Multiplex Detection of Antibiotic Residues in Milk: Application of MCR-ALS on Excitation-Emission Matrix Fluorescence (EEMF) Data Sets.
The presence of antibiotics and their metabolites in milk and dairy products is a serious concern because of their harmful effects on human health. In the current study, a novel synergistic bimetallic nanocluster with gold and silver as an emission fluorescence probe was investigated for the simultaneous determination of tetracycline (TC), ampicillin (AMP), and sulfacetamide (SAC) antibiotics in the milk samples using excitation-emission matrix fluorescence (EEMF) spectroscopy. The multivariate curve resolution-alternating least squares (MCR-ALS) method was implemented to analyze augmented EEMF data sets to quantify the multicomponent systems in the presence of interferences with considerable spectral overlap. A pseudo-univariate calibration curve of the resolved emission spectra intensity against the concentration of the mentioned antibiotics was linear in the range of 5-5000 ng mL-1 for AMP and 50-5000 ng mL-1 for TC and SAC. The calculated values of the limit of detection ranged between 1.4 and 14.6 ng mL-1 with a relative standard deviation (RSD) of less than 4.9%. The obtained results show that the EEMF/MCR-ALS methodology using an emission fluorescence probe is a powerful tool for the simultaneous quantification of TC, AMP, and SAC in complex matrices with highly overlapped spectra.


Tree-structured method for LUT inverse halftoning and for image halftoning.
Recently, the authors proposed a Look Up Table (LUT) based method for inverse halftoning of images. The LUT for inverse halftoning is obtained from the histogram gathered from a few sample halftone images and corresponding original images. Many of the entries in the LUT are unused because the corresponding binary patterns hardly occur in commonly encountered halftones. These are called nonexistent patterns. In this paper, we propose a tree structure which will reduce the storage requirements of an LUT by avoiding nonexistent patterns. We will demonstrate the performance on error diffused images and ordered dither images. Then, we introduce LUT based halftoning and tree-structured LUT (TLUT) halftoning. Even though TLUT method is more complex than LUT halftoning, it produces better halftones and requires much less storage than LUT halftoning.We will demonstrate how error diffusion characteristics can be achieved with this method. Afterwards, our algorithm will bet rained on halftones obtained by Direct Binary Search (DBS).The complexity of TLUT halftoning is higher than error diffusion algorithm but much lower than DBS algorithm. Also, the halftone quality of TLUT halftoning increases if the size of TLUT gets bigger. Thus, halftone image quality between error diffusion and DBS will be achieved depending on the size of tree-structure in TLUT algorithm.


Studies on absorption and hydrolysis of ethyl alpha-D-glucoside in rat intestine.
Ethyl alpha-D-glucoside (alpha-EG) is normally contained in Sake, which has been taken by Japanese people since ancient times. In this study, the intestinal absorption of alpha-EG was investigated using rat everted intestinal sac. Furthermore, the alpha-EG hydrolytic activity in rat intestine was compared with disaccharides hydrolytic activities, and the effects of alpha-EG on disaccharides hydrolysis were examined using crude enzyme preparation from rat intestinal acetone powder. Glucose liberated from alpha-EG was detected in a serosal solution of everted rat intestinal sac, but it was only less than 4% of absorbed intact alpha-EG. alpha-EG absorption into small intestinal tissue was reduced by elimination of sodium ion from the mucosal solution or under the presence of phlorizin. The hydrolytic activity for alpha-EG was detected in crude enzyme preparation from rat intestinal acetone powder, but it showed a low value as compared to those for disaccharides. alpha-EG showed mixed type inhibition for maltose and sucrose hydrolysis, but inhibitory concentrations of alpha-EG required for 50% inhibition for the maltose and sucrose hydrolysis were higher than those of arabinose and acarbose. In conclusion, a small amount of alpha-EG was hydrolyzed and most of it was absorbed via SGLT1 as an intact form in the rat small intestine, and the inhibitory effect of alpha-EG on disaccharides hydrolysis was weak.


Complex Ecological Phenotypes on Phylogenetic Trees: A Markov Process Model for Comparative Analysis of Multivariate Count Data.
The evolutionary dynamics of complex ecological traits-including multistate representations of diet, habitat, and behavior-remain poorly understood. Reconstructing the tempo, mode, and historical sequence of transitions involving such traits poses many challenges for comparative biologists, owing to their multidimensional nature. Continuous-time Markov chains are commonly used to model ecological niche evolution on phylogenetic trees but are limited by the assumption that taxa are monomorphic and that states are univariate categorical variables. A necessary first step in the analysis of many complex traits is therefore to categorize species into a predetermined number of univariate ecological states, but this procedure can lead to distortion and loss of information. This approach also confounds interpretation of state assignments with effects of sampling variation because it does not directly incorporate empirical observations for individual species into the statistical inference model. In this study, we develop a Dirichlet-multinomial framework to model resource use evolution on phylogenetic trees. Our approach is expressly designed to model ecological traits that are multidimensional and to account for uncertainty in state assignments of terminal taxa arising from effects of sampling variation. The method uses multivariate count data across a set of discrete resource categories sampled for individual species to simultaneously infer the number of ecological states, the proportional utilization of different resources by different states, and the phylogenetic distribution of ecological states among living species and their ancestors. The method is general and may be applied to any data expressible as a set of observational counts from different categories. [Comparative methods; Dirichlet multinomial; ecological niche evolution; macroevolution; Markov model.].


17β estradiol recruits GluN2B-containing NMDARs and ERK during induction of long-term potentiation at temporoammonic-CA1 synapses.
When circulating 17β estradiol (E2) is elevated to proestrous levels, hippocampus-dependent learning and memory is enhanced in female rodents, nonhuman primates, and women due to heightened synaptic function at hippocampal synapses. We previously reported that proestrous-like levels of E2 administered to young adult ovariectomized (OVX) female rats increases the magnitude of LTP at CA3 Schaffer collateral (SC)-CA1 synapses only when dendritic spine density, the NMDAR/AMPAR ratio, and current mediated by GluN2B-containing NMDA receptors (NMDARs) are simultaneously increased. We also reported that this increase in GluN2B-mediated NMDAR current in area CA1 is causally related to the E2-induced increase in novel object recognition, tying together heightened synaptic function with improved learning and memory. In addition to SC inputs, innervation from the entorhinal cortex in the temporoammonic (TA) pathway onto CA1 distal dendrites in stratum lacunosum-moleculare is critical for spatial memory formation and retrieval. It is not known whether E2 modulates TA-CA1 synapses similarly to SC-CA1 synapses. Here, we report that 24 hours post-E2 injection, dendritic spine density on CA1 pyramidal cell distal dendrites and current mediated by GluN2B-containing NMDARs at TA-CA1 synapses is increased, similarly to our previous findings at SC-CA1 synapses. However, in contrast to SC-CA1 synapses, AMPAR transmission at TA-CA1 synapses is significantly increased, and there is no effect on the LTP magnitude. Pharmacological blockade of GluN2B-containing NMDARs or ERK activation, which occurs downstream of synaptic but not extrasynaptic GluN2B-containing NMDARs, attenuates the LTP magnitude only in slices from E2-treated rats. These data show that E2 recruits a causal role for GluN2B-containing NMDARs and ERK signaling in the induction of LTP, cellular mechanisms not required for LTP induction at TA-CA1 synapses in vehicle-treated OVX female rats.


Quality by design: concepts for ANDAs.
Quality by design is an essential part of the modern approach to pharmaceutical quality. There is much confusion among pharmaceutical scientists in generic drug industry about the appropriate element and terminology of quality by design. This paper discusses quality by design for generic drugs and presents a summary of the key terminology. The elements of quality by design are examined and a consistent nomenclature for quality by design, critical quality attribute, critical process parameter, critical material attribute, and control strategy is proposed. Agreement on these key concepts will allow discussion of the application of these concepts to abbreviated new drug applications to progress.


Phosphate depletion therapy in two ectopic calcification syndromes.
Ectopic calcification may be a complication of a wide variety of pathologic conditions. Subcutaneous calcification frequently results in restriction of motion at joints in addition to cosmetic deformity. Parenchymal tissue calcification may result in decreased organ function. Dietary phosphate restriction and total body phosphate depletion with aluminum containing antacids were used in an attempt to decrease the deposition of subcutaneous calcium phosphate which occurs with two separate syndromes. Two subjects with hyperphosphatemic tumoral calcinosis were studied by metabolic balance, by long-term clinical evaluation, and routine laboratory and radiographic techniques before and after 1 year of phosphate depletion. One patient with a newly described syndrome--normocalcemic, hypercalciuric, subcutaneous calcification--was similarly studied. The etiology of this disorder is unknown. No consistent clinically significant evidence of regression of the lesions was noted in either syndrome, although one patient with tumoral calcinosis did demonstrate some regression of his lesions. It is not clear if this response failure was due to the intrinsic nature of the diseases or to failure of patient compliance secondary to a relatively unpalatable diet.


Development of a multi frequency pulse diagnostic ultrasound device.
Diagnostic ultrasound is a powerful tool for characterising a wide range of solutions, with devices such as the continuous wave Malvern Ultrasizer at the forefront. However to reduce capital cost and allow online application without reducing accuracy and application a new system was designed, built and made operational. The ultrafood system is a variable path length pulse system, which produces both time and frequency domain data that is repeatable and accurate compared to reference methods and values. The use of multiple distance measurement removes the need for reference fluid calibration and thermal expansion compensation.


Access to physiotherapy services.
A survey of community physiotherapy services operating within the National Health Service throughout England and Wales in 1980 showed a considerable increase in the availability of physiotherapy outside hospital, with 159 health districts (75 per cent) having some form of community physiotherapy. Additional information obtained about access by general practitioners to hospital physiotherapy departments showed that in 140 districts (66 per cent), some direct access was available.


A solid-state NMR and DFT study of compositional modulations in Al(x)Ga(1-x)As.
We have conducted (75)As and (69)Ga Nuclear Magnetic Resonance (NMR) experiments to investigate order/disorder in Al(x)Ga(1-x)As lift-off films with x∼ 0.297 and 0.489. We were able to identify all possible As(Al(n)Ga(4-n)) sites with n = 0-4 coordinations in (75)As NMR spectra using spin-echo experiments at 18.8 Tesla. This was achieved by employing high rf field strengths using a small solenoid coil and an NMR probe specifically designed for this purpose. Spectral deconvolution, using an evolutionary algorithm, complies with the absence of long-range order if a CuAu based order parameter is imposed. An unconstrained fit shows a deviation of the statistics imposed by this type of ordering. The occupational disorder in the Ga and Al positions is reflected in a distribution of the Electric Field Gradients (EFGs) experienced at the different arsenic sites. We established that this can be modelled by summing the effects of the first coordination sphere and a Czjzek type distribution resulting from the compositional variation in the Al/Ga sub-lattice in the higher coordination spheres. (69)Ga 3QMAS and nutation data exclude the presence of highly symmetric sites and also show a distribution in EFG. The experimentally obtained quadrupolar interactions are in good agreement with calculations based on Density Functional Theory (DFT). Using additivity of EFG tensors arising from distant charge perturbations, we could use DFT to model the EFG distributions of the n = 0-4 sites, reproducing the Czjzek and extended Czjzek distributions that were found experimentally. On the basis of these calculations we conclude that the (75)As quadrupolar interaction is sensitive to compositional modulations up to the 7th coordination shell in these systems.


Vertically resolved separation of dust and other aerosol types by a new lidar depolarization method.
This paper developed a new retrieval framework of external mixing of the dust and non-dust aerosol to predict the lidar ratio of the external mixing aerosols and to separate the contributions of non-spherical aerosols by using different depolarization ratios among dust, sea salt, smoke, and polluted aerosols. The detailed sensitivity tests and case study with the new method showed that reliable dust information could be retrieved even without prior information about the non-dust aerosol types. This new method is suitable for global dust retrievals with satellite observations, which is critical for better understanding global dust transportation and for model improvements.


Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma.
Immunotherapy for the treatment of metastatic melanoma remains a major clinical challenge. The melanoma microenvironment may lead to local T cell tolerance in part through downregulation of costimulatory molecules, such as B7.1 (CD80). We report the results from the first clinical trial, to our knowledge, using a recombinant vaccinia virus expressing B7.1 (rV-B7.1) for monthly intralesional vaccination of accessible melanoma lesions. A standard 2-dose-escalation phase I clinical trial was conducted with 12 patients. The approach was well tolerated with only low-grade fever, myalgias, and fatigue reported and 2 patients experiencing vitiligo. An objective partial response was observed in 1 patient and disease stabilization in 2 patients, 1 of whom is alive without disease 59 months following vaccination. All patients demonstrated an increase in postvaccination antibody and T cell responses against vaccinia virus. Systemic immunity was tested in HLA-A*0201 patients who demonstrated an increased frequency of gp100 and T cells specific to melanoma antigen recognized by T cells 1 (MART-1), also known as Melan-A, by ELISPOT assay following local rV-B7.1 vaccination. Local immunity was evaluated by quantitative real-time RT-PCR, which suggested that tumor regression was associated with increased expression of CD8 and IFN-gamma. The local delivery of vaccinia virus expressing B7.1 was well tolerated and represents an innovative strategy for altering the local tumor microenvironment in patients with melanoma.


Surgical management of the paralyzed eye.
Blindness is the most dreaded complication of an untreated paralyzed eyelid following injury to the facial nerve. Injuries to the facial nerve are mainly postsurgical. Assessment of neural injury using serial testing is important to be able to differentiate between temporary and permanent paralysis. In the former case, medical management could be sufficient and, in the latter case, a surgical procedure is required. The physician has the choice among several procedures to repair upper eyelid paralysis with the gold standard being the gold weight implant. Lower eyelid ectropion can be repaired using a lateral or medial canthal tightening procedure. If the lower eyelid ectropion is severe, a cartilage implant may be required.


The echinocandins: three useful choices or three too many?
Echinocandins act by inhibiting 1,3-beta-D-glucan synthesis in the fungal cell wall. The three licensed agents in this class, namely anidulafungin, caspofungin and micafungin, have a favourable pharmacological profile. These agents are narrow spectrum with clinically relevant activity against Candida and Aspergillus spp. Several trials have established the non-inferiority of these agents over existing agents in the treatment of invasive fungal infections. Caspofungin is also licensed for empirical antifungal therapy of presumed fungal infections in patients with febrile neutropenia. This paper reviews the literature on echinocandins.


Genetic characterization of Toxoplasma gondii isolates from Portugal, Austria and Israel reveals higher genetic variability within the type II lineage.
This study compared genetic diversity of Toxoplasma gondii isolates from Portugal, Austria and Israel. For this, we genotyped 90 T. gondii isolates (16 from Portugal, 67 from Austria and 7 from Israel) using 10 nested PCR-restriction length polymorphism (RFLP) genetic markers and 15 microsatellite (MS) markers. By PCR-RFLP typing, 7 isolates from Portugal chickens were identified as type II (ToxoDB #1 or #3), 4 were type III (ToxoDB #2) and the remaining 4 isolates have unique genotype pattern were designated as ToxoDB #254. One mouse virulent isolate from a bovine fetus (Bos taurus) in Portugal was type I (ToxoDB #10) at all loci and designated as TgCowPr1. All 67 isolates from Austria and 7 from Israel were type II (ToxoDB #1 or #3). By MS typing, many additional genetic variations were revealed among the type II and type III isolates. Phylogenetic analysis showed that isolates from the same geographical locations tend to cluster together, and there is little overlapping of genotypes among different locations. This study demonstrated that the MS markers can provide higher discriminatory power to reveal association of genotypes with geographical locations. Future studies of the type II strains in Europe by these MS markers will be useful to reveal transmission patterns of the parasite.


Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice.
The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, and growth hormone-releasing hormone. Microinjection of VIP or PACAP into the rodent suprachiasmatic nucleus (SCN) phase shifts the circadian pacemaker and VIP antagonists, and antisense oligodeoxynucleotides have been shown to disrupt circadian function. VIP and PACAP have equal potency as agonists of the VPAC(2) receptor (VPAC(2)R), which is expressed abundantly in the SCN, in a circadian manner. To determine whether manipulating the level of expression of the VPAC(2)R can influence the control of the circadian clock, we have created transgenic mice overexpressing the human VPAC(2)R gene from a yeast artificial chromosome (YAC) construct. The YAC was modified by a strategy using homologous recombination to introduce (i) the HA epitope tag sequence (from influenza virus hemagglutinin) at the carboxyl terminus of the VPAC(2)R protein, (ii) the lacZ reporter gene, and (iii) a conditional centromere, enabling YAC DNA to be amplified in culture in the presence of galactose. High levels of lacZ expression were detected in the SCN, habenula, pancreas, and testis of the transgenic mice, with lower levels in the olfactory bulb and various hypothalamic areas. Transgenic mice resynchronized more quickly than wild-type controls to an advance of 8 h in the light-dark (LD) cycle and exhibited a significantly shorter circadian period in constant darkness (DD). These data suggest that the VPAC(2)R can influence the rhythmicity and photic entrainment of the circadian clock.


Phonon thermal transport in a class of graphene allotropes from first principles.
Utilizing first principle calculations combined with the phonon Boltzman transport equation (PBTE), we systematically investigate the phonon thermal transport properties of α, β and γ graphyne, a class of graphene allotropes. Strikingly, at room temperature, a low lattice thermal conductivity κL of 21.11, 22.3, and 106.24 W m-1 K-1 is obtained in α, β and γ graphyne, respectively, which are much lower than that of graphene. We observe contributions from the phonon modes below the specified frequency and find that many optical phonon modes play critical roles in the phonon thermal transport. These optic modes participate in thermal transport, enhancing the phonon scattering process, thus leading to the low κL value. Our results provide insights into the thermal transport of graphyne, and forecast its potential applications for thermoelectric and thermal barrier coatings.


A pilot RNA-seq study in 40 pietrain ejaculates to characterize the porcine sperm microbiome.
The microbiome plays a key role in homeostasis and health and it has been also linked to fertility and semen quality in several animal species including swine. Despite the more than likely importance of sperm bacteria on the boar's reproductive ability and the dissemination of pathogens and antimicrobial resistance genes, the high throughput characterization of the swine sperm microbiome remains scarce. We carried RNA-seq on 40 ejaculates each from a different Pietrain boar and found that a proportion of the sequencing reads did not map to the Sus scrofa genome. The current study aimed at using these reads not belonging to pig to carry a pilot study to profile the boar sperm bacterial population and its relation with 7 semen quality traits. We found that the boar sperm contains a broad population of bacteria. The most abundant phyla were Proteobacteria (39.1%), Firmicutes (27.5%), Actinobacteria (14.9%) and Bacteroidetes (5.7%). The predominant species contaminated sperm after ejaculation from soil, faeces and water sources (Bacillus megaterium, Brachybacterium faecium, Bacillus coagulans). Some potential pathogens were also found but at relatively low levels (Escherichia coli, Clostridioides difficile, Clostridium perfringens, Clostridium botulinum and Mycobacterium tuberculosis). We also identified 3 potential antibiotic resistant genes from E. coli against chloramphenicol, Neisseria meningitidis against spectinomycin and Staphylococcus aureus against linezolid. None of these genes were highly abundant. Finally, we classified the ejaculates into categories according to their bacterial features and semen quality parameters and identified two categories that significantly differed for 5 semen quality traits and 13 bacterial features including the genera Acinetobacter, Stenotrophomonas and Rhodobacter. Our results show that boar semen contains a bacterial community, including potential pathogens and putative antibiotic resistance genes, and that these bacteria may affect its reproductive performance.


Lupus anticoagulants: pathogenesis and laboratory diagnosis.
The pathogenesis of the lupus anticoagulant (LA) has been the focus of much research over the past decade, and a plethora of laboratory tests have been developed to detect it. This essay reviews the nature of LA and its pathogenesis, and a number of approaches employed in its diagnosis. These range from well established tests such as the kaolin clotting time (KCT), activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom time (TSVT). The criteria for diagnosis are discussed, including pre-analytical variables such as sample preparation, and the effects of therapeutic anticoagulants used to treat thrombotic manifestations of the syndrome or an underlying disease process.


[Instrumental conditioned defensive reflex to electrical stimulation of the hippocampus in dogs].
In experiments on 6 dogs an instrumental defensive conditioned reflex was elaborated to electrical stimulation of the ventral and dorsal hippocampus. This reflex possessed the same characteristics as reflexes to distant stimuli: it became extinguished when the reinforcement was discontinued; it reappeared when the reinforcement was resumed, and it was subject to generalization. In the course of reflex elaboration, the hippocampus function underwent a substantial reorganization. Initially it consisted in inhibition of behavioural reactions; following the reflex elaboration, a general motor activity took place anticipating conditioned paw lift.


A highly porous medical metal-organic framework constructed from bioactive curcumin.
A highly porous bio-MOF, medi-MOF-1, constructed from Zn and the pharmaceutical ingredient curcumin has been successfully synthesized. It can display permanent porosity with a surface area as high as ca. 3002 m(2) g(-1), which exhibits great potential in bioapplications. Its ibuprofen delivery ability, biodegradation and cytotoxicity were also studied.


Narcolepsy in prepubertal children.
Narcolepsy was diagnosed in 51 children (29 boys). The age range was 2.1 to 11.8 years (mean, 7.9 +/- 3.1 years). A mean of three referrals was made before narcolepsy was considered. In 10 children, cataplexy was the presenting symptom. Thirty-eight children acknowledged sleep paralysis and 30 acknowledged hypnagogic hallucinations. All children had sleep studies; 31 exhibited rapid eye movement at sleep onset. The mean sleep latency was 1.5 minutes +/- 39 seconds on the Multiple Sleep Latency Test. All children had at least two sleep-onset rapid eye movement sleep episodes in this test. Forty-six children were HLA class II-positive for DQw6, and 45 were also positive for DRw15. Thirty (65%) families refused referrals to support and counseling groups. Teachers often refused to acknowledge a medical problem. During follow-up, all children presented at least once with depressive symptoms in reaction to their syndrome. Narcolepsy should be considered when evaluating children with behavioral and depressive symptoms.


Photophysical Analysis of Aggregation-Induced Emission (AIE) Luminogens Based on Triphenylamine and Thiophene: Insights into Emission Behavior in Solution and PMMA Films.
Aggregation-Induced Emission (AIE) luminogens have garnered significant interest due to their distinctive applications in different applications. Among the diverse molecular architectures, those based on triphenylamine and thiophene hold prominence. However, a comprehensive understanding of the deactivation mechanism both in solution and films remains lacking. In this study, we synthesized and characterized spectroscopically two AIE luminogens: 5-(4-(bis(4-methoxyphenyl)amino)phenyl)thiophene-2-carbaldehyde (TTY) and 5'-(4-(bis(4-methoxyphenyl)amino)phenyl)-[2,2'-bithiophene]-5-carbaldehyde (TTO). Photophysical and theoretical analyses were conducted in both solution and PMMA films to understand the deactivation mechanism of TTY and TTO. In diluted solutions, the emission behavior of TTY and TTO is influenced by the solvent, and the deactivation of the excited state can occur via Locally Excited (LE) or Planar Intramolecular Charge Transfer (PICT) state. In PMMA films, rotational and translational movements are constrained, necessitating emission solely from the LE state. Nevertheless, in the PMMA film, excimers-like structures form, resulting in the emergence of a longer wavelength band and a reduction in emission intensity. The zenith of emission intensity occurs when molecules are dispersed at higher concentrations within PMMA, effectively diminishing the likelihood of excimer-like formations. Luminescent Solar Concentrators (LSC) were fabricated to validate these findings, and the optical efficiency was studied at varying concentrations of luminogen and PMMA.


Injectable intratumoral depot of thermally responsive polypeptide-radionuclide conjugates delays tumor progression in a mouse model.
This study evaluated a biodegradable drug delivery system for local cancer radiotherapy consisting of a thermally sensitive elastin-like polypeptide (ELP) conjugated to a therapeutic radionuclide. Two ELPs (49 kDa) were synthesized using genetic engineering to test the hypothesis that injectable biopolymeric depots can retain radionuclides locally and reduce the growth of tumors. A thermally sensitive polypeptide, ELP(1), was designed to spontaneously undergo a soluble-insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP(2) was designed to remain soluble upon injection and to serve as a negative control for the effect of aggregate assembly. After intratumoral administration of radionuclide conjugates of ELPs into implanted tumor xenografts in nude mice, their retention within the tumor, spatio-temporal distribution, and therapeutic effect were quantified. The residence time of the radionuclide-ELP(1) in the tumor was significantly longer than the thermally insensitive ELP(2) conjugate. In addition, the thermal transition of ELP(1) significantly protected the conjugated radionuclide from dehalogenation, whereas the conjugated radionuclide on ELP(2) was quickly eliminated from the tumor and cleaved from the biopolymer. These attributes of the thermally sensitive ELP(1) depot improved the antitumor efficacy of iodine-131 compared to the soluble ELP(2) control. This novel injectable and biodegradable depot has the potential to control advanced-stage cancers by reducing the bulk of inoperable tumors, enabling surgical removal of de-bulked tumors, and preserving healthy tissues.


[Reactive airway dysfunction syndrome. Clinical case].
The reactive airway dysfunction syndrome (RADS) is a type of occupational asthma without any period of latency and induced by irritants of low molecular weight. It is a clinical illness diagnosed with scarce information of prevalence in our medical service, that is why it receives a deficient treatment with more morbidity. A clinical case of a 60 year old patient is reported with a sudden, intense and long exposure to clorhidric acid and the consequent development of RADS. We performed a complete study of her signs and symptoms as well as some diagnostic tests, such as respiratory function tests and a positive test to the clorhidric acid. Once the diagnosis was confirmed, the patient was treated with high doses of corticosteroids and bronchodilators of long action for a period of three months. She had complete remission of symptoms, with normal respiratory tests and return to her every day work activities. It is important to consider that this illness in patients with respiratory symptoms and exposed to irritants should receive an appropriate treatment, which makes a better prognosis of it.


Methotrexate Induces Apoptosis of Postpartum Placental Cytotrophoblasts.
Though methotrexate (MTX) is known to inhibit proliferation of trophoblasts derived from ectopic and intrauterine pregnancies, its action on trophoblasts derived from postpartum placenta remains questionable. This study was designed to ascertain the efficacy of MTX in inducing cell death of postpartum placental cytotrophoblasts (PPTC). Primary human cytotrophoblasts were isolated from placentae of 1st and 2nd trimester intrauterine pregnancies and from postpartum placentae. The isolated trophoblasts were identified based on the expression of cytokeratin 7. MTX-induced inhibition of proliferation of cytotrophoblasts was detected by flow cytometry combined with the WST-1 assay. Secretion of HCG-β and invasiveness were evaluated to assess the effect of MTX on blocking the differentiated cellular function of cytotrophoblasts in relation to the gestational age. The efficacy of MTX in inducing apoptosis of cytotrophoblasts was estimated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. MTX significantly inhibited the proliferation and differentiation of cytotrophoblasts. MTX-induced cell apoptosis of PPTC was confirmed by increased expression of Fas, FasL, Bax, cleaved caspases 3, 7, 8, and 9, and decreased expression of Bcl-2. MTX inhibits replication and differentiation of cytotrophoblasts and appears to be an efficient inducer of PPTC apoptosis.


Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria.
In tropical areas, where unsupervised use of antimalarial drugs is common, patients with an illness consistent clinically with severe malaria but with negative blood smears pose a management dilemma. Malaria pigment is evident in peripheral blood leukocytes in greater than 90% of patients with severe malaria. To characterize the clearance kinetics of parasitized erythrocytes and malaria pigment-containing leukocytes, sequential peripheral blood and intradermal smears were assessed in 27 adult Vietnamese patients with severe falciparum malaria. The clearance of parasitized erythrocytes and pigment-containing monocytes (PCMs) followed first order kinetics. The elimination of pigment-containing neutrophils (PCNs) was first order initially, but deviated from this when counts were low. Clearance of peripheral blood PCMs (median clearance time, 216 hours; range, 84 to 492 hours) was significantly slower than that of parasitized erythrocytes (median, 96 hours; range, 36 to 168 hours) or PCNs (median, 72 hours; range, 0 to 168 hours; P < .0001). Intradermal PCM clearance times were the longest of all (median, 12 days; range, 6 to 23 days; significantly longer than peripheral blood PCM clearance, P < .001). Twenty-one (88%) patients still had signs, symptoms, or laboratory features of severe malaria after parasite clearance but before phagocyte pigment clearance. Sixteen of the 23 surviving patients (70%; 95% confidence interval, 50% to 87%) still had intraleukocytic malaria pigment on peripheral blood films 72 hours after parasite clearance. Thus, by determining the distribution of malaria pigment in peripheral blood and intradermal phagocytes, the time since effective antimalarial treatment started can be estimated. Microscopy for intraleukocytic pigment is valuable in the differential diagnosis of severe febrile illnesses in malarious areas where uncontrolled use of antimalarial drugs is widespread.


Presenting symptoms and functional outcome of chronic subdural hematoma patients.
Patients with chronic subdural hematoma (CSDH) can present with a variety of signs and symptoms. The relationship of these signs and symptoms with functional outcome is unknown. Knowledge of these associations might aid clinicians in the choice to initiate treatment and may allow them to better inform patients on expected outcomes. To investigate if presenting signs and symptoms influence functional outcome in patients with CSDH. We conducted a retrospective analysis of consecutive CSDH patients in three hospitals. Glasgow Outcome Scale Extended (GOS-E) scores were obtained from the first follow-up visit after treatment. An ordinal multivariable regression analysis was performed, to assess the relationship between the different signs and symptoms on the one hand and functional outcome on the other adjusted for potential confounders. We included 1,307 patients, of whom 958 (73%) were male and mean age was 74 (SD ± 11) years. Cognitive complaints were associated with lower GOS-E scores at follow-up (aOR 0.7, 95% CI: 0.5 - 0.8) Headache and higher Glasgow Coma Scale (GCS) scores were associated with higher GOS-E scores. (aOR 1.9, 95% CI: 1.5-2.3 and aOR 1.3, 95% CI: 1.2-1.4). Cognitive complaints are independently associated with worse functional outcome, whereas headache and higher GCS scores are associated with better outcome. The increased probability of unfavorable outcome in patients with CSDH who present with cognitive complaints favors a more prominent place of assessing cognitive status at diagnosis.


Fracture zones in the Mid Atlantic Ridge lead to alterations in prokaryotic and viral parameters in deep-water masses.
We hypothesized that mixing zones of deep-water masses act as ecotones leading to alterations in microbial diversity and activity due to changes in the biogeochemical characteristics of these boundary systems. We determined the changes in prokaryotic and viral abundance and production in the Vema Fracture Zone (VFZ) of the subtropical North Atlantic Ocean, where North Atlantic Deep Water (NADW) and Antarctic Bottom Water (AABW) are funneled through this narrow canyon and therefore, are subjected to intense vertical mixing. Consequently, salinity, potential temperature, oxygen, PO4, SiO4, NO3 were altered in the NADW inside the VFZ as compared to the NADW outside of the VFZ. Also, viral abundance, lytic viral production (VP) and the virus-to-prokaryote ratio (VPR) were elevated in the NADW in the VFZ as compared to the NADW outside the VFZ. In contrast to lytic VP, lysogenic VP and both the frequency of lytically (FIC) and lysogenically infected cells (FLC) did not significantly differ between in- and outside the VFZ. Generally, FIC was higher than FLC throughout the water column. Prokaryotic (determined by T-RFLP) and viral (determined by RAPD-PCR) community composition was depth-stratified inside and outside the VFZ. The viral community was more modified both with depth and over distance inside the VFZ as compared to the northern section and to the prokaryotic communities. However, no clusters of prokaryotic and viral communities characteristic for the VFZ were identified. Based on our observations, we conclude that turbulent mixing of the deep water masses impacts not only the physico-chemical parameters of the mixing zone but also the interaction between viruses and prokaryotes due to a stimulation of the overall activity. However, only minor effects of deep water mixing were observed on the community composition of the dominant prokaryotes and viruses.


Permeation through phospholipid bilayers, skin-cell penetration, plasma stability, and CD spectra of α- and β-oligoproline derivatives.
After a survey of the special role, which the amino acid proline plays in the chemistry of life, the cell-penetrating properties of polycationic proline-containing peptides are discussed, and the widely unknown discovery by the Giralt group (J. Am. Chem. Soc. 2002, 124, 8876) is acknowledged, according to which fluorescein-labeled tetradecaproline is slowly taken up by rat kidney cells (NRK-49F). Here, we describe details of our previously mentioned (Chem. Biodiversity 2004, 1, 1111) observation that a hexa-β(3)-Pro derivative penetrates fibroblast cells, and we present the results of an extensive investigation of oligo-L- and oligo-D-α-prolines, as well as of oligo-β(2)h- and oligo-β(3)h-prolines without and with fluorescence labels (1-8; Fig. 1). Permeation through protein-free phospholipid bilayers is detected with the nanoFAST biochip technology (Figs. 2-4). This methodology is applied for the first time for quantitative determination of translocation rates of cell-penetrating peptides (CPPs) across lipid bilayers. Cell penetration is observed with mouse (3T3) and human foreskin fibroblasts (HFF; Figs. 5 and 6-8, resp.). The stabilities of oligoprolines in heparin-stabilized human plasma increase with decreasing chain lengths (Figs. 9-11). Time- and solvent-dependent CD spectra of most of the oligoprolines (Figs. 13 and 14) show changes that may be interpreted as arising from aggregation, and broadening of the NMR signals with time confirms this assumption.


Can We Trust Positive Findings of Intervention Research? The Role of Conflict of Interest.
In recent years, there has been increased attention to the issue of conflict of interest within prevention research. The aims of this paper are to discuss these developments and to relate them to discussions of conflict of interest in the broader scientific literature. Although there has been concern expressed about the extent to which conflicts of interest can be defined and measured, empirical research suggests that financial conflicts can be easily identified and assessed in meta-analyses focused on their effects on research quality. Research evidence also shows that conflict of interest is associated with use of flexible data analysis practices and the reporting of chance positive findings, both within prevention research and related disciplines such as public health and psychology. However, the overwhelming majority of published studies report positive results, and there are a number of other influences within academia (such as pressure to publish) that account for this and for the use of flexible data analysis practices. Accordingly, introducing measures to improve research quality in general, rather than just focusing on problems specific to research in which there is a clearly identifiable conflict of interest, may prove more effective and less controversial. Most such efforts focus on introducing greater transparency into research design, practice, and reporting. These both curtail employment of flexible data analysis practices and make their use transparent to investigators seeking to assess their effects on research quality. Also, requiring detailed disclosures of conflicts be reported by all investigators (not just senior authors) would improve current disclosure practices.


Optimization of In Vitro Expansion and Activation of Human Natural Killer Cells against Breast Cancer Cell Line.
Regarding to the increase of cancer deaths in recent years and disability of common therapies to eradicate cancers, as well as expansion of Natural Killer (NK) cell therapy, it seems so vital to find new useful therapies against cancers. Breast cancer is the second main cause of cancer death among women. As it is impossible for a majority of patients to receive NK cell therapy, an attempt was made to establish a low-cost and efficient method for expanding and activating NK cells against breast cancer cell line (MCF7). NK cells were isolated from Peripheral Blood Mononuclear Cells (PBMCs) applying either MACS based NK cell enrichment kit or antibodies and complement as cytotoxic method. Then, the NK cells were cultured in Stem Cell Growth Medium (SCGM) with feeder layer (irradiated PBMCs) along with PHA or OKT3. IL-2, IL-15 and IL-21 were used to expand NK cells and finally their cytotoxic activity was investigated by flow cytometry. Highly pure NK cells were obtained and no significant difference between the two isolation methods was found. Using IL-2 plus IL-15, the number of NK cells increased up to100 fold after 16 days. No significant effect was observed after IL-21 treatment. Our data indicated that cytotoxicity method can be considered a low-cost alternative for NK cell isolation kits. It seems that culturing NK cells for 14 days in either PHA or OKT3 supplemented SCGM medium would be more effective than culturing for 16 days in the presence of IL-21.


Delayed graft duodenal perforation due to impacted food five years after simultaneous pancreas-kidney transplantation: A case report.
Pancreas transplantation is the best treatment option in selected patients with type 1 diabetes mellitus. Here we report a patient with a nonmarginal duodenal perforation five years after a simultaneous pancreas-living donor kidney transplantation (SPLKT). A 31-year old male who underwent SPLKT five years previously presented with severe abdominal pain. He had a marginal duodenal perforation four years later, treated by primary closure and drainage. Biopsy of the pancreas and duodenum graft at that time showed chronic rejection in the pancreas and acute inflammation with an ulcer in the duodenum. At presentation, computerized tomography scan showed mesenteric pneumatosis with enteric leak and ileal dilatation proximal to the anastomotic site. We performed emergent laparotomy and found a 1.0cm perforation at the nonmarginal, posterior wall of the duodenum. Undigested fiber-rich food was extracted from the site and an omental patch placed over the perforation. An ileostomy was created proximal to the omega loop for decompression and a drain placed nearby. The postoperative course was unremarkable. There are only eight previous cases of graft duodenal perforation in the literature. Fiber-rich food residue passing through the anastomosis with impaction may have led to this perforation. When a patient is stable, even in the presence of delayed duodenal graft perforation, graft excision may not be necessary. Intraoperative exploration should include Doppler ultrasound examination of the vasculature to rule out thrombosis as a contributor to ischemia. Tissue biopsy should be performed to diagnose rejection.


Aldehyde dehydrogenase, Ald4p, is a major component of mitochondrial fluorescent inclusion bodies in the yeast Saccharomyces cerevisiae.
When Saccharomyces cerevisiae strain 3626 was cultured to the stationary phase in a medium that contained glucose, needle-like structures that emitted autofluorescence were observed in almost all cells by fluorescence microscopy under UV excitation. The needle-like structures completely overlapped with the profile of straight elongated mitochondria. Therefore, these structures were designated as mitochondrial fluorescent inclusion bodies (MFIBs). The MFIB-enriched mitochondrial fractions were successfully isolated and 2D-gel electrophoresis revealed that a protein of 54 kDa was only highly concentrated in the fractions. Determination of the N-terminal amino acid sequence of the 54-kDa protein identified it as a mitochondrial aldehyde dehydrogenase, Ald4p. Immunofluorescence microscopy showed that anti-Ald4p antibody specifically stained MFIBs. Freeze-substitution electron microscopy demonstrated that cells that retained MFIBs had electron-dense filamentous structures with a diameter of 10 nm in straight elongated mitochondria. Immunoelectron microscopy showed that Ald4p was localized to the electron-dense filamentous structures in mitochondria. These results together showed that a major component of MFIBs is Ald4p. In addition, we demonstrate that MFIBs are common features that appear in mitochondria of many species of yeast.


Use of prostaglandin E1 for maintaining the patency of the ductus arteriosus.
Prostaglandin E1 was utilized for maintaining the patency of the ductus arteriosus in 19 infants with congenital lesions whose survival depended on ist patency. Fourteen of the patients had lesions which required blood flow from the aorta to the pulmonary artery (cyanotic group); 11 of these were considered successful. Two of the failures were in older infants aged 13 days and 1 month. The remaining five trials were in patients who required a flow of blood from pulmonary artery to aorta (left heart and aortic defect group), two of whom were considered to have responded successfully to the prostaglandin E1 administration. Based on this experience, it is suggested that this method of treatment is of benefit in the cyanotic group in providing emergency medical care while awaiting surgical palliation. A similar benefit in the aortic arch defect group would seem to be less well demonstrated at this time.


An investigation of the affective experience of females at high risk for eating disorders in general and pathology-specific contexts.
Difficulties with emotional experiences have long been implicated in the development or maintenance of eating disorders (EDs). However, the vast majority of this work is theoretical or self-report, with few studies examining the somatic-affective experience of individuals with EDs under experimental conditions. The aim of the current study was to: i) examine physiological reactivity and subjective report of emotional experiences in response to ED pathology-specific and general affective film clips, and ii) examine the impact of film on body size estimation in females at risk for EDs. Females aged 14-24 years old of either high (N = 42) or low (N = 43) risk for EDs viewed pathology-specific and general affective film clips and provided their affective ratings and body-size estimations post film clips. Heart Rate and Skin Conductance Levels were recorded during each clip. High risk participants evidenced greater physiological arousal across conditions and in both general and pathology-specific affective contexts. Negative affect induced via the ED-pathology specific film clip had a greater impact on the high risk group's body-size estimations. Individuals at risk for EDs seem to experience greater physiological arousal and this may influence the experience of their bodies, or direct attention to their body as a way to attenuate unwanted emotion or due to somatic feedback.


ChemiRs: a web application for microRNAs and chemicals.
MicroRNAs (miRNAs) are about 22 nucleotides, non-coding RNAs that affect various cellular functions, and play a regulatory role in different organisms including human. Until now, more than 2500 mature miRNAs in human have been discovered and registered, but still lack of information or algorithms to reveal the relations among miRNAs, environmental chemicals and human health. Chemicals in environment affect our health and daily life, and some of them can lead to diseases by inferring biological pathways. We develop a creditable online web server, ChemiRs, for predicting interactions and relations among miRNAs, chemicals and pathways. The database not only compares gene lists affected by chemicals and miRNAs, but also incorporates curated pathways to identify possible interactions. Here, we manually retrieved associations of miRNAs and chemicals from biomedical literature. We developed an online system, ChemiRs, which contains miRNAs, diseases, Medical Subject Heading (MeSH) terms, chemicals, genes, pathways and PubMed IDs. We connected each miRNA to miRBase, and every current gene symbol to HUGO Gene Nomenclature Committee (HGNC) for genome annotation. Human pathway information is also provided from KEGG and REACTOME databases. Information about Gene Ontology (GO) is queried from GO Online SQL Environment (GOOSE). With a user-friendly interface, the web application is easy to use. Multiple query results can be easily integrated and exported as report documents in PDF format. Association analysis of miRNAs and chemicals can help us understand the pathogenesis of chemical components. ChemiRs is freely available for public use at http://omics.biol.ntnu.edu.tw/ChemiRs .


Modeling the relaxation time of DNA confined in a nanochannel.
Using a mapping between a Rouse dumbbell model and fine-grained Monte Carlo simulations, we have computed the relaxation time of λ-DNA in a high ionic strength buffer confined in a nanochannel. The relaxation time thus obtained agrees quantitatively with experimental data [Reisner et al., Phys. Rev. Lett. 94, 196101 (2005)] using only a single O(1) fitting parameter to account for the uncertainty in model parameters. In addition to validating our mapping, this agreement supports our previous estimates of the friction coefficient of DNA confined in a nanochannel [Tree et al., Phys. Rev. Lett. 108, 228105 (2012)], which have been difficult to validate due to the lack of direct experimental data. Furthermore, the model calculation shows that as the channel size passes below approximately 100 nm (or roughly the Kuhn length of DNA) there is a dramatic drop in the relaxation time. Inasmuch as the chain friction rises with decreasing channel size, the reduction in the relaxation time can be solely attributed to the sharp decline in the fluctuations of the chain extension. Practically, the low variance in the observed DNA extension in such small channels has important implications for genome mapping.


Sex differences in motives for use of complementary and alternative medicine among cancer patients.
There is evidence that the prevalence of complementary and alternative medicine (CAM) use is increasing especially among women. However, little is known about why there are sex differences in the use of CAM. This study investigated sex differences in motivations for use of CAM among adult cancer patients. A population-based telephone survey of CAM use. 178 male and 178 female cancer patients randomly selected from a statewide Cancer Surveillance System in Washington State. Demographics, complementary and alternative medicine use, lifestyle changes and four psychosocial variables: desire for personal control; internal locus of control; symptom distress; and perceived health status. Overall, 81.5% of women and 59.0% of men used some type of CAM. After adjusting for age and income, the relative odds that an alternative therapy user was female was 2.2 (95% CI 1.4-3.3)for alternative dietary supplements, 5.0 (95% CI 2.3-11.2) for categories of alternative providers, 2.2 (95% CI 1.2-4.2) for focused mental therapies and 1.4 (95% CI 0.9-2.2) for lifestyle changes. CAM use was positively associated with desire for personal control among both men and women (P = 0.05). However, the association of two factors, dissatisfaction with a conventional provider and cancer-related symptom distress with alternative dietary supplement use, was only modestly different for men and women (P < 0.10 for interaction). High cancer related symptom distress score and dissatisfaction with a conventional provider predicted increased dietary supplement use for men, but decreased dietary supplement use for women. Clinicians should be aware that men and women differ considerably in their use of CAM, which may reflect differences in their psychological needs as they cope with their cancer diagnosis and treatment.


Sports injury research. How to choose a study design.
In conducting a clinical study, one must determine the timing of the study. A cohort study may be either retrospective or prospective. A case-control study is retrospective and compares subjects with a particular condition to controls without that condition by evaluating events which preceded the development of the condition. A cross-sectional study examines subjects at one particular moment in time. Once the timing of a study is determined, the type of control group is selected. One may present an uncontrolled series or use historical or concurrent controls. The prospective, concurrently controlled series is the strongest of the above designs. The randomized clinical trial is the strongest study design and is employed to avoid the errors that are potentially present in non-randomized studies (Chapter 9). It is a prospective, concurrently controlled study design in which subjects are randomly allocated to two or more treatment modalities. The protocol specifies the population source, admission criteria, enactment of the procedure, and outcome determination for the study.


Preoperative detection of pancreatic insulinomas on multiphasic helical CT.
The objective was to analyze enhancement characteristics of insulinomas and to determine the ability of multiphase CT to localize these tumors. Prospective interpretations of multiphase helical CT scans were reviewed in 30 patients who had insulinomas resected over a 5-year period. CT scans were retrospectively reviewed to determine enhancement characteristics, tumor conspicuity in each phase of enhancement, and potential causes for false-negative findings. Sixty-three percent (19/30) of tumors were identified on CT prospectively. An additional six tumors were visualized in retrospect, allowing characterization of 25 (83%) of 30 tumors. Most tumors were hyperdense on at least one phase (n = 19), three tumors were hypoattenuating, and three were isodense and pedunculated. Insulinomas were most conspicuous on the early phase in 15 patients and in the portal venous phase in three. All tumors that underwent pancreatic phase imaging were seen (13/13), whereas three of 18 arterial and six of 25 portal venous phase findings were inconclusive for tumor. In the six examinations with false-negative findings in which the tumor could be seen in retrospect, two tumors were isodense and pedunculated, three were in close proximity to vessels, and one had a cystic appearance. Multiphasic CT has a moderate sensitivity in the detection of insulinomas. Most tumors are more conspicuous on the earlier phases of enhancement. The pancreatic phase may be more useful than the arterial phase. Potential sources of false-negative results include tumors adjacent to vessels, pedunculated morphology, or nonhyperattenuating lesions.


Reimbursement Matters: Overcoming Barriers to Clinical Trial Accrual.
Accrual to cancer clinical trials is suboptimal. Few data exist regarding whether financial reimbursement might increase accruals. The objective of this study was to assess perceptions about reimbursement to overcome barriers to trial accrual. This was a cross-sectional survey. Oncologists identified from the American Medical Association Physician Masterfile. We report descriptive statistics, associations of physician characteristics with perceptions of reimbursement, domains, and subthemes of free-text comments. Respondents (n=1030) were mostly medical oncologists (59.4%), ages 35-54 (67%), and male (75%). Overall, 30% reported discussing trials with >25% of patients. Barriers perceived were administrative/regulatory, physician/staff time, and eligibility criteria. National Cancer Institute cooperative group participants and practice owners were more likely to endorse higher reimbursement. Respondents indicated targeted reimbursement would help improve infrastructure, but also noted potential ethical problems with reimbursement for discussion (40.7%) and accrual (85.9%). Free-text comments addressed reimbursement sources, recipients, and concerns about the real and apparent conflict of interest. Though concerns about a potential conflict of interest remain paramount and must be addressed in any new system of reimbursement, oncologists believe reimbursement to enhance infrastructure could help overcome barriers to trial accrual.


The IPR inventory: development and psychometric characteristics.
The purpose of this study was to develop, validate, and norm a measure of dimensions of interpersonal relationships that are salient to nursing: social support, reciprocity, and conflict. The selection of these concepts was guided by social exchange and equity theories. In the first phase of the study, 44 respondents were interviewed to provide narrative data from which to develop items so that items would be grounded in lived experience. Content validity of items was judged by a panel of 11 experts. The revised 39-item instrument was tested in successive steps with a total of 340 students, patients, and community residents for reliability and validity, including internal consistency reliability, test-retest reliability, factor analysis, and three forms of validity assessment (theory testing, contrasted groups, and multitrait-multimethod comparison). The three subscales of social support, reciprocity, and conflict demonstrated repeated internal consistency and test-retest reliability. Strong evidence of construct validity was demonstrated for the social support and the conflict subscales; validity of the reciprocity subscale was equivocal.


Biosynthesis of phenylalanine from phenylacetate by Chromatium and Rhodospirillum rubrum.
Cultures of Chromatium strain D and Rhodospirillum rubrum incorporated (14)C from phenylacetate-1-(14)C during anaerobic growth. The radioactivity in the protein fraction of cells was mainly in phenylalanine. Phenylalanine from Chromatium cells grown in phenylacetate-1-(14)C was labeled at carbon 2. Incorporation of phenylacetate by Chromatium was decreased in the presence of exogenous phenylalanine, and de novo synthesis of phenylalanine from bicarbonate was less in medium containing either phenylalanine or phenylacetate. These organisms, and also certain anaerobic rumen bacteria, apparently carboxylate phenylacetate to synthesize the phenylalanine carbon skeleton. The mechanism of the carboxylation is unknown; however, it appears to be dependent upon anaerobic conditions, since R. rubrum did not synthesize phenylalanine from phenylacetate during aerobic growth in the dark.


Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones.
Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone.


Attitudes, Risk Behavior, and Noise Exposure among Young Adults with Hearing Problems: Identifying a Typology.
This study explored attitudes toward leisure noise, use of hearing protection, and perceived susceptibility to leisure-noise damage in young adults with hearing problems. Twelve participants aged between 18 and 35 years took part in a semistructured interview. Data were analyzed using framework analysis. The results showed that a positive attitude to noise, a passion for loud music, a lack of knowledge of the consequences of noise damage, and perceived low risk of hearing problems were associated with people not using earplugs. The aesthetics, comfort, perceived effects on music quality and attitude of others were all barriers to earplug use. Of those who had used earplugs, previous hearing-related symptoms and concern about future hearing damage were the main motivators for use. Four types of people were identified to describe the variation in attitudes and behaviors: those who had no change in behavior or concern about damage; those who were concerned and used earplugs; those who were concerned and avoided loud venues; and those who were concerned about communication difficulties only. Considering the wide variability, it may be more effective to shift attention from trying to change individual attitudes and behaviors to considering systemic changes to protect hearing, through ensuring the music industry and relevant authorities take greater responsibility.


Diabetes mellitus and sexual function in middle-aged and older women.
Diabetes mellitus is an established risk factor for sexual dysfunction in men, but its effect on female sexual function is poorly understood. We examined the relationship of diabetes to sexual function in middle-aged and older women. Sexual function was examined in a cross-sectional cohort of ethnically diverse women aged 40-80 years using self-administered questionnaires. Multivariable regression models compared self-reported sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (difficulty with lubrication, arousal, orgasm, or pain) among insulin-treated diabetic, non-insulin-treated diabetic, and nondiabetic women. Additional models assessed relationships between diabetic end-organ complications (heart disease, stroke, renal dysfunction, and peripheral neuropathy) and sexual function. Among the 2,270 participants, mean±standard deviation age was 55±9.2 years, 1,006 (44.4%) were non-Latina white, 486 (21.4%) had diabetes, and 139 (6.1%) were taking insulin. Compared with 19.3% of nondiabetic women, 34.9% of insulin-treated diabetic women (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.32-3.15) and 26.0% of non-insulin-treated diabetic women (adjusted OR 1.42, 95% CI 1.03-1.94) reported low overall sexual satisfaction. Among sexually active women, insulin-treated diabetic women were more likely to report problems with lubrication (OR 2.37, 95% CI 1.35-4.16) and orgasm (OR 1.80, 95% CI 1.01-3.20) than nondiabetic women. Among all diabetic women, end-organ complications such as heart disease, stroke, renal dysfunction, and peripheral neuropathy were associated with decreased sexual function in at least one domain. Compared with nondiabetic women, diabetic women are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women. II.


Impact of a community-based lifestyle intervention program on health-related quality of life.
The presence of risk factors for type 2 diabetes and cardiovascular disease, or the conditions themselves, contributes to lower health-related quality of life (HRQoL) among adults. Although community-based lifestyle intervention programs have been shown to be effective for improving risk factors for these diseases, the impact of these interventions on HRQoL has rarely been described. To examine changes in HRQoL following participation in the Group Lifestyle Balance program, a community translation of the Diabetes Prevention Program lifestyle intervention for adults with prediabetes and/or the metabolic syndrome. Participants enrolled in the 12-month, 22-session intervention program (N = 223) completed the EuroQol Health Questionnaire (EQ-5D-3L) at baseline, 6, and 12 months. Linear mixed-effects regression models determined change in EQ-5D-visual analog scale (VAS) and Index scores post-intervention. Mean EQ-5D-VAS was improved by +7.38 (SE = 1.03) at 6 months and by +6.73 (SE = 1.06) at 12 months post-intervention (both; p < 0.0001). Mean changes in EQ-5D index values were +0.00 (SE = 0.01; NS) and +0.01 (SE = 0.01; p < 0.05), respectively. Adjusted for age, baseline score, and achieving intervention goals, mean change in EQ-5D-VAS was +11.83 (SE = 1.61) at 6 months and +11.23 (SE = 1.54) at 12 months (both; p < 0.0001). Adjusted mean change in EQ-5D index value was +0.04 (SE = 0.01) at 6 months and +0.05 (SE = 0.01) at 12 months (both; p < 0.01). Participation in a community lifestyle intervention program resulted in improved HRQoL among adults with prediabetes and/or the metabolic syndrome. These benefits to HRQoL, together with improved clinical and behavioral outcomes, should increase the appeal of such programs for improving health.


[Occurrence of musculoskeletal complaints in Hordaland].
Musculoskeletal complaints are widespread and a major public health problem in western countries. Prevention and treatment are challenges because the aetiologic factors are not fully understood. Our objective was to estimate the prevalence of and identify possible risk factors for musculoskeletal complaints. A cross-sectional study including 11 566 men and 13 660 women aged 40-49 and 70-74 who completed a questionnaire in the Hordaland Health Study 1997-99. Musculoskeletal pain and/or stiffness lasting at least three months during the past year was reported by 4461 men (39 %) and 6713 women (49 %). Prevalence among women increased with age. Musculoskeletal complaints were associated with low educational attainment and smoking among both men and women 40-49 years old, and with high body mass index and low physical activity among women. Among the 70-74-year-olds, complaints were associated with low educational attainment among men and with smoking, high body mass index and low physical activity among women. A dose-response relationship between smoking and musculoskeletal complaints was found, with a stronger effect among women than men. Musculoskeletal complaints were common, the prevalence higher among women than men. The results indicate that musculoskeletal complaints may be prevented or reduced by smoking cessation.


[Hypoacusis and diabetes type II].
The relation between diabetes mellitus and hypoacusis is discussed since Jordao, who firstly pointed out to this association in 1854. The disparity of results according several studies are due, after other AA., to the heterogeneous of groups considered. Our study was done resorting to a patients selection and their classification in 2 homogeneous groups following different parameters: age; sex; years of course; verified angiopathic complications: peripheric vasculopathy, microalbuminuria, altered creatinine clearance; malady control: glycosylated hemoglobin. The task consisted in the study of audiometric tracings in 40 patients in order to verify statistic differences of auditive thresholds between the established groups. These courses corresponding to a sensorineural hearing loss with a deep in high tones. But no significatively worse thresholds in patients suffering other angiopathic disorders were detected.


Neurocognition as a predictor of transition to psychotic disorder and functional outcomes in ultra-high risk participants: Findings from the NEURAPRO randomized clinical trial.
Neurocognitive impairments experienced by individuals at ultra-high risk (UHR) for psychosis are potential predictors of outcome within this population, however there is inconsistency regarding the specific neurocognitive domains implicated. This study aimed to examine whether baseline neurocognition predicted transition to psychosis, or functional outcomes, at medium-term (mean = 3.4 years) follow-up, while controlling for other clinical/treatment variables associated with transition to psychosis. Analysis of data collected as part of a multi-centre RCT of omega-3 fatty acids and cognitive-behavioural case management (NEURAPRO) for UHR individuals was conducted on the 294 participants (134 males, 160 females) who completed neurocognitive assessment (Brief Assessment of Cognition for Schizophrenia) at baseline. Transition to psychosis was determined using the Comprehensive Assessment of At-Risk Mental States (CAARMS), and functioning was measured with the Global Functioning: Social and Role Scales. Mean baseline z-scores indicated that UHR participants performed a quarter to half a standard deviation below normative means in all domains (range mean z = -0.24 to -0.47), except for executive functioning (mean z = 0.16). After adjusting for covariates, poorer Executive (p = .010) and Motor (p = .030) functions were predictive of transition to psychosis. Processing Speed and Verbal Fluency were significant predictors of role functioning at 12 months (p = .004), and social functioning at medium-term follow-up (p = .015), respectively. Neurocognitive abilities are independent predictors of both transition to psychosis and functional outcomes within the UHR population. Further research is needed to determine the best combination of risk variables in UHR individuals for prediction of psychosis transition, functioning and other psychopathology outcomes.


Three-Dimensional Cinematic Rendering to Optimize Visualization of Cerebrovascular Anatomy and Disease in CT Angiography.
Three-dimensional cinematic rendering (3DCR) is an emerging postprocessing technique for computed tomography (CT) and CT angiography (CTA) that produces photorealistic, volumetric images. In contrast to conventional volume rendering techniques, 3DCR depicts life-like shadowing and surface reflection, which can improve the perception of depth and complex anatomic spatial relationships. This tool allows clinical neuroimagers to study, explore, and teach the complex relational anatomy of the cerebral vessels and skull in a more intuitive manner. The purpose of this report is to introduce the physical and optical principles behind 3DCR and to explore applications of 3DCR in modern cerebrovascular imaging. Using CTA source data, we describe our approach to visualizing cerebrovascular anatomy and disease and introduce three simple, reproducible techniques through a series of case vignettes. First, we show how selective manipulation of rendered models can imitate cadaveric dissection. Next, we discuss surface rendering as a means of recapitulating the neurologic physical exam. Last, we provide a step-by-step method of simulating the operating room perspective in visualizing cerebrovascular disease. In our experience, 3DCR proves most useful for visualizing structures at the vessel-skull interface, which can be difficult to assess with conventional imaging methods. 3DCR, therefore, complements traditional 2-dimensional and 3-dimensional imaging methods and serves as an emerging tool for neuroimagers to communicate with and educate other clinicians.


Phosphatidylinositol 3-kinase and Akt effectors mediate insulin-like growth factor-I neuroprotection in dorsal root ganglia neurons.
Insulin-like growth factor-I (IGF-I) protects neurons of the peripheral nervous system from apoptosis, but the underlying signaling pathways are not well understood. We studied IGF-I mediated signaling in embryonic dorsal root ganglia (DRG) neurons. DRG neurons express IGF-I receptors (IGF-IR), and IGF-I activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. High glucose exposure induces apoptosis, which is inhibited by IGF-I through the PI3K/Akt pathway. IGF-I stimulation of the PI3K/Akt pathway phosphorylates three known Akt effectors: the survival transcription factor cyclic AMP response element binding protein (CREB) and the pro-apoptotic effector proteins glycogen synthase kinase-3beta (GSK-3beta) and forkhead (FKHR). IGF-I regulates survival at the nuclear level through accumulation of phospho-Akt in DRG neuronal nuclei, increased CREB-mediated transcription, and nuclear exclusion of FKHR. High glucose increases expression of the pro-apoptotic Bcl protein Bim (a transcriptional target of FKHR). However, IGF-I does not regulate Bim or anti-apoptotic Bcl-xL protein expression levels, which suggests that IGF-I neuroprotection is not through regulation of their expression. High glucose also induces loss of the initiator caspase-9 and increases caspase-3 cleavage, effects blocked by IGF-I. These data suggest that IGF-I prevents apoptosis in DRG neurons by regulating PI3K/Akt pathway effectors, including GSK-3beta, CREB, and FKHR, and by blocking caspase activation.


Protocol for a Multicenter, Prospective, Observational Pilot Study on the Implementation of Resource-Stratified Algorithms for the Treatment of Severe Traumatic Brain Injury Across Four Treatment Phases: Prehospital, Emergency Department, Neurosurgery, and Intensive Care Unit.
Severe traumatic brain injury (sTBI) is a public health issue with great disparity among low- and middle-income countries where the implementation of evidence-based guidelines is challenging because resources are often unavailable. A consensus process including experts in the prehospital, emergency department, neurosurgery, and intensive care unit took place in Colombia to develop a set of stratified protocols called BOOTStraP, targeting resource-poor environments, but it has not been systematically implemented and tested. To identify the facilitators of, and barriers to, collecting data about patients with sTBI and to implement a stratified protocol across the treatment phases of prehospital, emergency department, neurosurgery, and intensive care unit in low-resource settings. We also aim to identify a possible association between adherence to these protocols and outcomes for these patients. A prospective, observational, before and after, pilot study will be performed in three phases as follows: before implementation, implementation, and after implementation. The BOOTStraP protocols will be implemented in three Colombian centers. We expect to find numerous barriers during the implementation phase. We also expect moderate adherence to the protocols. However, we expect to find an increase in the survival rate to hospital discharge and an improvement in neurological outcomes at discharge. This pilot study will serve as a first step to identify variables that are critical to successful implementation, to be considered for the design of a future large-scale international study to measure the effectiveness of resource-based protocols and to improve outcomes from sTBI.


5-HT2C receptor agonists as potential drugs for the treatment of obesity.
An association between the brain serotonin (5-HT) system and feeding has been postulated since the 1970's but it has only been in recent years that the nature of 5-HT-mediated hypophagia has become well understood, and the receptor subtypes responsible for the effect better defined. The invention and utilisation of subtype-selective 5-HT receptor antagonists has demonstrated that the 5-HT(2C) receptor is of paramount importance in this regard. Importantly, ethological studies of animal behaviour have shown that the hypophagia resulting from 5-HT(2C) receptor activation is likely to be a consequence of increased satiety and this is in contrast to hypophagia following 5-HT(2A) receptor activation. Furthermore, recent studies have also shown that 5-HT(2C) receptor agonists not only reduce feeding when acutely administered to rats or mice, they can also reduce body weight without inducing tolerance when administered chronically to obese animals. These observations have led researchers to conclude that selective 5-HT(2C) receptor agonists have the potential to be effective anti-obesity agents. Encouragingly, this suggestion is supported by both direct and indirect evidence from clinical studies. Indirect evidence stems from recent observations that the clinically effective anorectic agent d-fenfluramine exerts its hypophagic and weight-loss effects via 5-HT(2C) receptor activation. More direct clinical evidence derives from the use of the prototypical 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP), with which both acute hypophagia and body-weight loss have been observed. The current paper therefore reviews both the pre-clinical and clinical evidence supporting the use of 5-HT(2C) receptor agonists for the treatment of obesity and assesses the developments that have been made in this regard to date.


Evaluating the Effectiveness of Components of National Suicide Prevention Strategies.
Background: National suicide prevention strategies support development of suicide prevention activities and their evaluation. Aims: To describe components included in national suicide prevention strategies and analyze the potential contribution of individual components to reduce suicide rates. Method: We conducted a narrative review and statistical analysis of national suicide prevention strategies. The narrative review was based on a framework of 12 components and included 29 countries (14 lower middle-income countries [LMICs] and 15 high-income countries [HICs]) with a national suicide prevention strategy. The statistical analyses covered suicide mortality data for 24 countries with a national strategy (9 LMICs and 15 HICs). Results: The number of components adopted in national strategies ranged from 4 to 11, and training and education were included in 96.5% of strategies. Estimated period effects for total suicide rates in individual countries ranged from a significant decrease in the yearly suicide rate (RR = 0.80; 95% CI 0.69-0.93) to a significant increase (RR = 1.12; 95% CI 1.05-1.19). There were no changes in suicide mortality associated with individual components of national strategies. Limitations: The limitations of existing suicide mortality data apply to our study. Conclusion: Further detailed evaluations will help identify the specific contribution of individual components to the impact national strategies. Until then, countries should be encouraged to implement and evaluate comprehensive national suicide prevention strategies.


Thoracoscopic Implantation of an Array Electrode in the Pericardium Transverse Sinus to Reduce Defibrillation Threshold.
Among the implantable cardioverter defibrillator recipients, there is still a subgroup of patients in whom the defibrillation threshold is too high and the maximal shock output of the implantable cardioverter defibrillator can fail to terminate a ventricular arrhythmia. We report a new thoracoscopic minimally invasive approach to place a standard array electrode in the transverse pericardial sinus of a patient implanted with a cardiac resynchronization and defibrillation therapy device with persistent high defibrillation threshold. This approach was developed to achieve very low shock impedance with a consequent increase in the current flow and reduction of defibrillation threshold.


Fit and Tipsy? The Interrelationship between Cardiorespiratory Fitness and Alcohol Consumption and Dependence.
To examine whether higher levels of cardiorespiratory fitness are related to increased alcohol consumption and dependence among a large sample of adults attending a preventive medicine clinic. A cross-sectional study of 38,653 apparently healthy patients who visited the Cooper Clinic (Dallas, TX) for preventive medical examinations (1988-2019) and enrolled in the Cooper Center Longitudinal Study. The primary independent variable was cardiorespiratory fitness, based on a maximal treadmill test, and the dependent variables were alcohol consumption and dependence (self-reported). The relations between fitness category (low, moderate, high) and alcohol consumption (low, moderate, heavy) and suggested alcohol dependence (Cut down, Annoyed, Guilty, Eye opener score ≥2) among women and men were estimated via multivariable regression while adjusting for covariates (e.g., age, birth year cohort, marital status, and body mass index). Women within the moderate and high fitness categories had 1.58 (95% confidence interval [CI], 1.32-1.91) and 2.14 (95% CI, 1.77-2.58) greater odds of moderate/heavy alcohol consumption, respectively, in comparison to their low fitness counterparts. Similarly, moderate and high fit men had 1.42 (95% CI, 1.30-1.55) and 1.63 (95% CI, 1.49-1.80) times greater odds of moderate-to-heavy alcohol consumption, respectively, in comparison to the low fitness group. In addition, among men who were heavy drinkers (but not women), higher fitness levels were related to lower rates of suggested alcohol dependence. Specifically, these men had 45.7%, 41.7%, and 34.9% proportions of clinically relevant alcohol problems across low, moderate, and high fitness categories (adjusted P for trend <0.001). Higher fitness levels are significantly related to greater alcohol consumption among a large cohort of adult patients. Interventions focusing on increasing fitness (via physical activity promotion) might consider concurrently aiming to reduce alcohol consumption.


Prevalence of overweight and obesity in non-institutionalized people aged 65 or over from Spain: the elderly EXERNET multi-centre study.
Coupled with the growth of the older population, an increase in the prevalence of overweight and obesity in this age group has occurred in the last decades. The main aims of the present study were (i) to provide an updated prevalence of overweight and obesity in a representative sample of the Spanish elderly population; (ii) to calculate the prevalence of sarcopenic obesity (SO) and (iii) to analyse the relationships between adiposity measurements and lifestyle. A cross-sectional study was carried out in a sample of 3136 persons representative of the non-institutionalized population ≥65 years of age. Anthropometric measurements were obtained using standardized techniques and equipment. Overall, 84% of the population can be categorized as overweight and/or obese. The present study indicates that 67% of the Spanish elderly population has an increased percentage of fat mass and more than 56% suffer from central obesity. Moreover, SO is present in 15% of the Spanish elderly population. Finally, a strong relationship between both physically active and sedentary lifestyles and the level of adiposity was found. Prevalence of overweight and obesity among elderly people in Spain is very high and is still increasing. Lifestyle seems to be a determinant factor in the development of obesity among elderly people.


Patent foramen ovale.
Patent foramen ovale (PFO) is the most common anatomical cause of an interatrial shunt. It is usually asymptomatic but may cause paradoxical embolism, manifesting as stroke, myocardial infarction or visceral/peripheral ischaemia. PFO is a risk factor for stroke and may be associated with migraine with aura. New evidence suggests PFO closure reduces the risk of recurrent ischaemic stroke in a highly selected population of stroke survivors: those aged 60 years or younger with a cryptogenic stroke syndrome, a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation. They benefit from percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone. Current evidence does not support PFO closure in the treatment of migraine.


A wavelength-resolved electrochemiluminescence resonance energy transfer ratiometric immunosensor for detection of cardiac troponin I.
In this study, a wavelength-resolved electrochemiluminescence resonance energy transfer (ECL-RET) ratiometric immunosensor from Au nanoparticle functionalized graphite-like carbon nitride nanosheets (Au-g-C3N4) to Au nanoclusters (Au NCs) has been constructed for the first time. At a working voltage of 0 to -1.2 V, Au-g-C3N4 showed a strong cathodic ECL emission with a peak at 460 nm, which overlapped well with the absorption spectra of Au NCs thus stimulating the fluorescence emission of Au NCs at 610 nm. Moreover, within this voltage range, the Au NCs showed no ECL signal; therefore, they would not interfere with the detection of the system. We used cardiac troponin I (cTnI) as an analytical model to construct a sandwich immunosensor based on the ECL-RET ratiometric strategy. By measuring the responses of the ECL460 nm/FL610 nm ratio at different cTnI concentrations, the sensitive detection of cTnI with a wide range of 50 fg mL-1 to 50 ng mL-1 and a low detection limit of 9.73 fg mL-1 can be achieved. This work enriches the wavelength-resolved ECL-RET system and provides an innovative reference for the development of more efficient and sensitive ECL-RET ratiometry.


The information communication technologies in medicine.
The article discusses some aspects of information and communication technologies in medicine. In view of the COVID-19 pandemic, special attention is paid to development of telemedicine. The informational computer technologies are especially relevant where there is shortage of medical personnel. Taking into account that by the year 2035 there will be shortage of 12.9 million medical workers worldwide due to aging of population, increase in prevalence of non-communicable diseases, migration and turnover of medical personnel, remote consultations of patients are becoming increasingly relevant. The examples of information and communication technologies in health care that proved their effectiveness are given.


18F-4FMFES and 18F-FDG PET/CT in Estrogen Receptor-Positive Endometrial Carcinomas: Preliminary Report.
This article reports the preliminary results of a phase II clinical trial investigating the use of the estrogen receptor (ER)-targeting PET tracer 4-fluoro-11β-methoxy-16α-18F-fluoroestradiol (18F-4FMFES) and 18F-FDG PET in endometrial cancers. In parallel, noninvasive interventions were attempted to slow progression of 18F-4FMFES metabolites in the intestines to reduce abdominal background uptake. Methods: In an ongoing study, 25 patients who received prior pathologic confirmation of an ER-positive endometrial cancer or endometrial intraepithelial neoplasia agreed to participate in the ongoing clinical trial. Patients were scheduled for 18F-FDG and 18F-4FMFES PET/CT imaging in random order and within 2 wk. Patients were administered either 4 mg of loperamide orally before 18F-4FMFES tracer injection or repeated intravenous injection of 20 mg of hyoscine N-butylbromide during 18F-4FMFES PET/CT. Regions of interest covering the whole abdomen and excluding the liver, bladder, and uterus were drawn for the 18F-4FMFES PET images, and an SUV threshold of more than 4 was applied. The volume of the resulting region was compared between the different interventions to estimate the extent of the intestinal background uptake. Results: Repeated injection of hyoscine N-butylbromide substantially reduced the intestinal background volume, whereas loperamide had a significant but moderate effect. 18F-4FMFES tumor SUVmax ranged from 3.0 to 14.4 (9.4 ± 3.2), whereas 18F-FDG SUVmax ranged from 0 to 22.0 (7.5 ± 5.1). Tumor-to-background ratio was significantly higher for 18F-4FMFES (16.4 ± 5.4) than for 18F-FDG (7.4 ± 4.6). Significant differences were observed between grade 1 and higher-grade tumors concerning 18F-4FMFES uptake and contrast, 18F-FDG uptake, and the 18F-FDG/18F-4FMFES uptake ratio. Conclusion: It is possible to improve 18F-4FMFES abdominal background using hyoscine N-butylbromide. Both 18F-FDG and 18F-4FMFES PET are suitable for detection of ER-positive endometrial cancers, although 18F-4FMFES yielded a better tumor contrast than did 18F-FDG.


Oncostatin M, leukaemia-inhibitory factor and interleukin 6 trigger different effects on alpha1-proteinase inhibitor synthesis in human lung-derived epithelial cells.
Interleukin 6 (IL-6), oncostatin M (OSM) and leukaemia-inhibitory factor (LIF) share a common signal-transducing subunit in each of their receptors and thus mediate an overlapping spectrum of biological activities. Although all of these cytokines stimulate the production of alpha1-proteinase inhibitor (alpha1-PI) in hepatocyte-derived cells, only OSM is able to up-regulate levels of this inhibitor in epithelial cells originating from the lung. In this study we characterized human lung-derived epithelial-like HTB58 cells for their ability to synthesize alpha1-PI after treatment with IL-6, OSM and LIF. The results demonstrate that the resistance of HTB58 cells to the effects of IL-6 and LIF was not because of a lack of their individual functional receptors and suggest that OSM utilizes two different receptors, gp130/LIF receptor and gp130/OSM receptor, in lung-derived epithelial cells.


Chapter 15: Lessons learned from clinical trials of asthma.
The preponderance of clinical data suggest that inhaled corticosteroids (ICSs) are the preferred therapy for the long-term management of asthma, whereas oral or parental corticosteroids and short-acting beta(2)-adrenergic agonists remain the mainstay treatment of acute exacerbations. Allergen and tobacco avoidance are tenets to the practice of allergy-immunology and are beneficial in the treatment of asthma. Failure to avoid animal danders or fungi to which a patient with asthma is allergic is a risk factor for a fatal attack. First introduced in the 1970s, ICSs are the mainstay of pharmacotherapy to control airway inflammation and bronchial hyperresponsiveness in children and adults with asthma. ICSs reduce symptoms, exacerbations, hospitalizations, and deaths while improving quality of life and lung function. When used in combination with an ICS, essentially all clinical trials have indicated that long-acting beta(2)-adrenergic agonists are effective and safe. Leukotriene modifiers (LTMs) are effective in the treatment of persistent asthma, exercise-induced asthma, and aspirin-induced asthma but, in general, are less efficacious than ICSs when used as monotherapy to control asthma symptoms. Nevertheless, some patients respond to LTMs better than ICSs so a personalized approach to asthma pharmacotherapy is recommended. Not only is conventional (subcutaneous) allergen immunotherapy effective in patients with allergic asthma, immunotherapy (subcutaneous or sublingual) administered for rhinoconjunctivitis in children has been shown to reduce the development of asthma.


Influence of factors before and during medical school on choice of psychiatry as a specialty.
Prompted by the recruitment problem facing psychiatry, the authors investigated the influence of factors before and during medical school on choice of psychiatry. A questionnaire was completed by 392 of the 1982 graduates from 114 United States medical schools who entered a psychiatric training program in 1982. College courses, work experience, and experience with someone having a psychiatric disorder were the most positive "before" factors; the clinical psychiatric elective, the psychiatrist-patient relationship, inpatient experiences during the psychiatric clerkship, and control over practice hours were the most positive "during" factors.


Distribution of liver disease in a cohort of immigrants in Sicily: analysis of day-hospital admissions in a migration medicine unit.
The objective of this study was to evaluate the frequency of liver disease and its aetiology in a cohort of immigrants. We retrospectively examined the hospital discharge charts of all the immigrant patients presenting at our day hospital from July 2009 to June 2013, and after evaluating the anamnestic, clinical and laboratory data on these charts we identified subjects with liver disease and its various aetiologies. The total sample population consisted of 1218 patients, of whom 112 (9.2%) had a diagnosis of liver disease. More than two-thirds of the latter (67.8%) came from Africa, while 15.2% were from Asia and 17.0% from Eastern Europe. In most patients the disease was related to HBV (44.6%), followed by alcohol (25%) and then HCV or cryptogenic disease (both 15.2%). Forty-six patients had undergone liver biopsy, which showed eight cases of varying degrees of liver steatosis, 29 cases with a variable severity of chronic liver disease, eight cases with a definite picture of liver cirrhosis and one case of alcoholic hepatitis. These data show that a significant proportion of our immigrant population has liver disease and that the most frequent cause is hepatitis B infection.


The role of personality traits in inpatient pulmonary rehabilitation response in patients with chronic obstructive pulmonary disease.
The effectiveness of pulmonary rehabilitation (PR) is a critical issue for chronic obstructive pulmonary disease (COPD) patients. However, PR response is marked by a strong heterogeneity, partially unexplained to date. We hypothesized that personality traits defined by the Five-Factor Model could modulate the effect of inpatient-PR. The aim was to assess the associations between these five personality traits and PR outcomes. 74 persons with COPD admitted for a 5-week inpatient PR program had a personality assessment at the start of the program (T1). Exercise capacity, quality of life, sensory and affective dyspnea dimensions were assessed at T1 and at the end of the program (T2). Their evolution was evaluated using the delta score between T2 and T1. PR response was defined using the minimal clinically important change score for each of them. A composite response was established distinguishing the poor responders' group, made of patients who responded to 0, 1 or 2 parameters and the good responders' group, with patients who responded on 3 or 4 indicators. Logistic regressions analyses highlighted that those with a high level of openness [OR = 0.36, 95% CI = 0.15-0.74, p < 0.01] were less likely to respond on quality of life, controlling for socio-demographic factors and the severity of the disease. This study shows that the investigation of the personality constitutes an interesting perspective for better understanding the interindividual differences observed between patients in the PR response. Tailoring clinical intervention to the patient's personality could be a promising prospect for optimizing PR effectiveness.


Nerve repair using a vein graft filled with collagen gel.
It has been shown that a vein graft provides a good environment for axon regeneration in short nerve gaps. But the use of a vein graft for long nerve gaps is controversial because veins may collapse, due to their thin walls, and the surrounding scar tissue can cause constriction. In an attempt to improve results using the vein graft, the authors conducted the reported experiment by filling the lumen of the vein with collagen gel. A 15-mm rabbit peroneal nerve defect was bridged with a collagen-filled vein graft. On the contralateral side, the defect was bridged with the vein alone. When the regenerated tissue was examined 4 weeks, 8 weeks, and 12 weeks after grafting, the number and diameter of myelinated fibers were significantly increased, compared with the control group without collagen gel. This study found that in order to increase the efficacy of a vein graft for axonal regeneration, collagen gel might be an appropriate matrix material with which to fill the vein graft.