A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.
The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality. Processes and interventions that improve this situation are urgently needed. This study aims to evaluate the implementation of the "warfarin bundle," a package of interventions to improve the quality of anticoagulation and thereby clinical outcomes. The primary outcome for this study is TTR over the initial 3 months of warfarin therapy. Patients aged 18 years or older who are newly initiated on warfarin for venous thromboembolism, atrial fibrillation, or valvular heart disease will be enrolled and followed up for 3 months at clinics in Cape Town, South Africa, and Kampala, Uganda, where the warfarin bundle is implemented. A retrospective review of the clinical records of patients on warfarin treatment before implementation (controls) will be used for comparison. This study uses a mixed methods approach of the implementation of patient- and process-centered activities to improve the quality of anticoagulation. Patient-centered activities include the use of clinical dosing algorithms, adherence support, and root cause analysis, whereas process-centered activities include point-of-care INR testing, staff training, and patient education and training. We will assess the impact of these interventions by comparing the TTR and safety outcomes across the 2 groups, as well as the cost-effectiveness and acceptability of the package. We started recruitment in June 2021 and stopped in August 2022, having recruited 167 participants. We obtained ethics approval from the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee, the Provincial Health Research Committees in South Africa, the Joint Clinical Research Centre Institutional Review Board, Kampala, and the University of Liverpool Research Ethics Committee. As of February 2023, data cleaning and formal analysis are underway. We expect to publish the full results by December 2023. We anticipate that the "bundle of care," which includes a clinical algorithm to guide individualized dosing of warfarin, will improve INR control and TTR of patients in Uganda and South Africa. We will use these findings to design a larger, multisite clinical trial across several Sub-Saharan African countries. DERR1-10.2196/46710.


Differences in muscle endurance and recovery between fallers and nonfallers, and between young and older women.
Significant morbidity and mortality are associated with falls in older adults. We tested the hypothesis that older women with a history of falls demonstrate decreased muscle endurance and longer recovery times following fatiguing exercise. We evaluated dynamic endurance and recoverability of the quadriceps femoris of 29 young women (YW) (M age = 21.7), 26 older women with a history of falls (FA) (M age = 73.3), and 27 older women with no history of falls (NF) (M age = 71.2) using an isokinetic dynamometer. Subjects performed repeated maximal concentric knee extensions until the force output of two consecutive repetitions fell below 50% of their maximal voluntary contraction (MVC). Recovery was defined as the time required for the return of force output > or = 80% MVC for 2 consecutive repetitions, within a set consisting of 3 maximal contractions. One minute rest was allowed between sets. We collected electromyographic (EMG) data from the quadriceps during all testing to evaluate spectral shifts. ANOVA with a post-hoc Bonferroni-Dunn test revealed time to fatigue was significantly faster in FA than YW (p < .02) and in FA than NF (p < .05), but not different between YW and NF. Time to recovery was significantly slower in FA than YW (p = .01), but not different between YW and NF, or between FA and NF, EMG median frequency power shift (from the beginning to the end of the test) was significantly less in FA (p < .001) than either YW (p < .002) or NF (p < .05). Older women with a history of falls demonstrate decreased muscular endurance compared to YW and NF, and increased time to recover from fatiguing exercise when compared to young women.


Laryngeal resistance to respiratory airflow in humans.
Although vocal cord adduction has been observed during expiration, measurements of absolute values of resistance changes in man have not been reported in the literature. The authors measured resistance to translaryngeal respiratory airflow in inspiratory and expiratory phases of the respiratory cycle of four healthy, awake men during nasal breathing. It was found that, during quiet breathing through a decongested nose, translaryngeal resistance was 1.245 cm H2O/L per second in expiration and 0.354 cm H2O/L per second in inspiration (.005 < P < or = .01), for a percentage of approximately 25% and 50% of extrathoracic expiratory and inspiratory resistances, respectively. Voluntary hyperventilation decreased expiratory resistance, and a partial nasal obstruction abolished the statistical difference between translaryngeal inspiratory and expiratory resistance. These results are in agreement with previous observations of vocal cord movement and are consistent with an expiratory braking effect on airflow.


An electromyographic study of low-velocity rear-end impacts.
Experimental analysis was performed to determine the effects of low-velocity rear-end impacts on phasic and magnitudinal activity of the cervical muscles in expected and unexpected conditions. To determine the phasic response of the cervical muscles to increasing low-velocity rear-end impacts, and to compare the quantitative effects of awareness and unawareness of impending impact. The literature contains little information on the etiology of whiplash injuries. Animal and cadaver studies have yielded some insight into the phenomenon. However, in vivo studies of the cervical muscular response and head-neck kinematics to low-velocity impacts are rare. Seven healthy volunteers were subjected to rear-end impacts of 4.9, 8.8, 10.8, and 13.7 m/s2 acceleration at two levels of expectation: expected and unexpected. Bilateral electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were recorded. Triaxial accelerometers recorded the acceleration of the chair, torso at the shoulder level, and head of the participant. At an acceleration of 13.7 m/s2, the sternocleidomastoids generated up to 179% of their maximal voluntary contraction electromyogram, whereas the splenii and trapezii did not exceed 35% of their maximal voluntary contraction in most of the experimental conditions. Electromyographic variables were significantly affected by the levels of acceleration and expectation (P < 0.001). The onset time and peak electromyogram time for the sternocleidomastoid progressively decreased with increasing levels of acceleration. The kinetic variables and the electromyographic variables regressed significantly on the acceleration (P < 0.01), explaining from 96% to 100% of the variability. Muscle responses were greater with higher levels of acceleration. Because the muscular component of the head-neck complex plays a central role in the abatement of higher acceleration levels, it may be a primary site of injury in the whiplash phenomenon.


[Clinical analysis of different root treatment methods in acute Stanford type A aortic dissection].
Objective: To discuss the perioperative and follow-up results of different surgical methods for acute Stanford type A aortic dissection patients and analyzed the results. Methods: The clinic data of 351 acute Stanford type A aortic dissection patients received surgical therapy at Department of Thoracic and Cardiovascular Surgery, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital from January 2008 to December 2015 were analyzed retrospectively. There were 272 male and 79 female patients, aging from 22 to 83 years with a mean age of (52±13) years. According to root size, aortic valve structure and the status of dissection involvement, these patients were devided into three major groups: 218 cases with root reconstruction using Dacron felts, 34 cases with root reconstruction concomitant with aortic valve resuspension repair and 99 cases in with Bentall procedure. Proper shape based on the status of dissection involvement of Dacron patch was cut and put between the middle and outerlayer of aorta, then inside the inner layerone band Dacron felt was sutured with the aorta and the new middle layer with Dacron patch as mentioned above. In some cases the prolapsed aortic valve was re-suspended to the aortic cusp. Clinical outcomes among the 3 procedures were compared by χ(2) test, Fisher's exact test, t test and analysis of variance. Results: Cardiopulmonary bypass, cross-clamp, and circulatory arrest times of all the patients were (250±78), (171±70) and (31±10) minutes, respectively. The 30-day mortality was 9.2%(33/351), while no difference among the 3 procedures (9.6%, 8.8% and 9.1%). In the average follow-up time of (26.0±23.0) months (range from 0.5 to 90.0 months), survival rates were similar among the 3 procedures (77.7%, 77.4% and 77.8%). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (diameter of 50 mm). Conclusions: The indication of root management of acute Stanford type A aortic dissection is based on the diameter of aortic root, structure of aortic leaflets, and the dissection involvement. For most acute Stanford type A aortic dissection patients, aortic root reconstruction is a feasible and safe method.


A microbiological assay for estimating concentrations of camptothecin lactone in mouse tissues.
The marked sensitivity of the yeast Hansenula wingei NRRL Y-2340 strain 5 to a new antineoplastic alkaloid served as the basis for a logarithmic-ratio microbiological assay which has been developed for the estimation of concentrations of camptothecin lactone (or cytotoxic equivalents) in tissues of mice. The utility of this assay has been demonstrated by presenting data which show the concentrations of camptothecin lactone (or cytotoxic equivalents) detected in various tissues of mice at intervals following intraperitoneal injection of a 1 or 0.5 ld(10) dose of this drug.


Translation, Cross-cultural Adaptation, and Validation of the Dutch International Hip Outcome Tool-33 (iHOT-33 NL) in Young, Physically Active Individuals With Symptomatic Hip Joint Pathology.
Study Design Prospective cohort. Background The international Hip Outcome Tool-33 (iHOT-33), developed in English, has been shown to be a valid and reliable questionnaire for young, physically active individuals with symptomatic hip joint pathology. Objectives To translate and validate the iHOT-33 in Dutch (iHOT-33 NL) in the target population. Methods Translation and cross-cultural adaptation of the iHOT-33 were performed following existing guidelines. Young to middle-aged (18-50 years), active (Tegner activity score of 3 or greater) individuals presenting with symptomatic hip joint-related pain (numeric pain-rating score of 1 or greater) in a primary health care/hospital setting were included. The iHOT-33 NL, Hip disability and Osteoarthritis Outcome Score (HOOS), European Quality of Life-5 Dimensions questionnaire (EQ-5D), numeric pain-rating score, and Global Perceived Effect score were completed by 214 patients. Results The intraclass correlation coefficient for test-retest reliability was 0.92 (95% confidence interval: 0.88, 0.94). Smallest detectable changes at individual and group levels were, respectively, 16.7 and 1.1 points. The Cronbach alpha was .9. Principal-component analysis revealed 4 domains of the iHOT-33 NL. Of the hypotheses used for construct validity, 87% were confirmed. No floor and ceiling effects were detected for the iHOT-33 NL total score. The minimal important change was 10.7 points. Conclusion The iHOT-33 NL is a reliable and valid patient-reported outcome questionnaire for young, physically active individuals with symptomatic hip joint pathology. It can be used in research and clinical settings. J Orthop Sports Phys Ther 2018;48(4):289-298. doi:10.2519/jospt.2018.7610.


Unmet symptom management needs of nursing home residents with cancer.
Nursing home residents living with cancer have unacceptably high percentages of unrelieved pain and other symptoms. However, residents with cancer have received relatively little attention in the literature to date. This article provides an overview of previous symptom research for residents with cancer, explores clinical and organizational factors that impede effective symptom management, and proposes an agenda for future research and clinical practice. Residents with cancer have numerous symptoms that tend to be different from the symptoms of other nursing home residents. Symptom management for residents with cancer is often complicated by cognitive impairment, declining physical functioning, and comorbid illnesses. Barriers to symptom management include underuse of analgesics and hospice, nursing home staffing patterns, and lack of resources. Additional research is necessary to provide a more comprehensive understanding of residents with cancer, explore how organizational factors affect the care of residents with cancer, and evaluate interventions for effective symptom assessment and management. Collaboration of oncology nurses with clinicians and researchers in nursing home settings is needed to improve care for residents with cancer.


Management of Orbital Diseases.
Orbital diseases are common in dogs and cats and can present on emergency due to the acute onset of many of these issues. The difficulty with diagnosis and therapy of orbital disease is that the location of the problem is not readily visible. The focus of this article is on recognizing classical clinical presentations of orbital disease, which are typically exophthalmos, strabismus, enophthalmos, proptosis, or intraconal swelling. After the orbital disease is confirmed, certain characteristics such as pain on opening the mouth, acute vs. chronic swelling, and involvement of nearby structures can be helpful in determining the underlying cause. Abscesses, cellulitis, sialoceles, neoplasia (primary or secondary), foreign bodies, and immune-mediated diseases can all lead to exophthalmos, but it can be difficult to determine the cause of disease without advanced diagnostic imaging, such as ultrasound, magnetic resonance imaging, or computed tomography scan. Fine-needle aspirates and biopsies of the retrobulbar space can also be performed.


Evaluation of the efficiency under current use of human fibrinogen concentrate in trauma patients with life-threatening hemorrhagic disorders.
The aim of the study was to assess the influence of fibrinogen concentrate on survival when it is used in trauma patients with life-threatening hemorrhagic disorders. Secondly, to evaluate when the fibrinogen concentrate administration maximizes its efficacy, and to describe what other concomitant treatment the patients received in order to control their life-threatening hemorrhage. Retrospective, observational, and multicenter study was carried out in three trauma areas between June 2012 and June 2014. The totality of trauma patients with a documented life-threatening hemorrhage who received a fibrinogen concentrate prescription was included in the study. Demographic and analytical data, admission diagnosis, treatment indication, fibrinogen concentrate dose, survival after 1 and 7 days, hospitalization time, and concomitant blood product treatment were collected. One hundred and twenty-three patients were finally included. The mean dose of fibrinogen concentrate administered was 2.87 g. The mean initial fibrinogen plasma level was 1.49 g/l, which rose to 2.26 g/l. The number of patients who survived after 24 h was 80.49%, and 69.11% after 7 days. Lower fibrinogen plasma levels are statistically associated with a higher probability of death after 7 days (P = 0.004). The most suitable threshold to recommend the fibrinogen concentrate administration has been found to be 1.5 g/dl (P = 0006, after 24 h; P = 0.032, after 7 days). Finally, the most common concomitant treatment was the erythrocytes concentrate. A statistically significant relationship between lower fibrinogen plasma levels and a higher probability of death after 7 days has been found. Our data support the threshold of 1.5 g/l as the recommended level to administer fibrinogen concentrate in trauma patients.


Postnatal depression: a study of the predictive effects of postnatal anxiety.
The aim of this study was to evaluate the predictive effects of anxiety, experienced on the third day after delivery, on postnatal depression, evaluated around the sixth week postpartum. The subjects were 291 postpartum mothers who responded to a certain number of inclusion criteria. The EPDS (Edinburgh Postnatal Depression Scale) and the STAI (State-Trait Anxiety Inventory) were used to evaluate the anxious and depressive symptomatology on the third day postpartum and around the sixth week postpartum. The mothers who obtained scores indicating a probable risk of postnatal depression also completed the Beck Depression Inventory. We observed that 31% of the mothers showed postpartum blues symptomatology on the third day postpartum. Around the sixth week postpartum 13% of the mothers showed postnatal depression. The results suggest that the level of trait anxiety (β = 0.39; t = 3.64 p < 0.05) and more particularly the intensity of the postpartum blues symptomatology (β = 0.50; t = 6.88 p < 0.001) can predict the risk of postpartum depression. Furthermore, 17.9% of the mothers with postnatal depression around the sixth week postpartum were not detected by the EPDS on the third day after delivery. However, all these mothers were detected by the State-Trait anxiety inventory. A high level of anxiety during the first few days after delivery may contribute to the mothers' risk of developing postnatal depression. The early detection of high anxiety levels may enable the early screening of mothers at risk of developing postnatal depression.


Construction of Druglike 2-Amido Benzo[ d]imidazole Analogues via Desulfurative Cyclization of Thiourea Intermediate Resin on Solid-Phase.
A 2-amido benzo[ d]imidazole library has been constructed by solid-phase synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amino benzo[ d]imidazole resin through desulfurative cyclization of thiourea resin using 2-chloro-1,3-dimethylimidazolinium chloride and N, N-diisopropylethylamine in dichloromethane (DCM), and the resin is then functionalized by acylation at the 2-amine position to afford 2-amidobenzo[ d]imidazole resin. In the case of 2-amidobenzo[ d]imidazole resin having a p-I or m-NO2, the resin was further functionalized by Suzuki/Sonogashira-coupling ( p-I) and reduction to the primary amine ( m-NO2) followed by acylation. Finally, the functionalized 2-amido-benzo[ d]imidazole resin was cleaved from the polymer support by treatment with a cocktail of trifluoroacetic acid and DCM. As a result, we obtained 2-amidobenzo[ d]imidazole analogues in high yield and good purities.


Assessment of the accuracy of a three-dimensional imaging system for archiving dental study models.
The use of stone and plaster study models is an integral part of any dental practice and is required for research. Storage of study models is problematic in terms of space and cost. Ayoub et al.(1) introduced a new technique based on the recent advances in stereophotogrammetry for archiving dental study models in a digital format. However, assessment of the accuracy of the generated three-dimensional (3D) models has not been carried out yet. It was the aim of this study to evaluate the accuracy of this technique. A comparative assessment between direct measurements of dental study models and measurements of computer generated 3D images of the same study models was performed. Twenty-two dental study models stored at Glasgow Dental Hospital and School for the purposes of research were used in the study. The models were captured in three dimensions using a photostereometric technique and stored in digital format. Measurements were conducted directly on dental study models and on the computer generated 3D images using Euclidean Distance Matrix Analysis.(2) The difference between the two sets of measurements was statistically analysed using a two-sample t-test. The average difference between measurements of dental casts and 3D images was 0.27 mm. This difference was within the range of operator errors (0.10-0.48 mm) and was not statistically significant (P < 0.05). This study shows that it is possible to use 3D imaging to store dental study models for treatment monitoring and research with a satisfactory degree of accuracy.


Neurological Manifestations of Coronavirus Disease 2019 and Mpox in Pediatric Patients and Their Management: A State-of-the-Art Systematic Review.
There is an increasing number of cases being reported of neurological manifestations of Coronavirus disease 2019 (COVID-19) infection and Monkeypox (Mpox), both during the course of the infection and as a presenting symptom. We aim to review the neurological manifestations of COVID-19 and monkeypox in pediatric patients and their management. We conducted a systematic review that included cohort studies and case series or reports involving a pediatric population of patients with a confirmed COVID-19 or Mpox infection and their neurological manifestations. We searched the following electronic databases: PubMed, EMBASE, and Scopus. From 1136 articles identified, 127 studies were included. Headache, stroke, Guillain-Barré syndrome, seizure, nerve palsies, and multisystem inflammatory syndrome in children were the most common neurological symptoms caused by COVID-19, whereas encephalitis was commonly seen in patients with Mpox. Rare neurological manifestations of COVID-19 included cerebral venous sinus thrombosis, plexopathies, demyelinating disorders, encephalitis, etc., and rare neurological manifestations of Mpox included headache. Our review highlights the importance of investigating possible neurological manifestations and closely monitoring these patients to develop a better understanding of the treatment strategies that can be adopted.


Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes.
Recent studies have shown the ability of apelin to restore glucose tolerance in obese and insulin-resistant mice. Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) from the omega-3 family that has many beneficial effects in obesity-linked disorders. The aim of this study was to examine in vitro the effects of EPA on apelin secretion and gene expression in mature 3T3-L1 adipocytes. Treatment with EPA (100 and 200 microM) significantly increased basal (p<0.01) and insulin-stimulated (p<0.001) apelin secretion and gene expression in adipocytes. EPA also stimulated Akt phosphorylation, a down-stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes. Moreover, treatment with the PI3K inhibitor LY294002 completely blocked EPA-stimulatory action on apelin mRNA gene expression (p<0.001), but not modified the stimulatory effect of EPA on basal apelin secretion. Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms. These findings suggest that the mechanisms mediating EPA-induced apelin synthesis and/or secretion are complex, involving steps that are PI3K dependent and steps that are PI3K independent.


A new general regression-based approach for method comparison studies.
A scatter plot combined with correlation and regression analysis to assess the agreement between analytical methods that measure the same quantity has a long tradition in clinical chemistry. However, only when linearity is absolute this approach may be useful to estimate whether the methods under comparison produce the same errors in measurement. The aim of this study is to provide a new original regression-based tool which does not suffer from the problems of the classical regression/correlation method and that is also easy to use and to interpret. To evaluate the performance of the new method, the results of some analytical determinations were compared by the new procedure, the Bland-Altman test, Passing-Bablok regression and Mountain plot. All the tests used to compare the data allowed superimposable interpretations, both when methods under comparison were in agreement and in disagreement. The understanding of the new test is truly intuitive and it is reduced to the appraisal of how much the equation of the best-fit line (Y=X) is able to predict the value of the Y. The goodness of this prediction can be evaluated by the coefficient of determination, whose value is closely connected to the differences between the methods under comparison. The result of our simulation is that quite high agreement between the methods occurs for determination coefficient equal or greater than 0.98.


Posterior Temporary C1-2 Pedicle Screws Fixation for the Treatment of Unstable C1-2 Complex Fractures: Minimum of 2-Year Follow-Up.
Retrospective. To present rarely reported complex fractures of the upper cervical spine (C1-C2) and discuss the clinical results of the posterior temporary C1-2 pedicle screws fixation for C1-C2 stabilization. A total of 19 patients were included in the study (18 males and 1 female). Their age ranged from 23 to 66 years (mean age of 39.6 years). The patients were diagnosed with complex fractures of the atlas and the axis of the upper cervical spine and underwent posterior temporary C1-2 pedicle screws fixation. The patients underwent a serial postoperative clinical examination at approximately 3, 6, 9 months, and annually thereafter. The neck disability index (NDI) and the range of neck rotary motion were used to evaluate the postoperative clinical efficacy of the patients. The average operation time and blood loss were 110 ± 25 min and 50 ± 12 ml, respectively. The mean follow-up was 38 ± 11 months (range 22 to 60 months). The neck rotary motion before removal, immediately after removal, and the last follow-up were 68.7 ± 7.1°, 115.1 ± 11.7°, and 149.3 ± 8.9° (P < 0.01). The NDI scores before and after the operation were 42.7 ± 4.3, 11.1 ± 4.0 (P < 0.01), and the NDI score 2 days after the internal fixation was removed was 7.3 ± 2.9, which was better than immediately after the operation (P < 0.01), and 2 years after the internal fixation was removed. The NDI score was 2.0 ± 0.8, which was significantly better than 2 days after the internal fixation was taken out (P < 0.001). Posterior temporary screw fixation is a good alternative surgical treatment for unstable C1-C2 complex fractures.


Where to Focus Efforts to Reduce the Black-White Disparity in Stroke Mortality: Incidence Versus Case Fatality?
At age 45 years, blacks have a stroke mortality ≈3× greater than their white counterparts, with a declining disparity at older ages. We assess whether this black-white disparity in stroke mortality is attributable to a black-white disparity in stroke incidence versus a disparity in case fatality. We first assess if black-white differences in stroke mortality within 29 681 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort reflect national black-white differences in stroke mortality and then assess the degree to which black-white differences in stroke incidence or 30-day case fatality after stroke contribute to the disparities in stroke mortality. The pattern of stroke mortality within the study mirrors the national pattern, with the black-to-white hazard ratio of ≈4.0 at age 45 years decreasing to ≈1.0 at age 85 years. The pattern of black-to-white disparities in stroke incidence shows a similar pattern but no evidence of a corresponding disparity in stroke case fatality. These findings show that the black-white differences in stroke mortality are largely driven by differences in stroke incidence, with case fatality playing at most a minor role. Therefore, to reduce the black-white disparity in stroke mortality, interventions need to focus on prevention of stroke in blacks.


[Roles of spermidine in induced resistance of cucumber seedlings to Botrytis cinerea Pers].
Under the conditions of root substrate injection and foliar spray of different concentration spermidine, this paper measured the disease index, defense enzyme activities, and contents of disease resistance-related substances in cucumber (Cucumis sativus L.) seedlings infected by Botrytis cinerea Pers., aimed to investigate the roles of spermidine in induced resistance of cucumber seedlings to B. cinerea. The results showed that after treated with spermidine, the disease index decreased by 25.4%, phenylalanine ammonia lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO) activities increased by 48.4%, 635.9% and 38.9%, respectively, and total polyphenol, flavonoid and lignin contents increased significantly, compared with the control. All of these suggested that spermidine could induce the disease resistance of cucumber seedlings, and its optimum concentration was 150 mg L(-1).


Human Brain Project Partnering Projects Meeting: Status Quo and Outlook.
As the European Flagship Human Brain Project (HBP) ends in September 2023, a meeting dedicated to the Partnering Projects (PPs), a collective of independent research groups that partnered with the HBP, was held on September 4-7, 2022. The purpose of this meeting was to allow these groups to present their results, reflect on their collaboration with the HBP and discuss future interactions with the European Research Infrastructure (RI) EBRAINS that has emerged from the HBP. In this report, we share the tour-de-force that the Partnering Projects that were present in the meeting have made in furthering knowledge concerning various aspects of Brain Research with the HBP. We describe briefly major achievements of the HBP Partnering Projects in terms of a systems-level understanding of the functional architecture of the brain and its possible emulation in artificial systems. We then recapitulate open discussions with EBRAINS representatives about the evolution of EBRAINS as a sustainable Research Infrastructure for the Partnering Projects after the HBP, and also for the wider scientific community.


How do people construe objects when being observed?
The current research aims to explore how people construe objects when being observed (vs. in a private context). Using different manipulations of observation and measures of construal, we demonstrate that people are more likely to apply higher-level construals when observed than in a private context (Studies 1-3); this effect holds when controlling for arousal level (Study 2) and is obtained under conditions of observation but not the mere presence of others (Study 3). Studies 4-6 explore the underlying mechanism of this effect: adopting the perspectives of others in the presence of observers. Study 4 demonstrates that when observed, people align their own preferences to their inference of the preferences of others, but this effect is not present in a private context. In Study 5, a mediation analysis suggests that individuals prefer the high-level option when observed because they adopt the perspectives of others. In addition, the link between context and construal level is broken when participants are explicitly asked to focus on their own perspective when observed or to adopt the perspectives of others in a private context (Study 6). Finally, Study 7 examines implications for evaluation of gifts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Discarded Egg Yolk as an Alternate Source of Poly(3-Hydroxybutyrate-co-3-hydroxyhexanoate).
Many poultry eggs are discarded worldwide because of infection (i.e., avian flu) or presence of high levels of pesticides. The possibility of adopting egg yolk as a source material to produce polyhydroxyalkanoate (PHA) biopolymer was examined in this study. Cupriavidus necator Re2133/pCB81 was used for the production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) or poly(3HHx), a polymer that would normally require long-chain fatty acids as carbon feedstocks for the incorporation of 3HHx monomers. The optimal medium contained 5% egg yolk oil and ammonium nitrate as a nitrogen source, with a carbon/nitrogen (C/N) ratio of 20. Time course monitoring using the optimized medium was conducted for 5 days. Biomass production was 13.1 g/l, with 43.7% co-polymer content. Comparison with other studies using plant oils and the current study using egg yolk oil revealed similar polymer yields. Thus, discarded egg yolks could be a potential source of PHA.


Intermetallic compounds with 1D infinite tunnels. Syntheses and structures of AAu4In2 (A = K, Rb).
Four intermetallic compounds KxRb1-xAu4In2 (x = 0-1) synthesized by high-temperature solid-state reactions display 1D infinite tunnel constructions with Au-In frameworks. These compounds show small but different cation displacements in the tunnels and are also air and moisture inert at room temperature, even in concentrated HCl(aq).


Monolayered Silicon and Germanium Monopnictide Semiconductors: Excellent Stability, High Absorbance, and Strain Engineering of Electronic Properties.
The discovery of stable two-dimensional (2D) semiconductors with exotic electronic properties is crucial to the future electronic technologies. Using the first-principles calculations, we predict the monolayered Silicon- and Germanium-monopnictides as a new class of semiconductors owning excellent dynamical and thermal stabilities, prominent anisotropy, and high possibility of experimental exfoliation. These semiconductors, including the monolayered SiP, SiAs, GeP, and GeAs, possess wide bandgaps of 2.08-2.64 eV obtained by hybrid functional calculation. Under small uniaxial strains (-2 to 3%), dramatic modulations of their band structures are observed, and furthermore, all the 2D monolayers (MLs) can be transformed between indirect and direct semiconductors. The monolayered GeAs and SiP exhibits extraordinary optical absorption in the range of visible and ultraviolet (UV) light spectra, respectively. The exfoliation energies of these monolayers are comparable to graphene, implying a strong probability of successful fabrication by mechanical exfoliation. These intriguing properties of the monolayered silicon- and germanium-monopnictides, combined with their highly stable structures, offer tremendous opportunities for electronic and optoelectronic devices working under UV-visible spectrum.


Social objectives in cancer care: the example of palliative day care.
Social objectives are poorly specified and evaluated in cancer care. Palliative day care is an example where social objectives are often identified but research has focused on health-care outcomes. A literature review identifies four types of social objective: emotional and spiritual care, general social care, services for families and carers and creative arts. Social objectives include: distinguishing between therapeutic work and leisure and supportive interventions, promoting service continuity, reducing social isolation, increasing social interaction, reassuring introduction to palliative care, rehearsal of reactions to illness with a sympathetic audience, integration of families and carers into care services, respite for carers and creative work for three separable objectives. It is argued that interventions to achieve social objectives may be defined and evaluated in a measurable way. Similarly, social objectives and interventions can be specified at other stages in the cancer journey.


Polyacryloyl hydrazide: an efficient, simple, and cost effective precursor to a range of functional materials through hydrazide based click reactions.
Preparation and studies of ion exchangeable epoxy resins, stimuli responsive hydrogels, and polymer-dye conjugates have been accomplished through hydrazide based click reactions using polyacryloyl hydrazide (PAH) as the precursor. A convenient synthesis of PAH with quantitative functionality was achieved by treatment of polymethyl acrylate with hydrazine hydrate in the presence of tetra-n-butyl ammonium bromide. PAH was cured with bisphenol A diglycidyl ether (BADGE) at 60 °C to form transparent resins with superior mechanical properties (tensile strength = 2-40 MPa, Young's modulus = 3.3-1043 MPa, and ultimate elongation = 9-75%) compared to the conventional resins prepared using triethylene tetramine. The resins exhibited higher ion exchange capacities (1.2-6.3 mmol/g) compared to the commercial AHA ammonium-type (Tokuyama Co., Japan) membranes. An azo dye with aldehyde functionality was covalently attached to PAH through hydrazone linkage, and the dye labeled PAH exhibited colorimetric sensing ability for base and acids up to micromolar concentration. The swelling of the PAH based hydrogel varied in the range 4-450% depending on the pH and temperature of the medium. The hydrogels gradually released 30% of the original encapsulated dye in a period of 200 h. PAH-hydroxy naphthaldehyde conjugate released 75% of the original loading in ∼11 days at 37 °C and pH 5.0 through cleavage of the -CONHN═C- linkage. The study depicts the versatility of PAH as a precursor and inspires synthesis of a range of new materials based on PAH in the future.


The dendrimer impact on vesicles can be tuned based on the bilayer charge and the presence of albumin.
PAMAM (polyamidoamine) dendrimers are promising in biomedical applications that can interact with both the bilayer and . Here we employed giant unilamellar vesicles (GUVs) of two different charge densities to study the effect of albumin, one of the major in blood plasma, on the interactions between PAMAM dendrimers and membranes. The results show that albumin exacerbates the effect of dendrimers on the destabilization of the vesicles in terms of leakage, aggregation and collapse in particular for negatively charged vesicles while neutrally charged membranes are not affected. We conclude that the higher affinity of both albumin and PAMAM G6 towards negatively charged membranes explains their synergistic behavior in this case. In the case of neutral vesicles, the affinity between PAMAM G6 and albumin is stronger than that between PAMAM G6 (or albumin) and neutral vesicles, and thus no synergism is observed for the mixture during the interaction with neutral membranes.


Malignant nephrosclerosis in a patient with familial Mediterranean fever.
A 37-year-old man was admitted to our hospital for an evaluation of renal dysfunction and hypertension. The C-reactive protein level was 6.0 mg/dL, and the serum renin activity was extremely high. A renal biopsy showed malignant nephrosclerosis-like lesions with an onion skin pattern. He had a history of recurrent abdominal pain associated with periodic fevers above 38 degrees that resolved within three days. A MEditerranean FeVer (MEFV) gene analysis revealed that he was homozygous for the E148Q polymorphism (exon 2) and heterozygous for the L110P polymorphism (exon 2). The present case demonstrates that persistent subclinical inflammation can lead to malignant nephrosclerosis in familial Mediterranean fever patients with this genotype.


Developing a Data-driven Medication Indication Knowledge Base using a Large Scale Medical Claims Database.
Medication-indication knowledge base (KB) is useful for clinical care and also a key enabler for secondary use of observational health data. Over the years there are several indication KBs being developed, however, they were built based on curated data sources and thus may not reflect actual clinical practice. The longitudinal observational health data contain information about real world practice of medication indication, but were rarely used in KB construc- tion. A major challenge of leveraging them is the confounders in multi-medication multi-diagnoses relations. In this study, we proposed a sampling based approach that could explicitly handle the aforementioned confounders, and consequently detect more accurate medication-indication relations. Based on this method, we created a medication- indication KB that reflects actual clinical practice and has broad medication and indication coverages. Our work represents the first attempt to develop a medication-indication KB from a large scale observational health data in an automated and unsupervised manner.


Micelle-Based Adjuvants for Subunit Vaccine Delivery.
In the development of subunit vaccines with purified or recombinant antigens for cancer and infectious diseases, the design of improved and safe adjuvants able to efficiently target the antigen presenting cells, such as dendritic cells, represents a crucial challenge. Nanoparticle-based antigen delivery systems have been identified as an innovative strategy to improve the efficacy of subunit vaccines. Among them, self-assembled micellar nanoparticles from amphiphilic (macro)molecules have recently emerged as promising candidates. In this short review, we report on the recent research findings highlighting the versatility and potential of such systems in vaccine delivery.


Screening for dementia in Arabic: normative data from an elderly Lebanese sample.
Prevention and treatment of dementia is a global concern that requires involvement of international samples. The purpose of this study is to develop culturally sensitive norms based on normal older Lebanese adults using multiple cognitive screening measures translated into Arabic for regional use. Participants were 164 community dwelling older Lebanese adults without cognitive complaints. They were administered the following cognitive measures in Arabic: Alzheimer's Disease 8-item questionnaire, Montreal Cognitive Assessment, Mini Mental Status Exam, Modified Mini Mental Status, Brief Visuospatial Memory Test-Revised, Lebanese Digit Span, Cross-Linguistic Naming Test, and phonemic and semantic fluency tests. Sample characteristics and descriptive statistics for the demographically unadjusted raw scores are first presented (N = 164). Same-form test-retest reliability for each test were computed for 24 participants retested over 2-5 weeks, with reliabilities ranging from .55 to .90; Cronbach alpha coefficients ranged from .34 to .93. Two sets of normative data were constructed. First, base-rates for demographically unadjusted raw scores for the 5th, 10th and 15th percentiles are presented to identify relatively rare occurring performances. Second, using standardized regression-based procedures demographically corrected normative information adjusted for age, education and sex were generated for normative interpretation. Adapting cognitive tests for use in culturally and linguistically diverse regions of the world not only requires careful translation of test instructions and materials, but construction of culturally sensitive local norms. Our normative data should allow for more accurate identification of cognitive impairment and dementia in Arabic-speaking patients, especially those living in Lebanon.


Echocardiographic assessment of severity of aortic regurgitation.
An echocardiographic study of left ventricular diameter was made in 27 patients with aortic regurgitation. Comparison was made with a group of 21 normal subjects and a group of 6 patients with large left ventricles without valvar regurgitation. Total stroke volume, total left ventricular output, and ejection fraction were derived by the method of cubing the left ventricular diameter to give approximate left ventricular volumes at and-diastole and end-systole. The patients were assessed independently and placed into three grades of severity. The eechocardiographic dimensions of patients with mild aortic regurgitation were not significantly different from those of the normal subjects. With increasing severity of aortic regurgitation, there were increases in group values for left ventricular diameter, total stroke volume, and total left ventricular output. The ejection fraction was depressed below the normal range in only one patient with aortic regurgitation. It is concluded that echocardiographic measurement of left ventribular dimensions is of value in assessing the severity of aortic regurgitation.


Adaptive responses to tissue injury: role of heme oxygenase-1.
Tissue injury may result as a consequence of a physical, chemical, or biological insult. Such injury recruits an adaptive response to restore homeostasis and protect against further injury. One of the most prompt protective and adaptive responses by all tissues is the robust activation of the highly inducible, anti-inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1). HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is released from heme proteins to equimolar quantities of iron, carbon monoxide, and biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The beneficial effects of HO-1 expression are not merely due to heme degradation but are also attributed to the cytoprotective properties of the byproducts of the reaction. Manipulation of this enzymatic system in a myriad of disease models has provided substantial evidence to support its role as a cytoprotective enzyme and is therefore an emerging therapeutic molecule.


Barcoding quarantine nematodes and their close relatives: an update on the QBOL-project.
Identification of plant pests, in particular quarantine species, needs to be fast and accurate to enable timely plant protection measures. In addition, a false diagnosis can cause serious financial losses for trade and producers. It is now well established that genetically based diagnosis is a reliable alternative to the classical identification procedures generally based on morphological features, which usually require expert taxonomic skills. On the other hand, genetic diagnosis through the use of DNA-barcodes, i.e. stretches of DNA that contain taxon-specific information, can be performed by any skilled laboratory worker. The European Union 7th framework project QBOL aims to establish DNA-barcodes for all European quarantine organisms as well as their close relatives. The results and protocols will be disseminated in the publicly available and curated database Q-BANK. To enable genetically based identification requires knowledge of the genetic variation both within and between the species of interest as well as their close relatives. For the nematodes, several gene regions (the COI, COII, SSU, LSU and RNA polymerase subunit II) are being evaluated for their barcoding potential.


[ADLib system for rapid and flexible design of monoclonal antibodies].
Monoclonal antibodies (MAbs) have been utilized as research tools, as diagnostic reagents, and for antibody medicine. The preparation of MAbs involves laborious processes and normally takes months. Here we describe an ex vivo B cell-based antibody display system called the ADLib (Autonomously Diversifying Library) system, which enables us to select chicken B cell clones producing antibody against antigens of interest in a couple of weeks. The ADLib system is applicable to self- or highly conserved antigens, polysaccharide chains, peptides, and haptens.


Parent-reported symptoms of attention deficit hyperactivity disorder in children with intermittent exotropia before and after strabismus surgery.
To investigate the symptoms of attention deficit hyperactivity disorder (ADHD) as reported by parents in children with intermittent exotropia [X(T)] and to determine whether strabismus surgery for X(T) affects ADHD symptoms. Fifty-one consecutive children undergoing muscle surgery for X(T) were prospectively recruited. One parent of each child completed the ADHD rating scale IV (ADHD RS-IV) assessment consecutively before and one year after surgery. Patients whose preoperative scores were above the cut-off point, the 90th percentile based on a Korean sample, were regarded as demonstrating the ADHD trait. The impact of muscle surgery on ADHD symptoms was assessed by comparing the preoperative scores with the post-operative scores. Eight (15.7%) of the 51 patients demonstrated the ADHD trait. ADHD RS-IV scores following strabismus surgery significantly decreased in patients with the ADHD trait (p=0.014), while they did not differ in patients without the ADHD trait. Seven (87.5%) of the 8 patients with the ADHD trait showed improvement in their ADHD RS-IV scores after surgery. There was no difference in surgical success rates between X(T) patients with and without the ADHD trait. The ADHD trait was relatively common in children with X(T), and the parent-reported symptoms of the children with the ADHD trait improved after strabismus surgery. These results suggest that childhood X(T) may be one contributing factor to ADHD- related symptoms.


IgE, Reed-Sternberg cells, and eosinophilia in Hodgkin's disease.
Tissues containing Hodgkin's disease tumors of the nodular sclerosis and mixed cellularity subtypes are frequently infiltrated by numerous degranulating eosinophils that release granule proteins such as eosinophil peroxidase and major basic protein. Until recently, the causes of the eosinophil infiltration and degranulation in Hodgkin's disease tumors were unknown. Analysis of Hodgkin's disease tissues by a sensitive and specific immunoperoxidase technique has now demonstrated the extensive presence of IgE in the Reed-Sternberg cells and adjacent cells of Hodgkin's disease tumors. Because eosinophils express a cell-surface receptor (CD23) for IgE and degranulate in the presence of IgE deposits, the extensive eosinophilia that is frequently present in Hodgkin's disease tumors is, at least in part, attributable to the IgE deposits within the tumor. In this review, we discuss the possible mechanisms and biological significance of IgE-related eosinophilia in Hodgkin's disease.


Dual Modulation of Human P-Glycoprotein and ABCG2 with Prodrug Dimers of the Atypical Antipsychotic Agent Paliperidone in a Model of the Blood-Brain Barrier.
Many atypical antipsychotic drugs currently prescribed for the treatment of schizophrenia have limited brain penetration due to the efflux activity of ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB), including P-glycoprotein (P-gp) and ABCG2. Herein, we describe the design and synthesis of the first class of homodimeric prodrug dual inhibitors of P-gp and ABCG2. These inhibitors are based on the structure of the atypical antipsychotic drug paliperidone (Pal), a transport substrate for both transporters. We synthesized and characterized a small library of homodimeric bivalent Pal inhibitors that contain a variety of tethers joining the two monomers via ester linkages. The majority of our compounds were low micromolar to sub-micromolar inhibitors of both P-gp and ABCG2 in cells overexpressing these transporters and in immortalized human hCMEC/D3 cells that are derived from the BBB. Our most potent dual inhibitor also contained an internal disulfide bond in the tether (Pal-8SS) that allowed for rapid reversion to monomer in the presence of reducing agents or plasma esterases. To increase stability against these esterases, we further engineered Pal-8SS to contain two hindering methyl groups alpha to the carbonyl of the ester moiety within the tether. The resulting dimer, Pal-8SSMe, was also a potent dual inhibitor that remained susceptible to reducing conditions but was more resistant to breakdown in human plasma. Importantly, Pal-8SSMe both accumulated and subsequently reverted to the therapeutic Pal monomer in the reducing environment of BBB cells. Thus, these molecules serve two purposes, acting as both inhibitors of P-gp and ABCG2 at the BBB and as prodrugs, effectively delivering therapies to the brain that would otherwise be precluded.


Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes.
Growth plate chondrocytes play a pivotal role in promoting longitudinal bone growth. The current review represents a brief survey of the phenomena involved in this process at the cellular level; it delineates the contributions made by various activities during the course of the chondrocyte life cycle, notably proliferation and hypertrophy, and illustrates how the relative contributions may be modulated according to the particular needs of an organism at critical phases of growth. The cellular mechanisms by which a few well characterized growth-promoting substances exert their influences are discussed in the light of recent findings pertaining to epiphyseal plate chondrocytes in vivo.


Decision-aided sampling frequency offset compensation for reduced-guard-interval coherent optical OFDM systems.
We propose a decision-aided algorithm to compensate the sampling frequency offset (SFO) between the transmitter and receiver for reduced-guard-interval (RGI) coherent optical (CO) OFDM systems. In this paper, we first derive the cyclic prefix (CP) requirement for preventing OFDM symbols from SFO induced inter-symbol interference (ISI). Then we propose a new decision-aided SFO compensation (DA-SFOC) algorithm, which shows a high SFO tolerance and reduces the CP requirement. The performance of DA-SFOC is numerically investigated for various situations. Finally, the proposed algorithm is verified in a single channel 28 Gbaud polarization division multiplexing (PDM) RGI CO-OFDM experiment with QPSK, 8 QAM and 16 QAM modulation formats, respectively. Both numerical and experimental results show that the proposed DA-SFOC method is highly robust against the standard SFO in optical fiber transmission.


Sleep apnea syndrome: implications on cardiovascular diseases.
Global risk assessment is the standard of care for coronary artery disease management. In this setting, sleep apnea syndrome, which includes obstructive sleep apnea and central sleep apnea, is being increasingly recognized as a potentially modifiable risk factor for coronary artery disease. Emerging evidence points toward a cause and effect relationship between sleep apnea syndrome and medical conditions like insulin resistance, hypertension, heart failure, and myocardial ischemia. The effects of sleep apnea on coronary artery disease can be independent of many traditional risk factors. Continuous positive airway pressure has been shown to decrease inflammatory markers that are elevated in sleep apnea syndrome. Well-designed randomized controlled clinical trials are needed to better establish the role of sleep apnea in the genesis and progression of coronary artery disease.


Ca2+-independent activation of the endothelial nitric oxide synthase in response to tyrosine phosphatase inhibitors and fluid shear stress.
Fluid shear stress enhances NO formation via a Ca2+-independent tyrosine kinase inhibitor-sensitive pathway. In the present study, we investigated the effects of the protein tyrosine phosphatase inhibitor phenylarsine oxide and of fluid shear stress on endothelial NO production as well as on the membrane association and phosphorylation of the NO synthase (NOS) III. Phenylarsine oxide (10 micromol/L) induced an immediate and maintained NO-mediated relaxation of isolated rabbit carotid arteries, which was insensitive to the removal of extracellular Ca2+ and the calmodulin antagonist calmidazolium. This phenylarsine oxide-induced vasodilatation was unaffected by genistein but abrogated by the tyrosine kinase inhibitor erbstatin A. Incubation of native or cultured endothelial cells with phenylarsine oxide resulted in a time-dependent tyrosine phosphorylation of mainly Triton X-100-insoluble (cytoskeletal) proteins, along with a parallel change in the detergent solubility of NOS III, such that the enzyme was recovered in the cytoskeletal fraction. A similar, though slightly delayed, phenomenon was also observed after the application of fluid shear stress but not in response to any receptor-dependent agonist. Although Ca2+-independent NO formation was sensitive to erbstatin A, phenylarsine oxide treatment was associated with the tyrosine dephosphorylation of NOS III rather than its hyperphosphorylation. Proteins that also underwent redistribution in response to the tyrosine phosphatase inhibitor included paxillin, phospholipase C-gamma1, mitogen-activated protein kinase, and the tyrosine kinases Src and Fyn. We envisage that fluid shear stress and tyrosine phosphatase inhibitors may alter the conformation and/or protein coupling of NOS III, facilitating its interaction with specific phospholipids, proteins, and/or protein kinases that enhance/maintain its Ca2+-independent activation.


Metalloporphyrin molecular sieves based on Tin(IV)porphyrin phenolates.
[reaction: see text] The crystal and molecular structures of two six-coordinate tin(IV)porphyrin phenolate complexes show that infinite cylindrical channels of uniform pore dimension are formed along the crystallographic c-direction. The underlying recognition event responsible for the porosity is an extremely tight intermeshing of the meso-tolyl units between layers which is a result of Sn-O...H interactions. Thermogravimetric analysis and differential scanning calorimetry have been used to characterize the sieve-like materials.


Implications of nitrogen phloem loading for carbon metabolism and transport during Arabidopsis development.
Metabolite transport processes and primary metabolism are highly interconnected. This study examined the importance of source-to-sink nitrogen partitioning, and associated nitrogen metabolism for carbon capture, transport and usage. Specifically, Arabidopsis aap8 (AMINO ACID PERMEASE 8) mutant lines were analyzed to resolve the consequences of reduced amino acid phloem loading for source leaf carbon metabolism, sucrose phloem transport and sink development during vegetative and reproductive growth phase. Results showed that decreased amino acid transport had a negative effect on sink development of aap8 lines throughout the life cycle, leading to an overall decrease in plant biomass. During vegetative stage, photosynthesis and carbohydrate levels were decreased in aap8 leaves, while expression of carbon metabolism and transport genes, as well as sucrose phloem transport were not affected despite reduced sink strength. However, when aap8 plants transitioned to reproductive phase, carbon fixation and assimilation as well as sucrose partitioning to siliques were strongly decreased. Overall, this work demonstrates that phloem loading of nitrogen has varying implications for carbon fixation, assimilation and source-to-sink allocation depending on plant growth stage. It further suggests alterations in source-sink relationships, and regulation of carbon metabolism and transport by sink strength in a development-dependent manner.


Differential effects of nerve impulses on adrenergic storage vesicles in rat heart.
The effects of increasing and decreasing activity in sympathetic neurons on light (D420 = 1.05) and heavy (D420 = 1.15) populations of adrenergic vesicles have been determined. Norepinephrine (NE) was used as a marker for the soluble contents of the vesicles, and dopamine beta-hydroxylase was used as a marker for the vesicle membranes. Cold exposure was used to increase activity in the sympathetic nervous system. A 40% decrease in the NE content of the rat heart with no change in the activity of dopamine beta-hydroxylase was observed after 70 minutes at 5 degrees C. The fall in NE content was completely blocked by pretreating the animals with chlorisondamine. Separation of light and heavy populations of vesicles was achieved with linear sucrose density gradients. Cold stress of 70 minutes duration led to a marked decrease in the NE content of the light vesicles. Blocking adrenergic nerve impulses with chlorisondamine resulted in an increase in total NE in the heart but had no effect on dopamine beta-hydroxylase activity. The initial effect of chlorisondamine was to increase the NE content of the light vesicles. The administration of alpha-methyl-p-tyrosine for 6 hours caused an approximately equal loss of NE from both vesicle populations. The decrease in total heart NE was about 25% and could be prevented by pretreating the animals with chlorisondamine. These results suggest that the light vesicle fraction is involved in the rapid or short-term responses to changes in nerve impulse frequency. Changes in the NE content of the heavy vesicles in rat heart were seen only after longer times, suggesting that these particles may function only as auxiliary storage sites for the neurotransmitter.


Tumour necrosis factor enhances the therapeutic effect of mitoxantrone in human ovarian cancer xenograft.
The combination of Tumour Necrosis Factor (TNF) and mitoxantrone was evaluated for potential chemotherapeutic effect against a human ovarian cancer cell line A2774 hetero-transplanted in female nude mice. Both antitumour efficacy (relative survival and reduction of ascites) and toxicity (weight loss and liver toxicity) of TNF alone, mitoxantrone alone or TNF + mitoxantrone were evaluated. A significant difference (P < 0.002) was observed only among animals bearing tumours treated with mitoxantrone (0.012 mg/Kg) + TNF (5 x 10(5) U/Kg) and controls. No cytotoxic effects were observed for this combination. These observations provide a rationale for further evaluation of TNF + mitoxantrone based regimes for the treatment of recurrent ovarian cancer.


Microbiology on indoor air '99--what is new and interesting? An overview of selected papers presented in Edinburgh, August, 1999.
A multidisciplinary approach to microbiological implications of indoor air is fruitful for research as well as management of health and building problems. The Finnish and the Danish mold programs are examples of such productive collaborative studies. Dust samples taken from classrooms in schools where occupants complain of building-related symptoms (BRS) demonstrated an inflammatory potential in vitro, measured as a release of cytokine interleukin (IL)-8. An increase of the metabolite NO and liberation of tumor necrosis factor (TNF)-alpha and other cytokines during exposure were obtained in vivo, was presented based on these programs and on epidemiological studies on residential fungal contamination and health conducted in Canada and The Netherlands. New methods for assessing fungal exposure are PCA analysis for the toxigenic mold Stachybotrys chartarum and EPS-Asp/Pen for detecting of Aspergillus and Penicillium in dust. Based on a limited data set it is shown that emission rates of fungal spores are inversely proportional to relative humidity (RH), directly related to flow rate and to surface loading. Poor maintenance, risk constructions and risk materials are described in several studies as the main causes of water damage in buildings.


Altered expression of Fcgamma and complement receptors on B cells in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by B cell hyper-reactivity, autoantibody production, immune complex (IC) deposition, and multiple organ damage. The contribution of IC and B cell-mediated changes in the pathogenesis of SLE is well established, however, the exact role of IC-binding receptors expressed on B cells, Fcgamma receptors, and complement receptors CR1 and CR2 in these pathological processes is unclear. Development of lupus-like symptoms in mice defective for the inhibitory Fc-gammaRIIb and genetic association of certain FcgammaR genes with SLE demonstrate a significant role for these receptors but reports indicating alterations of Fcgamma or complement receptor-mediated B cell functions in human SLE are relatively few. The present review highlights a selected set of data including our own discussing the significance of animal models, genetics, and functional alterations of these IC-binding receptors in the etiopathogenesis of SLE.


Self-organization of pulsing and bursting in a CO2 laser with opto-electronic feedback.
We report a detailed investigation of the stability of a CO2 laser with feedback as described by a six-dimensional rate-equations model which provides satisfactory agreement between numerical and experimental results. We focus on experimentally accessible parameters, like bias voltage, feedback gain, and the bandwidth of the feedback loop. The impact of decay rates and parameters controlling cavity losses are also investigated as well as control planes which imply changes of the laser physical medium. For several parameter combinations, we report stability diagrams detailing how laser spiking and bursting is organized over extended intervals. Laser pulsations are shown to emerge organized in several hitherto unseen regular and irregular phases and to exhibit a much richer and complex range of behaviors than described thus far. A significant observation is that qualitatively similar organization of laser spiking and bursting can be obtained by tuning rather distinct control parameters, suggesting the existence of unexpected symmetries in the laser control space.


Mask Responses for Single-Pixel Terahertz Imaging.
Terahertz (THz) radiation meaning electromagnetic radiation in the range from 0.1 (3) to 10 (30) has the unique advantage of easily penetrating many obstructions while being non-hazardous to organic tissue since it is non-ionizing. A shortcoming of this domain is the limited availability of high-sensitivity detector arrays respective THz cameras with >1k pixels. To overcome the imaging limitations of the THz domain, compressive imaging in combination with an optically controllable THz spatial light modulator is a promising approach especially when used in a single-pixel imaging modality. The imaging fidelity, performance and speed of this approach depend crucially on the imaging patterns also called masks and their properties used in the imaging process. Therefore, in this paper, it is investigated how the image quality after reconstruction is specifically influenced by the different mask types and their properties in a compressive imaging modality. The evaluation uses an liquid-crystal display based projector as spatial light modulator to derive specific guidelines for the use of binary and true greyscale masks in THz single-pixel imaging setups respective THz single-pixel cameras when used in far-field applications e.g. stand-off security imaging.


Preliminary human study for possible alteration of serum immunoglobulin E production in perennial allergic rhinitis with fermented milk prepared with Lactobacillus gasseri TMC0356.
The fermented milk prepared with Lactobacillus gasseri TMC0356 was administered at 200 ml per day for 4 weeks to 15 subjects with high serum IgE levels and perennial allergic rhinitis. The serum total IgE concentration was significantly reduced after 28 days' exposure to the fermented milk (P <0.05) compared to that before the intervention. The serum IgE specific to Acari and those to Japanese cedar pollen also significantly declined (P <0.05). T helper 1 (Th1) cells in the composition of their peripheral blood mononuclear cells (PBMCs) significantly increased after 14 days (P <0.01) and after 28 days (P <0.05). These results suggest that the fermented milk prepared with L. gasseri TMC0356 may alter serum IgE concentration, at least partly by enhancement of Th1 immune responses of the subjects with high concentration of serum IgE. However, further studies are still necessary to know the underlying mechanisms by which the tested fermented milk could influence the host immunity.


Transient silylation of the guanosine O6 and amino groups facilitates N-acylation.
[reaction: see text] The formation of a guanosine derivative silylated at both the O6 and amino groups was identified by (15)N NMR. This intermediate allows facile reaction with acetyl chloride or phenoxyacetyl chloride to give in high yield the corresponding N-protected guanosine derivatives, suitable for use in RNA synthesis. The acetyl and phenoxyacetyl amino protecting groups are, respectively, 4 and 230 times more labile than the isobutyryl group to methylamine/ethanol deprotection.


Effects of presentation level on phoneme and sentence recognition in quiet by cochlear implant listeners.
The objectives of this study were to characterize the effects of presentation level on speech recognition in quiet by cochlear implant users with the Nucleus 22 SPEAK and Clarion v1.2 CIS speech-processing strategies, and to relate speech recognition at low presentation levels to stimulus audibility as measured by sound field thresholds. It was hypothesized that speech recognition performance in both Nucleus SPEAK and Clarion CIS participants would decrease as presentation level was decreased below 50 to 60 dBA, due to audibility limitations. However, it was expected that such level effects would be less severe in CIS participants than in SPEAK participants because the Clarion v1.2 device encodes a wider acoustic dynamic range (up to 60 dB) than the Nucleus 22 device (30 dB). Performance-intensity (P-I) functions for vowels, consonants and sentences in quiet were obtained from each participant. P-I functions incorporated speech levels of 70, 60, 50, 40 and 30 dBA. Subjects used their clinical speech processor maps and adjusted the loudness (volume/sensitivity) controls on their processors so that speech presented at 60 dBA was comfortably loud. Maps were created using default clinical procedures and were not adjusted to optimize sound field thresholds. Sound field thresholds and dynamic ranges were measured for warbled pure tones with frequencies of 250 to 6000 Hz. Consonant and sentence recognition showed strong level effects for both SPEAK and CIS participants, with performance decreasing substantially at levels below 50 dBA in most individuals. Vowel recognition showed weaker level effects. For all three speech materials, SPEAK and CIS participants demonstrated similar mean performance at 70 dBA; however, SPEAK participants showed larger reductions in performance than CIS participants with decreasing level. Sound field thresholds were more sensitive for CIS participants than for SPEAK participants, supporting the hypothesis that performance differences were related to audibility. Cochlear implant listeners are unable to maintain good speech recognition at low presentation levels due to reduced stimulus audibility, and this may significantly limit their ability to communicate in daily life. It is likely that audibility differences between SPEAK and CIS participants in the present study can be attributed at least partly to differences in the acoustic dynamic range used by the respective processors. However, several additional factors may have contributed to differences in audibility and perception of soft speech among individual listeners with both devices. These include the minimum and maximum electrical stimulation levels specified in participants' maps and the speech processor sensitivity setting used for testing.


Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.
Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats. MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization. PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (P=0.007). PF4618433 improved stroke volume (P=0.031) and cardiac output (P=0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (P=0.002) and fractional shortening (P=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (P=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI. Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.


Acoustic characteristics of phonation in "wet voice" conditions.
A perceptible change in phonation characteristics after a swallow has long been considered evidence that food and/or drink material has entered the laryngeal vestibule and is on the surface of the vocal folds as they vibrate. The current paper investigates the acoustic characteristics of phonation when liquid material is present on the vocal folds, using ex vivo porcine larynges as a model. Consistent with instrumental examinations of swallowing disorders or dysphagia in humans, three liquids of different Varibar viscosity ("thin liquid," "nectar," and "honey") were studied at constant volume. The presence of materials on the folds during phonation was generally found to suppress the higher frequency harmonics and generate intermittent additional frequencies in the low and high end of the acoustic spectrum. Perturbation measures showed a higher percentage of jitter and shimmer when liquid material was present on the folds during phonation, but they were unable to differentiate statistically between the three fluid conditions. The finite correlation dimension and positive Lyapunov exponent measures indicated that the presence of materials on the vocal folds excited a chaotic system. Further, these measures were able to reliably differentiate between the baseline and different types of liquid on the vocal folds.


Umbilical cord blood hematological parameters in predicting early onset neonatal sepsis (EOS) - a prospective cohort study.
In low and middle income countries, there is a need for affordable and accurate biomarkers to identify neonates at risk of early onset neonatal sepsis (EOS). Cord blood hematological parameters if reliable and accurate for the detection of EOS are cost effective and can reduce the need for repeated venipuncture in the neonate. In this prospective cohort study, the umbilical cord parameters of newborns with gestational age >34 weeks were collected. These neonates were followed up for 72 h and septic screen was employed in those babies who had risk factors or developed clinical features of sepsis. The cord blood parameters of the normal newborn and those who had sepsis were analyzed. A total of 513 neonates were enrolled for the study, 32 required septic screening of whom 13 neonates were found to meet the criteria for sepsis: either blood culture positive or sepsis screen positive with clinical features. Cord blood parameters were analyzed using independent t test. Red cell distribution width (RDW) and band cells were statistically significant (p 0.007 and 0.009 respectively) between the septic and normal neonates. Increased RDW had a sensitivity of 61.54 %, specificity of 54.60 %. Increased band cells with a cut off of >15 cells had a sensitivity of 7.7 % with specificity of 100 % with higher numbers in septic neonates. Increased RDW and band cells in combination had sensitivity of 61.54 % and specificity of 54.6 %. RDW and band cell can be potential markers of EOS in cord blood but require further study in a larger population.


Role of Synthetic Parameters on the Structural and Optical Properties of N,Sn-Copromoted Nanostructured TiO2: A Combined Ti K-Edge and Sn L2,3-Edges X-ray Absorption Investigation.
Sn-modification of TiO2 photocatalysts has been recently proposed as a suitable strategy to improve pollutant degradation as well as hydrogen production. In particular, visible light activity could be promoted by doping with Sn2+ species, which are, however, thermally unstable. Co-promotion with N and Sn has been shown to lead to synergistic effects in terms of visible light activity, but the underlying mechanism has, so far, been poorly understood due to the system complexity. Here, the structural, optical, and electronic properties of N,Sn-copromoted, nanostructured TiO2 from sol-gel synthesis were investigated: the Sn/Ti molar content was varied in the 0-20% range and different post-treatments (calcination and low temperature hydrothermal treatment) were adopted in order to promote the sample crystallinity. Depending on the adopted post-treatment, the optical properties present notable differences, which supports a combined role of Sn dopants and N-induced defects in visible light absorption. X-ray absorption spectroscopy at the Ti K-edge and Sn L2,3-edges shed light onto the electronic properties and structure of both Ti and Sn species, evidencing a marked difference at the Sn L2,3-edges between the samples with 20% and 5% Sn/Ti ratio, showing, in the latter case, the presence of tin in a partially reduced state.


Is human growth hormone an ergogenic aid?
Growth hormone (GH) was first isolated from the pituitary gland in the 1940s. It is believed that athletes have been abusing GH for its anabolic and lipolytic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. Most of our knowledge about GH abuse is anecdotal but a number of high-profile athletes have admitted using GH. Despite its widespread abuse, there is debate about whether GH is ergogenic. Indeed most scientific studies have not shown a performance enhancing effect. This review will address why this discrepancy of opinion between athletes and scientists exists and why the author believes that the scientists are wrong.


[The long term preservation of information in digital form: risks, stake and outline of practical solutions].
All information is now created, handled, stored and often used in digital form: we observe a formidable growth in the volume of data created, transmitted and archived. However, the obsolescence of technologies and the lack of appropriate organisation lead to a spectacular vulnerability to time after 5-10 years. Every sector of activity in today's society is concerned, public and private organizations, scientific research, etc. The ISO standard Reference Model for an Open Archival information System provides us with a high level of understanding of the problem to solve. This Model is essential for the emergence of practical solutions.


Role of ultrasonography in the differential diagnostics of neck masses.
Ultrasonography of 70 cases of palpable neck masses are analyzed. On the basis of histological diagnoses the cases are put into groups of cysts, tumors and other lesions of the neck. According to this grouping the aetiological factors are also discussed (congenital lesions: mainly cysts, lesions of the salivary glands and the parotid gland, thyroid and parathyroid diseases, vascular lesions). The diagnostic value of ultrasonography is calculated in view of the morphological signs of a given lesion. The specificity, sensitivity and the accuracy of ultrasonography in our material supports the view that in the differential diagnostics of neck masses ultrasonography is a useful, simple and effective tool.


Integrating Computation into Science Education.
The Current Insights feature highlights diverse perspectives on education from beyond the LSE community. In this installment, I have chosen articles that offer different perspectives on the surge of interest in integrating computation into science learning. These articles present theoretical frameworks, propose methodological approaches, and raise critical questions about the purpose and impact of making computation foundational to science education.


[Improvement of the non-invasive diagnosis of coronary heart disease using a new double-isotope method for the noninvasive determination of coronary transit times].
In conventional myocardial Thallium-201 scintigraphy, regional myocardial Thallium-201 activity is compared to the area of normal, i.e., maximal activity. In the presence of multivessel coronary artery disease, this mode of evaluation may yield false negative results. -In 87 patients suffering from coronary artery disease and in 26 controls, after simultaneous i.v. injection of Thallium-201 and Technetium-99m coronary transit times of Thallium-201 were determined as the interval between arrival of the tracer in the aortic root and the onset of its extraction in different myocardial areas. - Patients with hemodynamically significant coronary artery stenoses (greater than or equal to 75%) revealed a significant increase in coronary transit times over septum, apex, or posterolateral wall of the left ventricle. Using maximal coronary transit times, i.e., the largest of the regional values, an excellent discrimination between patients with severe coronary artery stenoses and controls was achieved. Following coronary vasodilatation with dipyridamole, even subcritical (50-75%) coronary artery stenoses could be detected with high sensitivity, since the shortening of coronary transit times in patients with subcritical stenoses was less pronounced as compared to controls. - Especially in the presence of diffuse three-vessel coronary artery disease, the quantitative assessment of regional coronary transit times yields important parametric data in addition to those obtained by conventional Thallium-201 scintigraphy combining static imaging with rapid sequence analysis of time-activity curves.


Bidirectional association between Bell's palsy and anxiety disorders: A nationwide population-based retrospective cohort study.
Bell's palsy and anxiety disorders share numerous risk factors (e.g., immune response, ischemia, and psychological stress). However, there have been no studies on the bidirectional temporal association between the two illnesses. In this study, we used the Taiwan National Health Insurance Research Database (NHIRD) to test the bidirectional association between Bell's palsy and anxiety disorders. We hypothesized that patients with Bell's palsy would have an increased risk of subsequent anxiety disorders later in life and that, conversely, those with anxiety disorders would have an increased likelihood of developing Bell's palsy later in life. We conducted two retrospective cohort studies using Taiwan's National Health Insurance Research Database (NHIRD). Study 1 included 8070 patients diagnosed with anxiety disorders and 32,280 controls without anxiety disorders who were matched with sex, age, and enrollment date to analyze the following risk of Bell's palsy among both groups. Study 2 included 4980 patients with Bell's palsy and 19,920 controls without Bell's palsy who were matched with sex, age, and enrollment date to analyze the following risk of anxiety disorders among both groups. The patient records selected for the studies were dated between January 1, 2000, and December 31, 2004. All subjects were observed until their outcomes of interest, death or December 31, 2009. After adjustment for age, sex, comorbidities, urbanization, and income, the hazard ratio (HR) for patients with anxiety disorders to contract Bell's palsy was 1.53 (95% CI, 1.21-1.94, P<.001), and the HR for patients with Bell's palsy to develop an anxiety disorder was 1.59 (95% CI, 1.23-2.06, P<.001). This study found a bidirectional temporal association between Bell's palsy and anxiety disorders. After one of these conditions develops, the morbidity rate for the other significantly increases. Additional studies are required to determine whether these two conditions share the same pathogenic mechanisms, and whether successfully treating one will reduce the morbidity rate for the other.


Confocal immunolocalization of bovine serum albumin, serum retinol-binding protein, and interphotoreceptor retinoid-binding protein in bovine retina.
Recently it has been shown that the transport as well as clearance of retinol from isolated rod photoreceptors requires an extracellular factor. Interphotoreceptor retinoid-binding protein (IRBP) is a component of the interphotoreceptor matrix (IPM) and is known to bind visual cycle retinoids. Serum albumin and serum retinol-binding protein (sRBP), proteins capable of binding retinoids, have also been reported to be components of the IPM. It is of interest to know the components present in the IPM that are capable of binding visual cycle retinoids and that also facilitate rhodopsin regeneration. The purpose of this study was to determine the localization of serum albumin, sRBP, and IRBP in bovine retina using immunofluorescence analysis. Fresh bovine eyes, obtained from a local abattoir, were fixed immediately after enucleation. Tissue sections (100 microm) were incubated with primary antibodies to bovine serum albumin (BSA), sRBP, and IRBP. Sections were washed then incubated 4 h with 4'-6-Diamidino-2-phenylindole (DAPI), Alexa Fluor(R) 488 goat antimouse, and Alexa Fluor 568 goat antirabbit secondary antibodies. Sections were analyzed using a laser scanning confocal microscope equipped with Nomarski optics. Western immunoblot analysis of bovine retinal tissues and protein standards was performed using the primary antibodies to BSA, sRBP, and IRBP to show specificity to their respective antigens. Immunoblot analysis showed that monoclonal anti-BSA was highly specific for BSA detecting only a single band at about 67 kDa. Antihuman sRBP and antibovine IRBP were also highly specific, recognizing a single band at about 25 and about 133 kDa, respectively. No immunopositive bands were observed in bovine neural retinal when probed with the anti-sRBP antibody; however, a single immunoreactive band at about 67 and about 133 kDa was detected in bovine neural retina by the anti-BSA and IRBP antibodies, respectively. Immunofluorescence analysis showed labeling for IRBP throughout the IPM. IRBP labeling was especially associated with the outer segments of photoreceptors and also with the apical surface of the retinal pigment epithelium. Immunofluorescence labeling for serum albumin was associated only with the lumen of retinal and choroidal blood vessels. Staining for both serum albumin and sRBP in the IPM was negative. Immunofluorescence analysis of fresh bovine eyes using antibodies to BSA and sRBP clearly shows that serum albumin and sRBP are not components of bovine IPM. IRBP, on the other hand, is localized to the IPM where it is available for the binding and transport of visual cycle retinoids. From these data we conclude that serum albumin and sRBP are not factors that could participate in the binding as well as transport of visual cycle retinoids in the IPM of bovine retina.


Bioactive glasses meet phytotherapeutics: The potential of natural herbal medicines to extend the functionality of bioactive glasses.
Herbal medicine, the use of plants or plant extracts with known beneficial biological effects to treat and/or prevent diverse health disorders, has been known for thousands of years. After their replacement by synthetic drugs in the beginning of the 20th century, plant derived therapeutic agents have been recently attaining more attention again. Phytotherapeutics, which can be extracted from a wide range of different herbal plants, are believed to have a broad spectrum of therapeutic effects and less negative side effects than synthetic drugs. On the other hand, it is often difficult to prove the therapeutic effect of herbal drugs due to their chemical complexity. In the last decade, research has focused increasingly on the relatively new concept of the combination of herbal drugs with modern engineered biomaterials in order to achieve synergy of their therapeutic effects. Even if several studies based on this concept have been published, no systematic overview of the performed investigations and their results is available. In this context, this review focuses on the combination of phytotherapeutics with bioactive glasses (BGs), which are bioactive and biodegradable materials capable of releasing biologically active ions being suitable for several applications as bone substituting and replacing materials as well as in the regeneration of soft and hard tissue. The literature search was carried out using the WEB OF SCIENCE® and SCOPUS® databases using a combination of relevant keywords. Besides giving an overview of the research done in the last years and summarizing the results obtained in those studies, the possible synergistic effects of herbal drugs in combination with BGs are critically discussed, and potential health risks are overviewed. Of all plant-derived drugs investigated so far, the coumarin family appears to be the one that has been most widely combined with BGs showing beneficial outcomes. Overall, the analysis of the literature has revealed the great potential of this organic-inorganic multi-functional system approach as an advantageous alternative to conventional medicine in several applications, but also highlights the need for more systematic in vivo studies to evaluate the effective time and dose dependent combined effects of BGs and phytotherapeutic agents.


[Malignant lymphoma of the orbit].
The authors describe a non-Hodgkin malignant large-cell B lymphoma with ample lymphocytes in a female patient with foci in the left breast and right orbit, with suspect skin foci and enlarged nodes in the mediastinum as revealed by computed tomography. In the differential diagnosis the authors reflected according to the course of the disease in addition to malignant lymphoma also on orbitocellulitis or a pseudotumour of the orbit. The remarkable feature is that the patient had already treatment on account of a multiple myeloma. The authors emphasize comprehensive treatment of the patient and the necessity of consultations with specialist of other medical disciplines associated with this disease. After radiotherapy total regression of the orbital finding occurred in the patient.


[Development of Western Hospitals in Shanghai in modern times-study of hospitals affiliated to the Municipal Council].
The first western hospital, Renji Hospital, was set up in Shanghai in 1844. Until 1943, 72 western hospitals were founded in public concession and among them 14 were affiliated to the Municipal Council. The establishment of Municipal Council affiliated hospitals marked the beginning of the Municipal Council offering service to the public. Apart from of Municipal Council affiliated hospitals, there were also western hospitals in the public concession created by social societies or individuals. The appearance of western hospitals promoted the change of object where people sought medical service, and embodied people's increased need of western medicine, which promoted the systemization of western medicine in China to some extent.


Destabilization of CAG trinucleotide repeat tracts by mismatch repair mutations in yeast.
To examine the genetic factors that affect the stability of disease-associated trinucleotide repeats, we have assessed the stability of CAG repeats in yeast strains with mutations in the mismatch repair system. We have found that both pms1 and msh2 mutations destabilize repeat tracts. Destabilization is evidenced both by the increased frequency of repeat length changes and in the pattern of changes that are observed. In wild-type cells repeats are relatively stable when CAG serves as the lagging strand template but relatively unstable when CTG serves as the lagging strand template. Large contractions in repeat length are the most common change. In pms1 and msh2 mutants the relatively stable tracts incur more tract length changes. In addition, many small deletions and some small additions, most often of one repeat unit, are frequent in repeats of the stable orientation. These small changes also are seen as a new class of events that occur in repeats in the unstable orientation. The results show that in yeast the mismatch repair system prevents small changes from occurring but cannot prevent larger changes from occurring.


The sulfonylurea receptor Sur is dispensable for chitin synthesis in Drosophila melanogaster embryos.
Chitin produced by membrane-inserted chitin synthases is an important constituent of the arthropod cuticle and midgut peritrophic matrix. Chitin synthesis inhibitors are common insecticides in pest control. As the target of sulfonylurea-derived insecticides such as diflubenzuron, the ABC transporter sulfonylurea receptor (Sur) has been postulated to be an essential cofactor of chitin synthesis. However, direct evidence for this assumption is missing. Here, a study has been made of the phenotype of Drosophila melanogaster larvae suffering completely eliminated Sur function. Taken together, it is found that cuticle architecture is normal and chitin amounts are not diminished in the cuticle of these animals, indicating that Sur is dispensable for chitin synthesis. The data obtained suggest that there must exist another sulfonylurea-sensitive ABC transporter that either instead of Sur is the true sulfonylurea-sensitive transporter involved in chitin synthesis or is able to substitute Sur function during cuticle formation. Identification and characterisation of this factor is pivotal for understanding the mode of action of sulfonylurea as insecticide.


Sensory exotropia associated with keratoconus and review of literature: strabismus and keratoconus.
To present a case of sensory strabismus due to keratoconus with an ipsilateral nodular lesion of the bulbar con-junctiva. The patient is a 17 year-old-boy. The fixing eye was the right eye and keratoconus in this eye was late onset. Vision in the left eye was poor and keratoconus was advanced in this eye. Due to longstanding of keratoconus and occurrence in the sensitive period, sensory exotropia had developed in the left eye. A nodular lesion of the bulbar conjunctiva was also present in the ipsilateral eye. Sensory exotropia is not unusual but to be due to longstanding keratoconus is not a usual strabismus. If keratoconus develops before 7 years of age, sensory strabismus can develop. We reported and reviewed literature that keratoconus seldom begins in the sensitive period where abnormal visual experience affects visual development and may induce sensory exotropia.


Evidence for a positive correlation between in vitro radiosensitivity of normal human skin fibroblasts and the occurrence of subcutaneous fibrosis after radiotherapy.
A colony-forming assay of human skin fibroblast radiosensitivity was established in our laboratory and applied to primary skin biopsies from 12 women belonging to an unselected group of patients who received postmastectomy radiotherapy 10-12 years prior to this study. The aim was to investigate the relationship between in vitro radiosensitivity and the occurrence of subcutaneous fibrosis after radiotherapy. Early generations of normal skin fibroblasts in exponential growth were irradiated at room temperature at a high dose-rate to estimate the surviving fraction of colony-forming cells after single doses ranging from 1 to 8 Gy. A linear-quadratic cell survival curve was fitted to the data and from these fits the surviving fraction at 3.5 Gy (SF3.5) was estimated. Replicate experiments of different cell generations were made to validate the assay, and the between-patients variability was significantly larger than the assay variability for both SF2(p = 0.002) and SF3.5 (p = 0.04). Patients were treated in the period 1978-1982 with a dose per fraction between 2.7 and 3.9 Gy, a total of 12 fractions at two fractions per week. They were evaluated with respect to the occurrence of marked subcutaneous fibrosis in a total of 36 independent treatment fields. In each treatment field the total dose and dose per fraction at the relevant dosimetric reference depth as well as the length of follow-up were recorded. A previously derived LQ mixture model was applied to these data in order to determine the probability of marked fibrosis in that particular field. From this probability and the actually observed fibrosis, the excess risk of fibrosis was calculated, and this was averaged over the three treatment fields to obtain a single measure of clinical radiosensitivity. Increasing values of SF3.5 were statistically significantly correlated with decreasing probabilities of developing subcutaneous fibrosis (p = 0.014, Spearman's rank correlation test). Thus, this pilot study has demonstrated a positive correlation between in vivo radiosensitivity and normal skin fibroblasts and the clinical expression of subcutaneous fibrosis.