Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders.
Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD.


Selective gas sorption within a dynamic metal-organic framework.
A microporous metal-organic framework 1 Co(NDC)(4,4'-Bipy)(0.5).G(x) (NDC = 2,6-naphthalenedicarboxylate; 4,4'-Bipy = 4,4'-bipyridine; G = guest molecules) was synthesized and structurally characterized of a doubly interpenetrated primitive cubic net. To make use of the framework flexibility, 1 was activated at temperatures of 150 and 200 degrees C to form 1a and 1b, respectively, exhibiting highly selective sorption behaviors of hydrogen over nitrogen-gas molecules.


Design, simulation and evaluation of uniform magnetic field systems for head-free eye movement recordings with scleral search coils.
The precise measurement of eye movements is important for investigating vision, oculomotor control and vestibular function. The magnetic scleral search coil technique is one of the most precise measurement techniques for recording eye movements with very high spatial (≈ 1 arcmin) and temporal (>kHz) resolution. The technique is based on measuring voltage induced in a search coil through a large magnetic field. This search coil is embedded in a contact lens worn by a human subject. The measured voltage is in direct relationship to the orientation of the eye in space. This requires a magnetic field with a high homogeneity in the center, since otherwise the field inhomogeneity would give the false impression of a rotation of the eye due to a translational movement of the head. To circumvent this problem, a bite bar typically restricts head movement to a minimum. However, the need often emerges to precisely record eye movements under natural viewing conditions. To this end, one needs a uniform magnetic field that is uniform over a large area. In this paper, we present the numerical and finite element simulations of the magnetic flux density of different coil geometries that could be used for search coil recordings. Based on the results, we built a 2.2 × 2.2 × 2.2 meter coil frame with a set of 3 × 4 coils to generate a 3D magnetic field and compared the measured flux density with our simulation results. In agreement with simulation results, the system yields a highly uniform field enabling high-resolution recordings of eye movements.


Segmentation and classification of burn images by color and texture information.
In this paper, a burn color image segmentation and classification system is proposed. The aim of the system is to separate burn wounds from healthy skin, and to distinguish among the different types of burns (burn depths). Digital color photographs are used as inputs to the system. The system is based on color and texture information, since these are the characteristics observed by physicians in order to form a diagnosis. A perceptually uniform color space (L*u*v*) was used, since Euclidean distances calculated in this space correspond to perceptual color differences. After the burn is segmented, a set of color and texture features is calculated that serves as the input to a Fuzzy-ARTMAP neural network. The neural network classifies burns into three types of burn depths: superficial dermal, deep dermal, and full thickness. Clinical effectiveness of the method was demonstrated on 62 clinical burn wound images, yielding an average classification success rate of 82%.


Charge exchange spectroscopy as a fast ion diagnostic on TEXTOR.
An upgraded charge exchange spectroscopy diagnostic has been taken into operation at the TEXTOR tokamak. The angles of the viewing lines with the toroidal magnetic field are close to the pitch angles at birth of fast ions injected by one of the neutral beam injectors. Using another neutral beam for active spectroscopy, injected counter the direction in which fast ions injected by the first beam are circulating, we can simultaneously measure a fast ion tail on the blue wing of the D(alpha) spectrum while the beam emission spectrum is Doppler shifted to the red wing. An analysis combining the two parts of the spectrum offers possibilities to improve the accuracy of the absolute (fast) ion density profiles. Fast beam modulation or passive viewing lines cannot be used for background subtraction on this diagnostic setup and therefore the background has to be modeled and fitted to the data together with a spectral model for the slowing down feature. The analysis of the fast ion D(alpha) spectrum obtained with the new diagnostic is discussed.


Infant expressions in an approach/withdrawal framework.
Since the introduction of empirical methods for studying facial expression, the interpretation of infant facial expressions has generated much debate. The premise of this article is that action tendencies of approach and withdrawal constitute a core organizational feature of emotion in humans, promoting coherence of behavior, facial signaling, and physiological responses. The approach/withdrawal framework can provide a taxonomy of contexts and the neurobehavioral framework for the systematic, empirical study of individual differences in expression, physiology, and behavior within individuals as well as across contexts over time. By adopting this framework in developmental work on basic emotion processes, it may be possible to better understand the behavioral principles governing facial displays, and how individual differences in them are related to physiology and behavioral function in context.


Inhibition of benzopyrene-diol-epoxide (BPDE)-induced bax and caspase-9 by cadmium: role of mitogen activated protein kinase.
Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other polynuclear aromatic hydrocarbons (PAHs). The mechanism underlying this synergism is not clearly understood. Present study demonstrates that (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in human leukemic HL-60 cells and others, and cadmium at non-cytotoxic concentration inhibits BPDE-induced apoptosis. We observed that BPDE treatment also activates all three MAP kinases e.g. ERK1/2, p38 and JNK in HL-60 cells, and inhibition of BPDE-induced apoptosis by cadmium is associated with down-regulation of pro-apoptotic bax induction/caspase-9 activation and up-regulation of ERK phosphorylation, whereas p38 MAP kinase and c-Jun phosphorylation (indicative of JNK activation) remain unaffected. Inhibition of ERKs by prior treatment of cells with 10muM U0126 relieves cadmium-mediated inhibition of apoptosis/bax induction/caspase-9 activation. Our results suggest that cadmium inhibits BPDE-induced apoptosis by modulating apoptotic signaling through up-regulation of ERK, which is known to promote cell survival.


Silver(i) complexes of bis- and tris-(pyrazolyl)azine derivatives - dimers, coordination polymers and a pentametallic assembly.
Silver(i) complexes of 2,4,6-tri(pyrazol-1-yl)pyridine (tpp), 2,4,6-tri(pyrazol-1-yl)pyrimidine (tpym), 2,4,6-tri(pyrazol-1-yl)-1,3,5-triazine (tpt) and 2,4-di(pyrazol-1-yl)-1,3,5-triazine (bpt) are reported. Dinuclear [Ag2(μ-tpp)2(MeCN)2][BF4]2·2MeCN and [Ag2(μ-tpym)2(MeCN)2][BF4]2 are formed from approximately planar [AgL(NCMe)]+ (L = tpp or bpym) centres, which dimerise via apical interactions to the pendant pyrazolyl donor on each ligand. Two polymeric solvatomorph phases [Ag2(μ-tpp)2][BF4]2·nMeNO2 were obtained by crystallising AgBF4 and tpp from nitromethane solution. One is composed of the same dimeric [Ag2(μ-tpp)2]2+ motif as the MeCN solvates, but with semibridging pyrazolyl substitutents replacing the solvent ligands. The other form has helicate [Ag2(μ-tpp)2]2+ dimers linked into chains by unsupported AgAg interactions. In contrast, [Ag5(μ3-tpym)4][BF4]5·2MeNO2 contains discrete pentametallic assemblies, of a flattened [Ag4(μ-tpym)4]4+ molecular square centred by the fifth silver ion. Three helical or linear 1D coordination polymer topologies are described for [Ag(μ-tpt)]X (X- = BF4- or ClO4-), where ditopic tpt ligands bind one silver ion in a [2 + 1] geometry and the other in bidentate, [1 + 1] or monodentate fashion. Finally, [Ag(bpt)]BF4 is a polymer of square planar silver ions linked by bis-bidentate bpt ligands. Most of the tpt and bpt structures include short anionπ contacts to the ligand triazinyl rings. Electrospray mass spectra confirm the oligomeric nature of the Ag/tpym and tpt complexes in MeNO2 solution.


Production and characterization of transgenic mice harboring mutant human UMOD gene.
Familial juvenile hyperuricemic nephropathy is caused by mutations in the UMOD gene encoding uromodulin. A transgenic mouse model was developed by introducing a human mutant UMOD (C148W) cDNA under control of the mouse umod promoter. Uromodulin accumulation was observed in the thick ascending limb cells in the kidney of transgenic mice. However, the urinary excretion of uromodulin in transgenic mice did not decrease and LC-MS/MS analysis indicated it was of mouse origin. Moreover, the creatinine clearance was not different between wildtype and transgenic animals. Consequently, the onset of the disease was not observed in transgenic mice until 24 weeks of age.


Modification of electrocyte membrane lipid composition induced by denervation.
1. We determined the effect of denervation on the lipid composition of the main electric organ and electrocyte postsynaptic membrane vesicles of Electrophorus electricus. 2. Lipid extracts of whole electric organ contain mainly cholesterol, triglycerides, phosphatidylcholine and phosphatidylethanolamine. After 30 days of denervation, the lipid composition of whole electric organ did not change appreciably. 3. Lipid extracts of the membrane vesicles were similar, except that they contained mainly free fatty acids rather than triglycerides. After 30 days of denervation, cholesterol concentration was increased and phospholipids were decreased in the membrane fraction, with higher relative concentrations of phosphatidylethanolamine and cerebrosides. 4. These results suggest that electrocyte membrane fluidity and permeability will change after 30 days of denervation.


[Determination of the integral doses in conventional x-ray studies and computed tomography of the skull].
Absorbed energy (integral dose) is a suitable measure of radiation exposure during radiodiagnostic examinations. The integral doses from conventional and CT examinations of the skull were determined, using an Alderson-Rando phantom. The absorbed energy of one exposure using a film-screen combination and for one plane of conventional tomogram is almost identical. Considering the total absorbed energy, lower doses are to be expected for CT than for conventional tomography. A survey view is associated with reduced radiation exposure.


Nerve entrapment syndromes of the lower limb.
The general features of entrapment are discussed. Common and less common lower limb entrapments are surveyed with consideration of differential diagnoses. Treatment modalities are summarised.


Global Profiling of Cellular Substrates of Human Dcp2.
Decapping is the first committed step in 5'-to-3' RNA decay, and in the cytoplasm of human cells, multiple decapping enzymes regulate the stabilities of distinct subsets of cellular transcripts. However, the complete set of RNAs regulated by any individual decapping enzyme remains incompletely mapped, and no consensus sequence or property is currently known to unambiguously predict decapping enzyme substrates. Dcp2 was the first-identified and best-studied eukaryotic decapping enzyme, but it has been shown to regulate the stability of <400 transcripts in mammalian cells to date. Here, we globally profile changes in the stability of the human transcriptome in Dcp2 knockout cells via TimeLapse-seq. We find that P-body enrichment is the strongest correlate of Dcp2-dependent decay and that modification with m6A exhibits an additive effect with P-body enrichment for Dcp2 targeting. These results are consistent with a model in which P-bodies represent sites where translationally repressed transcripts are sorted for decay by soluble cytoplasmic decay complexes through additional molecular marks.


Differences in transcriptomic and metabolomic analyses of metabolites of shoots on tea plants of different ages and relevant regulatory network.
To investigate differences in fresh leaves of tea plants at different ages in gene expression, metabolism, and dried tea quality, and to provide references to a deep exploration on metabolite differential accumulation of fresh leaves of tea plants at different ages as well as the regulation mechanism, two groups of fresh leaves from tea plants at different ages (group JP: 20-, 200-, and 1,200-year tea plants; group YX: 50-, 100-, and 400-year tea plants) were chosen as materials, and their differences in gene expression, metabolites, and metabolic regulatory network were investigated by transcriptomics and metabolomics. A total of 12,706 differentially expressed genes (DEGs) were screened from the fresh tea leaves in the JP group, of which tea-20 vs. tea-200 had the largest number of DEGs, up to 9,041 (4,459 down-regulated genes, 4,582 up-regulated genes). A total of 644 common genes in the fresh leaves of three different ages of tea plants in the JP group were differentially expressed. A total of 8,971 DEGs were screened from the fresh leaf samples of tea plants in the YX group, of which the number of DEGs obtained in the tea-50 vs. tea-400 comparison combination was the largest with a total of 3,723 (1,722 up-regulated genes and 2,001 down-regulated genes). A total of 147 common genes were differentially expressed in the fresh leaves of three different tree ages in the YX group. The pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two groups, and that the metabolic pathways of common significant enrichment included flavonoid biosynthesis, phenylpropane biosynthesis, carbon metabolism, amino acid biosynthesis, and plant pathogen interaction. The metabolomics results showed that 72 and 117 different metabolites were screened from the JP and YX groups, respectively. Most of the different metabolites in the two groups were flavonoids, phenolic acids, amino acids, and their derivatives. Among them, the number of down-regulated flavonoids in older tea plants is generally higher than the number of up-regulated flavonoids. Moreover, according to the sensory evaluation results of dried tea of fresh leaves from tea plants of different ages, tea-1200 and tea-400 showed the highest sensory evaluation scores in their groups. With increase in plant age, the fragrance of the tea was more elegant, and it changed from a dense scent to a faint scent; the tea tasted sweet and its freshness increased, while the sense of astringency was weakened and the concentration declined. Therefore, the quality difference of tea of different tree ages is mainly related to secondary metabolic pathways such as the flavonoid biosynthesis pathway. With increase in tea age, a large number of gene expression in the flavonoid biosynthesis pathway is down-regulated, which reduces the content of bitter flavonoid substances in fresh leaves and makes tea soup more mellow.


[Biofilm formation by antagonistic strains of oral Lactobacillus].
Highantagonistic strains of lactobacillus isolated from the oral cavity of healthy people, genetically identified as L. fermentum 39, L. rhamnosus 50, L. rhamnosus 24, showed high degree of autoaggregation, surface hydrophobicity, coaggregation, adhesion, and the ability to form biofilms. These strains can be used to create new probiotic drugs for the prevention and correction the dysbiosis of the oral cavity.


Osteoblast-derived factors promote metastatic potential in human prostate cancer cells, in part via non-canonical transforming growth factor β (TGFβ) signaling.
Transforming growth factor β (TGFβ) functions as a double-edged sword in prostate cancer tumorigenesis. In initial stages of the disease, TGFβ acts as a growth inhibitor upon tumor cells, whereas it in later stages of disease rather promotes invasion and metastatic potential. One well-known cellular source of TGFβ in the bone metastatic site is the bone-forming osteoblasts. Here we have studied the effects by osteoblast-derived factors on metastatic potential in several human prostate cancer cell lines. Effects on metastatic potential in prostate cancer cells by osteoblast-derived factors were studied in vitro using several methods, including Transwell migration and evaluation of formation of pro-migratory protrusions. Confocal microscopy was used to evaluate possible changes in differentiation state in tumor cells by analysis of markers for epithelial-to-mesenchymal transition (EMT). The Matrigel-on-top 3D culture method was used for further assessment of metastatic characteristics in tumor cells by analysis of formation of filopodium-like protrusions (FLPs). Osteoblast-derived factors increased migration of PC-3U cells, an effect less prominent in cells overexpressing a mutated type I TGFβ receptor (TβRI) preventing non-canonical TRAF6-dependent TGFβ signaling. Osteoblast-derived factors also increased the formation of long protrusions and loss of cell-cell contacts in PC-3U cells, suggesting induction of a more aggressive phenotype. In addition, treatment with TGFβ or osteoblast-derived factors of PC-3U cells in Matrigel-on-top 3D cultures promoted formation of FLPs, previously shown to be essential for metastatic establishment. These findings suggests that factors secreted from osteoblasts, including TGFβ, can induce several cellular traits involved in metastatic potential of PC-3U cells, further strengthening the role for bone cells to promote metastatic tumor cell behavior.


Macrophage activation by cord factor (trehalose 6,6'-dimycolate): enhanced association with and intracellular killing of Trypanosoma cruzi.
Cord factor (trehalose 6,6'-dimycolate[TDM] ), a mixture of 6,6'-diesters of alpha, alpha-D-trehalose with natural mycolic acids, has been described as having immunoregulatory and antitumor activities in vivo, although the relevant mechanisms of action remain unelucidated. In this work, we measured the effects of TDM on both mouse macrophage association with (i.e., the combined result of surface binding and uptake) and subsequent intracellular killing of Trypanosoma cruzi, the causative agent of Chagas' disease. Pretreatment of macrophage cultures with TDM for 16 h markedly increased both the ability of these cells to associate with T. cruzi and the rate of killing of parasites. The results obtained with macrophages treated with TDM after exposure to the parasites did not differ from those obtained with untreated macrophages, indicating that macrophage activation did not occur immediately after TDM treatment and was time dependent. The TDM effect was reversible since the extents of macrophage-parasite association and intracellular killing returned to normal levels 4 h after TDM treatment. Neither catalase, which scavenges hydrogen peroxide, nor sodium azide or potassium cyanide, which are inhibitors of peroxidase activity, significantly reduced the level of trypanosome killing by TDM-treated macrophages. TDM also increased the uptake of glutaraldehyde-killed T. cruzi and latex particles, suggesting that TDM could act mostly by enhancing phagocytosis and that increased cell association with the living trypanosomes did not necessarily depend on the macrophages becoming more susceptible to parasite invasion. These results indicate that TDM modulates macrophage function by augmenting both internalization and intracellular destruction. Hydrogen peroxide and peroxidase activity, postulated to be involved in phagocytic killing of T. cruzi, did not appear to be an absolute requirement for the killing of T. cruzi in TDM-treated macrophages.


Landmarks for rapid localization of the sphenopalatine foramen: A radiographic morphometric analysis.
Transnasal endoscopic sphenopalatine artery ligation is becoming the procedure of choice for surgical management of intractable posterior epistaxis. Landmarks for localization of the sphenopalatine foramen can assist in rapid surgical exposure of the sphenopalatine artery. This study examined distances from easily identified endoscopic surgical landmarks to the sphenopalatine foramen. By using computed tomography of the sinus to study radiologic anatomy in 50 adults, distances were measured between five simple endoscopic landmarks and the sphenopalatine foramen. The two-tailed t-test was used for statistical analysis. Right- and left-sided measurements were similar. The mean (standard deviation [SD]) anteroposterior distances to the sphenopalatine foramen were the following: from the maxillary line (36.7 ± 5.5 mm), anterior head of the middle turbinate (33.8 ± 6.7 mm), basal lamella (11.8 ± 1.9 mm), and choanal arch (-9.2 ± 1.4 mm). The mean (SD) distance in the vertical dimension from the nasal floor was 26.6 ± 2.6 mm. Female patients had statistically shorter distances to the sphenopalatine foramen from the maxillary line, anterior head of the middle turbinate, choanal arch, and nasal floor. Reliable endoscopic landmarks exist in relation to consistent anatomic structures and can be used to help quickly estimate the location of the sphenopalatine foramen at the onset of the procedure.


Sex-determining genes in mice: building pathways.
Sry is active in the mouse for a very brief period in somatic cells of the genital ridge to initiate Sertoli cell differentiation. SRY protein must act within the context of other gene products required for gonadal development and must itself act on one or more target genes that will ensure the further differentiation and maintenance of Sertoli cells. Over the last few years several genes have been found that have important roles in gonadal development and sex determination. These include genes encoding transcription factors such as Lhx9, Wt1, Sf1, Dax1, Gata4, Dmrt1 and Sox9, and some involved in cell cell signalling, including Amh, Wnt4 and Dhh. While more await discovery, it is now possible to start putting some of the known genes into pathways or networks. Sox9 probably occupies a critical role in mammals for both the initiation and maintenance of Sertoli cell differentiation. Data will be presented that are consistent with SRY acting directly on Sox9 to ensure its up-regulation. SF1 is also central to gonadal differentiation. Our results imply that it contributes to transcriptional activation of several relevant genes, not just those required for male development, including Sox9 and Amh, but also those that can have an antagonistic effect on Sertoli cell differentiation, such as Dax1. Progress in establishing other regulatory interactions will also be discussed.


Anesthetic management for percutaneous aortic valve implantation: an overview of worldwide experiences.
Transcatheter aortic valve implantation is an emergent technique for high risk patients with aortic stenosis. Transcatheter aortic valve implantation poses significant challenges about its management, due to the procedure itself (i.e. the passage of large stiff sheaths in diseased vessels, the valve dilatation and the prosthesis positioning during a partial cardiac standstill) and the population of elder and high-risk patients who undergo the implantation. Retrograde transfemoral approach is the most popular procedure and a great number of cases is reported. Nevertheless, there is not a consensus regarding the intraoperative anesthesiological strategies, which vary in the different Centers. Sedation plus local anesthesia or general anesthesia are both valid alternatives and can be applied according to patient's characteristics and procedural instances. Most groups started the implantation program with a general anesthesia; indeed, it offers many advantages, mainly regarding the possibility of an early diagnosis and treatment of potential complications, through the use of the transesophageal echocardiography. However, after the initial experiences, many groups began to employ routinely sedation plus local anesthesia for transcatheter aortic valve implantation and their procedural and periprocedural success demonstrates that it is feasible, with many possible advantages. Many aspects about perioperative anesthetic management for transcatheter aortic valve implantation are still to be defined. Aim of this work is to clarify the different management strategies through a review of the available literature published in pubmed till June 2011.


An empirical investigation of the influence of safety climate on organizational citizenship behavior in Taiwan's facilities.
Although the social exchange relationships between employers and employees are increasingly important to the performance of safety management systems, the psychological effects of work attitudes on this relationship have been less studied. Using a sample of first-line operators and their supervisors from 188 facilities in Taiwan which had Occupational Health and Safety Assessment Series 18000 (OHSAS 18000) certification, the current research conducted an empirical investigation of the influence of safety climate on organizational citizenship behavior (OCB). Work attitude was used to disclose the psychological effect. Research results indicated that (a) safety climate was a significant predicator of OCB, (b) the psychological effect significantly influenced social exchange relationships, and (c) job satisfaction showed a stronger mediating influence than organizational commitment due to the frequent top management turnover. Discussions and implications are also addressed.


Efficacy of Different Cone-beam Computed Tomographic Protocols in the Identification of Mesiobuccal Canals of Maxillary First Molars: A Tomographic and Ex Vivo Study.
Complementary methods of anatomic diagnosis, including cone-beam computed tomographic (CBCT) imaging, may be useful in the diagnosis of mesiobuccal (MB) canals of maxillary molars. Thirty-five maxillary first molars were subjected to ex vivo analysis and 4 CBCT protocols: i-CAT Classic (Imaging Sciences International, Hatfield, PA) (ICC group), i-CAT Next Generation (Imaging Sciences International) (ICN group), PreXion 3D (PreXion, San Mateo, CA) (16.8-second acquisition time; PX1 group), and PreXion 3D (33.5-second acquisition time; PX2 group). The images were evaluated by 2 calibrated endodontists who kept records following protocols previously published in the literature. Micro-computed tomographic imaging was used as the control. The correct identification of anatomic variations of MB roots was 54.3% (n = 19) in the ICC group, 65.7% (n = 23) in the ICN group, and 80.0% (n = 28) in the PX1 and PX2 groups. The probability of agreement between the ICC and the control groups was significantly different from the probability of agreement with the PX1 (P < .05) and PX2 (P < .05) groups. The other groups showed no significant differences compared with the control group. There was no difference in the probability of agreement between the tomographic protocols and the ex vivo results. The PX1 and PX2 groups were more effective for the diagnosis of MB canals. PX1 is the most suitable because it results in a shorter radiation time and diagnostic imaging similar to PX2. The single-canal anatomy was the most prevalent in the study.


Induction of tolerance in freshly isolated alloreactive CD4+ T cells by activated T cell stimulators.
Activated human T cells express major histocompatibility complex class II proteins, and their potential to present antigens to T cell clones has been documented extensively. The effect of such TT presentation on responder T cell clones has been shown to be the induction of tolerance, sometimes accompanied by activation. To investigate whether freshly isolated responder T cells are also susceptible to such induction of tolerance by activated T cells functioning as antigen-presenting cells (APC), we have used the capability of unprimed ex vivo T cells to respond in a proliferation assay in vitro to alloligands on professional APC. We show that purified human T cells ex vivo, when exposed to alloligand on activated T cells for primary allorecognition in vitro, fail to mount a proliferative response. Priming of responder CD4+ T cells with alloligand expressed on activated T cells results in the induction of nonresponsiveness to a subsequent challenge by competent allo-APC. This ability of activated, HLA-DR+ T cells to induce nonresponsiveness to subsequent challenge in bulk CD4+ T cell populations ex vivo has interesting implications for infections involving T cells such as human immunodeficiency virus.


Quantification of functional hand grip using electromyography and inertial sensor-derived accelerations: clinical implications.
Assessing hand injury is of great interest given the level of involvement of the hand with the environment. Knowing different assessment systems and their limitations generates new perspectives. The integration of digital systems (accelerometry and electromyography) as a tool to supplement functional assessment allows the clinician to know more about the motor component and its relation to movement. Therefore, the purpose of this study was the kinematic and electromyography analysis during functional hand movements. Ten subjects carried out six functional movements (terminal pinch, termino-lateral pinch, tripod pinch, power grip, extension grip and ball grip). Muscle activity (hand and forearm) was measured in real time using electromyograms, acquired with the Mega ME 6000, whilst acceleration was measured using the AcceleGlove. Electrical activity and acceleration variables were recorded simultaneously during the carrying out of the functional movements. The acceleration outcome variables were the modular vectors of each finger of the hand and the palm. In the electromyography, the main variables were normalized by the mean and by the maximum muscle activity of the thenar region, hypothenar, first interosseous dorsal, wrist flexors, carpal flexors and wrist extensors. Knowing muscle behavior allows the clinician to take a more direct approach in the treatment. Based on the results, the tripod grip shows greater kinetic activity and the middle finger is the most relevant in this regard. Ball grip involves most muscle activity, with the thenar region playing a fundamental role in hand activity. Relating muscle activation, movements, individual load and displacement offers the possibility to proceed with rehabilitation by individual component.


Coding-complete genomes of XBB.1.16, XBB.2.3, FL.4 (alias of XBB.18.104.22.168), and XBB.3 of SARS-CoV-2 Omicron isolated from Bangladesh.
We announce the coding-complete genomes of four different strains of SARS-CoV-2 Omicron lineages, XBB.1.16, XBB.2.3, FL.4 (alias of XBB.188.8.131.52), and XBB.3. These strains were obtained between October 2022 and May 2023 from nasopharyngeal swabs of four Bangladeshi individuals, while one of them had a travel history. Genomic data were produced by implementing ARTIC Network-based amplicon sequencing using the Oxford Nanopore Technology.


A giant intradiaphragmatic bronchogenic cyst: case report and literature review.
Bronchogenic cysts are congenital lesions developing during early embryogenesis. The intradiaphragmatic location is extremely rare. We present a giant bronchogenic cyst arising from the left crus of diaphragm. Based on our literature review results, intradiaphragmatic bronchogenic cysts have the following characteristics: 1) they are more common in female patients; 2) the patients are usually asymptomatic, or present with symptoms of chest pain, abdominal pain, and hiccups; 3) the cysts located in the left diaphragm are more than those in the right diaphragm, most of which are located in the area of the left diaphragm crus.


Assessing the reporting quality of adult neuro-oncology protocols, abstracts, and trials: Adherence to the SPIRIT and CONSORT statements.
Comprehensive and transparent reporting of clinical trial activity is important. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and Consolidated Standards of Reporting Trials (CONSORT) 2010 statements define the items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of adult neuro-oncology trial protocols and trial result articles. Adult primary and secondary brain tumor phase 3 trial protocols and result articles published after the introduction of the SPIRIT 2013 statement, were identified through searches of 4 electronic bibliographic databases. Following extraction of baseline demographic data, the reporting quality of independently included trial protocols and result articles was assessed against the SPIRIT and CONSORT statements respectively. The CONSORT-A checklist, an extension of the CONSORT 2010 statement, was used to specifically assess the abstract accompanying the trial results article. Percentage adherence (standard deviation [SD]) was calculated for each article. Seven trial protocols, and 36 trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 79.4% (SD: 0.11). Mean adherence of trial abstracts to CONSORT-A was 75.3% (SD: 0.12) and trial result articles to CONSORT was 74.5% (SD: 0.10). The reporting quality of adult neuro-oncology trial protocols and trial result articles requires improvement to ensure comprehensive and transparent communication of planned neuro-oncology clinical trials and results within the literature. Raising awareness by clinical triallists and implementing mandatory evidence of proof of adherence by journals should improve reporting quality.


The technological edge.
A self-retaining suprapubic port and a novel bladder retention mechanism have been developed to help overcome problems of infection and blockage during treatment of incontinence.


Aggressive dogs: assessment and treatment considerations.
The question of what to do with an aggressive dog involves clinical, legal, and ethical considerations. This first column on the subject addresses the clinical aspects from the standpoint of the general veterinarian.


Succinate induces hepatic fibrogenesis by promoting activation, proliferation, and migration, and inhibiting apoptosis of hepatic stellate cells.
Liver fibrosis is a progressive pathological process that accompanies wound healing; however, therapeutics for reversing hepatic fibrosis are unavailable. Activation of hepatic stellate cells (HSCs) play a critical role in liver fibrosis. Recent reports showed that succinate and its receptor, G-protein coupled receptor 91 (GPR91), act as signaling molecules during the activation of HSCs. However, the role of succinate in proliferation, apoptosis, and migration of HSCs has not been studied. In this study, we determined whether succinate regulates proliferation, apoptosis, and migration of HSCs and induces liver fibrosis in a mouse model. Succinate treatment not only induced activation of HSCs, but also increased the proliferation and migration of LX-2 HSCs and inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis, 100 mg/kg succinate or control PBS was administered by intraperitoneal injection to mice once a day for four weeks. There were significant molecular changes such as increased α-SMA and collagen type 1 production and increased production of inflammatory cytokines such as IL-6 and TNF-α, but not TGF-β, in the succinate-treated group compared to the control group. However, no morphological changes were observed in Masson's trichrome staining. In conclusion, the present study demonstrated that succinate induces activation, proliferation, and migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of succinate accumulation may be an effective method for reversing liver fibrosis by controlling HSC survival and growth.


Furosine: a suitable marker for assessing the freshness of royal jelly.
Fifteen commercial samples of royal jelly, consisting of 10 imported samples, and 5 samples of known origin obtained freshly harvested from beekeepers, were analyzed for protein, lysine, and furosine content. In addition, a commercial sample of royal jelly, at the beginning of its commercial shelf life, was stored for 10 months both at 4 degrees C and at room temperature in order to assess the development of the Maillard reaction (furosine) and relative nutritional damage (blocked lysine). The commercial royal jelly products contained different amounts of furosine, ranging from 37.1 to 113.3 mg/100 g protein, evidence of different storage times and conditions. The average furosine content of the royal jelly samples of known origin and harvesting was significantly lower than that of the imported samples (41.7 versus 73.6 mg/100 g protein, respectively). With regard to shelf life, furosine content increased significantly from 72.0 mg/100 g protein to 500.8 mg/100 g protein after 10 months of storage at room temperature, while it increased to a much lower level (100.5 mg/100 g protein) when the royal jelly was stored at 4 degrees C. However, nutritional damage, expressed as blocked lysine (calculated indirectly from the furosine content), was minor or negligible, 11.9 and 2.3% of total lysine, in samples stored at room temperature and at 4 degrees C, respectively. Lysine was determined by an innovative procedure based on high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). The results showed that furosine is a suitable index for assessing the quality and freshness of royal jelly.


The beneficial effect of testing: an event-related potential study.
The enhanced memory performance for items that are tested as compared to being restudied (the testing effect) is a frequently reported memory phenomenon. According to the episodic context account of the testing effect, this beneficial effect of testing is related to a process which reinstates the previously learnt episodic information. Few studies have explored the neural correlates of this effect at the time point when testing takes place, however. In this study, we utilized the ERP correlates of successful memory encoding to address this issue, hypothesizing that if the benefit of testing is due to retrieval-related processes at test then subsequent memory effects (SMEs) should resemble the ERP correlates of retrieval-based processing in their temporal and spatial characteristics. Participants were asked to learn Swahili-German word pairs before items were presented in either a testing or a restudy condition. Memory performance was assessed immediately and 1-day later with a cued recall task. Successfully recalling items at test increased the likelihood that items were remembered over time compared to items which were only restudied. An ERP subsequent memory contrast (later remembered vs. later forgotten tested items), which reflects the engagement of processes that ensure items are recallable the next day were topographically comparable with the ERP correlate of immediate recollection (immediately remembered vs. immediately forgotten tested items). This result shows that the processes which allow items to be more memorable over time share qualitatively similar neural correlates with the processes that relate to successful retrieval at test. This finding supports the notion that testing is more beneficial than restudying on memory performance over time because of its engagement of retrieval processes, such as the re-encoding of actively retrieved memory representations.


Antibodies to Klebsiella and Proteus microorganisms in ankylosing spondylitis and rheumatoid arthritis patients measured by ELISA.
Antibodies to Klebsiella oxytoca and Proteus mirabilis in 21 active ankylosing spondylitis (AS), 13 active rheumatoid arthritis (RA), 19 inactive RA patients and 18 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Elevated anti-Klebsiella antibodies were demonstrated in active AS patients compared to active RA (p less than 0.01), inactive RA patients (p less than 0.001) and controls (p less than 0.005). When measuring antibodies to Proteus, active RA patients showed higher levels of antibodies compared to active AS patients (p less than 0.005) and healthy controls (p less than 0.05). Further investigations are required to assess the role of Klebsiella and Proteus microorganisms in AS and RA respectively.


Evaluation of water, sanitation and hygiene program outcomes shows knowledge-behavior gaps in Coast Province, Kenya.
Water related diseases constitute a significant proportion of the burden of disease in Kenya. Water, sanitation and hygiene (WASH) programs are in operation nation-wide to address these challenges. This study evaluated the impact of the Sombeza Water and Sanitation Improvement Program (SWASIP) in Coast Province, Kenya. This study is a cluster randomized, follow-up evaluation that compared baseline (2007) to follow-up (2013) indicators from 250 households. Twenty-five villages were selected with probability proportional to size sampling, and ten households were selected randomly from each village. Follow-up data were collected by in-person interviews using pre-tested questionnaires, and analyzed to compare indicators collected at baseline. Cross-sectional results from the follow-up data were also reported. Statistically significant improvements from baseline were observed in the proportions of respondents with latrine access at home, who washed their hands after defecation, who treated their household drinking water and the average time to collect water in the dry season. However, this study also observed significant decreases in the proportion of respondents who washed their hands before preparing their food, or feeding their children, and after attending to a child who has defecated. The analysis also revealed a knowledge-behavior gap in WASH behaviors. SWASIP contributed to improvements from baseline, but further progress still needs to be seen. The findings challenge the assumption that providing infrastructure and knowledge will result in behavior change. Further understanding of specific, non-knowledge predictors of WASH related behavior is needed.


Emphasizing the pivotal role of fine-needle aspiration cytology in a case of recurrent malignant chondroid syringoma.
Fine-needle aspiration cytology (FNAC) features of malignant chondroid syringoma (MCS) are rarely documented. Here, we report a case of recurrent MCS, highlighting its interesting clinicopathologic features. Initially, we received cytology and histopathology slides (for review) of a 57-year-old woman who had undergone resection for an occipital MCS and later presented with recurrence. On reviewing the slides, cytology was consistent with recurrent MCS. However, tissue sections showed features of a malignant epithelial tumor with comedonecrosis and sebaceous differentiation owing to which a diagnosis of metastatic adenocarcinoma/malignant adnexal tumor was suggested. Due to an ambiguous histology, a repeat FNA was performed to perform immunocytochemistry (ICC) and oil-red O stains, which confirmed the diagnosis of MCS with sebaceous differentiation. Thus, in a situation where histology was inconclusive due to lack of representative sections, FNAC played a major role in resolving the diagnostic dilemma and facilitating an appropriate clinical management.


Enamel matrix proteins in the treatment of deep intrabony defects.
The present study evaluated the healing of enamel matrix derivative (EMD) proteins in the treatment of periodontal lesions with deep intrabony defects. Ten deep intrabony defects in 7 periodontal patients were treated and followed for 1 year. The sites had a probing depth (PD) > or = 8 mm; clinical attachment level (CAL) > or = 9 mm, and intrabony component depth > or = 5 mm. All subjects received therapy prior to surgery and had a plaque score (PI) < or = 10%. Full thickness flaps were elevated buccally and lingually, granulation tissue was removed from the defects, and the root surfaces were planed. A 24% EDTA gel was applied followed by the enamel matrix protein preparation. The flaps were closed with interrupted sutures. The patients rinsed with a chlorhexidine solution twice a day for 6 weeks. They were recalled every 2 weeks for 6 months for professional tooth cleaning and then every 4 weeks for an additional 6 months. The experimental sites were re-examined 6 and 12 months after regenerative surgery. At the 1-year examination, the mean CAL gain was 6.5 mm, the mean PD was 3.2 mm, and mean radiographic bone fill was 4.7 mm. The application of enamel matrix proteins in combination with open flap curettage and root planing resulted in a gain of CAL and bone fill in deep intrabony defects.


Social interaction, social competence, and friendship in children.
The relationship between social skills, social interaction, and popularity was examined. The subjects were 198 children in third and fourth grades in middle- and low-income schools. The relationships between number of friends, socioeconomic status, and grade level were studied in a 2 times 2 times 2 factorial design with 2 sets of dependent measures: (1) social skills were assessed by an experimenter testing each child individually on a set of tasks which included measures of the ability to label emotions in facial expressions, knowledge of how to make friends, giving help, and role-taking ability; and (2) social interaction in the classroom was assessed using a naturalistic observational system. Popular and unpopular children differed in their knowledge of how to make friends and on the referential-communication task. In the classroom, popular children distributed and received more positive reinforcement than unpopular children and spent less time daydreaming. Both grade and social class factors were significant. However, different patterns of results contributed to the main effect of friends and the grade-level main effect. The importance of assessing social skills which are first validated by reference to a criterion such as sociometric position was noted.


Effect of pulmonary surfactant on antimicrobial activity in vitro.
Time-kill curve experiments were performed with linezolid, doripenem, tigecycline, moxifloxacin, and daptomycin against Staphylococcus aureus and with colistin, moxifloxacin, and doripenem against Pseudomonas aeruginosa to evaluate the effect of porcine pulmonary surfactant on antimicrobial activity. Pulmonary surfactant significantly impaired the activities of moxifloxacin and colistin. When antibiotics are being developed for respiratory tract infections, the method described here might be used to preliminarily quantify the effect of pulmonary surfactant on antimicrobial activity.


Oral and dermatologic manifestations of HIV infection.
Because an estimated 1 million persons in the United States are infected with HIV, all physicians, especially those in primary care, need to be able to recognize the protean manifestations of the disease and make a diagnosis as early as possible. In this article, Drs Jewell and Sweet review the mucocutaneous conditions that occur in patients with HIV infection and discuss diagnostic clues and treatment.


An Interactive Mobile Phone-Website Platform to Facilitate Real-Time Management of Medication in Chronically ill Patients.
Poor adherence to medication is a prevalent issue that affects 50-60% of chronically ill patients. We present Medplan, a platform for patients/caregivers and healthcare professionals (HCPs) that aims to enhance adherence, increase patient medication knowledge, and facilitate communication between patients and HCPs. The Medplan platform was designed and developed by a multidisciplinary team composed of primary care and hospital physicians, pharmacists, patients, and developers. We questioned 62 patients in order to know their opinion about the different functions the app would incorporate and other possible features that should be taken into consideration. Medplan comprises a website for HCPs and an application (app) that is installed on the patient's phone. The app is available in Spanish, Catalan, and English. The patient's medication plan was introduced by the HCP and interfaced with the app. Each medicine is represented by an icon showing the indication of the treatment, the trade name, active ingredients, dose, and route of administration. Information about special requirements (e.g., need to take medication on an empty stomach), side effects, or lifestyle recommendations can also be provided. Additional functions include a medication reminder alarm system, by which patients can confirm whether or not they have taken the drug. Patients can self-track their adherence, and all data collected are sent automatically to the website for analysis by the HCP. Weekly motivation messages are sent to encourage adherence. A tool enabling interactive communication between patients and HCPs (primary care or hospital care) is also included. The app contains a feature enabling the HCP to verify the suitability of over-the-counter drugs. Medplan has the potential to significantly improve management of medication in chronically ill patients. A pilot study is being conducted to test whether Medplan is useful and effective.


Metal transport and remobilisation in a basin affected by acid mine drainage: the role of ochreous amorphous precipitates.
Metal-polluted mine waters represent a major threat to the quality of waters and sediments in a downstream basin. At the confluence between acidic mine waters and the unpolluted waters of the Gromolo Torrent (Liguria, North-West Italy), the massive formation of an ochreous amorphous precipitate takes place. This precipitate forms a soft blanket that covers the torrent bed and can be observed down to its mouth in the sea. The aim of this work is to evaluate the dispersion of metals in the Gromolo Torrent basin from the abandoned Cu-Fe sulphide mine of Libiola to the Ligurian Sea and to assess the metal remobilisation from the amorphous precipitates. The mineralogy of the superficial sediments collected in the torrent bed and the concentrations of different elements of environmental concern (Cu, Zn, Cd, Co, Cr, Mn, Ni, Pb, As, and Sb) were therefore analysed. The results showed that the precipitates contain high concentration of Fe, Al, Cu, and Zn, significantly modifying the bulk chemistry of the Gromolo Torrent sediments. In order to evaluate the possible remobilisation of ecotoxic elements from the amorphous precipitates, bulk leaching tests were performed with both deionised and seawater. Bulk leaching tests with deionised water mobilised primarily high Pb amounts, but also relatively high concentrations of Fe, Al, Cu, and Zn are released in the leachate. In seawater tests, Fe, Al, Cu, and Zn were released in smaller amounts, while other elements like Mn, Cd, Co, and Ni increased in the released fraction. Pb was still strongly released as in deionised water experiments. The results show that the interaction of precipitates and seawater can remobilise high concentrations of metals, thus affecting the surrounding environment.


Electrochemical Quantification of Glycated and Non-glycated Human Serum Albumin in Synthetic Urine.
A polymer-based electrode capable of specific detection of human serum albumin, and its glycated derivatives, is described. The sensor is constructed from a glass microscope slide coated with a synthesized, polythiophene film bearing a protected, iminodiacetic acid motif. The electrode surface is then further elaborated to a functional biosensor through deprotection of the iminodiacetic acid, followed by metal-affinity immobilization of a specific and high-affinity, albumin ligand. Albumin was then quantified in buffer and synthetic urine via electrochemical impedance spectroscopy. Glycated albumin was next bound to a boronic acid-modified, single-cysteine dihydrofolate reductase variant to quantify glycation ratios by square-wave voltammetry. The platform offers high sensitivity, specificity, and reproducibility in an inexpensive arrangement. The detection limits exceed the requirements for intermediate-term glycemic control monitoring in diabetes patients at 5 and 1 nM for albumin and its glycated forms, respectively.


Glucocorticoid-induced muscle atrophy: mechanisms and therapeutic strategies.
To analyze the mechanisms of action of glucocorticoids in causing muscle atrophy and to examine the therapeutic effect of testosterone as well as other treatment modalities in counteracting this adverse effect. We reviewed selected publications to analyze the mechanisms of glucocorticoid-induced muscle atrophy in animal models and in humans. The pathophysiologic features of glucocorticoid-induced hypogonadism and the possible relationship to the muscle atrophy in patients receiving glucocorticoids were assessed. The beneficial effects of testosterone on the muscles of hypogonadal and eugonadal men were also reviewed. Other measures such as exercise and glutamine and their possible therapeutic and preventive effects were examined in the context of hypercortisolemia. Glucocorticoids induce rapid muscle breakdown and proximal muscle atrophy. The mechanism of glucocorticoid-induced muscle atrophy relies on the degradation of the myosin heavy chain (catabolic effect), the most important contractile protein in muscle, associated with a decrease of its synthesis (antianabolic effect). One of the contributing factors in the development of muscle atrophy is hypogonadism that is induced by long-term glucocorticoid use. Androgen possesses anabolic and anticatabolic effects in vitro and in animal models. Androgens can be used safely to counteract the catabolic effects of cortisol. Other measures such as exercise, glutamine, and alanyl-glutamine are promising in animal models of glucocorticoid-induced muscle atrophy. This study suggests the possible efficacy of testosterone and glutamine on glucocorticoid-induced muscle atrophy. Testosterone and glutamine are natural biologic products with safe pharmacologic profiles, and their bioefficacy merits active research in humans.


A survey of physicians' attitude and approach to hormone replacement therapy during menopuase.
A major problem with postmenopausal hormone replacement therapy (HRT) is its relatively low long-term continuation rate. The aim of the present study was to assess the contribution of physicians to the low long-term continuation rate by surveying their attitude and approach to the use of HRT in postmenopausal women. A questionnaire was sent to registered members of the North American Menopause Society. Data were collected on demographics, medical education and affiliation, attitude to the use of HRT and its contraindications, and follow-up, strategies. The response rate was 21% (n = 218). Sixty-six percent of the physicians recommended HRT for every postmenopausal woman with no contraindications. and 11% also took age and/or time since menopause into consideration. Eighty-six percent claimed they would try to persuade symptom-free women not interested in HRT into changing their minds. There was no correlation between the time since completion of residency or affiliation with a medical school and physicians' attitude to prescribing HRT or contraindication to HRT, or management strategy. However, type of specialty was significantly correlated with physicians' tendency to recommend HRT. Specialists in menopause showed a lower tendency to unconditionally recommend HRT (in the absence of contraindications) (67%) than specialists in reproductive endocrinology (90%), infertility (90%). gynecology (83%), and perinatology (84%) (p < 0.006, C-measure = 0.25). The attitude toward HRT and the management strategies of members of the North American Menopause Society correlate with contemporary recommendations in the literature, indicating good training of young physicians and adequate updating of older ones. Thus, to increase the continuation rate of HRT, educational efforts should be directed primarily to the public rather than to medical professionals.


Apoptosis Induced via Gamma Delta T Cell Antigen Receptor "Blocking" Antibodies: A Cautionary Tale.
Mechanistic studies contribute greatly to our understanding of γδ T cell (γδTc) biology, aiding development of these cells as immunotherapeutic agents. The antibody blocking assay is an accepted method to determine the receptors involved in γδTc killing of tumor targets. Effectors and/or targets are preincubated with microgram quantities of monoclonal antibodies (mAb), often described by commercial sources to be useful for blocking assays. We and others have used such assays extensively in the past, correlating decreases in cytotoxicity against specific targets with involvement of the blocked receptor(s). However, we wondered whether other mechanisms might be at play beyond cytotoxicity inhibition. Indeed, administration of certain "blocking" mAb to the γδ T cell antigen receptor (γδTCR) induced γδTc death. Upon further investigation, we discovered that γδTc underwent apoptosis triggered by incubation with mAb to the γδTCR. This effect was specific, as no apoptosis was observed when αβ T cells (αβTc) were incubated with these mAb. Apoptosis was further potentiated by the presence of interleukin (IL)-2, often included in cytotoxicity assays; however, exogenous interleukin-2 (IL-2) did not contribute significantly to γδTc cytotoxicity against breast cancer cell lines. Here, we have investigated the usefulness of four mAb for use in blocking assays by assessing blocking properties in conjunction with their propensity to induce apoptosis in cultured primary human γδTc. We found that the 5A6.E9 clone was usually a better alternative to the commonly used B1 (or B1.1) and 11F2 clones; however, some variability in susceptibility to apoptosis induction was observed among donor cultures. Thus, viability assessment of primary effector cells treated with mAb alone should be undertaken in parallel with cytotoxicity assays employing blocking antibodies, to account for cytotoxicity reduction caused by effector cell death. Previous findings should be reassessed in this light.


Best practices in surgical abortion.
Surgical abortion in the first trimester comprises the majority of voluntary pregnancy interruptions performed in the United States. The majority of these procedures are done in outpatient settings with the patient under local anesthesia. Appropriate volume of and deep injection of local anesthetic can reduce pain associated with the procedure. Waiting between administration of the paracervical block and initiating the procedure does not affect pain. Intravenous administration of sedation and analgesia improves patient satisfaction but does not significantly affect pain ratings. Antibiotic prophylaxis is warranted. Vasopressin is useful for prevention of hematometra and hemorrhage. Less evidence supports the routine use of ergots. Preoperative cervical priming reduces the risk of cervical injury and uterine perforation. Attention to operative technique can reduce the risk of incomplete abortion. Routine postoperative care at 2 or 3 weeks is timed to identify complications and to reinforce pregnancy and sexually transmitted disease prevention.


Influence of macromolecular biosynthesis on cellular autolysis in Streptococcus faecalis.
The addition of several different antibiotics to growing cultures of Streptococcus faecalis, ATCC 9790, was found to inhibit autolysis of cells in sodium phosphate buffer. When added to exponential-phase cultures, mitomycin C (0.4 mug/ml) or phenethyl alcohol (3 mg/ml) inhibited deoxyribonucleic acid synthesis, but did not appreciably affect the rate of cellular autolysis. Addition of chloramphenicol (10 mug/ml), tetracycline (0.5 mug/ml), puromycin (25 mug/ml), or 5-azacytidine (5 mug/ml) to exponential-phase cultures inhibited protein synthesis and profoundly decreased the rate of cellular autolysis. Actinomycin D (0.075 mug/ml) and rifampin (0.01 mug/ml), both inhibitors of ribonucleic acid (RNA) synthesis, also reduced the rate of cellular autolysis. However, the inhibitory effect of actinomycin D and rifampin on cellular autolysis was more closely correlated with their concomitant secondary inhibition of protein synthesis than with the more severe inhibition of RNA synthesis. The dose-dependent inhibition of protein synthesis by 5-azacytidine was quickly diluted out of a growing culture. Reversal of inhibition was accompanied by a disproportionately rapid increase in the ability of cells to autolyze. Thus, inhibition of the ability of cells to autolyze can be most closely related to inhibition of protein synthesis. Furthermore, the rapidity of the response of cellular autolysis to inhibitors of protein synthesis suggests that regulation is exerted at the level of autolytic enzyme activity and not enzyme synthesis.


Are Mindfulness and Self-Compassion Related to Peace of Mind? The Mediating Role of Nonattachment.
Peace of mind is an important affective well-being valued in Chinese culture. Mindfulness and self-compassion could potentially promote peace of mind. However, the mechanisms underlying these effects were not well understood. The current cross-sectional study aimed to investigate whether nonattachment explained the effects of mindfulness and self-compassion on peace of mind. A sample of 364 Chinese adults was recruited from WeChat, a popular Chinese social media platform. Participants filled out an online survey including measures of dispositional mindfulness, self-compassion, nonattachment, and peace of mind. The results of correlation analyses revealed significant and positive associations among mindfulness, self-compassion, nonattachment, and peace of mind. Furthermore, nonattachment significantly mediated the associations between mindfulness and self-compassion with peace of mind. Moderated mediation analyses indicated that the relationships between mindfulness and self-compassion with nonattachment were stronger for women than for men. Gender did not moderate the direct effects of mindfulness and self-compassion on peace of mind, the relationship between nonattachment and peace of mind, and the mediating effects of mindfulness and self-compassion on peace of mind through nonattachment. These findings suggest that nonattachment may be a potential mechanism through which mindfulness and self-compassion promote peace of mind among Chinese adults. If the mediating effects are confirmed in future longitudinal and experimental studies, mindfulness and self-compassion interventions can emphasize nonattachment to optimize their effects on peace of mind. It may also be important to tailor mindfulness and self-compassion training for men and women given the gender differences in the relationships between mindfulness and self-compassion with nonattachment.


Punch Incision with Secondary Healing (PISH) Technique for Benign Facial Lesions: An Institutional Experience in 307 Patients.
Background Multiple or solitary facial lesions pose a unique challenge to the attending surgeon in terms of delivering the best cosmetic outcome. There are various methods in dealing with them and the preference of using them is based on the surgeon's experience, patient expectations, and availability of instruments. One such tool, skin-punch, primarily designed for a biopsy can play a very important therapeutic role in this era of keyhole surgery. In this paper, we assess the technique of punch incision with its combination of secondary healing for various facial lesion. Methods This observational study, a total of 307 patients with solitary or multiple benign facial lesions were treated with punch incision technique using 2 to 6 mm sterile, disposable skin biopsy punches. Subsequently, the wounds were managed with healing with secondary intention. Results In our series all superficial wounds epithelized by 7 to 14 days while the deeper lesions epithelized by 14 to 28 days. We had three recurrences which were managed by fusiform excision and one patient had surgical site infection which was managed conservatively. On application of our self-devised facial scar scoring system (SCAR or Scar Cosmesis Assessment and Rating) 3 on all the scars, the mean score was 6 at 1 year followup. Conclusion Punch incision with healing by secondary intention is a relatively easy, effective, single-stage office procedure. This method can be considered as an alternative method for the removal of various skin lesions, especially on face, thus providing a simple solution to complex problems.


Development of vocational training systems for patients with intellectual disability in Poland.
The problem of employment of people with intellectual disabilities is present in many countries. The literature on this topic draws attention to the fact that the improvement of the situation in this area is conditioned by changes in government policies, practices of employers and adequate preparation to undertake professional duties by persons with intellectual disabilities. The objective of this review was to explore the changes in vocational rehabilitation forms in Poland. As one of the ways to solve this problem since 1991 in Poland the so called Workshops of Vocational Therapy have been created. According to the regulations the Workshops were designed for adults with intellectual disabilities, aged over 16 years with a total incapacity of gaining an employment, for which occupational therapy was a form of social rehabilitation. The further step in this process was the establishment of Vocational Activation Centers, with which high hopes were associated. They were expected to be an intermediate link in the creation of career paths from rehabilitation forms ultimately to open labor market. In practice it turned out that the creation of these Centers in Poland has been too slow. This raised the necessity to change the attitude from the concept of matching the participant to work and to the new environment, which frequently ends as a trauma, to the concept of matching jobs to people. New initiatives and new rehabilitation programs are developed based on this attitude.


In-Hospital Complications and Resource Utilization Following Lumbar Spine Surgery in Patients with Parkinson Disease: Evaluation of the National Inpatient Sample Database.
Previous reports suggest that patients with Parkinson disease (PD) have elevated rates of complications following spine surgery; however, these reports are limited by small patient series. In this study, we used the National Inpatient Sample (NIS) database to compare in-hospital complications following elective lumbar spine surgery in patients with a diagnosis of PD and patients without PD. The NIS database was accessed to identify patients with PD and those without PD who underwent lumbar spine surgery. All patients identified had a diagnosis code consistent with degenerative lumbar spine pathology. The patients were evaluated for the presence or absence of PD and divided into 4 lumbar spine procedure groups: decompression alone, lateral fusion, posterior fusion, and anterior fusion technique. Propensity score matching (PSM) was performed for the PD versus non-PD patients in each procedure group to control for confounding demographic variables, and in-hospital complications were compared between the 2 groups. Between 2001 and 2012, a total of 613,522 lumbar spine surgery patient episodes were identified, of which 4492 (0.7%) involved a diagnosis of PD. Following PSM for patient age, sex, and race, the patients with PD were at increased risk for acute postoperative hemorrhagic anemia, increased blood transfusion requirements, and increased genitourinary, neurologic, and cardiac complications compared with the patients without PD. PSM analysis of the NIS database demonstrated that patients with PD are at increased risk for acute in-hospital complications and greater blood transfusion requirements than those without PD. Surgeons should be aware of the increased risks and differing requirements when treating spinal pathology in patients with PD.


Synthesis, characterization and antimicrobial evaluation of some new schiff, mannich and acetylenic Mannich bases incorporating a 1,2,4-triazole nucleus.
A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1H- and 13C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity.


Ligand binding kinetic studies on the hybrid hemoglobin alpha (human):beta (carp): a hemoglobin with mixed conformations and sequential conformational changes.
Oxygen and CO ligand binding kinetics have been studied for the hybrid hemoglobin (Hb) alpha (human):beta (carp), hybrid II. Valency and half-saturated hybrids were used to aid in the assignment of the conformations of both chains. In hybrid II, an intermediate S state occurs, in which one chain has R- and the other T-state properties. In HbCO at pH 6 (plus 1 mM inositol hexaphosphate), the human alpha-chain is R state and the carp beta-chain is T state. We have no evidence at this pH that the carp beta-chain ever assumes the R conformation. At pH 6, the human alpha-chain shows human Hb R-state kinetics at low fractional photolysis and T-state rates for CO ligation by stopped flow. At pH 7, the human-chain R-state rate slows toward a carp hemoglobin rate. The carp beta-chains, on the other hand, react 50% more rapidly in the liganded conformation than in carp hemoglobin, and while the human alpha-chains are in the R state, the two beta-chains appear to function as a cooperative dimer. In this hemoglobin, the chains appear to be somewhat decoupled near pH 7, allowing a sequential conformational change from the R state in which the beta-chains first assume T-state properties, followed by the alpha-chains. The rate of the R-T conformational change for the carp beta-chains is at least 300 times greater than that for the human alpha-chains. At pH 9, the R----T conformational transition rate is at least 200 times slower than that for human hemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)


[Activity and tolerance of a new anti-arrhythmia drug, Cibenzoline (Cipralan), administered orally)].
The authors studied the effect of a new anti-arrhythmic agent, the Cibenzoline in 9 patients suffering from numerous ventricular extrasystoles (on average 8 extrasystoles/minute). Efficacy was considered to be excellent in 3 cases (complete disappearance of extrasystoles) good in 3 cases (more than 90% decrease in the number of extrasystoles) and poor in 3 cases (these concerned two patients also resistant to all other anti-arrhythmic agents and one patient with an extreme variability of his arrhythmia from one day to another day). Clinical and biological tolerance was excellent. Electrocardiographic parameters in general remained stable, apart from in one case of severe cardiomegaly. The general rules usually accepted for adequate evaluation of the efficacy of an anti-arrhythmic agent are reviewed and discussed.


Synthesis and comparison of iso-structural f-block metal complexes (Ce, U, Np, Pu) featuring η6-arene interactions.
Reaction of the terphenyl bis(anilide) ligand [{K(DME)2}2LAr] (LAr = {C6H4[(2,6-iPr2C6H3)NC6H4]2}2-) with trivalent chloride "MCl3" salts (M = Ce, U, Np) yields two distinct products; neutral LArM(Cl)(THF) (1M) (M = Np, Ce), and the "-ate" complexes [K(DME)2][(LAr)Np(Cl)2] (2Np) or ([LArM(Cl)2(μ-K(X)2)])∞ (2Ce, 2U) (M = Ce, U) (X = DME or Et2O) (2M). Alternatively, analogous reactions with the iodide [MI3(THF)4] salts provide access to the neutral compounds LArM(I)(THF) (3M) (M = Ce, U, Np, Pu). All complexes exhibit close arene contacts suggestive of η6-interactions with the central arene ring of the terphenyl backbone, with 3M comprising the first structurally characterized Pu η6-arene moiety. Notably, the metal-arene bond metrics diverge from the predicted trends of metal-carbon interactions based on ionic radii, with the uranium complexes exhibiting the shortest M-Ccentroid distance in all cases. Overall, the data presents a systematic study of f-element M-η6-arene complexes across the early actinides U, Np, Pu, and comparison to cerium congeners.


Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes.
Thiazolidinediones may slow the progression of type 2 diabetes by preserving pancreatic beta-cells. The effects of pioglitazone (PIO) on structure and function of beta-cells in KKA(y), C57BL/6J ob/ob, and C57BL/KsJ db/db mice (genetic models of type 2 diabetes) were examined. ob/ob (n = 7) and db/db (n = 9) mice were randomly assigned to 50-125 mg.kg body wt-1.day-1 of PIO in chow beginning at 6-10 wk of age. Control ob/ob (n = 7) and db/db mice (n = 9) were fed chow without PIO. KKA(y) mice (n = 15) were fed PIO daily at doses of 62-144 mg.kg body wt-1.day-1. Control KKA(y) mice (n = 10) received chow without PIO. Treatment continued until euthanasia at 14-26 wk of age. Blood was collected at baseline (before treatment) and just before euthanasia and was analyzed for glucose, glycosylated hemoglobin, and plasma insulin. Some of the splenic pancreas of each animal was resected and partially sectioned for light or electron microscopy. The remainder of the pancreas was assayed for insulin content. Compared with baseline and control groups, PIO treatment significantly reduced blood glucose and glycosylated hemoglobin levels. Plasma insulin levels decreased significantly in ob/ob mice treated with PIO. All groups treated with PIO exhibited significantly greater beta-cell granulation, evidence of reduced beta-cell stress, and 1.5- to 15-fold higher levels of pancreatic insulin. The data from these studies suggest that comparable effects would be expected to slow the progression of type 2 diabetes, either delaying or possibly preventing progression to an insulin-dependent state.


Differentiation of mouse embryonic stem cells into neurons using conditioned medium of dorsal root ganglia.
Mouse embryonic stem (ES) cells, which are continuously growing cell lines, have a pluripotent ability to differentiate into various cell lineages in vitro including neurons. We investigated the effects of chick dorsal root ganglion (DRG) conditioned medium (CM) and nerve growth factor (NGF) on the directed differentiation of ES cells into neurons. Because DRGs from 8-day-old chick embryos are often used in bioassays of neurotrophic factors, DRGs may release soluble factors that can induce ES cell differentiation into neurons in a culture broth. When cultivated in a Dulbecco's modified Eagle's medium (DMEM)/F-12K medium containing DRG-CM or NGF, the ES cell colonies clearly showed neurite outgrowths. Of particular significance, the immunofluorescence analysis of ES cell colonies using an anti-betaIII-tubulin antibody indicated that the addition of DRG-CM effectively promoted the differentiation of ES cells into neurons. We confirmed the effect of DRG-CM addition on ES cell differentiation into neurons via neuronal stem cells by the immunofluorescence analysis of ES cell colonies. Thus, DRG-CM appeared to effectively promote ES cell differentiation into neurons.


Abnormal reactivity of the primary somatosensory cortex during the experience of pain in complex regional pain syndrome: a magnetoencephalograhic case study.
A 49-year-old male worker developed persistent pain in his left wrist after work strain injuries. Clinical symptoms met with criteria for Complex Regional Pain Syndrome (CRPS) type I. In the present study, the effect of the experience of pain on the somatotopy of the primary cortical hand representation was investigated. Somatosensory evoked magnetic fields (SEF) elicited by non-painful tactile stimulation at the index finger of the affected and the unaffected hand were recorded when experiencing pain elicited by a moderate physical load condition (holding a 1.6 kg object in the hand). It was shown that MEG and subjective responses to innocuous tactile stimuli were reduced when simultaneous nociceptive stimulation was applied. These findings suggest a gating effect in the central nervous system elicited by concurrent simultaneous information from two different somatosensory modalities (pain and tactile). The results revealed the existence of nociceptive-induced plastic changes in the central nervous system associated with CRPS type I.


Composting duck excreta enriched wood shavings: C and N transformations and bacterial pathogen reductions.
Composting of agricultural and domestic wastes is used increasingly to reduce weight, volume, and odor; destroy animal and plant pathogens; and improve the quality of end-products to be used as soil amendments and growth substrates. The objective of this study was to investigate the transformation of C and N and the survival of bacterial populations and pathogenic bacteria during in-vessel composting of duck excreta enriched wood shavings. Two feedstocks, collected on different dates, were composted (C1 and C2) in an enclosed hall system equipped with an electromechanical turner. Temperature was continuously recorded, whereas moisture content and bacterial counts were determined twice a week. Data showed that, although the N content of C2 was only half of that of C1, both materials were fully biostabilized at the end of the composting period as indicated by extractable lipid ratios. In the compost with the low C/N ratio (C1), all bacterial populations were eliminated, whereas fecal streptococci, total coliforms, and gram-negative bacteria were still present in C2 at the end of the composting period. Our results emphasize that the composting of manures and other organic wastes needs to be properly managed to stabilize C and N and to eliminate or reduce bacterial populations.


Anthropometric indices in relation to overweight and obesity among Turkish medical students.
The aim of this study was to present the reference anthropometric data associated with obesity for cardiovascular risk and metabolic diseases for healthy young adults in a Turkish population. The study group consisted of 1163 second-year medical students (650 women, 513 men) aged 20-25 years from Çukurova University in Adana and the measurements were made using a flexible standard measuring tape. The data were collected during the period 2007-2011. From 1163 medical students, the mean values of body mass index, circumferences of waist, hip, neck, mid-arm, thigh and calf were 20.89 ±1.6 kg/m(2), 73.15 ±5.1 cm, 95.35 ±4.8 cm, 30.32 ±1.37 cm, 24.12 ±1.75 cm, 47.23 ±3.26 cm and 34.36 ±2.19 cm respectively in women, while the same measurements were 21.98 ±1.67 kg/m(2), 77.73 ±5.81 cm, 95.64 ±4.81 cm, 35.61 ±1.43 cm, 25.60 ±1.84 cm, 44.10 ±3.26 cm and 34.92 ±2.08 cm respectively in men. Moreover, waist to hip ratio, waist to height ratio and neck to height ratio were respectively 0.76, 0.44 and 0.18 in women and 0.81, 0.43 and 0.19 in men. The precise knowledge of anthropometric data could be used as reference values for evaluating the body composition and fat distribution of Turkish young people.


Precise ranging for the multi-region by using multi-beam chaotic polarization components in the multiple parallel optically pumped spin-VCSELs with optical injection.
We present a novel scheme for the accurate ranging for the multi-region in the rectangular-shape target using numbers of the chaotic x polarization components in the multiple parallel optically pumped spin-VCSELs with optical injection, where these chaotic x polarization components possess the attractive features of the uncorrelation in time and space under different optical injection strengths, and fast dynamic with femtosecond magnitude. Utilizing these features, the accurate ranging to the position vectors of the multi-region targets can be achieved by correlating the multi beams of the time-delay reflected chaotic polarization radar probe waveforms with their corresponding reference waveforms. The further investigations show that the ranging to the multi-region targets possesses very low relative error, which is less than 0.28%. Their range resolutions can be achieved as high as 0.9mm, and exhibit excellent strong anti-noise performance by the optimization of some key parameters such as the injection strength, the amplitude of external light, linear birefringence, spin relaxation rate. The precise ranging to the multi-region targets based on the multiple parallel optically pumped spin-VCSEL with optical injection offers interesting perspectives for the potential applications in quality detection of the multi-region surfaces.


Projective identification: the analyst's involvement.
The author emphasises that what is projected into the analyst is a phantasy of an object relationship that evokes not only thoughts and feelings, but also propensities towards action. From the patient's point of view, the projections represent an attempt to reduce the discrepancy between the phantasy of some archaic object relationship and what the patient experiences in the analytical situation. For the analyst, too, there are impulses to function in ways that lead to a greater correspondence with some needed or desired phantasies. The interaction between the patient's and the analyst's needs may lead to the repetitive enactment of the painful and disturbing kind that is described. It may be very difficult for the analyst to extricate himself (or his patient) from this unproductive situation and recover his capacity for reflective thought, at least for a while. The difficulty is compounded when the projection into the analyst leads to subtle or overt enactments that do not initially disturb the analyst but, on the contrary, constitute a comfortable collusive arrangement, in which the analyst feels his role is congruent with some internal phantasy. It may be difficult to recognise the defensive function this interaction serves for both the patient and the analyst and the more disturbing phantasies it defends against.


Rituximab as induction therapy in relapsing eosinophilic granulomatosis with polyangiitis: A report of 6 cases.
Recently few reports have suggested a potential benefit of rituximab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). However, the current evidence is limited. We describe the efficacy and safety of rituximab in six patients with relapsing EGPA. Candidates for rituximab therapy were selected from a cohort of 118 patients with EGPA. The main indication for B-cells depletion was moderately severe or severe relapsing disease that was refractory to conventional immunosuppression. A primary end-point was a complete or partial remission within 3 to 6 months after rituximab administration. All six patients (four ANCA-positive and two ANCA-negative) had active EGPA manifesting by severe lung disease and/or deteriorating peripheral neuropathy. The median duration of follow-up after the first rituximab dose administration was 10 months. All patients rapidly responded to rituximab treatment, e.g. disappearance of lung infiltrates, improvement of asthmatic symptoms, at least partial recovery of motor and sensory function. Within 3 to 6 months, complete (4/6) or partial (2/6) remission was achieved in all patients. After switching to rituximab all patients except one discontinued cyclophosphamide or other immunomodulators. Four patients continued maintenance treatment with rituximab. One patient developed severe bronchospasm during infusion and two patients presented with moderately severe purulent bronchitis that was successfully treated with intravenous antibiotics. Our retrospective case series suggest that rituximab may be effective for induction of remission in selected EGPA patients. These data warrant further studies to evaluate safety and efficacy of rituximab in EGPA.


[Galectin-3 in Patients With Paroxysmal and Persistent Atrial Fibrillation and Metabolic Syndrome].
To evaluate serum galectin 3 and to determine the potential clinical value of this parameter in patients with atrial fibrillation - AF (paroxysmal and persistent) and metabolic syndrome (MS). We examined 100 patients with MS (50 with paroxysmal or persistent AF and 50 without arrhythmia) and 50 healthy persons. Serum galectin 3 measured by ELISA method, ECHO cardiography was performed to all examined persons. Galectin 3 in patients with MS and AF was higher, than in patients with MS without arrhythmia and much more higher than galectin 3 in healthy persons 0,72 (0,44;1,36), 0,44 (0,42;1,22) and 0,32 (0,28;0,42) ng/ml (<0,01). In patients with persistent AF levels of galectin 3 is higher than in patients with paroxysmal AF. Positive correlation between the levels of galectin 3 and duration arrhythmia was revealed (r=0,301; p<0,01). Higher level of galectin 3 was revealed in patients with frequent paroxysms of AF and ineffective antiarrhythmic therapy. Marker of myocardial fibrosis serum galectin 3 in patients with atrial fibrillation and metabolic syndrome is higher than in patients with the metabolic syndrome, without this arrhythmia and higher than in healthy controls. In patients with persistent AF level of galectin 3 was higher than in patients with paroxysmal AF.


Advancing tissue engineering by using electrospun nanofibers.
Electrospinning is a versatile technique that enables the development of nanofiber-based scaffolds, from a variety of polymers that may have drug-release properties. Using nanofibers, it is now possible to produce biomimetic scaffolds that can mimic the extracellular matrix for tissue engineering. Interestingly, nanofibers can guide cell growth along their direction. Combining factors like fiber diameter, alignment and chemicals offers new ways to control tissue engineering. In vivo evaluation of nanomats included their degradation, tissue reactions and engineering of specific tissues. New advances made in electrospinning, especially in drug delivery, support the massive potential of these nanobiomaterials. Nevertheless, there is already at least one product based on electrospun nanofibers with drug-release properties in a Phase III clinical trial, for wound dressing. Hopefully, clinical applications in tissue engineering will follow to enhance the success of regenerative therapies.


Spiro-Phthalides and Isocoumarins Isolated from the Marine-Sponge-Derived Fungus Setosphaeria sp. SCSIO41009.
Fourteen new polyketides classified as four phthalides, setosphalides A and B, 5- O-desmethylcolletotrialide, and ( S)-colletotrialide (1-4), three isocoumarin derivatives, exserolides I-K (5-7), four pyrones, setosphapyrones A-D (8-11), one furanone (12), and two depsidones (13 and 14), along with 17 known polyketides were isolated from cultures of the sponge-derived fungus Setosphaeria sp. SCSIO41009. The structures and absolute configurations of these new compounds (1-14) were determined by spectroscopic analyses, X-ray diffraction, chiral-phase HPLC analysis, modified Mosher's method, and comparison of ECD spectra to calculations. Setosphalides A (1) and B (2) are the first examples possessing a 5,5 spiroketal skeleton in phthalide derivatives. Botryorhodines I (13) and J (14) showed moderate antifungal activities against the phytopathogenic fungi Colletotrichum asianum and Colletotrichum acutatum. Compound 18 (7- O-demethylmonocerin) exhibited potent radical scavenging activity against DPPH.


The new Medicare bill: far-reaching effects on cancer treatment.
Recent legislation has dramatically changed the Medicare payment methods for drugs and drug administration services. A large net reduction in total payments will take effect in 2005 and is likely to have significant adverse effects on the delivery of care to cancer patients.


A pioneering study: oral clarithromycin treatment for feeding intolerance in very low birth weight preterm infants.
To examine the prokinetic effect of clarithromycin in very low birth weight (VLBW) preterm infants. VLBW preterm infants who have not achieved half of the full enteral feeding in the second week of life were enrolled in the study. The infants enrolled in the study were randomized. Twenty infants received oral clarithromycin (7.5 mg/kg, twice a day) and 20 control infants did not receive any treatment. Full enteral feeding was attained earlier in the clarithromycin group than in the control group [7 (6-9) versus 9 (9-11) days, respectively; p < .001]. Duration of parenteral nutrition and number of withheld feeds were significantly lower in the clarithromycin group (p = .013 and p < .001, respectively). Parenteral nutrition-associated cholestasis (n = 1 versus 3, p = .1) and length of hospital stay (50 versus 59 median days, p = .1) tend to be lower in the clarithromycin group without any statistical significance. We observed no adverse effect of clarithromycin therapy. Clarithromycin treatment in VLBW preterm infants resulted in better toleration of enteral feeding. Larger randomized controlled trials are needed to establish routine use of clarithromycin in the treatment of feeding intolerance.


[The historical condition in the spread of Sanqi (Panax notoginseng) in the Ming Dynasty].
A well-known and extensively applied Chinese herbs for promoting blood circulation and resolving blood stasis, San qi (Pana Notoginseng) is one of the medicinal plants first applied by the minority ethnic groups in southwestern China originally grown in Wenshan of Yunnan and Baise of Guangxi, China. The doctors in inland China began to know and apply it in the Ming Dynasty, indicating that the spread of medicine is restricted and influenced not only by geographical positions but also by social environments. The author suggests that it was the appropriate social environment, medical improvement inherited from previous generations and Li Shizhen's contributions that led to the spread of Sanqi (Panax notoginseng) in the Ming Dynasty.


Clinical epidemiological studies of women undergoing surgery for urogynaecological disorders.
This PhD thesis was performed during my employment at the Center for Clinical Epidemiology, Odense University Hospital and University of Southern Denmark, 2010-2013. It comprises an overview and four papers, two published in international peer-reviewed scientific journals, one under review, and one in draft. Urinary incontinence (UI) and pelvic organ prolapse (POP) are prevalent disorders among women worldwide, affecting their psychological and social wellbeing, with reductions in quality of life. Treatment options are conservative (e.g. pelvic floor exercises, weight loss, and bladder training), pharmacological, and surgical. Surgery has especially for UI undergone an improvement during the last decades with development of minimally-invasive sub-urethral sling procedures, and the number of surgeries has increased in Denmark and other countries. In a population of Danish women undergoing surgery for UI or POP, we aimed: to describe the establishment of the Danish Urogynaecological Database (DugaBase), and to evaluate the completeness and the validity of surgery registration in the DugaBase; to study patient reported outcome measures in Danish women undergoing urogynaecological surgery; to study the use of symptom-relieving drugs before and after surgery for UI; to study the use of antibiotics for urinary tract infection (UTI) before and after surgery for UI METHODS: Study I The completeness of DugaBase was assessed by comparing procedure codes in the DugaBase to iodes registered in the National Patient Registry, 2006-2010. The study also included review of medical journals from 200 women (computed randomly from DugaBase), representing 22 departments in Denmark. Information on selected variables was compared to registered data in the DugaBase. the National Patient Registry, the DugaBase, and medical records. Study II was based on a national cohort of women undergoing surgery for UI and POP registered in the DugaBase, 2006-2011. Clinical data and data from patient questionnaires were retrieved. the DugaBase. Study III+IV were cohort studies based on national register data and prescription data. A total of 2,151 women with a first time surgical procedure for UI within 1996-2010 were included. The data were supplemented with registry information on redeemed prescriptions on symptom-relieving drugs/antibiotics for UTI/oestrogen, comorbidity, and educational level and income. the Danish National Patient Registry, Odense University Pharmacoepidemiologic Database, and the Register for Education Statistics, and the Register of Family Income. Study I: A total of 16,509 procedures were registered in the DugaBase by 31 December 2010. The database completeness has increased from 38.2% to 93.2% during the years. According to the validation, all 200 medical records were retrieved. The overall percentage agreement between medical records and the DugaBase was at least 90% for selected key variables: procedure code, date, hospital department, use of antibiotics, prior surgery, height, weight, parity, and smoking. Study II: In the study period, 20,629 urogynaecological procedures were performed in Denmark and reported to the DugaBase. For approximately one third of these women, the patient questionnaires on severity of symptoms and quality of life were completed both pre- and postoperatively, and thus included. After both UI and POP surgery, more than 80% had improved symptoms and showed a significant improvement in quality of life. Study III: A total of 2,151 women with a primary UI procedure were included. Of these, 358 (16.6%) were exposed to symptom-relieving drugs preoperatively, and 1,793 (83.4%) were not. Preoperative usage of symptom-relieving drugs was the strongest risk factor of postoperative use, both within 0-60 days OR (adjusted) = 33.0 (95% confidence interval (CI) 20.0-54.7)) and 61-365 days OR (adjusted) = 7.2 (95% CI 5.4-9.6)). Adjusted for age, procedure type, calendar year, comorbidity, preoperative use of oestrogen, educational level, and personal annual income. Only a minority of preoperative non-users started using symptom-relieving drugs postoperatively. Study IV: The same study population as in study III. Of the 2,151 women, 496 (23.1%) were antibiotic users prior to surgery, and 1,655 (76.9%) were non-users. Preoperative usages of antibiotics for UTI was a strong risk factor of postoperative use of the same antibiotics, both within 0-60 days OR (adjusted) = 2.6 (95% CI 2.9-3.5), and within 61-356 days OR (adjusted) = 4.5 (95% CI 3.5-5.7)). Adjusted for age, procedure type, calendar year, comorbidity, preoperative use of oestrogen, educational level, and personal annual income. Comorbidity and procedure types were found to be significant risk factors as well, although less important than preoperative antibiotic use. Due to a high completeness and data of high validity the DugaBase offers a unique possibility for continuing quality assessment of urogynaecological surgery in Denmark, as well as for future research. Surgeries for UI and POP performed in Danish women were effective in alleviating symptoms of UI and POP and improvement in quality of life based on patient reported outcome measures. Our pharmacoepidemiological studies showed that preoperative use of symptom-relieving drugs and antibiotics for UTI were strong risk factors of postoperative usage of the same drugs.


Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances Viability.
Zebrafish embryos can attain a stable cryogenic state by microinjection of cryoprotectants followed by rapid cooling, but the massive size of the embryo has consistently led to failure during the convective warming process. Here we address this zebrafish cryopreservation problem by using gold nanorods (GNRs) to assist in the warming process. Specifically, we microinjected the cryoprotectant propylene glycol into zebrafish embryos along with GNRs, and the samples were cooled at a rate of 90 000 °C/min in liquid nitrogen. We demonstrated the ability to unfreeze the zebrafish rapidly (1.4 × 107 °C/min) by irradiating the sample with a 1064 nm laser pulse for 1 ms due to the excitation of GNRs. This rapid warming process led to the outrunning of ice formation, which can damage the embryos. The results from 14 trials (n = 223) demonstrated viable embryos with consistent structure at 1 h (31%) and continuing development at 3 h (17%) and movement at 24 h (10%) postwarming. This compares starkly with 0% viability, structure, or movement at all time points in convectively warmed controls (n = 50, p < 0.001, ANOVA). Our nanoparticle-based warming process could be applied to the storage of fish, and with proper modification, can potentially be used for other vertebrate embryos.