had a median of one disease site (range 1-3) and had received a median of one prior regimen (range 1-2). Carboplatin was administered (i.v.; AUC=6) every 3 weeks until disease progression or non-acceptable toxicity was reached. In total 169 cycles were administered (median 4 cycles/patient; range 1-8). Main toxicities were grade 2-3 anemia and grade 4 thrombocytopenia (22.5% of patients). Overall clinical response rate was 10% (4 partial responses); 26 patients (65%) had stable disease and 8 (20%) had disease progression. Median time to progression and median survival time were 90 and 187 days, respectively. One year survival rate was 13%. We conclude that carboplatin shows minimal toxicity with a discrete anti-tumor activity in patients with NSCLC and who are refractory to non-platinum combinations.


Navigation for surgical treatment of disorders of the cervical spine - A systematic review.
Computer-assisted navigation (CAN) is a well-established tool in spinal instrumentation surgery. Different techniques - each with specific advantages and disadvantages - are used in the cervical spine. A structured summary of different spinal navigation techniques and a review of the literature were done to discuss the advantages and disadvantages of specific navigation tools in the cervical spine. In cervical spine surgery, CAN increases the accuracy of pedicle screw placement, reduces screw mispositioning and leads to fewer revision surgeries. Due to the mobility of the cervical spine, preoperative CT followed by region matching or intraoperative CT are recommended. CAN increases pedicle screw placement accuracy and should be used in spinal instrumentation for the cervical spine whenever possible.


[The Studer orthotopic bladder after radical cystectomy--observation of more than 40 patients].
To perform our 5-years experience in 40 patienets with orthotopic bladder substitution in Studer's technic follow radical cystectomy. We created orthotopic neobladder using segment of terminal ileum in Studer's fashion in 40 patients. To decrease peristaltic and respectively bowel pressure, isolated segment was opened longitudinal and crossed sutured. This way we created a low pressure urinary reservoir. All patients were completely continent. Bladder capacity was 400-700 ml. At 4 years followup the patients didn't require correction in their therapy for metabolic disorder. Eight of the patients undergone this procedure died in 3-50 monts postoperatively for pelvic recurrence. Studer's orthotopic neobladder is an exellent alternative for patients undergone radical cystectomy. Thechnical ability decreases the operating time and surgical complications significantly.


Neonatal intestinal failure: Growth pattern and nutrition intakes in accordance with weaning from parenteral nutrition.
Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF. Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning. We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P < 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039). Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.


Portable electrochemical biosensor based on laser-induced graphene and MnO2 switch-bridged DNA signal amplification for sensitive detection of pesticide.
Developing portable, quantitative, and user-friendly analytical tools for sensitive pesticide assay is of significant importance for guaranteeing food safety. Herein, a novel electrochemical biosensor was constructed by integrating laser-induced graphene (LIG) electrode on polyimide (PI) foil and MnO2 nanosheets loaded on the paper for point-of-care test (POCT) of organophosphorus (OPs) residues. The principle of this biosensor relied on acetylcholinesterase (AChE)-catalyzed hydrolytic product-triggered disintegration of MnO2 nanosheets for releasing assistant DNA to initiate nicking enzyme-aided recycling amplification. In the presence of OPs, the activity of AChE was inhibited and could not initiate the cleavage of the electroactive molecules-labeled hairpin probe on the electrode, resulting in the maintenance of the electrochemical response to realize a "sign-on" determination of OPs. The proposed biosensor exhibited satisfactory analytical performance for OPs assay with a linear range from 3 to 4000 ng/mL and a limit of detection down to 1.2 ng/mL. Moreover, the biosensor was useful for evaluating the residual level of pesticides in the vegetables. Therefore, this novel biosensor holds great promise for OPs assay and opens a new avenue on the development of higher-performance POCT device for sensing applications in the environment and food safety fields.


Involvement of integrins and Src in insulin signaling toward autophagic proteolysis in rat liver.
Cell volume changes critically determine hepatic signal transduction and metabolism. Hepatocyte swelling by insulin contributes to p38(MAPK) activation leading to inhibition of autophagic proteolysis. Recently integrins were shown to sense hypoosmotic hepatocyte swelling. Here the role of integrins, Src, and focal adhesion kinase (FAK) in insulin signaling was investigated using the intact organ model of perfused rat liver. Insulin increases [Tyr(P)(418)]Src, [Tyr(P)(397)]FAK, and dual p38(MAPK) phosphorylation by about 2-fold. Infusion of the integrin-antagonizing hexapeptide GRGDSP or the Src inhibitor PP-2 prevented activation of Src and p38(MAPK) and, consequently, proteolysis inhibition by insulin. However, insulin-induced phosphorylation of IRbeta (Tyr(1158)) and protein kinase B (PKB, Ser(473)), as well as K(+)-uptake and cell swelling, was not reduced by the inhibitors. Both hypoosmotic swelling and insulin increase the plasma membrane levels of activated beta(1) integrin. Inhibition of insulin-induced swelling by furosemide largely abolished activation of beta(1) integrin and phosphorylation of Src, but not of PKB. Rapamycin does not affect either insulin-induced K(+)-retention and cell swelling or proteolysis inhibition, indicating that swelling-dependent proteolysis inhibition occurs independently from the mammalian target of rapamycin. The data suggest that sensing of cell swelling by integrins essentially contributes to insulin signaling, thereby defining a novel way of integrin involvement in growth factor signaling.


Determination of the new fluoroquinolone fleroxacin and its N-demethyl and N-oxide metabolites in plasma and urine by high-performance liquid chromatography with fluorescence detection.
A high-performance liquid chromatographic method is described for the determination of the new fluoroquinolone fleroxacin and its metabolites in plasma and urine. Plasma samples are deproteinized with acetonitrile, and, after evaporation and reconstitution of the supernatant, samples are analysed on a reversed-phase column. The limit of quantification is 10-20 ng/ml for the parent drug and 10 ng/ml for the metabolites, using a 0.2-ml sample. Urine samples are diluted with the mobile phase. An aliquot is then injected directly onto the column. The limits of quantification are 1 micrograms/ml for the parent drug and 0.5 micrograms/ml for the metabolites, using a 0.1-ml sample. The method has been successfully applied to pharmacokinetic studies of human volunteers and patients.


The prevalence, population structure and screening test specificity of penicillin-susceptible Staphylococcus aureus bacteremia isolates in Malmö, Sweden.
The objectives of this study were to examine the prevalence of penicillin-susceptible bacteremic Staphylococcus aureus in the Malmö area in 2014, to re-evaluate the phenotypic methods of penicillinase detection on these isolates, and to investigate the clonal distribution of penicillin-susceptible isolates. All non-redundant S. aureus from blood in the Malmö catchment area in southern Sweden 2014 were screened for penicillin susceptibility using PcG 1U disk diffusion, E-test PcG and the nitrocefin test. All isolates screened as likely susceptible were subjected to PCR for detection of penicillinase (blaZ) and spa-typing. Almost one out of three bacteremic isolates (80/257; 31.1%) were susceptible to penicillin. All screening methods except for the nitrocefin test alone had a low proportion of isolates falsely tested as susceptible, but no method used in the study had perfect specificity compared with PCR. Penicillin-susceptible isolates had a distinct phylogenetic distribution, and two clonal complexes (CC5 and CC45) constituted half of the isolates. Almost one third of S. aureus isolated from blood in southern Sweden in 2014 was susceptible to penicillin. Considering that intravenous penicillin has theoretical advantages compared with the standard treatment in the study area, we argue that routine testing of penicillin susceptibility should be reconsidered.