Trends in National Emergency Medicine Conference Didactic Lectures Over a 6-Year Period.
National conference didactic lectures have traditionally featured hour-long lecture-based presentations. However, there is evidence that longer lectures can lead to both decreased attention and retention of information. The authors sought to identify trends in lecture duration, lecture types, and number of speakers at four national emergency medicine (EM) conferences over a 6-year period. The authors performed a retrospective analysis of the length, number of speakers, and format of didactic lectures at four different national EM conferences over 6 years. The authors abstracted data from the national academic assemblies for the four largest not-for-profit EM organizations in the United States: American Academy of Emergency Medicine, American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine. There was a significant yearly decrease in the mean lecture lengths for three of the four conferences. There was an increase in the percentage of rapid fire sessions over the preceding 2 years with a corresponding decrease in the percentage of general educational sessions. There was no significant difference in the mean number of speakers per lecture. An analysis of 4210 didactic lecture sessions from the annual meetings of four national EM organizations over a 6-year period showed significant decreases in mean lecture length. These findings can help to guide EM continuing medical education conference planning and research.


Comparison of Two Treatment Modalities in Overactive Bladder: A Rapid Overview.
Overactive bladder is a syndrome of urgency with the absence of infection and is usually accompanied by frequency and nocturia. Both sacral neuromodulation (SNM) and intravesical botulinum toxin (BTX) injection are used contentiously in overactive bladder after failure of conservative management. We aimed to provide an updated comparative overview of BTX injection versus SNM in the treatment of overactive bladder. PubMed and Google scholar databases were explored starting from 2016 to 2022 to obtain relevant articles. English studies on adult population were included. Six articles included 648 participants were included in the current overview. Both BTX and SNM are comparable for the treatment of overactive bladder, with no major complications were reported. However, the use of SNM for refractory overactive bladder after failure of BTX was more successful and effective and resulted in patient satisfaction compared to the use of BTX after failure of SNM. Our update provides the latest comparative overview of outcomes of BTX versus SNM in the treatment of overactive bladder.


Carotenoid composition and vitamin A value of an Argentinian squash (Cucurbita moschata).
The carotenoid composition of butternut squash (Cucurbita moschata) cultivated in the province of Santiago del Estero, Argentina, was determined. The main carotenoids isolated were identified as beta-carotene (beta,beta-carotene), alpha-carotene (beta,epsilon-carotene), and lutein (beta,epsilon-carotene-3,3'-diol) and the minor carotenoids, as phytofluene (7,8,11,12,7',8'-hexahydro-psi,psi-carotene), zeta-carotene (7,8,7',8'-tetrahydro-psi,psi-carotene), neurosporene (7,8-dihydro-psi,psi-carotene), violaxanthin (5,6,5',6'- diepoxy-5,6,5',6'-tetrahydro-beta,beta-carotene-3,3'-diol) and neoxanthin (5,6-epoxy-6,7-didehydro-5,6,5',6'-tetrahydro-beta,beta- carotene-3,5,3'-triol). In some samples, 5,6,5',6'-beta-carotene diepoxide, (5,6,5',6'-diepoxy-5,6,5',6'-tetrahydro-beta,beta-carotene) and flavoxanthin (5,8-epoxy-5,8-dihydro-beta,epsilon-carotene-3,3'-diol) were detected. The presence of cis-isomers of beta,beta-carotene was also detected by HPLC. The vitamin A value obtained was 432 micrograms RE/100 g fresh sample, which indicates that this vegetable is an important source of provitamin A.


Comparative study of texture features in OCT images at different scales for human breast tissue classification.
Breast cancer is the second leading cause of death in women in the United States due to cancer. Early detection of breast cancerous regions will aid the diagnosis, staging, and treatment of breast cancer. Optical coherence tomography (OCT), a non-invasive imaging modality with high resolution, has been widely used to visualize various tissue types within the human breast and has demonstrated great potential for assessing tumor margins. Imaging large resected samples with a fast imaging speed can be accomplished by under-sampling in the spatial domain, resulting in a large image scale. However, it is unclear whether there is an impact on the ability to classify tissue types based on the selected imaging scale. Our objective is to evaluate how the scale at which the images are acquired impacts texture features and the accuracy of an automated classification algorithm. To this end, we present a comparative study of texture features in OCT images at two image scales for human breast tissue classification. Texture features and attenuation coefficients were inputs to a statistical classification model, relevance vector machine. The automated classification results from the two image scales were compared. We found that more informative tissue features are preserved in small image scale and accordingly, small image scale leads to more accurate tissue type classification.


Consumerism: do patients have power in health care?
In market rhetoric NHS patients are considered to be consumers of health care. This article considers what attributes and rights consumers have and analyses the possible forces limiting and/or driving their accedence into present day health care. While the term patient is associated with passivity, the term consumer conjure up notions of rights, power and empowerment. Consumer power may take two forms: the ability to make choices and legal rights. Yet within the NHS there are many forces that attempt to oppose and restrain consumer power.


Phase I study of temozolomide and lomustine in the treatment of high grade malignant glioma.
Systematic reviews and meta-analysis have demonstrated an improved prognosis by chemotherapy of malignant glioma patients. The effects of clinical research therefore have the aim to find more active drugs or new combination therapies. The combination of Temozolomide (TMZ) and nitrosoureas was evaluated preclinically with an evidence of therapeutic synergy. Based on these findings, we have carried out a phase I study with TMZ administered in low, prolonged doses of 75 mg/m2 per day, once a day for 21 days, escalated in cohorts of 3 patients, in combination with a fixed dose of Lomustine (CCNU) 100 mg/m2 orally on day 1. MTD was evident. The treatment was generally well tolerated. We did not observe bleeding or severe infections, as described for several combination chemotherapies with TMZ and other agents. In this study, for the first time in high grade malignant glioma, two orally administrated drugs were associated .TMZ 75 mg/m2 for 28 consecutive days and CCNU 100 mg/m2 on day 1 of every 6 weeks could be recommended as a safe treatment dosage. One of the ten patients evaluated for clinical response showed a partial response, while nine showed stability of disease, with a median duration of from 5 to 6 months.


The effects of a 45x potency of arsenicum album on wheat seedling growth -- a reproduction trial.
Independent replications of preclinical investigations of homeopathic potencies are rare. However, they are a necessary tool to determine the relevant factors modulating the effects of homeopathic potencies in preclinical systems. The goal of the present study was to reproduce a trial published in 1997. An Italian group of researchers investigated the effect of Arsenicum album 45x on the growth of wheat which had been previously poisoned with a material dose of Arsenicum album. The homeopathic treatment was associated with increased wheat shoot growth significantly different from the control group (+24%, p < 0.001). Wheat poisoned with a sublethal dose of Arsenicum album was cultivated in either Arsenicum album 45x, water 45x, or unpotentized water. After 7 days, shoot length was measured. Reproducibility was assessed in eight independent experiments. Arsenicum album 45x significantly inhibited wheat shoot growth (-3%) compared to treatment with unpotentized water and water 45x (p = 0.011 and p = 0.037). Within the experimental series performed in this reproduction trial, the effects of Arsenicum album 45x proofed to be reproducible. The wheat seed species used did not seem to have a significant impact on the experimental outcome. The result of this replication trial is a reversal of the original study, since Arsenicum album 45x inhibited wheat shoot growth instead of enhancing it. Nevertheless, high homeopathic potencies may induce statistically significant effects in biological systems. However, the magnitude and direction of these effects seem to depend on yet unknown parameters.


Peripheral Vestibulopathy Presenting as Acute Vertigo and Spontaneous Nystagmus with Negative Video Head Impulse Test.
To analyze acute vertigo showing spontaneous nystagmus with negative video head impulse test (vHIT). Retrospective chart analysis. Tertiary referral hospital. Over 16 months, 155 patients were identified with acute vertigo with spontaneous nystagmus. Of these 155, 30 (19.4%) were enrolled in this study because they did not show gain loss or catch-up saccades in both sides of the horizontal vHIT. Results of vestibular function tests (videonystagmography, horizontal vHIT, caloric test, and cervical vestibular-evoked myogenic potential [cVEMP]) and pure tone audiometry were analyzed. For all cases, magnetic resonance imaging with diffusion-weighted imaging was checked. Patients consisted of 17 with Ménière's disease and 7 with sudden sensorineural hearing loss with vertigo (SSNHL_V), and only 3 patients were finally diagnosed as having acute vascular stroke. Except for the loss of hearing on the lesion side, the direction of nystagmus or cVEMP asymmetry showed very different results. All 7 patients with SSNHL_V did not have canal paresis in the caloric test, but cVEMP amplitude was smaller on the lesion side for 6 patients. For patients with acute vertigo presenting spontaneous nystagmus with negative horizontal vHIT, it is important not only to focus on the diagnosis of acute vascular stroke but also to evaluate hearing because of the high possibility of Ménière's disease or SSNHL_V.


Development and Calibration of the Polar Organic Chemical Integrative Sampler (POCIS) for Neonicotinoid Pesticides.
Neonicotinoid pesticides are highly hydrophilic systemic insecticides that have been extensively used worldwide. To evaluate their environmental risks, the concentrations of these pesticides in the aquatic environment must be monitored. Although the polar organic chemical integrative sampler (POCIS) has proved to be a suitable passive sampler for many highly hydrophilic compounds, Oasis HLB (Waters) POCIS has shown limitations for the monitoring of neonicotinoid pesticides, such as short linear uptake ranges. In the present study we optimized POCIS for neonicotinoid pesticides by selecting suitable adsorbents and filters. The ENVI-Carb (Supelco) nonporous carbon-based adsorbent demonstrated a good balance between strong sorption and high recovery. Static renewal experiments showed that the our POCIS device using ENVI-Carb with a polyethersulfone membrane filter had a 3 d (dinotefuran) to 28 d (clothianidin, imidacloprid, acetamiprid, and thiacloprid) linear range, which is longer than that of HLB POCIS (≤1 [dinotefuran] to 14 d). The POCIS using ENVI-Carb with a polytetrafluoroethylene membrane had higher sampling rates (0.270 L/d [clothianidin] to 0.686 [imidacloprid] L/d) than those of the HLB POCIS for short-term deployment. The time-weighted average concentrations in actual river water measured by the new POCIS were in good agreement with those obtained by repeated grab sampling, within 30%. Moreover, POCIS detected 2 neonicotinoid pesticides that were not detected by grab sampling. Thus, the proposed POCIS is a promising tool for the monitoring of neonicotinoid pesticides. Environ Toxicol Chem 2020;39:1325-1333. © 2020 SETAC.


Pyrosequencing of the CYP2C9 -1766T>C polymorphism as a means of detecting the CYP2C9*8 allele.
The CYP2C9 c.449G>A (p.R150H, rs7900194) polymorphism, which confers the CYP2C9*8 allele, is common in persons of African descent and results in reduced clearance of the narrow therapeutic index drugs, warfarin and phenytoin. Because of significant homology in DNA sequence at the 449G>A locus among CYP2C genes, the 449G>A variant cannot be reliably detected via PCR-based genotyping assays that require a short PCR product, such as pyrosequencing. Herein, we propose genotyping for the CYP2C9 c.-1766T>C polymorphism via pyrosequencing as an alternative and accurate means of identifying the CYP2C9*8 allele.


Practice in 2050: caring science and a synthesis of views.
In this column nurses influenced by Watson's human caring theory and Eriksson's theory of caritative caring share their ideas about what nursing theory-guided practice will be like in 2050. Following these contributions about caring theories in 2050, is a synthesis of threads of relatedness across the volume 20 Practice Applications columns-all of which focus on possibilities for nursing theory-guided practice in 2050.


Estimate of the accelerated proliferation by protein tyrosine phosphatase (PTEN) over expression in postoperative radiotherapy of head and neck squamous cell carcinoma.
To estimate the impact of PTEN expression in terms of effective doubling time (T(d)) and dose per fraction which compensates the accelerated proliferation during the radiotherapy (D(prolif)) when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). Data were carried out from a recent paper comparing the local control rate (LCR) for patients with HNSCC that underwent a conventional (p-CF) or accelerated radiotherapy (p-CAIR) and a pretreatment assessment of PTEN expression. The impact of PTEN over expression was assessed using the Clinical Efficacy Factor (C) and assuming a plausible range of intrinsic radiosensitivity (α). Statistical analysis was made by evaluating the LCR from Kaplan-Meier curves and log-rank test with significance of 0.05. C indexes were 1.46 and 0.23 for the high- versus low-PTEN group, corresponding to a considerable reduction of doubling time of more than six times (6.6 versus 42.2 days). The median estimate of D(prolif) was 0.51 versus 0.08 Gy/day if referred to a median value in the adopted range of α. The PTEN expression has a significant implication on the clinical management of these patient groups. Our data support the hypothesis that the high-PTEN group would benefit from a hypo-fractionation with a reduction of the OTT to compensate for the increase in the proliferation rate, while the low-PTEN group could benefits from a hyper-fractionation which would result in a reduced toxicity for all the organs at risk.


Differences Between Takotsubo and the Working Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries.
Whether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs. A cohort study based on two prospective registries: TTS from the RETAKO registry (N:1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers (N:1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p < 0.001) and older (69.4 ± 12.5 vs. 64.5 ± 14.1 years; p < 0.001). Atrial fibrillation (AF) was more frequent in non-TTS MINOCAs (10.4 vs. 14.4%; p = 0.007). Psychiatric disorders were more prevalent in TTS (15.5 vs. 10.2%, p < 0.001). In-hospital mortality and complications were higher in TTS: 3.4 vs. 1.8%, (p = 0.015), and 25.8 vs. 11.5%, (p < 0.001). Global mortality before PS matching was 16.1% in non-TTS MINOCAs and 8.1% in TTS. Median follow-up was 32.4 months; after PS matching, TTS had fewer major adverse cardiovascular events (MACEs): hazard ratio (HR) 0.59; 95% CI 0.42-0.83. There were no differences in global mortality (HR 0.87; CI: 0.64-1.19), but TTS had lower cardiovascular mortality (HR 0.58; CI: 0.35-0.98). Compared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis.


Biomedical synthetic biology: an overview for physicians.
Synthetic bioiogy is a ,relatively new fieild of bologlcal research and development that focases on the engineering of genetic molecular machlnes wIth a specific predefined function. Plainly put the newly engineered organism functions as a machine. It can process information. manufature, heal and even diagnose. We just have to engineer It to do so. The famous quote "Biology Is the nanotechnology that works" is currently being put to the test on a worldwide scale. The application of these machines Is theoretically boundless. In laboratories worldwide synthetic biology technologies are being rationally designed to assist in diagnosis or disrupt disease mechnisms. In the not too distant future they are expected to reach the clinical setting. This new field should be distinguished from classic genetic engineering. The latter researches naturalfy found DNA segments via cloning. It is weakly associated with engineering. Synthetic biology focuses on the engineering of molecular biological machines for the benefit of mankind. This is done via synthetic (computer printed) DNA sequences, man-designed or altered in silico. In this article I will briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an independent fast-growing synthetic biology-sharing movement, and report on selected developing applications for medicine.


Sponge versus diaphragm for contraception.
The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm. The sponge, made of polyurethane impregnated with nonoxynol-9 (1g), releases 125 mg of the spermicide over 24 hours of use. Unlike the diaphragm, the sponge can be used for more than one coital act within 24 hours without the insertion of additional spermicide, and the sponge does not require fitting or a prescription from a physician. How the sponge compares with the diaphragm in terms of efficacy and continuation is not clear. To compare the efficacy and continuation rates of the sponge with the diaphragm (used with nonoxynol-9). Our a priori hypothesis was that the sponge would have higher rates for failure and discontinuation than the diaphragm. In April 2013, we searched the computerized databases MEDLINE, POPLINE, LILACS, CENTRAL, ClinicalTrials.gov and ICTRP.Earlier searches also included EMBASE. For the initial review, we searched the reference lists of relevant articles and book chapters.We also contacted investigators involved with the identified trials for other published or unpublished trials. We included randomized controlled trials comparing the vaginal contraceptive sponge (Today; Collatex) with any diaphragm used with nonoxynol-9 to prevent pregnancy. We examined the studies identified through the literature searches for possible inclusion and evaluated their methodological quality using the Cochrane guidelines. We entered data into RevMan and calculated Peto odds ratios for overall pregnancy and 12-month discontinuation using numbers of women as the denominator. We also abstracted 12-month cumulative life-table ratios for these same outcomes but were unable to aggregate these data. Two trials met the inclusion criteria. The sponge was significantly less effective in both trials in preventing overall pregnancy than was the diaphragm. In the larger USA trial, the 12-month cumulative life-table termination rates per 100 women for overall pregnancy were 17.4 for the sponge and 12.8 for the diaphragm. The rates were 24.5 for the sponge and 10.9 for the diaphragm in the UK trial.Similarly, discontinuation rates at 12 months were higher with the sponge than with the diaphragm (Odds ratio 1.31; 95% CI 1.07 to 1.59). Allergic-type reactions were more common with the sponge, although discontinuation for discomfort differed in the two trials.No new trials have been identified since the initial review. The sponge was less effective than the diaphragm in preventing pregnancy.Discontinuation rates were higher at 12 months as well.Other randomized controlled trials will be needed to resolve the potential role of spermicides in preventing sexually transmitted infections or in causing adverse effects


Carpal coalition: a rare coincidence with hand deficiencies.
Three cases in which congenital carpal fusion was associated with formation deficiencies of the hand are presented. In two patients with a lunate-triquetral and a capitate-hamate-trapezoid coalition, respectively, an ulnar deficient hand was also diagnosed. A subdivision of the first type of ulnar club hand deformities is proposed. Other skeletal anomalies included duplication of a phalanx and pseudoepiphysis of a metacarpal, respectively. In the latter case hypoplasia of the flexor tendons to the fingers, excluding the thumb, was also noted. In the third case, a proximal capitate-hamate coalition coexisted with aplasia of the flexor tendons to the middle finger.


Primary urothelial carcinoma of the prostate: A rare case report.
Prostatic urothelial carcinoma is a rare disease. Medical misdiagnosis rates remain high because there are no specific clinical symptoms or imaging features, which decreases patient survival. We report a case of prostatic urethral cancer confirmed by transrectal ultrasound-guided prostate biopsy because of an abnormal digital rectal exam. A 55-year-old man was referred to our hospital due to lower urinary tract symptoms that lasted for 5 years. On digital rectal examination, a hard and enlarged prostate was detected. Computed tomography, bone scintigraphy, and magnetic resonance imaging indicated benign prostatic hyperplasia. The patient underwent transrectal ultrasound-guided prostate biopsy. From the histopathological examination and immunohistochemical markers, a diagnosis of high-grade prostatic urothelial carcinoma was made. We excluded the possibility of urothelial cancer originating in the bladder lining after transurethral resection of the bladder. Radical cystoprostatectomy was performed, followed by 6 cycles of cisplatin and gemcitabine chemotherapy. Postoperative pathology showed primary urothelial carcinoma of the prostate. The patient recovered smoothly after surgery. After a 6-month follow-up, no evidence of local recurrence or metastatic disease was found. This case reminds clinicians that, for middle-aged men with suspicious digital rectal examinations, a diagnosis of prostatic urothelial carcinoma should be considered. Initial radical surgery followed by combination chemotherapy is suggested for therapeutic management.


White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study.
Both white matter hyperintensities (WMH) and lacunar infarcts have been associated with the development of depression in older subjects, although the relative importance of the two and the influence of lesion location and concomitant vascular disease are unclear. This study investigates the relationship between location and burden of WMH and lacunes on depressive features in older people. In a pan-European multicenter study of 626 older subjects, the authors examined the relationship between regional magnetic resonance imaging white matter hyperintensities, number of lacunar infarcts, depressive symptoms as assessed by the 15-item geriatric depression scale (GDS), cognitive status (Mini-Mental Status Examination), hypertension, and self-perceived health quality of life (QoL). The authors found depressive symptoms to be correlated with WMH rating in the frontal (N=626; Spearman's rho=0.161, p <0.001) and temporal (rho=0.14, p <0.001) but not occipitoparietal region (rho=0.07, p=0.07). Basal ganglia lacunes were only weakly correlated with GDS (rho=0.09, p=0.03), and lacunes in other regions showed no association. In a ordinal logistic regression model (controlling for QoL, Mini-Mental Status Examination, age, and with an interaction between WMH and hypertension), temporal WMH in the absence of hypertension independently predicted GDS, whereas neither history of stroke nor number of lacunar infarcts did. The authors compared left- versus right-sided WMH and found no effect of laterality on depressive symptoms. The results suggest that in this population of nondisabled older people, WMH have a greater influence on depressive symptoms than infarcts.


Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture.
Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a high-content 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications.


Clinical research for patient empowerment--a qualitative approach on the improvement of heart health promotion in chronic illness.
Concepts of health management and improved quality of health care are of growing importance. In this context, the concept of empowerment is widely accepted in health-related disciplines. The aim of the present study was to investigate whether theory-based empowerment, using motivational interviewing, can be facilitated within clinical research in patients with severe chronic diseases. We here present a qualitative in-depth interview study using grounded theory methodology. Participants were twenty-seven patients undergoing chronic haemodialysis who were taking part in a research programme investigating cardiovascular function in chronic renal failure (CRF) by ultrasound measurements and blood samples. With the exception of one patient, all interviewed patients emphasized the benefit of the detailed and structured information given. All patients pointed out a deepened understanding of cardiovascular health and its relation to CRF. Improved health knowledge was associated with a strengthened sense of control in our participants. This process resulted in high levels of patient satisfaction. Fifty percent of the interviewed patients were more likely to attend further education sessions with cardiologists and primary care practitioners to improve health management. Facilitating empowerment in a clinical research project is ethically essential and can positively enhance self-care-oriented, disease-specific skills in patients with severe chronic diseases. Clinical research may open up new avenues to additionally strengthen patient sovereignty in interdisciplinary health sciences.


Small intestinal bacterial overgrowth in patients with chronic pancreatitis.
To assess the prevalence of small intestinal bacterial overgrowth (SIBO) in chronic pancreatitis (CP), and analyze factors related with SIBO in CP. SIBO is to be considered a factor that worsens symptoms and nutritional status in patients with CP. However, the few studies evaluating the rate of SIBO in CP patients used nonuniform and nonstandardized procedures, and reported a wide range of positivity (0% to 92%). Those studies often investigated CP patients with previous resection surgery (cause of SIBO per se). CP patients and controls evaluated for SIBO by the H2 glucose breath test with a standard protocol. For CP patients, the relationship between test results, abdominal symptoms, and clinical and biochemical variables was analyzed. A total of 43 CP patients and 43 controls were enrolled. Of the CP patients, 8 had advanced disease (defined by M-ANNHEIM index) and none had undergone previous surgery. The glucose breath test positivity rate was higher in the CP patients than in the controls (21% vs. 14%), albeit without a significant difference (P=0.57). Mean fasting H2 excretion and mean H2 excretion at 120 minutes also had a trend toward higher levels in CP patients. There were no clinical differences between CP patients with or without SIBO, but there were nutritional differences for lower levels of vitamin D and higher levels of folate in these patients with SIBO. Our findings suggest that SIBO is not uncommon in uncomplicated CP patients. The lack of a significant difference compared with controls might be due to the study being underpowered. SIBO in CP patients does not seem to be related to peculiar clinical features, but it might affect nutritional status.


Decoherence-free subspaces in quantum key distribution.
We demonstrate that two recent innovations in the field of practical quantum key distribution (one-way autocompensation and passive detection) are closely related to the methods developed to protect quantum computations from decoherence. We present a new scheme that combines these advantages, and propose a practical implementation of this scheme that is feasible using existing technology.


Effects of karanjin on dimethylhydrazine induced colon carcinoma and aberrant crypt foci are facilitated by alteration of the p53/Bcl2/BAX pathway for apoptosis.
We investigated the effects of karanjin on dimethylhydrazine (DMH) induced colon cancer in rats. Male Wistar rats were injected with DMH followed by dextran sodium sulfate in drinking water for 7 days. Karanjin at doses of 50,100 and 200 mg/kg was administered orally for 18 weeks. Colon tissues were investigated using TUNEL analysis of apoptosis; histopathological assessment including number of aberrant crypt foci (ACF); immunohistochemical staining for Bcl-2-associated X protein (BAX), B-cell lymphoma 2 (Bcl2), p53 and proliferating cell nuclear antigen (PCNA); and antioxidant assay in vivo. We found that treatment with karanjin inhibited formation of ACF in the colon mucosa and reduced colon lesions. Karanjin treatment also increased the antioxidants, catalase, glutathione and superoxide dismutase. Immunostaining showed that karanjin treatment reduced BAX, p53 and PCNA levels and increased Bcl2 expression. The TUNEL assay revealed that karanjin induced apoptosis in the colon mucosa. Our findings suggest that karanjin can ameliorate colon carcinogenesis in rats by regulating BAX, Bcl2 and p53 pathways.


Training and proficiency of physicians' office personnel with a new diagnostic test for theophylline.
A new technology, enzyme immunochromatography, permits the quantitative measurement of therapeutic drug levels without the need for an instrument. The simplicity of this technology enables office personnel with minimal training to perform measurements of therapeutic drug concentrations in samples of whole blood within 20 minutes. A training program for office personnel was developed that could be given entirely by telephone. Records of the trainings were kept and subsequently analyzed. A follow-up study consisting of six proficiency sample mailings was done to determine the ability of the trained personnel to perform the test accurately. Additional data on split-sample analyses performed by physicians' office personnel were collected. The data indicate that the telephone training method was satisfactory for initial training, and that acceptable test performance continued over time by office personnel who had completed the training program.


Highly Conductive Metallic State and Strong Spin-Orbit Interaction in Annealed Germanane.
Similar to carbon, germanium exists in various structures such as three-dimensional crystalline germanium and germanene, a two-dimensional germanium atomic layer. Regarding the electronic properties, they are either semiconductors or Dirac semimetals. Here, we report a highly conductive metallic state in thermally annealed germanane (hydrogen-terminated germanene, GeH), which shows a resistivity of ∼10-7 Ω·m that is orders of magnitude lower than any other allotrope of germanium. By comparing the resistivity, Raman spectra, and thickness change measured by AFM, we suggest the highly conductive metallic state is associated with the dehydrogenation during heating, which likely transforms germanane thin flakes to multilayer germanene. In addition, weak antilocalization is observed, serving as solid evidence for strong spin-orbit interaction (SOI) in germanane/germanene. Our study opens a possible new route to investigate the electrical transport properties of germanane/germanene, and the large SOI might provide the essential ingredients to access their topological states predicted theoretically.


A Real-world What-Where-When Memory Test.
Episodic memory is a complex memory system which allows recall and mental re-experience of previous episodes from one's own life. Real-life episodic memories are about events in their spatiotemporal context and are typically visuospatial, rather than verbal. Yet often, tests of episodic memory use verbal material to be recalled (word lists, stories). The Real-World What-Where-When memory test requires participants to hide a total of 16 different objects in 16 different locations over two temporal occasions, 2 h apart. Another two hours later, they are then asked to recall which objects (What) they had hidden in which locations (Where) and on which of the two occasions (When). In addition to counting the number of correctly recalled complete what-where-when combinations, this task can also be used to test real-world spatial memory and object memory. This task is sensitive to normal cognitive aging, and correlates well with performance on other episodic memory tasks, while at the same time providing more ecological validity and being cheap and easy to run.


[Effects of amino acids on the survival of heat-exposed Drosophila].
To investigate the effects of amino acids on the survival of heat-exposed Drosophila and to select the amino acids that can protect the Drosophila from heat exposure, Drosophila melanogaster were fed with basic culture in 25 degrees C. The male virgin Drosophilas were distinguished from female. Both male and female virgin Drosophilas were divided respectively to the trail groups and control group with randomization. The trail groups were fed with culture supplying different amino acids in 37.5 degrees C. After 10 hours, the dead insects were counted every two hours until all of them were dead. The mortality rates of heat-exposed Drosophilas that feed in the culture added with the glutamine, arginine, phenylalanine, tyrosine and glutamic acid were obviously higher than that of control. The glutamine, arginine, phenylalanine, tyrosine and glutamic acid might increase survival time of heat-exposed Drosophila, but a dose-response relationship was not observed.


A new α-pyrone from the deep-sea actinomycete Nocardiopsis dassonvillei subsp. dassonvillei DSM 43111(T).
A new α-pyrone, nocapyrone S (1), together with five known compounds (2-6), were isolated from the deep-sea actinomycete Nocardiopsis dassonvillei subsp. dassonvillei DSM 43111(T). Their structures were determined by spectroscopic analyses. The absolute configuration of 1 was established by quantum approaches. Cytotoxic activity of 1 was evaluated against K562, MCF-7, SGC7901, A375, Hela, and HepG2 cell lines.


A comparison of the college experience for students with and without disabilities.
Students with intellectual and developmental disabilities (IDD) have joined the ranks of college students in pursuit of personal independence, community integration, and employment. To achieve these aims, there is a need for a strong understanding of the college experience for students with IDD, including identification of the academic, social, and personal challenges they face as well as the supports that are available to address those challenges. This research provides preliminary insights into the college experience for students with IDD by comparing the perceptions, attitudes, and activities of students with IDD to those of students without disabilities and students with mild learning disabilities (MLD). Our data suggest a number of similarities in the college experience for students with and without disabilities such as similar influences from family and teachers with respect to attending college. In addition, some surprising advantages expressed by students with IDD were found, such as reporting greater ease in developing close friendships than students with MLD. Considerations and discussion on the ways in which students with IDD benefit from the additional supports and services provided to them are also discussed.


[The role of laser Doppler flowmetry as a diagnostic criterion of impaired microcirculation of vesico-urethral segment and prostatic gland].
To study changes in microcirculation of the lower urinary tract in different diseases we used laser analyzer of capillary circulation LAKK-01. The control group consisted of 25 volunteers, the study group--of 65 patients with different vesico-urethral diseases. Normal values of microcirculation in the wall of the urinary bladder, prostatic gland and urethra were determined. These values were significantly reduced in patients with vesico-urethral disorders. Thus, alterations in microcirculation in different pathological conditions of the vesicourethral segment confirm the hypothesis of a direct involvement of microcirculation disorders in pathogenesis of many urological diseases.


Assessment of carboxyhemoglobin, hydrogen cyanide and methemoglobin in fire victims: a novel approach.
To establish the cause of death, carboxyhemoglobin (COHb), total hemoglobin (tHb), methemoglobin (MetHb), and hydrogen cyanide (HCN) were quantified in the blood of fire victims. We analyzed 32 out of 33 blood samples from forensic autopsy cases in a disastrous polyurethane mattress fire, which caused the deaths of 33 inmates at a prison in Argentina in 2006. The cadaveric blood samples were collected by femoral vein puncture. These samples were analyzed using the IL80 CO-oximeter system for tHb, MetHb, and COHb levels and by microdiffusion for HCN and COHb levels. Blood alcohol (ethanol) and drugs were examined by headspace gas chromatography-flame ionization detection (HS-GC-FID) and GC-mass spectrometry (MS), respectively. Polyurethane mattress samples were analyzed according to the California 117 protocol. The saturation of COHb ranged from 10% to 43%, tHb from 2% to 19.7%, MetHb from 0.10% to 35.7%, and HCN from 0.24 to 15mg/L. These HCN values are higher than the lethal levels reported in the literature. Other toxic components routinely measured (ethanol, methanol, aldehydes, and other volatile compounds) gave negative results in the 32 cases. Neither drugs of abuse nor psychotropic drugs were detected. The results indicate that death in the 32 fire victims was probably caused in part by HCN, generated during the extensive polyurethane decomposition stimulated by a rapid increase in temperature. We also considered the influence of oxygen depletion and the formation of other volatile compounds such as NOx in this disaster, as well as pathological evidence demonstrating that heat was not the cause of death in all victims. Furthermore, statistical analysis showed that the percentage values of COHb and MetHb in the blood were not independent variables, with χ(2)=11.12 (theoretical χ(2)=4.09, degrees of freedom=12, and α=0.05). However, no correlation was found between HCN and MetHb in the blood of the victims. This is the first report to assess the relationship between COHb and MetHb in forensic blood samples. We further discuss other factors that could lead to a lethal atmosphere generated by the fire and compare the data from this disaster with that of other published fire episodes.


[Application of MEMS microneedles array in biomedicine].
Microneedles array based on micro electro-mechanical system (MEMS) technology is one of important applications in biomedicine and brings a new means in biomedicine field. The prospect for the development of microneedles technology in precision drug injection, clinical monitoring and biochemistry test is and save broad. This paper describes three important applications of MEMS microneedles array in biomedicine field: biomedicine microneedles electrode, transdermal delivery of drugs and fluid extraction, and then summarizes their application elements and recent development. It explains the characteristics of microneedles, which provide painless, effective and save biomedical method in accordance with human requirements. In addition, a series of the fabrication technology of microneedles array is discussed.


Development of PSMA-PET-guided CT-based radiomic signature to predict biochemical recurrence after salvage radiotherapy.
To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.


Clinical variations in bullous pemphigoid with respect to early symptoms.
We report the clinical variations and the duration of prodromal symptoms in 20 patients with bullous pemphigoid. Nearly two-thirds of the patients had prodromal symptoms. THe duration of the prodromal eruptions was up to 6 weeks if papular and/or urticarial and up to 2 years if eczematous, before the blisters appeared. Evidently longer prodromal periods were found in the present study than in earlier investigations. It is not known when in the course of the disease the direct immunofluorescence will be positive. Two of our patients were immunofluorescence-positive 1 and 2 weeks respectively before the blisters appeared. A common clinical manifestation in this study was vesicles on palms and/or soles. These eruptions, particularly as an early symptom, may cause misinterpretation in patients with bullous pemphigoid.


Radiation-induced sarcoma: analysis of 46 cases.
A retrospective analysis was performed of 46 cases of sarcoma treated in our institution between 1989 and 2007 that occurred in a previously irradiated area. Eight male and 38 female patients had received radiotherapy, mainly for breast cancer and genitourinary tumours. The interval between irradiation and the diagnosis of sarcoma ranged from 1 to 54 years (median 15 y). The most common clinical findings were a mass, pain and skin dislocation. Angiosarcoma and sarcoma non-otherwise-specified were the most common histological types. Surgical resection was performed in 34 patients (74%) and 5-year survival was 45% when a radical resection was obtained. No 5-year survival was noticed after non-radical resection and in the absence of surgery. Stage and location of the sarcoma were other prognostic factors. Overall 5-year survival was 27% for the whole group.


A novel phosphoglucose isomerase (PGI)/phosphomannose isomerase from the crenarchaeon Pyrobaculum aerophilum is a member of the PGI superfamily: structural evidence at 1.16-A resolution.
The crystal structure of a dual specificity phosphoglucose isomerase (PGI)/phosphomannose isomerase from Pyrobaculum aerophilum (PaPGI/PMI) has been determined in native form at 1.16-A resolution and in complex with the enzyme inhibitor 5-phosphoarabinonate at 1.45-A resolution. The similarity of its fold, with the inner core structure of PGIs from eubacterial and eukaryotic sources, confirms this enzyme as a member of the PGI superfamily. The almost total conservation of amino acids in the active site, including the glutamate base catalyst, shows that PaPGI/PMI uses the same catalytic mechanisms for both ring opening and isomerization for the interconversion of glucose 6-phosphate (Glc-6-P) to fructose 6-phosphate (Fru-6-P). The lack of structural differences between native and inhibitor-bound enzymes suggests this activity occurs without any of the conformational changes that are the hallmark of the well characterized PGI family. The lack of a suitable second base in the active site of PaPGI/PMI argues against a PMI mechanism involving a trans-enediol intermediate. Instead, PMI activity may be the result of additional space in the active site imparted by a threonine, in place of a glutamine in other PGI enzymes, which could permit rotation of the C-2-C-3 bond of mannose 6-phosphate.


The PCPH oncoprotein antagonizes the proapoptotic role of the mammalian target of rapamycin in the response of normal fibroblasts to ionizing radiation.
Exposure of normal mouse fibroblasts (MEF3T3) to ionizing radiation (IR) resulted in a dose-dependent increase of mTOR mRNA and protein levels and the shuttling of the mTOR protein from its normal, predominantly mitochondrial location to the cell nucleus. The same IR doses that activated mTOR induced the phosphorylation of p53 on Ser(18) (mouse equivalent to human Ser(15)) and the subsequent transcriptional activation of PUMA, a known proapoptotic p53-target gene, and promoted apoptosis involving increased overall caspase activity, caspase-3 activation, cleavage of poly(ADP-ribose) polymerase (PARP) and classic protein kinase C (PKC) isoforms, and DNA fragmentation. The proapoptotic role of mTOR in this process was demonstrated by the fact that rapamycin, a mTOR inhibitor, blocked p53 Ser(18) phosphorylation, the induction of PUMA, and all other apoptosis events. Furthermore, the proapoptotic function of mTOR was also antagonized by the expression in MEF3T3 cells of the PCPH oncoprotein, known to enhance cell survival by causing partial ATP depletion. Tetracyclin (Tet)-regulated expression of oncogenic PCPH, or overexpression of normal PCPH, blocked both phosphorylation and nuclear shuttling of mTOR in response to IR. These results indicate that alterations in PCPH expression may render tumor cells resistant to IR, and perhaps other DNA-damaging agents, by preventing mTOR activation and signaling.


Gender-affirming Vaginoplasty and Vulvoplasty: An Initial Experience.
To describe the initial outcomes of a new multidisciplinary gender-affirming surgery (GAS) program comprised of plastic and urologic surgeons. We retrospectively examined consecutive patients who underwent gender-affirming vaginoplasty or vulvoplasty between April 2018 and May 2021. We used logistic regression modeling to analyze associations between preoperative risk factors and postoperative complications. Between April 2018 and May 2021, 77 genital GAS (gender-affirming surgery) procedures were performed at our institution (56 vaginoplasties, 21 vulvoplasties). All surgeries were performed in combination with urology and plastic surgery primarily using the perineal penile inversion technique. Mean patient age was 39.6 years, and mean BMI was 26.2 (Table 1a). The most common pre-existing conditions were hypertension and depression, with nearly 14% of patients reporting a previous suicide attempt. The complication rate for vaginoplasty was 53.7% within the first 30 days (Table 4). The most common complications were yeast infection (14.8%) and hematoma (9.3%). For vulvoplasty, the 30-day complication rate was 57.1%, with urinary tract infection (14.3%) and granulation tissue (9.5%) being the most common. 88.1% and 91.7% of the complications were Clavien-Dindo grade I or II for vaginoplasties and vulvoplasties, respectively. No association was found between preoperative patient factors and postoperative complications. Revision surgeries were performed for 38.9% of vaginoplasty patients during the study period, most commonly including urethral revision (29.6%), labia majoraplasty (20.4%), and labia minoraplasty (14.8%). Collaboration between urology and plastic surgery is a safe and effective means to establish a GAS program.


Carrageenan as a Sacrificial Binder for 5 V LiNi0.5 Mn1.5 O4 Cathodes in Lithium-Ion Batteries.
5 V-class LiNi0.5 Mn1.5 O4 (LNMO) with its spinel symmetry is a promising cathode material for lithium-ion batteries. However, the high-voltage operation of LNMO renders it vulnerable to interfacial degradation involving electrolyte decomposition, which hinders long-term and high-rate cycling. Herein, this longstanding challenge presented by LNMO is overcome by incorporating a sacrificial binder, namely, λ-carrageenan (CRN), a sulfated polysaccharide. This binder not only uniformly covers the LNMO surface via hydrogen bonding and ion-dipole interaction but also offers an ionically conductive cathode-electrolyte interphase layer containing LiSOx F, a product of the electrochemical decomposition of the sulfate group. Taking advantage of these two auspicious properties, the CRN-based electrode exhibits cycling and rate performance far superior to that of its counterparts based on the conventional poly(vinylidene difluoride) and sodium alginate binders. This study introduces a new concept, namely "sacrificial" binder, for battery electrodes known to deliver superior electrochemical performance but be adversely affected by interfacial instability.


Dynamic Cages-Towards Nanostructured Smart Materials.
The interest in capsular assemblies such as dynamic organic and coordination cages has blossomed over the last decade. Given their chemical and structural variability, these systems have found applications in diverse fields of research, including energy conversion and storage, catalysis, separation, molecular recognition, and live-cell imaging. In the exploration of the potential of these discrete architectures, they are increasingly being employed in the formation of more complex systems and smart materials. This Review highlights the most promising pathways to overcome common drawbacks of cage systems (stability, recovery) and discusses the most promising strategies for their hybridization with systems featuring various dimensionalities. Following the description of the most recent advances in the fabrication of zero to three-dimensional cage-based systems, this Review will provide the reader with the structure-dependent relationship between the employed cages and the properties of the materials.


Mushroom tyrosinase inhibition by two potent uncompetitive inhibitors.
Two new bi-pyridine compounds, [1,4'] Bipiperidinyl-1'-yl-naphthan-2-yl-methanone (I) and [1,4'] Bipiperidinyl-1'-yl-4-methylphenyl-methane (II) were synthesized and examined for inhibition of the catecholase activity of mushroom tyrosinase in 10 mM phosphate buffer pH 6.8, at 293 K using UV spectrophotometry. Inhibition kinetics indicated that they were uncompetitive inhibitors and the value of the inhibition constants were 5.87 and 1.31 microM for I and II, respectively, which showed high potency. Fluorescent studies confirmed the uncompetitive type of inhibition for these two inhibitors. The inhibition mechanism presumably comes from the presence of a particular hydrophobe site which can accommodate these inhibitors. This site could be formed due to a probable conformational change that was induced by binding of substrate with the enzyme.


Quantitative pathology in tissue MR spectroscopy based human prostate metabolomics.
At present, the clinical utility of metabolomic profiles of human prostate tissue relies on the establishment of correlations between metabolite data and clinical measurements, particularly pathological findings. Because metabolomics is a quantitative study, its clinical value can be rigorously investigated by determining its association with other quantitative measures. The human visual assessment of prostate tissue, however, introduces both inter- and intra-observer biases that may limit the reliability of its quantitations, and therefore, the strength of its correlations with metabolomic profiles. The aim of this study was to develop a simple, feasible protocol for the computer-aided image analysis (CAIA) of prostate pathology slides in order to achieve quantitative pathology from tissue samples, following metabolomic measurement with high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Thirty-eight samples from 29 prostatectomy cases were studied with HRMAS MRS. After spectroscopy analysis, samples were serial-sectioned, stained and visually assessed by pathologists. Cross-sections from these samples were then measured with the CAIA protocol. Results showed a two-fold difference between human visual assessments of the area percentages of tissue pathologies and CAIA area percentages obtained for the same features. Linear correlations were found between both metabolites indicative of normal epithelium and those indicative of prostate cancer, and the CAIA quantitative results. CAIA based quantitative pathology is more reliable than human visual assessment in establishing correlations useful for disease diagnosis between prostate pathology and metabolite concentrations.


Value of surgical resection and timing of therapy in patients with pancreatic cancer at high risk for positive margins.
Surgical resection remains the best chance at long-term survival in pancreatic cancer, though margin-positive resections are associated with diminished survival. We examined the effect of margin-positive resection on survival, as well as the role and timing of additional therapies through the National Cancer Database (NCDB). Patients with stage IIA-III pancreatic adenocarcinoma diagnosed from 2004 to 2013 were identified in NCDB. Survival was compared using univariate and multivariate Cox proportional hazards modelling for patients who underwent surgery with negative (R0), microscopically positive (R1) and macroscopically positive (R2) margins or non-surgical treatment. We further analysed patients by margin status, timing of additional therapy (neoadjuvant therapy (NAT) vs adjuvant therapy (AT) vs none) and clinical stage. We analysed 44 852 patients. Median survival (MS) for patients who did not undergo surgery was 10.3 months, compared with 19.7 months for R0 (P<0.001), 14.3 months for R1 (P<0.001) and 9.8 months (P=0.07) for R2 resections. NAT (MS 23.2 months) was associated with improved survival compared with AT (MS 21.5 months) in negative-margin patients and equivalent (MS 17.6 months) to AT (MS 16.8 months) in positive-margin patients. Survival for stage III NAT positive-margin patients (MS 19.8 months) was equivalent to AT after negative margins (MS 18.4 months, P=1.00). Improved R0 rates were seen with NAT (88% vs 81%, P<0.001), especially in stage III patients (85% vs 59%, P<0.001). R1 resections portend poorer survival than R0 but do not negate the benefit of surgery when additional therapy is given. NAT was associated with improved R0 rates and improved survival for stage III positive-margin patients.


A new model for random X chromosome inactivation.
X chromosome inactivation (XCI) reduces the number of actively transcribed X chromosomes to one per diploid set of autosomes, allowing for dosage equality between the sexes. In eutherians, the inactive X chromosome in XX females is randomly selected. The mechanisms for determining both how many X chromosomes are present and which to inactivate are unknown. To understand these mechanisms, researchers have created X chromosome mutations and transgenes. Here, we introduce a new model of X chromosome inactivation that aims to account for the findings in recent studies, to promote a re-interpretation of existing data and to direct future experiments.


Effect of oral 16,16-dimethyl prostaglandin E2 on gastric mucosal salicylate concentration in the rat.
The effect of 16,16-dimethyl prostaglandin E2 (DmPGE2), in doses subthreshold for antisecretory activity, were examined in female rats. The aims were to determine if DmPGE2 alters the disposition of acetylsalicylic acid (ASA) within the gastric mucosa and if DmPGE2 could attenuate the ulcerogenic effect of oral ASA. Gastric lesions occurred after an oral, but not an intravenous dose of 150 mg/kg ASA. Lesions could be prevented by pretreatment with 5 micrograms/kg DmPGE2 orally 30 min prior to ASA. DmPGE2 elevated fundic concentrations of both ASA and salicylic acid (SA) within the first hour when ASA was given orally. The ratio of the concentration of ASA/SA in fundus was not changed, indicating that DmPGE2 did not depress the fundic esterase activity. It is concluded that the cytoprotective effect of DmPGE2 is not related to a change in mucosal concentration or elimination of ASA or SA.


Kinetic relations of the Na-amino acid interaction at the mucosal border of intestine.
The relation between unidirectional influxes of Na and amino acids across the mucosal border of rabbit ileum was studied under a variety of conditions. At constant Na concentration in the mucosal bathing solution, amino acid influx followed Michaelis-Menten kinetics permitting determination of maximal influx and the apparent Michaelis constant, K(t). Reduction in Na concentration, using choline as substitute cation, caused an increase in K(t) for alanine but had no effect on maximal alanine influx. The reciprocal of K(t) was a linear function of Na concentration. Similar results were obtained for valine and leucine and these amino acids competitively inhibited alanine influx both in the presence and in the absence of Na. These results lead to a model for the transport system which involves combination of Na and amino acid with a single carrier or site leading to penetration of both solutes. The model predicts that alanine should cause an increase in Na influx and the ratio of this extra Na flux to alanine flux should vary with Na concentration. The observed relation agreed closely with predicted values for Na concentrations from 5 to 140 mM. These results support the hypothesis that interactions between Na and amino acid transport depend in part on a common entry mechanism at the mucosal border of the intestine.


The Arabidopsis Class III Peroxidase AtPRX71 Negatively Regulates Growth under Physiological Conditions and in Response to Cell Wall Damage.
The structure of the cell wall has a major impact on plant growth and development, and alteration of cell wall structural components is often detrimental to biomass production. However, the molecular mechanisms responsible for these negative effects are largely unknown. Arabidopsis (Arabidopsis thaliana) plants with altered pectin composition because of either the expression of the Aspergillus niger polygalacturonase II (AnPGII; 35S:AnPGII plants) or a mutation in the QUASIMODO2 (QUA2) gene that encodes a putative pectin methyltransferase (qua2-1 plants), display severe growth defects. Here, we show that expression of Arabidopsis PEROXIDASE71 (AtPRX71), encoding a class III peroxidase, strongly increases in 35S:AnPGII and qua2-1 plants as well as in response to treatments with the cellulose synthase inhibitor isoxaben, which also impairs cell wall integrity. Analysis of atprx71 loss-of-function mutants and plants overexpressing AtPRX71 indicates that this gene negatively influences Arabidopsis growth at different stages of development, likely limiting cell expansion. The atprx71-1 mutation partially suppresses the dwarf phenotype of qua2-1, suggesting that AtPRX71 contributes to the growth defects observed in plants undergoing cell wall damage. Furthermore, AtPRX71 seems to promote the production of reactive oxygen species in qua2-1 plants as well as plants treated with isoxaben. We propose that AtPRX71 contributes to strengthen cell walls, therefore restricting cell expansion, during normal growth and in response to cell wall damage.


Posterior urethral valves with vesical calculus: A rare association.
Posterior urethral valve and vesical calculus are individually among the most common causes of obstructive lower urinary complaints in children. There are very few reports of association between posterior urethral valves and bladder calculus. We report three such cases. This association of the vesical calculi with posterior urethral valves may lead to a delay in the diagnosis of the posterior urethral valves. The diagnosis of posterior urethral valves should be suspected in all children with vesical or urethral calculi who have persistence of symptoms even after removal of the calculi.


Engagement of CD40 antigen with soluble CD40 ligand up-regulates peptide transporter expression and restores endogenous processing function in Burkitt's lymphoma cells.
Cells from the EBV-associated tumor, Burkitt's lymphoma (BL), are known to be highly inefficient at endogenous processing of class I-restricted CTL epitopes due to a consistent loss of peptide transporters (TAP) and MHC expression. We investigated the potential of CD40 engagement to up-regulate the expression of class I-processing genes and to enhance the immunogenicity of these malignant cells toward EBV-specific CTLs. Here we show that engagement of CD40 Ag with soluble CD40 ligand (CD40L) up-regulates TAP-1 and HLA class I expression on BL cells. More importantly, analysis of the Ag-processing function, using a recombinant vaccinia virus to transiently express the EBV nuclear Ags, revealed that CD40L-treated BL cells consistently processed endogenously synthesized viral Ags for recognition by HLA class I-restricted, virus-specific CTLs. These findings raise the possibility that CD40L treatment of tumor cells might be exploited in immunotherapeutic protocols.


Gross signs and histopathology of branchiostegal blister disease (balloon disease): an idiopathic disease of farmed Macrobrachium rosenbergii (De Man).
The giant freshwater prawn, Macrobrachium rosenbergii, is facing increased threat due to disease as its culture becomes more widespread. A disease characterized by the swelling of the branchiostegal region and deformities of the appendages, named balloon disease by farmers, has caused considerable economic loss in the Nellore region of Andhra Pradesh, India. Clinical signs of diseased animals include a voluminous hypertrophy of some gill filaments and the inner area of the branchiostegite. By histology, hypertrophied areas at the level of the gill filaments or branchiostegite had an identical structure corresponding to a large cyst filled with a fluid containing a few free haemocytes, limited on one side by the cuticle and on the other by the subcuticular epithelial layer. Analysis of the diseased prawns did not reveal any pathogenic agent leading us to conclude that the disease is idiopathic, probably due to suboptimal water quality conditions.


Regional Cerebral Oxygen Saturation Decreases During Primary Hip Arthroplasty: An Analysis of Perioperative Regional Cerebral Oxygenation (rSO2), S100 Calcium-Binding Protein B (S100B) and Glial Fibrillary Acidic Protein (GFAP) Values. A Pilot Study.
BACKGROUND The incidence of postoperative cognitive dysfunction (POCD) after major joint arthroplasty is high. In the etiology of POCD, many factors have been cited, including thromboembolic complications. The incidence of cerebral embolization after lower extremity arthroplasty may be as high as 40-60%. The potential events of cerebral embolization could lead to a decrease in the regional cerebral oxygenation (rSO2) and increased serum levels of biochemical markers of brain damage. The objective of the study was to test whether there are any changes in the rSO2 values and serum markers of brain damage in patients who underwent total hip arthroplasty. MATERIAL AND METHODS Fifteen patients who underwent primary hip arthroplasty under spinal anesthesia were analyzed. The rSO2 was monitored using infrared spectroscopy. Biochemical analyses of S100 calcium-binding protein B (S100B) protein and fibrillary acidic protein (GFAP) serum concentrations were performed using immunoassay methods. RESULTS The values of rSO2 decreased during the surgery, but this was not related to mean arterial pressure variations or hemoglobin saturation. The concentration of S100B was increased compared to its preoperative values, and there were no changes in GFAP values. The changes in rSO2 readings correlated with the biomarkers' levels just after the surgery. CONCLUSIONS Our results suggest that S100B may be a more specific marker of astroglial damage in patients after primary total hip arthroplasty. The decrease in rSO2 readings may be due to micro-thromboembolic events that occurred during the surgery. However, the results of this study are preliminary, and further studies are needed to establish its clinical efficacy.


Multiple linear regression is a useful alternative to traditional analyses of variance.
Physiologists often wish to compare the effects of several different treatments on a continuous variable of interest, which requires an analysis of variance. Analysis of variance, as presented in most statistics texts, generally requires that there be no missing data and often that each sample group be the same size. Unfortunately, this requirement is rarely satisfied, and investigators are confronted with the problem of how to analyze data that do not strictly fit the traditional analysis of variance paradigm. One can avoid these pitfalls by recasting the analysis of variance as a multiple linear regression problem. When there are no missing data, the results of a traditional analysis of variance and the corresponding multiple regression problem are identical; when the sample sizes are unequal or there are missing data, one can use a regression formulation to analyze data that cannot be easily handled in a traditional analysis of variance paradigm and thus overcome a practical computational limitation of traditional analysis of variance. In addition to overcoming practical limitations of traditional analysis of variance, the multiple linear regression approach is more efficient because in one run of a statistics routine, not only is the analysis of variance done but also one obtains estimates of the size of the treatment effects (as opposed to just an indication of whether such effects are present or not), and many of the pairwise multiple comparisons are done (they are equivalent to t tests for significance of the regression parameter estimates). Finally, interaction between the different treatment factors is easier to interpret than it is in traditional analysis of variance.


Electrocardiographic abnormalities in patients admitted for hip fracture.
Several risk factors for falls and hip fractures have been recognised, but controversy still exists regarding the importance of rhythm and conduction abnormalities as potentially modifiable risk factors for recurrent falls. The aim of this study was to determine the prevalence of clinically relevant ECG abnormalities in patients with a hip fracture versus controls. The study was designed as a case-control study within consecutive hip surgery patients in an academic hospital. patients with traumatic hip fractures. patients undergoing planned hip surgery (non-traumatic). CASES and controls were 1:1 matched for age and gender. age ≥ 50 years. high-energy trauma, pathological and÷or previous hip fracture. ECGs were scored using predefined categories. Multivariate logistic regression was performed to calculate odds ratios (OR) and to correct for confounders. We included 888 patients (444 cases). Mean age was 70.9 years (SD 9.3), 70% were female. After correction for potential confounders we found the following associations between clinically relevant ECG abnormalities and hip fractures: atrial fibrillation OR 2.7 (95% CI 1.2-6.1), abnormal QTc prolongation OR 3.9 (2.2-6.8), sinus tachycardia OR 5.0 (2.1-11.8) and sinus bradycardia OR 0.3 (0.1-0.5). Univariately, several markers for decreased cardiac function were also associated with hip fractures. Hip fracture patients are at higher risk for ECG abnormalities than matched patients undergoing hip surgery for other indications. To potentially reduce the risk of future (injurious) falls, increased awareness of these ECG abnormalities is warranted to assess the need for further cardiovascular fall risk assessment.


Chlorine-35/37 NMR spectroscopy of solid amino acid hydrochlorides: refinement of hydrogen-bonded proton positions using experiment and theory.
Trends in the chlorine chemical shift (CS) tensors of amino acid hydrochlorides are investigated in the context of new data obtained at 21.1 T and extensive quantum chemical calculations. The analysis of chlorine-35/37 NMR spectra of solid L-tryptophan hydrochloride obtained at two magnetic field strengths yields the chlorine electric field gradient (EFG) and CS tensors, and their relative orientations. The chlorine CS tensor is also determined for the first time for DL-arginine hydrochloride monohydrate. The drastic influence of 1H decoupling at 21.1 T on the spectral features of salts with particularly small 35Cl quadrupolar coupling constants (CQ) is demonstrated. The chlorine CS tensor spans (Omega) of hydrochloride salts of hydrophobic amino acids are found to be larger than those for salts of hydrophilic amino acids. A new combined experimental-theoretical procedure is described in which quantum chemical geometry optimizations of hydrogen-bonded proton positions around the chloride ions in a series of amino acid hydrochlorides are cross-validated against the experimental chlorine EFG and CS tensor data. The conclusion is reached that the relatively computationally inexpensive B3LYP/3-21G* method provides proton positions which are suitable for subsequent higher-level calculations of the chlorine EFG tensors. The computed value of is less sensitive to the proton positions. Following this cross-validation procedure, /CQ(35Cl)/ is generally predicted within 15% of the experimental value for a range of HCl salts. The results suggest the applicability of chlorine NMR interaction tensors in the refinement of proton positions in structurally similar compounds, e.g., chloride ion channels, for which neutron diffraction data are unavailable.


A Data Set Comparison Method Using Noise Statistics Applied to VUV Spectrum Match Determinations.
It has been demonstrated that a pair of spectra exhibiting a coefficient of determination (R2) as low as 0.976 can originate from the same chemical species in one example, while a different pair of spectra exhibiting an R2 up to 0.9997 can originate from different chemical species. The R2 between spectra overlays depends on the signal-to-noise ratio, while the residual between any two spectra should look like noise only when the two spectra originate from the same chemical species. Numerical characteristics of the residual between two high-resolution spectra are invaluable toward the definitive elimination of many plausible matches of reference spectra to the sample spectra of analytes eluted from two-dimensional gas chromatography. Additionally, numerical characteristics beyond R2 facilitate a logical ranking of all plausible matches, making positive identification of a single-component analyte possible provided a reference spectrum exists for all plausible matches. Specifically, the experimental background noise is shown to follow a Gaussian distribution at all wavelengths, and a method is described to normalize the data such that the numerically adjusted noise distributions are independent of wavelength. The differences between matching spectra are further shown to exhibit numerical characteristics consistent with the background noise's Gaussian distribution, common to all wavelengths. Seven criteria are described for judging the similarity between spectra: R2 between the two spectra, R2 of a Q-Q plot with one axis being ideal Gaussian quantiles and the other axis being the distribution of the numerically adjusted residual quantiles, the maximum count of consecutive (by wavelength) signs in the residual, and the first four moments of the residuals. One exemplar application of the methodology is a definitive match of n-undecane, n-dodecane, and n-tridecane sample spectra to their corresponding reference spectrum, which is among the most challenging set of species within the volatility range of jet fuel to differentiate by spectral methods. While this example is a significant stress test of the approach, the utility of the methodology generally is in the subtle math and transparent criteria that unambiguously identify mismatches because the distributions of residuals between mismatching spectra are very clearly not Gaussian and have a high consecutive sign count, even in cases where the R2 between the compared spectra is ambiguous.


Genetic control of capsid length in bacteriophage T4. I. Isolation and preliminary description of four new mutants.
Four new mutants are described whose phenotypic expression affects the length of the head of bacteriophage T4D. All mutants produce some phenotypically normal phage particles. Mutant pt21-34 also produces at least two size classes of phage particle which have heads that are shorter than normal. The other three mutants, ptg19-2, ptg19-80, and ptg191, produce, in addition to phages with normal and with shorter-than-normal heads, giant phages with heads from 1.5 to at least 10 times the normal length. All mutations are clustered near gene 23. Giant phage particles have the following properties: they are infectious and contain and inject multiple genomes as a single continuous bihelical DNA molecule of greater-than-unit length. Their frequency, relative to the total plaque-former population, increases late in the infectious cycle. They have a normal diameter, variable length, and a buoyant density range in CsCl from equal to slightly greater than that of normal phage. The arrangement of capsomers is visible in the capsids, which are composed of cleaved gene 23 protein.


An l-RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis.
To facilitate isolation of l-aptamers with novel RNA-binding properties, we employed a cationic nucleotide, 5-aminoallyluridine, during the mirror image in vitro selection process. Through this effort, we identified a modified l-RNA aptamer (MlRA) capable of binding oncogenic precursor microRNA 19a (pre-miR-19a) with exceptional affinity, and we showed that cationic modification is absolutely critical for binding. Furthermore, formation of the MlRA-pre-miR-19a complex inhibited Dicer-mediated cleavage of the pre-miR, thus blocking formation of the mature functional microRNA. The MlRA reported here not only represents the first l-aptamer to be evolved by using modified nucleotides but also the first modified aptamer (of any type) to be selected against a structured RNA target. Our results demonstrate that functionalized l-aptamers, which are intrinsically nuclease-resistant, provide an attractive approach for developing robust RNA-binding reagents.


Women at work with breast cancer-related lymphoedema.
Little attention has been given to the impact of lymphoedema on breast cancer survivors' work experience. To describe the experience of work of breast cancer survivors with lymphoedema. A descriptive phenomenological method was used. Sixty-six in-depth interviews were completed with 22 participants in the United States. Three essential themes illuminating the meaning of working for breast cancer survivors with lymphoedema emerged, namely: having a visible sign of disability or a need for help; having physical limitations that made some women handicapped, while others felt inconvenienced; and, finally, some women had constant worries while others felt fortunate. Women endured emotional distress at work. Women whose jobs required heavy lifting and constant use of the affected limb, suffered profoundly from the physical and functional impact of having lymphoedema. Future research should focus on interventions that help employers to understand breast cancer survivors with lymphoedema and improve their working conditions.


A Concise and Highly Enantioselective Total Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines.
A concise asymmetric (>99:1 e.r.) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless-derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)-anti- and (-)-syn-mefloquine, respectively. The synthetic (+)-anti- and (-)-syn-mefloquine samples were derivatized with (S)-(+)-mandelic acid tert-butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X-ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)-anti- as well as (-)-syn-mefloquine.


Intermittent claudication and muscle fiber fine structure: morphometric data on mitochondrial volumes.
The mitochondrial volume densities (Vmit) of the different fiber types (type 1, type 2A, type 2B) were estimated in bilaterally obtained biopsies from 22 patients with unilateral intermittent claudication. These data, which were obtained from structurally intact fibers, were compared with clinical data from the same subject. In both the asymptomatic and symptomatic legs, Vmit 1 greater than Vmit 2A greater than Vmit 2B. Furthermore, Vmit 1 covariated with Vmit 2A and Vmit 2A with Vmit 2B in the asymptomatic legs (as in healthy subjects) but not in the symptomatic legs. Vmit 2 (mainly Vmit 2A) covariated with the age of the subjects in both legs. Vmit Tot was higher in the symptomatic legs than in the asymptomatic legs. This was mainly due to increase in the oxidative fibers, type 1 and type 2A. Usually, Vmit in the asymptomatic legs covariated significantly with the results of the functional tests (initial pain and maximum walking tolerance), while only Vmit 2A in the symptomatic legs showed such a correlation. However, the difference between the two legs concerning Vmit 1 was also correlated to the walking tolerance. Patients with high stenosis or occlusion showed higher Vmit Tot than did those with low obstacles. The results conclusively show that a fiber type-specific adaptation to ischemia occurs through an increase of mitochondrial content of oxidative fibers, which suggests that hypoxia may influence the control of synthesis or degradation of mitochondrial proteins.


Translatable mRNA changes in ethylene induced abscission zones of Phaseolus vulgaris (Red Kidney).
The wheat germ translation system was programmed with soluble RNA extracted from foliar abscission zones of Phaseolus vulgaris, These extracts were taken at various times after the induction of abscission. A translation product with a molecular weight of 42 kilodalton (kD) was only present after this treatment, though three other species 32, 27 and 17 kD increased substantially. The isozyme of cellulase with a pi of 9.5 could not be conclusively identified amongst the products though the 32 kD protein is probably chitinase. Comparison of the abscission zone translatable RNA with that from adjacent petiole and stem tissues showed the 17 kD protein developed in all these location. The 42, 32 and 27 kD bands were found predominantly in the zone and petiole.


Current Practices and Priority Issues Regarding Nutritional Assessment and Patient Satisfaction with Hospital Menus.
Patient satisfaction with hospital food enhances consumption and adequate intake of nutrients required for recovery from illness/injury and maintenance of health; accordingly, the nutrient content of the menu must balance patient preferences. This study of Ontario hospital foodservice departments collected data on current practices of analyzing the nutritional adequacy and assessing patient satisfaction with menus, and it explored perceptions of priority issues. Foodservice managers/directors from 57 of 140 (41%) hospitals responded to cross-sectional in-depth telephone interviews. Deductive analysis of responses to open-ended questions supplemented quantitative data from closed-ended questions. The hospitals without long-term care facilities (LTCFs) assessed regular (58%), therapeutic (53%), and texture-modified (47%) menus for nutritional adequacy. This differed from hospitals governing LTCFs where there was a higher frequency of assessment of regular (75%), therapeutic (75%), and textured-modified (66%) menus. Most departments (86%-94%) obtained patient satisfaction feedback at the departmental/corporate levels. Many identified budget and labour issues as priorities rather than assessing menus for nutritional adequacy and patient satisfaction. Hospital menus were not consistently assessed for nutritional adequacy and patient satisfaction; common assessment methodologies and standards were absent. Compliance standards seem to increase the frequency of menu assessment as demonstrated by hospitals governing LTCFs.


[Effects of land utilization of sewage sludge on crops and soils].
Effects of land utilization of sewage sludge on crops and soil environment were studied using sewage sludge from the Northern Shenyang Plant of Wastewater Treatment. The results showed that contents of nitrogen, phosphorus and organic matter in the soil were increased after the utilization of sewage sludge, thus being advantageous to growth and development of crops. The biomass of rice after having applied 22.5 and 45 t.hm-2 of sewage sludge was increased by 11.48%-11.83% compared with the control. There was no evident harmful effect of heavy methals from sewage sludge on quality of soil environment, agricultural products and underground water when the application of sewage sludge was controlled within the range of 45 t.hm-2.


Transparent organic upconversion devices for near-infrared sensing.
Transparent organic upconversion devices are shown in a night-vision demonstration of a real object under near-infrared (NIR) illumination in the dark. An extraordinarily high current gain - reflecting the on-off switching effect - greater than 15 000 at a driving voltage of 3 V is demonstrated, indicating the high sensitivity to NIR light and potential of using the proposed upconverter in practical applications. A maximum luminance exceeding 1500 cd m(-2) at 7 V is achieved. Unlike previous studies, where 2D aperture projection is reported, the current study shows 3D images of real objects under NIR illumination in the dark.


Recent Research Advances in Nano-Based Drug Delivery Systems for Local Anesthetics.
From a clinical perspective, local anesthetics have rather widespread application in regional blockade for surgery, postoperative analgesia, acute/chronic pain control, and even cancer treatments. However, a number of disadvantages are associated with traditional local anesthetic agents as well as routine drug delivery administration ways, such as neurotoxicity, short half-time, and non-sustained release, thereby limiting their application in clinical practice. Successful characterization of drug delivery systems (DDSs) for individual local anesthetic agents can support to achieve more efficient drug release and prolonged duration of action with reduced systemic toxicity. Different types of DDSs involving various carriers have been examined, including micromaterials, nanomaterials, and cyclodextrin. Among them, nanotechnology-based delivery approaches have significantly developed in the last decade due to the low systemic toxicity and the greater efficacy of non-conventional local anesthetics. Multiple nanosized materials, including polymeric, lipid (solid lipid nanoparticles, nanostructured lipid carriers, and nanoemulsions), metallic, inorganic non-metallic, and hybrid nanoparticles, offer a safe, localized, and long-acting solution for pain management and tumor therapy. This review provides a brief synopsis of different nano-based DDSs for local anesthetics with variable sizes and structural morphology, such as nanocapsules and nanospheres. Recent original research utilizing nanotechnology-based delivery systems is particularly discussed, and the progress and strengths of these DDSs are highlighted. A specific focus of this review is the comparison of various nano-based DDSs for local anesthetics, which can offer additional indications for their further improvement. All in all, nano-based DDSs with unique advantages provide a novel direction for the development of safer and more effective local anesthetic formulations.


Carotid artery disease: the influence of diabetes mellitus.
Patients with diabetes mellitus are more prone to stroke than non-diabetic patients. Using Duplex ultrasound imaging of the carotid bifurcation, we have found it possible to classify atherosclerotic plaques into four groups which appear to reflect the plaque pathology. Using this classification we have found that diabetics and non-diabetics have similar ultrasound plaque type distributions in symptomatic patients. Further subdivision of the diabetic patients on the basis of their mode of diabetic control has shown that insulin treated diabetics tend to show little evidence of intraplaque haemorrhage and ulceration. These features suggest that factors other than atherosclerosis at the carotid bifurcation may be responsible for the increased stroke risk in diabetic patients. Diabetic microangiopathy and reduced vessel compliance due to medial calcification have been suggested as possible factors. Insulin treatment of diabetics may protect against the development of occlusive atherosclerosis.


Design of an encodable tyrosine kinase-inducible domain: detection of tyrosine kinase activity by terbium luminescence.
Tyrosine kinases are critical mediators of intracellular signaling and of intracellular responses to extracellular signaling. Changes in tyrosine kinase activity are implicated in numerous human diseases, including cancers, diabetes, and pathogen infectivity. To address questions in tyrosine phosphorylation, we have designed a protein tyrosine kinase-inducible domain, a small, genetically encodable protein motif whose structure is dependent on its tyrosine phosphorylation state. Tyrosine kinase-inducible domain peptides are based on EF-hand loops in which a structurally critical Glu12 residue is replaced by tyrosine at residue 11 or at residue 15 of the protein. Tyrosine kinase-inducible domain peptides bind terbium(III) in a phosphorylation-dependent manner, showing strong terbium luminescence when phosphorylated but weak terbium luminescence when not phosphorylated. Lanthanide binding was confirmed by NMR. A tyrosine kinase-inducible domain peptide, pKID-Abl, was designed to incorporate a recognition sequence of the Abl kinase. Incubation of pKID-Abl with Abl kinase resulted in a large increase in terbium luminescence. This increase in luminescence was abolished when pKID-Abl and Abl kinase were incubated with the Abl kinase inhibitor Gleevec. In addition, incubation of phosphorylated pKID-Abl with the tyrosine phosphatase YOP resulted in a large reduction in terbium luminescence. pKID-Abl was employed as a fluorescent sensor of Abl tyrosine kinase activity in HeLa cell extracts, exhibiting low luminescence with extracts from serum-starved cells and increased luminescence using extracts from EGF-treated cells. These results indicate that tyrosine kinase-inducible domains may be used as sensors of tyrosine kinase and tyrosine phosphatase activity and in the detection of tyrosine kinase inhibitors.


From nurse to patient: A journey to healing.
The nurse manager of an oncology clinic in a major cancer center shares his personal experience as a COVID-19 patient with other health care workers. He has spent two weeks in intensive care and found himself on the brink of death. In a lively description, he underlines the aspect of care that contributed to his cure. This included the respect that his caregivers expressed to his values, his love of his family and his religious beliefs. The communication of the caregivers was always honest and compassionate. He learned that love is the strongest motivation to survive in the course of a life-threatening disease and that healing is possible even in the absence of cure.


Understanding and Exploitation of Neighboring Heteroatom Effect for the Mild N-Arylation of Heterocycles with Diaryliodonium Salts under Aqueous Conditions: A Theoretical and Experimental Mechanistic Study.
The mechanism of arylation of N-heterocycles with unsymmetric diaryliodonium salts is elucidated. The fast and efficient N-arylation reaction is interpreted in terms of the bifunctionality of the substrate: The consecutive actions of properly oriented Lewis base and Brønsted acid centers in sufficient proximity result in the fast and efficient N-arylation. The mechanistic picture points to a promising synthetic strategy where suitably positioned nucleophilic and acidic centers enable functionalization, and it is tested experimentally.


[Ultrasound diagnosis of fetal inflammatory response syndrome in women with preterm premature rupture of membrane].
The aim of this review is to analyze the existing possibilities of using ultrasound in the diagnosis of the fetal inflammatory response. Review. Gynekologicko-porodnická klinika, Fakultní nemocnice Ostrava. Preterm delivery is defined as a delivery before completed 37 weeks of gestation. Approximately one-thirdof these cases is associated with preterm premature rupture of membranes. About forty percent of preterm premature rupture of membranes is complicated by the fetal inflammatory response syndrome, which is associated with the development of severe perinatal morbidity. Recent prenatal diagnosis of the fetal inflammatory response syndrome is based on the invasive methods (amniocentesis, cordocentesis), which are limited by several risk factors accompanying these procedures and technical difficulties. Therefore, there is an effort to replace them by non-invasive approach. The development of ultrasound, as a diagnostic method through the last decade, and knowledge of pathophysiological and morphological changes in fetal organs associated with the fetal inflammatory response may lead to more specific diagnosis in the future and improvement of neonatal outcome. Early identification of fetuses affected by FIRS in pregnancies with PPROM is necessary for right management of these pregnancy pathology. At this moment, ultrasonography examination of fetal lineal vein and fetal echocardiography, seems to be suitable for diagnosing FIRS.


Complex phylogeography in Rhinoclemmys melanosterna: conflicting mitochondrial and nuclear evidence suggests past hybridization (Testudines: Geoemydidae).
We examined differentiation within the Colombian wood turtle Rhinoclemmys melanosterna, and among R. melanosterna and the closely allied species R. diademata, R.funerea and R. punctularia, based on 1060 base pairs of the mitochondrial cyt b gene. We also assessed the phylogenetic relationships among these species using 2050 bp of mtDNA (partial cyt b, 12S and 16S genes) and 3620 bp of nuclear DNA (partial Rag 1, Rag 2, C-mos, R35 and ODC genes). There is considerable phylogeographic structuring within R. melanosterna, with seven distinct clades distributed across the species' range. These clades correlate to some extent with previously described differences in the dorsal pattern of head coloration. Individual and combined analyses of mitochondrial and nuclear DNA indicated contradictory relationships among R. melanosterna, R. diademata, R. funerea and R. punctularia. Mitochondrial DNA sequences revealed R. melanosterna to be non-monophyletic with respect to R. diademata, R. funerea and R. punctularia. In contrast, R. melanosterna constituted a well-supported monophyletic clade using nuclear DNA. This conflict between mitochondrial and nuclear data suggests past gene flow among the allopatrically and parapatrically distributed species R. melanosterna, R. diademata, R. funerea and R. punctularia. Compared to the other Rhinoclemmys species, the taxa under study are weakly differentiated. To assess their taxonomic status, further research is warranted using additional nuclear markers and additional samples of R. diademata, R. funerea and R. punctularia. For the time being, a continued classification of R. melanosterna, R. diademata, R. funerea and R. punctularia as distinct species is justified owing to their allopatric and parapatric distributions, and to conserve the established usage of names that is based on morphological and karyotypic differentiation.


Combined monitoring of thoracic duct and lung lymph during E. coli sepsis in awake sheep.
A thoracic duct lymph fistula in combination with a lung lymph fistula in the awake sheep was used to evaluate effects of thoracic lymph diversion during a septic insult and to monitor systemic and local changes in the lung and gastrointestinal tract. Live Escherichia coli 10(9) kg-1 b.w. were infused in 9 sheep. After sepsis, arterial pressure, cardiac output, partial pressure of oxygen, leukocytes and platelets decreased significantly compared to baseline values. Pulmonary arterial pressure increased significantly throughout the experiment with peak values at 44 +/- 4 mmHg after 15 minutes. Lung lymph flow (QL) (n = 6) increased from 23 +/- 0.5 to 11.2 +/- 2.4 ml/30 minutes after 60 minutes. QL then decreased but remained elevated. Lymph to plasma protein concentration ratio (L/P) in lung lymph decreased from 0.62 +/- 0.02 during baseline to 0.47 +/- 0.04 after 60 minutes. L/P then increased and was, after 150 minutes, no longer different from baseline. These lung lymph data favor increased pulmonary microvascular permeability during sepsis. Lymph flow in the thoracic duct (QT) (n = 9) increased from 34.2 +/- 6 to 58.3 +/- 9 ml/30 minutes during the first 30 minutes after bacterial infusion. QT was, after 90 minutes, back to baseline but then progressively increased. L/P in thoracic lymph steadily increased from 0.56 +/- 0.03 to 0.78 +/- 0.04. Thromboxane B2 and 6-keto PGF1 alpha in thoracic duct and lung lymph increased significantly after bacterial infusion and remained elevated thereafter. Combined monitoring of thoracic duct and lung lymph enabled comparison of systemic and pulmonary reactions in septic sheep.