Molecular cloning and characterization of a complete Chinese hamster provirus related to intracisternal A particle genomes.
We report here the nucleotide sequence of a full-length Chinese hamster genomic proviral element, CHIAP34. CHIAP34 is 6,403 bp long with long terminal repeats of 311 bp at each end. The genetic organization of CHIAP34 was determined by comparison with intracisternal A particle (IAP) genetic elements from the mouse and Syrian hamster. Extensive homology at the nucleotide and deduced amino acid sequence levels was observed between CHIAP34 and the mouse and Syrian hamster IAP elements. CHIAP34 may represent a defective Chinese hamster IAP genetic element. The gag gene consists of 837 codons, of which 558 codons are in a single long open reading frame followed by several frameshifts. The pol gene begins with a -1 frameshift and consists of a long open reading frame of 753 codons followed by a short open reading frame of 103 codons. The putative env region contains multiple termination codons in all reading frames. CHIAP34 is representative of the predominant retroviral elements in the Chinese hamster ovary cell genome present at around 80 copies per haploid genome.


Semantic Representation of Context for Description of Named Rivers in a Terminological Knowledge Base.
The description of named entities in terminological knowledge bases has never been addressed in any depth in terminology. Firm preconceptions, rooted in philosophy, about the only referential function of proper names have presumably led to disparage their inclusion in terminology resources, despite the relevance of named entities having been highlighted by prominent figures in the discipline of terminology. Scholars from different branches of linguistics depart from the conservative stance on proper names and have foregrounded the need for a novel approach, more linguistic than philosophical, to describing proper names. Therefore, this paper proposed a linguistic and terminological approach to the study of named entities when used in scientific discourse, with the purpose of representing them in EcoLexicon, an environmental knowledge base designed according to the premises of Frame-based Terminology. We focused more specifically on named rivers (or potamonyms) mentioned in a coastal engineering corpus. Inclusion of named entities in terminological knowledge bases requires analyzing the context that surrounds them in specialized texts because these contexts convey specialized knowledge about named entities. For the semantic representation of context, this paper thus analyzed the local syntactic and semantic contexts that surrounded potamonyms in coastal engineering texts and described the semantic annotation of the predicate-argument structure of sentences where a potamonym was mentioned. The semantic variables annotated were the following: (1) semantic category of the arguments; (2) semantic role of the arguments; (3) semantic relation between the arguments; and (4) lexical domain of the verbs. This method yielded valuable insight into the different semantic roles that named rivers played, the entities and processes that participated in the events educed by potamonyms through verbs, and how they all interacted. Furthermore, since arguments are specialized terms and verbs are relational constructs, the analysis of argument structure led to the construction of semantic networks that depicted specialized knowledge about named rivers. These conceptual networks were then used to craft the thematic description of potamonyms. Accordingly, the semantic network and the thematic description not only constituted the representation of a potamonym in EcoLexicon, but also allowed the geographic contextualization of specialized concepts in the terminological resource.


Changes in soft tissue profile of African-Americans following extraction treatment.
The purpose of this investigation was to determine changes in soft tissue profile of African-Americans following orthodontic treatment involving extraction of four premolars. The sample consisted of pretreatment and postreatment lateral cephalometric radiographs of 30 males and 30 females of African-American descent exhibiting bimaxillary protrusion. The age of the patients ranged between 10 years 4 months and 17 years 6 months at the start of treatment. Average time between pretreatment and postreatment radiographs was 2 years 11 months in the male group and 3 years 3 months in the female group. Changes in the dentofacial complex and facial soft tissue as a result of treatment and growth were evaluated with cephalometric analysis. Student's t-tests were performed to compare differences. Nasolabial angle increased 9.1 degrees in males and 7.1 degrees in females. Upper lip procumbency relative to SnPg' decreased 1.5 mm in males and 1.7 mm in females. Lower lip retraction relative to SnPg' was 2.7 mm in males and 2.5 mm in females.


The Elusive Goal of Accountability in Graduate Medical Education.
Repeated calls for greater accountability of graduate medical education (GME) have been issued in recent years. In this context, Kenneth Ludmerer's Let Me Heal examines the issue of duty hours limits and paints a picture of failed accountability. The ways in which duty hours regulations have failed are discussed, pointing toward a need to focus on goals and outcomes (such as patient safety) rather than process (such as schedules and shift length).This Commentary considers key issues-who should be accountable, for what, and to whom?-and proposes a potential path for achieving accountability in GME. The author draws from consensus reports published by the Josiah Macy Jr. Foundation and the Institute of Medicine to outline the case for why the U.S. system of GME should be accountable to the public, to individual patients, and to the residents and fellows being educated. Domains of accountability include graduating competent physicians, producing the right workforce, and ensuring an efficient and cost-effective training process that is designed to protect patients. In addition, the author argues that GME should be accountable for providing trainees with reasonable working conditions and compensation.Key requirements for achieving meaningful GME accountability are proposed, including (1) a more effective partnership with the public; (2) explicit goals and assigned responsibilities, reflecting reasonable expectations of what GME can accomplish; (3) reliable metrics for GME outcomes; and (4) a governance system that provides coordination and has the authority to effect changes.


Direct detection and quantification of singlet oxygen during ischemia and reperfusion in rat hearts.
To detect singlet oxygen (1O2) in postischemic reperfused hearts, 5,8-endoperoxide, an oxidation product of beta-carotene, was used as a marker for 1O2 generation and was quantified using high-performance liquid chromatography (HPLC). Isolated rat hearts were subjected to ischemia for 5, 10, 20, 30, and 60 min followed by 10 min of reperfusion with buffer containing 25 microM beta-carotene. The coronary effluent was collected, extracted, and injected into the HPLC unit. The production of 5,8-endoperoxide was maximum during the first 2 min of reperfusion. Maximal accumulated amount of 1O2 was observed in hearts subjected to 60-min ischemia (36.2 +/- 1.7 nmol.10 min-1.g-1) as compared with 10-min ischemia (6.2 +/- 1.0 nmol.10 min-1.g-1). There was a good correlation between the amount of 1O2 production and cardiac function. Treatment with 25 mM histidine significantly decreased 5,8-endoperoxide from 7.02 +/- 0.47 to 0.98 +/- 0.11 nmol.min-1.g-1 (P < 0.01) and improved cardiac function in the group with 60-min ischemia. This study demonstrates that 1) the present method is useful and reliable for the measurement of 1O2 in the heart, 2) 1O2 production during reperfusion is dependent on the duration of initial ischemia, and 3) 1O2 is one of the major factors in postischemic reperfusion injury.


Sugar substitutes: their energy values, bulk characteristics, and potential health benefits.
Restriction of dietary energy extends life and reduces incidences of disease in animals. These benefits would likely extend to humans. However, diet restriction in animals imposes reductions of 30-50% in food intake, which is probably unacceptable to humans. Low-energy sweeteners used in beverages offer minor reductions in energy intake. However, they lack the bulk required for baked goods and other sugar-rich foods. Full-bulk sweeteners providing about one-half the energy of sugar are under development for such uses. Laxation limits their acceptable dose. Even within such limitations, they can help achieve the health benefits for humans indicated by diet restriction. D-Tagatose, a new candidate sweetener, is nearly as sweet as sucrose and has the bulk of sucrose, yet provides zero available energy. We discuss its potential contribution to human diet restriction along with its specific effect in delaying the aging effects of glycosylation.


Protein production, kinetic and biophysical characterization of three human dihydroorotate dehydrogenase mutants associated with Miller syndrome.
Miller syndrome is a rare Mendelian disorder caused by mutations in the gene encoding human dihydroorotate dehydrogenase (DHODH). Human DHODH, a Class II DHODH, is an integral protein of the inner mitochondrial membrane (IMM) catalyzing the fourth step of the de novo pyrimidine biosynthesis pathway. Here we present a summary of the state of knowledge regarding Miller syndrome in the absence of any current review on the topic. We then describe the production and characterization of three distinct DHODH missense mutations (G19E, E52G, R135C) associated with Miller syndrome by means of enzyme kinetics and biophysical techniques. These human DHODH mutants were produced both in E. coli and in insect cells using the baculovirus expression vector system. We can show that the effects of these mutations differ from each other and the wild-type enzyme with respect to decreased enzymatic activity, decreased protein stability and probably disturbance of the correct import into the IMM. In addition, our results show that the N-terminus of human DHODH is not only a structural element necessary for correct mitochondrial import and location of DHODH on the outer side of the IMM, but also influences thermal stability, enzymatic activity and affects the kinetic parameters.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.2023749 .


The effect of antibiotic rotation on colonization with antibiotic-resistant bacilli in a neonatal intensive care unit.
This study was designed to test whether rotation of antibiotics can reduce colonization with resistant Gram-negative bacilli in a neonatal intensive care unit (NICU). A monthly rotation of gentamicin, piperacillin-tazobactam, and ceftazidime was compared with unrestricted antibiotic use in side-by-side NICU populations (rotation team vs control team). Pharyngeal and rectal samples were obtained 3 times a week and tested for Gram-negative bacilli resistant to each of the rotation antibiotics. Pulsed-field gel electrophoresis analysis determined the numbers of genetically discordant resistant organisms on each team. The association between colonization with a resistant bacillus (the primary outcome) and team assignment was tested. A total of 1062 infants were studied during a 1-year period. A total of 10.7% infants on the rotation team versus 7.7% on the control team were colonized with a resistant bacillus. No interteam differences were distinguishable when the numbers of genetically discordant resistant organisms were normalized to the total number of team admissions. The incidence of nosocomial infection and mortality also were similar across teams. These data indicate that rotation of parenteral antibiotics according to the applied protocol has no detectable effect in decreasing the reservoir of resistant Gram-negative bacilli in a tertiary-care NICU.


Influence of Visceral Fat in the Outcomes of Colorectal Cancer.
To determine the relationship of visceral fat (VF) with the surgical outcome of the patients with colorectal cancer (CRC) submitted to curative surgery. Retrospective analysis of all patients submitted to CRC surgery during 3 years with a minimum of 5 years of follow-up. We assessed the length of hospital stay, complications, pathologic reports, surgical re-interventions and hospital re-admissions, relapses, survival time and disease-free time. VF was calculated based on patients' pre-operative CT-scan. The patients were divided into quartiles according to the VF area. Linear regression models and logistic regression models were used to establish a relationship between VF and all data collected. The study included 199 patients (129 with colon cancer [CC] and 70 with rectal cancer). The average area of VF was 115.7 cm2. Patients with CRC revealed a direct relationship between VF and postoperative complications (p = 0.043), anastomotic leakage (p = 0.009) and re-operation (p = 0.005). The subgroup of patients with CC had an inverse association between VF and lymph nodes harvested (p = 0.027). Survival analyses did not reveal significant differences. VF has an influence on postoperative complications, anastomotic leakage and re-operation. A negative influence of VF on lymph nodes harvested was observed on CC patients.


Morphology of in vitro generated ultrahigh molecular weight polyethylene wear particles as a function of contact conditions and material parameters.
Osteolysis in total joint replacements has been linked to ultrahigh molecular weight polyethylene (UHMWPE) wear particles. Although the biological response to these UHMWPE particles is poorly understood at present, it has been demonstrated that particle size and morphology are important factors in such a response. The goal of the present study was twofold: to develop a comprehensive set of particle size and shape descriptors, and to use these descriptors to analyze the effects of different contact conditions and material parameters during the wear process on the size and morphology of UHMWPE wear debris. The three parameters studied were average contact stress (6.9 and 13.8 MPa), macromolecular orientation of the UHMWPE with respect to the wear direction (0 degrees , 45 degrees , and 90 degrees ), and UHMWPE initial surface roughness (Ra = 1 and 3 microm). Tests were performed using pin on disk or cylinder on plate systems for 3 million cycles each. The results indicated that the initial surface roughness of the UHMWPE test samples had no effect on the morphology of UHMWPE wear particles. However, particle size and morphology were a function of the average contact stress and molecular orientation of the UHMWPE.


Submicron-Sized Vermiculite Assisted Oregano Oil for Controlled Release and Long-Term Bacterial Inhibition.
Oregano essential oil (OEO) is a natural compound consisting of potent antibiotic molecules. Its volatility is the major obstacle against the transportation and anti-bacterial performance. In this work, submicron-sized vermiculite (SMV) particles were prepared from Australian vermiculite clay by ball milling, and tested as a potential particulate-carrier for OEO. The loading of OEO by SMV can be easily achieved by mechanical mixing. Compared to raw vermiculite and free OEO, the OEO-loaded SMV displayed sustained isothermal release behaviour of OEO and demonstrated enhanced antibacterial performance in in vitro antibacterial tests against Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis). This study provides a facile and commercially viable approach in designing advantageous carriers for volatile actives in antimicrobial applications.


ECG Data Analysis with Denoising Approach and Customized CNNs.
In the last decade, the proactive diagnosis of diseases with artificial intelligence and its aligned technologies has been an exciting and fruitful area. One of the areas in medical care where constant monitoring is required is cardiovascular diseases. Arrhythmia, one of the cardiovascular diseases, is generally diagnosed by doctors using Electrocardiography (ECG), which records the heart's rhythm and electrical activity. The use of neural networks has been extensively adopted to identify abnormalities in the last few years. It is found that the probability of detecting arrhythmia increases if the denoised signal is used rather than the raw input signal. This paper compares six filters implemented on ECG signals to improve classification accuracy. Custom convolutional neural networks (CCNNs) are designed to filter ECG data. Extensive experiments are drawn by considering the six ECG filters and the proposed custom CCNN models. Comparative analysis reveals that the proposed models outperform the competitive models in various performance metrics.


Effects of dietary gamma-linolenic acid and prenatal ethanol on mouse brain and behavior.
Pregnant B6D2F mice were treated with ethanol (25% Kcal) from days 5-17 of gestation. The diet was supplemented with either 18 : 2n-6 [linoleic acid (LA)] or 18 : 3n-6 [gamma-linolenic acid (GLA)] throughout the study. Ethanol reduced 20 and 22 carbon n-6 and n-3 fatty acids in the brains of adult offspring. Feeding of GLA, compared with LA, increased levels of 20 : 3n-6 and 22 : 4n-6, but reduced 22 : 6n-3, particularly in the offspring of dams administered ethanol during gestation; adult brain weight was also lower in this group. Ethanol reduced the number of viable litters and adult body weight, and GLA reduced birth weight. Neither prenatal ethanol nor GLA affected open-field activity in adult males, nor did either treatment have an effect on the duration of immobility in the forced swimming test. However, GLA did affect circadian activity by increasing running wheel activity during the dark cycle, and decreasing it slightly during the light cycle. These results do not support a beneficial effect of GLA in preventing the developmental effects of ethanol; we suggest caution in the administration of high doses of GLA with ethanol during pregnancy.


Molecular determinants of human uveal melanoma invasion and metastasis.
The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of multiple phenotypes--similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to predict the clinical outcome of patients with uveal melanoma.


Multi-level predictors of psychological problems among methadone maintenance treatment patients in difference types of settings in Vietnam.
Methadone, a long-acting opioid agonist maintenance treatment (MMT) is used to treat opioid addiction by preventing opioid withdrawal and reducing cravings. However, it is important to note that mental conditions may persist, or even remain undetected while methadone maintenance treatment is ongoing. This study aimed to examine the level of psychological problems among MMT patients at public and private health facilities and identify associated factors. From January to September 2018, a cross-sectional study was performed in Nam Dinh province, one of the largest epicenters providing HIV/AIDS surveillance and treatment services in the North of Vietnam. 395 male respondents currently receiving MMT agreed to participate in a face-to-face interview. Depression, Anxiety and Stress Scale-21 (DASS-21) were used to assess psychological problems among patients. The percentage of patients suffering from mild to extremely severe anxiety was the highest among psychological problems (18%). 2.8% of participants had mild depressive symptoms and the percentage of those having mild or moderate stress was approximately 4%. In addition, the longer treatment duration, the lower mental health scores regarding three types of psychological problems. Respondents who received MMT services in public health facilities were more likely to have a higher score of all psychological problems. Participants who lived with partners or spouse, having higher monthly family income had a lower likelihood of having severe depression and stress status. Freelancers or blue-collars/farmers had lower score of depression and anxiety compared to people being unemployed. This study suggests that among our sample, MMT patients receiving treatment in public health facilities might have higher rate of psychological problems, including depression, anxiety, and stress than that of those in the private health facility. These results highlight the necessity of taking psychological counseling adequately for MMT patients and psychological assessment should be prioritized in the early stage of treatment.


Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers.
CTCs have extensively been used for the monitoring and characterization of metastatic prostate cancer, but their application in the clinic is still very scarce. Besides, the resistance mechanisms linked to prostate cancer treatment remain unclear. Liquid biopsies represent the most promising alternative due to the complexity of biopsying bone metastasis and the duration of the disease. We performed a prospective longitudinal study in CTCs from 20 castration-resistant prostate cancer patients treated with docetaxel. For that, we used CellSearch® technology and a custom gene expression panel with qRT-PCR using a CTCs negative enrichment approach. We found that CTCs showed a hybrid phenotype during the disease, where epithelial features were associated with the presence of ≥ 5 CTCs/7.5 mL of blood, while high relative expression of the gene MYCL was observed preferentially in the set of samples with < 5 CTCs/7.5 mL of blood. At baseline, patients whose CTCs had stem or hybrid features showed a later progression. After 1 cycle of docetaxel, high relative expression of ZEB1 indicated worse outcome, while KRT19 and KLK3 high expression could predisposed the patients to a worse prognosis at clinical progression. In the present work we describe biomarkers with clinical relevance for the prediction of early response or resistance in castration-resistant prostate cancer patients. Besides, we question the utility of targeted isolated CTCs and the use of a limited number of markers to define the CTCs population.


No "Self" Advantage for Audiovisual Speech Aftereffects.
Although the default state of the world is that we see and hear other people talking, there is evidence that seeing and hearing ourselves rather than someone else may lead to visual (i.e., lip-read) or auditory "self" advantages. We assessed whether there is a "self" advantage for phonetic recalibration (a lip-read driven cross-modal learning effect) and selective adaptation (a contrastive effect in the opposite direction of recalibration). We observed both aftereffects as well as an on-line effect of lip-read information on auditory perception (i.e., immediate capture), but there was no evidence for a "self" advantage in any of the tasks (as additionally supported by Bayesian statistics). These findings strengthen the emerging notion that recalibration reflects a general learning mechanism, and bolster the argument that adaptation depends on rather low-level auditory/acoustic features of the speech signal.


Fluctuating International Normalized Ratio in Patients Compliant on Warfarin: Could Gastroparesis Be the Cause?
Warfarin is the drug of choice to achieve therapeutic anticoagulation in patients with mechanical heart valves. Factors that interfere with the reliable absorption of warfarin may result in difficult to control international normalized ratio (INR) and can cause significant bleeding complications due to supra-therapeutic INR and thromboembolism from sub-therapeutic INR. The patient's non-compliance is an important factor leading to difficult to control INR but there are additional factors that should be considered in difficult cases when dietary and medication compliance are observed. Gastroparesis is one such predominant and overlooked factor. A 58-year-old African American female with a history of mechanical mitral valve who was on anticoagulation with warfarin was admitted multiple times, with frequent episodes of significant bleeding episodes and fluctuating INR between sub- and supra-therapeutic readings despite being on a relatively stable dose of Coumadin. She was eventually diagnosed with severe gastroparesis, which was the cause of her fluctuating INR. A case can be made to consider gastric motility testing in such patients, where achieving a therapeutic range for anticoagulation is difficult in the setting of medication and dietary compliance.


Using Laser Interference Lithography in the Fabrication of a Simplified Micro- and Nanofluidic Device for Label-free Detection.
Recently, we developed a label-free detection method based on optical diffraction, and implemented it in on our fabricated micro- and nanofluidic device. This detection method is simple and useful for detecting biomolecules, but the device fabrication consists of complicated processes. In this paper, we propose a simple method for fabricating the micro- and nanofluidic device; the fabrication combines laser interference lithography with conventional photolithography. The performance of a device fabricated by the proposed method is comparable to the performance of the device in our previous study.


Acute pancreatitis connected with hypercalcemia crisis in hyperparathyroidism: A case report.
The association between primary hyperparathyroidism (PHPT) and acute pancreatitis is rarely reported. Here we describe the process of acute pancreatitis-mediated PHPT induced by hypercalcemia in a male patient. Hypercalcemia induced by undiagnosed PHPT may be the causative factor in recurrent acute pancreatitis. We report a case of hypercalcemia-induced acute pancreatitis caused by a functioning parathyroid adenoma in a 57-year-old man. The patient initially experienced a series of continuous gastrointestinal symptoms including abdominal distension, abdominal pain, nausea, vomiting, electrolyte disturbance, renal dysfunction, and acute pancreatitis. Due to prolonged hypercalcemia, the patient subsequently underwent surgical resection of the parathyroid adenoma. Two weeks after surgery, his serum calcium, amylase, and lipase concentrations were normal. The patient had a good recovery after a series of other relevant therapies. Acute pancreatitis as the first presentation is a rare clinical symptom caused by PHPT-induced hypercalcemia.


Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study.
Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment. The study included 54 patients with MD who completed 10 courses (5 days per week) of rTMS as an add-on therapy. Thirty patients were treated in the combination group (120% resting motor threshold; left DLPFC, iTBS, 600 stimuli + right DLPFC, 1-Hz rTMS, 600 stimuli), while 24 patients were in the high-frequency rTMS (HF-rTMS) group (120% resting motor threshold; left DLPFC, 10-Hz rTMS, 3000 stimuli). The outcome was assessed based on the changes in scores of 24-item Hamilton Depression Scale (HAMD-24) and 14-item Hamilton Anxiety Scale (HAMA-14). Both depression and anxiety were significantly improved after 2 weeks of treatment by rTMS combined with medication. The combination of iTBS and LF-rTMS was significantly superior to HF-rTMS in improving the scores of HAMD-24 (P = 0.041) and HAMA-14 (P = 0.0095), and the response rate (P = 0.027). The pilot study showed that the combination of iTBS and LF-rTMS may hold promise as a potentially effective alternative therapy for MD due to its efficacy and time-saving benefit. The preliminary results shed light on the study of the efficacy and acceptability of the combination of iTBS and LF-rTMS for MD.


Bio-inspired surface modification of PEEK through the dual cross-linked hydrogel layers.
The biocompatible high-performance material PEEK (polyetheretherketone) is an attractive implant material, however, its hydrophobicity and high friction coefficients severely hinder its biomedical applications. Thus, it is inferred from the recent advances in surface modification technology, achieving the biomimetic natural joint lubrication systems on PEEK still remains a challenge. In view of the above, herein we proposed a novel two-step strategy to fabricate a "soft (dual cross-linked hydrogel) layer-hard (PEEK) substrate" texture that mimics the structure and function of soft cartilage on the hard basal bone in joints. At first, a layer of acrylic acid-co-acryl amide (AA-AM) hydrogel is anchored to the PEEK substrate through UV-initiated polymerization. In the second step, hydrogel coated PEEK substrate is immersed in ferric nitrate solution to create the secondary cross-linkage between Fe3+ and -COOH groups in the hydrogel. As a result, the consequential top-coat hydrogel layer not only transforms the surface wettability (hydrophobic to hydrophilic) but also provides scratch resistance to the underlying PEEK substrate. The modified specimens display low friction coefficients in water under different load conditions. In addition, the obtained surface exhibits a certain self-repairing ability due to its unique physically reversible network structure. Therefore, this work provides a promising strategy for broadening the use of PEEK in orthopedic implants.


[The inotropic action of acetylcholine on the heart ventricles during larval development in the frog Rana temporaria].
The effects of acetylcholine and other cholinergic drugs on the isolated electrically driven larval frog ventricles have been studied. The negative inotropic response to acetylcholine appeared as early as stage 33 of the larval development (the stages were determined according to Dabagian and Sleptsova, 1975) and persisted through all the developmental stages including metamorphosis. The response is muscarinic in origin since it was reproduced with a muscarinic agonist methylfurmetide, blocked with atropine but was not modified with tubocurarine. At the stage 41 and following stages, the sensitivity to acetylcholine was decreased while to methylfurmetide was not. The decreased sensitivity to acetylcholine is most likely due to increase of activity of cholinesterases in the myocardial tissues.


Malignant extrarenal rhabdoid tumour (MERT) with liver metastases as a rare cause of an esophageal tumor in a 57 years old patient.
Tumors with a rhabdoid phenotype are aggressive neoplasms with a dismal prognosis. Malignant extrarenal rhabdoid tumor (MERT) of the esophagus is an extremely rare disease with so far only 6 cases reported. We report on a 57-year-old male patient with rhabdoid tumor situated in the esophagus with metastases to the liver and local lymph nodes. Assuming an undifferentiated esophageal adenocarcinoma a palliative chemotherapy with 5-FU/folinic acid, oxaliplatin, and docetaxel (FLOT) was initiated which was changed towards a combination of doxorubicin and ifosphamide as immunohistochemistry of the primary and the liver metastases revealed a rhabdoid tumor. This treatment with doxorubicin and ifosphamide resulted in a short clinical and radiological response which lasted only for 2 months. Due to the bad general condition at the time of progression no further chemotherapy was initiated. The patient died due to tumor progression 6 months after initial diagnosis which is consistent with other reports on malignant extrarenal rhabdoid tumors (median survival of metastatic disease less than 6 months). Thus, metastatic MERT represents a disease with a poor prognosis and no established standard therapy.


The pregnant uterus as a psycho-endocrine organ.
The pathogenesis of preterm birth (PTB) is largely unknown and the endocrine stress pathway is likely to participate in the mechanisms allowing onset of labor. However, the vast majority of the studies evaluating psychosocial distress denied an association with PTB. Uterine contractility rather than PTB seems associated with distress in pregnancy.


Scopoletin expression in elicitor-treated and tobacco mosaic virus-infected tobacco plants.
Localized acquired resistance (LAR) characterizes a narrow zone of living cells expressing strong defense responses and surrounding cells undergoing a hypersensitive response (HR). In Samsun NN tobacco plants, tissues undergoing tobacco mosaic virus-induced or elicitor-induced LAR exhibit a strong blue fluorescence under UV light. We have shown that scopoletin and its glucoside, scopolin, accounted for the fluorescence: (1) both compounds were identified after extraction and purification by thin layer and high performance liquid chromatography; (2) there was a strict correlation between the occurrence of fluorescence and accumulation of high amounts of scopoletin; and (3) infiltration of commercial scopoletin caused a similar fluorescence to that occurring in LAR tissues. There was a 20-fold increase in scopoletin levels in LAR tissues compared to tissues treated with a non-HR dose of elicitor, while PR1 protein accumulated in similar amounts in both types of tissues. Scopoletin was able to suppress the elicitor-induced HR only when co-infiltrated with very low HR-dose of elicitor. These two observations suggested that, although scopoletin alone would not be able to control the development of the HR through its known antioxidant activity, it may nevertheless participate to such function of LAR tissues in combination with other antioxidant molecules.


Modulating Oxidative Stress in B Cells Promotes Immunotherapy in Food Allergy.
Allergen-specific immunotherapy (SIT) is the mainstay in the treatment of allergic diseases; its therapeutic efficacy is to be improved. Bacterial flagellin (FGN) has immune regulatory functions. This study investigates the role of FGN in promoting immunotherapy efficacy through modulating oxidative stress in regulatory B cells (Bregs). Blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. CD19+ CD5+ Bregs were purified from blood samples by flow cytometry cell sorting. A murine FA model was developed with ovalbumin as the specific antigen. The results showed that peripheral Bregs from FA patients showed lower TLR5-related signals and higher apoptotic activities. The peripheral Breg frequency was negatively correlated with serum FGN levels in FA patients. Exposure to a specific antigen in culture induced antigen-specific Breg apoptosis that was counteracted by the presence of FGN. FGN diminished specific antigen-induced oxidative stress in Bregs. The STAT3/MAPKp38/NF-κB signal pathway was involved in the FGN/TLR5 signal-promoted superoxide dismutase expression in Bregs. Administration of FGN promotes the SIT efficacy in suppressing experimental FA. In summary, administration of FGN promotes SIT efficacy on FA, suggesting that the combination of FGN and SIT can be a novel therapy that has the translational potential to be employed in the treatment of allergic diseases.


Characterization of prenatal healthcare for implementation of congenital toxoplasmosis surveillance program: cross-sectional study.
Prenatal toxoplasmosis remains a neglected disease worldwide and few government programs focusing on its prevention are available. Success in these programs has been extensively reported in the literature, yet the strategies used for their implementation, as a model for such actions in different communities, have not been described. To describe the aspects of prenatal care strategies in 13 municipalities within the regional healthcare unit of Araçatuba, in the northwestern region of the state of São Paulo in 2017, focusing on congenital toxoplasmosis. Descriptive study on prenatal healthcare within the Brazilian National Health System, in 13 participating municipalities. Data on serological tests, referral clinics, notifications, healthcare strategies, health education and drugs for infected children were requested through a questionnaire that was sent via e-mail to people responsible for healthcare services in these municipalities. Major differences relating to diagnoses, reference outpatient clinics, notifications, health education and healthcare and drugs for infected children were reported among the prenatal strategies of these 13 municipal healthcare services. The lack of standardized prenatal strategy in the study area may compromise the prevention of infection. However, our identification of each aspect of prenatal care corroborates the need to implement a healthcare surveillance program relating to congenital toxoplasmosis.


Pulmonary hypertension in patient with elevated homocystein level and blast injuries.
38-year-old man had chronic deep venous thrombosis (DVT) as a result of multiple injuries caused by an explosion of grenade 12 years ago, with recurrent pulmonary thromboembolisms and pulmonary hypertension which was unrecognized for a decade. Patient was admitted with a progressive dyspnea and exercise intolerance (NYHA II). The diagnosis was established according to clinical symptoms, transthoracic echocardiography, phlebography, lung scintigraphy and pulmonary angiography. Oral anticoagulant therapy was introduced and cava filter indicated to implant. During phlebography a floating thrombus was found in the inferior cava vein underneath renal vein. Implantation was delayed and patient received systemic fibrinolytic therapy with streptokinase (7500 000 UI within 4 days), followed by heparin infusion and warfarin. Post-fibrinolytic phlebography showed clear lumen of inferior vena cava. Fibrinolysis had also affected pulmonary hypertension-systolic pressure in the right ventricle measured by Doppler echocardiography decreased from 90 to 65 mmHg. Permanent intravenous cava filter was implanted.


The number of the Trf receptors on human hematopoietic cell lines is influenced by membrane phospholipids.
The effect of phospholipases and of inhibitors of phospholipases on the binding of 125I-Trf to human hematopoietic cell lines was investigated. The results showed that incubation of the cells with phospholipases or inhibitors of phospholipases elicited a significant reduction of the Trf binding. This phenomenon was related to a reduction of Trf binding sites without affecting the affinity of the receptors for Trf. These results suggest that the phospholipids of the cell membrane may modulate the binding of transferrin to its receptor.


Neuro-Immune Aspects of Schizophrenia with Severe Negative Symptoms: New Diagnostic Markers of Disease Phenotype.
The aim of the study was to analyze the immune-inflammatory profile of patients with paranoid schizophrenia and relate it to the severity of negative symptoms and the MRI data in order to identify biomarkers of schizophrenia severity, search for new approaches to therapy, and control its effectiveness. The main group included 51 patients with paranoid schizophrenia, the control group - 30 healthy subjects. Patients underwent MRI scans and immunological studies, which included an assessment of natural and adaptive immunity, the systemic level of key pro-inflammatory and anti-inflammatory cytokines, and other markers of inflammation. Disorders of immunity and immunoinflammatory profile in patients with paranoid schizophrenia with severe negative symptoms were revealed for the first time: in the presence of severe negative symptoms (>15 points according to the NSA-4 scale), the levels of humoral immunity factors, cytokines IL-10 and IL-12p40 and neurotrophin NGF were increased as well as the markers of systemic inflammation. Morphometric changes in the brain, typical for patients with schizophrenia, and also specific for patients with severe negative symptoms, were determined. The data analysis revealed correlations between the immune changes with structural changes in some of the brain areas, including the frontal cortex and hippocampus. Associations were found between the levels of anti-inflammatory IL-10, IL-12p40 cytokines and morphometric parameters of the brain, specific only for schizophrenic patients with severe negative symptoms. The interdisciplinary approach, combining brain morphometry with in-depth immunological and clinical studies, made it possible to determine neurobiological, immune, and neurocognitive markers of paranoid schizophrenia with severe negative symptoms. The results are important for further deciphering the pathogenesis of schizophrenia and its subtypes, as well as for the search for new approaches to the treatment of severe forms of the disease.


Factors Influencing Medical Personnel to Work in Primary Health Care Institutions: An Extended Theory of Planned Behavior.
In China, the primary health care institutions (PHCIs) have difficulty winning the trust of residents because of the shortage of medical personnel and the low level of skills. The government has advocated encouraging qualified doctors to work in PHCIs, but no obvious results are achieved. Based on the theory of planned behavior (TPB), this paper explores the factors affecting medical personnel seeking employment in PHCIs and then putting forward measures to improve the human resources construction of PHCIs. A three-stage survey was conducted to obtain the factors and a structural equation modeling (SEM) was applied to examine the relationship of the factors. We found that the factors affecting medical personnel to work in PHCIs include the specific conditions and work contents of PHCIs, as well as the family life and regional factors. Besides, there is a significant correlation and indirectness between these factors. Therefore, targeted measures can be proposed to improve the intention of medical personnel seeking employment in PHCIs. This study provides theoretical support for encouraging medical personnel to work in PHCIs and improving the primary health care system.


Links between the circadian rhythm, obesity and the microbiome.
Obesity is linked to a wide range of serious illnesses. In addition to the important impact on the health of the individual, obesity also has a substantial impact on the economy. Disruption of physiological day-night cycles could contribute to the increased incidence of obesity. According to the American National Sleep Federation, the percentage of the people who reported a sleep duration of six hours or less increased from 12 to 37 % over ten years. Insufficient sleep leads not only to an increase of the total calorie intake but changes the meal preference in favor of palatable foods and meals with high carbohydrate content. A decrease of leptin and increase of ghrelin levels caused by sleep deficiency can also play a role. In addition to the higher caloric intake, the timing of food consumption should be taken into account. The same meal eaten during the night versus the day is associated with increased postprandial glucose and triglyceride levels. The gut microbiome has also been recently understood as an endocrine system, with links between the gut microbiome and circadian rhythm changes possibly influencing increased obesity.


Electron self-exchange between Au140(+/0) nanoparticles is faster than that between Au38(+/0) in solid-state, mixed-valent films.
The well-defined one-electron steps in the voltammetry of solutions of the nanoparticles Au38(SC2Ph)24 and Au140(SC6)53 (SC2Ph = phenylethanethiolate; SC6 = hexanethiolate) enable preparation of solutions containing, for example, Au38(SC2Ph)24 and Au38(SC2Ph)24+(ClO4)- nanoparticles in known relative proportions. From these solutions can be cast dry, mixed-valent films demonstrably containing the same proportions. Electronic conduction in such mixed-valent films is shown to occur by a bimolecular electron self-exchange reaction at a rate proportional to the concentration product, [Au38][Au38+]. The observed Au38(+/0) rate constant, approximately 2 x 10(6) M(-1) s(-1), is much smaller than that previously observed for Au140(+/0) films (ca. 4 x 10(9) M(-1) s(-1); Wuelfing, W. P.; et al. J. Am. Chem. Soc. 2000, 122, 11465). To our knowledge, this is the first example of a significant size effect in metal nanoparticle electron-transfer dynamics. Thermal activation parameters for the electron-hopping conductivities of the two nanoparticles reveal that the rate difference is mainly caused by energy barriers (EA) for Au38(+/0) electron transfers that are larger by approximately 3-fold than those for Au140(+/0) electron transfers (ca. 20 vs 7 kJ/mol). Differences in pre-exponential terms in the activation equations for the two nanoparticles are a smaller contributor to the rate constant difference and can be partly ascribed to differences in tunneling distances.


Method development strategy for the analysis of anionic solutes by capillary electrophoresis.
A systematic approach to the development of methodology for the analysis of anionic solutes by capillary electrophoresis (CE) has been implemented. The strategy allows a rapid optimization of the experimental conditions and is based on the following steps: 1) A near optimum pH is chosen by inspection of the effective mobility versus pH curves of the sample components. The optimum pH lies in a region where the differences in the mobilities of all solutes are maximal. 2) An electrolyte system is selected by comparing the effective mobility of the electrolyte with the effective mobility of the primary components of the studied mixture. The appropriate electrolyte has a mobility as similar as possible to the mobility of the major components of the sample. 3) An initial experiment is run with the selected electrolyte system adjusted to the chosen pH and input values for other instrumental variables and electrolyte characteristics. 4) Depending on the degree of resolution obtained in the initial run, two important variables, the applied voltage and the electrolyte concentration, are then tuned in the proper direction, favoring the achievement of the highest resolution at the lowest possible analysis time. The proposed method development strategy was validated experimentally with a mixture of short-chained carboxylic acids and inorganic anions.


Contribution of ribavirin transporter gene polymorphism to treatment response in peginterferon plus ribavirin therapy for HCV genotype 1b patients.
Standard-dose ribavirin is crucial for the standard-of-care treatment of chronic hepatitis C virus (HCV) infection. Equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, is the main transporter that imports ribavirin into human hepatocytes. To determine whether single nucleotide polymorphisms (SNPs) at the SLC29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors. A total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNPs related to the IL28B, ITPA and SLC29A1 genes were genotyped using real-time detection polymerase chain reaction. Factors associated with sustained virological response (SVR) were analysed using multiple logistic regression analysis. Multivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR: age [P = 0.023, odds ratio (OR) = 0.97], gender (P = 0.0047, OR = 2.25), platelet count (P = 0.00017, OR = 1.11), viral load (P = 0.00026, OR = 0.54), IL28B SNP rs12979860 (P = 1.09 × 10(-7) , OR = 8.68) and SLC29A1 SNP rs6932345 (P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC29A1 and IL28B SNPs were also significantly associated with rapid virological response. The SNP at the major ribavirin transporter ENT1 gene SLC29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.


PatcherBot: a single-cell electrophysiology robot for adherent cells and brain slices.
Intracellular patch-clamp electrophysiology, one of the most ubiquitous, high-fidelity techniques in biophysics, remains laborious and low-throughput. While previous efforts have succeeded at automating some steps of the technique, here we demonstrate a robotic 'PatcherBot' system that can perform many patch-clamp recordings sequentially, fully unattended. Comprehensive automation is accomplished by outfitting the robot with machine vision, and cleaning pipettes instead of manually exchanging them. the PatcherBot can obtain data at a rate of 16 cells per hour and work with no human intervention for up to 3 h. We demonstrate the broad applicability and scalability of this system by performing hundreds of recordings in tissue culture cells and mouse brain slices with no human supervision. Using the PatcherBot, we also discovered that pipette cleaning can be improved by a factor of three. The system is potentially transformative for applications that depend on many high-quality measurements of single cells, such as drug screening, protein functional characterization, and multimodal cell type investigations.


Roles of plant retinoblastoma protein: cell cycle and beyond.
The human retinoblastoma (RB1) protein is a tumor suppressor that negatively regulates cell cycle progression through its interaction with members of the E2F/DP family of transcription factors. However, RB-related (RBR) proteins are an early acquisition during eukaryote evolution present in plant lineages, including unicellular algae, ancient plants (ferns, lycophytes, liverworts, mosses), gymnosperms, and angiosperms. The main RBR protein domains and interactions with E2Fs are conserved in all eukaryotes and not only regulate the G1/S transition but also the G2/M transition, as part of DREAM complexes. RBR proteins are also important for asymmetric cell division, stem cell maintenance, and the DNA damage response (DDR). RBR proteins play crucial roles at every developmental phase transition, in association with chromatin factors, as well as during the reproductive phase during female and male gametes production and embryo development. Here, we review the processes where plant RBR proteins play a role and discuss possible avenues of research to obtain a full picture of the multifunctional roles of RBR for plant life.


[A physiological validation for the early diagnosis of hypogalactia in women].
Colostrum cell composition observed during the first 24 hrs following delivery objectively reflects the degree of prelactation preparation of the breast. The state of neutrophilic leucocytes appeared to be the most informative in this respect. In normal lactation, maximal number of neutrophilic leucocytes was found during the first 24 hrs after delivery. The leucocyte inflow to the colostrum is highly increased in hypogalactia. Leucocytes aggregation which is the most characteristic for normal lactation did not occur in hypogalactia. The activity of alkaline phosphatase and myeloperoxidase of leucocytes is much higher in normal lactation and much lower in hypogalactia. The evaluation of alkaline phosphatase activity and sudanophilic lipids content shows no differences related to the lactation level.


The confusion effect in predatory neural networks.
A simple artificial neural network model of image reconstruction in sensory maps is presented to explain the difficulty predators experience in targeting prey in large groups (the confusion effect). Networks are trained to reconstruct multiple randomly conformed "retinal" images of prey groups in an internal spatial map of their immediate environment. They are then used to simulate prey targeting by predators on groups of specific conformation. Networks trained with the biologically plausible associative reward-penalty method produce a more realistic model of the confusion effect than those trained with the popular but biologically implausible backpropagation method. The associative reward-penalty model makes the novel prediction that the accuracy-group size relationship is U shaped, and this prediction is confirmed by empirical data gathered from interactive computer simulation experiments with humans as "predators." The model further predicts all factors known from previous empirical work (and most factors suspected) to alleviate the confusion effect: increased relative intensity of the target object, heterogeneity of group composition, and isolation of the target. Interestingly, group compaction per se is not predicted to worsen predator confusion. This study indicates that the relatively simple, nonattentional mechanism of information degradation in the sensory mapping process is potentially important in generating the confusion effect.


Independently driven four-probe method for local electrical characteristics in organic thin-film transistors under controlled channel potential.
We describe an independently driven four-probe method to investigate local channel mobility in organic field-effect transistors (OFETs). In OFET devices, probe-organic contact resistance affects device characteristics even in four-probe measurement because a change in contact resistance at the source probe induces a change in channel potential, resulting in different local carrier density. To overcome this problem, we introduced a feedback circuit between the source probe and a channel voltage probe to keep the channel potential constant. We demonstrate four-probe I-V measurement on a pentacene thin film (50 nm thick) under controlled channel potential. The feedback successfully enables us to separate contact resistance and channel resistance even under different contact conditions. We also measured four-probe resistance as a function of gate bias and channel probe position. The present results were in good agreement with two-dimensional model calculation by arranging four probes in a defect-free area; the mobility of the pentacene single grain was evaluated to be 0.25 cm(2)/(V s).


Health-related quality of life among 5-year survivors of esophageal cancer surgery: a prospective population-based study.
To clarify whether health-related quality of life (HRQL) can be restored in 5-year survivors of esophageal cancer surgery. The nationwide Swedish prospective and population-based cohort for this study consisted of patients with esophageal cancer who were treated surgically between 2001 and 2005 and were alive 5 years after surgery. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC QLQ-OES18 (the disease site-specific module for esophageal cancer) were used to assess HRQL 6 months, 3 years, and 5 years postoperatively. Paired t tests were used to evaluate changes in HRQL over time. Patients' HRQL was classified as improved, stable, or deteriorated. Multivariable linear regression was used to calculate mean score difference in HRQL with 95% CIs between patients and a background population according to HRQL category. Among 153 eligible patients alive after 5 years, 117 (76%) answered all HRQL assessments. Among a random sample of 6,969 Swedish adults representing the corresponding background population, 4,910 (70.5%) participated. For most patients, HRQL remained stable or improved over time, and their HRQL was comparable to that of the background population. Patients who deteriorated over time reported large and clinically significant mean score differences for all measures. For example, 5 years after surgery, physical function was stable or improved in 86% of patients and their mean score (87) was similar to that of the background population (88), but the 14% who deteriorated had a substantially lower mean score of 56. HRQL recovers to a level comparable to that in the background population in most patients who survive 5 years after esophagectomy for cancer, although a subgroup of patients has substantially worse HRQL.


Diagnostic performance of cone-beam computed tomography for scaphoid fractures: a systematic review and diagnostic meta-analysis.
Scaphoid fractures are the most common carpal fractures. Diagnosing scaphoid fractures is challenging. Recently, cone-beam computed tomography (CBCT) has been shown to be a promising strategy for diagnosing scaphoid fractures. The diagnostic performance of CBCT remains inconclusive in the literature. Through a systematic review and meta-analysis, our study aims to determine the diagnostic performance of CBCT for diagnosing scaphoid fractures. Five databases were searched up to March 25, 2020. We included prospective and retrospective studies describing the diagnostic accuracy of CBCT for scaphoid fractures in adult patients. QUADAS-2 tool was used to assess the quality of the included studies. Four studies (n = 350) were included in the meta-analysis. Three of the four studies had high bias risk. The result showed that CBCT had a pooled sensitivity of 0.88 and a pooled specificity of 0.99 for scaphoid fracture diagnosis. The heterogeneities of sensitivity and specificity were substantial. The area under the summary receiver operating characteristic curve was 0.98. No significant publication bias was observed. The result suggested that the diagnostic performance of CBCT for scaphoid fracture was excellent. The certainty of current evidence is low. Further well-designed studies with large sample sizes are warranted to confirm this finding.


Linear energy transfer dependence of the effects of carbon ion beams on adventitious shoot regeneration from in vitro leaf explants of Saintpaulia ionahta.
To determine the effects of carbon ion beams with five different linear energy transfer (LET) values on adventitious shoots from in vitro leaf explants of Saintpaulia ionahta Mauve cultivar with regard to tissue increase, shoots differentiation and morphology changes in the shoots. In vitro leaf explant samples were irradiated with carbon ion beams with LET values in the range of 31 approximately 151 keV/microm or 8 MeV of X-rays (LET = 0.2 keV/microm) at different doses. Fresh weight increase, surviving fraction and percentage of the explants with regenerated malformed shoots in all the irradiated leaf explants were statistically analysed. The fresh weight increase (FWI) and surviving fraction (SF) decreased dramatically with increasing LET at the same doses. In addition, malformed shoots, including curliness, carnification, nicks and chlorophyll deficiency, occurred in both carbon ion beam and X-ray irradiations. The induction frequency with the former, however, was far more than that with the X-rays. This work demonstrated the LET dependence of the relative biological effectiveness (RBE) of tissue culture of Saintpaulia ionahta according to 50% FWI and 50% SF. After irradiating leaf explants with 5 Gy of a 221 MeV carbon ion beam having a LET value of 96 keV/microm throughout the sample, a chlorophyll-deficient (CD) mutant, which could transmit the character of chlorophyll deficiency to its progeny through three continuous tissue culture cycles, and plantlets with other malformations were obtained.


Isolation of highly fusogenic variants of simian virus 5 from persistently infected cells that produce and respond to interferon.
A series of experiments were undertaken to examine how interferon and neutralizing antibodies influence the ability of simian virus 5 (SV5) (strain W3) to establish and maintain persistent infections in murine cells. In contrast to the rapid decline in SV5 protein synthesis observed in murine BALB/c fibroblasts (BF cells), which produce and respond to interferon, between 24 and 48 h postinfection there was no inhibition of virus protein synthesis in MSFI- cells, skin fibroblasts derived from alpha/beta-interferon receptor knockout BALB/c mice. Furthermore, the addition of anti-interferon antibodies to the culture medium of infected BF cells significantly reduced the observed decline in virus protein synthesis. Following infection of untreated BF cells, the majority replicated virus but survived the infection and eventually cleared the virus after 8 to 15 days. However, not all the cells were cured, and the cultures became persistently infected. Upon passage of persistently infected cultures, the virus fluxed between active and repressed states as a consequence of interferon production. This resulted in a balance being reached in which only 5 to 20% of the cells were infected at any one time. After 30 passages of the persistently infected cells, highly fusogenic virus variants arose (one of which was isolated and termed W3-f). W3-f remained as sensitive to interferon as the parental W3 isolate but, in the absence of interferon, spread much more rapidly than the parental W3 strain through BF cell monolayers. Sequence analysis revealed no deduced amino acid differences between the F proteins of W3 and W3-f. BF cell cultures persistently infected with W3-f were rapidly cleared of virus by the addition of virus-neutralizing antibodies to the culture medium. In contrast, neutralizing antibodies had little effect on the numbers of cells persistently infected with W3 over several passages. These results suggest that the ability of paramyxoviruses to cause cell-cell fusion may be selected for in vivo as a consequence of their adaptation to the interferon response rather than their need to escape from neutralizing antibodies. The significance of these observations with regard to persistent parainfluenza virus infections in vivo is further discussed.


The use of spiral CT in the detection and management of a permanent maxillary first molar with single root and single canal: A rare occurrence.
A sound knowledge of the normal tooth morphology and its numerous variations is essential to the success of endodontic therapy. While extra canals and lateral canals are routinely encountered and documented, there also exists the rare possibility of a fewer number of canals than normal. Early detection of such an occurrence is critical to the prevention of iatrogenic errors during endodontic treatment. The advent of spiral CT as a diagnostic tool serves as a much needed confirmation to understand the complex three dimensional anatomy of teeth. The aim of this case report is to highlight one such case reporting unusual morphology of the permanent maxillary first molar displaying single canal and single root, and the role of spiral CT in its detection and management. Key words:Permanent maxillary first molar, root canal anatomy, single root, single canal, Spiral CT.


Treatment of diabetes in the elderly. Addressing its complexities in this high-risk group.
Diabetes is becoming increasingly common in the elderly, affecting more than one person in five. In this group, type 2 diabetes is by far the more prevalent form. Despite this major public health concern, evidence-based information specific to older adults with diabetes is surprisingly lacking. Complicating the medical picture, the elderly commonly have a host of comorbidities that can influence diabetes treatment and therapeutic goals. Here, the authors present an overview of therapy, discussing the antidiabetic agents available and their best use in the older population with diabetes.


Serum osteocalcin is increased in patients with hyperthyroidism and decreased in patients receiving glucocorticoids.
Osteocalcin (OC) is a vitamin K-dependent protein which is synthesized by osteoblasts and is present in the circulation. We measured serum OC concentrations in 10 patients receiving corticosteroids (CS) for chronic obstructive pulmonary disease and in 9 hyperthyroid (HT) patients. Mean values ( +/- SE) were as follows: There was a significant correlation between OC and alkaline phosphatase (r = 0.607; P = 0.006) when CS and HT groups were combined. Elevated serum OC concentrations in hyperthyroid patients may reflect increased osteoblastic activity, while decreased levels in corticosteroid-treated patients may reflect decreased osteoblastic activity.


The central organization of the vagus nerve innervating the colon of the rat.
The extent to which the vagus nerve innervates the colon remains controversial. In 29 rats the tracer cholera toxin-horseradish peroxidase was injected into the cecum, the ascending, transverse, or descending colon or the rectum. For comparison, control injections were made into the stomach. For all areas of colon except the rectum, brainstem motoneuronal labeling was limited to the lateral third of the dorsal motor nucleus of the vagus nerve bilaterally. In contrast, gastric injections resulted in motoneuronal labeling limited to the medial portions of the nucleus. The number of labeled motoneurons was greatest following injection of the cecum, and it significantly decreased for the more distal areas of the colon. Colonic motoneuron dendrites projected into the nucleus of the solitary tract and within the dorsal motor nucleus of the vagus nerve. Sensory afferent terminal labeling was limited to the commissural and medial subnuclei of the nucleus of the solitary tract. For the rectum, sensory and motor labeling was limited to the spinal cord. The distribution of labeling within the vagal complex indicates that all regions of the colon, except the rectum, are innervated by the celiac and accessory celiac branches of the vagus nerve.


Prostates, pates, and pimples. The potential medical uses of steroid 5 alpha-reductase inhibitors.
The steroid 5 alpha-reductase enzyme is responsible for the formation of DHT from testosterone. DHT has been the major androgen implicated in the pathogenesis of benign prostatic hyperplasia, male pattern baldness, acne, and idiopathic female hirsutism. Although specific inhibitors of 5 alpha-reductase are not yet generally available for human use, it is expected that they will become available within the next several years. Based on biochemical, histologic, and anatomic information from animals given 5 alpha-reductase inhibitors, preliminary data on their use in humans, and knowledge gained from men with the inherited 5 alpha-reductase deficiency, it is expected that these 5 alpha-reductase inhibitors may have a major role in the medical management of benign prostatic hyperplasia. In addition, it is possible that these compounds will hold promise for the prevention of male pattern baldness and for the treatment of resistant acne and idiopathic hirsutism.


Fluxing of mantle carbon as a physical agent for metallogenic fertilization of the crust.
Magmatic systems play a crucial role in enriching the crust with volatiles and elements that reside primarily within the Earth's mantle, including economically important metals like nickel, copper and platinum-group elements. However, transport of these metals within silicate magmas primarily occurs within dense sulfide liquids, which tend to coalesce, settle and not be efficiently transported in ascending magmas. Here we show textural observations, backed up with carbon and oxygen isotope data, which indicate an intimate association between mantle-derived carbonates and sulfides in some mafic-ultramafic magmatic systems emplaced at the base of the continental crust. We propose that carbon, as a buoyant supercritical CO2 fluid, might be a covert agent aiding and promoting the physical transport of sulfides across the mantle-crust transition. This may be a common but cryptic mechanism that facilitates cycling of volatiles and metals from the mantle to the lower-to-mid continental crust, which leaves little footprint behind by the time magmas reach the Earth's surface.


Regulation by cAMP and vasoactive intestinal peptide of phosphorylation of specific proteins in striatal cells in culture.
We have studied three low molecular weight phosphoproteins, ARPP-16, ARPP-19, and ARPP-21 (cAMP-regulated phosphoproteins of Mr 16,000, 19,000, and 21,000, respectively) in reaggregate cultures from various regions of fetal mouse brain. ARPP-16 and ARPP-21 were detected only in striatal and cortical cultures. In contrast, ARP-19, which is structurally related to ARPP-16, was also present in reaggregate cultures prepared from thalamus and ventral and dorsal mesencephalon, as well as in monolayer cultures of astroglial cells. In striatal aggregates cultured over a 3-week period, the relative levels of ARPP-16, ARPP-21, and synapsin I/protein IIIa (synaptic vesicle-associated phosphoproteins closely related to each other and treated as a single entity in the present study) increased with time, whereas the level of ARPP-19 decreased. Incubation of striatal aggregates with 8-Br-cAMP, forskolin, or vasoactive intestinal peptide increased the phosphorylation of all these proteins. We conclude that the state of phosphorylation of two proteins enriched in specific neurons (ARPP-16 and ARPP-21) and two more widely distributed proteins (ARPP-19 and synapsin I/protein IIIa) is regulated by cAMP and vasoactive intestinal peptide in striatal cells in culture. These phosphoproteins may therefore play a role in mediating some of the actions of vasoactive intestinal peptide in the caudate-putamen.


An FXPRLamide neuropeptide induces seasonal reproductive polyphenism underlying a life-history tradeoff in the tussock moth.
The white spotted tussock moth, Orgyia thyellina, is a typical insect that exhibits seasonal polyphenisms in morphological, physiological, and behavioral traits, including a life-history tradeoff known as oogenesis-flight syndrome. However, the developmental processes and molecular mechanisms that mediate developmental plasticity, including life-history tradeoff, remain largely unknown. To analyze the molecular mechanisms involved in reproductive polyphenism, including the diapause induction, we first cloned and characterized the diapause hormone-pheromone biosynthesis activating neuropeptide (DH-PBAN) cDNA encoding the five Phe-X-Pro-Arg-Leu-NH(2) (FXPRLa) neuropeptides: DH, PBAN, and α-, β-, and γ-SGNPs (subesophageal ganglion neuropeptides). This gene is expressed in neurosecretory cells within the subesophageal ganglion whose axonal projections reach the neurohemal organ, the corpus cardiacum, suggesting that the DH neuroendocrine system is conserved in Lepidoptera. By injection of chemically synthetic DH and anti-FXPRLa antibody into female pupae, we revealed that not only does the Orgyia DH induce embryonic diapause, but also that this neuropeptide induces seasonal polyphenism, participating in the hypertrophy of follicles and ovaries. In addition, the other four FXPRLa also induced embryonic diapause in O. thyellina, but not in Bombyx mori. This is the first study showing that a neuropeptide has a pleiotropic effect in seasonal reproductive polyphenism to accomplish seasonal adaptation. We also show that a novel factor (i.e., the DH neuropeptide) acts as an important inducer of seasonal polyphenism underlying a life-history tradeoff. Furthermore, we speculate that there must be evolutionary conservation and diversification in the neuroendocrine systems of two lepidopteran genera, Orgyia and Bombyx, in order to facilitate the evolution of coregulated life-history traits and tradeoffs.


Common genetic variation in Neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain.
Structural and polymorphic variations in Neuregulin 3 (NRG3), 10q22-23 are associated with a broad spectrum of neurodevelopmental disorders including developmental delay, cognitive impairment, autism, and schizophrenia. NRG3 is a member of the neuregulin family of EGF proteins and a ligand for the ErbB4 receptor tyrosine kinase that plays pleotropic roles in neurodevelopment. Several genes in the NRG-ErbB signaling pathway including NRG1 and ErbB4 have been implicated in genetic predisposition to schizophrenia. Previous fine mapping of the 10q22-23 locus in schizophrenia identified genome-wide significant association between delusion severity and polymorphisms in intron 1 of NRG3 (rs10883866, rs10748842, and rs6584400). The biological mechanisms remain unknown. We identified significant association of these SNPs with increased risk for schizophrenia in 350 families with an affected offspring and confirmed association to patient delusion and positive symptom severity. Molecular cloning and cDNA sequencing in human brain revealed that NRG3 undergoes complex splicing, giving rise to multiple structurally distinct isoforms. RNA expression profiling of these isoforms in the prefrontal cortex of 400 individuals revealed that NRG3 expression is developmentally regulated and pathologically increased in schizophrenia. Moreover, we show that rs10748842 lies within a DNA ultraconserved element and homedomain and strongly predicts brain expression of NRG3 isoforms that contain a unique developmentally regulated 5' exon (P = 1.097E(-12) to 1.445E(-15)). Our observations strengthen the evidence that NRG3 is a schizophrenia susceptibility gene, provide quantitative insight into NRG3 transcription traits in the human brain, and reveal a probable mechanistic basis for disease association.


Persons of lesser values--moral argument and the "final solution".
For many persons, 'Holocaust-abomination' is a fixed point on their moral compass: if anything can be evil, it was. Yet at least one of the justifications deployed by its perpetrators (the eugenics argument) involves widely-held values concerning human health and procreation. Hence persons endorsing many current activities based on those values (e.g. genetic counselling) have been charged with being on a morally deplorable slippery slope. This paper sketches the necessary structure of a moral position capable of consistently embracing those values without placing its occupants on that slippery slope.


AIDS-associated Kaposi's sarcoma in female patients.
Kaposi's sarcoma (KS) is very unusual in Caucasian women with AIDS. We conducted a retrospective survey of 12 female AIDS patients with KS, including 11 Caucasian women. HIV infection was thought to have been acquired after sexual contact, intravenous drug use (nine cases) or blood transfusion (three cases). In these patients KS was often the first manifestation of AIDS and showed an aggressive course. The disease was associated with a severe immunodeficiency (CD4 T lymphocyte count less than 100 x 10(6)/l in 50% of cases) and a poor prognosis. In four patients, lesions first developed on areas of sexual contact, supporting the hypothesis that KS is a sexually transmitted disease.


Q-switched laser in an SMS cavity for inhibiting nonlinear effects.
In the design of high-power Q-switched fiber lasers, nonlinear effects often become barriers that prevent the scale up of pulse energy and peak power. New designs and components that could inhibit or suppress nonlinear effects are in high demand, particularly in all-fiber configurations. In this paper, we demonstrated a Q-switched Yb-doped fiber laser in a single-mode multimode single-mode (SMS) structure to inhibit fiber nonlinear effects. The laser-generated Q-switched pulses with a peak power close to 1 kW (pulse width and energy of 100 ns and 92 μJ, respectively). The output spectrum of this laser was compared with that of a Q-switched Yb-doped fiber laser built in a conventional configuration with similar output peak power. The results showed, for the first time to our knowledge, that the SMS Q-switched laser completely inhibited the stimulated Raman scattering and significantly reduced self-phase modulation.


mtDNA variation in the Buryat population of the Barguzin Valley: New insights into the micro-evolutionary history of the Baikal area.
Southern Siberian populations, including the Buryat, have been of great interest in investigating the exchanges between Eastern and Western Eurasia and understanding the peopling of Siberia and the New World. Previous studies mainly employed a phylogenetic approach, and thus used pooled samples to detect a maximum of variability. As different sampling strategies may result in different pictures of a population's evolutionary history, we proposed in this study to focus on a local Buryat population selected on the basis of geographical, archaeological and ethno-historical data. This study investigated a local population from the Barguzin Valley, on the north-western shores of Lake Baikal identified as the most likely place of Buryat origin. We analysed mitochondrial DNA (mtDNA) RFLPs markers, HVS-I and HVS-II sequences to discuss the genetic variability of this population, and to compare our local sample with pooled Buryat samples and neighbouring Siberian populations. The Barguzin Buryat sample shows depressed neutrality scores compared to the pooled Buryat sample, and different genetic affinities with the Mongol and Turco-Evenk populations. These results underline the need to use local samples, in addition to pooled samples, to investigate the history of human populations at the micro-evolutionary level.


Production of monoclonal antibodies specific for ganglioside GD3.
Four kinds of anti-GD3 monoclonal antibodies, DSG-1, -2, -3, and -4, of the IgM class were obtained by the immunization of BALB/c mice with enzootic bovine leukosis tumor tissue-derived ganglioside GD3 inserted into liposomes with Salmonella minnesota R595 lipopolysaccharides. The specificities of the monoclonal antibodies obtained were defined by complement-dependent liposome immune lysis assay and by enzyme immunostaining on thin-layer chromatography. The reactivities of the monoclonal antibodies obtained to four ganglioside GD3 variants [GD3(NeuAc-NeuAc), GD3(NeuAc-NeuGc), GD3(NeuGc-NeuAc), and GD3(NeuGc-NeuGc)] were tested. All of the monoclonal antibodies were found to react with GD3(NeuAc-NeuAc) and GD3(NeuAc-NeuGc) but not with GD3(NeuGc-NeuAc) or GD3(NeuGc-NeuGc). Furthermore, various purified glycosphingolipids were used to determine the specificity of these monoclonal antibodies. All 4 antibodies reacted only with ganglioside GD3 [GD3(NeuAc-NeuAc) and GD3(NeuAc-NeuGc)], but not with several gangliosides linking the GalNAc, Gal beta 1-3GalNAc, NeuAc alpha 2-3Gal beta 1-3GalNAc, or NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-3GalNAc residue to the Gal moiety of ganglioside GD3 (GD2, GD1b, GT1b, or GQ1b, respectively), ganglioside GT1a having the same terminal NeuAc alpha 2-8NeuAc alpha 2-3Gal residue as ganglioside GD3, other gangliosides, and neutral glycosphingolipids. These findings suggest that the 4 monoclonal antibodies obtained may be specific for the epitope of NeuAc-alpha 2-8Sia alpha 2-3Gal beta 1-4Glc residue of ganglioside GD3.


Factors Associated With Willingness To Report Intimate Partner Violence (IPV) to Police in South Korea.
Intimate partner violence (IPV) is a serious social problem in South Korea, but the IPV reporting rate to the police is not high enough. To reduce violence and further victimization, it is important for IPV (potential) victims to report to police. Thus, this study aimed to examine the factors associated with willingness to report IPV to police if they experience it using the 2013 Korean National Domestic Violence Survey data. A representative sample of 5,000 Korean participants, of whom 1,668 were males and 3,332 were females, were recruited using a stratified multistage sampling design. We found that the willingness to report IPV to the police was statistically significant when the participants were young, had strong knowledge of IPV-related laws, had lower levels of acceptance of violence, had lower levels of conservative gender role values, and when the seriousness of violence was higher for both male and female participants. However, having children and having experienced child abuse only affected women's willingness to report IPV to the police. Based on this study's findings, we then discussed policy implications to prevent further victimization, focusing on factors that are associated with willingness to report violence to the police.


Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70.
Increasing evidence has demonstrated that the heat shock protein 70 (HSP70) gene may be closely associated with tissue fibrosis; however, the association between HSP70 and liver fibrosis remains to be fully elucidated. The present study hypothesized that geranylgeranylacetone (GGA) exerts beneficial effects on liver fibrosis though upregulation of the expression of HSP70. Liver fibrosis was induced in rats using carbon tetrachloride (CCl4). The rats were subsequently divided into three groups: Control group, CCl4 model group and CCl4 model + GGA group. Liver fibrosis in the rats was evaluated using hematoxylin and eosin staining, Masson's trichrome staining and Sirius red staining. The levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were determined using an automated biochemistry analyzer. The levels of total hepatic hydroxyproline were also determined. The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting. The CCl4‑induced rats exhibited liver fibrosis, increased hydroxyproline content, impaired liver function, upregulated expression levels of the α‑SMA and TGF‑β1 pro‑fibrogenic proteins, and increased expression of HSP70, compared with the control group. These changes were attenuated by treatment with GGA. These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.


Purification and crystallization of 2,3-dihydroxybiphenyl 1,2-dioxygenase.
2,3-Dihydroxybiphenyl 1,2-dioxygenase, an enzyme of the biphenyl biodegradation pathway that cleaves the first of the aromatic rings, was purified to apparent homogeneity from Pseudomonas sp. strain LB400 that had been engineered to hyperexpress the bphC gene. The enzyme had a subunit molecular mass of 33.2 kDa as determined by SDS-polyacrylamide electrophoresis. Kinetic studies indicate a KM of 7 +/- 1 microM for 2,3-dihydroxybiphenyl. The enzyme is strongly inhibited by substrate (Kss = 300 +/- 10 microM). Catechol, 3-methylcatechol, and 4-methylcatechol were cleaved less efficiently and showed weaker substrate inhibition. 3,4-Dihydroxybiphenyl was not a substrate for the enzyme. Ammonium sulfate and polyethylene glycol 6000 were used as precipitants to obtain two different crystal forms. Crystals grown from ammonium sulfate and polyethylene glycol 6000 had space groups of P4(2)2(1)2 and I222, respectively. Electron microscopy indicates that the enzyme is an octamer (265 kDa) consisting of subunits arranged in two planar tetramers in a staggered conformation.


[Changes in the incidence and clinical features of ALS in the Koza, Kozagawa, and Kushimoto area of the Kii Peninsula--from the 1960s to the 2000s (follow-up study)].
In the 1960's, ALS was highly prevalent in the southern part of the Kii Peninsula, especially in the Koza, Kozagawa, and Kushimoto area (K area). Thereafter, the incidence of ALS was considered to have gradually decreased, and the disease almost disappeared in the 1980's. However, new patients have been continuously identified in this area, and indicating the importance of studying the changes in the incidences of ALS. This study investigated the characteristic clinical features and incidence of ALS in K area during the following periods: period I: between 1967 and 1971, period II: between 1989 and 1999, and period III: between 2000 and 2008. Data on all patients with motor neuron disease were collected for each year within these periods from medical doctors and medical staff of the regional public health center and municipal office. Neurologists on our research team examined and assessed each of these patients on the basis of the El Escorial criteria. Probable and definite ALS patients diagnosed by neurologists using the El Escorial criteria in K area during the research periods were collected. The crude incidence rate of ALS in K area were similar in period I, i.e. 6.0/100,000, and in period III, i.e., 5.7/100,000. The age-, and sex-adjusted incidence (considering the 2000 census) in women in K area during period III, especially in Kozagawa district, was higher than that in periods I and II. The adjusted incidence rate in Kozagawa district was 8.8/100,000, and was higher than that in other areas of the world. The clinical features of patients in this area were quite similar to those of patients with classical ALS. Five patients from 3 families with a family history of ALS and 2 patients without a family history presented with the clinical features of ALS and PDC during these research periods. The mean age at onset for period III was higher than that in period I (p < 0.01). The frequency of ALS patients with upper-extremity onset in period III was lower than that in period I (p = 0.05), whereas the frequency of patients with bulbar-onset has recently increased. Conclusion The result of present study indicate that the recent incidence of ALS in K area is high, the age of onset has recently become higher and the number of bulbar-onset patients has increased. All the abovementioned findings could be attributed to an increase in the senility rate in the population. Between 2000 and 2008, the age-adjusted incidence in ALS for women in K area, especially in the Kozagawa district, was high, indicating an increase in that the incidence of ALS among women in this area after 2000. The factors responsible for the high incidence of ALS in this area remain to be clarified.


[Psychosis-induced posttraumatic stress disorder. A rarely diagnosed symptom].
Patients with severe mental disorders encounter a rather high risk of also evolving symptoms of posttraumatic stress disorder (PTSD) as a result of psychotic experience. A wide overlap of symptoms makes the differentiation between "psychosis-induced PTSD" and "psychotic warning signs" difficult; nevertheless, the distinction is important as different therapy strategies must be envisaged. A case report of a psychosis-induced PTSD is given.


Topochemical models for prediction of anti-HIV activity of 4-benzyl pyridinone derivatives.
Relationship between topochemical indices and anti-HIV activity of 4-Benzyl pyridinone derivatives has been investigated. The values of molecular connectivity topochemical index (an adjacency based topochemical descriptor) Wiener's topochemical index (a distance based topochemical descriptor) and superadjacency topochemical index (an adjacency cum distance based topochemical descriptor) were calculated for each of the 32 compounds comprising the data set using an in-house computer program. The resultant data was analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned using these models to each of the compounds involved in the dataset which was then compared with the reported anti-HIV activity. Exceptionally high accuracy of prediction was observed using these models. These models offer vast potential for providing lead structures for the development of potent anti-HIV agents.


Communicating tailored risk information of cancer treatment side effects: Only words or also numbers?
The increased availability of patient reported outcome data makes it feasible to provide patients tailored risk information of cancer treatment side effects. However, it is unclear how such information influences patients' risk interpretations compared to generic population-based risks, and which message format should be used to communicate such individualized statistics. A web-based experiment was conducted in which participants (n = 141) read a hypothetical treatment decision-making scenario about four side effect risks of adjuvant chemotherapy for advanced colon cancer. Participants were cancer patients or survivors who were recruited from an online Dutch cancer patient panel. All participants received two tailored risks (of which the reference class was based on their age, gender and tumor stage) and two generic risks conveying the likelihood of experiencing the side effects. The risks were presented either in words-only ('common' and 'very common'), or in a combination of words and corresponding numerical estimates ('common, 10 out of 100' and 'very common, 40 out of 100'). Participants' estimation of the probability, accuracy of their estimation, and perceived likelihood of occurrence were primary outcomes. Perceived personal relevance and perceived uncertainty were secondary outcomes. Tailored risks were estimated as higher and less accurate than generic risks, but only when they were presented in words; Such differences were not found in the verbal and numerical combined condition. Although tailoring risks did not impact participants' perceived likelihood of occurrence, tailored risks were perceived as more personally relevant than generic risks in both message formats. Finally, tailored risks were perceived as less uncertain than generic risks, but only in the verbal-only condition. Considering current interest in the use of personalized decision aids for improving shared decision-making in oncology, it is important that clinicians consider how tailored risks of treatment side effects should be communicated to patients. We recommend both clinicians who communicate probability information during consultations, and decision aid developers, that verbal descriptors of tailored risks should be supported by numerical estimates of risks levels, to avoid overestimation of risks.


Induction of Frost Hardiness in Stem Cortical Tissues of Cornus stolonifera Michx. by Water Stress: II. Biochemical Changes.
A decrease of protein, RNAs, and starch, and an increase of sugar were observed in 3-day water-stressed red osier dogwood plants (Cornus stolonifera Michx.) when the frost hardiness increased from -3 to -6 C. As the frost hardiness increased to -11 C after 7 days of treatment, the starch continuously decreased, however, the proteins and RNAs increased with a continuous increase of sugar. Further water stress treatment had little effect on the changes of these chemicals. Control plants in short days showed similar gradual biochemical changes in patterns. From the results of frost hardiness increases, the pattern of biochemical changes, and the mechanism of the increased freezing resistance, it appears that the water stress and short days accomplished essentially the same physiological end(s) in inducing frost hardiness in red-osier dogwood.


Cranial neural crest recycle surface integrins in a substratum-dependent manner to promote rapid motility.
Cell migration is essential for proper development of numerous structures derived from embryonic neural crest cells (NCCs). Although the migratory pathways of NCCs have been determined, the molecular mechanisms regulating NCC motility remain unclear. NCC migration is integrin dependent, and recent work has shown that surface expression levels of particular integrin alpha subunits are important determinants of NCC motility in vitro. Here, we provide evidence that rapid cranial NCC motility on laminin requires integrin recycling. NCCs showed both ligand- and receptor-specific integrin regulation in vitro. On laminin, NCCs accumulated internalized laminin but not fibronectin receptors over 20 min, whereas on fibronectin neither type of receptor accumulated internally beyond 2 min. Internalized laminin receptors colocalized with receptor recycling vesicles and were subsequently recycled back to the cell surface. Blocking receptor recycling with bafilomycin A inhibited NCC motility on laminin, indicating that substratum-dependent integrin recycling is essential for rapid cranial neural crest migration.


Spectroscopy and stimulated emission of Nd(3+) in an acentric CsY(2)F(7) host.
The results of preliminary spectroscopic studies of new fluoride single-crystal CsY(2)F(7) that is activated by Nd(3+) ions are given. Direct evidence for the possibility of application of this ordered material as a laser host is given for the first time to our knowledge. Stimulated emission of Nd(3+) ions on the main intermultiplet transition is obtained under both nonselective flash-lamp pumping conditions and continuous Ar ion laser pumping conditions.


Diabetic nephropathy and pregnancy: the effect of ACE inhibitors prior to pregnancy on fetomaternal outcome.
Diabetic nephropathy is associated with an increase in perinatal mortality and morbidity in uncontrolled pregnant patients. Recently angiotensin-converting enzyme inhibitor (ACE-I) was shown to improve the disease status in non-pregnant subjects. The purpose of this study was to examine the effect of prepregnancy treatment of insulin-dependent diabetes mellitus (IDDM) nephrotic women with captopril angiotensin converting enzyme inhibitor (ACE-1), on maternal renal function throughout pregnancy and on the fetomaternal outcome. Eight IDDM nephrotic patients planning pregnancy were treated with captopril for a minimum of 6 months prior to conception together with intensive insulin management. Conception was allowed when proteinuria was < 500 mg/day and euglycaemia was achieved. At conception captopril was discontinued. At the beginning of captopril treatment, proteinuria was 1633 +/- 666 mg/day. At conception, proteinuria dropped to 273 +/- 146 mg/day (P = 0.0000) and increased gradually over the three trimesters to 593 +/- 515, 783 +/- 813, and 1000 +/- 1185 mg/day respectively (P = 0.2 between the trimesters); declining to 619 +/- 411 mg/day (P = 0.0002 vs conception) 3 months after delivery. Only in two patients (25%) did proteinuria exceed 1000 mg/day during pregnancy. There was no significant change in any of the other renal function tests: CCT, serum creatinine, uric acid, K+ and blood pressure. However, there were three cases of PET just prior to delivery. Maternal glycaemic control improved significantly prior to conception (P = 0.002) and remained euglycaemic (reflected by daily glucose profile, HbA1C and fructosamine) throughout gestation. Perinatal outcome was excellent. Captopril treatment before pregnancy has a prolonged protective effect on maternal renal functions during pregnancy and results in a favourable maternal-fetal outcome.


Ras p21 in breast tissue: associations with pathology and cellular localisation.
Immunocytochemistry with monoclonal antibody Y13-259 demonstrated p21 ras in paraffin sections of breast tissue from 171 women: 85 with invasive breast carcinoma, 14 with non-invasive carcinoma and 72 with benign changes only. Many different tissue elements contributed to ras expression. Semiquantitative assessment showed that intensity of immunostaining in the normal epithelium of large ducts, small extralobular ducts and terminal duct lobular units (TDLU) was usually exceeded by that of myoepithelial cells. Vascular smooth muscle and apocrine epithelium also stained strongly, but the flat epithelial cells lining cysts did not express detectable p21 ras. There was a progressive increase from normal epithelium through epithelial hyperplasia of usual type and atypical hyperplasia to carcinoma in situ, without further increase in invasive carcinoma. Expression in carcinomas was inversely related to oestrogen receptor content but independent of the prognosis-associated variables of size, histological type, vascular invasion or lymph node metastasis.