Bronchial reactivity to exercise in bronchial asthma.
In 65 asthmatics the behaviour of resistance during and following physical exercise was analyzed. There could be distinguished 3 types: I. Decrease of resistance during exercise. II. Decrease of resistance during exercise, but increase during recovery phase. III. Increase with a maximum of 8 to 15 min following exercise. The most frequent type was type II. Type III was characterized by lower initial values of FEV 1.0 and the highest relation between expiratory and inspiratory resistance. The strongest reaction to acetylcholine occurred in types II and III. The results speak in favour of the fact that vegetative irritability as well as mechanical factors are of special importance in exercise-induced asthma.


Perinadine A, a novel tetracyclic alkaloid from marine-derived fungus Penicillium citrinum.
[structure: see text] A novel tetracyclic alkaloid, perinadine A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structure was elucidated on the basis of spectroscopic data including 2D NMR spectra. Biogenetically, perinadine A (1) may be derived from citrinin (4), a well-known mycotoxin, and a scalusamide A-type pyrrolidine alkaloid.


Evolution of the Bifunctional Lead μ Agonist / δ Antagonist Containing the Dmt-Tic Opioid Pharmacophore.
Based on a renewed importance recently attributed to bi- or multifunctional opioids, we report the synthesis and pharmacological evaluation of some analogues derived from our lead μ agonist / δ antagonist, H-Dmt-Tic-Gly-NH-Bzl. Our previous studies focused on the importance of the C-teminal benzyl function in the induction of such bifunctional activity. The introduction of some substituents in the para position of the phenyl ring (-Cl, -CH(3), partially -NO(2), inactive -NH(2)) was found to give a more potent μ agonist / antagonist effect associated with a relatively unmodified δ antagonist activity (pA(2) = 8.28-9.02). Increasing the steric hindrance of the benzyl group (using diphenylmethyl and tetrahydroisoquinoline functionalities) substantially maintained the μ agonist and δ antagonist activities of the lead compound. Finally and quite unexpectedly D-Tic2, considered as a wrong opioid message now; inserted into the reference compound in lieu of L-Tic, provided a μ agonist / δ agonist better than our reference ligand (H-Dmt-Tic-Gly-NH-Ph) and was endowed with the same pharmacological profile.


Proposal of a one-dimensional electron gas in the steps at the LaAlO3-SrTiO3 interface.
The two-dimensional electron gas at the interface between LaAlO(3) and SrTiO(3) has become one of the most fascinating and highly debated oxide systems of recent times. Here we propose that a one-dimensional electron gas can be engineered at the step edges of the LaAlO(3)/SrTiO(3) interface. These predictions are supported by first-principles calculations and electrostatic modeling which elucidate the origin of the one-dimensional electron gas as an electronic reconstruction to compensate a net surface charge in the step edge. The results suggest a novel route to increasing the functional density in these electronic interfaces.


Spiny neurons of amygdala, striatum, and cortex use dendritic plateau potentials to detect network UP states.
SPINY NEURONS OF AMYGDALA, STRIATUM, AND CEREBRAL CORTEX SHARE FOUR INTERESTING FEATURES: (1) they are the most abundant cell type within their respective brain area, (2) covered by thousands of thorny protrusions (dendritic spines), (3) possess high levels of dendritic NMDA conductances, and (4) experience sustained somatic depolarizations in vivo and in vitro (UP states). In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials ("dendritic UP states") characterized by (i) fast rise, (ii) plateau phase lasting several hundred milliseconds, and (iii) abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates toward the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200-800 ms) steady depolarization (∼20 mV amplitude), which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states). We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.


Successful treatment of tremor in Wilson's disease by thalamotomy: A case report.
Little information is available on the surgical treatment of movement disorders in Wilson's disease. We report a successful outcome of left-sided stereotactic thalamotomy in a 30-year-old man with Wilson's disease, who had severe postural-kinetic tremor of both hands. The improvement was bilateral. Our case illustrates that stereotactic thalamotomy may be considered as an option in treating severe tremor in selected patients of Wilson's disease and merit further trials.


Validation of brain-derived signals in near-infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging.
Near-infrared spectroscopy (NIRS) is a convenient and safe brain-mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near-infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n-back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross-validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte-Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributions of the brain and soft-tissue hemodynamics to the NIRS signals, and found that the contribution ratios were quite different across different NIRS channels in reality, presumably because of the structural complexity of the frontotemporal regions. Hum Brain Mapp 38:5274-5291, 2017. © 2017 Wiley Periodicals, Inc.


Note: Model-based identification method of a cable-driven wearable device for arm rehabilitation.
Cable-driven exoskeletons have used active cables to actuate the system and are worn on subjects to provide motion assistance. However, this kind of wearable devices usually contains uncertain kinematic parameters. In this paper, a model-based identification method has been proposed for a cable-driven arm exoskeleton to estimate its uncertainties. The identification method is based on the linearized error model derived from the kinematics of the exoskeleton. Experiment has been conducted to demonstrate the feasibility of the proposed model-based method in practical application.


A Permanent Lisa.
This article describes one collaborative arts-based research project. Portrait artist Mark Gilbert considers lessons for art and healing from one patient, Lisa. Lisa took comfort in the permanence of portraiture amidst the uncertainties of tongue cancer.


Cellular expression of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in normal kidney structures and in renal cancer. Possible significance in immune response and in the clinicopathological correlation.
In this study we investigated the presence of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on renal cell cancer in 16 patients who underwent nephrectomy. In all cases, normal renal tissues presented ICAM-1 on the parietal epithelial cells lining Bowman's capsule while neither the visceral epithelium nor the glomerular endothelium were stained. The epithelial proximal and distal tubular cells were stained poorly (5 +/- 3 positive tubular cross sections/mm2). No renal cells were stained by the monoclonal antibody for LFA-1. In contrast, in renal cancer tissue we found 6 cases, negative for ICAM-1 and the others positive with a mean number of positive tubular cross sections of 52 +/- 37/mm2. In 10 cases staining with LFA-1 antibody was negative, while for the other cases the mean number of positive tubular cross sections was 11 +/- 8/mm2. Our results suggest that the expression of ICAM-1 and LFA-1 on the surface of malignant cells may explain the unusual clinical aspects of renal cell carcinoma, its association with the immune system, and clarify certain aspects of immunotherapy.


Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells.
Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson's disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H₂O₂). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H₂O₂ were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H₂O₂ were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.


A Cation-Driven Approach toward Deep-Ultraviolet Nonlinear Optical Materials.
The design of new materials with special performances is still a great challenge, especially for the deep-ultraviolet nonlinear optical materials in which it is difficult to balance large bandgaps and strong second harmonic generation responses due to their inverse relationship. Cation variation not only influences the whole structure frameworks but also directly participates in the formation of electronic structures, both of which could lead to the uncontrollability of the properties of the designed materials. Here, a novel approach, aiming at purposeful and foreseeable material designs, is proposed to characterize the role of cations. By the verification of several series of borates, the influences of cation variation on property changes are explored systematically. Accordingly, a feasible strategy of designing deep-ultraviolet nonlinear optical materials by substituting barium for lead has been concluded, which could obviously blue-shift the ultraviolet cutoff edge and maintain the relatively strong second harmonic generation response (more than 2 times of KH2PO4), achieving the property optimization, and especially works efficiently in fluorooxoborates. The property optimization design strategy and the cation characterization method are not only helpful in exploring nonlinear optical materials but also enlightening in material design and selection.


[Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles].
Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.


[Antiphlogistic and antipyretic effect of sodium salicylate in rats and rabbits].
Inflammatory processes were provoked in 35 rats by subcutaneous implantation of sterile cotton-wool pads and treated five days by means of various antiphlogistic substances. The action of sodium salicylate (administered alone or in conjunction with gamma-globulin or with glucose) proved similar to that of prednisolone which was given as control substance. Human gamma-globulin exhibited neither anti-inflammatory nor pro-inflammatory effects. Experiments with twelve rabbits revealed that the pyretogenic potential of sodium nucleinate, one per cent (0.01 g/kg body weight) was stronger than that of animal charcoal or peptone. Yet, the two latter substances may be used, as well. The antipyretic effect of sodium salicylate was not as intensive but just as reliable as that of aminophenazone, when both preparations were applied to rabbits with induced fever. Concomitant administration of glucose is recommended to prevent development of undesired side-effects, such as giddiness or ataxia.


Cancer mortality among shoe and leather workers in Massachusetts.
A proportional mortality analysis of death certificates of 2,798 shoe and leather workers demonstrated a statistically significant excess of bladder cancer among female shoe workers (PMR = 2.51, 95% confidence interval 1.23 to 5.12). A case-referent analysis of 289 leather workers, on whom detailed occupational information was available, demonstrated an association of lung cancer with work in leather-tanning jobs (odds ratio = 4.2, 95% confidence interval 1.09 to 16.2).


Predicting the vulnerability of great apes to disease: the role of superspreaders and their potential vaccination.
Disease is a major concern for the conservation of great apes, and one that is likely to become increasingly relevant as deforestation and the rise of ecotourism bring humans and apes into ever closer proximity. Consequently, it is imperative that preventative measures are explored to ensure that future epidemics do not wipe out the remaining populations of these animals. In this paper, social network analysis was used to investigate vulnerability to disease in a population of wild orang-utans and a community of wild chimpanzees. Potential 'superspreaders' of disease--individuals with disproportionately central positions in the community or population--were identified, and the efficacy of vaccinating these individuals assessed using simulations. Three resident female orang-utans were identified as potential superspreaders, and females and unflanged males were predicted to be more influential in disease spread than flanged males. By contrast, no superspreaders were identified in the chimpanzee network, although males were significantly more central than females. In both species, simulating the vaccination of the most central individuals in the network caused a greater reduction in potential disease pathways than removing random individuals, but this effect was considerably more pronounced for orang-utans. This suggests that targeted vaccinations would have a greater impact on reducing disease spread among orang-utans than chimpanzees. Overall, these results have important implications for orang-utan and chimpanzee conservation and highlight the role that certain individuals may play in the spread of disease and its prevention by vaccination.


A unique high-performance wide-range (10-1500 eV) spherical grating monochromator beamline.
A wide-spectral-range high-performance 6 m-spherical grating monochromator (6 m-SGM) beamline has been designed and is under construction at SRRC. Two different entrance slits, instead of additional mirrors, are used to optimize the overall performance. Six gratings are used to cover photon energies from 10 to 1500 eV. Movable entrance slits and bendable vertical focusing mirrors are used to enhance further the beamline performance. A bendable horizontal focusing mirror is used to improve the resolution and to focus the photon beam at the experimental station immediately after the exit slit. Several end-stations can be installed at the same time to utilize the beam time fully. The expected energy-resolving power, with both slit openings set at 10 micro m, is up to 15 000 and 40 000 for the high- and low-energy branches, respectively. A photon flux of 1 x 10(11) photons s(-1) can be obtained with an energy-resolving power of 20 000.


Indoor air problems and experiences of injustice in the workplace: A quantitative and a qualitative study.
This study explores subjective injustice experiences of individuals suffering from suspected or observed indoor air problems in their workplaces in two studies. We focus on injustice experiences because they influence how individuals cope with and recover from health problems. The first study reports associations between the perceived harmfulness of the indoor environment (ie, mold/inadequate ventilation) and subjective injustice experiences in workplaces in a representative sample of Finnish working-aged people (N = 4633). Altogether, 37% of the respondents perceived their workplaces' indoor environments to be harmful. Multivariate logistic regression analyses revealed that the risks of reporting subjective injustice experiences (eg, information, attitudes, and remuneration) were significantly higher for those reporting harmful indoor environments compared to those who reported no such problems (OR 1.28-1.95 for different situations). The second study explored injustice experiences more closely by qualitatively analyzing the content of 23 essays. These essays were written by people who suffered from suspected or observed indoor air problems in their workplaces. The respondents reported multidimensional experiences of injustice, which related to conflicts, and moral exclusions. Awareness of these psychosocial effects is important for the prevention of unnecessary escalation of psychosocial problems in workplaces with observed and suspected indoor air problems.


Meteorin-like levels are associated with active brown adipose tissue in early infancy.
Meteorin-like (METRNL) is a hormonal factor released by several tissues, including thermogenically active brown and beige adipose tissues. It exerts multiple beneficial effects on metabolic and cardiovascular systems in experimental models. However, the potential role of METRNL as brown adipokine in humans has not been investigated previously, particularly in relation to the metabolic adaptations taking place in early life, when brown adipose tissue (BAT) is particularly abundant. METRNL levels, as well as body composition (DXA) and circulating endocrine-metabolic variables, were assessed longitudinally in a cohort of infants at birth, and at ages 4 and 12 months. BAT activity was measured by infrared thermography at age 12 months. METRNL levels were also determined cross-sectionally in adults; METRNL gene expression (qRT-PCR) was assessed in BAT and liver samples from neonates, and in adipose tissue and liver samples form adults. Simpson-Golabi-Behmel Syndrome (SGBS) adipose cells were thermogenically activated using cAMP, and METRNL gene expression and METRNL protein released were analysed. Serum METRNL levels were high at birth and declined across the first year of life albeit remaining higher than in adulthood. At age 4 and 12 months, METRNL levels correlated positively with circulating C-X-C motif chemokine ligand 14 (CXCL14), a chemokine released by thermogenically active BAT, but not with parameters of adiposity or metabolic status. METRNL levels also correlated positively with infrared thermography-estimated posterior-cervical BAT activity in girls aged 12 months. Gene expression analysis indicated high levels of METRNL mRNA in neonatal BAT. Thermogenic stimulus of brown/beige adipocytes led to a significant increase of METRNL gene expression and METRN protein release to the cell culture medium. Circulating METRNL levels are high in the first year of life and correlate with indices of BAT activity and with levels of an established brown adipokine such as CXCL14. These data, in addition with the high expression of METRNL in neonatal BAT and in thermogenically-stimulated brown/beige adipocytes, suggest that METRNL is actively secreted by BAT and may be a circulating biomarker of BAT activity in early life.


CDP-choline to promote remyelination in multiple sclerosis: the need for a clinical trial.
Multiple sclerosis is a multifactorial chronic inflammatory disease of the central nervous system that leads to demyelination and neuronal cell death, resulting in functional disability. Remyelination is the natural repair process of demyelination, but it is often incomplete or fails in multiple sclerosis. Available therapies reduce the inflammatory state and prevent clinical relapses. However, therapeutic approaches to increase myelin repair in humans are not yet available. The substance cytidine-5'-diphosphocholine, CDP-choline, is ubiquitously present in eukaryotic cells and plays a crucial role in the synthesis of cellular phospholipids. Regenerative properties have been shown in various animal models of diseases of the central nervous system. We have already shown that the compound CDP-choline improves myelin regeneration in two animal models of multiple sclerosis. However, the results from the animal models have not yet been studied in patients with multiple sclerosis. In this review, we summarise the beneficial effects of CDP-choline on biolipid metabolism and turnover with regard to inflammatory and regenerative processes. We also explain changes in phospholipid and sphingolipid homeostasis in multiple sclerosis and suggest a possible therapeutic link to CDP-choline.


Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space.
Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which results in a toxic polyglutamine stretch within huntingtin, the protein it encodes. Understanding the normal function of this essential protein is vital to understanding the root of the disease, yet despite more than a decade of investigation, its role in the cell remains elusive. Identifying the subcellular localization of huntingtin and understanding its effects on global gene expression are critical to this endeavor. While most reports agree that huntingtin is predominantly a cytoplasmic protein, conflicting distribution patterns have been demonstrated at the subcellular level. Here, we examine wild-type huntingtin's localization in cultured cells by expressing the full-length human protein tagged with enhanced green fluorescent protein (EGFP) within its unspliced genomic context. In fibrosarcoma and neuroblastoma cells, huntingtin shows discrete punctate, perinuclear localization overlapping largely with the trans-Golgi and cytoplasmic clathrin-coated vesicles, implicating huntingtin in vesicle trafficking. To determine whether huntingtin is involved in trafficking a specific subset of proteins, we measured changes in global transcription levels in embryonic stem cells and neurons lacking huntingtin. Huntingtin null neurons exhibit a significant reduction in transcripts encoding proteins destined for the extracellular space, many of which are components of the extracellular matrix or involved in cellular adhesion, receptor binding and hormone activity. Together, these findings support a role for huntingtin in the intracellular trafficking of proteins required for the construction of the extracellular matrix.


Immunohistochemical identification of heparan sulphate proteoglycan in secondary systemic amyloidosis.
The distribution of proteoglycans in kidneys from patients with secondary (AA) systemic amyloidosis was investigated. Antisera reacting with the protein cores of chondroitin sulphate proteoglycan (CSPG), dermatan sulphate proteoglycan (DSPG) and heparan sulphate proteoglycan (HSPG) were used in conjunction with the peroxidase-antiperoxidase (PAP) method. HSPG was the only proteoglycan found to be specifically localized to the amyloid deposits. The staining was most intense on the endothelial side of the deposits in both the glomeruli and in the vessel walls. No staining was observed after absorption of the HSPG antiserum with a fraction of the amyloid preparations, corresponding in size to that reported for glomerular HSPG. The possible role of HSPG and endothelial cells in the pathogenesis of the amyloid deposits is discussed.


Giant panda BAC library construction and assembly of a 650-kb contig spanning major histocompatibility complex class II region.
Giant panda is rare and endangered species endemic to China. The low rates of reproductive success and infectious disease resistance have severely hampered the development of captive and wild populations of the giant panda. The major histocompatibility complex (MHC) plays important roles in immune response and reproductive system such as mate choice and mother-fetus bio-compatibility. It is thus essential to understand genetic details of the giant panda MHC. Construction of a bacterial artificial chromosome (BAC) library will provide a new tool for panda genome physical mapping and thus facilitate understanding of panda MHC genes. A giant panda BAC library consisting of 205,800 clones has been constructed. The average insert size was calculated to be 97 kb based on the examination of 174 randomly selected clones, indicating that the giant panda library contained 6.8-fold genome equivalents. Screening of the library with 16 giant panda PCR primer pairs revealed 6.4 positive clones per locus, in good agreement with an expected 6.8-fold genomic coverage of the library. Based on this BAC library, we constructed a contig map of the giant panda MHC class II region from BTNL2 to DAXX spanning about 650 kb by a three-step method: (1) PCR-based screening of the BAC library with primers from homologous MHC class II gene loci, end sequences and BAC clone shotgun sequences, (2) DNA sequencing validation of positive clones, and (3) restriction digest fingerprinting verification of inter-clone overlapping. The identifications of genes and genomic regions of interest are greatly favored by the availability of this giant panda BAC library. The giant panda BAC library thus provides a useful platform for physical mapping, genome sequencing or complex analysis of targeted genomic regions. The 650 kb sequence-ready BAC contig map of the giant panda MHC class II region from BTNL2 to DAXX, verified by the three-step method, offers a powerful tool for further studies on the giant panda MHC class II genes.


Sensory Distribution of the Lateral Cutaneous Nerve of Forearm After Ultrasound-Guided Block: Potential Implications for Thumb-Base Surgery.
Surgery of the wrist and hand commonly involves regional anesthesia of the median nerve and superficial radial nerve within the forearm. In this sonographic study, the contribution of the lateral cutaneous nerve of forearm (LCNF) to thumb cutaneous sensation was studied. Patients scheduled for thumb suspension arthroplasty (n = 35) were examined by ultrasound, with LCNF, median nerve, and superficial radial nerve identified. A single nerve was then injected with local anesthetic, and the area of cutaneous sensory loss mapped at 15 minutes. The remaining 2 nerves were then blocked for progression to theater. In 15 patients, the LCNF was blocked first at the antecubital fossa, where it was located posterior to the cephalic vein 9.1 (1.6) mm distal to the interepicondylar line. Bifurcation occurred further distally, 18 (2.6) mm from the interepicondylar line. In 14 of 15 cases, LCNF sensory distribution extended to the thumb base, 8.3 (7.8) mm distal to the radiocarpal joint. This study has demonstrated the LCNF to innervate the thumb base, indicating neural blockade of this nerve may be required for surgery of the basal thumb joint.


Doppler ultrasound in the diagnosis of renal transplant artery stenosis--value of resistive index.
Doppler ultrasound (DU) with angiographic correlation was performed in 19 hypertensive renal transplant recipients suspected for transplant artery stenosis. DU included calculation of the intrarenal resistive index (RI) and measurement of the maximum systolic velocity in the transplant artery. All 10 cases having a pathologically low RI (< or = 0.6) had a > or = 50% stenosis; specificity and positive predictive values were thus 100%. There were 5 false-negative diagnoses, sensitivity 67%. The measurement of maximum systolic velocity was feasible in only 15 cases (79%). Using a cut-off point of 2 m/s the sensitivity was 91% and there were 4 false-positive cases and one false-negative case. Balloon percutaneous transluminal angioplasty (PTA) was performed in 13 cases, of which 9 were successful. In all successful cases RI was < 0.6 after PTA. We conclude that low RI (< 0.6) is highly suggestive for transplant artery stenosis. RI may serve as an indicator of the hemodynamic success of PTA.


The quality of psychiatric residency : the assessment of programs and options for distributing psychiatric residents in the service of health care reform.
Recent health care reform initiatives proposed training fewer medical specialists, including psychiatrists, and determining the size and location of training programs via centralized regulatory mechanisms. Facing such potential future developments, the American Association of Directors of Psychiatric Residency Training appointed a Task Force on the Quality of Residency Programs to develop informed recommendations for the field. This paper describes the Task Force's considerations and recommendations concerning how the least damaging and most effective decisions could be made regarding the distribution of residency positions, program size, and the future funding of training stipends. The recommendations emphasize voluntary decisions, feedback from local and regional stakeholders regarding perceived needs and demands for psychiatrists, and Federal or regional funding of postgraduate training stipends that are not primarily tied to providing clinical services.


Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias.
Ranolazine is currently approved as an antianginal agent in patients with chronic angina (class IIA). Ranolazine exhibits antiarrhythmic effects that are related to its multichannel blocking effect, predominantly inhibition of late sodium (late INa) current and the rapid potassium rectifier current (IKr), as well as ICa, late ICa, and INa-Ca. It also suppresses the early and delayed after depolarizations. Ranolazine is effective in the suppression of atrial and ventricular arrhythmias (off-label use) without significant proarrhythmic effect. Currently, ongoing trials are evaluating the efficacy and safety of ranolazine in patients with cardiac arrhythmias; preliminary results suggest that ranolazine, when used alone or in combination with dronedarone, is safe and effective in reducing atrial fibrillation. Ranolazine is not currently approved by the US Food and Drug Administration as an antiarrhythmic agent.


Suppressing the Photocatalytic Activity of Zinc Oxide Electron-Transport Layer in Nonfullerene Organic Solar Cells with a Pyrene-Bodipy Interlayer.
Organic solar cells based on nonfullerene acceptors have recently witnessed a significant rise in their power conversion efficiency values. However, they still suffer from severe instability issues, especially in an inverted device architecture based on the zinc oxide bottom electron transport layers. In this work, we insert a pyrene-bodipy donor-acceptor dye as a thin interlayer at the photoactive layer/zinc oxide interface to suppress the degradation reaction of the nonfullerene acceptor caused by the photocatalytic activity of zinc oxide. In particular, the pyrene-bodipy-based interlayer inhibits the direct contact between the nonfullerene acceptor and zinc oxide hence preventing the decomposition of the former by zinc oxide under illumination with UV light. As a result, the device photostability was significantly improved. The π-π interaction between the nonfullerene acceptor and the bodipy part of the interlayer facilitates charge transfer from the nonfullerene acceptor toward pyrene, which is followed by intramolecular charge transfer to bodipy part and then to zinc oxide. The bodipy-pyrene modified zinc oxide also increased the degree of crystallization of the photoactive blend and the face-on stacking of the polymer donor molecules within the blend hence contributing to both enhanced charge transport and increased absorption of the incident light. Furthermore, it decreased the surface work function as well as surface energy of the zinc oxide film all impacting in improved power conversion efficiency values of the fabricated cells with champion devices reaching values up to 9.86 and 11.80% for the fullerene and nonfullerene-based devices, respectively.


Rapid Detection and Identification of Uveitis Pathogens by Qualitative Multiplex Real-Time PCR.
Infectious uveitis is a serious sight-threatening infection commonly caused by herpesviruses and Toxoplasma gondii. Etiologic diagnosis based on the clinical evaluation is often challenging. We developed and validated a multiplex real-time PCR assay coupled with high-resolution melting (HRM) for rapid detection and identification of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), and T. gondii. The assay was designed to target pathogen genome regions that yield products with distinct melting temperatures. Analytical specificity, sensitivity, and precision of HRM identification were determined. Clinical validation was performed by testing 108 intraocular fluids collected from eyes suffering with infectious uveitis (n = 30) and controls (n = 78). A nonoverlapping high-precision profile for each pathogen was generated following HRM (coefficient of variation 0%). The assay was highly sensitive, with a limit of detection of 20 genome copies for herpesviruses and 200 genome copies for T. gondii. The intra- and interassay variability of cycle threshold (Ct) measurement was ≤4% and ≤6%, respectively. Thirteen intraocular specimens collected from suspected cases of infectious uveitis were positive (mean Ct values varied from 19.4 to 27.7). Melting profiles of positive cases were consistent with HSV-2 (n = 5), VZV (n = 5), CMV (n = 2), and T. gondii (n = 1). Amplicon identities were confirmed by sequencing. Control intraocular samples from patients without a clinical diagnosis of infectious uveitis were all negative. This assay allows rapid, sensitive, and reliable detection and identification of the most common known causes of infectious uveitis, making early pathogen information-based intervention possible.


[Pseudotumoral form of abdominal tuberculosis: report of four cases].
To report the imaging features of four cases of pseudo-tumoral abdominal tuberculosis in order to demonstrate diagnostic difficulties, even in endemic areas, despite expanding imaging modalities. We have retrospectively reviewed four cases investigated in our hospital between 1998 and 2002. The first case concerned a 2 year and 6 month old boy admitted for a right iliac fossa mass. The other patients were 43 and 48 year old women admitted for epigastric mass and persistent epigastric pain with past history of treated tuberculosis respectively. The last was an 86 year old man investigated because progressive worsening of general health. Sonography (US) and computed tomography (CT) were performed in all four cases. Involvement of the ileocaecal region was noted in three cases. Large intestinal hypervascular mass in the pediatric case, heterogeneous mass with porta hepatis lymph node in the patient with past history of treated tuberculosis, pseudotumoral caecal wall thickening in the third case. The multiloculated pattern of the epigastric mass and its location initially suggested a diagnosis of pancreatic tumor. Abdominal tuberculosis is rare even in endemic areas. This diagnosis must be considered when imaging modalities depict a hypervascular soft tissue mass on Doppler examination with peripheral enhancement on CT scan.


A new mutation in exon 7 of NEMO gene: late skewed X-chromosome inactivation in an incontinentia pigmenti female patient with immunodeficiency.
Incontinentia pigmenti is an X-linked genodermatosis, lethal in males. Affected females survive because of X-chromosome dizygosity and negative selection of cells carrying the mutant X-chromosome, and for this reason the skewed X inactivation pattern is often used to confirm the diagnosis. The most frequent mutation is a deletion of part of the NEMO gene (NEMODelta4-10), although other mutations have been reported. Mutations of NEMO which do not abolish NF-kappaB activity totally permit male survival, causing an allelic variant of IP called hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID). We present a non-classical IP female patient who also suffered transient immunodeficiency because of a late and progressive selection against peripheral blood cells carrying an active mutated X-chromosome. This finding suggests that in the absence of known mutation the X-inactivation studies used in genetic counselling can induce mistakes with some female patients. At the age of 3 years and 6 months, all immunodeficiency signs disappeared, and the X-chromosome inactivation pattern was completely skewed. The low T cell proliferation and CD40L expression corroborate the important role of NEMO/ NF-kappaB pathway in T cell homeostasis. The decreased NEMO protein amount and the impaired IkBalpha degradation suggest that this new mutation, NM_003639: c.1049dupA, causes RNA or protein instability. To our knowledge, this is the first time that selection against the mutated X-chromosome in X-linked disease has been documented in vivo.


Dosimetry of 131I-labeled 81C6 monoclonal antibody administered into surgically created resection cavities in patients with malignant brain tumors.
The objective of this study was to perform the dosimetry of 131I-labeled 81C6 monoclonal antibody (MAb) in patients with recurrent malignant brain tumors, treated by direct injections of MAb into surgically created resection cavities (SCRCs). Absorbed dose estimates were performed for nine patients. Dosimetry was performed retrospectively using probe counts (during patient isolation) and whole-body and SPECT images thereafter. Absorbed doses were calculated for the SCRC interface and for regions of interest (ROIs) 1 and 2 cm thick, measured from the margins of cavity interface. Also, mean absorbed doses were calculated for normal brain, liver, spleen, thyroid gland, stomach, bone marrow and whole body. The average residence time for the SCRC was 111 h (65-200h). The average absorbed dose per unit injected activity (range) to the SCRC interface and ROIs 1 and 2 cm thick from the cavity interface were 31.9 (7.8-84.2), 1.9 (0.7-3.6) and 1.0 (0.4-1.8) cGy/MBq, respectively. Average absorbed doses per unit administered activity to brain, liver, spleen, thyroid, stomach, bone marrow and whole body were 0.18, 0.03, 0.08, 0.05, 0.02, 0.02 and 0.01 cGy/MBq, respectively. The high absorbed dose delivered to the SCRC interface may have produced an increase in cavity volume independent of tumor progression. At the maximum tolerated dose of 3700 MBq 131I-labeled 81C6 MAb, the absorbed doses to the SCRC interface and ROIs of 1 and 2 cm thickness were estimated to be 1180, 71 and 39 Gy, respectively. The estimated average absorbed dose to the brain was 6.5 Gy. There was no neurological toxicity and minimal hematologic toxicity at this maximum tolerated administration level.


Pulmonary arteriovenous fistula presenting as multiple brain abscess.
Pulmonary arteriovenous fisula is a rare condition in which there is abnormal connection between pulmonary arteries and veins. We describe this condition is an 18-year-old male who presented with cyanosis, clubbing, polycythemia and multiple brain abscesses. The patient was diagnosed as pulmonary arteriovenous fistula based on CT scan and on pulmonary angiography. The patient had a complete recovery after surgical drainage of brain abscess and excision of right upper lobe. After one year of follow up, there are no symptoms and there is complete reversal of cyanosis and polycythemia.


Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives.
As a therapeutic target for antitumor necrosis factor (TNF)-α interventions, UbcH5c is one of the key ubiquitin-conjugating enzymes catalyzing ubiquitination during TNF-α-triggered nuclear factor kappa B (NF-κB) activation. In the present study, three series of analogues were designed and synthesized from α-santonin, and their UbcH5c inhibitory activities were screened by Western blotting and NF-κB luciferase assay. Further BIAcore, in-gel fluorescence imaging, and immunoprecipitation assays demonstrated that compound 6d exhibited robust and specific inhibition of UbcH5c, exceeding that of the positive compound 1 (IJ-5). Mechanistic investigations revealed that compound 6d preferentially bound to and inactivated UbcH5c by forming a covalent adduct with its active site Cys85. Furthermore, compound 6d exhibited potent anti-inflammatory activity against complete Freund's adjuvant-induced adjuvant arthritis in vivo. These findings suggest that the novel α-santonin-derived UbcH5c inhibitor 6d is a promising lead compound for the development of new antirheumatoid arthritis (RA) agent.


Multitask protocols to evaluate activities of daily living performance in people with COPD: a systematic review.
People with chronic obstructive pulmonary disease (COPD) present symptoms such as dyspnea and fatigue, which hinder their performance in activities of daily living (ADL). A few multitask protocols have been developed to assess ADL performance in this population, although measurement properties of such protocols were not yet systematically reviewed. Areas covered: Studies were included if an assessment of the ability to perform ADL was conducted in people with COPD using a (objective) performance-based protocol. The search was conducted in the following databases: Pubmed, EMBASE, Cochrane Library, PEDro, CINAHL and LILACS. Furthermore, hand searches were conducted. Expert commentary: Up to this moment, only three protocols had measurement properties described: the Glittre ADL Test, the Monitored Functional Task Evaluation and the Londrina ADL Protocol were shown to be valid and reliable whereas only the Glittre ADL Test was shown to be responsive to change after pulmonary rehabilitation. These protocols can be used in laboratory settings and clinical practice to evaluate ADL performance in people with COPD, although there is need for more in-depth information on their validity, reliability and especially responsiveness due to the growing interest in the accurate assessment of ADL performance in this population.


Effects of soy consumption on serum lipids and apoproteins in peritoneal dialysis patients: a randomized controlled trial.
Lipid abnormalities, particularly high serum concentration of lipoprotein(a) [Lp(a)], are one of the major risk factors for cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. The present study was designed to investigate the effects of soy consumption on serum lipids and apoproteins, especially Lp(a), in PD patients. ♢ This study was a randomized clinical trial in which 40 PD patients (20 males, 20 females) were randomly assigned to either the soy or the control group. Patients in the soy group received 28 g/day textured soy flour (containing 14 g of soy protein) for 8 weeks, whereas patients in the control group received their usual diet, without any soy. At baseline and the end of week 8 of the study, 5 mL of blood was collected from each patient after a 12- to 14-hour fast and serum triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), apoprotein B100 (apo B100), apoprotein AI (apo AI), and Lp(a) were measured. ♢ In the present study, serum Lp(a) concentrations were above the normal range in 86% of the PD patients. Mean serum Lp(a) concentration was reduced significantly, by 41%, in the soy group at the end of week 8 compared to baseline (p < 0.01); the reduction was also significant compared to the control group (p < 0.05). During the study, mean serum Lp(a) concentration did not change significantly in the control group. There were no significant differences between the two groups in mean changes in serum triglyceride, total cholesterol, HDL-C, LDL-C, apo B100, or apoAI. ♢ The results of our study indicate that soy consumption reduces serum Lp(a) concentration, which is a risk factor for cardiovascular disease in peritoneal dialysis patients.


Fabrication of a metal membrane on a perforated polymer substrate by palladium aerosol activation and subsequent electroless plating.
Fabrication of a metal membrane on a perforated flexible poly(tetrafluoroethylene) (PTFE) substrate was developed by employing spark-generated palladium (Pd) aerosol activation and the subsequent electroless plating of Pd. After aerosol activation, Pd agglomerates of spark-generated primary particles (approximately 2.6 nm in diameter) with a face-centered-cubic structure were deposited uniformly on the PTFE substrate. Homogeneous Pd particles with an average size of 188 nm were tightly packed together to form a Pd membrane after Pd plating. The average plating rate of Pd during 30 min of plating at an activation intensity of 25 microg/cm(2) was 14.2 microg/cm(2) x min.


Gardening as a therapeutic intervention in mental health.
This article describes why one low-secure unit chose to initiate a horticultural therapy project and organise it as a 'workers' cooperative'. The therapeutic benefits of gardening are explored, particularly focusing on the social benefits. The article also discusses the issue of hope, which is an intrinsic requirement in gardening.


Decreased numbers of pulmonary blood vessels: reality or artifact?
A decrease in numbers of pulmonary arteries has been implicated in various forms of both human and experimental pulmonary hypertension. However, data in support of this hypothesis have not been conclusive. Especially, intravascular fixation under pressure and the size of the areas of lung tissue subjected to quantitation, may have influenced the results. In order to investigate these factors, we fixed lungs of ten normal rats in three different ways, i.e. by perfusion of the pulmonary vasculature, by immersing collapsed lungs and by instilling the fixative through the trachea with intact thoracic cavity. Subsequently, blood vessels were counted in histological sections. Our study illustrates that perfusion of vessels under pressure decreases the number of recognizable arteries. Also the small areas, used in previous studies for counting vessels, produce unreliable results. Our conclusion is that a decreased number of lung vessels as a factor in pulmonary resistance has not been conclusively demonstrated.


Granular Cell Tumor: Report of 13 Cases in a Veterans Administration Hospital.
Granular cell tumors (GCTs) are of neuroectodermal origin and account for 0.5% of soft tissue tumors. They are most prevalent in African-Americans in the fourth to sixth decades, with a predilection for the head and neck regions. GCTs usually resemble more common lesions and hence are difficult to diagnose preoperatively. The tumor is readily identified on needle biopsy. Although usually benign with a malignancy rate of only 2-3%, the malignant form has a reported 3-yr mortality of 60%. Clinical records of the Gulf Coast Veterans Healthcare System were surveyed for the period 1996-2016. Thirteen cases of GCT were found and reviewed for demographics, clinical course, method of diagnosis, management, and outcome. All patients had a solitary GCT. Eleven lesions were benign and two were atypical. Sites involved were skin (8), colon (2), larynx (1), bronchus (1), and esophagus (1) (see Table I). The two atypical lesions occurred in the skin and larynx. Skin tumors were slow-growing, painful nodules, and, except for the two with preoperative needle biopsies, were misdiagnosed as epidermal inclusion cysts, lipoma, and papillary condyloma. Two colon lesions resembling a sessile polyp and submucosal lipoma, respectively, were found on colonoscopy performed for occult blood in the stool. The bleeding was attributed to adenomatous polyps also present. An atypical laryngeal GCT, found on laryngoscopy for hoarseness, was removed by submucosal resection. A bronchial GCT, excised during bronchoscopy for atelectasis, required re-excision 3 mo later. The esophageal GCT was an incidental finding on EGD for a dilated esophagus and gastric outlet obstruction. The patient declined surgical excision and elected MRI follow-up. Granular cell tumors are infrequent and usually resemble more common lesions. Although almost always benign, the malignant form has a very poor prognosis. It is important to identify GCT preoperatively by fine-needle aspiration or core needle biopsy to improve outcome.


Prevalence of elevated Anti-p53 in Chinese patients with upper gastrointestinal or colorectal cancer.
The monitoring of anti-p53 auto-antibodies in the peripheral blood has been used in cancer management; however, their clinical significance alone is limited. This pilot study aimed to describe the prevalence of elevated anti-p53 in newly diagnosed or recurrent upper gastrointestinal cancer or colorectal cancer in Chinese subjects. It also evaluated whether the addition of anti-p53 to a set of established tumor markers would allow for the detection of additional cancer cases than when using these markers alone. A total of 573 subjects, including 187 healthy individuals, 169 patients with upper gastrointestinal cancer and 217 patients with colorectal cancer were included in this observational, prospective study. All subjects were required to provide up to 10 mL of blood. The following biomarkers were measured: anti-p53, carcinoembryonic antigen, cancer antigen (CA)19-9, and CA72-4. At the cutoff of 0.02 µg/mL, the sensitivity of anti-p53 in early-stage upper gastrointestinal cancer and colorectal cancer was 8.16% and 26.4%, and in late-stage disease was 7.81 and 28.0%, respectively. The specificity of anti-p53 in the healthy cohort at this cutoff was 98.4%. By adding anti-p53 to other tumor markers, the sensitivities were increased by 8.88%-9.47% in upper gastrointestinal cancer, and by 18.06%-25.00% in colorectal cancer; specificities decreased by 1%-2%. The addition of anti-p53 to established tumor markers may improve their diagnostic value for patients with colorectal cancer.


Noninvasive evaluation of HABP1 expression with 99mTc-labeled small-interference RNA in ovarian cancer.
Ovarian cancer is one of the most common gynecological cancers in women with a low 5-year survival rate. Evaluation of hyaluronic acid-binding protein 1 (HABP1) level can provide important information for the diagnosis and treatment of ovarian cancer. In this study, we designed a novel HABP1 probe based on 99mTc-radiolabeled small-interference RNA (siRNA) for detecting HABP1 expression noninvasively in vivo, thereby providing a new method for its diagnosis and treatment. A specific siHABP1 was selected because of its targetability and silencing effect. A negative control siRNA (NCsiRNA) with no homology with the human genome was used. SiHABP1 and NCsiRNA were radiolabeled with 99mTc using the bifunctional chelating agent hydrazinonicotinamide (HYNIC). The radiochemical purity and in vitro stability of the probe were determined by HPLC. The binding activity was measured by western blotting (WB) and RT-PCR. The HABP1-overexpressing human ovarian cancer cell line HO-8910 was used for cell uptake experiments, which were performed with or without transfection and measured with a gamma counter. HO8910-bearing mice were imaged at 1, 4, and 10 h, and biodistribution analysis was performed at 1, 4, 6, and 10 h after injection of 99mTc-HYNIC-siRNA. 99mTc-HYNIC-siHABP1 had high radiochemical purity and good in vitro stability, and showed the same binding capacity and silencing effect as siHABP1. SPECT imaging showed that tumors were clearly visualized at 10 h after injection of 99mTc-HYNIC-siHABP1 but not after 99mTc-HYNIC-NCsiRNA, implying specific binding. The biodistribution results were consistent with those of SPECT imaging. We showed that 99mTc-HYNIC-siHABP1 is a feasible probe for the noninvasive visualization of HABP1 expression in ovarian cancer.


MicroRNA-548c-3p inhibits T98G glioma cell proliferation and migration by downregulating c-Myb.
MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G1 cell cycle arrest and also inhibited the migration of the T98G cells in vitro. Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment.


Small heat shock protein 27 mutation in a Japanese patient with distal hereditary motor neuropathy.
Heat shock protein 27 (HSP27) belongs to a family of small heat shock proteins that play significant roles in the cellular stress response and are also involved in the control of protein-protein interactions as chaperons. Mutation in HSP27 has been identified as the cause of axonal Charcot-Marie-Tooth disease (CMT) and distal hereditary motor neuropathy (HMN). Heat shock protein 22 (HSP22) is a molecular counterpart of HSP27, and its mutation is another cause of distal HMN. We screened the mutation of HSP27 and HSP22 in 68 Japanese patients with axonal CMT or unclassified CMT and six Japanese patients with distal HMN. We detected a heterozygous P182S mutation of HSP27 in a patient with distal HMN, but we found no mutations in HSP22. Mutation in HSP27 may impair the formation of the stable neurofilament network that is indispensable for the maintenance of peripheral nerves.


Multilayered nanocomposite polymer colloids using emulsion polymerization stabilized by solid particles.
We report a versatile emulsion polymerization process in which solid nanoparticles are used as stabilizer, thereby replacing the role of surfactants, allowing for simple fabrication of armored nanocomposite polymer latexes. Use of a second conventional seeded emulsion polymerization step provides a straightforward route to more complex multilayered nanocomposite polymer colloids.


Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1, and regulatory T-cell induction.
Mammalian target of rapamycin (mTOR) is an important, yet poorly understood integrative kinase that regulates immune cell function. mTOR functions in 2 independent complexes: mTOR complex (mTORC) 1 and 2. The immunosuppressant rapamycin (RAPA) inhibits mTORC1 but not mTORC2 and causes a paradoxical reduction in anti-inflammatory interleukin (IL) 10 and B7-homolog 1 (B7-H1) expression by dendritic cells (DCs). Using catalytic mTOR inhibitors and DCs lacking mTORC2, we show that restraint of signal transducer and activator of transcription 3-mediated IL-10 and B7-H1 expression during DC maturation involves a RAPA-insensitive and mTORC2-independent mTOR mechanism. Relatedly, catalytic mTOR inhibition promotes B7-H1-dependent and IL-1β-dependent DC induction of regulatory T cells (Tregs). Thus, we define an immunoregulatory pathway in which RAPA-sensitive mTORC1 in DCs promotes effector T-cell expansion and RAPA-insensitive mTORC1 restrains T(reg) induction. These findings identify the first known RAPA-insensitive mTOR pathway that is not mediated solely by mTORC2 and have implications for the use of catalytic mTOR inhibitors in inflammatory disease settings.


Feasibility of feline coxofemoral arthroscopy using a supratrochanteric lateral portal: A cadaveric study.
To evaluate the feasibility of feline diagnostic coxofemoral arthroscopy. Ex vivo feline cadaveric descriptive study. Seven feline cadavers (14 hips). Gross dissection of two feline hips was performed to evaluate anatomic landmarks, guide arthroscopic portal development, and determine optimal limb positioning. A 1.9 mm, 0° arthroscope, inserted through a supratrochanteric lateral portal, was used to assess intraarticular structures in 12 feline cadaver hips. Arthroscopy was followed by gross dissection of periarticular soft tissues. Relative portal locations and damage to periarticular structures were recorded. Hips were disarticulated, and an India ink assay was performed to assess whether there was iatrogenic cartilage injury (ICI). Scope insertion was achieved in all hips. Articular cartilage of the femoral head and acetabulum, round ligament, joint capsule, transverse acetabular ligament, and dorsal acetabular rim were identified arthroscopically in all hips. Probe insertion and intra-articular structure palpation was achieved in all hips. Scope and instrument portals resulted in minimal periarticular muscle trauma. No sciatic nerve damage was detected. Minor partial thickness ICI was observed in all hips at the site of scope insertion. Focal full thickness ICI was noted in one hip. Arthroscopy of the feline coxofemoral joint allowed visual and probe evaluation of intra-articular structures without evidence of major periarticular neurovascular trauma. Iatrogenic cartilage injury occurred in all hips but severity of lesions was considered mild. Coxofemoral arthroscopy is feasible in cats and can be utilized as a diagnostic tool for minimally invasive joint evaluation.


Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice.
Smooth muscle cells (SMCs) and the extracellular matrix (ECM) are intimately associated in the aortic wall. Fbln4(SMKO) mice with an SMC-specific deletion of the Fbln4 gene, which encodes the vascular ECM component fibulin-4, develop ascending aortic aneurysms that have increased abundance of angiotensin-converting enzyme (ACE); inhibiting angiotensin II signaling within the first month of life prevents aneurysm development. We used comparative proteomics analysis of Fbln4(SMKO) aortas from postnatal day (P) 1 to P30 mice to identify key molecules involved in aneurysm initiation and expansion. At P14, the actin depolymerizing factor cofilin was dephosphorylated and thus activated, and at P7, the abundance of slingshot-1 (SSH1) phosphatase, an activator of cofilin, was increased, leading to actin cytoskeletal remodeling. Also, by P7, biomechanical changes and underdeveloped elastic lamina-SMC connections were evident, and the abundance of early growth response 1 (Egr1), a mechanosensitive transcription factor that stimulates ACE expression, was increased, which was before the increases in ACE abundance and cofilin activation. Postnatal deletion of Fbln4 in SMCs at P7 prevented cofilin activation and aneurysm formation, suggesting that these processes required disruption of elastic lamina-SMC connections. Phosphoinositide 3-kinase (PI3K) is involved in the angiotensin II-mediated activation of SSH1, and administration of PI3K inhibitors from P7 to P30 decreased SSH1 abundance and prevented aneurysms. These results suggest that aneurysm formation arises from abnormal mechanosensing of SMCs resulting from the loss of elastic lamina-SMC connections and from increased SSH1 and cofilin activity, which may be potential therapeutic targets for treating ascending aortic aneurysms.


Digestive tract reconstruction after laparoscopic proximal gastrectomy for Gastric cancer: A systematic review.
The incidence of gastroesophageal junction adenocarcinoma has gradually increased. Proximal gastrectomy or total gastrectomy is recommended for early gastric cancer of the upper third of the stomach. Because total gastrectomy is often accompanied by body mass loss and nutrient absorption disorders, such as severe hypoproteinemia and anemia, Proximal gastrectomy is more frequently recommended by researchers for early upper gastric cancer (T1N0M0) and Siewert II gastroesophageal junction cancer less than 4 cm in length. Although some functions of the stomach are retained after proximal gastrectomy, the anatomical structure of the gastroesophageal junction can be destroyed, and the anti-reflux effect of the cardia is lost. In recent years, as various reconstruction methods for anti-reflux function have been developed, some functions of the stomach are retained, and serious reflux esophagitis is avoided after proximal gastrectomy. In this article, we summarized the indications, advantages, and disadvantages of various classic reconstruction methods and latest improved reconstruction method including esophageal and residual stomach anastomosis, tubular gastroesophageal anastomosis, muscle flap anastomosis, jejunal interposition, and double-tract reconstruction.


Odd [n]Cumulenes (n = 3, 5, 7, 9): Synthesis, Characterization, and Reactivity.
In comparison to the omnipresent two- and three-dimensional allotropes of carbon, namely, graphite and diamond (as well as recent entries graphene, carbon nanotubes, and fullerenes), a detailed understanding of the one-dimensional carbon allotrope carbyne is not well established, and even the existence of carbyne has been a matter of controversy over the past decades. Composed of sp-hybridized carbon, carbyne could potentially exist in two forms, either as a polyyne (alternating single and triple bonds, expected to show a semiconducting behavior) or as a cumulene (all carbon atoms are connected via double bonds, predicted to show metallic behavior). Although a number of publications are available on the hypothetical structure and properties of carbyne, specific knowledge about its physical and spectroscopic characteristics is still unclear. In order to predict the properties of carbyne, the synthesis and study of model compounds, namely, polyynes and cumulenes, has been a promising avenue. The synthesis of polyynes has been extensively explored in the last decades, culminating with the isolation of a polyyne with 22 acetylene units, which allows extrapolation to the properties of carbyne. Extended cumulenes, on the other hand, have remained much less well-known, and specific studies of properties versus molecular length are quite limited. A limiting factor to the study of [n]cumulenes has been their dramatically increased reactivity, especially in comparison to polyynes of comparable length. For example, most known [7]cumulenes can only be handled in solution, while the polyynes of equivalent length (i.e., a triyne with three acetylene units) are quite stable. [9]Cumulenes are the longest derivatives studied to date. In this Account, we describe our efforts to design and synthesize odd [n]cumulenes (i.e., n = 3, 5, 7, 9) that are sufficiently persistent under ambient conditions to allow in depth characterization of physical and spectral properties. This goal has been achieved through modification of the end-capping groups by increasing the steric bulk and thereby shielding the reactive cumulene framework to provide stable [7]- and [9]cumulenes. An alternative route to stabilization is accomplished via encapsulation of the cumulene skeleton in a macrocycle, that is, formation of cumulene rotaxanes. The new sterically encumbered cumulenic products are reasonably stable under normal laboratory conditions, although some readily undergo cycloaddition reactions to give interesting products. We have explored preliminary trends for the reactivity of long [n]cumulenes. Finally, trends in the series of [n]cumulene model compounds are now discernible, including a thorough consideration of bond length alternation (BLA) in long [n]cumulenes using X-ray crystallographic analyses, as well as electronic properties via UV-vis spectroscopy and cyclic voltammetry.


Intraosseous glomus tumor of the great toe: a case report with review of the literature.
We report a case of intraosseous glomus tumor that presented as a painful lesion in the distal phalanx of the left great toe in a 21-year-old male. The radiographic appearance showed a well-circumscribed osteolytic lesion, and histological examination revealed solid nests of polygonal cells surrounding branching vasculatures consistent with a glomus tumor. Partial toe amputation resulted in complete alleviation of the patient's pain. Although glomus tumors commonly occur in the distal soft tissue of the extremities, they very rarely localize to bone. To the best of our knowledge, this is the first published report of a case of intraosseous glomus tumor localized to the toe.


Postoperative efficacy, safety, predictability, and visual quality of implantable collamer lens implantation versus small incision lenticule extraction in myopic eyes: a Meta-analysis.
To compare the postoperative efficacy, safety, predictability, and visual quality of implantable collamer lens (ICL) implantation versus small incision lenticule extraction (SMILE) in myopia eyes. PubMed, EMBASE, Web of Science, Cochrane Library and several Chinese databases were searched at May 2021 to select relevant studies in comparison of clinical outcomes between ICL implantation and SMILE for myopia. The primary outcomes were efficacy, safety, and predictability. And the secondary outcomes were postoperative higher-order ocular aberrations (HOAs), modulation transfer function cutoff frequency (MTF), objective scatter index (OSI), contrast sensitivity and a quality of vision (QoV) questionnaire. A total of 1036 eyes from 10 studies, of which 503 eyes underwent ICL implantation and 533 eyes underwent SMILE, were enrolled in this Meta-analysis. Pooled results revealed that ICL group had a better safety index and post-corrected distance visual acuity (CDVA) (P=0.007, <0.00001, respectively), and a lower percentage of eyes with a postoperative CDVA lost 1 line (P=0.007) than the SMILE group. No significant differences were found in comparison of the other primary outcomes. In the long-term follow-up (>6mo), ICL group had a lower total HOA, coma, and spherical aberration than SMILE group (P=0.003, <0.00001, 0.04). Yet higher trefoil was found in ICL group at 6mo after surgery (P=0.003). Additionally, ICL group also had a higher MTF value (P=0.02), and a higher contrast sensitivity score for spatial frequencies of 1.5, 6, and 12 cpds (P=0.02, 0.005, 0.02, respectively). And it also had a lower score of bothersome in QoV questionnaire than SMILE group (P=0.003). ICL implantation and SMILE have similar and comparable outcomes in term of the efficacy and predictability for correcting high myopia. However, ICL group is relatively safer and also has better visual quality in comparison of SMILE group.


Effect of fructose-rich high-fat diet on glucose sensitivity and atherosclerosis in nonhuman primate.
The present study examined a new model of impaired glucose tolerance (IGT) in a nonhuman primate fed with a high-fructose and high-fat (HFF) diet that contained 15% lard, 31% fructose, and 1% cholesterol. Female cynomolgus monkeys (age, 3-4 years) were divided into two groups: 1) those fed with normal control diet (N = 5) and 2) those fed with HFF diet (N = 5). In the HFF diet group, total cholesterol and low-density lipoprotein cholesterol in blood were significantly increased four- to fivefold when compared with the normal control diet group. No difference in the blood glucose, insulin, hemoglobin A1c, and triglyceride levels was detected between the two groups. Plasma levels of adiponectin, but not of resistin, were significantly higher in HFF diet at 20 weeks after HFF diet feeding. Oral glucose tolerance test was performed before HFF diet feeding and at 12 and 24 weeks after HFF diet feeding, but no significant changes in glucose sensitivity were observed even 24 weeks after HFF diet feeding. Twenty-four weeks after HFF diet feeding, accumulated foam cells and infiltrated macrophages were histologically detected in the thoracic aorta, in addition to a fatty liver. Interestingly, the pancreatic beta cells appeared normal in the HFF diet group. These results show that a chronic HFF diet does not induce IGT but can cause atherosclerotic lesions in conjunction with the generation of a fatty liver phenotype in cynomolgus monkey; however, the present results are very preliminary and they need to be validated in larger-scale studies in the future.


Impact on peritoneal membrane of use of icodextrin-based dialysis solution in peritoneal dialysis patients.
The usefulness of icodextrin-containing peritoneal dialysis (PD) solution for the management of body fluid and blood pressure has been reported. However, icodextrin PD solution is a foreign solution in the body, and the possible induction of intraperitoneal inflammation has been reported. In this study, we investigated at 6-month intervals the influence of icodextrin solution on peritoneal permeability and inflammatory reactions in patients in whom glucose solution had been changed to icodextrin solution for the overnight dwell. We enrolled 9 anuric PD patients (5 men, 4 women) of mean age 58 +/- 5.9 years (range: 45.6-64.8 years) into the study. The patients' mean duration of PD was 61.9 +/- 42 months (range: 6.7-142.5 months). The cause of end-stage renal disease was chronic glomerulonephritis in all patients. For evaluation ofperitoneal permeability, we performed peritoneal equilibration tests (PETs) immediately after an overnight dwell and determined the dialysate-to-plasma ratios of creatinine (D/P Cr), beta2-microglobulin (D/P beta2m), albumin (D/P Alb), immunoglobulin G (D/P IgG), and alpha2-macroglobulin (D/P alpha2m). We also measured interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) in overnight effluent as indices of inflammation and of the fibrinolysis-coagulation system. The evaluation was performed every 6 months for 24 months. The FDPs in effluent increased significantly at 6 months after the change to icodextrin solution, and IL-6 tended to increase. The D/P beta2m, D/P Alb, D/P IgG, and D/P alpha2m all significantly increased in the course of follow-up. In the PETs, the D/P Cr increased slightly, but the change was nonsignificant. At 30 months after the change to icodextrin solution, 1 patient was diagnosed as having a risk of encapsulating peritoneal sclerosis (pre-EPS). In this patient, rapid increases in IL-6, D/P Cr and macromolecular and small molecular D/P by PET were noted after the change to icodextrin solution. Steroids were administered after the diagnosis of pre-EPS, with the result that the IL-6 level rapidly decreased and the D/P Cr and D/P of small molecules and macromolecules slightly decreased. Icodextrin dialysis solution increased peritoneal permeability. Although the cause was unclear, icodextrin may have changed peritoneal reactivity. Long-term use of icodextrin PD solution requires further investigation.


Ultrasonographic Findings in Patients with Benign and Malignant Thyroid Nodules who underwent Ultrasound Guided Fine Needle Aspiration Cytology.
Patients with thyroid nodules represent common problem in daily routine of thyroidologists as well as other medical specialties. Fortunately only small number of thyroid nodules turns out to be malignant. Ultrasound is most frequently used imaging modality in the evaluation of thyroid nodules and certain ultrasonographic features are associated with greater risk for malignancy. The aim of our study was to evaluate the diagnostic performance of various ultrasonographic findings regarding thyroid malignancy. Between September 2012 and August 2013 a total of 592 patients with 694 nodules were included in the present study. They were evaluated for thyroid nodules as a part of routine work up at outpatient's unit of Institute of Pathophysiology and Nuclear Medicine, Medical Faculty, UKIM Skopje. In all patients thyroid ultrasound and fine needle aspiration cytology (FNAC) were performed. Surgically were removed 84 nodules and ultrasonography and cytology data were compared to histology results. From all examined ultrasonographic features, significant association with malignancy has been found for hypoechogenecity, marked central vascularisation, ultrasound suspicious nodules (including at least two suspicious features) and marginal for presence of microcalcifications. Highest sensitivity was obtained for hypoechogenecity, and highest specificity for microcalcifications and marked central vascularisation. Awareness of the suspicious ultrasound features is mandatory in order to optimize diagnostic and therapeutic approach to the vast number of patients with thyroid nodules.


The effect of dexmedetomidine sedation on patient and surgeon satisfaction during retinal surgery under sub-tenon's anesthesia: a randomized controlled trial.
The purpose of this study was to evaluate the effect of intraoperative dexmedetomidine sedation on patient's and surgeon's satisfaction during retinal surgery under sub-tenon's anesthesia. Forty-four patients scheduled for elective retinal surgery under sub-tenon's anesthesia were enrolled in this randomized controlled trial. The patients were divided into Dexmedetomidine (n = 22) and Control (n = 22) groups. Intravenous dexmedetomidine or 0.9% saline via infusion pump were administered continuously to the dexmedetomidine or control group, respectively. Ramsay sedation scale with a target level of 3-4 was used to assess adequacy of sedation. Perioperative pain, hemodynamic and respiratory data were collected, while satisfaction from patients and surgeon were assessed post-surgery using a 5-point satisfaction scale. Patient and surgeon satisfaction was higher in the dexmedetomidine group (P < 0.001, P = 0.002, respectively). The pain associated with sub-tenon's anesthesia and peripheral vitrectomy was lesser in the dexmedetomidine group than in the control group (P = 0.020). There was significant reduction of heart rate in the dexmedetomidine group (P = 0.001), but only one patient needed treatment with atropine. There was no respiratory effect on both groups. Dexmedetomidine sedation during retinal surgery improved satisfaction from both patient and surgeon without respiratory complication. It is a safe and preferable choice of sedation for retinal surgery.


Autecology of the tailed jay butterfly Graphium agamemnon (Lepidoptera : Rhopalocera : Papilionidae).
The Tailed Jay Graphium agamemnon is one of the attractive papilionid butterflies that enliven the environment of Visakhapatnam. It occurs throughout the year. It lays eggs singly on young leaves of the mast tree Polyalthia longifolia var. pendula (Annonaceae). The eggs take 3-4 days to hatch. The larvae go through 5 instars over a period of 15-16 days. The pupal period is 13-14 days. The total period from egg to adult emergence spans over 33-36 days. Based on this short life cycle, and larval and pupal development success studied every month, this butterfly can be multivoltine with a minimum of 7-8 broods in a year. Both CI and GR decreased with the age of larva, their average figures being 3.78 and 0.43 respectively. AD values are high (average 92%) and decreased through successive instars. Both ECD and ECI followed a similar pattern with an increase from instar I up to II, then a decrease up to IV and again an increase in instar V and the highest value is with fifth instar. Adults frequently visited flowers (12-35 flowers in a min) spending 1.0 to 3.2 seconds on a flower. The nectar concentration ranged between 16 and 58%. Peak foraging activity mostly fell between 0900-1000 h. The proboscis received pollen in most of the floral species visited, thus satisfying one of the characteristics of butterfly pollination. Being a fast and strong flier it is treated as "high energy" pollinator promoting cross-pollination.


High-resolution EEG source imaging of one-year-old children.
Recently we described an iterative skull conductivity and source location estimation (SCALE) algorithm for simultaneously estimating head tissue conductivities and brain source locations. SCALE uses a realistic FEM forward problem head model and scalp maps of 10 or more near-dipolar sources identified by independent component analysis (ICA) decomposition of sufficient high-density EEG data. In this study, we applied SCALE to 20 minutes of 64-channel EEG data and magnetic resonance (MR) head images from four twelve-months-of-age infants. For each child, we selected 15-16 near-dipolar independent components from multiple-model adaptive mixture ICA (AMICA) decomposition of their EEG data. SCALE converged to brain-to-skull conductivity ratio (BSCR) estimates in the 10-12 range and mostly compact gyral or sulcal cortical distributions for the IC sources.


How to prevent medication errors: a multidimensional scaling study to investigate the distinguishability between self-injection platform device variants.
Background: The importance of subcutaneous drug delivery using self-injection devices based on common device platforms continues to grow. The resulting broad adoption of potentially look-alike or similar devices, however, raises concerns over limited device distinguishability and ensuing risk of medication errors. The objective of the study is thus to understand whether and how users effectively distinguish between self-injection device variants. Methods: Seventy-four patients, caregivers, and healthcare professionals were asked to pairwise rate the similarity of eight platform autoinjector variants. Multidimensional scaling was then used to convert individual ratings into spatial configurations and thereby identify the attributes that influence device distinguishability. Results: Five different device attributes driving distinguishability were identified. Three of the attributes corresponded to single design features (the label color, device size and device shape). Two device attributes (the aspect ratio and chromaticity) combined distinct yet interrelated design features. Conclusions: The study provides initial empirical evidence that users are able to distinguish between device variants and as to what device attributes drive distinguishability. Furthermore, the results highlight patterns in how various user groups distinguish between device variants. These patterns relate with the user group characteristics (e.g. age, sight or dexterity) and the context of device usage (e.g. healthcare professionals).


Cocaine: analysis, pharmacokinetics, and metabolic disposition.
The ability to measure concentrations of cocaine in body fluids can contribute substantially to any investigation of cocaine's pharmacological effects. Design of research which involves the administration of cocaine must take into account current knowledge regarding the drug's pharmacokinetics. Cocaine's very rapid elimination from the body should be considered in attempting to understand patterns of cocaine abuse, and such phenomena as bingeing and acute tolerance. Accurate analysis of cocaine and/or its metabolites is essential to the diagnosis and evaluation of cocaine use whether for medical or forensic purposes. Appropriate selection of methods for analysis of cocaine depends upon the intended purpose of the assay, and correct interpretation of the data obtained upon knowledge of cocaine's kinetics and metabolic disposition.


Emerging Prospects for Nanoparticle-Enabled Cancer Immunotherapy.
One of the standards for cancer treatment is cancer immunotherapy which treats both primary and metastasized tumors. Although cancer immunotherapeutics show better outcomes as compared with conventional approaches of cancer treatment, the currently used cancer immunotherapeutics have limited application in delivering cancer antigens to immune cells. Conversely, in solid tumors, tumor microenvironment suppresses the immune system leading to the evasion of anticancer immunity. Some promising attempts have been made to overcome these drawbacks by using different approaches, for instance, the use of biomaterial-based nanoparticles. Accordingly, various studies involving the application of nanoparticles in cancer immunotherapy have been discussed in this review article. This review not only describes the modes of cancer immunotherapy to reveal the importance of nanoparticles in this modality but also narrates nanoparticle-mediated delivery of cancer antigens and therapeutic supplements. Moreover, the impact of nanoparticles on the immunosuppressive behavior of tumor environment has been discussed. The last part of this review deals with cancer immunotherapy using a combination of traditional interventional oncology approach and image-guided local immunotherapy against cancer. According to recent studies, cancer therapy can potentially be improved through nanoparticle-based immunotherapy. In addition, drawbacks associated with the currently used cancer immunotherapeutics can be fixed by using nanoparticles.


Eating behavior, weight problems and eating disorders in 101 long-term survivors of childhood-onset craniopharyngioma.
As a result of hypothalamic involvement and/or treatment-related hypothalamic damage, up to 75% of childhood craniopharyngioma patients develop hypothalamic obesity. Eating behavior was analyzed in 101 survivors of childhood craniopharyngioma, recruited from 1980 to 2001 in the HIT-Endo multicenter study, and in 85 body mass index (BMI)-matched healthy controls using the Inventory for Eating Behavior and Weight Problems (IEG) and the Inventory for Eating Disorders (ESI). Severely obese patients (BMI>8 SD; n=9) presented with pathological eating behavior, more weight problems, and eating disorders, as compared to obese (BMI 3-8 SD; n=44) and normal or overweight patients (BMI<3 SD; n=48). Craniopharyngioma patients with different degrees of obesity showed similar or even less pathological findings as compared to BMI-matched normal controls. Severe obesity is associated with pathological eating behavior/disorders in craniopharyngioma patients. As these disorders are not disease-specific, risk factors for hypothalamic obesity should be the focus of further craniopharyngioma research.


Acute cholecystitis - early laparoskopic surgery versus antibiotic therapy and delayed elective cholecystectomy: ACDC-study.
Acute cholecystitis occurs frequently in the elderly and in patients with gall stones. Most cases of severe or recurrent cholecystitis eventually require surgery, usually laparoscopic cholecystectomy in the Western World. It is unclear whether an initial, conservative approach with antibiotic and symptomatic therapy followed by delayed elective surgery would result in better morbidity and outcome than immediate surgery. At present, treatment is generally determined by whether the patient first sees a surgeon or a gastroenterologist. We wish to investigate whether both approaches are equivalent. The primary endpoint is the morbidity until day 75 after inclusion into the study. A multicenter, prospective, randomized non-blinded study to compare treatment outcome, complications and 75-day morbidity in patients with acute cholecystitis randomized to laparoscopic cholecystectomy within 24 hours of symptom onset or antibiotic treatment with moxifloxacin and subsequent elective cholecystectomy. For consistency in both arms moxifloxacin, a fluorquinolone with broad spectrum of activity and high bile concentration is used as antibiotic. October 2006 - November 2008. The trial was planned and is being conducted and analysed by the Departments of Gastroenterology and General Surgery at the University Hospital of Heidelberg according to the ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and the Good Clinical Practice guideline (GCP). ClinicalTrials.gov NCT00447304.


Prospective surveillance of neonatal meningitis.
Neonatal meningitis is a serious problem with a high mortality and frequent neurological sequelae. The incidence of neonatal meningitis was calculated and the aetiology, clinical and laboratory features, and the treatment of cases recorded prospectively over a 7 year 8 month period was documented. It was further investigated whether secondary meningitis had occurred after lumbar puncture. The estimated incidence of bacterial, viral, and fungal meningitis was 0.25, 0.11, and 0.02 per 1000 live births respectively. There were eight cases of early onset meningitis (seven definite, one probable) and group B streptococci accounted for six (75%) of these. Blood cultures were negative in only one of seven cases of definite early bacterial meningitis. Of the 15 late onset cases, Gram negative organisms accounted for six of the seven bacterial cases. The overall mortality was 26%. Of the 11 survivors of bacterial meningitis, three (27%) had significant neurological sequelae at follow up (between three months to three years later). As in the first 48 hours after birth an initial blood culture is unlikely to be negative if bacterial meningitis is present, lumbar puncture can be deferred if the procedure might exacerbate respiratory distress. Although approximately 1880 infants had a lumbar puncture during the review period, only one case of meningitis was found where it was possible that lumbar puncture in a bacteraemic infant may have caused meningeal infection. The incidence of this potential complication must therefore be low.


Can we continue research in splenectomized dogs? Mycoplasma haemocanis: old problem--new insight.
We report the appearance of a Mycoplasma haemocanis infection in laboratory dogs, which has been reported previously, yet, never before in Europe. Outbreak of the disease was triggered by a splenectomy intended to prepare the dogs for a hemorrhagic shock study. The clinical course of the dogs was dramatic including anorexia and hemolytic anemia. Treatment included allogeneic transfusion, prednisone, and oxytetracycline. Systematic follow-up (n = 12, blood smears, antibody testing and specific polymerase chain reaction) gives clear evidence that persistent eradication of M. haemocanis is unlikely. We, therefore, had to abandon the intended shock study. In the absence of effective surveillance and screening for M. haemocanis, the question arises whether it is prudent to continue shock research in splenectomized dogs.


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Assessment of Hypodontia Treatment of Maxillary Lateral Incisors in Adult Patients After 9 Years of Follow-up: A Retrospective Study.
To assess the effects of maxillary lateral incisor hypodontia treatment following the use of implantation procedures, fixed and removable dental prostheses, and change in the shape of the canine. Hypodontia treatment effects were retrospectively evaluated in 129 patients aged 18 to 60 years. The assessment covered esthetic, biologic, and functional aspects of the restored missing teeth within 9 years after treatment. The analysis of the findings took into account the percentage of positive effects of treatment for each method and assessment year and also included statistical tests based on the F statistic, which allowed comparison of the effectiveness of the applied methods of hypodontia treatment. In years 1 to 3, the effects of treatment were wholly positive; in subsequent years, the applied methods differed in terms of effectiveness. After 9 years, there was full clinical success for the implant-prosthetic method and for three-unit porcelain-fused-to-metal (PFM) fixed partial dentures (FPDs), 77.77% success for fiber-reinforced composite (FRC) FPDs, 73.68% for multi-unit PFM FPDs, 67.56% for canine shape change, and 23% for metal-alloy removable partial denture (RPD) prostheses. The results of this study indicate that the use of mini-implants with PFM crowns and three-unit PFM FPDs are the most effective treatment methods. A less favorable clinical effect was obtained with the use of FRC FPDs and multi-unit PFM FPDs. Changing the canine shape led to an acceptable clinical effect in over two-thirds of case histories. Metal-alloy RPD prostheses yielded the weakest effects.


Isolation of the heme-thiolate enzyme cytochrome P-450TYR, which catalyzes the committed step in the biosynthesis of the cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench.
The cytochrome P-450 enzyme (hemethiolate enzyme) that catalyzes the N-hydroxylation of L-tyrosine to N-hydroxytyrosine, the committed step in the biosynthesis of the cyanogenic glucoside dhurrin, has been isolated from microsomes prepared from etiolated seedlings of Sorghum bicolor (L.) Moench. The cytochrome P-450 enzyme was solubilized with the detergents Renex 690, reduced Triton X-100, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate and isolated by ion-exchange (DEAE-Sepharose) and dye (Cibacron blue and reactive red 120) column chromatography. To prevent irreversible aggregation of the cytochrome P-450 enzyme, the isolation procedure was designed without any concentration step--i.e., with dilution of the ion-exchange gel with gel filtration material. The isolated enzyme, which we designate the cytochrome P-450TYR enzyme, gives rise to the specific formation of a type I substrate binding spectrum in the presence of L-tyrosine. The microsomal preparation contains 0.2 nmol of total cytochrome P-450/mg of protein. The cytochrome P-450TYR enzyme is estimated to constitute approximately 20% of the total cytochrome P-450 content of the microsomal membranes and about 0.2% of their total protein content. The apparent molecular mass of the cytochrome P-450TYR enzyme is 57 kDa, and the N-terminal amino acid sequence is ATMEVEAAAATVLAAP. A polyclonal antibody raised against the isolated cytochrome P-450TYR enzyme is specific as monitored by Western blot analysis and inhibits the in vitro conversion of L-tyrosine to p-hydroxymandelonitrile catalyzed by the microsomal system. The cytochrome P-450TYR enzyme exhibits high substrate specificity and acts as an N-hydroxylase on a single endogenous substrate. The reported isolation procedure based on dye columns constitutes a gentle isolation method for cytochrome P-450 enzymes and is of general use as indicated by its ability to separate cytochrome P-450TYR from the cytochrome P-450 enzyme catalyzing the C-hydroxylation of p-hydroxyphenylacetonitrile and from cinnamic acid 4-hydroxylase.


TAVR Vs. SAVR in Intermediate-Risk Patients: What Influences Our Choice of Therapy.
To determine what influences patients and physicians to choose between transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in intermediate-surgical-risk patients with severe, symptomatic aortic stenosis. Advances in transcatheter valve technology, techniques, and trials demonstrating non-inferiority compared to surgical aortic valve replacement (SAVR) have led to expanded eligibility of transcatheter aortic valve replacement (TAVR) to both intermediate-risk patients in clinical practice and low-risk patients in pivotal trials. Since lower-risk individuals tend to be younger and good operative candidates, concerns of valve durability, procedure-related morbidity, and patient survivability require careful consideration. Results from the PARTNER II intermediate risk trials and SURTAVI trials have given us insight into the benefits and potential risks of both treatment modalities. In this article, we review the brief yet remarkable history of TAVR and discuss its role in the treatment of intermediate-surgical-risk patients.


Lactate oxidation at the mitochondria: a lactate-malate-aspartate shuttle at work.
Lactate, the conjugate base of lactic acid occurring in aqueous biological fluids, has been derided as a "dead-end" waste product of anaerobic metabolism. Catalyzed by the near-equilibrium enzyme lactate dehydrogenase (LDH), the reduction of pyruvate to lactate is thought to serve to regenerate the NAD(+) necessary for continued glycolytic flux. Reaction kinetics for LDH imply that lactate oxidation is rarely favored in the tissues of its own production. However, a substantial body of research directly contradicts any notion that LDH invariably operates unidirectionally in vivo. In the current Perspective, a model is forwarded in which the continuous formation and oxidation of lactate serves as a mitochondrial electron shuttle, whereby lactate generated in the cytosol of the cell is oxidized at the mitochondria of the same cell. From this perspective, an intracellular lactate shuttle operates much like the malate-aspartate shuttle (MAS); it is also proposed that the two shuttles are necessarily interconnected in a lactate-MAS. Among the requisite features of such a model, significant compartmentalization of LDH, much like the creatine kinase of the phosphocreatine shuttle, would facilitate net cellular lactate oxidation in a variety of cell types.


Evaluation of interactive computerized training to teach parents to implement photographic activity schedules with children with autism spectrum disorder.
Training parents of children with autism spectrum disorder can be a challenge due to limited resources, time, and money. Interactive computerized training (ICT)-a self-paced program that incorporates instructions, videos, and interactive questions-is one method professionals can use to disseminate trainings to broader populations. This study extends previous research on ICT by assessing the effect of ICT to teach three parents how to implement a photographic activity schedule using a systematic prompting procedure with their child. Following ICT, all parents increased their fidelity to implementation of an activity schedule during role-play sessions with an adult. Fidelity remained high during implementation with their child and maintained during a 2-week follow-up.