Quantification of iprodione in dry basil using silica gel supported titanium dioxide.
Iprodione is an agricultural fungicide that is difficult to detect in foods by HPLC because it coelutes with natural compounds in the food. We previously showed that food matrix could be degraded with titanium dioxide powder (TP). Here we describe an improved method for detection of iprodione using silica gel supported titanium dioxide (SGT). To synthesize SGT, titania-sol was mixed with diethanolamine, 2-propanol, and titanium tetraisopropoxide. After titania-sol was infiltrated into the silica gel (particle diameter 4 mm), the mixture was dried and then heated. Crude basil extract containing iprodione was mixed with SGT in a quartz vial, and the vial was irradiated with a UV light to selectively decompose the matrix interfering with the iprodione determination. In HPLC chromatograms of the treated solution, the interference peak decreased 35 times faster with SGT than with TP. When SGT (11 g) was added to the extract (20 mL) of dry basil (2 g), black light irradiation for 30 min was enough to quantify iprodione. The recovery rate of iprodione was 99.1%. Thus, the photocatalytic cleanup method using SGT is effective for analyzing residual iprodione in dry basil.


Pharmacokinetic and pharmacodynamic effects of UK-68,798, a new potential class III antiarrhythmic drug.
1. The pharmacokinetic and pharmacodynamic properties of UK-68,798, a novel selective potential class III antiarrhythmic agent, were studied in 18 patients with coronary artery disease. Three groups of four patients received intravenous doses of 1.5, 3.0 and 4.5 micrograms kg-1 respectively over 10 min. 2. UK-68,798 caused a mean increase in electrocardiographic QTc interval of 41, 40 and 81 ms, and in uncorrected QT interval of 36, 52 and 83 ms at the three dose levels. There were no significant effects on heart rate, blood pressure, PR interval and QRS duration. UK-68,798 was well tolerated with no significant adverse effects. 3. A dosing regimen using a loading infusion of two thirds of the total dose over 15 min with the remainder given over the following 45 min in six patients produced stable plasma concentrations and lengthening in QTc during the maintenance infusion. 4. There was a linear correlation between plasma concentration and change in QTc. The drug exhibited first-order kinetics with a mean clearance of 4.7 +/- 1.2 ml min-1 kg-1 and a mean terminal plasma half-life of 9.7 h. 5. UK-68,798 warrants further study as a selective potential Class III antiarrhythmic agent.


CTLA-4 (CD152) gene polymorphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region.
Graves' disease ((GD)is an autoimmune disease believed to be caused by a combination of environmental and genetic factors. The gene encoding cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)is one of the candidate genes for conferring susceptibility to thyroid autoimmunity. he aim of the study was to investigate the association between the exon 1 CTLA-4 gene polymorphism A(49)G and susceptibility to GD and Graves ' ophthalmopathy (GO)as well as its severity in a Polish population of the Lower Silesia region. We analyzed the A(49)G exon 1 CTLA-4 gene polymorphism in 99 unrelated Polish patients with GD, of whom 50 had clinically evident GO (NOSPECS class III and higher), and 154 matched healthy subjects from the Lower Silesia region. Genomic DNA was isolated from whole frozen blood using the NucleoSpin Blood kit. A/G transition was genotyped by polymerase chain reaction followed by labeling with the SnaPshot kit of PE Applied Biosystems and detected using an ABI PRISM 310 capillary genetic analyzer. The distribution of CTLA-4 exon 1 A(49)G enotype, allele, and phenotypic frequencies did not differ between patients with GD and healthy subjects. There was a significantly lower frequency of the AA genotype in the group of patients with clinically evident GO than in patients without severe GO (22% vs. 43%; p=0.02, OR=2.6). Our results showed that the AA genotype in patients with GD is associated with a lower risk of GO severity.


MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma.
microRNAs (miRNAs), small non-coding RNAs, are always aberrantly expressed in many diseases including human cancers. The aim of this study was to examine and determine the clinical significance of hsa-miR-31, hsa-miR-142-3p, hsa-miR-338-3p, and hsa-miR-1261 expression in esophageal squamous cell carcinoma (ESCC). Expression levels of four selected miRNAs, initially evaluated by microarray, were validated by qRT-PCR. Various statistical methods were used to analyze the relationship between miRNA expression and clinicopathologic features and prognosis in 91 patients with ESCC. MiR-31 and miR-142-3p expression were correlated to histological differentiation in ESCC (P < 0.05, Student's t-test); high miR-142-3p expression was associated with a poor prognosis in all 91 ESCC patients (P = 0.014, log-rank) and identified as an independent prognostic factor in ESCC (P = 0.017, univariate Cox; P = 0.022, multivariate Cox). More importantly, stratified analysis indicated that high miR-142-3p expression was correlated to a poor prognosis within good-prognosis groups comprised of ESCC patients with small tumor size, negative lymph node metastasis, or early stage (all P < 0.05). The main findings suggest that miR-142-3p is involved in the progression of ESCC and is a potential prognostic biomarker for ESCC.


Oscillatory concentration pulses of some divalent metal ions induced by a redox oscillator.
Oscillations in the concentration of divalent ions Cd(2+), Ca(2+), Zn(2+), Co(2+) and Ni(2+) are induced by adding these species to the BrO(3)(-)-SO(3)(2-) chemical oscillator in a flow reactor. Producing periodic pulses in the concentrations of these non-redox ions extends our earlier approach to generating forced periodic behavior. Instead of driving pH-dependent equilibrium reactions of the target ion by a pH oscillator backward and forward, we now couple a redox core oscillating reaction to two consecutive reactions taking place between the components of the oscillator and the target element. In the systems examined here, the oscillatory reductant SO(3)(2-) binds the free metal ion in a MSO(3) precipitate, reducing its level to a minimal value when [SO(3)(2-)] is high, followed by release of the metal ion when the sulfite is oxidized by BrO(3)(-).


Mitochondrial Activity and Ethanol Accumulation in Ice-encased Winter Cereal Seedlings.
Cold-hardened dark-grown seedlings of winter wheat (Triticum aestivum L.) and winter rye (Secale cereale L.) are killed during total encasement in ice at -1 C at a rate related to the initial cold hardiness of the cultivars. Few plants remain alive after 7 days of encasement. Nonhardened seedlings are rapidly killed in ice. The respiratory properties of mitochondria isolated from plants after increasing periods of ice encasement decline slowly, and activity is little impaired when intact plants are about 50% killed. Electron microscopy indicates that mitochondrial structure is not disrupted until 3 weeks of ice encasement. Ethanol accumulates in hardened and nonhardened plants in ice, but at levels which are not toxic to the plants.


Guidelines for Collection of Biological Samples for Clinical and Forensic Toxicological Analysis.
This article aims to review general procedures for sampling of routinely collected as well as on alternative samples that may provide additional information regarding intoxication. These approaches may be applied whenever sample collection for clinical and forensic toxicology is required and should be considered as general guidelines that must be adapted to each specific case. It is expected that this article will help toxicologists and other forensic experts to accomplish their mission, since the toxicological result is first influenced by the quality and quantity of the sample available for analysis. These guidelines were approved by the European Council of Legal Medicine.


[Frontier migration and employment: facts and questions].
"Frontier labor migration in Argentina is closely linked with poverty and social exclusion.... The first part of this article concerns the impact of frontier migrants in the urban labor market on the basis of information collected by the Permanent Household Survey (EPH) in October 1993 and October 1994 in Greater Buenos Aires area, where, as per the last Population Census, over 50% of residents from frontier countries are settled. The second part focuses on the case study of Bolivian migrant workers who have found their own place in Argentine markets...in the field of vegetable-growing in the green belts surrounding bigger cities, sometimes including peddling of their product in urban areas by female family members." (SUMMARY IN ENG)


Enhanced Anti-Brain Metastasis from Non-Small Cell Lung Cancer of Osimertinib and Doxorubicin Co-Delivery Targeted Nanocarrier.
Currently, the treatment of brain metastases from non-small cell lung cancer (NSCLC) is rather difficult in the clinic. A combination of small molecule-targeted drug and chemo-drug is a promising therapeutic strategy for the treatment of NSCLC brain metastases. But the efficacy of this combination therapy is not satisfactory due to the blood-brain barrier (BBB). Therefore, it is urgent to develop a drug delivery system to enhance the synergistic therapeutic effects of small molecule-targeted drug and chemo-drug for the treatment of NSCLC brain metastases. T7 peptide installed and osimertinib (AZD9291) loaded intracellular glutathione (GSH) responsive doxorubicin prodrug self-assembly nanocarriers (T7-DSNPs/9291) have been developed as a targeted co-delivery system to enhance the combined therapeutic effect on brain metastases from NSCLC. In vitro cell experiments, including intracellular uptake assay, in vitro BBB transportation, and MTT assay were used to demonstrate the efficacy of T7-DSNPs/9291 in NSCLC brain metastasis in vitro. Real-time fluorescence imaging analysis, magnetic resonance imaging analysis, and Kaplan-Meier survival curves were used to study the effect of T7-DSNPs/9291 on an animal model in vivo. T7-DSNPs/9291 could significantly enhance BBB penetration of AZD9291 and doxorubicin via transferrin receptor-mediated transcytosis. Moreover, T7-DSNPs/9291 showed significant anti-NSCLC brain metastasis effect and prolonged median survival of an intracranial NSCLC brain metastasis animal model. T7-DSNPs/9291 is a potential drug delivery system for the combined therapy of brain metastasis from NSCLC.


Bimodal Response to Shiga Toxin 2 Subtypes Results from Relatively Weak Binding to the Target Cell.
There are two major antigenic forms of Shiga toxin (Stx), Stx1 and Stx2, which bind the same receptor and act on the same target but nonetheless differ in potency. Stx1a is more toxic to cultured cells, but Stx2 subtypes are more potent in animal models. To understand this phenomenon in cultured cells, we used a system that combines flow cytometry with a fluorescent reporter to monitor the Stx-induced inhibition of protein synthesis in single cells. We observed that Vero cells intoxicated with Stx1a behave differently than those intoxicated with Stx2 subtypes: cells challenged with Stx1a exhibited a population-wide loss of protein synthesis, while cells exposed to Stx2a or Stx2c exhibited a dose-dependent bimodal response in which one subpopulation of cells was unaffected (i.e., no loss of protein synthesis). Cells challenged with a hybrid toxin containing the catalytic subunit of Stx1a and the cell-binding subunit of Stx2a also exhibited a bimodal response to intoxication, while cells challenged with a hybrid toxin containing the catalytic subunit of Stx2a and the cell-binding subunit of Stx1a exhibited a population-wide loss of protein synthesis. Other experiments further supported a primary role for the subtype of the B subunit in the outcome of host-Stx interactions. Our collective observations indicate that the bimodal response to Stx2 subtypes is due to relatively weak binding between Stx2 and the host cell that reduces the total functional pool of Stx2 in comparison to that of Stx1a. This explains, in part, the molecular basis for the differential cellular toxicity between Stx1a and Stx2 subtypes.


Treatment-induced changes in tumor oxygenation predict photodynamic therapy outcome.
Photodynamic therapy (PDT) requires oxygen to cause tumor damage, yet therapy itself can deplete or enhance tumor oxygenation. In the present work we measured the PDT-induced change in tumor oxygenation and explored its utility for predicting long-term response to treatment. The tissue hemoglobin oxygen saturation (SO(2)) of murine tumors was noninvasively measured by broadband diffuse reflectance spectroscopy. In initial validation studies, the oxyhemoglobin dissociation curve for mouse blood was accurately recreated based on measurements during deoxygenation of a tissue phantom of mouse erythrocytes. In vivo studies exhibited excellent correlation between carbogen-induced changes in SO(2) and pO(2) of radiation-induced fibrosarcoma tumors measured by reflectance spectroscopy and the Eppendorf pO(2) histograph, respectively. In PDT studies radiation-induced fibrosarcoma tumor SO(2) was measured immediately before and after Photofrin-PDT (135 J/cm(2), 38 mW/cm(2)). Animals were subsequently followed for tumor growth to a volume of 400 mm(3) (time-to-400 mm(3)) or the presence of tumor cure (no tumor growth at 90 days after treatment). In animals that recurred, the PDT-induced change in tumor SO(2), i.e., relative-SO(2) (SO(2) after PDT/SO(2) before PDT) was positively correlated with treatment durability (time-to-400 mm(3)). The predictive value of relative-SO(2) was confirmed in a second group of animals with enhanced pre-PDT oxygenation due to carbogen breathing. Furthermore, when all of the animals were considered (those that recurred and those that were cured) a highly significant association was found between increasing relative-SO(2) and increasing probability of survival, i.e., absence of recurrence. As independent variables, the SO(2) after PDT, the pre-PDT tumor volume, and light penetration depth all failed to predict response. As an independent variable, the SO(2) before PDT demonstrated a weak negative association with treatment durability; this association was driven by a correlation between decreasing pre-PDT SO(2) and increasing relative-SO(2). These data suggest that monitoring of PDT-induced changes in tumor oxygenation may be a valuable prognostic indicator.


Bombesin stimulates adhesion, spreading, lamellipodia formation, and proliferation in the human colon carcinoma Isreco1 cell line.
The neuropeptide bombesin and its mammalian homologue, gastrin-releasing peptide (GRP), enhance proliferation in some but not all human tumor cell lines. The pathophysiological relevance of the bombesin/GRP receptor (GRP-R), which is expressed in 30% of human colon tumor cell lines and in 24-40% of native tumors, has not been clearly assessed at this time. We studied the effects of bombesin in the recently characterized human colon carcinoma Isreco1 cell line. Competitive reverse transcription-PCR showed a high GRP-R mRNA level in Isreco1 cells, and binding studies confirmed the expression of bombesin/GRP-subtype receptors (Kd = 0.42 nM; Bmax = 18,000 sites/cell). Exposure to bombesin resulted in an increase of intracellular calcium concentrations. Bombesin (1 nM) induced cell spreading at 24 h (21.7+/-1.6% versus 6.4+/-0.8% in control cells; P<0.01) and markedly increased the formation of lamellipodia. In addition, adhesion of Isreco1 cells to collagen I-coated culture dishes was stimulated in the presence of 1 nM bombesin (69+/-6% versus 42+/-1% in control cells; P<0.01). Finally, bombesin significantly increased [3H]thymidine uptake by Isreco1 cells in a dose-dependent manner, with a first significant response at 0.1 nM and a maximal effect at 100 nM bombesin (192.2+/-9.7% of control). These results clearly indicate that bombesin exerts morphological, adhesive, and proliferative effects on Isreco1 cells, suggesting that expression of the bombesin/GRP-R may contribute to the malignant properties of colon carcinoma cells.


Changes in cerebrospinal fluid enzyme activity after severe head injury. Diagnostic and prognostic values.
We studied CSF CK and LDH isoenzyme activities in 27 patients with severe head injury and in 10 patients with chronic hydrocephalus not related to trauma. CSF enzymes showed an increased activity immediately after trauma, contrasting with the low values measured in the patients with hydrocephalus. In severe head injury, we found a correlation between enzyme release and brain dysfunction assessed according to two methods: the Glasgow coma scale (GCS), and the Liège coma scale (LCS) which uses elements of the GCS and the study of 5 brain stem reflexes. The correlation between enzyme activity and the Liège coma scores is better than that observed with the Glasgow coma scores. High enzyme activity is associated with a bad outcome at six months. It has a prognostic value on so far as it reflects the severity of traumatic structural brain damage.


Patterns of CRISPR/Cas9 activity in plants, animals and microbes.
The CRISPR/Cas9 system and related RNA-guided endonucleases can introduce double-strand breaks (DSBs) at specific sites in the genome, allowing the generation of targeted mutations in one or more genes as well as more complex genomic rearrangements. Modifications of the canonical CRISPR/Cas9 system from Streptococcus pyogenes and the introduction of related systems from other bacteria have increased the diversity of genomic sites that can be targeted, providing greater control over the resolution of DSBs, the targeting efficiency (frequency of on-target mutations), the targeting accuracy (likelihood of off-target mutations) and the type of mutations that are induced. Although much is now known about the principles of CRISPR/Cas9 genome editing, the likelihood of different outcomes is species-dependent and there have been few comparative studies looking at the basis of such diversity. Here we critically analyse the activity of CRISPR/Cas9 and related systems in different plant species and compare the outcomes in animals and microbes to draw broad conclusions about the design principles required for effective genome editing in different organisms. These principles will be important for the commercial development of crops, farm animals, animal disease models and novel microbial strains using CRISPR/Cas9 and other genome-editing tools.


The Importance of Providing Play and Learning Materials for Children with Physical Disabilities in Saudi Arabia: The Perceptions of Parents.
The purposes of this exploratory, qualitative research are to (a) examine the parental role in providing materials to facilitate learning and play for children with physical disabilities, and (b) identify the difficulties expressed by parents that affect the support provided to their children with physical disabilities. We conducted semi-structured interviews with 21 Saudi Arabian parents of children with physical disabilities to identify the parental role in providing play and learning materials as well as the challenges identified by parents in providing this support. Parents recommended that they initiate and maintain contact with other parents of children with physical disabilities and with associated organisations. Parents also recommended that teachers welcome parents to be involved in support of their children with physical disabilities, especially in the provision of play and learning materials. The authors conclude that disability awareness programs for peers and staff members may improve physical and psychological health for children with physical disabilities.


Primary melanoma of the prostate: case report and review of the literature.
Primary melanoma of the prostate has an extremely rare incidence. Only five cases have been reported in the literature and prognosis is poor. The most likely origin of prostatic melanoma is the transitional epithelium of the prostatic urethra. Surgical care for primary melanoma of mucosal sites is less well established than for primary cutaneous melanoma, but excision of the primary is recommended if the patient has no systemic disease. Here, we describe a case of primary malignant melanoma of the prostate. A 37-year-old male patient with history of both chemo- and radiation therapy for Hodgkin's disease was admitted to the University Hospital Heidelberg on suspicion of pleomorphic sarcoma of the bladder. In-house diagnostic work-up revealed a malignant melanoma of the prostate. We then performed radical prostatectomy with extended lymphadenectomy. Despite presumably curative surgery, the patient suffered from early relapse of disease with pulmonary metastasis. Systemic chemotherapy and subsequent immuno-oncologic treatment was thereafter initiated. Since prostatic melanoma is a rare disease and a melanoma metastasis of unknown primary is the differential diagnosis, a multidisciplinary approach including early imaging to rule out possible metastases and to search for another potentially existing primary is advisable. To prevent complications related to local tumor progression and to receive tissue for mutational analysis, we recommend complete surgical resection to reduce the tumor mass. Novel immune and targeted oncologic therapies can lead to an improved survival in some cases and support of clinical trials is needed.


Evolution of fucosyltransferase genes in vertebrates.
Cloning and expression of chimpanzee FUT3, FUT5, and FUT6 genes confirmed the hypothesis that the gene duplications at the origin of the present human cluster of genes occurred between: (i) the great mammalian radiation 80 million years ago and (ii) the separation of man and chimpanzee 10 million years ago. The phylogeny of fucosyltransferase genes was completed by the addition of the FUT8 family of alpha(1,6)fucosyltransferase genes, which are the oldest genes of the fucosyltransferase family. By analysis of data banks, a new FUT8 alternative splice expressed in human retina was identified, which allowed mapping the human FUT8 gene to 14q23. The results suggest that the fucosyltransferase genes have evolved by successive duplications, followed by translocations, and divergent evolution from a single ancestral gene.


A DNAzyme-based label-free fluorescent probe for guanosine-5'-triphosphate detection.
Guanosine-5'-triphosphate (GTP) plays a key role in many important biological processes of cells. It is not only a primer for DNA replication and one of the four essential nucleoside triphosphates for mRNA synthesis, but also an energy source for translation and other important cellular processes. It can be converted to adenine nucleoside triphosphate (ATP), and the intracellular GTP level is closely related to the specific pathological state, so it is crucial to establish a simple and accurate method for the detection of GTP. Deoxyribozymes have unique catalytic and structural properties. One of the deoxyribozymes which is named DK2 with self-phosphorylation ability can transfer a phosphate from GTP to the 5' end in the presence of manganese(ii), while lambda exonuclease (λexo) catalyzes the gradual hydrolysis of double-stranded DNA molecules phosphorylated at the 5'-end from 5' to 3', but cannot cleave the 5'-OH end. The fluorescent dye SYBR Green I (SG I) can bind to dsDNA and produce significant fluorescence, but it can only give out weak fluorescence when it is mixed with a single strand. Here, we present a novel unlabeled fluorescence assay for GTP based on the self-phosphorylation of deoxyribozyme DK2 and the specific hydrolysis of λexo. Owing to the advantages of simple operation, high sensitivity, good specificity, low cost and without fluorophore (quenching group) labeling, this method has great potential in biological applications.


Validation of a Questionnaire to Assess Smoking Habits, Attitudes, Knowledge, and Needs among University Students: A Pilot Study among Obstetrics Students.
In Italy, smoking is still widespread among a relatively high percentage of young people. This study aimed to develop and validate a questionnaire to assess smoking habits, passive smoke exposure, electronic cigarette (e-cig) and heated tobacco product (HTP) use, attitudes, knowledge, and needs among undergraduates. A questionnaire consisting of 84 items was developed starting from a literature review and existing questionnaires. A two-round validation was performed by a team of 10 experts. The item-level content validity index (I-CVI), the scale-level content validity index (S-CVI), and the kappa statistics k, taking into account chance agreement, were calculated from the experts' rating. The questionnaire was emailed to 114 students from the Obstetrics Degree of the University of Milan (Italy) to be pilot tested. After the second round of validation, all indexes were above the respective acceptability criteria: the I-CVI was 1.00 for all but three items, k was >0.74 ("excellent") for all items, and the S-CVI was 0.964. Eighty-nine students participated in the survey: 17 classified themselves as smokers, eight as new product users, and four as former smokers, 72% students declared to routinely spend free time with smokers, while almost all students believed that healthcare professionals play a pivotal role in preventing smoking towards their patients and society. This questionnaire will be used in a survey among students from the University of Milan as a first step for future campaigns targeting health promotion.


[HLA-mismatched bone marrow transplantation with post-transplant cyclophosphamide for pediatric patients with aplastic anemia].
Post-transplant cyclophosphamide (PTCy) has improved the efficacy of HLA-mismatched hematopoietic cell transplantation (HCT) by decreasing the risk of graft-versus-host disease (GVHD) and nonrelapse mortality. If an HLA-matched donor is not available, GVHD prophylaxis with PTCy can also be used for HLA-mismatched HCT in patients with pediatric aplastic anemia (AA). We report two cases of pediatric AA that were treated with HLA-mismatched HCT with reduced-intensity conditioning and PTCy. We administered 50 mg/kg/day Cy for GVHD prophylaxis on days 3 and 4, and tacrolimus and mycophenolate mofetil (or methotrexate) were initiated from day 5. In both the cases, the time to engraftment was favorable and GVHD and infection were controllable. PTCy probably allows us to expand donor candidates in pediatric AA when an HLA-matched donor is not available; however, further studies regarding optimal conditioning regimens and late complications are required.


Validity of the self-report on drug use by university students: correspondence between self-reported use and use detected in urine.
The purpose of this work was to determine the validity of a self-report on recent drug use (cocaine and cannabis) in a sample of university students of both sexes and to explore the role of attitudes toward substance use as related to this report. The subjects (506) were volunteers aged 17-35 years (who received an economic incentive) recruited at the University of Almería (Spain). The results were analyzed on the basis of correspondence between the self-report of recent use and a urine test. Three logistic regression analyses between self-reported use and attitudes toward drugs were also performed. The results show that the convergent validity of the self-report of drug use and the urine test is quite satisfactory, with percentages of agreement varying from .89 to .98 and Kappa of .66 and .56 for cannabis and cocaine, respectively. Sensitivity of the self-report is 57.1% (cocaine) and 91.8% (cannabis), and specificity is 99.4% (cocaine) and 89.6% (cannabis). The differences found in correspondence between the two substances are discussed with regard to self-reported attitudes on drug use.


High Visceral Fat in Female Breast Cancer Patients Correlates with the Risk of Progression after Adjuvant Chemotherapy.
Clinical and epidemiological evidence indicate that obesity is associated with the risk and progression of breast cancer. Body mass index (BMI) as a measure of adiposity does not precisely describe individual body composition and adipose tissue distribution. We aimed to investigate the association between body composition and the efficiency of adjuvant chemotherapy as well as post-treatment progress among female breast cancer patients. Participants included 199 females with stage I-III breast cancer. Body composition, including body fat mass, visceral fat level, and skeletal muscle mass, was assessed based on the bioelectrical impedance analysis (BIA). The Kaplan-Meier survival curves, log-rank test, and Cox proportional-hazards model were used to estimate the effects of body composition as prognostic factors on survival. Postmenopausal women had a higher proportion of visceral fat compared to premenopausal women (64% vs. 33.87%, P < 0.001). Compared with those with normal visceral fat level, patients with high visceral fat level were older (P < 0.001), had higher body fat mass (p < 0.001), skeletal muscle mass (P = 0.013), minerals (P = 0.011), protein (P = 0.036), triglycerides (P = 0.038), cholesterol (P = 0.022), and low-density lipoprotein cholesterol (LDL-C) (P = 0.015). A more prolonged disease-free survival (DFS) was noted in patients with a normal visceral fat level as compared to patients with a high visceral fat level (hazard ratio [HR] 1.9, 95% CI 1-3.5; adjusted HR 1.77, 95% CI 0.932-3.36). A high visceral fat level in female patients with breast cancer is associated with a shorter DFS after adjuvant chemotherapy. Body composition alongside BIA provides a quick and noninvasive approach to identify breast cancer patients with a higher risk of cancer progression.


[Parental age and genetic risks for the offspring].
Despite numerous studies, the age-related risk of genetic defects in the offspring remains poorly understood. It is clear that the frequency at birth of some mendelian disorders is related to advanced paternal age, but this relationship is heterogeneous and varies from one disorder to another. Similarly, it has been proposed that among commonly observed birth defects, a subgroup of cases may be due to new unrecognized dominant mutations of paternal origin. Finally, despite many years of enquiry, increasing maternal age remains the only incontrovertible factor associated with human aneuploidy.


Larvicidal activity of the extracts from different parts of the plant Solanum xanthocarpum against important mosquito vectors in the arid region.
Larvicidal efficacy of the aqueous and methanol extracts from green unripe and yellow ripe fruits, seeds, leaves and roots of the plant Solanum xanthocarpum was evaluated against Anopheles culicifacies, Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus, the important mosquito vectors prevalent in the arid region. Studies were carried out on late 3rd orearly 4th instarlarvae of these species using standard WHO technique. Based on concentration mortality data LC50 and LC90 values along with their fiducial limits, regression equation, chi-square (chi2)/heterogeneity of the response have been determined bylog probit regression analysis. The 24 hr LC50 values as observed for aqueous extracts for green unripe and yellow ripe fruits were 112.7, 498.2 and 846.3 mg l(-1) and 104.7, 267.7and 832.2 mg l(-1) for Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus respectively. However, the 24 hr LC50 values formethanol extracts of yellow ripe fruits and seeds were 51.6, 52.2, 118.3 and 157.1 mg l(-1) and 66.9, 73.7, 123.8 and 154.9 mg l(-1) for the above four vector species respectively. The results showed that larvae of anophelines were much more susceptible as compared to culicines to both the aqueous and methanol extracts from fruits and seeds of the plant tested. The methanol extracts were found 2-5 times more effective as compared to the aqueous extracts. The chi-square values calculated during the analysis did not show any heterogeneity of the response. Experiments conducted with aqueous and methanol extracts from leaves and roots of this plant species didn't show any larvicidal activity against any of the mosquito species tested. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides.


[Hyperlipoproteinemia, a factor of severity in acute pancreatitis].
The authors make a retrospective analysis of 95 cases of acute pancreatitis hospitalized between 1975 and 1979. In 3,8% of all the cases the acute pancreatitis was associated with hyperlipoproteinemia. The study of the 4 patients involved revealed the primary origin of hyperlipoproteinemia as a result of alimentary abuse in 3 of the cases. In a fourth case the increased serum lipoproteins were due to prolonged use of contraceptives. From the clinical viewpoint, pancreatitis associated with hyperlipoproteinemia was more severe, with signs of shock and collapse, respiratory failure, high serum nitrogen an hyperglycemia. The blood and the serum had a lactescent aspect, with a thick layer of chylomicrons. The serum and blood values for lipids were higher than 4000 mg%. The increase in the amount of lipids was especially due to high triglycerides values. From the anatomopathologic viewpoint the 4 patients presented as acute cases of cholecysto-pancreatitis with major and extensive haemorrhagic necrosis which involved almost the entire pancreas. The evolution of the four patients was difficult. Two of the patients recovered after a long hospitalization, and had definitive sequels - insulin-dependent diabetes. The other two patients died following septic complications (bronchopneumonia and visceral gangrene), and hypovolemia due to upper digestive haemorrhage.


In silico assembly of Alzheimer's Abeta16-22 peptide into beta-sheets.
Recent studies suggest that soluble oligomers of amyloid-forming peptides have toxic effects in cell cultures. In this study, the folding of three Alzheimer's A beta(16-22) peptides have been simulated with the activation-relaxation technique and a generic energy model. Starting from randomly chosen states, the predicted lowest energy structure superposes within 1 A rms deviation from its conformation within the fibrils. This antiparallel structure is found to be in equilibrium with several out-of-register antiparallel beta-sheets and mixed parallel-antiparallel beta-sheets, indicating that full structural order in the fibrils requires larger aggregates. Folding involves the formation of dimers followed by the addition of a monomer and proceeds through a generalized mechanism between disordered and native alignments of beta-strands.


The genomic signature of splicing-coupled selection differs between long and short introns.
Understanding the function of noncoding regions in the genome, such as introns, is of central importance to evolutionary biology. One approach is to assay for the targets of natural selection. On one hand, the sequence of introns, especially short introns, appears to evolve in an almost neutral manner. Whereas on the other hand, a large proportion of intronic sequence is under selective constraint. This discrepancy is largely dependent on intron length and differences in the methods used to infer selection. We have used a method based on DNA strand asymmetery that does not require comparison with any putatively neutrally evolving sequence, nor sequence conservation between species, to detect selection within introns. The strongest signal we identify is associated with short introns. This signal comes from a family of motifs that could act as cryptic 5' splice sites during mRNA processing, suggesting a mechanistic justification underlying this signal of selection. Together with an analysis of intron length and splice site strength, we observe that the genomic signature of splicing-coupled selection differs between long and short introns.


3-D printed injection system for capillary electrophoresis.
Commercial systems for capillary electrophoresis are designed for the unattended analysis of several samples, and are usually large, complex, and expensive. We report a compact system for manual injection of a single sample in capillary electrophoresis, which is ideal for method development and for student training. The injector consists of two parts that are manufactured by three-dimensional printing (STL and STEP files are included as ESI). One part is immobile and holds an electrode for powering electrophoresis and a gas line for pressurized injection and pumping fluids through the capillary. The second part is removable and is used to hold washing solutions, separation electrolyte, or sample. Conventional machining is used to tap holes to hold the electrode, separation capillary, gas line, and safety interlock. The system is used for either pressure or electrokinetic sample injection, and can be used to pump fluids through the capillary for changing background electrolytes and reconditioning the capillary between runs. We coupled the injection system to our high-dynamic range laser-induced fluorescence detector and evaluated the system by performing capillary zone electrophoresis on solutions of fluorescein. Electrokinetic injection produced a linear response across five orders of magnitude dynamic range (slope of the log-log calibration curve was 1.02), concentration detection limits of 5 pM, and mass detection limits of 1 zmol. Pressure injection produced a linear response across at least four orders of magnitude (slope of the log-log calibration curve was 0.92), concentration detection limits of 2 pM, and mass detection limits of 10 zmol.


Nongenomic testosterone calcium signaling. Genotropic actions in androgen receptor-free macrophages.
Steroid hormones exert genotropic actions through members of the nuclear receptor family. Here, we have demonstrated genotropic actions of testosterone that are independent of intracellular androgen receptors (iAR). Through plasma membrane androgen receptors (mAR), testosterone induces a rapid rise in the intracellular free Ca(2+) concentration of iAR-free murine RAW 264.7 macrophages. This nongenomic testosterone signaling, which is independent of both iAR and estrogen receptors, does not in itself activate either the mitogen-activated protein kinase (MAPK) families ERK1/2, p38, and JNK/SAPK, the stably and transiently transfected c-fos promoter, or NO production. In the context of lipopolysaccharide (LPS) signaling, however, testosterone attenuates LPS activation of the c-fos promoter and NO production, which is abolished by the intracellular Ca(2+) chelator BAPTA. Testosterone also attenuates the LPS activation of p38 but not that of ERK1/2 and JNK/SAPK, and this attenuation is abrogated by BAPTA. Moreover, the p38 inhibitor, SB 203580, largely reduces LPS activation of the c-fos promoter and NO production, and the remaining levels are no longer regulated by testosterone. This study is the first to provide information on genotropic actions of mAR-mediated nongenomic testosterone Ca(2+) signaling by cross-talk with the LPS signaling pathway through p38 MAPK with impact on cell function.


Perioperative coronary spasm and right ventricular ischemia.
Perioperative coronary spasm after coronary bypass surgery is increasingly recognized as a possible cause of circulatory collapse. Most of the reported cases involved the right coronary artery (RCA). A case where transient right coronary spasm provoked right ventricular ischemia and collapse is described.


Soil residue analysis and degradation of saflufenacil as affected by moisture content and soil characteristics.
Saflufenacil dissipation in soils under different moisture conditions is not available in the scientific literature. The objective of this study was to evaluate saflufenacil degradation and persistence in soils from rice regions under field capacity (non-flooded) and saturated (flooded) conditions. The accelerated solvent extraction (ASE) residue analytical method developed to conduct the study resulted in recovery greater than 80% for the combinations of soils and moisture conditions. Saflufenacil degradation was faster at field capacity for all soils, except for Morey soil. Herbicide half-life was 28.6, 15.0 and 23.1 days under field capacity treatments and 58.8, 36.9 and 79.7 under saturated conditions for Nada, Crowley and Gilbert soils respectively. A half-life no longer than 80 days was observed for the combination of soils and moisture treatments. An ASE method was developed and used to extract saflufenacil from soil samples. Half-life averaged among soils was 59 and 33 days for saturated and field capacity respectively. Saflufenacil persistence in the environment was 2-3 times longer under flooded conditions for most of the soils studied.


A case of dilated cardiomyopathy with massive left ventricular thrombus after use of a sibutramine-containing slimming product.
Sibutramine, which acts as an anti-obesity drug by inhibiting reuptake of serotonin and norepinephrine, has now been banned due to cardiovascular adverse effects. However, despite being banned, it is not uncommon for people to purchase products with sibutramine or its analogues used as adulterants in non-prescription slimming products or health foods available on the internet. Sibutramine has been associated with rare but serious adverse reactions such as cardiac arrhythmia including QT interval prolongation, myocardial infarction, and cardiomyopathy, as well as increases in blood pressure and pulse rate. Here, we report a case of a 32-year-old male who presented with dilated cardiomyopathy with massive left ventricular thrombus after taking unauthorized sibutramine-containing slimming pills sold over the internet.


Should total omentectomy be performed for advanced gastric cancer?: The role of omentectomy during laparoscopic gastrectomy for advanced gastric cancer.
In the era of minimally invasive surgery, laparoscopic partial omentectomy (LPO) has seen widespread use as a curative surgical procedure for early gastric cancer. However, scientific evidence of the extent of omentectomy during laparoscopic gastrectomy remains unclear for advanced gastric cancer (AGC). We analyzed 666 eligible patients who underwent laparoscopic gastrectomy for AGC with curative intent between 2014 and 2018. Surgical outcome and postoperative prognosis were compared between LPO and laparoscopic total omentectomy (LTO) groups after 2:1 propensity score matching with age, sex, body mass index, tumor size, pT stage, pN stage, gastrectomy type, and clinical T stage as covariates. After extensive matching, there was no significant difference in pathologic or clinical stages between the LPO (n = 254) and LTO (n = 177) groups. LPO provided a significantly shorter operation time than LTO (199.2 ± 64.8 vs. 248.1 ± 68.3 min, P < 0.001). Pulmonary complication within postoperative 30 days was significantly lower in the LPO group (4.4 vs. 10.3%, P = 0.018). In multivariate analysis, LTO was the independent risk factor for pulmonary complication (odds ratio [OR] 2.53, 95% confidence interval [95% CI] 1.12-5.73, P = 0.025), which became more obvious in patients with a Charlson's comorbidity index of 4 or higher (OR 27.43, 95% CI 1.35-558.34, P = 0.031). The 5-year overall survival rate (OS) and 3-year recurrence-free survival (RFS) rates were not significantly different between the two groups, even after stage stratification. LPO provided significantly shorter operation time and less pulmonary complication than LTO without compromising 5-year OS and 3-year RFS for AGC. LTO was the independent risk factor for pulmonary complications, which became more evident in patients with severe comorbidities.


Discharge Opioids are Unnecessary Following Radical Cystectomy.
To show that zero-opioid discharges after both open and robotic cystectomy are feasible and to examine the impact of zero-opioid discharges on patient interaction with the physician's office. One hundred seven patients who underwent either open or robotic radical cystectomy from March 1, 2020 to December 30, 2020 were identified. Patient demographics, perioperative data, and 30 day pain related outcomes including phone calls, office visits, requests for pain medication, emergency department visits, and readmissions were abstracted from the chart. We then examined variables associated with a zero-opioid discharge. Thirty-two patients were discharged with an opioid prescription (Median Oral Morphine Equivalents Prescribed = 90) and 75 were discharged without an opioid prescription. On regression analysis, age (OR 1.07, 95% CI [1.02-1.12]) and pathology (OR 0.36, 95% CI[0.14-0.9]) remained significantly associated with post-operative opioid prescriptions. There were no differences in the percent of patients presenting to the emergency department, being readmitted, calling the office, calling the office regarding pain, or requesting opioid prescriptions within 30 days of discharge, or the number of post-operative office visits (P >.05 for all). Patients can safely be discharged home without opioids following cystectomy, regardless of robotic or open approach. Age and pathology are predictors of the need for an opioid prescription on discharge. These patients did not have increased follow-up visits, phone calls, or requests for pain medication.


Activin-binding protein is present in pituitary.
A binding protein for activin was purified from bovine pituitary by affinity chromatography on dextran sulfate-Sepharose CL-4B and activin-Affi-Gel 10. A 52,700-fold purification over the starting crude homogenate was achieved. The purified preparation showed two bands of 36 and 33 kilodalton in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. The ability of each form of the protein to specifically bind activin was determined by ligand blot analysis and binding competition study. Each protein was found to have the same NH2-terminus and its sequence was identical to that of follistatin, which is a specific inhibitor of identical to that of follistatin, which is a specific inhibitor of FSH release. Moreover, the binding protein was shown to inhibit the spontaneous FSH release from cultured pituitary cells as does follistatin. These properties are the same as activin-binding protein that we have obtained from rat ovary. These results support a conclusion that activin-binding protein/follistatin exists also in the pituitary. Activin-binding protein has an ability to inhibit the activin-induced augmentation of FSH release from cultured pituitary cells as does inhibin. However, the inhibitory pattern by the binding protein was quite distinct from that of inhibin, suggesting that there may be different mechanism(s) for their antagonistic actions. Stoichiometric inhibition as shown by gel filtration analysis indicates that activin-binding protein binds activin to form an inactive equimolar complex having neither stimulatory nor inhibitory activity for FSH secretion by the pituitary. These findings suggest that activin is actually involved in FSH secretion in the pituitary and that the activin action in the pituitary is regulated by activin-binding protein/follistatin.


Tremor and β(2)-adrenergic agents: is it a real clinical problem?
Tremor is one of the most characteristic adverse effects following administration of β(2)-adrenergic agonists. It is reported by around 2-4% of patients with asthma taking a regular β(2)-adrenergic agonist and is induced by both short-acting and long-acting agents. Tremor associated with β(2)-adrenergic agonists is dose-related and may occur more commonly with oral dosing. The exact mechanism for tremor induction by β(2)-adrenergic agonists is still unknown, but there is some evidence that β(2)-adrenergic agonists act directly on muscle. An early explanation of the tremor was that β(2)-adrenoceptor stimulation shortens the active state of skeletal muscle, which leads to incomplete fusion and reduced tension of tetanic contractions. More recently, tremor has been correlated closely with hypokalaemia. A possible diverse impact of different modes of administration of β(2)-adrenergic agonists on tremorogenic responses has been suggested but solid evidence is still lacking. In any case, the desensitization of β(2)-adrenoceptors that occurs during the first few days of regular use of a β(2)-adrenergic agonist accounts for the commonly observed resolution of tremor after the first few doses. Therefore, tremor is not a really important adverse effect in patients under regular treatment with a β(2)-adrenergic agonist.


SGK regulates pH increase and cyclin B-Cdk1 activation to resume meiosis in starfish ovarian oocytes.
Tight regulation of intracellular pH (pHi) is essential for biological processes. Fully grown oocytes, having a large nucleus called the germinal vesicle, arrest at meiotic prophase I. Upon hormonal stimulus, oocytes resume meiosis to become fertilizable. At this time, the pHi increases via Na+/H+ exchanger activity, although the regulation and function of this change remain obscure. Here, we show that in starfish oocytes, serum- and glucocorticoid-regulated kinase (SGK) is activated via PI3K/TORC2/PDK1 signaling after hormonal stimulus and that SGK is required for this pHi increase and cyclin B-Cdk1 activation. When we clamped the pHi at 6.7, corresponding to the pHi of unstimulated ovarian oocytes, hormonal stimulation induced cyclin B-Cdk1 activation; thereafter, oocytes failed in actin-dependent chromosome transport and spindle assembly after germinal vesicle breakdown. Thus, this SGK-dependent pHi increase is likely a prerequisite for these events in ovarian oocytes. We propose a model that SGK drives meiotic resumption via concomitant regulation of the pHi and cell cycle machinery.


Searching for success: boys, family aspirations, and opportunities in Gabon, ca. 1900-1940.
Boys growing up in rural Gabon between 1900 and 1940 negotiated with many challenges: the rise of migrant labor, famines and hardships brought on by World War I, the growth of Christianity and African-based spiritual traditions, and the undermining of clans, which had been the main form of social and political organization in the nineteenth century. Parents, extended family members, missionaries, and European businesses recruited boys to serve their varied interests. Boys in turn developed new self-understandings by leaving their homes as students, workers, and clients of older men. This article examines the life histories of four boys to trace the successes and challenges that individual boys encountered in this turbulent era. Interestingly, older biological relatives of boys generally succeeded in maintaining their authority over children living far from home, although the education and wages that boys received forced older men to offer boys more benefits.


Induction of blister-causing antibodies by a recombinant full-length, but not the extracellular, domain of the pemphigus vulgaris antigen (desmoglein 3).
Pemphigus vulgaris (PV) is mediated by autoantibodies to desmoglein 3, the pemphigus vulgaris antigen (PVA). PVA and an extracellular domain of PVA-Ig fusion protein (PV-Ig) can completely adsorb the blister-causing Abs from PV patient sera, suggesting that the extracellular segment of PVA might be sufficient to induce pathogenic Abs. To test this, we immunized rabbits with either PVA or its extracellular domain (EPVA) expressed in insect cells in our laboratory. When Igs were passively transferred from these rabbits into neonatal mice, anti-PVA, but not the anti-EPVA, induced blisters. To understand the basis for their differential pathogenic effects, we examined the properties of these sera. Both sera showed comparable ELISA titers and indirect immunofluorescence reactivity against monkey esophagus, a source of native PVA. Moreover, EPVA, like PVA adsorbed blister-causing Abs from sera of PV patients and rabbits immunized with PVA. In contrast, when IgG preparations were incubated with fura-2-AM (acetyloxymethyl ester)-loaded human keratinocytes in culture, only IgG from anti-PVA serum induced intracellular calcium mobilization. These data showed that PVA but not EPVA can elicit Abs that induced blisters in neonatal mice and mediate intracellular signaling through calcium mobilization.


Ruptured Hepatocellular Carcinoma: Current Status of Research.
Ruptured hepatocellular carcinoma (rHCC) is considered a rare and life-threatening manifestation; when it happens, it often requires acute and positive intervention. At present, the mechanism of rHCC development is gradually being understood while there are many kinds of rHCC treatment. From our clinical observation, the prognosis of rHCC patients is not as poor as it is currently believed. It may not be appropriate to include all patients with rHCC in T4. The incidence of ruptured hepatocellular carcinoma is now rising. Especially in the Asian region, it can even reach 10% - 15%. The most common symptom of HCC rupture is abdominal pain, and there are now a variety of treatments for hepatocellular carcinoma rupture. With aggressive treatment, rHCC patients can also achieve a better prognosis. The patient's condition varies on admission, so the treatment methods will also be different. It is critical to identify prognostic factors simultaneously, and rHCC can be effectively managed by focusing on important prognostic factors. A review was carried out to analyze diagnosis, mechanism, treatment, and prognostic risk factors on this disease condition during the current situation; it is hoped that it will provide better guidance for clinicians. Moreover, patients with rHCC were managed hierarchically to prolong their prognosis.


Emotions and personal health information management: some implications for design.
This work reflects on the translation of a paper-based information system into an electronic one, taking account of the emotional dimension of material artifacts. A qualitative analysis carried out through semi-structured interviews enabled us to describe laypeople's healthcare practices, and specifically the use of "pediatric booklets", which are paper health diaries designed to provide parents with a repository of the most relevant clinical data about their children. Our analysis reveals that parents' use of the booklet does not depend only on the clinical relevance of the information contained in it. Its success rather depends on practices that reshape the booklet's original meaning. In particular, parents use booklets as containers for other clinical records, and they consider them more as objects of affection and symbols of their caring for their children than as clinical tools with instrumental value in themselves. In the discussion we consider the risks of dematerializing health information tools by underestimating the relevance of the emotional side.


Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virus.
Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and sequence variants in CCR5 regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggesting CCR5 may have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. One CCR5 variant contained a 4-base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of this CCR5 promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker-assisted selection. However, because of the large impact on transcription and because CCR5 has roles in inflammation, recruitment of effector cells, and cell-mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep.


Peptides affect the intake of specific nutrients and the sympathetic nervous system.
Food intake can be increased or decreased after either central or peripheral administration of peptides. Galanin, neuropeptide Y, opioid peptides, growth-hormone-releasing hormone, and desacetyl-melanocyte stimulating hormone increase food intake whereas insulin, glucagon, cholecystokinin, anorectin, corticotropin-releasing hormone, neurotensin, bombesin, cyclo-his-pro, and thyrotropin-releasing hormone reduce food intake. Many of these peptides have reciprocal effects on food intake and sympathetic activity with those peptides that stimulate food intake reducing sympathetic activity and vice versa. In addition, neuropeptide Y specifically increases carbohydrate intake. Galanin and opioid peptides on the other hand increase fat intake whereas enterostatin reduces fat intake. Glucagon decreases protein intake. The effect of peptides on specific nutrients suggests that peptides may work in part by modulating basic feeding mechanisms to lead to the selection of specific nutrients from the diet. This hypothesis might be called a nutrient-specific model of peptide-induced food intake.


Lidocaine 5% Patch for Treatment of Acute Pain After Robotic Cardiac Surgery and Prevention of Persistent Incisional Pain: A Randomized, Placebo-Controlled, Double-Blind Trial.
To test the hypotheses that lidocaine 5% patches decrease the severity of acute pain and incidence of persistent incisional pain after robotic cardiac valve surgery. A randomized, placebo-controlled, double-blind trial. Tertiary care academic medical center. Patients having robotic cardiac valve surgery. Patients having robotic cardiac valve surgery were randomly assigned to 5% lidocaine patches or identical-appearing placebo patches. Patches were applied around each incision 12 hours/day until pain resolved, or for 6 months. Supplemental opioid was provided by patient-controlled analgesia or orally. Pain was initially evaluated with a Visual Analog Scale, and subsequently by telephone with a Verbal Response Scale and the Pain Disability Index (our primary outcome) after 1 week, 1 month, 3 months, and 6 months. Global Perceived Effect, a measure of patient satisfaction, was simultaneously recorded. Repeated-measures analysis of variance and generalized estimating equations were our primary statistical tools. Acute pain scores and opioid use were low, as was the incidence of persistent pain. Lidocaine 5% patches did not influence any measure of acute or persistent incisional pain. Estimated difference (95% CI) in mean Pain Disability Index for Lidocaine patch minus placebo was -2.5 (95% CI -7.1, 2.1), P = 0.28. Lidocaine 5% patches did not reduce acute or persistent pain in patients having robotic thoracic surgery, though pain scores were low in both treatment groups. Clinicians should choose alternative analgesic approaches in these patients.


[Influence of various hemostatic methods on ovarian reserve function in women with ovarian endometriotic cyst treated by laparoscopic cystectomy].
To investigate the influence on ovarian reserve function in treatment of ovarian endometriotic cyst by laparoscopic cystectomy with various hemostasis management. From September 2007 to August 2008, 61 patients with bilateral ovarian endometriotic cyst in Peking University First Hospital and Anzhen Hospital Affiliated to Capital University of Medicine were treated by laparoscopic cystectomy. Those patients were divided into two groups randomly, which were 28 patients in suture group and 33 patients in electro coagulation during the operation. Blood samples were obtained from the patients before the operation, on the day 2 or 3 of the second menstrual cycle after operation and the first menstrual cycle after 6 months operation. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)) were tested. At the same time, total antral follicles (F(0)) and mean ovarian stromal peak systolic blood flow velocity (PSV) were detected by transvaginal ultrasonography to evaluate ovarian reserve function. There was no significant difference in patients' clinical characteristics and ovarian reserve function between two groups (P > 0.05). In the suture group, the serum level of FSH were (10.2 +/- 2.0) U/L before operation, (11.0 +/- 2.2) U/L on day 2 or 3 of the second menstrual cycle and (11.5 +/- 2.5) U/L on day 2 or 3 of the first menstrual cycle after 6 months'operation respectively. In comparison of data before operation, it exhibited significant difference (P < 0.05); F(0) were 8.9 +/- 2.6 before operation, 7.8 +/- 2.1 on day 2 or 3 of the second menstrual cycle and 7.6 +/- 2.4 on day 2 or 3 of the first menstrual cycle after 6 months' operation. When compared with data before operation, it showed significant difference (P < 0.05); PSV were (0.104 +/- 0.017) m/s before operation, (0.084 +/- 0.016) m/s on day 2 or 3 of the second menstrual cycle, (0.086 +/- 0.022) m/s on day 2 or 3 of the first menstrual cycle after 6 months' operation, it also showed significant difference between preoperation and postoperation (P < 0.01). In the electro coagulation group, the serum level of E(2) were (166 +/- 19), (196 +/- 57), (205 +/- 65) pmol/L, serum level of FSH were (10.0 +/- 1.5), (12.2 +/- 2.6), (13.4 +/- 4.5) U/L, F(0) were 8.9 +/- 2.0, 6.5 +/- 2.0, 6.2 +/- 2.5 (P < 0.01); PSV were (0.101 +/- 0.016), (0.072 +/- 0.021), (0.067 +/- 0.024) m/s before operation and on day 2 or 3 of the second menstrual cycle after operation and the first menstrual cycle after 6 months operation. They all showed significant difference between preoperation and postoperation. In the second menstrual cycle post operation (on day 2 or 3), the data of F(0) and PSV were statistically different between the two groups (P < 0.05); in the first menstrual cycle 6 months after the operation (on day 2 or 3), The serum level of E(2), F(0) and PSV were statistically different between the two groups (P < 0.05). It suggested that ovarian reserve function would be decreased in treatment of bilateral ovarian endometriotic cyst by laparoscopic cystectomy, it was more serious when electro coagulation hemostasis were given.


Safety evaluation on concomitant immunization with inactivated poliomyelitis vaccine produced from Sabin strains and other vaccines (from 2015 to 2020).
To evaluate the safety of concomitantly administering inactivated poliomyelitis vaccine produced from Sabin strains (sIPVs) with other vaccines. A descriptive analysis was carried out on adverse events following immunization (AEFI) based on the administration of sIPV alone or concomitant with other vaccines (from 2015 to 2020) using data from the national AEFI surveillance system of China (CNAEFIS). All adverse reactions (ADRs) of the concomitant immunization were coded using a medical dictionary for regulatory activities (MedDRA) before comparison. The CNAEFIS reported a total of 9130 sIPV-related AEFI cases, including 6842 AEFI cases collected after immunization with sIPV alone and 2288 AEFI cases collected after immunization of sIPV concomitant with other vaccines. The combination of sIPV with diphtheria, tetanus and pertussis vaccine (DTaP) was correlated with the highest frequency of AEFI, which accounted for 53.50% of all 2288 AEFI cases. After MedDRA-based coding, the most frequent ADR was fever (70.18%), followed by erythema and swelling at the injection site (6.95%), induration at the injection site (3.85%), dermatitis allergy (3.56%) and urticaria (1.55%). A statistically significant difference (P < .001) was found between sIPV immunization and sIPV immunization concomitant with other vaccines for general reactions (95.36% and 93.22%, respectively) and abnormal reactions (4.64% and 6.78%, respectively). No new safety signal is found for sIPV administered concomitantly, although its administration with other vaccines may increase the occurrence of abnormal reactions. Vaccine manufacturers should focus on the safety of administering sIPV with DTaP and carry out relevant clinical studies when necessary.


[Frecuency of adverse events during the hygiene of the critical care patient].
The hygiene of the patient in critical condition is a common nursing technique in the intensive care unit, which does not mean that doing it is exempt of risk for the patient's state. We carry out a study to measure the frequency of the appearance of certain adverse events during the hygiene care and their clinical repercussion.Hygiene of the critical patients was monitored, measuring the appearance of certain events at the time of hygiene and until one hour after to assess if the complications were at the moment or had a greater repercussion on the state of the patient.During the study period, some adverse event appeared in 48% (CI 95%: 43-52) of the hygiene performed while none appeared in 52% (CI 95%: 48-56) of it. The events that appeared most frequently were: desaturation in 18% (CI 95%: 15-21) of the hygiene performed, the deadaptation of the mechanical ventilation in 11% (CI 95%: 9-14), arterial hypertension in 21% (CI 95%: 18-25) and arterial hypotension in 11% (CI 95%: 9-14). The intracranial hypertension appeared in 42% (CI 95%: 26-61) of the hygiene performed to patients who were carriers of intraventricular catheter, 9% (CI 95%: 2-25) continued with elevated values 1 hour after concluding the hygiene. The rest of the events monitored presented a lower frequency, although the appearance of one episode of cardiorespiratory arrest and two of auricular fibrillation with rapid ventricular response, one of which required cardioversion, stand out. We conclude that it is an essential job of the nursing staff to correctly assess the risks that the performance of hygiene means for the critical patient, so that the technique should be applied rationally and under strict monitoring and control.


Stratification of axillary lymph node metastasis risk with breast magnetic resonance imaging in breast cancer.
Aims: To develop a model based on breast MRI to stratify axillary lymph node metastasis (ALNM) in breast cancer. Patients & methods: A total of 134 eligible patients were used to build a predicting model, which was validated with an independent group of 57 patients and evaluated for accuracy and sensitivity. Results: A model based on breast MRI was developed and yielded total accuracy of 82.5% and sensitivities of 94.3, 64.3 and 62.5% to predict patients with no, low and heavy ALNM burden, respectively, in the validation group. Conclusion: A noninvasive model based on breast MRI was developed to preoperatively stratify ALNM in breast cancer; its performance needs to be validated and improved in future research.


Temporal and Site-Specific ADP-Ribosylation Dynamics upon Different Genotoxic Stresses.
The DNA damage response revolves around transmission of information via post-translational modifications, including reversible protein ADP-ribosylation. Here, we applied a mass-spectrometry-based Af1521 enrichment technology for the identification and quantification of ADP-ribosylation sites as a function of various DNA damage stimuli and time. In total, we detected 1681 ADP-ribosylation sites residing on 716 proteins in U2OS cells and determined their temporal dynamics after exposure to the genotoxins H2O2 and MMS. Intriguingly, we observed a widespread but low-abundance serine ADP-ribosylation response at the earliest time point, with later time points centered on increased modification of the same sites. This suggests that early serine ADP-ribosylation events may serve as a platform for an integrated signal response. While treatment with H2O2 and MMS induced homogenous ADP-ribosylation responses, we observed temporal differences in the ADP-ribosylation site abundances. Exposure to MMS-induced alkylating stress induced the strongest ADP-ribosylome response after 30 min, prominently modifying proteins involved in RNA processing, whereas in response to H2O2-induced oxidative stress ADP-ribosylation peaked after 60 min, mainly modifying proteins involved in DNA damage pathways. Collectively, the dynamic ADP-ribosylome presented here provides a valuable insight into the temporal cellular regulation of ADP-ribosylation in response to DNA damage.


Strict management of a pregnant patient with giant coronary artery aneurysm due to Kawasaki disease.
Coronary artery aneurysms (CAA) may occur in Kawasaki disease (KD). Patients with giant CAA (diameter >8 mm), in particular, have higher risk of myocardial infarction. Previous reports have demonstrated the necessity of anticoagulation therapy in such cases. The management of patients with KD complicated by giant CAA later in life, however, remains controversial. Here, we describe the strict management in the case of a 28-year-old pregnant Japanese woman with KD with giant CAA (diameter, 11 mm). Instead of warfarin, the patient was given low-dose aspirin and i.v. unfractionated heparin during pregnancy to prevent thrombosis in the giant CAA. At 38 weeks of gestation, she had spontaneous delivery of a healthy baby. No thrombotic or bleeding complications were observed. The strict anticoagulation therapy resulted in successful pregnancy and delivery without any adverse events.


A novel in vivo method to detect DNA sequence variation.
Mismatch repair detection (MRD) is an in vivo method that uses a change in bacterial colony color to detect DNA sequence variation. DNA fragments to be screened for variation are cloned into two MRD plasmids, and bacteria are transformed with heteroduplexes of these constructs. The resulting colonies are blue in the absence of a mismatch and white in the presence of a mismatch. MRD is capable of detecting a single mismatch in a DNA fragment as large as 10 kb in size. In addition, MRD has the potential for analyzing many fragments simultaneously, offering a powerful method for high-throughput genotyping and mutation detection in a large genomic region.


[Nomenclature and classification of complications. Standard procedure at the Heidelberg University Orthopedic Clinic].
In order to get a better data management of complications in orthopedic surgery and in order to get comparable statistics a standardisation of nomenclature and classification of complications is demanded since 1.1.1997. The Orthopedic University Clinic of Heidelberg started with a register of all early complications of all inpatients. According to a standardized nomenclature all occurred complications the doctors put in the data of complications in a database. These data were controlled, complemented and classified by members of the quality management group. This guideline consists of five parts: catalogue of diagnoses, general and special definitions, classification and an allocation table of diagnoses to grades of severity.


Amphetamine, mazindol, and fencamfamin in narcolepsy.
Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and fencamfamin hydrochloride 60 mg daily. Each drug was given for four weeks and the effects compared. In these dosages the reported frequency of attacks of narcolepsy was roughly halved with each treatment, dexamphetamine 30 mg daily being only slightly more potent than 10 mg. The subjective effects of Dexedrine tablets and Spansules could not be distinguished by most patients. Effects on mood, alertness, and sympathomimetic side effects were largely inseparable with all these drugs, but a decrease in appetite was not reported by patients with narcolepsy.


The biomechanical effects of multilevel posterior foraminotomy and foraminotomy with double-door laminoplasty.
The aim of this study is to evaluate the biomechanical effects of multilevel foraminotomy and foraminotomy with double-door laminoplasty compared with foraminotomy with laminectomy. Using fresh human cadaveric specimens (C2-T1), sequential injuries were created in the following order: intact, bilateral foraminotomies (C3-C4, C4-C5, C5-C6), laminoplasty (C3-C6) using hydroxyapatite spacer, removal of the spacers, and laminectomy. Changes in the rotations of each vertebra in each injury status were measured in six loading modes: flexion, extension, right and left lateral bending, and right and left axial rotation. Foraminotomy alone and following laminoplasty showed no significant differences in motion compared with intact except in axial rotation. After removal of the spacers and following laminectomy, the motion increased significantly in flexion and axial rotation. The ranges of initial slack showed similar trends when compared with the results at maximum load. Clinical implications of these observations are presented.


[Approaching the new patient and innovations].
The SARS-CoV-2 pandemic has accelerated the process of healthcare digitalization. This paradigm shift is a challenge for both healthcare professionals and patients. This article discusses the opinions of patients with different levels of familiarity with new technologies, as well as the perspective of healthcare professionals on new patients and technological innovations.


Letting off steam.
Sport and keeping fit are good for the body and the mind. For Anna Mawston, a small animal vet, football has been her lifelong passion and she finds it a good way to relax after a day in practice.


15-deoxy-Delta12,14-prostaglandin J2 induces renal epithelial cell death through NF-kappaB-dependent and MAPK-independent mechanism.
The peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand 15d-PGJ2 induces cell death in renal proximal tubular cells. However, the underlying molecular mechanism(s) remains unidentified. The present study was undertaken to examine the roles of reactive oxygen species (ROS), mitogen-activated protein kinase, and NF-kappaB in opossum kidney (OK) cell death induced by 15d-PGJ2. Treatment of OK cells with 15d-PGJ2 resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. 15d-PGJ2 increased ROS production and the effect was inhibited by catalase and N-acetylcysteine. The 15d-PGJ2-induced cell death was also prevented by these antioxidants, suggesting that the cell death was associated with ROS generation. The PPARgamma antagonist GW9662 did not prevent the 15d-PGJ2-induced cell death. 15d-PGJ2 caused a transient activation of extracellular signal-regulated kinase (ERK). However, inhibitors (PD98059 and U0126) of MEK, an ERK upstream kinase, did not alter the 15d-PGJ2-induced cell death. Transfection with constitutively active MEK and dominant-negative MEK had no effect on the cell death. 15d-PGJ2 inhibited the NF-kappaB transcriptional activity, which was accompanied by an inhibition of nuclear translocation of the NF-kappaB subunit p65 and impairment in DNA binding. Inhibition of NF-kappaB with a NF-kappaB specific inhibitor pyrrolidinecarbodithioate and transfection with IkappaBalpha (S32A/36A) caused cell death. These results suggest that the 5d-PGJ2-induced OK cell death was associated with ROS production and NF-kappaB inhibition, but not with MAPK activation.


Estimating speech spectra for copy synthesis by linear prediction and by hand.
Linear prediction is a widely available technique for analyzing acoustic properties of speech, although this method is known to be error-prone. New tests assessed the adequacy of linear prediction estimates by using this method to derive synthesis parameters and testing the intelligibility of the synthetic speech that results. Matched sets of sine-wave sentences were created, one set using uncorrected linear prediction estimates of natural sentences, the other using estimates made by hand. Phoneme restrictions imposed on linguistic properties allowed comparisons between continuous and intermittent voicing, oral or nasal and fricative manner, and unrestricted phonemic variation. Intelligibility tests revealed uniformly good performance with sentences created by hand-estimation and a minimal decrease in intelligibility with estimation by linear prediction due to manner variation with continuous voicing. Poorer performance was observed when linear prediction estimates were used to produce synthetic versions of phonemically unrestricted sentences, but no similar decline was observed with synthetic sentences produced by hand estimation. The results show a substantial intelligibility cost of reliance on uncorrected linear prediction estimates when phonemic variation approaches natural incidence.


Compassion fatigue in pediatric hematology, oncology, and bone marrow transplant healthcare providers: An integrative review.
Compassion fatigue (CF), which includes burnout and secondary traumatic stress, is highly prevalent among healthcare providers (HCPs). Ultimately, if left untreated, CF is often associated with absenteeism, decreased work performance, poor job satisfaction, and providers leaving their positions. To identify risk factors for developing CF and interventions to combat it in pediatric hematology, oncology, and bone marrow transplant (PHOB) HCPs. An integrative review was conducted. Controlled vocabulary relevant to neoplasms, CF, pediatrics, and HCPs was used to search PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Web of Science MEDLINE. Inclusion criteria were the following: English language and PHOB population. Exclusion criteria were the following: did not address question, wrong study population, mixed study population where PHOB HCPs were only part of the population, articles about moral distress as this is a similar but not the same topic as CF, conference abstracts, and book chapters. A total of 16 articles were reviewed: 3 qualitative, 6 quantitative, 3 mixed methods, and 4 non research. Three themes were explored: (1) high-risk populations for developing CF, (2) sources of stress in PHOB HCPs, and (3) workplace interventions to decrease CF. PHOB HCPs are at high risk of developing CF due to high morbidity and mortality in their patient population. Various interventions, including the use of a clinical support nurse, debriefing, support groups, respite rooms, and retreats, have varying degrees of efficacy to decrease CF in this population.


Introduction To Monte Carlo Simulation.
This paper reviews the history and principles of Monte Carlo simulation, emphasizing techniques commonly used in the simulation of medical imaging.


Complex formation of human T-cell leukemia virus type I p40tax transactivator with cellular polypeptides.
We examined cellular components which associate with p40tax, the viral transactivation molecule of human T-cell leukemia virus type I. Such molecules were searched by immunoprecipitation with polyclonal and monoclonal antibodies specific for p40tax. Two cellular proteins with molecular masses of 95 kDa (p95) and 60 kDa (p60) were specifically coprecipitated with p40tax from extracts of all p40tax-producing cell lines but not from p40tax-negative cell lines. The p60 component was also shown to associate with p40tax in vitro, by using radiolabel-chase experiments. Rabbit antisera specific for p60 and p95 were prepared by immunization with electrophoretically purified molecules. While anti-p95 antiserum coprecipitated p40tax, no p40tax could be identified in immunoprecipitates by using a polyclonal anti-p60 antiserum. The partial amino acid sequence of p60 demonstrated that p60 is identical to the human 60-kDa heat shock protein (a member of the chaperonin family of proteins). Although the biological significance of the complex formation of p40tax with p95 and p60 has yet to be determined, it may be that the complex formation is one of the mechanisms by which the biological activity of p40tax can be regulated.


Japanese linguistic validation of the ureteral stent symptom questionnaire.
We validated the Japanese version of the ureteral stent symptom questionnaire in patients with an indwelling ureteric stent. The English version of the ureteral stent symptom questionnaire was translated into Japanese using a multistep process by three urologists and two independent translators. A total of 70 patients with indwelling ureteral stents completed the Japanese ureteral stent symptom questionnaire, as well as validated instruments, namely, the International Prostate Symptom Score or Overactive Bladder Symptom Score and the EuroQoL 5-dimension questionnaires. Patients completed questionnaires at 2 weeks after stent insertion and 4 weeks after stent removal. The second group included 87 healthy individuals who agreed to complete the questionnaires. The reliability of the Japanese version was evaluated for internal consistency using Cronbach's α test. Psychometric properties of the questionnaire were analyzed, and included convergent validity, sensitivity to change and discriminant validity. A total of 70 cases and 87 controls were suitable for the analysis. A comparison of patients with ureteric stents and healthy individuals was carried out, and the convergent validity determined by the correlation between other instruments and the corresponding ureteral stent symptoms questionnaire domains was satisfactory (P < 0.05). Internal consistencies (Cronbach's α coefficients 0.73-0.80) were satisfactory, except for the sexual matters domain. Test-retest reliability was good, except for the sexual matters domain (Spearman's coefficient 0.71-0.93). The Japanese version of the ureteral stent symptom questionnaire proved to be a reliable and robust instrument for the evaluation of ureteral stent-associated morbidity for both men and women.


ECG compression: evaluation of FFT, DCT, and WT performance.
This work investigates a set of ECG data compression schemes to compare their performances in compressing and preparing ECG signals for automatic cardiac arrhythmia classification. These schemes are based on transform methods such as fast Fourier transform (FFT), discrete cosine transform (DCT), wavelet transform (WT), and their combinations. Each specific transform is applied to a pre-selected data segment from the MIT-BIH database and then compression is performed in the new domain. These transformation methods are known as an important class of ECG compression techniques. The WT has been shown as the most efficient method for further improvement. A compression ratio of 7.98 to 1 has been achieved with a percent of root mean square difference (PRD) of 0.25%, indicating that the wavelet compression technique offers the best performance over the other evaluated methods.


Adaptive Resistance to Dual BRAF/MEK Inhibition in BRAF-Driven Tumors through Autocrine FGFR Pathway Activation.
Combined MAPK pathway inhibition using dual BRAF and MEK inhibitors has prolonged the duration of clinical response in patients with BRAFV600E-driven tumors compared with either agent alone. However, resistance frequently arises. We generated cell lines resistant to dual BRAF/MEK inhibition and utilized a pharmacologic synthetic lethal approach to identify a novel, adaptive resistance mechanism mediated through the fibroblast growth factor receptor (FGFR) pathway. In response to drug treatment, transcriptional upregulation of FGF1 results in autocrine activation of FGFR, which potentiates extracellular signal-regulated kinases (ERK) activation. FGFR inhibition overcomes resistance to dual BRAF/MEK inhibitors in both cell lines and patient-derived xenograft (PDX) models. Abrogation of this bypass mechanism in the first-line setting enhances tumor killing and prevents the emergence of drug-resistant cells. Moreover, clinical data implicate serum FGF1 levels in disease prognosis. Taken together, these results describe a new, adaptive resistance mechanism that is more commonly observed in the context of dual BRAF/MEK blockade as opposed to single-agent treatment and reveal the potential clinical utility of FGFR-targeting agents in combination with BRAF and MEK inhibitors as a promising strategy to forestall resistance in a subset of BRAF-driven cancers.


Identification by RT-PCR and immunolocalization of arginine vasopressin in rat pancreas.
Arginine vasopressin (AVP), a hormone of the hypothalamic pituitary axis, has been described in several peripheral tissues, including pancreas. To demonstrate the ectopic synthesis of AVP at the pancreatic level, we explored the expression of the AVP-neurophysin-II (AVP-NP-II) precursor gene by reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing and attempted to localise the peptide by immunocytochemistry in normal rat pancreas. Primers designed at the 3' and 5' ends of the AVP-NP-II gene, RT-PCR, and automatic sequencing of PCR products from rat pancreas revealed transcripts of the predicted size with an identical sequence to those from the hypothalamus. In addition, AVP antiserum revealed immunoreactive material of perivascular localisation. These data provide the first direct evidence for the presence of AVP transcripts in rat pancreatic tissue, whereas concurrent immunodetection of this hormone offers further support for the potential role of ectopic AVP in local regulation of the secretory activity of the pancreas.


Nonlinear finite-element analysis of the lower cervical spine (C4-C6) under axial loading.
This study was conducted to develop a detailed, nonlinear three-dimensional geometrically and mechanically accurate finite-element model of the human lower cervical spine using a high-definition digitizer. This direct digitizing process also offers an additional method in the development of the finite-element model for the human cervical spine. The biomechanical response of the finite-element model was validated and corresponded closely with the published experimental data and existing finite-element models under axial compressive loading. Furthermore, the results indicated that the cervical spine segment response is nonlinear with increasing stiffness at higher loads. As a logical step, a parametric study was conducted by evaluating the biomechanical response related to the changes in the modeling techniques of the finite-element model and the mechanical properties of the disk annulus. Variations of the predicted horizontal disk bulge were investigated under axial compressive displacements for the normal model, the model without facet articulations, and the model without nucleus. Removal of nucleus fluids causes an inward bulge of the inner annulus layers, with the displacement magnitude dependent on external loads. The result indicates that the nucleus fluid plays an important role in cervical spine mechanics. Simulated facetectomy indicates a decrease in the stiffness of the cervical spine. The study shows that, in reality, the stiffness of the lower cervical spine depends closely on factors such as the spinal geometry and physical properties, thereby resulting in various force and displacement responses.


Involvement of Peroxidase and Indole-3-acetic Acid Oxidase Isozymes from Pear, Tomato, and Blueberry Fruit in Ripening.
Protein extracts were obtained from climacteric fruits (pear, tomato) and nonclimacteric fruits (blueberry) during various stages of ripening. The use of a gel electrophoresis technique revealed a consistent reinforcement in indoleacetic acid oxidase but not in peroxidase isozymes during ripening. The significance of the results is discussed in relation to the resistance of fruits to ripening and ethylene action.


Toxicity study of ethanolic extract of Chrysanthemum morifolium in rats.
Chrysanthemum morifolium extract (CME) has many pharmacological effects, and the effective components of CME are luteolin and apigenin which have been reported with cytotoxicity in vitro. The purpose of this study was to evaluate the safety of CME in Sprague-Dawley (S-D) rats. In the acute toxicity study, a single oral dose of 15 g/kg body weight (bw) CME was administered to rats, then the rats were observed for 14 d. No treatment-related death was observed, and the maximal tolerance dose estimated was greater than 15 g/kg bw in rats. In the long-term toxicity study, the rats were administered daily by gavage at dose levels of 320, 640, and 1280 mg/kg bw/d for consecutive 26 wk followed by 4 wk recovery period. The results showed that no toxicological changes in body weight, food, and water consumption, hematologic examination, blood biochemical examination, organ weight, and microscopic histopathologic examination were found in any treatment group. Therefore, CME is considered to be safe in general in rats at the limited dose level.


Daughters-in-law as caregivers: how and why do they come to care?
This exploratory qualitative study examines the family dynamics and socio-structural factors which explain how and why some women become caregivers to in-laws. As well, it explores prevailing attitudes about care by in-laws. Material is drawn retrospectively from three previous studies of caregivers in Montreal, Quebec, including 10 semi-structured interviews with daughters-in-law and 72 interviews with spousal and child caregivers. An exploratory framework of the factors which are determinant in becoming a daughter-in-law caregiver is proposed which includes such elements as: social and cultural norms regarding family responsibility for eldercare; social and cultural norms regarding the place and the rights of the elderly; rules of family relations, couple dynamics, gender dynamics and family availability.


An RFID-based intelligent vehicle speed controller using active traffic signals.
These days, mass-produced vehicles benefit from research on Intelligent Transportation System (ITS). One prime example of ITS is vehicle Cruise Control (CC), which allows it to maintain a pre-defined reference speed, to economize on fuel or energy consumption, to avoid speeding fines, or to focus all of the driver's attention on the steering of the vehicle. However, achieving efficient Cruise Control is not easy in roads or urban streets where sudden changes of the speed limit can happen, due to the presence of unexpected obstacles or maintenance work, causing, in inattentive drivers, traffic accidents. In this communication we present a new Infrastructure to Vehicles (I2V) communication and control system for intelligent speed control, which is based upon Radio Frequency Identification (RFID) technology for identification of traffic signals on the road, and high accuracy vehicle speed measurement with a Hall effect-based sensor. A fuzzy logic controller, based on sensor fusion of the information provided by the I2V infrastructure, allows the efficient adaptation of the speed of the vehicle to the circumstances of the road. The performance of the system is checked empirically, with promising results.


Suicide by poisoning.
An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event. Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of cases.


Maximizing functional photoreceptor differentiation from adult human retinal stem cells.
Retinal stem cells (RSCs) are present in the ciliary margin of the adult human eye and can give rise to all retinal cell types. Here we show that modulation of retinal transcription factor gene expression in human RSCs greatly enriches photoreceptor progeny, and that strong enrichment was obtained with the combined transduction of OTX2 and CRX together with the modulation of CHX10. When these genetically modified human RSC progeny are transplanted into mouse eyes, their retinal integration and differentiation is superior to unmodified RSC progeny. Moreover, electrophysiologic and behavioral tests show that these transplanted cells promote functional recovery in transducin mutant mice. This study suggests that gene modulation in human RSCs may provide a source of photoreceptor cells for the treatment of photoreceptor disease.


Preparation of starch macrocellular foam for increasing the dissolution rate of poorly water-soluble drugs.
Starch macrocellular foam (SMF), a novel natural bio-matrix material, was prepared by the hard template method in order to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Nitrendipine (NDP) was chosen as a model drug and was loaded into SMF by the solvent evaporation method. SMF and the loaded SMF samples (NDP-SMF) were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy. In vitro drug release studies showed that SMF significantly increased the dissolution rate of NDP. In vivo studies showed that the NDP-SMF tablets clearly increased the oral bioavailability of NDP in comparison with the reference commercial tablets. All the results obtained demonstrated that SMF was a promising carrier for the oral delivery of poor water-soluble drugs.


HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation.
Costello syndrome is a rare condition comprising mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy, and/or atrial tachycardia), tumor predisposition, and skin and musculoskeletal abnormalities. Recently mutations in HRAS were identified in 12 Japanese and Italian patients with clinical information available on 7 of the Japanese patients. To expand the molecular delineation of Costello syndrome, we performed mutation analysis in 34 North American and 6 European (total 40) patients with Costello syndrome, and detected missense mutations in HRAS in 33 (82.5%) patients. All mutations affected either codon 12 or 13 of the protein product, with G12S occurring in 30 (90.9%) patients of the mutation-positive cases. In two patients, we found a mutation resulting in an alanine substitution in position 12 (G12A), and in one patient, we detected a novel mutation (G13C). Five different HRAS mutations have now been reported in Costello syndrome, however genotype-phenotype correlation remains incomplete.


A cross-talk between DNA methylation and H3 lysine 9 dimethylation at the KvDMR1 region controls the induction of Cdkn1c in muscle cells.
The cdk inhibitor p57kip2, encoded by the Cdkn1c gene, plays a critical role in mammalian development and in the differentiation of several tissues. Cdkn1c protein levels are carefully regulated via imprinting and other epigenetic mechanisms affecting both the promoter and distant regulatory elements, which restrict its expression to particular developmental phases or specific cell types. Inappropriate activation of these regulatory mechanisms leads to Cdkn1c silencing, causing growth disorders and cancer. We have previously reported that, in skeletal muscle cells, induction of Cdkn1c expression requires the binding of the bHLH myogenic factor MyoD to a long-distance regulatory element within the imprinting control region KvDMR1. Interestingly, MyoD binding to KvDMR1 is prevented in myogenic cell types refractory to the induction of Cdkn1c. In the present work, we took advantage of this model system to investigate the epigenetic determinants of the differential interaction of MyoD with KvDMR1. We show that treatment with the DNA demethylating agent 5-azacytidine restores the binding of MyoD to KvDMR1 in cells unresponsive to Cdkn1c induction. This, in turn, promotes the release of a repressive chromatin loop between KvDMR1 and Cdkn1c promoter and, thus, the upregulation of the gene. Analysis of the chromatin status of Cdkn1c promoter and KvDMR1 in unresponsive compared to responsive cell types showed that their differential responsiveness to the MyoD-dependent induction of the gene does not involve just their methylation status but, rather, the differential H3 lysine 9 dimethylation at KvDMR1. Finally, we report that the same histone modification also marks the KvDMR1 region of human cancer cells in which Cdkn1c is silenced. On the basis of these results, we suggest that the epigenetic status of KvDMR1 represents a critical determinant of the cell type-restricted expression of Cdkn1c and, possibly, of its aberrant silencing in some pathological conditions.


Development of x-ray mirror foils using a hot plastic deformation process.
In this paper, we present a silicon reflector developed through a hot plastic deformation process and used as a lightweight, high-angular-resolution x-ray mirror. We deformed the silicon substrate using conical dies with a curvature radius of 100 mm. The measured radii of the reflector were approximately 100 µm greater than the design values. Due to a gap between the die and the reflector toward the edge, it is probable that the substrate did not reach the yield point, and an elastic spring back occurred. In addition, we have evaluated the x-ray imaging capability of the plastically deformed silicon reflector for the first time, to the best of our knowledge. The estimated angular resolution is 1.76 arc min from the entire reflector, and 0.52 arc min in the best region. For the enhancement of the imaging capability, we may improve the shape of die and determine the best parameter set for the deformation.