Low-Intensity Femtosecond Radiation Activates the Natural Defenses of Mice in vivo.
The possibility of induction of cytogenetic damage in the bone marrow, changes in the cellularity of lymphoid organs and blood composition in mice irradiated with low-intensity femtosecond laser radiation at a power flux density of 5.1, 10.4, and 52 mJ/cm2 (0.5 mW for 5, 10, and 50 s) in vivo was shown. Using the radiation adaptive response test (0.1 Gy + 1.5 Gy), it was found that, when mice were exposed to femtosecond laser radiation in high doses, the body's natural defenses were activated in the same narrow range of energy flux density (2-16 mJ/cm2) as in the case of X-ray irradiation in a dose of 0.1 Gy (4 mJ/cm2). The data obtained suggest a similar mechanism of activation of the body's natural defense upon exposure to low doses of both ionizing and non-ionizing radiation.


Bio-inspired co-deposited preparation of GO composite loose nanofiltration membrane for dye contaminated wastewater sustainable treatment.
The fully separation of dye/salt through loose nanofiltration membranes is of great significance for the sustainable development paradigm of textile wastewater. However, the current loose nanofiltration membranes suffer low separation efficiency and complex preparation. Herein, by one-step co-deposition, we develop graphene oxide (GO) composite loose nanofiltration membranes with low negatively charged surface. Our membrane possesses unconventional high pure water permeation of 71.7 LMH/bar, 92.9 % rejection for Methyl blue (MB) and 98.8 % rejection for Congo red (CR). Benefiting from the large interlayer distance of GO nanosheets and low negatively charged surface, membrane achieves high dyes/salts separation with satisfactory permeation to salts (94.3 % of Na2SO4, 97.6 % of MgSO4, 98.3 % of MgCl2 and 99.0 % of NaCl). The CR/salt mixed solutions exhibit similar removal rates to their constituents' single dye or salt solutions (CR rejection is up to more than 97 % and the permeations of all salts are above 93 %). At the same time, binary dyes mixtures (Congo red and Methyl orange) can also be effectively separated. Furthermore, the membrane shows a relatively desirable antifouling property. The flux recovery still remains at 85.9 % after three cycling filtrations. This study provides a facile approach to prepare highly-efficient loose nanofiltration membranes for wastewater sustainable remediation.


Berberine promotes peri-implant osteogenesis in diabetic rats by ROS-mediated IRS-1 pathway.
Accompanying with diabetes mellitus-induced osteoporosis (DM-OS), diabetic patients show poor peri-implant osteogenesis after implantation for dentition defect. Berberine (BBR), a candidate oral hypoglycemic agent, is a promising agent for treating DM-OS. In this study, BBR was applied on DM rats and high-glucose-cultured bone mesenchymal stem cells (BMSCs) to investigate its therapeutic mechanism on DM-OS, thus laying a theoretical basis for the future application of BBR in implant restoration. Phenotypes were assessed in the DM rats after 4 w of gavage with BBR. Furthermore, BMSCs were cultured with high glucose and BBR. Cell Counting Kit-8, 2',7'-dichlorofluorescin diacetate (H2 DCF-DA), quantitative real-time PCR (qRT-PCR), and western blot were performed to estimate the cell proliferation, oxidative stress, and osteogenic differentiation. Moreover, the DM rats treated with BBR and insulin receptor substrate-1 anti-sense oligonucleotide (IRS-1-ASO) underwent a 4-w implant-healing period and then micro computed tomography (Micro-CT) and histology were performed to verify the mechanism. Results showed that the 4-w administration of BBR markedly improved the glucose metabolism and bone metabolism in the DM rats. in vitro experiments revealed that BBR alleviated high-glucose-inhibited osteogenesis of the BMSCs by upregulating reactive oxygen species (ROS)-mediated IRS-1 signaling. Besides, injection of IRS-1-ASO abolished the BBR promotion of implant osseointegration in the DM rats. In conclusion, targeting ROS-mediated IRS-1 signaling, BBR acted as an efficient agent to advance osseointegration in DM, which indicated that BBR use is a good strategy for future implants restoration in diabetic patients.


Determining the functional sensibility of the hand in patients with peripheral nerve repair: Feasibility of using a novel manual tactile test for monitoring the progression of nerve regeneration.
Case-controlled cohort study. Sensory function is difficult to observe during nerve regeneration processes. Traditional sensory tests are limited to identifying the level of functioning hand sensation for sensory stimulus is given passively to the cutaneous surface of the hand. To examine the outcome changes in the manual tactile test (MTT), Semmes-Weinstein monofilament (SWM) and 2-point discrimination (2PD) tests for patients with nerve repair and to investigate the concurrent validity of MTT by comparing it with the results of traditional tests. Fifteen patients with nerve injury of the upper limbs were recruited, along with 15 matched healthy controls. The MTT, SWM, and 2PD tests were used to examine the sensory status of the subjects. Three subtests (barognosis, roughness differentiation, and stereognosis) in MTT showed that the patients improved with time. A moderate and mild correlation was found between the MTT and 2PD results and between the barognosis and SWM results. The MTT provides practical and functional perspectives on detecting nerve progression during the courses of degeneration and regeneration. IV.


High spatial resolution spectroscopy in the elemental microanalysis and imaging of biological systems.
The application of analytical electron microscopy to the high spatial resolution study of biological systems is reviewed. Specimen preparation, quantitative analysis, capabilities and limitations are all discussed, principally in the context of energy-dispersive X-ray analysis. Results are presented using both current techniques and the developing quantitative image analysis. Finally the role of new instrumental approaches, including electron energy loss spectrometry, is discussed.


Low resistin levels in adipose tissues and serum in high-fat fed mice and genetically obese mice: development of an ELISA system for quantification of resistin.
Obesity is a major risk factor for insulin resistance. Resistin, an adipocyte-derived hormone-like molecule, is considered to serve as an important link between obesity and insulin resistance. However, the physiological role of resistin and the mechanism by which it neutralizes insulin action are still unclear. There are also conflicting reports that cast doubt on the cause of insulin resistance. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) system for quantification of mouse resistin levels, analyzed in relation to insulin resistance. C57BL/6J mice fed high-fat diet compared with normal diet had low resistin levels (by 70%, P<0.01) in epididymal adipose tissues. Genetically obese mice, db/db and KK-A(y), had hyperinsulinemia and hyperglycemia but low resistin levels (decreases by 83 and 90%, both P<0.01) compared with C57/BL6J mice in epididymal adipose tissues. Serum resistin levels determined by Western blotting showed a similar pattern to those in adipose tissues. Resistin levels in adipose tissues correlated with serum adiponectin concentrations positively (r=0.49). Our results indicate that the novel ELISA system is suitable for measurement of resistin levels in adipose tissues. The results do not support a role for resistin in insulin resistance.


Progress in the application of 3D-printed sodium alginate-based hydrogel scaffolds in bone tissue repair.
In recent years, hydrogels have been widely used in the biomedical field as materials with excellent bionic structures and biological properties. Among them, the excellent comprehensive properties of natural polymer hydrogels represented by sodium alginate have attracted the great attention of researchers. At the same time, by physically blending sodium alginate with other materials, the problems of poor cell adhesion and mechanical properties of sodium alginate hydrogels were directly improved without chemical modification of sodium alginate. The composite blending of multiple materials can also improve the functionality of sodium alginate hydrogels, and the prepared composite hydrogel also has a larger application field. In addition, based on the adjustable viscosity of sodium alginate-based hydrogels, sodium alginate-based hydrogels can be loaded with cells to prepare biological ink, and the scaffold can be printed out by 3D printing technology for the repair of bone defects. This paper first summarizes the improvement of the properties of sodium alginate and other materials after physical blending. Then, it summarizes the application progress of sodium alginate-based hydrogel scaffolds for bone tissue repair based on 3D printing technology in recent years. Moreover, we provide relevant opinions and comments to provide a theoretical basis for follow-up research.


Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors.
Monoamine oxidase-B (MAO-B) inhibitor has been used as neuroprotectants to treat the motor deficits of Parkinson's disease (PD). We designed and synthesized a class of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. The compounds have various inhibitory effects, with compound 6a having a K(i) value of 0.26 μM. Their promising activity in vitro suggests potential use in the treatment of PD.


Does Same-Day Postoperative Increased Intraocular Pressure Affect Endothelial Cell Density After Descemet Membrane Endothelial Keratoplasty?
High intraocular pressure (IOP) is common in association with intracameral air and gas tamponade after Descemet membrane endothelial keratoplasty (DMEK); yet its influence on endothelial cell survival is unknown. Our aim was to determine the effect of high IOP measured 2 hours after DMEK on 1-month endothelial cell density (ECD). The influence of other potentially relevant factors was also investigated. Retrospective, consecutive series. Inclusions: low-to-moderate risk DMEK surgery alone or combined with phacoemulsification. previous penetrating keratoplasty or glaucoma surgery; grafts with any of the following in the first month: rebubble, rejection, or graft failure. Sixty-two grafts met inclusion with 60 having IOP recorded at 2 hours. Thirty-eight percent (23/60) had IOP >30 mm Hg and 22% (13/60) had IOP >40 mm Hg at 2 hours. All grafts with IOP >30 mm Hg had air released and immediate normalization of pressure. One-month ECD (mean ± standard error of mean) was 1872 ± 58 cells/mm, representing cell loss of 29.8 ± 2.0%. Two-hour IOP was highly insignificant against 1-month ECD when tested as a continuous variable (P = 0.78). Lower 1-month ECD was statistically correlated with lower donor count (P = 0.002) and combined DMEK-phaco surgery (P = 0.01) on univariate and multivariate analysis. Insignificant factors (P > 0.05) against 1-month ECD included patient age, sex and race, surgical indication (Fuchs endothelial dystrophy vs. non-Fuchs endothelial dystrophy), and donor age. Increased IOP at 2 hours is common after DMEK, but does not seem to influence early endothelial cell survival. One-month ECD was influenced by donor counts and combined cataract surgery.


Retroperitoneal malignant extra-gastrointestinal neuroectodermal tumor with EWSR1::CREM fusion and IL-6-related systemic inflammatory symptoms: a case report.
Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept.


Dimorphic Fungal Infections in HIV/AIDS Patients with non-TB Chronic Cough at Mulago Hospital, Kampala, Uganda.
Dimorphic fungi cause infection following inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into the yeast phase which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some cases they may persist and cause fungal disease characterized by formation of granulomas in the infected tissues, which may mimic MTB. To explore if dimorphic fungi play any role in pulmonary disease among XpertTB/RIF Negative HIV Patients with chronic cough attending ISS Clinic at Mulago hospital Uganda. Sputum samples were collected from 175 consented HIV infected patients attending ISS Clinic. Upon Xpert/RIF test at ISS Clinic 21 of these tested positive, the 154 negative sputum samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR using specific primers was used to detect a target sequency in the gene of each dimorphic fungi of interest, the resulting amplicons were electrophoresed on a 2% gel then visualized under UV light. Blastomyces dermatitidis and Tarolomyces marneffei were detected in 16.4% of the studied participants, with 9.1% and 7.1% respectively and 83.8% of the participant sample had no dimorphic fungi. Coccidiodes immitis, Paracoccidiodes brasiliensis and Histoplasma capsulatum were not detected in any of the participants. Dimorphic fungi play a role in pulmonary disease among the HIV/AIDS with non- TB chronic in Uganda.


Integrating drones in response to public health emergencies: A combined framework to explore technology acceptance.
The aim of the study was to propose and test an integrated model combining the technology acceptance model (TAM), task-technology fit (TTF), social motivation, and drone-related perceived risks to explore the intention to use drones in public health emergencies (PHEs). We conducted a survey among the Israeli population, yielding a sample of 568 participants. Structural equation modeling was implemented to test the research hypotheses. The results showed that our integrated model provided a robust and comprehensive framework to perform an in-depth investigation of the factors and mechanisms affecting drone acceptance in PHEs. First, ease of use, attitudes, individual-technology fit, task-technology fit, and social influence significantly and directly influenced users' behavioral intention to utilize drone technology. Second, attitudes were significant mediators of the effects of social influence and perceived risks on the intention to use drones. Finally, significant relationships between TAM, TTF, social motivation, and perceived risks were also observed. Theoretical aspects and practical implications-which can serve as the basis for shaping a positive development in drone public acceptance in PHEs and in general-are discussed.


Health science student teachers' perceptions of teacher competence: A qualitative study.
Health science teacher competence is multifaceted and continuously changing according to national and international healthcare standards. Organizational restructuring and emphasis on cost effectiveness is changing the scope of health science teachers' practical work and their role in healthcare (worldwide). This study aimed to describe student teachers' perceptions of the competencies needed to work as an educator in the healthcare field. Objective of study was to gain new knowledge which can be used in the development of teacher education programs in nursing science and to define a broader definition of the health science educators. A qualitative study was conducted. Data were collected from 23 Finnish students completing a master's degree in teaching in the healthcare context using focus group interviews. The data were analyzed by inductive content analysis. The student teachers identified eight main categories of teacher competence: leadership and management competence; evidence-based practice competence; subject competence; ethical competence; pedagogical competence; collaboration competence; internationalization competence; and continuous professional development competence. This study identified essential teacher competencies that can be evaluated among students to develop health science teacher curricula. The findings can be used in follow-up studies or comparative research to investigate competence differences between novice and experienced teachers.


[(1R*,3S*,4S*)-3-(2-Hy-droxy-benzo-yl)-1,2,3,4-tetra-hydro-1,4-ep-oxy-naphthalen-1-yl]methyl 4-nitro-benzoate.
The relative stereo- and regiochemistry of the racemic title compound, C25H19NO7, were established from the crystal structure. The fused benzene ring forms dihedral angles of 77.3 (1) and 60.3 (1)° with the hy-droxy-substituted benzene ring and the nitro-substituted benzene ring, respectively. The dihedral angle between the hy-droxy-substituted benzene ring and the nitro-substituted benzene ring is 76.4 (1)°. An intra-molecular O-H⋯O hydrogen bond closes an S(6) ring. In the crystal, weak C-H⋯O hydrogen bonds connect the mol-ecules, forming layers parallel to (100). Within these layers, there are weak π-π stacking inter-actions with a ring centroid-ring centroid distance of 3.555 (1) Å.


An assay procedure for the comparative irritancy testing of esters in the tigliane and daphnane series.
A method is described for testing of diterpene esters for irritancy. The technique involves the application of acetone solutions of the toxins to the inside ears of female LACA mice. The number of mice responding per group and the log10 dose data were evaluated using probit analysis with the assistance of a computer program. This evaluation has the advantage that approximations inherent with an arithmetical evaluation were eliminated, and limits may be placed upon the standard deviation of the irritant dose 50% (ID50). In addition, the use of a chi2 test automatically eliminated results which were not attributed to random biological variation. Observations of the time to onset and the persistence of the inflammation have led to the suggestion that daphnane orthoester diterpenes may elicit their effect by means of a direct action at a receptor site in skin, whereas the tigliane O-acyl esters may in part act by causing more general tissue damage.


Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope.
A high-throughput screening protocol for evaluating chimeric, self-sufficient P450 biocatalysts and their mutants against a panel of substrates was developed, leading to the identification of a number of novel biooxidation activities.


The spontaneous smile in dynamic motion.
The purpose of this study was to record and analyze the dynamic nature of spontaneous smiles. Fifteen children (9 girls and 6 boys; average age, 10.5 years) were filmed with a hidden camera while they watched a funny cartoon video. Spontaneous smiles were recorded, and the video frames were digitized. Time-graphs of the measurements were constructed, and plots of the movement of the mouth points were drawn. Facial measurements showed that the upper lip elevated by 28%, relative to the rest position, and the mouth increased in width by 27%. The corners of the mouth moved laterally and superiorly at an angle of approximately 47 degrees . Time analysis showed that the smiles developed in a staged fashion. The first stage (attack phase) was the shortest, lasting an average 500 ms. It was followed by a sustaining phase that included waxing and waning. The smile ended with a fade-out stage. The second and third stages were of variable duration and could be interrupted by the attack phase of a subsequent smile. The dynamics of the spontaneous smile and the findings of this study raise concerns about the validity of a single photographic capture for esthetic assessment and treatment planning.


Multi-objective models of waste load allocation toward a sustainable reuse of drainage water in irrigation.
The present study proposes a waste load allocation (WLA) framework for a sustainable quality management of agricultural drainage water (ADW). Two multi-objective models, namely, abatement-performance and abatement-equity-performance, were developed through the integration of a water quality model (QAUL2Kw) and a genetic algorithm, by considering (1) the total waste load abatement, and (2) the inequity among waste dischargers. For successfully accomplishing modeling tasks, we developed a comprehensive overall performance measure (E wla ) reflecting possible violations of Egyptian standards for ADW reuse in irrigation. This methodology was applied to the Gharbia drain in the Nile Delta, Egypt, during both summer and winter seasons of 2012. Abatement-performance modeling results for a target of E wla = 100 % corresponded to the abatement ratio of the dischargers ranging from 20.7 to 75.6 % and 29.5 to 78.5 % in summer and in winter, respectively, alongside highly shifting inequity values. Abatement-equity-performance modeling results for a target of E wla = 90 % unraveled the necessity of increasing treatment efforts in three out of five dischargers during summer, and four out of five in winter. The trade-off curves obtained from WLA models proved their reliability in selecting appropriate WLA procedures as a function of budget constraints, principles of social equity, and desired overall performance level. Hence, the proposed framework of methodologies is of great importance to decision makers working toward a sustainable reuse of the ADW in irrigation.


Colonial history and global economics distort our understanding of deep-time biodiversity.
Sampling biases in the fossil record distort estimates of past biodiversity. However, these biases not only reflect the geological and spatial aspects of the fossil record, but also the historical and current collation of fossil data. We demonstrate how the legacy of colonialism and socioeconomic factors, such as wealth, education and political stability, impact the global distribution of fossil data over the past 30 years. We find that a global power imbalance persists in palaeontology, with researchers in high- or upper-middle-income countries holding a monopoly over palaeontological knowledge production by contributing to 97% of fossil data. As a result, some countries or regions tend to be better sampled than others, ultimately leading to heterogeneous spatial sampling across the globe. This illustrates how efforts to mitigate sampling biases to obtain a truly representative view of past biodiversity are not disconnected from the aim of diversifying and decolonizing our discipline.


The Gulfwatch contaminants monitoring program in the Gulf of Maine: Are its data being used for ocean protection, with special reference to Nova Scotia, Canada?
The Gulfwatch Contaminants Monitoring Program is part of the Canada-US, Gulf of Maine Council on the Marine Environment (GOMC). Programs monitoring legacy toxic substances, i.e., chemical contaminants, such as Gulfwatch, collect and analyse environmental samples (e.g., blue mussels), interpret the data, and report on chemical levels and trends (spatial and temporal) in coastal waters. This study explored the extent to which its extensive information (data, reports, papers) has been used broadly and by Nova Scotia, a GOMC member. A mixed-methods study was conducted, using quantitative and qualitative metrics. Citations to some Gulfwatch papers and analysis of use of the Gulfwatch website showed that its data and information were accessed, mostly by government departments. However, interviews revealed that the departments were not using the data to inform Nova Scotia provincial coastal policy or practices. Recommendations are presented to improve the visibility and use of information provided by long-term, environmental monitoring programs.


Mass spectrometry based methods for the discrimination and typing of mycobacteria.
Identification and typing of mycobacteria is very important for epidemiology, susceptibility testing and diagnostic purposes. This paper describes the development and validation of the alternative methods for species identification and typing of mycobacteria based on a matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-ToF MS). Altogether there were 383 clinical isolates analyzed which include 348 strains of Mycobacterium tuberculosis complex (MTBC) (342 strains of M. tuberculosis and 6 strains of M. bovis) and 35 strains of nontuberculous mycobacteria (NTM) represented by 16 different species. Direct bacterial profiling (DBP) by means of MALDI-ToF MS was carried out. Cluster analysis of DBP mass spectra divided them into two large separate groups corresponding to MTBC and NTM, and also demonstrated the possibility of isolate identification at the species level. Spoligotyping protocol based on mass spectrometry was developed and validated, it matched completely to classical spoligotyping data. Our results suggest that MALDI-ToF MS has potential as a rapid and reproducible platform for the identification and typing of Mycobacterium species.


Nitrogen and fluorine co-doped green fluorescence carbon dots as a label-free probe for determination of cytochrome c in serum and temperature sensing.
As an important biomarker, the analysis of cytochrome c (Cyt c) plays a crucial role in cell-apoptosis or even cancer diagnosis. This work develops a label-free probe for Cyt c using the nitrogen and fluorine co-doped carbon dots (N, F-CDs) which were facile prepared through solvothermal method with 3, 4-difluorophenylhydrazine as precursor. The N, F-CDs have an average diameter of 3.4 nm, and can form a quite stable colloidal solution. The N, F-CDs show bright yellow-green fluorescence, excitation/emission wavelengths 475/530 nm, and a relatively high fluorescence quantum yield of 16.9%. Interestingly, the N, F-CDs indicate a linear and reversible variation of emission intensity with a sensitivity of -1.11% per ℃ in the temperature range from 25 to 60 ℃. Inner filter effect (IFE) between N, F-CDs and Cyt c turns the fluorescence of N, F-CDs from "on" to "off". The sensor possesses the excellent anti-interference ability towards the main components of plasma. Under optimum conditions, there is a linear relationship between fluorescence intensity function (F0-F) and the concentration of Cyt c in the range of 0.5-25 μΜ with a limit of detection (LOD) (S/N = 3) of 0.25 μM. Finally, the developed method has been successfully used to detect Cyt c in human serum sample with satisfactory recoveries in a range of 93.14-110.40%.


Effects of 3-h hypothermia after neonatal hyperthermic hypoxic-ischemic encephalopathy in rat models on behavioral prognosis and anatomical and histological features after growth.
To clarify the effects of 3-h hypothermia on learning ability and motor function after growth, employing neonatal rat models with hyperthermic hypoxic-ischemic encephalopathy (HIE). We divided all rats into three groups: N (adult rats after neonatal hyperthermic HIE without subsequent 3-h hypothermia), H (adult rats after neonatal hyperthermic HIE with subsequent 3-h hypothermia) and Sham (S) groups. We evaluated their malfunctions with the rota-rod test and the step-down passive avoidance test. We also analyzed the cerebrum width and the hippocampal CA1 area of the insulted hemisphere. In the rota-rod test, the result of the N group was significantly worse than that of the S group. In the step-down passive avoidance test, the result of the N group was significantly worse than those of the S and H groups. The longest cerebrum width and the hippocampal CA1 area of the insulted hemisphere of the N group were significantly smaller than those of the S and H groups. Neonatal hyperthermic hypoxic-ischemic insult restricts motor function and learning ability after growth, and such neuronal malfunctions can be relieved by hypothermia for 3 h soon after neonatal HIE.


Sequential Nonlinear Filtering of Local Motion Cues by Global Motion Circuits.
Many animals guide their movements using optic flow, the displacement of stationary objects across the retina caused by self-motion. How do animals selectively synthesize a global motion pattern from its local motion components? To what extent does this feature selectivity rely on circuit mechanisms versus dendritic processing? Here we used in vivo calcium imaging to identify pre- and postsynaptic mechanisms for processing local motion signals in global motion detection circuits in Drosophila. Lobula plate tangential cells (LPTCs) detect global motion by pooling input from local motion detectors, T4/T5 neurons. We show that T4/T5 neurons suppress responses to adjacent local motion signals whereas LPTC dendrites selectively amplify spatiotemporal sequences of local motion signals consistent with preferred global patterns. We propose that sequential nonlinear suppression and amplification operations allow optic flow circuitry to simultaneously prevent saturating responses to local signals while creating selectivity for global motion patterns critical to behavior.


Assisted wet deposition targeted synthesis of Co-N coordination single-atom catalysts for efficient Fenton-like catalytic degradation of micropollutants.
Assisted wet deposition methods to localize the active phase metal on the carrier surface and prevent atomic aggregation during conventional heat treatment are strongly preferred. Herein, single-atom cobalt catalysts (SA-Co-PCN) with different metal-central content were target-prepared using a combination of impregnation and secondary annealing on polymerized carbon nitride (PCN) through reticular confinement. Fitting the coordination configuration of the Co-N pathway within the first coordination shell according to quantitative EXAFS indicated that the ligancy of Co-N was 4. The removal efficiency of representative micropollutants in the SA-Co-PCN/PMS system achieved 100% within 15 min. The outstanding degradation properties of micropollutants were ascribed to the SA-Co-PCN boosts PMS to a 1O2-dominated system. Moreover, the effects of substituents on the degradation behavior and ecotoxicology of sulfonamides (SAs) in PMS-activated systems were investigated in depth. The combination of DFT theoretical calculations and LC-MS further confirmed that the similar electron-rich sites on the SAs molecules allowed for commonality in the degradation pathway. Both S-N bond and C-S bond fragments became the initial attack and cleavage sites in the series of SAs. Ecotoxicity predictions indicated that most intermediates of SAs exhibited lower acute and chronic toxicity, especially acute toxicity, than the parent compounds. ENVIRONMENTAL IMPLICATION: Assisted wet deposition to localize the active phase metal on the carrier surface allows easy target formation of single-atom cobalt catalysts (SA-Co-PCN), which could boost PMS to a 1O2-dominated system for efficient oxidation of typical micropollutants. The degradation behavior and ecotoxicology of sulfonamides in the SA-Co-PCN/PMS system were investigated in depth, revealing that most intermediates of sulfonamides exhibited lower acute and chronic toxicity, especially acute toxicity, than the parent compounds. This work provides a strategy for the development of facilely prepared single-atom catalysts and contributes to the development and application potential of PMS advanced oxidation technology for water pollution control.


Laboratory and numerical investigation of transport processes occurring above and within a saltwater wedge.
Salt wedges divide coastal groundwater flow regime into two distinct regions that include a freshwater region above the saltwater-freshwater interface and a saltwater region below the interface. Several recent studies have investigated saltwater transport in coastal aquifers and the associated flow and mixing processes. Most of these studies, however, have either focused on studying the movement of salt wedge itself or on studying contaminant transport processes occurring above the wedge. As per our knowledge, so far no one has completed laboratory experiments to study contaminant transport processes occurring within a saltwater wedge. In this study, we completed laboratory experiments to understand contaminant transport dynamics occurring within a saltwater wedge. We used a novel experimental approach that employed multiple neutral-density tracers to map and compare the mixing and transport processes occurring above and within a saltwater wedge. The experimental data were simulated using SEAWAT, and the model was used to further investigate the saltwater flow and transport dynamics within a wedge. The laboratory data show that the transport rates active within the wedge are almost two orders of magnitude slower than the transport rates active above the wedge for the small-scale experimental system which is characterized by very low level of mixing. The numerical results, however, postulate that for large-scale systems involving higher levels of mixing (or dispersion) the transport rate active within the wedge could be comparable or even higher than the rates active above the wedge. More field or laboratory studies completed under high dispersion conditions are needed to further test this hypothesis.


Etoposide (VP-16) uptake by tumour spheroids and activity in the presence of Brij 30, formulation additives and sodium salicylate.
A number of additives typically used in the formulation of poorly soluble drugs can be shown to influence drug transport across various physiological barriers. Multicellular spheroids from a human neuroblastoma cell line (NB1-G) were used to investigate the effect of etoposide in solution, as its commercial formulation, Vepesid, in the presence of a nonionic surfactant, Brij 30, and a hydrotropic agent, sodium salicylate. Enhanced growth delay, apparently related to increased drug uptake, was observed both with the Vepesid and the sodium salicylate formulations. Brij 30, however, showed no enhancement of growth delay or drug uptake at a concentration at which it was not in itself cytotoxic. Significant morphological changes in the spheroid were observed at higher concentrations of additives, particularly with Brij 30, emphasizing the fact that many formulation additives cannot be used with impunity in tissue culture systems. The enhanced uptake of drug into tumour cells and potential synergy between additive and drug is worthy of further investigation.


Lipemia retinalis: case report and review of the literature.
We report the case of a 12-week-old boy presenting with increased cholesterol and triglyceride levels. Examination revealed lipemia retinalis. Genetic evaluation demonstrated lipoprotein lipase deficiency. The patient was treated with dietary restrictions, which resulted in rapid clinical improvement.


Genetic variations in recurrent astrocytic tumors detected by restriction landmark genomic scanning.
The genetic mechanisms associated with recurrence of advanced astrocytic tumors are poorly understood. We therefore analyzed 24 biopsy specimens from 12 patients with a recurrent astrocytic tumor by a two-dimensional gel electrophoresis method, termed restriction landmark genomic scanning (RLGS). Four spot changes were commonly present in the primary astrocytomas, indicating that the corresponding gene alterations were early events in the development of this tumor type. Altered spots were more frequent and of different distribution in recurrent tumors than in the primary astrocytomas. In particular, specifically increased intensity for spots on chromosomes 9-12 and 18 were observed in the secondary tumors, suggesting a relation with recurrence. The same spot changes observed in primary tumors were also found in the respective secondary lesions but with strikingly different densities in some cases, suggesting increased genetic instability. The altered segments provide important candidate regions for the search for genes involved in events leading to progression and more malignant recurrent tumors.


Luteal phase support with progesterone does not improve pregnancy rates in patients undergoing ovarian stimulation with letrozole.
Does luteal phase support with vaginal progesterone improve clinical pregnancy rates in patients undergoing ovarian stimulation with letrozole? This was a retrospective cohort study of patients undergoing ovarian stimulation with letrozole paired with intrauterine insemination (IUI) or timed intercourse (TIC) from January 2018 to October 2021. The primary outcome of clinical pregnancy rate (CPR) was calculated for cycles with and without luteal phase progesterone support. Univariate logistic regressions were done to evaluate predictor variables for CPR. Clinically important covariates including age, body mass index, anti-Müllerian hormone concentration, diagnosis of ovulatory dysfunction and multifollicular development were included in a multivariate analysis evaluating the relationship between luteal progesterone use and odds of clinical pregnancy. Secondary outcomes including spontaneous abortion, biochemical pregnancy and ectopic pregnancy were calculated. Live birth rates were calculated for cycles in a secondary analysis. A total of 492 letrozole ovarian stimulation cycles in 273 patients were included. Of these cycles, 387 (78.7%) used vaginal progesterone for luteal support and 105 (21.3%) did not. The unadjusted CPR per cycle was 11.6% (45/387) with progesterone and 13.3% (14/105) without progesterone (P = 0.645). After adjusting for significant covariates including age, BMI, diagnosis of ovulatory dysfunction and multifollicular development, the odds for clinical pregnancy were not significantly improved in cycles with exogenous progesterone (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.48-2.75, P = 0.762). A follow-up analysis demonstrated that live birth rate was 10.7% (41/384) with and 12.5% (13/104) without luteal progesterone, respectively (P = 0.599). Luteal support with vaginal progesterone does not significantly improve CPR in ovarian stimulation cycles using letrozole.


The mathematical whisker: A review of numerical models of the rat׳s vibrissa biomechanics.
The vibrissal system of the rat refers to specialized hairs the animal uses for tactile sensory perception. Rats actively move their whiskers in a characteristic way called "whisking". Interaction with the environment produces elastic deformation of the whiskers, generating mechanical signals in the whisker-follicle complex. Advances in our understanding of the vibrissal complex biomechanics is of interest not only for the biological research field, but also for biomimetic approaches. The recent development of whisker numerical models has contributed to comprehending its sophisticated movements and its interactions with the follicle. The great diversity of behavioral patterns and complexities of the whisker-follicle ensemble encouraged the creation of many different biomechanical models. This review analyzes most of the whisker biomechanical models that have been developed so far. This review was written so as to render it accessible to readers coming from different research areas.


[Dangers of ocusert therapy (author's transl)].
According to many publications, patients who wear Ocusert often loosed their medicamental pocket. We observed a case, who developed an acute angle-block-glaucoma. This was a reason for us, to represent the dangers of Ocusert-therapy. A glaucoma with narrow angle of the anterior chamber should be regarded as a contraindication.


Effective injection in pulsed splitless mode for impurity profiling of methamphetamine crystal by GC or GC/MS.
Gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) are commonly used for the impurity profiling of illegal drugs. For the impurity profiling of methamphetamine, it is very important to obtain information about impurities related to the manufacturing route and the precursor chemicals [B. Remberg, A.H. Stead, Drug characterization/impurity profiling, with special focus on methamphetamine: recent work of the United Nations International Drug Control Programme, Bull. Narcotics LI (1999) 97-117 ]. There are many artifact impurities arising from the preparation of samples and conditions of GC. Moreover, some impurities pose a barrier to the statistical processing of methamphetamine profiling. We investigated capillary GC analysis using pulsed splitless (PS/L) injection to minimize the thermal decomposition of impurities at the injection port and improve the transfer of samples into the column. We confirmed that the optimal conditions of PS/L-mode are 230 degrees C (injection temperature), 50 psi (pulsed pressure) and 1.1 min (pulsed time) for the methamphetamine profiling. Based on the impurity profiles of 48 methamphetamine crystals in PS/L-mode, we can achieve very easy handling and obtained, good results.


The incidence of pediatric invasive pneumococcal disease in Chiba prefecture, Japan (2003-2005).
The purpose of the study is to evaluate the incidence, spectrum of clinical manifestations and outcome of invasive pneumococcal disease (IPD) in children in Chiba prefecture, Japan. To determine the precise incidence of IPD in Chiba prefecture, we implemented a retrospective survey of the period from 2003 to 2005. A written questionnaire was sent to 45 hospitals that have pediatric wards, and information was obtained from all hospitals. The questionnaire included the clinical diagnosis, patient's age, underlying disease, prognosis and antimicrobial susceptibility of the isolated strains. During the 3 study years, 130 patients were diagnosed with IPD. The mean annual incidence rates of IPD among children <2 and <5 years were 19.5-23.8 and 12.6-13.8 per 100,000, respectively. Among 130 patients with systemic infection, 66 patients had bacteremia, 39 had pneumonia and 16 had meningitis. Five patients had neurological sequelae and 2 patients died. Seventy-four out of 115 isolates (64.3%) exhibited resistance to penicillin G. The annual incidence of pediatric IPD has remained constant during the study period. Two-third of isolated strains were at least partially resistant to penicillin G. Establishment of appropriate antibiotic therapy against IPD due to penicillin-resistant strains and the introduction of pneumococcal conjugate vaccines are emergent issues in Japan.


Associations Among Lactation, Maternal Carbohydrate Metabolism, and Cardiovascular Health.
In mammalian reproductive physiology, lactation follows pregnancy; growing evidence suggests that disruption of this physiology affects a woman's lifetime risk of metabolic disease. These differences may reflect lactation-induced mobilization of fat stores and modulation of maternal stress reactivity. In addition, confounders may play a role: women who breastfeed for long durations are more likely to engage in other healthy behaviors, and obesity and insulin resistance may interfere with breastfeeding physiology. These findings underscore the importance of evidenced-based care to enable women to achieve their infant feeding goals.


The effects of alternative splicing on transmembrane proteins in the mouse genome.
Alternative splicing is a major source of variety in mammalian mRNAs, yet many questions remain on its downstream effects on protein function. To this end, we assessed the impact of gene structure and splice variation on signal peptide and transmembrane regions in proteins. Transmembrane proteins perform several key functions in cell signaling and transport, with their function tied closely to their transmembrane architecture. Signal peptides and transmembrane regions both provide key information on protein localization. Thus, any modification to such regions will likely alter protein destination and function. We applied TMHMM and SignalP to a nonredundant set of proteins, and assessed the effects of gene structure and alternative splicing on predicted transmembrane and signal peptide regions. These regions were altered by alternative splicing in roughly half of the cases studied. Transmembrane regions are divided by introns slightly less often than expected given gene structure and transmembrane region size. However, the transmembrane regions in single-pass transmembranes are divided substantially less often than expected. This suggests that intron placement might be subject to some evolutionary pressure to preserve function in these signaling proteins. The data described in this paper is available online at http://www.affymetrix.com/community/publications/affymetrix/tmsplice/.


Enzyme- and immuno-histochemical localization of kallikrein. II. The human kidney.
Localization of kallikrein in the human kidney was investigated by two markers: kallikrein-like activity and kallikrein antigenicity. Kallikrein-like activity was demonstrated enzyme-histochemically by using a synthetic substrate for kallikrein, pro-phe-arg-naphthyl-ester. Kallikrein antigenicity was demonstrated by the unlabelled antibody peroxidase-antiperoxidase method using an antiserum against human urinary kallikrein. The kallikrein-like activity was localized in the proximal tubular cells without any corresponding kallikrein antigenicity. Neither kallikrein-like activity nor kallikrein antigenicity was noticed in any other tubular cell. These results are contrary to those in the ductal cells of the human parotid gland where the kallikrein-like activity and the kallikrein antigenicity were identical in their locations. The peroxidase-antiperoxidase method revealed, for the first time, kallikrein antigenicity both in the interstitium and in the basement membrane region of Bowman's capsule and of all the tubules, possibly representing circulating glandular kallikreins deposited in the renal tissue. Thus, the present findings are consistent with the hypothesis that the urinary (renal) kallikreins are derived from circulating glandular kallikreins.


Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL.
Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and represents 2-8% of all non-Hodgkin's lymphomas. The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appears curative. Encouraging results have been reported with high-dose chemotherapy with autologous stem-cell transplantation (autoSCT). However, a plateau in disease-free survival was not observed in relapsed MCL on the autoSCT trials. Promisingly, alloSCT appears to induce durable remissions via a graft-versus-lymphoma (GVL) effect. Donor lymphocyte infusions (DLIs), by virtue of a GVL effect, have been shown to induce durable remissions in a few cases with refractory MCL that recur after alloSCT. In this article, we review the literature on the evidence of the GVL effects in MCL and describe a patient with relapsed MCL shortly after high-dose chemotherapy with autoSCT. The patient was then successfully treated with Bu/Cy/VP-16 for an alloSCT followed by DLIs in a stepwise fashion. MNCs > 10 x 10(8)/kg were collected by two large-volume leukaphereses from the donor. Harvested stem cells from the 2(nd) day were cryopreserved for the future use as prophylactic DLIs to be given in a stepwise fashion. Cyclosporin and methotrexate were used for GVHD prophylaxis. He had achieved only a partial response by D+64 post transplant. G-CSF-primed cryopreserved DLIs were then infused on D+64 and D+92 to enhance the GVL effect. Grade 3 intestinal GVHD developed 20 days after the 2(nd) DLI and was partially controlled with the combination of cyclosporin, prednisone, and mycophenolate mofetil. Clinical complete remission was observed at D+112, and maintained until the last follow-up day (D+615). Our findings suggest that alloSCT followed by prophylactic DLIs may offer a curative approach to refractory MCL.


Inteins.
Lennon and Belfort introduce inteins - protein introns - and describe how they escape host proteins, their uses in biotechnology, where they are found in nature, and their role in post-translational regulation.


Consistency of transesophageal echocardiography and angiography in grading paravalvular regurgitation during transcatheter aortic valve replacement.
The Valve Academic Research Consortium 3 (VARC-3) standardizes the classification criteria and Doppler parameters for paravalvular regurgitation (PVR) by echocardiography. However, the consistency between transesophageal echocardiography (TEE) and angiography in grading (using the VARC-3 criteria) of PVR during transcatheter aortic valve replacement (TAVR) is unclear. Forty-six patients who underwent TEE and angiography during TAVR were retrospectively included. All patients had complete baseline information, TEE and angiography data. The Doppler parameters measured by TEE included the circumferential extent of PVR, regurgitation volume, regurgitation fraction, and the effective regurgitant orifice area. PVR was classified into four grades: absent, mild, moderate and severe. The weighted kappa coefficient was used to analyze the consistency between the two techniques. Kendall's W coefficient was used to evaluate the consistency of parameters measured by TEE. Among all patients, there were 43 cases (93.5%) with consistent assessments between TEE and angiography. PVR was observed in 19 cases. TEE assessed mild PVR in 17 cases and moderate PVR in two cases; Angiography assessed mild PVR in 14 cases and moderate PVR in two cases. The weighted kappa coefficient between angiography and the circumferential extent of PVR, regurgitation volume, regurgitation fraction, and the effective regurgitant orifice area respectively was .84, .79, .74, .85 (P < .001). Kendall's W coefficient was .83 (P < .001). TEE and angiography had strong consistency in the grading (using the VARC-3 criteria) of PVR during TAVR. TEE was a convenient diagnostic tool to quantify and grade PVR during TAVR.


Applications for oral research in microgravity - lessons learned from burning mouth syndrome and ageing studies.
The negative consequences of microgravity for the human body are central aspects of space travel that raise health problems. Altered functions of the same systems and treatment options are common points of spaceflight physiology, age-related diseases, and oral medicine. This work emphasizes the convergence of knowledge between pathophysiological changes brought on by aging, physiological reactions to microgravity exposure, and non-pharmacological and non-invasive treatment methods that can be used in spaceflight. Sarcopenia, peripheral nerves alterations, neuromotor plaque in the masticatory muscles, lingual, labial, and buccal weakness, nociplastic pain in oral mucosal diseases, and microgravity, as well as soft tissue changes and pathologies related to chewing and swallowing, corticomotor neuroplasticity of tongue, and swallowing biomechanics, are of particular interest to us. Neurologic disease and other pathologies such as recovery from post-stroke dysphagia, nociplastic pain in glossodynia, sleep bruxism, and obstructive sleep apnea have been studied and, in some cases, successfully treated with non-invasive direct and transcranial magnetic stimulation (TMS) methods in recent decades. An interdisciplinary team from medical specialties, engineering, and biophysics propose an exploratory study based on the parallelism of ageing and space physiology, along with experiment scenarios considering TMS and non-invasive direct methods.


Healthcare resource utilization of maribavir versus investigator-assigned therapy in transplant recipients with cytomegalovirus infection refractory (with or without genotypic resistance) to prior treatment: Exploratory analysis of the Phase 3 SOLSTICE trial.
Cytomegalovirus (CMV), a common post-transplant infection, is associated with increased healthcare resource utilization. In the Phase 3 SOLSTICE trial, maribavir was superior to investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, and cidofovir) for CMV viremia clearance at Week 8 in transplant recipients with confirmed refractory CMV infection with/without resistance. This exploratory analysis evaluated hospital admissions of patients during the SOLSTICE trial. Patients were randomized to maribavir (400 mg twice daily) or IAT for an 8-week treatment phase with a 12-week follow-up. After ≥3 weeks of treatment, patients on IAT who met pre-specified criteria could enter a maribavir rescue arm (8-week maribavir treatment, 12-week follow-up). Adjusted hospitalization rates and length of hospital stay (LOS) were estimated using negative binomial models adjusting for the time in the relevant study phase. Subgroup analysis for the maribavir rescue arm was conducted. Overall, 352 patients were randomized (maribavir: 235; IAT: 117); 22 entered the maribavir rescue arm. After adjusting for treatment exposure, patients on maribavir had a 34.8% reduction in hospitalization rate and 53.8% reduced LOS (days/person/year) versus IAT during the treatment phase. No significant differences between treatments were observed during the follow-up phase, although in both arms, hospitalization rates were lower than in the treatment phase. In the maribavir rescue arm, hospitalizations were 60.6% lower on/after maribavir rescue versus pre-rescue treatment (p = 0.008). In patients requiring post-transplant CMV treatment, hospitalization rate and LOS were lower for maribavir than IAT, and hospitalization rates were lower on/after maribavir rescue than pre-rescue. Reducing hospitalizations can alleviate the burden on patients and healthcare systems.


[Gamma heavy chain disease associated with aggressive B lymphoma in the context of myelodysplastic syndrome].
Heavy chain disease is a rare entity characterized by the production of incomplete immunoglobulin heavy chain without associated light chain. It is a B-cell lymphoproliferation, categorized according to the immunoglobulin involved. It is often associated with lymphomas but also with autoimmune diseases. We report the case of a 70-year-old patient who presented a gamma-type heavy chain disease, associated with a diffuse large B-cell lymphoma in the context of myelodysplastic syndrome. This is the first case of diffuse large B-cell lymphoma associated gamma heavy chain disease described in the context of myelodysplastic syndrome.


Improved Renal Recovery with Eculizumab Therapy among Children with High Prevalence of Mutation-Associated Atypical Hemolytic Uremic Syndrome: A Retrospective Cohort Study.
Genetic defects that determine uncontrolled activation of the alternative complement pathway have been well documented, which account for approximately 40-60% of atypical hemolytic uremic syndrome (aHUS) cases worldwide. In Saudi Arabia, nearly half of the marriages are consanguineous, resulting in a high prevalence of such genetic diseases. Recent studies have demonstrated the effectiveness of eculizumab against aHUS. We report our experience of using plasma therapy or/and eculizumab to treat children with aHUS in a tertiary care center in Saudi Arabia and to compare their clinical characteristics, genetic mutations, and treatment outcomes. A retrospective cohort study was conducted between January 2010 and May 2017. Data, including demographic parameters, clinical presentation, hospital stay duration, need for dialysis, renal recovery, genetic mutations, and outcomes, were obtained from electronic medical records of all eligible patients. Overall, 21 children with aHUS were included, of which 12 (57.1%) received eculizumab therapy and 9 (42.9%) received only plasma therapy. End-stage renal disease occurred in 7 children (33.3%), of which 4 (57.1%) received only plasma therapy and 3 (42.9%) received eculizumab therapy whose genetic mutations were not related to the complement dysregulation system. No child who received eculizumab therapy showed recurrence; however, 3 children (33.3%) who received plasma therapy alone showed recurrence. Genetic mutations were detected in 12/20 (60%) of those who underwent genetic screening. Children who received eculizumab therapy showed good renal recovery and maintained remission compared with children who received plasma therapy alone. Genetic mutations were detected in 60% of the patients, which was associated with a high prevalence of consanguineous marriages.


Changes in mean trabecular orientation in the medial condyle of the proximal tibia in osteoarthritis.
In osteoarthritis of the knee, degenerative changes occur in the articular cartilage and underlying subchondral bone, particularly of the medial tibial condyle. Cancellous bone sclerosis that accompanies osteoarthritis is not only the result of an increase in bone volume fraction but also a change in trabecular structure. In a comparison with age-matched controls (n = 4), osteoarthritis (n = 11) demonstrated a significant (P < or = 0.05) increase in bone volume fraction and trabecular thickness. Overall trabecular orientation in the osteoarthritic group was more vertical or perpendicular to the articular surface than the control group (P < or = 0.05) especially in the trabeculae of the cancellous bone layer closest to the articular surface. These alterations in trabecular bone structure could have significant consequences for the mechanical properties of osteoarthritic bone.


4-Hydroxytamoxifen binds to estrogen receptors and inhibits the growth of human endometrial cancer cells in vitro.
Effects of 4-hydroxytamoxifen, a major metabolite of tamoxifen, on the proliferation of cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in primary culture. Competitive binding studies showed that 4-hydroxytamoxifen effectively binds to cytoplasmic estrogen receptors (ER) in uterine adenocarcinomas. Of 20 endometrial adenocarcinomas examined, five tumors were successfully grown in primary cell culture. The addition of 4-hydroxytamoxifen (1 nmol/l to 1 mumol/l) in a medium supplemented with estrogen-free serum resulted in a dose-dependent inhibition of the growth of cancer cells in two tumors having ER. However, 4-hydroxytamoxifen did not affect the growth in the culture system of the remaining three tumors, in which ER were absent in two tumors but were present in one. These results strongly suggest that tamoxifen has a direct growth-inhibitory effect on human endometrial adenocarcinoma possibly through ER in the tumor.


The need for biochemical testing in beta-enolase deficiency in the genomic era.
Glycogen storage disease type XIII (GSDXIII) is a very rare inherited metabolic myopathy characterized by autosomal-recessive mutations in the ENO3 gene resulting in muscle β-enolase deficiency, an enzymatic defect of the distal part of glycolysis. Enzyme kinetic studies of two patients presenting with exertion intolerance and recurrent rhabdomyolysis are reported. Next generation sequencing confirmed patient 1 was homozygous for p.E187K in ENO3, while patient 2 was homozygous for p.C357Y. ENO3 variants pathogenicity was confirmed by functional studies in skeletal muscle. p.E187K caused extremely low total enolase activity. p.C357Y was associated with a higher level of residual activity but kinetic studies showed a lower maximum work rate (V max). This study illustrates that GSDXIII may be caused by either null mutations leading to β-enolase deficiency or by mutations that alter the enzyme's kinetic profile. This study highlights the importance of carrying out functional studies as part of the diagnostic process following the identification of variants with next generation sequencing.


Strategies for interprofessional education: the Interprofessional Team Objective Structured Clinical Examination for midwifery and medical students.
This paper provides an overview of the processes involved in implementing an interprofessional education (IPE) strategy in a recently established School of Human Development at the University of Nottingham. The merger of the academic divisions of child health, midwifery, obstetrics and gynaecology was a deliberate initiative to create an organisational infrastructure intended to enhance opportunities for interprofessional collaborations in research and education. As a first step, a small group of academic midwives and obstetricians formed a project group to find the best way of facilitating IPE for medical and midwifery students at undergraduate level. A discussion is provided of the work the project group undertook to: determine an agreed definition of IPE; decide an action research approach was needed; determine the ways in which teaching and learning strategies were to be implemented, evaluated and compared; and identify the factors inhibiting and enhancing developments. Evaluations have demonstrated that the Interprofessional Team Objective Structured Clinical Examination (ITOSCE) focusing on intrapartum scenarios is effective in promoting interprofessional learning. Both medical and midwifery students and facilitators agree that team working and understanding each other's roles has been enhanced and that although resource intensive, IPE is worth the time and effort involved.


Cellular interactions and oligodendrocyte differentiation in vitro.
The aim of the present study was to understand the role of cellular interactions in the choice of the oligodendroglial differentiation route by bipotential progenitors (O-2A progenitors) of oligodendrocytes (OL) and type-2 astrocytes (AS). Cell populations enriched in 0-2A progenitors, obtained from mixed rat cortical glial cultures, were subcultured at low density in BME+10% fetal calf serum on a poly-L-lysine (PLL) substrate (controls) or on a substrate of purified type-1 AS killed by air drying (K-AS), in order to study the interactions between the two cell types independently of the soluble mitogen(s) secreted by type-1 AS. While on PLL the progenitors differentiated into type-2 AS within a week, on K-AS many of them differentiated into OL. However, on K-AS O-2A progenitors proliferated more than on PLL, and this proliferation appeared to be related to unknown polypeptide components of the extracellular matrix produced by type-1 AS. The preferential differentiation of O-2A progenitors into OL on K-AS may thus be partly related to the higher density achieved by the cells on this substrate. This hypothesis is supported by the observation that purified O-2A progenitors subcultured at high density on PLL largely differentiated into OL. The effect of cell density on lineage decision appeared to be related to the secretion of high molecular weight autocrine differentiation factors by O-2A lineage cells.


Asprosin Exacerbates Endothelium Inflammation Induced by Hyperlipidemia Through Activating IKKβ-NF-κBp65 Pathway.
Vascular endothelium dysfunction caused by endothelium inflammation is a trigger of numerous cardiovascular diseases. Vascular endothelium inflammation often occurs in patients with obesity. Asprosin (ASP) derived from white adipose tissue plays important roles in maintaining glucose homeostasis. However, effect of ASP on the vascular endothelium inflammation induced by hyperlipidemia and its underlying mechanism remains largely unclear. In this study, models of vascular endothelium inflammation were established to investigate the effect of ASP on the endothelium inflammation both in vivo and in vitro. Our data in vivo showed that recombinant ASP or high-fat diet (HFD) significantly increased the circulating levels of IL-6 and TNF-α and enhanced the adhesion of macrophages to endothelia characterized by the expression increase of CD68, ICAM-1, and VCAM-1 in rats. However, neutralization of ASP with an ASP specific antibody (AASP) significantly antagonized the changes induced by HFD. Similarly, our data in vitro also showed that ASP treatment elevated the expressions of IL-6, TNF-α, and ICAM-1 as well as VCAM-1. More important, our data revealed that the pro-inflammation effect of ASP was achieved by activating the IKKβ-NF-κBp65 pathway other than the oxidative stress pathway both in vivo and in vitro. In conclusion, our results demonstrate that ASP is a pro-inflammation player in the obesity-associated endothelium dysfunction. The findings would provide a novel target for the prevention and treatment of obesity-related cardiovascular diseases.


Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides.
Pro-apoptotic and pro-inflammatory ceramides are crucially involved in atherosclerotic plaque development. Local cellular ceramide accumulation mediates endothelial apoptosis, especially in type 2 diabetes mellitus, which is a major cardiovascular risk factor. In recent years, large extracellular vesicles (lEVs) have been identified as an important means of intercellular communication and as regulators of cardiovascular health and disease. A potential role for lEVs as vehicles for ceramide transfer and inductors of diabetes-associated endothelial apoptosis has never been investigated. A mass-spectrometric analysis of human coronary artery endothelial cells (HCAECs) and their lEVs revealed C16 ceramide (d18:1-16:0) to be the most abundant ceramide in lEVs and to be significantly increased in lEVs after hyperglycemic injury to HCAECs. The increased packaging of ceramide into lEVs after hyperglycemic injury was shown to be dependent on neutral sphingomyelinase 2 (nSMase2), which was upregulated in glucose-treated HCAECs. lEVs from hyperglycemic HCAECs induced apoptosis in the recipient HCAECs compared to native lEVs from untreated HCAECs. Similarly, lEVs from hyperglycemic mice after streptozotocin injection induced higher rates of apoptosis in murine endothelial cells compared to lEVs from normoglycemic mice. To generate lEVs with high levels of C16 ceramide, ceramide was applied exogenously and shown to be effectively packaged into the lEVs, which then induced apoptosis in lEV-recipient HCAECs via activation of caspase 3. Intercellular transfer of ceramide through lEVs was confirmed by use of a fluorescently labeled ceramide analogue. Treatment of HCAECs with a pharmacological inhibitor of nSMases (GW4869) or siRNA-mediated downregulation of nSMase2 abrogated the glucose-mediated effect on apoptosis in lEV-recipient cells. In contrast, for small EVs (sEVs), hyperglycemic injury or GW4869 treatment had no effect on apoptosis induction in sEV-recipient cells. lEVs mediate the induction of apoptosis in endothelial cells in response to hyperglycemic injury through intercellular transfer of ceramides.


Characterization of extracellular Ca2+ -dependent full-type hyperactivation in ejaculated boar spermatozoa preincubated with a cAMP analog.
Ejaculated boar spermatozoa exhibit two types of hyperactivation: full and non-full. Full-type hyperactivation is characterized by the asymmetrical bending of the entire middle piece-principal piece and a twisting/figure-eight-like trajectory, and can be induced by simple incubation with CaCl2 after preincubation with a cAMP analog (Sp-5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole-3',5'-cyclic monophosphorothioate [cBiMPS]). Here, we compared the sperm flagellar motility after treatments with elevators of [Ca2+ ]i (cBiMPS/CaCl2 , thimerosal, procaine, and 4-aminopyridine) to characterize the regulatory mechanism of extracellular Ca2+ -dependent, full-type hyperactivation in ejaculated boar spermatozoa, and examined the possible involvement of Transient receptor potential cation channel subfamily C member 3 (TRPC3) in this event using the specific inhibitor Pyr3. Full-type hyperactivation was induced by a 60-min incubation with CaCl2 following a 180-min preincubation with cBiMPS but without Ca2+ . Thimerosal-treated spermatozoa exhibited full-type hyperactivation in a manner independent of extracellular Ca2+ ; conversely, this was not observed in procaine- or 4-aminopyridine-treated spermatozoa. A 20-min treatment with Pyr3 between preincubation with cBiMPS and incubation with CaCl2 , significantly suppressed the normal phenotype. These observations indicated that mechanisms underlying full-type hyperactivation in spermatozoa incubated with CaCl2 after preincubation with cBiMPS are different from those in the thimerosal-treated spermatozoa. Furthermore, indirect immunofluorescence localized TRPC3 in the upper segment of the middle piece, which bends asymmetrically during full-type hyperactivation but not in non-full-type hyperactivation, suggesting that TRPC3 may be involved in the extracellular Ca2+ -dependent full-type hyperactivation in ejaculated boar spermatozoa.


The mission of therapeutics.
Gerald Klerman's career as a researcher was marked by a strong interest in mood disorders. He was particularly interested in pathways to depressive episodes and their treatment. In this lecture entitled "The Mission of Therapeutics," the emphasis is placed on the integration of two developmental pathways representing biologic/genetic factors and psychosocial/environmental factors. Recent work on the role of childhood adversity and current stressors is reviewed, as well as biologic pathways and correlates. Finally, using treatment outcome as a window on pathogenesis is suggested as a strategy for understanding the interaction of biologic and psychosocial parameters in the onset of and recovery from episodes of depressive illness.


Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.
Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.


Postinduction positron emission tomography assessment of N2 nodes is not associated with ypN2 disease or overall survival in stage IIIA non-small cell lung cancer.
Induction therapy is often recommended for patients with clinical stage IIIA-N2 (cIIIA/pN2) lung cancer. We examined whether postinduction positron emission tomography (PET) scans were associated with ypN2 disease and survival of patients with cIIIA/pN2 disease. We performed a retrospective review of a prospectively maintained database to identify patients with cIIIA/pN2 non-small cell lung cancer treated with induction chemotherapy followed by surgery between January 2007 and December 2012. The primary aim was the association between postinduction PET avidity and ypN2 status; the secondary aims were overall survival, disease-free survival, and recurrence. Persistent pathologic N2 disease was present in 61% of patients (61 out of 100). PET N2-negative disease increased from 7% (6 out of 92) before induction therapy to 47% (36 out of 77) afterward. The sensitivity, specificity, and accuracy of postinduction PET for identification of ypN2 disease were 59%, 55%, and 57%, respectively. Logistic regression analysis indicated that postinduction PET N2 status was not associated with ypN2 disease. Of the 39 patients with both pre- and postinduction PET N2-avidity, 25 (64%) had ypN2 disease. The 5-year overall survival was 40% for ypN2 disease versus 38% for N2-persistent disease (P = .936); the 5-year overall survival was 43% for postinduction PET N2-negative disease versus 39% for N2-avid disease (P = .251). The 5-year disease-free survival was 34% for ypN2-negative disease versus 9% for N2-persistent disease (P = .079). Postinduction PET avidity for N2 nodes is not associated with ypN2 disease, overall survival, or disease-free survival in patients undergoing induction chemotherapy for stage IIIA/pN2 disease.


Role of crosslinking in fiber formation.
The synthesis of elastin by smooth muscle cells is demostrated by amino acid analyses and the presence of lysine-derived crosslinks. The data reveal that the ratio of allysine to aldol decreases with time in culture. The presence of insoluble elastin correlates well with the presence of the reduced aldol condensate in these cells. If the formation of the desmosines occurs by the condensation of the aldol and dehyrolysinonorleucine, the presence of the latter may be rate-limiting since the cells display little or no dehydrolysinonorleucine. Several peptides containing the desmosine crosslink were purified and partially sequenced. The data indicate that desmosines crosslink two polypeptide chains and that both desmosine and isodesmosine are present in the same primary sequence approximately equally substituted. A possible role for tyrosine in the regulation of desmosine formation is presented.


Surgical Fellowships Demonstrate Variable Improvement in Gender Representation Despite Greater Female Enrollment in General Surgery Residencies.
Despite increasing female representation in General Surgery (GS) residency training programs, proportional improvement of female enrollment in surgical fellowships has yet to be quantified. We aimed to assess if female enrollment in surgical fellowships has improved at an equivalent rate in 7 different surgical fellowship options after GS. Data were collected from Accreditation Council for Graduate Medical Education (ACGME) resources which disclosed active resident and fellow characteristics. Gender identification was self-reported by residents to ACGME. Gender data collected for GS programs and surgical fellowships including Surgical Critical Care, Colon, and Rectal Surgery, Pediatric Surgery, Plastic Surgery, Surgical Oncology, Thoracic Surgery, and Vascular Surgery from annual reports. Pearson Chi-squared analysis was conducted between GS residencies and fellowship programs in their corresponding years using Stata15 software. In all years examined, fellowships in Vascular, Thoracic, and Plastic Surgery had significantly lower female enrollment in proportion to the number of female GS residents (p = <0.02). In all years examined, Surgical Oncology, Pediatric, Colon and Rectal, and Surgical Critical Care had female enrollment that was, at minimum, proportional to female enrollment in GS residency, indicating equitable gender representation. Surgical Oncology (2016), Pediatric (2020) and Surgical Critical Care (2016) fellowships each had 1 year where female enrollment was significantly higher than General Surgery. The enrollment of female surgeons in Plastic, Vascular, and Thoracic Surgery fellowships has not improved proportionally despite an increase in female GS residents. These results suggest the possibility of persistent factors that deter female enrollment in Vascular, Thoracic and Plastic Surgery fellowships that are not present to the same degree in fields with equitable fellowship female enrollment. Female representation in surgical fellowships is vital to improving gender diversity in all disciplines of surgery, particularly academic surgery.


Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds.
Oxidative stress and mitochondrial dysfunction are early events in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Mitochondria are important key players in cellular function based on mitochondrial energy production and their major role in cell physiology. Since neurons are highly depending on mitochondrial energy production due to their high energy demand and their reduced glycolytic capacity mitochondrial dysfunction has fatal consequences for neuronal function and survival. The transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2) is the major regulator of cellular response to oxidative stress. Activation of Nrf2 induces the transcriptional regulation of antioxidant response element (ARE)-dependent expression of a battery of cytoprotective and antioxidant enzymes and proteins. Moreover, activation of Nrf2 protects mitochondria from dysfunction and promotes mitochondrial biogenesis. Therefore, the Nrf2/ARE pathway has become an attractive target for the prevention and treatment of oxidative stress-related neurodegenerative diseases. Small food-derived inducers of the Nrf2/ARE pathway including l-sulforaphane from broccoli and isoliquiritigenin from licorice displayed promising protection of mitochondrial function in models of oxidative stress and neurodegenerative diseases and represent a novel approach to prevent and treat aging-associated neurodegenerative diseases.


New antiamebic acridines. II. Synthesis and DNA binding of a series of 9-acridanones and 9-iminoacridines.
A series of novel 9-acridanones and 9-iminoacridines has been prepared and investigated by a number of spectroscopic techniques in order to determine the nature and extent of the binding of these compounds to DNA. Results are discussed with reference to antiamebic activity in vitro.


Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes.
We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinicopathological features. Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor-associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays. Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer-specific survival (BCSS). We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure- and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR = 1.55; p = 0.0172) and BCSS (HR = 2.10; p < 0.001). Clinicopathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer-related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.


Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.
To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.


A novel and sensitive electrochemical sensor based on nanoporous gold for determination of As(III).
Three-dimensional porous gold nanoparticles (NPG) were synthesized in situ on indium-doped tin oxide (ITO) substrates by a green and convenient one-step electrodeposition method to achieve super-sensitive As(III) detection. The introduction of NPG method not only greatly improves the electron transfer capacity and surface area of sensor interface but provides more active sites for As(III) enrichment, thus boosting sensitivity and selectivity. The sensor was characterized by scanning electron microscopy, energy dispersion spectroscopy, differential pulse anode stripping voltammetry (DPASV), and electrochemical impedance to evaluate its morphology, composition, and electrochemical performance. The wall thickness of NPG was customized by optimizing the concentration of electroplating solution, dissolved electrolyte, deposition potential, and reaction time. Under optimal conditions, the electrochemical sensor showed a wide linear range from 0.1 to 50 μg/L As(III), with a detection limit (LOD) of 0.054 μg/L (S/N = 3). The LOD is far below 10 μg/L, the recommended maximum value by the world health organization for drinking water. Stability, reproducibility, and repeatability of NGP/ITO were determined to be 2.77%, 4.9%, and 4.1%, respectively. Additionally, the constructed sensor has been successfully applied to determine As(III) in three actual samples, and the results are in good agreement with that of hydride generation atomic fluorescence spectrometry (AFS). Graphical abstract.


Copper and nutrition in Helix pomatia (L.).
1. In Helix pomatia the efficiency of assimilation of both food (lettuce) and copper is always high, even when the food has been artificially enriched with copper. In short-term feeding experiments with lettuce containing 1390 (±420)ppm copper about 97% of the metal ingested remains in the snail. 2. The availability of copper in the faeces is independent of the type of food and does not differ much from the availability of the metal in untreated lettuce. About half of the metal can be extracted by 0.1 M HCl, whereas the other half is liberated only by ashing. 3. The concentration of copper in the organs of a natural population of H. pomatia varied between 20 and 120 ppm (dry weight). Being by far the largest organ the foot contains most of this copper. After the snails have fed on copper-enriched food for three weeks the concentration of copper increases mainly in the alimentary tract and in the midgut gland, but no one organ is capable of concentrating copper to a much higher degree than another. In winter animals which had been feeding on copper-enriched food prior to hibernation, the concentration of copper in several organs may reach values that are from 10 to 40 times higher than those in summer animals. 4. When snails begin to feed on copper-enriched food the concentration of the metal increases quickly in the anterior alimentary tract. After three days a striking increase in the midgut gland takes place, followed, after five days, by a further accumulation of copper in the tissues of the alimentary tract, mainly of the intestine. In the albumen gland and in the foot the concentration of copper remains more or less constant. 5. In midgut and albumen gland more than 90% of the total copper is so tightly bound that it can be liberated only by ashing, whereas in the walls of the alimentary tract between 55 and 70% of the copper can be extracted with 0.1 M HCl. 6. If gastropods and isopods are compared with regard to the efficiency of their assimilation of copper it can be shown that this remains high as long as the ingestion of food (dry weight) does not exceed approximately 3% of fresh body weight per day.


Automated analysis of a novel anti-epileptic compound, CGP 33,101, and its metabolite, CGP 47,292, in body fluids by high-performance liquid chromatography and liquid-solid extraction.
Automated procedures for the determination of CGP 33,101 in plasma and the simultaneous determination of CGP 33,101 and its carboxylic acid metabolite, CGP 47,292, in urine are described. Plasma was diluted with water and urine with a pH 2 buffer prior to extraction. The compounds were automatically extracted on reversed-phase extraction columns and injected onto an HPLC system by the automatic sample preparation with extraction columns (ASPEC) automate. A Superlosil LC-18 (5 microns) column was used for chromatography. The mobile phase was a mixture of an aqueous solution of potassium dihydrogen phosphate, acetonitrile and methanol for the assay in plasma, and of an aqueous solution of tetrabutylammonium hydrogen sulfate, tripotassium phosphate and phosphoric acid and of acetonitrile for the assay in urine. The compounds were detected at 230 nm. The limit of quantitation was 0.11 mumol/l (25 ng/ml) for the assay of CGP 33,101 in plasma, 11 mumol/l (2.5 micrograms/ml) for its assay in urine and 21 mumol/l (5 micrograms/ml) for the assay of CGP 47,292 in urine.


Bloodless cannulation of the ascending aorta.
Bloodless cannulation of the aorta can be accomplished easily. A full thickness stab wound prior to insertion of the cannula is unnecessary as the aorta's inner layers have little strength.


Translocation (11;14) in B-cell lymphoproliferative disorders.
A number of chromosomes other than chromosome No. 8 participate in formation of the 14q+ marker in lymphoproliferative disorders. Among them is chromosome No. 11 which appears to be important because its break points are constant; it is also possibly significant because of its participation in cytogenetic alterations in B-cell disorders.


Nurse logs: A common seedling strategy in the Permian Cathaysian flora.
Nurse logs are common in modern forests from boreal to temperate and tropical ecosystems. However, the evolution of the nurse-log strategy remains elusive because of their rare occurrence in the fossil record. We report seven coniferous nurse logs from lowermost to uppermost Permian strata of northern China that have been colonized by conifer and sphenophyllalean roots. These roots are associated with two types of arthropod coprolites and fungal remains. Our study provides the first glimpse into plant-plant facilitative relationships between late Paleozoic gymnosperms and sphenopsids. Detritivorous arthropods and fungi appear to have been crucial for the utilization of nurse logs in Permian forests. The phylogenetically distant roots demonstrate that nurse-log interaction was a sophisticated seedling strategy in late Paleozoic humid tropical forests, and this approach may have been adopted and developed by a succession of plant groups leading to its wide representation in modern forest ecosystems.


Experience with a two-staged pedicled flexor tendon graft.
A two-staged technique for flexor tendon grafting in Zone 2 is described using a silicone rubber rod which is replaced at the second stage by a somersaulted superficialis tendon graft sutured end-to-end to profundus tendon at the lumbrical level. The results are analysed.


Developing and Validating the Narcissistic Personality Scale (NPS) among Older Thai Adults Using Rasch Analysis.
Being older could be stressful, especially among people with narcissistic personality disorders. Nevertheless, the tool is yet to be available among older Thai individuals. The study aimed to develop a tool to detect symptoms of narcissistic personality, and to validate its psychometric properties among older Thai adults. The Narcissistic Personality Scale (NPS) was developed based on nine domain symptoms of narcissistic personality disorder from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), consisting of 80 items. The original scale was field-tested using Rasch analysis for item reduction, rendering a final 43 items. NPS was further investigated among 296 seniors aged 60 years old. Rasch analysis was used to assess its construct validity. Of 43 items, 17 were further removed as infit or outfit mean square >1.5. The final 26-item NPS met all necessary criteria of unidimensionality and local independence without differential item functioning due to age and sex, and good targeting with subjects. Person and item reliability were 0.88 and 0.95, respectively. No disordered threshold or category was found. The NPS is a promising tool with a proven construct validity based on the Rasch measurement model among Thai seniors. This new questionnaire can be used as outcome measures in clinical practice.


Biological correlates of early life stressful events in major depressive disorder.
Major depressive disorder (MDD) is the most common psychiatric disorder and responds for important psychosocial consequences. Stressful life events, especially early life stress (ELS), contribute to an increased probability to develop MDD, leading in particular to severe and chronic manifestation and unfavorable treatment outcome. The association between ELS and MDD seems to have biological bases, consisting in dysregulations occurring at different levels. The aim of this narrative review is to propose an overview of the literature ranging from genetic, epigenetic, expression and protein to neuroimaging correlates underlying this relationship. A search on Pubmed of studies assessing biological correlates of ELS in MDD development, focusing on human studies conducted in both peripheral and brain tissues, was performed. Evidence indicated that the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic, dopaminergic, neurotrophin and oxytocin systems might play a role in the mediation between ELS and MDD. The most consistent results were found for genetic and epigenetic studies and indicated a joint involvement of the systems mentioned. Expression studies are less numerous and point to an involvement of stress-related systems. Concerning protein studies, the main mediators are markers related to the inflammatory and immune systems. Neuroimaging studies aiming at evaluating brain alterations connecting ELS and MDD in relation to biomarkers indicated the hippocampus, the amygdala and the frontal cortex as important anatomical mediators. These findings can build the bases for future research and clinical interventions; indeed, the clarification of biological mechanisms mediating the relationship between ELS and MDD can lead to new and individualized preventive and therapeutic possibilities.


Effect of acid rain on pine needles as food for capercaillie in winter.
The effects of long-range air pollution on the chemical composition of needles of Scots pinePinus sylvestris and consequences for capercaillieTetrao urogallus feeding on the needles were studied. Samples of pine needles from localities receiving different amounts of acid rain were taken in early March. Concentrations of N and P were highest in needles from the most acidified areas, and N concentration was 35% higher in the most heavily polluted area than in the least polluted. Secondary chemicals decreased significantly with increasing acidification. Concentrations of Cd in pine needles were closely correlated with the acid deposition levels, with highest concentrations in the most polluted area. Al concentration also increased with increasing acidification. These results provide evidence that acid rain increases the nutritive value of pine needles through a fertilizing effect. Enhanced levels of certain metals are considered too low to be directly toxic to capercaillie. However, behavioural anomalies cannot be excluded.


Treatment of central nervous system B lymphoproliferative syndrome by local infusion of a B cell-specific monoclonal antibody.
A 9-month-old infant developed Epstein-Barr virus-induced lymphoproliferative syndrome with mediastinal and central nervous system localizations, associated with mediastinal tuberculosis, 5 months after heart transplantation. As a combination of anti-B cell antibodies (CD21- and CD24-specific) and recombinant interferon alpha 2b, given intravenously, was not effective on the central nervous system disease, the anti-CD21 antibody was infused intrathecally via an Ommaya reservoir. High local concentrations of monoclonal antibodies were achieved, with no adverse effects. A dramatic clinical response was obtained, with clearance of abnormal cells from the cerebrospinal fluid and a clear reduction in the abnormalities on the brain images. The patient is well 7 months later. This observation indicates that treatment of B lymphoproliferative syndrome with central nervous system localization is feasible using a nontoxic, local B cell-specific approach.


Radon survey in caves from Mallorca Island, Spain.
This study reports radon concentration in the most representative caves of Mallorca, identifying those in which the recommended action level is exceeded, thus posing health risks. Two show caves (Campanet and Artà) and three non-touristic caves (Font, Drac, Vallgornera) were investigated. Data were collected at several locations within each cave for three different periods, from March 2013 to March 2014. Except for Vallgornera, where only one monitoring period was possible, and Artà in which low values were recorded throughout the year, a clear seasonal variability, with higher values during the warm seasons and lower during winter time is prominent. Radon concentrations differed markedly from one cave to another, as well as within the same cave, ranging from below detection limit up to 3060 Bq·m(-3). The results of this study have significant practical implications, making it possible to provide some recommendation to cave administrators and other agencies involved in granting access to the investigated caves.


A novel nuclear protein in rat ventral prostate. Androgen-dependent and age-related change.
A novel protein was found in the nuclei of rat ventral prostate. This protein has a molecular weight of about 21 kDa as measured by SDS-polyacrylamide gel electrophoresis. It showed a characteristic change between 3 and 84 weeks after birth in close association with the level of testosterone in the blood. After castration, the level of the 21-kDa protein decreased to 1/60 of normal in 7 days, but on daily injection of testosterone the level was restored to normal in 8 days and to twice the normal level in 14 days. Unlike H1 and H1(0) histone and high mobility group proteins, the 21-kDa protein was not extracted with 5% HClO4, but was partially extracted with 0.35 M NaCl. The 21-kDa protein was not found in kidney, liver, or bain, suggesting that it is specific to the ventral prostate.


Sensitive Child, Disturbed Kid: Stigma, Medicalization, and the Interpretive Work of Israeli Mothers of Children with ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is a rapidly globalizing medical category, and there is a need to attend to the on the-ground processes through which laypeople deploy the ADHD label in different local contexts. Based on in-depth interviews with Israeli mothers of children with ADHD, this article explores how mothers, as lay actors in the social field of diagnosis, interpreted the origins and meanings of their child's 'troubles'. The temporal perspective on mothers' meaning-making processes revealed a progression of four common phases through which mothers revisited their understanding of ADHD, and recast their own responsibilities and moral roles. We found that mothers' self-understanding was crucially impacted by the invisibility of the disability and the fact that diagnosis did not fully relieve them from blame for their children's stigmatizing behavior. While not all mothers accepted the validity of the diagnosis, participating in the medicalization of their child's condition allowed them to reach similar pragmatic and narrative goals. We discuss the cultural and institutional features of the Israeli ADHD landscape that shape mothers' narratives of their children, and their relations with expertise. We point to a culturally unique framing of children with ADHD in Israel as those characterized by emotional vulnerability and risk of social exclusion.


Twice-a-day radiotherapy for T3 squamous cell carcinoma of the glottic larynx.
Between March 1978 and April 1986, 21 previously untreated patients with T3 squamous cell carcinoma of the true vocal cord received radical courses of twice-a-day radiotherapy (120 cGy twice daily) to total doses of 7,440-7,680 cGy. The rate of local control at the primary site was 67% after radiotherapy. The ultimate control rate after salvage surgery was 83%. Five-year absolute and cause-specific survival rates were 59% and 81%, respectively. It is concluded that radiotherapy is a rational approach for many patients with T3 glottic cancer.