Progressive taper technology: rationale and clinical technique for the new ProTaper universal system.
ProTaper Universal has produced a comprehensive yet simple solution for dentists in search of a single, versatile system that solves major endodontic problems from access to obturation. The key in high-performance endodontics is to produce the most and the best while doing the least. We know this as leverage. Breakthrough safety and simplicity features, combined with optimum efficiency, are at the heart of ProTaper Universal. The net intentional result of these newest endodontic technologies is that the practitioner can predictably and consistently produce exceptional patient outcomes (Figures 15 to 20).


Platelet interactions with polylysine coated beads: a microscopic and chemical analysis.
Gel filtered human platelets were mixed with polylysine coated polyacrylamide beads. Platelet binding to individual beads within one preparation was variable, yet high and the bound platelets appeared to involve non-activated platelets. Some cells appeared to be in contact with more than one bead. When the attachment process was neutralized with 1 mg/ml of polyanionic dextran sulfate, significantly fewer platelets remained attached to the beads. Platelets which were recovered in the washes also were non-activated. Attached cells were capable of being activated and underwent release reactions when exposed to either ADP or thrombin. Release reactions were monitored by the liberation of either serotonin or beta-thromboglobulin. Platelets which were iodinated prior to attachment gave evidence that the failure to neutralize the bead before vortexing resulted in lower specific activities of bound iodine/protein.


Dissolution behavior of CaO-MgO-SiO2 -based multiphase bioceramic powders and effects of the released ions on osteogenesis.
In the present study, the dissolution behavior of the CaO-MgO-SiO2 -based multiphase bioceramic powders as well as the effects of released ions on osteogenesis was investigated. In the dissolution process, Ca, Mg, and Si ions could be dissolved out from the powders. The incorporation of Mg could slow down the degradation rate of the powders so that to reduce the local concentration of Ca and Si ions. In return, the dissolution of Ca and Si ions leading to the formation of a porous SiO2 -rich layer could enhance the readsorption of free Mg ions in solution and thus down-regulate the concentration of Mg ions. In addition, the released ions exhibited both positive and negative synergistic effects on osteogenesis with a concentration-dependent manner. Trace amount of released Si ions could stimulate cell proliferation and osteogenic differentiation in the presence of Ca and Mg ions. The optimal concentration of Ca-Mg-Si ion combination to promote osteogenesis was existed in the 1/4 diluted extract, whereas a slightly inhibitory effect on cell proliferation and ALP activity was observed in the 1/2 diluted extract with higher concentration of Ca and Si ions . All above results suggested that the ion dissolution behavior of the CaO-MgO-SiO2 -based multiphase bioceramic could be regulated via adjustment of the composition so that released ions could be maintained at an appropriate composite concentration to cooperatively regulate the osteogenesis. This research provided an experimental basis for further optimization and application of CaO-MgO-SiO2 -based multiphase bioceramics with controlled ion dissolution and excellent physicochemical and biological properties. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3159-3168, 2017.


Delayed presentation of cerebral schistosomiasis presenting as a tumor-like brain lesion.
Schistosomiasis is the second most common parasitic infection worldwide. North America is a nonendemic area. However, there are occasional case reports among travelers and immigrants from endemic regions. We describe a case of a 55-year-old Canadian woman who presented with first episode of seizure. Her magnetic resonance imaging scan revealed a mass-like lesion involving the left anterior temporal lobe. The lesion showed T1 hypo- and T2 hyperintense with perilesional brain edema. On post-gadolinium-enhanced T1-weighted sequence, the lesion showed multiple small nodular and linear enhancements, also called an "arborized" appearance. Initially, the lesion was thought to be a malignant tumor. She underwent left anterior temporal lobe resection. Histologic examination showed parasitic eggs with a characteristic lateral spine consistent with Schistosoma mansoni infection. Upon subsequent questioning, it was revealed that the patient lived in Ghana from the ages of 8-10 years and she visited Ghana again 10 years prior for two weeks. She recalled swimming in beaches and rivers. Latent disease, as in this case with presentation, many years or decades after presumed exposure is rare but has been reported. Characteristic magnetic resonance imaging findings may suggest the diagnosis and facilitate noninvasive work-up.


Practical aspects of delivering hereditary cancer risk counseling.
The primary element involved in the practical delivery of hereditary cancer risk counseling is the development of a cancer genetics service. This service should involve a multidisciplinary core of specialists, aim to identify at-risk individuals and their families, and provide comprehensive genetic counseling with the option of genetic testing. This article examines the development of a cancer genetics service beginning with the fundamentals of patient ascertainment, location, staffing, and billing. It also reviews the elements involved in the provision of genetic counseling services, including formalized risk assessment and risk communication. Finally, we review novel modes of delivery of genetic counseling including the use of telephone counseling and telemedicine as a means of expanding the scope of this service and extending its reach to individuals who might otherwise not have access to a risk assessment clinic. Overall, this presentation can serve as a resource for identifying the practical aspects involved in the delivery of hereditary cancer risk counseling and their subsequent integration into the workings of a proficient cancer genetics service able to identify and serve at-risk patients and their family members.


Attractive Serial Dependence in the Absence of an Explicit Task.
Attractive serial dependence refers to an adaptive change in the representation of sensory information, whereby a current stimulus appears to be similar to a previous one. The nature of this phenomenon is controversial, however, as serial dependence could arise from biased perceptual representations or from biased traces of working memory representation at a decisional stage. Here, we demonstrated a neural signature of serial dependence in numerosity perception emerging early in the visual processing stream even in the absence of an explicit task. Furthermore, a psychophysical experiment revealed that numerosity perception is biased by a previously presented stimulus in an attractive way, not by repulsive adaptation. These results suggest that serial dependence is a perceptual phenomenon starting from early levels of visual processing and occurring independently from a decision process, which is consistent with the view that these biases smooth out noise from neural signals to establish perceptual continuity.


[The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion].
Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion. Results: The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P<0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA (r=0.670, P=0.001 in MPE and r=0.002, P=0.001 in BEP). Conclusions: B7-H4 is a potential tumor marker in diagnosing the benign and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.


TRIM21 promotes inflammation by ubiquitylating NF-κB in T cells of oral lichen planus.
Oral lichen planus (OLP) is a mucocutaneous inflammatory disease affecting 1% general population. Tripartite motif-containing protein 21 (TRIM21) shows a significant role in OLP. This study aimed to explore the function and mechanism of TRIM21 in T cells of OLP. Differential gene expression profile in OLP versus healthy controls (HCs) was constructed by RNA sequencing. Protein expression level and infiltration sites of TRIM21 in OLP were detected by immunoblot, immunohistochemistry, and immunofluorescence. Expression of proinflammatory cytokines and chemokines including IL-6, TNF-α, ICAM1, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3+ TRIM21hi T cells were measured by quantitative real-time polymerase chain reaction analysis. Downstream pathways and substrates of TRIM21 were explored by immunoblot and immunoprecipitation. Whether TRIM21 ubiquitination its substrate and ubiquitination form were tested by ubiquitination assay in vitro. Compared with HCs, TRIM21 exhibited a higher level in OLP, which expressed mainly in CD3+ T lymphocytes in OLP tissues. Overexpressed TRIM21 enhanced the expression of IL-6, TNF-α, CXCL1, CXCL8, CXCL9, and CXCL11 in CD3+ T cell line through ubiquitinating nuclear factor-κB (NF-κB) via a lysine 63 (K63) linkage, which eventually activating NF-κB signaling pathway. In OLP, TRIM21 promoted inflammation through ubiquitylating NF-κB and activating NF-κB signaling pathway.


Care and supportive measures in school-aged children with prenatal substance exposure.
Prenatal exposure to substances, including alcohol, opiates, and a number of illicit drugs, may have a negative impact on fetal development. Studies have shown that substance exposure can influence a child's neurodevelopment and the need for care and supportive measures. In this study, we aimed to investigate the care status and the level of supportive measures in school-aged children prenatally exposed to alcohol and other substances. This study included children aged between 6 and 14 years who were referred to Haukeland University Hospital in Norway with developmental impairment and a history of prenatal substance exposure. Participants were classified according to their main prenatal exposure to either alcohol or other substances. Information on care status and supportive measures was obtained from medical records and participants' caregivers. We also compared the use of supportive measures for children placed into foster care before and after 1 year of age. A total of 111 (87% of 128 referrals) eligible children participated in the study. Of these 111 children, 96 (86%) were in foster care, of whom 29 (30%) were placed into foster care during their first year of life and 83 out of 90 (92%) had supportive measures, including reinforced foster care and school or social support. A high proportion of the sample lived in foster care and received supportive measures. Findings may reflect an increased need of care and support in school-aged children with prenatal substance exposure, highlighting the importance of awareness among caregivers and public agencies.


Melatonin Balance the Autophagy and Apoptosis by Regulating UCP2 in the LPS-Induced Cardiomyopathy.
To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2.


Effects of folic acid upon filopodia of Dictyostelium discoideum vegetative amoebae.
Living vegetative D, discoideum amoebae were studied to determine whether their filopodia respond to folic acid, a chemoattractant for these cells. Exponentially growing amoebae (ca. 10 micron diameter) exhibit 5-30 micron long filopodia; at stationary phase, aggregation competent amoebae have numerous multibranched filopodia up to 100 micron long. Folic acid was observed to stimulate production, elongation, and branching of filopodia with its effects progressively changing as the amoebae approach aggregation. Filopodial construction was also found to be dependent upon Mg2+ levels. The significance of these results is discussed with respect to progressive changes within the vegetative phase as well as to the mechanisms of amoeboid movement, pseudopodial activity, and chemotaxis.


Stimuli-responsive hydrogel membranes coupled with biocatalytic processes.
A nanostructured signal-responsive thin hydrogel membrane was coupled with enzyme-based systems to yield "smart" multisignal-responsive hybrid systems with built-in "logic". The enzyme systems transduce biochemical input signals into structural changes of the membrane, thus resulting in the amplification of the biochemical signals and their transformation into the gated transport of molecules through the membrane. Coupling of the biocatalytic systems with a stimuli-responsive membrane is a promising approach for the development of materials that can regulate transport and release of chemicals/drugs by receiving and processing the biochemical information via biochemical reactions.


Males with neonatal hyperbilirubinemia examined at 18 years of age.
An 18 years follow-up study of 55 males with neonatal hyperbilirubinemia born in 1962/63 was done at the military draft board examinations in 1981. The medical and psychological tests were compared to the tests of the total cohort of Norwegian conscripts. Of those examined at 18 years of age 7.3% was unfit for military service, compared to 6.2% in the total cohort. Ten organ systems were clinically examined with no significantly increased frequency of unfitness among the index cases. Intelligence testing was done on 39 of the studied subjects, the mean score being the same as in the total cohort of Norwegian conscripts. However, the seven infants with a positive Coombs' test and hyperbilirubinemia for 5 days or more had a significantly lower mean intelligence score than the national average.


Water-Use Characteristics and Physiological Response of Moso Bamboo to Flash Droughts.
Frequent flash droughts can rapidly lead to water shortage, which affects the stability of ecosystems. This study determines the water-use characteristics and physiological mechanisms underlying Moso bamboo response to flash-drought events, and estimates changes to water budgets caused by extreme drought. We analyzed the variability in forest canopy transpiration versus precipitation from 2011-2013. Evapotranspiration reached 730 mm during flash drought years. When the vapor pressure deficit > 2 kPa and evapotranspiration > 4.27 mm·day-1, evapotranspiration was mainly controlled through stomatal opening and closing to reduce water loss. However, water exchange mainly occurred in the upper 0-50 cm of the soil. When soil volumetric water content of 50 cm was lower than 0.17 m3·m-3, physiological dehydration occurred in Moso bamboo to reduce transpiration by defoliation, which leads to water-use efficiency decrease. When mean stand density was <3500 trees·ha-1, the bamboo forest can safely survive the flash drought. Therefore, we recommend thinning Moso bamboo as a management strategy to reduce transpiration in response to future extreme drought events. Additionally, the response function of soil volumetric water content should be used to better simulate evapotranspiration, especially when soil water is limited.


Asthma phenotypes identified by latent class analysis in the ISAAC phase II Spain study.
Classification of respiratory symptoms may help to identify different underlying asthma phenotypes reflecting differences in aetiology and prognosis of wheezing disease among children. To determine childhood asthma phenotypes based on respiratory symptoms from a widely used questionnaire to further classify phenotypes in international settings. Between 2000 and 2002 cross-sectional studies were performed in four centres in Spain. Parental questionnaires were used to collect information on allergic diseases in more than 4000 children aged 8-12 years. In addition, objective markers for allergic sensitization and bronchial hyperresponsiveness (BHR) were measured. Latent class analyses (LCA) were applied to identify subgroups of children according to respiratory symptoms, and then the association of these groups with relevant clinical features such as concomitant allergic disease symptoms, atopy and BHR was studied. We found seven classes, one corresponding to healthy children, three classes related to wheeze and three other classes mainly related to congestion and coughed-up phlegm. These tentative phenotypes differed in severity of symptoms and also in clinical correlates such as BHR and allergic sensitization. Atopy was more predominant in the 'wheeze phenotypes' whereas concomitant 'allergic' symptoms were most frequent in two of the 'wheeze phenotypes' and one of the 'cough phenotypes'. LCA on reported symptoms in a cross-sectional survey allowed different subgroups with meaningful clinical correlates to be defined. It remains to be investigated to what extent these groups also have different aetiologies, prognoses and therapeutic needs.


An IMU-Aided Body-Shadowing Error Compensation Method for Indoor Bluetooth Positioning.
Research on indoor positioning technologies has recently become a hotspot because of the huge social and economic potential of indoor location-based services (ILBS). Wireless positioning signals have a considerable attenuation in received signal strength (RSS) when transmitting through human bodies, which would cause significant ranging and positioning errors in RSS-based systems. This paper mainly focuses on the body-shadowing impairment of RSS-based ranging and positioning, and derives a mathematical expression of the relation between the body-shadowing effect and the positioning error. In addition, an inertial measurement unit-aided (IMU-aided) body-shadowing detection strategy is designed, and an error compensation model is established to mitigate the effect of body-shadowing. A Bluetooth positioning algorithm with body-shadowing error compensation (BP-BEC) is then proposed to improve both the positioning accuracy and the robustness in indoor body-shadowing environments. Experiments are conducted in two indoor test beds, and the performance of both the BP-BEC algorithm and the algorithms without body-shadowing error compensation (named no-BEC) is evaluated. The results show that the BP-BEC outperforms the no-BEC by about 60.1% and 73.6% in terms of positioning accuracy and robustness, respectively. Moreover, the execution time of the BP-BEC algorithm is also evaluated, and results show that the convergence speed of the proposed algorithm has an insignificant effect on real-time localization.


N-Trifluoroacetyl derivatives as pharmacological agents. II. Trifluoroacetanilides: synthesis and antiinflammatory activity.
The analogy with the anti-inflammatory trifluoromethane-sulfonanilides prompted us to the synthesis of a series of trifluoroacetanilides which were found to maintain the pharmacological properties of the analog sulfonanilides. Many of the obtained compounds inhibited either the carrageenin-induced rat paw edema and the adjuvant-induced arthritis; some showed better anti-inflammatory properties than indomethacin and phenylbutazone. Acute toxicity and ulcerogenic effects were significantly lower than those of reference drugs.


Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide.
This article reports the synthesis of a new class of conjugates containing a nucleobase, a peptidic epitope, and a saccharide and the evalution of their gelation, biostability, and cell compatibility. We demonstrate a facile synthetic process, based on solid-phase peptide synthesis of nucleopeptides, to connect a saccharide with the nucleopeptides for producing the target conjugates. All the conjugates themselves (1-8) display excellent solubility in water without forming hydrogels. However, a mixture of 5 and 8 self-assembles to form nanofibers and results in a supramolecular hydrogel. The proteolytic stabilities of the conjugates depend on the functional peptidic epitopes. We found that TTPV is proteolytic resistant and LGFNI is susceptible to proteolysis. In addition, all the conjugates are compatible to the mammalian cells tested.


Skin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes.
Staphylococcal scalded skin syndrome and toxic shock syndrome are associated with exfoliatins and superantigens, respectively; and are easy to distinguish in their usual presentation. However, there is confusion about the mild forms of these 2 staphylococcal diseases. These mild forms are both designated as "staphylococcal scarlet fever" despite differences in their pathophysiology and clinical presentation. Our study aimed to distinguish between the clinical characteristics of the rash associated with exfoliatins and the rash associated with superantigens. Patients were selected from the French National Reference Center for Staphylococci. We retrospectively compared the clinical characteristics of patients with a generalized rash during Staphylococcus aureus infection. Patients who met the criteria of staphylococcal scalded skin syndrome or toxic shock syndrome were excluded. The patients were classified into 2 groups depending on the presence of a gene coding for exfoliatin or for superantigenic toxin. We included 13 cases with exfoliatin and 9 with superantigens. The patients of the exfoliatin group were more likely to have facial involvement, fold involvement and a superficial focus of infection. In the second group, S. aureus was isolated from a deeper focus in 8 of 9 patients. Mild forms of S. aureus toxin-mediated infection affect the pediatric population. Examination made it possible to distinguish an exanthema associated with an exfoliatin from one associated with a superantigen. This early clinical distinction results in differences in management.


Factors Associated With Esophagus Cancers in Togo, Sub-Saharan Africa.
Esophagus cancer is cancer of poor prognosis, of often late diagnosis. The objective of this study was to describe the factors associated with esophagus cancers in the Togolese population. It was a retrospective descriptive, cross-sectional study, on esophagus cancers histologically diagnosed at the Pathological Laboratory of Lomé over a period of 31 years (1990-2021). We have collected 144 cases of esophagus cancer. The average age of patients was 57 ± 12 years, and the sex ratio was 2.34. The most applicant service was the service of Hepato Gastroenterology of CHU Campus (30.6%). Alcohol (57.6%), tobacco (45.8%) were the most present risk factors. Biopsies were the most addressed (97.2%). The average duration of symptom evolution was 6.42 months and the main symptom at the time of diagnosis was dysphagia (36.8%). The location of cancer was the lower third for 71.5% of cases. At histology, epidermoid carcinoma was the dominant type (90.3%). Male sex was statistically associated with the occurrence of epidermoid carcinoma and female sex with the occurrence of adenocarcinoma (P < .001). Alcohol, smoking, and consumption of hot foods were statistically associated with the occurrence of epidermoid carcinoma in this study (P < .05). Esophagus cancer remains a serious condition for late diagnosis. These are mainly epidermoid carcinomas and having alcohol and tobacco as risk factors. The awareness of the population on the main risk factors would reduce the incidence of oesophagus cancers within the Togolese population.


Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide.
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have become increasingly popular as both diabetic and weight loss therapies. One effect of this class of medication is delayed gastric emptying, which may impact the risk of aspiration during anesthesia delivery. In this prospective study, we used gastric ultrasound to evaluate the presence of solid gastric contents in both supine and lateral positions after an eight-hour fast in those taking GLP-1RA compared with controls. Participants underwent a second ultrasound evaluation two hours later after drinking 12 fluid ounces of water (approximately 350 mL). Twenty adults voluntarily enrolled, giving a total of ten participants in each group. In the supine position, 70% of semaglutide participants and 10% of control participants had solids present on gastric ultrasound (risk ratio [RR], 3.50; 95% confidence interval [CI], 1.26 to 9.65; P = 0.02.) In the lateral position, 90% of semaglutide participants and 20% of control participants had solids identified on gastric ultrasound (RR, 7.36; 95% CI, 1.13 to 47.7; P = 0.005). Two hours after drinking clear liquids, the two groups did not differ in the lateral position, but in the supine position, 90% of control group participants were rated as empty compared with only 30% of semaglutide group participants (P = 0.02). This study provides preliminary evidence that GLP-1RAs may affect gastric emptying and residual gastric contents following an overnight fast and two hours after clear liquids, which may have implications for aspiration risk during anesthetic care.


The biochemical composition of the actomyosin network sets the magnitude of cellular traction forces.
The regulation of cellular force production relies on the complex interplay between a well-conserved set of proteins of the cytoskeleton: actin, myosin, and α-actinin. Despite our deep knowledge of the role of these proteins in force production at the molecular scale, our understanding of the biochemical regulation of the magnitude of traction forces generated at the entire-cell level has been limited, notably by the technical challenge of measuring traction forces and the endogenous biochemical composition in the same cell. In this study, we developed an alternative Traction-Force Microscopy (TFM) assay, which used a combination of hydrogel micropatterning to define cell adhesion and shape and an intermediate fixation/immunolabeling step to characterize strain energies and the endogenous protein contents in single epithelial cells. Our results demonstrated that both the signal intensity and the area of the Focal Adhesion (FA)-associated protein vinculin showed a strong positive correlation with strain energy in mature FAs. Individual contents from actin filament and phospho-myosin displayed broader deviation in their linear relationship to strain energies. Instead, our quantitative analyzes demonstrated that their relative amount exhibited an optimum ratio of phospho-myosin to actin, allowing maximum force production by cells. By contrast, although no correlation was identified between individual α-actinin content and strain energy, the ratio of α-actinin to actin filaments was inversely related to strain energy. Hence, our results suggest that, in the cellular model studied, traction-force magnitude is dictated by the relative numbers of molecular motors and cross-linkers per actin filament, rather than the amounts of an individual component in the cytoskeletal network. This assay offers new perspectives to study in more detail the complex interplay between the endogenous biochemical composition of individual cells and the force they produce.


Cartesian and non-Cartesian responses in LGN, V1, and V2 cells.
Cell responses to drifting Cartesian (parallel) and non-Cartesian (concentric, radial, and hyperbolic) stimuli were recorded in and beyond the classical receptive field (CRF) in the lateral geniculate nucleus (LGN), V1, and V2 of anesthetized monkeys. Many cells were equally responsive to Cartesian and non-Cartesian, especially concentric, gratings. Around 15% of cells in each area were significantly more responsive to concentric compared to parallel gratings; however, cells significantly more responsive to parallel compared to concentric gratings were more numerous in the cortex. While many cells responded to hyperbolic and radial gratings, few were most responsive to these gratings. Cell selectivity decreased for Cartesian and increased for non-Cartesian gratings from V1 to V2 and the relative response varied as a function of stimulus extent with respect to the CRE. Complex, nonoriented, nondirectional cells with a low aspect ratio (AR) responded best to non-Cartesian gratings. These results cannot be fully explained using Gabor linear/energy models of simple and complex receptive fields (RFs) although such models predict some cells to respond equally to Cartesian and non-Cartesian gratings. Cells significantly more responsive to non-Cartesian gratings can be accounted for by CRF selectivity influenced by modulation from the nonclassical receptive field (nCRF). The present study shows that Cartesian/non-Cartesian selectivity is not an emergent property of V4 cells but is present at all levels of early visual processing being subserved by a subset of cells with specific tuning properties.


DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization.
Upon DNA damage, p53 has been shown to be modified at a number of N-terminal phosphorylation sites including Ser15 and -33. Here we show that phosphorylation is induced as well at a novel site, Ser20. Phosphorylation at Ser15, -20 and -33 can occur within minutes of DNA damage. Interestingly, while the DNA-binding activities of p53 appear to be dispensable, efficient phosphorylation at these three sites requires the tetramerization domain of p53. Substitution of an artificial tetramerization domain for this region also permits phosphorylation at the N-terminus, suggesting that oligomerization is important for DNA damage-induced signalling to p53.


A multivariate logistic regression analysis in predicting malignancy for patients with ovarian tumors.
Our objective was to improve the preoperative diagnosis of ovarian malignancy using a multivariate logistic regression analysis on the basis of demographic, serologic, gray-scale morphological, and Doppler variables. One hundred seventy-one patients with ovarian tumors (120 benign, 51 malignant including 9 tumors of low malignant potential) were studied with transvaginal B-mode, color, and pulsed Doppler ultrasonography before surgery. Based on the gray-scale ultrasound imaging, each tumor was classified as a unilocular cyst, multilocular cyst, unilocular cyst with solid parts, multilocular cyst with solid parts, or solid tumor. Intratumoral blood flow velocity waveforms were recorded on all tumors except unilocular cyst and were evaluated for resistance index (RI) and peak systolic velocity (PSV). Serum CA 125 levels were also measured. Twenty tumors were unilocular cysts and were all benign. Seventy tumors including all unilocular cysts which showed no flows were all benign. The remaining 101 tumors (50 benign, 51 malignant including 9 tumors of low malignant potential) presented intratumoral blood flows. Univariate and multivariate logistic regression analyses were conducted to identify variables predictive of ovarian malignancy in these 101 tumors. The variables included age, menstrual state, serum CA 125 levels, B-mode classification, RI, and PSV. In univariate analysis, menopause, the positivity of CA 125 (> or = 35 U/ml), and PSV larger than or equal to 10.4 cm/s were found to be significantly associated with malignant tumors. The PSV value of 10.4 cm/s was the median in benign tumors. Multivariate analysis showed that serum CA 125 levels (> or = 35 U/ml) (P = 0.002) and PSV (> or = 10.4 cm/s) (P < 0.001) were to be independent predictors of malignancy. These results suggest that intratumoral PSV is the strongest means of differentiating benign from malignant ovarian tumors with suspicious gray-scale ultrasonographic findings.


Outer membrane permeability of Acinetobacter calcoaceticus mediates susceptibility to rat polymorphonuclear leukocyte granule contents.
Growth of Acinetobacter calcoaceticus on specific alkanes altered the outer membrane permeability of the organism, as indicated by a change in sensitivity to the antibiotic actinomycin D. As the carbon length of the alkane energy source decreased, outer membrane permeability and susceptibility to actinomycin D increased. Concomitant with the increase in outer membrane permeability, A. calcoaceticus became more susceptible to the oxygen-independent antimicrobial activity of extracted contents from rat polymorphonuclear leukocyte granules. Individual fractions of granule extract possessed no antimicrobial activity against A. calcoaceticus. The alkane-induced change in outer membrane permeability was not associated with alterations of lipopolysaccharide O antigen. An outer membrane permeability mechanism, independent of changes in lipopolysaccharide content, mediating susceptibility to the oxygen-independent antimicrobial activity of rat polymorphonuclear leukocyte granule contents is suggested.


Not such a small diagnosis: small cell carcinoma of the prostate.
Small cell carcinoma (SCC) is an aggressive malignancy most commonly described in the lung. We present a case of a 61-year-old male who presented with a neck swelling and was subsequently found to have metastatic SCC of the prostate. Clinicians should be aware that it metastasizes early. Unlike conventional prostate adenocarcinoma, it is not a prostate-specific antigen (PSA) secreting tumor hence serum levels do not correlate with disease severity, and a low PSA reading may give false reassurance. In the future, further studies on genomic typing and novel targeted therapies may achieve better clinical outcomes for patients with this aggressive type of prostate cancer.


Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.
Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins. In addition to the 16 mutations described previously, we report 19 novel mutations. These data indicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support the wide heterogeneity of molecular defects in this rare disease.


Health impact assessment: a tool to help policy makers understand health beyond health care.
Health impact assessment (HIA)--a combination of methods to examine formally the potential health effects of a proposed policy, program, or project--has received considerable interest over the past decade internationally as a practical mechanism for collaborating with other sectors to address the environmental determinants of health and to achieve more effectively the goals of population health promotion. Demand for HIA in the United States seems to be growing. This review outlines the common principles and methodologies of HIA and compares different approaches to HIA. Lessons learned from the related field of environmental impact assessment and from experience with HIA in other countries are examined. Possible avenues for advancing both the field and the broader goals of population health promotion are outlined.


The Test of Variables of Attention (TOVA): internal consistency (Q₁ vs. Q₂ and Q₃ vs. Q₄) in children with attention deficit/hyperactivity disorder (ADHD).
The internal consistency of the Test of Variables of Attention (TOVA) was examined in a cohort of 6- to 12-year-old children (N = 63) strictly diagnosed with ADHD. The internal consistency of errors of omission (OMM), errors of commission (COM), response time (RT), and response time variability (RTV) of different test conditions (stimulus infrequent condition [Q₁ vs. Q₂] and stimulus frequent condition [Q₃ vs. Q₄]) was assessed via correlation analyses. All TOVA index scores under investigation assessing its internal consistency exhibited statistically significant correlations. All correlations fell in the moderate-high range.


[Models of self knowledge].
The main purpose of this paper is to analyze some different explanatory models of self - knowledge, belonging to Contemporary analytic philosophy. As a starting point, I will focus on self-ascriptions of mental states of the likes of "I have a headache", "I am thinking about my son", "I desire to shock my father", namely, the so-called "avowals". In the first part, I will point out what I take to be the set of characteristics of avowals that any theory about self-knowledge should account for. In the second part, I will present and contrast with one another the main theoretical explanatory models that have been put forward to give the required account.


A Pulsed Thermographic Imaging System for Detection and Identification of Cotton Foreign Matter.
Detection of foreign matter in cleaned cotton is instrumental to accurately grading cotton quality, which in turn impacts the marketability of the cotton. Current grading systems return estimates of the amount of foreign matter present, but provide no information about the identity of the contaminants. This paper explores the use of pulsed thermographic analysis to detect and identify cotton foreign matter. The design and implementation of a pulsed thermographic analysis system is described. A sample set of 240 foreign matter and cotton lint samples were collected. Hand-crafted waveform features and frequency-domain features were extracted and analyzed for statistical significance. Classification was performed on these features using linear discriminant analysis and support vector machines. Using waveform features and support vector machine classifiers, detection of cotton foreign matter was performed with 99.17% accuracy. Using frequency-domain features and linear discriminant analysis, identification was performed with 90.00% accuracy. These results demonstrate that pulsed thermographic imaging analysis produces data which is of significant utility for the detection and identification of cotton foreign matter.


Assessment of Semi-automated Computed Tomographic Measures of Segmental Perfusion Defects in a Swine Model (Sus scrofa) of Intermediate Coronary Lesions.
Computed tomographic myocardial perfusion (CTP) imaging is a tool that shows promise in emergent settings for defining the hemodynamic significance of coronary artery disease. In this study, we examined the accuracy with which the transmural perfusion ratio (TPR) derived through semiautomated CTP analysis reflected segmental perfusion defects associated with intermediate coronary artery lesions in swine. Lesions (diameter stenosis, 65% ± 11%) of the left anterior descending coronary artery (LAD) were created in 10 anesthetized female swine (weight, 47.5 ± 1.9 kg) by using a pneumatic occlusion device implanted on the LAD. Occluder inflation pressures were adjusted to maintain fractional flow reserve (FFR, 74.3 ± 1.7) during adenosine infusion (140ug/kg/min). Static CTP imaging using a stress-rest protocol and segmental TPR derived from semiautomated CT perfusion software was compared with microsphere-derived TPR (mTPR) by using a 16-segment model and polar mapping. Intermediate LAD stenosis was verified through multiplanar coronary CT angiography. Receiver operating characteristic analysis identified an optimal threshold for segmental perfusion defects for intermediate lesions (TPR threshold, ≤0.80); however, the area under the receiver operating characteristic curve was 0.58, and the overall accuracy was 63%. At this threshold, the sensitivity and specificity were 65% and 61%, and the positive and negative predictive values were 61% and 65%, respectively. Although CTP-TPR illustrated segmental perfusion defects with intermediate lesions, the disparity between CTP-TPR and mTPR measures of segmental perfusion suggests that further advances in analysis software may be necessary to improve the localization of segmental defects for intermediated lesions.


Direct molecular analysis of Malassezia species from the clinical samples of patients with pityriasis versicolor.
Species identification of Malassezia using culture-dependent methods is time-consuming due to their fastidious growth requirements. This study aimed to evaluate a rapid and accurate molecular method in order to diagnose the pityriasis versicolor (PV) and identify Malassezia species from direct clinical samples. Skin scraping or tape samples from patients with PV and healthy volunteers as the control group were collected. Diagnosis of PV was confirmed by direct microscopic examination. The DNA extraction was performed according to the steel-bullet beating method. Polymerase chain reaction-restriction fragment length polymorphism assay using HhaI restriction enzyme was applied for the identification and differentiation of Malassezia species. The PCR method was able to detect Malassezia in 92.1% of specimens which were also confirmed with microscopic examination. Statistically, a significant association was observed between the results of the two assays (P < 0.001). Moderate agreement was identified between the two methods to diagnose the PV in both populations (Kappa: 0.55). Considering microscopic examination as the gold standard method for confirmation of PV, the sensitivity, specificity, positive predictive value, and negative predictive value values of the PCR assay for recognition of PV were 85%, 75%, 92%, and 60%, respectively. M. globosa and M. restricta were the most prevalent species isolated from patients. In this study, the two-step molecular method based on the amplification of the D1/D2 domain and digestion of the PCR product by one restriction enzyme was able to diagnose and identify Malassezia directly from clinical samples. Consequently, it can be said that the molecular-based method provides more facilities to identify fastidious species, such as M. restricta.


Coinfection with HIV and tropical infectious diseases. I. Protozoal pathogens.
The brunt of the human immunodeficiency virus (HIV) pandemic has been borne disproportionately by resource-poor regions of the world, where tropical infectious diseases continue to hold greatest sway. As a result, our understanding of the epidemiological, biological, and clinical interactions between HIV and tropical pathogens has lagged, compared with our understanding of the interactions between HIV and pathogens that are common in the industrialized world. Because of the current rapid expansion of HIV care in the tropics, with increasing resources being made available, an overview of the available data is timely. Tropical protozoa are discussed here; other tropical pathogens are discussed in a related mini-review in this issue of Clinical Infectious Diseases.


Ductal carcinoma of the parotid gland.
A case of ductal carcinoma of the parotid gland is described. The medical literature contains only 13 previous reports on this kind of adenocarcinoma of the parotid gland. The tumour is characterized by its histologic resemblance to ductal carcinomas of the breast and prostate. The course of previously described cases suggests that this tumour has a highly aggressive biological behaviour.


Depressive symptoms as an underlying factor of the sensation of dry mouth.
The purpose of this survey was to study the sensation of oral dryness and its underlying factors in the 55-year-old population of Oulu (a medium-sized Finnish town), 780 of whom (77%) participated. In addition to the examination of oral health status and salivary flow rate measurements, depressive symptoms were determined on the basis of the Zung Self-Rating Depression Scale (ZSDS). The participants were also interviewed about their health, medication, physical health, physical activity, smoking habits, alcohol consumption, and factors related to their work. The prevalence of subjective sensations of dry mouth was 25.8% among men and 33.3% among women (p = 0.025). A statistically significant association was found between a subjective sensation of dry mouth and a low unstimulated flow rate, regular smoking, xerogenic medication, and the presence of at least one illness connected with dry mouth. Those who had a sensation of dry mouth also thought their physical condition and their health to be poorer and more often had a high rate of depressive symptoms. After the confounding factors had been added stepwise into the logistic regression model, depressive symptoms were still significantly associated with the sensation of oral dryness. When evaluating the causes of the sensation of dry mouth, the possibility of depression as an underlying factor should be considered.


The role of consensus interferon in the current treatment of chronic hepatitis C viral infection.
The current standard-of-care for chronic hepatitis C viral infection is treatment with pegylated interferon (PegIFN) plus ribavirin for 24 to 48 weeks. Approximately 50% of HCV-infected patients achieve a sustained viral response (SVR) to this treatment. However, the remaining patients either respond during treatment but relapse upon treatment cessation, respond minimally, or do not respond at all. Much research effort has been expended in attempting to predict those patients who will achieve viral eradication with PegIFN/ribavirin treatment, and it is now clear that those who have either a rapid virologic response (RVR) by week 4 of treatment or a complete early virologic response (cEVR, HCV RNA qualitative negative) by week 12 will go on to achieve SVR at very high rates (70%-90%). Several trials have been completed in patients that fail to achieve RVR or cEVR. These trials include strategies of extending duration of therapy, induction regimens, or retreatment with similar and dissimilar alfa interferons. A recent study of 696 genotype 1 patients treated with both PegIFN and weight-based ribavirin revealed that only 1.6% (4/246) of patients without RVR or cEVR achieved SVR. Consensus interferon, a wholly synthetic interferonalfa, is one of the agents that has been utilized in patients that fail treatment with PegIFN/ribavirin. This molecule has been demonstrated to have a very high affinity for the interferon-alfa receptor, and laboratory studies have demonstrated that it has high levels of antiviral activity. In order to optimally utilize consensus interferon, it is important to understand its unique mechanism of action. In addition, the latest research showing the importance of achieving RVR or cEVR should be reviewed, along with strategies for utilizing consensus interferon in re-treatment, or more specifically upon identification of on-treatment failure in historically difficult-to-treat patients.


Intrusive parenting and child externalizing behaviors across childhood: The antecedents and consequences of child-driven effects.
Many developmental theorists have studied the mutual influences in parent-child dyads. However, absent from this area of work are longitudinal studies that examine how child elicited changes in the home environment in turn shape children's own long-term development and adjustment. The current study addresses this limitation by operationalizing child-driven effects in a multilevel model to predict children's adjustment through age 15 (n = 1,364). From 24-months to 7 years of age, children's externalizing behaviors predicted increases in mothers' intrusive parenting behaviors. These child-driven effects were particularly salient for non-White children and mothers who were at risk socioeconomically. More important, these elicited changes in mothers' intrusive parenting as a result of children's externalizing behaviors during early childhood, in turn, predicted children's externalizing behaviors through age 15. When taken together, these findings suggest that children have the potential to shape their own development in the long-term by initiating changes in their home environment. Accordingly, interventions designed to mitigate children's externalizing behaviors may need to address, not only general parenting practices, but also specific and efficient parenting strategies in response to children's behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Comment on "Top-down versus bottom-up control of attention in the prefrontal and posterior parietal cortices".
Buschman and Miller (Reports, 30 March 2007, p. 1860) described the activity of ensembles of neurons in parietal and frontal cortex of monkeys performing visual search for targets that were easy or hard to distinguish from distractors. However, their conclusions are called into question by discrepancies between their results and publications from other laboratories measuring the same neural process.


Insights into the crystal structure of BRD2-BD2 - phenanthridinone complex and theoretical studies on phenanthridinone analogs.
Bromodomain and extra-terminal family proteins recognize the acetylated histone code on chromatin and participate in downstream processes like DNA replication, modification, and repair. As part of epigenetic approaches, BRD2 and BRD4 were identified as putative targets, for the management of chronic diseases. We have recently reported the discovery of a new scaffold of the phenanthridinone-based inhibitor (L10) of the second bromodomain of BRD2 (BRD2-BD2). Here, we present the crystal structure of the BRD2-BD2, refined to 1.4 Å resolution, in complex with β-mercaptoethanol (a component of the protein buffer). The β-mercaptoethanol covalently links to C425 of BD2 in the acetyl-lysine binding pocket, to form a modified cysteine mercaptoethanol (CME). The CME modification significantly hinders the entry of ligands into the BD2 binding pocket, suggesting that β-mercaptoethanol should be removed during protein production process. Next, to confirm whether phenanthridionone scaffold is a new inhibitor family of BRD2-BD2, we have determined the crystal structure of BD2 in complex with 6(5H)-Phenanthridinone (a core moiety of L10), refined to 1.28 Å resolution. It confirmed that the phenanthridinone molecule, unambiguously, binds to BD2. Moreover, we performed molecular docking and molecular dynamic studies on selected phenanthridinone analogs. The predicted L10 analogs are stable with essential hydrophobic and hydrophilic interactions with BD2 during molecular dynamic simulations. We propose that the predicted phenanthridinone analogs may be potential molecules for inhibiting the BD2 function of acetylated histone recognition.


Treatment adherence to an antiretroviral regime: the lived experience of Native Hawaiians and kokua.
Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity of people living with HIV, but treatment efficacy relies on strict adherence that is difficult for many consumers to manage. Results presented in this article are based on semi-structured in-depth interviews with Native Hawaiian consumers (n = 6) who reported moderate to low levels of overall HAART adherence, and based on their kokua, or primary support. All interviews were recorded on audiotape, transcribed verbatim, and analyzed using Grounded Theory methods. Research questions that guided the inquiry, included: What are the challenges of Hawaiians who report moderate to low levels of HAART adherence? How does non-adherence occur? What is the role of the kokua (primary caregiver) and/or family members in treatment adherence? What types of support enhance adherence? The unpredictability of living with HIV was a major challenge to adherence. Symptom distress and active use of alcohol and other drugs interfered with the capacity to appropriately adhere. Two patterns of non-adherence were identified: interrupted regime and intermittent use. Tangible and emotional types of support, sometimes delivered in culture-specific ways, were viewed as helpful in maintaining compliance and in resuming the regime when difficulties arose. The findings complement extant research on HAART by providing an understanding of adherence as a lived experience among Native Hawaiians and their kokua.


[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period].
We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.


A descriptive study of pressure sores: the prevalence of pressure sores and the characteristics of patients.
A descriptive study was carried out within a public health services area in Sweden in order to determine the incidence of pressure sores in acute and long-term care. Methods of prevention, treatment and the characteristics of patients were also noted. The criteria for the assessment of pressure sores were: skin discolouration, epithelial damage and damage to the full thickness of the skin. The data were collected by means of interviews during 1 week in February, 1980. It was found that within the public health services area there was a pressure sore frequency of 4%; i.e. 71 patients of a total of 1776 had pressure sores. Some of these patients had more than one pressure sore; the total number of sores was 109. The methods of prevention and treatment were numerous. The patients who developed pressure sores were predominantly women over 65 years of age, incontinent, and with poor mobility.


Change in Quality of Life for Patients with Irritable Bowel Syndrome following Referral to a Gastroenterologist: A Cohort Study.
Irritable bowel syndrome (IBS), a chronic functional condition, considerably reduces quality of life (QoL) and referral to gastroenterology is common. Until now, however, the impact of seeing a gastroenterologist for IBS on patients' QoL and utility has not been assessed. Patients referred with "probable IBS" to the Nottingham Treatment Centre between October 2012 and March 2014 were invited to complete a QoL questionnaire (EuroQol-5 Dimension) before their first appointment. Patients with confirmed IBS who completed this baseline assessment were sent follow-up questionnaires three and twelve months later. Global QoL and utility were measured at each time point and change from baseline calculated. Paired t-tests analysed the significance of any change. Of 205 invited patients, 69 were eligible and recruited. Response at three and twelve months was 45% and 17% respectively. Median global QoL at baseline was 67.5 (Interquartile range [IQR] 50.0 to 80.0), with a mean increase of 3.25 (95% confidence interval [CI] -5.38 to 11.88) three months later and a mean decrease of -1.82 (95% CI -16.01 to 12.38) after one year. The median utility at baseline was 0.76 (IQR 0.69 to 0.80), with a mean increase of 0.06 (95%CI -0.01 to 0.14) at three months and no change, 0.00 (-0.16 to 0.16), after one year. Patients experienced a small but not statistically significant increase in QoL and utility three months after seeing a gastroenterologist for IBS, which was not maintained. Gastroenterology referral does not appear to appreciably improve Qol for most people with IBS.


Inhibitory action of pig alpha-fetoprotein through early activated thymocyte surface Na+, K+-adenosinetriphosphatase.
An immunomodulatory effect of pig alpha-fetoprotein (AFP) on early phytohaemagglutinin (PHA)-stimulated intact thymocytes from piglets was analyzed. The activity of surface-localized Na+, K+-adenosinetriphosphatase was estimated, as the early reaction of mitogen-stimulated T-lymphocytes. A high inhibition of PHA-stimulated enzyme activity was found in the presence of AFP. The reaction was dependent of PHA concentration when using a constant AFP concentration. The highest AFP-induced decrease in PHA-induced Na+, K+-ATPase activity was 72%. AFP was isolated by a new technique based on salting out in ammonium sulphate and acetate buffer solutions. A gentle, simple and rapid procedure makes it possible to obtain AFP in a high degree of purity with preserved biological activity. The presented results can contribute to understanding the molecular aspects of AFP immunoregulation of lymphocyte reactivity in vitro.


Bolstering Skin Grafts With a Surgical Scrub Brush: A Cost-effective Solution.
Objective: The objective of this article is to review the methods currently used for the bolstering of skin grafts and compare their advantages and disadvantages with those of the dry, sterile surgical scrub brush. We report a series of cases performed at a single institution and compare the cost-effectiveness, application, and limitations of this method with other options for skin graft bolstering. Methods: A PubMed search using the parameters "(bolster) AND skin graft" was conducted, yielding 85 results. A total of 40 publications met the criteria for our literature review. The costs of the foam bolsters utilized as stents for skin grafts were obtained from the Central Supply and Resource Division of the University of Louisville Hospital for a cost analysis. The cost per square centimeter of each bolster material was calculated. Results: At $0.003/cm2, the 3M Reston foam is the most inexpensive of the 3 bolster materials analyzed. The dry, sterile surgical scrub brush has a similar cost at $0.006/cm2 but carries the advantage of sterility. The material cost of negative pressure wound therapy is $0.47/cm2, and the cost of the system as a whole makes it a much more expensive alternative. In 6 patients with defects of varying size and location, the scrub brush bolster showed a near 100% graft take and no complications. Conclusions: The dry, sterile surgical scrub brush presents a readily available and low-cost option for the stenting of small skin grafts and should be considered a viable method in the armamentarium of available skin graft bolsters.


Tuberculous granuloma: a rare cause of a non-healing ulcer.
A 78-year-old woman on ciclosporin for aplastic anaemia presented to her general practitioner with a 2 cm cystic swelling on the right side of her forehead. After a period of 8 months the lesion ruptured and, despite good wound care, failed to heal over a period of seven further months. Imaging demonstrated an invasive process and a biopsy was taken, which showed granulomatous inflammation that stained positively for mycobacteria. Further investigation with cross-sectional imaging revealed no other sites of disease. The only history of exposure to tuberculosis was 64 years prior to presentation. Differential diagnoses of mycetoma, autoimmune disease and non-tuberculous mycobacterial infection were considered, but culture confirmed tuberculosis. This case demonstrates an unusual presentation of isolated cutaneous tuberculosis in a patient with suppressed immune function.


Sustained-release bupropion overdose: a new entity for Australian emergency departments.
Bupropion hydrochloride (Zyban, Glaxo Wellcome Australia, Melbourne, Vic., Australia) was released in Australia in November 2000 as adjunctive therapy to assist with smoking cessation, having previously been used as an antidepressant in the US since 1989. The toxicity profile of bupropion hydrochloride in overdose differs considerably from other antidepressants, with prominent neurological manifestations and little cardiovascular toxicity. A case of bupropion overdose demonstrating the typical toxic syndrome is presented, together with a review of the literature and a discussion of the magnitude of the demand for bupropion and of the potential differences in presentation of overdoses in Australia.


Sputum Processing Method for Lateral Flow Immunochromatographic Assays to Detect Coronaviruses.
Coronavirus causes an infectious disease in various species and crosses the species barriers leading to the outbreak of zoonotic diseases. Due to the respiratory diseases are mainly caused in humans and viruses are replicated and excreted through the respiratory tract, the nasal fluid and sputum are mainly used for diagnosis. Early diagnosis of coronavirus plays an important role in preventing its spread and is essential for quarantine policies. For rapid decision and prompt triage of infected host, the immunochromatographic assay (ICA) has been widely used for point of care testing. However, when the ICA is applied to an expectorated sputum in which antigens are present, the viscosity of sputum interferes with the migration of the antigens on the test strip. To overcome this limitation, it is necessary to use a mucolytic agent without affecting the antigens. In this study, we combined known mucolytic agents to lower the viscosity of sputum and applied that to alpha and beta coronavirus, porcine epidemic diarrhea virus (PEDV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively, spiked in sputum to find optimal pretreatment conditions. The pretreatment method using tris(2-carboxyethyl)phosphine (TCEP) and BSA was suitable for ICA diagnosis of sputum samples spiked with PEDV and MERS-CoV. This sensitive assay for the detection of coronavirus in sputum provides an useful information for the diagnosis of pathogen in low respiratory tract.


Xenotropic Mouse Gammaretroviruses Isolated from Pre-Leukemic Tissues Include a Recombinant.
Naturally-occurring lymphomagenesis is induced by mouse leukemia viruses (MLVs) carried as endogenous retroviruses (ERVs). Replicating the ecotropic MLVs recombines with polytropic (P-ERVs) and xenotropic ERVs (X-ERVs) to generate pathogenic viruses with an altered host range. While most recovered nonecotropic recombinants have a polytropic host range, the X-MLVs are also present in the pre-leukemic tissues. We analyzed two such isolates from the AKR mice to identify their ERV progenitors and to look for evidence of recombination. AKR40 resembles the active X-ERV Bxv1, while AKR6 has a Bxv1-like backbone with substitutions that alter the long terminal repeat (LTR) enhancer and the envelope (env). AKR6 has a modified xenotropic host range, and its Env residue changes all lie outside of the domain that governs the receptor choice. The AKR6 segment spanning the two substitutions, but not the entire AKR6 env-LTR, exists as an ERV, termed Xmv67, in AKR, but not in the C57BL/6 mice. This suggests that AKR6 is the product of one, not two, recombination events. Xmv67 originated in the Asian mice. These data indicate that the recombinant X-MLVs that can be generated during lymphomagenesis, describe a novel X-ERV subtype found in the AKR genome, but not in the C57BL/6 reference genome, and identify residues in the envelope C-terminus that may influence the host range.


Extracellular fluid volume: A suitable indexation variable to assess impact of bariatric surgery on glomerular filtration rate in patients with chronic kidney disease.
Bariatric surgery (BS) might be a nephroprotective treatment in obese patients with chronic kidney disease (CKD), and the non-linear relation between body surface area (BSA) and extracellular fluid volume (ECFV) in obese people raises the question of the most relevant way to scale glomerular filtration rate (GFR) for assessing renal function changes after BS. We screened 1774 BS candidates and analysed 10 consecutive participants with CKD stage 3. True GFR (mGFR), measured by the renal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA), was scaled either to BSA (mGFRBSA) or to ECFV measured by 51Cr-EDTA distribution volume (mGFRECFV) before and one year after BS. The 10 candidates for BS had a mean body mass index of 43.3 ± 3.6 kg/m2 and a mean GFR of 48 ± 8 mL/min/1.73 m2. Six participants had a sleeve gastrectomy and four had a Roux-en-Y gastric bypass. One year after BS, ECFV decreased (23.2 ± 6.2 to 17.9 ± 4.3 L, p = 0.001), absolute mGFR was not significantly modified (74 ± 23 versus 68 ±19 mL/min), mGFRBSA did not change significantly (53 ± 18 versus 56 ± 17 mL/min/1.73 m2) whereas mGFRECFV significantly increased (42 ± 13 versus 50 ± 14 mL/min/12.9 L, p = 0.037). The relation between mGFRECFV and mGFRBSA was different from the identity line before (p = 0.014) but not after BS (p = 0.09). There is a difference between mGFRBSA and mGFRECFV following BS and the latter might better reflect the adequacy between renal function and corpulence.


Potentiation of natural killer cell activity of human lymphocytes in vitro: the participation of interferon in stimulation with Staphylococcus aureus Cowan I bacteria but not with protein A.
In the previous paper we reported that human natural killer (NK) cell activity was augmented greatly by preincubation with Staphylococcus aureus Cowan I bacteria (SpA CoI) or its Protein A. We examined here whether the augmentation with these stimulants is ascribable to the direct activation of NK cells or mediated by some soluble factors produced by the stimulants. It was found that a significant amount of interferon (IFN) was produced by the SpA CoI-stimulation but not by the Protein A-stimulation, although the latter usually induced augmentation of NK-cell activity not less than SpA CoI-stimulation. IFN produced by SpA CoI was considered to belong to alpha-type IFN, because it was stable at pH 2.0 and could be neutralized effectively by anti-IFN alpha antibody. Kinetics of NK-cell activation by SpA CoI (but not by Protein A) were very similar to those by IFN alpha. Furthermore, augmentation of NK-cell activity with SpA CoI-stimulated supernatant was inhibited almost completely by diluted anti-IFN alpha antibody, whereas augmentation with Protein A-stimulated supernatant could not be abolished by the same treatment. It was, therefore, suggested that augmentation of NK-cell activity with SpA CoI might be ascribable in most part to the IFN induced, whereas Protein A can stimulated NK or T cells directly or soluble factors other than IFN might work as well.


Outcome of thoracic esophageal carcinoma in blacks in the inner city.
This report is based on 45 cases of cancer of the thoracic esophagus in blacks residing in a socioeconomically depressed area of the inner city of South-Central Los Angeles. There were 30 men and 15 women, ranging in age from 26 to 89 years. Preoperative management, contraindications of surgery, and overall results are specified. The operative mortality rate was 14%. As a means of restoring continuity of the alimentary tract after resection of esophageal carcinoma, the stomach was preferred, although the colon was used in two instances. Five-year survival in this series was 14% in the operative group and 13% in the radiotherapy group; one of the surgical patients is still alive, and another one survived for 72 months. In the radiation group, no such incidence occurred. It is therefore concluded that surgery is the optimal palliation if there is an acceptable risk of mortality. When operative risks are unacceptable radiation therapy is used.


Strength and viscoelastic properties of anisotropic rat skin after treatment with desmotropic drugs.
Male Sprague-Dawley rats were treated 10 times either with 2 or 10 mg/kg s.c. prednisolone acetate or with 300 or 1,000 mg/kg p.o. D-penicillamine or with 100 or 300 mg/kg p.o. aminoacetonitrile bisulfate. Samples of dorsal skin were tested either longitudinally or perpendicularly to the body axis. Relaxation and hysteresis experiments were performed at different degrees of elongation. Finally, ultimate values were measured. In all groups, ultimate strain was much higher perpendicularly than longitudinally to the body axis. A dose-dependent increase of all parameters indicating strength or elasticity was found after prednisolone acetate treatment, whereas the indicators of viscosity showed a decrease. D-Penicillamine treatment decreased all parameters of strength and elasticity and increased viscosity and plasticity. Aminoacetonitrile bisulfate induced biphasic changes: after high-dose treatments strength and elasticity were increased and viscosity decreased. The results are discussed in view of changes of biochemical composition and cross-linking of collagen.


[The use of Doppler in the diagnosis of intracardiac shunts in adults].
Conventional and color Doppler represent a major addition to ultrasound cardiography and the evaluation of intracardiac shunts, in adults as well as children. Above all, it concerns interauricular and interventricular communications and patent ductus arteriosus. The Doppler is superior to ultrasonography in several conditions such as the diagnosis of very small communications, muscular interventricular communications and multiple shunts. It enables to quantify the magnitude of the shunts either by determination of the area of the color flow or, more precisely, by measurement of the ratio pulmonary output/aortic output. In addition, the Doppler presents the advantage of determining the pressures in the right heart.


Microscopic colitis with granuloma which responded to steroid therapy.
We present a patient with chronic watery diarrhea and weight loss, in whom colonoscopic findings were consistent with microscopic colitis, but histopathological examination revealed granulomatous inflammation. A 67-year-old Japanese female with a several year history of chronic watery diarrhea and body weight loss was admitted to our hospital. Her laboratory data showed hypoalbuminemia and high levels of serum immunoglobulin G and C-reactive protein. Colonoscopic findings were grossly normal. Histopathology showed inflammatory cell infiltrates with non-necrotizing granulomas and multinucleated giant cells, indicating that this was not conventional microscopic colitis, lymphocytic colitis or collagenous colitis. After treatment with prednisolone her symptoms and laboratory data improved dramatically, and she went into remission without the necessity of further steroid treatment.


A New 1,5-Dihydroxy-4-methoxyisoquinoline from Scolopendra subspinipes mutilans.
A new isoquinoline, 1,5-dihydroxy-4-methoxyisoquinoline (1), was obtained from Scolopendra subspinipes mutilans. Compound 1 showed moderate cytotoxicity on tumour cells with IC50 values ranging from 13 to 26 μm against five esophageal squamous cancer cells whereas low cytotoxicity against normal human esophageal epithelial cells. Isoquinoline ring oxidized at C(1), C(4), and C(5) can enhance its cytotoxicity. In addition, compound 1 showed potent inhibitory effect (inhibition rate > 50% at 13 μm) on cell migration in human umbilical vein endothelial cells. This article mainly studies the structure and activity of 1, and more modification of 1 as a potential anticancer agent.


AIDS and the rights of the individual: toward a more sophisticated understanding of discrimination.
AIDS is the first public health crisis in America to arise after the mid-century civil rights revolution. Reflecting the values of the civil rights movement, public health experts have drawn attention to the dangers of discrimination against individuals who are sick or at risk, and generally have expressed a preference for voluntary over compulsory measures to limit the spread of the illness. Remarkably, government officials--judges, legislators, and administrators--have largely acceded to the views of these experts. This perspective indicates a more sophisticated understanding of discrimination issues throughout society; experience with AIDS may itself help to transform and refine ideas about individual rights, especially the constitutional conception of "equal protection under the law."


Structural characterization of human melanoma-associated antigen p97 with monoclonal antibodies.
Monoclonal antibodies were used to study p97, a human melanoma-associated antigen (MAA). Four hybridomas, designated 4.1, 96.5, 118.1, and 8.2, were obtained by fusing mouse myeloma cells with spleen cells from mice immunized with human melanoma cells. Antibodies 4.1 and 8.2 were IgG1; antibodies 96.5 and 118.1 were IgG2a. Sequential immunoprecipitation (IP) and sodium-dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that all 4 antibodies recognized the same 97 kilodalton (kD) protein. Binding studies with 125I-labeled antibody showed that antibodies 4.1 and 96.5 bound the same epitope, p97a. Antibodies 118.1 and 8.2 defined epitopes p97b and p97c, respectively. Six monoclonal antibodies (M17, L1, L10, R10, I12, and K5) specific for gp95, a kD melanoma cell surface glycoprotein were also tested. Sequential IP showed that these antibodies bound p97; p97 and gp95 are thus identical. Binding studies showed that antibody m17 bound epitope p971, and antibodies L1, L10, and R19 bound epitope p97c. Antibodies I12 and K5 defined 2 other epitopes, p97d and p97e, respectively. SDS-PAGE under nonreducing conditions indicated that p97 is monomeric, probably with intrachain disulfide bonds. Cell-surface labeling of sialic acid residues and neuraminidase digestion showed that p97 is a sialoglycoprotein. Digestion of p97 with papain or trypsin produced a stable 40 kD fragment, which expressed epitopes p971, p97b, and p97c, but not p97d or p97e.


Stretchable Transparent Conductive Films from Long Carbon Nanotube Metals.
Flexible transparent conductors are an enabling component for large-area flexible displays, wearable electronics, and implantable medical sensors that can wrap around and move with the body. However, conventional conductive materials decay quickly under tensile strain, posing a significant hurdle for functional flexible devices. Here, we show that high electrical conductivity, mechanical stretchability, and optical transparency can be simultaneously attained by compositing long metallic double-walled carbon nanotubes with a polydimethylsiloxane substrate. When stretched to 100% tensile strain, thin films incorporating these long nanotubes (≈3.2 µm on average) achieve a record high conductivity of 3316 S cm-1 at 100% tensile strain and 85% optical transmittance, which is 194 times higher than that of short nanotube controls (≈0.8 µm on average). Moreover, the high conductivity can withstand more than 1000 repeated stretch-release cycles (switching between 100% and 0% strain) with a retention approaching 96%, whereas the short nanotube controls exhibit only 10%. Mechanistic studies reveal that long tubes can bridge the microscale gaps generated during stretching, thereby maintaining high electrical conductivity. When mounted on human joints, this elastic transparent conductor can accommodate large motions to provide stable, high current output. These results point to transparent conductors capable of attaining high electrical conductivity and optical transmittance under mechanical strain to allow large shape changes that may take place in the operation and use of flexible electronics.


Absolute measurement of low gas flow by means of the spectral analysis of the thermal wave.
A new technique has been developed for determination of the very low gas flow velocity by means of the spectral analysis of the thermal waves. It is assumed that the transmitter signal is made of sine waves. By employing the Fourier analysis of the detector signals, the phase shifts of the relevant harmonic component of the frequency function were determined. The flow velocity has been obtained by a nonlinear regression analysis of the measured phase shifts values. This method allows for the flow of gas to be measured in a range from 5 to 500 cm/s.


Geochemical and Hydrologic Factors Controlling Subsurface Transport of Poly- and Perfluoroalkyl Substances, Cape Cod, Massachusetts.
Growing evidence that certain poly- and perfluoroalkyl substances (PFASs) are associated with negative human health effects prompted the U.S. Environmental Protection Agency to issue lifetime drinking water health advisories for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in 2016. Given that groundwater is a major source of drinking water, the main objective of this work was to investigate geochemical and hydrological processes governing the subsurface transport of PFASs at a former fire training area (FTA) on Cape Cod, Massachusetts, where PFAS-containing aqueous film-forming foams were used historically. A total of 148 groundwater samples and 4 sediment cores were collected along a 1200-m-long downgradient transect originating near the FTA and analyzed for PFAS content. The results indicate that unsaturated zones at the FTA and at hydraulically downgradient former domestic wastewater effluent infiltration beds both act as continuous PFAS sources to the groundwater despite 18 and 20 years of inactivity, respectively. Historically different PFAS sources are evident from contrasting PFAS composition near the water table below the FTA and wastewater-infiltration beds. Results from total oxidizable precursor assays conducted using groundwater samples collected throughout the plume suggest that some perfluoroalkyl acid precursors at this site are transporting with perfluoroalkyl acids.


Large-scale purification of hepatitis B surface antigen.
Hepatitis B surface antigen was concentrated and purified from plasma by two simple steps of purification. In the first step the antigen was purified 24-fold by polyethylene glycol precipitation. An additional 10-fold purification was achieved by batchwise adsorption to hydroxylapatite and subsequent elution with 0.02 M sodium phosphate buffer.


EcoHealth and the Determinants of Health: Perspectives of a Small Subset of Canadian Academics in the EcoHealth Community.
EcoHealth is an emerging field that examines the complex relationships among humans, animals, and the environment, and how these relationships affect the health of each of these domains. The different types of determinants of health greatly influence human health and well-being. Therefore, EcoHealth's ability to improve human, animal, and environmental health and well-being is, in part, influenced by its ability to acknowledge and integrate the determinants of health. However, our previous research demonstrates that the academic EcoHealth literature had a low, uneven engagement with the determinants of health. Accordingly, to make sense of this gap, our research aim is to better understand the views of a small subset of the Canadian EcoHealth community about EcoHealth and the determinants of health relative to EcoHealth. We used a qualitative research design involving seven semi-structured interviews, which were analyzed using thematic analysis. Our findings suggest a tension across themes and a lack of conceptual engagement with the determinants of health. As we consider a future with rapid, unsustainable changes, we expect the identification and integration of the different types of determinants of health within EcoHealth to be imperative for EcoHealth to attain its goal of improving the health and well-being of humans, animals, and the environment.


Binding to chaperones allows import of a purified mitochondrial precursor into mitochondria.
Refolding of the acid-unfolded precursor to mitochondrial aspartate aminotransferase (pmAAT) is inhibited when cytosolic Hsc70 is included in the refolding reaction (Artigues, A., Iriarte, A., and Martinez-Carrion, M. (1997) J. Biol. Chem. 272, 16852-16861). At low molar excess of Hsc70 pmAAT is recovered in insoluble aggregates containing equal amounts of Hsc70. However, in the presence of a large excess of Hsc70, refolding of pmAAT is still arrested, but the enzyme remains in solution. Similar behavior was observed with two other cytosolic chaperones, bovine Hsp90 and yeast Ydj1. Coimmunoprecipitation of pmAAT using Hsc70 antibodies confirmed the formation of soluble Hsc70-pmAAT complexes at high concentrations of the chaperone. Data from analytical centrifugation, sedimentation in glycerol gradients, and partial purification of the soluble complexes indicate that multiple Hsc70 molecules bind per pmAAT polypeptide chain. The absence of catalytic activity together with the protease susceptibility of pmAAT bound to Hsc70, Hsp90, or Ydj1 suggest that these chaperones bind and maintain pmAAT in a partially unfolded state, analogous to the import-competent conformation of the protein synthesized in cell-free extracts. Remarkably, the purified pmAAT bound to Hsc70 or Ydj1, but not to Hsp90, is imported by isolated mitochondria in a reticulocyte lysate-dependent manner. Thus, both Hsc70 and Ydj1 can trap an import-competent folding intermediate of pmAAT, but productive binding and import into mitochondria require the collaboration of additional cytosolic factors from the lysate.


Ultrasensitive detection of DNA sequences in solution by specific enzymatic labeling.
We present a newly developed technique for the direct detection of very low concentrations of specific nucleic acid sequences in homogeneous solution based on a polymerase extension reaction. This method consists of synthesizing a highly fluorescent nucleic acid reporter molecule using a sequence of the target as a template. Synthesis of the reporter molecule is accomplished by hybridizing a short complementary oligonucleotide primer to the target and extending the reporter using a polymerase and free nucleotides. One of these nucleotides is partially labeled with a fluorophore. The reaction sample is then flowed through the capillary cell of a single molecule detector. Detection of the reporter signifies the presence of the target being sought. Under carefully selected conditions, fluorescence from the reporter molecule is much stronger than that of the free nucleotide background over the detection time. We have derived practical equations that allow us to determine an optimal range of values for the relative reporter and free-nucleotide concentrations. This method allows for the rapid, direct detection of individual targets at femtomolar concentrations without the use of an amplification procedure, such as the polymerase chain reaction.


Environmental health effects of brick kilns in Kathmandu valley.
Brick kilns operating in Kathmandu valley are known to be a leading cause of air pollution. The main objective of this study was to assess the effect of brick kilns on environment and human health. This study has been done at Duwakot VDC in Bhaktapur. This study was conducted during brick kilns operating and not operating periods. Different methods were used for data collection, such as household environmental health survey, school health examination, and air quality measurement for total suspend particles, particulate matter of size less than 10 microns, Sulphur Dioxide, Oxides of Nitrogen, and Carbon Monoxide. A total of 330 individuals were interviewed during household environmental survey and majority of them expressed about smoke related respiratory discomfort at home and surrounding. Out of 141 school children who underwent thorough physical health examination, 79 students were from Ganesh Public School (located near to brick kilns) and 62 were from Nabin English School (far away from brick kilns). Statistically significant high odds ratios for respiratory problems like tonsillitis (4.17 95% CI 2.05, 8.45) and acute pharyngitis (4.08 95% CI 2.01, 8.33) were observed among the students from Ganesh Public School. Average value of particulate matter of size less than 10 microns and total suspend particles for the pre operation time was 0.029 mg/m3 and 0.033 mg/m3 respectively whereas, it reached 0.050 mg/m3 and 0.056 mg/m3 respectively during the brick kiln operation time. The concentration of various air pollutants was higher during the operation of brick kilns at Duwakot. Similarly, the health status of the school children attending the school close to the vicinity of the brick kilns was worse compared to the students attending the school away from the brick kilns.


Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT).
To investigate factors associated with treatment-related pneumonitis in non-small-cell lung cancer patients treated with concurrent chemoradiotherapy. We retrospectively analyzed data from 223 patients treated with definitive concurrent chemoradiotherapy. Treatment-related pneumonitis was graded according to Common Terminology Criteria for Adverse Events version 3.0. Univariate and multivariate analyses were performed to identify predictive factors. Median follow-up was 10.5 months (range, 1.4-58 months). The actuarial incidence of Grade > or =3 pneumonitis was 22% at 6 months and 32% at 1 year. By univariate analyses, lung volume, gross tumor volume, mean lung dose, and relative V5 through V65, in increments of 5 Gy, were all found to be significantly associated with treatment-related pneumonitis. The mean lung dose and rV5-rV65 were highly correlated (p < 0.0001). By multivariate analysis, relative V5 was the most significant factor associated with treatment-related pneumonitis; the 1-year actuarial incidences of Grade > or =3 pneumonitis in the group with V5 < or =42% and V5 >42% were 3% and 38%, respectively (p = 0.001). In this study, a number of clinical and dosimetric factors were found to be significantly associated with treatment-related pneumonitis. However, rV5 was the only significant factor associated with this toxicity. Until it is better understood which dose range is most relevant, multiple clinical and dosimetric factors should be considered in treatment planning for non-small-cell lung cancer patients receiving concurrent chemoradiotherapy.


[Use of dual-energy computed tomographic angiopulmonography in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary artery thromboendarterectomy].
To estimate the contribution of dual-energy computed tomographic (CT angiopulmonography t o a diagnostic algorithm in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and its role in the evaluation of postoperative changes. CT angiopulmonography was performed on the 64-slice Discovery HD 750 system (GE Healthcare) using the dual-energy scanning mode (140 and 80 kV). The examination results in patients with CTEPH were analyzed. All the patients were found to have typical CT signs of CTEPH: abnormal contrast enhancement of the pulmonary arteries, their dilatation and tortuosity; signs of right cardiac overload: right ventricular dilatation and/or hypertrophy, bronchial artery dilatation, decreased peripheral vascular pattern, mosaic pulmonary perfusion, and wedge-shaped perfusion defects on the iodine maps. Mosaic pulmonary perfusion areas were also found in all the patients. Perfusion defects were more clearly visualized when dual-energy CT by constructing iodine perfusion maps was used. Analyzing the perfusion maps in 6 patients operated on revealed a 20-50% reduction in perfusion deficit. Information on the vascular bed and pulmonary perfusion may be obtained in patients with CTEPH within one investigation, which is important to plan surgical treatment. Construction of iodine pulmonary perfusion maps allows evaluation of perfusion recovery after artery thromboendarterectomy.


Gizzerosine-induced histopathological lesions in broiler chicks.
1. The aim of this study was to investigate pathomorphological changes in broiler chicks fed with different doses of gizzerosine, a substance produced during the heat treatments of fish meal. 2. The experiment was carried out in Ross broiler chicks which were divided into three groups: group A received 100% of non-medicated commercial mash for broiler chicks. During an experimental 5-d period, 50% of commercial mash was replaced with unheated fish meal (0.65 ppm gizzerosine) in group B and in group C with heated fish meal (1.15 ppm gizzerosine). Fourteen chicks from each group were killed every day. Samples of gastrointestinal and lymphoid organs, lung, pancreas, liver, brain and kidney tissue were sampled for histopathological analysis. Organs were embedded in paraffin and stained with hematoxylin-eosin stain and using periodic acid-Schiff reagent (PAS) and Sudan III (frozen sections). 3. Necropsy did not reveal notable differences between treated groups. There were no significant histopathological changes in immunocompetent organs nor in the lungs, the pancreas, the kidney or the brain. Sharply demarcated multiple vacuoles were observed in the myocardium in group C toward the end of the experiment. In group C, the prevalent changes in the gizzard and the proventriculus were slight to severe cuticle erosions and oedema of the lamina propria with or without multiple vacuoles, respectively, towards the end of the experiment. The most prominent changes toward the end of the experiment were dispersed cell vacuolisation in duodenal, jejunual, ileal and caecal lamina propria in group C. 4. In conclusion, it should be emphasised that extra-gizzard gizzerosine-induced lesions are probably not mediated by H2-receptor stimulation, but could be a consequence of cellular hypoxia.


[Changes in hemostasis in ischemic heart disease].
The relationship between changes in blood coagulation, the occurrence and severity of risk factors of ischemic heart disease and the clinical condition of the patient was investigated. The at risk group of patients 42.2% had more than 3 pathological parameters. Intravascular blood coagulation was not activated in any of the patients. In patients with acute myocardial infarction (MI), 62.2% had more than 3 pathological parameters on the first day of MI development. Demonstrable activation of intravascular blood coagulation was found in 28.2% of these patients. On day 5 of MI, activation of intravascular blood coagulation was recorded in 57.7% of the patients treated by classical approach and in 15.4-30.8% of the patients on thrombolytic treatment. In the at risk group, primary hemostasis and the fibrinolytic system were more affected, in patients with MI the whole hemostatic mechanism was involved. On day 5 of MI, in patients with classical therapy pathological laboratory findings still persisted or were even more deteriorated, particularly increases in fibrinogen level. At that time, in patients on thrombolytic therapy no substantial changes of initial values were recorded. No correlation was found to exist between changes in hemostasis and the risk profile or between changes in hemostasis and the clinical severity of MI. The obtained results justify the administration of antithrombotic substances, especially in patients with unstable angina pectoris. On observing time constraints, administration of thrombolytics is justified in MI. (Fig. 9, Ref. 25.)


[Association between polymorphisms of cytokine genes and the rate of multiple sclerosis progression].
A genetic predisposition due to the polygenic system responsible for the formation of immune response plays a key role in the development of multiple sclerosis. We genotyped the following polymorphisms: TNFα (rs1800629), TNFRSF1A (rs4149584), CD40 (rs6074022 and rs11086998) using TaqMan technology. The significant genotype effect on the disability index on EDSS and rate of MS progression was found. The association between GA and AA TNFα genotypes and higher average annual frequency of exacerbations was revealed. Genotypes CC (rs6074022) and GG (rs11086998) were associated with the higher disability level. Genotype CC (rs11086998) was associated with the higher rate of MS progression. The results may be used as potential predictors of high rate of MS progression and allow to tailor treatment on early stages of the disease.


International sexual harassment.
This paper on international sexual harassment begins with a presentation of the definitions, models, and consequences of sexual harassment. Following this discussion, a description is given of a nine-country research program that examined reactions to academic sexual harassment. A brief review of incidence studies and international laws related to sexual harassment are also included.


Pleistocene refugia and genetic diversity patterns in West Africa: Insights from the liana Chasmanthera dependens (Menispermaceae).
Processes shaping the African Guineo-Congolian rain forest, especially in the West African part, are not well understood. Recent molecular studies, based mainly on forest tree species, confirmed the previously proposed division of the western African Guineo-Congolian rain forest into Upper Guinea (UG) and Lower Guinea (LG) separated by the Dahomey Gap (DG). Here we studied nine populations in the area of the DG and the borders of LG and UG of the widespread liana species, Chasmanthera dependens (Menispermaceae) by amplified fragment length polymorphism (AFLP), a chloroplast DNA sequence marker, and modelled the distribution based on current as well as paleoclimatic data (Holocene Climate Optimum, ca. 6 kyr BP and Last Glacial Maximum, ca. 22 kyr BP). Current population genetic structure and geographical pattern of cpDNA was related to present as well as historical modelled distributions. Results from this study show that past historical factors played an important role in shaping the distribution of C. dependens across West Africa. The Cameroon Volcanic Line seems to represent a barrier for gene flow in the present as well as in the past. Distribution modelling proposed refugia in the Dahomey Gap, supported also by higher genetic diversity. This is in contrast with the phylogeographic patterns observed in several rainforest tree species and could be explained by either diverging or more relaxed ecological requirements of this liana species.