Midterm Results of a New Rotating Hinge Knee Implant: A 5-Year Follow-Up.
In the current study, we investigated midterm results of a new rotating hinge total knee arthroplasty (EnduRo prosthesis), which uses a new bearing material (CFR PEEK). We prospectively analysed data of 50 patients with a minimum follow-up of 5 years. In 24 (48%) patients, a primary implantation was performed and 26 (52%) were revision cases. Clinical and radiographic examinations were performed preoperatively as well as postoperatively after 3 and 12 months and annually thereafter. The Knee Society Score (KSS), WOMAC, Oxford Knee Score (OKS), and range of motion (ROM) were used for clinical assessment. KSS, WOMAC, OKS, and ROM significantly improved between the preoperative and the follow-up investigations. The overall survival rate with revision for any reason as an endpoint was 77.9% after five years. The number of complications was significantly higher in the revision group (p = 0.003). The EnduRo prosthesis provides highly satisfying clinical and functional results in severe primary as well as in revision cases. Implant-associated complications were rare. However, in cases of revision surgery, the risk for complications was considerably high, mostly related to previous joint infections and poor soft tissue quality.


Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2.
NF-E2 binding sites, located in distant regulatory sequences, may be important for high level alpha- and beta-globin gene expression. Surprisingly, targeted disruption of each subunit of NF-E2 has either little or no effect on erythroid maturation in mice. For p18 NF-E2, this lack of effect is due, at least in part, to the presence of redundant proteins. For p45 NF-E2, one possibility is that NF-E2-related factors, Nrf-1 or Nrf-2, activate globin gene expression in the absence of NF-E2. To test this hypothesis for Nrf-2, we disrupted the Nrf-2 gene by homologous recombination. Nrf-2-deficient mice had no detectable hematopoietic defect. In addition, no evidence was found for reciprocal upregulation of NF-E2 or Nrf-2 protein in fetal liver cells deficient for either factor. Fetal liver cells deficient for both NF-E2 and Nrf-2 expressed normal levels of alpha- and beta-globin. Mature mice with combined deficiency of NF-E2 and Nrf-2 did not exhibit a defect in erythroid maturation beyond that seen with loss of NF-E2 alone. Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is not the result of compensation by Nrf-2.


Redox Biology of Right-Sided Heart Failure.
Right-sided heart failure is the major cause of death among patients who suffer from various forms of pulmonary hypertension and congenital heart disease. The right ventricle (RV) and left ventricle (LV) originate from different progenitor cells and function against very different blood pressures. However, differences between the RV and LV formed after birth have not been well defined. Work from our laboratory and others has accumulated evidence that redox signaling, oxidative stress and antioxidant regulation are important components that define the RV/LV differences. The present article summarizes the progress in understanding the roles of redox biology in the RV chamber-specificity. Understanding the mechanisms of RV/LV differences should help develop selective therapeutic strategies to help patients who are susceptible to and suffering from right-sided heart failure. Modulations of redox biology may provide effective therapeutic avenues for these conditions.


Ecological assessment of the dysexecutive syndrome using execution of a cooking task.
Patients with a dysexecutive syndrome often have severe disabilities in daily life activities. The aims of this study were to use a naturalistic experimental task to assess patients' disabilities, and to study the nature of the cognitive disorders underlying them. Execution of a cooking task involving multi-tasking (Chevignard et al., 2000) was studied in 45 patients with a dysexecutive syndrome following acquired brain injury. Patients made significantly more errors and were slower than controls; more than half of the patients did not achieve the goal and demonstrated dangerous behaviours. Those results were significantly correlated to the results of the Six Elements Task and to a behavioural questionnaire. They were also correlated to brain injury severity and to patients' cooking habits. This naturalistic assessment is clinically relevant to better assess patients' dysexecutive impairments in complex activities of daily living. Correlations of the results in the cooking task with the neuropsychological assessment highlighted the role of the dysexecutive syndrome in patients' disabilities, indicating control alterations rather than planning disorders, difficulty in dealing with the environment, and inhibiting inappropriate actions. The role of attention and prospective memory was also underlined, whereas other cognitive functions did not influence task performance.


Screening for depression in middle-aged and older puerto rican primary care patients.
Brief depression screens have recently been developed, but their use in older or minority populations has not been studied. To date, optimal depression screens and optimal cutpoints have not been identified for middle-aged and older Hispanic primary care patients. This study compares multiple versions of four depression screening tools--Center for Epidemiologic Studies-Depression Scale (CES-D), Geriatric Depression Scale, Yale 1-question screen, and PRIME-MD 2-question screen--to the Composite International Diagnostic Interview (CIDI), the World Health Organization's diagnostic interview, which has been validated in adult Latino populations, to assess convergent validity. Three hundred and three Puerto Rican primary care patients age 50 and older completed all screens and the CIDI in a face-to-face interview. Sensitivity and specificity for each screen were calculated, and receiver operator characteristic curves were generated. Between 34% and 61% of patients screened positive for depression, depending on the measure, with 12% meeting DSM-IV criteria for major depression (CIDI). The 10-item CES-D worked best to identify major depression in this population, with a sensitivity of 84% and specificity of 64% using a cutpoint of 3. The 10-item CES-D, which takes about 2 minutes to administer, is a useful tool for identifying Puerto Rican patients in need of an in-depth mental health evaluation in a primary care setting. A lower cutpoint of 3 (instead of the conventional cutpoint of 4) is recommended for optimal sensitivity and specificity.


[Ego-state Therapy: Psychotherapy for Multiple Personality Disorders].
The author describes ego-state therapy. This psychotherapy is used for treating multiple personality disorders. The author mentions the theoretical background of this method, and practical points. Initially, ego-state therapy was developed as a type of hypnotherapy, but it evolved as a safe therapeutic method in combination with trauma processing therapies. The author presents a case study, and discusses the clinical significance of this treatment.


Complications and conversions of pediatric videosurgery: the Italian multicentric experience on 1689 procedures.
The aim of this study was to evaluate the incidence and management of complications of videosurgical procedures that occurred during a 4-year period in eight Italian pediatric surgery centers. Between 1996 and 1999, 2305 videosurgical procedures were performed in 11 centers of pediatric surgery. The data from 3 centers, for a total of 616 procedures, were largely incomplete and were thus excluded from the study. We analyzed the data from 8 centers only, for a total of 1689 laparoscopic or thoracoscopic operations on patients aged between 15 days and 16 years. The type of operations performed ranged from basic videosurgical interventions, such as varicocelectomy and cryptorchidism, to advanced laparoscopic procedures, such as splenectomy, total colectomy, and esophageal achalasia. Each patient's file was examined for any complications that may have occurred during the surgical procedure and for a record of how these were managed. We recorded 79 complications (4.6%) in our series. In 57 cases (72.2%) the problem was solved by videosurgery. Twenty-two cases (27.8%) required conversion to open surgery. There was no mortality in our series. At a maximum follow-up of 4 years, all children were alive and had no problems related to the videosurgical complications. We believe that the routine use of open laparoscopy in pediatric patients is a key factor to avoiding complications related to the Veress needle and blind introduction of the first trocar. Moreover, the surgeon's laparoscopic experience, the correct indications for laparoscopic surgery, and the verification of the laparoscopic equipment before surgery are also important rules to follow to reduce the incidence of complications. In the beginning, it is preferable to have the assistance of an expert laparoscopic surgeon to decrease the complications related to the learning curve period.


Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection.
Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.


[Microbial content of the air in poultry houses].
The industrial animal-breeding complex is characterized as an ecotechnical system the function of which is determined by the action of antropogenic factors. It has been demonstrated that up to now the stress of antropogenic activity has been laid on the optimization of the abiotic factors. The control and optimization of the biotic factors has constituted a problem for industrial poultry breeding, especially important being the microbial content of air. Investigations have shown that with the industrial raising of birds air microbism has assumed the importance of a factor that lowers the effectiveness of the technologies applied. The factors have been discovered that govern the extent of microbial contamination of air. Results of experiments in productional poultry houses and climatic chambers have led to the offer of measures aimed at limiting the microbial contamination of air in the industrial raising of birds.


Barriers and Facilitation Measures Related to People With Mental Disorders When Using the Web: A Systematic Review.
Mental disorders (MDs) affect almost 1 in 4 adults at some point during their lifetime, and coupled with substance use disorders are the fifth leading cause of disability adjusted life years worldwide. People with these disorders often use the Web as an informational resource, platform for convenient self-directed treatment, and a means for many other kinds of support. However, some features of the Web can potentially erect barriers for this group that limit their access to these benefits, and there is a lack of research looking into this eventuality. Therefore, it is important to identify gaps in knowledge about "what" barriers exist and "how" they could be addressed so that this knowledge can inform Web professionals who aim to ensure the Web is inclusive to this population. The objective of this study was to provide an overview of existing evidence regarding the barriers people with mental disorders experience when using the Web and the facilitation measures used to address such barriers. This study involved a systematic review of studies that have considered the difficulties people with mental disorders experience when using digital technologies. Digital technologies were included because knowledge about any barriers here would likely be also applicable to the Web. A synthesis was performed by categorizing data according to the 4 foundational principles of Web accessibility as proposed by the World Wide Web Consortium, which forms the necessary basis for anyone to gain adequate access to the Web. Facilitation measures recommended by studies were later summarized into a set of minimal recommendations. A total of 16 publications were included in this review, comprising 13 studies and 3 international guidelines. Findings suggest that people with mental disorders experience barriers that limit how they perceive, understand, and operate websites. Identified facilitation measures target these barriers in addition to ensuring that Web content can be reliably interpreted by a wide range of user applications. People with mental disorders encounter barriers on the Web, and attempts have been made to remove or reduce these barriers. As forewarned by experts in the area, only a few studies investigating this issue were found. More rigorous research is needed to be exhaustive and to have a larger impact on improving the Web for people with mental disorders.


Reactive plasmacytic lesions of the bone marrow.
A consecutive series of 1,000 bone marrow aspirates was analyzed for percentage of plasma cells, incidence of plasmacytic satellitosis, associated clinical disease states, lymphoid follicles, lipid granulomas, hemosiderin content, and various combinations thereof. Plasmacytosis was a common finding, and tended to parallel the presence of lymphoid follicles, lipid granulomas and plasmacytic satellitosis. The latter is emphasized as a normal phenomenon, may reflect morphologically a physiologic response of the B cell system to antigenic stimulation, and is conspicuously absent in plasmacytic neoplasia. Various secretory forms of plasma cells are illustrated.


Primary systemic treatment with weekly doxorubicin monotherapy in women with locally advanced breast cancer; clinical experience and parameters predicting outcome.
Sixty-three patients (median age 64 years) with locally advanced breast cancer (T3, T4 and/or N2) were treated with primary 'neoadjuvant' chemotherapy given as weekly doxorubicin monotherapy (14 mg/m2 per dose). Seven patients had solitary distant metastasis at the time of diagnosis. Twenty-eight patients (45%) achieved 'partial response' to primary chemotherapy. Twenty-nine patients (46%) had 'stable disease', and 6 patients (9%) had 'progressive disease' during treatment. Following chemotherapy, 52 patients were subjected to surgery and another 4 patients had surgery performed after radiotherapy. Surgery was considered impossible in only three patients. After a median observation time of 23 months, local recurrences were observed in 2 patients, one with progressive disease and one with stable disease during chemotherapy. Univariate analyses revealed that large tumour size, high histological grade and high mitotic frequency were associated with poor primary response to chemotherapy. Recent studies have demonstrated a correlation between p53-mutations and chemotherapy response.


Transcarotid artery revascularization can safely be performed with regional anesthesia and no intensive care unit stay.
Hospital resource use is under constant review, and the extent and intensity of postoperative care requirements for vascular surgical procedures is particularly relevant in the setting of the coronavirus disease 2019 pandemic and its impact on staffed intensive care unit (ICU) beds. We sought to evaluate the feasibility of regional anesthesia (RA) and low-intensity postoperative care for patients undergoing transcarotid artery revascularization (TCAR) at our institution. All patients undergoing TCAR at a single institution from 2018 to 2020 were reviewed. Perioperative management (anticoagulation and antiplatelet therapy, hemodynamic monitoring, neurovascular examination, nursing instructions) was standardized by use of an institutional protocol. Anesthetic modality was at the surgeon's preference. Patients were transferred to a postanesthesia care unit for 2 hours followed by the step-down unit, to a postanesthesia care unit for 4 hours followed by the floor, or alternatively transferred to the ICU. Intravenous (IV) blood pressure medications could be administered at all environments except the floor. Recovery location and length of stay were recorded. A total of 83 patients underwent TCAR during the study period. The mean age 72 ± 9 years and 59% were male. Thirty-six percent were symptomatic. RA was used for 84% with none converted to general anesthesia (GA) intraoperatively. Postoperatively, 7 of the 83 patients (8%) included in this study were monitored in an ICU overnight (decided perioperatively), mostly for patients with prior neurological symptoms, but in 1 case for postoperative neurological event and in another owing to pulseless electrical activity arrest. Six patients required IV antihypertensives and eight required IV vasoactive support postoperatively. The mean length of ICU stay was 3.7 ± 5.1 days. The mean length of hospital stay for all patients was 2.4 ± 3.3 days. The length of stay for patients undergoing TCAR with GA was higher than those undergoing TCAR with RA (4.2 ± 4.9 days vs 1.4 ± 1.2 days, respectively; P = .066). The incidence of stroke, death, and myocardial infarction was 2.4%. There was one postoperative stroke considered to be a recrudescence of prior stroke, and one respiratory arrest fatality in a frail patient with neck hematoma both of whom were treated under GA. Using perioperative care protocols, TCAR can safely be performed while avoiding both GA and an ICU stay in most patients.


Honey bee behaviours within the hive: Insights from long-term video analysis.
The combined behaviours of individuals within insect societies determine the survival and development of the colony. For the western honey bee (Apis mellifera), individual behaviours include nest building, foraging, storing and ripening food, nursing the brood, temperature regulation, hygiene and defence. However, the various behaviours inside the colony, especially within the cells, are hidden from sight, and until recently, were primarily described through texts and line drawings, which lack the dynamics of moving images. In this study, we provide a comprehensive source of online video material that offers a view of honey bee behaviour within comb cells, thereby providing a new mode of observation for the scientific community and the general public. We analysed long-term video recordings from longitudinally truncated cells, which allowed us to see sideways into the cells in the middle of a colony. Our qualitative study provides insight into worker behaviours, including the use of wax scales and existing nest material to remodel combs, storing pollen and nectar in cells, brood care and thermoregulation, and hygienic practices, such as cannibalism, grooming and surface cleaning. We reveal unique processes that have not been previously published, such as the rare mouth-to-mouth feeding by nurses to larvae as well as thermoregulation within cells containing the developing brood. With our unique video method, we are able to bring the processes of a fully functioning social insect colony into classrooms and homes, facilitating ecological awareness in modern times. We provide new details and images that will help scientists test their hypotheses on social behaviours. In addition, we encourage the non-commercial use of our material to educate beekeepers, the media and the public and, in turn, call attention to the general decline of insect biomass and diversity.


Value of MR pancreatography in the evaluation of patients with chronic pancreatitis.
To determine the diagnostic accuracy of magnetic resonance (MR) pancreatography and to define its role in the imaging work-up of patients with severe chronic pancreatitis. Thirty-two patients (13 men and 19 women; 15-84 years old; mean age, 48 years) with severe chronic pancreatitis diagnosed using cross-sectional imaging, examination using contrast medium (endoscopic retrograde cholangiopancreatography, pseudocyst injection) and/or surgical findings underwent MR pancreatography performed using a two-dimensional multi-slice fast spin echo technique. All patients underwent transabdominal pancreatic sonography and computed tomography (CT) was performed in 12 patients. Two observers independently assessed the MR pancreatograms for pancreatic duct dilatation and pancreatic duct abnormalities. Compared to the final diagnosis, the accuracy of MR pancreatography in revealing complications of chronic pancreatitis was calculated and its role in the radiological work-up of patients with chronic pancreatitis evaluated. When compared to the final diagnosis, MR pancreatography showed the following sensitivity, specificity and diagnostic accuracy: for filling defects in pancreatic duct, 56-78%, 100% and 87-94%, respectively; for strictures, 75-88%, 92-96% and 88-94%, respectively; and for pseudocysts 100%, 100% and 100%, respectively. Filling defects were correctly diagnosed in all patients when MR pancreatography was interpreted in combination with cross-sectional imaging. Contrast pancreatography was required for the complete evaluation of strictures and communication with pseudocysts. MR pancreatography is poorly sensitive but specific in revealing pancreatic duct filling defects and strictures. However, when MR pancreatography is interpreted in combination with sonography and CT, it provides sufficient information to plan therapy in the majority of patients.


Hexameric RSF1010 helicase RepA: the structural and functional importance of single amino acid residues.
In the known monoclinic crystals the 3-dimensional structure of the hexameric, replicative helicase RepA encoded by plasmid RSF1010 shows 6-fold rotational symmetry. In contrast, in the cubic crystal form at 2.55 A resolution described here RepA has 3-fold symmetry and consists of a trimer of dimers. To study structure-function relationships, a series of repA deletion mutants and mutations yielding single amino acid exchanges were constructed and the respective gene products were analyzed in vivo and in vitro. Hexamerization of RepA occurs via the N-terminus and is required for NTP hydrolysis. The C-terminus is essential both for the interaction with the replication machinery and for the helicase activity. Functional analyses of RepA variants with single amino acid exchanges confirmed most of the predictions that were based on the published 3-dimensional structure. Of the five motifs conserved in family 4 helicases, all residues conserved in RepA and T7 gp4 helicases participate in DNA unwinding. Residues K42, E76, D77, D139 and H178, proposed to play key roles in catalyzing the hydrolysis of NTPs, are essential for RepA activity. Residue H178 of motif H3 couples nucleotide consumption to DNA strand separation.


Direct measurement of thermal fluctuation of high-Q pendulum.
We have achieved a direct measurement of the thermal fluctuation of a pendulum in an off-resonant and wide frequency region using a laser interferometric gravitational-wave detector. These measurements have been well identified for over one decade by an agreement with a theoretical prediction, which is derived by a fluctuation-dissipation theorem. Thermal fluctuation was dominated by the contribution of resistances in coil-magnet actuator circuits. When we tuned these resistances, the noise spectrum also changed according to a theoretical prediction. The measured thermal noise level corresponds to a high quality factor on the order of 10(5) of the pendulum.


Emigrant etherist: the medical and scientific influence of John Henry Hill Lewellin (1818-86), pioneer anaesthetist and surgeon and patron of botany in Australia.
The pioneer anaesthetists in Australia came from varying professional backgrounds. To the influence of Belisario in Sydney. Pugh in Launceston and Buchanan in Stroud, can be added the role of John Henry Hill Lewellin (1818-86). Lewellin immigrated from Scotland to become a pioneer Melbourne etherist and surgeon from 1852. Born in India, he studied surgery at Bart's Hospital in London (1842) and as a Member of the Royal College of Surgeons from that year, practised as a surgeon and dentist in Glasgow. On 19 December 1746 he was the first to use the newly discovered ether in anesthetic practice in Glasgow, and one of the first to do so in the United Kingdom. He emigrated to Melbourne in 1852, where he achieved considerable success in the management of tetanus with ether. He was an active member of the Medical Society of Victoria and a vigorous participant in its clinical discussions. As a surgeon, Lewellin pursued a significant community role in the broader Melbourne society of the day. He served as a Magistrate, became Vaccination Officer in Victoria and, as an active doctor-soldier, served with sequential promotions finally to the rank of Surgeon-Major in the Volunteer Force (Rifles) of the Colony. He became a patron of science and a supporter of the Melbourne botanist, Ferdinand von Mueller. Of all his prodigious scientific writing, von Mueller dedicated Volume 8 of his Fragmenta to his surgical colleague, as one 'who is a most skillful physician' and later as 'a most generous promoter of my investigations'. Lewellin's legacy, in his pioneering contributions as an early anaesthetist in two continents, lives on in the scientific names of two floral species which perpetuate his name.


[Records and documentation system. Its location within a program of alimentary, nutritional and metabolic intervention].
To present the Records and Documentation System of the Metabolic, Nutrient and Feeding Intervention Program (PRINUMA), as conducted by the Nutritional Support Group (GAN) of the "Hermanos Ameijeiras" Hospital (Havana City, Cuba). Every action conducted upon the patient must have a document backup. Likewise, this action should be exhaustively described in a Standerdized Operating Procedure (SPO). The Records and Documentation System must provide with: (1) Primmary records for registering the actions conducted upon the patients, (2) SOP manuals gathering the actions prescribed in the PRINUMA for the recognition, treatment and prevention of hospital malnutrition (HM), and (3) Computerized clinical registries for storing, manipulation and dissemination of data collected by the GAN during its local operation. The ISO 9001-9003 standard was adopted for describing the actions prescribed by the PRINUMA into the corresponding SOPs. Access 7.0 for Windows (Microsoft, USA) was used for the programming and operation of the GAN'S computerized Clinical Registry. Three phases were defined for the implementation of this System: I: start-up (minimal); II: extended; III: total (global). System implementation is in phase II. A Procedure Manual has been written with clinical, anthropometric, dietetic, dietotherapeutical and analytical actions prescribed by the PRINUMA for the treatment of HM. There is a second Manual reuniting the actions fostered by the PRINUMA's Quality Control & Assurance and the Records & Documentations Systems. GAN also has a Nutritional Clinical History and a computerized Clinical Registryt serving as digital counterpart of the former. The Registry stores data of varying type collected from over 1.800 patients attended in the 8 years of the GAN existence. The implementation of the PRINUMA's Records and Documentation System has allowed the elaboration of judgements about the utility and safety of the intervention measures installed in the institution by the GAN. Likewise, the System has supported the research activity of the Group, and has been particularly useful in the conduction of continuous education activities within the institution.


Registries and databases-A European perspective.
Registries will enable cohort studies to be performed, which are usually considered to be the best quality of observational studies. The quality of data of registries can be increased if is it possible to merge results ('crosstalk') between registries. A prerequisite for that is an agreed uniform core set of data to be collected and uniform definitions on the items to be collected. This paper discusses problems and barriers with existing registries and provides recommendations from an EMA workshop (European Medicines Agency), for core common data sets and how to secure the quality of data collected. The PedNet registry including >2200 children with haemophilia is presented as an example of a registry/cohort study.


Pattern recognition. Classification of therapeutic agents according to pharmacophores.
One of the preprocessing methods used in pattern recognition-factor analysis-is shown to be well suited to the derivation of structure-activity relationships. Applications of the procedure developed are illustrated using sets of compounds which are of accepted therapeutic utility.


Oral triazolam pretreatment for intravenous sedation.
This double-blind, controlled clinical trial assessed the anxiety relief provided by oral triazolam given before intravenous sedation. Twenty-two healthy adults undergoing third-molar surgery with intravenous sedation were enrolled in this study. Subjects were randomly assigned to receive either 0.25 mg of triazolam p.o. or an identically appearing placebo 45 to 60 min before venipuncture. Immediately before test drug administration, subjects completed the Corah Anxiety Scale, a Visual Analog Scale (VAS) assessing state anxiety, and the Interval Scale of Anxiety Response (ISAR). The VAS and ISAR were repeated immediately before venipuncture. Intravenous sedation medications consisted of fentanyl, midazolam, and methohexital. At 24 hr, assessments of the venipuncture and global experience were obtained. Results indicated that the characteristics of the triazolam and placebo patients were similar at baseline. With triazolam pretreatment, both the VAS and ISAR scores decreased significantly. Dose requirements for conscious sedation medications were decreased in the triazolam group. Patients rated the venipuncture experience significantly less unpleasant when pretreated with triazolam, and global ratings of the overall surgical experience favored triazolam. An oral-intravenous combination sedation technique using 0.25 mg of triazolam may have a significant therapeutic advantage for outpatient oral surgery.


[Iatrogenic tension pneumothorax following faulty positioning of gastric tube].
A 74-year-old man was admitted with respiratory insufficiency and required mechanical ventilation. Enteral nutrition was given via a nasogastric feeding tube, but persistent food retention occurred. The chest X-ray showed the nasogastric tube to be in the right pleural space. After the tube was withdrawn the patient developed a tension pneumothorax and a closed-tube thoracostomy was performed. The patient's recovery was uneventful, with resolution of the pneumothorax. It is necessary to be alert with respect to the tube position, which, if doubtful, should be checked by chest X-ray. Recognition of an aberrant position is necessary to minimize related morbidity.


NPY signaling through Y1 receptors modulates thalamic oscillations.
Neuropeptide Y is the ligand of a family of G-protein coupled receptors (Y(1) to Y(6)). In the thalamus, exogenous and endogenously released NPY can shorten the duration of thalamic oscillations in brain slices from P13 to P15 rats, an in vitro model of absence seizures. Here, we examine which Y receptors are involved in this modulation. Application of the Y(1) receptor agonist Leu(31)Pro(34)NPY caused a reversible reduction in the duration of thalamic oscillations (-26.6+/-7.8%), while the Y(2) receptor agonist peptideYY((3-36)) and the Y(5) receptor agonist BWX-46 did not exert a significant effect. No Y receptor agonist affected oscillation period. Application of antagonists of Y(1), Y(2) and Y(5) receptors (BIBP3226, BIIE0246 and L152,806, respectively) produced results consistent with those obtained from agonists. BIBP3226 caused a reversible disinhibition, an effect that increases oscillation duration (18.2+/-9.7%) while BIIE0246 and L152,806 had no significant effect. Expression of NPY is limited to neurons in the reticular thalamic nucleus (nRt), but Y(1) receptors are expressed in both nRt and adjacent thalamic relay nuclei. Thus, intra-nRt or nRt to relay nucleus NPY release could cause Y(1) receptor mediated inhibition of thalamic oscillations.


[Temporal distribution, sources, and risk assessment of polycyclic aromatic hydrocarbons in sediment core from Miyun reservoir].
The temporal distribution of polycyclic aromatic hydrocarbons (PAHs) was measured in sediment core from Miyun reservoir, and the possible sources and the potential risk assessment also have been identified. The aim of the present work is to understand the temporal trend of PAHs in Miyun reservoir recently. The concentrations of sigma PAH16 in sediment ranged from 618.5 ng/g to 1087.9 ng/g, and roughly, increased continuously from the bottom (16 cm under the surface) to the surface sediment. The PAHs in sediment core were mainly composed of phenanthrene and fluorene. The concentrations of phenanthrene and fluorene in sediment core were 236.1-417.9 ng/g and 91-130.8 ng/g, respectively. Both of them accounted for 47.2%-58.1% of the sigma PAH16 in sediments. Nevertheless, high-rings aromatic hydrocarbons (5-6 rings) were increased steadily in recent years. PAHs compositional profile indicated that the main source of PAHs was originated from the combustion of coal and biomass. However, the vertical profiles of Flu/Flu + Pyr and INP/INP + BghiP ratios suggested that the vehicles emission was increased very recently. Risk assessment suggested that PAHs in sediment from Miyun reservoir was no significant biological impairment, and low toxicological risk of PAHs was found up to now.


Collective and negotiated design for a clinical trial addressing smoking cessation supports for Aboriginal and Torres Strait Islander mothers in NSW, SA and Qld - developing a pilot study.
Tobacco smoking leads to one in five deaths of Aboriginal Australians and accounts for 17% of the reversible health gap. One in two Aboriginal women are reported to smoke during pregnancy, with no effective strategies currently available for health practitioners to utilise for supporting Aboriginal women. Aboriginal community participation in primary health research is crucial to implementing ethical research, with a clear benefit to the people and communities involved. However, currently there is little evidence on how Aboriginal programs and interventions are being developed in partnership with Aboriginal people and communities. 'Indigenous Counselling and Nicotine (ICAN) QUIT in Pregnancy' aims to address the prevalence of smoking during pregnancy by enhancing health providers' training in offering evidence-based smoking cessation care to Aboriginal mothers during pregnancy. This paper outlines the participatory research approach adopted for the developmental phase of the 'ICAN QUIT in Pregnancy' project developed in partnership with two Aboriginal Community-Controlled Health Services in NSW, and negotiation processes undertaken to implement a pilot intervention across NSW, SA and Qld.


Genetic algorithms: principles of natural selection applied to computation.
A genetic algorithm is a form of evolution that occurs on a computer. Genetic algorithms are a search method that can be used for both solving problems and modeling evolutionary systems. With various mapping techniques and an appropriate measure of fitness, a genetic algorithm can be tailored to evolve a solution for many types of problems, including optimization of a function of determination of the proper order of a sequence. Mathematical analysis has begun to explain how genetic algorithms work and how best to use them. Recently, genetic algorithms have been used to model several natural evolutionary systems, including immune systems.


Gynecomastia as the initial manifestation of hyperthyroidism.
To present two new cases of gynecomastia as the initial manifestation of hyperthyroidism. We describe detailed case reports of two men with breast enlargement who were found to have hyperthyroidism, and we review the related literature. Two men sought medical assistance because of unilateral tender gynecomastia. In one of these patients, thyroid, gonadal, and prostate examinations showed normal findings at the time of initial assessment, and symptoms of hyperthyroidism developed later. In our other patient with gynecomastia, other symptoms of hyperthyroidism--for example, nervousness, irritability, palpitations, and fatigue--had been present for a prolonged period but had been considered "normal" by the patient. In both patients, the hyperthyroidism was treated with radioiodine. Breast pain disappeared in both patients, and breast enlargement disappeared in one patient and was decreased in the other patient after euthyroidism was achieved. Review of the literature disclosed only two similar cases. Because of the rarity of gynecomastia as the initial symptom of hyperthyroidism, we believe that thyroid function tests are not indicated in the workup of patients whose major complaint is gynecomastia.


Nitrosocarbonyl-Henry and Denitration Cascade: Synthesis of α-Ketoamides and α-Keto Oximes.
An unprecedented Henry reaction of in situ generated nitrosocarbonyl intermediates and concomitant denitration cascade has been developed. The reaction is catalyzed by organic base at room temperature offering α-ketoamides, a demanding scaffold for drug discovery, in high yields. An alteration of substitution pattern also produced α-keto oximes, a high-value synthon. The protocol features operational simplicity and broad substrate scope.


Expression of cell cycle/growth regulator genes in human hepatocellular carcinoma and adjacent normal liver tissues.
We investigated the gene expression of the cell cycle/growth regulators in hepatocellular carcinoma (HCC) through the usage of Atlas human cancer array membranes, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Northern blot. Hybridization of cDNA array membrane was performed with alpha-32P-labeled cDNA probes synthesized from RNA, isolated from HCC and adjacent non-cirrhotic normal liver. RT-PCR of 24 paired specimens and Northern blot of 4 paired specimens were used to confirm the expression patterns of the cell cycle/growth regulator genes identified by Atlas array hybridization. Among 79 genes related to cell cycle/growth regulators, transcription factor DP2 (TFDP-2) and E2F-3 were up-regulated, whereas dual-specificity mitogen-activated protein kinase kinase 1 (MAPKK1) and cell division protein kinase 3 (CDK3) were down-regulated in HCC. RT-PCR of TFDP-2 gave result consistent with Atlas human cancer cDNA array findings. Northern blot analysis of TFDP-2 and E2F-3 of 4 paired specimens all showed up-regulation in HCC compared to normal liver tissues. The results obtained from Atlas microarray provided for the first time a liver cancer-specific expression profile, which identified the gene expressions comprehensively and systematically. The findings may lead to better understanding of the mechanism of onset and progression of HCC. The rapid and high-throughout method of profiling gene expression by cDNA array provides an overview of the key factors that may be involved in HCC. Some genes are reported for the first time in HCC.


A new in vitro model of polymyositis reveals CD8+ T cell invasion into muscle cells and its cytotoxic role.
The hallmark histopathology of PM is the presence of CD8+ T cells in the non-necrotic muscle cells. The aim of this study was to clarify the pathological significance of CD8+ T cells in muscle cells. C2C12 cells were transduced retrovirally with the genes encoding MHC class I (H2Kb) and SIINFEKL peptide derived from ovalbumin (OVA), and then differentiated to myotubes (H2KbOVA-myotubes). H2KbOVA-myotubes were co-cultured with OT-I CD8+ T cells derived from OVA-specific class I restricted T cell receptor transgenic mice as an in vitro model of PM to examine whether the CD8+ T cells invade into the myotubes and if the myotubes with the invasion are more prone to die than those without. Muscle biopsy samples from patients with PM were examined for the presence of CD8+ T cells in muscle cells. The clinical profiles were compared between the patients with and without CD8+ T cells in muscle cells. Analysis of the in vitro model of PM with confocal microscopy demonstrated the invasion of OT-I CD8+ T cells into H2KbOVA-myotubes. Transmission electron microscopic analysis revealed an electron-lucent area between the invaded CD8+ T cell and the cytoplasm of H2KbOVA-myotubes. The myotubes invaded with OT-I CD8+ T cells died earlier than the uninvaded myotubes. The level of serum creatinine kinase was higher in patients with CD8+ T cells in muscle cells than those without these cells. CD8+ T cells invade into muscle cells and contribute to muscle injury in PM. Our in vitro model of PM is useful to examine the mechanisms underlying muscle injury induced by CD8+ T cells.


bbThermodynamic quantities and Urmia Sea water evaporation.
The relation between climatic parameters (relative air humidity) and the water activity of the Urmia Sea water determines the possible maximum evaporation of the lake. Using the Pitzer thermodynamic approach, the activity of the Urmia Lake water during evaporation was calculated and compared to the present relative air humidity above the water. Present climatic conditions allow the Urmia Sea water to evaporate down to water with activity of 0.55, corresponding to the lowest air humidity measured over the lake. This water activity falls in the range of halite precipitation, while carnalite precipitation starts at somewhat lower (a H2O = 0.499) point. Our dynamic model predicts that for air humidity as low as 55% (reflecting present climate conditions), the Urmia Sea level may drop to as low as 1270 m (i. e., 1270 m above mean sea level). At that point, the lake water volume will have a volume of 11 km3. For the sake of comparison, at the beginning of 1990, the level of the lake was 1275 m, its volume was 25 km3, and its surface area was 5145 km2.


The von Neumann basis in non-Cartesian coordinates: application to floppy triatomic molecules.
We extend the periodic von Neumann basis to non-Cartesian coordinates. The bound states of two isomerizing triatomic molecules, LiCN/LiNC and HCN/HNC, are calculated using the vibrational Hamiltonian in Jacobi coordinates. The phase space localization of the basis functions leads to a flexible and accurate representation of the Hamiltonian. This results in significant savings compared to a basis localized just in coordinate space. The favorable scaling of the method with dimensionality makes it promising for applications to larger systems.


Infectious disease complications of simultaneous pancreas kidney transplantation.
Although technical success rate of simultaneous pancreas kidney (SPK) transplantation in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy has improved, morbidity remains high due to infection and rejection. The purpose of this study was to analyse infections encountered in our series of SPK transplants, using a restrictive antibiotic prophylaxis policy. We reviewed all infectious diseases after 66 consecutive bladder-drained SPK transplantations in 64 IDDM patients with end-stage renal disease due to diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was introduced. For post-operative urinary tract or opportunistic infection, no prophylaxis was given. Overall mean infection rate was 2.9 infections/ patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI) were seen in 30% of the patients, with Enterococci present in 47%. Logistic regression showed one day cefamandole prophylaxis to be associated with SSI, but there was no significant influence of SSI on either graft or patient survival. Forty-eight percent of all infections were lower urinary tract infections (UTI). There were 59 first UTIs (89%), probably related to long-term Foley catheter use, and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not cause mortality or graft loss. Five grafts were lost due to infection (SSI three times, post-transplant lymphoproliferative disease twice). Only one patient died because of infection (2%). Infectious diseases after SPK transplantation caused significant morbidity but did not influence either patient or graft survival. A change in prophylactic policy for both SSI as well as recurrent UTI, combined with earlier Foley removal, may lower incidences of these infections.


RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.
In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.


Reductive Deuteration of Nitriles: The Synthesis of α,α-Dideuterio Amines by Sodium-Mediated Electron Transfer Reactions.
The first general reductive deuteration of nitriles under single-electron transfer conditions has been developed for the synthesis of α,α-dideuterio amines. This practical and cost-efficient protocol requires only bench stable and commercially available sodium dispersions and EtOD- d1 and allows for the reductive deuteration of a variety of nitriles in excellent yields and deuterium incorporations.


[Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) with the A3243G mutation of the tRNALeu(UUR) gene of mtDNA in native American haplogroup B2].
Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisystemic disorders. This disease has mainly been associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups. A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and siblings, all of them asymptomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms. All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome.


Bipolar stimulation of a three-dimensional bidomain incorporating rotational anisotropy.
A bidomain model of cardiac tissue was used to examine the effect of transmural fiber rotation during bipolar stimulation in three-dimensional (3-D) myocardium. A 3-D tissue block with unequal anisotropy and two types of fiber rotation (none and moderate) was stimulated along and across fibers via bipolar electrodes on the epicardial surface, and the resulting steady-state interstitial (phi e) and transmembrane (Vm) potentials were computed. Results demonstrate that the presence of rotated fibers does not change the amount of tissue polarized by the point surface stimuli, but does cause changes in the orientation of phi e and Vm in the depth of the tissue, away from the epicardium. Further analysis revealed a relationship between the Laplacian of phi e, regions of virtual electrodes, and fiber orientation that was dependent upon adequacy of spatial sampling and the interstitial anisotropy. These findings help to understand the role of fiber architecture during extracellular stimulation of cardiac muscle.


Skin aging 2003: recent advances and current concepts.
In developed countries, interest in cutaneous aging is in large part the result of a progressive, dramatic rise over the past century in the absolute number and proportion of the population who are elderly. The psychosocial, as well as physiologic, effects of skin aging on older persons have created a demand for a better understanding of the aging process and particularly for effective interventions. Skin aging is a complex process determined by the genetic endowment of the individual and by environmental factors. The appearance of old skin and the clinical consequences of skin aging have been well-known for centuries, but it is only in the past 50 years that mechanisms and mediators have been pursued systematically. Still, within a relatively short time, there has been tremendous progress, a progress greatly enhanced by basic gerontologic research using immunologic, biochemical, and in particular, molecular biologic approaches.


In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish.
Atherosclerosis (AS) commonly occurs in the regions of the arterial tree with haemodynamic peculiarities, including local flow field disturbances, and formation of swirling flow and vortices. The aim of our study was to confirm low-density lipoprotein (LDL) concentration polarization in the vascular system in vitro and in vivo, and investigate the effects of LDL concentration polarization and flow field alterations on atherosclerotic localization. Red fluorescent LDL was injected into optically transparent Flk1: GFP zebrafish embryos, and the LDL distribution in the vascular lumen was investigated in vivo using laser scanning confocal microscopy. LDL concentration at the vascular luminal surface was found to be higher than that in the bulk. The flow field conditions in blood vessel segments were simulated and measured, and obvious flow field disturbances were found in the regions of vascular geometry change. The LDL concentration at the luminal surface of bifurcation was significantly higher than that in the straight segment, possibly owing to the atherogenic effect of disturbed flow. Additionally, a stenosis model of rabbit carotid arteries was generated. Atherosclerotic plaques were found to have occurred in the stenosis group and were more severe in the stenosis group on a high-fat diet. Our findings provide the first ever definite proof that LDL concentration polarization occurs in the vascular system in vivo. Both lipoprotein concentration polarization and flow field changes are involved in the infiltration/accumulation of atherogenic lipids within the location of arterial luminal surface and promote the development of AS.


Characterization of Thiomonas delicata arsenite oxidase expressed in Escherichia coli.
Microbial arsenite oxidation is an essential biogeochemical process whereby more toxic arsenite is oxidized to the less toxic arsenate. Thiomonas strains represent an important arsenite oxidizer found ubiquitous in acid mine drainage. In the present study, the arsenite oxidase gene (aioBA) was cloned from Thiomonas delicata DSM 16361, expressed heterologously in E. coli and purified to homogeneity. The purified recombinant Aio consisted of two subunits with the respective molecular weights of 91 and 21 kDa according to SDS-PAGE. Aio catalysis was optimum at pH 5.5 and 50-55 °C. Aio exhibited stability under acidic conditions (pH 2.5-6). The V max and K m values of the enzyme were found to be 4 µmol min-1 mg-1 and 14.2 µM, respectively. SDS and Triton X-100 were found to inhibit the enzyme activity. The homology model of Aio showed correlation with the acidophilic adaptation of the enzyme. This is the first characterization studies of Aio from a species belonging to the Thiomonas genus. The arsenite oxidase was found to be among the acid-tolerant Aio reported to date and has the potential to be used for biosensor and bioremediation applications in acidic environments.


Distal femur nonunion patients can expect good outcomes.
The purpose of this study is to describe our experience with distal femur nonunions and to report on the functional recovery of patients treated for these injuries. Twenty-two patients with an established distal femur nonunion were identified and followed prospectively. Results were compared with a control group consisting of 18 similar patients who had sustained an acute distal femur fracture. Compared with acute fracture patients, patients with a nonunion were more likely to have had an open fracture at initial injury (p = 0.02) and required a longer time to heal after final surgery (p = 0.054). No demographic variables were found to be predictive of complications, Short Musculoskeletal Functional Assessment scores, or time to union. These results show that patients with a distal femoral nonunion can expect to attain similar ultimate outcomes to patients receiving treatment for an acute distal femur fracture. Unlike the development of nonunions following other types of fracture, such as the hip, distal femur nonunions do not portend poor functional outcomes as long as bone union is achieved.


Interhemispheric interactions during sentence comprehension in patients with aphasia.
Right-hemisphere involvement in language processing following left-hemisphere damage may reflect either compensatory processes, or a release from homotopic transcallosal inhibition, resulting in excessive right-to-left suppression that is maladaptive for language performance. Using fMRI, we assessed inter-hemispheric effective connectivity in fifteen patients with post-stroke aphasia, along with age-matched and younger controls during a sentence comprehension task. Dynamic Causal Modeling was used with four bilateral regions including inferior frontal gyri (IFG) and primary auditory cortices (A1). Despite the presence of lesions, satisfactory model fit was obtained in 9/15 patients. In young controls, the only significant homotopic connection (RA1-LA1), was excitatory, while inhibitory connections emanated from LIFG to both left and right A1's. Interestingly, these connections were also correlated with language comprehension scores in patients. The results for homotopic connections show that excitatory connectivity from RA1-to-LA1 and inhibitory connectivity from LA1-to-RA1 are associated with general auditory verbal comprehension. Moreover, negative correlations were found between sentence comprehension and top-down coupling for both heterotopic (LIFG-to-RA1) and intra-hemispheric (LIFG-to-LA1) connections. These results do not show an emergence of a new compensatory right to left excitation in patients nor do they support the existence of left to right transcallosal suppression in controls. Nevertheless, the correlations with performance in patients are consistent with some aspects of both the compensation model, and the transcallosal suppression account for the role of the RH. Altogether our results suggest that changes to both excitatory and inhibitory homotopic and heterotopic connections due to LH damage may be maladaptive, as they disrupt the normal inter-hemispheric coordination and communication.


Stroke in children in Yaounde, Cameroon.
Thirty five children aged 5 months to 15 years suffering from stroke were studied from August 1984 to July 1990 from two hospitals in order to determine the incidence, the etiological factors and the short term outcome of the stroke. The average annual incidence was 1.85 per 1000 pediatric hospitalizations. There was a progressive rise in the number of cases from 1985, with a peak in 1990. Motor impairment of one half of the body was the commonest clinical feature seen in 97.1% of the cases. Other clinical signs were: facial paralysis (62.9%) and aphasia (28.6%). The main etiological factors were: homozygous sickle cell disease (31.4%), heart disease (17.1%), cerebral malaria (14.3%) and meningitis (14.3%). No causative factor was identified in 7 patients (20%). The mortality rate was low (2.9%) and all the children had neurological deficit after a mean hospital stay of 15 days. Laboratory investigations including lipid analysis, platelet count, and skull X-rays proved to be of no diagnostic value. However, computed tomography (CT) scan confirmed the diagnosis of ischemic stroke whenever it could be done.


Single-Walled Carbon Nanotube Chiral Selectivity Exhibited by Commercially Available Hydrogels of Varying Composition.
Despite the commercial availability of many different hydrogel formulations, the effective gel-based purification of single-walled carbon nanotubes (SWNT) remains exclusive to the gel Sephacryl S-200. In this study, 12 commercially available gels and two custom-synthesized gels were investigated for their ability to effectively purify SWNT, as determined through quantification of SWNT adsorption, elution, chiral selectivity, and overall process efficiency. The ability of each gel to separate SWNT was found to correlate with physiochemical properties, such as hydrogel pore size, the presence of ionic ligands, and both polysaccharide backbone and cross-linker compositions. While Sephacryl S-200 demonstrated superior separation efficiency and chiral selectivity among the gels studied, Superose 6 was found to adsorb more SWNT than Sephacryl S-200 per cm2 of the gel surface area and exhibited a unique preference for the (7,3) and (7,5) SWNT chiralities, in contrast to the established selectivity of Sephacryl S-200 for the (6,5) chirality. Collectively, this work both identifies gels that exhibit unique SWNT chiral selectivity and provides insights into the rational design of gels tailored for SWNT purification.


KRAS-mutant colon cancer cells respond to combined treatment of ABT263 and axitinib.
Significant challenges to develop selective and effective pharmacological inhibitors for important oncoproteins like RAS continue impeding the success to treat cancers driven by such mutations. In the present study, the ABT263 and axitinib combination imposed synergistic effects on RAS-mutant colon cancer cells. The combination inhibited in vitro and in vivo growth of the cancer cells by enhancing apoptosis. Furthermore, AKT and Wnt/β-catenin signaling pathways were slightly down-regulated by the combination in KRAS-mutant colon cancer cells. The current results indicate that oncogene addiction can be targeted for therapy in colon cancer cells harboring the RAS-mutant. Therefore, targeting oncogene addiction can be a viable strategy for treating refractory cancers driven by important oncogenes, such as KRAS, which are otherwise difficult to be targeted by small molecules.


Tuneable intramolecular intermetallic interactions as a new tool for programming linear heterometallic 4f-4f complexes.
Statistical mechanics predicts that the design of pure organized heteropolymetallic chains of metal ions bound to linear receptors depends on controlled deviations from the mixing rule DeltaE(MiMj) = 1/2 (DeltaE(MiMi) + DeltaE(MjMj)), whereby DeltaE(MiMj) is the intramolecular intermetallic interaction between neighboring metal i and metal j along the receptor. A thorough investigation of linear polymetallic trivalent lanthanide triple-stranded helicates shows that such deviations are amplified by an increase in the nuclearity of the final complexes and are thus easily evidenced in the tetranuclear heterobimetallic helicates [La(4-y)Lu(y)(L6)3](12+) (y = 0-4). The chemical and physical origins of this unprecedented behavior are discussed together with its practical consequences for programming pure heteropolymetallic 4f-4f complexes.


Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.
Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging SNAr reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.


Post-traumatic posterior radial head subluxation. Two case reports.
Two women, 33 and 55 years of age, with post-traumatic posterior radial head dislocation were treated by open reduction. Normal apposition of the radius to the capitellum was achieved. Although excellent range of motion was restored in both patients, the possibility of post-traumatic arthritis must be determined by long-term follow-up observations.


Measuring young adolescent perceptions of relationships: A vignette-based approach to exploring gender equality.
This paper reports the development and baseline data of a vignettes-based measure of gender equality. Vignettes were developed through 3-day long focus groups. After piloting in 13 sites and repiloting a revised version in 6 countries, responses were categorized by the construct tapped and a scoring system developed. Finalized vignettes were then tested in DR Congo, Ecuador and China. Young adolescents can successfully respond to vignettes; and can differentiate self from hypothetical protagonists of same and opposite sex. Response differences by sex of respondent and protagonist were statistically significant across a range of scenarios and settings. This is the first vignettes-based measure for young adolescents assessing young adolescent perceptions of relationships differentiated by sex of the protagonist.


[Effect of ischemia and postischemic reperfusion on fatty acid oxidation in heart mitochondria].
During permanent coronary artery occlusion (1 and 4 h) the respiratory rate of rabbit heart mitochondria with palmitoyl-CoA, palmitoyl carnitine and acetate was progressively reduced to a similar extent. Oxidation of palmitoyl carnitine was incomplete, whereas beta-oxidation of palmitoyl carnitine was not altered significantly. Postischemic reperfusion (3 h) promoted the recovery of mitochondrial respiration. The data obtained suggest that in both the control and ischemia, palmitate oxidation is limited by outer carnitine palmitoyltransferase but not limited by the tricarboxylic acid cycle and respiratory chain.


Primary cultures of feline acinar cells: dissociation, culturing, and viral infection.
A technique for dissociating and plating of feline parotid acinar cells by enzymatic dispersion with collagenase and trypsin is presented. Viability of the cultured cells was determined by: 1) estimating cellular growth with visual cell counts and by [3H]thymidine incorporation; 2) observing the lack of uptake of vital dyes by the cultured cells: 3) making light, phase contrast, and electron microscopic morphological examinations; and 4) determining the lack of amylase secretion without stimulation, and the evidence of amylase secretion in response to isoproterenol. The cultured feline parotid acinar cells were infected with feline rhinotracheitis virus, a member of the herpes group. Evidence for viral infection was morphological and by indirect fluorescent antibody studies. The viral infected cells also showed no amylase release without stimulation and demonstrated an initial response to a beta-adrenergic agonist by secretion of amylase, but repeated stimulation of the virally infected cells did not produce amylase secretion.


Indomethacin-induced colonic ulceration and bleeding.
To report a case of nonsteroidal antiinflammatory drug (NSAID)-induced lower gastrointestinal (GI) bleeding. A patient in whom short-term ingestion of indomethacin was associated with colonic ulceration and significant gastrointestinal bleeding is described. The bleeding ulceration of the ascending colon, associated in our patient with short-term indomethacin intake, confirms previous reports of the drug's deleterious effect on the lower GI tract. The incidence of NSAID injury of the small intestinal colon may be higher than that previously reported. A prospective study of NSAID users could assess the magnitude of lower GI lesions, concomitant with upper GI evaluation, and help determine limitations in the use of this drug class.


Discharge planning for the child with infantile spasms.
Infantile spasms is a type of seizure disorder usually occurring within the first 24 months of life. The standard treatment is intramuscular injections of repository corticotropin (HP ACTHAR gel). The child with infantile spasms is at risk for developmental delay, even if the seizures are controlled. The parents' grief reaction to this prognosis may affect their ability to learn and implement the treatment plan. Discharge planning for children and families is extensive and must begin at the time of the child's admission to the hospital.


Phenolic Derivatives from the Root Bark of Oplopanax horridus.
Four new phenolic derivatives, including two phenylpropanoid glycosides, one benzoate glycoside, and one lignan glycoside, together with one known glyceride, were isolated from the root bark of Oplopanax horridus. The structures of the new compounds were elucidated as 3-{4-[(6-O-acetyl-β-D-glucopyranosyl) oxy]-3,5-dimethoxyphenylpropanoic acid (1), (+)-[5,6,7,8-tetrahydro-7- (hydroxylmethyl)-10,11-dimehoxydibenzo[a,c][8]annulen-6-yl]methyl β-D-glucopyranoside (2), (+)-methyl 4-[6-O-{3-hydroxy-3-methyl-5-(1-methylpropyl)oxy]-5-oxopentanoyl}-4-O-(β-D-glucopyranosyl)-β-D-glucopyranosyl)oxy]-3-methoxybenzoate (3), and 2-methoxy-4-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl 6-O-{3-hydroxy-3-methyl-5-[(1-methylpropyl)oxy]-5-oxopentanoyl-4-O-β-D-glucopyranosyl-β-D-glucopyranoside (4) on the basis of spectroscopic techniques including NMR and MS analyses. The known compound was identified as glycer-2-yl ferulate (5) by comparing its physical and spectral data with those reported in the literature.


Family violence.
Violence within family differs in significant respects from criminal assultiveness. Failure to differentiate these two forms of violence contributes to the ineffectiveness of the criminal justice system. Love relationships account for the majority of homicides; however, the fiction of the criminal as the killer persists because of the entertainment media. Prevention requires comprehension of the causes and construction of typology of violence.


Yeasts of the soil - obscure but precious.
Pioneering studies performed in the nineteenth century demonstrated that yeasts are present in below-ground sources. Soils were regarded more as a reservoir for yeasts that reside in habitats above it. Later studies showed that yeast communities in soils are taxonomically diverse and different from those above-ground. Soil yeasts possess extraordinary adaptations that allow them to survive in a wide range of environmental conditions. A few species are promising sources of yeast oils and have been used in agriculture as potential antagonists of soil-borne plant pathogens or as plant growth promoters. Yeasts have been studied mainly in managed soils such as vineyards, orchards and agricultural fields, and to a lesser extent under forests and grasslands. Our knowledge of soil yeasts is further biased towards temperate and boreal forests, whereas data from Africa, the Americas and Asia are scarce. Although soil yeast communities are often species-poor in a single sample, they are more diverse on the biotope level. Soil yeasts display pronounced endemism along with a surprisingly high proportion of currently unidentified species. However, like other soil inhabitants, yeasts are threatened by habitat alterations owing to anthropogenic activities such as agriculture, deforestation and urbanization. In view of the rapid decline of many natural habitats, the study of soil yeasts in undisturbed or low-managed biotopes is extremely valuable. The purpose of this review is to encourage researchers, both biologists and soil scientists, to include soil yeasts in future studies.


Role of cardiac imaging in Anderson-Fabry cardiomyopathy.
The Anderson-Fabry disease (AFD, or simply Fabry Disease, FD; MIM #301500) is a rare X-linked lysosomal storage disorder (Xq22.1) characterized by progressive renal failure, leading to morbidity through cardio- and cerebro-vascular involvement. Despite the classic phenotype, only cardiac involvement (cardiac variant of AFD; MIM 301500) is frequent in about 40% of male and 28% of female AFD patients, as reported by the Fabry Registry ( https://www.registrynxt.com ). Morphologically, the cardiac characteristic of the disease, occurs as left ventricular hypertrophy, is accompanied by myocardial fibrosis. Cardiologists may come across these patients during clinical and instrumental evaluation in individuals with non-specific symptoms such as chest pain and arrhythmias, or after instrumental evidence of left ventricular hypertrophy/hypertrophic cardiomyopathy (HCM; MIM 192600). A comprehensive cardiological work-up, including a cardiological visit, a baseline electrocardiogram (ECG) and imaging by both echocardiography (ECHO) and magnetic resonance (MRI) enables identification of the cardiac involvement in patients with a proven diagnosis of AFD. The heart involvement is present in up to 75% of AFD patients irrespective of their sex. Involvement includes ECG and echocardiography features which suggest AFD and not HCM. Cardiac imaging plays an important role in detecting this sub-type of cardiomyopathy, which, since 2001, has benefited from the introduction of the enzyme replacement therapy (ERT) in symptomatic and pre-symptomatic patients.


The utility of the balance error scoring system for mild brain injury assessments in children and adolescents.
The Balance Error Scoring System (BESS) is widely recognized as an acceptable assessment of postural control for adult patients following a mild traumatic brain injury (mTBI) or concussion. However, the measurement properties of the BESS as a post-mTBI assessment test for younger patients are not well understood. The purpose of this study was to evaluate the utility of the BESS as a post-mTBI assessment test for children and adolescents aged 8 to 18 years through 2 investigations: (1) a retrospective medical records review of the relationship among age, BESS scores, and other common post-mTBI assessment tests; and (2) a prospective study comparing BESS scores for a cohort of children with a recent mTBI and BESS scores for a cohort of matched healthy peers. Age was found to be significantly correlated with several of the BESS measures and the total BESS score (P < 0.05). Significant differences were observed between the injured and healthy cohorts for 3 of the BESS measures and the total BESS score. However, the observed differences were not likely to be clinically meaningful. Cumulatively, evidence from the literature and the results of these studies indicate that the BESS may be limited for producing accurate assessments of younger athletes' post-mTBI postural control abilities. Future research recommendations include testing of modified versions of the BESS or other alternatives for post-mTBI postural control assessments with younger individuals.


Close-range attraction of female oriental fruit moths to herbal scent of male hairpencils.
A blend of ethyl trans-cinnamate, methyl 2-epijasmonate, methyl jasmonate, and (R)-(-)-mellein, identified from the hairpencils of male Oriental fruit moths, attracts sex pheromone-releasing females several centimeters away. The chemicals thereby duplicate the behavioral effect elicited by hairpencil-displaying males during courtship; the chemicals also produce the herbal scent emanating from the hairpencils.


The Role of Oxidative Stress Modulators in Breast Cancer.
Latest data from International Agency for Cancer Research shows that breast cancer is the leading cancer site in women and is the leading cause of death among female cancers. Induction of reactive oxygen species (ROS) and oxidative stress as a consequence of impaired balance between prooxidants and antioxidants are suggested to be involved in induction and progression of breast cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal cells. However increased antioxidant defence which balances the oxidative status within the cancer cells suggests that high ROS levels may prevent tumorigenesis via various mechanisms. These contradictory roles of ROS and oxidative stress in breast cancer let scientists investigate potential oxidative stress modulators as anticancer strategies. In the present review we address the mechanisms of ROS production in breast cancer cells, the role of impaired oxidative status as well as the benefits of introducing oxidative stress modulators in therapeutic strategies in breast cancer. This review is focusing more on melatonin which we have been working on during the last decade. Our data, in accordance with the literature, suggest an important role for melatonin in breast cancer prevention and adjuvant therapy.


Structural studies on the decameric S. typhimurium arginine decarboxylase (ADC): Pyridoxal 5'-phosphate binding induces conformational changes.
Enteric pathogens such as Salmonella typhimurium colonize the human gut in spite of the lethal acidic pH environment (pH < 2.5) due to the activation of inducible acid tolerance response (ATR) systems. The pyridoxal 5'-phosphate (PLP)-dependent enzyme, biodegradative arginine decarboxylase (ADC, encoded by AdiA), is a component of an ATR system. The enzyme consumes a cytoplasmic proton in the process of arginine degradation to agmatine. Arginine-agmatine antiporter (AdiC) exchanges the product agmatine for arginine. In this manuscript, we describe the structure of Salmonella typhimurium ADC (StADC). The decameric structure assembled from five dimers related by a non crystallographic 5-fold symmetry represents the first apo-form of the enzyme. The structure suggests that PLP-binding is not a prerequisite for oligomerization. Comparison with E. coli ADC reveals that PLP-binding is accompanied by the movement and ordering of two loops (residues 150-159 and 191-197) and a few active site residues such as His256 and Lys257. A number of residues important for substrate binding are disordered in the apo-StADC structure indicating that PLP binding is important for substrate binding. Unlike the interactions between 5-fold related protomers, interactions that stabilize the dimeric structure are not pH dependent.


Arterial permeability to labeled protein.
Labeled albumin, which was administered intravenously, was detected, with the use of a scintillation counter, in the aortic wall of rabbits. Relative to weight, the permeability index was highest in the aortic arch and abdominal aorta and lowest in the medial thoracic aorta. Angiotensin II and various mediators were found to increase the permeability of the aortic wall.


Oligofunctional amphiphiles featuring geometric core group preorganization: synthesis and study of Langmuir and Langmuir-Blodgett films.
Based on the principle of supramolecular preorganization, a new type of oligofunctional amphiphile, of which compounds 1-4 are representative structures, has been designed and synthesized. The typical feature of their structure is a highly rigid and geometrically well-defined central unit composed of ethynylene substituted aromatic spacers with different numbers of amphiphilic segment groups (also of a rigid geometric design) attached to it. The molecules form well-defined Langmuir films when spread from a solution at the air/water interface or when a 10(-4) M aqueous CaCl2 solution was used as the subphase. By analysis of the surface pressure-surface area (pi-A) isotherms, information on the packing behavior and orientation of the amphiphilic molecules depending on the molecular structure could be obtained. Morphological characterization of the dynamic process of monolayer compression at the air/water interface was carried out by Brewster angle microscopy, illustrating several phase states visualized as snap shots. Thin monolayer films produced on a 10(-4) M aqueous CaCl2 subphase can be transferred to a mica solid support by the Langmuir-Blodgett technique. Tapping mode atomic force microscopy reveals a surface topography of the monofilms composed of 1 and 3 that differ in roughness and also in the properties of elasticity, hardness and adhesive strength. X-Ray crystal structure analysis of three relevant intermediate compounds of the synthesis were successfully determined giving an indication of the potential structural features inherent in the new amphiphiles.


Retinal vein occlusion: genetic predisposition and systemic risk factors.
The role of systemic risk factors (age, smoking, diabetes, arterial hypertension) in the development of retinal vein occlusion (RVO) is well established. However, the association of RVO with genetic predisposition to thrombosis remains poorly understood. The aim of the study was to assess any possible additional effect of genetic predisposition to the already well known 'classical' risk factors of RVO in a cohort of elderly Greek patients. Fifty-one elderly patients with RVO and 51 healthy individuals matched for age and sex were evaluated for systemic risk factors (smoking, diabetes, dyslipidemia, arterial hypertension) and coagulation defects (lupus anticoagulant, natural inhibitors of coagulation). Additionally, genotyping was performed for mutations/polymorphisms involved in haemostasis such as: FV G1691A, FV G4070A, FIIG 20210A, MTHFR C677T and A1298C, PAI-1-675 4G/5G, F XIII exon 2G/T, EPCR A4600G and G4678C. We identified systemic risk factors in the majority of the patients Hypertension (P=0.001), dyslipidemia (P=0.029) and diabetes (P=0.01) are associated with RVO in the majority of the patients. The prevalence of prothrombotic risk factors was not significantly different in the patients with RVO compared to controls. Apart from systemic risk factors, genetic predisposition to thrombosis does not seem to have an important association with RVO in this group of elderly patients.


Ocular spirorchiidiosis in sea turtles from Brazil.
The causes of the beaching and death of sea turtles have not been fully clarified and continue to be studied. Mild, moderate and severe lesions caused by spirorchiidiosis have been seen for decades in different organs and were recently defined as the cause of death of a loggerhead turtle. In the present study, eyes and optic nerves were analysed in green sea turtles with spirorchiidiosis and no other debilitating factors. Injuries to the optic nerve and choroid layer were described in 235 animals (90%) infected with spirorchiids. Turtles with ocular spirorchiidiosis are approximately three times more likely to be cachectic than turtles with spirorchiidiosis without ocular involvement.


Polysaccharide peptide (PSP) restores immunosuppression induced by cyclophosphamide in rats.
Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were investigated by determining lymphocyte proliferation, Natural killer (NK) cell formation, IgG and IL-2 concentration, WBC count and the weight of organs after rats were treated with or without CPA in the presence or absence of PSP. The results demonstrated that PSP possessed immunopotentiating effect, being effective in restoring CPA-induced immunosuppression such as depressed lymphocyte proliferation, Natural Killer cell function, production on white blood cell and the growth of spleen and thymus in rats as well as in increasing both IgG and IL-2 production on which CPA did not have significant effects under the conditions of our experiments. PSP can partly restore CPA-induced immunosuppression. Based on our findings and the data accumulated so far, it was suggested that PSP should be considered as an useful adjuvant especially combined with CPA or other chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP restores the immunosuppression induced by CPA is unclear.


Fire fighter vision standards.
Fire fighting is a physically and visually demanding occupation. Because of the severe visual demands and the high costs of nonperformance it is necessary to establish minimum vision levels that become requirements for new fire fighters. These vision standards must be based as nearly as possible upon the specific visual needs of the occupational tasks. This paper examines the visual tasks of fire fighters and recommends visual standards.


Cercosporoid leaf pathogens from whorled milkweed and spineless safflower in California.
Two cercosporoid species are respectively described from Mexican whorled milkweed (Asclepias fascicularis), and spineless safflower (Carthamus tinctorius) from California. Passalora californica represents a new pathogen on Asclepias fascicularis, while Ramularia cynarae is confirmed on Carthamus tinctorius and Cynara cardunculus (Asteraceae), and an epitype designated. Pathogenicity is also established for both pathogens based on Koch's postulate.


Predictors of in-hospital mortality present at admission among patients hospitalised because of decompensated heart failure.
Chronic heart failure (HF) is associated with a poor prognosis and causes considerable mortality. The aim of this study was to identify the admission characteristics useful to predict in-hospital mortality in patients admitted because of decompensation of HF. We evaluated 414 patients (age 76.2 years, 57% women). The hospital mortality rate was 11.1%. We identified 4 independent predictors of mortality: low Barthel index (odds ratio 1.03; 95% confidence interval 1.01-1.04), creatinine level >200 mumol/l (odds ratio 3.40; 95% confidence interval 1.51-7.66), peripheral oedema (odds ratio 3.12; 95% confidence interval 1.28-7.58) and the protective effect of the new onset of the disease (odds ratio 0.2; 95% confidence interval 0.08-0.77). In conclusion, the mortality of patients admitted to the hospital with an exacerbation of HF can be predicted if either poor functional capacity, renal insufficiency, peripheral oedema or previous diagnoses of HF are present. This clinical finding may help clinicians in their decision making in HF in the emergency room.


A proteomic analysis of the acute effects of high-intensity exercise on skeletal muscle proteins in fasted rats.
Quantitative proteomics is a technique that allows for large-scale comparison of the levels of individual proteins present in a biological sample. This technique has not previously been applied to examine the response of skeletal muscle proteins to an acute bout of exercise. In the present study, quantitative proteomics was applied to investigate whether the levels of individual skeletal muscle proteins are acutely affected by a short bout of high-intensity exercise. Gastrocnemius muscle was sampled from fasted rats either at rest, immediately following 3 min of high-intensity exercise or after 30 min of recovery. Muscle samples were submitted to two-dimensional gel electrophoresis and 61 of the resulting protein spots were selected for quantitative analysis. It was found that skeletal muscle protein levels were generally not acutely affected by a short bout of high-intensity exercise, with only four of the 61 proteins selected for analysis being significantly altered. These altered proteins were identified using liquid chromatography electrospray ionization-tandem mass spectrometry as creatine kinase, troponin T and a combination of heat shock 20 kDa protein and adenylate kinase 1. In conclusion, quantitative proteomics is sensitive enough to detect acute changes in skeletal muscle protein levels in response to exercise. We have found that the levels of most individual skeletal muscle proteins are not immediately altered in response to a short bout of high-intensity exercise and recovery in fasted rats.


Voice Characteristics in Patients with Thyroid Disorders.
This study investigated acoustic and perceptual characteristics of the voice of patients with thyroid gland disorders such as hypothyroidism and hyperthyroidism immediately after the diagnosis was made and six months later, after using drug therapy. The study includes 20 female outpatients with hypothyroidism and 27 female outpatients with hyperthyroidism. The criterion for the selection of the patients was a thyroid gland disorder medical diagnosis, no history of voice disorders and absence of other possible causes of voice changes. Acoustic, perceptual and aerodynamic parameters were assessed. Acoustic analysis was performed by specific software. Experienced speech and language pathologists made perceptual voice assessment by using grade, roughness, breathiness, asthenia, and strain (GRBAS) scale. Significant differences in patients with hypothyroidism were established on parameter amplitude perturbation, jitter and noise-to-harmonics ratio between pretreatment and posttreatment period, in which patients took drug therapy. In group of patients with hyperthyroidism significant difference was noted only on aerodynamic parameter maximum phonation time. There were a significant differences in all perceptual parameters in both groups of patients (p<0.05) in pre and posttreatment, except on grade and asthenia parameter in the group of patients with hypothyroidism and parameter grade was borderline insignificant in the group of patients with hyperthyroidism. Voice quality is affected by thyroid disease. Thyroid gland disorders cause minor changes in acoustic voice parameters of patients with hypothyroidism and hyperthyroidism, but perceptual deviations in these patients are especially noticeable.


Perceiving Animacy From Deformation and Translation.
In a cartoon, we often receive an animacy impression from a dynamic nonanimate object, such as a sponge or a flour sack, which does not have an animal-like shape. We hypothesize that the animacy impression of a nonanimal object could stem from dynamic patterns that are possibly fundamental for biological motion perception. Here we show that observers recognize the animacy of human jump actions from the combination of deformation and translation. We extracted vertical motion vectors from the uppermost and lowermost points in point-light jumper stimuli and assigned the vectors to a uniform rectangle. The participants' task was to rate the animacy and jump impressions for the rectangle. Results showed that both animacy and jump impressions for the rectangle movements were comparable to those for the original point-light movements. The impressions decreased for stimuli having a deformation or translation component alone, which was extracted from the original motion vectors. By mathematically simulating deformation and translation in a human jump, we also found that the temporal relation between deformation and translation plays a critical role in the determination of jump impressions but only has a moderate effect for animacy impressions. On the basis of the results, we discuss how cartoon techniques take advantage of the properties of biological motion perception.


The comet assay in Ceraeochrysa claveri (Neuroptera: Chrysopidae): A suitable approach for detecting somatic and germ cell genotoxicity induced by agrochemicals.
Some agrochemicals are genotoxic to several organisms. Nevertheless, few protocols are currently available for measuring the toxicogenetic effects of these compounds in target and non-target field-collected species of insects important to agriculture. Herein, we used the species Ceraeochrysa claveri (Neuroptera: Chrysopidae), a non-target predator insect, to investigate the ability of an azadirachtin-based biopesticide (Azamax™) to induce DNA damage. The alkaline version of the comet assay was standardized to evaluate genetic instability caused by the toxicant in somatic (gut) and germ (nurse cells and oocytes) cells of C. claveri. For this, C. claveri larvae were distributed into three groups (10/each) and treated with Azamax™ at 0, 0.3% or 0.5% throughout the larval stage. DNA damage (tail intensity) was measured in adult insects, four days after emerged. The data showed that both doses of Azamax™ (0.3% and 0.5%) were able to significantly (p < 0.05) increase DNA damage in somatic and germ cells of C. claveri. In conclusion, C. claveri (intestinal and ovarian cells) was a sensitive bioindicator for identifying Azamax™ genotoxic potential, whereas the comet assay was a useful tool for detecting the genotoxic hazard of the pesticide in the field-collected insect species. Given that estimation of adverse effects of pollutants on ecosystems is an essential component of environmental risk assessment, the approach used can be recommended to estimate the ecotoxicity of agricultural chemicals.


Emergence of an ST1326 (CG258) Multi-Drug Resistant Klebsiella pneumoniae Co-harboring mcr-8.2, ESBL Genes, and the Resistance-Nodulation-Division Efflux Pump Gene Cluster tmexCD1-toprJ1 in China.
CG258 is the dominant carbapenemase-producing Klebsiella pneumoniae clone worldwide and treatment of infections caused by this clone relies largely on the last-line antibiotics, colistin, and tigecycline. However, the emergence and global dissemination of mcr and tmexCD1-toprJ1 genes have significantly compromised their clinical applications. CG258 K. pneumoniae carrying both mcr and tmexCD1-toprJ1 have not been reported. A colistin-resistant strain T698-1 belonging to ST1326, a member of CG258, was isolated from the intestinal sample of a patient and characterized by the antimicrobial susceptibility testing, conjugation assay, WGS and bioinformatics analysis. It was resistant to colistin, tetracycline, aminoglycoside, fluoroqinolone, phenicols, sulfonamide, and some β-lactams, and positive for mcr-8.2, tmexCD1-toprJ1, and ESBL genes (bla DHA-1 and bla CTX-M-15). The tmexCD1-toprJ1 gene cluster was located in an multi-drug resistant (MDR) region flanked by TnAs1 elements on an IncHI1B/FIB plasmid. The genetic context of tmexCD1-toprJ1 was slightly distinct from previously reported Tn5393-like structures, with an IS26 element disrupting the upstream Tn5393 and its adjacent genetic elements. The mcr-8.2 gene was inserted into the backbone of an IncFII/FIA plasmid with the genetic context of ISEcl1-mcr-8.2-orf-ISKpn26. To our knowledge, this is the first report of co-occurrence of mcr-8.2 and tmexCD1-toprJ1 in a CG258 K. pneumoniae strain. Though this strain is tigecycline sensitive, the acquisition of colistin and tigecycline resistance determinants by the endemic CG258 K. pneumoniae clone still poses a serious public health concern. CG258, which became resistant to multiple last resort antibiotics, would be the next emerging superbug.


Self-healing, self-adhesive, stretchable and flexible conductive hydrogels for high-performance strain sensors.
Conductive hydrogels have been widely studied for their potential application as wearable sensors due to their flexibility and biocompatibility. However, the simultaneous incorporation of excellent stretchability, toughness, conductivity, self-healing, and adhesion via a simple method remains a great challenge. Herein, a multifunctional hydrogel with self-adhesion, self-healing, conductivity, and mechanical properties was fabricated by ionic cross-linking of chitosan (CS), the acrylic acid (AA) polymer, and tea polyphenols (TPs) in the presence of graphitized carbon nanotubes (CNTs) in this work. The resultant hydrogel has unique self-healing properties (94.11% for strain self-healing and 90.60% for stress self-healing) and mechanical properties. The fracture stress was 0.075 MPa when the strain was 1184%, and the toughness reached 0.48 MJ m-3. The synergistic effect of free ions and CNTs endows the hydrogel with an excellent electrical conductivity (6.67 S m-1). Moreover, the hydrogel can adhere to various organic and inorganic materials. It exhibits repeatable self-adhesion to human skin and can be peeled off completely without any residual, irritation or allergic reactions. Additionally, the hydrogel also has good strain sensitivity and exhibits stable output signals in motion monitoring of the human body as a biosensor. Therefore, this work provides a new prospect for the design of multifunctional hydrogels for their potential applications in wearable biosensors.


Children at risk for schizophrenia: converging lines of evidence.
This article summarizes major findings from the risk-for-schizophrenia literature. On the basis of a review of the results of 24 high-risk studies, common themes in the risk-for-schizophrenia literature are discussed. It is concluded that there are a number of cross-study findings documenting child and family attributes associated with increased risk for schizophrenia.


Cloning and sequencing of a Rhodothermus marinus gene, bglA, coding for a thermostable beta-glucanase and its expression in Escherichia coli.
A gene library of the thermophilic eubacterium, Rhodothermus marinus, strain 21, was prepared in pUC18 and used to transform Escherichia coli. Of 5400 transformants, two produced halos on lichenan plates after Congo-red staining. Restriction mapping showed that the two clones shared an overlapping 1200-bp DNA fragment, which was used for DNA sequencing. Five potential methionine (Met) translational-initiation codons were identified. A putative signal peptide of 30 amino acids was identified with a hydrophobic core of nine hydrophobic amino acids. The molecular mass of the mature enzyme was estimated to be 29.7 kDa. A comparison of the primary protein sequence of beta-glucanase of Rhodothermus marinus with other glycosyl hydrolases showed 38.5% identity to the C-terminal part of the beta-1,3-glucanase of Bacillus circulans and limited identity to bacterial endo-beta-1,3-1,4-glucanases. The amino acid sequence showed high similarity to regions surrounding the catalytic Glu residue of bacterial beta-glucanases. A gene fragment of 889 bp containing the catalytic domain was overexpressed in E. coli using the pET23, T7-phage RNA polymerase system. The enzyme showed activity on lichenan, beta-glucan and laminarin but not on CMC cellulose or xylan. The expressed enzyme was purified by heat treatment of the host. The enzyme had a temperature and pH optima of 85 degrees C and pH 7.0, respectively, and was shown to retain full activity after incubation for 16 h at 80 degrees C and have a half life of 3 h at 85 degrees C.


Reid on olfaction and secondary qualities.
Thomas Reid is one of the primary early expositors of the "dual-component" theory of perception, according to which conscious perception constitutively involves a non-intentional sensation accompanied by a noninferential perceptual belief. In this paper, I will explore Reid's account of olfactory perception, and of odor as a secondary quality. Reid is often taken to endorse a broadly Lockean picture of secondary qualities, according to which they are simply dispositions to cause sensations. This picture creates problems, however, for Reid's account of how we perceive secondary qualities, including odors. Given Reid's insistence that we come to be aware of odors only by inferring a causal relation to obtain between them and our olfactory sensations, it seems that he cannot allow for direct, noninferential perceptual awareness of odors. Since his general account of perception invokes noninferential perceptual beliefs to explain perceptual awareness, it seems that Reid must either reject this general account for the case of olfactory perception (and supplant it with something else), or else deny that we ever actually perceive odors. I will attempt to reconcile these ideas by appeal to Reid's doctrine of "acquired perception," which involves the incorporation of learned conceptual representations into perceptual states via perceptual learning. Reidian acquired perception enables genuine olfactory perceptual acquaintance with odors despite the dependence of the semantic properties of the relevant representations on causal relations to sensations. In exploring these issues, I hope to illuminate several features of Reid's account of perception and demonstrate its interest to contemporary theorizing about conscious perception-especially olfaction-in the process. Reid's theory of olfaction remains a live, coherent option for present-day theorists.