Complexity of Plasmodium falciparum infection and genetic variations associated with differences in parasite clearance time in two Malian villages.
Effective approaches to fight against malaria include disease prevention, an early diagnosis of malaria cases, and rapid management of confirmed cases by treatment with effective antimalarials. Artemisinin-based combination therapies are first-line treatments for uncomplicated malaria in endemic areas. However, cases of resistance to artemisinin have already been described in South-East Asia resulting in prolonged parasite clearance time after treatment. In Mali, though mutations in the K13 gene associated with delayed clearance in Asia are absent, a significant difference in parasite clearance time following treatment with artesunate was observed between two malaria endemic sites, Bougoula-Hameau and Faladje. Hypothetically, differences in complexity of Plasmodium falciparum infections may be accounted for this difference. Hence, the aims of this study were to assess the complexity of infection (COI) and genetic diversity of P. falciparum parasites during malaria treatment in Bougoula-Hameau and Faladje in Mali. Thirty (30) patients per village were randomly selected from 221 patients enrolled in a prospective artesunate monotherapy study conducted in Faladje and Bougoula-Hameau in 2016. All parasitemic blood samples of patients from enrollment to last positive slide were retained to assess malaria parasite COI and polymorphisms. DNA were extracted with a Qiagen kit and Pfcsp and Pfama1 encoding gene were amplified by nested PCR and sequenced using the Illumina platform. The parasite clearance time (PCT) was determined using the parasite clearance estimator of Worldwide Antimarial Resistance Network (WWARN). Data were analyzed with R®. The median number of genetically distinct parasite clones was similar at enrollment, 7 (IQR of 5-9) in Faladje and 6 (IQR of 4-10) in Bougoula-Hameau (p-value = 0.1). On the first day after treatment initiation, the COI was higher in Faladje (6; CI:4-8) than in Bougoula-Hameau (4; CI:4-6) with a p-value =0. 02. Overall, COI was high with higher PCT. Finally, there was a low genetic diversity between Faladje and Bougoula-Hameau. This study demonstrated that the difference in PCT observed between the two villages could be due to differences in the complexity of infection of these two villages.


Educational theory into practice: development of an infection control link nurse programme.
Nationally, 9-10% of hospital in-patients acquire an infection during their admission. These infections are a major source of avoidable morbidity, mortality and additional resource use. Many could be prevented by use of effective infection control practi ces. However, the theory-practice gap affects compliance with infection control procedures in the same way that it affects other areas of nursing practice. Infection control link nurse groups have been implemented by some infection control nurses as a me thod of improving practice at clinical level. However these programmes often rely upon traditional models of nurse education, which may not meet the educational needs of link nurses. This will limit the ability of link nurses to implement theory in pract ice. This paper discusses the application of educational theory to an infection control link nurse programme. It explains why each aspect of the programme is important, and why traditional models are not suitable. By applying theory to the practice of in fection control education, it should be possible to develop a group of infection control link nurses who are clinical opinion leaders. These staff will be ideally placed to influence practice using a number of different strategies, which should in turn r educe the theory-practice gap at clinical level.


Effects of Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin on Episodic Memory in Healthy Older Adults.
Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline.


Aortic Isthmus Narrowing after Endovascular Repair of Acute Traumatic Aortic Transection.
The traumatic transection is located in the normal sized aortic isthmus where the angle is curved. We found a reversal of upper and lower blood pressure differences among patients who underwent thoracic endovascular aortic repair (TEVAR) for transection of the thoracic aorta. We investigated the isthmus stenosis in patients who underwent TEVAR for aortic injury using computed tomography. Sixteen patients who underwent TEVAR for transection were divided in two groups: the aortic narrowing (AN) group and the non-aortic narrowing (NAN) group. AN was defined as stent graft folding more than 5 mm at the isthmus confirmed by computed tomography. The length of aorta at isthmus, pseudoaneurysm, and angle of isthmus were measured. AN was noted in five patients (31.3%). The area index in the NAN group (2.16±0.35 cm2/m2) was larger than that in the AN group (1.74±0.77 cm2/m2). The size of the pseudoaneurysm in the NAN group (31.9±4.2 mm) was smaller than that in the AN group (37.4±7.5 mm). The distance from the subclavian artery in the NAN group (15.7±9.3 mm) was longer than that in the AN group (8.4±3.2 mm) but not statistically significant. The angle of the isthmus in the NAN group (131±6 degrees) was larger than that in the AN group (107±3 degrees), and this was the only statistically significant difference (P=0.002). AN by stent graft folding should be considered when performing TE-VAR in aortic injury with an acute angle of the isthmus less than 110 degrees.


Alterations in porcine gastric mucin during the development of experimental ulceration.
Bile duct ligation in the pig results in ulceration of the pars oesophagea (oesophagogastric junction) within 48 h with 100% reproducibility. This work describes novel observations made during development of such ulcers using an endoscope introduced at intervals postoperatively via a Thomas gastric cannula. Macroscopic and histological changes were recorded and compared with quantitative and qualitative changes in crude mucus scrapings and purified mucins. Crude mucus scrapings of the cardiac gland region had a higher protein content in the ulcerated states than in the normals. After bile duct ligation, the (degraded) mucin glycopeptide/total protein ratio was higher in partially purified mucus from pre-ulcerated and ulcerated stomachs as compared with normal samples. The quantity of purified mucin was less in samples from ulcerated stomachs, and the N-acetylgalactosamine and fucose contents were also decreased. It is possible that these changes resulted in the failure of the mucus barrier and the development of oesophagogastric junction ulceration.


C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.
Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors exert divergent contributions to the development of antifungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking Ag-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival, and migration. Whereas Card9 signaling is essential, C-type lectin receptors offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells.


Reciprocity in autistic and typically developing children and adolescents with and without mild intellectual disabilities.
The assessment of autism in individuals with mild intellectual disabilities (MID) is complicated because of the overlap between autistic traits and intellectual limitations. Impaired social emotional reciprocity is a core diagnostic criterion for autism. However, it is unknown whether reciprocal behaviour differs between MID individuals with or without an autism spectrum disorder (ASD). This study explored differences in reciprocal behaviour of 35 children and adolescents with MID (intelligence quotient 50-85): 15 with ASD (ASD-MID) and 20 with typical development (TD-MID) using the Interactive Drawing Test (IDT). ASD-MID participants showed a lower quality of reciprocal behaviour compared with TD-MID participants. The difference in quality of reciprocal behaviour between ASD-MID and TD-MID participants was not significantly related with Peabody Picture Vocabulary Test scores and thus not attributable to verbal capacity. The IDT is likely to reflect the child's inclination to display reciprocal behaviour in everyday situations, as its scale scores were meaningfully associated with the level of social cognition assessed with the Social Responsiveness Scale. Thus, the IDT seems well suited for measuring impairments in reciprocal behaviour in children and adolescents with MID.


Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines.
Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide. We compared the activity of ARN versus bicalutamide on prostate cancer cell lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN and bicalutamide on the expression cytoplasmic/nuclear kinetics of AR, AR-V7 variant, phosphorylated AR, as well as the levels of the AR downstream proteins prostate-specific antigen and TMPRSS2, under exposure to testosterone and/or hypoxia. The effects on autophagic flux (LC3A, p62, TFEB, LAMP2a, cathepsin D) and cell metabolism-related enzymes (hypoxia-inducible factor 1α/2α, BNIP3, carbonic anhydrase 9, LDHA, PDH, PDH-kinase) were also studied. The 22Rv1 cell line responded to testosterone by increasing the nuclear entry of AR, AR-V7, and phosphorylated AR and by increasing the levels of prostate-specific antigen and TMPRSS2. This effect was strongly abrogated by ARN and to a clearly lower extent by bicalutamide at 10 μmol/l, both in normoxia and in hypoxia. ARN had a stronger antiproliferative effect than bicalutamide, which was prominent in the 22Rv1 hormone-responsive cell line, and completely repressed cell proliferation at a concentration of 100 μmol/l. No effect of testosterone or of antiandrogens on autophagy flux, hypoxia-related proteins, or metabolism enzyme levels was noted. The PC3 and DU145 cell lines showed poor expression of the proteins and were not responsive to testosterone. On the basis of in-vitro studies, evidence has been reported that ARN is more potent than bicalutamide in blocking the AR pathway in normoxia and in hypoxia. This reflects a more robust, dose-dependent, repressive effect on cell proliferation.


Induced pluripotent stem cells for cardiovascular disease: from product-focused disease modeling to process-focused disease discovery.
Induced pluripotent stem (iPS) cell technology offers an unprecedented opportunity to study patient-specific disease. This biotechnology platform enables recapitulation of individualized disease signatures in a dish through differentiation of patient-derived iPS cells. Beyond disease modeling, the in vitro process of differentiation toward genuine patient tissue offers a blueprint to inform disease etiology and molecular pathogenesis. Here, we highlight recent advances in patient-specific cardiac disease modeling and outline the future promise of iPS cell-based disease discovery applications.


Assay methods based on proximity-enhanced reactions for detecting non-nucleic acid molecules.
Accurate and reliable detection of biological molecules such as nucleic acids, proteins, and small molecules is essential for the diagnosis and treatment of diseases. While simple homogeneous assays have been developed and are widely used for detecting nucleic acids, non-nucleic acid molecules such as proteins and small molecules are usually analyzed using methods that require time-consuming procedures and highly trained personnel. Recently, methods using proximity-enhanced reactions (PERs) have been developed for detecting non-nucleic acids. These reactions can be conducted in a homogeneous liquid phase via a single-step procedure. Herein, we review three assays based on PERs for the detection of non-nucleic acid molecules: proximity ligation assay, proximity extension assay, and proximity proteolysis assay.


The study of the third heart sound in relation to the left ventricular filling and wall movement by echocardiography.
The left ventricular filling and wall movement were investigated in subjects with a third heart sound or ventricular gallop by echocardiography. Nine patients with ventricular gallop, who had left ventricular volume overload disease, and 6 normal subjects with a third heart sound had higher normalized peak rate of increase of the left ventricular dimension (peak dD/dT/D) than 10 normal subjects without a third heart sound (p less than 0.01). The normalized lengthening rate in the rapid filling phase was also higher in patients with ventricular gallop than in normal subjects without a third heart sound (p less than 0.05). The time from the second heart sound to peak dD/dT/D and rapid filling time did not show statistically significant values between subjects with ventricular gallop or a third heart sound and those without a third heart sound. These results suggest that higher peak filling, larger filling volume in the rapid filling phase and more abrupt cessation of the outward movement of the left ventricular wall may be a cause of the production of ventricular gallop in patients with left ventricular volume overload and of the physiological third heart sound.


Pseudomonas capsici sp. nov., a plant-pathogenic bacterium isolated from pepper leaf in Georgia, USA.
Three phytopathogenic bacterial strains (Pc19-1T, Pc19-2 and Pc19-3) were isolated from seedlings displaying water-soaked, dark brown-to-black, necrotic lesions on pepper (Capsicum annuum) leaves in Georgia, USA. Upon isolation on King's medium B, light cream-coloured colonies were observed and a diffusible fluorescent pigment was visible under ultraviolet light. Analysis of their 16S rRNA gene sequences showed that they belonged to the genus Pseudomonas, with the highest similarity to Pseudomonas cichorii ATCC 10857T (99.7 %). The fatty acid analysis revealed that the majority of the fatty acids were summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), C16 : 0 and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). Phylogenomic analyses based on whole genome sequences demonstrated that the pepper strains belonged to the Pseudomonas syringae complex with P. cichorii as their closest neighbour, and formed a separate monophyletic clade from other species. Between the pepper strains and P. cichorii, the average nucleotide identity values were 91.3 %. Furthermore, the digital DNA-DNA hybridization values of the pepper strains when compared to their closest relatives, including P. cichorii, were 45.2 % or less. In addition, biochemical and physiological features were examined in this study and the results indicate that the pepper strains represent a novel Pseudomonas species. Therefore, we propose a new species Pseudomonas capsici sp. nov., with Pc19-1T (=CFBP 8884T=LMG 32209T) as the type strain. The DNA G+C content of the strain Pc19-1T is 58.4 mol%.


Implementation strategies for the patient safety reporting system using Consolidated Framework for Implementation Research: a retrospective mixed-method analysis.
Healthcare-related adverse events occur because of complex healthcare systems. The patient safety reporting system is a core component of patient safety initiatives in hospitals. However, hospital management often encounters a cultural barrier with its implementation and struggles to overcome the same. Implementation science would be useful for analysing implementation strategies. This study determines the effects of the implemented strategy on an increase in the number of patient safety reports and the determinants of successful implementation, using the implementation framework. Mixed method analysis was performed in Fujita Health University Hospital (FHUH), a large volume hospital in Japan. We identified strategies to implement the patient safety reporting system by scrutinising internal documents using the Consolidated Framework for Implementation Research (CFIR). The electronic reporting systems developed in 2004 in the FHUH and the number of reports were analysed using the staff data and hospital volumes. Reports (n = 110,058) issued between April 2004 and March 2020 were analysed. The number of reports increased from 2004 to 2008 and from 2013 to 2019, reaching 14,037 reports per year. Between 2009 and 2012, the FHUH experienced a stagnation period where the number of reports were not increasing. From the qualitative materials, we identified 74 strategies which contributed to the implementation of the patient safety reporting system. Among these, the domain of 'intervention characteristics' in the CFIR contained 12 strategies, 'outer settings' contained 20, 'inner settings' contained 21, 'characteristics of individuals' contained 8, and 'process' contained 13. There were two concentrated periods of the implemented strategies, the number was 17 in 2007 and 10 in 2016. These concentrated periods preceded a remarkable increase in the number of patient safety reports. A safety culture had been fostered in FHUH in the study period. A relationship between number of strategies and development of a reporting culture was observed. The intensity of adequate strategies was needed for implementation of patient safety reporting system. Therefore, the implementation framework is useful for analysing patient safety initiatives for safety culture.


Far-field coherent backscatter enhancement from random aggregations of scatterers and comparisons to backscattering from single isolated spheres.
Coherent backscatter enhancement (CBE), a multiple scattering phenomenon, may cause an enhancement of up to a factor of two in the average intensity backscattered from a random aggregation of scatterers. In the ocean, CBE may occur when a fish school or a bubble cloud is remotely illuminated. The research reported here explored the possibility that CBE might be used to remotely discriminate between an aggregation of many scatterers and a single isolated scattering object. For this investigation, the far-field harmonic acoustic pressure backscattered from aggregations of randomly placed omnidirectional point scatterers was determined from numerical solution of the equations from Foldy [(1945) Phys. Rev. 67(3,4), 107-119], and compared to equivalent results from single spherical scatterers having hard surfaces, pressure-release surfaces, or aggregation-matched effective-medium properties. Interestingly, CBE causes a spherical aggregation to backscatter as much or more sound than a single perfectly reflecting sphere of the same size when (ka)1/2(ks)-4/5(kσs1/2)3/4 ≥ 2.3, where k is the acoustic wave number, a is the aggregation radius, s is the average spacing between scatterers, and σs is a scatterer's cross section. And, backscattered intensity samples (in dB) from all simulated aggregations followed an extreme value distribution, a finding that supports the conventional use of backscatter statistics for remote aggregation-versus-single-object discrimination.


Long-term results of valve replacement with the CarboMedics prosthetic heart valve.
This study examined the long-term results of the CarboMedics prosthetic heart valve. Between July 1990 and May 2000, 256 CarboMedics valve prostheses (120 single aortic, 62 single mitral, and 34 double aortic/mitral) were implanted into 216 patients (mean age 57.8 years). The mean follow-up was 57.7 +/- 36 months (maximum 133 months) with a total of 1,038.4 patient years. Patient survival, including operative deaths, was 85.1% at 10 years. Linearized rates for various complications were thromboembolism 0.39% per patient year, bleeding events 0.39% per patient year; prosthetic valve endocarditis 0.29% per patient year, nonstructural dysfunction 0.87% per patient year, and reoperation 0.39% per patient year. There were no valve thrombosis or structural valve failures in this series. The probabilities of freedom from thromboembolism and reoperation at 10 years were 96.3% and 93.1%, respectively. In conclusion, the CarboMedics valve can be used satisfactorily with a low incidence of thromboembolism and valve thrombosis.


Up-to-date estimates of cancer patient survival even with common latency in cancer registration.
In an era of ongoing improvement in cancer patient survival, available long-term survival figures from cancer registries are often outdated and too pessimistic for two reasons: first, delay in availability of cancer registry data, typically in the order of a few years, and, second, application of cohort-based methods of survival analysis, which provide survival estimates for patients diagnosed many years ago. We developed a model-based period analysis approach aimed to overcome both problems. We provide extensive empirical evaluation of our approach by comparing its performance with that of previously available methods for monitoring of 5- and 10-year relative survival, with the use of data from the nationwide Finnish Cancer Registry of 490,279 patients ages >/=15 years and diagnosed with one of 20 common forms of cancer between 1953 and 1997. We show that, in most cases, the model-based approach predicts 5- and 10-year relative survival expectations of newly diagnosed patients quite closely and much better than any of the previously available methods, including standard period analysis. We conclude that the model-based approach may enable deriving up-to-date cancer survival rates even with the common latency in availability of cancer registry data.


Fibroblast Growth Factor and Mineral Metabolism Parameters among Prevalent Kidney Transplant Patients.
Background. Chronic kidney disease (CKD) related mineral bone disorders persist after kidney transplantation, but little is known about the relationship between fibroblast growth factor-23 (FGF-23) and mineral metabolism in prevalent post-transplant patients. Objectives. To examine mineral metabolism parameters and their relationship to FGF-23 and parathyroid hormone (PTH) in prevalent kidney transplant patients. Methods. Cross-sectional study of 106 kidney transplant patients enrolled November 2005-October 2009 at Tufts Medical Center (TMC), Boston. Results. The prevalence of hypophosphatemia was 34%, hypercalcemia 3%, and elevated PTH levels 66%, at a median (25th-75th percentile) duration of 12.8 (7.5-30.9) months post-transplant. Males had significantly higher levels of PTH (P = 0.04) and lower levels of serum phosphate (P = 0.002). Serum PTH levels did not relate to eGFR, corrected calcium levels or serum phosphate. FGF-23 levels were above the reference limits in 7% of patients; higher levels were associated with higher serum phosphate and PTH levels after adjustment for transplant kidney function. Conclusion. FGF-23 is an important driver of mineral metabolism in prevalent transplant patients. Its modulatory role in mineral metabolism homeostasis may be heightened as feedback suppression of PTH is disturbed. Its role in long term cardiovascular and graft outcomes needs further study.


[Improved diagnosis of pregnancy-associated gynaecological emergencies via rapid beta-HCG test (author's transl)].
A pregnancy-related disorder was identified by a rapid radioimmunoassay or serum chorionic gonadotropin in 151 out of 600 women (25%) with lower abdominal pain or bleeding, while a routine pregnancy test in urine was positive in only 7% of these cases. In 60 patients with ectopic pregnancy the rapid hCG-RIA was positive in 90% as compared with 10% for the routine pregnancy test. In patients with evidence of intrauterine pregnancy (80 cases) the rapid hCG-RIA was positive in 99% and routine pregnancy test in 39%. The clinical sensitivity of the hCG-RIA was 95%, specificity 96% and predictive value 88%. These figures should introduce a considerable improvement in the routine diagnosis of early intra- and extrauterine pregnancy-related disorders.


Child health care in changing times.
Unprecedented transformations in the financing and organization of child health care are driving change in the practice of pediatrics at a remarkably fast pace. The health care needs of children also are evolving, reflecting changing disease patterns, new technologies, and shifting socioeconomic and demographic characteristics of children and families. Changes in the financing and organization of child health services catalyzed by managed care and legislative initiatives need to be responded to proactively by the pediatric community. Yet, the anticipated health care needs of children also must be addressed as models for both pediatric training and practice in the future are developed. This article summarizes briefly these changes in health care services and in child health needs, addresses training implications, and discusses several initiatives the pediatric community is undertaking to develop guidelines for training pediatricians for the 21st century.


Inequality in analgesic prescription in Spain. A gender development issue.
It is well known that sex differences in analgesic prescription are not merely the logical result of greater prevalence of pain in women, since this therapeutic variability is related to factors such as educational level or social class. This study aims to analyse the relationship between analgesic prescription and gender development in different regions of Spain. Cross-sectional study of sex-differences in analgesic prescription according to the gender development of the regions studied. Analgesic prescription, pain and demographic variables were obtained from the Spanish Health Interview Survey in 2006. Gender development was measured with the Gender Development Index (GDI). A logistic regression analysis was conducted to compare analgesic prescription by sex in regions with a GDI above or below the Spanish average. Once adjusted by pain, age and social class, women were more likely to be prescribed analgesics than men, odds ratio (OR) = 1.74 (1.59-1.91), as residents in regions with a lower GDI compared with those in region with a higher GDI: ORWomen = 1.26 (1.12-1.42), ORMen = 1.30 (1.13-1.50). Women experiencing pain in regions with a lower GDI were more likely than men to be treated by a general practitioner rather than by a specialist, OR = 1.32 (1.04-1.67), irrespective of age and social class. Gender bias may be one of the pathways by which inequalities in analgesic treatment adversely affect women's health. Moreover, research into the adequacy of analgesic treatment and the possible medicalisation of women should consider contextual factors, such as gender development.


Immediate complications following hip and knee arthroplasty: does race matter?
Black race has been associated with a higher rate of complications following total joint arthroplasty, such as infection, deep vein thrombosis, pulmonary embolism, and death. We hypothesized that there would be no significant association between black race and adverse outcome when medical conditions were adjusted for. Data on 585,269 patients from the Nationwide Inpatient Samples were assessed by multivariable logistic regression analysis. Black race was significantly associated with postoperative complication and death. Comorbidities do not account for racial differences in adverse events. Black race was an independent predictive factor for increased complications and death following hip and knee arthroplasty.


Lung Ultrasound Combined With Procalcitonin for a Diagnosis of Ventilator-Associated Pneumonia.
Lung ultrasound is a valuable imaging tool in the diagnosis of community-acquired pneumonia. However, its diagnostic accuracy in ventilator-associated pneumonia (VAP) has not been fully investigated. The aim of this study was to evaluate the diagnostic performance of the combination of a lung ultrasound with procalcitonin (PCT) in mechanically ventilated subjects with symptoms suggestive of pneumonia. A prospective study of 124 subjects with suspected VAP in 2 multidisciplinary ICUs was conducted between December 2016 and October 2017. Lower respiratory tract specimens were collected from all the subjects at enrollment and on the following 3 d. PCT assays were performed within 1 h of enrollment. Lung ultrasound and then computed tomography of the chest were performed within 24 h to detect lung consolidations. The subjects were divided into VAP and non-VAP groups according to the results of a computed tomography of the chest and semi-quantitative culture of the lower respiratory tract sample. A total of 124 subjects were included (48 in the VAP group and 76 in the non-VAP group). A positive lung ultrasound result combined with PCT of ≥0.25 ng/mL diagnosed VAP, with a sensitivity and specificity of 81.3 and 85.5%, respectively. The area under the receiver operating characteristic curve was significantly higher for lung ultrasound combined with PCT than for a white blood cell count, PCT, C-reactive protein, or Clinical Pulmonary Infection Score alone. A combination of lung ultrasound and PCT was accurate in the diagnosis of VAP. Lung ultrasound is a useful lung-imaging tool to assist VAP diagnosis.


Predictive role of neutrophil-percentage-to-albumin, neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios for mortality in patients with COPD: Evidence from NHANES 2011-2018.
This study evaluated the predictive roles of hematologic inflammatory biomarkers including neutrophil-percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR) for mortality in community-dwelling individuals with chronic obstructive pulmonary disease (COPD). This longitudinal study extracted data of adults 40-79 years who had physician-diagnosed COPD from the United States (US) National Health and Nutrition Examination Survey (NHANES) 1999-2018. Cox regressions determined the associations between NPAR, NLR, ELR and their components, with all-cause mortality, cardiovascular disease (CVD) mortality and mortality from chronic lower respiratory disease (CLRD). Receiver operating characteristic (ROC) curve analysis estimated the predictive performances of these biomarkers for 5-year all-cause mortality. Data of 1158 subjects were analysed. After adjustment, higher NPAR was significantly associated with increased all-cause and CVD mortality, and mortality from CLRD (adjusted hazard ratio [aHR] = 1.14, 1.15 and 1.16). Higher NLR was associated with an increased all-cause and CVD mortality (aHR = 1.16 and 1.29). Higher neutrophil was associated with increased all-cause mortality and mortality from CLRD (aHR = 1.13 and 1.34). Albumin was associated with decreased all-cause and CVD mortality (aHR = 0.91 and 0.86). ELR, eosinophil or lymphocyte was not significantly associated with either mortality outcomes. Adjusted AUC of NPAR and NLR in predicting 5-year all-cause mortality were 0.808 (95% CI: 0.722-0.845) and 0.799 (95% CI: 0.763-0.835), respectively. In community-dwelling US adults with COPD, increased NPAR and NLR are associated with mortality risks. NPAR outperforms the other hematologic inflammatory biomarkers in predicting 5-year all-cause mortality.


Transcriptomic and metabolic analyses reveal the potential mechanism of increasing steroidal alkaloids in Fritillaria hupehensis through intercropping with Magnolia officinalis.
Fritillaria hupehensis, a well-known medicinal perennial herb, is used as an antitussive and an expectorant. Continuous cropping and monoculture cultivation usually negativly affect the growth of F. hupehensis. Compared with the monoculture system, the F. hupehensis-Magnolia officinalis intercropping system significantly increases the yield of F. hupehensis. However, changes in steroidal alkaloid metabolites (the most important bioactive components) and their molecular regulatory mechanisms in F. hupehensis intercropping system remain unclear. We performed comparative transcriptomic and metabolomic analyses of F. hupehensis bulbs grown in monocropping and intercropping systems. A total of 40 alkaloids were identified, including 26 steroidal alkaloids, 4 plumeranes, 3 phenolamines, 1 pyridine alkaloid, and 6 other alkaloids. The results showed that intercropping significantly increased the levels of peimine, peiminine, hupehenine, korseveridine, verticinone N-oxide, delafrine, tortifoline, pingbeinone, puqienine B, puqienine E, jervine, ussuriedine, hydroxymandelonitrile, N-feruloylputrescine, and N-benzylmethylene isomethylamine in F. hupehensis, but decreased the levels of indole, p-coumaroylputrescine, and N-benzylformamide. Transcriptome sequencing identified 11,466 differentially expressed unigenes in F. hupehensis under the intercropping system, of which 5,656 genes were up-regulated and 5,810 genes were down-regulated. We proposed a possible steroidal alkaloid biosynthesis pathway, in which 12 differentially expressed genes were identified. The higher expressions of these genes in the intercropping system positively correlated with the high accumulation of peimine, peiminine, and hupehenine, further validating our proposal. Moreover, the biological processes of oxidative phosphorylation and plant hormone signal transduction, cytochrome P450 enzymes, ATP-binding cassette transporters, and transcription factors may play pivotal roles in the regulation of steroidal alkaloid biosynthesis. This study revealed the underlying molecular mechanisms of intercropping in improving steroidal alkaloids in F. hupehensis at the transcriptome and metabolome levels. These findings provided a theoretical foundation for sustainable development of this ecological planting method.


Medial Meniscus Posterior Root Repair Using a Transtibial Technique.
The meniscal roots are critical in maintaining the normal shock absorbing function of the meniscus. If a meniscal root tear is left untreated, meniscal extrusion can occur rendering the meniscus nonfunctional resulting in degenerative arthritis. Two main repair techniques are described: (1) suture anchors (direct fixation) and (2) sutures pulled through a tibial tunnel (indirect fixation). Meniscal root repair using a suture anchor technique is technically challenging requiring a posterior portal and a curved suture passing device that can be difficult to manipulate within the knee. We present a technique for posterior medial meniscus root repair using 3 sutures (1 leader, 2 cinch), standard arthroscopy portals, and transtibial fixation. Overall, this technique simplifies a challenging procedure and allows for familiarity and efficiency.


Addressing dichotomous data for participants excluded from trial analysis: a guide for systematic reviewers.
Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data. The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials. This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered 'non-adherent to the protocol' but for whom data are available, and participants with missing data. Systematic reviewer authors should include data from 'non-adherent' participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events. This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.


Characterization of adenovirus type 2 transcriptional complexes isolated from infected HeLa cell nuclei.
HeLa cell nuclei, isolated 17 h after infection with human adenovirus type 2 (Ad2), were treated with 200 mM ammonium sulfate. The extract (S200 fraction) contained 50 to 70% of the nonintegrated Ad2 DNA, which was in the form of nucleoprotein complexes. These complexes contained native, intact Ad2 DNA (with the exception of replicative intermediates) and could be partially purified and resolved by velocity gradient centrifugation. Using high-salt (200 mM ammonium sulfate) incubation conditions, more than 95% of the nuclear RNA polymerase activity belonged to class B. About 45% of the class B enzyme molecules bound to DNA in the nuclei (those "engaged" in RNA synthesis) were released from the nuclei in the form of Ad2 transcriptional complexes by treatment with 200 mM ammonium sulfate. At least 90% of the RNA synthesized in high salt in the nuclei or in the S200 fraction was Ad2 specific, and essentially all of this RNA was complementary to the l strand of Ad2 DNA. These findings are compatible with what is known about Ad2-specific RNA synthesis in vivo. The analysis of the RNA synthesized from partially purified transcriptional complexes supports the contention that its transcription is almost entirely asymmetric, and that the asymmetry observed in vivo is not a consequence of the rapid degradation of h-strand transcripts. The RNA synthesized in vitro in the absence of detectable RNase activity sedimented with a maximum size of 35 to 40S. Less than 5% of the nuclear or the S200 fraction RNA polymerase activity was class C when assayed under non-reinitiating conditions. Although much of the RNA synthesized by the class C enzyme was Ad2 specific, 5.5S virus-associated RNA was not the predominant product. The isolation of Ad2 DNA transcriptional complexes provides an attractive system for further characterizing the Ad2 DNA template used for transcription and for studying the regulation of the expression of the Ad2 genome during the productive infection cycle.


Retinal safety and toxicity study of artesunate in vitro and in vivo.
Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. ART below 5μM was safe for IMG cells in vitro. Both 2.5 and 5 μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 μM significantly decreased TNF-α gene expression while ART of 100 μM significantly increased IL-10 in the mouse retina. Intravitreal injection of 100 μM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.


Inflammasome Signaling: A Novel Paradigm of Hub Platform in Innate Immunity for Cancer Immunology and Immunotherapy.
Inflammasomes are fundamental innate immune mechanisms that promote inflammation and induce an inflammatory form of programmed cell death, pyroptosis. Pyroptotic inflammasome has been reported to be closely associated with tumorigenesis and prognosis of multiple cancers. Emerging studies show that the inflammasome assembly into a higher-order supramolecular complex has been utilized to evaluate the status of the innate immune response. The inflammasomes are now regarded as cellular signaling hubs of the innate immunity that drive the production of inflammatory cytokines and consequent recruitment of immune cells to the tumor sites. Herein, we provided an overview of molecular characteristics and biological properties of canonical and non-canonical inflammasome signaling in cancer immunology and immunotherapy. We also focus on the mechanism of regulating pyroptotic inflammasome in tumor cells, as well as the potential roles of inflammasome-mediated pyroptotic cell death in cancers, to explore the potential diagnostic and therapeutic markers contributing to the prevention and treatment of cancers.


Involvement of the CXCL12 System in the Stimulatory Effects of Prenatal Exposure to High-Fat Diet on Hypothalamic Orexigenic Peptides and Behavior in Offspring.
Exposure to a high fat diet (HFD) during gestation stimulates neurogenesis and expression of hypothalamic orexigenic neuropeptides that affect consummatory and emotional behaviors. With recent studies showing a HFD to increase inflammation, this report investigated the neuroinflammatory chemokine, CXCL12, and compared the effects of prenatal CXCL12 injection to those of prenatal HFD exposure, first, by testing whether the HFD affects circulating CXCL12 in the dam and the CXCL12 system in the offspring brain, and then by examining whether prenatal exposure to CXCL12 itself mimics the effects of a HFD on hypothalamic neuropeptides and emotional behaviors. Our results showed that prenatal exposure to a HFD significantly increased circulating levels of CXCL12 in the dam, and that daily injections of CXCL12 induced a similar increase in CXCL12 levels as the HFD. In addition, prenatal HFD exposure significantly increased the expression of CXCL12 and its receptors, CXCR4 and CXCR7, in the hypothalamic paraventricular nucleus (PVN) of the offspring. Finally, the results revealed strong similarities in the effects of prenatal HFD and CXCL12 administration, which both stimulated neurogenesis and enkephalin (ENK) expression in the PVN, while having inconsistent or no effect in other regions of the hypothalamus, and also increased anxiety as measured by several behavioral tests. These results focus attention specifically on the CXCL12 chemokine system in the PVN of the offspring as being possibly involved in the stimulatory effects of prenatal HFD exposure on ENK-expressing neurons in the PVN and their associated changes in emotional behavior.


Rovibrational Considerations for the Monomers and Dimers of Magnesium Hydride and Magnesium Fluoride.
Magnesium is an understudied chemical element that is quite useful in materials science and may be an essential astrochemical building block for grain formation in proto-planetary disks. This work provides quantum chemical prediction for the vibrational and rovibrational spectra of the structurally similar magnesium hydride and magnesium fluoride monomers and dimers. Magnesium fluoride is commonly utilized in infrared-observing windows and is a known terrestrial mineral, sellaite. Magnesium hydride is likely to exist in various astrophysical environments. Comparison of the anharmonic quantum chemical spectral data computed in this work to known gas phase values for MgH2 is excellent with the computed 1584.1 cm-1 antisymmetric Mg-H stretch less than 5 cm-1 below experiment for example. The condensed phase vibrational attributions of the dimer, however, are less comparable with the present results potentially indicating that some of the previous assignments may need to be revisited. The magnesium fluoride monomer and dimer have no previous vibrational experimental results reported, and the work here should be solid predictions as to their spectral features for comparison either to laboratory work or potentially even to interstellar observations.


Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology.
To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. In 2013, OSCE mean score was 7.1±0.6 with none RT receiving a failing score while the MCQ score was 6.5±0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7±0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4±0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs.


Lineage-specific variation in slow- and fast-X evolution in primates.
Theories predict that the evolutionary rates of X-linked regions can differ from those of autosomal regions. The male-biased mutation theory predicts a slower rate of neutral substitution on the X chromosome (slow-X evolution), as the X spends less time in male germlines, where more mutations originate per generation than in female germlines. The fast-X theory, however, predicts a faster rate of adaptive substitution on the X chromosome when newly arising beneficial mutations are, on average, partially recessive (fast-X evolution), as the X enjoys a greater efficacy of positive selection. The slow- and fast-X processes are expected to interact as the degree of male-biased mutation can in turn influence the relative rate of adaptive evolution on the X. Here, we investigate lineage-specific variation in, and the interaction of, slow- and fast-X processes using genomic data from four primates. We find consistent evidence for slow-X evolution in all lineages. In contrast, evidence for fast-X evolution exists in only a subset of lineages. In particular, the marmoset lineage, which shows the strongest evidence of fast-X, exhibits the lowest male mutation bias. We discuss the possible interaction between slow- and fast-X evolution and other factors that influence the degrees of slow- and fast-X evolution.


Effects of overexpression and inhibited expression of thymosin, an actin-interacting protein from Bombyx mori, on BmNPV proliferation and replication.
Previous study showed that exogenously applied recombinant thymosin from Bombyx mori (BmTHY) reduces B. mori nucleopolyhedrovirus (BmNPV) proliferation in silkworm. Which stands to reason that BmTHY in B. mori is crucial for the defense against BmNPV. However, little is known about the effect of endogenously overexpressed or repressed BmTHY on B. mori resistance to virus infection. To study this issue, we constructed an overexpression and inhibited expression systems of BmTHY in BmN cells. The viral titer and the analysis from the quantitative real-time polymerase chain reaction (PCR) revealed that overexpression of BmTHY decreased the copies of BmNPV gene gp41, which goes over to inhibit the proliferation of BmNPV in BmN cells, while the inhibited expression of BmTHY significantly enhanced viral proliferation in infected BmN cells. These results indicated that endogenous BmTHY can inhibit BmNPV proliferation and replication in infected BmN cells. Furthermore, Co-IP showed that BmTHY could bind to actin in BmN cells. Also, the overexpression or inhibited expression of BmTHY shifted the ratio of F/G-actin in infected BmN cells. Lastly, the BmTHY, an actin-interacting protein, might be one of the key host factors against BmNPV, which inhibits viral proliferation and replication in BmN cells.


Surgical indications in endemic goiter. Pre- and postoperative care.
The authors express their opinion with respect to anatomo-clinical forms of endemic goiter. First they suggest preoperative thyroid re-equilibration to avoid postoperative complications such as hypothyroidism or recurrence. Then operative indications for endocrine goiter, especially in an endemic area are discussed. Opinions are also expressed with respect to diffuse parenchymatous (endemic) goiter, nodular and polynodular goiter together with the various forms that may have a nodular or polynodular aspect both anatomically and as localization. Extemporaneous examination is viewed by the authors as compulsory in all such goiters, whereas preoperative thyroid puncture is counterindicated. Surgical care of mixed endemic goiter (diffuse hyperplasia with nodules imbedded in the hyperplasia) is also reviewed. It is recommended that each operation be preceded by an adequate preoperative treatment, for which therapeutic schemes are indicated as well as postoperative care directions taking into account the anatomo-clinical form. The surgical approach recommended is subtotal thyroidectomy. The paper also provides some statistical figures concerning surgery in the Institute of Endocrinology in Bucharest.


[The Insufficiency Type of Metabolic Balance and Nutritional Status in Patient With Heart Failure].
A lot of data has been accumulated at present on the metabolic and nutritional insufficiency in patients with chronic heart failure (CHF). Researchers have noted an actuality of the study of nutritional and metabolic insufficiency in CHF patients as independent factors affecting the course of CHF and because of its relationship with triggers of inflammation, sympathetic-adrenal system, and markers of functional state of the cardiovascular system (CVS). In some works attention has been given to relationship of nutritional and metabolic insufficiency with autonomic regulation of cardiac rhythm. Attempts have been made to systematize obtained data, create contemporary pathophysiological portrait of CHF development and highlight prevailing mechanisms of progression of the disease. This review summarizes accumulated data on nutritional insufficiency in patients with CHF and systematizes metabolic changes according to types of metabolism and CHF functional class. We have also made an attempt of creating figurative representation of pathophysiological mechanism of development of nutritional insufficiency in CHF. We have emphasized the problem of inadequate knowledge on contribution of inflammatory markers in development of nutritional insufficiency especially in patients with I-II functional classes of CHF. We also present suggestions concerning strategy of studying nutritional insufficiency in CHF, its classification according to CHF functional class, stratification of risk factors of its development, and the methods of its prevention and correction.


Mechanisms of action of brain insulin against neurodegenerative diseases.
Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.


[Solitary fibrous thoracic tumor: a rare tumor with unpredictable course].
A 68-year-old woman presented chest pain and exercise-induced dypnea for one year. Diagnosis was a thoracic solitary fibrous tumor. These tumors are very rare. Clinical outcome is generally good except in 13% of the cases with a malignant component. Complete surgical resection is required.


Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris.
As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes.


Simulation of emission tomography using grid middleware for distributed computing.
SimSET is Monte Carlo simulation software for emission tomography. This paper describes a simple but effective scheme for parallel execution of SimSET using NetSolve, a client-server system for distributed computation. NetSolve (version 1.4.1) is "grid middleware" which enables a user (the client) to run specific computations remotely and simultaneously on a grid of networked computers (the servers). Since the servers do not have to be identical machines, computation may take place in a heterogeneous environment. To take advantage of diversity in machines and their workloads, a client-side scheduler was implemented for the Monte Carlo simulation. The scheduler partitions the total decay events by taking into account the inherent compute-speeds and recent average workloads, i.e., the scheduler assigns more decay events to processors expected to give faster service and fewer decay events to those expected to give slower service. When compute-speeds and sustained workloads are taken into account, the speed-up is essentially linear in the number of equivalent "maximum-service" processors. One modification in the SimSET code (version 22.214.171.124) was made to ensure that the total number of decay events specified by the user is maintained in the distributed simulation. No other modifications in the standard SimSET code were made. Each processor runs complete SimSET code for its assignment of decay events, independently of others running simultaneously. Empirical results are reported for simulation of a clinical-quality lung perfusion study.


1-alkoxyallene as an effective precursor for regio- and stereocontrolled allylation reactions with aliphatic aldehydes via bis-stannylation.
Bis-stannylation of 1-(methoxy)methoxyallene yields (E)-(3-(methoxymethoxy)prop-2-ene-1,2-diyl) bis-tributylstannane (2) as a highly reactive allylation reagent. Stereoselective reactions of functionalized stannane 2 with a variety of aldehydes provide good yields of 1,2-diol derivatives. Reactions with alpha-alkoxyaldehydes proceed with chelation-controlled addition to afford efficient constructions of 3,4-anti-4,5-syn-relationships in stereotriads bearing three differentiated oxygen (alkoxy and hydroxy) substituents. Mechanistic considerations are presented, and derivatives for NMR experiments support the stereochemical assignments. An X-ray diffraction study is included.


Rheumatic symptoms following adjuvant therapy for breast cancer.
Twenty-three women with a diagnosis of breast cancer who subsequently developed new nonmetastatic rheumatic symptoms, and/or had a history of rheumatic symptoms prior to their diagnosis of breast cancer, were identified from the oncology and rheumatology practices of a 400-bed tertiary-care teaching hospital. For each patient a structured telephone interview and detailed chart review were conducted. Of eight women with no previous rheumatic history (Group I), four developed polyarthritis (1 seropositive), three fibromyalgia, and one spondylosis after the diagnosis of breast cancer, which in four cases occurred during or shortly after cyclophosphamide-based combination chemotherapy, in two cases during tamoxifen therapy, and in one case after radiotherapy only. Of 15 women who had previous rheumatic symptoms (Group II), 12 developed worse and/or new symptoms, five after chemotherapy and seven on tamoxifen. In both groups the symptoms had a significant negative impact on functional status, and in some cases resolution was only partial even after many years of followup. Prospective studies are needed to determine the incidence, risk factors, and optimal management of nondestructive polyarthropathy or fibromyalgia in women who receive systemic adjuvant therapy for breast cancer.


Roles of the GcvA and PurR proteins in negative regulation of the Escherichia coli glycine cleavage enzyme system.
When Escherichia coli was grown in medium containing both inosine and glycine, the PurR repressor protein was shown to be responsible for a twofold reduction from the fully induced glycine cleavage enzyme levels. This twofold repression was also seen by measuring beta-galactosidase levels in cells carrying a lambda gcvT-lacZ gene fusion. In this fusion, the synthesis of beta-galactosidase is under the control of the gcv regulatory region. A DNA fragment carrying the gcv control region was shown by gel mobility shift assay and DNase I footprinting to bind purified PurR protein, suggesting a direct involvement of the repressor in gcv regulation. A separate mechanism of purine-mediated regulation of gcv was shown to be independent of the purR gene product and resulted in an approximately 10-fold reduction of beta-galactosidase levels when cells were grown in medium containing inosine but lacking the inducer glycine. This additional repression was dependent upon a functional gcvA gene, a positive activator for the glycine cleavage enzyme system. A dual role for the GcvA protein as both an activator in the presence of glycine and a repressor in the presence of inosine is suggested.


Is age of onset of Crohn's disease governed by mutations in NOD2/caspase recruitment domains 15 and Toll-like receptor 4? Evaluation of a pediatric cohort.
Crohn's disease (CD) is caused by a combination of environmental and genetic factors. It is not clear at present whether age of onset (AOO) is a random event or dictated by genotype or environmental factors. Mutations in the NOD2/caspase recruitment domains 15 (CARD15) and in the Toll-like receptor 4 (TLR4) gene have been associated with increased susceptibility for CD. We sought to determine whether single or multiple mutations in these genes are linked to earlier susceptibility for CD. A cohort of 189 patients with CD (82 pediatric onset, 107 adult onset) were genotyped for three disease-associated single-nucleotide polymorphisms (SNPs), one haplotype association (JW1-SNP5), and one background polymorphism (P268S) of the NOD2/CARD15 gene and for two SNPs of TLR4. Analysis of heterozygosity, homozygosity, alleles, and haplotypes of cohort on age or pediatric onset was performed. AOO ranged from 8 mo to 68 y. The presence of the three NOD2/CARD15 and two TLR4 mutations, the NOD2/CARD15 JW haplotype, compound heterozygosity, and homozygosity were not associated with AOO. Presence of P268S in the absence of known NOD2/CARD15 mutations was correlated with increasing age and adult onset of CD, whereas pediatric-onset disease was associated with male gender and the wild-type NOD2/CARD15 haplotype. Mutations in NOD2/CARD15 and TLR4 are not significantly associated with AOO in our population. Mutations that are not in linkage disequilibrium with the background mutation P268S of the NOD2/CARD15 gene probably play a more significant role in pediatric-onset disease.


Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans.
Galectin-1 is a member of the galectin family of glycan-binding proteins and occurs as an approximately 29.5-kDa noncovalent homodimer (dGal-1) that is widely expressed in many tissues. Here, we report that human recombinant dGal-1 bound preferentially and with high affinity (apparent K(d) approximately 2-4 microM) to immobilized extended glycans containing terminal N-acetyllactosamine (LN; Galbeta1-4GlcNAc) sequences on poly-N-acetyllactosamine (PL; (-3Galbeta1-4GlcNAcbeta1-)(n)) sequences, complex-type biantennary N-glycans, or novel chitin-derived glycans modified to contain terminal LN. Although terminal Gal residues are important for dGal-1 recognition, dGal-1 bound similarly to alpha3-sialylated and alpha2-fucosylated terminal LN, but not to alpha6-sialylated and alpha3-fucosylated terminal LN. The binding specificity of human recombinant dGal-1 was similar to that observed with purified bovine heart-derived dGal-1. Unexpectedly, dGal-1 bound free ligands in solution with relatively low affinity and displayed no preference for extended glycans, indicating that dGal-1 preferentially recognizes extended glycans only when they are surface-bound, such as found on cell surfaces. Human dGal-1 also bound to both native and desialylated human promyelocytic HL-60 cells with similar affinity as observed for immobilized long chain PL. Binding to these cells was reduced upon treatment with endo-beta-galactosidase, which cleaves PL sequences, indicating that cell-surface PLs are ligands. To test the role of dimerization in dGal-1 binding, we examined the binding of a mutated form of dGal-1 that weakly dimerizes (monomeric Gal-1 (mGal-1)) and a covalently dimerized (chemically cross-linked) form of mGal-1 (cd-mGal-1). dGal-1 and cd-mGal-1 had similar affinities that were both approximately 3.5-fold higher for immobilized PL than observed for mGal-1, suggesting that dGal-1 acts as a dimer to cross-link terminal LN units on immobilized PL. These results indicate that dGal-1 functions as a dimer to recognize LN units on extended PLs on cell surfaces.


Should influenza vaccination be mandatory for healthcare workers?
Each year, many healthcare organizations deal with low influenza immunization rates among staff. Mandatory influenza vaccination programs may be considered in order to address this issue. These types of programs have caused controversy in the past, as staff has argued that they infringe upon their liberties and right to autonomy. However, if viewed from a public health perspective, mandatory vaccination programs are beneficial for both employees and patients and can be justified. When individuals make the decision to work in the medical field, it is assumed that their values align with those of the organization for which they work. This overrides their right to autonomy, since they are expected to put the safety of their patients ahead of their own personal interests. Although some may argue that receiving a flu shot is unsafe, evidence has demonstrated the opposite, and the minimal discomfort that may result from a vaccine is not enough to negate the responsibilities that healthcare workers have toward the patients they serve.


Impact of population size on incidence of rubella and measles in comparison with that of other infectious diseases.
A strong dependency of rubella and measles epidemics on population size was confirmed by 2 types of plots: the cumulative frequency distribution of number of cases per prefecture and the slope of the log-log plots of number of cases per prefecture on the y-axis vs. prefecture population size on the x-axis. These parameters were found to be constant and unique to each infectious agent. The broader cumulative frequency distribution and steeper slope of the log-log plots were characteristic to measles and rubella, i.e., a higher population size was correlated with a disproportionate high incidence of measles and rubella. No such tendency was found in other infections with possible exceptions of pertussis and keratoconjunctivitis. The dependency of rubella and measles on population density was examined by log-log plots of patient number/population vs. population density, which revealed strong population density dependency of rubella; the dependency of measles on population density was equivocal.


[In vitro activity of beta-lactam antibiotics and their sensitivity to beta-lactamase].
beta-lactamase production was evaluated by chromogenic cephalosporin 87/312 in 116 E. coli isolated from clinical sources. Such test revealed beta-lactamase production in 54 strains out of 116 (46%): MICs of eight beta-lactam antibiotics (Ampicillin, Piperacillin, Cefazoline, Cephaloridine, Cephalexine, Cefuroxime, Cefotaxime, Cefotaxime) were determined using a miniaturized dilution broth method. Cefotaxime and Ceftriaxome and Ceftriaxone showed the highest antibacterial activity. All beta-lactamases produced by E. coli strains under examination were isolated and purified by ultrasonic disruption and high speed centrifugation. Sensitivity of the eight antibiotics to purified beta-lactamases was assessed by a spectrophotometric method that utilizes the velocity of cytochrome c reduction. The sensitivity to beta-lactamases was reflected in the in vitro activity of the antibiotics as assessed by the determination of the MICs.


Making sense of the agenda for change. Modernising the NHS pay system.
The government has announced its intention to reorganise the pay structure of the NHS. Three years on from the launch of the initiative, NATN Professional Officer, John Beesley, explains why the government decided on the undertaking, its implications for perioperative practitioners, and why nurses need to make their views and opinions known.


Determination of aflatoxins in peanut butter, using two liquid chromatographic methods: collaborative study.
Two methods for determining aflatoxins in peanut butter, one using normal phase and the other reverse phase liquid chromatography (LC), were studied by 8 and 10 collaborators, respectively. Fluorescence detection was used for the determinative step in both methods. For reverse phase LC, aflatoxins B1 and G1 were converted to B2a and G2a; for normal phase LC, a silica gel-packed flow cell was placed in the irradiating light path of the detector. The samples included spiked and naturally contaminated peanut butter with total aflatoxin levels from about 5 to 20 ng/g and controls in a balanced pair design. For the normal phase LC method, recoveries of B1, B2, G1, and G2 from spiked samples averaged 79, 92, 74, and 88%, respectively; for the reverse phase method, the recoveries were 103, 104, 89, and 163%. For the normal phase LC method, pooled repeatabilities were 20, 23, 28, and 17% for B1, B2, G1, and G2, respectively; for the reverse phase method, the repeatabilities were 19, 22, 38, and 31%. For the normal phase method, pooled reproducibilities were 34, 33, 39, and 34% for B1, B2, G1, and G2, respectively; for the reverse phase method, the reproducibilities were 32, 46, 51, and 52%. Both methods show an improved limit of detection and better within-laboratory precision over current AOAC methods; however, between-laboratory precision is no better, and the reverse phase method shows evidence of interferences being measured. For these reasons and because of no benefits of present value, neither method was submitted for adoption as official first action.


Archean phosphorus recycling facilitated by ultraviolet radiation.
Of the six elements incorporated into the major polymers of life, phosphorus is the least abundant on a global scale [E. Anders, M. Ebihara, Geochim. Cosmochim. Acta 46, 2363-2380 (1982)] and has been described as the "ultimate limiting nutrient" [T. Tyrrell, Nature 400, 525-531 (1999)]. In the modern ocean, the supply of dissolved phosphorus is predominantly sustained by the oxidative remineralization/recycling of organic phosphorus in seawater. However, in the Archean Eon (4 to 2.5 Ga), surface waters were anoxic and reducing. Here, we conducted photochemical experiments to test whether photodegradation of ubiquitous dissolved organic phosphorus could facilitate phosphorus recycling under the simulated Archean conditions. Our results strongly suggest that organic phosphorus compounds, which were produced by marine biota (e.g., adenosine monophosphate and phosphatidylserine) or delivered by meteorites (e.g., methyl phosphonate) can undergo rapid photodegradation and release inorganic phosphate into solution under anoxic conditions. Our experimental results and theoretical calculations indicate that photodegradation of organic phosphorus could have been a significant source of bioavailable phosphorus in the early ocean and would have fueled primary production during the Archean eon.


Recent advances in the management of ventricular tachyarrhythmias.
Ventricular arrhythmias are an important cause of cardiovascular morbidity and mortality, particularly in those with structural heart disease, inherited cardiomyopathies, and channelopathies. The goals of ventricular arrhythmia management include symptom relief, improving quality of life, reducing implantable cardioverter defibrillator shocks, preventing deterioration of left ventricular function, reducing risk of arrhythmic death, and potentially improving overall survival. Guideline-directed medical therapy and implantable cardioverter defibrillator implantation remain the mainstay of therapy to prevent sudden cardiac death in patients with ventricular arrhythmias in the setting of structural heart disease. Recent advances in imaging modalities and commercial availability of genetic testing panels have enhanced our mechanistic understanding of the disease processes and, along with significant progress in catheter-based ablative therapies, have enabled a tailored and more effective management of drug-refractory ventricular arrhythmias. Several gaps in our knowledge remain and require further research. In this article, we review the recent advances in the diagnosis and management of ventricular arrhythmias.


Biphasic regulation of transcription factor nuclear factor-kappaB activity in human endothelial cells by lysophosphatidylcholine through protein kinase C-mediated pathway.
Lysophosphatidylcholine (lysoPC), which is generated in oxidized LDL (Ox-LDL) and abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induces several endothelial genes expressed in atherosclerotic arterial walls. Nuclear factor-kappa B (NF-kappaB), a pleiotropic transcription factor, plays an important role in regulation of expression of various genes implicated in atherosclerosis. We have previously reported that lysoPC transferred from Ox-LDL to endothelial surface membrane activates endothelial protein kinase C (PKC), leading to modulated endothelial functions. This study was aimed at determining whether lysoPC could modulate activity of transcription factors in cultured human umbilical vein endothelial cells (HUVECs) by using electrophoretic mobility shift assay. LysoPC was found to increase DNA-binding activity of NF-kappaB in HUVECs within 15 minutes, which peaked at 1 to 2 hours and subsequently declined to the baseline level at 6 hours. Lower concentrations (5 to 15 micromol/L) of lysoPC markedly increased NF-kappaB activity, but higher concentration (50 micromol/L) of lysoPC inhibited the activity. Phorbol 12-myristate 13-acetate, a potent activator of PKC, also augmented NF-kappaB activity in HUVECs, mimicking the effects of lysoPC; furthermore, calphostin C and chelerythrine chloride, specific PKC inhibitors, and alpha-tocopherol, a clinically potent PKC inhibitor, suppressed the lysoPC-induced NF-kappaB activation. These results indicate that lysoPC regulates NF-kappaB activity in a biphasic manner dependent on its concentrations and incubation time in human endothelial cells and the endothelial PKC activation may in part be involved in the lysoPC-induced NF-kappaB activation. Thus, the time course and the positive and negative biphasic regulatory actions of lysoPC on NF-kappaB activity in endothelial cells might exhibit a unique effect of lysoPC in arterial walls on the different stages of atherosclerosis.


Individualized Early Prediction of Familial Risk of Dyslexia: A Study of Infant Vocabulary Development.
We examined early vocabulary development in children at familial risk (FR) of dyslexia and typically developing (TD) children between 17 and 35 months of age. We trained a support vector machine to classify TD and FR using these vocabulary data at the individual level. The Dutch version of the McArthur-Bates Communicative Development Inventory (Words and Sentences) (N-CDI) was used to measure vocabulary development. We analyzed group-level differences for both total vocabulary as well as lexical classes: common nouns, predicates, and closed class words. The generalizability of the classification model was tested using cross-validation. At the group level, for both total vocabulary and the composites, the difference between TD and FR was most pronounced at 19-20 months, with FRs having lower scores. For the individual prediction, highest cross-validation accuracy (68%) was obtained at 19-20 months, with sensitivity (correctly classified FR) being 70% and specificity (correctly classified TD) being 67%. There is a sensitive window in which the difference between FR and TD is most evident. Machine learning methods are promising techniques for separating FR and TD children at an early age, before they start reading.


Chemical and physical agents of work-related cardiovascular diseases.
This article summarizes the state of the art in research on cardiovascular diseases (CVD) and occupational exposure. The major chemical and physical agents are considered and the methodological difficulties of epidemiological surveys are discussed. Work-related CVD, like all occupational disorders, are changing continuously as a consequence of modifications in industrial processes, improvements in preventative measures, and the tertiarization of the economy. The cornerstones of a preventative strategy of CVD are still based on environmental monitoring and medical surveillance, but at the same time on multidisciplinary and multicentred scientific research. Where possible, health promotion will include more general programmes directed at changing personal risk factors.


Characterization of a self-assembled monolayer based on a calix[4]crown-5 derivate: fabrication of a chemical sensor sensitive to calcium.
The synthesis and self-assembled monolayer (SAM) formation of a calix[4]crown-5 derivative are reported. Several techniques, including electrochemistry, atomic force microscopy (AFM), Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and contact angle measurements have been applied to characterise the monolayer film designed for chemical sensor applications. The recognition properties of this SAM for metal cations has been investigated using impedance spectroscopy (IS) showing an electrochemical response proportional to calcium ion concentration in the range from 10(-7) M to 10(-2) M. This response is related to microscopic changes at the gold surface induced by selective binding by the immobilised calixarene.


Production of Brassica carinata protein hydrolyzates with a high Fischer's ratio using immobilized proteases.
Brassica carinata protein isolates were hydrolyzed using the digestive enzymes trypsin, chymotrypsin, and carboxypeptidase A in order to obtain hydrolyzates with a high Fischer's ratio. The proteases were immobilized using two glyoxyl-agarose supports of different porosity, 4 and 10% agarose gels, in order to evaluate the effect of substrate diffusion into the support containing the enzyme on the hydrolytic process. Reaction time, substrate concentration, and the enzyme to substrate ratio were optimized in an attempt to increase the Fischer's ratio in the resulting hydrolyzates. Gel filtration chromatography of a hydrolyzate with a degree of hydrolysis of 36% yielded a fraction that represented 31% of the total hydrolyzed proteins and had a Fischer's ratio of 28.3 with a phenylalanine + tyrosine content below 1.5%. This material could be used for preparing special diets when there is a need to increase the supply of branched amino acids and/or reduce the intake of aromatic amino acids.


Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery.
Metabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states. The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse, and to compare the biomarkers extracted from different biofluids (plasma, stool, and urine) in terms of characterizing acute and chronic stages of this intestinal fluke infection. Twelve female NMRI mice were infected with 30 E. caproni metacercariae each. Plasma, stool, and urine samples were collected at 7 time points up to day 33 post-infection. Samples were also obtained from non-infected control mice at the same time points and measured using (1)H nuclear magnetic resonance (NMR) spectroscopy. Spectral data were subjected to multivariate statistical analyses. In plasma and urine, an altered metabolic profile was already evident 1 day post-infection, characterized by reduced levels of plasma choline, acetate, formate, and lactate, coupled with increased levels of plasma glucose, and relatively lower concentrations of urinary creatine. The main changes in the urine metabolic profile started at day 8 post-infection, characterized by increased relative concentrations of trimethylamine and phenylacetylglycine and lower levels of 2-ketoisocaproate and showed differentiation over the course of the infection. The current investigation is part of a broader NMR-based metabonomics profiling strategy and confirms the utility of this approach for biomarker discovery. In the case of E. caproni, a diagnosis based on all three biofluids would deliver the most comprehensive fingerprint of an infection. For practical purposes, however, future diagnosis might aim at a single biofluid, in which case urine would be chosen for further investigation, based on quantity of biomarkers, ease of sampling, and the degree of differentiation from the non-infected control group.


A case of ocular cardiac reflex in a child with blunt ocular trauma.
An 11-year-old boy re-presented with refractory vomiting 18 h after blunt facial and head trauma. Initial CT of the brain performed at his first visit was normal. He was found to have a heart rate of 56 bpm (age appropriate 65-100 bpm) with a blood pressure 90/60 mm Hg. Physical examination revealed an injected sclera and limited vertical movement of the left eye. Neurological examination revealed no focal deficits, but a Glasgow Coma Scale of 14, with mild confusion, depressed mental status and diplopia on upward gaze. Performing upward gaze extra ocular movements exacerbated the patient's bradycardia and confirmed the presence of the oculocardiac reflex. High-resolution CT of orbits demonstrated a left orbital floor fracture with entrapment of the left inferior rectus muscle. Surgical correction resolved his bradycardia.


Recent advances in clinical low-vision care.
In the past decade there has been a growth in the awareness of the impact that low vision has on the individual and on society in general. The clinical eye-care professions have become more conscious of their responsibility to assist partially sighted patients and low-vision care is becoming a specialty area within optometry and ophthalmology. This paper reviews recent advances in the optical devices and prescribing procedures that have contributed to improving the care that is available to assist low-vision patients with distance-vision tasks, near-vision tasks and visual-field problems.


Descriptive Study on a Nationwide Exploratory Questionnaire Survey of Emergency Contraceptive Pills and Their Sexual History and Knowledge in Japan.
A shift towards obtaining emergency contraceptives without a prescription have been discussed in Japan. In response to this social background, we aimed at investigating the background of sexual intercourse, emergency contraceptive use, and knowledge of sexual and reproductive health education among women of reproductive age in Japan. In this study, we conducted a national wide cross-sectional questionnaire survey using a total of 4 web-based domains (background, sexual history, emergency contraceptives, and sexual and reproduction-related knowledge) composed of 50 questions. We obtained responses from a total of 4,631 participants of varying age groups (18-25, 26-35, and 36-45 years old) and 47 prefectures (84 to 118 from each prefecture). Among participant responses, 69.7% are sexually active, of which 49.0% had experiences of sexual intercourse with an unknown person. The responses from a total of 737 participants who have sexual intercourse, know of emergency contraceptives, and have experienced a situation that necessitated the use of emergency contraceptives, were analyzed. Of these participants, 46.4% (342/737) took emergency contraceptives, while 43.6% (321/737) participants did not take emergency contraceptives. Participants who have the knowledge for obtaining emergency contraceptives through the correct means were 52.6% (2438/4631). This study showed that approximately half of participants may not have correct knowledge of emergency contraceptives. In addition, approximately half of sexually active participants are facing unintended pregnancies due to a lack of sexual and reproductive awareness. Hence, comprehensive sex education is necessary to achieve social and regulatory changes centered on emergency contraceptives.


Preparing Tomorrow's Doctors to Care for Patients With Autism Spectrum Disorder.
People with autism spectrum disorder (ASD) and other developmental disabilities have poorer health and face unique barriers to health care compared to people without disabilities. These health disparities can be partially attributed to physicians' limited knowledge about caring for patients with developmental disabilities. The purpose of this study was to determine the effectiveness of ASD training for medical students. Our training included a lecture and a panel presentation that featured people with ASD and family members. Students reported improved knowledge, skills, confidence, and comfort in caring for patients with ASD.


Contractile reserve but not tension is reduced in monocrotaline-induced right ventricular hypertrophy.
The objective of this study was to evaluate the role of right ventricular hypertrophy on developed tension (F(dev)) and contractile reserve of rat papillary muscle by using a model of monocrotaline (Mct)-induced pulmonary hypertension. Calcium handling and the influence of bicarbonate (HCO(3)(-)) were also addressed with the use of two different buffers (HCO(3)(-) and HEPES). Wistar rats were injected with either Mct (40 mg/kg sc) or vehicle control (Con). Isometrically contracting right ventricular papillary muscles were studied at 80% of the length of maximal developed force. Contractile reserve (1 - F(dev)/F(max)) was calculated from F(dev) and maximal tension (F(max)). Calcium recirculation was determined with postextrasystolic potentiation. Both groups of muscles were superfused with either HCO(3)(-) (Con-B and Mct-B, both n = 6) or HEPES (Con-H and Mct-H, both n = 6) buffer. With hypertrophy, contractions were slower but F(dev) was not changed. However, F(max) was decreased (P < 0.05). With HCO(3)(-), F(max) decreased from 23.8 +/- 6.5 mN.mm(-2) in Con-B, to 13.7 +/- 3.3 mN.mm(-2) in Mct-B. With HEPES, it decreased from 16.3 +/- 3.5 mN.mm(-2) (n = 6, Con-H) to 8.3 +/- 1.6 mN.mm(-2) (Mct-H). Contractile reserve during hypertrophy was therefore also decreased (P < 0.05). With HCO(3)(-), it decreased from 0.73 +/- 0.03 (Con-B) to 0.55 +/- 0.04 (Mct-B). With HEPES, it decreased (P < 0.001) from 0.64 +/- 0.07 (Con-H) to 0.19 +/- 0.06 (Mct-H). The recirculation fraction decreased (P < 0.05) from 0.59 +/- 0.04 in Con-B to 0.44 +/- 0.04 in Mct-B. We conclude that contractile reserve and recirculation fraction are impaired during hypertrophy, with a stronger effect under HEPES than HCO(3)(-) superfusion.


Raman spectral conformational order indicators in perdeuterated alkyl chain systems.
Conformational order indicators for perdeuterated alkyl chain systems are identified in the Raman spectra of nonadecane-d40, polyethylene-d4, and stearic acid-d35. Six spectral indicators are identified: I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172], I[nu(C-C)G]/I[nu(C-C)T], I[nu(s)(CD3)]/I[nu(a)(CD2)2172], I[nu(s)(CD2)]/I[nu(a)(CD2)2172], and the full width at half-maximum (fwhm) and frequency of the nu(s)(CD2) mode. Among these indicators, the ratio of I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172] is considered a primary indicator of conformational order, since it responds to alkyl chain conformational changes in a manner similar to the I[nu(a)(CH2)]/I[nu(s)(CH2)] primary indicator for hydrogenated systems. Other indicators are correlated to this primary indicator to derive a better understanding of the effect of structural attributes on conformational order in perdeuterated alkyl chain systems. These Raman spectral order indicators are applicable to any perdeuterated alkyl-containing system including lipids, biological membranes, alkylsilane-based chromatographic stationary phases, and self-assembled monolayers.


A toolbox for mimicking gastrointestinal conditions in children: Design and evaluation of biorelevant dissolution media for mimicking paediatric gastric- and small intestinal conditions.
The goal of the present work was to develop an in vitro toolbox to evaluate the oral administration of dosage forms to children of different age groups and under different administration conditions (fasted/fed). Based on current data on the gastrointestinal physiology of children, a set of new biorelevant media was designed to mimic the composition and physicochemical properties of resting gastric and resting small intestinal fluid in children of different age groups. In addition, guidelines were developed on how to generate fasted and fed state gastric and small intestinal fluids by combining these media with age-specific drinking volumes or portions of already established simulated paediatric breakfast meals, respectively. These fluids can simulate the conditions in the paediatric stomach and small intestine after administration of a dosage form in the fasting state or after a breakfast. The in vitro toolbox was evaluated using the example of pre-school children with a total of five paediatric medicines. Results from the corresponding set of in vitro studies highlight the importance of addressing patient-specific characteristics rather than downscaling existing adult in vitro models.


Physiological responses to psychological challenge under hypnosis in patients considered to have the hyperventilation syndrome: implications for diagnosis and therapy.
Thirty patients who were considered to have the hyperventilation syndrome on clinical grounds (history and observation) were referred for testing: 29 patients completed a forced hyperventilation provocation test, and 28 underwent hypnosis during which time a psychological challenge was introduced which was meaningful to each individual patient. In 19/27 of these patients the PetCO2 fell by an average of 18.2 mmHg and persisted spontaneously for more than three minutes. In 10 normal controls studied in a similar fashion there was an average fall of 5 mmHg. The difference in response between responders and controls/non-responders was highly significant (P less than 0.001). A review of the literature is presented for comparison. It is considered that a psychological challenge under hypnosis may have important implications for diagnosis and therapy in some patients considered to have the hyperventilation syndrome.


Orygmatobothrium spp. (Cestoda: Tetraphyllidea) from triakid sharks in Argentina: redescription of Orygmatobothrium schmitti and description of a new species.
Two species of Orygmatobothrium were found inhabiting triakid sharks collected from the coast of Buenos Aires Province, Argentina. Orygmatobothrium schmittii from Mustelus schmitti is redescribed, including new information on the microtrich pattern. Orygmatobothrium juani n. sp. from Mustelus fasciatus can be distinguished from all other species in the genus using the following combination of characters: worm length, number of proglottids, number of testes, testes distribution, size of eggs, ornamented egg shell, shape of bothridial cleft at level of the marginal accessory sucker, and the extension of vitelline follicles. Species in Orygmatobothrium share a common microtrich pattern with the distal bothridial surface covered with maisiform microtriches interspersed with filiform microtriches, a proximal bothridial surface covered with trifid microtriches, with a medial projection conspicuously larger than the lateral basal projections interspersed with filiform microtriches, an inner and outer surface of the accessory sucker and glandulomuscular organ covered with short filiform microtriches, the scolex proper and cephalic peduncle surface covered with bladelike microtriches, and the germinative zone and entire strobila covered with scutes formed by densely packed filiform microtriches. This general configuration is basically similar to the microtrich pattern described in species of Orectolobicestus and Paraorygmatobothrium.


Nucleotide sequences of mouse genomic loci including a gene or pseudogene for U6 (4.8S) nuclear RNA.
We have isolated four clones which hybridize with U6 (4.8S) nuclear RNA, a mammalian small nuclear RNA(nRNA), from DNA of BALB/C mouse liver. Their restriction maps are totally different from each other, indicating that they derived from different loci in the mouse genome. The nucleotide sequences around the hybridizing region in the three clones have been determined. One clone gives a gene that is co-linear with the U6 RNA. There is a sequence TATAAAT beginning 31 nucleotides upstream of the gene, which may suggest that the U6 RNA is transcribed by RNA polymerase II. The other two clones contain a pseudogene for the U6 RNA which has 7 or 9 nucleotide changes from the RNA. The pseudogenes are surrounded by radically different sequences from those surrounding the gene, and they are closely linked to a pseudogene for another snRNA, 4.5S-I RNA, or a part of highly repetitive an interspersed sequence B1.


The incidence of femoral neck fractures in New Zealand.
This study reviews the incidence of femoral neck fractures in New Zealand Maoris and non-Maoris. A comparison made with corresponding overseas studies shows that the New Zealand non-7aori age-sex incidence is one of the highest yet observed. Maori women are shown to have an incidence of hip fracture significantly lower than non-Maori women. These results are discussed in the light of the current debate on the aetiology of femoral neck fractures.


Power Doppler Ultrasound Assessment of A1 Pulley. A New Target of Inflammation in Psoriatic Arthritis?
Objective: To determine the prevalence of grey scale and power Doppler (PD) ultrasound (US) features of A1 pulley inflammation in a cohort of psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) patients. Methods: Sixty patients (30 with PsA and 30 with RA) were consecutively enrolled. The main clinimetric indexes were recorded, and US assessment of A1 pulleys from second to fifth fingers bilaterally was carried out. The presence of A1 pulley inflammation, defined as PD signal within a thickened pulley, was registered. Results: A1 pulley inflammation was found in 15 of 240 fingers (6.3%) of eight PsA patients (26.7%) and in one of 240 fingers (0.4%) of one RA patient (3.3%) (p < 0.01 and p = 0.03, respectively). Seven of eight PsA patients (88%) with at least one inflamed A1 pulley had a moderate/high disease activity score. The regression linear analysis (R 2 = 0.36, adjusted R 2 = 0.31) showed that A1 pulley inflammation was correlated with Disease Activity Index for Psoriatic Arthritis (DAPSA) (β = 0.43, p = 0.03). Conclusion: US A1 pulley inflammation appears to be relatively common at patient level in PsA, seems to be a characteristic feature of PsA compared to RA, and correlates with DAPSA.


[Comparison of 3 metrifonate dosages in mass chemotherapy of Schistosoma haematobium].
The metrifonate standard cure consisted of three doses of 7.5 to 10 mg/kg at a fortnight interval. These repeated doses increase the total cost of the treatment and the number of incomplete cures. We wanted to verify whether a reduced cure gets still a good efficacy. 286 people from three villages situated near Niamey (Niger) where treated at random with either 1, 2 or 3 doses of 10 mg/kg metrifonate. Before treatment the mean egg-output was 40 eggs/10 ml; 4 months later the cure rate was different only between the 1 dose trial and the 3 doses one. Moreover, this rate is low (35.3%) and the mean egg-output is also low (40.3%) for one dose. These results are more significant according to the first mean egg-output level. Below 5 eggs/10 ml, the cure rate is good with 2 or 3 doses (62% and 70%, 4 months later treatment), between 6 and 50 eggs/10 ml the results are still acceptable (55 and 53%). On the other hand, above 50 eggs these results are insufficient even with 3 doses. The single dose does not give sufficient result even in low egg-output.