Cardiac effects of cocaine: a review.
Over the past 15 years, there has been a dramatic increase in the abuse of purified cocaine preparations throughout the industrialized world. The potential lethality of the drug is now recognized, and a growing series of case reports indicate that cardiotoxicity may be an important factor in the morbidity and mortality associated with the drug. Acute myocardial infarction is a demonstrated risk both in subjects with and without pre-existent coronary artery disease. The arrhythmogenic potential of cocaine is less clear and appears to have been overemphasized, although several documented cases of ventricular arrhythmia following cocaine use have been reported. Cardiomyopathy and myocarditis associated with cocaine have also been described, but an etiologic relationship is presently inferential. Based upon presumed pathophysiologic mechanisms, beta adrenergic blocking agents are recommended for arrhythmias, and calcium channel blocking agents and/or nitrates for ischemic syndromes related to cocaine. It is emphasized that these recommendations are based upon a paucity of relevant clinical studies, and controlled clinical trials to establish their efficacy have not been performed.


The FPase properties and morphology changes of a cellulolytic bacterium, Sporocytophaga sp. JL-01, on decomposing filter paper cellulose.
Sporocytophaga sp. JL-01 is a sliding cellulose degrading bacterium that can decompose filter paper (FP), carboxymethyl cellulose (CMC) and cellulose CF11. In this paper, the morphological characteristics of S. sp. JL-01 growing in FP liquid medium was studied by Scanning Electron Microscope (SEM), and one of the FPase components of this bacterium was analyzed. The results showed that the cell shapes were variable during the process of filter paper cellulose decomposition and the rod shape might be connected with filter paper decomposing. After incubating for 120 h, the filter paper was decomposed significantly, and it was degraded absolutely within 144 h. An FPase1 was purified from the supernatant and its characteristics were analyzed. The molecular weight of the FPase1 was 55 kDa. The optimum pH was pH 7.2 and optimum temperature was 50°C under experiment conditions. Zn(2+) and Co(2+) enhanced the enzyme activity, but Fe(3+) inhibited it.


A Novel Antiplatelet Aggregation Target of Justicidin B Obtained From Rostellularia Procumbens (L.) Nees.
The present study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. Firstly, we found that the ethyl acetate extraction obtained from R. procumbens could inhibit platelet aggregation. Then, gene chip was used to investigate differentially expressed genes and blood absorption compounds were investigated using high performance liquid chromatography-mass spectrometry characterization (LC-MS). Depending on the results of gene chip and LC-MS, the targets of blood absorption compounds were predicted according to the reverse pharmacophore matching model. The platelet aggregation-related genes were discovered in databases, and antiplatelet aggregation-related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the DAVID database, and the network was constructed using Cytoscape software. We found that integrin αIIbβ3 had a highest degree, and it was almost the intersection of all pathways. Then, blood absorption compounds were screened by optical turbidimetry. Western blot (WB) revealed that justicidin B separated from the ethyl acetate fraction may inhibit the expression of integrin αIIbβ3 protein. For the first time, we used Prometheus NT.48 and MST to detect the stability of this membrane protein to optimize the buffer and studied the interaction of justicidin B with its target protein. To our best knowledge, this is the first report to state that justicidin B targets the integrin αIIbβ3 protein. We believe that our findings can provide a novel target protein for the further understanding of the mechanism of R. procumbens on platelet aggregation.


Effect of reperfusion on myocardial infarct, and the accuracy of estimating infarct size from serum creatine phosphokinase in the dog.
This study was designed to determine the effect of coronary reperfusion on (1) myocardial infarct size and (2) the accuracy of previously reported methods for estimation of infarct size serum creatine phosphokinase (CPK) values. Thirty mongrel dogs, chronically prepared, were studied in the awake state, and were divided into four groups according to the period or left circumflex coronary artery (LCCA) occlusion. Group 1: permanent occlusion (24 h) in nine dogs; group 2: 45 min occlusion (eight dogs); group 3: 1 h occlusion (five dogs); and group 4: 3 h occlusion (eight dogs). Serial blood samples were drawn for 24 h following the beginning of occlusion and were used to determine total and isoenzyme levels of CPK, and lactic dehydrogenase isoenzymes. All dogs were sacrified 24 h after the beginning of occlusion and were anatomically examined. The extent of anatomical myocardial infarction was determined and compared with the extent of myocardial infarction as estimated from serial serum CPK values. Total serum CPK increased significantly in all groups and was associated with the appearance of CPK-MB isoenzyme and an increase in LDH1,2 (LDH1 greater than LDH2) in most dogs. Total serum CPK increased within an hour after reperfusion and the mean values in groups 2, 3, and 4 were significantly high (P less than 0.05) than serum CPK values in group 1 in the period from 110 min to 4 after occlusion. These data demonstrate that reperfusion after 45 min to 3 h of coronary occlusion results in an earlier appearance of total serum CPK. The anatomical infarction in group 1 averaged 28% +/- 3% (SEM) of the total heart and was significantly larger than infarct size in all groups with reperfusion. In contrast, estimated infarction calculated from total CPK in group 1 was not significantly different from the reperfused groups. Although there was correlation between estimated and anatomical infarction, the data in each group showed that anatomical infarct size could not be accurately estimated from total serum CPK.


Difference of concentration of placental soluble fms-like tyrosine kinase-1(sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in severe preeclampsia and normal pregnancy.
Placental soluble fms-like tyrosine kinase-1 (sFlt-1) which is an antagonist of vascular endothelial growth factor and placental growth factor (PIGF), is considered as one of etiology factors cause endothelial damage in preeclampsia due to increase of sFlt-1 level that change vascular endothelial integrity. This study aims to analyze the difference of sFlt-1 and PlGF concentration in severe preeclampsia and normal pregnancy, and the correlation between both in occurrence of severe preeclampsia. This is case control study involving 18 subjects with severe preeclampsia and 19 subjects with normal pregnancy as controls who met inclusion and exclusion criteria. Concentration of sFlt-1 and PlGF are measured with ELISA. Statistical analysis is performed with Chi square test, Fisher's exact test, T test, Mann-Whitney test, and Spearman's rank correlation test. This study results in no significant difference in characteristics of gestational age, and parity in both study groups. Median concentration of sFlt-1 in severe preeclampsia is higher (20,524.75 pg/mL) compared with normal pregnancy (6820.4 pg/mL). Concentration of PlGF is lower in severe preeclampsia (47 pg/mL) compared with normal pregnancy (337 pg/mL). sFlt-1 concentration is higher in severe preeclampsia compared to normal pregnancy. PlGF concentration is lower in severe preeclampsia compared to normal pregnancy. Ratio of sFlt-1 and PlGF concentration is significantly correlated in both severe preeclampsia and normal pregnancy. There is a significant negative correlation between the concentration of sFLt-1 and PlGF in normal pregnancy.


Embolization of cranial dural arteriovenous fistulae with ONYX: Indications, techniques, and outcomes.
The purpose of this study was to establish the role of the liquid embolic agent, ONYX, in the treatment of cranial dural arteriovenous fistulae (DAVFs) and to redefine the indications, techniques and outcomes of treatment with ONYX. This is a retrospective study of 25 DAVF patients who underwent endovascular treatment with ONYX between February 2006 and July 2008. All patients of DAVF presenting in this period were treated with ONYX. Anatomic cure (i.e., complete angiographic closure of the fistula) was achieved in a single session and through a single arterial pedicle injection in 21 out of 25 patients (cure rate of 84%). Out of four patients with residual fistulae, one achieved cure that was evident on a control angiogram obtained at 3 months while three had no vascular access for further embolization and so were referred for radiosurgery. There was only one recurrence seen in angiograms obtained at the end of one year and this patient was re-embolized successfully with ONYX. Complications were seen in two patients. ONYX embolization of DAVFs has revolutionized the endovascular treatment of DAVFs, achieving high cure rates in a single session with minimal complications. Transarterial ONYX embolization should be the first option for all locations, except cavernous DAVFs.


Cloning and expression of a Pseudomonas 3 alpha-hydroxysteroid dehydrogenase-encoding gene in Escherichia coli.
A bacterial strain, B-0831, which produced 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD) was isolated and identified as belonging to the genus, Pseudomonas. Molecular weights of the purified 3 alpha HSD, determined by SDS-PAGE and by chromatography on Sephacryl S-200, were about 25 and 50 kDa, respectively. A genomic library of Pseudomonas sp. B-0831, prepared in the plasmid vector pACYC184, was screened with probes based on the amino acid (aa) sequence of the protein to obtain the plasmid, p3 alpha HSD1, identified by hybridization with the probes, that contained a 2.4-kb insert from Pseudomonas DNA. When the 1.4-kb SphI fragment of p3 alpha HSD1 was inserted into the vector, pUC118, and introduced into Escherichia coli DH1 under the control of lacZ promoter in the vector, the transformants produced 200-fold more 3 alpha HSD intracellularly than Pseudomonas sp. B-0831. Sequence analysis of the 3 alpha HSD gene revealed that an ORF encoding 3 alpha HSD consists of 254 aa, with a calculated M(r) of 25,761, suggesting that the enzyme consists of homodimer subunits.


[Diurnal variation and responses of corticoids to dexamethasone and ACTH before and after adrenal surgery in primary aldosteronism].
We studied diurnal variation and the responses of plasma corticoids to dexamethasone and ACTH before and after adrenal surgery in 11 patients with primary aldosteronism. Diurnal variation of plasma corticoids was examined in all cases. Before adrenal surgery, plasma aldosterone (Ald) was higher at all times, deoxycorticosterone (DOC) was high value at 5:00 and then normal value, 11-deoxycortisol (S) was high value at 5:00 and 9:00, thereafter normal value, while corticosterone (B) and cortisol (F) were almost normal value at all times. The circadian rhythm was observed in these corticoids. Dexamethasone (2 mg/day) was administered to 8 patients for 10 days. Plasma Ald and DOC were significantly suppressed only at 5:00, while B, S and F almost suppressed at all times. After dexa suppression, the circadian rhythm of Ald still observed, while the diurnal variation of the other corticoids was even. ACTH (1 microgram) was injected intravenously to 9 patients. Responses of DOC, B and Ald were higher, and of S and F were almost normal. Diurnal variation of plasma corticoids was observed after 1 month of adrenal surgery. Ald was lower, the other corticoids were normal values. ACTH (1 microgram) was injected to the same case before surgery. Responses of these corticoids to ACTH were slightly lower. Contents of Ald in adenoma tissues were higher than those in adjacent and normal adrenal tissues, and the contents of the other corticoids in adenoma tissue were almost normal value. As these results showed, before surgery these corticoids were secreted from adenoma without ACTH, although these were responsible to ACTH, and the presence of regulative factor of circadian rhythm except ACTH was suggested. After surgery, not only the responses to ACTH of mineralocorticoids but these of glucocorticoids decreased.


NR5A1 prevents centriole splitting by inhibiting centrosomal DNA-PK activation and β-catenin accumulation.
Adrenogonadal cell growth and differentiation are controlled by nuclear receptor NR5A1 (Ad4BP/SF-1) that regulates the expression of adrenal and gonadal genes. In addition, SF-1 also resides in the centrosome and controls centrosome homeostasis by restricting the activity of centrosomal DNA-PK and CDK2/cyclin A. Here we show that SF-1 depletion resulted in centriole splitting and amplification due to aberrant activation of DNA-PK in the centrosome of mouse adrenocortical Y1 cells. In the absence of SF-1, GSK3β was aberrantly phosphorylated during G1 phase and β-catenin was accumulated in the centrosome, but not in the nucleus. DNA-PK inhibitor vanillin reversed these phenomena. SF-1 overexpression led to inhibition of centrosomal DNA-PK activation caused by SF-1 depletion. Both full-length SF-1 and truncated SF-1 devoid of its DNA-binding domain rescued the multiple centrosome phenotype caused by SF-1 depletion, indicating that the effect of SF-1 in the centrosome is not contributed by its DNA-binding domain. Furthermore, SF-1 interacted with cyclin A in the centrosome, but not in the nucleus. Depletion of SF-1 also resulted in centriole splitting, genomic instability and reduced growth of mouse testicular Leydig MA10 cells. Centrosomal DNA-PK signaling triggers the accumulation of β-catenin, leading to centrosome over-duplication and centriole splitting. This cascade of centrosomal events results in genomic instability and reduced cell numbers.


Effect of p-amino-diphenyl ethers on hepatic microsomal cytochrome P450.
The present paper aims to investigate whether p-amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether are inhibitors as well as inducers of P450. Mice were given daily intraperitoneal (ip) injections of p-amino-2',4'-dichlorodiphenyl ether (0.25 mmol/kg) or p-amino-4'-methyldiphenyl ether (0.25 mmol/kg) for 4 days and tested at 24 h and 48 h after the last dose injection. The results showed the mice pentobarbital sleeping time was shorter and the P450 content of hepatic microsome increased significantly in the group pretreated with p-amino-4'-methyldiphenyl ether when compared with the control group, while in mice pretreated with p-amino-2',4'-dichlorodiphenyl ether the hepatic microsome P450 content increased but the pentobarbital sleeping time was extended in clear contrast to the control group. The sleeping time of the phenobarbital group (80 mg/kg daily ip injection for 4 days) was shortened at 24 h after the last injection with increased P450 content of hepatic microsome, but it showed no difference at 48 h. The zoxazolamine-paralysis times of mice treated with p-amino-2',4'-dichlorodiphenyl ether were longer than those of the control mice, while the same dose of zoxazolamine did not lead to paralysis in mice pretreated with BNF. p-Amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether inhibited the activity of 7-ethoxyresorufin O-deethylase from rat hepatic microsome induced by BNF in vitro by 70.0% and 50.1% respectively. These results suggest that p-amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether are inhibitors as well as inducers of P450.


Overexpression of aquaporin 4 in articular chondrocytes exacerbates the severity of adjuvant-induced arthritis in rats: an in vivo and in vitro study.
The dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known. This study was aimed to investigate the expression of aquaporin 4 (AQP4) in articular chondrocytes of adjuvant-induced arthritis (AIA) rats and its involvement in AIA development. Thirty rats were divided into normal and AIA group (n = 15). Rat AIA was induced by intradermal injection of complete Freund's adjuvant and evaluated by secondary paw swelling and histological assessments on knee joint damage. Localization and protein expression of AQP4 in articular cartilage were examined by immunohistochemistry and western blot. In vitro study, AIA articular chondrocytes were cultured and treated with acetazolamide, an AQPs inhibitor. AQP4 protein level, cell proliferation and mRNA levels of type-II collagen (COII) and aggrecan were measured by western blot, MTT assay and real-time PCR, respectively. The results of immunohistochemistry and western blot indicated that AQP4 showed higher protein levels in cartilage tissues of AIA rats than that of normal rats. Correlation analysis revealed that AQP4 protein level in cartilage tissues of AIA rats remarkably correlated positively with secondary paw swelling on day 26 after AIA induction as well as pathological scores on joint damage. Additionally, acetazolamide treatment effectively decreased AQP4 protein level, increased cell proliferation and mRNA levels of COII and aggrecan, suggesting AQP4 inhibition by acetazolamide could normalize the dysfunction of AIA articular chondrocytes in vitro. Our data provide certain experimental evidence that AQP4 over-expression in articular chondrocytes aggravated AIA severity and might be a novel target for RA treatment.


Long-term modulation of respiratory network activity following anoxia in vitro.
Neural networks that produce rhythmic behaviors require flexibility to respond to changes in the internal and external state of the animal. It is important to not only understand how a network responds during such perturbations but also how the network recovers. For example, the respiratory network needs to respond to and recover from temporary changes in oxygen level that can occur during sleep, exercise, and respiratory disorders. During a temporary decrease in oxygen level, there is an increase in respiratory frequency followed by a depression that can lead to complete apnea. Here we used a mouse brain stem slice preparation as a model system to examine the recovery of respiratory network activity after brief episodes of anoxia. We found the respiratory network recovers from a single anoxic episode with a transient increase in fictive respiratory frequency. Although repetitive anoxia does not elicit a greater frequency increase, it does elicit a longer lasting frequency increase persisting < or =90 min. Thus there is a centrally mediated long-lasting influence on the respiratory network elicited by decreased oxygen levels. This modulation occurs as a prolonged facilitation of fictive respiratory frequency after brief repetitive but not single anoxic exposure. These data are important to consider in the context of disorders such as sleep apnea in which brief periodic anoxic episodes are experienced.


A defined substrate technology for the enumeration of microbial indicators of environmental pollution.
The examination of water and other environmental sources for microbial pollution is a major public health undertaking. Currently, there are two accepted methods in use: the multiple-tube fermentation (MTF) and the membrane filtration (MF) tests. Both methods are designed to enumerate the secondary indicator group, total coliforms. Both tests suffer several inherent limitations, including a time delay of three to seven days to obtain a definitive result, the subjective nature of the test interpretation, and the inability to provide directly useful public health information. A defined substrate technology, originally used to enumerate specific bacterial species from mixtures in clinical urine specimens, was applied to water testing; the technology was constituted to enumerate simultaneously both total coliforms and the primary indicator bacterium E. coli. Examination of environmental isolates of these two classes of target microbes showed sensitivity equal to available methods, with potentially greater specificity. It was not subject to inhibition by bacteria other than the targets, grew injured coliforms, did not require confirmatory tests, and the maximum time to a positive was 24 hours. The defined substrate technology provides both regulatory and directly useful public health information.


Toxicity reduction in an industrial nitro-aromatic wastewater plant: an assessment and a proposed improvement.
In this study, the performance of a typical Chinese industrial nitro-aromatic wastewater project (operational capacity: 3,000 m(3)d(-1)) was evaluated using chemical properties and toxicity data. Additionally, the relationship between the removal of organic pollutants and toxicity reduction was investigated throughout the whole-process wastewater treatment. Current advanced treatment reduced the dissolved organic carbon by 40% compared with biologically treated wastewater effluent (BTWE), but the acute toxicity and early life-stage toxicity increased significantly. For instance, the acute toxicity of the current advanced treated wastewater was 450% greater than that of the untreated BTWE. With the aim of effectively decreasing the toxicity of the effluent, several efficient adsorption technologies were assessed and compared for further treatment of BTWE. Coagulation and/or oxidation coupled with activated carbon adsorption, hypercrosslinked resin adsorption, or MIEX(®) technology was helpful for improving chemical indices and reducing toxicity. Among these adsorption treatment technologies, hypercrosslinked resin adsorption was more effective at removing most of the toxicants than MIEX(®) technology, and it also had better regeneration efficiency and mechanical properties compared with activated carbon. Therefore, hypercrosslinked resin adsorption may be a promising technology for enhancing organic pollutant removal and toxicity reduction of BTWE from nitro-aromatic factories.


Using movies in family medicine teaching: A reference to EURACT Educational Agenda.
Cinemeducation is a teaching method where popular movies or movie clips are used. We aimed to determine whether family physicians' competencies as listed in the Educational Agenda produced by the European Academy of Teachers in General Practice/Family Medicine (EURACT) can be found in movies, and to propose a template for teaching by these movies. A group of family medicine teachers provided a list of movies that they would use in cinemeducation. The movies were categorised according to the key family medicine competencies, thus creating a framework of competences, covered by different movies. These key competencies are Primary care management, Personcentred care, Specific problem-solving skills, Comprehensive approach, Community orientation, and Holistic approach. The list consisted of 17 movies. Nine covered primary care management. Person-centred care was covered in 13 movies. Eight movies covered specific problem-solving skills. Comprehensive approach was covered in five movies. Five movies covered community orientation. Holistic approach was covered in five movies. All key family medicine competencies listed in the Educational Agenda can be taught using movies. Our results can serve as a template for teachers on how to use any appropriate movies in family medicine education.


Treatment of Raynaud's phenomenon with ketanserin, a selective antagonist of the serotonin2 (5-HT2) receptor.
Ketanserin, a selective antagonist of the 5-HT2 receptor, was evaluated in a 4-week open pilot trial of 30 patients with Raynaud's phenomenon. Moderate or marked relief was reported in 15 of 18 (83%) patients with systemic sclerosis, whereas only 4 of 12 (33%) patients with Raynaud's phenomenon of other etiology received such benefit (P less than 0.01). These subjective ratings were supported by the results of serial digital strain gauge plethysmography during controlled cold challenge. Additional clinical findings suggested that ketanserin therapy facilitated the healing of ischemic digital ulcerations and reduced hand edema in patients with systemic sclerosis. These findings lend support to the hypothesis that serotonin is an important element in the pathogenesis of systemic sclerosis.


[Dissection of the internal carotid artery. Personal case reports and a review of the literature].
The clinical and angiographic features of 20 patients affected by internal carotid artery dissection are reported. In one patient the neurological signs were related to a traumatic event, in two cases the symptoms presented after hyperextension of the neck during athletic events, while their onset was apparently spontaneous in the remaining 17 patients. Plain CT was normal in 14 cases and positive for ischemic necrosis in 6 patients. Angiography demonstrated extensive/segmental stenosis of the internal carotid lumen in 12 cases (60%), pseudoaneurysmal dilatation in 3 cases (15%), and complete carotid occlusion in 5 patients (25%). The "double lumen" feature was seen in 3 cases at the origin of the dissection. One patient died, surgical ligature of the internal carotid artery was performed in two cases, while the other patients received medical treatment with platelet inhibitors, except for the young patient affected by post-traumatic artery dissection. Complete recovery was observed in 82% of the patients. Follow-up angiograms demonstrated normal recanalization of the internal carotid artery in 4 out of 6 patients; one of them had two false aneurysms which following angiograms demonstrated to be completely resolved. Regression of stenosis was observed in 6 of the remaining patients by Doppler US. On the whole, the recanalization of the internal carotid artery was observed in 59% of cases. Angiographic findings seemed not to play a decisive role in the prognosis of carotid dissections, which largely depends on the overall patient's condition and on the presence/absence of ischemic cerebral damages.


A Case of Chronic Thromboembolic Pulmonary Hypertension in a High-Altitude Dweller.
Chronic hypoxia causes sustained pulmonary vasoconstriction and vascular remodeling leading to development of pulmonary hypertension in high-altitude residents. Although pulmonary hypertension is of mild to moderate degrees in most cases, some high-altitude residents may develop severe pulmonary hypertension. We report a case of a 47-year-old female highlander of Kyrgyz ethnicity who presented with exertional breathlessness and echocardiographic signs of severe pulmonary hypertension, who was diagnosed as having chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, this is the first documented case of severe CTEPH in a high-altitude dweller. This case illustrates that causes other than hypoxia may underlie and/or contribute to severe pulmonary hypertension in residents of high altitude.


EXPERIMENTAL VIABLE VACCINE AGAINST PULMONARY COCCIDIOIDOMYCOSIS IN MONKEYS.
Converse, John L. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.), Merida W. Castleberry, and Ernest M. Snyder. Experimental viable vaccine against pulmonary coccidioidomycosis in monkeys. J. Bacteriol. 86:1041-1051. 1963.-Monkeys (Macaca mulatta) vaccinated by subcutaneous injection in the forearm with from 10 to 10(8) viable Coccidioides immitis arthrospores were protected against respiratory challenge with approximately 7000 viable arthrospores administered 6 months after vaccination. Protection was evident from: the healthy appearance throughout 4 months after respiratory challenge; negative chest X rays at 15, 30, 60, and 120 days; and only very minor histopathological pulmonary changes on autopsy at 120 days, with negative lung cultures in 80% of the animals. This was in striking contrast to the outward clinical appearance of control monkeys that were unvaccinated or had received nonviable arthrospore vaccines. These monkeys showed severe disease (loss of weight, accelerated respiration, severe coughing, general debilitation), positive X rays, massive pulmonary destruction, positive lung cultures, and death of five of nine animals. The appearance of spherules (very few in number, accompanied by very minor pathological changes) in the lungs of some of the "dissemination controls" (subcutaneous viable vaccination without respiratory challenge) indicated possible dissemination from the primary cutaneous infection, although oral transmission from the cutaneous lesions could not be ruled out.


Four decades of anal cancer in Tasmania, Australia: what do the case data tell us?
Anal cancer is a rare cancer analogous to cervical cancer, largely caused by exposure to oncogenic human papillomavirus. We have sought to study this disease in the epidemiologically distinct population of Tasmania. Medical records at all tertiary and secondary referral centres in Tasmania were audited for records with corresponding International Classification of Diseases (ICD)-10 codes. Statistical significances of trends were evaluated using Fisher's exact test, logistic regression or linear regression. Of ~1350 screening records, 170 cases of anal cancer were found with patient presentation during 1973-2010, corresponding to 132 patients. This cohort was mostly female (66.7%), with squamous cell histology (81.8%) and anal canal primaries (72.0%). Most cases were detected at Stage II or below and the majority remained disease-free after treatment. Relatively few cases had documentation of typical risk factors for anal cancer, such as HIV seropositivity, a history of cancer or smoking. After 2000, there was a trend towards a lower stage at presentation, correlating with an increased 5-year survival. After 2000, no anal margin tumours presented beyond Stage II; nearly half were detected in situ and none were fatal. For anal canal tumours, there was virtually no change in the mean stage at detection or in survival. This is the first case series of anal cancer in Tasmania. We find that in many ways, including symptoms and pathology at presentation, epidemiology is typical. However, our cohort is distinct in its paucity of known risk groups, including HIV-positive people, those with a history of cancer and smokers.


Risk factors for underimmunization in poor urban infants.
To assess risk factors for underimmunization in poor urban infants. Prospective cohort study. A large municipal teaching hospital in the Midwest. A total of 464 healthy, full-term newborn infants delivered at a large municipal teaching hospital who were to be discharged to the care of their mothers. Mothers were interviewed 24 to 72 hours post partum regarding personal and financial characteristics and 9 to 12 months later to determine where immunizations had been received. Immunization status at 3 and 7 months of age. Despite availability of free vaccine to most patients, only 67% had received their first set of immunizations by 3 months of age, and only 29% were up-to-date by 7 months of age. Marital status, coresidence with the infant's grandmother, adequacy of prenatal care, and perceived barriers to care were significant independent predictors of initiation of immunizations by 3 months and completion of immunization by 7 months. Poverty was also an independent predictor of immunization status at 7 months. Perceived susceptibility to common symptoms and perceived benefit of medical care to prevent disease were inversely related to immunization status at 7 months. These data suggest that poor urban infants of single mothers and of mothers who received inadequate prenatal care, and those not living with their grandmother should be targeted for tracking and follow-up to ensure adequate immunization. The provision of free vaccine alone will not guarantee adequate immunization coverage of poor urban children.


Gamma-Ray and Radio-Frequency Radiation from Thunderstorms Observed from Space and Ground.
Terrestrial gamma ray flashes (TGFs) are a class of enigmatic electrical discharges in the Earth's atmosphere. In this study, we analyze an unprecedentedly large dataset comprised of 2188 TGFs whose signatures were simultaneously measured using space- and ground-based detectors over a five-year period. The Gamma-ray Burst Monitor (GBM) on board the Fermi spacecraft provided the energetic radiation measurements. Radio frequency (RF) measurements were obtained from the Global Lightning Dataset (GLD360). Here we show the existence of two categories of TGFs - those that were accompanied by quasi-simultaneous electromagnetic pulses (EMPs) detected by the GLD360 and those without such simultaneous EMPs. We examined, for the first time, the dependence of the TGF-associated EMP-peak-amplitude on the horizontal offset distance between the Fermi spacecraft and the TGF source. TGFs detected by the GBM with sources at farther horizontal distances are expected to be intrinsically brighter and were found to be associated with EMPs having larger median peak-amplitudes. This provides independent evidence that the EMPs and TGFs are produced by the same phenomenon, rather than the EMPs being from "regular" lightning in TGF-producing thunderstorms.


Control of calcium oxalate crystal structure and cell adherence by urinary macromolecules.
Crystal polymorphism is exhibited by calcium oxalates in nephrolithiasis, and we have proposed that a shift in the preferred crystalline form of calcium oxalate (CaOx) from monohydrate (COM) to dihydrate (COD) induced by urinary macromolecules reduces crystal attachment to epithelial cell surfaces, thus potentially inhibiting a critical step in the genesis of kidney stones. We have tested the validity of this hypothesis by studying both the binding of monohydrate and dihydrate crystals to renal tubule cells and the effect of macromolecular urinary solutes on crystal structure. Renal tubule cells grown in culture bound 50% more CaOx monohydrate than dihydrate crystals of comparable size. The effects of macromolecules on the spontaneous nucleation of CaOx were examined in HEPES-buffered saline solutions containing Ca2+ and C2O4(2-) at physiologic concentrations and supersaturation. Many naturally occurring macromolecules known to be inhibitors of crystallization, specifically osteopontin, nephrocalcin and urinary prothrombin fragment 1, were found to favor the formation of calcium oxalate dihydrate in this in vitro system, while other polymers did not affect CaOx crystal structure. Thus, the natural defense against nephrolithiasis may include impeding crystal attachment by an effect of macromolecular inhibitors on the preferred CaOx crystal structure that forms in urine.


Suffering for science: the effects of implicit social demands on response to experimentally induced pain.
In two experiments subjects rated their pain during baseline trials of cold pressor and finger pressure pain. After various instructional treatments, they were posttested with these same stimuli. As in previous studies, we found in both experiments that coping suggestions significantly reduced reported pain. Experiment 1, however, demonstrated that subjects often refrained from using available cognitive coping strategies to reduce pain unless they had been given explicit permission to do so. Experiment 2 replicated this finding and also showed that explicit permission to "do whatever you can to reduce pain" was as effective as a coping suggestion in decreasing reported pain. These findings indicate that subjects' interpretation of what is appropriate responding in the test situation determines how they choose to cope with the painful stimulation. Thus standard experimental procedures for assessing baseline levels of pain implicitly lead subjects to refrain from coping and thereby tend to underestimate their ability to control pain. Moreover, suggestions and other instructional techniques for coping with pain may produce much of their effect not by teaching subjects new coping skills but instead by giving them permission to use already available coping strategies.


Targeting dynamic hyperinflation in moderate-to-severe asthma: a randomised controlled trial.
Dynamic hyperinflation is highly prevalent in moderate-to-severe asthma, which may significantly impede activities of daily life. We hypothesised that dynamic hyperinflation in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on dynamic hyperinflation in moderate-to-severe asthma patients and explored the relationships between inflammatory markers and changes in dynamic hyperinflation. In this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing dynamic hyperinflation, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured, and underwent lung function and dynamic hyperinflation testing. After adjustment for potential confounders, dynamic hyperinflation was significantly reduced by 28.1% in the triamcinolone group and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in dynamic hyperinflation was greater in patients with higher blood eosinophils at baseline (r=-0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099). This exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment.


Suppression of natural killer cell activity by splenocyte transplantation in a rat model of endometriosis.
One immune characteristic of endometriosis is a decrease in natural killer (NK) cell activity. This study was performed to determine whether an abnormal immune reaction in an endometriosis animal model could be transferred to an animal of the same species. An endometriosis model was prepared using 8 week old female rats by grafting a small section of one uterine horn onto the mesentery, followed 4 weeks later by removal of the spleen and remaining uterine horn. Splenocytes, that had been depleted of macrophages were injected via the tail vein, and NK cell activity of splenocytes was determined 4 days later. The uterus was simultaneously investigated immunohistochemically for immune cells. There was a control group (untreated; group 1), a control-splenocyte injection group (group 2), an experimental endometriosis model group (group 3) and an endometriosis model splenocyte injection group (group 4). Splenocyte NK cell activity was decreased in group 3 to 42.0% of that of group 1 and in group 4 to 38.9%. Immunohistologically, the number of NK cells in groups 3 and 4 markedly decreased to 62.0 and 55.1% of group 1 respectively. It was demonstrated that abnormal immunity caused by allograft of immune cells could recur in an endometriosis rat model.


Effect of Thermal Treatments and Ion Substitution on Sintering and Crystallization of Bioactive Glasses: A Review.
Bioactive glasses (BGs) are promising materials for bone regeneration due to their ability to bond with living bone tissue. However, thermal stability and mechanical properties of BGs need improvement for better clinical performance. In this paper, we present an overview of the influence of different ions on the sintering and crystallization of BGs. Specifically, this review focuses on the impact of thermal treatments on the crystallization of 45S5 and other significant BG compositions. Potential applications of these thermally treated BGs, such as scaffolds, BG-based composites, and thermally sprayed coatings, are explored. Moreover, the substitution of ions has been investigated as a method to enhance the thermal properties of BGs. Notably, zinc, potassium, and strontium have been studied extensively and have demonstrated promising effects on both the thermal and the mechanical properties of BGs. However, it is important to note that research on ion inclusion in BGs is still in its early stages, and further investigation is necessary to fully comprehend the effects of different ions on sintering and crystallization. Therefore, future studies should focus on optimizing the ion substitution method to improve the thermal, mechanical, and even biological properties of BGs, thereby enhancing their potential for various biomedical applications.


Dectin-1-Independent Macrophage Phagocytosis of Mycobacterium abscessus.
Mycobacterium abscessus, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with chronic airway diseases. Although knowledge pertaining to molecular mechanisms of host defense against NTM is increasing, macrophage receptors that recognize M. abscessus remain poorly defined. Dectin-1, a C-type lectin receptor identified as a fungal receptor, has been shown to be a pathogen recognition receptor (PRR) for both M. tuberculosis and NTM. To better understand the role of Dectin-1 in host defense against M. abscessus, we tested whether blocking Dectin-1 impaired the uptake of M. abscessus by human macrophages, and we compared M. abscessus pulmonary infection in Dectin-1-deficient and wild-type mice. Blocking antibody for Dectin-1 did not reduce macrophage phagocytosis of M. abscessus, but did reduce the ingestion of the fungal antigen zymosan. Laminarin, a glucan that blocks Dectin-1 and other PRRs, caused decreased phagocytosis of both M. abscessus and zymosan. Dectin-1-/- mice exhibited no defects in the control of M. abscessus infection, and no differences were detected in immune cell populations between wild type and Dectin-1-/- mice. These data demonstrate that murine defense against M. abscessus pulmonary infection, as well as ingestion of M. abscessus by human macrophages, can occur independent of Dectin-1. Thus, additional PRR(s) recognized by laminarin participate in macrophage phagocytosis of M. abscessus.


Maternal contributions to the development of masculine sexual behavior in laboratory rats.
Maternal licking was manipulated by lining the nasal passages of rat dams with polyethylene tubing to interfere with their olfactory competence. Olfactory cues from pups elicit maternal licking and handling, particularly of anogenital regions, and dams with olfactory deficits were observed to lick their pups less. Mature male and female offspring of these dams and their controls were gonadectomized, treated with testosterone propionate, and tested for masculine sexual behavior. The male offspring of dams that provided less maternal licking had longer ejaculatory latencies, longer post-ejaculatory intromission latencies, and longer inter-intromission intervals than controls. Female offspring of the intubed dams performed fewer mounts and intromissions, had longer intromission latencies, and longer inter-intromission intervals. It was concluded that stimulation from maternal licking contributes toward the development of a mechanism that underlies the timing of copulatory rate.


The metabolic, locomotor and sex-dependent effects of elevated temperature on Trinidadian guppies: limited capacity for acclimation.
Global warming poses a threat to many ectothermic organisms because of the harmful effects that elevated temperatures can have on resting metabolic rate (RMR) and body size. This study evaluated the thermal sensitivity of Trinidadian guppies (Poecilia reticulata) by describing the effects of developmental temperature on mass, burst speed and RMR, and investigated whether these tropical fish can developmentally acclimate to their thermal conditions. These traits were measured following exposure to one of three treatments: 70 days at 23, 25, 28 or 30°C (acclimated groups); 6 h at 23, 28 or 30°C following 70 days at 25°C (unacclimated groups); or 6 h at 25°C following 70 days in another 25°C tank (control group). Body mass was lower in warmer temperatures, particularly amongst females and individuals reared at 30°C. The burst speed of fish acclimated to each temperature did not differ and was marginally higher than that of unacclimated fish, indicative of complete compensation. Conversely, acclimated and unacclimated fish did not differ in their RMR at each temperature. Amongst the acclimated groups, RMR was significantly higher at 30°C, indicating that guppies may become thermally limited at this temperature as a result of less energy being available for growth, reproduction and locomotion. Like other tropical ectotherms, guppies appear to be unable to adjust their RMR through physiological acclimation and may consequently be susceptible to rising temperatures. Also, because larger females have higher fecundity, our data suggest that fecundity will be reduced in a warmer climate, potentially decreasing the viability of guppy populations.


Prostaglandins E2 and F2 alpha and acetylcholinesterase activity in the slices of some structures in the cat's brain.
Prostaglandins E2 and F2 alpha at small concentrations inhibit the acetylcholinesterase activity in slices of caudate nucleus, thalamus and hypothalamus of the cat brain in vitro condition. Prostaglandin E2 (PGE2) at concentrations of 0.35 microM and 0.70 microM produces a dose-dependent inhibition of acetylcholinsteratse activity in slices of caudate nucleus, thalamus and hypothalamus. Higher concentration of PGE2 (2.1 microM) produces less inhibition of acetylcholinesterase activity than smaller concentration of PGE2. The highest concentration of PGE2 (6.3 microM) produces even less inhibition of the same enzyme, which is not significant to the control values of the enzyme activity. Prostaglandin F2 alpha (PGF2 alpha ) inhibits acetylcholinesterase activity in slices of thalamus and hypothalamus of the cat brain in a dose-dependent manner. In caudate nucleus the highest concentration of PGF2 alpha produces somewhat less inhibition than smaller concentration of that prostaglandin. These results are discussed in the context of established potentiating effect of small doses of prostaglandins of gross behavioural changes induced by cholinomimetic substances.


[Results of measurements of local doses with film-dosimeters (author's transl)].
In medical x-ray departments, industrial facilities and nuclear reactors, local radiation was measured with film dosimeters in more than 1700 different places. These were fixed over a period of about 30 days in different spots of the controlled rooms. The obtained measurements are classified into different groups. The advantage of film dosimeters compared with usual measurements of the dose rates is the fact that they give an average of the real dose over a period of time at low cost. The obtained results are of interest for radioprotection technique.


Comparison of Antimicrobial Activity between Chemical Disinfectants on Contaminated Orthodontic Pliers.
To compare the antimicrobial activity of the chemical substances--70% isopropyl alcohol, 2% glutaraldehyde (GTA) and 0.25% peracetic acid (PAA) in disinfecting orthodontic pliers contaminated in vitro with Streptococcui mutani, Staphylococci aureui and Candida albicani. Distal end cutter pliers were divided into five groups: group 1 (negative control--sterilized pliers), group 2 (positive control--sterilized plier, subsequently contaminated), group 3 (disinfected with 70% isopropyl alcohol, friction method), group 4 (disinfected with 2% GTA, immersion method for 30 minutes), group 5 (disinfected with 0.25% peracetic acid (PAA), immersion method for 10 minutes). After the pliers were treated with one disinfectant and submitted to microbiological evaluation (by counting colony forming units), they were submitted to the same cleansing, sterilizing and contaminating processes, and were used in the following groups (crossover and washout study). The two-factor analysis of variance (ANOVA) test, followed by the Tukey test, was used to compare the groups. The results showed that there was no statistically significant difference between the three tested disinfectants. Although there were no statistically significant differences between the disinfectants, the chemical agents 2% glutaraldehyde and 0.25% PAA were effective in inhibiting the growth of the three microorganisms tested; however, 70% isopropyl alcohol was unable to completely eliminate S. aureui. The chemical substances 2% glutaraldehyde and 0.25% PAA completely eliminated the microorganisms tested.


Purification and characterization of two isoforms of glucose 6-phosphate dehydrogenase (G6PDH) from Chlorella vulgaris C-27.
Two kinds of isoforms of glucose 6-phosphate dehydrogenase (G6PDH) were purified from cells of a freezing-tolerant strain, Chlorella vulgaris C-27, by sequential steps of chromatography on five kinds of columns, including a HiTrap Blue column which showed excellent separation of the isoforms from each other. The two isoforms (G6PDH1 and G6PDH2) were purified up to 109-fold and 197-fold with specific activity of 14.4 and 26.0 U/mg-protein, respectively. G6PDH1 showed an apparent Mr of 200,000 with a subunit Mr of about 58,000, whereas G6PDH2 showed an apparent Mr of 450,000 with a subunit Mr of about 52,000. The kinetic parameters were measured and several enzymatic features of the isoforms, such as effects of metal ions on the enzyme activity, were clarified, which showed that the two isoforms were different from each other in many respects. Among the effective ions, Cd2+ showed marked stimulating effects on both isoforms. G6PDH1 and G6PDH2 seem to be a cytosolic and a chloroplastic type, respectively, as judged by their sensitivity to DTT, and also from the results of sequence similarity searches using their N-terminal and internal amino acid sequences.


5-Androstene-3β,17β-diol promotes recovery of immature hematopoietic cells following myelosuppressive radiation and synergizes with thrombopoietin.
5-Androstene-3β,17β-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.


Early identification of permanent myocardial damage after coronary surgery is aided by repeated measurements of CK-MB.
ECG diagnosis of myocardial infarction after cardiac surgery is associated with major pitfalls and enzyme diagnosis is interfered by unspecific elevation unrelated to permanent myocardial injury. Sustained release of troponin-T is a marker of permanent myocardial injury if renal function is maintained. However, early identification of perioperative myocardial infarction is desirable and therefore the usefulness of creatine kinase monobasic (CK-MB) kinetics to detect myocardial injury early after coronary surgery was investigated. Two hundred and eighty-six patients undergoing coronary surgery were studied with respect to release of enzymes and troponin-T preoperatively and postoperatively 3 and 8 h after unclamping the aorta, and every morning postoperative days 1-4. CK-MB peak was found at 3 h (n = 145), 8 h (n = 103) and 16-20 h after unclamping (n = 38). Depending on when the CK-MB peak was recorded different demographic and perioperative characteristics were found. A sustained release of troponin-T was characteristic for the group with the CK-MB peak at 16-20 h after unclamping. If CK-MB is measured only once it may be advisable to do it on the first postoperative morning as these measurements provided the best discrimination between patients with and without sustained elevation of troponin-T. However, repeated sampling provides additional information that aids in the early identification of permanent myocardial injury particularly in patients with borderline elevations of CK-MB.


Noninvasive ventilation after intubation and mechanical ventilation.
Patients with chronic airflow obstruction who are difficult to wean from mechanical ventilation are at increased risk of intubation-associated complications and mortality because of prolonged invasive mechanical ventilation. Noninvasive positive pressure ventilation may revert most of the pathophysiological mechanisms associated with weaning failure in these patients. Several randomized controlled trials have shown that use of noninvasive ventilation to achieve earlier extubation in difficult-to-wean patients or in patients who develop respiratory failure after apparently successful extubation can result in reduced periods of endotracheal intubation and complication rates and improved survival. However, this is not a consistent finding, and the currently available published data with outcome as the primary variable are exclusively from patients who had pre-existing lung disease. In addition, the patients were haemodynamically stable, with a normal level of consciousness, no fever and a preserved cough reflex. It remains to be seen whether noninvasive positive pressure ventilation has a role in other patient groups and situations, such as prevention of postextubation failure or unplanned extubation. The technique is, however, a useful addition to the therapeutic armamentarium for a group of patients who pose a significant clinical and economic challenge.


Preparation and characterization of nanoaggregates self-assembled by lithocholic acid and N-trimethyl modified chitosan derivatives.
A novel kind of chitosan derivatives (CS-LA-TM) were synthesized by grafting hydrophobic molecules of lithocholic acid (LA) and quaternization. CS-LA-TM and micelle-like self-aggregates were characterized by FTIR, 1H NMR, fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). The critical micelles concentration (CMC) ranging from 0.009 mg/mL to 0.030 mg/mL decreased with increasing of the degree of substitution (DS) of LA, pH of medium but with decreasing of the degree of quaternization (DQ) of amino groups. The TEM images demonstrated that spherical CS-LA-TM nanoaggregates with uniform size were formed by self-assembly. The sizes (100-200 nm) of CS-LAs-TMs nanoaggregates increased with increasing of DS, DQ, and can be easily controlled by pH of medium, which may confer the nanoaggregates potential as delivery systems for anticancer drugs, or DNA and siRNA.


Nutritional Status Is Associated With Survival Following Spinal Surgery in Patients With Metastatic Spinal Tumors.
Background Preoperative and postoperative nutritional statuses are reported to influence the outcomes and complications of multidisciplinary treatment, including patient survival. However, a causal relationship between nutritional status and survival following spinal surgery has not been demonstrated in patients with metastatic spinal tumors. The present study was, therefore, designed to evaluate the correlation between the nutritional status and survival following spinal surgery in patients with metastatic spinal tumors. Methods Nutritional status was evaluated using the Japanese version of the modified Glasgow prognostic score (JmGPS), C-reactive protein-to-albumin ratio (CAR), prognostic nutrition index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), which were calculated from the results of preoperative laboratory tests. The survival period was defined as the interval between the day preoperative data were obtained and the day of death. Results Data from 57 of 113 consecutive surgeries were retrieved. The CAR, JmGPS, and PNI were significantly correlated with the survival period (CAR, r = -0.576, P < 0.01; JmGPS, r = -0.537, P < 0.01; PNI, r = 0.316, P = 0.02). Furthermore, patients with 0 points on the JmGPS had significantly longer survival. Using receiver operating characteristic curves, CAR cutoffs of ≥0.880 and ≤0.220 were found to be optimal in predicting the 90- and 180-day postoperative survival, respectively. Conclusions The findings of the present study indicate that preoperative assessment of the JmGPS, CAR, and PNI has utility in estimating nutritional status and predicting survival following spinal surgery in patients with metastatic spinal tumors.


DNA-based prenatal diagnosis of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1).
Eleven fetuses at risk for the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) were studied using DNA markers and the results were compared with the results of electron microscopy (EM) of chorionic villus specimens from pregnancies in the first or early second trimester of pregnancy. In four cases, the prenatal diagnosis was made independently with both methods, and in seven cases, the EM diagnosis was confirmed postnatally or from autopsy material using RFLP analysis. The two methods gave concordant results in all cases. The DNA analysis based on RFLP haplotypes also for the first time facilitates reliable carrier diagnostics. RFLP analysis based on polymorphic markers closely linked to the INCL locus is now available for prenatal diagnosis of this fatal brain disease, whose biochemical background is totally unknown and for which no treatment is available.


Dynamics of two granules.
We study the dynamics of two particles that interact only when in contact. In this sense, although not in every particular, the interactions mimic those in granular materials. The detailed solution of the dynamics allows an analysis of the backscattering behavior of the first particle and of the energy dissipation in the system as a function of various parameters.


Tensile Strength Improvements of Ramie Fiber Threads through Combination of Citric Acid and Sodium Hypophosphite Cross-Linking.
Ramie (Boehmeria nivea) is believed to be one of the strongest natural fibers, but it still remains behind synthetic materials in terms of tensile strength. In this study, ramie materials were prepared to evaluate the modification crosslinking effect of natural fiber. The aim is to optimize various concentrations of citric acid (CA) crosslinking by adding Sodium hypophosphite (NaPO2H2), which is activated at different temperatures, to obtain the highest tensile mechanical strength. This crosslinking effect has been confirmed by FTIR to show the esterification process in the molecular structure of cellulose. The changes in the character of the fiber surface were analyzed by SEM. The tensile strength increased from 62.33 MPa for 0% CA to 124-172.86 MPa for decorticated fiber with a CA concentration of 0.75-1.875% (w/w). A significant increase in tensile strength was observed more than 19 times when CA/SHP 1% was treated at an activation temperature of 110 °C with a superior tensile strength of 1290.63. The fiber crosslinked with CA/SHP should be recommended for application of Natural Fiber Reinforced Polymer Composite (NFRPC), which has the potential to use in functional textile and industrial sector automotive or construction.


[Diagnosis of primary lung cancers].
Symptoms of bronchial cancers are varied and misleading, source of late diagnosis which had to be avoided by systematic suspicion in front of all symptoms from a "high-smoker". Fiberoptic bronchoscopy is the best exam for anatomic diagnosis of central forms. It is normal in peripheral forms but may yet be useful by directed samplings. If negative, it may be necessary to perform thoracotomy or transthoracic needle punction if surgery is contra-indicated. Pretherapeutic assessment of loco-regional and metastatic extension has recently profited by new imaging and endoscopic techniques, useful to the best realisation of TNM classification.


Physicochemical, Rheological, and Sensory Characteristics of Yogurt Fermented by Lactic Acid Bacteria with Probiotic Potential and Bioprotective Properties.
The applicability of two lactic acid bacterial strains with probiotic potential and bioprotective properties as additions in the starter culture in yogurt fermentation was examined. The studied strains, Lactobacillus delbrueckii subsp. bulgaricus KZM 2-11-3 and Lactiplantibacillus plantarum KC 5-12, inhibited the growth of Kluyveromyces lactis, Kluyveromyces marxianus, and Saccharomyces cerevisiae. The strain L. delbrueckii subsp. bulgaricus KZM 2-11-3 directly inhibited Escherichia coli. The important characteristics for the quality of the yogurt product, such as physicochemical parameters during fermentation and storage, rheological characteristics, and sensory changes during the storage of samples were determined. The yogurt samples with the strains did not differ in most parameters from the control yogurt with the commercial starter. The added strains showed stable viability in the yogurt samples during storage. The yogurt sample with L. delbrueckii subsp. bulgaricus KZM 2-11-3 and the sample with both strains based on the total evaluation were very similar to the control yogurt with the commercial starter. Using these strains as probiotic supplements to enrich the starter cultures in yogurt production will contribute to developing new products with benefits to human health.


The scid defect results in much slower repair of DNA double-strand breaks but not high levels of residual breaks.
Severe combined immune deficiency (scid) mice fail to produce mature B and T cells and are sensitive to ionizing radiation. They contain a mutation in the 460-kDa catalytic subunit of the DNA-dependent protein kinase that is involved in both V(D)J rejoining and DNA double-strand break (DSB) repair. The kinetics of DSB rejoining was quantified in both scid cells and the parental C.B-17 cells after three different doses of X irradiation: 3, 7.5 and 10 Gy. Repair of DNA DSBs was determined using pulsed-field gel electrophoresis, Southern hybridization and phosphor image analysis. After X irradiation, the cells were allowed to repair at 37 degrees C for up to 1 h or up to 24 h. The most profound difference between the two cell lines was the greatly reduced rate of the slow component of DSB repair in scid cells. C.B-17 cells repaired most of the damage within 1 h, whereas scid cells required 4 to 6 h to reach a similar level after the same dose. No residual or unrepairable DSBs were detected in either cell line 24 h after doses as high as 10 Gy. The scid cells subjected to two doses of 1.5 Gy separated by increasing amounts of time showed no ability to repair sublethal damage between doses, whereas C.B-17 cells receiving two doses of 3.75 Gy separated by increasing periods did show increased levels of survival. These results indicate that scid cells can repair radiation-induced DNA DSBs, although at a reduced rate, but they lack the ability to undergo repair of sublethal damage.


Retention by sex and race of 1968-1972 U.S. medical school entrants.
With expanding class sizes and increased proportions of women and minority group medical students, questions are frequently asked concerning recent trends in retention and graduation rates. In this article the authors report on a national Association of American Medical Colleges study of new entrants in the 1968 through 1972 first-year classes of U.S. medical schools and place this study in historical perspective. They note that recent attrition rates are only about half that of the 9 percent reported in the last national AAMC study of 1949-1958 entrants. Although the retention rate for women and for underrepresented minorities is still slightly less than that for white males, the gap appears to be narrowing. Suggestions for optimum retention include: (a) enlarging the pool of minority applicants, (b) improving the techniques of student selection, and (c) increasing the flexibility of academic programs in the medical schools.


Programming Cell Adhesion for On-Chip Sequential Boolean Logic Functions.
Programmable remodelling of cell surfaces enables high-precision regulation of cell behavior. In this work, we developed in vitro constructed DNA-based chemical reaction networks (CRNs) to program on-chip cell adhesion. We found that the RGD-functionalized DNA CRNs are entirely noninvasive when interfaced with the fluidic mosaic membrane of living cells. DNA toehold with different lengths could tunably alter the release kinetics of cells, which shows rapid release in minutes with the use of a 6-base toehold. We further demonstrated the realization of Boolean logic functions by using DNA strand displacement reactions, which include multi-input and sequential cell logic gates (AND, OR, XOR, and AND-OR). This study provides a highly generic tool for self-organization of biological systems.


6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes.
In this study, we demonstrated that the two ginger-derived components have a potent and unique pharmacological function in 3T3-L1 adipocytes via different mechanisms. Both pretreatment of 6-shogaol (6S) and 6-gingerol (6G) significantly inhibited the tumor necrosis factor-alpha (TNF-alpha) mediated downregulation of the adiponectin expression in 3T3-L1 adipocytes. Our study demonstrate that (1) 6S functions as a PPARgamma agonist with its inhibitory mechanism due to the PPARgamma transactivation, and (2) 6G is not a PPARgamma agonist, but it is an effective inhibitor of TNF-alpha induced c-Jun-NH(2)-terminal kinase signaling activation and thus, its inhibitory mechanism is due to this inhibitory effect.


Temperature- and solvent-dependent binding of dihydrogen in iridium pincer complexes.
Mixtures of deuterium labeled complexes (p-XPOCOP)IrH2-xDx (1-6-d0-2) {POCOP = [C6H2-1,3-[OP(tBu)2]2] X = MeO (1), Me (2), H (3), F (4), C6F5 (5), and ArF = 3,5-(CF3)2-C6H3 (6)} have been generated by reaction of (p-XPOCOP)IrH2 complexes with HD gas in benzene followed by removal of the solvent under high vacuum. Spectroscopic analysis employing 1H and 2D NMR reveals significant temperature and solvent dependent isotopic shifts and HD coupling constants. Complexes 1-6-d1 in toluene and pentane between 296 and 213 K exhibit coupling constants JHD of 3.8-9.0 Hz, suggesting the presence of an elongated H2 ligand, which is confirmed by T1(min) measurements of complexes 1, 3, and 6 in toluene-d8. In contrast, complex 6-d1 exhibits JHD = 0 Hz in CH2Cl2 or CDCl2F whereas isotopic shifts up to -4.05 ppm have been observed by lowering the temperature from 233 to 133 K in CDCl2F. The large and temperature-dependent isotope effects are attributed to nonstatistical occupation of two different hydride environments. The experimental observations are interpreted in terms of a two component model involving rapid equilibration of solvated Ir(III) dihydride and Ir(I) dihydrogen structures.


The nursing shortage. Implications for military nurses.
Trends relative to nursing vacancies are expected to exist into the next decade. Unlike the cyclical shortages of the past, this shortage may not resolve itself. The authors present five major factors in nursing that have led to the shortage and that contribute to its continuation. Because military nurses provide much manpower in the healthcare industry, shortages in their ranks will affect the entire healthcare system. The five factors were applied to the military nursing force to demonstrate that the military also feels the pinch of the current nursing shortage.


Critical Thinking Disposition and Skills in Dental Students: Development and Relationship to Academic Outcomes.
Critical thinking is a key element of complex problem-solving and professional behavior. An ideal critical thinking measurement instrument would be able to accurately predict which dental students are predisposed to and capable of thinking critically and applying such thinking skills to clinical situations. The aims of this study were to describe critical thinking disposition and skills in dental students at the beginning and end of their first year, examine cohort and gender effects, and compare their critical thinking test scores to their first-year grades. Volunteers from three student cohorts at the University of British Columbia were tested using the California Critical Thinking Disposition Inventory and California Critical Thinking Skills instruments at the beginning and end of their first year. Based on the preliminary findings, one cohort was retested at graduation when their final-year grades and clinical advisor rankings were compared to their critical thinking test scores. The results showed that students who entered dental school with higher critical thinking scores tended to complete their first year with higher critical thinking scores, achieve higher grades, and show greater disposition to think critically at the start of the program. Students who demonstrated an ability to think critically and had a disposition to do so at the start of the program were also likely to demonstrate those same attributes at the completion of their training. High critical thinking scores were associated with success in both didactic and clinical settings in dental school.


Contact allergy and medicinal herbs.
Herbal treatments are becoming increasingly popular, and are often used for internal as well as dermatological conditions, both externally as well as orally. The prevalence of contact sensitization against several plants especially of the Compositae family is quite high in Europe. Sensitization seems to occur relatively frequent with a few species such as arnica, elecampane and tea tree (oil), and occurs rarely with the majority. Testing for plant allergy is problematic because of the limited number of commercially available standardized patch test substances and the danger of active sensitization when testing with plants, parts thereof, or individual extracts. Knowledge about the allergic potential of plants is limited. Although plants are regarded as critical allergens by dermatologists, the number of reported cases of contact dermatitis is relatively small. Many widely used substances are not licensed as drugs or cosmetics. While the positive effects are frequently questionable or limited, the side effects are often more evident. Adverse effects of herbal medicines are an important albeit neglected subject in dermatology, which deserves further systematic investigation.


A study of the gait characteristics of patients with chronic osteoarthritis of the knee.
There is scant information at present on the effects of severe osteoarthritis (OA) of the knee joint on gait. In the present study the kinematic and kinetic parameters of gait and the pattern of activation of four lower limb muscles were examined during walking at a self-selected pace on level ground. The spatiotemporal parameters of gait were also computed. Measurements were made using a three-dimensional optico-electronic motion analysis system integrated with a force plate and telemetered electromyography. Fifty-eight patients with severe OA of the knee and 25 age-matched healthy control subjects were examined. Patients demonstrated a significantly reduced walking speed, shorter stride length and a more prolonged stance phase of the gait cycle compared with the control subjects. They also had less range of motion at the hip, knee and ankle, joints and generated less moments and powers at the ankle and more moments at the knee than the control group. The differences were statistically significant for all parameters except the degree of ankle plantar flexion in stance. Activation of the rectus femoris muscle was prolonged in the patients group. It is concluded that the observed gait abnormalities were due to instability of the knee joint in stance. This may have important clinical implications for the rehabilitation of patients with severe OA of the knee.


Management of diabetes by obstetrician-gynecologists.
To examine the rates of diagnosis and treatment of diabetes mellitus by ACOG Fellows in pregnant and nonpregnant patients. We sent a questionnaire to 1250 ACOG Fellows. Thirty-nine percent responded. Responses were examined for potential differences between recently and less recently trained obstetrician-gynecologists. Ninety-six percent of obstetricians routinely screen for gestational diabetes mellitus (GDM). Fifty-five percent of obstetrician-gynecologists screen for diabetes in nonpregnant patients if there is a history of diabetes in the patient's family. Moreover, 33% care for women with type-1 diabetes mellitus, and 39% for women with type-2 diabetes mellitus who are not pregnant. Sixty-two percent believed that their patients with GDM are at increased risk for developing nongestational diabetes later in life, and 71% will recommend an evaluation of glucose tolerance in the future for these women. Finally, 99% are willing to prescribe oral contraceptives to women diagnosed previously with GDM. Obstetrician-gynecologists are aware of the need to screen for GDM and the importance of postpartum follow-up in GDM patients to detect type-2 diabetes mellitus. This practice is important because half of the 14 million people with type-2 diabetes mellitus are unaware they have this disorder, and many learn about it only after a serious complication has occurred.


[Refractory anemia with an excess of blasts: evidence for 2 evolving groups in a group of 56 patients].
Cytological and kinetic findings in 56 patients with refractory anemia with excess blasts (RAEB) were studied. The different statistical methods used produce similar results: our group of patients can be separated by cytological parameters in two populations (overt leukemic or hematologically stable evolution). Different functional lesions may be responsible for these two types; pluripotential stem cell dysfunction in the first case and abnormality of the granulocytic committed stem cell in the second. A score, based on a small number of simple and reliable parameters, is able to distinguish these two populations.


The uptake of hippuran in kidney slices employed as a viability test.
125J Hippuran uptake in slices from rabbit kidneys was measured in kidneys damaged by warm ischaemia alone as well as by warm ischaemia combined with 24 hours of cold ischaemia. The Hippuran uptake was calculated as the ratio between radioactivity in the slices and the activity in the incubation medium as a slice/medium ratio (S/M). S/M was unchanged after 15 minutes, 30 minutes and 1 hour of warm ischaemia, while in kidneys exposed to 2 hours of warm ischaemia a 15% decrease in S/M ratio compared with control values was noted. A 53% decrease was observed after 3 hours of warm ischaemia and 73% and 91% after 4 and 5 hours respectively. Twenty-four hours of cold ischaemia alone did not alter the Hippuran uptake, but prolonging this with 15 minutes of warm ischaemia precipitated a significant fall (25%) in S/M. This value remained constant during the first hour of warm ischaemia, but a fall of 64% was observed after 2 hours of warm and 24 hours of cold ischaemia. These findings were in agreement with experiments on kidneys damaged by arterial occlusion and recirculated. Two hours of warm ischaemia was the maximal damage the kidneys could endure and still regain normal function. After simple preservation methods with Collins solution for 24 hours, 1 additional hour of warm ischaemia was the maximal ischaemic damage the kidney was able to withstand. Hippuran uptake in kidney slices appears to be well correlated to the kidneys' ability to regain normal function after ischaemic damage.


The limited prognostic value of liver histology in children with biliary atresia.
Background and rationale for the study. The aim of the study was to determine the prognostic value of histopathological findings with special care to the severity of liver fibrosis at the moment of hepatoportoenterostomy (HPE) in children with biliary atresia (BA). We performed analysis of 142 wedge liver biopsies taken at the time of HPE. All patients were operated by the same surgical team between 1995 and 2007. According to the outcome 6 months after HPE patients were divided into prognostic groups: group 1-bilirubin level < 2 mg% (n = 65), group 2-bilirubin level > 2 mg% (n = 77). Liver biopsies were re-evaluated according to the extended histopathological protocol and then were compared between the prognostic groups. Survival with native liver (SNL) estimates were performed in regard to severity of liver fibrosis. Survival with native liver estimates after 2, 5 and 10 years in patients after successful operation were 96%, 91%, 75% vs. 30%, 11%, and 5% if operation failed (p < 0.001). There was no difference between groups in the following variables: fibrosis (p = 0.69), portal inflammation (p = 0.99), lobular inflammation (p = 0.95), cholangiolitis (p = 0.23), accumulation of bile pigments (zone 1:p = 0.49; zone 2:p = 0.51; zone 3:p = 0.48), bile plugs in canaliculi (p = 0.12), bile plugs in ducts (p = 0.32), bilirubinostasis in hepatocytes (p = 0.45), bile ductular proliferation (p = 0.59), ductal plate malformation (p = 0.12), focal necrosis (p = 0.44), giant cell transformation (p = 0.45), haematopoesis (p = 0.52), ductopenia (p = 0.46), microabscesses (p = 0.49), ballooning of hepatocytes (p = 0.08). The actuarial 5/10-year SNL was not dependent on severity of liver fibrosis (log-rank test p = 0.84). The severity of fibrosis corresponded neither with the age at HPE nor with the laboratory findings before operation but increased the risk of portal hypertension. Liver histology at the time of HPE is of limited value in prognosis making in BA.


Origin of Osteoclasts: Osteoclast Precursor Cells.
Osteoclasts are multinucleated bone-resorbing cells and a key player in bone remodeling for health and disease. Since the discovery of osteoclasts in 1873, the structure and function of osteoclasts and the molecular and cellular mechanisms of osteoclastogenesis have been extensively studied. Moreover, it has been well established that osteoclasts are differentiated in vitro from myeloid cells such as bone marrow macrophages or monocytes. The concept showing that osteoclasts are derived from a specific population (named osteoclast precursor cells [OCPs]) among myeloid cells has been long hypothesized. However, the specific precursor population of osteoclasts is not clearly defined yet. A growing body of work provides evidence of the developmental origin and lifespan of murine osteoclasts, particularly in vivo. Here, we review the emerging evidence that supports the existence of OCPs and discuss current insights into their identity.


Quantitative assessment of new MRI-based measurements to differentiate low and high stages of pelvic organ prolapse using support vector machines.
The objective of this study was to quantitatively assess the ability of new MRI-based measurements to differentiate low and high stages of pelvic organ prolapse. New measurements representing pelvic structural characteristics are proposed and analyzed using support vector machines (SVM). This retrospective study used data from 207 women with different types and stages of prolapse. Their demographic information, clinical history, and dynamic MRI data were obtained from the database. New MRI measurements were extracted and analyzed based on these reference lines: pubococcygeal line (PCL), mid-pubic line (MPL), true conjugate line (TCL), obstetric conjugate line (OCL), and diagonal conjugate line (DCL). A classification model using SVM was designed to assess the impact of the features (variables) in classifying prolapse into low or high stage. The classification model using SVM can accurately identified anterior prolapse with very high accuracy (>0.90), and apical and posterior prolapse with good accuracy (0.80 - 0.90). Two newly proposed MRI-based features were found to be significant in the identification of anterior and posterior prolapse: the angle between TCL and MPL for anterior prolapse, and the angle between DCL and PCL for posterior prolapse. The overall accuracy of posterior prolapse identification increased from 47% to 80% when the newly proposed MRI-based features were taken into consideration. The proposed MRI-based measurements are effective in differentiating low and high stages of pelvic organ prolapse, particularly for posterior prolapse.


Ceramidase enhances phospholipase C-induced hemolysis by Pseudomonas aeruginosa.
We previously reported the purification, molecular cloning, and characterization of a neutral ceramidase from Pseudomonas aeruginosa strain AN17 (Okino, N., Tani, M., Imayama, S., and Ito, M. (1998) J. Biol. Chem. 273, 14368-14373; Okino, N., Ichinose, S., Omori, A., Imayama, S., Nakamura, T., and Ito, M. (1999) J. Biol. Chem. 274, 36616-36622). Interestingly, the gene encoding the enzyme is adjacent to that encoding hemolytic phospholipase C (plcH) in the genome of Pseudomonas aeruginosa, which is a well known pathogen for opportunistic infections. We report here that simultaneous production of PlcH and ceramidase was induced by several lipids and PlcH-induced hemolysis was significantly enhanced by the action of the ceramidase. When the strain was cultured with sphingomyelin or phosphatidylcholine, production of both enzymes drastically increased, causing the increase of hemolytic activity in the cell-free culture supernatant. Ceramide and sphingosine were also effective in promoting the production of ceramidase but not that of PlcH. Furthermore, we found that the hemolytic activity of a Bacillus cereus sphingomyelinase was significantly enhanced by addition of a recombinant Pseudomonas ceramidase. TLC analysis of the erythrocytes showed that ceramide produced from sphingomyelin by the sphingomyelinase was partly converted to sphingosine by the ceramidase. A ceramidase-null mutant strain caused much less hemolysis of sheep erythrocytes than did the wild-type strain. Sphingosine was detected in the erythrocytes co-cultured with the wild-type strain but not the mutant strain. Finally, we found that the enhancement of PlcH-induced hemolysis by the ceramidase occurred in not only sheep but also human erythrocytes. These results may indicate that the ceramidase enhances the PlcH-induced cytotoxicity and provide new insights into the role of sphingolipid-degrading enzymes in the pathogenicity of P. aeruginosa.


Utility of ultrasonographic examination in catheter-related infections in peritoneal dialysis: a clinical approach.
Peritoneal dialysis- (PD) related infections continue to be a major cause of morbidity and mortality in patients on renal replacement therapy via PD. However, despite the great efforts in the prevention of PD-related infectious episodes, approximately one third of technical failures are still caused by peritonitis. Recent studies support the theory that ascribes to exit-site and tunnel infections a direct role in causing peritonitis. Hence, prompt exit site infection/tunnel infection diagnosis would allow the timely start of the most appropriate treatment, thereby decreasing the potential complications and enhancing technique survival. Ultrasound examination is a simple, rapid, non-invasive and widely available procedure for tunnel evaluation in PD catheter-related infections. In case of an exit site infection, ultrasound examination has greater sensitivity in diagnosing simultaneous tunnel infection compared to the physical exam alone. This allows distinguishing the exit site infection, which will likely respond to antibiotic therapy, from infections that are likely to be refractory to medical therapy. In case of a tunnel infection, the ultrasound allows localizing the catheter portion involved in the infectious process, thus providing significant prognostic information. In addition, ultrasound performed after two weeks of antibiotic administration allows monitoring patient response to therapy. However, there is no evidence of the usefulness of ultrasound examination as a screening tool for the early diagnosis of tunnel infections in asymptomatic PD patients.


The impact of the April 1992 civil unrest on the Los Angeles REI WIC program and its participants.
This paper discusses the findings of a study conducted in south central Los Angeles in August 1992 among women in the Special Supplemental Food Program for Women, Infants, and Children. The goals of the study were to determine the current demographics of WIC participants; examine the financial hardship, need for relief services, and extent of hunger resulting from the civil unrest of April 1992; look at the effects of the unrest on different ethnic groups; determine the unmet need for WIC services; and evaluate the State and local WIC responses to the unrest. The 1,189 respondents were approximately 77 percent Latina, 20 percent African American, and 3 percent white. Half or more were recent immigrants, 19 percent were pregnant and parenting adolescents, 74 percent were school dropouts, and 56 percent were single mothers. Only 1 percent had any problems using WIC vouchers after the unrest, although more than half of their grocery stores had closed. Thirty-five percent experienced food deficits in their households, and 33 percent of those who applied for emergency food stamps had trouble getting them. Four percent said their children had gone to bed hungry in the last week, and 9 percent said they, the respondents, had as well. Only 2 percent needed shelter, and 1 percent became homeless, but 6 percent had family members who lost jobs due to the unrest. This study suggests that the chronically substandard conditions under which many families in south central Los Angeles live affect them more profoundly than did the dramatic consequences of the civil unrest.


Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria.
Microtubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondrial motility in rat cortical neurons. Cantharidin is known to inhibit protein phosphatase 2A (PP2A). We therefore tested two other inhibitors of PP2A: LB-100 and okadaic acid. LB-100 increased mitochondrial motility, but okadaic acid did not. To resolve this discrepancy, we knocked down expression of the catalytic subunit of PP2A (PP2CA). This long-term inhibition of PP2A more than doubled retrograde transport of axonal mitochondria, confirming the importance of PP2A as a regulator of mitochondrial motility and as the likely mediator of cantharidin's effect.


Design optical antenna and fiber coupling system based on the vector theory of reflection and refraction.
A Cassegrain antenna system and an optical fiber coupling system which consists of a plano-concave lens and a plano-convex lens are designed based on the vector theory of reflection and refraction, so as to improve the transmission performance of the optical antenna and fiber coupling system. Three-dimensional ray tracing simulation are performed and results of the optical aberrations calculation and the experimental test show that the aberrations caused by on-axial defocusing, off-axial defocusing and deflection of receiving antenna can be well corrected by the optical fiber coupling system.


Inhibition of specific degradation of 57-kDa protein in royal jelly during storage by citrate buffer.
We have previously shown that ethylenediaminetetraacetic acid (EDTA) suppresses the storage-dependent degradation of 57-kDa protein, which is a possible marker for freshness and quality of royal jelly (RJ) through the inhibition of a proteinase in RJ. We suggested that EDTA could be useful as a preservative agent to maintain the quality of RJ. Here, we report the effects of other metal chelators, di- or tricarboxylic acids such as citric acid and malic acid, on proteinase activity in RJ and the specific degradation of 57-kDa protein during storage. Various carboxylic acids inhibited the proteinase activity in RJ, but did not suppress storage-dependent degradation of 57-kDa protein. However, when RJ was stored with various carboxylate buffers (pH 4.0) at 40 degrees C, the degradation of 57-kDa protein during storage was suppressed through the inhibition of proteinase in RJ. Among the buffers, citrate buffer (pH 4.0) effectively inhibited the decrease of 57-kDa protein concentration in RJ during storage. These results suggest that citrate buffer (pH 4.0) could be available as a new preservative agent to maintain the quality of RJ.


Synthesis, computational studies and assessment of in vitro inhibitory activity of umbelliferon-based compounds against tumour-associated carbonic anhydrase isoforms IX and XII.
Coumarins are widely diffused secondary metabolites possessing a plethora of biological activities. It has been established that coumarins represent a peculiar class of human carbonic anhydrase (hCA) inhibitors having a distinct mechanism of action involving a non-classical binding with amino acid residues paving the entrance of hCA catalytic site. Herein, we report the synthesis of a small series of new coumarin derivatives 7-11, 15, 17 prepared via classical Pechmann condensation starting from resorcinol derivatives and suitable β-ketoesters. The evaluation of inhibitory activity revealed that these compounds possessed nanomolar affinity and high selectivity towards tumour-associated hCA IX and XII over cytosolic hCA I and hCA II isoforms. To investigate the binding mode of these new coumarin-inspired inhibitors, the most active compounds 10 and 17 were docked within hCA XII catalytic cleft.


[Role of the family physician in mental and social problems in homes for the aged].
Based on Dutch nationally representative data, this article reports on the number of psychological and social problems that residents of homes for the elderly (n = 2893) present to their general practitioner (GP). Furthermore, the number of encounters residents with psychological or social problems have with the general practice and the interventions which the GP applies are described. A comparison is made with elderly patients living independently (n = 28056). In a three-month period the GP found psychological problems in 33 per cent of the patients from homes for the elderly. For elderly patients living independently this was 17%. Controlling for background variables the patients from homes for the elderly still show considerably more psychological problems. Social problems are reported less frequently to GP's; 8% of patients from homes for the elderly and 5% of patients living independently report these problems. After controlling for background variables no statistically significant differences were found. The most frequently used intervention is the prescription of drugs. In both groups almost 80% of the respondents received drugs. Referral to mental health care is the least frequently used intervention. Many patients living in homes for the elderly have psychological or social problems. This implies a high workload for the GP. However, no evidence is found that GP's treat their patients in homes for the elderly differently from those living independently.


Children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia: A randomized controlled trial.
Topical anesthesia has been widely advocated as an important component of atraumatic administration of intraoral local anesthesia. The aim of this study was to use direct observation of children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia. Forty-eight children participated in this randomized controlled clinical trial. They received two separate inferior alveolar nerve block or primary maxillary molar infiltration injections on contralateral sides of the jaws by both cotton-roll vibration (a combination of topical anesthesia gel, cotton roll, and vibration for physical distraction) and control (routine topical anesthesia) methods. Behavioral pain reactions of children were measured according to the author-developed face, head, foot, hand, trunk, and cry (FHFHTC) scale, resulting in total scores between 0 and 18. The total scores on the FHFHTC scale ranged between 0-5 and 0-10 in the cotton-roll vibration and control methods, respectively. The mean ± standard deviation values of total scores on FHFHTC scale were lower in the cotton-roll vibration method (1.21 ± 1.38) than in control method (2.44 ± 2.18), and this was statistically significant (P < 0.001). It may be concluded that the cotton-roll vibration method can be more helpful than the routine topical anesthesia in reducing behavioral pain reactions in children during local anesthesia administration.


Surface plasmon resonance in eccentric femtosecond-laser-induced fiber Bragg gratings.
Highly localized refractive index modulations are photo-written in the core of pure silica fiber using point-by-point focused UV femtosecond pulses. These specific gratings exhibit a comb-like transmitted amplitude spectrum, with polarization-dependent narrowband cladding mode resonances. In this work, eccentric gratings are surrounded by a gold sheath, allowing the excitation of surface plasmon polaritons (SPP) for radially-polarized light modes. The spectral response is studied as a function of the surrounding refractive index and a maximum sensitivity of 50 nm/RIU (refractive index unit) is reported for a well-defined cladding-mode resonance among the spectral comb. This novel kind of plasmonic fiber grating sensor offers rapidity of production, design flexibility, and high temperature stability.


Blood flow response in small intestinal loops at different depths during negative pressure wound therapy of the open abdomen.
High closure rates of the open abdomen have been reported following negative pressure wound therapy (NPWT). However, the method has occasionally been associated with increased development of intestinal fistulae. We have previously shown that the application of NPWT to the open abdomen causes a decrease in microvascular blood flow in the small intestinal loop and the omentum adjacent to the visceral protective layer of the dressing. In this study we investigate whether the negative pressure affects only small intestinal loops lying directly below the dressing or if it also affects small intestinal loops that are not in direct contact with the dressing. Six pigs underwent midline incision and application of NPWT to the open abdomen. The microvascular blood flow was measured in four intestinal loops at different depths from the visceral protective layer, at two different locations: beneath the dressing and at the anterior abdominal wall, before and after the application of NPWT of -50, -70, -100, -120, -150 and -170 mmHg, using laser Doppler velocimetry. Negative pressures between -50 and -170 mmHg caused a significant decrease in the microvascular blood flow in the intestinal loops in direct contact with the visceral protective layer. A slight, but significant, decrease in blood flow was also seen in the intestinal loops lying beneath these loops. The decrease in microvascular blood flow increased with the amount of negative pressure applied. No difference in blood flow was seen in the intestinal loops lying deeper in the abdominal cavity. A decrease in blood flow was seen in the upper two intestinal loops located apically and anteriorly, but not in the lower two, indicating that this is a local effect and that pressure decreases with distance from the source. A long-term decrease in blood flow in the intestinal wall may induce ischaemia and secondary necrosis in the intestinal wall, which could promote the development of intestinal fistulae. We believe that NPWT of the open abdomen is a very effective treatment, but that it could be improved by gaining more knowledge on the mechanisms involved.