The effects on suicide rates of an educational intervention for front-line health professionals with suicidal patients (the STORM Project).
The opportunity to study district-wide educational interventions on suicide rates is rarely available. In 1997, the authors carried out a district-wide training programme for primary care, accident and emergency, and mental health workers (47% of eligible staff trained), and demonstrated improvements in skills, attitude and confidence among the recipients of the training. Suicide rates (including definite suicides and undetermined deaths) and population statistics were collected for a district and region of England from official sources from 1993-2001. A before-and-after (1994-1996 and 1998-2000) training intervention analysis was conducted on suicide rates. The suicide rate in 1994-1996 was 8.8 per 100 000 before our educational intervention and unchanged at 8.6 per 100 000 in 1998-2000 after it (p = 0.783). Brief educational interventions to improve the assessment and management of suicide for front-line health professionals in contact with suicidal patients may not be sufficient to reduce the population suicide rate.


Is the intensity of Schneiderian symptoms related to handedness and speech disorder in subjects with psychosis?
To explore the links between Schneiderian first-rank symptoms (FRS), handedness and speech disorder in subjects with psychosis. A Schneiderian score was calculated by summing seven items of the Scale for the Assessment of Positive Symptoms (SAPS) exploring first-rank symptoms in 33 hospitalized patients presenting with psychotic symptoms. Speech disorder was rated using the Scale for the Assessment of Thought, Language and Communication Disorders (TLC). Handedness was assessed using the Edinburgh Handedness Inventory. Higher Schneiderian score was independently predicted by reduced right-hand preference and by lower TLC score. The associations between Schneiderian score and lateralisation or speech disorder were independent from level of psychotic and depressive symptoms, and from categorical diagnosis. The present study adds further support to the hypothesis that loss of normal cerebral asymmetry may be implicated in the emergence of FRS.


Effects of monoclonal antibodies to bovine and Paracoccus denitrificans cytochromes c on reactions with oxidase, reductase and peroxidase.
The effects of monoclonal antibodies to bovine and Paracoccus denitrificans cytochromes c (Kuo, L.M. and Davies, H.C. (1983) Mol. Immunol. 20, 827-838) in the reactions of the cytochromes c with cytochrome c oxidase, reductase and peroxidase were studied. Spectrophotometric assays were employed, under conditions where binding of cytochrome c to the enzymes appears to be rate-limiting. Less than stoichiometric amounts of antibodies to P. denitrificans cytochrome c added to the cytochrome rendered some of it nonoxidizable or nonreducible by the P. denitrificans membrane-bound electron transport system and decreased the rate constant with the remaining cytochrome c. The antibodies appear to affect both electron transport reactions (blocking effects) with the oxidase and reductase and binding effects (effects on rate constants) and to distinguish between the two. Different ratios of antibody site to cytochrome c gave different extents of blocking of the reductase as compared with the oxidase reaction. Differences were also apparent in the effect of these antibodies on the reaction of yeast peroxidase and the oxidase with the P. denitrificans cytochrome c. Antibodies to bovine and P. denitrificans cytochromes c had considerably less effect on the reactions of the bovine cytochrome with bovine oxidase and reductase. One antibody was inhibitory to the oxidase reaction with bovine cytochrome c, but not to that with the reductase. Also, an antibody which inhibited the oxidase reaction had no effect on the reaction with yeast peroxidase. The data give evidence that the interaction areas on cytochrome c for oxidase and reductase and peroxidase are not identical, although they may be nearby.


Repair of ultraviolet light damage to the DNA of cultured human epidermal keratinocytes and fibroblasts.
Pure cultures of dermal fibroblasts and epidermal keratinocytes have been obtained from a single biopsy of newborn foreskin. The cells were labeled, exposed to several doses of UV light, and allowed to repair in the dark for 16 hr. The number of pyrimidine dimers before and after repair was assessed by measuring the numbers of sites in the DNA sensitive to a specific UV endonuclease. At all doses used, the extent of repair was similar in the cultured keratinocytes and cultured fibroblasts.


Increased Rates of Late Periprosthetic Fractures in Larger Hydroxyapatite-Coated Cementless Stems: Are Collared Stems a Better Alternative for Total Hip Arthroplasty?
Cementless hip stems are widely used for total hip arthroplasty (THA) and have demonstrated excellent survivorship. This study aimed to investigate the effects of stem size and calcar collars on rates of revision due to periprosthetic fracture. All primary THA procedures recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from September 1999 to December 2021 for a diagnosis of osteoarthritis using a single cementless hip stem with modern bearings were included. The primary outcome measure was revision due to periprosthetic fracture. Stems were divided into 2 groups for comparison, large (size 14 to 20) and small-medium (6 to 13). A subanalysis was performed for collared stems. A total of 59,518 primary THA procedures were included. The cumulative percent revision for periprosthetic fracture was significantly higher for large stems compared to small-medium stems (hazard ratio [HR] = 1.57 [95% confidence interval {CI} 1.18, 2.09] P = .002). Furthermore, collared stems had significantly lower revision rates due to late periprosthetic fracture compared to collarless variants (2 week + HR = 4.55 [95% CI 3.23, 6.42], P < .001). Large collarless stems were found to have greater revision rates due to fracture compared to small-medium collarless stems (HR = 1.55 [95% CI 1.13, 2.12] P = .006), but no difference was found between collared groups (HR = 1.37 [95% CI 0.68, 2.78] P = .382). Large cementless hip stems have a higher rate of revision due to periprosthetic fracture compared to small-medium stems. Using a collared stem reduces the rate of periprosthetic fracture.


Analysis of high-throughput ancient DNA sequencing data.
Advances in sequencing technologies have dramatically changed the field of ancient DNA (aDNA). It is now possible to generate an enormous quantity of aDNA sequence data both rapidly and inexpensively. As aDNA sequences are generally short in length, damaged, and at low copy number relative to coextracted environmental DNA, high-throughput approaches offer a tremendous advantage over traditional sequencing approaches in that they enable a complete characterization of an aDNA extract. However, the particular qualities of aDNA also present specific limitations that require careful consideration in data analysis. For example, results of high-throughout analyses of aDNA libraries may include chimeric sequences, sequencing error and artifacts, damage, and alignment ambiguities due to the short read lengths. Here, I describe typical primary data analysis workflows for high-throughput aDNA sequencing experiments, including (1) separation of individual samples in multiplex experiments; (2) removal of protocol-specific library artifacts; (3) trimming adapter sequences and merging paired-end sequencing data; (4) base quality score filtering or quality score propagation during data analysis; (5) identification of endogenous molecules from an environmental background; (6) quantification of contamination from other DNA sources; and (7) removal of clonal amplification products or the compilation of a consensus from clonal amplification products, and their exploitation for estimation of library complexity.


Chemical reactions involved in penicillin allergy: kinetics and mechanism of penicillin aminolysis.
In view of the fundamental importance of the reaction of penicillins with amino groups of proteins to the penicillin allergy, the aminolysis of benzylpenicillin by various amines was kinetically investigated. The formation rate constants, kamide, of benzylpenicilloylamides were determined at 35 degrees, 45 degrees and 60 degrees (mu equals 0.5), and found to obey the general rate law: kamide equals k1[amine] + k2[amine H+] [amine] + k3[amine]2 + k4[amine]aoh. All of the amines exhibited the unassisted nucleophilic rate constant, k1. The relative importance of the other kinetic terms depends on the basicity and the chemical structure of amines. The reaction mechanism of penicillin aminolysis was discussed. Bronsted relations for k1, k2 and k3, except for hydrazines, were satisfactory.


Isolation of large mononuclear Ia-positive veiled cells from the mouse thoracic duct.
Veiled cells (VC), are not normally present in the mouse thoracic duct lymph (TDL). However, TDL from mesenteric lymph-adenectomized (MLNX) mice contained about 1% VC. After exposure to whole body irradiation of 350-500 rads., or 800 rads., 1.5% and 7% VC respectively were present in the TDL. These cells could be enriched further by density gradient centrifugation on 14.5% metrizamide, about 60-70% VC being present in the cells from the interface. The VC had long sweeping cytoplasmic extensions or veils which were continuously extended and retracted when the VC were incubated at 37 degrees C. Electron microscopy revealed that the VC had a lobulated nucleus, and that the cytoplasm contained many mitochondria, a well-developed Golgi zone, rough endoplasmic reticulum and a few lysosomes. The cells were strongly Ia positive and over 70% showed adenosine triphosphatase activity. These features of the mouse VC from the TDL are similar to those described for VC isolated from different sources in other experimental animals and from the afferent lymph in man.


[On the possibility of reducing systemic side-effects of isoproterenol eyedrops by means of topical propranolol (author's transl)].
Topical administration of Isoproterenol reduces the intraocular pressure in glaucomatous eyes, but produces systemic side-effects (tachycardia arterial hypotension) that make its clinical use unadvisable. Such side-effects are significant when the concentration of Isoproterenol is 4 and 5%. Pre-treatment of the contralateral eye with a solution of Propranolol 1%, 30 and 60 min. before Isoproterenol instillation, markedly reduces systemic side-effects, without diminishing the ocular hypotensive effectiveness.


The evolution of the environmental Kuznets curve hypothesis assessment: A literature review under a critical analysis perspective.
Environmental changes based on factors like urbanization, population, economic growth, increase in energy consumption, and agricultural intensification are never far from the top of any agenda. The topics of environmental degradation and climate change cannot be confined to a single country or region but need to be addressed on a global scale. If the focus is on the relationship between environmental degradation and economic growth, then one hypothesis that is comprehensively used as an empirically model is the widely known Environmental Kuznets Curve. A substantial amount of research has been published about the Environmental Kuznets Curve, and this present study provides a detailed and extensive literature review of more than 200 articles from 1998 to 2022 to explain and assess its evolution. This literature review provides in detail the Environmental Kuznets Curve relationship under analysis, the additional variables included, the type of analysis and methods performed, the relationships obtained, and if the turning point is calculated. Furthermore, this comprehensive literature points out critical issues and gaps in the Environmental Kuznets Curve analysis. It is important to note that there are components that are not considered in the Environmental Kuznets Curve analysis. The Environmental Kuznets Curve only focuses on production and overlooks the impact of the consumption of imported goods on the environment. Consequently, environmental improvements from technological progress will be offset, and economic growth will result in more environmental degradation. This goes against the change in consumer behaviour which occurs with a rise in income, which is one basic assumption of the Environmental Kuznets Curve. The relocation of pollutant industries and consequent relocation of emissions could distort the emissions trajectory over the economic growth path and is also not considered in the Environmental Kuznets Curve analysis. On the other hand, the growth path traced by the inverted U-shaped is not efficient, and the environmental damage provoked in the first phases of the EKC might not be repairable. Therefore, technological progress, climate finance, and energy transition could improve the Environmental Kuznets Curve assessment.


Inhibition of condensation in human chromosomes induced by the thymidine analogue 5-iododeoxyuridine.
Human lymphocyte cultures were treated with iododeoxyuridine. This 5-halogenated thymidine analogue induces distinct undercondensations of the heterochromatin of human chromosome 9. The condensation of the other heterochromatic regions on chromosomes 1, 15, 16 and Y is also inhibited, but to a lesser extent. Optimum cell culture conditions required for the induction of undercondensations were determined. Up to 90% of mitotic cells reveal chromosome 9 heterochromatin decondensations when the substance is present in quantities of 1 x 10(-4) M during the last 7 h before cell fixation. In addition, examples of the usefulness of 5-IUDR in the analysis of chromosome aberrations involving chromosome 9 are presented. The interaction between 5-IUDR and chromosomal DNA, the modification of chromosomal proteins and factors inducing chromosomal decondensations are discussed.


Lipid polymorphism induced by surfactant peptide SP-B(1-25).
Pulmonary surfactant protein B (SP-B) is an essential protein for lowering surface tension in the alveoli. SP-B(1-25), a peptide comprised of the N-terminal 25 amino-acid residues of SP-B, is known to retain much of the biological activity of SP-B. Circular dichroism has shown that when SP-B(1-25) interacts with negatively charged lipid vesicles, it contains significant helical structure for the lipid compositions and peptide/lipid ratios studied here. The effect of SP-B(1-25) on lipid organization and polymorphisms was investigated via DSC, dynamic light scattering, transmission electron microscopy, and solid-state NMR spectroscopy. At 1-3 mol% peptide and physiologic temperature, SP-B(1-25) partitions at the interface of negatively charged PC/PG lipid bilayers. In lipid mixtures containing 1-5 mol% peptide, the structure of SP-B(1-25) remains constant, but (2)H and (31)P NMR spectra show the presence of an isotropic lipid phase in exchange with the lamellar phase below the T(m) of the lipids. This behavior is observed for both DPPC/POPG and POPC/POPG lipid mixtures as well as for both the PC and PG components of the mixtures. For 1-3 mol% SP-B(1-25), a return to a single lamellar phase above the lipid mixture T(m) is observed, but for 5 mol% SP-B(1-25) a significant isotropic component is observed at physiologic temperatures for DPPC and exchange broadening is observed in (2)H and (31)P NMR spectra of the other lipid components in the two mixtures. DLS and TEM rule out the formation of micellar structures and suggest that SP-B(1-25) promotes the formation of a fluid isotropic phase. The ability of SP-B(1-25) to fuse lipid lamellae via this mechanism, particularly those enriched in DPPC, suggests a specific role for the highly conserved N-terminus of SP-B in the packing of lipid lamellae into surfactant lamellar bodies or in stabilizing multilayer structures at the air-liquid interface. Importantly, this behavior has not been seen for the other SP-B fragments of SP-B(8-25) and SP-B(59-80), indicating a critical role for the proline rich first seven amino acids in this protein.


Studies with flavin analogs provide evidence that a protonated reduced FMN is the substrate-induced transient intermediate in the reaction of Escherichia coli chorismate synthase.
Chorismate synthase catalyzes the 1,4-elimination of phosphate and the C-(6-pro-R) hydrogen from 5-enolpyruvylshikimate 3-phosphate (EPSP) to generate chorismate. Although this reaction does not involve an overall change in redox state, the enzyme requires reduced FMN. To investigate the role of the flavin in catalysis we have employed chemically modified flavins: 1- and 5-deaza-, 2- and 4-thio-, 6-hydroxy-, 8-nor-6-methyl-, 8-methyl-sulfonyl-, 8-chloro-, 8-fluoro-, 8-nor-methyl-, 8-S-methyl-, 8-methoxy, 8-mercapto- and 8-amino-FMN. Photoreduction of 4-thio-FMN in the presence of chorismate synthase at pH 7.5 produced a reduced flavin species with an absorbance maximum at lambda = 410 nm indicative of monoanionic, reduced 4-thio-FMN. Binding of 8-mercapto- and 6-hydroxy-FMN to chorismate synthase in the presence of EPSP or (6R)-6-fluoro-EPSP resulted in an increase of the flavin analogs' pKa values by 4 and 1 pH units, respectively. On the basis of these findings it is concluded that chorismate synthase preferentially binds neutral flavin species, including the protonated reduced form, rather than anionic flavin species in the presence of EPSP or the 6-fluoro-substrate analog. Further support for this conclusion was obtained using 5-deaza- and 4-thio-FMN. Addition of EPSP to enzyme-bound, reduced 5-deaza-FMN produced spectral changes consistent with protonation of the flavin. Photoreduction of 4-thio-FMN in the presence of enzyme and the (6R)-6-fluoro-EPSP generated a reduced flavin species with absorbance properties of a neutral, reduced 4-thio-flavin. These results and their implications for the nature and kinetic properties of an observed flavin intermediate are discussed in the context of a possible role of reduced flavin as an electron donor to bound EPSP.


Rapid construction of solid-state magnetic resonance powder spectra from frequencies and amplitudes as applied to ESEEM.
In many Fourier-transform spectroscopies, such as pulse magnetic resonance (NMR, EPR), time-domain signals are acquired. Parameters are extracted from these signals by fitting numerical simulations to the experimental data. At present, simulations are often performed in frequency domain (FD). These computations generate a list of frequencies and amplitudes associated with the complex exponential components evolving during one or several variable time intervals. In order to compare simulations with experiments, this peak list is converted to a finite-length time-domain (TD) signal. This can be achieved either by directly evoluting the exponentials in time (direct method) or by rounding their frequencies and binning their amplitudes into a frequency-domain array (histogram method). The first approach is equivalent to a brute-force TD simulation and is slow for a large number of peaks. The second approach is a fast, but very crude approximation and is usually applied without considering in detail the errors involved. A third method introduced and illustrated here is based on the convolution and deconvolution of a short finite impulse response filter kernel. This convolution approach is much faster than the direct method and by orders of magnitude more accurate than the histogram method. For both TD and FD signals a detailed analysis of the errors and of the associated computational costs is presented. The convolution approach is applicable to any simulation problem where TD signals consist of a large number of complex exponentials. In particular, it is the method of choice for simulating 1D and 2D electron spin echo envelope modulation (ESEEM) spectra of disordered systems.


[Accidents in equestrian sports : Analysis of injury mechanisms and patterns].
Equestrian sports are one of the most popular forms of sport in Germany, while also being one of the most accident-prone sports. Furthermore, riding accidents are frequently associated with a high degree of severity of injuries and mortality. Nevertheless, there are insufficient data regarding incidences, demographics, mechanisms of accidents, injury severity and patterns and outcome of injured persons in amateur equestrian sports. Accordingly, it was the aim of the present study to retrospectively analyze these aspects. A total of 503 patients were treated in the emergency room of the Hannover Medical School because of an accident during recreational horse riding between 2006 and 2011. The female gender was predominantly affected with 89.5 %. The mean age of the patients was 26.2 ± 14.9 years and women (24.5 ± 12.5 years) were on average younger than men (40.2 ± 23.9 years). A special risk group was girls and young women aged between 10 and 39 years. The overall injury severity was measured using the injury severity score (ISS). Based on the total population, head injuries were the most common location of injuries with 17.3 % followed by injuries to the upper extremities with 15.2 % and the thoracic and lumbar spine with 10.9 %. The three most common injury locations after falling from a horse were the head (17.5 %), the upper extremities (17.4 %), the thoracic and lumbar spine (12.9 %). The most frequent injuries while handling horses were foot injuries (17.2 %), followed by head (16.6 %) and mid-facial injuries (15.0 %). With respect to the mechanism of injury accidents while riding were predominant (74 %), while accidents when handling horses accounted for only 26 %. The median ISS was 9.8 points. The proportion of multiple trauma patients (ISS > 16) was 18.1 %. Based on the total sample, the average in-hospital patient stay was 5.3 ± 5.4 days with a significantly higher proportion of hospitalized patients in the group of riding accidents. Fatal cases were not found in this study but the danger of riding is not to be underestimated. The large number of sometimes severe injuries with ISS values up to 62 points can be interpreted as an indication that recreational riding can easily result in life-threatening situations. Girls and young women could be identified as a group at particular risk. It has been demonstrated in this study that the three most common injury locations after falling from a horse were the head, the upper extremities, the thoracic and lumbar spine. The most frequent injury locations while handling horses were foot injuries, followed by head and mid-facial injuries.


Transition from paediatric to adult care in cystic fibrosis.
In the decades since cystic fibrosis (CF) was first clinically defined in the 1930s, there have been many advancements in the treatment and management of this disease. Initially it was considered a disease of childhood where the majority of those affected died before reaching adolescence. Now, through advancements in management and treatment, the vast majority of those affected will live into adulthood. Therefore, paediatric and adult CF services must collaborate to ensure that young people and their families experience a positive and supportive transition into adult services. Key aspects of transition will be discussed, including when to begin the transition process, who should coordinate this and how the transition process should be structured. Challenges of the transition process and potential pitfalls when transition does not run smoothly will also be discussed, as well as tools that may be used to support a positive transition for young people and their families. To familiarise readers with factors that make the transition process positive.To make suggestions regarding the application of the transition process.To highlight factors which may impact on the success of the transition process and the risks associated with disengagement at the point of transition.To discuss tools which can be used by care teams to ensure a smooth transition process.


Genome-wide DNA methylome and transcriptome changes induced by inorganic nanoparticles in human kidney cells after chronic exposure.
The unique physicochemical properties make inorganic nanoparticles (INPs) an exciting tool in diagnosis and disease management. However, as INPs are relatively difficult to fully degrade and excrete, their unintended accumulation in the tissue might result in adverse health effects. Herein, we provide a methylome-transcriptome framework for chronic effects of INPs, commonly used in biomedical applications, in human kidney TH-1 cells. Renal clearance is one of the most important routes of nanoparticle excretion; therefore, a detailed evaluation of nanoparticle-mediated nephrotoxicity is an important task. Integrated analysis of methylome and transcriptome changes induced by INPs (PEG-AuNPs, Fe3O4NPs, SiO2NPs, and TiO2NPs) revealed significantly deregulated genes with functional classification in immune response, DNA damage, and cancer-related pathways. Although most deregulated genes were unique to individual INPs, a relatively high proportion of them encoded the transcription factors. Interestingly, FOS hypermethylation inversely correlating with gene expression was associated with all INPs exposures. Our study emphasizes the need for a more comprehensive investigation of INPs' biological safety, especially after chronic exposure.


Nurse executive director effectiveness: a systematic review of the literature.
This report systematically reviews studies of nurse executive director effectiveness to identify recurring themes that might inform current practice and future research. Increasing competition in healthcare markets is increasing the demands on nurse executive directors. There is a need to identify factors that contribute to effectiveness in the role so that these can be developed and effectiveness improved. Reports were identified using electronic databases, an internet search and review of references in all reports initially identified. The methodology of these reports was reviewed and recurring themes were identified. Ten themes that might be associated with nurse executive director effectiveness emerged from the review. The literature relating to nurse executive director effectiveness is limited but there are sufficient recurring themes to inform current practice and to investigate in new research.


Simultaneous removal of acid green 25 and mercury ions from aqueous solutions using glutamine modified chitosan magnetic composite microspheres.
In this current work, the magnetic composite microsphere containing glutamine modified chitosan and silica coated Fe3O4 nanoparticles (CS-Gln-MCM) has been successfully prepared and extensively characterized, which is a kind of biodegradable materials. CS-Gln-MCM shows enhanced removal efficiency for both acid green 25 (AG25), an amphoteric dye, and mercury ions (Hg(2+)) from water in the respective while measured pH range compared with chitosan magnetic composite microsphere (CS-MCM) without modification. It is due to the fact that the grafted amino acid provides a variety of additional adsorption active sites and diverse adsorption mechanisms are involved. In AG25 and Hg(2+) aqueous mixture, the modified adsorbents bear preferential adsorption for AG25 over Hg(2+) in strong acidic solutions ascribed to multiple interactions between AG25 and CS-Gln-MCM, such as hydrogen bonding and electrostatic interactions. While, in weak acidic conditions, an efficient simultaneous removal is observed for different adsorption effects involved in aforementioned two pollutants. Besides, CS-Gln-MCM illuminates not only short equilibrium time for adsorption of each pollutant less than 20.0 min but also rapid magnetic separation from water and efficient regeneration after saturated adsorption. Therefore, CS-Gln-MCM bears great application potentials in water treatment.


Relationship of body mass index and dental caries with oral health related quality of life among adolescents of Udupi district, South India.
To evaluate the relationship of body mass index (BMI) and dental caries with oral health related quality of life (OHRQoL) among adolescents of Udupi district, India. A cross-sectional survey of 13-15-year-old adolescents was conducted. A self-administered questionnaire was used to collect information on age, gender, type of school, frequency of sugar consumption and child oral impacts on dental performances (OIDP). Weight, height and dental caries were recorded as per standard guidelines. Of 456 children, 34.4 % were overweight/obese. There was a significant difference in the distribution of overweight/obese adolescents with respect to age, gender and frequency of sugar consumption. The prevalence of impacts ranged from 7.4-32.8 % in low normal and 12.9-49.7 % in overweight/obese adolescents. Impacts while eating were most frequently reported in both low normal (32.8 %) and overweight/obese (49.7 %) adolescents. There was a significantly higher mean for overweight/obese than low normal adolescents for items related to "eating", "speaking", "sleeping", "smiling", "emotional status", OIDP total score and caries. BMI and decayed teeth (DT) showed significant association with OIDP-Additive score. Adolescents with caries and increased BMI had poor OHRQoL.


Ozone distribution in remote ecologically vulnerable terrain of the southern Sierra Nevada, CA.
Ozone concentration spatial patterns remain largely uncharacterized across the extensive wilderness areas of the Sierra Nevada, CA, despite being downwind of major pollution sources. These natural areas, including four national parks and four national forests, contain forest species that are susceptible to ozone injury. Forests stressed by ozone are also more vulnerable to other agents of mortality, including insects, pathogens, climate change, and ultimately fire. Here we analyze three years of passive ozone monitor data from the southern Sierra Nevada and interpolate landscape-scale spatial and temporal patterns during the summer-through-fall high ozone concentration period. Segmentation analysis revealed three types of ozone exposure sub-regions: high, low, and variable. Consistently high ozone exposure regions are expected to be most vulnerable to forest mortality. One high exposure sub-region has been documented elsewhere as being further vulnerable to increased drought and fire potential. Identifying such hot-spots of forest vulnerability has utility for prioritizing management.


Exudative pleural effusion following thoracoscopic pulmonary vein isolation for paroxysmal atrial fibrillation.
Surgical treatments for atrial fibrillation are gaining popularity. We present a case of post-cardiac injury syndrome following thoracoscopic pulmonary vein isolation.


Podophyllotoxin, steganacin and combretastatin: natural products that bind at the colchicine site of tubulin.
A large number of antimicrotubule agents are known that bind to tubulin in vitro and disrupt microtubule assembly in vitro and in vivo. Many of these agents bind to the same site on the tubulin molecule, as does colchicine. Of these, the natural products podophyllotoxin, steganacin and combretastatin are the subjects of this review. For each of these, the chemistry and biochemistry are described. Particular attention is given to stereochemical considerations. Biosynthetic pathways for podophyllotoxin and congeners are surveyed. The binding to tubulin and the effects on microtubule assembly and disassembly are described and compared. In addition, structural features important to binding are examined using available analogs. Several features significant for tubulin interaction are common to these compounds and to colchicine. These are described and the implications for tubulin structure are discussed. The manifold results of applying these agents to biological systems are reviewed. These actions include effects that are clearly microtubule mediated and others in which the microtubule role is less obvious. Activity of some of these compounds due to inhibition of DNA topoisomerase is discussed. The range of species in which these compounds occur is examined and in the case of podophyllotoxin is found to be quite broad. In addition, the range of species that are sensitive to the effects of these compounds is discussed.


New Techniques for Optimization of Donor Lungs/Hearts.
Injuries sustained by donor heart and lung allografts during the transplantation process are multiple and cumulative. Optimization of allograft function plays an essential role in short- and long-term outcomes after transplantation. Therapeutic targets to prevent or attenuate injury are present in the donor, the preservation process, during transplantation, and in postoperative management of the recipient. The newest and most promising methods of optimizing donor heart and lung allografts are found in alternative preservation strategies, which enable functional assessment of donor organs and provide a modality to initiate therapies for injured allografts or prevent injury during reperfusion in recipients.


Rapid prototyping of database systems in human genetics data collection.
This work examines some of the problems encountered in developing small and large database application systems involving human genetics data collection efforts that include data on individuals as well as family pedigree data. Rapid prototyping of a database application requires software tools to produce the application with little or no programming. Features of MEGADATS-4 that provide for rapid prototyping and for producing stand-alone applications are examined.


Potentialities and limitations of computer-aided design and manufacturing technology in the nonextraction treatment of Class I malocclusion.
Computer-aided design and manufacturing (CAD-CAM) systems have assisted orthodontists to position brackets virtually. The purpose of this study was to evaluate if a CAD-CAM system could predict the orthodontic treatment outcome of patients with Angle Class I malocclusion with mild crowding or spacing and with no need for orthodontic extraction. Using the American Board of Orthodontics Cast-Radiograph Evaluation (ABO-CRE) and color map superimposition, the treated occlusion was compared with the virtual final occlusion of 24 young adults with Class I occlusion. Using eXceed software (eXceed, Witten, Germany), we created the final occlusion prediction for each patient (virtual set up group). A digital model of the final occlusion of each patient was created (treated occlusion group). ABO-CRE score was used to compare groups. In addition, a color map was created for all subjects to access the mean and range values between the virtual set up model and treated occlusion model of each patient. Random and systematic errors were calculated. In addition, chi-square and t test were used. Comparisons between virtual set up occlusion and treated occlusion showed statistically significant differences in 3 out of 7 measurements: interproximal contact score was larger for treated than virtual occlusion (0.45 mm and 0.04 mm, respectively), and the treated occlusion showed larger values than the virtual occlusion for occlusal contacts (14.13 mm and 7.62 mm, respectively) and overjet (7.37 mm and 0.66 mm, respectively). Although the treated occlusion showed a larger score than the virtual occlusion (50.41 mm and 34.58 mm, respectively), there is no significant difference between both. Root angulation decreased (from 1.95 ± 1.29 to 0.65 ± 0.71) because of the treatment. ABO-CRE overall score presents no difference between groups. In addition, CAD-CAM setup occlusion closely predicts the final teeth alignment and leveling with interarch relationships showing less ABO-CRE score deduction.


Antibacterial activity of silver doped hydroxyapatite toward multidrug-resistant clinical isolates of Acinetobacter baumannii.
Bacteria Acinetobacter baumannii is a persistent issue in hospital-acquired infections due to its fast and potent development of multi-drug resistance. To address this urgent challenge, a novel biomaterial using silver (Ag+) ions within the hydroxyapatite (HAp) lattice has been developed to prevent infections in orthopedic surgery and bone regeneration applications without relying on antibiotics. The aim of the study was to examine the antibacterial activity of mono-substituted HAp with Ag+ ions and a mixture of mono-substituted HAps with Sr2+, Zn2+, Mg2+, SeO32- and Ag+ ions against the A. baumannii. The samples were prepared in the form of powder and disc and analyzed by disc diffusion, broth microdilution method, and scanning electron microscopy. The results from the disc-diffusion method have shown a strong antibacterial efficacy of the Ag-substituted and mixture of mono-substituted HAps (Sr, Zn, Se, Mg, Ag) toward several clinical isolates. The Minimal Inhibitory Concentrations for the powdered HAp samples ranged from 32 to 42 mg/L (Ag+ substituted) and 83-167 mg/L (mixture of mono-substituted), while the Minimal Bactericidal Concentrations after 24 h of contact ranged from 62.5 (Ag+) to 187.5-292 mg/L (ion mixture). The lower substitution level of Ag+ ions in a mixture of mono-substituted HAps was the cause of lower antibacterial effects measured in suspension. However, the inhibition zones and bacterial adhesion on the biomaterial surface were comparable. Overall, the clinical isolates of A. baumannii were effectively inhibited by substituted HAp samples, probably in the same amount as by other commercially available silver-doped materials, and such materials may provide a promising alternative or supplementation to antibiotic treatment in the prevention of infections associated with bone regeneration. The antibacterial activity of prepared samples toward A. baumannii was time-dependent and should be considered in potential applications.


Current Patterns of Treatment and Outcomes in Advanced Melanoma at a Single Institution.
Treatment of advanced melanoma has been transformed by novel systemic therapies. The purpose of this study is to describe the current utilization patterns of immunotherapies with respect to survival outcomes in advanced melanoma. We performed a retrospective cohort study of patients with Stage 3 and 4 melanoma at our institution (2009-2019). Primary outcomes included overall survival (OS) and progression free survival (PFS). Kaplan-Meier survival analysis and Cox proportional hazards regression analysis evaluated associations between covariates and survival outcomes. Of 244 patients, 5-y OS was 62.4%. Lymphovascular invasion (hazard ratio [HR] = 2.462, P = 0.030) was associated with shorter PFS whereas female gender (HR = 0.324, P = 0.010) was associated with longer PFS. Residual tumor (HR = 146, P = 0.006) and Stage 4 disease (HR = 3.349, P = 0.011) were associated with shorter OS. Use of immunotherapy increased from 2% to 23% over the study period, and use of neoadjuvant immunotherapy also increased up to 2016. Timing of immunotherapy administration was not significantly associated with survival. Of the 193 patients who received 2 or more treatment types, the most common treatment sequence was surgery followed by immunotherapy (n = 117, 60.6%). Immunotherapy is increasingly used for treatment of advanced melanoma. In this heterogeneous cohort, there was no significant association between timing of immunotherapy and survival outcomes.


Procrastination as evidence of executive functioning impairment in college students.
Research addressing procrastination behavior has historically focused upon personality and situational factors to explain the nature of this problematic behavior. Although researchers have identified personality traits that are closely associated with procrastination behavior, the literature is sparse in addressing other possible explanations, particularly those related to brain functioning. Considering that procrastination is described with terms such as "poor time management," "lack of planning," and "poor judgment," amongst others, one might consider whether executive functioning systems are functioning adequately in these individuals. Individuals who demonstrate difficulties with executive functioning tend to share the same characteristics that are applied to those who procrastinate.Preliminary self-report research by Jurado and Rosselli found that undergraduates who reported higher levels of procrastination, also reported high levels of executive functioning difficulties. This research project replicated and extended these findings utilizing three common neuropsychological measures of executive functioning. The results from these measures demonstrated that individuals who showed impairment in executive functioning also reported difficulties with executive functioning and procrastination.


CNS relapse of acute myelogenous leukemia masquerading as pseudotumor cerebri.
An 18-year-old man in remission from acute myelogenous leukemia 3 years after a bone marrow transplant presented with signs of pseudotumor cerebri, including headache, visual changes, and papilledema. He manifested elevated opening pressure on lumbar puncture and positive cytology, with a concurrent normal bone marrow aspirate and biopsy. He was diagnosed with an isolated central nervous system relapse of acute myeloid leukemia. Although the precise etiology remains elusive, this case demonstrates that pseudotumor cerebri must remain within the differential diagnosis after other complications are excluded, particularly in persons with underlying hematologic malignancies.


Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in Denmark.
Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS. We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients, or emergency-room visitors) in the Danish National Patient Registry and compared them with adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining the date of admission or laboratory findings as the index date. We characterized these cohorts by demographics, comorbidity, medication use, and laboratory and histopathologic findings. We identified 1139 patients with hospital-recorded NS and 5268 patients with nephrotic proteinuria and hypoalbuminemia; of these, 760 patients were identified in both cohorts. Within 1 year of the first record of nephrotic proteinuria and hypoalbuminemia, 18% had recorded hospital diagnoses indicating the presence of NS, and 87% had diagnoses reflecting any kind of nephropathy. Among patients identified with nephrotic proteinuria and hypoalbuminemia, their most recent eGFR was substantially lower (median of 35 versus 61 ml/min per 1.73 m2), fewer underwent kidney biopsies around the index date (34% versus 61%), and the prevalence of thromboembolic disease (25% versus 17%) and diabetes (39% versus 18%) was higher when compared with patients with hospital-recorded NS. Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they have a lower eGFR and more comorbidities. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS.


Structure of the C3b binding site of CR1 (CD35), the immune adherence receptor.
Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that mediates the immune adherence phenomenon, a fundamental event for destroying microbes and initiating an immunological response. It fulfills this role through binding C3b/C4b-opsonized foreign antigens. The structure of the principal C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three complement control protein modules (modules 15-17) in an extended head-to-tail arrangement with flexibility at the 16-17 junction. Structure-guided mutagenesis identified a positively charged surface region on module 15 that is critical for C4b binding. This patch, together with basic side chains of module 16 exposed on the same face of CR1, is required for C3b binding. These studies reveal the initial structural details of one of the first receptor-ligand interactions to be identified in immunobiology.


The effect of thrombocytapheresis on hemogram and biochemistry parameters in patients with essential thrombocytemia.
Essential thrombocythemia is one of the chronic myeloproliferative neoplasms characterized by clonal proliferation of myeloid cells with variable morphological maturation and hematopoietic activity.It is characterized by excessive clonal platelet production with a tendency to thrombosis and bleeding. Thrombocytapheresıs is the removal of platelets by apheresis techniques. Thrombocytapheresıs is generally recommended in patients with essential thrombocythemia with acute, severe thrombotic or hemorrhagic events. The study included 39 patients who were diagnosed with essential thrombocythemia, started cytoreductive and aspirin therapy, and underwent thrombocytapheresıs due to the development of acute severe thrombotic or hemorrhagic events, diagnosed in the adult hematology clinic of İnönü University Turgut Ozal Medical Center. Hemogram and biochemistry values of the patients were scanned retrospectively. After thrombocytapheresıs, a statistically significant difference was found between the first and last measurements of hemoglobin, mean platelet volume, White blood cell, neutrophil, platelet, platelet distribution width, creatine, lactate dehydrogenase, fibronogen and calcium levels of the patients. The use of thrombocytapheresıs in patients with essential thrombocytosis causes a rapid decrease in platelet values as well as an effect on hemogram and biochemistry parameters. Other hemogram and biochemistry parameters such as platelet value should be monitored in patients.


Ideology as resistance: a supervisory challenge.
A number of contemporary psychiatric schools of thought, in addition to enriching the field, may be employed by the psychiatric trainee in the service of resistances to learning and growth. These phenomena are surveyed and the implications for supervision discussed.


Re-evaluation of the inheritance for root-knot nematode resistance in the Upland cotton germplasm line M-120 RNR revealed two epistatic QTLs conferring resistance.
We report a second major QTL for root-knot nematode resistance in the highly resistant Upland cotton line M-120RNR and show epistasis between two resistant QTLs with different mechanisms conferring resistance. In an earlier study, we identified a major QTL on Chromosome 11 associated with resistance to root-knot nematode in the M-120 RNR Upland cotton line (Gossypium hirsutum L.) of the Auburn 623 RNR source. Herein, we re-evaluated the genetics of the resistance to root-knot nematode in the M-120 RNR × Pima S-6 population by linkage mapping using recently published SSR markers. The QTL analysis detected two regions significantly associated with the resistance phenotype. In addition to the QTL previously identified on Chromosome 11 (qMi-C11), a major QTL was identified on Chromosome 14 (qMi-C14). The resistance locus on qMi-C11 originated from the Clevewilt parent, while the qMi-C14 locus originated from the other resistant parent, Mexico Wild Jack Jones. The qMi-C14 locus had logarithms of odds score of 17 and accounted for 45 % of the total phenotype variation in egg production. It was also associated with galling index, but the percent variation explained was only 6 %, suggesting that the qMi-C11 locus had a much stronger effect on root gall suppression than egg production, while the qMi-C14 locus had a stronger effect on egg production than galling. The results also suggest that the transgressive segregation observed in the development of Auburn 623 RNR was due to the pyramiding of at least two main effect QTLs as well as an additive-by-additive epistatic effects between the two resistant loci. The SSRs markers tightly linked to the qMi-C11 and qMi-C14 loci will greatly facilitate the improvement of RKN resistance in cotton via marker-assisted breeding.


Endoscopic cartilage butterfly myringoplasty in children.
The present study evaluated the results of the graft success rate and hearing gain of children who underwent endoscopic inlay butterfly myringoplasty due to chronic otitis media. The study included 32 pediatric patients aged between 8 and 17, who had endoscopic inlay butterfly myringoplasty with the diagnosis of chronic otitis media between September 2012 and January 2015 in Elazig Training and Research Hospital Otorhinolaryngology Clinic and Firat University Otorhinolaryngology Clinic. All patients' demographics, perforation size, and hearing status were examined. Tympanic membrane perforation was ≤3mm in 12 patients and between 3 and 6mm in 20 patients. The air-bone gap (ABG) of the patients was 18.5±6.29dB preoperatively, 8.81±3.53dB postoperatively second month, 8.09±3.55dB postoperatively sixth month, and 7.96±3.32dB postoperatively 12th month. Two (6.3%) of the patients had postoperative myringitis. Two (6.3%) patients had recurrent perforation in the postoperative follow-ups. In children, endoscopic inlay butterfly tympanoplasty is a surgical technique with short duration, high graft success, effective hearing reconstruction, and high levels of postoperative patient comfort.


Aromatic Aza-Claisen Rearrangement of Arylpropargylammonium Salts Generated in situ from Arynes and Tertiary Propargylamines.
The charge-accelerated aza-Claisen rearrangement of ammonium salts serves as a key step in the construction of complex nitrogen-containing molecules. However, much less attention has been paid to the aromatic aza-Claisen rearrangement than to the aliphatic one. Herein, we report an unprecedented aromatic aza-Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary propargylamines, delivering structurally diverse 2-propargylanilines in moderate to good yields with high regioselectivity. This rearrangement proceeds in the absence of strong bases or transition metals, is compatible with moisture and air, tolerates a wide variety of functional groups, and is amenable to forming 11- to 13-membered heterocycles with a triple bond. The 2-propargylaniline products were treated with aluminum chloride in ethanol to afford multisubstituted indoles in moderate to excellent yields. Finally, a series of deuterium-labeling experiments was performed to elucidate the reaction mechanism.


Determination of mechanisms of myocardial ischemic injury by 31P-MRS effect of catecholamine on ischemic hearts.
To investigate mechanisms of development in ischemic myocardial injury, intracellular pH and high energy phosphates in perfused guinea-pig hearts were monitored by 31P-MRS. Intracellular ATP content decreased to 1.2% and 26.4% of control during 60 minutes global ischemia, respectively with and without preischemic administration of isoproterenol. Intracellular pH declined to 6.48 and 6.03 respectively. Postischemic cardiac function was severely impaired by isoproterenol. ATP breakdown had little influence on intracellular pH in ischemic hearts. It was verified that inotropic agents can progress ischemic myocardial injury, and that contractile recovery is more correlated with the residual ATP level than intracellular pH.


Direct quantification of autologous serum albumin leakage after burn injury in mice.
The current technique determining the extent of capillary leakage after injury is to measure the leakage of dye-labeled foreign albumin. A recent report, however, demonstrated that albumin leakage is dependent upon the type of fluorescent dye used for labeling. We chose to develop and test a technique for determining the extent of vascular albumin leakage after burn injury without the use of dyes. Skin and blood samples were harvested at 3h and 7 days after burn injury in mice. Total skin lysates and extracts as well as sera were analyzed for albumin leakage. Coomassie staining and Western blot analyses of skin preparations followed by the densitometric measurement revealed increased levels of albumin, suggesting that the leakage of serum albumin started within 3h after burn injury. Instead of employing dye-labeled foreign albumin, the use of SDS-polyacrylamide gel electrophoresis of tissue extracts followed by Coomassie staining will allow for a simple and direct quantification of autologous albumin leakage due to burn as well as other types of injury.


Open-label, prospective, randomized comparison of propofol and sevoflurane for laryngeal mask anesthesia for magnetic resonance imaging in pediatric patients.
Magnetic resonance imaging (MRI) for pediatric patients often requires deep sedation or anesthesia because they must remain completely immobile for a relatively long period to obtain high-quality images. The aim of this study was to compare the effectiveness of propofol i.v. or inhalation of sevoflurane anesthesia with the laryngeal mask airway (LMA) for children undergoing MRI. Children aged 2 to 6 years with American Society of Anesthesiologists' physical status of I to II who were scheduled for MRI were enrolled in this study and randomly divided into 2 groups. The propofol group was administered propofol 4 mg/kg i.v. followed by infusion of 150 microg/kg x min(-1). Patients in the sevoflurane group were induced with sevoflurane 8% by face mask and maintained with an air/oxygen mixture followed by sevoflurane 1.5%. Data recorded included age, weight, scan time, LMA insertion, removal, and recovery times, hemodynamic parameters, complications, pediatric anesthesia emergence delirium (PAED) scale score, child movement, and MRI interruption. A higher PAED score indicated a higher level of delirium. Eighty-eight children were enrolled and randomized to treatment. Nine children were excluded from analysis due to protocol violations. After completion of the study, there were 37 children in the propofol group (male/female, 18/19; mean [SD] age, 42.1 months; weight, 15.2 [4.9] kg; scan time, 20.5 [4.6] min) and 42 in the sevoflurane group (male/female, 15/27; mean [SD] age, 44.4 [26.1] months; weight, 15.1 [5.2] kg; scan time, 20.6 [4.8] min). No significant differences were found between the study groups with regard to age, weight, scan time, and hemodynamic parameters at baseline and during the study period. Mean LMA insertion, removal, and recovery times were significantly longer in the propofol group (4.8, 5.2, and 8.8 minutes, respectively) than in the sevoflurane group (3.3, 2.5, and 3.9 minutes, respectively) (P < 0.05). The mean PAED score in the propofol group was significantly lower than that in the sevoflurane group (mean [SD], 6.1 [4.0] vs 10.5 [3.7]; P < 0.05). The percentage of MRI interruption in the propofol group was significantly higher than that in the sevoflurane group (4 [11%] vs 0, respectively; P < 0.05). No episodes of hypotension or bradycardia occurred during the study, and alterations in the propofol infusion rate or sevoflurane concentration were not necessary. One child vomited in the sevoflurane group during the postoperative period. This small study found that sevoflurane, at the doses used in this study, provided shorter induction and faster recovery times than i.v. propofol for LMA anesthesia in these selected children undergoing MRI. The percentage of MRI interruption in the propofol group was significantly higher than that in the sevoflurane group. Sevoflurane was associated with a significantly higher score on the PAED scale, indicating greater emergence delirium.


Acute morphine administration alters the power of local field potentials in mesolimbic pathway of freely moving rats: Involvement of dopamine receptors.
Increasing number of evidence support the role of ventral tegmental area (VTA) and nucleus accumbens (NAc) in mediating the opiate effects as the two critical components of brain reward pathway. It is believed that VTA to NAC dopaminergic projections mediate the reinforcing effects induced by opioid drugs. Although numerous studies have investigated mechanisms of reward processing in these brain regions, alterations of local field potentials (LFPs), as an index of total synaptic currents, has not been previously addressed. In the present study, thin metal electrodes were implanted in both VTA and shell sub-region of NAc to simultaneously record the spontaneous LFPs in freely moving rats. After one week recovery period, a single dose of morphine was systemically administered and the LFP recording was performed 15, 30, 45 and 60 post-injection. Also, in order to assess the role of dopamine system, two groups of animals were pre-treated by selective antagonists of dopamine type-1 and type-2 receptors 15 min prior to morphine injection. The obtained results indicated that in VTA, acute morphine administration potentiates the power of all LFP frequency bands (i.e. delta, theta, alpha, beta and gamma). However, in NAc shell, theta wave was significantly attenuated by morphine and other components were not affected. In addition, pre-treatment with both antagonists prevented the observed effect of morphine on LFP power suggesting the involvement of dopamine receptors in this process. Future studies should address mechanisms of dopamine-morphine interactions. It is also valuable to focus on acute and chronic effects of morphine on LFP power and assessment of the observed effects following naloxone challenge.


Modulating cerebello-thalamocortical pathways by neuronavigated cerebellar repetitive transcranial stimulation (rTMS).
Increasing evidence suggests that dysfunctions of the cortico-cerebello-thalamocortical circuit are involved in the pathophysiology of neuropsychiatric disorders. This study explores the effects of cerebellar repetitive transcranial magnetic stimulation (rTMS) on cerebello-thalamocortical pathways. Ten healthy volunteers received MRI-guided rTMS in four separate sessions (120% motor threshold, 1000 stimuli) over either the medial or the right lateral cerebellum using frequencies of 1 and 10 Hz. Motor cortex excitability was assessed before and after the intervention by paired-pulse transcranial magnetic stimulation. Depending on stimulation frequency, cerebellar rTMS differentially modified intracortical inhibition. Low frequency rTMS increased short intracortical inhibition (SICI), whereas high frequency rTMS had no significant effect on SICI. These results suggest that rTMS over the cerebellum can modulate cerebello-thalamocortical pathways in a frequency-specific manner.


PD-L1 and PD-1 expression are correlated with distinctive clinicopathological features in papillary thyroid carcinoma.
Immune checkpoint blockade targeting PD-1/PD-L1 has shown efficacy in several types of cancers. However, the correlation between PD-L1/PD-1 expression and the specific clinicopathological features in papillary thyroid carcinoma (PTC) has not been investigated. We examined the immunohistochemical expression of PD-L1, PD-1, and BRAF V600E on whole-tissue sections from 126 cases of primary PTC more than 1 cm in size. The correlation between the PD-L1/PD-1 expression and the clinicopathological features was evaluated. PD-L1 was positively expressed in 53.2% PTCs, and its expression was positively correlated with rich tumor-infiltrating lymphocytes (TILs), background chronic lymphocytic thyroiditis (CLT), female gender, absence of psammoma bodies, and PD-1 expression. Among these parameters, rich TILs, female gender, and absence of psammoma bodies were independent factors affecting PD-L1 expression on the multivariate logistic regression analysis. PD-1 expression was detected in the TILs and was positively correlated with rich TILs, background CLT, and absence of stromal calcification. Lack of stromal calcification was an independent factor affecting PD-1 expression. Neither PD-L1 nor PD-1 expression showed significant correlation with BRAF V600E expression. Our results show that the distinctive pathological features of PTCs, including TILs, background CLT, female gender, psammoma bodies, and stromal calcification, are useful parameters for predicting PD-L1 or PD-1 expression.


Ileocecal, colonic, and peritoneal tuberculosis: role of imaging in diagnosis. A case report and literature review.
Tuberculosis is a widespread infectious disease that still remains a deadly global health problem and a condition that is life-threatening if misdiagnosed. Extrapulmonary manifestations are prevalent in the endemic areas but limited to the immunocompromised and immigrants in economically developed areas. False diagnostic situations rely on non-specific investigatory findings, the wide spectrum of clinical manifestations, and problems in discriminating between inflammation and neoplasms of the bowel. For an early diagnosis, a high index of suspicion and correlation of clinical and imaging aspects, as well as findings from colonoscopy, tissue biopsy, and microbiologic assessments, are necessary. We present a case of a patient with non-specific abdominal symptoms, mimicking a clinical syndrome of neoplastic impregnation, finally diagnosed as ileal tuberculosis with peritoneal involvement. We stress the importance of ultrasonography as a primary method of investigation, having an important role in raising the suspicion of an infectious bowel disease, as well as the role of contrast-enhanced ultrasound examination.


Receipt of Pediatric Weight-Related Counseling and Screening in a National Sample After the Expert Committee Recommendations.
It is uncertain whether children of all weight classifications receive the recommended screening and counseling and if these affect weight status in the subsequent year. Data from the 2008-2011 Medical Expenditures Panel Survey were used to examine associations between weight classification and receipt of weight-related screening and counseling from the pediatric provider (n = 9835). Body mass index (BMI) z-score in the subsequent year was modeled as a function of the BMI z-score in year 1. Normal and overweight children have lower odds than obese children of receiving counseling regarding diet (adjusted odds ratio [AOR] = 0.58, 95% confidence interval [CI] = 0.50-0.68; AOR = 0.75, 95% CI = 0.63-0.89, respectively) and exercise (AOR = 0.56, 95% CI = 0.48-0.65; AOR = 0.75, 95% CI = 0.64-0.89, respectively). Counseling was associated with a small increase in BMI z-score in the subsequent year (β = 0.06, 95% CI = 0.01-0.11), as was maternal weight class. Recommendations to focus prevention on the family unit may reduce childhood overweight and obesity.


Technique of color Doppler quantification of vascularity in transplanted kidneys.
A new technique for the quantification of vascularity based on the analysis of color Doppler images is described. We utilized velocity information obtained directly from cineloops transferred to a computer for off-line analysis. This methodology was used in transplanted kidneys to assess parenchymal vascularity on the basis of percentage color pixel density and mean flow velocity in mid-kidney cross-sectional regions of interest and the distance from the most peripheral color pixels to the capsule of the kidney. Other color Doppler quantitative methods have lacked reproducibility, and therefore before evaluation of the clinical usefulness of this technique, intraobserver reproducibility and interobserver reliability were assessed in 42 patients; no statistically significant variation was demonstrated. In 13 patients with normally functioning transplants, the mean maximum color pixel density was 34.7+/-13.4%, the mean flow velocity was 5.2+/-0.9 cm/second, and the mean distance to the capsule was 3.3+/-1.1 mm.


[The diagnosis of the main histological types of lung cancer by means of cytological smears (author's transl)].
The paper emphasizes the possibility to distinguish types I, II and III (WHO classification) of lung cancer not only by means of single cells, but also of tissue solids in cytological smears. The morphologic criteria of tissue solids and their special patterns in the different main types of lung cancer are described.


Metal-Organic Framework Aerogel for Full pH Range Operation and Trace Adsorption of Arsenic in Water.
The UiO-66-NH2 aerogel has been designed to remove As(III) and As(V) in the full pH range with a long lifetime. The efficiency of the aerogel for trace removal from river water samples at the sub-ppb level has been demonstrated. The feasibility for practical uses has been evaluated by breakthrough experiments operated at a liquid hourly space velocity (LHSV) of 38 h-1 using a real water sample with a significant capacity of 284 mg g-1. The UiO-66-NH2 aerogel provides a lifetime of over 600 min, which is one of the highest lifetimes among the reported adsorbents for arsenic decontamination.


Low sucrose levels promote extensive Streptococcus mutans-induced dental caries.
One-tenth percent sucrose significantly promotes dental caries induced by Streptococcus mutans in young gnotobiotic rats. Maximum caries activity was observed in rats provided a purified diet containing 3% sucrose.


The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis.
Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications.


Variations in the critical cycle length inducing rate dependent bundle branch block.
In five patients with tachycardic RDBBB (rate dependent bundle branch block), variations in the critical CL (cycle length) inducing RDBBB were investigated. In one patient, independent of changes in the preceding CL, the critical CL inducing RDBBB was invariable, extending over two years. In the other patients, the critical CL inducing RDBBB varied within a comparatively short period. However, when RDBBB was maintained for only a few cycles, the critical CL allowing reversion to normal conduction was always longer than the critical CL inducing RDBBB here, in all patients except one. In one patient such a distinct difference in CL could not be disclosed because the critical CL inducing RDBBB varied from cycle to cycle. These observations suggest that independent of variations in the refractory period of the blocked bundle branch, the critical CL allowing reversion to normal conduction was considerably longer than this refractory period in all patients. The possible mechanisms by which RDBBB could be maintained are discussed. The most probable mechanism appears to be "true" unidirectional block in the affected bundle branch, in which the refractory period for the retrogradely conducted impulse is shorter than that for the anterogradely conducted impulse.


Influences of barriers to cessation and reasons for quitting on substance use among treatment-seeking smokers who report heavy drinking.
We examined behavioral and cognitively-based quit processes among concurrent alcohol and tobacco users and assessed whether smoking and drinking were differentially influenced. Participants were 200 treatment-seeking smokers (37.50% female; Mage = 30.72; SD = 12.68) who reported smoking an average of 10 or more cigarettes daily for at least one year. Barriers to cessation (BCS) and reasons for quitting (RFQ) were generally correlated with substance use. BCS moderated the relationship between quit methods and cigarette use such that quit methods were negatively associated with smoking, particularly among those with more BCS. RFQ moderated the association between quit methods and cigarette use such that quit methods were negatively linked with smoking among those with fewer RFQ, but positively linked with smoking among those with more RFQ. Two 3-way interactions emerged. The first 3-way indicated that among individuals with fewer RFQ, quit methods was negatively associated with smoking, and this was strongest among those with more BCS. However, among those with more RFQ, smoking and quit methods were positively associated, particularly among those with more BCS. The second 3-way showed that among those with fewer RFQ, quit methods was negatively linked with drinking frequency, and this was strongest among those with more BCS. However, among those with fewer BCS, drinking and quit methods were positively linked. The relationship between behavioral and cognitively-based quit processes and substance use is not straightforward. There may be concurrent substance-using individuals for whom these processes might be associated with increased substance use.


The spinal cord and brain in myelodysplasias.
This chapter defines various neurological abnormalities and terms specific to the management of spina bifida and related disorders..


Secondary batteries with multivalent ions for energy storage.
The use of electricity generated from clean and renewable sources, such as water, wind, or sunlight, requires efficiently distributed electrical energy storage by high-power and high-energy secondary batteries using abundant, low-cost materials in sustainable processes. American Science Policy Reports state that the next-generation "beyond-lithium" battery chemistry is one feasible solution for such goals. Here we discover new "multivalent ion" battery chemistry beyond lithium battery chemistry. Through theoretic calculation and experiment confirmation, stable thermodynamics and fast kinetics are presented during the storage of multivalent ions (Ni(2+), Zn(2+), Mg(2+), Ca(2+), Ba(2+), or La(3+) ions) in alpha type manganese dioxide. Apart from zinc ion battery, we further use multivalent Ni(2+) ion to invent another rechargeable battery, named as nickel ion battery for the first time. The nickel ion battery generally uses an alpha type manganese dioxide cathode, an electrolyte containing Ni(2+) ions, and Ni anode. The nickel ion battery delivers a high energy density (340 Wh kg(-1), close to lithium ion batteries), fast charge ability (1 minute), and long cycle life (over 2200 times).


Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing.
Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma.


Quantitative interactions between Pb2+ and Ca2+ homeostasis in cultured osteoclastic bone cells.
Cellular calcium homeostasis and calcium-mediated cell functions are conceptually attractive processes to be involved in the manifestation(s) of lead toxicity including impaired skeletal growth and cardiovascular and neurological dysfunction. Knowledge of Ca:Pb and Pb:Ca ratios in different structural and functional compartments of cells is essential for identifying, characterizing, and understanding the significance of Pb2+-Ca2+ interactions. Experiments were conducted to characterize the steady-state kinetic distribution and behavior of 45Ca in primary cultures of murine osteoclastic bone cells. Bone cells, derived from mouse calvaria, were enriched for osteoclasts by a sequential collagenase digestion and maintained in primary culture for 1 week. Cultures were labeled with 45Ca for two or 24 hr and the kinetic parameters were obtained by analysis of 45Ca washout curves. Cellular metabolism was based upon a model with three kinetic pools of intracellular Ca2+ containing approximately 45, 25, and 30% of the total cell calcium. In addition, we describe quantitative measurements of Ca:Pb and Pb:Ca ratios at important functional cell sites of Ca2+ transport and storage in intact cells. The intracellular relationships of Ca2+ and Pb2+ were calculated concurrently in individual cultures, using kinetic analysis of dual-label 45Ca and 203Pb washout curves. The Ca:Pb ratios of the rate constants and half-times were approximately 1:1, supporting the concept of similar cellular metabolism of the two elements. The Ca:Pb ratios for the kinetic pools and fluxes were considerably higher than 1:1. These in situ Ca:Pb relationships should be useful for designing and evaluating Ca-Pb studies with calmodulin, isolated mitochondria, and other individual components of the calcium messenger system. Moreover, these data demonstrate both similarities and differences in the kinetic distribution and behavior of Ca2+ and Pb2+ in osteoclastic bone cells.


Treatment strategies with vitamin E and C in autologous intraperitoneal ovarian transplantation and its impact on ovarian surface epithelium and follicle reserve.
The objective of this study was to assess the impact of Vitamin E (Vit E) and Vitamin C (Vit C) on markers of the oxidant-antioxidant system, ovarian follicle reserves, and the surface epithelium in autologous intraperitoneal ovarian transplantation conducted in rats. The study aimed to investigate how these antioxidants influence various aspects related to transplantation outcomes, including oxidative stress markers, the preservation of follicle reserves, and the condition of the surface epithelium. A total of 20 adult female Wistar Albino rats were included in the study and randomly assigned to four different groups. Group 1, consisting of 5 rats, served as the control group and underwent a surgical procedure where their abdomens were opened and closed without any further intervention. Group 2, also consisting of 5 rats, underwent ovarian transplantation. In Group 3, comprising 5 rats, an intraperitoneal (IP) administration of 20 mg/kg body weight (b.w.) of Vitamin E (Vit E) was given 15 min prior to ovarian transplantation. Lastly, in Group 4, which included 5 rats, an IP administration of 50 mg/kg body weight (b.w.) of Vitamin C (Vit C) was given 15 min before ovarian transplantation. Vaginal cytology was performed in order to monitor the estrus phase in the rats. Biochemically, tissue and serum malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) levels were measured. Histopathologically, the number of dysplastic changes in the ovarian surface epithelium and primordial, primary, secondary, Graaffian, and atretic follicles were examined. Dysplastic changes in the surface epithelium of Group 2 were found to be significantly higher than in Group 1 and 4 (p < 0.02). In Group 2, the ovarian follicle reserves (primordial, primary, secondary, and Graaffian follicles) were significantly lower than in other groups (p < 0.02). In addition, a significant decrease in SOD levels was found in Group 2 compared to other groups (p < 0.02). The study showed that Vit E and Vit C in autologous intraperitoneal ovarian transplantation preserved the ovarian follicle reserve. Vit C was found to be more effective than Vit E.


Trunnionosis in metal-on-polyethylene total hip arthroplasties: Report two cases.
Several studies have discussed trunnionosis in metal-on-metal total hip arthroplasties. However, trunnionosis in metal-on-polyethylene total hip arthroplasties has been less frequently discussed. In this study, trunnionosis in two male patients undergoing metal-on-polyethylene total hip arthroplasty, which was done to treat femoral head osteonecrosis were reported and discussed adequately. Total hip arthroplasties (THA) were done for the treatment of femoral head osteonecrosis in these cases. In the first case, trunnionosis occurred one year after the revision of the primary THA, and in the second case occurred ten years after the primary THA. Both of these cases were presented with reduced range of motion. After surgery, the symptoms were resolved, and the patients remained complication-free until the last follow-up. This report raises awareness regarding the importance of trunnionosis as a serious complication of modular total hip arthroplasty.


Bilateral total cataract as the presenting feature of celiac disease.
An 18-year-old male presented to the ophthalmology department with bilateral total subluxated cataract. On systemic examination, he was found to have grossly short stature, multiple severe bony deformities, hypogonadism and partial adontia. Detailed work-up revealed a biochemical and radiologic picture consistent with osteomalacia, which had resulted from malabsorption secondary to celiac disease, confirmed histopathologically. To the best of our knowledge, this is the first reported case of bilateral cataract as the presenting feature of celiac disease. Malabsorption leading to hypocalcemia along with chronic diarrhea itself may have contributed to the development of bilateral cataract.


Protease-activated receptor-2 (PAR-2) in brain microvascular endothelium and its regulation by plasmin and elastase.
Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus. We have reported earlier that primary cultures of rat brain capillary endothelial (RBCE) cells express at least two receptors for thrombin: PAR-1 and PAR-3. In the present study we show that PAR-2 activation by trypsin or by the PAR-2 agonist peptide (SLIGRL) evokes [Ca(2+) ](i) signal in RBCE cells. Taking advantage of RBCE cells expressing PAR-1 and PAR-2, we show that trypsin activates both receptors. The relative agonist activity of trypsin and thrombin on PARs of RBCE cells compared with that of SLIGRL were 112% and 48%, respectively, whereas the potency of trypsin was 10(5) -fold higher than that of SLIGRL. Because under pathological conditions other proteases such as plasmin or leukocyte elastase may reach the cells of the blood-brain barrier, we investigated the effect of these proteases on RBCE cells. Elastase evoked a small increase in [Ca(2+) ](i) but preincubation of cells with elastase dose-dependently reduced the trypsin-induced [Ca(2+) ](i) signal. Plasmin had a 30% inhibitory effect on the trypsin-induced response, and reduced the SLIGRL signal by 20%. It is concluded that PAR-2 is functional in brain capillary endothelium, and that the main fibrinolytic proteases, plasmin and elastase, may regulate PAR-2 signalling under pathological conditions.


Identification and characterization of a protease (EuRP-61) from Euphorbia resinifera latex.
A serine protease designated as EuRP-61 was purified from Euphorbia resinifera latex. The N-terminal sequence of 15 amino acids of EuRP-61 supported the conclusion that the enzyme was a serine protease because its amino acid sequence had homology (between 50 and 70% identities) with the subtilisin-like proteases of other plants. EuRP-61 had a molecular weight estimated at 61 kDa analyzed by MALDI-TOF MS. The enzyme could cleave human fibrinogen with optimal conditions at pH 5.0 and 45 °C. The enzyme had a broad range of pH stability from 1 to 14 and tolerance to denaturation up to a temperature of approximately 65-66 °C. EuRP-61 hydrolyzed fibrinogen with a Michaelis constant (Km) of 4.95 ± 0.1 μM; a maximal velocity (Vmax) of 578.1 ± 11.81 ng min-1; and a catalytic efficiency (Vmax/Km) of 116.8 ± 1 ng μM-1 min-1. EuRP-61was crystallized under the condition of sodium iodide (0.2 M), Bis-Tris propane (0.1 M, pH 8.5) and PEG3350 (20%) by the sitting-drop method. The crystal belonged to space group P212121, with unit cell dimension a = 109.91, b = 67.38 and c = 199.45 Å and diffracted X-ray to 2.53 Å resolution. The crystal structure of EuRP-61 will be explored further by special phase solving techniques.


Commentary: the cognitivist oversell and comments on symposium contributions.
During the 1980s the behavior therapy movement was infiltrated by cognitivists, people who believe that all maladaptive fears are based on wrong beliefs and all can be overcome by cognitive correction. This article asserts and defends the following propositions: (1) There are numerous maladaptive fears demonstrably immune to cognitive correction but removable by deconditioning. (2) These conditioning based fears constitute the majority, but there are also some based on mistaken beliefs. (3) Proponents of the cognitivist viewpoint have overrated the outcomes of cognitive therapy, because they have not realized the fact that conditioned anxiety is often inadvertently weakened by simultaneous competing emotions (nonspecific therapeutic effects). (4) This overrating led to the fiction that cognitive-behavior therapy is behavior therapy's best resource to overcome non-psychotic depression, a fiction that was exposed by cognitive-behavior therapy's inferior performance in the National Institute of Mental Health's Collaborative Research Project. (5) There is data to suggest that use of the full resources of behavior therapy would have produced notably superior results. The commentary concludes with comments on the other contributions to the symposium, From Behavior Theory to Behavior Therapy.


The effects of cochlear implantation on middle ear function: A prospective study.
Although sound conduction mechanisms may influence by cochlear implantation (CI), it is not very clear whether, how, and to what extent these mechanisms may be influenced the pediatric population. Wideband tympanometry (WBT) is a sensitive tool to evaluate alternations in the middle ear mechanics in a wide frequency range. The current study aimed to explore CI's impacts on sound conduction across the middle ear cavity using WBT in pediatrics. In a prospective design, 35 unilaterally implanted children (<24 months of age) with normal temporal bone anatomy were included in this study. Traditional tympanometry (226-Hz) and WBT measures were compared for each child in the implanted and non-implanted ears preoperatively and three months postoperatively. No significant changes in the "static acoustic admittance" and "peak pressure" parameters were observed between the pre-CI and post-CI conditions in the implanted and non-implanted ears in the 226-Hz tympanometry test. Wideband absorbance recordings before CI surgery exhibited a double-peaked pattern over a frequency range of 250 to 8000 Hz. The pre- and postoperative acoustic energy absorbance comparisons indicated a significantly reduced mid-frequency (1260 to 3175 Hz) and high-frequency (5040 to 8000 Hz) absorbance in the implanted ears. However, our results indicated no significant differences in sound absorbance between the pre- and postoperative conditions in non-implanted ears. Our findings suggested that WBT is a more sensitive method than traditional tympanometry for monitoring the mechanical status of the middle ear after cochlear implantation in pediatrics. Cochlear implantation in young children can significantly reduce mid- and high-frequency acoustic absorbance measured by WBT.


Calcium ionophore-induced de-encryption of tissue factor in monocytes is associated with extensive cell death.
Cell surface tissue factor (TF) is normally encrypted, but can be activated by various cellular perturbations. Exposure of TF bearing cells to calcium ionophore has been reported to increase TF activity, de-encrypt TF, by phosphatidylserine (PS)-dependent and -independent mechanisms. Our aim has been to examine at the single cell level, if increased cell surface PS coincided with increased cell surface TF antigen, and cell death (necrosis, 7-AAD-intercalation), and relate this to monocyte- and microparticle (MP)-associated procoagulant activity. We exposed lipopolysaccharide-stimulated, human, elutriation-purified, cryopreserved TF bearing monocytes to increasing concentrations of calcium ionophore (A23187) and measured procoagulant activity in cells and supernatants. These measurements were compared with quantification of cell surface TF and PS (Annexin V) and of cell necrosis (7-AAD) by flow cytometry, and complemented by confocal microscopy. We observed that calcium ionophore increased cellular and MP-associated TF activity, but not cell surface TF antigen. The discrepancy between TF activity and TF antigen coincided with a dose-dependent increase in the number of cells expressing PS. These cells were to a large extent necrotic and many of them also expressed TF. We suggest such TF positive dying cells to contribute to the discordance between TF activity and TF expression. Calcium ionophore also increased MP-associated TF activity and release of MPs may be a way to disseminate procoagulant activity. Our findings emphasize the importance of adequately assessing cell death and taking into consideration its possible role in experiments with calcium ionophore.


KTR2: a new member of the KRE2 mannosyltransferase gene family.
The KTR2 gene from Saccharomyces cerevisiae was identified by polymerase chain reaction amplification of genomic DNA using primers derived from regions of high homology between the products of three yeast genes, KRE2, YUR1 and KTR1. The product encoded by the KTR2 gene is a predicted type II membrane protein of 425 amino acid residues with a short cytoplasmic N-terminus, a membrane-spanning region and a large lumenal domain containing residues with a short cytoplasmic N-terminus, a membrane-spanning region and a large lumenal domain containing four potential N-glycosylation sites. Ktr2p has 58% identity with Yur1p, 39% with Ktr1p and 34% with Kre2p. One member of this gene family, KRE2 (also known as MNT1; Häusler and Robbins, 1992), encodes an alpha-1,2 mannosyltransferase which adds the third mannose onto O-linked glycoprotein side-chains (Häusler et al., 1992). In contrast to KRE2 null mutants, which produce shortened (two-mannose) chains, mutants harboring a KTR2 gene disruption synthesize O-linked chains with the wild-type patterns of five mannose residues. A null mutation in KTR2 leads to partial resistance to killer toxin and hints that KTR2, which encodes a putative mannosyltransferase, is involved in extracellular matrix assembly.


Eight-year trajectories and predictors of cognitive function in community-dwelling Korean older adults with cardiovascular diseases.
This study aims to identify longitudinal patterns and predictors of cognitive function trajectories among Korean older adults with cardiovascular diseases. This study is a longitudinal panel analysis based on secondary data. Data from the the Korean Longitudinal Study of Ageing (KLoSA) were used for analysis. The KLoSA is a representative panel survey of older Koreans. We analyzed responses from 301 participants aged ≥65 years who completed the same survey more than three times out of five waves between 2012 and 2020. Latent class growth modeling identified two trajectories of cognitive function in older people with cardiovascular diseases: "low and declining" (n = 81, 26.9%) and "high and declining" (n = 220, 73.1%). Participants in "the low and declining trajectory group" were more likely to have a low educational level, weak handgrip strength, depression, and low social participation at baseline than those in "the high and declining trajectory group." Our results indicate a need to develop community-based tailored interventions for improving handgrip strength, mental health, and social participation in delaying cognitive decline in older people with cardiovascular diseases considering their educational level. Healthcare providers should be more concerned about older people with a weaker handgrip, depression, and low social activities as a high-risk group for cognitive decline over time in cardiovascular care. Therefore, it is necessary to evaluate them early with standardized tools and make subsequent strategies for the older population with cardiovascular diseases.


Liver Fat Quantification With Ultrasound: Depth Dependence of Attenuation Coefficient.
The primary aim was to estimate the influence of various depths on ultrasound attenuation coefficient (AC) of multiple vendors in the liver. The secondary aim was to evaluate the impact of region of interest (ROI) size on AC measurements in a subset of participants. This Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was carried out in two centers using AC-Canon and AC-Philips algorithms and extracting AC-Siemens values from ultrasound-derived fat fraction algorithm. Measurements were performed positioning ROI upper edge (3 cm size) at 2, 3, 4, 5 cm from the liver capsule with AC-Canon and AC-Philips and at 1.5, 2, 3 cm with Siemens algorithm. In a subset of participants, measurements were obtained with 1 and 3 cm ROI size. Univariate and multivariate linear regression models and Lin's concordance correlation coefficient (CCC) were used for statistical analysis as appropriate. Three different cohorts were studied. Sixty-three participants (34 females; mean age: 51 ± 14 years) were studied with AC-Canon, 60 (46 females; mean age: 57 ± 11 years) with AC-Philips, and 50 (25 females; 61 ± 13 years) with AC-Siemens. There was a decrease in AC values per 1 cm increase in depth in all. In multivariable analysis, the coefficient was -0.049 (-0.060; -0.038 P < .001) with AC-Canon, -0.058 (-0.066; -0.049 P < .001) with AC-Philips and -0.081 (-0.112; -0.050 P < .001) with AC-Siemens. AC values with 1 cm ROI were significantly higher than those obtained with 3 cm ROI at all depths (P < .001) but the agreement between AC values obtained with different ROI size was excellent (CCC 0.82 [0.77-0.88]). There is depth dependence in AC measurement that affects results. A standardized protocol with fixed ROI's depth and size is needed.


The cognitive-enhancing properties of modafinil are limited in non-sleep-deprived middle-aged volunteers.
Modafinil is a selective wakefulness-promoting agent that has been shown to enhance cognitive performance under conditions of sleep deprivation but which has equivocal effects in normal young volunteers. In a double-blind parallel group design study, 45 non-sleep-deprived middle-aged volunteers (20 men and 25 women, aged 50-67 years) were randomly allocated to receive two capsules containing placebo, 100 or 200 mg modafinil, and 3 h later they completed 100 mm visual analogue scales of mood and bodily symptoms, before and after an extensive battery of cognitive tests [pen and paper and the Cambridge Neuropsychological Test Automated Battery (CANTAB)]. There were no significant treatment-associated changes in ratings of mood or bodily symptoms and no significant effects on most of the cognitive tests used in this study. The group treated with modafinil (200 mg) was significantly faster in a simple colour naming of dots and also significantly better in a test of constructional ability (Clock Drawing Test) compared with the placebo group. However, subjects in the 200-mg group also made significantly more total errors in the Intra/Extradimensional Set Shift (ID/ED) task than both the other groups. Thus, this study found limited evidence of cognitive-enhancing properties of modafinil in healthy middle-aged volunteers.


Experience with mechanical contrast medium injection at selective coronary angiography.
This is a report of our experiences with the automatic contrast medium injector at selective coronary angiography during 836 examinations, and the quantitative evaluation of 193 single injections. Using average injection volumes per single injection of 5.0 ml for the left and 2.5 ml for the right coronary artery, a clear reduction of the quantity of contrast medium at constant definition can be registered. The variability in increase in the injection flow from 0 up to the peakflow appears to be important according to the anatomic and pathologic facts. Frequently a contrast medium reflux occurs out of the coronary ostium into the aorta. On the whole, automatic injection at selective coronary angiography is a reproducible and extensible method with few risks.


Hybrid Bis-Histidine Phenanthroline-Based Ligands to Lessen Aβ-Bound Cu ROS Production: An Illustration of Cu(I) Significance.
We here report the synthesis of three new hybrid ligands built around the phenanthroline scaffold and encompassing two histidine-like moieties: phenHH, phenHGH and H'phenH', where H correspond to histidine and H' to histamine. These ligands were designed to capture Cu(I/II) from the amyloid-β peptide and to prevent the formation of reactive oxygen species produced by amyloid-β bound copper in presence of physiological reductant (e.g., ascorbate) and dioxygen. The amyloid-β peptide is a well-known key player in Alzheimer's disease, a debilitating and devasting neurological disorder the mankind has to fight against. The Cu-Aβ complex does participate in the oxidative stress observed in the disease, due to the redox ability of the Cu(I/II) ions. The complete characterization of the copper complexes made with phenHH, phenHGH and H'phenH' is reported, along with the ability of ligands to remove Cu from Aβ, and to prevent the formation of reactive oxygen species catalyzed by Cu and Cu-Aβ, including in presence of zinc, the second metal ions important in the etiology of Alzheimer's disease. The importance of the reduced state of copper, Cu(I), in the prevention and arrest of ROS is mechanistically described with the help of cyclic voltammetry experiments.


Developmental, sexual and reproductive differences in habituation shown by the guppy (Poecilia reticulata).
Behavioural arousal responses of guppies (Poecilia reticulata) were observed to repeated presentation of 2 seconds increased illumination at 30 second intervals. Habituation of responses occurred more rapidly in males than in females and habituation in females was related to their reproductive state. Exposure of gravid females for 8 days to a daily series of stimuli resulted in their young having enhanced habituation postnatally. The results are discussed in relation to developmental and possible hormonal influences on arousal and its habituation in fish.


Inhibitory effects of clonidine on the allergen-induced wheal-and-flare reactions in patients with extrinsic asthma.
We investigated the possibility that clonidine, an alpha 2-adrenoceptor agonist, can reduce the wheal-and-flare reactions induced by intradermal injections of allergen in patients with extrinsic asthma. Ten adult subjects with asthma with positive skin tests to one or several pollens were selected. They received, in random order and double-blind manner, clonidine (two doses, each 75 micrograms) or placebo for 3 days, and then, after a 1-week washout period, they crossed over to the other treatment for 3 days. Treatment with clonidine reduced the area of wheal-and-flare reaction induced by allergen without significantly changing the blood pressure or the plasma cortisol level. There was a drop in the histamine content of leukocytes and in the number of eosinophils in peripheral blood after allergen challenge during the placebo treatment, whereas clonidine prevented these changes. The results suggest that treatment with clonidine can reduce the inflammatory reactions induced by allergens in subjects with extrinsic asthma.


Mechanism of force generation by myosin heads in skeletal muscle.
Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. Although many features of the dynamic performance of muscle are determined by the rates of attachment and detachment of myosin and actin, the primary event in force generation is thought to be a conformational change or 'working stroke' in the actin-bound myosin head. According to this hypothesis, the working stroke is much faster than attachment or detachment, but can be observed directly in the rapid force transients that follow step displacement of the filaments. Although many studies of the mechanism of muscle contraction have been based on this hypothesis, the alternative view-that the fast force transients are caused by fast components of attachment and detachment--has not been excluded definitively. Here we show that measurements of the axial motions of the myosin heads at ångström resolution by a new X-ray interference technique rule out the rapid attachment/detachment hypothesis, and provide compelling support for the working stroke model of force generation.