The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells.
The influence of interindividual variability is not typically assessed in traditional toxicological studies. Given that chemical exposures occur in heterogeneous populations, this knowledge gap has the potential to cause undue harm within the realms of public health and industrial and municipal finances. A recent report from the National Research Council (NRC) suggests that when accounting for interindividual variation in responses, traditionally assumed nonlinear dose-response relationships (DRRs) for noncancer-causing endpoints would better be explained with a linear relationship within the low-dose region. To address this knowledge gap and directly test the NRC's assumption, this study focused on assessing the DRR between 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) exposure and immune suppression in a cohort of unique human donors. Human B cells were isolated from 51 individual donors and treated with logarithmically increasing concentrations of TCDD (0-30 nM TCDD). Two endpoints sensitive to TCDD were assessed: (1) number of IgM-secreting B cells and (2) quantity of IgM secreted. The results show that TCDD significantly suppressed both the number of IgM-secreting B cells and the quantity of IgM secreted (P < .05). Statistical model comparisons indicate that the low-dose region of the two DRRs is best explained with a nonlinear relationship. Rather than assuming low-dose linearity for all noncancer-causing DRRs, our study suggests the need to consider the specific mode of action of toxicants and pharmaceuticals during risk-management decision making.


Expression of C/EBP alpha, beta and delta in fetal and postnatal subcutaneous adipose tissue.
The C/EBP (CCAAT/enhancer binding protein) family of transcription factors (C/EBP alpha, beta, and delta) has been implicated in the development and the metabolic regulation of adipocytes from in vitro studies, yet the function of these factors, particularly CEBP beta and delta, in vivo has not been characterized. To assess the role of these factors in vivo, subcutaneous adipose, tissue from fetal and postnatal pigs was examined for C/EBP alpha, beta, and delta expression in developing and mature adipocytes. Western blot analysis of fetal adipose tissue showed a progressive increase of C/EBP alpha expression in 50, 75 and 95 day old fetuses. C/EBP beta and delta proteins were not observed in fetal adipose tissue. These results were confirmed with immunohistochemical studies of fetal adipose showing enhanced C/EBP alpha expression in the nuclei of adipocytes and cells closely associated with adipose cell clusters from 75 and 95 day old fetuses. For the same tissues only light background staining with no differential enhancement was found for C/EBP beta and delta. In postnatal adipose tissue C/EBP alpha and C/EBP beta protein were expressed in both 8 day old postnatal and mature (180 day) pigs. C/EBP delta reactive products were found in postnatal tissues however, their molecular weights were lower than that found in fetal pig liver. Our data suggest that adipose cell terminal differentiation proceeds in the pig fetus without the expression of C/EBP beta and delta and that these factors may have a more important role in fully differentiated adipose cells in postnatal tissue.


Development of solid lipid nanoparticles containing ionically complexed chemotherapeutic drugs and chemosensitizers.
The purpose of this study was to develop and characterize a solid lipid nanoparticle (SLN) system containing an anionic polymer for the delivery of cationic antineoplastic agents and chemosensitizers. Ionic complexation was utilized to enhance the loading of these highly water-soluble drugs. The influence of anionic compounds and polymers on drug partition and loading into SLNs was investigated, and dextran sulfate (DS) was found to be the most suitable among those studied. SLNs loaded with doxorubicin and various model chemosensitizers (e.g., verapamil) were thus prepared by incorporating DS using a microemulsion method. The particle size was measured with photon correlation spectroscopy. The mean diameter of the SLNs ranged from 180 to 300 nm, depending on the type and content of the drug and the polymer. The particles possessed weakly negative surface charges as determined by zeta potential measurements. Most polymer-loaded SLNs released half of the drug in the first a few hours and the remaining drug in 15 h or more. The presence of counterions in the medium, especially divalent ions, promoted drug release. Dual drug (doxorubicin/verapamil or quinidine/verapamil)-loaded DS-SLNs were also formulated, which released both drugs without noticeable interference to each other. These studies have laid the foundation for a "one-bullet" dosage form that may provide convenient and effective delivery of multiple drug treatment of tumors.


[Physiopathology of alveolar bone].
Bone tissue is a dynamic system in which the net balance between resorption and apposition defines the final osseous form. This process occurs in minute asynchronous foci and results from a cascade of activations, cooperations and inhibitions of specialized cells (osteoblasts and osteoclasts). The alveolar bone resorption due to periodontal disease is a complex and dynamic chain reaction in which both osteoclasts and osteoblasts have a role in the hormonal interactions occurring during the course of the resorption activity. Both microbial and host factors as prostaglandins, endotoxins and lipoteic acid seems to be able in activating bone resorption. However bone resorption can be interchanged with repair formative episodes, more or less intense, which can delay the destructive process.


Natural vertical transmission of dengue virus in Aedes albopictus (Diptera: Culicidae) in Kerala, a southern Indian state.
The natural occurrence of vertical transmission of dengue viruses in Aedes albopictus (Skuse) mosquitoes was examined in the state of Kerala in southern India. Adults and larvae of Ae. albopictus collected from Kerala were screened for dengue viruses by using enzyme-linked immunosorbent assay with dengue-specific monoclonal antibodies. The possibility of the vertical transmission of dengue virus in Ae. albopictus was further evidenced by the detection of the virus in field-collected adult males as well as females emerged from field-collected larvae. Two pools, one pool from the adult males and one pool from the emerged females derived from field-collected larvae, were collected in the relatively hot months of June and March, respectively, and found to be positive for dengue virus antigen. Dengue serotype 2 virus was isolated from field-collected male adults in Kerala. These findings suggest that dengue virus is maintained in Ae. albopictus mosquitoes during the dry season by vertical transmission in nature.


[Severe opportunistic infections in HIV-positive adults in sub-Saharan Africa].
The threat for opportunistic diseases in HIV-infected adults in sub-Saharan Africa is characterized by a higher frequency of tuberculosis and invasive bacterial diseases than in Europe and by the presence of malaria. Since these three infections may occur early after the onset of immuno-deficiency, HIV-infected patients with less than 200 CD4/mm3 are more likely to develop an infectious episode with severe morbidity in sub-Saharan Africa than in Europe. For this reason the WHO now recommends starting cotrimoxazole prophylaxis at 350 and even 500 CD4/mml in sub-Saharan Africa. The question of whether antiretroviral treatment should also be initiated "earlier" in sub-Saharan Africa than in Europe has also been raised.


Bilateral absence of the superior vena cava presenting with superior vena cava syndrome: A case report.
Bilateral absence of the superior vena cava (SVC) is a very rare congenital vascular anomaly that is mainly asymptomatic. In this report, we describe an adult male patient with bilateral absence of the SVC presenting with SVC syndrome. Blood from the upper body returned to the right atrium via the superficial thoracoepigastric veins, the great saphenous veins, the common femoral veins, and the inferior vena cava.


Investigation of relations between absorption band positions and crystalline environment in Pb2+-doped alkali halides.
The relationships between sp energy levels (A, B and C bands) as well as the charge transfer band (D band) of Pb(2+)-doped alkali halides and the crystalline environment were thoroughly investigated by means of dielectric theory of chemical bonds for complex crystals. It is found that the coordination number of the central ion, the bond volume polarizability, and the fractional covalence of the chemical bond between the central ion and the nearest anion are the major factors influencing the positions of A, B, C and D bands of Pb(2+). Our model has successfully built links between the E(A), E(B), E(C) and E(D) of Pb(2+) and the environmental factor h. Results indicated that the energies of sp levels and the charge transfer band of Pb(2+) all decrease with increase of h. The h has a linear relationship with the sp energy levels, and an exponential relationship with the charge transfer band. The model calculation results are in good agreement with experimental data. The current model can serve as a prediction tool and can be applied to assign and reassign the A, B, C and D band positions of Pb(2+). The model predicts the positions of B, C and D bands of NaF:Pb(2+) at 7.516, 8.688 and 12.796 eV, respectively; the D band of CsCl:Pb(2+), CsBr:Pb(2+) and CsI:Pb(2+) at 6.633, 6.389 and 5.275 eV, respectively. We reassign the C band of Pb(2+) in NaBr as 5.276 eV but not the reported 5.636 eV, which is more reasonable to be ascribed to the charge transfer band.


Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases?
The adipose tissue represents a large amount of adult tissues. For long time, it was considered as a poorly active overgrown and undesirable tissue even if its usefulness was demonstrated in reconstructive surgery. It was studied for its main involvement in energy metabolism and disorders as diabetes and obesity. More recently, its endocrine functions emerged and appeared to play a key role in many physiological situations such as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. These cells can display a macrophagic or endothelial potential according to their environment and could be now considered as vascular progenitors. Differentiation of various adipose derived cell subsets towards functional cardiomyocytes, osteoblasts, haematopoietic and neural cells was also obtained in vitro. Altogether, these data emphasise the need to consider with a new look preadipocyte status and adipose tissue biology. These spectacular data, together with the fact that adipose tissue is easy to obtain lead to numerous and promising perspectives in regenerative medicine. They highlight the concept that progenitor cells from adipose tissue constitute an alternative for cells-based strategies designed for the treatment of cardiovascular diseases.


Prevalence of erectile dysfunction in patients with chronic kidney disease: a systematic review and meta-analysis.
Growing evidence reports that chronic kidney diseases (CKD) might play a role in erectile dysfunction (ED), but limited knowledge is available. Therefore, we performed a systematic review up to 21/08/2019 to investigate the associations between CKD and ED. The main analysis reported the prevalence of ED as absolute estimates (in %) with their 95% confidence intervals (CIs) and across CKD stages (when specified), hemodialysis and transplant, calculating the p for interaction across strata. Among 291 studies, we included 34 articles with 5986 men. We found an overall prevalence of 76% (95%CI: 72-79) with a high degree of heterogeneity (I2 = 84.2%; p < 0.0001). Analyzing the data by CKD stage, we found a significant higher prevalence of ED in CKD (78%; 95%CI: 75-81%; I2 = not possible) compared with hemodialysis stage (prevalence = 77%; 95%CI: 73-80%; I2 = 84.5) or to patients undergoing transplant (prevalence = 64%; 95%CI: 54-74%; I2 = 54%) (p across strata = 0.036). Considering the high prevalence of ED in men with CKD, health care practitioners should focus on issues of sexual health in men with CKD. Given the advancements in dialysis and therapy and the associated advancements in survival and life expectancy, maintaining the patients' sexual function is important for their well-being and quality of life.


Industrial-scale production of inactivated poliovirus vaccine prepared by culture of Vero cells on microcarrier.
In 1980, the authors reported preliminary results of large-scale production of inactivated poliovirus vaccine in which virus was produced in Vero cell culture on a microcarrier. For this first stage of development, 150-liter tanks were used. The virus is now produced in 1,000-liter tanks. The main point concerning the quality of Vero cells, namely the absence of tumorigenicity, has been demonstrated, qualifying them for use in the Institut M erieux cell bank. The purity of the cell line has also been determined by checking for the absence of bacteria, fungi, mycoplasmas, and viruses. The search for oncornavirus and for reverse transcriptase activity was carried out, and the results were negative but are not described in this paper. The quality of the purification process was checked by a search for residual cellular DNA in concentrated, purified, and inactivated vaccine. With use of a molecular hybridization procedure, a specific probe was prepared to detect approximately 50 pg of DNA per filter. The preliminary results show that the purification procedure fulfills the World Health Organization's requirements. T1 oligonucleotide mapping has also shown the identity of poliovirus RNA extracted from virus grown on Vero cells and that from primary monkey kidney cells. These data have led to the awarding of a license by the French government to the Institut M erieux for production of this new, reassessed, inactivated poliovirus vaccine.


Column chromatography-free solution-phase synthesis of a natural piper-amide-like compound library.
We have achieved an efficient solution-phase parallel synthesis of a library of natural piper-amide-like compounds from the bifunctional β-phosphono-N-hydroxy-succinimidyl ester intermediate. The primary important feature in our study is the construction of natural-product-like molecules through the adaptation of sophisticated organic reactions that create water-soluble byproducts for a chromatography-free purification. This simple and efficient method rapidly provides a combinatorial library of high yield and purity. The library was evaluated against GPCR targets to demonstrate its potential use as a tool for drug discovery and in chemical biology.


Effect of hyperbaric oxygen on apoptosis in neonatal hypoxia-ischemia rat model.
We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% oxygen). Apoptotic cell death was examined in the injured cortex and hippocampus tissue. Caspase-3 expression and activity increased at 18 and 24 h after the hypoxia-ischemia insult. At 18-48 h, poly(ADP-ribose) polymerase (PARP) cleavage occurred, which reduced the band at 116 kDa and enhanced the band at 85 kDa. There was a time-dependent increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells. A single HBO treatment (100% oxygen, 3 ATA for 1 h) 1 h after hypoxia reduced the enhanced caspase-3 expression and activity, attenuated the PARP cleavage, and decreased the number of TUNEL-positive cells observed in the cortex and hippocampus. These results suggest that the neuroprotective effect of HBO is at least partially mediated by the reduction of apoptosis.


Distinct ACC Neural Mechanisms Underlie Authentic and Transmitted Anxiety Induced by Maternal Separation in Mice.
It is known that humans and rodents are capable of transmitting stress to their naive partners via social interaction. However, a comprehensive understanding of transmitted stress, which may differ from authentic stress, thus revealing unique neural mechanisms of social interaction resulting from transmitted stress and the associated anxiety, is missing. We used, in the present study, maternal separation (MS) as a stress model to investigate whether MS causes abnormal behavior in adolescence. A key concern in the analysis of stress transmission is whether the littermates of MS mice who only witness MS stress ("Partners") exhibit behavioral abnormalities similar to those of MS mice themselves. Of special interest is the establishment of the neural mechanisms underlying transmitted stress and authentic stress. The results show that Partners, similar to MS mice, exhibit anxiety-like behavior and hyperalgesia after witnessing littermates being subjected to early-life repetitive MS. Electrophysiological analysis revealed that mice subjected to MS demonstrate a reduction in both the excitatory and inhibitory synaptic activities of parvalbumin interneurons (PVINs) in the anterior cingulate cortex (ACC). However, Partners differed from MS mice in showing an increase in the number and excitability of GABAergic PVINs in the ACC and in the ability of chemogenetic PVIN inactivation to eliminate abnormal behavior. Furthermore, the social transfer of anxiety-like behavior required intact olfactory, but not visual, perception. This study suggests a functional involvement of ACC PVINs in mediating the distinct neural basis of transmitted anxiety.SIGNIFICANCE STATEMENT The anterior cingulate cortex (ACC) is a critical brain area in physical and social pain and contributes to the exhibition of abnormal behavior. ACC glutamatergic neurons have been shown to encode transmitted stress, but it remains unclear whether inhibitory ACC neurons also play a role. We evaluate, in this study, ACC neuronal, synaptic and network activities and uncover a critical role of parvalbumin interneurons (PVINs) in the expression of transmitted stress in adolescent mice who had witnessed MS of littermates in infancy. Furthermore, inactivation of ACC PVINs blocks transmitted stress. The results suggest that emotional contagion has a severe effect on brain function, and identify a potential target for the treatment of transmitted anxiety.


Influence of different flours and starches on gluten-free bread aroma.
The aim of this research was to study the effect of different gluten-free flours (yellow and white corn, rice, oat, teff, buckwheat, amaranth and quinoa) and starches (wheat, corn and potato) on the generation of volatile compounds in the fermented doughs and crumbs. Volatile compounds were analyzed by static headspace-gas chromatography/mass spectrometry (SHS-GC/MS). Nine fermentation and lipid oxidation volatile compounds were evaluated, which were found to be the same from dough to crumb but vary in levels. Concentrations of compounds produced during fermentation were higher in doughs whereas those from lipid oxidation were higher in crumbs. The type of flour/starch affected the concentration of these volatile compounds. The proportions of ethanol and 2/3-methylbutanol (fermentation compounds) were higher in dough from yellow and white corn, rice and oat while the proportions of hexanal, 1-pentanol and 2,4-decadienal (lipid oxidation compounds) were higher in the doughs made with starches. The proportions of ethanol and 2/3-methylbutanol were higher in quinoa and amaranth crumbs whilst hexanal, 1-pentanol and 2,4-decadienal were higher in yellow and white corn crumbs.


Optimal Halbach Permanent Magnet Designs for Maximally Pulling and Pushing Nanoparticles.
Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nano-particles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell's equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm(3) volume optimal Halbach design yields a ×5 greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤ 1 Tesla), size (≤ 2000 cm(3)), and number of elements (≤ 36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤ 5°), thus yielding practical designs to improve magnetic drug targeting treatment depths.


Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice.
Under stress conditions, cells in living tissue die by apoptosis or necrosis depending on the activation of the key molecules within a dying cell that either transduce cell survival or death signals that actively destroy the sentenced cell. Multiple extracellular (pH, heat, oxidants, and detergents) or intracellular (DNA damage and Ca(2+) overload) stress conditions trigger various types of the nuclear, endoplasmic reticulum (ER), cytoplasmatic, and mitochondrion-centered signaling events that allow cells to preserve the DNA integrity, protein folding, energetic, ionic and redox homeostasis, thus escaping from injury. Along the transition from reversible to irreversible injury, death signaling is highly heterogeneous and damaged cells may engage autophagy, apoptotic, or necrotic cell death programs. Studies on multiple double- and triple- knockout mice identified caspase-8, flip, and fadd genes as key regulators of embryonic lethality and inflammation. Caspase-8 has a critical role in pro- and antinecrotic signaling pathways leading to the activation of receptor interacting protein kinase 1 (RIPK1), RIPK3, and the mixed kinase domain-like (MLKL) for a convergent execution pathway of necroptosis or regulated necrosis. Here we outline the recent discoveries into how the necrotic cell death execution pathway is engaged in many physiological and pathological outcome based on genetic analysis of knockout mice.


Learning in a task of complex auditory streaming and identification.
Adult humans were studied for improvements in their ability to segregate natural whole speech in background noise, in 6 test sessions spaced with a very wide range of inter-session interval (ISI) ranging from minutes to weeks apart so as to examine the effect of this parameter on initial (early) and late components of perceptual learning. Improvements were found even with spacings of 3 weeks between the punctate task sessions. All subjects showed similar total learning amounts but there were sex- and ISI-dependent differences in learning patterns, which we indexed by dividing the overall exponentially-decreasing learning pattern into an early phase between the first two sessions and a later phase between the second and sixth sessions. Males tested at all ISIs and females tested at short (2, 5 and 15 min) and long (1-21 days) ISIs showed small amounts of early-phase learning and large amounts of late-phase learning. However, females tested at intermediate (30 min and 1h) ISIs showed only early learning, i.e., faster learning given that the total learning was the same. This sex- and ISI-specific deviant pattern could be changed to the standard pattern by interposing an overnight interruption that included sleep amongst test sessions. Thus, improvement in this complex auditory streaming and identification task can occur even with very brief and widely-spaced exposure, generally through a standard pattern of slower overall learning, but also through a sex- and ISI-specific deviant pattern of very rapid early learning which can be modulated by interposed delay unlike the standard pattern.


[Musculoskeletal rehabilitation and bone. Application of motivation theory for rehabilitation of the elderly].
Selection and application of the exercise programs for rehabilitation of the elderly should not only be based on a short-term efficiency, but also be based on the self- determination and motivation of the participants themselves. In this paper, we will review the functional improvement of the elderly by Tai Chi, Hula, Ball Exercise, and Arcade Games, and will discuss about the motivation theory to apply in practice. The intrinsic motivation is the essential element of the theory and is composed of enjoyment, interest and satisfaction.


Genetic relationships among calving ease, calving interval, birth weight, and weaning weight in the Asturiana de los Valles beef cattle breed.
The aim of this paper was to estimate direct and maternal genetic parameters for calving ease (CE), birth weight (BrW), weaning weight (WW), and calving interval (CI) to assess the possibility of including this information in beef cattle improvement programs. Field data, including a total of 59,813 animals (1,390 sires and 1,147 maternal grand sires) from the Asturiana de los Valles beef cattle breed, were analyzed with a multivariate linear model. Estimates of heritability for direct genetic effects (CED, CID, BrWD, and WWD) were 0.191 +/- 0.019, 0.121 +/- 0.013, 0.390 +/- 0.030, and 0.453 +/- 0.035, respectively, whereas those for maternal genetic effects (CEM, BrWM, and WWM) were 0.140 +/- 0.015, 0.208 +/- 0.020, and 0.138 +/- 0.022, respectively. Genetic correlations between direct or maternal genetic effects across traits were, in general, positive and moderate to low. However, genetic correlation for the pair CED-BrWD was positive and high (0.604 +/- 0.064). Genetic correlations between the direct and maternal genetic effects within a trait were negative and moderate (-0.219 +/- 0.097 for CE, -0.337 +/- 0.080 for BrW, and -0.440 +/- 0.102 for WW). Genetic correlations for CED-BrWM and CED-WWM were -0.121 +/- 0.090 and -0.097 +/- 0.113, respectively. The genetic correlation for CEM-CID was unfavorable (0.485 +/- 0.078), and those for CEM-BrWD (-0.094 +/- 0.079) and CEM-WWD (-0.125 +/- 0.082) were low and negative. The genetic correlation between CID and WWM was favorable (-0.148 +/- 0.106). Overall, the data presented here support the hypothesis that maternal effects for CE and BrW are not the same and that the genetic relationships between CI and maternal effects for WW in beef cattle follow a similar pattern to that reported between CI and milk yield in dairy cattle. Moreover, the need to include direct and maternal breeding values in beef cattle selection programs is suggested.


Alternative thermodiffusion interface for simultaneous speciation of organic and inorganic lead and mercury species by capillary GC-ICPMS using tri-n-propyl-lead chloride as an internal standard.
An alternative thermodiffusion interface (TDI) was designed and constructed for the effective online coupling of capillary gas chromatography (cGC) and inductively coupled plasma mass spectrometry (ICPMS). Pb(2+), (CH3)3Pb(+), (C2H5)3Pb(+), Hg(2+), CH3Hg(+) and C2H5Hg(+) were derived as Pb(C4H9)4, (CH3)3PbC4H9, (C2H5)3PbC4H9, (C4H9)2Hg, CH3HgC4H9, and C2H5HgC4H9 when butyl magnesium bromide was employed as a derivatization reagent for a proof-of-concept study, avoiding the loss of their species specific information. All these derivatives together with the neutral fully saturated (CH3)4Pb and (C2H5)4Pb could be quantitatively separated within 7 min using a 15 m long capillary column, allowing the determination and speciation of organic and inorganic Pb and Hg species in a single run. The method detection limits (3sigma) for Me4Pb, Et4Pb, Me3Pb(3+), Pb(2+), MeHg(+), EtHg(+), and Hg(2+) are 0.07, 0.06, 0.04, 7.0, 0.09, 0.1, and 0.2 pg g(-1), respectively. Moreover, tri-n-propyl-lead chloride was synthesized and used as an alternative internal standard for the accurate and simultaneous speciation analysis of Pb and Hg in complicated environmental and biological samples for the first time. This cGC-TDI-ICPMS method was validated by analyzing Pb and Hg species in certified reference materials and then was applied to simultaneous speciation analysis of Pb and Hg in real-life samples. It is expected that these approaches can be extended to the speciation of other organometallic compounds after suitable modifications and so will aid in monitoring the occurrence, pathways, toxicity, and/or biological effects of these compounds in the environment and in organisms.


The genome of the Antarctic-endemic copepod, Tigriopus kingsejongensis.
The Antarctic intertidal zone is continuously subjected to extremely fluctuating biotic and abiotic stressors. The West Antarctic Peninsula is the most rapidly warming region on Earth. Organisms living in Antarctic intertidal pools are therefore interesting for research into evolutionary adaptation to extreme environments and the effects of climate change. We report the whole genome sequence of the Antarctic-endemic harpacticoid copepod Tigriopus kingsejongensi . The 37 Gb raw DNA sequence was generated using the Illumina Miseq platform. Libraries were prepared with 65-fold coverage and a total length of 295 Mb. The final assembly consists of 48 368 contigs with an N50 contig length of 17.5 kb, and 27 823 scaffolds with an N50 contig length of 159.2 kb. A total of 12 772 coding genes were inferred using the MAKER annotation pipeline. Comparative genome analysis revealed that T. kingsejongensis -specific genes are enriched in transport and metabolism processes. Furthermore, rapidly evolving genes related to energy metabolism showed positive selection signatures. The T. kingsejongensis genome provides an interesting example of an evolutionary strategy for Antarctic cold adaptation, and offers new genetic insights into Antarctic intertidal biota.


Retinal models: comparison of electronic absorption spectra in the gas phase and in methanol solution.
An accurate study on several models of the 11-cis-retinal protonated Schiff base (PSB) has been performed both in vacuo and in methanol solution. Condensed phase calculations have been carried out making use of the ASEP/MD method, which permits the employment of the same high-level ab initio calculations usually applied in gas phase studies as well as a detailed description of the solvent structure around the solute through molecular dynamics simulations of the complete system. The solute structure was completely optimized in vacuo and in solution at the CASSCF level and/or MP2 level, and the CASPT2 method was applied for the calculation of the vertical transition energies and solvent shift values. Our results reproduce and explain the main features of the experimental absorption spectra of the 11-cis-retinal PSB. Two well-resolved bands can be identified in vacuo (separated by roughly 1.0 eV), whereas only a single broad band is observed in solution. This fact is explained by the existence of two almost degenerate excited states in methanol. The inclusion of two methyl groups at the iminium end of the system permits the reproduction of the experimental solvent shift value.


The combination of psychotherapy and pharmacotherapy in the treatment of borderline patients.
The combination of psychotherapy and pharmacotherapy may offer some borderline patients a more effective treatment than either modality alone. The author reviews evidence from recent studies demonstrating the strengths and weaknesses of each modality separately; discusses the indications and contraindications for combined treatment; considers the special complications introduced in conducting such a combined treatment with borderline patients; and presents some strategies for addressing these complications.


[Cooperative learning for improving healthy housing conditions in Bogota: a case study].
This was a community-based effort at constructing an educational proposal orientated towards self-empowerment aimed at improving the target population's sanitary, housing and living conditions through cooperative learning. A constructivist approach was adopted based on a programme called "Habitat community manger". The project involved working with fifteen families living in the Mochuelo Bajo barrio in Ciudad Bolívar in Bogotá, Colombia, for identifying the most relevant sanitary aspects for improving their homes and proposing a methodology and organisation for an educational proposal. Twenty-one poor housing-related epidemiological indicators were identified which formed the basis for defining specific problems and establishing a methodology for designing an educational proposal. The course which emerged from the cooperative learning experience was designed to promote the community's skills and education regarding health aimed at improving households' living conditions and ensuring a healthy environment which would allow them to develop an immediate habitat ensuring their own welfare and dignity.


Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis.
Disseminated leishmaniasis (DL) differs from other clinical forms of the disease due to the presence of many non-ulcerated lesions (papules and nodules) in non-contiguous areas of the body. We describe the histopathology of DL non-ulcerated lesions and the presence of CD4-, CD20-, CD68-, CD31- and von Willebrand factor (vW)-positive cells in the inflamed area. We analysed eighteen biopsies from non-ulcerated lesions and quantified the inflamed areas and the expression of CD4, CD20, CD68, CD31 and vW using Image-Pro software (Media Cybernetics). Diffuse lymphoplasmacytic perivascular infiltrates were found in dermal skin. Inflammation was observed in 3-73% of the total biopsy area and showed a significant linear correlation with the number of vW+ vessels. The most common cells were CD68+ macrophages, CD20+ B-cells and CD4+ T-cells. A significant linear correlation between CD4+ and CD20+ cells and the size of the inflamed area was also found. Our findings show chronic inflammation in all DL non-ulcerated lesions predominantly formed by macrophages, plasmacytes and T and B-cells. As the inflamed area expanded, the number of granulomas and extent of the vascular framework increased. Thus, we demonstrate that vessels may have an important role in the clinical evolution of DL lesions.


Influence of panting frequency on thoracic gas volume measurements in chronic obstructive pulmonary disease.
Frequency dependence of thoracic gas volume (Vtg) and phase angles between volume and mouth pressure signals were evaluated in 10 normal subjects and in 31 patients with bronchitis, who panted sequentially at 0.8 Hz and 2.5 Hz during the same occlusion. A slight negative frequency dependence of Vtg (-1.2 +/- 0.9%/Hz, -m +/- SD), accompanied by a very small phase lag of volume with respect to pressure variations (-1.5 +/- 0.9 degrees at 2.5 Hz) was found in normal subjects. In contrast, patients with bronchitis exhibited a mild positive frequency dependence of Vtg (+ 0.5 +/- 1.7%/Hz and + 0.8 +/- 2.3%/Hz in subjects with normal and increased airway resistance, respectively), whereas the volume signal slightly led the pressure signal at 2.5 Hz. Both the frequency dependence and the phase difference increased when the subjects with the largest airway resistance did not support their cheeks during the panting maneuvers. The data confirm previous indirect evidence that Vtg is, in most instances, accurately measured by Boyle's law in mild and moderate chronic airway obstruction.


Role of metabolic feedback regulation in glucose production of running rats.
Hepatic glucose production (Ra) was studied in phlorizin (P)- and saline (C)-infused rats running for 35 min at 21 m/min in the postabsorptive state (series I) or 18 m/min in the fed state (series II). Phlorizin-induced increase in glucose clearance would increase or not affect Ra, depending on whether metabolic feedback mechanisms or central command from central nervous system (CNS), respectively, regulate Ra during exercise. Initial exercise-induced increases in Ra were similar in P and C rats of both series, although glucose clearance was higher and plasma glucose lower, however not hypoglycemic, in P rats. After 5 min of exercise, Ra remained similar in P and C rats in series I, whereas in series II, Ra increased almost twice as much in P compared with C rats. In both series muscle glycogenolysis and lipolysis were higher in P than in C rats. The results suggest a central command regulation of Ra from CNS motor centers and that this primary setting may be modulated by metabolic feedback mechanisms. Hypoglycemia is not needed to activate metabolic feedback. A variety of substrates rather than glucose specifically is mobilized by metabolic feedback mechanisms associated with decreased glucose availability.


Change in Aortic Neck Diameter after Endovascular Aortic Aneurysm Repair.
Implications of aortic neck dilatation following endovascular aneurysm repair (EVAR) are unclear. Previous studies are limited to comparisons of individual, early generation devices. We compared aortic neck dilatation among contemporary stent grafts. We reviewed preoperative and postoperative computed tomographic angiograms for EVARs performed from 2008-2014. Images were analyzed using 3-dimensional centerline reconstructions. Aortic neck diameter was measured in orthogonal planes at and 10 mm below the lowest renal artery. Device type and main body graft diameter were obtained from operative reports. Eighty-six patients were analyzed with a median radiologic follow-up of 21.9 months (range: 4-64). Stent grants implanted included 26 Cook Zenith, 26 Gore Excluder, 22 Medtronic Endurant, 10 Endologix Powerlink, and 2 Trivascular Ovation devices. Mean device oversizing was 13.6 ± 11.5% and did not vary by device type (P = 0.54). Most patients (86.0%) experienced increases in aortic neck diameter during follow-up, with a mean increase of 1.3 ± 2.2 mm (5.9 ± 9.3%) and 3.3 ± 0.6 mm (8.9 ± 2.5%) at 30 day and latest follow-up scans, respectively. Repeated-measures analysis further demonstrated a significant increase in mean neck dilatation during follow-up (P < 0.001). Neck dilatation was not significantly different across different devices (P = 0.233). However, there was a moderate positive correlation between percent change in neck diameter and degree of oversizing, which was statistically significant (rs = 0.41, P < 0.001). Type Ia endoleak was observed in 2 patients and was associated with greater mean neck dilatation (8.8 ± 3.3 mm vs. 3.35 ± 2.71, P = 0.041). There was no relationship between changes in neck diameter and sac regression/expansion. Aortic neck diameter increases consistently over time following EVAR. The degree of neck dilatation correlates with degree of device oversize but not with device type.


Deciphering Rho-associated, coiled-coil-containing protein kinase in diabetic nephropathy: small steps towards a giant leap.
Diabetic nephropathy is a public health problem worldwide. Our understanding of the molecular machinery, as well as the clinical therapies for diabetic nephropathy, has evolved dramatically in recent years. However, even with this progress, there are residual risks of kidney failure and cardiovascular events in patients with diabetes. Rho-associated, coiled-coil-containing protein kinase (ROCK) is activated in response to various pathologic stimuli in the context of diabetes. The contribution of ROCK has been investigated in vivo using gene deletion rodent models and specific inhibitors, which are providing key insights into the pathologic function of ROCK in diabetic nephropathy. ROCK has two isoforms, ROCK1 and ROCK2. Both isoforms are expressed in the kidney, including mesangial cells, podocytes, and endothelial cells. ROCK1 blunts AMP-activated protein kinase (AMPK), while ROCK2 negatively regulates peroxisome proliferator-activated receptor α (PPARα) to inhibit fatty acid oxidation, both of which lead to structural and functional impairment of glomeruli in diabetes. Of note, ROCK signaling is activated in the kidney of animal models and patients with diabetes. In addition, an observational study has shown that fasudil hydrochloride, an ATP-competitive selective ROCK inhibitor, significantly attenuated proteinuria among patients with diabetes. These findings highlight the promising prospects for the development of a ROCK-centered approach against the progression of diabetic nephropathy.


[Evaluation of the usefulness of selective chromogenic agar medium (chromID VRE) and multiplex PCR method for the detection of vancomycin-resistant enterococci].
Accurate and early detection of vancomycin-resistant enterococci (VRE) is critical for controlling nosocomial infection. In this study, we evaluated the usefulness of a selective chromogenic agar medium and of multiplex PCR for detection of VRE, and both these techniques were compared with the conventional culture method for VRE detection. We performed the following 3 methods for detecting VRE infection in stool specimens: the routine culture method, culturing in selective chromogenic agar medium (chromID VRE, bioMérieux, France), and multiplex PCR using the Seeplex® VRE ACE Detection kit (Seegene Inc., Korea) with additional PCR for vanC genes. We isolated 109 VRE strains from 100 stool specimens by the routine culture method. In chromID VRE, all the isolates showed purple colonies, including Enterococcus gallinarum and E. raffinosus, which were later identified using the Vitek card. All VRE isolates were identified by the multiplex PCR method; 100 were vanA-positive E. faecium, 8 were vanA- and vanC-1-positive E. gallinarum, and 1 was vanA-positive E. raffinosus. For VRE surveillance, culturing the isolates in chromID VRE after broth enrichment appears to be an accurate, rapid, and easy method for routine screening test. Multiplex PCR is relatively expensive and needs skilled techniques for detecting VRE, but it can be an auxiliary tool for rapid detection of genotype during a VRE outbreak.


Social anxiety and perception of early parenting among American, Chinese American, and social phobic samples.
Emotionally distant and controlling child-rearing attitudes have been reported to characterize the parents of American or western European social phobics in previous research. However, the notion that these parental attitudes may be associated with social anxiety only in some cultures has not been investigated. The present study examined social anxiety among American social phobics and American and Chinese/Chinese American volunteer samples and how it may relate to their parents' child-rearing attitudes. Multivariate analyses of variance revealed overall group differences. Both volunteer samples reported lower levels of anxiety than social phobics. Parents of Chinese/Chinese Americans and social phobics were reported to be similar in their (1) isolation of children from social activities; (2) over-emphasis of others' opinions; and (3) use of shame tactics for discipline (more so than American volunteers' parents). However, parents of nonsocial phobics were more likely to attend family social activities than social phobics' parents. Overall, the association between a reported parenting style emphasizing others' opinions and shame tactics and social anxiety in their adult children was more evident in both American samples than among Chinese/Chinese Americans.


Analysis of cell populations in crescentic glomerulonephritis.
The cell types present in the crescents were studied in 5 human patients with crescentic glomerulonephritis: two cases of systemic lupus erythematosus, one case of hemolytic uremic syndrome and two cases of rapidly progressive glomerulonephritis. Frozen sections of renal biopsies were studied by immunofluorescence, using murine monoclonal antibodies (orthoclones) against specific antigens on the membrane of human peripheral blood cells, and by histochemical methods. Monocytes (OKM1+, OKIa+ cells) but no lymphocytes (OKT+ cells), were detected in the crescentic glomeruli. Subsets of T lymphocytes (inducer-helper and cytotoxic-suppressor) were detected in the interstitium. Non-specific esterase-positive cells were observed in the glomeruli and in small numbers in the crescents. Fibrinogen deposits were present in the crescents of four of the five cases studied. No immunoglobulins (IgG, IgM, IgA) or complement (C1q, C3) deposits were detected in the crescents. Fibrinogen, immunoglobulins and complement were present in the glomerular tufts.


[Financial burden on caregivers of schizophrenic patients: a comparison between parents and spouses].
Part II of this study will explore more accurately, how caregivers of schizophrenic patients perceive the financial burdens of the disease. 42 In-depth-interviews with parents and spouses of schizophrenic patients were analysed using a qualitative-interpretative technique. When talking about their living situation, caregivers tended to keep away from the topic of financial charges; often they played down objective financial disadvantages or didn't assess them as burdensome. Considerable financial burdens were reported by parents of young patients still living in the parents' household and by spouses in families with very low income. Financial burdens are usually superimposed by other problems of the caregivers, such as dealing with acute episodes and sorrow about the future. Thus, not only the material, but also the immaterial costs of caregivers should be taken into consideration when taking health policy decisions.


Quantitative analysis of mRNA encoding MUC1, MUC2, and MUC5AC genes: a correlation between specific mucin gene expression and sialomucin expression in non-small cell lung cancer.
The expression of mucins is important for tumor invasiveness and metastasis. In our previous report (Am. J. Respir. Crit. Care Med. 1997; 155:1419-1427), non-small cell lung cancers bearing sialomucin expression tended to relapse earlier than those without sialomucin. However, it remained unclear whether the expression of sialomucin in lung cancer is caused by an abnormal glycosylation process or by the expression of a specific mucin gene product. To address this problem, we established a modified quantitative competitive polymerase chain reaction (QC-PCR) analysis. RNA internal standards of MUC1, MUC2, and MUC5AC non-tandem repeat sequences were constructed, and known copy numbers of mucin RNA internal standards were introduced into reverse transcription-polymerase chain reactions (RT-PCR) for each mucin gene in order to compete with native mucin gene RNA during the reaction. The RNA of Gbeta-like gene (a housekeeping gene) was used as internal control for the RNA analysis. Twenty-five lung cancer tissues (13 adenocarcinomas and 12 squamous cell carcinomas) were used for analysis. Mann-Whitney rank sum test was applied to compare the expression amounts of different mucin genes in tissues. The results revealed that adenocarcinoma expressed higher amounts of MUC5AC gene than did squamous cell carcinoma (P = 0.03). The expression amount of MUC5AC correlated positively with the expression status of sialomucin (P = 0.012). Further studies are anticipated to elucidate the underlying mechanism contributing to this phenomenon.


[Identification of the differentially expressed genes between primary breast cancer and paired lymph node metastasis through combining mRNA differential display and gene microarray].
To identify and clone the genes related to breast cancer metastasis through comparing the mRNA expression profiling between primary breast cancer and paired lymph node metastasis. First, primary breast cancer cells and paired lymph node metastasis tissues were used to identify their differentially expressed genes by using mRNA differential display, and fragments of differentially expressed genes were obtained by gel cutting and cloning to pGEM-T vector, then sequencing and blasting with the GenBank for their homologous genes. Then, the obtained genes were validated by using reverse dot blot hybridization and gene microarray. Finally, the mRNA expression levels in the 7 breast cancer cell lines with different metastasis behaviors were detected by real-time RT-PCR. The mRNA expression profiling of the metastatic breast cancers in lymph node was similar to that of their primary cancers. 16 differentially expressed gene fragments were obtained from mRNA differential display; four of them were found to be unknown genes, and had been accepted by the GenBank, with the accession numbers BG518428, BG518429, BM005520, and BM005521. Of the other 12 genes, 8 were known genes, and 4 were genes with known sequences but unknown functions. The kinesin-like DNA binding protein (KNSL4) and dihydropyrimidine dehydrogenase (DYPD) were down-regulated in the metastatic tissues in comparison with the paired primary tissues, which was identified by both radioactivity-labeled reverse dot blot hybridization and fluorescence-labeled gene microarray hybridization. KNSL4 mRNA expression had a down-regulation trend with increasing metastatic ability of breast cancer cell lines. The gene expression profiling of the lymph node metastasis is almost similar to that of their primary breast cancer, indicating that the metastatic cancer cells in lymph node are the subclone with higher metastasis ability of the primary cancer cells, and that some differentially expressed genes between them may be involved in the change of metastasis phenotype. KNSL4 and DYPD are potential metastasis-related genes, and KNSL4 mRNA expression is correlated with metastasis behaviors of the breast cancer cell lines, suggesting that KNSL4 may play an important role in the metastasis process of breast cancer.


Exploring the distinct immunological reactions of bovine neutrophils towards major and minor pathogens responsible for mastitis.
Bovine mastitis is primarily caused by a group of bacteria known as Staphylococcus and Streptococcus. However, additional types of bacteria, such as bovine non-aureus staphylococci and mammaliicocci (NASM) as well as lactic acid bacteria (LAB), are considered minor pathogens and have less impact on cows. Modulating bovine neutrophil activities and gene expressions in response to bacterial stimuli prompted the cells to execute effector functions to combat udder infections. Although neutrophils can manage major mastitis-causing bacteria, this strategy has not been tested against minor pathogens, i.e. NASM, Weissella spp. Our main objective was to investigate how neutrophils interacted with major and minor pathogens during in vitro bacterial stimulation. The results reveal that neutrophils performed offensive duties regardless of the type of bacteria encountered. Neutrophils generated high levels of reactive oxygen species, efficiently phagocytosed both types of bacteria, and facilitated extracellular killing by releasing NET structures against all bacteria. In addition, neutrophils migrated preferentially towards the majors rather than the minors, although myeloperoxidase (MPO) degranulation did not differ substantially across bacteria. Furthermore, the killing capacity of neutrophils was not dependent on any particular bacterium. The correlation of effector functions is intimately linked to the up-regulation of genes associated with the above functions, except for IL6, which was down-regulated. Furthermore, neutrophil apoptosis can be modulated by altering apoptosis-associated genes in response to harmful stimuli. These findings provide valuable information on how neutrophils react to major and minor mastitis-causing bacteria. However, future research should explore the interplay between minor pathogens and the host's responses.


Current Surge of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants in China Could Be Threatening as the Asian Games 2023 Flags Off in September: Foolproof Cautionary Measures Are Suggested.
Despite normalcy having almost returned in the lives of people throughout the world post-coronavirus disease-19 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the danger still looms over the fears of development and propagation of a newer SARS-CoV-2 variant. The movement of people globally has reached the pre-pandemic level, and this augmentation increased surveillance regarding the emergence of lethal SARS-CoV-2 variants. International sports events are among the potential avenues where the virus could cause serious impact. Therefore, the organization of such events should be planned and executed meticulously to avoid viral transmission and minimize the health effects of infections on the sportspersons and the local people. Additionally, there could be dissemination of the infections to the native countries of the participants and visitors while they return to their homes. Through this editorial, we prompt caution to the organizers and the event-hosting nation's administration regarding the potential threat and suggest measures to avoid any medical emergencies related to COVID-19.


Topological origin and not purely antisymmetric wave functions of many-body states in the lowest Landau level.
In this paper, we recall the topological approach to quantum Hall effects. We note that, in the presence of a magnetic field, trajectories representing elements of the system's braid group are of cyclotron orbit type. In two-dimensional spaces, this leads to the restriction of the full braid group, π1(Ω)-loopless generators (exchanges of MN coordinates or classical particles) are unenforceable. As a result, the identification of a possible Hall-like state comes down to the identification of a possible subgroup of π1(Ω). The latter follows from the connection between the one-dimensional unitary representation of the system's braid group and particle statistics (unavoidable for any correlated state). In this work, we implement the topological approach to derive the lowest Landau-level pyramid of fillings. We point out that it contains all mysterious odd-denominator filling factors-like [Formula: see text], [Formula: see text] or [Formula: see text]-not trivial to explain within the standard picture. We also introduce, explicitly, cyclotron subgroup generators for all derived fractions. Preliminary results on wave functions, supported by several Monte Carlo calculations, are presented. It is worth emphasizing that not all proposed many-body functions are purely antisymmetric-they, however, transform in agreement with the scalar representations of the system's braid group. The latter is enforced by standard quantization methods.


ANK3 Gene Polymorphism Rs10994336 Influences Executive Functions by Modulating Methylation in Patients With Bipolar Disorder.
Background: A large body of evidence suggests that epigenetic modification including DNA methylation plays a critical role in BD's pathogenesis while the identification of methylation quantitative trait loci (meQTLs) shed light on the interpretation of the function of genetic variants in non-coding regions. The intronic single nucleotide polymorphism (SNP) rs10994336 within the ANK3 has emerged as one of the most replicated risk variants for bipolar disorder (BD) in genome-wide association studies. Whether rs10994336 functions as a meQTL to mediate the association between genotype and phenotype remains unclear. Method: A total of 154 patients with BD and 181 healthy controls (HC) were recruited. The genotypes of rs10994336 and methylation levels of CpG sites within ANK3 were tested. Executive functions were assessed using a computerized version of the Wisconsin Card Sorting Test (WCST). Results: Bipolar disorder patients with the risk-T allele of rs10994336 scored lower on tests of executive function compared to homozygous CC carriers, after controlling for age, gender, and education level. No significant difference was found in HC individuals. The risk-T allele is associated with a lower methylation level of CpG site cg02172182 in HC after multiple corrections and replicated in the BD group in the same direction. Further mediation analysis revealed that the cg02172182 methylation significantly mediated the association between the polymorphism rs10994336 and PE index of WCST in patients with BD. Conclusion: Our study suggests that BD-related genetic variant rs10994336 in ANK3 impacts executive functions by modulating ANK3 methylation, supporting the theory that methylation acts as a mediator between genotype and phenotype.


Race and delayed kidney allograft function.
Allograft survival among black recipients is poorer than among whites. Delayed allograft function is associated with a significant reduction in renal allograft survival. The relationship between delayed allograft function and black race is incompletely specified and was the focus of this investigation. A non-concurrent study of 325 recipients of cadaveric allografts followed for the occurrence of delayed allograft function defined as dialysis during the first week following transplantation for the principal analysis. A secondary definition of delayed allograft function was formulated based on the serum creatinine 2 weeks after transplantation. Unadjusted and adjusted logistic regression analysis were used to examine the unconfounded relationship between race and delayed allograft function. Fifty-seven of 91 (62.6%) black recipients experienced delayed allograft function compared to 113 of 234 (48.3%) whites. The odds ratio for black race as a predictor of delayed allograft function was 1.80, P=0.02, (95% CI, 1.09, 2.95). This finding was stable despite adjustment for other predictors of delayed allograft function in a multivariate model, but the precision of this estimate was less (P=0.10) because of missing data. Additionally, adjusted models with imputed values for missing covariates, models using a secondary definition of delayed allograft function, and models excluding patients whose cyclosporin therapy was delayed, all consistently demonstrated a similar association between black race and delayed allograft function. This study demonstrated an increased risk of delayed allograft function among black recipients. This relationship may play a role in the poorer allograft outcomes experienced by black recipients. Given the negative effect of delayed allograft function on allograft survival, efforts to identify its modifiable risk factors should be a high priority.


Xamoterol in severe heart failure. The Xamoterol in Severe Heart Failure Study Group.
516 patients with New York Heart Association class III and IV heart failure despite treatment with diuretics and angiotensin converting enzyme inhibitors were randomised in a double-blind between-group comparison to xamoterol 200 mg (352) or placebo (164) twice daily for 13 weeks. There was no difference between the treatments in loss of clinical signs. Visual analogue scale and Likert scores indicated that breathlessness was less severe with xamoterol, but there was no difference in exercise duration or total work done. Xamoterol reduced maximum exercise heart rate and systolic blood pressure, did not affect the number of ventricular premature beats after exercise, showed no arrhythmogenic activity, and had variable (agonist and antagonist) effects on 24 h heart rate. On intention-to-treat analysis 32 (9.1%) patients in the xamoterol group and 6 (3.7%) patients in the placebo group died within 100 days of randomisation (p = 0.02).


Companions' contributions to information gathering in Chinese outpatient clinical interaction.
Patients are commonly accompanied to visit clinicians in Chinese outpatient clinics. Although there has been extensive research on the roles of companions in asymmetric interactions within medical settings, there is a paucity of conversation analytic studies that examine the active participation and contributions of companions on an equal footing in medical consultations. How companions on an equal footing participate and contribute in Chinese outpatient clinical consultations remains under-explored. By employing video recordings of three-party consultations in the Chinese orthopaedic outpatient clinic as the data and adopting conversation analysis as the method, this study investigated how companions participated in and contributed to the information-gathering activity and how their contributions were interactionally negotiated and managed by clinicians and adult patients over sequences of interaction. We showed that companions negotiated epistemic rights in reporting and repairing the information about medical problems in the patients' epistemic domain and displayed different levels of encroachment on patients' epistemic rights by endorsing patients' responses, repairing the information in patients' responses, and offering information directly to clinicians. Companions also exerted deontic authority and shaped the trajectory of the consultations by hindering or facilitating the progressivity of the interaction. We argued that companions' contributions to the information-gathering activity might reflect the family-centred model of the doctor-patient relationship in the Chinese orthopaedic outpatient clinic. Clinicians are suggested to open up opportunities for companions' participation and contributions while respecting patients' rights, especially when there is a collision of knowledge claims between patients and their companions.


Ports minimization with mini-port and liver flexible retractor: an ergonomic and aesthetic alternative for single port in laparoscopic gastric bypass.
The laparoscopic access, with its classically known benefits, pushed implementation in other components, better ergonomy and aesthetic aspect. To minimize the number and diameter of traditional portals using miniport and flexible liver retractor on bariatric surgery. This prospective study was used in patients with less than 45 kg/m2, with peripheral fat, normal umbilicus implantation, without previous abdominoplasties. Were used one 30° optical device with 5 mm in diameter, four accesses (one mini of 3 mm to the left hand of the surgeon, one of 5 mm to the right hand alternating with optics, one of 12 mm for umbilical for surgical maneuvers as dissection, clipping, in/out of gauze, and one portal of 5 mm for the assistant surgeon), resulting in a total of 25 mm linear incision; additionally, one flexible liver retractor (covered with a nelaton probe to protect the liver parenchyma, anchored in the right diaphragmatic pillar and going out through the surgeon left portal) to visualize the esophagogastric angle. In selected patients (48 operations), gastric bypass was performed at a similar time to the procedures with larger diameters (5 or 6 portals and 10 mm optics, with sum of linear incision of 42 mm) including oversuture line on excluded stomach, gastric tube and mesenteric closing. The non sutured portal of 3 mm and the two of 5 mm with subdermal sutures, were hardly visible in the folds of the skin; the one of 12 mm was buried inside the umbilicus or in the abdominoplasty incision. Minimizing portals is safe, effective, good ergonomic alternative with satisfactory aesthetic profile without need for specific instruments, new learning curve and limited movement of the instruments, as required by the single port.


Three-Dimensional Liver Surgery Simulation: Computer-Assisted Surgical Planning with Three-Dimensional Simulation Software and Three-Dimensional Printing<sup/>.
To perform accurate hepatectomy without injury, it is necessary to understand the anatomical relationship among the branches of Glisson's sheath, hepatic veins, and tumor. In Japan, three-dimensional (3D) preoperative simulation for liver surgery is becoming increasingly common, and liver 3D modeling and 3D hepatectomy simulation by 3D analysis software for liver surgery have been covered by universal healthcare insurance since 2012. Herein, we review the history of virtual hepatectomy using computer-assisted surgery (CAS) and our research to date, and we discuss the future prospects of CAS. We have used the SYNAPSE VINCENT medical imaging system (Fujifilm Medical, Tokyo, Japan) for 3D visualization and virtual resection of the liver since 2010. We developed a novel fusion imaging technique combining 3D computed tomography (CT) with magnetic resonance imaging (MRI). The fusion image enables us to easily visualize anatomic relationships among the hepatic arteries, portal veins, bile duct, and tumor in the hepatic hilum. In 2013, we developed an original software, called Liversim, which enables real-time deformation of the liver using physical simulation, and a randomized control trial has recently been conducted to evaluate the use of Liversim and SYNAPSE VINCENT for preoperative simulation and planning. Furthermore, we developed a novel hollow 3D-printed liver model whose surface is covered with frames. This model is useful for safe liver resection, has better visibility, and the production cost is reduced to one-third of a previous model. Preoperative simulation and navigation with CAS in liver resection are expected to help planning and conducting a surgery and surgical education. Thus, a novel CAS system will contribute to not only the performance of reliable hepatectomy but also to surgical education.


Host-Parasite Interactions in Human Malaria: Clinical Implications of Basic Research.
The malaria parasite, Plasmodium, is one of the oldest parasites documented to infect humans and has proven particularly hard to eradicate. One of the major hurdles in designing an effective subunit vaccine against the malaria parasite is the insufficient understanding of host-parasite interactions within the human host during infections. The success of the parasite lies in its ability to evade the human immune system and recruit host responses as physiological cues to regulate its life cycle, leading to rapid acclimatization of the parasite to its immediate host environment. Hence understanding the environmental niche of the parasite is crucial in developing strategies to combat this deadly infectious disease. It has been increasingly recognized that interactions between parasite proteins and host factors are essential to establishing infection and virulence at every stage of the parasite life cycle. This review reassesses all of these interactions and discusses their clinical importance in designing therapeutic approaches such as design of novel vaccines. The interactions have been followed from the initial stages of introduction of the parasite under the human dermis until asexual and sexual blood stages which are essential for transmission of malaria. We further classify the interactions as "direct" or "indirect" depending upon their demonstrated ability to mediate direct physical interactions of the parasite with host factors or their indirect manipulation of the host immune system since both forms of interactions are known to have a crucial role during infections. We also discuss the many ways in which this understanding has been taken to the field and the success of these strategies in controlling human malaria.


Predictors of low cardiac output syndrome after isolated aortic valve surgery.
Low cardiac output syndrome (LCOS), defined as the need for postoperative intraaortic balloon pump or inotropic support for >30 minutes in the intensive care unit, remains a relatively common complication of aortic valve (AV) surgery. The aim of this study is to identify the preoperative predictors of LCOS in patients undergoing isolated AV surgery. We conducted a retrospective review of data prospectively entered into an institutional database. Between 1990 and 2003, 2255 patients underwent isolated AV surgery with no other concomitant cardiac surgery. The independent predictors of LCOS and operative mortality (OM) were determined by stepwise logistic regression analysis. The overall prevalence of LCOS was 3.9%. The independent predictors of LCOS were (odds ratio in parentheses) renal failure (5.0), earlier year of operation (4.4), left ventricular ejection fraction <40% (3.6), shock (3.2), female gender (2.8), and increasing age (1.02). Overall OM was 2.9%. The OM was higher in patients who experienced LCOS (38% versus 1.5%; P<0.001). The independent predictors of mortality were (odds ratio in parentheses) preoperative renal failure (8.3), urgency of surgery (3.4), previous stroke (2.9), congestive heart failure (2.6), previous cardiac surgery (2.3), hypertension (1.7), and small AV size (1.3). Low-output syndrome is associated with significantly increased morbidity and mortality. Novel strategies to preserve renal function, optimization of preexisting heart failure symptoms, and avoidance of prosthesis-patient mismatch may reduce the incidence of LCOS and lead to improved results after AV surgery.


Strong electronic consequences of intercalation in cuprate superconductors: the case of a trigonal planar AuI(3) complex stabilized in the Bi(2)Sr(2)CaCu(2)O(y) lattice.
Recently, a molecular AuI(3) complex was stabilized in the interlayer space of the Bi(2)Sr(2)CaCu(2)O(y) (Bi2212) high-T(c) superconducting phase, adopting an exceptional D(3)(h) structure (Choy, J.-H.; et al. J. Phys.Chem. B 2000, 104, 7273). If the gold were formally Au(III), a strong Jahn-Teller distortion to T- and Y-shaped structures would be expected. In this work, we try to understand the structural preferences of AuI(3) in both the gas phase and the Bi2212 lattice, as well as the influence of the AuI(3) intercalation on the superconductor lattice. What we think actually happens is that there is an effective electron transfer from the s-type Bi lone pair to the gold, increasing the formal oxidation state of Bi from +3 to +5 and decreasing that of Au from +3 to +1. A trigonal Au(I) trihalide is just fine. The DFT results confirm in the Bi-rich regions the same kind of electron transfer as encountered on the EHT level of theory, but they reveal additional complexities of the problem. The effect of the Bi to intercalating molecule electron transfer on the cuprate layer may be important, quite apart from this specific example, in tuning superconductivity in the cuprates.


Limitations in the use of 18F-FDG PET in the pre-operative staging of gastric cancer: A case series.
Positron emission tomography (PET) is a mainstay in the preoperative evaluation of various cancers. In gastric cancer however, its role in the initial staging remains contentious. Presented is a case series of three gastric patients wherein the use of fluorodeoxyglucose (18F-FDG) PET/CT (computer tomography) as part of the initial staging was inconsequential to treatment, demonstrating its limited role in the staging of primary gastric cancer. We analyzed retrospective data from 12/1/2010 to 10/31/2016 of patient with gastric cancer whose initial staging included a PET/CT. Only patients 18 years and older with gastric and gastro-oesophageal junction cancers were included. The data was derived from a single institution. Management of patients involved both an academic institution and a community practice. Of the three cases reported, an FDG-avid mass with minimal FDG uptake was reported in a single case and no FDG-avid lesion was reported in the other two. Neither of the patients underwent an endoscopic ultrasound for lack of availability. While various imaging studies such as endoscopic ultrasound have an established role in the initial staging, the role of FDG-PET is yet to be established and its routine use remains contentious. Based on our clinical experience and review of the literature, we believe FDG-PET/CT imaging is of limited clinical and cost effective value in the initial staging workup of gastric cancer.


Comparative effects of medium-chain fatty acids or phytobiotics-based feed additives on performance, caecum microbiota, volatile fatty acid production and intestinal morphology of broilers.
Antibiotic growth promoters have been utilized in broiler nutrition to alleviate the negative effects of the pathogenic microbes to promote performance. However, after the prohibition of antibiotics because of the increasing disclosure related to public health issues, various products have been developed as alternatives. This study was carried out to determine the effects of medium-chain fatty acids (MCFAs) or phytobiotics (essential oils [EOs] and alkaloids [ALKs]), blended feed additives on the growth performance, jejunum histomorphology, and cecal microbiota of broiler chickens. A total of 765 male Ross 308 chicks were randomly distributed into 5 experimental groups, each having 9 replicates with 17 chicks. The experimental procedures were as follows: a control group without supplementation (T1); control group+ MCFAs and EOs blend (T2); control group+ different EOs blend (T3); control group+ ALK sanguinarine (T4); and control group+ EOs and ALK piperine mixture (T5). The results showed that, broilers fed with MCFAs blended with EOs had significantly greater body weight gain during overall period in comparision to the control and T3 groups. Further, only MCFAs blended with EOs group significantly improved jejnum morphology in comparison with the control group (p ≤ 0.05). Besides, the MCFAs blended with EOs group significantly elevated propionate, acetate and butyrate concentration, and decreased the concentration of branch chain fatty acids in caecum (p ≤ 0.05). The results indicated that, the combination of MCFAs and EOs seems to have improvement effects and could be preferred as an efficient feed additive in broiler production.


Folding intermediates of wild-type and mutants of barnase. II. Correlation of changes in equilibrium amide exchange kinetics with the population of the folding intermediate.
There is an unanswered question from previous studies of 1H/2H-exchange of amide protons of barnase. Under certain conditions, there is a relatively abrupt change from EX2 towards EX1 kinetics as the temperature is slightly increased. The change in kinetics for different mutants is not directly related to their changes in stability. We have measured the stability of the folding intermediate of barnase (I) in 2H2O under a variety of conditions and calculated its population at different temperatures. The change in kinetics correlates with the change in the population of the folding intermediate. At higher temperatures and pH, the free energy of I becomes higher than that of the denatured state, D, and the kinetics becomes EX1. The data fit a simple kinetic scheme. Such changes in kinetics may be used to detect the presence of intermediates in the folding reaction at equilibrium in native conditions, but cannot distinguish whether they are on or off-pathway.


Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives.
Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.


T and B lymphocyte populations in uterus draining lymph nodes at estrus and diestrus in Wistar rats.
In this paper, data are presented on the characterization of uterus draining lymph nodes (UDLN) B and T lymphocytes of virgin rats at estrus (E) and diestrus (D). We established that the T/B lymphocyte relationship in the UDLN is less than one at estrus and more than one at diestrus. This is due to a decrease in the percentage and in the total number of mature T cell population in association with a decrease in the percentage of the OX8 subset in the UDLN at estrus. This situation may be related to an increase in estrogens known to produce thymic involution. These changes were not observed when we studied peripheral (popliteal) lymph nodes. The changes observed in the UDLN T cell population at estrus could be under hormonal control and we think that this condition may be important to prepare the immune system for an eventual pregnancy.


Disseminated Histoplasma capsulatum infection presenting as genital ulcerations.
Histoplasma capsulatum infection in adults is most often subclinical but can result in disseminated disease with weight loss, fever, hepatosplenomegaly, and oropharyngeal ulcerations. Genital ulceration as the presenting sign of the disease has been reported rarely. A 63-year-old woman presented with multiple vaginal ulcerations due to chronic disseminated H capsulatum infection. Initial diagnosis was made by Papanicolaou and Giemsa-stained vulvar smears. Ketoconazole therapy resulted in clearing of the lesions in 5 weeks. Chronic disseminated histoplasmosis is an insidious and potentially fatal disease that can present rarely as genital mucocutaneous ulcerations in women. Prompt presumptive diagnosis can be accomplished by examination of smears obtained by ulcer abrasion, permitting institution of appropriate therapy.


Phenotypic plasticity in the cercarial indices of human and rodent samples of Schistosoma mansoni (Digenea: Schistosomatidae).
In the epidemiology of schistosomiasis, the cercarial index (CI) has been used for several purposes, including the identification of the species of vertebrate host involved in transmission in a particular setting. The CI of samples of Schistosoma mansoni of human (BH) and rodent (CMO) origin have now been compared, in an attempt to identify morphological markers on cercariae that would indicate whether the eggs from which the cercariae have developed were produced in humans or in rodents. After silver-nitrate impregnation of the cercariae, the CI (and their reaction norms) for the antero-dorsal (AD), antero-lateral (AL) and tail-stem (U) sensory receptors were investigated. The data analysis was based on linear-regression methods, Levene's test for the equality of variances, pooled-variance independent t-tests, and discriminant analysis. The results indicated that CI varied with vertebrate-host origin, that the AD reaction norms were more consistent and plastic than the other reaction norms investigated, that there appeared to be no simple allometric relationship between any of the CI investigated and cercarial body length, and that the BH sample gave larger standard deviations and a higher incidence of mis-classification than the CMO, indicating some developmental instability in the sample of human origin. The relative instability of the BH sample was, however, possibly the result of the experimental procedures. As the parasites used to produce the BH sample had been isolated from humans fairly recently and then routinely maintained in mice, host-induced selection could have affected the sample, altering its CI and their reaction norms. The results of the discriminant analysis indicated that, of the indices investigated, AD was the best morphological marker for distinguishing human and rodent samples of S. mansoni.


Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and the upstream sequence of the Otx2 gene in embryonal carcinoma cells.
Vertebrate Hox and Otx genes encode homeodomain-containing transcription factors thought to transduce positional information along the body axis in the segmental portion of the trunk and in the rostral brain, respectively. Moreover, Hox and Otx2 genes show a complementary spatial regulation during embryogenesis. In this report, we show that a 1821-base pair (bp) upstream DNA fragment of the Otx2 gene is positively regulated by co-transfection with expression vectors for the human HOXB1, HOXB2, and HOXB3 proteins in an embryonal carcinoma cell line (NT2/D1) and that a shorter fragment of only 534 bp is able to drive this regulation. We also identified the HOXB1, HOXB2, and HOXB3 DNA-binding region on the 534-bp Otx2 genomic fragment using nuclear extracts from Hox-transfected COS cells and 12.5 days postcoitum mouse embryos or HOXB3 homeodomain-containing bacterial extracts. HOXB1, HOXB3, and nuclear extracts from 12.5 days postcoitum mouse embryos bind to a sequence containing two palindromic TAATTA sites, which bear four copies of the ATTA core sequence, a common feature of most HOM-C/HOX binding sites. HOXB2 protected an adjacent site containing a direct repeat of an ACTT sequence, quite divergent from the ATTA consensus. The region bound by the three homeoproteins is strikingly conserved through evolution and necessary (at least for HOXB1 and HOXB3) to mediate the up-regulation of the Otx2 transcription. Taken together, our data support the hypothesis that anteriorly expressed Hox genes might play a role in the refinement of the Otx2 early expression boundaries in vivo.


Evaluation of gastric emptying with the "uncut" Roux en Y technique.
Ten patients with benign gastric or duodenal disorders were consecutively included in the protocol evaluation of gastric emptying after the "uncut" Roux en Y to prevent the Roux en Y syndrome. There were no clinical complications. Its performance was not more complex from a technical viewpoint, and its morbility could be less that in other procedures. There are 2 important objections to the development of this procedure. First, the gastric emptying study shows no difference with the traditional Roux en Y emptying. And second, a definitive closure of the afferent fold is not achieved with the non-cutting linear stapling, the endoscopic control 6 months after surgery showing repermeation of the fold in 80% of the patients. The use of the technique was brought to a halt for its results were outside the standards of the protocol.


Cobalt and copper pyridylmethylphosphonates with two- and three-dimensional structures and field-induced magnetic transitions.
Two novel metal pyridylmethylphosphonates, namely, [Co(4-pmp)] (1) and [Cu(4-pmp)(H2O)] (2), (4-pmpH2 = 4-pyridylmethylphosphonic acid), have been hydrothermally synthesized and characterized by X-ray diffraction, infrared spectroscopy, elemental analysis, and thermogravimetric analysis. In compound 1, each {PO3C} tetrahedron is corner-shared with three {CoNO3} tetrahedra and vice versa, thus forming a one-dimensional (1-D) inorganic chain along the a axis containing 8-membered rings of [(Co-O-P-O)2]. The inorganic chains are further connected by a 4-pmp(2-) ligand, generating a 2-D layered structure. Compound 2 displays a three-dimensional (3-D) framework structure, in which the inorganic layers are pillared by the pyridyl groups of the ligand, generating a 3-D pillared-layered structure. The magnetic properties of 1 and 2 have been studied. Compounds 1 and 2 behave as metamagnets at low temperature. The critical fields are about 70 kOe for 1 and 47 kOe for 2 at 1.8 K.


Gonadotropin-releasing hormone couples to 3',5'-cyclic adenosine-5'-monophosphate pathway through novel protein kinase Cdelta and -epsilon in LbetaT2 gonadotrope cells.
GnRH regulates the reproductive system by stimulating synthesis and release of gonadotropins. GnRH acts through a receptor coupled to multiple intracellular events including a rapid phosphoinositide turnover. Although the cAMP pathway is essential for gonadotrope function, the ability of GnRH to induce cAMP, as well as the coupling mechanisms involved, remain controversial. In this study, we established that GnRH increases intracellular cAMP levels in a concentration-dependent manner in LbetaT2 gonadotrope cells (maximal increase, 2.5-fold; EC(50), 0.30 nm), and this was further evidenced by GnRH activation of a cAMP-sensitive reporter gene. The GnRH effect was Ca(2+) independent, mimicked by the phorbol ester phorbol 12-myristate 13-acetate, and blocked by the protein kinase C (PKC) inhibitor bisindolylmaleimide, indicating that the GnRH effect was mediated by PKC. Pharmacological inhibition of conventional PKC isoforms with Gö6976 did not prevent GnRH-induced cAMP production, whereas down-regulation of novel PKCdelta, -epsilon, and -theta by a long-term treatment with GnRH markedly reduced it. Expression of dominant-negative (DN) mutants of PKCdelta or -epsilon but not PKCtheta impaired GnRH activation of a cAMP-sensitive promoter, demonstrating that PKCdelta and -epsilon are the two endogenous isoforms mediating GnRH activation of the adenylyl cyclase (AC) pathway in LbetaT2 cells. Accordingly, we identified by RT-PCR and immunocytochemical analysis, two PKC-sensitive AC isoforms, i.e. AC5 and AC7 as potential targets for GnRH. Lastly, we showed that only sustained stimulation of GnRH receptor significantly increased cAMP, suggesting that in vivo, the cAMP signaling pathway may be selectively recruited under intense GnRH release such as the preovulatory GnRH surge.


Pre-Molecular Assessment of Self-Processes in Neurotypical Subjects Using a Single Cognitive Behavioral Intervention Evoking Autobiographical Memory.
In the last 20 years, several contributions have been published on what concerns the conceptual and empirical connections between self-processes. However, only a limited number of publications addressed the viability of those processes to characterize mental health in neurotypical subjects with a normative pattern of neurodevelopment. Furthermore, even fewer experiments focused explicitly on the complexity of studying neurotypical phenomenal data. On the one hand, this normative pattern is commonly associated with mental health and a multifaceted self-concept and well-being. On the other hand, well-being is often related to a healthy cognitive life. However, how such intricate and complex relation between self-processes is established in neurotypical subjects requires further evidence. The novelty of this work is thus studying the first-person experience, which is correlated with the mental events aroused by a cognitive behavioral intervention. The prior methodology that led to the complete characterization of a neurotypical sample was already published by the authors, although the materials, the methods, the sample screening, and the sample size study required further explanation and exploration. This paper's innovation is hence the phenomenological assessment of subjects' self-regulation, which is used for mental health profiling, providing the basis for subsequent molecular typing. For that matter, a convenience sample of 128 (19-25-year-old) neurotypical young adults, healthy university students at the University of Lisbon, non-medicated and with no serious, uncontrolled, or chronic diseases, are characterized according to their cognitive functioning and self-concept. The procedure comprised (i) a mental status examination (psychological assessment) and (ii) a psychological intervention, i.e., a single cognitive behavioral intervention (intervention protocol). The psychological assessment was a standardized and structured clinical interview, which comprised the use of 4 psychological scales complementary to the classical Mental Status Examination (MSE). The intervention protocol applied a combined exercise of psychophysical training and autobiographical-self memory-recalling. The results permitted identifying and isolating four different subgroups (self awareness, self consciousness, reflective self, and pre-reflective self) in neurotypical subjects with discrete self-processes. The outcome of this study is screening four different aspects of self-reflection and the isolation between various forms of self-directed attention and their interconnections in these four mental health strata. The practical implication of this study is to fulfill an a priori pre-molecular assessment of self-regulation with separate cognitive characteristics. The reliability of these mental strata, their distinct neurophysiology, and discrete molecular fingerprint will be tested in a future publication by in silico characterization, total protein profiling, and simultaneous immunodetection of the neuropeptide and neuroimmune response of the same participants.


Outcome of autosomal dominant polycystic kidney disease patients on peritoneal dialysis: a national retrospective study based on two French registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).
Pathological features of autosomal dominant polycystic kidney disease (ADPKD) include enlarged kidney volume, higher frequency of digestive diverticulitis and abdominal wall hernias. Therefore, many nephrologists have concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to analyse survival and technique failure in ADPKD patients treated with PD. We conducted two retrospective studies on patients starting dialysis between 2000 and 2010. We used two French registries: the French Renal Epidemiology and Information Network (REIN) and the French language Peritoneal Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same parameters were determined for ADPKD patients on PD (n = 797) and compared with those of non-ADPKD patients on PD (n = 12 059). A total of 5291 ADPKD patients and 12 059 non-ADPKD patients were included. Analysis of the REIN registry found that ADPKD patients treated with PD represented 10.91% of the ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher serum albumin levels (38.8 ± 5.3 versus 36.8 ± 5.7 g/dL, P < 0.0001) and were less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD patients was positively associated with the occurrence of a kidney transplantation but not with death [hazard ratio 1.15 (95% confidence interval 0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and better survival. ADPKD status was not associated with an increased risk of technique failure or an increased risk of peritonitis. According to our results, PD is proposed to a selected population of ADPKD patients, PD does not have a negative impact on ADPKD patients' overall survival and PD technique failure is not influenced by ADPKD status. Therefore PD is a reasonable option for ADPKD patients.


Buonocore Memorial Lecture. Dentin caries: progression and clinical management.
A fundamental issue of restorative treatment is assessing the different conditions of cases not only from tooth-to-tooth but also from the activity of each caries lesion and the size of the cavity. In addition, restorative treatment is sometimes carried out for prosthetic and cosmetic purposes and involves cutting sound, unaffected dentin. These aspects are outlined in classic textbooks and are based on the principles described by Black (1908). However, each factor and its relative importance has changed over the years. Significant time has been devoted to improving the important technical aspects of performing restorative treatment. Traditionally, these aspects have primarily been related to cavity design, choice of restorative material and the clinical procedures involved. In this context, Dr Michael Buonocore's contributions must be recognized because the adhesive technique he introduced has become an integral part of modern operative dentistry. Operative dentistry today also focuses on cavity design and selecting restorative materials. Less effort has been placed on incorporating what is known about the pattern of caries progression and how it relates to caries removal or excavation. Although the reaction pattern of the pulp-dentin organ is quite different in terms of the nature of active (rapid-progressing) and arrested (slow-progressing) lesions, no widespread major distinction has been made regarding the different restorative treatment approaches in these situations. This presentation updates the progression and clinical management of dentin caries and how it relates to treating deep caries lesions.


[Trends of utilization of information technologies in clinical laboratory and pathology domain].
The life expectancy of the Japanese population is one of longest in the world. Society is aging, with fewer children, increasing the total national medical payment in Japan. This situation has forced the Government to reduce the payment and to increase the efficiency of the medical system, so information technologies are expected to contribute to these policies. Electronic patient record systems (EPR) were expected to be used widely, but only 23% of clinical training hospitals have implemented them. This is mainly due to the lack of incentives and large costs to install EPR. Standardization is a good method to reduce system construction cost and increase its quality. New global IHE activities are expected to solve these problems with methodologies of workflow analyses, standard applications, tests and demonstrations. Laboratory information systems (LIS) have a long history and tradition of standard interfaces for connecting computers with analyzers. IHE activities for LIS are providing easy and secure connections with hospital information systems (HIS). Pathology departments also have their own information systems. IHE activities for pathology were launched in 2005, and we are now developing in collaboration with the international IHE pathology working group, HL7 SIG pathology and DICOM WG-26. Pathologists and technical experts in Japanese laboratories are encouraged to join IHE activities to ensure good results.


South African recommendations for the management of rheumatoid arthritis: an algorithm for the standard of care in 2013.
Updated treatment recommendations for the therapy of rheumatoid arthritis (RA) in South Africa advocate early diagnosis, prompt initiation of disease-modifying anti-rheumatic drugs (DMARDs), and an intense treatment strategy where disease activity is assessed with a composite score such as the Simplified Disease Activity Index (SDAI). Frequent assessments and escalation of therapy are necessary until low disease activity (LDA) (SDAI ≤11) or ideally remission (SDAI ≤3.3) is achieved. Synthetic DMARDs may be used as monotherapy or in combination, and can be co-prescribed with low-dose corticosteroids if necessary. Biologic DMARD therapy should be considered for patients who have failed a 6-month trial of at least 3 synthetic DMARDs. All RA patients in SA are at increased risk of tuberculosis (TB), in particular patients using anti-tumour necrosis factor (TNF) biologic therapy. These recommendations provide practical suggestions for the screening and management of TB and other comorbidities, and offer an approach to monitoring of RA patients.


Enhancement of ovulation by luteinizing hormone in cyclic albino rats.
Treatment of cyclic albino rats with equine luteinizing hormone (LH) on the afternoon of proestrus significantly enhanced ovulatory capacity. The number of ova shed and the healthy corpora lutea in the ovaries were significantly increased. Ovarian proteolytic enzymes also increased significantly with LH treatment. The histologically normal graafian follicles bound to become atretic in the vehicle-treated animals were altogether absent in the LH-treated rats on the day of estrus. These results indicate that LH enhances the number of ovulations by reducing the preovulatory follicles from atresia and facilitates their rupture by increasing the amount of proteolytic enzymes in them. A single injection of porcine follicle stimulating hormone (FSH), human chorionic gonadotrophin (hCG), and pregnant mare's serum gonadotrophin (PMSG) given separately was ineffective in inducing superovulation in cyclic albino rats.