Gene expression of an arthrobacter in surfactant-enhanced biodegradation of a hydrophobic organic compound.
Surfactants can affect the biodegradation process and the fate of hydrophobic organic compounds (HOCs) in the environment. Previous studies have shown that surfactants can enhance the biodegradation of HOCs by increasing cell surface hydrophobicity (CSH) and membrane fluidity. In this study, we took this work one step further by investigating the expression levels of three genes of Arthrobacter sp. SA02 in the biodegradation of phenanthrene as a typical HOC at different concentrations of sodium dodecyl benzenesulfonate (SDBS), which is a widely used surfactant. The Δ9 fatty acid desaturase gene codes for Δ9 fatty acid desaturase, which can convert saturated fatty acid to its unsaturated form. The ring-hydroxylating dioxygenase (RHDase) and the 1-hydroxyl-2-naphthoate dioxygenase (1H2Nase) genes code for the RHDase and 1H2Nase enzymes, respectively, which play a key role in decomposing doubly hydroxylated aromatic compounds. The results show that these three genes were upregulated in the presence of SDBS. On the basis of the genetic and physiological changes, we proposed a pathway that links the gene expression with the physiological phenomena, including CSH, membrane fluidity, and intracellular degradation. This study advances our understanding of the surfactant-enhanced biodegradation of HOCs at the gene level, and the proposed pathway should be further validated in the future.


IgE influences the number and function of mature mast cells, but not progenitor recruitment in allergic pulmonary inflammation.
Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcepsilonRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE(-/-) animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE(-/-) mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.


Show-through cancellation in scans of duplex printed documents.
In scanning pages with double-sided printing, often the printing on the back-side shows through in the scan of the front-side because the paper is not completely opaque. This show-through is an undesirable artifact that one would like to remove. In this paper, the phenomenon of show-through is analyzed using first physical principles to obtain a simplified mathematical model. The model is linearized using suitable transformations and simplifying approximations. Based on the linearized model, an adaptive linear filtering scheme is developed for the electronic removal of show-through using scans of both sides of the document. Experimental results demonstrating the effectiveness of the method developed are presented.


Effects of source coherence and aperture array geometry on optical sectioning strength in direct-view microscopy.
Laser sources offer a possible solution to the problem of low light throughput in direct-view microscopes (DVMs). However, coherent source DVMs have been shown to suffer from problems such as increased sidelobes in the depth response because of coherent cross talk between neighboring apertures. We explore theoretically how source coherence affects the depth responses of DVMs by employing various aperture spacings and number of apertures. We show that, contrary to expectation, closely spaced apertures can result in decreased full width at half-maximum of the depth response curve. We explain this as an effect of destructive interference when cross talk between neighboring apertures occurs. Using apertures arranged in a square grid as an example, we move on to show that the use of aperture arrays that consist of regularly arranged apertures can accentuate the problematic sidelobes of the depth response. We show that arranging pinholes in a rectangular grid rather than a square grid can improve the optical sectioning strength significantly. Finally, by examination of the depth responses corresponding to the infinite-pinhole-array limit, we make some general statements about source coherence and the characteristics of arrays that are likely to perform well.


Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows.
The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d -6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d -6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na+ and K+) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na+ and K+ concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single injection of cabergoline after the last milking would facilitate drying-off by enhancing mammary gland involution.


The KIPHO5 gene encoding a repressible acid phosphatase in the yeast Kluyveromyces lactis: cloning, sequencing and transcriptional analysis of the gene, and purification and properties of the enzyme.
A secreted phosphate-repressible acid phosphatase from Kluyveromyces lactis has been purified and the N-terminal region and an internal peptide have been sequenced. Using synthetic oligodeoxyribonucleotides based on the sequenced regions, the genomic sequence, KIPHO5, encoding the protein has been isolated. The deduced protein, named KIPho5p, consists of 469 amino acids and has a molecular mass of 52520 Da (in agreement with the data obtained after treatment of the protein with endoglycosidase H). The purified enzyme shows size heterogeneity, with an apparent molecular mass in the range 90-200 kDa due to the carbohydrate content (10 putative glycosylation sites were identified in the sequence). A 16 amino acid sequence at the N-terminus is similar to previously identified signal peptides in other fungal secretory proteins. The putative signal peptide is removed during secretion since it is absent in the mature secreted acid phosphatase. The gene can be induced 400-600-fold by phosphate starvation. Consensus signals corresponding to those described for Saccharomyces cerevisiae PHO4- and PHO2-binding sites are found in the 5' region. Northern blot analysis of total cellular RNA indicates that the KIPHO5 gene codes for a 1.8 kb transcript and that its expression is regulated at the transcriptional level. Chromosomal hybridization indicated that the gene is located on chromosome II. The KIPHO5 gene of K. lactis is able to functionally complement a pho5 mutation of Sacch. cerevisiae. Southern blot experiments, using the KIPHO5 gene as probe, show that some K. lactis reference strains lack repressible acid phosphatase, revealing a different gene organization for this kind of multigene family of proteins as compared to Sacch. cerevisiae.


Columnar Iridium(III) Metallomesogens Based on Polycatenar Pyridyltetrazolate with Ambipolar Carrier Mobility Behavior.
In this paper, we have designed and synthesized a series of neutral liquid-crystalline iridium(III) complexes based on polycatenar 2,5-diphenylpyridine and pyridyltetrazolate derivatives. Iridium(III) complexes all display highly emissive behavior with photoluminescence quantum yields in the range of 0.45-0.66 and a maximum emission wavelength at ∼563 nm. Hexagonal columnar mesophases of iridium(III) complexes can be obtained by changing the number and length of peripheral alkoxyl chains attached to a 2,5-diphenylpyridine ligand (main ligand) and a pyridyltetrazolate ligand (auxiliary ligand). Moreover, experimental results of the charge transport properties for these iridium(III) complexes, which were measured by the space charge limited-current method, exhibit ambipolar carrier mobility behavior. In particular, the liquid-crystalline iridium(III) complexes can self-organize into one-dimensional (1D) nanostructure after thermal annealing treatment in their liquid-crystalline phase. The devices based on liquid crystal film display improved charge transport behavior compared with that of the devices based on polycrystalline film, indicating 1D nanostructure is beneficial to charge carrier injection and transportation.


Muscimol inactivation of the dorsal hippocampus impairs contextual retrieval of fear memory.
Some models of hippocampal function have suggested a role of the hippocampus in contextual memory retrieval. We have examined this hypothesis by assessing the impact of reversible inactivation of the dorsal hippocampus (DH) on the context-specific expression of latent inhibition, a decrement in conditional responding produced by preexposure to a to-be-conditional stimulus. In Experiment 1, rats received tone preexposure either in the context that would later be used for extinction testing (context A) or in a different context (context C); a third group of rats did not receive tone preexposure. All rats then received fear conditioning, which consisted of tone-footshock pairings, in a third distinct context (context B). The following day conditional fear to the tone was assessed in one of the preexposure contexts (context A) by measuring freezing during a tone extinction test. Rats preexposed and tested in the same context exhibited less freezing to the tone than either rats preexposed and tested in different contexts or non-preexposed rats. These results indicate that the expression of latent inhibition is context specific. In Experiment 2, DH inactivation eliminated the context-specific expression of latent inhibition. Compared with saline-infused rats, rats infused with muscimol into the DH exhibited low levels of tone freezing independent of whether they had received tone preexposure in the test context or in a different context. Experiment 3 revealed normal contextual discrimination in rats after DH inactivation. These results suggest the DH is required for contextual memory retrieval in a latent inhibition paradigm.


Stacking textured films on lattice-mismatched transparent conducting oxides via matched Voronoi cell of oxygen sublattice.
Transparent conducting oxides are a critical component in modern (opto)electronic devices and solar energy conversion systems, and forming textured functional films on them is highly desirable for property manipulation and performance optimization. However, technologically important materials show varied crystal structures, making it difficult to establish coherent interfaces and consequently the oriented growth of these materials on transparent conducting oxides. Here, taking lattice-mismatched hexagonal α-Fe2O3 and tetragonal fluorine-doped tin oxide as the example, atomic-level investigations reveal that a coherent ordered structure forms at their interface, and via an oxygen-mediated dimensional and chemical-matching manner, that is, matched Voronoi cells of oxygen sublattices, [110]-oriented α-Fe2O3 films develop on fluorine-doped tin oxide. Further measurements of charge transport characteristics and photoelectronic effects highlight the importance and advantages of coherent interfaces and well-defined orientation in textured α-Fe2O3 films. Textured growth of lattice-mismatched oxides, including spinel Co3O4, fluorite CeO2, perovskite BiFeO3 and even halide perovskite Cs2AgBiBr6, on fluorine-doped tin oxide is also achieved, offering new opportunities to develop high-performance transparent-conducting-oxide-supported devices.


Dental Technicians' Pneumoconiosis.
A 40-year-old female dental technician visited our hospital for the investigation of a chest X-ray abnormality. Chest computed tomography demonstrated centrilobular nodules and lung volume reduction, and her serum KL-6 level was elevated. A histological analysis of the specimens obtained on a surgical lung biopsy showed peribronchiolar fibrosis with pigmented macrophages and cholesterol clefts. An energy-dispersive X-ray analysis showed that these lung tissues contained some metals, including indium. The serum indium level was also elevated. We diagnosed this patient with pneumoconiosis caused by exposure to sandblasting certain dental metals. This is the first reported case of pneumoconiosis in a dental technician associated with exposure to indium.


Soluble CD4 enhances simian immunodeficiency virus SIVagm infection.
The CD4 molecule is expressed on T-helper cells and serves as the cellular receptor for the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for the simian immunodeficiency viruses SIVmac and SIVagm. HIV-1, HIV-2, and SIVmac infectivity can be blocked by monoclonal antibodies (MAbs) directed against the CD4 molecule and by soluble CD4 proteins (sCD4). In the present study, we demonstrated not only lack of inhibition, but 10- to 100-fold sCD4-dependent enhancement of SIVagm infectivity of human T-cell lymphoma lines, although SIVagm infection was blocked by MAbs OKT4a and Leu3a. SIVagm enhancement with sCD4 was suppressed by MAbs OKT4a and Leu3a to levels observed without addition of sCD4. The infectivity of all four tested SIVagm variants was enhanced by sCD4 on all tested lymphoma cell lines. These results suggest a second step (second or secondary receptor) required for enhancing virus entry into the cell and may have serious implications for approaches to the treatment of acquired immunodeficiency syndrome on the basis of modified sCD4 molecules.


Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography.
Contrast-enhanced micro-computed tomography (CEμCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEμCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEμCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEμCT method for 3D characterization of articular cartilage.


[Analysis of on medication rules for Qi-deficiency and blood-stasis syndrome of chronic heart failure based on data mining technology].
To analyze the medication features and the regularity of prescriptions of traditional Chinese medicine in treating patients with Qi-deficiency and blood-stasis syndrome of chronic heart failure based on modern literature. In this article, CNKI Chinese academic journal database, Wanfang Chinese academic journal database and VIP Chinese periodical database were all searched from January 2000 to December 2015 for the relevant literature on traditional Chinese medicine treatment for Qi-deficiency and blood-stasis syndrome of chronic heart failure. Then a normalized database was established for further data mining and analysis. Subsequently, the medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system(V2.5), association rules, improved mutual information algorithm, complex system entropy clustering and other mining methods. Finally, a total of 171 articles were included, involving 171 prescriptions, 140 kinds of herbs, with a total frequency of 1 772 for the herbs. As a result, 19 core prescriptions and 7 new prescriptions were mined. The most frequently used herbs included Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma), Fuling(Poria), Renshen(Ginseng Radix et Rhizoma), Tinglizi(Semen Lepidii), Baizhu(Atractylodis Macrocephalae Rhizoma), and Guizhi(Cinnamomum Ramulus). The core prescriptions were composed of Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma) and Fuling(Poria), etc. The high frequent herbs and core prescriptions not only highlight the medication features of Qi-invigorating and blood-circulating therapy, but also reflect the regularity of prescriptions of blood-circulating, Yang-warming, and urination-promoting therapy based on syndrome differentiation. Moreover, the mining of the new prescriptions provide new reference and inspiration for clinical treatment of various accompanying symptoms of chronic heart failure. In conclusion, this article provides new reference for traditional Chinese medicine in the treatment of chronic heart failure.


Two pediatric allergists' sojourn in the People's Republic of China.
One cannot visit modern day mainland China without being impressed with the apparent vastness of the population which seems ever on the move. While manifestations of allergic disease among Chinese children resemble those seen in western countries, some factors peculiar to China, such as life style, diet, housing and absence of household pets, influence age of onset and geographic distribution of some allergic syndromes in Chinese children.


One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD.
It is still unclear whether in patients with chronic coronary artery disease (CAD) the improvements in myocardial perfusion and left ventricular (LV) function induced by revascularization persist in the long run. This study was planned to evaluate the 1-yr effects of successful revascularization on myocardial perfusion and LV function in patients with CAD and to assess the accuracy of thallium imaging in the prediction of functional recovery 1 yr after revascularization. Thirty-eight patients with chronic CAD who were revascularized (experimental group) underwent, while off drugs, 201Tl tomography, two-dimensional echocardiography and radionuclide angiography before and after a 1-yr follow-up. Twenty-nine patients with similar characteristics who were not revascularized (control group) and completed the 1-yr follow-up were also studied. Regional thallium activity was quantitatively measured in 13 segments per patient. Systolic function was assessed by echocardiography in corresponding segments. In the experimental group, at baseline, on the basis of regional LV function and thallium uptake, 276 segments were normal, 169 dysfunctional-viable and 49 nonviable. After revascularization, the majority (75%) of the dysfunctional-viable segments at baseline showed functional recovery at follow-up, whereas the majority (81%) of the nonviable segments at baseline did not. Simultaneously, LV ejection fraction increased 4 wk after revascularization (from 39% +/- 9% to 42% +/- 10%, p < 0.01) and remained unchanged after 1-yr (43% +/- 8%, p < 0.01 versus baseline study). LV wall-motion score index after 1 yr was reduced (from 1.68 +/- 0.4 to 1.42 +/- 0.3, p < 0.001) as compared with baseline. On the contrary, in the control group, no change in myocardial perfusion and LV function was detected after the 1-yr follow-up. In patients with chronic CAD, successful coronary revascularization induces a stable improvement in myocardial perfusion and LV function, which is still detectable after a 1-yr follow-up. Furthermore, preserved thallium uptake in dysfunctional regions is predictive of functional recovery after revascularization.


Growth hormone stimulation of lipolysis and cyclic AMP levels in perifused fat cells.
A rapid, sustained lipolytic response to growth hormone (GH; 20 microgram/ml) was observed in experiments using the perifused fat cell system. No lipolytic response to this agent was observed when fat cells were incubated by the traditional flask incubation method, although isoproterenol stimulated lipolysis in this preparation. In experiments using flask incubated fat cells, isoproterenol increased cyclic AMP content while GH had no effect. However, in the presence of theophylline, isoproterenol and GH significantly increased cyclic AMP levels. In perifused fat cells, both isoproterenol and GH significantly increased cyclic AMP levels in the absence of theophylline. The presence of adenosine deaminase resulted in significant increases in the lipolytic response to isoproterenol and unmasked a lipolytic response to GH when the flask-incubated fat cell system was used. The antilipolytic action of adenosine was determined in perifused fat cells. It was found that the lipolytic response to GH was at least 10 times as sensitive to the inhibitory action of adenosine as was the lipolytic response to isoproterenol. It is concluded that the lipolytic response to GH in the flask-incubation method is prevented by the accumulation of adenosine. This rapid lipolytic response is unmasked in the perifused fat cell system because adenosine fails to accumulate as it is washed from the cell population by the constantly flowing buffer.


Relationship between use of electronic health record features and health care quality: results of a statewide survey.
Electronic health records (EHRs) are widely viewed as useful tools for supporting the provision of high quality healthcare. However, evidence regarding their effectiveness for this purpose is mixed, and existing studies have generally considered EHR usage a binary factor and have not considered the availability and use of specific EHR features. To assess the relationship between the use of an EHR and the use of specific EHR features with quality of care. A statewide mail survey of physicians in Massachusetts conducted in 2005. The results of the survey were linked with Healthcare Effectiveness Data and Information Set (HEDIS) quality measures, and generalized linear regression models were estimated to examine the associations between the use of EHRs and specific EHR features with quality measures, adjusting for physician practice characteristics. A stratified random sample of 1884 licensed physicians in Massachusetts, 1345 of whom responded. Of these, 507 had HEDIS measures available and were included in the analysis (measures are only available for primary care providers). Performance on HEDIS quality measures. The survey had a response rate of 71%. There was no statistically significant association between use of an EHR as a binary factor and performance on any of the HEDIS measure groups. However, there were statistically significant associations between the use of many, but not all, specific EHR features and HEDIS measure group scores. The associations were strongest for the problem list, visit note and radiology test result EHR features and for quality measures relating to women's health, colon cancer screening, and cancer prevention. For example, users of problem list functionality performed better on women's health, depression, colon cancer screening, and cancer prevention measures, with problem list users outperforming nonusers by 3.3% to 9.6% points on HEDIS measure group scores (all significant at the P < 0.05 level). However, these associations were not universal. Consistent with past studies, there was no significant relationship between use of EHR as a binary factor and performance on quality measures. However, availability and use of specific EHR features by primary care physicians was associated with higher performance on certain quality measures. These results suggest that, to maximize health care quality, developers, implementers and certifiers of EHRs should focus on increasing the adoption of robust EHR systems and increasing the use of specific features rather than simply aiming to deploy an EHR regardless of functionality.


Programmable Self-Assembly of Nanoplates into Bicontinuous Nanostructures.
Self-assembly is the process by which individual components arrange themselves into an ordered structure by changing the shapes, components, and interactions. It has enabled us to construct an extensive range of geometric forms on many length scales. Nevertheless, the potential of two-dimensional polygonal nanoplates to self-assemble into extended three-dimensional structures with compartments and corridors has remained unexplored. In this paper, we show coarse-grained Monte Carlo simulations demonstrating self-assembly of hexagonal/triangular nanoplates via complementary interactions into faceted, sponge-like "bicontinuous polyhedra" (or infinite polyhedra) whose flat walls partition space into a pair of mutually interpenetrating labyrinths. Two bicontinuous polyhedra can be self-assembled: the regular (or Platonic) Petrie-Coxeter infinite polyhedron (denoted {6,4|4}) and the semi-regular Hart "gyrangle". The latter structure is chiral, with both left- and right-handed versions. We show that the Petrie-Coxeter assembly is constructed from two complementary populations of hexagonal nanoplates. Furthermore, we find that the 3D chiral Hart gyrangle can be assembled from identical achiral triangular nanoplates decorated with regioselective complementary interaction sites. The assembled Petrie-Coxeter and Hart polyhedra are faceted versions of two of the simplest triply periodic minimal surfaces, namely, Schwarz's primitive and Schoen's gyroid surfaces, respectively, offering alternative routes to those bicontinuous nanostructures, which are widespread in synthetic and biological materials.


Calmodulin sensitive phosphodiesterase of porcine cerebral cortex: kinetic behavior, calmodulin activation, and stability.
The calmodulin sensitive phosphodiesterase of porcine cerebral cortex was characterized in terms of kinetic behavior, calmodulin activation, and stability. This enzyme displayed non-Michaelis-Menten kinetics in the presence or absence of calmodulin. The apparent affinity for cyclic GMP was higher than that for cyclic AMP but at saturating levels of substrate, this enzyme catalyzed the hydrolysis of cyclic AMP at a greater rate than it did cyclic GMP. The affinity of this enzyme for calmodulin was about 20-fold lower than usually reported. The apparent loss of phosphodiesterase activity after storage was found to be due to a strong association with container surfaces and could be prevented or reversed by the presence of 0.1% Triton X-100.


The Epidemiology of Sarcopenia.
The aim of this review is to describe the epidemiology of sarcopenia, specifically prevalence, health outcomes, and factors across the life course that have been linked to its development. Sarcopenia definitions involve a range of measures (muscle mass, strength, and physical performance), which tend to decline with age, and hence sarcopenia becomes increasingly prevalent with age. Less is known about prevalence in older people in hospital and care homes, although it is likely to be higher than in community settings. The range of measures used, and the cutpoints suggested for each, presents a challenge for comparing prevalence estimates between studies. The importance of sarcopenia is highlighted by the range of adverse health outcomes that strength and physical performance (and to a lesser extent, muscle mass) have been linked to. This is shown most strikingly by the finding of increased all-cause mortality rates among those with weaker grip strength and slower gait speed. A life course approach broadens the window for our understanding of the etiology of sarcopenia and hence the potential intervention. An example is physical activity, with increased levels across midadulthood appearing to increase muscle mass and strength in early old age. Epidemiologic studies will continue to make an important contribution to our understanding of sarcopenia and possible avenues for intervention and prevention.


India-United States Dialogue on Traditional Medicine: Toward Collaborative Research and Generation of an Evidence Base.
Therapies originating from traditional medical systems are widely used by patients in both India and the United States. The first India-US Workshop on Traditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as a collaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) of the Government of India, the US National Cancer Institute (NCI), National Institutes of Health, and the Office of Global Affairs, US Department of Health and Human Services. It was attended by Indian and US policymakers, scientists, academics, and medical practitioners from various disciplines. The workshop provided an opportunity to open a dialogue between AYUSH and NCI to identify promising research results and potential topics for Indo-US collaboration. Recommendations that emerged from the workshop underlined the importance of applying rational and scientific approaches for drug development; standardizing traditional medicine products and procedures to ensure reliability and reproducibility; promotion of collaboration between Indian traditional medicine practitioners and researchers and US researchers; greater integration of evidence-based traditional medicine practices with mainstream medical practices in India; and development of training programs between AYUSH and NCI to facilitate crosstraining. Several positive developments took place after the thought-provoking deliberations.


Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital.
Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.


[Study on delegation. Dental activities by students in dental practices].
Some dental students in the Netherlands have a job in a dental practice next to their study, as the Individual Health Care Professions Act (introduced in 1997 as Law BIG) allows. The aim of the study was to determine how many dental students of the Academie Centre for Dentistry Amsterdam actually work in a dental practice, which kinds of dental activities they perform and whether these meet the requirements of the Act mentioned before. All dental students (n = 947) received a questionnaire by e-mail. The response was 44% (427 students). Of these students, 71% had a job next to their study; 25% worked in a dental practice. Study progress and age were positively correlated with working in a dental practice. Their activities mainly involved chair assistance, giving brushing instructions and fluoride applications, and dental cleaning. These students asseemed that they were better informed about the Individual Health Care Professions Act than other students. The source of this information was not, however, the practice where they worked. It was evident, moreover, that they felt the need for more information concerning the delegation of restricted dental activities.


Brief exposure to systemic hypoxia enhances plasticity of the central nervous system in spinal cord injured animals and man.
We have known for many decades that animals that sustain injuries to the neuraxis, which result in respiratory impairment, are able to develop rapid neural compensation for these injuries. This compensation, which is linked to the systemic hypoxia resulting from damage to the respiratory apparatus, is a potent manifestation of neural plasticity. Hypoxia-induced plasticity is also applicable to somatic neural systems that regulate motor activity in extremity muscles. We report on recent developments in our understanding of the mechanisms underlying this seemingly beneficial action of acute intermittent hypoxia (AIH). AIH improves breathing in animal models of spinal cord injury, and increases strength and endurance in individuals with incomplete spinal injuries. The role of AIH as a therapeutic intervention remains to be confirmed but it has proved to be well tolerated for use in humans with no adverse effects reported to date. The effects of AIH emerge rapidly and persist for several hours raising the possibility that the intervention may serve as a priming mechanism for facilitating rehabilitation and promoting recovery after neurologic injury in man. AIH is emerging as a potent and relatively inexpensive modality for inducing neuroplasticity, so it may prove feasible to use AIH in a clinical setting.


Undiagnosed coeliac disease in a father does not influence birthweight and preterm birth.
There is conflicting evidence regarding the effect of coeliac disease (CD) in the father on birthweight and preterm birth. We investigated the association between paternal CD and birthweight and preterm birth. Medical records of all singleton live-born children in Denmark between 1 January 1979 and 31 December 2004 were linked to information about parents' diseases. Fathers who were diagnosed with CD were then identified. Fathers with CD were considered treated if they were diagnosed before pregnancy and untreated if they were diagnosed after the date of conception. The outcome measures were: birthweight, small-for-gestational age (birthweight<10th centile for gestational age) and preterm birth (<37 weeks). We compared the offspring of men without CD (n = 1 472 352) and offspring of those with CD [untreated (n = 138) and treated (n = 473)]. There was no significant association between untreated CD in the father and birthweight (adjusted mean difference = -3 g; [95% CI -46, 40]) or preterm birth (adjusted odds ratio (OR) = 0.86, [95% CI 0.53, 1.37]) (compared with no CD). There was some evidence for an association between treated paternal CD and birthweight (adjusted mean difference = -81 g; [95% CI -161, -3]), but not preterm birth (adjusted OR = 1.76, [95% CI 0.95, 3.26]). Untreated paternal CD was not associated with an increased risk of reduced birthweight, or of preterm birth. There was some evidence that diagnosis and presumed treatment of paternal CD with a gluten-free diet is associated with reduced birthweight.


Asymmetric cross-strain protection for amphibians exposed to a fungal-metabolite prophylactic treatment.
Chytridiomycosis, an infectious disease of amphibians caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), poses an imminent conservation threat. The global spread of Bd has led to mass mortality events in many amphibian species, resulting in at least 90 species' extinctions to date. Exposure to Bd metabolites (i.e. non-infectious antigenic chemicals released by Bd) partially protects frogs during subsequent challenges with live Bd, suggesting its use as a prophylactic treatment and potential vaccine. However, we do not know whether Bd metabolite exposure protects against strains beyond the one used for treatment. To address this knowledge gap, we conducted a 3 × 2 experiment where we exposed adult Cuban treefrogs, Osteopilus septentrionalis, to one of three treatments (Bd metabolites from California-isolated strain JEL-270, Panamá-isolated strain JEL-419, or an artificial spring water control) and then challenged individuals with live Bd from either strain. We found that exposure to Bd metabolites from the California-isolated strain significantly reduced Bd loads of frogs challenged with the live Panamá-isolated strain, but no other treatments were found to confer protective effects. These findings demonstrate asymmetric cross-protection of a Bd metabolite prophylaxis and suggest that work investigating multiple, diverse strains is urgently needed.


Amenorrhoea after discontinuing combined oestrogen-progestogen oral contraceptives.
Out of 210 women seen at the Middlesex Hospital with secondary amenorrhoea the 63 who developed it after stopping oral contraceptives were fully investigated. Five had organic disease sufficient to account for the amenorrhoea (one had severe diabetes, one a pituitary tumour, and three premature ovarian failure); two patients had galactorrhoea (one of whom also had the pituitary tumour); two had anorexia nervosa.Of the 63 women 40 (63%) had suffered from amenorrhoea or prolonged or irregular menstrual cycles before taking the pill, and this suggested that combined oestrogen-progestogen oral contraceptives should be used with caution for women with irregular menstruation.Nineteen patients wished to become pregnant and 12 have so far done so after treatment with clomiphene or gonadotrophins.In another study 204 women recorded when their first menstrual cycle occurred after stopping the pill. Seventy-four had a cycle longer than five weeks but only five exceeded three months, and only one of the five had more than six months' amenorrhoea. These results confirm that the incidence of amenorrhoea after stopping oral contraceptives is low.


Growth, yield and seed composition of native Australian legumes with potential as grain crops.
Many Australian native legumes grow in arid and nutrient-poor environments. Yet few Australian herbaceous legumes have been investigated for domestication potential. This study compared growth and reproductive traits, grain yield and seed composition of 17 native Australian legumes with three commercial grain legumes. Seed yields of seven native legumes were > 40% of Cicer arietnum, with highest seed yields and harvest indices in Glycine sp. (14.4 g per plant, 0.54 g g(-1) ) and Lotus cruentus (10.2 g per plant, 0.65 g g(-1) ). Five native species flowered earlier than field pea (Pisum sativa) (109 days), though many were slower to flower and set seed. Largest seeds were found in Glycine canescens (17 mg), with seed of other native species 14 times smaller than commercial cultivars. Seed composition of many native legumes was similar to commercial cultivars (200-330 g protein kg(-1) dry weight (DW), 130-430 g dietary fibre kg(-1) DW). Two Cullen species had high fat content (>110 g kg(-1) DW) and Trigonella sauvissima had the highest crude protein content (370 g kg(-1) DW). The seed composition and reproductive traits of some wild native Australian legumes suggest they could offer potential as grain crops for soils and environments where the current grain legumes are uneconomic. Further evaluation of genetic diversity, especially for seed size, overall productivity, and reproductive development is needed.


Obesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators.
The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota-gut-brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the "expanded endocannabinoid (eCB) system" or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.


Total body irradiation of chronic lymphocytic leukemia. Relationship between therapeutic response and prognosis.
There is lack of evidence to date that treatment of chronic lymphocytic leukemia (CLL) alters the natural history of disease or influences survival. In the present series, total body irradiation (TBI) produced a range of therapeutic responses among patients with active, progressive CLL. One-third of patients experienced virtually complete clinical and hematologic remissions with the initial course of TBI. These patients did not differ from the less complete responders with respect to age or sex, degree of lymphocytosis in the peripheral blood, incidence of anemia and/or thrombocytopenia, or the frequency of constitutional symptoms. However, the patients with complete remissions noted a return to normal performance status, had fewer serious infections, demonstrated recovery from depressed immunoglobulin levels, and had significantly longer survival. These data indicate that TBI is capable of inducing remissions which modify the course of disease in patients with CLL and that prognosis has a direct correlation with the response to therapy.


[Causes of exploratory thoracotomies in lung cancer].
Exploratory thoracotomies were studied in 80 patients with inoperable lung cancer. The X-ray and computed tomography findings were analyzed retrospectively. The main causes of inoperability of lung cancer were determined. The authors consider that CT findings are of greater importance as compared with the routine X-ray examination and linear tomography for determining the lung cancer operability.


A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer's disease.
Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.


Pharmacology of retinotectal transmission in the goldfish: effects of nicotinic ligands, strychnine, and kynurenic acid.
The goal of this study was to evaluate different neurotransmitters and their receptors that might be involved in retinotectal transmission in the goldfish. Sections of tectum were isolated and maintained in vitro while pharmacological agents were administered via the tissue bath. Field potentials were elicited by electrical stimulation of the optic nerve and recorded at 50 micron depth intervals, and profiles of current source densities (CSDs) were computed from the second spatial derivatives of these potentials. The preparations were treated with low [Ca2+]/high [Mg2+] media, various cholinergic agonists and antagonists, eserine, strychnine, or kynurenic acid, via the tissue bath. Prior to treatment, depth profiles of these in vitro field potentials and CSDs closely resembled those previously reported in vivo, including 2 prominent sink-source pairs with their sinks in the superficial optic neuropil, followed by a smaller and more prolonged sink-source pair of opposite polarity. These were rapidly and reversibly eliminated by low [Ca2+]/high [Mg2+] bathing media, and substantially reduced by 0.5 or 1.0 mM kynurenic acid. By contrast, d-tubocurarine (d-TC; up to 0.16 mM) reduced peak response amplitudes by less than 40%, eliminated the third sink-source pair, and more than doubled the duration of decay of sink-source pairs 1 and 2 in a concentration-dependent manner. Strychnine had a similar action to d-TC but was slightly more potent. The time course and amplitudes of responses were not much affected by the following nicotinic agonists or antagonists (concentrations in microM): mecamylamine, 50; dihydro-beta-erythroidine, 50; nicotine, 200; tetramethylammonium, 500; ACh (protected by eserine, 20), 200; alpha-bungarotoxin, 2 microM for 2.5 hr, and 0.4 microM for up to 10.5 hr; and lophotoxin, 32 microM for up to 94 min. Eserine (20 microM) and carbachol (200 microM) increased peak response amplitudes by up to 80% within 5-10 min, and amplitudes remained elevated during 20-33 min of continued treatment. The onset of the effects of d-TC, strychnine, and kynurenic acid began in 5-10 min and was completed in 30 min or less, indicating that test substances could adequately penetrate into the interior of the isolated sections of tectum. The failure of these cholinergic ligands to prevent postsynaptic responses indicates that excitatory retinotectal transmission does not depend on an intact nicotinic (or other cholinergic) system, as previously proposed. The action by kynurenic acid suggests the involvement of an excitatory amino acid neurotransmitter in retinotectal transmission.(ABSTRACT TRUNCATED AT 400 WORDS)


Splenectomy alters blood pressure response to incremental treadmill exercise in horses.
Six intact (IN) and five splenectomized (SP) mares were subjected to an incremental exercise test to examine the effects of splenectomy on blood pressure responses during exercise. During the test the horses ran up a 6 degree grade on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s every 1 min until heart rate (HR) reached a plateau. Hemodynamic data were collected continuously and analyzed for the last 18 s of the 4, 5, 6, and 7 m/s steps of the exercise test. There were no differences (P > 0.05) between the groups for resting means for any parameter measured in the study. HR increased (P < 0.05) in both groups of horses during exercise with significantly greater HR in the SP horses during the first two steps of the test. There were no differences (P > 0.05) in maximal HR between the groups. Right atrial pressure (RAP) did not change during exercise in the SP horses; however, it did increase 20 mmHg (493%, P < 0.05) in the IN horses. Right ventricular pressure (RVP) increased (P < 0.05) during exercise with no differences (P > 0.05) between the groups. Right ventricular maximum change in pressure over time increased (P < 0.05) in a similar fashion in both groups of animals. Mean arterial pressure (MAP) increased 29 mmHg (30%, P < 0.05) in SP horses, reaching a plateau by the 5 m/s step of the test.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and implementation of the Women Leaders in Medicine Program at a multispecialty health care system.
Physicians in the USA are experiencing burnout symptoms at alarming rates, with women surpassing men. Many modalities are used to combat burnout. Leadership training is one proven strategy. Baylor Scott & White Health developed a program of systematic leadership development with quantitative and qualitative surveys and feedback from the 200 female participants of the pilot year. The Women Leaders in Medicine Program invited all Baylor Scott & White Health female physicians in both Central and North Texas to leadership training, which focused on (1) peer networking, (2) leadership skill building, and (3) mentoring, advocacy, and sponsorship with system leaders. The program was well received and highlighted the need for more in-person networking and skill-building opportunities for this demographic. Based on the data collected, the investigators are confident that this program is feasible for replication in diverse clinical settings for all female physicians.


Reliable and Valid Survey-Based Measures to Assess Quality of Care in Home-Based Serious Illness Programs.
Background: There is a pressing need for standardized measures to assess the quality of home-based serious illness care. Currently, there are no validated quality measures that are specific to home-based serious illness programs (SIPs) and the unique needs of their patients. Objective: To develop and evaluate standardized survey-based measures of serious illness care experiences for assessing and comparing quality of home-based serious illness care programs. Methods: From October 2019 through January 2020, we administered a survey to patients who received care from 32 home-based SIPs across the United States. Using the 2263 survey responses, we assessed item performance and constructed composite measures via factor analysis, evaluated item-scale correlations, estimated reliability, and examined validity by regressing overall ratings and willingness to recommend care on each composite. Results: The overall survey response rate was 36%. Confirmatory factor analyses supported five composite quality measures: Communication, Care Coordination, Help for Symptoms, Planning for Care, and Support for Family and Friends. Cronbach's alpha estimates for the composite measures ranged from 0.69 to 0.85, indicating adequate internal consistency in assessing their underlying constructs. Interprogram reliability ranged from 0.67 to 0.80 at 100 completed surveys per measure, meeting common standards for distinguishing between programs' performance. Together, the composites explained 45% of the variance in patients' overall care ratings. Communication, Care Coordination, and Planning for Care were the strongest predictors of overall ratings. Conclusion: Our analyses provide evidence of the feasibility, reliability, and validity of proposed survey-based measures to assess the quality of home-based serious illness care from the perspective of patients and their families.


Effectiveness of outpatient parenteral antimicrobial therapy (OPAT) for patients with cranial infection.
Outpatient parenteral antimicrobial therapy (OPAT) is a well-established and cost-effective method for improving the efficient use of healthcare resources. However, only a few centres in Germany perform it. Here we analysed OPAT for the treatment of patients with cranial infections in our neurosurgical department. This retrospective study analysed patients with cranial infections and the need for intravenous (i.v.) antimicrobial treatment between 2018 and 2021.All diagnosed intracranial infections were defined into two infection categories such as long-term antimicrobial treatment and short-term antimicrobial treatment. All included patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. We identified a total of 45 patients treated with OPAT for cranial infections. Intradural involvement was present in 40 cases (88.9%). The average length of hospital stay for this cohort after surgical treatment was 45 ± 15 days. 5 patients were treated for soft tissue/skin infection. Surgery was not required in this cohort. The mean hospital stay for this cohort was 8 ± 6 days. Gram-positive organisms were isolated in most cases (53.3%). The most common pathogens were Staphylococcus aureus followed by other Staphylococcus species. For all included patients, OPAT was performed after discharge for an average of 43.1 ± 14 days. There were five cases of readmission due to treatment failure. No serious adverse events or complications of OPAT were observed. OPAT enables better patient-centred healthcare close to home. The length of hospital stay can be reduced and adverse events due to prolonged hospitalisation can be avoided.


Visualization of sample introduction in liquid chromatography columns. The effect of the frit diameter.
A previously developed on-column detection technique using 35 mm SLR cameras [J. Chromatogr. A 826 (1998) 1] was employed to visualize colored sample bands as they elute through frits of differing diameter. Head fittings containing a 4.0 mm frit and a 15.9 mm frit were mounted in a 17 mm I.D. glass column packed with C18 silica with an average particle size of 21 microns. A carbon tetrachloride mobile phase of matching refractive index to that of the silica provides clarity along the column diameter during band migration. The photographs of the migrating sample zones were scanned and analyzed with appropriate imaging software. The smallest diameter frit induced severely parabolic sample distributions at the column inlet compared to the larger frit. Local axial dispersion coefficient values, expressed as local reduced plate height, were calculated as well as local zone velocities at the column inlet. The results demonstrate clearly the need to match the diameter of the inlet frit to the I.D. of the column so as to avoid the initial onset of zone broadening due to the frit.


Fibroblast growth factor receptor 2 IIIc as a therapeutic target for colorectal cancer cells.
A high percentage of colorectal carcinomas overexpress a lot of growth factors and their receptors, including fibroblast growth factor (FGF) and FGF receptor (FGFR). We previously reported that FGFR2 overexpression was associated with distant metastasis and that FGFR2 inhibition suppressed cell growth, migration, and invasion. The FGFR2 splicing isoform FGFR2IIIb is associated with well-differentiated histologic type, tumor angiogenesis, and adhesion to extracellular matrices. Another isoform, FGFR2IIIc, correlates with the aggressiveness of various types of cancer. In the present study, we examined the expression and roles of FGFR2IIIc in colorectal carcinoma to determine the effectiveness of FGFR2IIIc-targeting therapy. In normal colorectal tissues, FGFR2IIIc expression was weakly detected in superficial colorectal epithelial cells and was not detected in proliferative zone cells. FGFR2IIIc-positive cells were detected by immunohistochemistry in the following lesions, listed in the order of increasing percentage: hyperplastic polyps < low-grade adenomas < high-grade adenomas < carcinomas. FGFR2IIIc immunoreactivity was expressed in 27% of colorectal carcinoma cases, and this expression correlated with distant metastasis and poor prognosis. FGFR2IIIc-transfected colorectal carcinoma cells showed increased cell growth, soft agar colony formation, migration, and invasion, as well as decreased adhesion to extracellular matrices. Furthermore, FGFR2IIIc-transfected colorectal carcinoma cells formed larger tumors in subcutaneous tissues and the cecum of nude mice. Fully human anti-FGFR2IIIc monoclonal antibody inhibited the growth and migration of colorectal carcinoma cells through alterations in cell migration, cell death, and development-related genes. In conclusion, FGFR2IIIc plays an important role in colorectal carcinogenesis and tumor progression. Monoclonal antibody against FGFR2IIIc has promising potential in colorectal carcinoma therapy.


Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation.
A complex interrelationship exists between sleep and somatotropic activity. In humans, intravenous injections of growth hormone-releasing hormone (GHRH) given during sleep consistently stimulate slow-wave (SW) sleep, particularly when given in the latter part of the night. In the present study, the possible somnogenic effects induced under similar conditions by GH-releasing peptide (GHRP) were investigated in seven young healthy men. Bolus intravenous injections of GHRP-2 (1 microgram/kg body wt) or saline, in randomized order, were given after 60 s of the third rapid-eye-movement period. All GHRP injections were immediately followed by transient prolactin elevations and by GH pulses of a magnitude within or around the upper limit of the physiological range. Except for a nonsignificant tendency to increased amounts of wakefulness during the 1st h after the injection, no effects of GHRP-2 administration on sleep were detected. There was in particular no enhancement of SW sleep. Thus, in contrast to GHRH, late-night single injections of GHRP-2 at a dosage resulting in similar GH elevations have no stimulatory effects on SW sleep. The present data provide evidence against the involvement of the GHRP axis in human SW sleep regulation.


The value of intravesical prostaglandin E2 and F2 alpha in women with abnormalities of bladder emptying.
A clinical study of intravesical prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) in the treatment of 13 female patients with difficulties in emptying their bladder is reported. Urodynamic investigations were performed before and after instillation of the drug. Although 3 patients had some reduction in residual urine volume, the remainder showed no obvious change and no patient experienced subjective improvement. In 6 patients, biopsies of the vesical mucosa were taken before and after instillation in order to measure the uptake of prostaglandin by the mucosa, but no conclusions could be drawn from these measurements. Although prostaglandins are known to have contractile effects on the detrusor muscle, the results of this study suggest that intravesical PGE2 and PGF2 alpha have no therapeutic value in the treatment of voiding dysfunction and residual urine.


Short communication: Inadequate vitamin D exacerbates parathyroid hormone elevations in tenofovir users.
Parathyroid hormone (PTH) elevations are associated with reduced bone mineral density and adverse health outcomes and have been reported in patients with HIV infection. We aimed to examine the impact of vitamin D status and tenofovir (TDF) use on PTH levels among HIV-infected patients receiving combination antiretroviral therapy (cART). Demographics, medication and supplement use, and clinical data, including 25-hydroxyvitamin D [25(OH)D] and PTH, were collected on 45 HIV-infected men on ART. Suboptimal vitamin D status was defined as 25(OH)D < 30 ng/ml. The relationship between antiretroviral agents, suboptimal 25(OH)D, and PTH levels was examined. Among subjects with suboptimal vitamin D status, PTH values greater than or equal to the ULN (87 pg/ml) were more common among TDF users than nonusers: 41% versus 0% (p = 0.018); and median PTH was higher in TDF users: 80 pg/ml versus 55 pg/ml (p = 0.02). Among TDF users, PTH was higher in the group with suboptimal 25(OH)D (p = 0.045). Multivariable linear regression showed that PTH was independently and directly related to TDF use (p = 0.017) and inversely related to 25(OH)D (p = 0.017). PTH was not related to the estimated glomerular filtration rate (p = 0.9). In this cross-sectional study of HIV-infected men on ART, the use of TDF and the level of 25(OH)D were independently associated with PTH levels. Because TDF is a potent and widely used antiretroviral drug, information about cofactors that may exacerbate its side effects is of significant clinical value.


Moyamoya Disease in Children: Results From the International Pediatric Stroke Study.
This study aimed to describe children with moyamoya disease from an international multicenter stroke database, and explore risk factors for stroke recurrence. We reviewed data of children >28-days old with moyamoya disease enrolled in the International Pediatric Stroke Study from January 2003 to March 2013. A total of 174 children from 32 sites and 14 countries had moyamoya disease; median age 7.4 years, 49% male. Of these, 90% presented with ischemic stroke, 7.5% with transient ischemic attack, and 2.5% with hemorrhagic stroke. One-third of patients had moyamoya syndrome. Stroke recurrence was 20% over median follow-up of 13 months; 9% had multiple recurrences. Children treated with surgical revascularization were less likely to have stroke recurrence ( P = .046). Moyamoya disease accounted for 8% of arterial strokes in this international pediatric stroke registry. One-third of pediatric patients with moyamoya disease have an underlying syndromic condition. Surgical revascularization is effective at reducing the incidence of stroke recurrence.


Gastroduodenal ulcer bleeding in elderly patients on low dose aspirin therapy.
To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin (LDA) therapy. A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used, and these groups were compared in several factors. These groups were compared in terms of length of hospital stay, presence/absence of hemoglobin (Hb) decrease, presence/absence of blood transfusion, Forrest I, percentage of Helicobacter pylori infection, presence/absence of underlying disease, and percentage of severe cases. The percentage of blood transfusion (62.6% vs 47.7 %, P < 0.001), Hb decrease (53.8% vs 40.8%, P < 0.001), and the length of hospital stay (23.5 d vs 16.7 d, P < 0.001) were significantly greater in those on drug therapy. The percentage of blood transfusion (65.3% vs 47.8%, P < 0.001), Hb decrease (54.2% vs 42.1%, P < 0.001), and length of hospital stay (23.3 d vs 17.5 d, P < 0.001) were significantly greater in the elderly. In comparison with the LDA monotherapy group, the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned (16.1% vs 34.0%, P = 0.030). Meanwhile, among those on LDA monotherapy, there was no significant difference between elderly and non-elderly (16.1% vs 16.0%, P = 0.985). A combination of LDA with antithrombotic drugs or non-steroidal anti-inflammatory drugs (NSAIDs) contributes to aggravation. And advanced age is not an aggravating factor when LDA monotherapy is used.


Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1- Dysfunctional State.
T cells recognize several types of antigens in tumors, including aberrantly expressed, nonmutated proteins, which are therefore shared with normal tissue and referred to as self/shared-antigens (SSA), and mutated proteins or oncogenic viral proteins, which are referred to as tumor-specific antigens (TSA). Immunotherapies such as immune checkpoint blockade (ICB) can activate T-cell responses against TSA, leading to tumor control, and also against SSA, causing immune-related adverse events (irAE). To improve anti-TSA immunity while limiting anti-SSA autoreactivity, we need to understand how tumor-specific CD8+ T cells (TST) and SSA-specific CD8+ T (SST) cells differentiate in response to cognate antigens during tumorigenesis. Therefore, we developed a genetic cancer mouse model in which we can track TST and SST differentiation longitudinally as liver cancers develop. We found that both TST and SST lost effector function over time, but while TST persisted long term and had a dysfunctional/exhausted phenotype (including expression of PD1, CD39, and TOX), SST exited cell cycle prematurely and disappeared from liver lesions. However, SST persisted in spleens in a dysfunctional TCF1+PD-1- state: unable to produce effector cytokines or proliferate in response to ICB targeting PD-1 or PD-L1. Thus, our studies identify a dysfunctional T-cell state occupied by T cells reactive to SSA: a TCF1+PD-1- state lacking in effector function, demonstrating that the type/specificity of tumor antigen may determine tumor-reactive T-cell differentiation.


A 21-day schedule of gemcitabine and cisplatin administration in the treatment of advanced non-small cell lung carcinoma: a phase II study.
To evaluate the efficacy and toxicity of gemcitabine and cisplatin combination chemotherapy, we conducted a phase II study of this regimen in patients with advanced non-small cell lung carcinoma (NSCLC). From June 2001 to August 2003, 36 chemotherapy-naive patients with stage IIIB or IV NSCLC were enrolled. The median age was 59 years (range, 42 to 75 years), and performance status was 0 or 1. Eleven patients had stage IIIB disease, and 25 patients had stage IV disease. 1,000 mg/m(2) of gemcitabine was administered on day 1 & 8, and 60 mg/m(2) of cisplatin was administered on day 1. Each cycle was repeated every 21 days. Everyone subject who participated were assessable. A total of 160 cycles of chemotherapy were delivered, and the median number of chemotherapy courses was 3.5 (range, 2 to 9). Two patients (5.6%) achieved a complete response, and 14 patients (38.9%) achieved a partial response. The overall response rate was 44.5% (95% confidence interval [CI], 32.5 to 56.5%). The median follow-up duration was 9.3 months. The median time to disease progression was 8.6 months (95% CI 7.4 to 9.9 months), and median survival time was 12.2 months (95% CI, 10.5 to 12.9 months). Grade 3/4 neutropenia occurred in 9 patients (25.0%), neutropenic fever occurred in 3 patients (8.3%), and grade 3/4 thrombocytopenia occurred in 7 patients (19.5%). Mild forms of non-hematologic toxicities, such as nausea, vomiting or skin reactions, were observed. The combination of gemcitabine and cisplatin in a 21-day schedule is an effective regimen for patients with NSCLC in its advanced stages.


Susceptibility of oral bacteria to antibacterial photodynamic therapy.
Effective methods for managing the oral microbiome are necessary to ensure not only the oral but also the systemic health of a human body. The purpose of this study was to determine the sensitivity of four photosensitizers (PSs) to blue light in six representative oral bacterial species that cause intraoral diseases. The following six strains were investigated: Actinomyces israelii, Enterococcus faecium, Fusobacterium nucleatum, Lactobacillus gasseri, Streptococcus mutans, Veillonella parvula. PS stock solutions (1 mg/ml) were prepared by dissolving curcumin and protoporphyrin-IX in dimethyl sulfoxide, and resazurin and riboflavin in distilled water. The inoculation of 20 ml of a bacterial suspension cultured for 24 hours was mixed with 1,980 ml of each test solution, and then a light source was placed in front of the mixture. The irradiation wavelength was 405 nm and its applied energy was 25.3 J. The independent-samples t-test and one-way analysis of variance within groups were performed to compare the antibacterial effects in the four PSs. The antibacterial susceptibility when using different PSs and visible blue-light irradiation differed between the bacterial strains. Antibacterial photodynamic therapy that includes light exposure and PSs can be used to control the oral bacteria strains related to oral disease.


The affordability of adding a direct-acting oral anticoagulant to the national list of essential medicine for patients with non-valvular atrial fibrillation in Thailand: a budget impact analysis.
Atrial fibrillation (AF) can lead to a significant health and economic burden to society. This study aimed to assess the net budget impact of direct-acting oral anticoagulants (DOACs) instead of warfarin for stroke prevention in patients with non-valvular AF from the payer's perspective. A budget model over a 5-year period was used. Dabigatran 150 mg, dabigatran 110 mg, apixaban 5 mg, rivaroxaban 20 mg, edoxaban 60 mg, and edoxaban 30 mg were included. Inputs were retrieved from published literature. Adoption rate of DOACs started at 5% and subsequently had a 5% increase in each year. Net budget impact (NBI) and sensitivity analyses were performed. The average NBI over the 5-year horizon for all DOACs ranged from 12.3 M USD to 13.9 M USD. Dabigatran 150 mg had the highest NBI, while edoxaban 30 mg had the lowest NBI. The average NBI/patient/year ranged from 63.03 USD - 70.75 USD. Of all DOACs, edoxaban 30 mg, apixaban 5 mg, and edoxaban 60 mg are the top 3 lowest NBI. Together with cost-effectiveness evidence, those DOACs should be considered to be listed on the National List of Essential Medicine in Thailand.


The synthesis and secretion of fatty acid ethyl esters from HepG2 cells are stimulated by lipoproteins and albumin.
Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by the esterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma after ethanol ingestion bind to lipoproteins and albumin. In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid to generate 3H-FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE acceptors. The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium. These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage.


Effects of ideomotor apraxia on functional outcomes in patients with right hemiplegia.
The aim of this study was to investigate the effect of ideomotor apraxia on activities of daily living and to determine if the presence of apraxia interferes with rehabilitation. This study was conducted on 47 patients with right hemiplegia. All the patients were assessed at their admission and discharge, respectively, for apraxia by Ideomotor Apraxia Test, for daily living activities by Functional Independence Measure (FIM, Santa Clara Valley Medical Center, San Jose, California, USA), for cognitive functions by Mini Mental State Examination (MMSE), and for language components by Gulhane Aphasia Test (GAT). The effects of apraxia presence and time course on FIM, MMSE, and GAT scores were investigated. Presence of apraxia was found to have significant effect on all test scores (P<0.05). Time course had the main significant effect on FIM, MMSE, and GAT scores (P<0.05). Interaction effect of both presence of apraxia and time course on the test scores was not significant either. In other words, apraxic and nonapraxic patients seemed to gain benefits from the neurological rehabilitation. However, mean FIM scores of apraxic patients during discharge have failed to reach the mean FIM scores of nonapraxic patients during admission. Apraxia is considered as an important determinant in the dependence of patients with stroke in their activities of daily living. For this reason, during the initial assessment of patients with right hemiplegia, apraxia should be tested, and the presence of apraxia as well as its severity should be determined.


The preliminary transcript map of a human skeletal muscle.
By sequencing 11,405 individual expressed sequence tags (ESTs) from a cDNA library of a human skeletal muscle, we identified 1945 individual transcripts, 725 of which showed no correspondence with known human genes. We report here the chromosomal localization of 267 of these, obtained by radiation hybrid (RH) mapping. The map position of additional 242 ESTs from the same library, corresponding to known human genes, is also reported. The resulting information provides a preliminary genomic transcriptional profile of a human muscle. Several genes occur in clusters on different chromosomes. Moreover, chromosomes 17, 19, 21 and X appear to be significantly rich in muscle ESTs. By analysing several collections of ESTs from different tissues, we observed significant deviations in the distribution of ESTs by chromosome in fetal heart, adult brain and adult retina, supporting the hypothesis that a non-random localization of genes expressed in specific tissues might not be uncommon. The selective concentration of expressed genes in some chromosomes and in specific chromosomal subregions in a given tissue might reflect the existence of batteries of genes under the same control mechanisms, regulating tissue-specific gene expression.


The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.
Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.


Hematuria in breast cancer: don't forget bladder metastases!
The bladder is a rare site for breast cancer metastases, and only occasional reports are present in the literature. Most cases coexist with synchronous metastases elsewhere, but isolated cases of a single metastatic localization in the urinary bladder have been reported. The most common symptoms of a metastatic localization of breast cancer to the urinary bladder are hematuria and voiding dysfunction. Herein we present three cases of urinary bladder metastasis from breast carcinoma, all presenting with gross hematuria as the only symptom. After a review of the relevant literature, we discuss the clinical and histological characteristics unique to our cases, highlighting potential clinical and pathological diagnostic pitfalls and differential diagnoses.


Efficient microwave assisted synthesis of metal-organic framework UiO-66: optimization and scale up.
A highly efficient and scalable microwave assisted synthesis of zirconium-based metal-organic framework UiO-66 was developed. In order to identify the best conditions for optimizing the process, a wide range of parameters was investigated. The efficiency of the process was evaluated with the aid of four quantitative indicators. The properties of the materials prepared by microwave irradiation were compared with those synthesized by conventional heating, and no significant effects on morphology, crystal size, or defects were found from the use of microwave assisted heating. Scale up was performed maintaining the high efficiency of the process.


Diagnosis and treatment of delirium.
Delirium is not a clinical entity but a symptom-complex of manifold etiology. Its presence signifies acute cerebral insufficiency and often represents a medical and/or psychiatric emergency.Though some forms of delirium have distinctive features, the fundamental phenomena are common to all, with clouding of consciousness the sine qua non. The condition has two major components: (1) the basic "acute brain syndrome" and (2) associated release phenomena.Clinicians must first make the vital differentiation between delirium and "functional" mental disorder, then proceed with the elucidation of the underlying diagnosis and the concurrent organization of symptomatic and etiologic treatment.Proper treatment combines management of the acute brain syndrome with general and specific procedures for control of the underlying condition. Dealing with the symptom-complex itself involves the principles and practice of sedation, hydration, and nutrition, nursing care and supportive measures. Provided the basic organic condition is treatable, the prognosis today is usually good.


RNA-Seq Profiling of Intact and Enucleated Oocyte SCNT Embryos Reveals the Role of Pig Oocyte Nucleus in Somatic Reprogramming.
The specific molecular mechanisms involved in somatic reprogramming remain unidentified. Removal of the oocyte genome is one of the primary causes of developmental failure in cloned embryos, whereas intact oocyte shows stronger reprogramming capability than enucleated oocyte. To identify the reason for the low efficiency of cloning and elucidate the mechanisms involved in somatic reprogramming by the oocyte nucleus, we injected pig cumulus cells into 539 intact MII oocytes and 461 enucleated MII oocytes. Following activation, 260 polyploidy embryos developed to the blastocyst stage whereas only 93 traditionally cloned embryos (48.2% vs. 20.2%, P < 0.01) reached blastocyst stage. Blastocysts generated from intact oocytes also had more cells than those generated from enucleated oocytes (60.70 vs. 46.65, P < 0.01). To identify the genes that contribute to this phenomenon, two early embryos in 2-cell and 4-cell stages were collected for single-cell RNA sequencing. The two kinds of embryos were found to have dramatically different transcriptome profiles. Intact oocyte nuclear transfer embryos showed 1,738 transcripts that were up-regulated relative to enucleated cloned embryos at the 2-cell stage and 728 transcripts that were down-regulated (|log2Ratio| ≥ 5). They showed 2,941 transcripts that were up-regulated during the 4-cell stage and 1,682 that were down-regulated (|log2Ratio| ≥ 5). The most significantly enriched gene ontology categories were those involved in the regulation of binding, catalytic activity, and molecular transducer activity. Other genes that were notably up-regulated and expressed in intact oocyte nuclear transfer embryos were metabolic process. This study provides a comprehensive profile of the differences in gene expression between intact oocyte nuclear transfer embryos and traditional nuclear transfer embryos. This work thus paves the way for further research on the mechanisms underlying somatic reprogramming by oocytes.


[Familial Alzheimer's disease with presenilin 2 N141I mutation. A case report].
Alzheimer's disease (AD) is the most common form of dementia. Approximately 0.5 per cent of all AD is caused by single major gene mutations and autosomal dominant inheritance. These familial types with early-onset (EOFAD) usually display dementia before the age of 60. Such mutations have been found in the gene encoding amyloid precursor protein (APP), and in the genes encoding presenilin 1 (PSEN1) or presenilin 2 (PSEN2). We herein report the case of a German patient with a EOFAD and a missense mutation at codon 141 (N141I) of the PSEN2 gene. The patient came to our psychiatric clinic for the first time when she was 49 years old. During the following 3 years, her Mini-Mental-State-Examination (MMSE) score dropped from 14 to 0 points. Positron emission tomography with [18F] Fluorodeoxyglucose (18F-FDG PET) demonstrated glucose reduction left parietal and in the pre-cuneus region. Follow-up 18F-FDG PET studies showed progressive hypometabolism of both temporoparietal lobes and left frontal lobe.


Management of amiodarone extravasation with intradermal hyaluronidase.
The case of a patient who experienced extravasation while receiving amiodarone via a peripheral infusion and was treated with intradermal hyaluronidase is reported. A 60-year-old Caucasian man arrived at the emergency department after a motor vehicle collision. The patient was noted to have a subdural hematoma, multiple rib fractures, sternal body fracture, abdominal wall injury, left clavicle fracture, right humerus fracture, and vertebral fractures. His medical history included hypertension, atrial fibrillation, and stroke with residual right-sided weakness. On postoperative day 1, the patient developed atrial fibrillation and was started on i.v. amiodarone. Treatment resulted in conversion to sinus rhythm, but the patient again developed atrial fibrillation on postoperative day 5. During the morning hours of postoperative day 6, the patient experienced a peripheral i.v. line extravasation of amiodarone in his left arm. The amiodarone drip was discontinued, and amiodarone 400 mg orally twice daily was started. The nursing staff was instructed to treat the patient for the amiodarone extravasation with traditional nonpharmacologic measures, including warm compresses and elevation of the extremity. After extravasation, the patient reported severe pain at the site. Due to the patient's continued complaints of pain and the expanding area of induration, the interdisciplinary team elected to proceed with intradermal hyaluronidase. The patient reported significantly decreased pain and was discharged to inpatient rehabilitation on postoperative day 10 without any significant adverse effects. Administration of intradermal hyaluronidase after amiodarone extravasation was associated with decreased expansion of erythema and warmth as well as an improvement in patient-reported pain scores without any noted adverse effects.


[Fragment of the all-Ukrainian investigation of the microflora sensitivity to antibacterial preparations in patients with intra-abdominal surgical infection].
All-Ukrainian investigation of microflora sensitivity to antibacterial preparations in patients with intraabdominal infection (IAI) have included studying of microbial landscape of the abdominal cavity content in IAI, and the causing agents sensitivity to main antibacterial preparations was determined, including those, manufactured by corporation "Arterium" (Ukraine).


TNFα-mediated Hsd11b1 binding of NF-κB p65 is associated with suppression of 11β-HSD1 in muscle.
The activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone (11-dehydrocorticosterone (11-DHC)) (in mice) into the active glucocorticoid (GC) cortisol (corticosterone in mice), can amplify tissue GC exposure. Elevated TNFα is a common feature in a range of inflammatory disorders and is detrimental to muscle function in diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease. We have previously demonstrated that 11β-HSD1 activity is increased in the mesenchymal stromal cells (MSCs) by TNFα treatment and suggested that this is an autoregulatory anti-inflammatory mechanism. This upregulation was mediated by the P2 promoter of the Hsd11b1 gene and was dependent on the NF-κB signalling pathway. In this study, we show that in contrast to MSCs, in differentiated C2C12 and primary murine myotubes, TNFα suppresses Hsd11b1 mRNA expression and activity through the utilization of the alternative P1 promoter. As with MSCs, in response to TNFα treatment, NF-κB p65 was translocated to the nucleus. However, ChIP analysis demonstrated that the direct binding was seen at position -218 to -245 bp of the Hsd11b1 gene's P1 promoter but not at the P2 promoter. These studies demonstrate the existence of differential regulation of 11β-HSD1 expression in muscle cells through TNFα/p65 signalling and the P1 promoter, further enhancing our understanding of the role of 11β-HSD1 in the context of inflammatory disease.


Molecular and Quantum Mechanical Study for the Separation of Cefprozil in the Presence of Its Alkaline Degradation Product Using RP-HPLC with UV Detection.
A reversed-phase HPLC method (RP-HPLC) with UV detection was developed and validated for the quantitative determination of cefprozil, a second-generation cephalosporin. Due to β-lactam ring instability under alkaline conditions, this RP-HPLC method was applied for the determination of cefprozil in the presence of its possible degradation product. The interactions that govern the separation process with stationary phase were investigated at both molecular and quantum mechanical levels. Moreover, electrostatic potential maps were generated to determine the sites of interaction with mobile phase. The suggested method was validated in compliance with International Conference on Harmonization guidelines and successfully applied for the determination of cefprozil in its commercial pharmaceutical formulation.


Characteristics of ambulatory care clinics and pharmacists in Veterans Affairs medical centers. IMPROVE investigators. Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers.
The type and extent of ambulatory care clinical pharmaceutical services in selected Veterans Affairs medical centers (VAMCs) were studied as part of a larger project. Questionnaires were sent to the 174 VAMCs to determine the extent of clinical pharmacy activity in ambulatory care clinics, characteristics of outpatient pharmacies and clinics, and characteristics of ambulatory care pharmacists in VAMCs and to identify sites for the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) project. Fifty VAMCs responded to the survey. There were 512 ambulatory care clinics within these VAMCs. There was some pharmacist coverage in 75% of the clinics. The highest pharmacist coverage was in walk-in refill, therapeutic drug monitoring, and anticoagulation clinics. Clinical pharmacists at 68% of the VAMCs had prescribing privileges in ambulatory care clinics. Clinical pharmacists managed 29.9% of the clinics. The types of clinics most commonly managed by pharmacists were therapeutic drug monitoring, anticoagulation, walk-in refill, and lipid clinics. Nurse practitioners or physician assistants also were providing primary care in 41% of the clinics. There were 242 ambulatory care clinical pharmacy specialists practicing in the 50 VAMCs. Of these, 41.3% had three years or less of ambulatory care experience. Most pharmacists were in the clinic five days per week. A Pharm.D. degree was the highest degree obtained for 76.9%. Ambulatory care pharmaceutical services are common in VAMCs and are being provided by numerous clinical pharmacists.


An analysis of binding at the opioid receptor based upon an agonist/antagonist two-state model.
Experimental binding data for a number of opioid agonists and antagonists in homogenate of rat brain membranes at 0 degrees have been analyzed in terms of the two-state Snyder-Pert receptor model. By means of iterative nonlinear regression techniques, it was possible to evaluate the affinity constants characterizing the binding of each drug at the agonist and antagonist states of the receptor. In addition, the role of Na+ in determining the state of the receptor has been described quantitatively. The findings of this study are discussed in terms of the index, fr, which provides a theoretical measure of the fraction of receptors existing in the agonists state. The graph of fr as a function of drug concentration may be reasonably interpreted as an ideal dose-response curve which might be obtained if the drug were introduced directly at the receptor. The implications of the findings with respect to receptor operation are discussed. Although the binding constants have not been found under physiological conditions, the results indicate that the receptor mechanism remains essentially intact in the brain membrane preparation.


Toward Bioluminescent Materials by Plasma Treatment of Microfibrous Nonwovens, Followed by Immobilization of One or Both Enzyme(s) (Luciferase and FMN Reductase) Involved in Luminescent Bacteria.
Bioluminescent living organisms emit light through a specific biocatalyzed reaction involving a luciferin substrate and a luciferase enzyme. The present work investigated the possibility of creating optimal luminescence by immobilization of one or both the enzymes Luciferase (Luc) and FMN reductase (Red) involved in a bioluminescent bacterial system onto a plasma-activated microfibrous PET nonwoven. Parameters affecting the catalytic activity and efficiency of the bacterial system in aqueous medium were determined by luminescence intensity measurements using a luminometer. Two types of plasma, air atmospheric plasma (ATMP) and cold remote plasma (CRPNO) treatment, were used to activate the PET nonwoven. Further, one or both enzyme(s) were immobilized using a physical adsorption technique, without or with the use of natural biopolymers (gelatin and starch) and bovine serum albumin-BSA protein, to improve enzyme stability and activity. Coimmobilization of both Red and Luc enzymes on the CRPNO plasma-activated nonwoven in the presence of BSA led to the maximum luminescence. As high as 60,000 RLU equivalent to that of an LED light used for calibration was observed and showed stable intensity up to 6 min. Fiber surface analysis was tested using wettability tests (water contact angle and capillary uptake), while scanning electron microscopy, atomic force microscopy, and electron spectroscopy for chemical analysis showed changes in fiber surface morphology and chemical functional groups. A considerable increase in "N" atom content after coimmobilization of enzymes in the presence of BSA was detected. This study is the first successful attempt to use a biomimetic strategy for immobilization of enzymes involved in bacterial luminescence on a plasma-activated microfibrous nonwoven in an attempt to attain bioluminescent materials.


Peptides as carrier for tumor diagnosis and treatment.
The specific binding of peptides to their receptors can be used to meet the key requirement in tumor targeting: selective addressing of neoplasm. Because of their small size, peptides exhibit faster blood clearance and higher target-to-background ratios compared to macromolecular compounds. In radiopharmacy, these advantages have been attended, and radiolabelled receptor-binding peptides have emerged as a new class of radiopharmaceuticals. Over the last years, nuclear medicine has evaluated various peptides for tumor scintigraphy. The challenge is to label bioactive peptides without affecting their receptor binding properties. Size, plasma protein binding, lipophilicity and sensitivity to proteolysis are to be considered, as well as biodistribution, metabolism and excretion characteristics. The variety of experiences gained in the development of peptide analogues and radiolabelling methods, and latest results from in vitro, in vivo and clinical studies will be presented. The tumor receptor-targeting approach with peptides can be extended to cancer chemotherapy. One of the major problems in classic chemotherapy is the non-specific toxicity of most anticancer agents against normal cells. Coupling cytotoxic drugs to macromolecular carriers has been shown to be a promising approach for efficient drug targeting. In the past few years, peptides were introduced as carriers. Different conjugates, composed of a peptide carrier and a cytotoxic moiety, have been investigated so far. Anticancer drugs were coupled to analogues of luteinizing hormone-releasing hormone, bombesin, somatostatin and neuropeptide Y. Suitable candidates maintained their binding affinity and could preserve the cytotoxic activity in vitro and in vivo, resulting in a peptide-mediated selective chemotherapy.


Innovative Combination Treatment to Expand the Indications of Particle Therapy: Spacer Placement Surgery Using Bio-Absorbable Polyglycolic Acid Spacer.
Particle therapy (PT) has favorable dose distribution and high curability. However, radiotherapy for malignant tumors adjacent to the gastrointestinal tract is contraindicated owing to its low tolerance. To overcome this, combination treatment with surgery to make a space between the tumor and adjacent gastrointestinal tract followed by PT has been developed. Several materials have been used for the spacer, and we have recently developed the absorbable polyglycolic acid (PGA) spacer, which has been used since 2019. This study is the first report of consecutive case series of spacer placement surgery using the PGA spacer. Fifty consecutive patients undergoing spacer placement surgery with the PGA spacer were evaluated. Postoperative laboratory data, morbidity related to the treatment, and spacer volume after treatment were evaluated. There were no treatment-related deaths, and all but two patients completed combination treatment. The median ratios of post-operative PGA spacer volume to the pre-treatment volume were 96.9%, 87.7%, and 74.6% at weeks 2, 4, and 8, respectively. The spacer volume was maintained at 80% at 7 weeks and was predicted to be 50% at 15 weeks and 20% in 24 weeks. Spacer placement surgery using the PGA spacer was feasible and tolerable. The PGA spacers maintained sufficient thickness during the duration of subsequent PT. Combination treatment using the PGA spacer is innovative and has the potential to become a new standard curative local treatment.


Spatial and temporal variation of biochemical biomarkers in Gobius niger (Gobiidae) from a southern Mediterranean lagoon (Bizerta lagoon, Tunisia): Influence of biotic and abiotic factors.
This study aims at evaluating both the influence of natural and some anthropogenic pressures on spatio-temporal variations on biomarker responses in sedentary benthic fish Gobius niger. For this purpose, variability of biotransformation enzymes and oxidative stress parameters response were studied in six stations from Bizerta lagoon as well as a reference station located in Ghar El Melh lagoon. Biomarker responses were shown to vary according to both physico-chemical parameters and anthropogenic pressures, but no influence of sex was reported. Based on multivariate analyses, the responses of biomarkers, obtained after covariate analysis in order to weigh the effect of physico-chemical parameters, allowed us to discriminate all stations, with a good classification rate for those that are highly contaminated. Altogether, this study shows the usefulness of G. niger as a sentinel species and stresses the necessity of integrating natural variables for data interpretation.