Intra-bone marrow-bone marrow transplantation facilitates hemopoietic recovery including dendritic cells.
In this report, we provide evidence using a serial bone marrow transplantation (BMT) protocol that intra-bone marrow (IBM)-BMT (IBM-BMT) can efficiently reconstitute the hemopoietic system with cells of donor origin, in contrast to conventional intravenous (IV)-BMT (IV-BMT). Furthermore, the hematolymphoid system of secondary recipients that had received bone marrow cells (BMCs) from primary recipients treated with IBM-BMT recovered earlier than that of the secondary recipients of BMCs from primary recipients treated with IV-BMT. This was the case when the Lin-/c-kit+ progenitor cells of the secondary and tertiary recipients were examined. These findings indicate that IBM-BMT can facilitate the development of not only cells of various lineages but also the effective generation and, more importantly, the maintenance of the progenitor cells. Furthermore, we show that IBM-BMT can reconstitute the dendritic cell (DC) subsets (myeloid and lymphoid DCs), which are critical for the initiation of both adaptive and innate immune responses. The frequency of both myeloid and lymphoid DC subsets was approximately equal to that of normal age-matched untreated controls and, after second and third BMT, this ratio was close to that observed in the normal controls. However, the lymphoid DCs were clearly reduced in the secondary and tertiary recipients of BMCs from mice that had received IV-BMT. Therefore, the development of DC subsets is also normally maintained in the IBM-BMT group.


Chemical and biological consequences of oxidatively damaged guanine in DNA.
Of the four native nucleosides, 2'-deoxyguanosine (dGuo) is most easily oxidized. Two lesions derived from dGuo are 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy)∙dGuo. Furthermore, while steady-state levels of 8-oxodGuo can be detected in genomic DNA, it is also known that 8-oxodGuo is more easily oxidized than dGuo. Thus, 8-oxodGuo is susceptible to further oxidation to form several hyperoxidized dGuo products. This review addresses the structural impact, the mutagenic and genotoxic potential, and biological implications of oxidatively damaged DNA, in particular 8-oxodGuo, Fapy∙dGuo, and the hyperoxidized dGuo products.


[Involuntary admissions in accordance to the Mental Health Act (PsychKG) - what are the strongest predictors?].
Involuntary psychiatric admissions under the Mental Health Act increased significantly nationwide. Little is known, however, about the influencing factors of this phenomenon. The aim of this regional cross-sectional study in North Rhine-Westphalia was to compare voluntary and involuntary psychiatric admissions (under the PsychKG NRW) regarding personal, institutional, social-psychiatric and demographic characteristics. A retrospective analysis of hospital admission registers over a period of 6 years with over 200 000 cases was conducted. Elderly patients with dementia were most frequently involuntarily admitted. The existence of a locked ward in hospitals did not per se increase involuntary admissions, whereas the scope and quality of local social-psychiatric services had a major impact. Social-psychiatric services and home-treatment must be strengthened to achieve lower involuntary admission rates and to further improve the quality of mental health care all over Germany.


A new method of histologic dating of human endometrium in the luteal phase.
Morphometric analysis was performed on 70 endometrial biopsy specimens collected from a population of fertile women. Of the 17 morphometric measurements that were performed on each endometrial biopsy, only 5 were required to achieve a highly significant correlation with chronologic dating based on luteinizing hormone surge (R = 0.99). The result of histologic dating, based on morphometric analysis of endometrial biopsies collected from a separate, unbiased population, correlated strongly and significantly with chronologic dating (r = 0.98, P less than 0.0001). The correlation was better than that achieved when histologic dating was performed according to the conventional dating criteria (r = 0.88, P less than 0.001).


A temperature-responsive release cellulose-based microcapsule loaded with chlorpyrifos for sustainable pest control.
Controlled pesticide release in response to environmental stimuli by encapsulating pesticide in carrier is a feasible approach to improve the effective utilization rate. Here, a temperature-responsive release microcapsule loaded with chlorpyrifos (CPF@CM) was prepared from n-hexadecane-in-water emulsions via interfacial polymerization. The microcapsule was consisted of nanofibrillated cellulose (NFC) as the shell wall material and isophorone diisocyanate (IPDI) as the crosslinker. The prepared CPF@CM had pesticide-loading efficiency (33.1 wt%) and favorable adhesion on the surface of cucumber and peanut foliage compared with conventional formulation. Additionally, CPF@CM could protect chlorpyrifos against photodegradation effectively. The in vitro release test showed that microcapsule had adjustable controlled-release characteristics with the change in temperature based on phase transition of the n-hexadecane core. Bioassay studies showed that control efficacy of CPF@CM microcapsule against P. xylostella was positively correlated with temperature because of temperature-induced changes in release rate. The acute toxicity of CPF@CM to zebrafish was reduced more than 5-fold compared with that of CPF technical. These results indicated that the microcapsule release system has great potential in the development of an effective and environmentally friendly pesticide formulation.


Inverse gas chromatography for natural fibre characterisation: Identification of the critical parameters to determine the Brunauer-Emmett-Teller specific surface area.
Inverse gas chromatography (IGC) is an alternative technique to determine the specific surface area of natural fibres. Natural fibres have a complex surface chemistry and unique microstructure that challenge the current capabilities to perform surface characterisation. This study investigated the influence of multiple parameters on the measured Brunauer-Emmett-Teller (BET) specific surface area for samples of flax, kenaf and BioMid(®) cellulose fibres using IGC. The BET surface area of kenaf and flax differed with 0.51m(2)g(-1) and 1.35m(2)g(-1) respectively, the former being similar to the cellulose fibres (0.54m(2)g(-1)). The data was calculated under conditions where the BET equation showed good linearity (R(2)⩾0.995). Repeatability was excellent so that two runs sufficed to obtain representative BET surface area values. The findings showed the choice of solvent was important for all specimens to avoid any misleading data comparison due to molecular orientation effects that impact the adsorbent-adsorbate interactions. The higher surface area of the flax sample, and its higher variability, was correlated with a higher surface roughness observed under optical microscopy. Packing the chromatography column with long or chopped fibres produced results that were statistically insignificant.


Pharmacologic stress testing: mechanism of action, hemodynamic responses, and results in detection of coronary artery disease.
Pharmacologic stress testing may be used in the diagnosis of coronary artery disease and risk assessment. The stress agents may be divided into those that produce primary coronary vasodilation (dipyridamole, adenosine, or adenosine triphosphate) and those that produce secondary vasodilation as a result of increase in myocardial oxygen demand (dobutamine and arbutamine). Assessment of myocardial perfusion and function can be made by single-photon imaging, positron emission tomography, two-dimensional echocardiography, magnetic resonance imaging, and contrast angiography. For assessment of myocardial perfusion, either thallium 201-labeled or technetium-labeled perfusion imaging agents may be used. This article will focus on the mechanisms of action, hemodynamic responses, and results of pharmacologic imaging in detecting coronary artery disease. The use of pharmacologic stress testing in risk assessment will be discussed in a separate article.


Identification of phosphoproteins regulated by gibberellin in rice leaf sheath.
To identify the gibberellin (GA) signaling components involved in rice leaf sheath elongation process, protein phosphorylation changed by GA3 was analyzed. The protein kinase activities in rice leaf sheath were assessed in an in-gel kinase assay using SDS-polyacrylamide gel containing histone III-S as a substrate. The activity of a putative 54-kDa calcium dependent protein kinase (CDPK) in cytosolic fraction in rice leaf sheath increased significantly by GA3. Further, phosphorylation status of the proteins changed by GA3 in rice leaf sheath were detected by in vitro protein phosphorylation followed by two-dimensional polyacrylamide gel electrophoresis and the phosphoproteins were identified by mass spectrometry. Sixty phosphoproteins was detected after in vitro protein phosphorylation and the phosphorylation of 7 proteins was enhanced by GA3 treatment. The addition of GA3 treated cytosolic fraction of leaf sheath further increased the phosphorylation of 4 proteins, glyoxalase-I, cytoplasmic malate dehydrogenase, glyceraldehydes-3-phosphate dehydrogenase and another unknown protein. The protein kinase inhibitor, staurosporine inhibited the phosphorylation of these proteins in vitro. Other hormones, particularly, indole acetic acid, 6-benzylaminopurine and abscisic acid did not change the phosphorylation status of these proteins. The identified proteins did not show any change by GA3 treatment at transcription level. The abundance of glyoxalase-I and cytoplasmic malate dehydrogenase remained unchanged by GA3 treatment as detected on 2D-gel by silver staining, unlike for glyceraldehydes-3-phosphate dehydrogenase. Results suggest that the phosphoproteins, glyoxalase-I and cytoplasmic malate dehydrogenase in rice leaf sheath could be important signaling components of GA3, downstream to 54-kDa CDPK.


Performance of a Translucent Activator for LipiFlow Vectored Thermal Pulse (VTP) Treatment of Meibomian Gland Dysfunction.
Investigator feedback was used to assess the clinical use of the LipiFlow® System with the new translucent Activator Clear to successfully complete LipiFlow® treatments. This was a prospective, open-label clinical investigation. A total of 88 eyes (44 subjects) were treated using the LipiFlow® System with the new Activator Clear. Subjects diagnosed with bilateral meibomian gland dysfunction (MGD) were enrolled in the study. Each investigator performed a complete LipiFlow® treatment with the translucent Activator on both eyes of each subject. Investigators completed a questionnaire assessing the clinical use of the Activator Clear on a 5-point scale (1 - very difficult or strongly disagree, 3 - neutral, 5 - very easy or strongly agree). The new translucent Activator provided successful LipiFlow® treatments in 100% of cases, with 95% confidence interval of (96%, 100%). Additionally, the investigators agreed or strongly agreed that the translucent components of the Activator Clear made it easy to access and position the activator with confidence on the subject's eye. The overall investigators' impressions on usage and functionality of LipiFlow® System with the translucent Activator were very positive. The Activator Clear enables doctors with efficient and confident positioning around patient eyelids to ensure successful LipiFlow® treatment when used as indicated.


The association between malnutrition and oral health status in elderly in long-term care facilities: a systematic review.
Malnutrition is a common problem in the elderly. It is not clear if oral health is associated to malnutrition in this population. The aim of this systematic review is to determine whether an association exists between oral health and malnutrition in the elderly in a long-term care facility. Systematic review. Medline, Cochrane and Cinahl were systematically searched for to identify articles published between January 1985 and May 2011. Reference lists were checked for additional publications. Publications were included if they explored the association between oral health status and malnutrition. As no consensus about terminology was found, a sensitive filter was developed. The methodological quality of the studies was assessed. Two independent reviewers performed all methodological steps. Sixteen studies met the criteria for inclusion. Eleven studies used a multivariate approach; nine of these found an association between oral health status and malnutrition. Four studies found a relationship between masticatory problems and malnutrition. Five studies found an association between malnutrition and dental condition, number of oral problems, tongue alteration, problems with saliva flow, and candidiasis. Overall, the methodological quality of the studies was medium. Tentative evidence indicates an independent association between oral health status and malnutrition in the elderly residing in a long-term care facility. Caution is needed for the interpretation of these results because of the absence of a gold standard to define and assess malnutrition and oral health status and the presence of methodological limitations throughout the studies.


Chemical analysis of phenolic glycosides: art, facts, and artifacts.
Phenolic glycosides have been the subject of considerable interest in recent ecological and systematic studies, especially those involving the Salicaceae. But these compounds are markedly labile in aqueous media, and the consequences of spontaneous degradation for valid interpretation of results have been largely ignored by researchers. We found that freeze-drying and oven-drying of leaf samples from several Populus and Salix species produced dramatic changes in the total and relative concentrations of specific phenolic glycosides, when compared to analyses of fresh material. Extraction in aqueous and alcoholic media for extended (24 h) periods also effected changes in glycoside concentrations. Alterations in phenolic glycoside concentrations, interconversions among glycosides, and production of artifactual glycosides result from a series of hydrolytic reactions. These deleterious effects can be best (but not entirely) avoided by the use of fresh plant material, cold, nonaqueous extraction solvents, and short extraction times. Because individual phenolic glycosides exhibit very different biological activities against herbivores, we caution ecologists to use utmost care in the performance and interpretation of phenolic glycoside assays.


Identification of differentially expressed proteins in chemotherapy-sensitive and chemotherapy-resistant diffuse large B cell lymphoma by proteomic methods.
In the present study, we employed proteomic methods to identify and quantitate differentially expressed proteins between diffuse large B cell lymphoma (DLBCL) tissues with low and high sensitivity to combinatorial cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and explored protein networks associated with DLBCL chemoresistance to CHOP. For proteomics analysis, DLBCL tissues were collected from 14 untreated patients. Two-dimensional gel electrophoresis combined with mass spectrometry (MS) were employed to identify and quantitate differentially expressed proteins in DLBCL tissues with low or high sensitivity to CHOP chemotherapy in vitro. Nineteen proteins showing an over twofold change in the MS/MS ions score between the low sensitivity and the high sensitivity groups were identified as differentially expressed proteins and confirmed by Western blot analyses. Immunohistochemical analyses were performed in DLBCL tissue samples from 98 patients who had received four cycles of CHOP chemotherapy, which showed that expressions of the identified CHOP sensitivity biomarkers were significantly associated with therapeutic outcomes of DLBCL, suggesting that the biomarkers could be used to predict DLBCL patient outcomes. This study provides important insights into understanding the molecular basis for development of multi-drug chemoresistance in DLBCL, which may serve as a basis for identification of novel therapeutic targets and biomarkers involved in the emergence and maintenance of DLBCL resistance to CHOP.


Preparation and characterization of micro/nanocellulose reinforced PVDF/wood composites.
Polyvinylidene fluoride (PVDF) is commonly used in the chemical, electronic, and petrochemical industries because of its chemical and physical attributes. This study aimed to make novel PVDF-based composite with a high loading of silanized wood powder and micro/nanocellulose fibers, where glycerol acts as both a dispersant and a plasticizer all-in-one composite application for the first time. The purpose was also extended to systematically investigate their mechanical properties and melt flow. Results have demonstrated the efficiency of utilizing the cellulose fibers in bio-composites. With the addition of 30 wt% of filling materials, When the content of silanized cellulose fibers in glycerol dispersion is 25 wt%, the flexural strength and tensile strength reach the maximum value 72.30 MPa and 52.28 MPa. The experimental results indicate that silanized micro/nanocellulose fiber-reinforced PVDF/wood composites are a promising composite formula to help improve performance and reduce costs. It is an excellent example of utilizing biomass resources as a renewable/recyclable, sustainable and low-cost material to reduce the use of petroleum-based polymer, and improve the mechanical properties of composites.


Ichthyophthirius multifiliis Fouquet and Ichthyophthiriosis in Freshwater Teleosts.
The ciliate Ichthyophthirius multifiliis is an important pathogen of freshwater teleosts occurring in both temperate and tropical regions throughout the world. The disease, ichthyophthiriosis, accounts for significant economic losses to the aquaculture industry, including the ornamental fish trade, and epizootics in wild fish populations can result in mass kills. This review attempts to provide a comprehensive overview of the biology of the parasite, covering the free-living and parasitic stages in the life cycle, host-parasite interactions, and the immune response of host and immune evasion strategies by the parasite. Emphasis on the immunological aspects of infection within the fish host, including molecular studies of i-antigens, reflects the current interest in this subject area and the quest to develop a recombinant vaccine against the disease. The current status of methods for the control of ichthyophthiriosis is discussed, together with new approaches in combating this important disease.


Associations Between Primary Care Providers and Staff-Reported Access Management Challenges and Patient Perceptions of Access.
Optimizing patients' access to primary care is critically important but challenging. In a national survey, we asked primary care providers and staff to rate specific care processes as access management challenges and assessed whether clinics with more of these challenges had worse access outcomes. Study design: Cross sectional. National Primary Care Personnel Survey (NPCPS) (2018) participants included 6210 primary care providers (PCPs) and staff in 813 clinics (19% response rate) and 158,645 of their patients. We linked PCP and staff ratings of access management challenges to veterans' perceived access from 2018-2019 Survey of Healthcare Experiences of Patients-Patient Centered Medical Home (SHEP-PCMH) surveys (35.6% response rate). The NPCPS queried PCPs and staff about access management challenges. The mean overall access challenge score was 28.6, SD 6.0. The SHEP-PCMH access composite asked how often veterans reported always obtaining urgent appointments same/next day; routine appointments when desired and having medical questions answered during office hours. We aggregated PCP and staff responses to clinic level, and use multi-level, multivariate logistic regressions to assess associations between clinic-level access management challenges and patient perceptions of access. We controlled for veteran-, facility-, and area-level characteristics. Veterans at clinics with more access management challenges (> 75th percentile) had a lower likelihood of reporting always receiving timely urgent care appointments (AOR: .86, 95% CI: .78-.95); always receiving routine appointments (AOR: .74, 95% CI: .67-.82); and always reporting same- or next-day answers to telephone questions (AOR: .79, 95% CI: .70-.90) compared to veterans receiving care at clinics with fewer (< 25th percentile) challenges. Findings show a strong relationship between higher levels of access management challenges and worse patient perceptions of access. Addressing access management challenges, particularly those associated with call center communication, may be an actionable path for improved patient experience.


Desulfonylative Methenylation of β-Keto Sulfones.
A one-step strategy for the synthesis of α-methenyl ketones from β-keto sufones is reported. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step.


A novel serine esterase expressed by cytotoxic T lymphocytes.
Cytotoxic T (Tc) lymphocytes recognize and lyse target cells and are thought to serve as an important defence against viral infections and possibly against neoplasms. The nature of the receptors responsible for antigen recognition by these cells is becoming clearer, but the molecular mechanisms responsible for their cytolytic activity remain largely unknown. The possibility that proteases are involved in this process has been suggested by the effects of certain inhibitors. Here we demonstrate that clones of murine Tc cells possess considerable trypsin-like esterase activity when assayed by a sensitive colorimetric assay. This activity was blocked completely by two serine esterase inhibitors, diisopropylfluorophosphoridate (DFP) and phenylmethylsulphonyl fluoride (PMSF), but not by N alpha-tosyl lysyl chloromethyl ketone (TLCK). The use of 3H-DFP as an affinity-labelling reagent demonstrated that the esterase activity resides in a protein of relative molecular mass (Mr) 28,000 (28K). A wide variety of other lymphocytes, including those from thymus, spleen and lymph node, established lines of B cells and noncytotoxic T cells, and clones of T helper cells, had about 300-fold less esterase activity than the Tc-cell clones and far smaller amounts of the DFP-reactive 28K protein. However, in thymocytes the esterase activity increased 20-50-fold and the 28K protein became more prominent 4 days after these cells had been stimulated in vitro to generate Tc cells.


Preventing accidental decannulations following tracheostomy.
Tracheostomy in infants and children is associated with a high rate of accidental decannulation in the early postoperative period. Eighty-eight patients underwent tracheostomy from 1980 to 1985, and 22 were sutured in place. Accidental decannulation occurred in 31.8% of the nonsutured and 4.5% of the sutured tracheostomies. We advocate suturing tracheostomy tubes in place in infants and children and describe a simple suture technique for this purpose.


Immediate changes in pupil size following Laser in situ keratomileusis (LASIK): Pupillometry study.
To investigate the impact of laser in situ keratomileusis (LASIK) on the change in pupil size immediately after the procedure. In a prospective study, measurement of pupil size was assessed in 70 eyes of 35 consecutive patients using a hand-held pupillometer before and immediately after LASIK in mesopic condition at the refractive eye center, Riyadh, Saudi Arabia. The pupil showed mild dilation immediate after LASIK. Mean pupil size before LASIK was 4.10 ± 0.74 and immediate after was 4.74 ± 0.82, P value <0.0001. No association was found with age, sex, central corneal thickness or pre-operative refractive measurements (CCT). There is a change in pupil size that immerses immediately after LASIK; postulations suggested for pupillary dilation include the effect of suction ring, post-operative steroid eye drops, dark room, pain and anxiety.


Current state of scanning micromanipulator applications with the carbon dioxide laser.
The development of the scanning system AcuBlade has considerably enhanced carbon dioxide laser energy delivery, improving cutting and ablation modes. The scanning system can be applied with the 2 available high-powered pulsed waves, SuperPulse and UltraPulse. This study was conducted to determine whether there are any differences in phonosurgery between the SuperPulse and UltraPulse lasing applications with regard to thermal diffusion into the surrounding tissues, healing time, and clinical results. Thirteen patients with bilateral and similar vocal fold lesions underwent operation--one side in SuperPulse mode and the other side in UltraPulse mode. The parameters for phonosurgery were depth of 0.2 mm, 10 W, single pulse, and 0.10 second for SuperPulse, and 2 passes, 10 W, single pulse, and 0.10 second for UltraPulse. Incisions were sharper with UltraPulse, making the surgery easier, but at the first postoperative follow-up visit, after 8 to 10 days, no differences were observed in the presentation, the healing, or the vibration of the 2 vocal folds. Coagulation along the incision line was 25 microm for SuperPulse and 15 microm for UltraPulse (median values). In comparison with SuperPulse, the UltraPulse carbon dioxide laser made the procedure easier, but did not improve the clinical outcome.


SCAR markers linked to the common bean rust resistance gene Ur-13.
Rust in common bean (Phaseolus vulgaris L.) is caused by Uromyces appendiculatus Pers.:Pers. (Unger) which exhibits a high level of pathogenic diversity. Resistance to this disease is conditioned by a considerable number of genes. Pyramiding resistance genes is desirable and could be simplified by the use of molecular markers closely linked to the genes. The resistance gene Ur-13, present in the South African large seeded cultivar Kranskop, has been used extensively in the local breeding program. The purpose of this study was the development of a molecular marker linked to Ur-13. An F(2) population derived from a cross between Kranskop and a susceptible (South African) cultivar Bonus was used in combination with bulked segregant analysis utilizing the amplified fragment length polymorphism (AFLP) technique. Seven AFLP fragments linked significantly to the rust resistance and five were successfully converted to sequence characterized amplified region (SCAR) markers. The co-dominant SCAR markers derived from a 405 bp EAACMACC fragment, KB 126, was located 1.6 cM from the gene. Two additional SCAR markers and one cleaved amplified polymorphic sequence marker were located further from the gene. The gene was mapped to linkage group B8 on the BAT 93/Jalo EEP 558 core map (chromosome 3).


Calcium signaling of in situ chondrocytes in articular cartilage under compressive loading: Roles of calcium sources and cell membrane ion channels.
Mechanical loading on articular cartilage can induce many physical and chemical stimuli on chondrocytes residing in the extracellular matrix (ECM). Intracellular calcium ([Ca2+ ]i ) signaling is among the earliest responses of chondrocytes to physical stimuli, but the [Ca2+ ]i signaling of in situ chondrocytes in loaded cartilage is not fully understood due to the technical challenges in [Ca2+ ]i imaging of chondrocytes in a deforming ECM. This study developed a novel bi-directional microscopy loading device that enables the record of transient [Ca2+ ]i responses of in situ chondrocytes in loaded cartilage. It was found that compressive loading significantly promoted [Ca2+ ]i signaling in chondrocytes with faster [Ca2+ ]i oscillations in comparison to the non-loaded cartilage. Seven [Ca2+ ]i signaling pathways were further investigated by treating the cartilage with antagonists prior to and/or during the loading. Removal of extracellular Ca2+ ions completely abolished the [Ca2+ ]i responses of in situ chondrocytes, suggesting the indispensable role of extracellular Ca2+ sources in initiating the [Ca2+ ]i signaling in chondrocytes. Depletion of intracellular Ca2+ stores, inhibition of PLC-IP3 pathway, and block of purinergic receptors on plasma membrane led to significant reduction in the responsive rate of cells. Three types of ion channels that are regulated by different physical signals, TRPV4 (osmotic and mechanical stress), T-type VGCCs (electrical potential), and mechanical sensitive ion channels (mechanical loading) all demonstrated critical roles in controlling the [Ca2+ ]i responses of in situ chondrocyte in the loaded cartilage. This study provided new knowledge about the [Ca2+ ]i signaling and mechanobiology of chondrocytes in its natural residing environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:730-738, 2018.


The ability of normal and language-impaired children to produce grammatical corrections.
The ability of normal and language-impaired children to correct grammatical violations of word order was examined. Ten language-impaired and 10 linguistically normal subjects were sampled from the following age levels: 6, 7, 8, 9, and 10 years, resulting in a total of 100 subjects. Using a procedure designed to focus attention on language form, each of the children performed a task requiring the correction of 10 sentences containing word order errors. Normal 6-, 7-, and 8-year-olds performed significantly better than their language-impaired age-matched peers. In addition, the performance of language-impaired 9-, and 10-year-olds was superior to that of the younger impaired groups. In the normal groups, the only age level differences were produced by the 6-year-olds, who performed significantly more poorly than two of the older (8- and 10-year-old) groups.


Clonal analysis of T lymphocytes isolated from ovarian carcinoma ascitic fluid. Phenotypic and functional characterization of T-cell clones capable of lysing autologous carcinoma cells.
T lymphocytes isolated from ascitic fluid of patients with stage III-IV ovarian carcinoma were cloned by means of a microculture system that allows cloning of virtually all peripheral blood human T lymphocytes. Under these experimental conditions, 15% to 42% of ascitic T cells gave rise to clonal progenies that were analyzed for different functional capabilities. Of the clones obtained, 36%-70% had cytolytic activity in a PHA-dependent assay (using P815 as target cells) that allowed detection of cytolytic cells of any specificity. About one-half of the cytolytic clones lysed the NK-sensitive K562 target cells as well. In addition, 30%-50% of the total clones released IL-2 upon stimulation with PHA for 24 hr. In all patients analyzed a variable proportion (11%-56% of all cytolytic clones) had cytolytic activity against autologous tumor cells. Some of these clones have been analyzed in more detail: 18/21 expressed the T4-T8+ phenotype, whereas the remaining 3 were T4+ T8-. Only one out of 6 clones tested lysed allogeneic ovarian carcinoma cells as well, while 5/8 had a definite NK-like activity. Finally, all 8 clones tested were inhibited by anti-T11 and 7/8 by anti-T8 monoclonal antibody.


Nuclear Transcription Factor Kappa B Downregulation Reduces Chemoresistance in Bone Marrow-derived Cells Through P-glycoprotein Modulation.
Nuclear transcription factor kappa B (NF-κB) is associated with many types of refractory cancer. However, despite multiple strategies to treat cancer and novel target drugs, multidrug resistance still causes relapses. The best-characterized mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein (P-gp). Because the direct inhibition of this protein is very toxic, other methods of multidrug resistance (MDR) regulation have been proposed. The MDR-1 promoter sequence contains a κB site, which is recognized by NF-κB. The aim of this work was to characterize whether NF-κB modulation changes the response of bone marrow-derived cells (BMDCs) to chemotherapy. We exposed BMDCs to etoposide and doxorubicin, two of the most used antineoplastic drugs. BMDCs presented high tolerance to these drugs, which correlated with high intrinsic P-gp activity and strong protein expression of NF-κB. To determine the mechanism behind the poor sensitivity of BMDCs to chemotherapy, we blocked the activity of the heterodimer protein NF-κB using the pharmacological inhibitor Bay 11-7085 and through the transfection of an adenovirus negative mutant of I kappa B alpha. The multidrug resistance phenotype of BMDCs was reversed by inhibiting the NF-κB pathway, and this change was accompanied by a decrease in P-gp activity. NF-κB is a possible target for improving the antineoplastic response.


[Place of indocyanine green coupled with fluorescence imaging in research of breast cancer sentinel node].
The sentinel node has a fundamental role in the management of early breast cancer. Currently, the double detection of blue and radioisotope is recommended. But in common practice, many centers use a single method. However, with a single detection, the risk of false negatives and the identification failure rate increase to a significant extent and the number of sentinel lymph node detected and removed is not enough. Furthermore, the tracers used until now show inconveniences. The purpose of this work is to present a new method of detection, using the green of indocyanine coupled with fluorescence imaging, and to compare it with the already existing methods. The method combined by fluorescence and isotopic is reliable, sure, of fast learning and could constitute a good strategy of detection. The major interest is to obtain a satisfactory number of sentinel nodes. The profit could be even more important for overweight patients. The fluorescence used alone is at the moment not possible. Wide ranging studies are necessary. The FLUOTECH, randomized study of 100 patients, comparing the isotopic method of double isotope technique and fluorescence, is underway to confirm these data.


Herbal medicine foot bath for the treatment of diabetic peripheral neuropathy: protocol for a randomized, double-blind and controlled trial.
As a common complication of diabetes, the incidence of diabetic peripheral neuropathy (DPN) is 60-70% worldwide. DPN is a major risk factor for diabetic foot, which may lead to foot ulceration and even amputation. The treatment of DPN remains challenging. Our preliminary study demonstrated that the external application of Tangbi Waixi (TW) decoction to the lower extremities relieved clinical symptoms and improved nerve conduction velocity in DPN patients. The aim of this study was to verify the efficacy of TW among DPN patients and evaluate the herb mixture's safety using rigorous methodological designs. This study is a multicenter, double-blind, randomized controlled trial. A total of 640 DPN patients will be recruited and randomized to receive a foot bath with either the TW decoction or control drug. Participants will be assessed at baseline and 12 and 24 weeks after treatment. The primary outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary outcomes were nerve conduction velocity, blood glucose, blood lipids, serum inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ-5D) and TCM symptom scores. This multicenter, prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of foot bath treatment with TW decoction. Positive results would provide a novel treatment regimen for DPN patients. Chinese Clinical Trial Registry, ChiCTR-IOR-16009331 . Registered on 8 October 2016.


Characterization of metabolically healthy obese Brazilians and cardiovascular risk prediction.
The aim of this study was to identify metabolically healthy obese individuals (MHOs) and their characteristics, as well as to estimate cardiovascular risk using the Framingham score. In all, 258 adult individuals, with body mass index ≥30 kg/m(2), and no report of diabetes mellitus or cardiovascular disease, were classified according to their metabolic state considering two criteria: rhe National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the homeostasis model assessment (HOMA). Biochemical, anthropometric, and body composition characteristics were compared between MHOs and metabolically unhealthy obese (MUO) individuals according to each criterion. Cardiovascular risk was estimated using the Framingham score. MHOs exhibited smaller waist circumference and lower body fat percentage, as well as lower blood glucose, triacylglycerols, and insulin levels, in addition to higher high-density lipoprotein cholesterol concentration, when HOMA criterion (P < 0.05) and associated criteria were adopted. The estimated cardiovascular risk was similar between the two groups according to the HOMA index; however, the risk was significantly lower according to the ATP III guidelines. Obese individuals at intermediate and high risk showed higher body fat percentage compared with those individuals at low risk. MHOs had biochemical and anthropometric characteristics, such as lower body mass index, waist circumference, percent fat mass, glucose, triacylglycerols, and increased high-density lipoprotein, that made them different from those individuals classified as MUO. The latter exhibited increased risk for cardiovascular disease according to the Framingham score, when using the ATP III criterion alone or in conjunction with the HOMA index.


Progesterone receptor and SRC-1 participate in the regulation of VEGF, EGFR and Cyclin D1 expression in human astrocytoma cell lines.
Astrocytomas are the most common primary brain tumors in humans. It has been reported that vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), cyclin D1 and progesterone receptor (PR) expression levels are elevated in patients with high-grade astrocytomas. Progesterone (P) regulates astrocytomas growth through its interaction with PR, which recruits coregulatory proteins such as steroid receptor coactivator-1 (SRC-1) that are required for efficient transcriptional activation. The regulation of VEGF, EGFR and cyclin D1 expression by P in human astrocytoma cells is not known. We studied the role of PR and SRC-1 in the expression of VEGF, EGFR and cyclin D1 mediated by P in human astrocytoma cell lines grade III (U373) and IV (D54). P significantly increased VEGF and EGFR mRNA expression after 12h of treatment in D54 cells that was reflected at protein level 24h after treatment. This effect was blocked by the PR antagonist, RU 486. In U373 cells cyclin D1 mRNA and protein expression was induced by P after 6 and 8h of treatment, respectively, and this effect was blocked with RU 486. Transfection with short hairpin RNA targeting coactivator SRC-1 significantly reduced VEGF expression after 24h of treatment. Collectively, our results indicate that P regulates VEGF and EGFR expression in D54 cells and cyclin D1 expression in U373 through PR, and that SRC-1 participates in the regulation of VEGF expression.


Quad Tendon Autograft for Posterior Cruciate Ligament Reconstruction Using Transseptal and Posteromedial Portals.
We describe a surgical technique for reconstruction of the posterior cruciate ligament with quad tendon autograft using transseptal portal. We place the guide for the tibial socket through the posteromedial portal instead of transnotch, which is the most common practice. The use of the transseptal portal allows good visualization during the drilling of the tibial socket to protect the neurovascular bundle while avoiding the use of fluoroscopy. The advantage of using the posteromedial approach is the easy placement of the drill guide and to option to pull the graft once through the posteromedial portal and a second time through the notch, which helps passing the "killer turn." The quad tendon is harvested with a bone block that is placed in the tibial socket and fixed with screws in the tibial and femoral side.


Consequences of manipulation in organizations: two studies on its effects on emotions and relationships.
This investigation analyzes the correlates of manipulation in organizations with respect to employees' emotions and interpersonal relationships. In Study 1, twelve tactics were identified as manipulative from a set of 115 tactics. For example: "steer the other person subliminally in a certain direction by using clever arguments," "form covert networks or coalitions," "pretend to build trust and to help the other person with work," "withhold, filter, or falsify information," and "interpret the existing rules in own way, exploit ambiguity." In Study 2, manipulative cases (N = 208) were analyzed. Factor analyses showed three factors of postmanipulation emotions (evaluation, potency, activation). Results showed that the evaluative emotions were significantly more negative and activated emotions were less negative among manipulated employees than among manipulators, whereas the potency emotions in both groups were not significantly different. The deterioration that manipulation caused in relationships was perceived less by manipulators than by the manipulated employees. Conclusions about interpersonal mistrust's resistance to change after manipulation are explained.


Pathology Behind Constant Watery Vaginal Discharge: A Rare Case of Uterine Cervical Minimal Deviation Adenocarcinoma.
Minimal deviation adenocarcinoma (MDA) of uterine cervix is a rare malignant disease with rather poorer prognosis partially due to the early misdiagnosis. Hence, better understanding of early-stage symptoms is critical. We report a case of a 39-year-old woman came to hospital with a chief complaint of "a watery vaginal discharge for 9 months". She was further diagnosed as having uterine cervical minimal deviation adenocarcinoma in cervical LEEP specimen and MDA stage IIIC1 (FIGO 2018 staging-after correction) in post-hysterectomy histopathology. Currently, the definitive treatment is hysterectomy with adjuvant therapy based on staging. This article gives concise symptoms, history, and images of MDA colposcopy finding and histopathology, through the whole process of diagnosis and treatment for future clinical reference.


Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.
To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.


Intramural hematoma and dissection involving ascending aorta: the clinical features and prognosis.
The clinical features and remedies of acute aortic intramural hemorrhage (IMH) are well discussed. This study prospectively analyzes the features compared with those of Type A aortic dissection, and evaluate the treatment modalities and the prognosis with Type A IMH managed by our original program, Eighty-six consecutive patients consisted of acute type A IMH (n = 36) and dissection (n = 50) were diagnosed between January 1994 and March 2002. Patients with IMH were older (mean 67 and 60, P = 0.0017), more hypertensive (P = 0.0015), not hyperlipidemic (P = 0.0042) than those with dissection. The incidences of preoperative pericardial effusion and aortic regurgitation were significantly lower in patients with intramural hematoma than with dissection, respectively (8:28 versus 22:28, P = 0.0366, 4:32 versus 22:28, P = 0.0011). Urgent operation was performed for the patients of IMH with cardiac tamponade or rupture and all dissections. Uncomplicated patients of the patients with IMH were treated medically. Late surgical conversion was applied for the medical treated case on any condition with persistent pain, progression to type A dissection, ruptured aneurysm, or aneurysmal enlargement (>60 mm). Operative mortality, late cardiovascular event, and long-term survival were evaluated statistically. Ten urgent surgical repairs were performed with type A IMH patients and one patient died postoperatively. The rest 26 patients were treated medically. The mean follow up period was 39 +/- 28 months. Among the 26 patients, seven were converted surgical intervention. Cardiovascular event free curve on the 26 patients (Kaplan-Meier, CI: 95%) was 65.6% (45.9-85.3), 59.1% (37.5-80.6) at 2, 4 years. There were six dissection and six IMH patients death during follow up. Two of IMH patients died from cardiovascular event. The actuarial survival rate (Kaplan-Meier, CI: 95%) was 87.5% (76.0-99.1):87.9% (66.2-97.1), 81.7% (66.2-97.1):87.9% (78.8-97.0) at 2, 4 years (P = 0.8393). Type A IMH tends to occur in older, more hypertensive and not hyperlipidemic patients, showed lower incidences of preoperative aortic valve regurgitation and pericardial effusion than dissection. Medical treatment alone was not enough to manage all type A IMH patients, and 47.2% (17/36) of the patients needed surgical intervention. Urgent surgical repair was not necessary for all type A IMH patients to achieve favorable surgical outcome with careful follow-up using imaging modality.


Effects of Escherichia Coli-derived Recombinant Human Bone Morphogenetic Protein-2 Loaded Porous Hydroxyaptite-based Ceramics on Calvarial Defect in Rabbits.
Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (P<0.05). The average new bone formation % (new bone area per total defect area) of NC, BO, HA, and HA-BMP at 4-week after surgery were 12.65±5.89%, 29.63±6.99%, 28.86±6.17% and 49.56±8.23%, respectively. However, there was no statistical difference in the bone formation between HA and BO groups. HA-BMP promoted more bone formation than NC, BO and HA alone. Thus, using E. coli-derived rhBMP-2 combined with porous HA-based ceramics can promote new bone formation.


A short synthesis of antimalarial peroxides.
A concise and efficient synthesis of two simplified diastereomeric analogues of a natural peroxide is presented. Both compounds could be isolated in high purity and fully identified. They exhibited moderate antimalarial activity.


Soy polysaccharide in an enteral diet: Effects on rat intestinal cell proliferation, morphology and metabolic function.
The present study was conducted to compare the effect of soy polysaccharide (SP)-supplemented and fibre-free enteral diets and a normal chow diet on intestinal and colonic adaptation of rat gastrointestinal morphometrics and cytokinetics. Results showed that the fibre-free diet caused a significant decrease in various gut parameters, such as cell proliferation, tissue wet weight, and intestinal brush border enzymes, when compared to the normal gut of chow-fed rats. However the SP-supplemented enteral diet resulted in a significant improvement in several parameters in most regions along the gastrointestinal tract, when compared to orally-fed animals. These studies demonstrate that significant changes occur in the intestine as a result of enteral diets, with regional variation. Furthermore, the results demonstrate that SP stimulates crypt cell proliferation which could, in part, hasten recovery from intestinal mucosal damage. The addition of SP to enteral diets seems potentially advantageous.


Today's minimal requirements for a practical dental office infection control and exposure control program.
The current climate in society regarding infectious diseases in general, and herpes, hepatitis, and HIV infections in particular, dictates that today's dental practices must use effective infection control techniques. The Occupational Safety and Health Administration continues to inspect, cite, and fine health care facilities. More states are implementing regulations concerning the operation of health care facilities. Patients are becoming more sophisticated in their scrutinizing of the dental and medical professions' approach to asepsis. Media coverage of exposure incidents is becoming more intense. All these factors leave dentists no choice; they must implement appropriate infection control techniques. The life-time cost of effective infection control is far less than one malpractice settlement. Implementation of an effective infection control program to promote dental asepsis can be cost-effective. In addition, it can be a practice builder.


Mesenchymal Stem Cells with Granulocyte Colony-Stimulating Factor Reduce Stress Oxidative Factors in Parkinson's Disease
Recent studies have shown that bone marrow mesenchymal stem cells (BMSCs) have a putative ability to promote neurogenesis and produce behavioral and functional improvement. Our previous study demonstrated that co-treatment of granulocyte colony-stimulating factor (G-CSF) and BMSCs have beneficial effects on Parkinson's models. The main purpose of this research was to investigate the effects of these two factors on oxidative stress factors in the brain of Parkinson's rat. Adult male Wistar rats (weighing 200–250 g) were used and randomly divided into five groups of seven each. To create the Parkinson's model, 6-OHDA was injected into the left substantia nigra pars compacta. The BMSCs (2 × 106) and G-CSF (75 µg/kg) were used for treatment after creating the PD model. After four weeks, the brains of rats were removed and processed for immunohistochemical studies, such as tyrosine hydroxylase-positive neurons as well as analysis of oxidative stress factors. The results showed that the injected BMSCs could cross the BBB. The injected cells are also able to settle in different areas of the brain. Analyses of the brain oxidative stress factors showed that G-CSF and BMSCs reduced the expression of malondialdehyde and induced the activity of superoxide dismutase, glutathione, and peroxidase ferric reducing ability of plasma. Co-administration of G-CSF and BMSC reduced the expression of pro-inflammatory cytokines and induced the activity of antioxidant enzymes; however, neurogenesis increased in the brain.


Plasma asymmetric dimethylarginine in active rheumatoid arthritis: links with oxidative stress and inflammation.
Endothelial dysfunction and accumulation of asymmetric dimethylarginine (ADMA) have been identified as independent predictors of future cardiovascular events in patients with coronary artery disease. The aim of the study was to investigate the factors that determine increased accumulation of ADMA, an endogenous inhibitor of nitric oxide synthesis, in patients with rheumatoid arthritis (RA). We studied 46 consecutive patients with RA (39 women, 7 men; mean age, 57 years [range, 23-75 years]) with active disease (mean Disease Activity Score 28 [DAS28], 5.2), without clinically overt cardiovascular disease and 50 controls matched for age, sex, hypertension, blood cholesterol, and glucose. We assessed the plasma levels of ADMA, symmetric dimethylarginine (SDMA), L‑arginine, and the marker of oxidative stress, 8‑iso‑prostaglandin F2α (8‑iso‑PGF2α). ADMA and SDMA levels were significantly higher in the RA group than in controls (0.58 ±0.081 vs. 0.46 ±0.045 μmol/l, P <0.0001; 0.45 ±0.07 vs. 0.36 ±0.046 μmol/l, P <0.0001; respectively). ADMA levels in the RA group correlated positively with fibrinogen (r = 0.70, P <0.00001), C‑reactive protein (CRP; r = 0.88, P <0.00001), DAS28 (r = 0.44, P = 0.002) and Health Assessment Questionnaire scores (r = 0.39, P = 0.008), but not with age, renal function, or the medications used. 8‑iso‑PGF2α correlated positively with ADMA (r = 0.82), SDMA (r = 0.72), CRP (r = 0.76), fibrinogen (r = 0.57) (all, P <0.0001) and DAS28 (r = 0.44, P = 0.003). Regression analysis models showed that CRP was the only independent predictor of 8‑iso‑PGF2α and ADMA levels in RA. Our study is the first to show positive associations between plasma ADMA levels and the production of 8‑isoprostanes and CRP in RA.


Characteristics of emergency medicine fellowships.
Little has been reported in the literature on the characteristics of existing and planned emergency medicine fellowships. To help answer important questions about fellowships, a 28-question survey was developed by representatives from the University Association for Emergency Medicine education and fellowship committees, the Emergency Medicine Residents' Association, and a health services researcher. This questionnaire was sent to all emergency medicine residency directors and known emergency medicine fellowship programs. The results of our survey indicate that there are 18 current and 11 planned fellowships. The fellowships primarily last one year, are research oriented, and place a large emphasis on toxicology, emergency medical services, and critical care. They are based mostly in university or university-affiliated hospitals, and will graduate physicians who stay in academic emergency medicine. The major problems with fellowships include inadequate funding and lack of adequate candidates.


Arrhythmias in patients with acute coronary syndrome in the first 24 hours of hospitalization.
In patients with acute coronary syndrome (ACS), we sought to: 1) describe arrhythmias during hospitalization, 2) explore the association between arrhythmias and patient outcomes, and 3) explore predictors of the occurrence of arrhythmias. In a prospective sub-study of the IMMEDIATE AIM study, we analyzed electrocardiographic (ECG) data from 278 patients with ACS. On emergency department admission, a Holter recorder was attached for continuous 12-lead ECG monitoring. Approximately 22% of patients had more than 50 premature ventricular contractions (PVCs) per hour. Non-sustained ventricular tachycardia (VT) occurred in 15% of patients. Very few patients (≤ 1%) had a malignant arrhythmia (sustained VT, asystole, torsade de pointes, or ventricular fibrillation). Only more than 50 PVCs/hour independently predicted an increased length of stay (p < .0001). No arrhythmias predicted mortality. Age greater than 65 years and a final diagnosis of acute myocardial infarction independently predicted more than 50 PVCs per hour (p = .0004). Patients with ACS seem to have fewer serious arrhythmias today, which may have implications for the appropriate use of continuous ECG monitoring.


Ascorbic acid addition during dehydration improves garlic shoot tip cryopreservation but does not affect viral load.
Cryopreservation is known be an effective method for virus elimination in garlic. However, oxidative damage during the cryopreservation seriously affects the survival of garlic after cryopreservation. Ascorbic acid (AsA) can reduce oxidative damage and improve regrowth following cryopreservation, and its effect may be influenced by the step during which it is added. In this study, AsA was added at the osmoprotection (O) and dehydration (DE) steps of cryopreservation. By observing the dynamic changes in cell viability and reactive oxygen species (ROS) components with different AsA treatments, AsA has been linked to the reduced accumulation of ROS in the shoot tips. Increased gene expression levels of antioxidant enzymes also explained the ROS scavenging effect of AsA. The correlation analysis between cell viability, ROS, membrane lipid peroxidation-related indicators and antioxidant-related indicators showed that membrane lipid peroxidation caused by excess ROS was the main factor affecting cell viability. Ascorbic acid added during dehydration minimized the accumulation of ROS from dehydration to dilution and alleviated the oxidative damage during cryopreservation. Thus, the survival and regrowth of the garlic was significantly improved after cryopreservation. Dehydration was found to be the suitable step for the addition of AsA during garlic cryopreservation. We further evaluated the virus elimination effect under optimal AsA treatment. However, there was no significant difference in virus content in regenerated plants when compared with the control.


Unusual subarachnoid metastasis of an intracranial chordoma in infancy.
The authors report a case of large clivus chordoma in a 61/2-year-old child with multiple subarachnoid metastatic dissemination over the cerebellar hemispheres and spinal cord.


EMG amplitude distribution changes over the upper trapezius muscle are similar in sustained and ramp contractions.
To investigate whether global motor unit recruitment to compensate for muscle fatigue during sustained contraction and to regulate force increase during ramp contraction are controlled in similar manners in the upper trapezius muscle. Fourteen subjects performed a 10-s ramp contraction from 0% to 90% of maximal voluntary contraction (MVC) and a 3-min sustained contraction at 25% MVC. Both contractions involved isometric shoulder elevation with a multi-channel surface electromyographical grid placed on the skin above the muscle. To evaluate the global muscle activation pattern, the changes in spatial amplitude distribution of the sustained and the ramp contraction were examined and compared. In both contraction types, the upper part of the trapezius muscle was spatially non-uniform (inhomogeneous) activated. Throughout the sustained contraction, the amplitude distribution of the upper trapezius muscle became more similar to the amplitude distribution at higher force levels. These findings support the hypothesis that global motor unit recruitment to compensate for muscle fatigue during a sustained contraction, and to regulate force increase during a ramp contraction is controlled in a similar manner. Consequently, they confirm fundamental principles of motor unit activation based on recordings of limited motor unit samples.


Are we ignoring the role of urban forests in intercepting atmospheric microplastics?
Occurrences and characteristics of atmospheric microplastics(MPs) have been widely studied by previous studies, while the mitigation of airborne MPs pollution was not well understood. In this study, atmospheric samples of MPs were collected in pairs on the rooftop and under trees composed of representative afforested species Ficus microcarpa in Chengdu, Southwest China, to explore whether trees could intercept MPs. Results showed that the daily life of human beings and textile industries of urban areas were sources of airborne MPs as revealed by chemical compositions and air trajectories. The trees with the high coverage degree (88%) and large three-dimensional spaces formed by leaves did have the ability to intercept high-density MPs with small sizes under the force of gravity. The intercepting rate was about 16.3%, 12,593 n/m2 of fibers and 347.69 kg of MPs could be intercepted by urban forests for one year. However, threshold values of rainfall intensity (12 mm/d) and rainfall amounts (14 mm) were found to limit the intercepting mechanism, and intercepting effects decrease with the increase of rainfall amounts (r =-0.71). This work provides quantitative evidence that elucidated urban forests may act as receptors of airborne MPs, thus improving the air quality and human health.


Ischemic ST segment depression in leads V2-V3 as the presenting electrocardiographic feature of posterolateral wall myocardial infarction.
In this study of 14 patients hospitalized with a first event of myocardial infarction, maximal ST segment depression in precordial leads V2 and V3 was the sole ECG finding during chest pain in the first 24 hours of evolving posterolateral infarction, based upon further two-dimensional echocardiographic examination and cardionuclear imaging. Other ECG findings compatible with posterolateral infarction such as the appearance of Q waves in leads V5 and V6, increased R/S ratio in leads V1 and V2, and a diminution of R wave amplitude in leads 1, aVL, V5, and V6 were relatively delayed manifestations in the majority of patients. The clinical course of all patients was benign. It therefore seems reasonable to conclude that ST segment depression in leads V2 and V3 in the absence of reciprocal ECG changes may represent the initial ECG finding of posterolateral infarction in the suitable clinical context of an acute coronary event.


Screening of a microvascular endothelial cDNA library identifies rabaptin 5 as a novel autoantigen in Alzheimer's disease.
The pathogenesis of Alzheimer's disease (AD) includes the participation of the immune system. To identify antigenic targets in AD, we screened a human microvascular endothelial cell cDNA library with sera from patients with AD, and we identified rabaptin 5 (RABPT5). We detected serum IgG specific to RABPT5 in 65% of patients with AD and in 35% of patients with systemic lupus erythematosus, but in no healthy controls. Our results demonstrated a massive redistribution of this protein in the cytoplasm of endothelial and neuronal cells in apoptosis. In conclusion, we identified RABPT5 as a novel autoantigen in AD.


Computational redesign of the Escherichia coli ribose-binding protein ligand binding pocket for 1,3-cyclohexanediol and cyclohexanol.
Bacterial periplasmic-binding proteins have been acclaimed as general biosensing platform, but their range of natural ligands is too limited for optimal development of chemical compound detection. Computational redesign of the ligand-binding pocket of periplasmic-binding proteins may yield variants with new properties, but, despite earlier claims, genuine changes of specificity to non-natural ligands have so far not been achieved. In order to better understand the reasons of such limited success, we revisited here the Escherichia coli RbsB ribose-binding protein, aiming to achieve perceptible transition from ribose to structurally related chemical ligands 1,3-cyclohexanediol and cyclohexanol. Combinations of mutations were computationally predicted for nine residues in the RbsB binding pocket, then synthesized and tested in an E. coli reporter chassis. Two million variants were screened in a microcolony-in-bead fluorescence-assisted sorting procedure, which yielded six mutants no longer responsive to ribose but with 1.2-1.5 times induction in presence of 1 mM 1,3-cyclohexanediol, one of which responded to cyclohexanol as well. Isothermal microcalorimetry confirmed 1,3-cyclohexanediol binding, although only two mutant proteins were sufficiently stable upon purification. Circular dichroism spectroscopy indicated discernable structural differences between these two mutant proteins and wild-type RbsB. This and further quantification of periplasmic-space abundance suggested most mutants to be prone to misfolding and/or with defects in translocation compared to wild-type. Our results thus affirm that computational design and library screening can yield RbsB mutants with recognition of non-natural but structurally similar ligands. The inherent arisal of protein instability or misfolding concomitant with designed altered ligand-binding pockets should be overcome by new experimental strategies or by improved future protein design algorithms.


CO2 to succinic acid - Estimating the potential of biocatalytic routes.
Microbial carbon dioxide assimilation and conversion to chemical platform molecules has the potential to be developed as economic, sustainable processes. The carbon dioxide assimilation can proceed by a variety of natural pathways and recently even synthetic CO2 fixation routes have been designed. Early assessment of the performance of the different carbon fixation alternatives within biotechnological processes is desirable to evaluate their potential. Here we applied stoichiometric metabolic modeling based on physiological and process data to evaluate different process variants for the conversion of C1 carbon compounds to the industrial relevant platform chemical succinic acid. We computationally analyzed the performance of cyanobacteria, acetogens, methylotrophs, and synthetic CO2 fixation pathways in Saccharomyces cerevisiae in terms of production rates, product yields, and the optimization potential. This analysis provided insight into the economic feasibility and allowed to estimate the future industrial applicability by estimating overall production costs. With reported, or estimated data of engineered or wild type strains, none of the simulated microbial succinate production processes showed a performance allowing competitive production. The main limiting factors were identified as gas and photon transfer and metabolic activities whereas metabolic network structure was not restricting. In simulations with optimized parameters most process alternatives reached economically interesting values, hence, represent promising alternatives to sugar-based fermentations.


Liming effects of poultry litter derived biochar on soil acidity amelioration and maize growth.
Crop production in acid soils is facing enormous challenges due to low soil quality associated with an increase in the acidification rate and aluminum toxicity. Despite comprehensive prior work with biochar application on nutrient availability and crop productivity in acid soils, little information is available about the recommendation or standardization of biochar application rates that are more suitable for soil fertility improvement under different soil environments (physico-chemical properties) for maximizing the benefits of biochar applications and minimizing the potential environmental risk. Thus, the objective of this study was to investigate the effectiveness of poultry litter (PL) and poultry litter biochar (PLB) in ameliorating the fertility of acid soils through incubation and pot experiments. The soil was amended with different materials as follows; lime (1 g kg-1), PL (5, 10 and 15 g kg-1) and PLB (5, 10 and 15 g kg-1) along with control (non-amended). A pot experiment was also conducted using similar treatments to observe the responses of maize crop to the different amendments. The results indicated an increase in the pH and a decrease in exchangeable acidity in lime, PL and PLB amended soils. Lower soil pH, base cations and soil available phosphorus (P), and higher exchangeable acidity were found in control than the amended soils. Compared to PL and lime, PLB achieved greater increase rate in soil pH and reduction rate in soil exchangeable acidity with increased soil exchangeable base cations. An increase in soil available calcium (Ca) was observed in the lime treatment, while in PL and PLB treatments, there was an increase in soil available Ca, magnesium (Mg), potassium (K) and P. Application of the amendments increased availability of nitrogen (N), P, K, Ca and Mg relative to the control for maize in the pot experiment. When PL and PLB amendments were compared, it was found that the PLB was the best choice for the amelioration of acid soils as well as nutrient uptake by maize plants. It is suggested that application of PLB at the rate of 15 g kg-1 is suitable for maize growth in acid soils.


Effects of Breaking Sitting by Standing and Acute Exercise on Postprandial Oxidative Stress.
Sedentary behavior, which includes sitting and TV viewing, has been identified as an independent risk factor for type 2 diabetes and cardiovascular disease. Breaking sedentary behavior improves metabolic health such as postprandial glycaemia and insulinemia. However, the mechanisms underlying this effect are unclear. Here, we examined whether breaking sitting by standing and acute exercise reduces postprandial oxidative stress. Fifteen participants performed 3 trials (sitting, standing, and exercise), each lasting 2 days, in a randomised order. On day one of sitting trial, participants sat in a chair. For the standing trial, the participants stood 6 times, for a 45-minute period each time. For the exercise trial, the participants walked or ran at approximately 60% of age-predicted maximum heart rate for 30 minutes. On day two of each trial, participants rested and consumed the standardised breakfast and lunch. Blood samples were collected in the morning and afternoon on day one, and fasting and at 2, 4, and 6 hours postprandially on day two. The concentrations of serum derivatives of reactive oxygen metabolites (d-ROMs) measured at 4 hours (P = 0.064) and 6 hours (P = 0.071) tended to be higher than that in the fasting state in the sitting trial, but not standing and exercise trial (two-factor analysis of variance (ANOVA), trial × time interaction, P = 0.006). Our results indicate the importance of reducing sitting time for improving postprandial oxidative stress status.


Image-guided radiotherapy.
We present the updated recommendations of the French society for oncological radiotherapy on image-guided radiotherapy (IGRT). The objective of the IGRT is to take into account the anatomical variations of the target volume occurring between or during the irradiation fractions, such as displacements and/or deformations, so that the delivered dose corresponds to the planned dose. This article presents the different IGRT devices, their use and quality control, and quantify the possible additional dose generated by each of them. The practical implementation of IGRT in various tumour locations is summarised, from the different "RecoRad™" guideline articles. Adaptive radiotherapy is then detailed, due to its complexity and its probable development in the next years. The place of radiation technologist in the practice of IGRT is then specified. Finally, a brief update is proposed on the delicate question of the additional dose linked to the in-room imaging, which must be estimated and documented at a minimum, as long as it is difficult to integrate it into the calculation of the dose distribution.


Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1.
Elastic laminae are extracellular matrix constituents that not only contribute to the stability and elasticity of arteries but also play a role in regulating arterial morphogenesis and pathogenesis. We demonstrate here that an important function of arterial elastic laminae is to prevent monocyte adhesion, which is mediated by the inhibitory receptor signal regulatory protein (SIRP) alpha and Src homology 2 domain-containing protein-tyrosine phosphatase (SHP)-1. In a matrix-based arterial reconstruction model in vivo, elastic laminae were resistant to leukocyte adhesion and transmigration compared with the collagen-dominant arterial adventitia. The density of leukocytes within the elastic lamina-dominant media was about 58-70-fold lower than that within the adventitia from 1 to 30 days. An in vitro assay confirmed the inhibitory effect of elastic laminae on monocyte adhesion. The exposure of monocytes to elastic laminae induced activation of SIRP alpha, which in turn activated SHP-1. Elastic lamina degradation peptides extracted from arterial specimens could also activate SIRP alpha and SHP-1. The knockdown of SIRP alpha and SHP-1 by specific small interfering RNA diminished the inhibitory effect of elastic laminae, resulting in a significant increase in monocyte adhesion. These observations suggest that SIRP alpha and SHP-1 potentially mediate the inhibitory effect of elastic laminae on monocyte adhesion.


Glucocorticoid-induced growth inhibition with enhanced expression of ductal epithelium of human salivary gland adenocarcinoma cells transplanted into athymic nude mice.
The effect of glucocorticoid on growth and the histologic features of adenocarcinoma induced in nude mouse by the inoculation of neoplastic epithelial cells of salivary duct origin (HSG) were studied. Subcutaneous injection of dexamethasone (low-dose group: 0.05 micrograms/g, high-dose group: 0.25 micrograms/g) four times a week for 8 weeks significantly (P less than 0.05) inhibited tumor growth, and in one mouse the tumor had almost completely disappeared by the middle of the sixth week of treatment. In addition, dexamethasone induced an apparent luminal structure in the tissue section of the tumor and enhanced the immunoperoxidase reaction to epithelial membrane antigen. The results indicate that dexamethasone inhibited the proliferation of HSG cells in the nude mouse transplantation system probably by inducing the cellular differentiation of the HSG cells toward the more differentiated ductal epithelia via glucocorticoid receptors.


Addition of AT1 blocker fails to overcome resistance to ACE inhibition in adriamycin nephrosis.
Angiotensin-converting enzyme (ACE) inhibitors provide renoprotection, but there is considerable interindividual variability in therapeutic efficacy, with residual proteinuria and progressive renal function loss in many individuals. This requires additional strategies to optimize therapy response, particularly for individuals with a poor response to ACE inhibition. We studied whether co-treatment with an angiotensin II subtype 1 (AT1) receptor antagonist (AII-A) improves the individual antiproteinuric response of maximal ACE inhibition in established adriamycin nephrosis. Rats were instituted on lisinopril (75 mg/L) six weeks after disease induction. After two weeks rats were re-stratified for residual proteinuria to continue this regimen, to a higher dose of lisinopril (150 mg/L) or to co-treatment with the AII-A L 158,809 for another four weeks. Groups on monotherapy AII-A and vehicle served as controls (all groups N=15). Lisinopril lowered proteinuria by 63% from 741 to 246 g/day (range of percentage change -90 to +2%). Neither increasing the dose of the ACE inhibitor nor addition of AII-A to ACE inhibition improved the antiproteinuric efficacy on a group or individual level: non-responders remained non-responders. All drug categories reduced hard end-points of focal glomerulosclerosis to a similar degree. ACE inhibition has variable renal protective efficacy in the adriamycin model. Neither increasing the dose of the ACE inhibitor beyond the optimal level nor co-treatment with AII-A overcome the individual therapy resistance. Thus, in established adriamycin nephrosis, blockade of the renin-angiotensin system at two different levels offers no additional benefit over ACE inhibition alone, either on the group or individual level.


Convulsion following intravenous fluorescein angiography.
Tonic-clonic seizures followed intravenous fluorescein injection for fundus angiography in a 47-year-old male. Despite precautions this adverse reaction recurred on re-exposure to intravenous fluorescein.


Effect of disease and drug treatment on blood serotonin and monoamine oxidase B activity in Parkinson's disease.
Serotonin (5-hydroxytryptamine, 5HT) content and monoamine oxidase (MAO) activity were determined in whole blood of patients with Parkinson's disease (PD) with and without drug treatment and compared with controls. From that comparison a significant reduction in platelet 5HT became apparent in PD. Selegiline, which was always used in combination with L-dopa, not only inhibited MAO activity, as expected, but it also appeared to induce an increase in 5HT content.


Haploidentical stem cell transplantation for children with high-risk leukemia.
The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced-intensity conditioning regimen for high-risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell-depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10(6)/kg (range, 4.00-20.20 × 10(6)/kg); CD3+: 0.88 × 10(5)/kg (0.11-1.35 × 10(5)/kg); and CD56+: 71.30 × 10(6)/kg (31.50-131.80 × 10(6)/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13-50 months post-HSCT. Three patients died after bone marrow relapse, while only one died of transplant-related causes. Virus reactivation was the main post-transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD. HI-HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high-risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries.


Protection of endogenous enkephalin degradation from peptidases in human serum by actinonin.
This paper describes a new method for detecting the endogenous enkephalin level in human serum without interference from serum peptidases and contaminating proteins. The method consists of a combination of addition of a peptidase inhibitor, actinonin to serum and dialysis. The activity of enkephalin degrading enzymes was completely abolished by actinonin. Furthermore, contaminating proteins which interfered with RIA assay of enkephalins were removed by the dialysis process. This combination process enabled precise detection of the concentration of enkephalin-like substances in human serum. The mean normal serum level of leucine-enkephalin assayed by this method in 12 healthy volunteers was 93.4 pg/ml.


Mass spectrometry imaging of glucosinolates in Arabidopsis flowers and siliques.
Glucosinolates are multi-functional plant secondary metabolites which play a vital role in plant defence and are, as dietary compounds, important to human health and livestock well-being. Knowledge of the tissue-specific regulation of their biosynthesis and accumulation is essential for plant breeding programs. Here, we report that in Arabidopsis thaliana, glucosinolates are accumulated differentially in specific cells of reproductive organs. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), distribution patterns of three selected compounds, 4-methylsulfinylbutyl (glucoraphanin), indol-3-ylmethyl (glucobrassicin), and 4-benzoyloxybutyl glucosinolates, were mapped in the tissues of whole flower buds, sepals and siliques. The results show that tissue localization patterns of aliphatic glucosinolate glucoraphanin and 4-benzoyloxybutyl glucosinolate were similar, but indole glucosinolate glucobrassicin had different localisation, indicating a possible difference in function. The high resolution images obtained by a complementary approach, cryo-SEM Energy Dispersive X-ray analysis (cryo-SEM-EDX), confirmed increased concentration of sulphur in areas with elevated amounts of glucosinolates, and allowed identifying the cell types implicated in accumulation of glucosinolates. High concentration of sulphur was found in S-cells adjacent to the phloem in pedicels and siliques, indicating the presence of glucosinolates. Moreover, both MALDI MSI and cryo-SEM-EDX analyses indicated accumulation of glucosinolates in cells on the outer surface of the sepals, suggesting that a layer of glucosinolate-accumulating epidermal cells protects the whole of the developing flower, in addition to the S-cells, which protect the phloem. This research demonstrates the high potential of MALDI MSI for understanding the cell-specific compartmentation of plant metabolites and its regulation.


The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial.
Two low-dose levonorgestrel intrauterine contraceptive systems (LNG-IUSs; total content 13.5 mg [average approx. 8 μg/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 μg/24 hours over the first year; LNG-IUS 13]) have previously been shown to be highly effective (3-year Pearl Indices: 0.33 and 0.31, respectively), safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18-25 vs 26-35 years), or body mass index (BMI, <30 vs ≥30 kg/m2). Nulliparous and parous women aged 18‒35 years with regular menstrual cycles (21‒35 days) requesting contraception were randomized to 3 years of LNG-IUS 8 or LNG-IUS 13 use. In the LNG-IUS 8 and LNG-IUS 13 groups, 1432 and 1452 women, respectively, had a placement attempted and were included in the full analysis set; 39.2%, 39.2% and 17.1% were 18-25 years old, nulliparous and had a BMI ≥30 kg/m2, respectively. Both systems were similarly effective regardless of age, parity or BMI; the subgroup Pearl Indices had widely overlapping 95% confidence intervals. Placement of LNG-IUS 8 and LNG-IUS 13 was easier (p < 0.0001) and less painful (p < 0.0001) in women who had delivered vaginally than in women who had not. The complete/partial expulsion rate was 2.2-4.2% across all age and parity subgroups and higher in parous than in nulliparous women (p = 0.004). The incidence of pelvic inflammatory disease was 0.1-0.6% across all age and parity subgroups: nulliparous and younger women were not at higher risk than parous and older women, respectively. The ectopic pregnancy rate was 0.3-0.4% across all age and parity subgroups. Across all age and parity subgroups, the 3-year completion rate was 50.9-61.3% for LNG-IUS 8 and 57.9-61.1% for LNG-IUS 13, and was higher (p = 0.0001) among older than younger women in the LNG-IUS 8 group only. LNG-IUS 8 and LNG-IUS 13 were highly effective, safe and well tolerated regardless of age or parity. Clinical trials.gov NCT00528112.


Comparative evaluation of the efficacy of ozone therapy and low level laser therapy on oral mucosal wound healing in rat experimental model.
The aim of the present study was to evaluate and compare the effectiveness of ozone therapy and low-level laser therapy (LLLT) on healing of oral mucosal wounds in rats through histological assessment. Thirty male Wistar rats were employed in this study. Following a 5-mm surgical wound created on the buccal mucosa, the rats were randomly distributed into 3 groups of 10: (1) ozone group (treated with topical gaseous ozone), (2) laser group (treated with LLLT), and (3) control group (received no treatment). Following the sacrifice of rats on day 21, samples were taken from rats' buccal mucosa for histological assay and scoring. The data were analyzed using Mann-Whitney test. Ozone and laser groups demonstrated reduced acute inflammation scores compared to control group (p=.01), while no significant differences were observed between the ozone and laser groups (p = 1.00). Similarly, ozone and laser groups showed higher histological tissue repair scores than the control group (p=.00), and no difference was found between ozone and laser groups (p=.76). On the other hand, no significant difference in expression of TNF-α (p=.33) and TGF-β1 (p=.13) was identified between ozone, laser and control samples. The present study demonstrated that both adjunctive ozone therapy and LLLT with a 940 nm diode laser provided significant improvement in parameters of acute inflammation and tissue repair in surgical oral mucosal wounds in rats.


Thickness and internal adjustment of monolithic resin composite milled crowns: Effect on the load-bearing capacity under fatigue.
To evaluate the fatigue failure load (FFL), cycles for fatigue failure (CFF) and survival rates of different occlusal thicknesses of resin composite simplified crowns with internal adjustments (IA) or without as control (C). 30 monolithic simplified crowns of CAD/CAM resin composite (Tetric CAD, Ivoclar) were milled in three different occlusal thicknesses (0.5 mm, 1.0 mm, and 1.5 mm). Half of the crowns were submitted to restricted adjustment with diamond burs on the crown's inner surface and half remained milled without internal adjustment. The samples were treated and adhesively luted onto a prosthetic preparation made of epoxy resin reinforced by glass-fiber substrate. The sets were subjected to a fatigue test (cyclic fatigue: initial load of 200 N; step-size of 50 N; 10,000 cycles/step; 20 Hz; maximum load: 2800 N).Microscopic analysis of tested representative samples was performed. The fatigue data were statistically analyzed (α= 0.05) and the micrograpic images were qualitatively evaluated. All specimens from groups 1.0C and 1.5C survived the cyclic loads, while all 0.5C samples failed during the test. The 1.0IA and 1.5IA crowns showed no statistical difference for FFL (2530 N= 2670 N) and CFF (471,000 cycles= 499,000 cycles) between them, and they were both statistically superior to the 0.5IA (FFL= 1812.50 N; CFF= 327,500 cycles). The 1.0 mm and 1.5 mm crowns presented superior fatigue behavior (2530 N-2800 N) compared to the 0.5 mm crowns (1812 N-2140 N), whether internal adjustment was performed or not. A statistically significant difference was found for FFL and CFF of 0.5 mm crowns with and without internal adjustment, with a deleterious impact of the adjustment for both parameters (FFL and CFF: 0.5C > 0.5IA). Resin composite milled crowns can bear high cyclic fatigue loads despite thickness, although thicker crowns had better mechanical behavior; however, the internal adjustment in the composite resin crown leads to a detrimental effect on its fatigue behavior, which presents a risk of mechanical failure due to premature fatigue.


An on-line computer data bank of monoclonal antibodies that recognize allergens--invitation for entries.
Monoclonal antibodies that recognize allergens are potentially extremely useful reagents for use in a variety of applications, including highly specific and sensitive assays for the standardization of allergen extracts and the measurement of environmental allergens, epitope mapping of allergens, comparison of IgE-binding determinants, and the immunolocalization of allergens in thin sections. Although monoclonal antibodies have many properties that enable them to be shared internationally, it is difficult to know from the literature what monoclonal antibodies are available and, in some cases, what are the individual characteristics of the antibodies. We are organizing an on-line data base of information about allergen-reactive monoclonal antibodies, which can be accessed by computer with international telecommunications networks. Each record of a monoclonal antibody includes details, if they are known, of allergen source and name, antibody production, complimentary antigenic determinant, names and addresses of the owners, availability of the antibody, and other important information. Investigators who have produced monoclonal antibodies that react with allergens are invited to submit details of the antibodies for inclusion in the data base.


Promoter-specific inhibition of transcription by antibiotics which act on DNA gyrase.
Nalidixic acid, novobiocin and coumermycin specifically inhibit phage promoter-dependent transcription of the trp operon in phi 80 ptrp but not transcription from the authentic trp promoter. The nalidixic acid inhibition is not observed in an E. coli strain containing a nalAr mutation. These results indicate that DNA gyrase is involved in transcription.


Nucleoside transport and metabolism in lymphocytes, polymorphonuclear cells and cerebral synaptosomes.
The salvage of nucleosides dominates over de novo biosynthesis in lymphocytes, polymorphonuclear cells (PMN) and in central neutral nervous system (CNS) in higher organisms. Earlier works in our laboratory have shown that the salvage of deoxycytidine (dCyd) did not correlate with DNA synthesis. The uptake and metabolism of dCyd was higher in undifferentiated germinal center lymphocytes and in follicles comparing to more differentiated cells. Recently we have compared the transport of thymidine (dThd), dCyd, uridine (Urd) and adenosine (Ado) in the three cell systems in which the salvage of nucleosides is dominating. It was found that dCyd was transported 30 times more effectively into lymphocytes than into PMN and synaptosomes, while Urd was transported about the same rate into the two cells and into synaptosomes. All transport processes could be inhibited by dipyridamole, NBRPR, papaverine and dilazep. The dCyd and dThd was phosphorylated even at 0 degrees C up to TTP and dCTP without incorporation into DNA and into liponucleotides. Our results show that the processes of transport-phosphorylation, as well as the processes of DNA-CDP-phospholipid synthesis are tightly coupled to each other in intact cells and organelles.


Pharmacogenetics and obstetric anesthesia.
The ultimate goal of pharmacogenetics research is to help doctors tailor doses of medicines to a person's unique genetic make-up, making medicines safer and more effective for everyone. Although there still are no guidelines and immediate clinical implications for practitioners providing analgesia or anesthesia, it is essential to realize that trial-and-error pharmacotherapy and one-size-fits-all dogmas are bound to die. This review briefly outlines the genetic variability of pharmacokinetics and pharmacodynamics and discusses selected fields relevant to obstetric anesthesiologists for whom the challenges of translating pharmacogenetics to clinical practice hopefully are on their way.


Structure in personal networks: Constructing and comparing typologies.
A recurrent finding in personal network research is that individual and social outcomes are influenced not just by the kind of people one knows, but also by how those people are connected to each other: that is, by the structure of one's personal network. The different ways in which a person's social contacts know and interact with each other reflect broader variations in personal communities and social structures, and shape patterns and processes of social capital, support, and isolation. This article proposes a method to identify typologies of network structure in large collections of personal networks. The method is illustrated with an application to six datasets collected in widely different circumstances and using various survey instruments. Results are compared with those from another recently introduced method to extract structural typologies of egocentric networks. Findings show that personal network structure can be effectively summarized using just three measures describing results of the Girvan-Newman algorithm for cohesive subgroup detection. Structural typologies can then be extracted through cluster analysis on the three variables, using well-known clustering quality statistics to select the optimal typology. Both typology detection methods considered in the article capture significant variation in personal network structures, but substantial levels of disagreement and cross-classification emerge between them. I discuss differences and similarities between the methods, and potential applications of the proposed typologies to substantive research on a variety of topics, including structures and transformations of personal communities, social support, and social capital.


Spontaneously occurring staphylococcal mutants resistant to clinically achievable concentrations of ciprofloxacin and temafloxacin.
The frequency of spontaneously occurring mutants resistant to 0.5, 1, 2, 4 and 8 micrograms of temafloxacin or ciprofloxacin per milliliter was documented with four Staphylococcus aureus and four Staphylococcus epidermidis strains. Resistant mutants were recovered at two- to four-fold the MIC of either drug, and they displayed cross-resistance to other fluoroquinolones. Resistance to temafloxacin occurred at frequencies lower than those observed with equal concentrations of ciprofloxacin. Resistance to greater than four-fold the MIC of either drug was not detected (frequencies less than 10(-10).


Soluble expression, purification, and characterization of recombinant human flotillin-2 (reggie-1) in Escherichia coli.
Large scale production of recombinant human flotillin-2 (reggie-1) is desirable for structural and biochemical studies. However, as the major lipid rafts specific hydrophobic protein, flotillin-2 was difficult to be expressed as soluble and functional form in prokaryotic system. In this study, we first cloned and expressed human flotillin-2 in Escherichia coli with five different fusion tags: poly-histidine, glutathione S-transferase (GST), thioredoxin (TRX), N-Utilization substance (NusA) and maltose binding protein (MBP). We screened the expression level and solubility of the five flotillin-2 fusion proteins, the best MBP tagged flotillin-2 was then large scale produced. The optimized purification procedure included two steps of chromatography: Ni-NTA affinity chromatography and anion exchange chromatography. The typical yield was 36.0 mg soluble and functional recombinant flotillin-2 from 1 L of culture medium with purity above 97%. The activity of recombinant flotillin-2 was verified by pull-down assay with flotillin-1, showing that the purified recombinant flotillin-2 can specifically interact with flotillin-1. The circular dichroism (CD) spectroscopy showed that recombinant flotillin-2 had a very stable secondary structure dominated by α-helix, β-turn and random structure.


Environmental degradation, renewable energy, and economic growth nexus: Assessing the role of financial and political risks?
Sustainable development goal (SDG), which focuses on affordable and sustainable energy, provides a practical solution to realize sustainable growth. In addition, this target can encourage the realization of SDG 13 (climate action). However, factors like political and financial risk can impact climate actions and renewable energy. Therefore, this research extends the debate on the ecological footprint (EF) mitigation and achievement of SDGs by evaluating the renewable energy, political risk, financial risk, and EF nexus in an Environment Kuznets Curve (EKC) framework from 1986 to 2018. Panel data for the Association of Southeast Asian Nations (ASEAN) is estimated using second-generation approaches. The CuP-FM test results indicated that the EKC is present in ASEAN in the context of renewable energy, financial risk, and political risk. Furthermore, the findings revealed that controlling political and financial risks is a useful mitigation strategy because EF decreases as these risks are reduced. Notably, a decrease in EF has been linked to the use of renewable energy. These results are verified by using CO2 emissions as an alternative proxy for environmental degradation. Moreover, both financial and political risk Granger cause renewable energy and economic growth indicating that controlling financial and political risk is necessary for sustainable development.


Clinical practice recommendations for the diagnosis and treatment of X-linked hypophosphatemia: A consensus based on the ADAPTE method.
The objective of this project was to adapt to our setting following a systematic process based on the ADAPTE method the first clinical practice guidelines on X-linked hypophosphatemia (XLH) that were published in 2019. The adaptation of the guidelines to our application and implementation setting was carried out in three phases -start-up, adaptation, and finalization- by a group of experts involved in the management of patients with XLH. Following the original guide, the recommendations agreed by the group that elaborated the guidelines for diagnosis, frequency and scope of visits and specific follow-up in children and adults are presented. On the other hand, recommendations are established for both age groups with conventional treatment, as well as with burosumab in children or adults and those related to the controversial use of growth hormone in children. Suggestions are also proposed regarding the monitoring and management of musculoskeletal disorders and orthopedic treatment in children, dental health and hearing, and neurosurgical complications. Finally, a series of questions and areas are raised in order to deepen the possible future investigation. These recommendations constitute the systematic adaptation to our setting of the first evidence-based clinical practice guide for the diagnosis and management of XLH and we hope that they can contribute to the adequate management of the disease.