Proximal Femur Replacements for an Oncologic Indication Offer a Durable Endoprosthetic Reconstruction Option: A 40-year Experience.
Proximal femur replacements (PFRs) are an effective surgical option to treat primary and metastatic tumors causing large bony defects in the proximal femur. Given the relative rarity of these indications, current studies on PFR for oncologic indications are generally limited by patient volume or relatively short-term follow-up. Because recent advances in systemic therapy have improved the prognosis of patients who undergo limb salvage surgery for musculoskeletal tumors, data on the long-term durability of endoprosthetic reconstructions have become increasingly important. (1) How does the long-term survival of cemented bipolar PFRs compare with patient survival in patients who underwent PFR for benign, aggressive, and metastatic tumors? (2) What are common reasons for revisions of primary PFRs? (3) Which factors are associated with survival of primary PFRs? (4) What is the survivorship free from conversion of bipolar PFRs to THA? Between January 1, 1980, and December 31, 2020, we treated 812 patients with an endoprosthetic reconstruction for an oncologic indication. All patients who underwent a primary PFR for an oncologic indication were included in this study. The study cohort consisted of 122 patients receiving a primary PFR. Eighteen patients did not reach a censored endpoint such as death, revision, or amputation within 2 years. Thirty-three patients died within 2 years of their surgery. Of the 122 patients with primary PFRs, 39 did not reach a censored endpoint and have not been seen within the past 5 years. However, the mean follow-up time for these patients was longer than 10 years. The Social Security Death Index was queried to identify any patients who may have died but might not have been captured by our database To allow for adequate follow-up, endoprosthetic reconstructions performed after December 31, 2020 were excluded. The mean age at the time of the index surgery was 48 ± 22 years. The mean follow-up time of surviving patients was 7 ± 8 years. All PFRs were performed using a bipolar hemiarthroplasty with a cemented stem, and all implants were considered comparable. Demographic, oncologic, procedural, and outcome data including prosthesis survival, patient survival, complication rates, and rates of conversion to THA were analyzed. Patient, prosthesis, and limb salvage survival rates were generated, with implant revision as the endpoint and death as a competing risk. Statistical significance was defined as p < 0.05. Generally, patients with benign or low-grade (Stage I) disease outlived their implants (100% patient survival through 30 years; p = 0.02), whereas the opposite was true in patients with high-grade, localized Stage II disease (64% patient survival at 5 years [95% CI 49% to 76%]; p = 0.001) or widespread Stage III metastatic disease (6.2% patient survival at 5 years [95% CI 0.5% to 24%]; p < 0.001). Primary PFR implant survival at 5, 10, 20, and 30 years was 97% (95% CI 90% to 99%), 81% (95% CI 67% to 90%), 69% (95% CI 46% to 84%), and 51% (95% CI 24% to 73%), respectively. Eight percent (10 of 122) of primary PFRs were revised for any reason. The most common causes of revision were aseptic loosening (3% [four of 122]), infection (3% [three of 122]), breakage of the implant (2% [two of 122]), and tumor progression (1% [one of 122]). Follow-up time was the only factor that was associated with revision of primary PFRs. Neither segment length nor stem length were associated with revision of primary. Six percent (seven of 122) of PFRs were converted to THA at a mean 15 ± 8 years from the index procedure. Survivorship free from conversion to THA (accounting for death as a competing risk) was 94% (95% CI 85% to 99%), 86% (95% CI 68% to 94%). and 77% (95% CI 51% to 91%) at 10, 20, and 30 years, respectively. Cemented bipolar PFRs for an oncologic indication are a relatively durable reconstruction technique. Given the relative longevity and efficacy of PFRs demonstrated in our study, especially in patients with high-grade or metastatic disease where implant survival until all-cause revision was longer than patient survival, surgeons should continue to seriously consider PFRs in appropriate patients. The relative rarity of these reconstructions limits the number of patients in this study as well as in current research; thus, further multi-institutional collaborations are needed to provide the most accurate prognostic data for our patients. Level III, therapeutic study.


[Exploration on the appraisal of Chinese medical lawsuit cases in the Republican period].
Since the doctor-patient relationship was increasingly tense during the Republican period, Chinese medical lawsuit cases happened frequently due to various sorts of dispute, and had become the focus in both medical and judiciary fields. During this period, the Chinese medical professionals were highly concerned about the rights of medical appraisal and opposed the appraisal made only by western medical professionals alone. Through the establishment of various sorts of appraisal units by professional community, academic groups, and medical colleges, endeavor were made to improve the appraisal level of professionalization and objectivity.


G-protein betagamma subunit-dependent phosphorylation of 62-kDa protein in the early signaling pathway of starfish oocyte maturation induced by 1-methyladenine.
In starfish oocytes, maturation is induced by a hormone, 1-methyladenine (1-MA), that binds to the receptors exposed to the outer surface of the plasma membrane. The signal of 1-MA stimulates the heterotrimeric G protein, resulting in dissociation of the betagamma subunit of G protein (Gbetagamma) from a pertussis toxin-sensitive Gi-type alpha subunit. To investigate the targets for Gbetagamma, we analyzed 1-MA- or Gbetagamma-dependent phosphorylation using in vivo and in vitro systems. A 62-kDa protein was phosphorylated immediately after 1-MA treatment in intact oocytes. In the cell-free preparations, the 62-kDa protein was also phosphorylated on serine residue(s) immediately after addition of 1-MA or Gbetagamma. The Gbetagamma-dependent phosphorylation of the 62-kDa protein was inhibited by wortmannin or LY294002, which are mechanistically different inhibitors of phosphatidylinositol 3-kinase (PI3K). LY294002 also inhibited Gbetagamma- as well as 1-MA-induced maturation of oocytes. Taken together, these results indicate that the 62-kDa protein functions downstream of Gbetagamma and PI3K in the early signaling pathway of 1-MA-induced starfish oocyte maturation. The phosphorylation of the 62-kDa protein may be required for the activation of maturation-promoting factor.


Trabeculectomy with mitomycin C combined with direct cauterization of peripheral iris in the management of neovascular glaucoma.
To determine the outcomes of trabeculectomy with mitomycin C (MMC) combined with direct cauterization of peripheral iris before iridectomy in the management of neovascular glaucoma (NVG), and to demonstrate the effect of this surgical technique on decreasing the incidence of intraoperative bleeding and early postoperative hyphema. This prospective study was based on 72 eyes of 72 patients with NVG who underwent primary trabeculectomy with MMC combined with direct cauterization of peripheral iris before iridectomy. The patients were evaluated for intraoperative and early postoperative complications such as hyphema, and operative success rates. Operative success was defined as an intraocular pressure (IOP) < or =22 mm Hg (+/-medical therapy) in the absence of phthisis. The mean IOP and the mean number of antiglaucomatous medications at baseline and at the posttrabeculectomy sixth month were compared by paired Student t test. The mean preoperative IOP was 39.3+/-5.6 mm Hg (range, 29 to 60 mm Hg) whereas it was 20.02+/-4.3 mm Hg (range, 14 to 38 mm Hg) at the postoperative sixth month. The mean preoperative number of antiglaucoma medications was 3.2+/-0.4 (range, 2 to 4) but it reduced to 1.8+/-0.6 (range, 1 to 4) at the postoperative sixth month. These differences were statistically significant (P<0.00001). The IOP was < or =22 mm Hg (+/-medical therapy) in 69 eyes (95.8%) at the postoperative first week, in 62 eyes (86.1%) at the postoperative first month, in 60 eyes (83.3%) at the postoperative third month and in 48 eyes (66%) at the postoperative sixth month. Hyphema occurred in 15 eyes (20.8%) within the first week of the surgery. In 12 eyes it was transient; however, in 3 eyes irrigation of anterior chamber was required. Trabeculectomy with MMC combined with direct cauterization of peripheral iris decreases the incidence of both intraoperative bleeding, and early postoperative hyphema, and provides reduction of IOP and the number of antiglaucomatous medications in cases with NVG in a 6-month follow-up period.


Serum Cystatin C as a Biomarker in Diffuse Large B-Cell Lymphoma.
Elevated serum levels of cystatin C are found to be related to poor outcome and metastatic potential of some malignant disorders. To evaluate the clinical prominence of serum cystatin C in diffuse large B-cell lymphoma (DLBCL), blood samples were obtained from 58 patients at the time of diagnosis and paired blood samples were obtained from 22 patients at the time of remission. Also, serum cystatin C level was measured in matched healthy controls. Serum cystatin C levels were significantly more elevated in DLBCL patients than in controls (p < 0.0001). Furthermore, paired-sample analysis revealed that pretreatment cystatin C levels were reduced significantly in patients who achieved remission after therapy (p = 0.016). High serum cystatin C levels were correlated with age over 60 years (p = 0.049), extra-nodal involvement (p = 0.005) and with high serum lactate dehydrogenase (LDH) (p < 0.013). Elevated serum cystatin C levels were associated with extra-nodal involvement and they were significantly reduced to normal range after the remission. However, Kaplan-Meier curves revealed no survival difference in the pretreatment serum cystatin C levels. Therefore, serum cystatin C may be a novel biomarker that reflects tumor burden in DLBCL but bears no prognostic significance regarding survival.


Neonatal death in Marshall-Smith syndrome.
Marshall-Smith syndrome is characterized by accelerated skeletal maturation, failure to thrive and dysmorphic features. Since 1971, twenty cases of MSS have been reported. We describe another patient with a very early death demonstrating the clinical variability of the syndrome and the importance of systematic X rays of the skeleton for determining the causes of fetal or neonatal death.


Designing immunoconjugates for cancer therapy.
Antibody-drug conjugates (ADCs), as well as antibody conjugates of protein toxins (immunotoxins) and cytokines (immunocytokines), are showing clinical efficacy, with manageable toxicities, in cancer treatment. The utility of an ADC is governed by the antibody and the target, as well as by the drug-linker component of the conjugate. The conjugation site, conjugating group, drug/antibody ratios and site-specific conjugation for product homogeneity are all aspects to consider in optimizing the ADC and enhancing its therapeutic window. Immunotoxin and immunocytokine construction by recombinant methods can be modulated to improve efficacy and reduce toxicity. The Dock-and-Lock (DNL) platform technology provides a flexible approach to assemble mono- or bispecific constructs carrying multiple toxin or cytokine molecules for targeted therapy. Conjugation chemistry and recombinant technologies have had a significant impact on the therapeutic prospects of immunoconjugates, particularly in hematopoietic diseases. Continued concerted efforts from different scientific disciplines are needed, together with newer treatment paradigms, for greater progress in the more challenging therapy of solid tumors.


Derivation of iPSCs after culture of human dental pulp cells under defined conditions.
Human dental pulp cells (hDPCs) are a promising resource for regenerative medicine and tissue engineering and can be used for derivation of induced pluripotent stem cells (iPSCs). However, current protocols use reagents of animal origin (mainly fetal bovine serum, FBS) that carry the potential risk of infectious diseases and unwanted immunogenicity. Here, we report a chemically defined protocol to isolate and maintain the growth and differentiation potential of hDPCs. hDPCs cultured under these conditions showed significantly less primary colony formation than those with FBS. Cell culture under stringently defined conditions revealed a donor-dependent growth capacity; however, once established, the differentiation capabilities of the hDPCs were comparable to those observed with FBS. DNA array analyses indicated that the culture conditions robustly altered hDPC gene expression patterns but, more importantly, had little effect on neither pluripotent gene expression nor the efficiency of iPSC induction. The chemically defined culture conditions described herein are not perfect serum replacements, but can be used for the safe establishment of iPSCs and will find utility in applications for cell-based regenerative medicine.


Estimated detection distance of a baiji's (Chinese river dolphin, Lipotes vexillifer) whistles using a passive acoustic survey method.
Source levels and phonation intervals of whistles produced by a free-ranging baiji (Chinese river dolphin) were measured in the seminatural reserve of Shishou in Hubei, China. A total of 43 whistles were recorded over 12 recording sessions. The mean dominant frequency (the frequency at the highest energy) was 5.7 kHz (s.d. = 0.67). The calculated source level was 143.2 dB rms re 1 microPa (s.d. = 5.8). Most phonation intervals were shorter than 460 s, and the average interval was 205 s (s.d. = 254). Theoretical detection range of baiji's whistle was 6600 m at the present study site, but it could reduce a couple of hundred meters in practical noisy situation in the Yangtze River. Sporadic phonation (205 s interval on average) with relatively faint signal of baiji was considered to be difficult to be detected by a towing hydrophone system. Stationed monitoring or slow speed towing of hydrophones along the river current is recommended.


Exploring access to government-led support for children with disabilities in Bangladesh.
While access to support for individuals with disabilities has attracted international attention, children with disabilities and their families continue to face a range of barriers that limit their timely access to the needed support, including health service. This is even worse for children with disabilities living in resource poor settings like Bangladesh. The objective of this study was to determine the extent to which families of children with disabilities have knowledge about and access to government support for their children with disabilities in Bangladesh. We employed a cross-sectional study among 393 families of children with disabilities who sought services from the Centre for the Rehabilitation of the Paralysed for their children with disabilities in Bangladesh. We used chi-square test to measure the association between categorical variables and, Mann-Whitney U-test to compare mean across different sub-groups. Overall, family members of children with disabilities have limited knowledge about and access to government support. We found a significant association between knowledge and access to government support (p<0.001). Family members with children with disabilities aged younger than six years had less access to government support (p<0.001). We thus concluded with an urgent call on government agencies and service providers to provide relevant and timely information to families of children with disabilities to enable them to access the needed support.


Balloon catheter sinuplasty in young children.
Balloon catheter sinuplasty (BCS) for chronic rhinosinusitis (CRS) was found to be successful in adults. The safety and feasibility of BCS in children has been recently established. The purpose of this study was to study the outcome of this technology in CRS in children. A prospective, multicenter, nonrandomized evaluation was performed on patients with CRS. Thirty-two children between the ages of 2 and 11 years were enrolled. Safety was assessed by rate of adverse events. Effectiveness was assessed using the Sino-Nasal (SN)-5 quality-of-life questionnaire for children with CRS at 52 weeks follow-up. Thirty-two children were enrolled of which 24 completed their 52 weeks follow-up. No adverse events were reported because of the procedure. SN-5 score improved from a mean of 4.9 at baseline to a mean of 2.95 at 52 weeks (p < 0.0001). Twelve (50%) children had a significant improvement of their SN-5 (>-1.5), 7 (29%) had moderate improvement (>-1.0 and <-1.5), 2 (8%) had mild improvement (>-0.5 and <-1.0), 1 (4%) remained the same, and 2 (8%) had worsening scores. Balloon catheter dilation of the sinus ostia in children was safe and a significant number showed improvement of their SN-5 at 1 year follow-up. Additional studies comparing balloon sinuplasty to other modalities of treatment in children are needed to determine its efficacy in the treatment of CRS in children.


Place learning strategy of substantia nigra pars compacta-lesioned rats.
The substantia nigra pars compacta (SNc) and the dorsal striatum are often considered to be necessary for stimulus-response (S-R) habit learning, whereas the dorsal hippocampus is considered to be necessary for relational (declarative) memory. Spatial learning is a kind of relational learning that occurs when a rat is released from different locations (variable start) in a water maze to find a submerged platform that is kept in a constant location. However, when the rat is always released from the same starting position (constant start), it can learn to find the platform oriented by a fixed configuration of cues, that is, by S-R learning. To test the critical role of the SNc in S-R and relational learning, the authors tested adult male Wistar rats, sham-operated or with a lesion in the SNc, in these 2 versions of the water maze task. The SNc lesion was induced by bilateral intranigral infusion of 0.5 micromol 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Although the SNc-lesioned rats learned the variable-start version as effectively as sham rats did, they were significantly impaired in learning the constant-start version of the task.


Oral- and pharyngeal-cancer patients' perceived symptoms and health.
The purpose of this study was to describe the perceived eating problems, general symptoms, and general health of a group of oral- and pharyngeal- cancer patients before surgery in order to facilitate nursing care planning. A total of 29 patients (20 men and nine women) participated. Two groups were formed: in group 1, 13 patients participated before and, in group 2, 16 patients participated after the presurgical radiotherapy. Questionnaires were used to collect data. Eating disabilities were evident in both groups. The patients who had had their radiation therapy experienced problems such as bad taste function, mouth dryness, difficulties in chewing, and mouth pain more frequently than those who had not been treated. Only five patients in group 2 ate solid food, compared with 10 in group 1. Shoulder and back pain and feelings of worry and anxiety were perceived as the most frequent general symptoms. Most of the patients perceived their general health as being rather good, but some indicated poor health, several symptoms, poor appetite, and/or severe eating problems. Patients with oral and pharyngeal cancer should be carefully assessed before surgery because of their disparity of symptoms and disabilities so as to identify those who need specific nursing interventions.


Synchrotron radiation sources - present capabilities and future directions.
Many of the more than 40 operational light sources around the world have achieved performance levels that exceed initial design goals. These accomplishments are reviewed, along with concepts and proposals for sources with performance levels exceeding those of present sources. These include storage rings with lower electron-beam emittance than present third-generation rings and free-electron lasers (FELs). It now appears that the highest performance sources will be based on linacs rather than storage rings. This is because emittance originates differently and scales differently with electron energy for rings and linacs, so that the lowest electron-beam emittance can be achieved in high-energy linacs equipped with high-brightness electron sources. Such electron beams can be used to provide X-ray beams with very high brightness and coherence in sub-picosecond pulses in a single pass through a small-gap short-period undulator by spontaneous emission, and with even higher beam brightness and coherence by stimulated coherent emission in an FEL. Designs for such FEL sources, and associated research and development, are underway at several laboratories.Work supported by the US Department of Energy, Office of Basic Energy Sciences, contract DE-AC03-76SF00515.


Accurate Size and Size-Distribution Determination of Polystyrene Latex Nanoparticles in Aqueous Medium Using Dynamic Light Scattering and Asymmetrical Flow Field Flow Fractionation with Multi-Angle Light Scattering.
Accurate determination of the intensity-average diameter of polystyrene latex (PS-latex) by dynamic light scattering (DLS) was carried out through extrapolation of both the concentration of PS-latex and the observed scattering angle. Intensity-average diameter and size distribution were reliably determined by asymmetric flow field flow fractionation (AFFFF) using multi-angle light scattering (MALS) with consideration of band broadening in AFFFF separation. The intensity-average diameter determined by DLS and AFFFF-MALS agreed well within the estimated uncertainties, although the size distribution of PS-latex determined by DLS was less reliable in comparison with that determined by AFFFF-MALS.


Skeletonization and Isolation of the Glissonean and Venous Branches in Liver Surgery With an Ultrasonic Scalpel Technology.
This study describes a novel technique for skeletonization and isolation of Glissonean and venous branches during liver surgery using a harmonic scalpel (HS). Hepatic resections with HS were performed with the skeletonization and isolation technique in 50 patients (HS group). Variables evaluated were blood loss, operative time, biliary leak, and morbidity. The results were compared with 50 hepatic resections that were performed using a previously established technique: Cavitron ultrasonic surgical aspirator with electric cautery, ligatures, and hemoclips (NHS group). The HS group had shorter total operative times (285 versus 358 minutes; P = 0.01), less blood loss (389 versus 871 mL; P = 0.034), and less crystalloid infusion (2744 versus 3299 mL; P = 0.027) compared with the NHS group. Postoperative liver function and complication rates were similar when comparing the two groups. These data demonstrate that HS is a simple, easy, and effective instrument for the skeletonization and isolation of vessels during liver transection.


A Novel Real-Time Path Servo Control of a Hardware-in-the-Loop for a Large-Stroke Asymmetric Rod-Less Pneumatic System under Variable Loads.
This project aims to develop a novel large stroke asymmetric pneumatic servo system of a hardware-in-the-loop for path tracking control under variable loads based on the MATLAB Simulink real-time system. High pressure compressed air provided by the air compressor is utilized for the pneumatic proportional servo valve to drive the large stroke asymmetric rod-less pneumatic actuator. Due to the pressure differences between two chambers, the pneumatic actuator will operate. The highly nonlinear mathematical models of the large stroke asymmetric pneumatic system were analyzed and developed. The functional approximation technique based on the sliding mode controller (FASC) is developed as a controller to solve the uncertain time-varying nonlinear system. The MATLAB Simulink real-time system was a main control unit of a hardware-in-the-loop system proposed to establish driver blocks for analog and digital I/O, a linear encoder, a CPU and a large stroke asymmetric pneumatic rod-less system. By the position sensor, the position signals of the cylinder will be measured immediately. The measured signals will be viewed as the feedback signals of the pneumatic servo system for the study of real-time positioning control and path tracking control. Finally, real-time control of a large stroke asymmetric pneumatic servo system with measuring system, a large stroke asymmetric pneumatic servo system, data acquisition system and the control strategy software will be implemented. Thus, upgrading the high position precision and the trajectory tracking performance of the large stroke asymmetric pneumatic servo system will be realized to promote the high position precision and path tracking capability. Experimental results show that fifth order paths in various strokes and the sine wave path are successfully implemented in the test rig. Also, results of variable loads under the different angle were implemented experimentally.


Proteome Landscape during Ripening of Solid Endosperm from Two Different Coconut Cultivars Reveals Contrasting Carbohydrate and Fatty Acid Metabolic Pathway Modulation.
Cocos nucifera L. is a crop grown in the humid tropics. It is grouped into two classes of varieties: dwarf and tall; regardless of the variety, the endosperm of the coconut accumulates carbohydrates in the early stages of maturation and fatty acids in the later stages, although the biochemical factors that determine such behavior remain unknown. We used tandem mass tagging with synchronous precursor selection (TMT-SPS-MS3) to analyze the proteomes of solid endosperms from Yucatan green dwarf (YGD) and Mexican pacific tall (MPT) coconut cultivars. The analysis was conducted at immature, intermediate, and mature development stages to better understand the regulation of carbohydrate and lipid metabolisms. Proteomic analyses showed 244 proteins in YGD and 347 in MPT; from these, 155 proteins were shared between both cultivars. Furthermore, the proteomes related to glycolysis, photosynthesis, and gluconeogenesis, and those associated with the biosynthesis and elongation of fatty acids, were up-accumulated in the solid endosperm of MPT, while in YGD, they were down-accumulated. These results support that carbohydrate and fatty acid metabolisms differ among the developmental stages of the solid endosperm and between the dwarf and tall cultivars. This is the first proteomics study comparing different stages of maturity in two contrasting coconut cultivars and may help in understanding the maturity process in other palms.


[Application of collimator broad correction three dimensional ordered subsets expectation maximization for regional cerebral blood flow measurement].
Autoradiography (ARG) has been used for quantitative analysis of the cerebral blood flow using 123I-IMP, and the regional cerebral blood flow (rCBF) can be assessed more accurately with scatter and attenuation correction. Currently, the filtered back projection (FBP) method is generally used for image reconstruction. However, we anticipate obtaining more accurate rCBF by the ordered subsets expectation maximization method with collimator broad correction three dimensional ordered subsets expectation maximization (3D-OSEM). In the present study, we optimized the processing conditions to quantify rCBF using the 3D-OSEM method and compared them with the FBP method. Regarding the method, we determined the subsets and iteration, compared rCBF values using a profile curve, and compared them with the rCBF values obtained by the XeCT (Xenon-enhanced computed tomography)/CBF method. We found that in the 3D-OSEM method using 90 direction collection and 1.72 mm/pixel, the most accurate image was obtained around subset 9 and iteration 10. In addition, as compared to the profile curve and the XeCT/CBF method, the thalamus rCBF was high in the 3D-OSEM method with a good correlation with that of the XeCT/CBF. Accordingly, we concluded that the 3D-OSEM method can improve the decrease in rCBF due to blurring of the distance between the source (i.e., a structure located in the central part of the brain such as the thalamus and the collimator).


Using structured pathology data to predict hospital-wide mortality at admission.
Early prediction of in-hospital mortality can improve patient outcome. Current prediction models for in-hospital mortality focus mainly on specific pathologies. Structured pathology data is hospital-wide readily available and is primarily used for e.g. financing purposes. We aim to build a predictive model at admission using the International Classification of Diseases (ICD) codes as predictors and investigate the effect of the self-evident DNR ("Do Not Resuscitate") diagnosis codes and palliative care codes. We compare the models using ICD-10-CM codes with Risk of Mortality (RoM) and Charlson Comorbidity Index (CCI) as predictors using the Random Forests modeling approach. We use the Present on Admission flag to distinguish which diagnoses are present on admission. The study is performed in a single center (Ghent University Hospital) with the inclusion of 36 368 patients, all discharged in 2017. Our model at admission using ICD-10-CM codes (AUCROC = 0.9477) outperforms the model using RoM (AUCROC = 0.8797 and CCI (AUCROC = 0.7435). We confirmed that DNR and palliative care codes have a strong impact on the model resulting in a decrease of 7% for the ICD model (AUCROC = 0.8791) at admission. We therefore conclude that a model with a sufficient predictive performance can be derived from structured pathology data, and if real-time available, can serve as a prerequisite to develop a practical clinical decision support system for physicians.


FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.
Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression.


Phaseolus vulgaris lectins: A systematic review of characteristics and health implications.
Legume lectins are carbohydrate-binding proteins of non-immune origin. Significant amounts of lectins have been found in Phaseolus vulgaris beans as far back as in the last century; however, many questions about their potential biological roles still remain obscure. Studies have shown that lectins are anti-nutritional factors that can cause intestinal disorders. Owing to their ability to act as toxic allergens and hemagglutinins, the Phaseolus vulgaris lectins are of grave concern for human health and safety. Nonetheless, their potential beneficial health effects, such as anti-cancer, anti-human immunodeficiency virus (anti-HIV), anti-microbial infection, preventing mucosal atrophy, reducing type 2 diabetes and obesity, promoting nutrients absorption and targeting drugs, are of immense interest. The significance of Phaseolus vulgaris lectins in biological researches and the potential biomedical applications have placed tremendous emphasis on the development of purification strategies to obtain the protein in pure and stable forms. These purification strategies entail considerations such as effects of proteolysis, heating, gamma radiation, and high-hydrostatic-pressure that can have crucial outcomes in either eliminating or improving bioactivities of the lectins. Thus, up-to-date research findings of Phaseolus vulgaris lectins on different aspects such as anti-nutritional and health impacts, purification strategies and novel processing trends, are systematically reviewed.


[Treatment of osteonecrosis of femoral head by core decompression combining with autologous cortical sustaining bone and cancellous bone graft].
To study the effect of core decompression combining with autologous cortical sustaining bone and cancellous bone graft in treating osteonecrosis of the femoral head (ONFH). From February 2004 to May 2008, 64 patients (77 hips) with ONFH were treated with core decompression combining with autologous cortical sustaining bone and cancellous bone graft, including 45 males and 19 females and aging 23 to 60 years with an average age of 43 years. There were 51 cases of unilateral ONFH and 13 cases of bilateral ONFH. ONFH was caused by alcohol in 39 cases (47 hips), by steroid in 21 cases (26 hips), and by trauma in 4 cases (4 hips). The disease course was 1-12 years. The pain time was 2-14 months (average 7 months). All the cases underwent imageology and postoperation pathology examination to confirm the diagnosis of ONFH. According to Association Research Circulation Osseous (ARCO) international classification of osteonecrosis, 17 cases (23 hips) were classified as stage I A, 2 cases (3 hips) as stage I B, 21 cases (24 hips) as stage II A, 2 cases (2 hips) as stage II B, 4 cases (4 hips) as stage II C, and 18 cases (21 hips) as stage III A. The outcome was evaluated both clinically by Harris score and radiologically by imageology. A total of 59 cases (69 hips) were followed up for 12-62 months with an average of 32.1 months. The Harris score was 87.12 +/- 8.68 at 12 months after operation, showing significant difference (P < 0.05) when compared with the preoperative one (68.38 +/- 14.49). The results were excellent in 39 hips, good in 18 hips, fair in 6 hips, and poor in 6 hip; and the excellent and good rate was 82.6%. Radiographic evaluation was 21 hips (30.4%) of grade I, 42 hips (60.9%) of grade II, and 6 hips (8.7%) of grade III. One case had the complication of ilium bone donor site, 21 cases had little pain or numbness, and the other cases had no uncomfortable complication. The method of core decompression combining with autologous cortical sustaining bone and cancellous bone graft can improve the means of bone grafts, prevent the collapse of the femoral head, and is less traumatic than common procedures. Clinical effects are obvious and effective.


A potential mechanism of slowed pubertal maturation after chronic administration of sodium valproic acid.
Sodium valproic acid (VPA) occasionally delays pubertal maturation in children and gonadal and skeletal growth in juvenile, seizure-prone, inbred DBA/2J mice. Fourteen-day-old mice received either VPA or control solution, and the medial preoptic area (mPOA) of the hypothalamus was studied after 4, 7, 10, 14, or 18 days by immunocytochemically processing for gonadotropin-releasing hormone (GnRH). Significant differences were found for the proportion of bipolar to unipolar neurons in the mPOA. VPA may slow pubertal maturation by altering neurochemical systems that normally play an important role in timing maturation of the GnRH pulse generator.


Should minors be considered as potential living liver donors?
For many patients, living donor liver transplantation represents their only hope of receiving a lifesaving graft. In certain (albeit rare) cases, a minor will be the only suitable donor. Living liver donation by minors has been reported in several countries. In the academic literature and professional guidelines, little attention is paid to the development of an ethical framework for this practice. The focus is frequently limited to the donation of regenerative tissues and kidneys. However, liver donation differs in important respects because of the increased medical risks and the lack of substitute therapies. Therefore, in this article, we assess whether living liver donation by minors is ethically appropriate. We argue that living liver donation by minors is justifiable only if minors possess the capacity to consent to donation or if the procedure is in their best interests. Although minors may possess adult-like levels of cognitive maturity, they lack sufficient psychosocial maturity to give valid consent to donation. In addition, living liver donation is generally not in a minor's best interests. With respect to the latter, the potential psychological benefits that a minor may experience as a result of living liver donation are insufficiently empirically supported and are unlikely to outweigh the short- and long-term medical and psychological risks. Therefore, we conclude that minors should not be considered as potential living liver donors.


Lymphangiogenic Gene Expression Is Associated With Lymph Node Recurrence and Poor Prognosis After Partial Hepatectomy for Colorectal Liver Metastasis.
To investigate the relevance of lymphangiogenic gene expression in primary and liver metastasis of colorectal cancer (CRC) and identify determinants of lymphatic invasion. Lymphatic development promoting vascular endothelial growth factor C (VEGFC) is associated with poor outcome in primary CRC. For colorectal liver metastasis (CRLM), intrahepatic lymph invasion and lymph node metastasis are poor prognostic factors. Exact biological factors promoting lymphatic involvement remain elusive, just as the association with molecular subtypes of CRC. We designed a lymphangiogenic gene set (VEGFC, Nrp-2, PDPN, LYVE-1, MRC1, CCL-21) and applied it to large datasets of CRC. Gene expression of the lymphangiogenic signature was assessed in resected CRLM specimens by Rt-QPCR. In vitro experiments were performed with colon cancer cell line Colo320 (high Nrp-2 expression) and human dermal microvascular lymphatic endothelial cells (LECs). Lymphangiogenic gene expression was associated with poor prognosis in both primary and liver metastasis of CRC. CRLM with high expression of consensus molecular subtype-4 identifier genes also exhibited high lymphangiogenic gene expression. Lymph node recurrence following CRLM resection was associated with high expression of VEGFC and Nrp-2. Blocking Nrp-2 significantly reduced invasion of Colo320 cells through an LEC monolayer. Lymphangiogenic gene expression is correlated with worse prognosis and consensus molecular subtype-4 in both primary and liver metastatic CRC. VEGFC and Nrp-2 expression may be predictive of lymph node involvement in recurrence after resection of CRLM. Nrp-2, expressed on both tumor and LECs, may have a mechanistic role in lymphatic invasion and is a potential novel target in CRC.


Combination chemotherapy plus levamisole in the treatment of disseminated malignant melanoma. A Southwest Oncology Group study.
Two hundred-eighty patients were randomized to receive either BCNU, hydroxyurea and imidazole carboxamide (BHD), BHD plus levamisole, or high-dose DTIC plus actinomycin D. There was no difference in response rate in the three groups (24%, 25% and 22%). Females responded better than males and, as expected, those with a better performance status responded more favorably than those with poor performance status. Patients whose primary site of melanoma was on the extremities did significantly better than those melanomas originating on the trunk or head and neck. Patients with lymphocyte counts greater than 2000/mm3 fared better than those with lymphopenia. Those responders who received high-dose DTIC plus actinomycin D had a significantly longer length of response than those receiving the immunotherapy limb. This was also true in those patients who had a prior disease-free interval of greater than 6 months before being placed in this study. Although there was no difference in survival from the start of treatment in all patients, those patients receiving high-dose DTIC plus actinomycin D and who had a prior disease-free interval of greater than 6 months, had significantly superior survival when compared to the immunotherapy limb. It is concluded that the addition of Levamisole to BHD does not improve response rate and may in certain subsets be detrimental to disease-free response and survival. High-dose DTIC plus actinomycin D is equally effective to BHD.


Samarium- and Ytterbium-Grafted Periodic Mesoporous Silica for Carbon Dioxide Capture and Conversion.
Immobilized coordination compounds of Lewis acidic metals are powerful catalytic components of systems for the cycloaddition of CO2 to epoxides that do not require sophisticated coordination frameworks to harness the metal center and modulate its activity. Surface organometallic chemistry (SOMC) is a valuable methodology to prepare well-defined and site-isolated surface complexes and coordination compounds on metal oxides, with ligand environments easily adjustable to a targeted catalytic reaction. In this work, the SOMC methodology is applied to prepare SmII, YbII, and SmIII alkoxide surface complexes on periodic mesoporous (organo)silica of distinct pore symmetry/size for application in the CO2 cycloaddition reaction. The surface complexes are readily accessible by the grafting of the bis(trimethylsilyl)amide precursors LnII[N(SiMe3)2]2(THF)2 (Ln = Sm, Yb) and SmIII[N(SiMe3)2]3, followed by ligand exchange with alcohols (ethanol and neopentanol). The use of periodic mesoporous supports led to hybrid materials with relatively high surface areas and pore sizes, affording good performance in CO2 capture and in the cycloaddition of CO2 to epoxides under mild conditions (60-80 °C, 1-10 bar). In terms of catalytic performance, recyclability, and low amount of added nucleophile TBAX (X = Br, I), the most active materials prepared in this work compare well to a variety of previously reported SOMC-derived surface complexes and to other heterogeneous Lewis acids displaying more elaborate ligand environments.


Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial.
We are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container). In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia. The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], -3.4 to 25.6) and 12.0% (95% CI, -0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively. The impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period.


Origins of sulfur in coal: importance of the ester sulfate content of peat.
The sulfur found in coal stems in large part from sulfur incorporation at the peat-forming stage. Ester sulfate (a carbon-oxygen-sulfur linkage) is a major contributor to the sulfur in peat and thus is an important determiner of the quantity and forms of sulfur eventually found in coal.


[Breeding sites of Glossina palpalis s.1. pupae in a transitional woodland area in Ivory Coast].
Search for pupae of G. palpalis s.1. was conducted from February to December 1981 in the Bouaflé area, Ivory Coast. 1909 pupae were collected from 70 breeding sites after 518 hours of search. Pupae were found both in the dry and the rainy seasons. The vegetation and the nature of the soil seem to be two inseparable factors for the creation and the maintenance of Glossina breeding sites in the study area. In localities with high pig population density, a greater number of pupae were found either at the edge of the village or at a distance not exceeding 500 m from the houses. This observation confirms peridomestic behaviour of G. palpalis s.1. in these localities. On the contrary, in localities with low pig population density or without pigs, peridomestic breeding was not observed; all the pupae were found at a distance 500 m to 3 km away from the houses, in coffee and cocoa plantations and in woodlands. The epidemiological significance of the distribution of G. palpalis s.1. breeding sites in the study area is discussed.


Biopharmaceutical studies on hydantoin derivatives. IV. Factors affecting bioavailability of 5,5-diphenylhydantoin in dog.
Several factors affecting the bioavailability of 5,5-diphenylhydantoin (I) and its sodium salt (I-Na) were examined in dogs in relation to meal and following results were obtained. The bioavailability of I was not appreciably affected by the volume of coadministered water in the range of 30-120 ml. The bioavailability of I was most excellent when I was administered 0.5 h after meal. Food intake 0.5 h after drug administration enhanced appreciably the bioavailability, but that 2 h after drug administration did hardly affect the bioavailability. The extent of bioavailability of I-Na was almost 100% of the dose in the range of 100-400 mg/dog when it was administered 0.5 h after meal. While, when I-Na was administered in the fasting state, the extent of bioavailability was about 60% of the dose. Food-induced enhancement of the bioavailability of I was independent of the food constituents. The bioavailability of I was increased about 1.5-fold and 2-fold with 10-fold increase in the specific surface area of I, in the nonfasting and the fasting states, respectively. In the experiments using the dogs with the chronically implanted fistula in the common bile duct, it was found that the bile was not a major factor contributing to the food-induced enhancement of the bioavailability of I. There was a good correlation between the bioavailability of I in dog and that in man.


An exploratory international survey of the assessments and interventions used by occupational therapists and physiotherapists during the hospitalization of people with Guillain-Barré syndrome.
Guillain-Barré syndrome is a rare neurological condition. Although some people make a substantial functional recovery, almost half require intensive rehabilitation. Data were collected using a cross-sectional survey which investigated the assessments and interventions used by occupational therapists and physiotherapists for people with Guillain-Barré syndrome. Seventy valid responses were received from 10 countries. The survey highlighted four factors about current practice: (i) practitioners did not identify the use of formal clinical guidelines or protocols for Guillain-Barré Syndrome treatment of the upper limb; (ii) a range of standardized and non-standardized assessment and goal-setting tools are utilized; (iii) interventions include passive and active range of motion exercises, and the prescription of upper limb/hand splints; and (iv) interdisciplinary practice is common in the intensive care unit and during acute phases of Guillain-Barré syndrome, whereas discipline-specific work is more common during rehabilitation. A range of goal-setting and assessment tools are used by occupational therapists and physiotherapists during the hospitalization of people with Guillain-Barré syndrome. The type and duration of interventions vary and may reflect the lack of international protocols for Guillain-Barré syndrome rehabilitation.


An intersubunit lock-and-key 'clasp' motif in the dimer interface of Delta class glutathione transferase.
Structural investigations of a GST (glutathione transferase), adGSTD4-4, from the malaria vector Anopheles dirus show a novel lock-and-key 'Clasp' motif in the dimer interface of the Delta class enzyme. This motif also appears to be highly conserved across several insect GST classes, but differs from a previously reported mammalian lock-and-key motif. The aromatic 'key' residue not only inserts into a hydrophobic pocket, the 'lock', of the neighbouring subunit, but also acts as part of the 'lock' for the other subunit 'key'. The 'key' residues from both subunits show aromatic ring stacking with each other in a pi-pi interaction, generating a 'Clasp' in the middle of the subunit interface. Enzyme catalytic and structural characterizations revealed that single amino acid replacements in this 'Clasp' motif impacted on catalytic efficiencies, substrate selectivity and stability. Substitutions to the 'key' residue create strong positive co-operativity for glutathione binding, with a Hill coefficient approaching 2. The lock-and-key motif in general and especially the 'Clasp' motif with the pi-pi interaction appear to play a pivotal role in subunit communication between active sites, as well as in stabilizing the quaternary structure. Evidence of allosteric effects suggests an important role for this particular intersubunit architecture in regulating catalytic activity through conformational transitions of subunits. The observation of co-operativity in the mutants also implies that glutathione ligand binding and dimerization are linked. Quaternary structural changes of all mutants suggest that subunit assembly or dimerization basically manipulates subunit communication.


[Continuous arteriovenous hemofiltration in the newborn].
Acute renal failure (ARF) in newborns and infants is a serious postoperative complication. Peritoneal dialysis is considered the treatment of choice, but is often impossible postoperatively. In adult patients or older children, continuous arteriovenous hemofiltration (CAVH) has been established for 10 years. In 1985, Ronco published case reports on four newborn infants treated with CAVH using a specially designed hemofilter. In between, a few more case reports have been published. We report a case of postoperative septic ARF in an 8-week-old girl with a body weight of 4000 g. We used the Minifilter (Amicon Corp.) connected to a femoral arterial Shaldon catheter and initially a central venous line, later a subclavian Shaldon catheter. Intermittent hemodialysis without ultrafiltration was performed as well. With ultrafiltration rates of 2 to 24 ml/h, mean 12.8 ml/h, we achieved an impressive loss of weight and the pulmonary function improved. The baby died on the 5th day of CAVH treatment of septic multiorgan failure. Even though the small patient did not survive, we demonstrated the feasibility of the method in newborns. CAVH is recommended for overhydrated babies with oligoanuric ARF, but it is not sufficient as a substitute for dialysis in these patients.


Molecular Basis of Human Diseases and Targeted Therapy Based on Small-Molecule Inhibitors of ER Stress-Induced Signaling Pathways.
The Endoplasmic Reticulum (ER) provides a conserved protein quality control system and plays a fundamental role in cell growth and homeostasis. Disturbances in the ER homeostasis may originate especially from hypoxia, glucose deficiency, presence of mutant proteins, that directly impair protein folding capacity and after deposition of unfolded and misfolded proteins within ER lumen trigger ER stress conditions. This subsequently activates the Unfolded Protein Response (UPR) branches, which have a dual pro-adaptive or pro-apoptotic role depending on the severity and time of duration of ER stress conditions. This review is the first to offer a detailed overview on molecular mechanisms of all major ER stress-dependent signaling branches, that are activated through three specific ER transmembrane receptors of impaired protein folding: Protein kinase RNA (PKR)-like ER kinase (PERK), Inositol-requiring enzyme-1 (IRE1) and Activating transcription factor 6 (ATF6). Molecular crosstalk among ER transmembrane receptors-dependent pathways determines a final UPR response, but the recent data reported that especially PERK over-activation has a significant impact on the development and progression of a wide spectrum of disease entities. Based on these findings, small-molecules, highly specific PERK inhibitors may provide effective, groundbreaking treatment strategy against human diseases. However, after foregoing in vitro cellular and in vivo animal models conducted examination, supplementary investigations of PERK inhibitors are required for their further clinical use. Future research may answer the question of how to minimize toxicity and side effects of characterized small-molecule PERK inhibitors, that may be used, as breakthrough drugs, alone or in combination with currently known models of therapy.


Mechanisms of ATII-to-ATI Cell Differentiation during Lung Regeneration.
The alveolar epithelium consists of (ATI) and type II (ATII) cells. ATI cells cover the majority of the alveolar surface due to their thin, elongated shape and are largely responsible for barrier function and gas exchange. During lung injury, ATI cells are susceptible to injury, including cell death. Under some circumstances, ATII cells also die. To regenerate lost epithelial cells, ATII cells serve as progenitor cells. They proliferate to create new ATII cells and then differentiate into ATI cells [1,2,3]. Regeneration of ATI cells is critical to restore normal barrier and gas exchange function. Although the signaling pathways by which ATII cells proliferate have been explored [4,5,6,7,8,9,10,11,12], the mechanisms of ATII-to-ATI cell differentiation have not been well studied until recently. New studies have uncovered signaling pathways that mediate ATII-to-ATI differentiation. Bone morphogenetic protein (BMP) signaling inhibits ATII proliferation and promotes differentiation. Wnt/β-catenin and ETS variant transcription factor 5 (Etv5) signaling promote proliferation and inhibit differentiation. Delta-like 1 homolog (Dlk1) leads to a precisely timed inhibition of Notch signaling in later stages of alveolar repair, activating differentiation. Yes-associated protein/Transcriptional coactivator with PDZ-binding motif (YAP/TAZ) signaling appears to promote both proliferation and differentiation. We recently identified a novel transitional cell state through which ATII cells pass as they differentiate into ATI cells, and this has been validated by others in various models of lung injury. This intermediate cell state is characterized by the activation of Transforming growth factor beta (TGFβ) and other pathways, and some evidence suggests that TGFβ signaling induces and maintains this state. While the abovementioned signaling pathways have all been shown to be involved in ATII-to-ATI cell differentiation during lung regeneration, there is much that remains to be understood. The up- and down-stream signaling events by which these pathways are activated and by which they induce ATI cell differentiation are unknown. In addition, it is still unknown how the various mechanistic steps from each pathway interact with one another to control differentiation. Based on these recent studies that identified major signaling pathways driving ATII-to-ATI differentiation during alveolar regeneration, additional studies can be devised to understand the interaction between these pathways as they work in a coordinated manner to regulate differentiation. Moreover, the knowledge from these studies may eventually be used to develop new clinical treatments that accelerate epithelial cell regeneration in individuals with excessive lung damage, such as patients with the Acute Respiratory Distress Syndrome (ARDS), pulmonary fibrosis, and emphysema.


Potent spinal analgesia elicited through stimulation of NTS2 neurotensin receptors.
Intrathecal administration of the neuropeptide neurotensin (NT) was shown previously to exert antinociceptive effects in a variety of acute spinal pain paradigms including hotplate, tail-flick, and writhing tests. In the present study, we sought to determine whether some of these antinociceptive effects might be elicited via stimulation of low-affinity NTS2 receptors. We first established, using immunoblotting and immunohistochemical techniques, that NTS2 receptors were extensively associated with putative spinal nociceptive pathways, both at the level of the dorsal root ganglia and of the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal administration of NT or selective NTS2 agonists on acute thermal pain. Both NT and NTS2 agonists, levocabastine and Boc-Arg-Arg-Pro-Tyrpsi(CH2NH)Ile-Leu-OH (JMV-431), induced dose-dependent antinociceptive responses in the tail-flick test. The effects of levocabastine and of JMV-431 were unaffected by coadministration of the NTS1-specific antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl)carboxylamino]tricyclo)22.214.171.124.(3.7))-decan-2-carboxylic acid (SR48692), confirming that they were NTS2 mediated. In contrast, the antinociceptive effects of NT were partly abolished by coadministration of SR48692, indicating that NTS1 and NTS2 receptors were both involved. These results suggest that NTS2 receptors play a role in the regulation of spinal nociceptive inputs and that selective NTS2 agonists may offer new avenues for the treatment of acute pain.


Calmodulin conformational changes in the activation of protein kinases.
The conformation of Ca2+/calmodulin changes from extended when free in solution to compact when bound in peptide complexes. The extent and kinetics of calmodulin compaction in association with Ca2+/calmodulin-dependent protein kinases (CaMKs), as well as target peptides, were investigated by fluorescence, resonance energy transfer and stopped-flow kinetics. Compaction of Ca2+/calmodulin labelled with resonance energy-transfer probes in association with target peptides was rapid (>350 s(-1)). With the target enzymes smooth-muscle myosin light-chain kinase, CaMKIV and CaMKII, the rates of calmodulin compaction were one-two orders of magnitude lower compared with those of the peptides and in the case of alphaCaMKII, ATP binding and Thr(286) auto-phosphorylation were required for calmodulin compaction. In the absence of nucleotides, Ca2+/calmodulin bound to alphaCaMKII in extended conformations, initially probably attached by one lobe only. Kinetic data suggest that in the activation process of Ca2+/calmodulin-dependent protein kinases, productive as well as unproductive complexes are formed. The formation of productive complexes with Ca2+/calmodulin thus may determine the rate of activation.


Hexamethylene bisacetamide (HMBA) simultaneously targets AKT and MAPK pathway and represses NF kappaB activity: implications for cancer therapy.
Hexamethylene Bisacetamide (HMBA) is a hybrid polar compound originally developed as a differentiation inducing agent. We show in this study that HMBA can inhibit activation of several NF kappaB target genes in both lung and breast cancer cell lines. Furthermore, consistent with its ability to inhibit NF kappaB function, HMBA can also sensitize cells to apoptosis. We show that HMBA mediates inhibition of the Akt and ERK/MAPK cascade, both of which are critical for cell survival and proliferation and are well known regulators of NF kappaB activation. We also show that PTEN negative breast cancer cells which have hyper activation of the PI3K/Akt pathway show increased sensitivity to growth inhibitory effects of combination of HMBA and TNFalpha. Furthermore, HMBA can decrease the kinase activity of the IKK complex leading to defective phosphorylation of I kappaB alpha and Ser536 of p65. This study gives mechanistic insight into the mechanism of action of HMBA, provides the rationale for the potential use of HMBA in combination with various existing kinase inhibitors in combination therapy and also suggests useful biomarkers for monitoring tumor response to HMBA.


Claudin-3-deficient C57BL/6J mice display intact brain barriers.
The tight junction protein claudin-3 has been identified as a transcriptional target of the Wnt/β-catenin signaling pathway regulating blood-brain barrier (BBB) maturation. In neurological disorders loss of claudin-3 immunostaining is observed at the compromised BBB and blood-cerebrospinal fluid barrier (BCSFB). Although these observations support a central role of claudin-3 in regulating brain barriers' tight junction integrity, expression of claudin-3 at the brain barriers has remained a matter of debate. This prompted us to establish claudin-3-/- C57BL/6J mice to study the role of claudin-3 in brain barrier integrity in health and neuroinflammation. Bulk and single cell RNA sequencing and direct comparative qRT-PCR analysis of brain microvascular samples from WT and claudin-3-/- mice show beyond doubt that brain endothelial cells do not express claudin-3 mRNA. Detection of claudin-3 protein at the BBB in vivo and in vitro is rather due to junctional reactivity of anti-claudin-3 antibodies to an unknown antigen still detected in claudin-3-/- brain endothelium. We confirm expression and junctional localization of claudin-3 at the BCSFB of the choroid plexus. Our study clarifies that claudin-3 is not expressed at the BBB and shows that absence of claudin-3 does not impair brain barrier function during health and neuroinflammation in C57BL/6J mice.


Matching With Doses in an Observational Study of a Media Campaign Against Drug Abuse.
Multivariate matching with doses of treatment differs from the treatment-control matching in three ways. First, pairs must not only balance covariates, but also must differ markedly in dose. Second, any two subjects may be paired, so that the matching is nonbipartite, and different algorithms are required. Finally, a propensity score with doses must be used in place of the conventional propensity score. We illustrate multivariate matching with doses using pilot data from a media campaign against drug abuse. The media campaign is intended to change attitudes and intentions related to illegal drugs, and the evaluation compares stated intentions among ostensibly comparable teens who reported markedly different exposures to the media campaign.


Dysphagia caused by spindle cell lipoma of hypopharynx: presentation of clinical case and literature review.
Spindle cell lipoma of the hypopharynx is an extremely rare entity. Here, we present the first case of this lesion originated in the cricopharyngeal region, with symptoms of chronic progressive dysphagia, which can be confused with other pathologies; endoscopic and magnetic resonance imaging (MRI) evaluation are the methods of choice for its diagnostic approach. The best therapeutic approach is endoscopic resection with rapid recovery and few complications. Long-term followup is recommended, either endoscopic or imaging, given that it can be confused with an undiagnosed liposarcoma; additionally, its long-term behavior is unknown.


Disease activity of patients with chronic urticaria receiving COVID-19 vaccines.
Cutaneous adverse events after receiving a COVID-19 vaccine were identified. The disease activity of urticaria after a COVID-19 vaccine has never been explored in chronic urticaria patients. To evaluate disease activity of chronic urticaria after receiving a COVID-19 vaccine. A prospective cross-sectional study was conducted in chronic urticaria patients aged 18 or above who visited Siriraj Hospital between July and September 2021, and received the first and second dose of COVID-19 vaccine. The status prior to vaccination, including disease activity, disease control and disease severity was assessed by a urticaria activity score over seven days, urticaria control test, and modified medication score. The disease activity after vaccination was recorded. A total of 130 patients with a mean age of 45.9 ± 14.7 were enrolled in this study. Adenoviral and inactivated vaccines were administered to 85 (65.4%) and 45 patients (34.6%), respectively. Exacerbation was reported in 20 cases (15.4%) after the first dose and 17 cases (13.1%) after the second dose. Nine patients (45%) reported exacerbation after both the first and second dose. The majority of patients only had wheal, while three patients reported wheal with angioedema. No anaphylaxis was reported. Factor predicting exacerbation was concurrent thyroid disease (aRR 2.78, p < 0.01). Approximately 15% of chronic urticaria patients reported exacerbation after receiving a COVID-19 vaccination. No serious events were observed. Chronic urticaria patients should be vaccinated against COVID-19 after a discussion of the risk of disease flare-up.


A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model.
Persistent infection with human papillomavirus (HPV) is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV) produced in Escherichia coli (E.coli), with Gardasil quadrivalent vaccine (4vHPV, Merck & Co.) as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively), and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA) and Enzyme-Linked Immunosorbent Assay (ELISA). Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb) and total immunoglobulin G (IgG) antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24-64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV.


The radial artery in reoperative coronary bypass surgery:.
Failure of saphenous vein grafts (SVG) is a significant cause for coronary reoperation (redo CABG). The radial artery (RA) because of its availability, and versatility is well suited to use (together with internal thoracic arteries (ITA) in redo CABG, especially to replace failed SVG. We evaluated our experience where the RA was a major conduit in redo CABG over the past 5 years. From July 1996 to June 2002, 590 consecutive patients underwent redo CABG where one or both RA(s) were used, together with LITA or RITA. The mean age was 67.3 years, 82% were male, and 19% diabetic, 419 (71%) had Class III or IV angina, 135 (23%) had left main stenosis, and 210 (36%) had an LVEF < 0.50. There were a total of 877 RA conduits (303 single, 287 bilateral), 518 new LITA or RITA. A mean of 2.8 new distal anastomoses constructed 92% (2.6 per patient)of the arterial grafts. Follow-up was at 1 month, 3 months, and then yearly. The results were compared with 6466 primary CABG performed in the same time frame, and with a prior cohort of 741 consecutive patients having redo CABG without an RA in which identical operative techniques had otherwise been used. The 30-day mortality was 3.9% (23 patients). Morbidity was low. Perioperative myocardial infarction occurred in 16 (2.7%) patients, stroke in 10 (1.7%), sternal infection in 10 (1.7%), donor site infection in 2 (0.3%), and IABP use in 23 patients (3.9%)-including 10 preoperatively. The results were better when compared to a prior cohort of 741 patients with redo CABG (1991 to 1996) without use of the RA. The results were inferior to that of the contemporary primary CABG. Operative mortality was 3.9% versus 0.9%, p = 0.002, myocardial infarction 2.7% versus 0.8%, p = 0.03. The use of the RA (together with ITA) in redo CABG achieved total arterial revascularization in 92% of cases and is associated with excellent results, at least equal to or superior to those achieved previously.


[Effect of patellar non-resurfacing on clinical results after total knee arthroplasty/].
To evaluate the influence of patellar non-resurfacing on the effectiveness after total knee arthroplasty (TKA). Between April 2008 and April 2011, 163 patients with degenerative osteoarthritis of the knee underwent TKA without patellar resurfacing, and the clinical data were retrospectively analyzed. There were 65 males and 98 females, with a mean age of 63 years (range, 54-78 years). According to Outerbridge classification for cartilage degeneration, 22 cases were classified as grade I, 38 cases as grade II, 64 cases as grade III, and 39 cases as grade IV. There was no significant difference in gender, age, and sides among patients at 4 grades (P > 0.05). The intraoperative tourniquet-using time and postoperative complications were recorded; the knee society score (KSS), patella score (PS), patients' satisfaction, and anterior knee pain [using visual analogue scale (VAS)] were used to evaluate the knee function. X-ray films were routinely taken to observe the position of the prosthesis and the patella. The mean tourniquet-using time was 125 minutes (range, 90-150 minutes). All incisions obtained healing by first intention, and no early postoperative complication occurred. All patients were followed up 2-5 years (mean, 3.6 years). The KSS and PS scores were significantly improved at 6 months and last follow-up when compared with preoperative scores (P < 0.05), but no significant difference between at 6 months and last follow-up (P > 0.05). Significant differences in KSS and PS scores were found among patients with different grades of cartilage degeneration at preoperation (P < 0.05), but no significant difference at last follow-up (P > 0.05). At last follow-up, 7 patients experienced anterior knee pain (mild pain in 5, moderate pain in 2). The results of satisfaction were very satisfied in 90 cases, satisfied in 66 cases, not certain in 5 cases, and not satisfied in 2 cases. No significant difference was found in satisfaction and anterior knee pain among patients with different grades of cartilage degeneration (P > 0.05). Patellar non-resurfacing has no effect on the effectiveness after TKA.


[Pleural diseases: an unusual cause of cough].
The parietal pleura contains myelinated sensitive nerve fibers as well as mechanoreceptors which coordinate the breathing muscles. The small volume of fluid within the pleural space is in dynamic balance: hydrostatic and colloid-osmotic pressures maintain a constant flow of fluid from the parietal to the visceral pleura, which turns into pleural effusion under pathological conditions. Separation of transudate from exudate is best done by calculation of the protein and LDH ratios in the pleural fluid and in serum. Transudates of cardiac origin are due to congestive left heart failure alone. In detecting subpulmonary pleural effusion, ultrasonography is more accurate than X-ray in lateral decubitus. Pleural exudate is investigated by chemical, microbiological and cytological examination of the fluid, complemented by pleural biopsy, fibre bronchoscopy and thoracoscopy. In this way less than 10% of pleural effusions remain unexplained.


Comparative genomics on FGF16 orthologs.
We have previously reported comparative genomics analyses on FGF3, FGF4, FGF6, FGF7, FGF8, FGF10, FGF11, FGF17, FGF18, FGF19, FGF20, FGF22 and FGF23 genes. Here, we performed comparative genomics analyses on FGF1, FGF2, FGF5, FGF9, FGF12, FGF13, FGF14, FGF16 and FGF21 genes, and further characterized the FGF16 gene. Chimpanzee FGF16, chicken fgf16, and zebrafish fgf16 genes were identified within NW_121938.1, NW_060344.1, and CR855117.3 genome sequences, respectively. Chimpanzee FGF16 (207 aa), chicken fgf16 (207 aa), and zebrafish fgf16 (203 aa) showed 100%, 89.9%, and 79.2% total amino-acid identity with human FGF16. Because FGF16, FGF9, and FGF20 constitute FGF subfamily without N-terminal signal peptide, we next searched for uncharacterized FGF9 or FGF20 orthologs. Zebrafish fgf9 gene was identified within BX927112.11 genome sequence, and chicken fgf20 gene within NW_060349.1 genome sequence. Although N-terminal part was divergent, middle and C-terminal parts were well conserved among vertebrate FGF16, FGF9 and FGF20 orthologs. Phylogenetic analyses revealed that zebrafish fgf9 and fgf20 were more related to each other than to their chicken or mammalian orthologs. TCF/LEF binding site and TATA box were well conserved among the human FGF16, rat Fgf16, and mouse Fgf16 promoters. Because nuclear complex consisting of TCF/LEF (TCF1, TCF3, TCF4 or LEF1), beta-catenin, PYGO (PYGO1 or PYGO2) and Legless (BCL9 or BCL9L) binds to the TCF/LEF-binding site to up-regulate WNT/beta-catenin target genes, FGF16 gene was characterized as the evolutionarily conserved target of the WNT/beta-catenin signaling pathway, just like FGF18 and FGF20 genes. These facts indicate that FGF16, FGF18 and FGF20 are pharmacogenomics targets in the field of oncology and regenerative medicine.


Role of substituents on the properties of some polysaccharides.
This paper concerns the influence of the chemical structure on the physical properties of some polysaccharides. Especially, we proposed to discuss the role of the substituents on these properties. In some cases, non-carbohydrate substituents play a minor role on rheological properties in the presence of a salt excess as shown on xanthan and succinoglycan. The rheology of aqueous solution of these stereoregular polysaccharides is controlled by the conformation (helical conformation) whose stability is not largely influenced by these substituents. On the other hand, the interaction between galactomannan and xanthan depends on the presence of acetyl substituents on xanthan but also on the xanthan conformation. However, for polymers such as gellan, XM-6 or BEC 1615, complete deacetylation induces the ability to form physical gels in given thermodynamic conditions. The presence of carbohydrate substituents or short side chains was also examined. Especially in the gellan family, the role of position of substitution (position 3 on the glucose unit C or position 6 on the A glucose) was presented. It is concluded that the substituents giving the higher stability for the helical conformation (higher DeltaH and Tm values) also cause a lower salt sensitivity for the helical stability. The role of the substituents on the properties is also described for natural polymers and their chemically or enzymatically modified derivatives.


Effects of colonization of a bacterial endophyte, Azospirillum sp. B510, on disease resistance in tomato.
A plant growth-promoting bacteria, Azospirillum sp. B510, isolated from rice, can enhance growth and yield and induce disease resistance against various types of diseases in rice. Because little is known about the interaction between other plant species and this strain, we have investigated the effect of its colonization on disease resistance in tomato plants. Treatment with this strain by soil-drenching method established endophytic colonization in root tissues in tomato plant. The endophytic colonization with this strain-induced disease resistance in tomato plant against bacterial leaf spot caused by Pseudomonas syringae pv. tomato and gray mold caused by Botrytis cinerea. In Azospirillum-treated plants, neither the accumulation of SA nor the expression of defense-related genes was observed. These indicate that endophytic colonization with Azospirillum sp. B510 is able to activate the innate immune system also in tomato, which does not seem to be systemic acquired resistance.


Temperature and pH effects on plant uptake of benzotriazoles by sunflowers in hydroponic culture.
This article describes a systematic approach to understanding the effect of environmental variables on plant uptake (phyto-uptake) of organic contaminants. Uptake (and possibly phytotransformation) of xenobiotics is a complex process that may differ from nutrient uptake. A specific group of xenobiotics (benzotriazoles) were studied using sunflowers grown hydroponically with changes of environmental conditions including solution volume, temperature, pH, and mixing. The response of plants to these stimuli was evaluated and compared using physiological changes (biomass production and water uptake) and estimated uptake rates (influx into plants), which define the uptake characteristics for the xenobiotic. Stirring of the hydroponic solution had a significant impact on plant growth and water uptake. Plants were healthier, probably because of a combination of factors such as improved aeration and increase in temperature. Uptake and possibly phytotransformation of benzotriazoles was increased accordingly. Experiments at different temperatures allowed us to estimate an activation energy for the reaction leading to triazole disappearance from the solution. The estimated activation energy was 43 kJ/mol, which indicates that the uptake process is kinetically limited. Culturing plants in triazole-amended hydroponic solutions at different pH values did not strongly affect the biomass production, water uptake, and benzotriazole uptake characteristics. The sunflowers showed an unexpected capacity to buffer the solution pH.


Abdominal aortic aneurysm--online methods of patient education.
The authors present some of the most important online methods of patient education on diagnosis and treatment of abdominal aortic aneurysm (easy-to-read articles, medical journal with patient pages, patient guides, brochures, illustrations, animations, and frequently asked questions).


The Effects of High-Temperature Weather on Human Sleep Quality and Appetite.
High-temperature weather appears in high frequency, big strength, and long duration in the summer. It is therefore important to study the effects of high-temperature weather on sleep quality and appetite. Ten healthy college students were selected as subjects. The experiment conditions were divided by the daily maximum temperature into 28 °C, 32 °C, 36 °C, and 38 °C. The objective sleep quality was measured by an intelligent sleep monitoring belt, and the subjective sleep quality was measured by a questionnaire survey. The subjective appetites were assessed by a visual analog scale (VAS), and the objective appetites were assessed by the meal weight and the meal time. For sleep quality, the objective results indicated that the sleep quality at 32 °C was the best, followed by 28 °C, while the sleep quality at 36 °C and 38 °C was the worst. Significant effects were mainly reflected in sleep duration and shallow sleep. The subjective results showed that temperature had significant effects on sleep calmness, difficulty in falling asleep, sleep satisfaction, and sleep adequateness. For appetite, the VAS results indicated that high temperatures mainly led to a reduction of appetite at lunch time. The meal weights of lunch were larger than those of supper except for 28 °C, and the meal time of lunch and supper was longer than that of breakfast. The meal time of lunch was longer than that of supper except for 36 °C. This paper can provide a study method and reference data for the sleep quality and appetite of human in high-temperature weather.


Health-related quality of life and satisfaction with case management in cancer survivors.
To (i) investigate the characteristics of health-related quality of life and satisfaction with case management and (ii) to identify factors associated with health-related quality of life in cancer survivors. The level of health-related quality of life can reflect treatment efficacy and satisfaction with cancer care. A cross-sectional study design was adopted. Subjects from the outpatient setting of a cancer centre in northern Taiwan were recruited by consecutive sampling. A set of questionnaires were employed, including a background information form, case management service satisfaction survey (CMSS) and The European Quality of Life Scale (EQ-5D). Descriptive statistics were used to examine levels of health-related quality of life and satisfaction with case management. Pearson's correlation was used to identify relationships between treatment characteristics, satisfaction with case management and health-related quality of life. Multiple stepwise regression was used to identify factors associated with health-related quality of life. A total of 252 cancer patients were recruited. The three lowest scores for items of health-related quality of life were mobility, self-care and usual activities. Cancer survivors with higher mobility, less pain and discomfort, and lower anxiety and depression were more likely to have better health-related quality of life. Mobility, pain and discomfort, and anxiety and depression are important predictive factors of high health-related quality of life in cancer survivors. In clinical care, patients' physical mobility, pain and discomfort, and anxiety and depression are important indicators of health-related quality of life. Case managers should include self-care and symptom management into survivorship care plans to improve health-related quality of life during survival after treatment concludes.


Narrowband tunable VUV radiation generated by nonresonant sum- and difference-frequency mixing in xenon and krypton.
Nonresonant sum- and difference-frequency mixing of the fundamental omega(L) and the second harmonic omega(UV) radiation of a powerful narrowband pulsed dye laser system excited by an Nd:YAG laser (lambda(L) = 5500-6500 A) generates intense VUV radiation in krypton and xenon with the frequency omega(VUV) = 2omega(UV) micro omega(L). The sum-frequency is tunable in spectral regions of negative dispersion between 1100 and 1300 A. The maximum VUV pulse power exceeds 20 W (5 x 10(10) photons/pulse). VUV light pulses with up to 60 W (2.3 x 10(11) photons/pulse) are provided by the difference-frequency at wavelengths between 1850 and 2070 A. In addition the conversion process omega(VUV) = 2omega(UV) - omega(IR) (omega(IR) is the frequency of the Nd:YAG laser) generates radiation in the wavelength range of 1595-1866 A. With present laser systems the tuning range of the difference-frequency could be extended to wavelengths as short as 1226 A. The sum- and difference-frequency conversion will thus provide intense coherent VUV light continuously tunable between 1100 and 2100 A.


Zebrafish model of posttraumatic epilepsy.
Posttraumatic epilepsy (PTE) is defined as recurrent and unprovoked seizures occurring >1 week after traumatic brain injury (TBI). Animal studies of PTE are lengthy and expensive. In this study, we developed a cost-effective PTE animal model using zebrafish to bridge the gap between in vitro studies and low-throughput animal studies. We used two different sets of parameters (G1 and G2) to induce closed-head TBI in adult zebrafish using pulsed high-intensity focused ultrasound. Injured fish and naive controls were evaluated for behavioral deficits and spontaneous behavioral seizure activity up to 21 days postinjury (DPI). We also assessed behavioral seizure susceptibility to a subconvulsive dose of pentylenetetrazole (PTZ; 2.5 mmol·L-1 ) and recorded electrophysiological signals to confirm seizure activity up to 40 DPI. In addition, we investigated injury-related changes in the blood-brain barrier and expression levels of various proteins altered in rodent and human TBI. The G2 parameters resulted in a more severe TBI, with a mortality rate of 25%, as well as motor dysfunction and heightened anxiety persisting at 21 DPI. One hundred percent of the G2 group showed spontaneous myocloniclike behavior, and 80% demonstrated tonic-clonic-like behavioral seizures by 21 DPI. Such activities were not detected in the naive group. After the application of 2.5 mmol·L-1 PTZ, 100% of injured zebrafish had cloniclike seizures at 21 DPI, versus 30% of the naive group. We also demonstrated electrographic seizure activity at 40 DPI, which was not detected in the naive controls. Lastly, we observed acute blood-brain barrier dysfunction and increased levels of HMGB1 and ratios of phosphorylated/total Akt and tau through 21 DPI. Together, the results indicate that severe TBI in the adult zebrafish leads to similar behavioral and physiological changes to those of more traditional models, including the development of PTE, and suggest this may be a useful model that can accelerate research in TBI/PTE.


Sairey Gamp: generating fact from fiction.
Australian midwives today are generally employed by maternity hospitals as obstetric or maternity nurses and specialize in only one area of the childbirthing process, under the umbrella of medicine. This is quite different to the provision of midwifery care in the nineteenth and early twentieth centuries in Australia, when childbirthing took place within a home setting, with a community midwife in attendance under the umbrella of the household. Australian midwives are now attempting to regain some of the autonomy that they believe was possessed by midwives of the past by being professionally accredited to operate as independent midwives. The de-institutionalization of childbirthing cannot simply come about by giving midwives accreditation to operate as autonomous practitioners, as the forces that led society to institutionalize childbirthing practices, as well as the avenues for change, are complex. This paper examines one of the forces behind that change: the denigration of the image of the community midwife by the medical and nursing professions, through the character of Sairey Gamp created by Charles Dickens. By examining the historical terrain and the historical influences that led to the demise of the community midwife, we can provide answers for debate on the present status of the midwife.


Breakfast Is Brain Food? The Effect on Grade Point Average of a Rural Group Randomized Program to Promote School Breakfast.
Adolescents frequently miss breakfast which may impact cognitive, academic, and health outcomes. This analysis describes the effect of a trial to assess school level changes to increase breakfast consumption on grade point average (GPA). Sixteen rural Minnesota high schools were randomized to a policy and environmental change intervention or delayed intervention (control) group. Baseline screening identified, randomly selected and enrolled 9th and 10th grade students who eat breakfast ≤3 times per school week for assessment. Mean unweighted GPA was provided by 13 schools for 636 students. Student-level and administrative data were used for sociodemographic and free or reduced-price meals (FRPM). Linear mixed models and latent class analysis (LCA) were used to assess change in GPA. Students were 54% female, 76% white, and 34% received FRPM. Unweighted cumulative GPA mean = 2.82 (0.78) at baseline. There was no significant intervention effect on GPA postintervention or 1-year follow-up. LCA revealed two classes: "higher" (N = 495) and "lower" (N = 141) resource. There was an intervention effect among low-resource students from baseline to 1-year post only among the control condition (delayed intervention). In combination with the full study results, increasing breakfast consumption may have an impact particularly for low resource students.


Binocular head-mounted chromatic pupillometry can detect structural and functional loss in glaucoma.
The aim of this study is to evaluate the utility of binocular chromatic pupillometry in detecting impaired pupillary light response (PLR) in patients with primary open-angle glaucoma (POAG) and to assess the feasibility of using binocular chromatic pupillometer in opportunistic POAG diagnosis in community-based or telemedicine-based services. In this prospective, cross-sectional study, 74 patients with POAG and 23 healthy controls were enrolled. All participants underwent comprehensive ophthalmologic examinations including optical coherence tomography (OCT) and standard automated perimetry (SAP). The PLR tests included sequential tests of full-field chromatic stimuli weighted by rods, intrinsically photosensitive retinal ganglion cells (ipRGCs), and cones (Experiment 1), as well as alternating chromatic light flash-induced relative afferent pupillary defect (RAPD) test (Experiment 2). In Experiment 1, the constricting amplitude, velocity, and time to maximum constriction/dilation were calculated in three cell type-weighted responses, and the post-illumination response of ipRGC-weighted response was evaluated. In Experiment 2, infrared pupillary asymmetry (IPA) amplitude and anisocoria duration induced by intermittent blue or red light flashes were calculated. In Experiment 1, the PLR of POAG patients was significantly reduced in all conditions, reflecting the defect in photoreception through rods, cones, and ipRGCs. The variable with the highest area under the receiver operating characteristic curve (AUC) was time to max dilation under ipRGC-weighted stimulus, followed by the constriction amplitude under cone-weighted stimulus and the constriction amplitude response to ipRGC-weighted stimuli. The impaired PLR features were associated with greater visual field loss, thinner retinal nerve fiber layer (RNFL) thickness, and cupping of the optic disk. In Experiment 2, IPA and anisocoria duration induced by intermittent blue or red light flashes were significantly greater in participants with POAG than in controls. IPA and anisocoria duration had good diagnostic value, correlating with the inter-eye asymmetry of visual field loss. We demonstrate that binocular chromatic pupillometry could potentially serve as an objective clinical tool for opportunistic glaucoma diagnosis in community-based or telemedicine-based services. Binocular chromatic pupillometry allows an accurate, objective, and rapid assessment of retinal structural impairment and functional loss in glaucomatous eyes of different severity levels.


THz pulse generation from shaped femtosecond laser pulses interaction with gas-plasma.
Photocurrent and its THz pulse generation from shaped two-color femtosecond laser pulses interaction with gas-plasma are investigated numerically. An opaque filter is used to block some frequency components of the dispersed laser pulse to generate a new shaped pulse. Although the filter decreases the pump laser energy, this method can generate broad, tunable THz pulses. It is found that the width and the position of the filter affect the THz pulse directly because this method generates a different laser pulse shape. In addition, THz generation is also a periodic function of the second harmonic pulse phase.


Different PD-MCI criteria and risk of dementia in Parkinson's disease: 4-year longitudinal study.
The Movement Disorder Society Task Force (MDS-TF) has proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI). We hypothesized that the risk of dementia (PDD) varies across the different cutoff schemes allowed. A longitudinal study followed 121 non-demented PD patients for up to 4.5 years. In Part One, unique groups of patients were identified as PD-MCI at baseline using the MDS-TF requirement of two impaired cognitive test scores, with both scores classified as impaired at either (i) 2 s.d., (ii) 1.5 s.d. or (iii) 1 s.d. below normative data; relative risk (RR) of PDD was assessed at each criterion. In Part Two, the whole sample was reassessed and (i) RR of PDD determined when two impairments at 1.5 s.d. existed within a single cognitive domain, followed by (ii) RR of PDD in the unique group whose two impairments at 1.5 s.d. did not exist within a single domain (i.e., only across two domains). Twenty-one percent of patients converted to PDD. Part One showed that the 1.5 s.d. criterion at baseline is optimal to maximize progression to PDD over 4 years. Part Two, however, showed that the 1.5 s.d. cutoff produced a high RR of PDD only when two impairments were identified within a single cognitive domain (7.2, 95% confidence interval (CI)=3.4-16.6, P<0.0001; 51% converted). The RR when the 1.5 s.d. impairments occurred only across two different domains, was nonsignificant (1.7, CI=0.5-7.4, P=0.13; 11% converted) and similar to using a 1 s.d. criterion (1.9, CI=0.3-4.3, P=0.13; 8% converted). If the intent of a PD-MCI diagnosis is to detect increased risk of PDD in the next 4 years, optimal criteria should identify at least two impairments at 1.5 s.d. within a single cognitive domain.


'Bleeding' flowers of Ceropegia gerrardii (Apocynaceae-Asclepiadoideae) mimic wounded insects to attract kleptoparasitic fly pollinators.
Kleptomyiophily, where flowers imitate wounded insects to attract 'kleptoparasitic' flies as pollinators, is one of the most specialized types of floral mimicry and often involves physical trapping devices. However, the diversity of pollinators and functional floral traits involved in this form of mimicry remain poorly understood. We report a novel example of kleptomyiophily in the nontrapping flowers of Ceropegia gerrardii and explore the floral traits responsible for attracting pollinators. The pollinators, reproductive biology and floral traits (including epidermal surfaces, spectral reflectance and the composition of nectariferous petal secretions and scent) were investigated. Attractive volatiles were identified using electrophysiological and behavioural experiments. Ceropegia gerrardii was predominantly pollinated by kleptoparasitic Desmometopa spp. (Milichiidae) flies. The flower corollas extrude a protein- and sugar-containing secretion, similar to the haemolymph of wounded insects, on which the flies feed. Floral scent was chemically similar to that of injured honey bees. Four out of 24 electrophysiologically active compounds, all released by injured honey bees, were identified as key players in pollinator attraction. Our results suggest that C. gerrardii flowers chemically mimic wounded honey bees to attract kleptoparasitic flies and reward them with a secretion similar to the haemolymph on which they would normally feed.


IT investments can add business value.
Investment in information technology (IT) is costly, but necessary to enable healthcare organizations to improve their infrastructure and achieve other improvement initiatives. Such an investment is even more costly, however, if the technology does not appropriately enable organizations to perform business processes that help them accomplish their mission of providing safe, high-quality care cost-effectively. Before committing to a costly IT investment, healthcare organizations should implement a decision-making process that can help them choose, implement, and use technology that will provide sustained business value. A seven-step decision-making process that can help healthcare organizations achieve this result involves performing a gap analysis, assessing and aligning organizational goals, establishing distributed accountability, identifying linked organizational-change initiatives, determining measurement methods, establishing appropriate teams to ensure systems are integrated with multidisciplinary improvement methods, and developing a plan to accelerate adoption of the IT product.


Identification of genes associated with tumorigenesis of meibomian cell carcinoma by microarray analysis.
Meibomian cell carcinoma (MCC) is a malignant tumor of the meibomian glands located in the eyelids. No information exists on the cytogenetic and genetic aspects of MCC. There is no report on the gene expression profile of MCC. Thus there is a need, for both scientific and clinical reasons, to identify genes and pathways that are involved in the development and progression of MCC. We analyzed the gene expression profile of MCC by the microarray technique. Forty-four genes were upregulated and 149 genes were downregulated in MCC. Differential expression data were confirmed for 5 genes by semiquantitative RT-PCR in MCC tumors: GTF2H4, RBM12, UBE2D3, DDX17, and LZTS1. We found dysregulation of two major pathways in MCC: MAPK and JAK/STAT. Clusters of genes on chromosomes 1, 12, and 19 were dysregulated in MCC. The data presented here will facilitate the identification of specific markers and therapeutic targets for the treatment of MCC patients.


Anterior decompression and stabilization with methylmethacrylate and a bone bolt for treatment of pathologic fractures of the cervical spine. A report of two cases.
A 48-year-old woman and a 61-year-old man were treated for pathologic fractures of the cervical vertebral bodies that caused neurologic defect. In both patients an anterior decompression was performed with the removal of the diseased vertebrae. Immediate stability was obtained with a bone bolt imbedded in methylmethyacrylate. Both patients are functioning satisfactorily without any external support of the cervical spine four years and one and one-half years after their respective operations. This method is applicable only in carefully selected cases.