An experimental investigation of the modifiability of the temporal structure of spontaneous speech.
This study attempted to test the hypothesis that the temporal structure of spontaneous speech is modifiable by reinforcing and punishing pauses, of a certain duration, in an operant conditioning situation. Pause rate was significantly affected by these contingencies: moreover, rate of change was rapid, indicating a "prepared" association between pausing and such contingencies. This study also attempted to test the hypothesis that there is a class of noncognitive pauses in monologue by punishing UPs to determine if UPs can be eliminated without affecting speech content. Although this manipulation did lead to a decline in pause rate, a significant increase in the amount of filled hesitation, particularly in repetition, resulted. This suggests that the overall amount of hesitation is fixed by the cognitive demands of the task but that a speaker is able to adapt to different interactional contexts by varying the category of hesitation used for cognitive planning.


Bcl-2/Bcl-xL inhibitor navitoclax increases the antitumor effect of Chk1 inhibitor prexasertib by inducing apoptosis in pancreatic cancer cells via inhibition of Bcl-xL but not Bcl-2.
In our previous study, we showed that prexasertib, a checkpoint kinase 1 (Chk1) inhibitor, enhances the effects of standard drugs for pancreatic cancer, including gemcitabine (GEM), S-1, and the combination of GEM and S-1 (GS). The combination of prexasertib and GS has a strong antitumor effect and induces apoptosis in pancreatic cancer cells by downregulating anti-apoptotic protein Bcl-2. In the present study, we investigated the combined effect of GEM, S-1, and prexasertib with a selective Bcl-2 inhibitor (venetoclax) and a non-selective Bcl-2 inhibitor (navitoclax) in SUIT-2 pancreatic cancer cells. An MTT assay revealed that the combination of prexasertib with navitoclax showed a synergistic effect but the combination with venetoclax did not. Investigation of the pancreatic cancer cell lines SUIT-2, MIA PaCa-2, and BxPC-3 revealed that BxPC-3 also showed a high synergistic effect when combined with prexasertib and navitoclax but not venetoclax. Mechanistic analysis of the combined effect showed that apoptosis was induced. Bcl-2 knockdown with siRNA and prexasertib treatment did not induce apoptosis, whereas Bcl-xL knockdown with siRNA and prexasertib treatment resulted in strong induction of apoptosis. In addition, among the three cell lines, the combined effect of prexasertib and navitoclax resulted in increased apoptotic cell death because the protein expression levels of Bcl-xL and Chk1 were higher. Our results demonstrate that the combination of prexasertib and navitoclax has a strong antitumor effect and induces apoptosis in pancreatic cancer cells by downregulating Bcl-xL. Simultaneous inhibition of Chk1 and Bcl-xL could be a new strategy for treating pancreatic cancer.


[Third French Cancer Plan: Six years at the service of the French people].
The implementation of the third Cancer Plan, which began in January 2014, was completed in 2019. With nearly 90% of the actions carried out, this Plan was marked by the collective mobilisation of all stakeholders to reduce the burden of cancer in our country. Real successes have been recorded. But the progress made must not make us forget the pain and suffering endured by those affected by this disease, their families, loved ones and caregivers. Cancer continues to be a life-changing experience for those who face it. In this fight, progress in medicine, research, the quality and safety of care, progress in social support, support in returning to work and to a normal life are all hopes for all patients and their loved ones. They have only been possible thanks to the mobilisation of everyone and the dedication of the care teams. Many battles have been fought over the years and the results obtained are the best encouragement to continue the efforts. We must now amplify and improve our collective action. The ambitious objective of massively reducing the burden of cancer in the lives of the French must mobilise us all for the next decade.


Pathologic and molecular aspects of soft tissue sarcomas.
This article retains the conventional approach to the classification of soft tissue sarcomas, dividing them into several major histogenetic categories based on their overall microscopic appearance, tissue differentiation pattern, and biologic potential. The author advocates a multimodal approach, in which four distinctive data sets--clinical, radiographic, microscopic, and, in some cases, molecular--are considered to establish the diagnosis and treatment plan. Such step-wise analysis is more likely to lead to consistency and accuracy as compared with an intuitive approach based on fragmentary data. The author describes individual lesions of soft tissue as clinicopathologic entities and believes that they can be more accurately diagnosed and appropriately treated with the help of data generated by a multidisciplinary team. In addition, this article emphasizes the need to use emerging molecular techniques that can provide important clues for both diagnosis and prognosis.


Anxiety in male nursing students at Kamuzu College of Nursing.
Anxiety is a usual and expected occurrence among nursing students. Male students are confronted with additional anxieties, especially in Malawi, due to role expectations for men. A 31-item questionnaire eliciting potentially anxiety provoking situations was presented to the 24 male nursing students at Kamuzu College of Nursing in Lilongwe, Malawi. The results of this small study suggest a high level of anxiety among these male students, and dissatisfaction about the information presented to them upon entering the Nursing Programme. The men felt particular stress about role differences between nurses and other male health workers.


Exploring characteristics of bioelectricity generation and dye decolorization of mixed and pure bacterial cultures from wine-bearing wastewater treatment.
This study uncovered microbial characteristics of bioelectricity generation and dye decolorization in single-chamber microbial fuel cells (MFCs) using activated sludge for wine-containing wastewater treatment. Phylogenetic tree analysis on 16S rRNA gene fragments indicated that the predominant strains on anodic biofilm in acclimatized MFCs were Gamma-Proteobacteria Aeromonas punctata NIU-P9, Pseudomonas plecoglossicida NIU-Y3, Pseudomonas koreensis NIU-X8, Acinetobacter junii NIU-Y8, Stenotrophomonas maltophila NIU-X2. Our findings showed that the current production capabilities of these pure strains were only ca. 10% of those of their mother activated sludge, indicating that synergistic interactions among microbes might be the most influential factor to maximize power generation in MFCs. Plus, these electrochemically active strains also performed reductive decolorization of C.I. reactive blue 160, suggesting that bioelectricity generation might be directly associated to azo dye decolorization to deal with electron transfer on anodic biofilm in MFCs.


Histology and biology of metastatic chondroblastoma. Report of a case with a review of the literature.
This case report of a metastasizing chondroblastoma with a review of the literature was undertaken to gain a better understanding of the biologic behavior of this exceedingly rare tumor and thus to facilitate its clinical management. The lung was by far the most frequent metastatic site. Thus, all 7 patients with a proven metastatic chondroblastoma recorded up to now including the present case had developed multiple pulmonary metastases. The interval between the initial diagnosis of the primary and manifestation of lung metastases proved to be long, with a mean of 8.4 years. The average survival time was at least 12.3 years. The mean interval between diagnosis of metastatic disease and death amounted to at least 6.3 years. The histomorphologic features of metastatic chondroblastoma, its local recurrences and of the metastatic lesions differed in no way from conventional chondroblastomas. Because of the lack of cellular criteria of malignancy it is impossible to predict the potential biologic behavior of chondroblastomas, in particular with respect to their ability to metastasize. However, the presence of tumor emboli in the primary lesion is highly suggestive of a subsequent development of metastatic disease. The delayed induction of hematogenous metastases is best explained by a limited growth potential of the tumor cells. In case of a large primary tumor--especially in flat bones--with soft tissue invasion or in the presence of tumor emboli an aggressive surgical approach is suggested. When lung metastases have developed their surgical removal is recommended to hopefully prolong live expectancy or even to obtain a curative effect.


In vitro and in vivo aphrodisiac properties of Corchorus depressus Linn. on rabbit corpus cavernosum smooth muscle relaxation and sexual behavior of normal male rats.
Corchorus depressus Linn. has been used as an aphrodisiac in traditional Indian medicine to treat male sexual dysfunction and impotency. The petroleum ether, chloroform, ethyl acetate, n-butanol and aqueous fractions of 95% methanol extract of Corchorus depressus were screened initially for their in vitro aphrodisiac activity on rabbit corpus cavernosum smooth muscle. The chloroform fraction (CDC) was found to be the most active and therefore investigated further on general mating behavior, libido and potency of normal male Wistar albino rats in comparison with the standard drug, Sildenafil citrate. Animals were divided into the following groups: Control, SC CDC 100, CDC 200, and CDC 400, who received saline, Sildenafil citrate or the chloroform fraction of Corchorus depressus at doses of 100, 200 or 400mg/kg b.wt., respectively. The route of administration for all the groups was oral dosing, which was once in a day for 45 days. To analyze the mating behavior, female rats with estrus phase were used. The chloroform fraction of methanolic extract of Corchorus depressus significantly reduced ML, IL, PEI and III. There was a significant increase in the MF, IF and EL and serum testosterone levels throughout the study period. The potency test significantly increased erections, quick flips, long flips and total reflex. In vitro aphrodisiac activity was significantly higher in chloroform fraction at a concentration of 25.0mg/ml, which induced 71.4% relaxation. The combined results of the above mentioned models indicate that the chloroform fraction of Corchorus depressus produces a significant increase in sexual activity as exhibited by 25mg/ml in vitro and 400mg/kg in vivo. In comparison with the control, all the drug-treated groups have shown drug-induced effects for a few parameters. In vitro and in vivo studies provide valuable experimental evidence that the chloroform fraction of methanolic extract of Corchorus depressus possesses aphrodisiac property. This study further substantiates the ethnopharmacological claims of Corchorus depressus as a sexual stimulating agent and offers a significant potential for studying the effect on male sexual response and its dysfunctions.


The social construction of cancer chemotherapy toxicity: the case of Taiwan.
Chemotherapy toxicity hinders cancer treatment outcomes. Healthcare professionals educated in biomedical-oriented systems tend to label patients who refuse or discontinue chemotherapy as "noncompliant." How diverse discourses in public texts related to chemotherapy toxicity, which may significantly shape patients' actions, has not been formally explored. The aims of this study were to explore the 2 dominant discourses in Taiwan related to chemotherapy toxicity within their sociocultural context and to ascertain how chemotherapy toxicity is constructed in the texts of journals and newspapers. Public, medical, and nursing texts about chemotherapy from 1950 to 2010 were collected and analyzed using Foucaultian discourse analytical techniques; juxtaposing dominant and marginalized discourses, we identified cultural themes. In traditional Chinese medicine, toxic chemotherapy drugs are believed to interfere with circulation of energy flow and blood and to disturb the harmony of yin/yang in the body. Findings indicate that biomedical and traditional Chinese medical doctors do not agree about the best management of chemotherapy toxicity. Moreover, lay knowledge and patient voices regarding chemotherapy toxicity are often ignored in medical discourses. Cultural beliefs and covert power relations between diverse medical traditions shape patients' experiences of chemotherapy toxicity. The preferential use by patients of traditional Chinese medicine over biomedicine to manage chemotherapy toxicity sustains its pivotal role. The disparity of perceptions between healthcare professionals and patients regarding chemotherapy toxicity needs to be thoroughly assessed. Thus, culturally specific nursing care models may be developed.


Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: a study of 518,294 patients at a tertiary referral center.
The authors determined the incidence of cardiac arrest and predictors of survival following perioperative cardiac arrest in a large population of patients at a tertiary referral center. Medical records of patients who experienced cardiac arrest in the perioperative period surrounding noncardiac surgery between January 1, 1990, and December 31, 2000, were reviewed. Logistic regression identified characteristics associated with immediate (>or= 1 h) and hospital survival, with P <or= 0.01 considered statistically significant. Cardiac arrest occurred in 223 of 518,294 anesthetics (4.3 per 10,000) during the study period. Frequency of arrest for patients receiving general anesthesia decreased over time (7.8 per 10,000 during 1990-1992; 3.2 per 10,000 during 1998-2000). The frequency of arrest during regional anesthesia (1.5 per 10,000) and monitored anesthesia care (0.7 per 10,000) remained consistent. Immediate survival after arrest was 46.6%, and hospital survival was 34.5%. Twenty-four patients (0.5 per 10,000) had cardiac arrest related primarily to anesthesia. From multivariate analysis, patients who experienced arrest due to bleeding were less likely to survive hospitalization (P = 0.001). Survival was also lower for patients who experienced arrest during nonstandard working hours (P = 0.006) and for patients who had protracted hypotension before arrest (P < 0.001). The overall frequency of arrest for patients receiving anesthesia decreased during the study period. Most arrests were not due to anesthesia-related causes, and most patients experiencing anesthesia-related arrest survived to hospital discharge. Although many factors determining survival may not be amenable to modification, the fact that arrests during nonregular working hours had worse outcomes may indicate that the availability of human resources influences survival.


An international comparison of the burden of illness in patients with dyspepsia.
This study investigates the symptoms and the impact of symptoms on health-related quality of life (HRQL) in patients consulting with dyspepsia. Consecutive patients with a diagnosis of dyspepsia were recruited from primary and secondary care in Germany, Hungary, Italy, Poland, South Africa and Spain. Investigators assessed symptom frequency and severity, and subjects completed the following questionnaires: the Gastrointestinal Symptom Rating Scale (GSRS), the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire, the Hospital Anxiety and Depression (HAD) scale and the Short Form 36 (SF-36). 853 dyspepsia patients were included. Mean GSRS scores showed that patients were most troubled by abdominal pain and indigestion. QOLRAD scores indicated that symptoms caused emotional distress, food/drink problems and reduced vitality, with a lesser effect on sleep and physical functioning. Mean SF-36 scores were lower than mean normative values for all domains, indicating that patients had a worse HRQL than the normal population, particularly for Bodily Pain, Role Physical and Role Emotional. Of patients in each country, 18-43% were anxious and 11-21% were depressed. Patients with dyspepsia have reduced HRQL because their symptoms - particularly abdominal pain and indigestion - cause emotional distress, problems with food and drink, and impaired vitality.


Venous thromboembolism and prophylaxis therapy after elective spine surgery: a population-based study.
Currently, there is no generalized consensus regarding perioperative prophylaxis of venous thromboembolism (VTE) in patients undergoing spine surgery. In the absence of large-scale studies, we aimed to use national data to study the association between anticoagulant prophylaxis and VTE in spine surgical patients. Our secondary outcomes were hematoma and blood transfusion. We included anterior cervical discectomy and fusion (ACDF) and posterior lumbar fusion (PLF) cases from 2006 to 2016 recorded in the Premier Healthcare database. Anticoagulant prophylaxis was categorized into aspirin, regular heparin, and low molecular weight heparin given on the day of surgery. Mixed-effects models measured the association between anticoagulation categories and outcomes. Cohorts were adjusted to reduce the risk of "confounding by indication" and to distinguish between prophylactic and therapeutic use of anticoagulants. We report odds ratios (OR) and Bonferroni-corrected confidence intervals (CI). Among 83,839 individuals undergoing ACDF and PLF, 0.45% (n = 374) had a hematoma, 8.1% (n = 6,769) received a blood transfusion, and 0.13% (n = 113) experienced VTE. After adjustment for relevant covariates, prophylactic aspirin (OR, 1.48; CI, 1.17 to 1.86) and regular heparin (OR, 2.01; CI, 1.81 to 2.24) were associated with increased odds of blood transfusion. No detectable differences in the odds of hematoma or VTE were observed for any anticoagulant. Although low molecular weight heparin was used much less frequently than regular heparin, it was associated with a lower incidence of transfusion compared with aspirin and regular heparin. All three anticoagulants were associated with similar incidence of VTE and hematoma. Varying subgroup-specific VTE risks may further inform future studies to identify patients expected to benefit the most from chemical thromboprophylaxis.


Rociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions.
Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the majority of the patients with such driver mutations, all targeted therapies are limited by the eventual development of resistance mechanisms. EGFR T790M mutation is a common resistance mechanism after treatment with first or second generation EGFR tyrosine kinase inhibitors (TKI). Rociletinib is one of the third generation EGFR TKIs with activity against T790M and activating EGFR mutations while sparing the wild-type EGFR. In this review, we discuss the current understanding and available data on rociletinib, including the side effects associated with the medication. We will also review the BEAMing plasma test to detect T790M mutation without the need for repeat biopsy. Lastly, we review the potential resistance mechanisms after progression on rociletinib, and future directions. It is important to note that there are other 3(rd) generation EGFR TKIs with activity against T790M already approved by the US FDA (osimertinib) and many others in development. Future research will focus on figuring out which patients can benefit the most from a particular medication with minimal side effects, and further resistance mechanisms after rociletinib.


Calcaneonavicular Coalition with Naviculocuneiform and Cuneiform-First Metatarsal Coalitions A Case Report.
Coalitions involving three joints of the midfoot are rare. To our knowledge, this is the first report of a patient having fibrocartilaginous coalition of the calcaneonavicular joint along with partial osseous fusion of the naviculocuneiform (Chopart's joint) and medial cuneiform-first metatarsal joints. These multi-coalition pathologies are challenging to address operatively as pain can persist even after recognizing and surgically addressing each coalition in a patient.


Standards medical students set for themselves when preparing for the final MBBS examination.
Determining whether the standard of an examination is appropriate is a difficult task. It is important for examiners and examinees to be aware of the standard of the examination. We compared the examination standards perceived by medical students with that of the examiners. A descriptive comparative study was carried out on a sample of final-year medical students from the Faculty of Medicine, University of Colombo. All final-year students of a given year of intake were requested to devise true/false type, negatively marked, 5-response multiple-choice questions at a standard they thought suitable for students sitting the final MBBS examination in Paediatrics. Ambiguous and wrongly worded questions were excluded. A "mock" multiple-choice question paper of randomly selected student generated multiple-choice questions was held a fortnight prior to the final paediatric examination. The students were unaware that the multiple-choice questions in the "mock" examination had been devised by their peers. Marks obtained at the "mock" and final examinations were compared and the difficulty index was calculated for both papers. Correlation between marks obtained at the 2 multiple-choice question papers was moderate (r = 0.67) and significant (P <0.01). The mean marks for the "mock" examination, 47.1% [standard deviation (SD) +/-9.2], and for the final examination, 58.9% (SD +/-8.7), showed a statistically significant difference (P <0.0001). This study showed that student-set multiple-choice questions correlated significantly with those of the university but were of a tougher standard.


Mesoporous silica nanoparticles: facile surface functionalization and versatile biomedical applications in oncology.
Mesoporous silica nanoparticles (MSNs) have received increasing interest due to their tunable particle size, large surface area, stable framework, and easy surface modification. They are increasingly being used in varying applications as delivery vehicles including bio-imaging, drug delivery, biosensors and tissue engineering etc. Precise structure control and the ability to modify surface properties of MSNs are important for their applications. This review summarises the different synthetic methods for the preparation of well-ordered MSNs with tunable pore volume as well as the approaches of drugs loading, especially highlighting the facile surface functionalization for various purposes and versatile biomedical applications in oncology. Finally, the challenges of clinical transformation of MSNs-based nanomedicines are further discussed.


Preparation of fucoidan-shelled and genipin-crosslinked chitosan beads for antibacterial application.
In this study, a fucoidan-shelled chitosan bead was developed with the purpose of oral delivery of berberine to inhibit the growth of bacteria. The cross-linking level and swelling property of the beads were affected by the pH value and the composition of the genipin/fucoidan combined gelling agent. The drug release of the berberine-loaded beads was faster in simulated gastric fluid (pH 1.2) than those in simulated intestinal fluid (pH 7.4). Furthermore, a nanoparticles/beads complex system was developed by incorporation of berberine-loaded chitosan/fucoidan nanoparticles in the fucoidan-shelled chitosan beads. The nanoparticles/beads complex served as a drug carrier to delay the berberine release in simulated gastric fluid, with an estimated lag time of 2 h. Our results showed that the berberine-loaded beads and nanoparticles/beads complex could effectively inhibit the growth inhibition of common clinical pathogens, such as Staphylococcus aureus and Escherichia coli, and have the advantage of continually releasing berberine to inhibit the growth of the bacteria over 24 h.


[Relapsing polychondritis. A case report].
A case of evident bilateral relapsing auricular polychondritis is presented. The literature published on this subject is reviewed and the possibility of oligosymptomatic clinical presentations is considered.


Successful melanoma triage by a virtual lesion clinic (teledermatoscopy).
A Virtual Lesion Clinic (VLC) using teledermatoscopy was established to improve efficiency of the melanoma referral pathway. To assess diagnostic accuracy and to compare wait-times and costs of VLC and conventional clinics. Patients with suspected melanoma referred from primary care into a publicly funded health system attended local skin imaging centres, rather than hospital outpatient clinics. A teledermatologist assessed each lesion choosing specialist assessment/excision, General Practitioner (GP) follow-up, to re-image in 3 months, or self-monitoring/no concern. 613 skin lesions in 310 patients were evaluated over 12 months. Median time between receipt of referral and attendance at the VLC was 9 days compared to 26.5 days for standard outpatient assessment. Sixty-six percent (404/613) of lesions were considered benign, and 12% (73/613) were suspicious for melanoma. Of 129 lesions excised, 98 were skin cancers including 48 histologically confirmed melanomas with one spitzoid tumour of unknown malignant potential (STUMP), i.e. one melanoma per 1.59 suspected lesions biopsied and one melanoma in every 12.8 referred to the service. There were 49 non-melanoma skin cancers (NMSC). Teledermatoscopic diagnosis of melanomas was found to have a positive predictive value (PPV) of 63%. Compared to the conventional clinic, cost reductions from running the VLC for 1 year were in excess of NZ$364,000 (or NZ$1174/patient seen). The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system.


In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.
Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other β-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. Merck & Co. Inc., Kenilworth, New Jersey, USA.


Imaging of acute disseminated encephalomyelitis.
Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease of the central nervous system typically affecting the gray and the white matter of the brain and spinal cord in multiple locations. In the acute stages, ADEM is characterized histologically by perivenous edema, demyelination, and infiltration with macrophages and lymphocytes, with relative axonal sparing, whereas the late course of the disease is characterized by perivascular gliosis.


Assessment of activated sludge viability with flow cytometry.
The aim of the study was to evaluate the applicability of fluorescent dyes and multiparameter flow cytometry for the rapid and direct viability/activity assessment of activated sludge samples taken from wastewater treatment plants. Viability and activity of the biomass were estimated respectively through cellular membrane integrity, staining with SYBR Green I and Propidium Iodide, and through fluorogenic dyes capable of detecting enzymatic activity, as FDA and BCECF-AM. A procedure has been developed to disaggregate sludge flocs before dyes staining and cytometric analysis. The developed procedure allows a high recovery of bacteria with good accuracy and repeatability, and minimize the damage of the cells suspension obtained from the disaggregation of the flocs. These measurements were applied to estimate the two main parameters required to define the biological activated sludge process: the endogenous decay rate and the specific growth rate in exponential phase with high F/M ratio. Oxygen utilization rate measurements (OUR) were conducted to conventionally monitor the activity of the biomass. The preliminary data are encouraging and support the possibility to investigate bacteria dynamics on wastewater treatment plants.


Placental deficiency of interleukin-10 (IL-10) in preeclampsia and its relationship to an IL10 promoter polymorphism.
The placenta is pivotal in the acceptance of the feto-placental unit by the maternal immune system. Imbalance at the maternal-fetal interface of tissue pro- and anti-inflammatory cytokines may be partly involved in disease causation. Previous work has shown conflicting levels of IL-10. IL-10 levels have been shown to increase, decrease, or remain unchanged in women with preeclampsia. This study examines the difference in serum and placental IL-10 expression in women with preeclampsia and investigates if the IL10 (-1082) A promoter polymorphism contributes to lower concentrations. In a prospective case-control study of 12 women with preeclampsia and 31 controls we assessed serum IL-10 by ELISA, placental mRNA by quantitative PCR and protein by immunohistochemistry as well as placental IL10 promoter genotype. Comparisons were made with non-parametric tests where necessary and chi-square. We found a significant reduction in placental IL-10 mRNA and protein expression in women with preeclampsia compared to controls. Women with the AA IL-10 promoter genotype expressed less placental IL-10 mRNA compared to women with AG or GG genotype. There was no difference in serum IL-10 concentrations between different genotypes. Preeclampsia is associated with a deficiency of placental IL-10. Placental AA genotype in the promoter region results in significantly less placental IL-10.


Long-term immunological changes in azathioprine-treated MS patients.
The long-term immunological effects of azathioprine treatment have been investigated in 8 multiple sclerosis patients with different course of disease, chronic progressive (CP) or relapsing progressive (RP). We studied fluctuations in peripheral blood mononuclear cell subsets, IgG, IgM and soluble vascular cell adhesion molecule-1 (sVCAM-1), before and after 2 (T24) and 3 (T36) years of therapy. We observed a significant decrease in CD8+ cells over time and a trend to lower percentage of CD3-CD56+ cells at T24 and T36. CD4+CD45RA+ cells in MS patients were lower than in healthy controls before therapy and reached values similar to those of healthy controls at T24 and T36. The remaining immunological parameters did not show any significant fluctuations.


Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology.
A transferable plasmid encoding SHV-12 extended-spectrum beta-lactamase, TEM-116, and aminoglycoside resistance was responsible for two sequential clonal outbreaks of Enterobacter cloacae and Acinetobacter baumannii bacteria. A similar plasmid was present among isolates of four different bacterial species. Recognition of plasmid transfer is crucial for control of outbreaks of multidrug-resistant nosocomial pathogens.


Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart.
Extensive in vitro studies and clinical evidence (MERLIN trial) indicate an antiarrhythmic potential of ranolazine, a novel antianginal agent. Programmed electrophysiologic testing was performed to quantify ranolazine's effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms. Effects of ranolazine (9.2 +/- 2.1 microM, plasma level) on surface ECG, right ventricular effective refractory period (ERP), and repetitive extrasystole (RE), ventricular fibrillation (VF), and defibrillation (DFT) thresholds were determined in 29 normal closed-chest anesthetized pigs. The single extrastimulus method was employed for ERP and for RE and VF thresholds. DFT(50) was determined using an up-down testing protocol with an implantable cardioverter-defibrillator. Ranolazine increased rate-corrected QT interval from 490 +/- 30 to 527 +/- 24 ms (P < 0.05) but did not alter T(peak)-T(end) interval (59 +/- 8 to 62 +/- 11, P = 0.65). ERP increased by 40 +/- 6 ms (P < 0.001). Compared with baseline, ranolazine raised RE threshold from 20 +/- 6 to 34 +/- 9 mA (P < 0.001) and VF threshold from 38 +/- 4 to 48 +/- 10 mA (P < 0.05). DFT(50) was unchanged (baseline: 14 +/- 2 J; ranolazine: 14 +/- 2 J; P = 0.6), whereas diastolic pacing threshold increased from baseline pulse width of 0.07 +/- 0.03 to 0.17 +/- 0.07 ms (P < 0.01) with 1V pulse amplitude. Ranolazine, at therapeutic concentrations, produces a mild increase in QT interval and a marked increase in both RE and VF thresholds. Thus, ranolazine does not augment and may improve dispersion of ventricular repolarization, suggesting a potential antiarrhythmic action. Ranolazine is unlikely to affect the margin of safety of defibrillation, given no significant effect on DFT, but could result in a mild increase in pacing threshold.


Freestanding three-dimensional core-shell nanoarrays for lithium-ion battery anodes.
Structural degradation and low conductivity of transition-metal oxides lead to severe capacity fading in lithium-ion batteries. Recent efforts to solve this issue have mainly focused on using nanocomposites or hybrids by integrating nanosized metal oxides with conducting additives. Here we design specific hierarchical structures and demonstrate their use in flexible, large-area anode assemblies. Fabrication of these anodes is achieved via oxidative growth of copper oxide nanowires onto copper substrates followed by radio-frequency sputtering of carbon-nitride films, forming freestanding three-dimensional arrays with core-shell nano-architecture. Cable-like copper oxide/carbon-nitride core-shell nanostructures accommodate the volume change during lithiation-delithiation processes, the three-dimensional arrays provide abundant electroactive zones and electron/ion transport paths, and the monolithic sandwich-type configuration without additional binders or conductive agents improves energy/power densities of the whole electrode.


Microtubule alterations and mutations induced by desoxyepothilone B: implications for drug-target interactions.
Epothilones, like paclitaxel, bind to beta-tubulin and stabilize microtubules. We selected a series of four leukemia sublines that display increasing levels of resistance to the epothilone analog desoxyepothilone B (dEpoB). The dEpoB cells selected in 30-140 nM were approximately 15-fold cross-resistant to paclitaxel, while 300 nM selected cells were 467-fold resistant to this agent. The dEpoB-selected cells are hypersensitive to microtubule destabilizing agents, and express increased levels of class III beta-tubulin and MAP4. A novel class I beta-tubulin mutation, A231T, that affects microtubule stability but does not alter paclitaxel binding, was identified. The 300 nM selected cells acquired a second mutation, Q292E, situated near the M loop of class I beta-tubulin. These cells fail to undergo drug-induced tubulin polymerization due to dramatically reduced drug binding. The dEpoB-resistant leukemia cells provide novel insights into microtubule dynamics and, in particular, drug-target interactions.


Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.
Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported. An 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely. This report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose.


Assisted Physical Exercise and Stress in Preterm Neonates.
To evaluate the markers of stress before and after a session of assisted physical exercise in infants born before 35 weeks' gestation. 25 infants born at 280/7 to 346/7 weeks were subjected to assisted physical exercise daily for about 10-15 min at one week of postnatal age or 33 weeks of post menstrual age, whichever was later. Primary outcome was salivary cortisol and secondary outcome was Premature infant pain profile (PIPP) score. Outcomes were measured, on day 5 (±1) of exercise. There was no difference in salivary cortisol between baseline and immediately after (P=0.16), at 90 min (P=0.6) or 120 min (P=0.7) after exercise. Salivary cortisol was lower at 30 min after exercise as compared to baseline (mean difference -0.08 µg/dL; 95% CI -0.16 to -0.002; P=0.04). The median (IQR) PIPP score was significantly higher at 5 min into exercise (4 (3-6) vs 4 (3-5); P=0.04) and at completion of exercise 6 (4-8) vs 4 (3-5); P<0.01), as compared to baseline. Assisted physical exercise does not seem to result in stress in premature infants.


Perceptions of preparedness: How hospital-based orientation can enhance the transition from academic to clinical learning.
Clinical placements are essential for applied learning experiences in health professions education. Unfortunately, there is little consensus on how best to prepare learners for the transition between academic and clinical learning. We explored learners' perceptions of hospital-based orientation and resulting preparedness for clinical placement. Sixty-three learners participated in a total of 18 semi-structured focus groups, during their clinical placements. Data were analyzed thematically. We organized learners' perceptions of hospital-based orientation that support their preparedness for placement into three themes: (1) adequate site orientation for learner acquisition of organization acumen and (2) clinical preceptor training to support unit/service and (3) individual components. Thoughtful attention to hospital-based orientation can support learners in transitioning from academic to clinical learning. Hospital organizations should attend to all three components during orientation to better support learners' preparedness for clinical learning.


Tracking spindle checkpoint signals from kinetochores to APC/C.
Accurate chromosome segregation during mitosis is critical for maintaining genomic stability. The kinetochore--a large protein assembly on centromeric chromatin--functions as the docking site for spindle microtubules and a signaling hub for the spindle checkpoint. At metaphase, spindle microtubules from opposing spindle poles capture each pair of sister kinetochores, exert pulling forces, and create tension across sister kinetochores. The spindle checkpoint detects improper kinetochore-microtubule attachments and translates these defects into biochemical activities that inhibit the anaphase-promoting complex or cyclosome (APC/C) throughout the cell to delay anaphase onset. A deficient spindle checkpoint leads to premature sister-chromatid separation and aneuploidy. Here, we review recent progress on the generation, propagation, transmission, and silencing of the spindle checkpoint signals from kinetochores to APC/C.


Serial measurement of Epstein-Barr viral load in peripheral blood in pediatric liver transplant recipients during treatment for posttransplant lymphoproliferative disease.
Few data are available describing the natural history of the Epstein-Barr virus (EBV) viral load after the diagnosis of EBV-associated posttransplant lymphoproliferative disease (PTLD). Accordingly, we prospectively followed the EBV viral load after the diagnosis of EBV/PTLD in seven pediatric orthotopic liver transplant recipients. EBV viral loads were serially measured by quantitative competitive polymerase chain reaction of the peripheral blood from pediatric patients with PTLD and correlated with the clinical course of these children. Viral loads >200 genome copies/10(5) peripheral blood lymphocytes were considered consistent with an increased risk of PTLD. Viral loads <200 obtained during treatment for PTLD were considered evidence of "clearance" of EBV; subsequent loads >200 were considered evidence of virologic "rebound." The mean EBV viral load at the time of diagnosis of PTLD was 1029. All patients "cleared" their EBV viral load during the treatment of PTLD; patient and graft survival in this series was 100%. The mean time to clearance of EBV from the peripheral blood (18.8 days) was similar to the mean time to onset of first rejection (13.8 days). EBV viral load at the time of diagnosis of rejection after PTLD was always <100. A rebound in the EBV viral load to >200 was noted in five of seven patients a median of 3.5 months (range 2.3-13 months) after the diagnosis of EBV/PTLD. However, none of these children has had any evidence of PTLD recurrence. Clearance of the EBV viral load from the peripheral blood seems to correlate with restoration of the host's immune response as noted both by the regression of the PTLD and the onset of rejection. Late rebound of the EBV viral load is common and does not seem to predict disease recurrence.


Muscle and skin sympathetic activities in Ross syndrome.
Ross syndrome (RS) is a rare degenerative disorder characterized by tonic pupil, areflexia and anhydrosis. The underlying lesion affects postganglionic skin sympathetic nerve fibers whereas the postganglionic muscle sympathetic branch is thought to be spared. Microneurography explores both skin and muscle peripheral sympathetic branches and it does not usually detect peripheral sympathetic outflow in either branch in chronic autonomic failure syndromes. The aim of this study was to record sympathetic activity by microneurography for the first time in RS patients to confirm the selective involvement of skin sympathetic nerve activity (SSNA) with spared muscle sympathetic nerve activity (MSNA). We studied seven patients (49 ± 14 years, four males) with a typical clinical picture and skin biopsy findings. Patients underwent cardiovascular reflexes and microneurography from the peroneal nerve (anhydrotic skin) to record MSNA, SSNA and the corresponding organ effector responses (skin sympathetic response-SSR and skin vasomotor response-SVR) in the same innervation field. The absence of sympathetic bursts was established after exploring at least three different corresponding nerve fascicles. Twenty age-matched healthy subjects served as controls. RS patients complained of diffuse anhydrosis and they showed tonic pupil and areflexia. Cardiovascular reflexes were normal. All patients displayed absent SSNA, SSR and SVR whereas MSNA was always recorded showing normal characteristics. Microneurographic study of sympathetic activity from affected skin confirmed the selective involvement of skin sympathetic activity with spared muscle sympathetic activity and it may represent the neurophysiological hallmark of the disease. Microneurography together with clinical and skin biopsy findings may contribute to RS diagnosis. Our data also suggest that autonomic damage in RS does not involve cardiovascular activity.


[Antimutagenic properties of bacteria: a review].
Lactic acid and propionic acid bacteria, bifidobacteria, and fecal enterococci associated with the activity of humans and animals caused antimutagenic effects (AME) on many test systems designed for detecting point mutations and chromosomal aberrations. Bacterial cells and some of their metabolites attenuate the mutagenic action of several genotoxic agents, and this effect is mediated by the mechanism of dysmutagenesis and/or bioantimutagenesis. Possible mechanisms of various AMEs and possible practical applications of antimutagenic properties of bacteria are discussed.


An evaluation of the use made of cosmetic and functional prostheses by unilateral upper limb amputees.
There is currently a distinction drawn between a prosthesis considered to be provided for purely cosmetic reasons and a functional prosthesis provided to enable the amputee to achieve basic hand function. Using video analysis the study reported in this paper demonstrates that for non-manipulative actions cosmetic prostheses are actively used in the performance of everyday tasks as frequently as functional prostheses. The study provides evidence for a cosmetic prosthesis to be presented to an amputee as a realistic initial prosthesis and not as the option of last resort if a functional prosthesis is rejected. It is also recommended that training is provided in the use of cosmetic prostheses in two-handed tasks.


Pulmonary hydroxyproline content and production following treatment of mice with O,S,S-trimethyl phosphorodithioate.
The systemic administration of O,S,S-trimethyl phosphorodithioate (OSS), a contaminant of various organophosphorus insecticides, induces delayed damage to rat and mouse lung tissue. The lesion, particularly in the rat, closely resembles that produced by butylated hydroxytoluene (BHT) in mice. Although the time course of cell damage and repair has been studied in both species, it is not clear whether excess collagen, indicative of fibrosis, is deposited. Changes in pulmonary hydroxyproline content and synthesis, indices of collagen metabolism, were analysed in mice treated with 45 mg/kg OSS. A significant increase in total lung hydroxyproline was evident 21 days after treatment compared to both pair-fed and ad libitum controls. This increase was not augmented by subsequent treatment with 35 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or exposure to 70% oxygen for 7 days. The rate at which lung tissue synthesized hydroxyproline was increased 7-14 days after treatment with OSS. These data demonstrate that treatment of mice with OSS results in changes indicative of pulmonary fibrosis. However, in contrast to some other lung-toxic chemicals, this lesion was not enhanced by subsequent treatment with BCNU or hyperoxia.


Elimination of glucose contamination from adipocyte glycogen extracts.
Glycogen was quantified in rat adipocytes by isolation using conventional KOH digestion and ethanol precipitation, followed by hydrolysis and spectrophotometric assay of the glucose product. A concentration of 0.193+/-0.020 micromol glucosyl units/10(6)cells was recorded. When this procedure was modified by including a 4h incubation with glucose oxidase prior to glycogen hydrolysis, the glycogen concentration was found to be 0.055+/-0.008 micromol glucosyl units/10(6) cells. Therefore in adipocytes, conventional glycogen assays give substantial overestimates due to incomplete removal of glucose during glycogen isolation. Contaminant glucose can be scavenged in a simple manner by incubation with glucose oxidase prior to glycogen hydrolysis.


Is there an effect of immunoglobulins and G-CSF on neutrophil phagocytic activity in preterm infants?
The percentage of neutrophils phagocytosing group B streptococci (GBS) in vitro was determined in ten healthy preterm infants (< 32 weeks of gestation) and adult controls by using an acridine orange fluorescence whole blood assay. When GBS were opsonized with adult serum, no difference in phagocytic activity was found between both groups after 10 and 30 min (preterms: 40% and 68%, adults: 32% and 56%, respectively). Phagocytosis rates in preterm infants decreased significantly to 6% and 18% (at 10 and 30 min) when pool serum of preterm infants was used instead. Supplementation of the preterm serum with either intravenous immunoglobulin or IgM-enriched immunoglobulin did not change the results significantly. The addition of granulocyte colony-stimulating factor (G-CSF) accelerated phagocytosis significantly after 10 min, but did not increase the overall phagocytic activity after 30 min in either group. Hence the potential benefits of intravenous immunoglobulins and G-CSF in neonatal sepsis may not be attributable to an immediate increase in and direct effect on neutrophil phagocytic activity.


Some aspects of Leucocytozoon caulleryi reinfection in chickens.
The role of first- and second-generation schizonts in acquired immunity to Leucocytozoon caulleryi in chickens was studied. The chickens, which had recovered from a primary infection with various doses of sporozoites at 22-95 days of age, were challenged with sporozoites. First-generation merozoites were found in all of the challenged chickens, but no second-generation merozoites and gametocytes were seen in 30 of 32 chickens challenged with sporozoites. Almost all of the chickens that had recovered from a primary infection with sporozoites showed complete resistance to reinfection, and those that had recovered from a primary infection with first-generation merozoites showed resistance to reinfection with sporozoites. These results indicate that the second-generation schizont of L. caulleryi appears to be more immunogenic than the first-generation schizont and that some immune factors acquired by the chickens in the second generation of schizogony may inhibit the development of second-generation schizonts.


Host size and sex allocation of parasitoids in a gall forming community.
The sex ratios of three Mesopolobus species were found to vary in different hosts in a gall-forming community in Berkshire. These relationships were consistent with Charnov's host size-sex ratio hypothesis (Charnov 1979). Due to the segregation of host species on different species of Quercus, it was possible to conduct a geographical variation experiment proposed by Charnov et al. (1981). The results of this experiment suggest that the parasitoids have a fixed 'rule of thumb' and are not flexible in their sex allocation in response to changes in host size distribution. The data, therefore, do not support the prediction of Charnov's hypothesis. Problems associated with this kind of field experiment are discussed.


Reversible inhibition of the induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells.
The induction of DNA polymerase of herpes simplex virus type 2 in HeLa cells was inhibited by 2-mercapto-1-(beta-4-pyridethyl)benzimidazole added at an early time after infection. However, the inhibitory effect was easily released by removal of the inhibitor. Since the drug disorganizes nucleolar structure and prevents its function in HeLa cells in a reversible manner, it is possible that nucleoli are involved in the induction of DNA polymerase of this virus.


Chitosan oligosaccharide (GO2KA1) improves postprandial glycemic response in subjects with impaired glucose tolerance and impaired fasting glucose and in healthy subjects: a crossover, randomized controlled trial.
The antidiabetic and hypoglycemic effects of chitosan have been reported in previous studies. We have previously shown that chitosan oligosaccharide reduces postprandial blood glucose levels in vivo. We conducted a short-term crossover study to support the results of the previous study. The study was a randomized, double-blind, controlled crossover trial completed at one clinical research site. Subjects with impaired glucose tolerance and impaired fasting glucose and healthy subjects were randomly assigned to consume one of two different experimental test capsules that differed in only the sample source (GO2KA1 vs placebo), and all subjects were instructed to consume the 75 g sucrose within 15 min. After a 7-day interval, the subjects consumed the other capsules that were not consumed on the first day. We assessed blood glucose levels using a 2-h oral sucrose tolerance test. The study was registered at clinicaltrials.gov (NCT03650023). The test group showed significantly lower blood glucose levels at 60 min (p = 0.010) and postprandial blood glucose areas under the curve (p = 0.012). The change in blood glucose levels at 60 min was significantly lower in the test group than in the placebo group (p = 0.017). Based on the results of this study, the consumption of chitosan oligosaccharide (GO2KA1) supplements with a meal can effectively reduce postprandial blood glucose levels, which is relevant to the prevention of diabetes.


Mechanistic toxicity assessment of differently sized and charged polystyrene nanoparticles based on human placental cells.
Nanoplastics, as emerging contaminants, may be degraded from microplastics and released into aquatic systems globally, which pose threats to human health via ingestion with food or water. Although plastic fragments have been isolated from placental tissues in pregnant women, little is known about the direct toxicity of nanoplastics on human placental cells that plays a critical role in maintaining healthy growth of fetus. This study explored the mechanistic toxicity of polystyrene nanoplastics (PS-NPs) with different sizes (25, 50, 100 and 500 nm) and surface charges (-NH2, -COOH and unlabeled) on human placental cells. Results showed that PS-NPs had size- and surface charge-specific toxicity pattern. The smaller the PS-NP size was, the greater the toxicity induced on human placental cells. In terms of surface charges, NH2-labeled PS-NPs caused greater effects on cytotoxicity, inhibition of protein kinase A (PKA) activity, oxidative stress, and cell cycle arrest compared to COOH-labeled and unmodified PS-NPs. PS-NPs also induced size- and surface charge-dependent expression profiles of genes involved in various and interrelated toxicity pathways. In particular, PS-NPs increased intracellular reactive oxygen species in human placental cells, which can induce DNA damage and lead to cell cycle arrest in G1or G2 phase, inflammation and apoptosis. Our findings provide empirical evidences that the negative effects of nanoplastics on human placental cells, and highlight the necessity to conduct risk assessment of nanoplastics on female reproduction and fetal development.


Clinical validation of an edge detection algorithm for two-dimensional echocardiographic short-axis images.
The purpose of this study was to validate an edge detection algorithm for short-axis two-dimensional echocardiographic studies in a protocol that stimulated its implementation at multiple clinical laboratories. Six short-axis two-dimensional echocardiographic studies were solicited from each of five clinical laboratories. A single cardiac cycle from each of the resulting 30 studies was entered into the computer system. Five expert observers came to the laboratory on separate occasions and traced endocardial borders from the short-axis studies on 2 separate days. The computer algorithm generated borders on each frame of the cardiac cycles on the basis of regions of search defined by the observers. Of the 30 original studies, five were considered excellent, seven were good, nine were poor, and nine were technically inadequate by consensus of the five observers. The correlation coefficient for computer-defined borders with manually defined borders in the excellent quality studies was 0.985. Interobserver variability was expressed as the mean percent area difference for all possible pairings of observers. The mean percent area differences were decreased from +/- 9.8% to +/- 5.3%, +/- 12.5% to +/- 8.4%, and +/- 17.4% to +/- 15.6% when comparing observer with computer-generated borders in the excellent, good, and poor quality studies, respectively. Intraobserver variability was expressed as decrease in mean percent area difference on corresponding frames between days 1 and 2. Intraobserver variability was decreased from +/- 6.5% to +/- 4.5%, +/- 10.8% to +/- 7.0%, and +/- 14.0% to +/- 11.9%, respectively. All reductions in variability were statistically significant at p less than 0.01. Observer acceptance of computer-defined borders was estimated at 94%, 93%, and 97% for excellent, good, and poor quality studies, respectively. Once the observer defined a region of search, computer process time to generate all borders in the cardiac cycle was approximately 4 minutes. The conclusion is that the algorithm produces accurate, reliable, and acceptable borders.


Towards economic geographies beyond the Nature-Society divide.
This article suggests an approach to economic-geographic quantification that is relevant to engaging the socionatural blurring of an Anthropocene. It develops representations of commodities and of economies that draw upon concepts of absolute, relative, and relational space to help move beyond legacies of the Nature-Society divide in economic-geographic thought. To supplement familiar ways of knowing commodities as bounded objects with associated single values (prices), the piece rereads input-output approaches, providing accounts of how commodities enfold relations among socionatural phenomena. It quantifies and maps the activities and flows of the global economy in 2007 in terms of their embodied carbon emissions, labor times, and harvested land areas alongside their monetary values. Comparing the perspectives that result, it identifies empirical and theoretical challenges that a political-industrial ecology could help address.


Trapezial metastasis as the first indication of primary non-small cell carcinoma of the lung.
Metastasis to the bones of the hand and wrist is not common, and its discovery may reveal an advanced primary tumor located centrally. Clinically, hand metastasis is hard to differentiate from other more common hand pathologies. Its rarity, coupled with a lack of unique clinical manifestations, makes hand and wrist metastasis difficult to diagnose. However, its diagnosis is critical to initiate an appropriate course of treatment. We present a patient in whom lung carcinoma metastasis to the trapezium was definitively diagnosed upon surgical management of symptoms that were consistent with thumb carpometacarpal arthritis.


[Complexity index and analysis of digestive endoscopies at a university hospital].
In Spain neither the cost of digestive endoscopies nor the complexity index (CI) have been objectively estimated. Consequently, the profitability of an endoscopy unit cannot be evaluated. 1: To classify endoscopies according to the time taken to accomplish them in order to estimate the CI and determine the relative value unit (RVU). 2: To evaluate the cost of each examination in order to determine the profitability of endoscopy as a diagnostic and therapeutic tool. 3: To measure unnecessary delays in examinations and to determine whether there are differences in the time an examination takes according to the endoscopist's experience and the patient's age or sex. The cost per hour of an endoscopy room was estimated by dividing the cost per year of employees, equipment, maintenance and the hospital's general costs between the hours of work per year of the endoscopy team. The time taken to perform endoscopies was estimated and the result was used to calculate the RVI, the CI and the cost of 500 consecutive endoscopies. The annual cost amounted to 349,617.69 E. Staffing costs represented 65.5%, of which 56.3% were direct costs. Gastroscopy was taken as the RVU (cost = 27.52 E). Anoscopy was the simplest procedure (RVU = 0.61, cost = 15.08 E) and colonoscopy plus polypectomy was the most complex procedure (RVU = 4.41, cost = 74.28 E). The greater the experience of the member of staff performing the procedure, the less time it took (p < 0.01). CI was lowest for anoscopy (URV = 0.61) and highest for total colonoscopy plus polypectomy (URV = 4.41). Cost and exploration time depended on the endoscopist's experience. Staff represented the highest percentage of cost.


Replacement therapy against increased hydroxyurea toxicity in pituitary or adrenal ablated rats.
The main rat adrenocortical hormone, corticosterone, the mineralocorticoid, 11-deoxycorticosterone (DCA) acetate given alone or together (2:1 ratio) twice daily at doses of 2-4 and 1-8 mg/kg, DCA enanthate given in a single injection of 20 mg/kg 0-3 days before the beginning of the experiments and a highly-concentrated injectable extract of the adrenal cortex (4 mg/kg as hydrocortisone twice a day) given by the intramuscular route, delay and partially protect against the increased toxicity following administration of the anticancer drug, hydroxyurea (800 mg/kg/day for 5 days) in adrenalectomized or hypophysectomized animals (80-100% lethality; in control non ablated rats 0-10% lethality). ACTH1-24 (tetracosactide) also proved effective in pituitary ablated rats. The best protection was afforded with the joint administration of corticosterone and DCA (2-4 and 1-2 mg/kg twice a day) or with corticosterone alone at doses (4 mg/kg twice a day) capable of giving plasma levels, six hours after administration on the third day, similar to those observed in non ablated rats receiving HYD in the morning. The adrenocortical hormones may replace a possible unique defense mechanism against drug toxicity, which is lacking in pituitary or adrenal ablated rats.


Augmentative and alternative communication (AAC) in pediatric cochlear implant recipients with complex needs: A scoping review.
Augmentative and alternative communication (AAC) encompasses all forms of unaided and aided modes of communication, but typically excludes codified language such as spoken words or American Sign Language (ASL). In pediatric patients with a documented additional disability (population of interest), deficits in communication may pose a barrier to language development. While forms of AAC are frequently mentioned in the literature, recent innovations have permitted the use of high-tech AAC in the rehabilitation process. Our objective was to review the implementation of AAC in pediatric cochlear implant recipients with a documented additional disability. A scoping review of existing literature examining the use of AAC in pediatric CI recipients was conducted in the PubMed/MEDLINE and Embase databases. Studies with pediatric cochlear implant recipients with a concomitant diagnosis requiring additional therapeutic intervention outside the scope of standard post-CI follow-up care and rehabilitation from 1985 to 2021 met inclusion criteria (population of interest). Studies limited to spoken or formal sign language (e.g., American Sign Language, ASL) as communication modalities were excluded. Four hundred twenty studies were screened of which 29 were included. 13 were prospective, 10 were retrospective, 1 was cross-sectional, and 5 were case reports. Of these 29 studies, 378 patients met the inclusion criteria (age <18, CI user, additional disability, utilized AAC). Fewer studies (n = 7) utilized AAC as the primary intervention for investigation. Autism spectrum disorder, learning disorder, and cognitive delay were frequently mentioned as additional disabilities in conjunction with AAC. Unaided forms of AAC included gesture/behavior, informal sign, and signed exact English, while aided AAC included a Picture Exchange Communication System (PECS), Voice Output Communication Aids (VOCA), and touchscreen programs such as TouchChat® HD. Various audiometric and language development outcome measures were mentioned, most commonly the Peabody Picture Vocabulary Test (PPVT) (n = 4) and the Preschool Language Scale, Fourth Edition (PLS-4) (n = 4). There is a gap in the literature regarding the use of aided and high-tech AAC in pediatric CI users with a documented additional disability. Given the use of multiple different outcome measures, additional exploration of the intervention of AAC is warranted.


Aberrant alterations of the expressions and S-nitrosylation of calmodulin and the downstream factors in the brains of the rodents during scrapie infection.
The aberrant alterations of calmodulin (CaM) and its downstream substrates have been reported in some neurodegenerative diseases, but rarely described in prion disease. In this study, the potential changes of Ca2+/CaM and its associated agents in the brains of scrapie agent 263K-infected hamsters and the prion infected cell line SMB-S15 were evaluated by various methodologies. We found that the level of CaM in the brains of 263K-infected hamsters started to increase at early stage and maintained at high level till terminal stage. The increased CaM mainly accumulated in the regions of cortex, thalamus and cerebellum of 263K-infected hamsters and well localization of CaM with NeuN positive cells. However, the related kinases such as total and phosphorylated forms of CaMKII and CaMKIV, as well as the downstream proteins such as CREB and BDNF in the brain of 263K-infected hamsters were decreased. Further analysis showed a remarkable increase of S-nitrosylated (SNO) form of CaM in the brains of 263K-infected hamsters. Dynamic analysis of S-nitrosylated CaM showed the SNO form of CaM abnormally increases in a time-dependent manner during prion infection. Compared with that of the normal partner cell line SMB-PS, the CaM level in SMB-S15 cells was increased, meanwhile, the downstream proteins, such as CaMKII, p-CaMKII, CREB, as well as BDNF, were also increased, especially in the nucleic fraction. No SNO-CaM was detected in the cell lines SMB-S15 and SMB-PS. Our data indicate an aberrant increase of CaM during prion infection in vivo and in vitro.


Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons.
The identification of surface proteins restricted to subsets of embryonic axons and growth cones may provide information on the mechanisms underlying axon fasciculation and pathway selection in the vertebrate nervous system. We describe here the characterization of a 135 kd cell surface glycoprotein, TAG-1, that is expressed transiently on subsets of embryonic spinal cord axons and growth cones. TAG-1 is immunochemically distinct from the cell adhesion molecules N-CAM and L1 (NILE) and is expressed on commissural and motor neurons over the period of initial axon extension. Moreover, TAG-1 and L1 appear to be segregated on different segments of the same embryonic spinal axons. These observations provide evidence that axonal guidance and pathway selection in vertebrates may be regulated in part by the transient and selective expression of distinct surface glycoproteins on subsets of developing neurons.


Intraparenchymal papillary meningioma of brainstem: case report and literature review.
Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.


A novel selective ternary platform fabricated with MgAl-layered double hydroxide/NiMn2O4 functionalized polyaniline nanocomposite deposited on a glassy carbon electrode for electrochemical sensing of levodopa.
In this study, a novel selective electrochemical sensor was fabricated for determination of levodopa (LD) using a glassy carbon electrode modified with MgAl-layered double hydroxide/NiMn2O4 functionalized polyaniline nanocomposite (LDH/NMO/PANI) and its successful formation was confirmed by various techniques. Owing to the high surface area and outstanding conductivity features provided by the combination of MgAl-LDH, NiMn2O4 and PANI nanoparticles, this ternary nanocomposite exhibited excellent electrochemical activity towards the detection of LD compared with the electrode modified by the pristine MgAl-LDH and MgAl-LDH/NiMn2O4 binary nanocomposite. In addition, enormous quantities of amine and imine functional groups on the surface of PANI lead to a strong affinity for attachment to organic molecules such as LD. The ternary nanocomposite modified electrode exhibited excellent analytical parameters such as wide linear response from 0.1 to 100 μM with very low detection limit of 0.005 μM, good reproducibility and long-term stability which are superior among the LD electrochemical sensors. Besides, the constructive sensor possessed acceptable selectivity for recognition of LD in the presence of a variety of potentially interfering species and can also effectively avoid the interference of dopamine (DA) and ascorbic acid (AA). Consequently, the LDH/NMO/PANI/GC electrode was effectively applied to detect LD in human plasma and urine samples with good recoveries, ranging from 98.0-100.1% and it shows potential usage in clinical researches.


[Rectal hemorrhage as the first manifestation of prostatic carcinoma].
An uncommon case of prostatic carcinoma presenting as rectal hemorrhage is described. The diagnostic and therapeutic aspects are discussed and the importance of distinguishing this condition from rectal carcinoma is underscored. The clinical features of a patient with invasive prostatic carcinoma presenting as rectal hemorrhage are described. Rectal involvement by invasive prostatic carcinoma should be suspected in patients consulting for a rectal pathology, particularly if the patient has a previous history of prostatism or carcinoma of the prostate. The incidence of rectal involvement by prostatic carcinoma has been reported to range from 1 to 11%.


Suprachoroidal hemorrhage during cataract surgery in a vitrectomized eye.
We report a case of surprachoroidal hemorrhage (SCH) that occurred during cataract surgery in a previously vitrectomized eye. The only sign of SCH was a progressive shadow obscuring the red reflex. There was no increase in intraocular pressure (IOP), shallowing of the anterior chamber, or iris prolapse. Postoperatively, the SCH gradually resolved without complications, leaving a series of subretinal pigmentary lines. Surgeons should be aware that the signs normally expected in SCH may not develop in vitrectomized eyes. Obscuration of the red reflex may be the only sign of the hemorrhage, and when this happens, it may be prudent to keep the IOP elevated and suture the incision at the end of the procedure.


Repair and biochemical protection in life shortening of mice exposed to fractionated X-irradiation.
Male mice of the BALB/c+ strain were exposed to X-rays at fractionation intervals of 7, 15, 30, and 60 days. One group received a mixture of radioprotectors, another AET (only 30 days fractionation), a third one served as control. The doses ranged, dependent on the treatment, from 300--1500 R. When survival was corrected for acute death, the control and AET treated animals died after an accumulated dose of about 2000 R whereas those treated with a mixture of radioprotectors died after about 4000 tr. Bone marrow failure and lung damage is the main cause of death within the initial 200 days after start of the exposure. At later times, fibrotic changes and in particular glomerulosclerosis are observed.


Hepatocyte growth factor: Effects on immune-mediated heart diseases.
There is growing evidence of the potential role of hepatocyte growth factor (HGF) in various cardiovascular diseases. In addition to the beneficial effects of HGF in myocardial infarction, heart failure, and occlusive peripheral arterial disease, administration of HGF effectively suppresses acute and chronic cardiac allograft rejection and autoimmune myocarditis. The present review summarizes recent advances in the utility of HGF for heart diseases, especially immune-mediated heart diseases. Possible mechanisms of action in the suppression of T-cell-mediated immunity are also discussed.


Practolol peritonitis. A study of 16 cases and a survey of small bowel function in patients taking beta adrenergic blockers.
Sixteen patients with practolol peritonitis are described. Dense peritoneal thickening and adhesions caused small bowel stasis and obstruction with characteristic radiology and histology. The disease was best treated by surgery though complications were frequent and three of 16 patients died. Ocular and skin involvement were common. Fifty four asymptomatic patients who had taken a beta adrenoceptor blocking drug for more than 12 months were studied. Seven were found to have radiological abnormalities of the small bowel. These changes were associated with propranolol, oxprenolol and practolol therapy. It is not known whether they are related to practolol peritonitis.


Daily fluctuations in water potential and associated ionic changes in Atriplex canescens.
Water potential (Ψ) measurements of Atriplex canescens at the base of the Red Desert near Tipton in Wyoming, revealed a range between-15.5 to-45.1 bars. Minimum values coincided with the lowest air and soil temperatures, maximum with the greatest atmospheric evaporative demand. Change in Ψ exceeded 12 bars h-1 during periods of rapidly moving storm systems. Changes in Ψ appeared to be independent of plant size, age, sex, and the spatial location of plants. Chemical analyses revealed that xylem sap was up to three times more concentrated at high than at low Ψ. It was observed that the flow rate of sap was greater at lower than at higher Ψ and that the increase in water movement accounted for the dilution of the baseline concentration of sap solutes. Together, Ca, Mg, K and Na contributed 58% of the mean osmolality of the xylem sap; the dominant ions, however, were K and Cl. We suggest that the ability of the species to respond rapidly to changing atmospheric conditions affords it a distinct advantage in a harsh environment.


Absorption spectra of bone.
Absorption spectra of human bone and its two major constituents (collagen and apatite) were obtained in the wavelength region extending from 2000 to 12,000 A. In the last two cases a minimum transmission (maximum absorption) was uniformly observed in the ultraviolet region. The two samples after exposure to ultraviolet radiations show a shift in the peak positions. Absorption peaks in the total bone spectra are not reproducible in its two constituents. After exposure to UV radiations the position of maximum absorption is displaced. A possible interpretation of the observed results is presented.


Diffusion of an innovation: adoption of MRI.
"Diffusion of Innovation" is a marketing theory that predicts the pattern of adoption of new products, with specific characteristics of the product determining the rate of adoption. This article attempts to determine whether MRI fits the predicted pattern. A computer Medline search to assess the number of articles printed on MRI shows that MRI is being adopted more slowly than CT, but like CT, MRI is following the pattern predicted by the Diffusion Theory.


Association of PON2 Gene Polymorphisms (Ser311Cys and Ala148Gly) With the Risk of Developing Type 2 Diabetes Mellitus in the Chinese Population.
Background: The association between paraoxonase 2 (PON2) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been extensively investigated in the Chinese population with conflicting results. In this study, we systematically evaluated the association between PON2 Ser311Cys and Ala148Gly polymorphisms and T2DM risk by pooling all relevant studies. Methods: We searched PubMed, Embase, CNKI, and Wanfang databases for the studies. The strength of association was determined by the allelic, homozygous, heterozygous, recessive, and dominant genetic models and measured as odds ratio (OR) and 95% confidence interval (CI), under fixed- or random-effect models. Results: There was no significant association between PON2 Ser311Cys polymorphism and T2DM under any of the genetic models: allelic (OR = 1.06, 95% CI = 0.77-1.45; P = 0.721), heterozygous (OR = 1.13, 95% CI = 0.87-1.45; P = 0.362), dominant (OR = 1.10, 95% CI = 0.80-1.51; P = 0.562), recessive (OR = 0.87, 95% CI = 0.48-1.58; P = 0.648), homozygous (OR = 0.94, 95% CI = 0.47-1.89; P = 0.865). Similarly, no significant association was found in PON2 Arg148Gly polymorphism under any of the models: allelic (OR = 1.17, 95% CI = 0.91-1.50; P = 0.218), heterozygous (OR = 1.28, 95% CI = 0.94-1.74; P = 0.117), dominant (OR = 1.25, 95% CI = 0.93-1.67; P = 0.142), recessive (OR = 0.99, 95% CI = 0.52-1.88; P = 0.973), homozygous (OR = 1.08, 95% CI = 0.57-2.07; P = 0.808). Conclusions: The PON2 Ser311Cys and Ala148Gly polymorphisms were not associated with the risk of developing T2DM in the Chinese population.


Effect of prenatal treatment on mother to child transmission of Toxoplasma gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.
The aim of prenatal serological screening for toxoplasmosis is to identify and treat maternal infection as soon as possible in order to prevent transmission of the parasite to the fetus. However, despite widespread provision of prenatal toxoplasma screening across Europe, the effectiveness of prenatal treatment is uncertain. The study aimed to determine the effect of the timing and type of prenatal treatment on mother to child transmission of Toxoplasma gondii. A cohort of 554 infected pregnant women were identified in Lyon, France between 1987 and 1995 and their children were followed to determine congenital infection status. We determined the effect of prenatal treatment on transmission by examining the effect of the delay between maternal seroconversion and start of treatment. We also compared the effect of the type of treatment and no treatment on the risk of mother to child transmission. Analyses were adjusted for gestation at maternal seroconversion. Compared to treatment within 4 weeks from seroconversion, the adjusted odds ratios (OR) for mother to child transmission after a treatment delay of 4-7 weeks was 1.29 (95% CI : 0.61, 2.73) and after more than 8 weeks, 1.44 (95% CI : 0.60, 3.31). The adjusted OR associated with spiramycin alone compared with pyrimethamine-sulfadiazine treatment was 0.91 (95% CI : 0.45, 1.84) and the OR for no treatment compared with pyrimethamine-sulfadiazine treatment was 1.06 (95% CI : 0.37, 3.03). The authors hypothesize that the absence of an effect of prenatal treatment is due to transmission before the start of treatment.


Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease.
A 61-year-old man developed subacute progressive dementia, general fatigue, a tonic-clonic seizure, and a decreased level of consciousness. He had a past history of chronic hepatitis type C and was diagnosed as having hepatic encephalopathy due to hyperammonemia. His level of consciousness did not improve even though the serum ammonia level improved. In addition, he had repeated general myoclonic seizures. Head MRI (diffusion-weighted imaging) showed high signal intensities in the right thalamus and the cerebral cortices in the frontal, temporal and parietal lobes (predominantly on the right side). An electroencephalogram (EEG) showed periodic lateralized epileptic discharges (PLEDs). Cerebrospinal fluid analysis revealed high total tau protein and 14-3-3 protein levels. This case was diagnosed as Creutzfeldt-Jakob disease (CJD) based on these clinical data. However, the patient gradually improved without specific treatment. The differential diagnosis was reconsidered, and an increased erythrocyte sedimentation rate and positive serum anti-SS-A and anti-SS-B antibodies were noted. A diagnosis of Sjögren syndrome (SjS) was finally made based on a biopsy of a minor salivary gland showing infiltration of lymphocytes around the gland ducts. Steroid therapy (prednisolone 40mg/day orally) was given, and his clinical condition improved. The lesions on the head MRI decreased, and the EEG findings normalized. This case suggests that SjS has a wide spectrum, including neurological disorders, and that SjS should be considered in the differential diagnosis of CJD.


Degradation kinetics of the main carbohydrates in birch wood during hot water extraction in a batch reactor at elevated temperatures.
Hot water extraction of wood at elevated temperatures may be a suitable method to produce hemicellulose-lean pulps and to recover xylan-derived products from the water extract. In this study, water extractions of birch wood were conducted at temperatures between 180 and 240 °C in a batch reactor. Xylan was extensively removed, whereas cellulose was partly degraded only at temperatures above 180 °C. Under severe extraction conditions, acetic acid content in the water extract was higher than the corresponding amount of acetyl groups in wood. In addition to oligo- and monosaccharides, considerable amounts of furfural and 5-hydroxymethylfurfural (HMF) were recovered from the extracts. After reaching a maximum, the furfural yield remained constant with increasing extraction time. This maximum slightly decreased with increasing extraction temperature, suggesting the preferential formation of secondary degradation products from xylose. Kinetic models fitting experimental data are proposed to explain degradation and conversion reactions of xylan and glucan.


Circulating [Met]enkephalin and catecholamine responses to acute hypotension and hypertension in anaesthetized greyhounds.
The effects of either hypotension induced by sodium nitroprusside or hexamethonium or hypertension produced by angiotensin II or noradrenaline on the circulating levels of methionine enkephalin ([Met]enkephalin)-like immunoreactivity (MLI), adrenaline and noradrenaline in anaesthetized greyhounds were examined. Nitroprusside infusions (200 and 400 micrograms min-1) induced a fall in blood pressure accompanied by significant rises in plasma MLI and catecholamine concentrations. Concomitant administration of a high dose of naloxone did not alter the fall in blood pressure produced by nitroprusside but was associated with greater rises in circulating MLI and catecholamines when compared to nitroprusside alone, suggesting that [Met]enkephalin is not involved in the hypotensive action of nitroprusside. Intravenous hexamethonium (2.5 mg kg-1) provoked a fall in blood pressure which was not associated with any changes in plasma MLI. However, it produced a fall in plasma noradrenaline and a rise in plasma adrenaline. Thus it appears that neural mechanisms are required, at least in part, for the release of MLI. Angiotensin II (1.25 micrograms kg-1 min-1) and noradrenaline (8 micrograms kg-1 min-1) infusions produced an elevation in blood pressure without altering the circulating MLI levels. Study of the molecular forms of circulating MLI, before and during hypotension, revealed that the large molecular weight enkephalin-containing peptides with approximate molecular sizes of 18kD and 8kD were the predominant forms both in the basal and stimulated states. It is concluded that circulating [Met]enkephalin is not involved in the tonic control of blood pressure but it may modulate catecholamine release following hypotension as part of the stress response.


Functional and psychological outcomes of delayed lower limb amputation following failed lower limb reconstruction.
The purpose of this study was to evaluate the functional and psychological outcomes of patients who underwent delayed lower limb amputation following failed limb salvage surgery. This retrospective, descriptive study evaluated functional outcomes using the Sickness Impact Profile (SIP) and Short Form-36 (SF-36) in 12 patients. Inclusion criteria included patients who underwent limb reconstruction and delayed amputation between July 2006 and December 2014, with an age range between 18 and 80 years of age, the ability to ambulate independently, a time interval between the last salvage procedure and amputation greater than six months, and a minimum follow-up of 24 months. Patients were contacted via telephone by the principal investigator and both the Sickness Impact Profile (SIP) and Short Form-36 (SF-36) were completed. Descriptive analysis (means and standard deviation) was used to determine outcomes for both SIP and SF-36 health profiles. Ten patients who had amputations following failed reconstruction (2006-2014) with a mean age of 53±10years were interviewed. Six patients had a SIP <5, three patients scored between five and 10 points and one scored >10 points. The main deficit on the SF-36 was in the physical component. The SF-36 scores demonstrated a mean score of 40.8±11.5 for the physical component, and 57.4±7.9 for the mental component. Three patients returned to work after amputation and continued performing their pre-injury duties as farmers. Three other patients returned to work, but were allocated to administrative duties. Two patients were pensioners at the time of their injuries, and the only female patient was a housewife. One patient went into early retirement. The results of this study strongly suggest that delayed amputation following failed limb salvage surgery can still result in good and satisfactory outcomes in the majority of patients and achieves results similar to early amputation and limb reconstruction techniques.


Choroidal metastasis as the presenting feature in a case of testicular choriocarcinoma.
A twenty-six year old male with decreased vision in right eye was diagnosed with non-rhegmatogenous retinal detachment. Further evaluation revealed a yet undiagnosed left testicular mass found to be choriocarcinoma on histopathology. Chemotherapy resulted in complete remission; however, there was no improvement in vision. There is a substantial risk of visual loss in the presence of ocular metastatic lesions. Early detection and treatment is highly effective in terms of tumor control and a more favorable survival and visual outcome. The onus of the ocular diagnosis lies on the ophthalmologist. The presence of a testicular origin tumor must be considered in a young male with intraocular metastasis.


Associated factors for accelerated growth in childhood: a systematic review.
Several studies have shown that accelerated growth in the postnatal period is critical for the development of chronic diseases. The term catch-up has been used for the accelerated growth of children who have suffered some sort of restriction of nutrition or oxygen supply. However, accelerated growth has been observed among children who have an appropriate birth weight for their gestational age (AGA) and with no apparent morbidity. Therefore, this systematic review was carried out on the associated factors of accelerated growth, or catch-up, using the Medline/Pubmed database. Only cohort studies written in Portuguese, English or Spanish, with children between zero and 12 years old who presented accelerated growth or catch-up as the outcome were included. Out of the 2,155 articles found, 9 were selected. There is no uniformity in the operational definition of accelerated growth, or in the concept of catch-up. According to this review, accelerated growth is associated with primiparity, maternal smoking during pregnancy, lower birth weight, and early weaning. The main limitations in the available literature are the high number of follow-up losses and the lack of control for confounding factors. The determinants of accelerated growth still need to be studied further, especially among AGA children.


Osteogenic Potential of Decellularized Tooth Matrix.
We studied the possibility of using decellularized tooth matrix as a scaffold to restore bone tissue. It was found that mesenchymal stem cells underwent spontaneous osteogenic differentiation on the decellularized tooth matrix, which makes it possible to use it as a natural allograft in the treatment of resorption of alveolar bone tissue.


Amylin modulates the formalin-induced tonic pain behaviours in rats.
Amylin is a peptide from the calcitonin gene-related peptides (CGRP) family that is expressed by nociceptors. Amylin may modulate pain via a spinal action. The effect of amylin's administration on the formalin test of acute and tonic pain was evaluated. Amylin's ability to modulate neuronal activity was analysed by c-Fos expression at the spinal cord lumbar 4-5 region (L4-5) and brain. Amylin subcutaneous administration 20 min prior, but not immediately before formalin, shortened the interphase and anticipated the beginning of the tonic pain phase. Amylin reduced the number of activated spinal cord neurons. Blockade of spinal amylin-receptors by prior L4-5 intrathecal administration of an amylin-receptor antagonist (AC187) attenuated these effects, whereas intrathecal BIBN4096 (CGRP-receptor antagonist) did not, proving that part of amylin's effects were spinally mediated via amylin-receptors. The locus coeruleus and other areas involved in descending modulation and affective responses to pain showed an increased number of activated neurons upon amylin subcutaneous administration, suggesting a role for supraspinal areas in some observed effects. L4-5 intrathecal injection of amylin or AC187 showed that both ligands attenuated tonic pain, but blockade of the amylin-receptor action by AC187 decreased further the number of paw jerks in this period. Overall, data suggested that amylin modulates pain with an inflammatory component and the autoanalgesic/inhibitory mechanisms occurring in the interphase of the formalin test. Amylin might have affected the nociceptive system at different levels (spinal cord and brain), explaining the different effects observed according to the time of amylin injection. WHAT DOES THIS STUDY ADD?: Amylin modulated formalin interphase and tonic pain behaviours probably by targeting spinal neurons and affecting supraspinal areas involved in affective and modulatory components of pain. Activation of spinal amylin-receptors may contribute to the initiation of inflammatory pain mechanisms.


High resolution imaging of cerebral small vessel disease with 7 T MRI.
Small vessel disease (SVD) refers to all pathological processes that affect the small vessels of the brain. SVD is an important cause of acute stroke, but is also a leading cause of aging-related cognitive decline and dementia, due to more insidious brain parenchymal damage. The introduction of high field strength MRI (7 T) is likely to offer important new perspectives on the role of SVD in these disorders. In this overview we illustrate the opportunities that 7 T MRI offers in high resolution vascular imaging. In particular, we will show the capability of 7 T MRI to depict the small arteries and veins in the brain, the vascular wall of intracranial arteries, perivascular spaces, and microvascular parenchymal lesions, including microbleeds and microinfarcts.


Two approximately 300 kilodalton Plasmodium falciparum proteins at the surface membrane of infected erythrocytes.
Two very large Plasmodium falciparum proteins are identified as constituents of the infected erythrocyte membrane. Sera were obtained from Aotus monkeys that had been repeatedly infected with asexual P. falciparum from one of four strains. The capacity of these sera to block in vitro cytoadherence of infected erythrocytes and agglutinate intact infected cells was determined. The sera were also used to immunoprecipitate protein antigens from detergent extracts of 125I-surface labeled or biosynthetically radiolabeled infected erythrocytes. For each serum/antigen combination, precipitation of only one protein correlated with the ability of the serum to interfere with cytoadherence and agglutinate infected cells. This malarial protein, denoted Pf EMP 1 (P. falciparum-erythrocyte-membrane-protein 1) bore strain-specific epitope(s) on the cell surface and displayed size heterogeneity (Mr approximately 220,000-350,000). Pf EMP 1 was strongly labeled by cell-surface radioiodination but was a quantitatively very minor malarial protein. Pf EMP 1 was distinguished by its size, surface accessibility and antigenic properties from a more predominant malarial protein in the same size range (Pf EMP 2) that is under the infected erythrocyte membrane at knobs. Monoclonal antibodies and rabbit antisera raised against Pf EMP 2 were used to show that this size heterogeneous antigen was indistinguishable from the previously described MESA (mature parasite infected erythrocyte surface antigen), identified by precipitation with rabbit antisera raised against the MESA hexapeptide repeats. Antibodies raised against Pf EMP 2/MESA did not precipitate Pf EMP 1. We conclude that Pf EMP 1 is either directly responsible for the cytoadherence phenomenon, or is very closely associated with another as yet unidentified functional molecule. Pf EMP 2/MESA must have a structural property/function that is important under the host cell membrane.


Kidney transplantation from deceased donors with elevated serum creatinine.
Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years.


Phase II study assessing lapatinib added to letrozole in patients with progressive disease under aromatase inhibitor in metastatic breast cancer-Study BES 06.
This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.