Characterization of peroxidases in lignifying peach fruit endocarp.
Developing peach (Prunus persica L. Batsch ;Redskin') fruit were used to characterize the role of peroxidases in lignification. During development, the endocarp of these drupes becomes lignified while the mesocarp remains parenchymatous. Acidic peroxidase from lignifying endocarp were similar to those of the fleshy mesocarp. The endocarp had a larger amount and number of basic peroxidases than the mesocarp. Cultured peach leaf cells are thought to be lignified because their walls give a positive reaction with phloroglucinol-HCI. These cells also secreted a basic peroxidase. Peroxidases were difficult to extract from endocarp tissue as they lignified. This was also demonstrated by tissue printing on nitrocellulose. Flesh, but not endocarp peroxidase was evident in tissue prints. This suggests that tissue printing may fail to reveal the presence of enzymes which are firmly attached to the cell.


A novel cadmium(II) coordination polymer containing two kinds of independent one-dimensional chain.
The structure of the title compound, catena-poly[[cadmium(II)-di-μ-chlorido-μ-(1,4-diazoniabicyclo[2.2.2]octane-1-carboxylato)] [[aquachloridocadmium(II)]-di-μ-chlorido] dihydrate], {[Cd(C₈H₁₅N₂O₂)Cl₂][CdCl₃(H₂O)]·2H₂O}n, contains two kinds of independent one-dimensional chain, viz. {[Cd(C₈H₁₅N₂O₂)Cl₂]⁺}n and {[CdCl₃(H₂O)]⁻}n, and uncoordinated water molecules. Each CdII cation in the {[Cd(C₈H₁₅N₂O₂)Cl₂]⁺}n chain is octahedrally coordinated by two pairs of bridging chloride ligands and two O atoms from different bridging carboxylate groups. CdII cations in the {[CdCl₃(H₂O)]⁻}n chain are also octahedrally surrounded by four bridging chloride ligands, one terminal chloride ligand and one coordinated water molecule. Hydrogen bonds between solvent water molecules and these two independent chains generate a three-dimensional framework containing two-dimensional zigzag layers.


Detection of Lesions Underlying Intractable Epilepsy on T1-Weighted MRI as an Outlier Detection Problem.
Pattern recognition methods, such as computer aided diagnosis (CAD) systems, can help clinicians in their diagnosis by marking abnormal regions in an image. We propose a machine learning system based on a one-class support vector machine (OC-SVM) classifier for the detection of abnormalities in magnetic resonance images (MRI) applied to patients with intractable epilepsy. The system learns the features associated with healthy control subjects, allowing a voxelwise assessment of the deviation of a test subject pattern from the learned patterns. While any number of various features can be chosen and learned, here we focus on two texture parameters capturing image patterns associated with epileptogenic lesions on T1-weighted brain MRI e.g. heterotopia and blurred junction between the grey and white matter. The CAD output consists of patient specific 3D maps locating clusters of suspicious voxels ranked by size and degree of deviation from control patterns. System performance was evaluated using realistic simulations of challenging detection tasks as well as clinical data of 77 healthy control subjects and of eleven patients (13 lesions). It was compared to that of a mass univariate statistical parametric mapping (SPM) single subject analysis based on the same set of features. For all simulations, OC-SVM yielded significantly higher values of the area under the ROC curve (AUC) and higher sensitivity at low false positive rate. For the clinical data, both OC-SVM and SPM successfully detected 100% of the lesions in the MRI positive cases (3/13). For the MRI negative cases (10/13), OC-SVM detected 7/10 lesions and SPM analysis detected 5/10 lesions. In all experiments, OC-SVM produced fewer false positive detections than SPM. OC-SVM may be a versatile system for unbiased lesion detection.


Synthesis of 1,2-dihydroxyindolizidines from 1-(2-pyridyl)-2-propen-1-ol.
1-(2-Pyridyl)-2-propen-1-ol, obtained by vinylation of commercially available picolinaldehyde, resulted a good starting material for the synthesis of the indolizidine skeleton. In particular, a simple process involving bromination, reduction, and nucleophilic substitution (via elimination and addition) allowed an easy conversion of the starting material into (±)-lentiginosine in ~27% overall yield.


Purification and properties of Acid phosphatase from plump and shriveled seeds of triticale.
A major triticale (X Triticosecale Wittmack) endosperm acid phosphatase (EC 22.214.171.124) (APase) from sib-lines producing plump and shriveled seed was purified 140- and 230-fold to a specific activity of 94 and 153 micromoles per minute per milligram protein respectively, by ammonium sulfate fractionation, ion-exchange chromatography, chromatofocusing, affinity column chromatography, and gel filtration. The purified enzyme from both materials is a monomeric glycoprotein with an apparent molecular weight of 45,700 +/- 500 containing 12% carbohydrate and an apparent isoelectric point of pH 5.9. It hydrolyzes tri- and di-phosphate of nucleosides as well as phosphate esters and exhibits characteristics of ATP-hydrolase and phosphatase. About 2-fold more of the APase was isolated from shriveled seeds, and the purified enzyme exhibited 3- and 5-fold higher V(max) for p-nitrophenyl phosphate and ATP, respectively, than that of plump seed. The I(50) for Pi concentration was 5.5-fold higher in APase of shriveled seed than the plump one. These varied quantitative and kinetic properties substantiate the role of APase in lines with shriveled seeds being reduction of starch accumulation by depleting substrates and energy supply in the cytosol.


Peripheral vision in matching-to-sample procedures.
Eye-tracking has been used to investigate observing responses in matching-to-sample procedures. However, in visual search, peripheral vision plays an important role. Therefore, three experiments were conducted to investigate the extent to which adult participants can discriminate stimuli that vary in size and position in the periphery. Experiment 1 used arbitrary matching with abstract stimuli, Experiment 2 used identity matching with abstract stimuli, and Experiment 3 used identity matching with simple (familiar) shapes. In all three experiments, participants were taught eight conditional discriminations establishing four 3-member classes of stimuli. Four different stimulus sizes and three different stimulus positions were manipulated in the 12 peripheral test phases. In these test trials, participants had to fixate their gaze on the sample stimulus in the middle of the screen while selecting a comparison stimulus. Eye movements were measured with a head-mounted eye-tracker during both training and testing. Experiment 1 shows that participants can discriminate small abstract stimuli that are arbitrarily related in the periphery. Experiment 2 shows that matching identical stimuli does not affect discrimination in the periphery compared to arbitrarily related stimuli. However, Experiment 3 shows that discrimination increases when stimuli are well-known simple shapes.


RNase 7 in Cutaneous Defense.
RNase 7 belongs to the RNase A superfamily and exhibits a broad spectrum of antimicrobial activity against various microorganisms. RNase 7 is expressed in human skin, and expression in keratinocytes can be induced by cytokines and microbes. These properties suggest that RNase 7 participates in innate cutaneous defense. In this review, we provide an overview about the role of RNase 7 in cutaneous defense with focus on the molecular mechanism of the antimicrobial activity of RNase 7, the regulation of RNase 7 expression, and the role of RNase 7 in skin diseases.


Research on the Intervention Countermeasures and Mental Health Status of College Music Teachers from the Perspective of Positive Psychology.
The goal of education is to train people who are well-rounded and educate people with heart through teachers and determine the direction for the growth of life. Psychological education is one of the top ten education systems in colleges and universities. The psychological health of college teachers is the key to teaching and education. Colleges and universities attach great importance to teachers' educational level and scientific research achievements, pay attention to teachers' instrumental value, and pay little attention to teachers' mental health. Therefore, this study aims to study the mental health status and prevention measures of college music teachers from the perspective of positive psychology. By combining the qualitative method with the quantitative method, this study carries out questionnaire survey and interview on "mental health" of music teachers in four universities and then puts forward relevant intervention countermeasures. Research shows that only one-fifth of the teachers believed that they had received psychological counseling from the school and successfully solved their own problems; nearly 60% of music teachers said that the psychological counseling provided by the school lacked pertinence and professionalism, and lacked practical solutions to their own problems. This shows that the psychological intervention strategies adopted by Chinese colleges and universities for music teachers are far from the expected results.


Radial dose distribution, dose to water and dose rate constant for monoenergetic photon point sources from 10 keV to 2 MeV:EGS4 Monte Carlo model calculation.
A comprehensive set of dose distributions from monoenergetic photon-emitting isotropic point sources in a medium can be used as a reference database for the dosimetry of photon emitter sources in that medium. Data of this type for water over the photon energy range from 15 keV to 2 MeV have been published based on calculations using a one-dimensional photon transport model. The present work, based on a previously published EGS4 Monte Carlo code, updates the classic data set of Berger and provides more extensive calculations than previously available. Air kerma strength per unit photon emission rate from an isotropic point emitter is obtained as a function of energy using published data for mass energy absorption coefficients. The TG-43 dose rate constant for water as a function of energy is calculated for monoenergetic photon emitters as the ratio of dose rate to water at 1 cm to air kerma strength for unit photon emission rate. Results for the radial dose distribution agree well with the data of Berger between 40 and 400 keV. For energies > or =500 keV, a previously undescribed buildup region for the radial dose function is identified. Thickness of the buildup region ranges from 1 mm at 500 keV to 8 mm at 2 MeV. Between 15 and 30 keV, the radial dose function within a few millimeters of the emitter is calculated to be 4%-5% higher than values derived from Berger's data. The maximum dose rate constant for monoenergetic photon emitters occurs at an energy of 60 keV, and has the value 1.355 cGy h(-1)U(-1), where U is the unit of air kerma strength, 1 microGy m2 h(-1). This would correspond to the maximum hypothetical dose rate constant for a brachytherapy photon source emitting photons of energy < or =2 MeV.


[Age-related changes in the kidney of patients with mild mesangial proliferative glomerulonephritis].
In order to clarify age-related changes in kidneys, the renal function and histological changes were evaluated in 962 patients with mild mesangial proliferative glomerulonephritis (Mes PGN) whose ages ranged from 7 to 82 years. The glomerular filtration rate (GFR) (Ccr), renal plasma flow (RPF) (CPAH) and PSP excretion rate were significantly lower in nephritic patients than in normal subjects. Age-related decreases of GFR, RPF, PSP excretion rate and maximal urine specific gravity in Fishberg concentration test were found in both groups. Serum levels of creatinine, urea nitrogen and uric acid were significantly higher in nephritic patients than in the normal population. Age-related increases of those parameters were found in both groups. The incidence of sclerotic glomeruli was almost same as that of the normal population estimated by Kaplan et al. The incidence of arterio- and arteriolosclerosis was also higher than that of normal subjects estimated by Bell. Thus, arterio- and arteriolosclerosis seems to be more age-dependent than glomerulosclerosis in patients with mild Mes PGN. In conclusion, renal functions decrease and renal arteriolar lesions increase gradually in proportion to aging. Mes PGN, even mild, can accelerate the physiological age-related decrease of renal function.


[Endoparasite infestation of the stomach and intestinal tract of feral rabbits from the Leipzig region].
Investigations on the infestation with endoparasites in stomach and gut of feral rabbits from the region of Leipzig. During the hunting periods in the years 1976 till 1979 the viscera of 122 wild rabbits shot in two different biotopes in the area of Leipzig were examined for endoparasites. 63.11% harboured Ctenotaenia ctenoides and Cittotaenia denticulata and 8.19% Cysticercus pisiformis. Graphidium strigosum was demonstrated in 36.88%, Trichostrongylus retortaeformis in 82.78%, Passalurus ambiguus in 13.11% and Trichuris leporis in 7.13% of the rabbits. 71.13% of the rabbits shed oocysts of six different species of intestinal coccidia in their faeces and Eimeria stiedai--infections were diagnosed in the livers of 1.63% of the rabbits. Regional differences were demonstrated in the frequency of Graphidium strigosum-, Passalurus ambiguus- and tapeworm infestations of the wild rabbits examined.


"Cut and Sew" Transformations via Transition-Metal-Catalyzed Carbon-Carbon Bond Activation.
The transition metal-catalyzed "cut and sew" transformation has recently emerged as a useful strategy for preparing complex molecular structures. After oxidative addition of a transition metal into a carbon-carbon bond, the resulting two carbon termini can be both functionalized in one step via the following migratory insertion and reductive elimination with unsaturated units, such as alkenes, alkynes, allenes, CO and polar multiple bonds. Three- or four-membered rings are often employed as reaction partners due to their high ring strains. The participation of non-strained structures generally relies on cleavage of a polar carbon-CN bond or assistance of a directing group.


[Experience with the combination atovaquone-proguanil in the treatment of uncomplicated Plasmodium falciparum malaria--report of 112 cases].
The purpose of this open non-comparative retrospective study was to evaluate the efficacy and tolerance of Malarone for management of uncomplicated imported Plasmodium falciparum malaria. A total of 112 non-immune adult patients were included between 1999 and 2001. Excellent responses in terms of both clinical symptoms and parasite control were achieved within 4 days after the beginning of treatment in all cases. No recurrence was observed after 28 days of individual followup. Tolerance was satisfactory with no adverse events except for occasional, minor gastrointestinal upset. Based on our experience, Malarone appears to be effective, well-tolerated, and suitable for routine management of uncomplicated imported Plasmodium falciparum malaria.


Long-term control of melanoma adrenal metastasis treated with radiotherapy.
Melanoma remains a large global burden with a significant proportion of patients succumbing to metastatic disease. The adrenal gland is a common area for metastasis with surgical treatment as the main modality. Radiotherapy is less utilised in this setting with uncertainty over deliverability and efficacy. Here, we present the details and outcomes of 20 patients treated with radiotherapy, with or without systemic therapy, for melanoma adrenal metastasis in a single institute. Twenty patients were identified from radiation treatment and medical records from between 2015 and 2019 at our institution. Three patients had bilateral radiotherapy treatments and therefore 23 adrenal lesions were analysed. Demographics, indications for treatment, radiotherapy methodology and outcomes were recorded. Outcomes were based on serial 18F FDG PET/computerized tomography scans reporting using the PERCIST criteria. The most common indication for radiotherapy was oligo-progressive disease (70%) followed by symptom palliation. Eight (35%) of the treatments were delivered by stereotactic ablative body radiotherapy. Twelve (60%) patients had concurrent immunotherapy. Twenty of twenty-three (87%) adrenal lesions had an initial response to treatment with 12 (60%) maintaining local control until death or end of follow-up. Median adrenal-specific progression-free survival was 13 months. Four patients (17%) required salvage adrenalectomy. Symptom palliation was achieved in the majority of patients for which it was indicated and there were no grade three toxicities. The median time from radiotherapy to change of immunotherapy treatment was 4 months. Radiotherapy for melanoma adrenal metastasis is effective and deliverable. With the majority of patients achieving a palliative and clinically relevant durable response, adrenalectomy can be reserved as a salvage option.


Patients' perception of the practice of anaesthesia in a teaching hospital in Northern Jordan: a survey.
Despite big leaps of progress in its scope, the practice of anesthesia is still suffering from poor public image, especially in developing countries. Little research investigated the public awareness of anesthesia in the Middle East. This study aimed to examine the perception of the practice of anaesthesia among Jordanian patients. A standard questionnaire with 29 questions was administered through personal interview to consenting patients. Questions tested patients' correct knowledge of the identity of anesthetists, their roles and scope of their practice. Awareness was measured using the frequency of correct answers to each survey question. A total awareness score was calculated as the percentage ratio of the number of correct answers to the total number of questions. We classified this score into: Poor< 50%. Moderate 50-75%, and Good > 75% to reflect patient's overall perception of anesthetists and their roles. Effects of demographic variables on results were also investigated. Appropriate statistical tests were used to summarize and compare results. A total of 513 patients admitted for elective surgery were sequentially approached for enrolment. Five hundred and five patients were enrolled. Most patients identified anesthesia as a separate practice from surgery (86%). The anaesthetist was identified as a physician by only 37% of patients. Equal importance to both anaesthetists and surgeons was assumed by 71.5% of patents. Only 15% of patients showed good level of total knowledge of anaesthetist roles, while 51% scored poorly. Highest awareness was of anaesthetist's preoperative roles (65.1%). Age was the only demographic factor affecting studied awareness (P = 0.009). Although the importance of anesthetist is well perceived among Jordanian patients, there is still some ignorance in their knowledge of the details of anesthesia practice. Active communication efforts and patient education by anesthetists are needed to improve the public status of the specialty.


Mothers' experiences of sharig breastfeeding or breastmilk co-feeding in Australia 1978-2008.
While the concept of breastfeeding in contemporary Western culture is of a mother breastfeeding her own baby or babies, others have replaced the mother as provider of breastmilk, for a variety of reasons, through most periods of human existence. Existing policies for the sharing of this bodily fluid, milk, appear to have been written without the benefit of a detailed examination of the actual experiences of the mothers and babies involved. This study attempts to fill this information gap by investigating the sharing of breastfeeding or expressed breastmilk by Australian women in a recent thirty-year period, 1978-2008. The objective of this study was to explore the mothers' experiences of sharing breastfeeding or human milk including: the circumstances in which this bodily fluid was freely shared; what screening process, if any, was used before the milk of another mother was accepted; the mothers' feelings about the experience; the reported attitudes of others; and the children's behaviour when put to the breast of someone other than the mother. The underpinning reason for the sharing of breastfeeding or breastmilk was the desire of mothers to provide human milk to their babies, exclusively, including while they were absent or temporarily unable to breastfeed. Most mothers were selective about those with whom they would share breastfeeding or breastmilk.


The future developments in endoscopy.
Gastrointestinal endoscopy has seen great changes over recent years, and the future seems bright. Looking forward, some advances in technology can be predicted, but the current financial climate may limit their widespread adoption. Increasing subspecialisation with continuing service development and quality assurance are likely to form the basis of the major changes over the next 5 years. Increasing juxtaposition between laparoscopic and endoscopic procedures presents the most exciting opportunities over the 10-year timeframe. This article extrapolates current trends to try to predict the different possibilities for endoscopy over the next decade.


The shifting locus of risk-reduction: the critical role of HIV infected individuals.
This article discusses the shifting locus of control over risk-reduction and examines its implications for the care and support of HIV-positive individuals. We begin by presenting a brief history of the continuum of HIV related risk, illustrating the ways in which advances in risk-assessment and intervention have led to this important shift. Second, we discuss the current state of risk assessment and intervention as it relates to three factors: (a) the point along the continuum of risk at which risk assessment and intervention occurs; (b) the locus of control over risk reduction; and (c) the distinction between primary and secondary risk reduction efforts. Finally, we discuss the meaning of HIV risk and the role of HIV-positive individuals in the new geometry of care that integrates treatment and prevention. How is HIV-risk defined and understood? Who is of risk to whom&#63 Who is responsible for reducing risk&#63.


[Discrimination of varieties of apple using near infrared spectra based on principal component analysis and artificial neural network model].
A new method for the discrimination of varieties of apple by means of near infrared spectroscopy (NIRS) was developed. First, principal component analysis (PCA) was used to compress thousands of spectral data into several variables and describe the body of spectra, the analysis suggested that the cumulate reliabilities of PC1 and PC2 (the first two principle components) were more than 98%, and the 2-dimentional plot was drawn with the scores of PC1 and PC2. It appeared to provide the best clustering of the varieties of apple. The loading plot was drawn with PC1 and PC2 through the whole wavelength region. The fingerprint spectra, which were sensitive to the variety of apple, were obtained from the loading plot. The fingerprint spectra were applied as ANN-BP inputs. Seventy five samples from three varieties were selected randomly, then they were used to build discrimination model. This model was used to predict the varieties of 15 unknown samples; the distinguishing rate of 100% was achieved. This model is reliable and practicable. So the present paper could offer a new approach to the fast discrimination of varieties of apple.


Changes in corneal innervation during postnatal development in normal rats and in rats treated at birth with capsaicin.
This study was undertaken to learn more about the keratitis that follows the neonatal administration of capsaicin to rats. In the first part of the study the density and pattern of corneal innervation were followed throughout postnatal development in litters of control rats and in rats that received capsaicin as neonates. In rats treated with capsaicin, the density of corneal innervation was lower than that of control rats until 28 days of age. Thereafter nerve fiber sprouting was observed within the corneas of capsaicin-treated rats. By 56 days of age the capsaicin-treated rats had a denser corneal innervation than did control rats. In the second part of the study the incidence and severity of the corneal trophic changes induced by capsaicin were studied in litters of rats treated with chronic tarsorrhaphy and in litters raised in the dark. Neither of these manipulations altered the incidence or severity of keratitis. These observations demonstrate that sprouting of the remaining corneal axons is related temporally to the previously observed decrease in keratitis. Furthermore the more severe keratitis observed in early postnatal life does not appear to be related to physical injury of the cornea.


Retrospective case series analysis of the factors determining immediate implant placement.
Implant placement at the time of extraction has become an acceptable treatment option. The formation of a restorative treatment plan frequently requires the removal of questionable and hopeless teeth. This retrospective case series analysis reports the reasons for tooth removal before immediate implant placement and provides a rationale for removing questionable and hopeless teeth. Root length is also analyzed as related to tooth loss. Between September 1986 and December 1998, 460 teeth were removed from 282 patients. Reasons for removal were advanced periodontal disease, endodontic complications, nonrestorable caries, roots fractures, short roots (< 14 mm in length), root resorption, and loosened posts. Implants were placed at the time of extraction. Tallies, frequency distributions, and percentages were used to determine individual and multiple reasons for extraction. For teeth with short roots, computerized measurements were made from periapical x-rays. Advanced periodontal disease and restored endodontically treated teeth with posts were the primary reasons for tooth extraction. Dental implants replaced 305 maxillary and 155 mandibular teeth.


Solid-phase synthesis of novel 7,8-functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4-thioxotriazine derivatives via cyclization reactions of dithiocarboxy resin bound pyrazoles.
A general method is described for the solid-phase synthesis of novel 7,8-functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4-thioxotriazine derivatives. The sequence developed for this purpose is based on cyclization reactions of resin-bound 3,4-functionalized-5-amino-1-dithiocarboxypyrazoles 4 and 5, promoted by reaction with various isocyanates. The resin-bound pyrazoles produced by cyclization reactions of cyanocarboimidates 8 or 3-ethoxyacrylonitriles 9 with Merrifield resin linked hydrazine dithiocarbazate 3, serve as key intermediates for subsequent bicyclic heterocycle diversification. Reactions of the resin-bound 5-amino-1-dithiocarboxy pyrazoles 4 and 5 with various aryl isocyanates produce the novel 7,8-functionalized pyrazolo[1,5-a][1,3,5]-2-oxo-4-thioxotriazine derivatives 6 and 7 in good yields and high purities.


Arabidopsis thaliana regulatory element analyzer.
In the Arabidopsis thaliana regulatory element analyzer (AtREA) server, we have integrated sequence data, genome-wide expression data and functional annotation data in three application modules which will be useful to identify major regulatory targets of a user-provided cis-regulatory element (CRE), study different features of CRE distribution and evaluate the role of a set of CREs in the regulation of gene expression--independently as well as in combination with other user-provided CREs. AtREA is freely available at http://www.bioinformatics.org/grn/atrea.html.


Safety and efficacy of endoscopic ultrasound-guided gastroenterostomy using double balloon occlusion methods: a clinical retrospective study in 36 patients with malignant gastric outlet obstruction.
Background and study aims Gastric outlet obstruction (GOO) is common in the late stage of many malignant tumors of the digestive system. Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is commonly used for palliative treatment of malignant GOO. The objective of this study was to investigate the safety, efficacy, and prognosis of EUS-GE in treatment of malignant GOO in Chinese patients. Patients and methods This was a retrospective, single-center study with 36 consecutive patients with malignant GOO who were treated with EUS-GE. The main outcome measures were technical success rate, clinical success rate, incidence of adverse events (AEs), and median survival time. Results A total of 36 patients with malignant GOO underwent double-balloon-assisted EUS-GE between March 2017 and June 2019 in our hospital. GOO occurred mainly in elderly men (mean age 69.0 years, M:F 0.89). The most common etiology of GOO was pancreatic cancer (41.7 %). The most common obstruction site was the second part of the duodenum (63.9 %). The technical success rate was 100 % (36/36). The clinical success rate was 94.4 % (34/36). Median time for the total procedure was 52 minutes (range 34 - 156 min). Median time for determination of puncture site was 20 minutes (range 15 - 28 min). Median time between puncture and successful delivery of the stent was 38 minutes (range 19 - 128 min). The GOOSS score was 0.2 before EUS-GE. The GOO Scoring System (GOOSS) score was 2.2 at 15 days after the EUS-GE ( P = 0.001). The GOOSS score was still higher than 2 during a median follow-up period of 89 days. AEs were observed in nine patients (25.0 %) and 13 total AEs occurred. One patient died as a result of delayed stent migration and bleeding. Mean length of hospital stay was 5.8 ± 4.7 days. The median survival period was 103 days. The rate of GOO recurrence was 2.7 % (1/36). Conclusion EUS-GE was associated with increased safety and efficacy for treatment of malignant GOO in Chinese Mainland.


Three-dimensional morphometry of the A2 segment of the anterior cerebral artery with neurosurgical relevance.
Most prior morphometry data regarding the A2 segment of the anterior cerebral artery (ACA) have been based on cadaveric measurements. With newer imaging modalities, surgical techniques, and minimally invasive procedures, new standards for the anatomy of this vessel are necessary. A novel computer-based data system was used to analyze the three-dimensional (3D) morphometry of 230 A2 segments. In addition, tortuosity (TI) and deviation indices (DI) for this segment were calculated. The mean internal diameter of the A2 segment was 1.86 mm, and segments tended to be larger in men and on left sides. A2 segments were asymmetrical in 43%, and this was more common in women. Lengths tended to be greater on right sides and in men. Volumes were greater in men and increased with age, which was statistically significant. These gender differences were found to be statistically significant (P < 0.05), for both volume and diameter. TI was equal among sides, but DI was more often greater on right sides. The correlation coefficient ratio for length and DI was statistically significant. It is important to understand various 3D morphometrical differences particularly between genders. By constructing blood flow simulation models and during revascularization procedures, surgeons are able to gain a better understanding of each patient's vascular anatomy. These additional 3D data regarding the anatomy of the postcommunicating parts of the ACA may be useful to the neurosurgeon and interventional neuroradiologist. These data may assist with an earlier diagnosis of pathologies affecting the 3D morphology of the ACA.


Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema.
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a syndrome that may be associated with many conditions, including malignancy. Three further cases of paraneoplastic RS3PE are described and the literature is reviewed. Paraneoplastic RS3PE is more frequently associated with solid tumors, in particular adenocarcinoma. The two clinical characteristics suggestive of paraneoplastic RS3PE are systemic sign/symptoms and the poor response to corticosteroid therapy.


Broad Promotes Neuroepithelial Stem Cell Differentiation in the Drosophila Optic Lobe.
Brain development requires the generation of the right number, and type, of neurons and glial cells at the right time. The Drosophila optic lobe, like mammalian brains, develops from simple neuroepithelia; they first divide symmetrically to expand the progenitor pool and then differentiate into neuroblasts, which divide asymmetrically to generate neurons and glial cells. Here, we investigate the mechanisms that control neuroepithelial growth and differentiation in the optic lobe. We find that the Broad/Tramtrack/Bric a brac-zinc finger protein Broad, which is dynamically expressed in the optic lobe neuroepithelia, promotes the transition of neuroepithelial cells to medulla neuroblasts. Loss of Broad function causes neuroepithelial cells to remain highly proliferative and delays neuroepithelial cell differentiation into neuroblasts, which leads to defective lamina and medulla. Conversely, Broad overexpression induces neuroepithelial cells to prematurely transform into medulla neuroblasts. We find that the ecdysone receptor is required for neuroepithelial maintenance and growth, and that Broad expression in neuroepithelial cells is repressed by the ecdysone receptor. Our studies identify Broad as an important cell-intrinsic transcription factor that promotes the neuroepithelial-cell-to-neuroblast transition.


Neighborhood perceptions and parent outcomes in family based prevention programs for Thai adolescents: the role of program engagement.
Due to concerns over Thai adolescent risky behaviors, effective prevention strategies are needed. Determining the role neighborhood context plays in program engagement and outcomes may inform these strategies. This study includes 170 mother-adolescent pairs (M = 13.44, SD = .52) in Bangkok, Thailand in a prevention program for adolescent substance use and sexual risk. Neighborhoods were related to engagement, which was critical to outcomes. Neighborhood disorganization was related to confidence in program effects and program completion. Completion was related to increased ATOD communication. Neighborhood cohesion was related to less program enjoyment, while neighborhood social control was related to more enjoyment. Enjoyment was related to increased ATOD communication and formation and monitoring of alcohol rules. Prevention strategies should focus on neighborhood contexts and enhancing engagement.


[Sequencing and analysis of the complete genome of a rabies virus isolate from Sika deer].
One DRV strain was isolated from Sika Deer brain and sequenced. Nine overlapped gene fragments were amplified by RT-PCR through 3'-RACE and 5'-RACE method, and the complete DRV genome sequence was assembled. The length of the complete genome is 11863bp. The DRV genome organization was similar to other rabies viruses which were composed of five genes and the initiation sites and termination sites were highly conservative. There were mutated amino acids in important antigen sites of nucleoprotein and glycoprotein. The nucleotide and amino acid homologies of gene N, P, M, G, L in strains with completed genomie sequencing were compared. Compared with N gene sequence of other typical rabies viruses, a phylogenetic tree was established . These results indicated that DRV belonged to gene type 1. The highest homology compared with Chinese vaccine strain 3aG was 94%, and the lowest was 71% compared with WCBV. These findings provided theoretical reference for further research in rabies virus.


[Late opacification of a polymethylmethacrylate (PMMA) intraocular lens: case report].
The use of intraocular lenses was a great advance in visual recovery after cataract surgery. Although usually with good biocompatibility, some alterations in the intraocular lens material may occur after implantation. Polymethylmethacrylate was the first intraocular lens material to be used on a large scale and assumed to be inert and well-tolerated. We present a rare case of late opacification of a polymethylmethacrylate lens, discussing important aspects of its management such as the indication for intraocular lens exchange.


Evaluation of ultraviolet C for disinfection of endocavitary ultrasound transducers persistently contaminated despite probe covers.
To determine the rate of bacterial and viral contamination of endocavitary ultrasound probes after endorectal or endovaginal examination with the use of probe covers and to evaluate the antimicrobial efficacy of a disinfection procedure consisting of cleaning with a disinfectant-impregnated towel followed by disinfection with ultraviolet C (UVC) light. Endovaginal or endorectal ultrasound examinations were performed for 440 patients in 3 institutions. All probes were covered by a condom or sheath during the examination. For bacterial analysis, 1 swab was applied lengthwise across one-half the surface of the probe just after removal of the probe cover. The second swab was similarly applied over the probe immediately after the end of a 2-step process consisting of cleaning with a towel impregnated with a disinfectant spray and a 5-minute UVC disinfection cycle. Swabs were applied onto plates and incubated for 48 hours. The number of colony-forming units was counted, and organisms were identified. A similar protocol was used for viral detection of Epstein-Barr virus, human cytomegalovirus, and human papillomavirus, except that an additional swab was applied along the entire external surface of the probe cover before its removal. Viruses were detected by means of a polymerase chain reaction-based protocol. After removal of probe covers, contamination by pathogenic bacteria was found for 15 (3.4% [95% confidence interval, 2.0%-5.6%]) of 440 probes, and viral genome was detected on 5 (1.5% [95% confidence interval, 0.5%-3.5%]) of 336 probes. After cleaning with a towel impregnated with a disinfectant spray and disinfecting with UVC light, neither bacterial pathogenic flora nor viral genome was recovered from the probe. Endocavitary ultrasound probes may carry pathogens after removal of covers under routine conditions. A disinfection procedure consisting of cleaning with a disinfectant-impregnated towel followed by disinfection with UVC may provide a useful method for disinfecting endocavitary ultrasound probes.


The natural history of symptomatic COVID-19 during the first wave in Catalonia.
The natural history of coronavirus disease 2019 (COVID-19) has yet to be fully described. Here, we use patient-level data from the Information System for Research in Primary Care (SIDIAP) to summarise COVID-19 outcomes in Catalonia, Spain. We included 5,586,521 individuals from the general population. Of these, 102,002 had an outpatient diagnosis of COVID-19, 16,901 were hospitalised with COVID-19, and 5273 died after either being diagnosed or hospitalised with COVID-19 between 1st March and 6th May 2020. Older age, being male, and having comorbidities were all generally associated with worse outcomes. These findings demonstrate the continued need to protect those at high risk of poor outcomes, particularly older people, from COVID-19 and provide appropriate care for those who develop symptomatic disease. While risks of hospitalisation and death were lower for younger populations, there is a need to limit their role in community transmission.


Perspectives on leadership: moving out of the corner of our room.
Perspectives on leadership developed through a career as a nurse leader are shared, including the author's guiding vision, a valuing of nursing as knowledge work, how to create a learning organization that supports professional practice, and other lessons learned through experience. Readers are urged to find the leadership voice within, be courageous, engage surrounding opportunities, and be guided by their vision of what nursing should be in the future.


Morphogenesis in the fetal rat proximal colon: effects of cytochalasin D.
Two major morphogenetic events, epithelial conversion and fold formation, occur in the proximal rat colon during the last week of gestation. To evaluate the role of actin microfilaments in these two developmental processes, explants from the proximal colon of 19 day fetal rats were cultured in the presence of vehicle (0.1% dimethylsulfoxide), 0.1, 1.0, or 10 micrograms/ml of cytochalasin D (CD) for 24-48 hr. Explants as well as 19, 20, and 21 day in vivo controls were prepared for light, fluorescence, and electron microscopy. The distribution of actin filaments was determined by rhodamine-conjugated phalloidin binding and ultrastructural analysis of tissue fixed in the presence of tannic acid. Prior to fold formation, phalloidin binding was enhanced along the entire epithelial-mesenchymal interface. At the onset of fold formation, focal areas of intense fluorescence appeared at irregular intervals along the base of the stratified epithelium. Within 1 day, these focal intensities were localized at the apex of small forming folds. Additional changes occurring at the epithelial-mesenchymal interface in association with fold formation included: 1) ruffling of the previously smooth basal lamina, 2) a shape change in the subjacent mesenchymal cells from elongate to cuboidal along with the appearance of numerous processes abutting the basal lamina, and 3) a unique orientation of the associated collagen fibrils in some presumptive folds. Fold formation was inhibited in > 93% of explants cultured in the presence of 1.0 micrograms/ml CD. These explants appeared to be arrested precisely at the onset of fold formation. Epithelial conversion was also incomplete in these explants. These findings indicate an active role for actin in both fold formation and epithelial conversion.


Randomized clinical trial and follow-up study of cost-effectiveness of laparoscopic versus conventional Nissen fundoplication.
Laparoscopic Nissen fundoplication (LNF) has essentially replaced its conventional open counterpart (CNF). An economic evaluation of LNF compared with CNF based on prospective data with adequate follow-up is lacking. Data from two consecutive studies (a randomized clinical trial (RCT) of 57 patients undergoing LNF and 46 undergoing CNF that was terminated prematurely, and a follow-up study of 121 consecutive patients with LNF) were combined to determine incremental cost-effectiveness 1 year after surgery. Mean operating time, reoperation rate and hospital costs of LNF were lower in the second series. The mean overall hospital cost per patient was euro 9126 for LNF and euro 6989 for CNF at 1 year in the initial RCT, and euro 7782 in the second LNF series. The success rate of both LNF and CNF at 1 year was 91 per cent in the RCT, and LNF was successful in 90.1 per cent in the second series. A cost reduction of euro 998 for LNF would cancel out the cost advantage of CNF. Similarly, if the reoperation rate after LNF decreased from 0.05 to below 0.008 and/or if the mean duration of sick leave after LNF was reduced from 67.2 to less than 61.1 days, the procedure would become less expensive than CNF. Complications, reoperation rate and quality of life after both operations were similar. Including reinterventions, the outcome at 1 year after LNF and CNF was similar. In a well organized setting with appropriate expertise, the cost advantage of CNF may be neutralized.


Measuring CP Violating Phase in Beauty Baryon Decays.
One of the outstanding problems in physics is to explain the baryon-antibaryon asymmetry observed in nature. According to the well-known Sakharov criterion for explaining the observed asymmetry, it is essential that CP violation exist. Even though CP violation has been observed in meson decays and is an integral part of the standard model (SM), measurements in meson decays indicate that CP violation in the SM is insufficient to explain the observed baryon-antibaryon asymmetry. The SM predicts the existence of yet to be observed CP violation in baryon decays. A critical test of the SM requires that CP violation be measured in baryon decays as well, in order to verify that it agrees with the measurement using meson decays. In this Letter we propose a new method to measure the CP violating phase in b baryons, using interference arising implicitly due to Bose symmetry considerations of the decaying amplitudes.


Ribosomal RNA antitermination in vitro: requirement for Nus factors and one or more unidentified cellular components.
Using an in vitro transcription assay, we have successfully demonstrated read through of a Rho-dependent terminator by the ribosomal RNA antitermination system. The assay used a DNA template containing a promoter-antiterminator-terminator arrangement, RNA polymerase, termination factor Rho, antitermination factors NusA, NusB, NusE, and NusG, and a cellular extract depleted of NusB. Terminator read-through was highly efficient only in the presence of the extract and Nus factors, suggesting that an as yet uncharacterized cellular component is required for ribosomal antitermination. The NusB-depleted extract had no activity in the absence of NusB, confirming an absolute requirement for this protein in ribosomal RNA antitermination. The DNA template requirements were the same as those previously established in vivo; transcription of a wild-type boxA sequence is both necessary and sufficient to promote RNA polymerase modification into a terminator-resistant form.


Dynamic changes of resting state connectivity related to the acquisition of a lexico-semantic skill.
The brain undergoes adaptive changes during learning. Spontaneous neural activity has been proposed to play an important role in acquiring new information and/or improve the interaction of task related brain regions. A promising approach is the investigation of resting state functional connectivity (rs-fc) and resting state networks, which rely on the detection of interregional correlations of spontaneous BOLD fluctuations. Using Morse Code (MC) as a model to investigate neural correlates of lexico-semantic learning we sought to identify patterns in rs-fc that predict learning success and/or undergo dynamic changes during a 10-day training period. Thirty-five participants were trained to decode twelve letters of MC. Rs-fMRI data were collected before and after the training period and rs-fc analyses were performed using a group independent component analysis. Baseline connectivity between the language-network (LANG) and the anterior-salience-network (ASN) predicted learning success and learning was associated with an increase in LANG - ASN connectivity. Furthermore, a disconnection between the default mode network (DMN) and the ASN as well as the left fusiform gyrus, which is critically involved in MC deciphering, was observed. Our findings demonstrate that rs-fc can undergo behaviorally relevant changes within 10 training days, reflecting a learning dependent modulation of interference between task specific networks.


Antihypertensive therapy. Concepts and new agents.
Over the past decade we have witnessed a metamorphosis in the treatment of hypertension. First, nonpharmacological modalities are employed and are followed by a stepped-care program with pharmacological entities including diuretic, beta-adrenergic receptor blocking, antiadrenergic, angiotensin-inhibiting, and vasodilating agents. Precisely how beta-adrenergic blocking drugs reduce arterial pressure still remains to be elucidated, and we still do not understand precisely how the diuretics, direct-acting smooth muscle relaxants, or even the angiotensin-converting enzyme inhibitors work. Nevertheless, it is clear that clinical studies directed toward these questions as well as toward other new classes of antihypertensive agents (including how the calcium-entry blockers, serotonin inhibitors, and others affect vascular smooth muscle contractility) should provide continued enlightenment as to the pathogenesis and pathophysiology of essential hypertension.


Myriad Manifestations of 3-Beta-Hydroxysteroid Dehydrogenase 2 Deficiency-A Tale of Two Infants.
3-Beta-hydroxysteroid dehydrogenase type 2 (3β-HSD2) deficiency is a rare variety of congenital adrenal hyperplasia. Based on the severity of the enzymatic defect, it can present with a salt-wasting crisis in both sexes to undervirilization in males and virilization in females. We report two cases of infants with extremes of presentation of this congenital adrenal hyperplasia. First was a 28-day-old child presenting with a salt-wasting crisis while the other was a one-month-old child presenting with ambiguous genitalia. Clinical exome sequencing of the first child confirmed the diagnosis and we report a novel mutation of this gene, while the second child was diagnosed biochemically by raised synacthen-stimulated 17-OH-pregnenolone. The first case was managed with glucocorticoid and mineralocorticoid supplementation, while the second child was managed conservatively. Due to variable presentations, 3β-HSD2 deficiency should be kept as a differential diagnosis while evaluating a child with congenital adrenal hyperplasia.


Education and mental health: Do psychosocial resources matter?
Prevalence rates for mental health problems are higher when an individual's socioeconomic status (SES) is low, but the underlying mechanisms are not clearly understood. We investigated associations between education as indicator for SES and depressive symptoms as well as positive mental health (PMH). Moreover, we hypothesized that low education is associated with a lack of psychosocial resources and more daily hassles, which in turn mediate the relationships between education and mental health. In a German representative sample (N = 7937), we cross-sectionally first examined whether a person's educational level was associated with depressive symptoms and PMH. Educational level was defined as the highest academic qualification achieved. Second, we investigated whether also sense of control, resilience, delay of gratification, cultural activity and daily hassles followed gradients along the educational level. Third, we investigated whether they mediated the relationship between education and mental health. Results showed that depressive symptoms measured by items from the DASS-42 depression subscale were more prevalent for persons with a low educational level, PMH operationalized by the Positive Mental Health Scale was equally distributed, and all psychosocial characteristics followed the gradient of educational level. In addition, the group with a high school diploma was particularly burdened. Structural equation modeling indicated that the associations between education and mental health were mediated by all psychosocial characteristics and daily hassles, apart from the delay of gratification. In the group with the lowest educational level the model fit indices for depressive symptoms and PMH were acceptable (χ2 = 10007.243 (627), CFI = 0.869, RMSEA = 0.04 (90% CI [0.04, 0.04], SRMR = 0.05; and χ2 = 12779.968 (741), CFI = 0.86, RMSEA = 0.05 (90% CI [0.05, 0.05], SRMR = 0.05), respectively). The effect size Pm refers to the proportion of the total effect that is mediated by one or more variables ("M"), and the effect size of all indirect effects in the model for depressive symptoms was Pm = .80 and for PMH it was Pm = .68. The results support our hypotheses that low education is associated with less psychosocial resources, which in turn serve together with daily hassles as pathways between education and depressive symptoms as well as PMH. Building on these findings, longitudinal studies are necessary to investigate causality.


Glutathione transferase activity and isoenzyme composition in primary human breast cancers.
The human glutathione transferases (GSTs) are a multigene family of detoxication enzymes with patterns of expression that are both tissue specific and genetically determined. Changes in the levels of one or more GST isoenzymes have been associated with the development of anticancer drug resistance in cultured cell lines. In this study, total GST activity and GST isoenzyme composition have been determined for 45 primary human breast carcinomas using a 1-chloro-2,4-dinitrobenzene substrate assay and Western blotting, respectively. The GST activity ranged from 5-208 mU/mg protein with a mean of 67 mU/mg protein (+/- 44 SD). GST-pi) isoenzyme protein was detectable on Western blots in 44 of 45 samples. Mu Class GST protein was detected in 18 of 38 samples and undetectable in 20 of the 38 samples tested. By polymerase chain reaction analysis of genomic DNA, the absence of mu class GST in breast tumors was determined to be due to the deletion of the gene for GST-mu in the DNA of those tumors. None of the 43 primary human breast cancer samples tested contained detectable alpha class GST protein. Neither the total GST activity of tumor samples, the quantity of GST-pi protein, nor the presence or absence of mu class GST correlated with other factors known to be of prognostic significance including tumor size, nodal status, estrogen receptor protein positivity, or progesterone receptor protein positivity. Substantial differences exist among primary breast carcinomas in both the amount of GST activity and GST isoenzyme composition. However, these are not tightly linked either to tumor stage or to hormone receptor status. Whether the levels of these enzymes are independent predictors of either risk of recurrence or response to anticancer therapy has yet to be tested directly.


Smoking, cortisol and nicotine.
Cigarette smoking is associated acutely with elevated cortisol levels. However, the results of comparisons of cortisol levels in smokers and non-smokers have been inconsistent, and the significance of cortisol responses in smoking cessation is unclear. Here we describe one study comparing the cortisol profiles of smokers and nonsmokers over the day, and a second investigation in which cortisol was monitored during smoking cessation. In the first study, we collected saliva samples from 196 middle-aged men and women on working and weekend days repeatedly through the day. On both working and weekend days, cortisol levels were significantly higher in smokers after adjustment for age, gender and grade of employment. Cortisol responses to waking (the increase between waking and 30 min) were also greater in smokers. The elevation in cortisol among smokers is generally attributed to nicotine exposure. Nicotine replacement therapy substantially improves abstinence rates, and has become a standard component of smoking cessation treatments, but the effects of nicotine replacement on cortisol are not known. In the second study, cortisol was monitored over 6 weeks of abstinence in 112 smokers treated with behavioural support and 15 mg nicotine patches. Smoking cessation was accompanied by an abrupt decrease in salivary cortisol, and this was sustained over the abstinence period. There was a marginal association between the decrease in cortisol and smoking relapse rates. These results suggest that the nicotine supplied through patches was not sufficient to block the cortisol reduction following smoking cessation. The contribution of these findings to understanding the role of neuroendocrine function in smoking is described.


Cognitive screening test in primary care: cut points for low education.
To establish the diagnostic accuracy of the Brazilian version of the General Practitioner Assessment of Cognition (GPCOG-Br) compared to the Mini-Mental State Examination (MMSE) in individuals with low educational level. Ninety-three patients (≥ 60 years old) from Brazilian primary care units provided sociodemographic, cognitive, and functional data. Receiver operating characteristics, areas under the curve (AUC) and logistic regressions were conducted. Sixty-eight patients with 0-4 years of education. Cases (n = 44) were older (p = 0.006) and performed worse than controls (n = 49) on all cognitive or functional measures (p < 0.001). The GPCOG-Br demonstrated similar diagnostic accuracy to the MMSE (AUC = 0.90 and 0.91, respectively) and similar positive and negative predictive values (PPV/NPV, respectively: 0.79/0.86 for GPCOG-Br and 0.79/0.81 for MMSE). Adjusted cut-points displayed high sensitivity (all 86%) and satisfactory specificity (65%-80%). Lower educational level predicted lower cognitive performance. The GPCOG-Br is clinically well-suited for use in primary care.


Fourier Transform Emission Spectroscopy of CuCl.
The electronic spectra of CuCl were observed in the 18 000 cm(-1) to 25 000 cm(-1) spectral region using a Bruker IFS 120 HR Fourier transform spectrometer (FTS) and with the FTS associated with the McMath-Pierce Solar Telescope at Kitt Peak. On the basis of ab initio calculations, the labels for the electronic states were revised, and the a(3)Sigma(+)(1)-X(1)Sigma(+) 0-0 band, the b(3)Pi(0)-X(1)Sigma(+) 0-0, 1-0, and 0-1 bands, the b(3)Pi(1)-X(1)Sigma(+) 0-0, 1-0, and 0-1 bands, the A(1)Pi-X(1)Sigma(+) 0-0, 1-0, and 0-2 bands, and the B(1)Sigma(+)-X(1)Sigma(+) 0-0 and 1-0 bands were measured. Improved spectroscopic constants were obtained for the excited and ground states. Copyright 2001 Academic Press.


Nucleation study for an undercooled melt of intermetallic NiZr.
Electrostatic levitation is applied in order to undercool liquid glass forming NiZr significantly below its melting temperature. For NiZr large undercoolings are found to be highly reproducible with this experimental method. One single NiZr sample of high purity is undercooled 200 consecutive times which leads to a distribution function of undercooling temperatures. Within a statistical approach of classical nucleation theory, the undercooling distribution is analyzed yielding parameters, e.g., a pre-exponential factor of KV ≈ 1035 m-3 s-1, which indicates homogeneous nucleation. This result is consistent with the crystallization behavior of NiZr at high undercooling and with the corresponding microstructural analysis. Since NiZr is a representative of the very common CrB structure type, with 132 isostructural phases existing, understanding its nucleation behavior adds important knowledge to the nucleation of binary alloys in general.


Effect of a long acting beta-adrenoceptor blocker on diurnal variation of cardiac dysrhythmias.
To investigate circadian variation of cardiac arrhythmias ambulatory electrocardiogram monitoring was carried out before and after one week's treatment with a long acting beta-adrenoceptor blocker, nadolol, in 26 patients who presented with symptoms attributable to arrhythmias. Analysis of the 24 hour profile of premature ventricular contractions showed a significantly (P less than 0.05) higher frequency during midday to midnight than between midnight and midday. The frequency of supraventricular tachycardia was significantly (P less than 0.05) higher during the periods from 12.00 hours to 16.00 hours (11.0 +/- 12) and 16.00 hours to 20.00 hours (11.3 +/- 11) than during the periods of 00.00 hours to 04.00 hours (3.6 +/- 3) and 04.00 hours to 08.00 hours (6.0 +/- 8). The period of the highest incidence of all arrhythmias was between 16.00 hours to 24.00 hours, and that of lowest during the period between 04.00 hours to 12.00 hours (P less than 0.01). After one week's treatment with nadolol the frequency of all arrhythmias was strikingly reduced but their pattern of occurrence remained unchanged. These studies suggest that patients who present with symptoms attributable to arrhythmias tend to have these more frequently during the physical and mental activities of the day and evening presumably due to the accompanying sympathetic overactivity.


Vaccination is the most effective and best way to avoid the disease of COVID-19.
Most of the vaccines that are effective against SARS-CoV-2 have used the following functional strategies: inactivated viruses, live attenuated viruses, viral vector-based vaccines, subunit vaccines, recombinant proteins, and DNA/RNA vaccines. Among the vaccines that stimulate the host's immune system with the help of DNA are: undergoing Phase 2/3 trials including INO-4800 (International Vaccine Institute; Inovio Pharmaceuticals), Symvivo, Canada-COVID19 (AnGes, Inc.); GX-19 (Genexine, Inc.). BNT162b2 and mRNA-1273 vaccines were made by BioNTech/Pfizer/Fosun Pharma group and Moderna/NIAID group, respectively, which are considered as types of RNA vaccines. Vaccines that are based on the viral vector are AstraZeneca, Sputonium, and Johnson-Jensen. Among the inactive viral vaccines, the following can be mentioned: CoronaVac (Sinovac) WIBP vaccine (Wuhan Institute of Biological Products, Sinopharm), BBIBPCorV (Beijing Institute of Biological Products, Sinopharm), BBV152/Covaxin (Bharat Biotech, ICMR, National Institute of Virology) And among the protein-based/subunit vaccines, the following can be counted: NVX-CoV2373: (Novavax); SCB-2019 vaccine (Clover Biopharmaceuticals AUS Pty Ltd.); Covax-19 (GeneCure Biotechnologies; Vaxine Pty Ltd.) mRNA vaccines, viral vector vaccines, and protein subunit vaccines cannot cause disease because these vaccines stimulate the immune system to produce antibodies against virus proteins instead of the virus itself (or its antigen). MRNA vaccines increase SARS-CoV-2 proteins and ultimately stimulate the production of T and B lymphocytes. The epidemic of HCoVs and their destructive and harmful effects on life has caused the scientific community to seek the production of an effective and efficient vaccine before its catastrophic release. We all need to know that none of us will be healed until the other is healed. The purpose of this review article is to present a selection of existing knowledge in the field of fighting and preventing the coronavirus.


Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy.
The search for effective methods for detecting cancers at very early stages is currently a top priority of cancer research. While numerous oncogenes have been identified in and associated with human cancers, the last 50 years of molecular and genetic studies have not led to a breakthrough in either the diagnosis or the treatment of cancers. Therefore, the role of oncogenes in carcinogenesis is still unclear, as is their usefulness in the diagnosis of human cancers. In the present review, we discuss the concept of oncogenes and summarize the current approaches for the early detection of human cancers based on antibodies arrays.


Tumor necrosis factor alpha inhibits erythroid differentiation in human erythropoietin-dependent cells involving p38 MAPK pathway, GATA-1 and FOG-1 downregulation and GATA-2 upregulation.
The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) has been linked to inflammation- and cancer-related anemia, which reduces both quality of life and prognosis of patients. The aim of this study was to reveal molecular mechanisms linked to the inhibition of erythroid differentiation by TNFalpha. In this study, we showed that the inhibition of erythropoietin (Epo)-mediated differentiation by TNFalpha lead to a downregulation of hemoglobin synthesis and was correlated to a modulation of key erythroid transcription factors. Thus, a reverse of the transcription factor GATA-1/GATA-2 balance normally present during erythropoiesis, as well as a downregulation of the cofactor of GATA-1, friend of GATA-1 (FOG-1), and the coregulating transcription factor nuclear factor erythroid 2 (NF-E2) was observed after TNFalpha treatment. Moreover, we showed a reduction of GATA-1/FOG-1 interaction due to a reduced transcription of GATA-1 and a proteasome-dependent FOG-1 degradation after TNFalpha treatment. These changes led to an inhibition of erythroid gene expression including Epo receptor (EpoR), alpha- and gamma-globin, erythroid-associated factor (ERAF), hydroxymethylbilane synthetase (HMBS), and glycophorin A (GPA). An analysis of distinct signaling pathway activations then revealed an activation of p38 by TNF, as well as a corresponding involvement of this mitogen-activated protein kinase (MAPK) in the cytokine-dependent inhibition of erythroid differentiation. Indeed the p38 inhibitor, SB203580, abrogated the inhibitory effect of TNFalpha on the major erythroid transcription factor GATA-1 as well as erythroid marker expression in Epo-induced TF-1 cells. Overall, these data contribute to a better understanding of cytokine-dependent anemia, by giving first hints about key erythroid transcription factor modulations after TNFalpha treatment as well as an involvement of p38 in the inhibition of erythroid differentiation.


Cis and trans regulatory elements in NPHS2 promoter: implications in proteinuria and progression of renal diseases.
Podocin (NPHS2) expression in podocytes is associated with variable degrees of proteinuria and progression to renal failure in different glomerular diseases that suggests different expression profiles in NPHS2 promoter. Three functional polymorphisms in NPHS2 promoter (-51T, -116T, and -535 insCTTTTTT(3)) were found determining strong downregulation (-73, -59, and -82%, respectively) of the reporter gene expression when transfected in podocytes. Electrophoretic mobility shift assay experiments showed that all wild-type variants (-51G, -116C, and -535 insCTTTTTT(2)) formed specific DNA-protein complexes with podocyte nuclear extracts that were abolished by the presence of the rare forms (-51T, -116T, and -535 insCTTTTTT(3)). In the case of -51G, upstream stimulatory factor-1 (USF1) was identified as the specific trans element in accord to binding inhibition experiments and USF1 RNAi silencing. Haplotype analysis of 204 normal controls and 545 patients with renal diseases (308 immunoglobulin (Ig)A nephropathy and 237 focal segmental glomerulosclerosis) evidenced that -116/-51 and -535/P2OL formed two blocks in strong linkage disequilibrium in both normal and pathological cohorts. The high NPHS2 promoter profile -116C/-51G haplotype was more frequent in patients with IgA nephropathy (P-value=0.005) and was associated with a better clinical outcome in terms of proteinuria and creatinine levels. Overall our study describes functional variants of NPHS2 promoter and characterizes trans-acting elements that modulate podocin expression in the kidney. High producer NPHS2 promoter haplotypes seem protective in patients with chronic glomerular diseases.


A quantitative analysis of tumor specific monoclonal antibody uptake by human melanoma xenografts: effects of antibody immunological properties and tumor antigen expression levels.
The time-dependent (5 min-72 h) localization of 3 radiolabeled anti-melanoma monoclonal antibodies (MAbs 436, IND1, and 9.2.27) was studied in paired label experiments in small (4-12 mg) s.c. human melanoma xenografts (SK-MEL-2 and M21) in athymic nude mice. MAb 436 recognizes a Mr 125,000 cell surface melanoma-associated glycoprotein antigen (125 kDa-MAA); MAbs IND1 and 9.2.27 recognize a high molecular weight melanoma-associated antigen, but with equilibrium association constants differing by 2 orders of magnitude (10(8)-10(10) M-1). The two tumors were found to differ in their antigen expression levels and in both interstitial and vascular volumes. Accumulation of MAbs in both tumors was determined primarily by antigen expression levels and also by physiological factors such as vascular permeability and vascular volume; at the dose administered (20 micrograms/mouse), differences in MAb affinity among specific MAbs had minimal effect on accumulation. Quantitative flow cytometry measurements showed that antigen expression in vivo differed from that of cultured tumor cells. In vivo, expression of the Mr 125,000 MAA decreased by a factor of about 2.5 in both tumors. In contrast, the in vivo expression of the high molecular weight MAA decreased in M21 tumors but increased by 2.0-3.5-fold in SK-MEL-2 tumors. Data were analyzed using a three-compartment pharmacokinetic model (C. Sung et al., Cancer Res., 52:377-384, 1992) to provide plasma-to-tissue transport constants (k), the interstitial fluid flow rate (L), and estimates of the in vivo interstitial MAb binding site concentration (B0). For all MAbs, the plasma-to-tissue transport constants were consistently greater for M21 tumors (0.44-0.85 microliter/min/g) than for SK-MEL-2 tumors (0.28-0.66 microliter/min/g), and values of k for both tumors were approximately 1 order of magnitude greater than those for skeletal muscle (0.06-0.08 microliter/min/g). The model-estimated binding site concentration of melanoma-specific antibodies was 15-70 times lower than that predicted by experimental measurements of tumor antigen concentrations. Factors that may contribute to this discrepancy include inaccessibility of tumor cell binding sites to MAb and MAb catabolism. In summary, these results indicate that, for the MAb dose used in this study, variables pertaining to the tumor target (i.e., antigen expression levels, vascular volume, and vascular permeability) are the most important for determining MAb accumulation in tumors.


Iris-Claw Lens Implantation in a Patient with Iridoschisis.
BACKGROUND Iridoschisis is a rare condition defined as a separation of anterior iris stroma from the posterior stroma and muscle layers. The etiopathogenesis of iridoschisis is not fully understood. We report the case of uveitis-glaucoma-hyphema (UGH) syndrome related to the iris-claw lens implantation in a patient with iridoschisis, and propose an alternative approach to aphakia correction. CASE REPORT A 47-year-old male was referred to our department with bilateral iridoschisis, associated lens subluxation, mature cataract, and secondary glaucoma. The patient underwent bilateral surgery, with entirely different anterior segment results depending on the method of artificial lens implantation. To the best of our knowledge, iris-claw implantation in iridoschisis and the potential association of iridoschisis with increased risk of UGH syndrome, have not been reported previously. CONCLUSIONS Due to the possibly increased risk of UGH syndrome in patients with iridoschisis, one may consider treating aphakia by implantation of scleral fixated lenses, rather than iris-claw lenses.


Neural Correlates of Social Influence Among Cannabis Users.
Although peer influence is an important factor in the initiation and maintenance of cannabis use, few studies have investigated the neural correlates of peer influence among cannabis users. The current review summarizes research on the neuroscience of social influence in cannabis users, with the goal of highlighting gaps in the literature and the need for future research. Brain regions underlying peer influence may function differently in cannabis users. Compared to non-using controls, regions of the brain underlying reward, such as the striatum, show greater connectivity with frontal regions, and also show hyperactivity when participants are presented with peer information. Other subcortical regions, such as the insula, show hypoactivation during social exclusion in cannabis users, indicating that neural responses to peer interactions may be altered in cannabis users. Although neuroscience is increasingly being used to study social behavior, few studies have specifically focused on cannabis use, and therefore it is difficult to draw conclusions about social mechanisms that may differentiate cannabis users and controls. This area of research may be a promising avenue in which to explore a critical factor underlying cannabis use and addiction.


[Stability studies of sulfated polyguluronic acid ester].
To test the stability of marine polysaccharide drug sulfated polyguluronic acid ester. Four methods including high performance gel chromatography (HPGC), poly-acrylamide gel electrophoresis (PAGE), UV scan of absorbance between 200 and 800 nm and gelatin nephelometry were established. Samples were tested in high temperature, high humidity, strong light and accelerated test conditions. The methods were used to test the changes of the parameters including molecular weight, molecular weight distribution, absorbance between 200 and 800 nm, free sulfate, with which we could estimate the stability of sulfated polyguluronic acid ester could be estimated. The four methods were suitable to test the stability of sulfated polyguluronic acid ester and the sample were stable in the conditions as before except in high temperature. Sulfated polyguluronic acid ester has good stability.


Urinary tract infections in the era of newer immunosuppressant agents: a tertiary care center study.
We studied the incidence and the risk factors predisposing to post transplantation urinary tract infection (UTI) and the association with use of different immunosuppressive regimens. We performed a retrospective analysis of 152 recipients of renal transplantation over a period of two years. Seventy one (46.71%) patients had culture positive UTI, Escherichia coli (45.1%) being the commonest. Thirty four (22.39%) patients had acute rejection and 14.4% of those had suffered UTI in the early post transplant period. Immunosuppression included induction with various antibodies and maintenance on antirejection medications. Trimethoprim-sulphamethoxazole was given as prophylaxis throughout the period. The UTI was treated according to microbiological sensitivity. 2.8% died due to urosepsis. In our retrospective analysis renal transplant recipients under the age of 45, female gender and diabetics suffered more UTI. Combination therapy with micro-emulsion form of cyclosporine A, prednisolone and azathioprine developed more UTI (P= 0.0418).


Exploring a proposed WHO method to determine thresholds for seasonal influenza surveillance.
Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.


[Research progress of prediction of bacterial sRNA genes and their targets--a review].
Bacterial sRNAs are a class of non-coding RNAs with 40-500 nucleotides in length. Most of them function as posttranscriptional regulation of gene expression through binding to the translation initiation region of their target mRNAs. In view that prediction of sRNAs and their targets provides support for experimental identification, some prediction methods have been developed for both of them in recent years. In this review, we firstly gave an overview of methods for prediction of sRNA genes, which are classified into three categories, namely, comparative genomics-based, transcription units-based and machine learning-based prediction methods. Secondly, the methods for sRNA target prediction are classified into two types, which are sequence alignment-based method and prediction of RNA secondary structure-based method, respectively. Finally, the principles, advantages and limitations of each kind of method are discussed, and perspectives for prediction methods of sRNA and their targets is pointed out.


Homogeneous liquid-liquid extraction of rare earths with the betaine-betainium bis(trifluoromethylsulfonyl)imide ionic liquid system.
Several fundamental extraction parameters such as the kinetics and loading were studied for a new type of metal solvent extraction system with ionic liquids. The binary mixture of the ionic liquid betainium bis(trifluoromethylsulfonyl)imide and water shows thermomorphic behavior with an upper critical solution temperature (UCST), which can be used to avoid the slower mass transfer due to the generally higher viscosity of ionic liquids. A less viscous homogeneous phase and mixing on a molecular scale are obtained when the mixture is heated up above 55 °C. The influence of the temperature, the heating and cooling times, were studied for the extraction of neodymium(III) with betaine. A plausible and equal extraction mechanism is proposed in bis(trifluoromethylsulfonyl)imide, nitrate, and chloride media. After stripping of the metals from the ionic liquid phase, a higher recovery of the ionic liquid was obtained by salting-out of the ionic liquid fraction lost by dissolution in the aqueous phase. The change of the upper critical solution temperature by the addition of HCl or betaine was investigated. In addition, the viscosity was measured below and above the UCST as a function of the temperature.


Angiographic evaluation of flow distribution in sequential and composite arterial grafts for three vessel disease.
We sought to delineate the effects of the severity of target lesions and their combinations on the occurrence of competitive flow, especially in the composite Y-graft and to establish an optimal strategy for graft arrangement and patient selection. We reviewed early and late angiograms of 2514 bypass grafts in 601 patients, who underwent off-pump coronary revascularization to three-vessel vascular regions using the internal thoracic artery (ITA) and radial artery (RA) without aortic manipulation. As a standard technique, the left anterior descending artery (LAD) was bypassed with the in situ ITA, and the left circumflex and right coronary arteries (RCA) were bypassed with the composite RA. Bypass flow was graded as antegrade, competitive or no flow. The early patency rate was 98.1% (2466/2514), while competitive flow was detected in 6.4% (162/2514). For the LAD, the individual and sequential in situ ITA provided lower incidence of competitive flow than the composite graft (0.3% (1/298) versus 7.6% (23/303), P < 0.0001). Regarding the RA to non-LAD bypass, 86.3% (113/131) of competitive flow occurred at the distal end of the I- or Y-graft, and the cumulative patency rate was significantly lower than that of sequential proximal anastomosis (80.1 versus 56.6% at 5 years, P < 0.0001). The number of sequential anastomoses did not affect the cumulative patency rate (P = 0.09). For the composite Y-graft to three-vessel regions, the rate of antegrade flow in patients with 76-100% stenosis in both the LAD and the RCA was 95.7% (178/186), which was significantly higher than that of 78.1% (100/128) in patients with 76-100% stenosis in the LAD and 51-75% stenosis in RCA (P < 0.0001). Sequential and composite grafting was considered reliable, exclusively in appropriately selected situations. To secure entire patency of the Y-graft to three-vessel regions, balanced bypass flow toward LAD and RCA would be crucial.


Pathological features and prognosis of lobular carcinoma in Egyptian breast cancer patients.
To illustrate the differences between invasive lobular and ductal carcinomas (ILCs and IDCs) in terms of baseline demographics, pathologic features and recurrence in Egyptian breast cancer patients. Retrospective analysis of breast cancer patients diagnosed and treated between 2000 and 2008 was performed. 176 (8.5%) and 1758 (85%) cases were diagnosed with ILC and IDC, respectively. Compared with IDC, ILC was less observed in patients under 35 years of age (3.4 vs 9.3%; p = 0.009), and was associated with more bilaterality (p = 0.001), advanced tumor stage (p = 0.027) and nodal involvement (p = 0.004). On the other hand, IDC was significantly associated with more luminal B-like phenotype (16.9 vs 8.1%; p < 0.001) and more HER2-enriched disease (11.5 vs 2.7%; p < 0.001). At a median follow-up time of 64 months, ILC histology was independently associated with better disease-free survival (hazard ratio: 0.58; 95% CI: 0.36-0.93; p = 0.023). Bone and peritoneal relapses were more common in ILC, while lung relapses were more common in IDC. ILC has distinct biologic and prognostic features that may warrant different therapeutic approaches.


Aspects of the use of endosseous palatal implants in orthodontic therapy.
Control of anchorage is one of the fundamental aspects in orthodontics and dentofacial orthopedics. Osseointegrated implants provide such an anchorage in a reliable fashion, as has been demonstrated in orthodontic use of dental implants inserted for prosthetic reasons. More recently, special implants have been introduced that serve as temporary anchorage in orthodontics. One example is the Straumann Orthosystem (Institut Straumann AG, Waldenburg, Switzerland), which is inserted in the midsagittal area of the palate. Owing to the reduced bone height available in the palate, only short implants should be considered; surface enlargement by texturing and the achievement of good primary stability are prerequisite for success. The use of a palatal implant provides a continuous stable anchorage for patients with compromised periodontal anchorage potential, as well as in cases in which compliance is not dependable or cases with esthetic considerations in which the use of extraoral anchorage aids or Class II elastics may be problematic. Minimal stress on the patient, combined with maximal anchorage, distinguishes this promising new treatment modality for the orthodontist cooperating with an oral surgeon. The treatment concept is well aligned with the emphasized need for integral treatment in dentistry, especially of the adult patient.


Intracellular characterization of song-specific neurons in the zebra finch auditory forebrain.
Auditory neurons in the forebrain nucleus HVc (hyperstriatum ventrale pars caudale) are highly sensitive to the temporal structure of the bird's own song. These "song-specific" neurons respond strongly to forward song, weakly to the song with the order of the syllables reversed, and little or not at all to reversed song. To investigate the cellular mechanisms underlying these responses, in vivo intracellular recordings were made from adult HVc neurons. Song-specific cells could be divided into those that responded strongly throughout autogenous song (tonic cells) and those that responded with bursts of action potentials at specific points during the song (phasic cells). Phasic cells were hyperpolarized during autogenous song, even though this stimulus also elicited the strongest response. Less hyperpolarization was seen to the same song with the syllables in reverse order, and none was seen to reversed song. The responses of both types of song-specific cells contained high-frequency bursts of action potentials. The bursts of the phasic cells showed attenuation of the action potential height and lack of full repolarization after each spike. This type of bursting was significantly correlated with the amount of hyperpolarization before each burst in phasic cells and nonauditory cells that generated such bursts spontaneously. These data suggest that song-specific neurons use longlasting hyperpolarization as a mechanism to integrate auditory context, an important component of temporal order selectivity. Hyperpolarization also may increase the precision of spike timing, which could be important for the neural code subserving song learning and production.


A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice.
Gene targeting in mouse embryonic stem (ES) cells can be used to generate single gene mutations or defined multi-megabase chromosomal rearrangements when applied with the Cre- loxP recombination system. While single knockouts are essential for uncovering functions of cloned genes, chromosomal rearrangements are great genetic tools for mapping, mutagenesis screens and functional genomics. The conventional approach to generate mice with targeted alterations of the genome requires extensive molecular cloning to build targeting vectors and DNA-based genotyping for stock maintenance. Here we describe the design and construction of a two-library system to facilitate high throughput gene targeting and chromo-somal engineering. The unique feature of these libraries is that once a clone is isolated, it is essentially ready to be used for insertional targeting in ES cells. The two libraries each bear a complementary set of genetic markers tailored so that the vector can be used for Cre- loxP -based chromosome engineering as well as single knockouts. By incorporating mouse coat color markers into the vectors, we illustrate a widely applicable method for stock maintenance of ES cell-derived mice with single gene knockouts or more extensive chromosomal rearrangements.


B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis.
Human endothelial cells (ECs) provide costimulatory signals sufficient to activate resting memory T cells to produce IL-2 and IFN-gamma, at least in part through CD58-CD2 interactions. Recently, the B7-like molecule, B7-H1 (PD-L1), was described and shown to regulate T cell activation; however, there are conflicting reports on whether it stimulates or inhibits T cell cytokine synthesis. B7-H1 is not expressed constitutively by ECs; however, it is rapidly induced by IFN-gamma, and synergistically by IFN-gamma and TNF. In inflamed skin, B7-H1 is expressed by a subset of microvessels, and by keratinocytes, but is barely detectable in normal skin. Blocking the interaction of EC-expressed B7-H1 with its T cell ligand, programmed death-1 (PD-1), using a PD-1-Fc fusion protein, or by blocking B7-H1 expression with morpholino antisense oligonucleotides, augments expression of IL-2 and IFN-gamma, implicating B7-H1 as a negative regulator of cytokine synthesis. However, signaling through PD-1 does not affect induction of the activation markers CD25 or CD69 on T cells, suggesting that its effects are specific to cytokine synthesis. The suppressive effects of B7-H1 on cytokine expression are proportional to the strength of the primary stimulus, allowing for B7-H1 to determine the level of T cell activation in response to ECs. Our results demonstrate that B7-H1 negatively regulates cytokine synthesis in T cells activated by ECs.


Chronic administration of estradiol produces a triphasic effect on serum concentrations of gonadotropins and messenger ribonucleic acid for gonadotropin subunits, but not on pituitary content of gonadotropins, in ovariectomized ewes.
To determine the acute and chronic effects of estradiol on synthesis and secretion of LH and FSH, ovariectomized ewes were administered estradiol via silastic capsules for 0 h, 12 h, 1 day, 2 days, 4 days, 8 days, 16 days, or 32 days (n = 5/group). Concentrations of GnRH in the median eminence began to decrease within 12 h and were lower (p less than 0.05) than in control ewes from 1 to 4 days after estradiol administration was begun. Serum concentrations of LH were decreased relative to pretreatment control levels from 1 to 10 h, elevated during a preovulatory-like surge from 11 to 22 h, and then decreased and remained below 1 ng/ml for the duration of the experiment. Serum concentrations of FSH followed a pattern similar to those for LH except that the magnitude of change was smaller. Treatment with estradiol initially (12 h) reduced (p less than 0.05) quantities of mRNA for alpha-, LH beta-, and FSH beta-subunits, after which the quantities of mRNA for the subunits returned to near or above control levels by Day 2. After 8 days of treatment the amounts of mRNAs for gonadotropin subunits were again less (p less than 0.05) than those of controls, and they remained suppressed through Day 32. Pituitary concentrations of LH and FSH decreased (p less than 0.05) during the first day of treatment and remained suppressed for the duration of the experiment. Thus, estradiol had a triphasic effect on secretion of gonadotropins and steady-state levels of mRNA for the gonadotropin subunits, but not on pituitary content of gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)


Echocardiographic predictors of successful versus unsuccessful mitral valve repair in ischemic mitral regurgitation.
Mitral valve (MV) annuloplasty is the standard surgical technique for the management of ischemic mitral regurgitation (MR). However, < or = 1/3 of patients develop recurrent MR after annuloplasty. Therefore, we sought to identify the preoperative echocardiographic parameters that predict annuloplasty failure in patients with ischemic MR. Intraoperative transesophageal echocardiograms from 365 patients who underwent MV repair for ischemic MR were reviewed. Of the 365 patients, 297 (81%) had satisfactory outcomes with < 2+ MR, and 68 (19%) had recurrent MR (> or = 2+) during a mean follow-up of 269 days. The mitral annular parameters, including mitral annular diameter, tethering height, and tethering area of the mitral leaflets, were determined in 3 different echocardiographic views. On multiple logistic stepwise regression analysis, a higher mitral annular diameter, higher tethering area, and higher MR severity were identified as independent predictors for failure of MV repair (p < 0.0001). In conclusion, these results demonstrated that preoperative echocardiographic findings can be used to identify patients with ischemic MR at increased risk of repair failure. These echocardiographic measurements should be used to guide the cardiologist and cardiac surgeon in the choice of MV repair versus replacement in patients with ischemic MR.


Epinephrine effects on insulin-glucose dynamics: the labeled IVGTT two-compartment minimal model approach.
The hyperglycemic effects of epinephrine (Epi) are established; however, the modulation of Epi-stimulated endogenous glucose production (EGP) by glucose and insulin in vivo in humans is less clear. Our aim was to determine the effect of exogenously increased plasma Epi concentrations on insulin and glucose dynamics. In six normal control subjects, we used the labeled intravenous glucose tolerance test (IVGTT) interpreted with the two-compartment minimal model, which provides not only glucose effectiveness (S(G)(2*)), insulin sensitivity (S(I)(2*)), and plasma clearance rate (PCR) at basal state, but also the time course of EGP. Subjects were randomly studied during either saline or Epi infusion (1.5 microg/min). Exogenous Epi infusion increased plasma Epi concentration to a mean value of 2,034 +/- 138 pmol/l. During the stable-label IVGTT, plasma glucose, tracer glucose, and insulin concentrations were significantly higher in the Epi study. The hormone caused a significant (P < 0.05) reduction in PCR in the Epi state when compared with the basal state. The administration of Epi has a striking effect on EGP profiles: the nadir of the EGP profiles occurs at 21 +/- 7 min in the basal state and at 55 +/- 13 min in the Epi state (P < 0.05). In conclusion, we have shown by use of a two-compartment minimal model of glucose kinetics that elevated plasma Epi concentrations have profound effects at both hepatic and tissue levels. In particular, at the liver site, this hormone deeply affects, in a time-dependent fashion, the inhibitory effect of insulin on glucose release. Our findings may explain how even a normal subject may have the propensity to develop glucose intolerance under the influence of small increments of Epi during physiological stress.


Mechanisms of Binding of Antimicrobial Peptide PGLa to DMPC/DMPG Membrane.
PGLa belongs to a class of antimicrobial peptides showing strong affinity to anionic bacterial membranes. Using all-atom explicit solvent replica exchange molecular dynamics with solute tempering, we studied binding of PGLa to a model anionic dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) bilayer. Due to a strong hydrophobic moment, PGLa upon binding adopts a helical structure and two distinct bound states separated by a significant free energy barrier. In these states, the C-terminus helix is either surface bound or inserted into the bilayer, whereas the N-terminus remains anchored in the bilayer. Analysis of the free energy landscape indicates that the transition between the two states involves a C-terminus helix rotation permitting the peptide to preserve the interactions between cationic Lys amino acids and anionic lipid phosphorus groups. We calculated the free energy of PGLa binding and showed that it is mostly governed by the balance between desolvation of PGLa positive charges and formation of electrostatic PGLa-lipid interactions. PGLa binding induces minor bilayer thinning but causes pronounced lipid redistribution resulting from an influx of DMPG lipids into the binding footprint and efflux of DMPC lipids. Our in silico results rationalize the S-state detected in NMR experiments.


[Guizhi Fuling capsule / pill treatment for chronic pelvic inflammatory disease:a systematic review of randomized clinical trials].
This systematic review aims to systematically evaluate the efficacy and safety of Guizhi Fuling Capsule/Pill on the treatment of chronic pelvic inflammatory disease. We searched CNKI datebases,WanFang,SinoMed,PubMed,Embase,The Cochrane Library from the inception to February 2017,to collect randomized controlled trials(RCTs)of Guizhi Fuling Capsule/Pill in treating chronic pelvic inflammation disease.Two reviewers independently screened literature,extracted date and assessed the risk of bias of included studies.Then,the risk assessment of included references was evaluated according to criteria recommended by Cochrane Handbook 5.3.A total of 30 RCTs involving 3 586 patients were finally included.30 studies reported the clinical efficacy,the result of meta-analysis showed that:compared with the western medicine group,Guizhi Fuling (capsule,pill) combined with western medicine could significantly improve the clinical efficacy [RR=1.20,95%CI(1.16,1.23)];3 studies reported recurrence rate,the result of meta-analysis showed that:compared with the western medicine,Guizhi Fuling (capsule,pill) combined with western medicine could decrease the recurrence rate [RR=0.33,95%CI(0.18,0.62)]; Their secondary indicators mainly included hs-CRP, plasma viscosity ratio and tumor necrosis factor and fibrin,the result of meta-analysis showed that: Guizhi Fuling (capsule,pill) combined with western medicine was better than western medicine in terms of anti-inflammatory and improving blood circulation.17 studies reported adverse reactions,most of the adverse events were the irritation of gastrointestinal tract. The result showed that: compared with the western medicine group, the incidence of adverse reactions in Guizhi Fuling (capsule,pill) combined with western medicine group is low.Guizhi Fuling(capsule,pill) did not increase the adverse reactions. The available evidence suggests that: Guizhi Fuling(capsule, pill) compared with the western medicine group, Guizhi Fuling (capsule,pill) combined with western medicine was more effective than the western medicine group in terms of clinical efficacy, recurrence rate, anti-inflammatory and plasma viscosity.Due to the limited quality and quantity of included studies,more high quality RCTs are needed to verify the above conciusion.


Correlation of multiple proteins with clinic-pathological features and its prognostic significance in colorectal cancer with signet-ring cell component.
Primary colorectal cancer (CRC) with signet-ring cell (SRC) component is a distinct tumor of colon and rectum, and its prognosis is very poor. Reliable markers to predict the poor clinical outcome of this subgroup cancer remains undetermined. Therefore, we perform this study to investigate the prognosis value of seven proteins in CRC with SRC component . This study involved 117 patients diagnosed with CRC with SRC component between January 2008 and August 2015 at Fudan University Shanghai Cancer Center. The samples from these patients were analyzed by immunohistochemistry to reveal the expression levels of p53, p21, E-cadherin, COX-2 (Cyclo-oxygenase-2), Bcl-2, CD44 and Ki-67. Kaplan-Meier analysis and log-rank testing were performed to estimate survival. Subsequently, a Cox proportional hazard model was used to calculate hazard ratios for the risk of death. The p21, p53, COX-2, E-cadherin, Bcl-2, CD44 and Ki-67 expression were detected in 60.5%, 61.3%, 69.7%, 68%, 28.6%, 62.2% and 75.6% of the samples, respectively. The positive expression of p53 (p=0.017) and the negative expression of COX-2 (p=0.001) or E-cadherin (p=0.047) in CRC with SRC component were significantly associated with decreased overall survival, but the other expression levels were not. In a multivariate analysis, the negative expression of COX-2 was found to be an independent prognostic factor for poorer overall survival (hazard ratio, 0.37; 95% confidence interval, 0.19 to 0.75, p=0.003) CONCLUSIONS: The COX-2 positive expression in CRC patients with SRC component had a poorer outcome than patients who were COX-2-negative. Therefore, COX-2 could be considered as an indicator for appropriate treatment and intensive follow-up in these subgroup patients.


Suicide among AIDS patients.
I studied 25 cases of suicide in people diagnosed as having the acquired immunodeficiency syndrome (AIDS) or who thought that they had that disorder, during 1985-1989. Case reports are presented. A discussion ensues concerning the occurrence of this phenomenon and the medical examiner's role in AIDS' public health situation in general.