[Changes in sodium pump transport activity and Na+, K+-ATPase expression level following lymphocytes activation in humans].
Ouabain-inhibitable rubidium influxes, intracellular sodium content (Nai), and alpha 1-subunit abundance have been studied in human blood lymphocytes, stimulated by phytohemagglutinin (PHA) or by the phorbol 12,13-dibutyrate (PDBu), and calcium ionophore--ionomycin. It is shown that at early stages of PHA-induced activation, the Na/K pump expression (as determined by Wesrn blots of alpha 1 protein in membrane fractions of total cell lysates) does not change, and the increase in Rb influx is due to the increase in Nai and results from the enhanced transport activity of Na/K pumps present in plasma membrane. During the late stages of G0-->G1-->S transit (16-48 h), the increase in Rb influx occurs without changes in Nai, and monensin increases both Nai, and the Rb influx via the Na/K pump. To the end of the first day of mitogen activation, the alpha 1 protein content was found to increase by 5-7 times. A correlation was revealed between changes in ouabain-inhibitable Rb influxes, alpha 1 protein abundance, and the proliferation rate. It is concluded that blasttransformathion of normal human lymphocytes is accompanied by the increase in membrane-associated pool of alpha 1-subunit of Na+,K(+)-ATPase, and the enhanced activity of sodium pump during the G0-->G1-->S progression is provided by increased number of Na+,K(+)-ATPase pumps in plasma membrane.


Validation of ANAM for cognitive screening in a mixed clinical sample.
The Automated Neuropsychological Assessment Metrics (ANAM) is a library of computer based tests designed to measure cognitive function at a single time-point or longitudinally for detection of cognitive change. This study sought to validate ANAM as a cognitive screening tool for presence of confirmed neuropsychological diagnosis in an outpatient setting. Retrospective data analysis was conducted for 139 patients referred for outpatient neuropsychological assessment. Clinical diagnosis was made independent of ANAM test results and resulted in a diagnostic mix of both neurologic and psychologic etiologies. ANAM scores predictive of presence of confirmed diagnosis were identified using multiple logistic regression and the predictive ability of the resulting model was quantified using receiver operator characteristic analysis. Sensitivity and specificity for the ANAM when combined with anger and depressive symptom scores were 71% and 91%, respectively, with a positive predictive value of 97.5 and negative predictive value of 40.4. This combined approach provided the greatest accuracy for individual tests as well as the composite score of the ANAM in identifying those who received a subsequent clinical diagnosis. Although data should be replicated in larger samples, these results suggest that ANAM may have predictive value and may be a useful screening tool for identifying those who would likely benefit from neuropsychological services.


Synchronous carcinoma and lymphoma of the breast.
Primary breast lymphoma is a rare entity. Furthermore, extranodal marginal zone B-cell lymphoma affecting the breast is exceedingly rare. We report a unique case of invasive lobular carcinoma diagnosed simultaneously with an extranodal marginal zone B-cell lymphoma of the breast. A literature review demonstrated 2 reports of synchronous invasive ductal carcinoma and mucosa-associated lymphoid tissue lymphoma affecting the breast; however, there is a paucity of cases demonstrating different malignancies affecting the same breast tissue in a particular patient, especially in the setting of lobular carcinoma. As such, there are no clear guidelines on the optimal management of such synchronous tumors. Herein, the diagnostic and management issues are explored.


Formation and maturation of autophagosomes in higher eukaryotes: a social network.
Autophagy, a self-eating process conserved from yeast to mammals, is critical for maintaining cell homeostasis. It involves the formation of a double-membrane structure, called the autophagosome, and its subsequent delivery to lysosomes for degradation of sequestrated materials. Our knowledge about autophagy has greatly expanded over the last two decades, mainly due to studies of a set of autophagy-related (ATG) genes identified from yeast genetic screens. Autophagy in higher eukaryotes is far more complicated, because it involves steps that are not present in yeast. These include the formation of extensive contacts between the ER and the isolation membrane (IM, autophagosome precursor), and the maturation of nascent autophagosomes into degradative autolysosomes via fusion with vesicles generated from the endolysosomal compartment. Recent studies have discovered factors that act at these unique steps, greatly advancing our molecular understanding of autophagy in higher eukaryotes.


Polymeric precipitants for the crystallization of macromolecules.
Nine different water soluble polymers reported to strongly affect the properties and structure of water were evaluated for their use in crystallizing a series of 24 different proteins, viruses, and conventional small molecules. All of the polymers produced crystals of some of the molecules and viruses tested, and of the 24 molecules tested, 14 were crystallized. In a number of cases, crystals of the molecules and viruses were obtained under very different conditions than were ever previously used. Because the selection of polymers employed here represents only a sampling of those available to experimenters, we conclude that the potential range of such polymers useful in macromolecular and small molecule crystallization may be very broad.


Evaluation of diagnostic tests when there is no gold standard. A review of methods.
To generate a classification of methods to evaluate medical tests when there is no gold standard. Multiple search strategies were employed to obtain an overview of the different methods described in the literature, including searches of electronic databases, contacting experts for papers in personal archives, exploring databases from previous methodological projects and cross-checking of reference lists of useful papers already identified. All methods available were classified into four main groups. The first method group, impute or adjust for missing data on reference standard, needs careful attention to the pattern and fraction of missing values. The second group, correct imperfect reference standard, can be useful if there is reliable information about the degree of imperfection of the reference standard and about the correlation of the errors between the index test and the reference standard. The third group of methods, construct reference standard, have in common that they combine multiple test results to construct a reference standard outcome including deterministic predefined rules, consensus procedures and statistical modelling (latent class analysis). In the final group, validate index test results, the diagnostic test accuracy paradigm is abandoned and research examines, using a number of different methods, whether the results of an index test are meaningful in practice, for example by relating index test results to relevant other clinical characteristics and future clinical events. The majority of methods try to impute, adjust or construct a reference standard in an effort to obtain the familiar diagnostic accuracy statistics, such as sensitivity and specificity. In situations that deviate only marginally from the classical diagnostic accuracy paradigm, these are valuable methods. However, in situations where an acceptable reference standard does not exist, applying the concept of clinical test validation can provide a significant methodological advance. All methods summarised in this report need further development. Some methods, such as the construction of a reference standard using panel consensus methods and validation of tests outwith the accuracy paradigm, are particularly promising but are lacking in methodological research. These methods deserve particular attention in future research.


Haemorheology in diabetic foot.
A prospective study was undertaken to study the haemorheology in patients with diabetic foot lesions. Haemorheology of 30 patients with foot lesions and 30 age and sex matched controls was studied. The haemorheological parameters evaluated were whole blood and plasma viscosity and RBC filter ability. Plasma viscosity was significantly increased (p < 0.05). It substantiates the need for using rheomodulators in management of diabetic foot lesions.


Discovery of novel andrographolide derivatives as cytotoxic agents.
The natural diterpenoid andrographolide (1) exhibits various biological activities. Seventeen derivatives of 1 were prepared via esterification and etherification of 14-dehydroxy-11,12-didehydroandrographolide (2). Most derivatives demonstrated significant inhibition against tumor cell growth. The most active compounds, 3b and 3c, had GI50 values of 1.46-9.19 μM against A549, DU145, KB and KB-Vin tumor cells. In an immunocytochemical study, treatment with compound 3c disrupted microtubule dynamics in PC-3 cells, but caused no accumulation of metaphase cells, which is a phenotype dissimilar from that of 1. This difference suggests that structural modification of 1 resulted in a shift in the underlying molecular mechanism.


Tandem mass spectrometric analysis of quaternary ammonium pesticides.
A detailed MS(n) study on an ion trap instrument of the quaternary ammonium pesticides paraquat, diquat, difenzoquat, mepiquat and chlormequat reveals a number of ions not reported previously, and has allowed examination of the fragmentation pathways. A number of transitions that are highly specific to each quat have been identified. Optimal ion trap operating conditions determined using Simplex optimisation can promote either detection of a particular fragmentation transition or a range of MS/MS product ions with a high overall signal response. Thus, fragmentation conditions were optimised to enhance the specificity or sensitivity of MS/MS methods.


Ductal drainage or resection for chronic pancreatitis.
We report a 10 year review comparing the results of pain relief after three procedures for chronic pancreatitis: Whipple pancreatoduodenectomy, modified Puestow side-to-side longitudinal pancreaticojejunostomy and distal pancreatic resection. Results of follow-up review at 6 months, 2 years and 5 years were tabulated. Five year follow-up data were available on more than 80 percent of patients. The proportion of good results for pain relief decreased with the passage of time regardless of the procedure performed. Although equally good results are obtained after either pancreatoduodenectomy or pancreaticojejunosotomy, we conclude that in the presence of a dilated duct, the procedure of choice is pancreaticojejunostomy. If the duct is not dilated, we then favor pancreatoduodenectomy, after which the pain relief is significantly better (p = 0.05) than after distal resection. Our data show that, for all factors evaluated, the poorest pain relief was obtained after distal resection. Therefore that procedure has limited value when used specifically for relief of pain in chronic pancreatitis, except in the uncommon circumstance when the disease is confined to the distal part of the gland. Our study also shows that patients who have more radical distal resection have no better pain relief than those who have 50 percent distal resection.


Exercise training modalities and strategies to improve exercise performance in patients with respiratory disease.
Pulmonary rehabilitation is an evidence-based, multidisciplinary, comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and whose daily living activities are often restricted. Pulmonary rehabilitation programs are designed to improve the physical and emotional condition of people with chronic respiratory disease and to promote long-term adherence to health-enhancing behavior. Exercise training is at the core of pulmonary rehabilitation (PR) programs. The benefits of exercise training include decreased dyspnea, improved health-related quality of life, fewer days of hospitalization, and decreased health-care utilization. To gain PR benefits, patients should be able to complete an exercise training program, preferably with high intensity exercise, and it is likely that these benefits will translate into a change from a pattern of a sedentary lifestyle to a physically active lifestyle. Chronic respiratory patients, namely COPD patients, have a low exercise tolerance due to multiple factors, such as dynamic hyperinflation and peripheral muscle dysfunction. In this article, the authors describe a variety of modalities and strategies to overcome exercise limitations and improve the effects of exercise training.


The disposition of pyrimethamine in the rat isolated perfused liver: the effect of suramin.
The pharmacokinetics of pyrimethamine (0.5 mg) were determined in the rat isolated perfused liver in the presence of suramin (17.75 mg). The clearance, half life, area under the curve, and volume of distribution of pyrimethamine were unaffected by the concurrent administration of suramin, as was the hepatic sub-cellular disposition of the drug. This report is of relevance to the future concurrent administration of suramin and pyrimethamine in West Africa.


A Philophthalmid Eyefluke from a Human in Japan.
Philophthalmid eyeflukes are cosmopolitan parasites of birds and occasionally of mammals, including humans. A gravid adult of Philophthalmus sp. was found from the bulbar conjunctiva of a 64-yr-old woman in Japan, who was diagnosed with acute conjunctivitis. The parasite was morphologically most similar to Philophthalmus hegeneri, but distinctive in lacking an esophagus and in having clearly lobed testes. The DNA sequence analysis of genes for nuclear 28S ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 supported the identification at generic level. The morphological and molecular analyses strongly suggest that the eyefluke from a human in Japan should be treated as an undescribed species of Philophthalmus. The occurrence of human philophthalmosis is very rare. As far as we know, a total of 11 human cases have been reported worldwide to date.


The NH2-terminal 14-16 amino acids of mitochondrial and bacterial thiolases can direct mature ornithine carbamoyltransferase into mitochondria.
Unlike most mitochondrial matrix proteins, the mitochondrial 3-oxoacyl-CoA thiolase [EC 2.3.1.16] is synthesized with no cleavable presequence and possesses information for mitochondrial targeting and import in the mature protein. This mitochondrial thiolase is homologous with the mature portion of peroxisomal 3-oxoacyl-CoA thiolase and acetoacetyl-CoA thiolase [EC 2.3.1.9] of Zoogloea ramigera along the entire sequence. A hybrid gene encoding the NH2-terminal 16 residues (MALLRGVFIVAAKRTP) of the mitochondrial thiolase fused to the mature portion of rat ornithine carbamoyltransferase [EC 2.1.3.3] (lacking its own presequence) was transfected into COS cells, and subcellular localization of the fusion protein was analyzed. Cell fractionation and immunocytochemical analyses showed that the fusion protein was localized in the mitochondria. These results indicate that the NH2-terminal 16 residues of the mitochondrial thiolase function as a noncleavable signal for mitochondrial targeting and import of this enzyme protein. The fusion protein containing the NH2-terminal 14 residues (MSTPSIVIASARTA) of the bacterial thiolase was also localized in the mitochondria. On the other hand, the fusion protein containing the corresponding portion (MQASASDVVVVHGQRTP) of the peroxisomal thiolase appeared not to be localized to the mitochondria. These results show that the import signal of mitochondrial 3-oxoacyl-CoA thiolase originated from the NH2-terminal portion of the ancestral thiolase. The ancestral enzyme might have already possessed a mitochondrial import activity when mitochondria appeared first, or that it might have acquired the import activity during evolution by accumulation of point mutations in the NH2-terminal portion of the enzyme.


[Portal hypertension and angiogenesis].
The pathophysiological background of the haemodynamic changes in chronic portal hypertension is still only partly understood. An important factor is the so-called "forward theory", explaining the systemic and especially splanchnic vasodilation observed. Nitric oxide (NO) is an important mediator of this vasodilatory state. Structural as well as vascular changes seem to be causative factors in this vasodilation. These alterations can be studied by a newly-developed in vivo angiogenesis assay. Rats with portal hypertension show increased angiogenesis and NO appears to be a mediator of this finding. The interaction(s) of NO with other angiogenic molecules is now being explored. A better understanding of these structural vascular changes may help to develop new therapeutic strategies in the future.


Acute Myelogeneous Leukemia (M0/M1) with novel chromosomal abnormality of t(14;17) (q32; q11.2).
Acute Myelogeneous Leukemia (AML) is a heterogeneous disease with respect to morphology, immunophenotype, and genetic rearrangements. Multiple recurrent chromosomal aberrations have been identified by conventional cytogenetic analysis. In this study, we report a case whose clinical features were suggestive of AML-M1 subtype with t(14;17) (q32; q11.2) karyotype involving rearrangement of chromosomal segments 17q11.2 and 14q32. This is the first report of novel chromosomal translocation in this subset of AML and has not yet been reported elsewhere. This rearrangement may include certain cancer associated oncogene(s) or genes involved in the differentiation like retionic acid receptor alpha (RARA), which may confer differentiation blockage and/or proliferation advantage.


Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder.
Some evidence suggests an association between genetic variants within the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), CREB binding protein (CREBBP) and cAMP response element-modulator (CREM) and several psychiatric disorders. The present study investigated whether some single nucleotide polymorphisms (SNPs) within these genes could be associated with major depressive disorder (MDD) and bipolar disorder (BD) and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. The sample comprised 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls. Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively, were recorded. All p-values were 2-tailed, and statistical significance was conservatively set at the 0.006 level in order to reduce the likelihood of false positive results. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that the 14 SNP under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.


[Effectiveness of cochlear implantation in children with auditory neuropathy and cochlear nerve aplasia].
The aim of this study is to assess of cochlear implantation in children with auditory neuropathy and cochlear nerve aplasia by using Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR). Twenty one children with cochlear implants participated in this study. They all received cochlear implant surgery at our hospital from January 2004 to October 2010. All children had hearing aid trial and hearing and speech rehabilitation before surgery at least three months.Nine children (7 male, 2 female) were diagnosed with auditory neuropathy, twelve (7 male, 5 female) with cochlear nerve aplasia. Twenty children (10 male, 10 female) with sensorineural hearing loss served as a control group. All the children received cochlear implant for more than six months. Forty two children with normal hearing served as another control group which were divided into three subgroups according to their age.Group A included 18 children aged under two yrs, group B consisted of 16 children aged from two to four yrs and group C comprised eight children aged above four yrs. CAP and SIR were used to evaluate among all the children and the scores were compared. The CAP scores of children with auditory neuropathy, cochlear nerve aplasia, sensorial neural hearing loss and the three subgroups children with normal hearing were 4.44 ± 1.50, 4.83 ± 1.69, 4.55 ± 1.66, 5.22 ± 1.11, 6.75 ± 0.45 and 7.00 ± 0.00 respectively, and SIR scores were 2.66 ± 1.11, 2.33 ± 1.15, 2.40 ± 0.75, 2.56 ± 1.04, 4.12 ± 0.81 and 5.00 ± 0.00 respectively. There were significant differences among the six groups for CAP scores(χ(2) = 35.481, P < 0.001) and SIR scores(χ(2) = 40.549, P < 0.001).No significant differences for CAP and SIR scores were observed between children with auditory neuropathy/cochlear nerve aplasia and sensorial neural hearing loss as well as group A (P > 0.05 for each), and there were significant differences were shown between children with auditory neuropathy/cochlear nerve aplasia and group B as well as group C (P < 0.01 for each aplasia). The auditory and speech capabilities of children with auditory neuropathy and cochlear nerve deficiency can can get benefits from cochlear implants as children with sensorineural hearing loss, however not achieve the level of those with normal hearing after cochlear implantation. The long term effects still need follow-up and evaluation.


The generation of monoclonal anti-idiotype antibodies to human B cell-derived leukemias and lymphomas.
We developed murine anti-idiotype monoclonal antibodies for each of four patients with B cell-derived leukemias and lymphomas. Idiotypic immunoglobulin was isolated from mouse X human tumor-cell hybridomas or from patients' serum and was used to immunize mice for the development of murine anti-idiotype monoclonal antibodies. Each patient's anti-idiotype antibodies demonstrated reactivity restricted to the immunizing immunoglobulin, thereby limiting their therapeutic utility to a single individual. In addition, we isolated isotype switch variants of hybridomas producing monoclonal anti-idiotypic antibody. The restricted specificity of these antibodies was found to be of value for the analysis of the extent of malignant B cell infiltration in a variety of tissues from several patients. Large populations of idiotype-bearing cells were detectable in biopsy specimens from patients K.T. and L.H. In contrast, although bone marrow specimens from patient G.D. were apparently devoid of morphologically abnormal cells, a small, highly fluorescent population of cells was demonstrable underscoring the potential utility of these antibodies for posttreatment evaluation as well as for therapy. In a fourth patient, H.M., anti-idiotype antibodies developed against the circulating macroglobulin isolated from his plasma failed to react with either his circulating or bone marrow hairy cell leukemia cells. However, examination of an enlarged inguinal lymph node revealed the presence of a large number of idiotype-bearing cells. Thus, the presence of two distinct malignant B cell clones were discovered in this individual through the use of anti-idiotype monoclonal antibodies. Anti-idiotype antibodies, therefore, represent a highly specific tool for the evaluation and potential therapy of B cell malignancies in individual patients.


[Changes in the osmotic resistance of the erythrocytes in thermal trauma and the role of free-radical oxidation].
Reduced erythrocyte osmotic resistance against the background of elevated blood level of TBA-reactive products was recorded in experimental thermic injury (of IIIa-IIIb degree, involving 15-20 per cent of the body surface). Under the influence of alpha-tocopherol, parallel with the restriction of free-radical oxidation (FRO) activity, there was a rise in erythrocyte membrane osmotic resistance. FRO participation in the mechanisms of reduced erythrocyte osmotic resistance in thermic injury is discussed.


[Learning process of nursing: planning and insert into matrizes curriculum].
The objective of this study was to analyze the approach used to teach the nursing process based on the class plans of courses that evidence the concept and method bases of the nursing process in superior education institutions in a state capital of Northeast Brazil. Results showed that the courses are mostly theoretical, with amendments and concept bases emphasizing the theoretical-philosophical support of the nursing process, as well as on the study of the phases comprising it. Furthermore, it was shown there was an expression and prevalence of cognitive and psychomotor objectives and the use of traditional methodology.


Reduced Radial Displacement of the Gastrocnemius Medialis Muscle After Electrically Elicited Fatigue.
Assessments of skeletal-muscle functional capacity often necessitate maximal contractile effort, which exacerbates muscle fatigue or injury. Tensiomyography (TMG) has been investigated as a means to assess muscle contractile function after fatigue; however, observations have not been contextualized by concurrent physiological measures. To measure peripheral-fatigue-induced alterations in mechanical and contractile properties of the plantar-flexor muscles through noninvasive TMG concurrently with maximal voluntary contraction (MVC) and passive muscle tension (PMT) to validate TMG as a gauge of peripheral fatigue. Pre- and posttest intervention with control. University laboratory. 21 healthy male volunteers. Subjects' plantar flexors were tested for TMG parameters, along with MVC and PMT, before and after either a 5-min rest period (control) or a 5-min electrical-stimulation intervention (fatigue). Temporal (contraction velocity) and spatial (radial displacement) contractile parameters of the gastrocnemius medialis were recorded through TMG. MVC was measured as an indicator of muscle fatigue, and PMT was measured to assess muscle stiffness. Radial displacement demonstrated a fatigue-associated reduction (3.3 ± 1.2 vs 4.0 ± 1.4 mm, P = .031), while contraction velocity remained unaltered. In addition, MVC significantly declined by 122.6 ± 104 N (P < .001) after stimulation (fatigue). PMT was significantly increased after fatigue (139.8 ± 54.3 vs 111.3 ± 44.6 N, P = .007). TMG successfully detected fatigue, evident from reduced MVC, by displaying impaired muscle displacement accompanied by elevated PMT. TMG could be useful in establishing skeletal-muscle fatigue status without exacerbating the functional decrement of the muscle.


Muscle involvement in rheumatoid arthritis: clinicopathological study of 21 symptomatic cases.
The aim of the current study was to analyze the frequency and characteristics of symptomatic myopathies occurring in rheumatoid arthritis (RA) patients, to correlate these findings with clinical data, and to evaluate their therapeutic implications. All RA patients from a cohort of 350 RA patients from a single institution who developed muscular symptomatology during an 8-year period were included in the study (n = 21). Clinical and laboratory data and electromyographic results were recorded in all cases, and an open muscle biopsy was performed. Weakness and muscle atrophy were the most common symptoms. Serum creatine kinase was increased in 8 cases (38%). Histopathologic study showed type 2 atrophy in 12 cases. In 13 cases, a treatable disease was diagnosed: dermatomyositis (n = 2), d-penicillamine-related dermatomyositis (n = 2), polymyositis (n = 1), muscular mononuclear cell infiltration (n = 3), polyarteritis nodosa (n = 1), glucocorticoid myopathy (n = 3), and toxic chloroquine myopathy (n = 1). In all but 1 patient, muscular clinical response to new therapy and/or drug withdrawal was satisfactory. Although symptomatic muscular involvement in RA is low (6% in the current series), we have found that nearly two thirds of cases were caused by potentially treatable conditions, mainly myositis or toxic myopathies.


[What to expect from dialysis in the future?].
The number of people with end stage kidney failure is increasing worldwide, mainly due to aging of the population. Hence the need for renal replacement therapy is continually expanding. Kidney transplantation, haemodialysis and peritoneal dialysis are currently the gold standard of renal replacement therapy. These three techniques have all their specific advantages and shortcomings. Facing the high complication rate of actual techniques, an increasingly migrant population and the growing desire to respect the environment, alternatives are needed. New techniques that might improve some of these points are in development and will be reviewed in this article.


Developing a sociological framework for dually diagnosed women.
This exploratory study was conducted with the purpose of enumerating both particular social stressors (e.g., the presence of trauma) and the incidence of a comorbid diagnosis (i.e., personality disorder[s] and substance abuse) on a sample of women in a residential therapeutic community. The women in the study were assessed within the first 3 weeks following admission into drug treatment, and then again 6 months after leaving the program. The initial assessment generally took 2 hours and consisted of the Structured Clinical Inventory for DSM-III-R-Patient edition (SCID-II), Addiction Severity Index (ASI), and the Millon Clinical Multiaxial Inventory-II (MCMI-II). Clinically significant scores on the MCMI-II antisocial and borderline personality scales were noted in this study. This study found women with histories of delinquent and/or criminal behavior before drug use were more likely to have used more types of drugs and have used multiple drugs together. These women also tended to have had a history of being abused, either emotionally, physically, or sexually. This group was also less successful on all outcome measures during 6-month follow-up. Moreover, the lifetime incidence of emotional, physical, and sexual abuse reported for this group at the baseline assessment was high--57.1% emotional abuse, 48.9% physical abuse, and 39.7% sexual abuse. These results are consistent with the research literature that indicates abuse plays a central role in the development and chronic effect of personality disorders and, in particular, posttraumatic stress disorder.


Acute suppurative salpingitis with concomitant intrauterine pregnancy.
A 20-year-old woman presented to the emergency department with a history of lower abdominal pain and recent loss of consciousness. She was admitted with a primary diagnosis of abdominal pain; ectopic pregnancy was ruled out. The culture of the endocervix was positive for Neisseria gonorrhoeae. Surgical exploration of the pelvis was performed, and histological analysis of the specimen showed an acute suppurative salpingitis and an intrauterine pregnancy. The patient was placed on intravenous antibiotics. Postoperative course was unremarkable, and the patient was discharged on oral antibiotics. Although a rare entity acute suppurative salpingitis with concomitant intrauterine pregnancy are not mutually exclusive. Ectopic pregnancy should be the presumptive diagnosis when clinical presentation is consistent with pelvic inflammatory disease and pregnancy especially in the first trimester. Patients who are pregnant and exhibit clinical signs and symptoms that are consistent with salpingitis should be admitted for aggressive management of their high-risk pregnancy. Fetal wastage seems to be significant in spite of aggressive management. Endocervical culture for N gonorrhoeae should be obtained from all pregnant patients with follow-up treatment pending culture results. The following is a case presentation along with a review of the existing cases in the English literature and discussion of the possible pathogenesis and clinical outcome of this entity.


Synthesis and biological evaluation of new dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, substituted with various saturated and unsaturated side chains via palladium catalyzed cross-coupling reactions.
The syntheses of a series of dipyrrolo[3,4-a:3,4-c]carbazole-1,3,4,6-tetraones, substituted in 10-position with saturated and unsaturated side chains, via palladium catalyzed cross-coupling reactions, are described. These compounds can be considered as granulatimide bis-imide analogues. Their inhibitory activity toward Chk1 kinase and their antiproliferative activities in vitro in four tumor cell lines are reported.


Difficult Patients in the Emergency Department: Personality Disorders and Beyond.
Physician-patient encounters in clinical settings, especially in the emergency department, can be of varying degrees of difficulty. Medically complicated, challenging cases can be paradoxically rewarding, whereas psychologically driven difficulty is frustrating and counterproductive for patient care. This article presents 3 different complementary perspectives on difficult patients: clinical presentations, manifestations of personality traits and disorders in clinical settings, and how physician feelings may affect care. Management strategies are discussed.


Yeast Infections in Solid Organ Transplantation.
Invasive candidiasis (IC) remains the most common invasive fungal infection following solid-organ transplant (SOT), but risk factors are evolving. Current challenges include infection due to drug resistant non-albicans and emerging novel species such as Candida auris. Preventive antifungal use in SOT needs to be re-examined in light of these current challenges. Cryptococcosis is the second most common IFI following SOT. Cryptococcus gattii is an emerging pathogen that can have reduced in-vitro susceptibility to antifungal agents. Cryptococcus associated IRIS in SOT is a clinical entity that warrants heightened awareness for timely recognition and management.


A population genetic study on the Ag polymorphism in South African Indians and Negroids.
Two population samples from South Africa, i.e. 555 Bantu-speaking Negroids and 75 Indians, were tested for selected immunogenetic specificities comprising the Ag polymorphism. Within the Negroid sample a new Ag phenotype (i.e. the 49th) was discovered. Interpopulational comparisons involving the present two, as well as three previously studied samples, reveal characteristic differences in regard to the frequency distribution of Ag phenotypes, to the Ag allele frequencies and to the occurrence of Ag haplotypes. These results are discussed. All the data could be interpreted satisfactorily in terms of the genetic model regarding the Ag system as postulated by Bütler and his co-workers.


Gender differences in the correlates of self-referent word use: authority, entitlement, and depressive symptoms.
Past research shows that self-focused attention is robustly positively related to depression, and women are more likely than men to self-focus in response to depressed mood (e.g., R. Ingram, 1990; S. Nolen-Hoeksema, 1987). The goal of the current study was to further delineate gender differences in the correlates of self-focus as measured through the frequency of spontaneous use of self-referencing words. The frequency of such word use during a life history interview was correlated with self-reports, observations by clinically trained interviewers, and personality judgments by acquaintances. Results indicated that the relationship between self-reference and observations of depressive symptoms was stronger for women than men, and the relationship between self-reference and narcissistic authority and entitlement was stronger for men than for women. Acquaintance ratings supported these correlates. These findings illuminate the importance of using multiple measures and paying attention to gender differences in research on self-focus.


Dysfunction of SERCA pumps as novel mechanism of methylglyoxal cytotoxicity.
A novel pathway of methylglyoxal (MGX)-induced apoptosis via sarcoplasmic reticulum Ca2+-ATPase (SERCA) is presented. Interaction of SERCA1 with MGX was investigated by molecular docking and experimentally in a cell-free system. MGX concentration- and time-dependently decreased SERCA1 activity. A significant increase of sarcoplasmic reticulum (SR) carbonylation was found in the concentration range of 1-10 mM caused by MGX and a decrease of thiol groups at the concentrations of 5 and 40 mM. Affinities of SERCA1 to ATP and Ca2+ were not influenced by MGX, however decreases of Vmax related to both binding sites were observed. Molecular docking indicated binding of MGX at the cytosolic region of SERCA1, inducing conformational changes in the cytosolic-transmembrane interface. This interaction resulted in conformational changes in the cytosolic region (FITC fluorescence decrease) as well as in the transmembrane region of SERCA1 (Trp fluorescence decrease) without direct binding to the cytosolic ATP or transmembrane Ca2+ binding sites. Regarding the MGX inhibitory effect in a cell-free system and similarities of SERCA1 to its other isoforms, proapoptotic properties of MGX may be expected in cellular systems. At cellular level, MGX induced a decrease of SERCA2b expression in the pancreatic INS-1E β-cell line. This was accompanied by cell viability decrease, increase in apoptosis, impaired insulin secretion and elevation of basal intracellular Ca2+ levels. Decreased expression of SERCA2b may contribute to induction of apoptosis of pancreatic β-cells.


Activated sludge versus aerated lagoon treatment of kraft mill effluents containing beta-sitosterol and stigmasterol.
In the present study the performance of an activated sludge system (AS) and an aerated lagoon (AL) are compared for the treatment of kraft cellulose effluents. Both reactors were operated at organic loading rates (OLR) up to 9 g COD/L. d. The activated sludge system presented better performance at high OLR than the aerated lagoon with removal percentages of 57-67% and 95% of COD and BOD(5), respectively. The removal percentages of specific compounds were always slightly higher in the case of the AS than in the AL with exception of the total phenolic compounds which concentration increased in the former. Furthermore the analyzed fractions from the effluents indicated that in the AS the compounds were fully removed while in the case of the aerated lagoon were transformed into compound with low molecular weight P2 (5 kD < MW < 10 kD). In the case of the AS system the increase of the total phenolic compounds concentrations was corroborated with the increase of the fractions P2, P3 and P4. The studied phytosterol were removed from the effluent at concentrations up to 2 mg/L in percentages close to 100% mainly by adsorption in the case of the AL and by a combining adsorption and mainly degradation in the AS. The BOD(5) concentration in the effluent of both systems fulfilled the requirements of the Chilean regulations for effluent discharge indicating the feasibility of aerobic treatment of this kind of effluents.


The implications of resistance to antiviral agents for herpesvirus drug targets and drug therapy.
Antiviral drug resistance is an area of increasing clinical importance in treatment of a number of viruses including herpes simplex virus (HSV) and human cytomegalovirus (CMV). Work with these herpesviruses illustrates the value of studies of drug resistance. Novel aspects of drug mechanisms, such as a CMV gene product that contributes to ganciclovir phosphorylation, can be identified via drug resistance mutations. Drug targets such as the HSV DNA polymerase that are involved in drug recognition can be dissected by sequencing of drug-resistance mutations, which can point to alternate therapeutic strategies. Analysis of virus mutants in animal models and in patient populations can help assess the value of viral proteins such as the HSV thymidine kinase and ribonucleotide reductase as drug targets and the pathogenic potential of drug resistant mutants. Such studies reveal a broad spectrum of alterations conferring resistance and emphasize the importance of heterogeneous populations of virus in resistance and pathogenesis and the need to develop alternate therapies.


First year medical students' attitudes and knowledge about AIDS.
Medical students attitudes and resulting behaviors about treating HIV-infected patients are critical and will become increasingly so in the years ahead. An anonymous self-administered questionnaire of 135 first year medical students at Boston University School of Medicine conducted in May 1988 queried students' knowledge of HIV transmission; concerns about contracting HIV; ethical and legal responsibilities; attitudes about testing for HIV and treatment of HIV-infected patients; the effect the epidemic poses for their medical careers; changes in personal sexual and drug use practices. Results indicate that students' careers are being affected because they are worried about contracting HIV, that the epidemic will affect their final choice of specialty, and that they believe they should be allowed to refuse to treat AIDS patients during their medical school training. The findings raise serious questions concerning why medical students hold these beliefs and suggest that students' willingness to care for AIDS patients may be a function of their level of knowledge and understanding of HIV infection and the disease AIDS. The results have implications for curriculum reform to address the AIDS crisis.


Imagined positive emotions and inhibitory control: the differentiated effect of pride versus happiness.
Inhibitory control is a cognitive mechanism that contributes to successful self-control (i.e., adherence to a long-term goal in the face of an interfering short-term goal). This research explored the effect of imagined positive emotional events on inhibition. The authors proposed that the influence of imagined emotions on inhibition depends on whether the considered emotion corresponds to the attainment of a long-term goal (i.e., pride) or a short-term goal (i.e., happiness). The authors predicted that in an antisaccade task that requires inhibition of a distractor, imagining a happiness-eliciting event is likely to harm inhibitory processes compared with imagining a pride-eliciting event, because the former but not the latter primes interfering short-term goals. The results showed that imagining a happiness-eliciting event decreased inhibition relative to imagining a pride-eliciting event. The results suggest a possible mechanism underlying the role of imagined positive emotions in pursuit of goals that require self-control.


An organoruthenium complex overcomes ABCG2-mediated multidrug resistance via multiple mechanisms.
Multidrug resistance mediated by the overexpression of ABC transporters is a major challenge in cancer chemotherapy. Here, we report the synthesis of an organoruthenium complex, RuF, that was designed to surmount multidrug resistance by combining ABCG2 inhibition and cancer cell cytotoxicity, yielding synergistic efficacy.


(-)-3-Isothujone, a small nonnitrogenous molecule with antinociceptive activity in mice.
(-)-3-Isothujone and (+)-3-thujone were examined for antinociceptive activity using the hot-plate and Nilsen tests. In the hot plate test (-)-3-isothujone (ED50 = 6.5 mg/kg) was found to be codeine-like and equipotent with (-)-delta9-tetrahydrocannabinol while the racemic material was essentially half as potent as the levoratatory isomer. (+)-3-Thujone was inactive in both antinociceptive tests as were several structural analogues of the 3-thujones. As with the THC's less antinociceptive activity was observed in the Nilsen test than in the hot-plate assay. Acute toxicities for the 3-thujones were determined and vastly improved synthetic procedures have been developed for two long-known but difficulty accessible 3-thujanols.


[Screening for MRSA: unnecessary, expensive and potentially harmful].
Screening for MRSA and isolation of colonized patients have been largely advocated as a measure to reduce MRSA transmission and infection. However, the evidence for the efficacy of this strategy is poor, while costs and potential side effects are considerable. Therefore, screening should not longer be considered as an appropriate measure to control spread of MRSA.


Accumulation of retinol in the liver after prolonged hyporetinolemia in the vitamin A-sufficient rat.
We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VA-sufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6-treated rats compared with controls from 7.5 h throughout 7 days of infusion (P < 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days (P < 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41% lower in rhIL-6-treated rats compared with controls (P < 0.05). These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. A plausible consequence of the effect of rhIL-6-induced hyporetinolemia is that by 7 days tissues that are dependent on plasma retinol may become deprived of VA. These results have important implications in understanding the mechanism by which measles infection induces hyporetinolemia and VA deficiency of extrahepatic tissues.


Effects of tolmetin sodium dihydrate on normal and postsurgical peritoneal cell function.
Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement. NSAIDs are known to inhibit the metabolism of arachidonic acid to prostaglandins, which in turn modulate a variety of macrophage functions. Studies presented here examine the effects of tolmetin administration on peritoneal resident and post-surgical leukocyte functions, such as phagocytosis, the release of superoxide anion and tumoricidal activity. Rats, either non-surgical or following peritoneal surgery, were injected i.p. with tolmetin. At various times after treatment, the rats were sacrificed and peritoneal cells collected by lavage. The phagocytic capability of peritoneal leukocytes was transiently decreased 5-7 days after the administration of tolmetin to normal animals. However, administration of tolmetin during surgery extended the length of time that phagocytic capability was enhanced. In non-surgical controls, there was an elevation in superoxide anion release and tumoricidal activity 24 h after tolmetin administration. Superoxide anion release was suppressed at days 5 and 7 after treatment, but returned to control levels by day 14. Intraoperative administration of tolmetin significantly elevated superoxide anion release at days 3 and 5, phagocytosis at days 7 and 14 and tumoricidal activity at day 3. These studies suggest that compounds which suppress prostaglandin synthesis can modulate the function of resident and post-surgical peritoneal cells.


Neonatal exposure of female ferrets to testosterone alters sociosexual preferences in adulthood.
Sociosexual preferences in adult female ferrets, as measured in a choice arena, were altered by neonatal exposure to exogenous testosterone. Adult female ferrets showed a preference for males which did not depend on the presence of gonadal steroids, because gonadectomized and gonadectomized estrogen-treated females showed identical preferences for males. Adult castrated males showed no preference for females unless these males were treated with testosterone. A similar no-preference pattern was found in adult females that had received testosterone neonatally. Females exposed neonatally to dihydrotestosterone or estradiol exhibited the normal females' male-oriented preference. These results indicate that testosterone secreted by the testes in the developing male may interrupt the phenotypic female development pattern and hence prevent the emergence of a homosexual preference in adulthood in the male ferret.


Automation to improve efficiency of field expedient injury prediction screening.
Musculoskeletal injuries are a primary source of disability in the U.S. Military. Physical training and sports-related activities account for up to 90% of all injuries, and 80% of these injuries are considered overuse in nature. As a result, there is a need to develop an evidence-based musculoskeletal screen that can assist with injury prevention. The purpose of this study was to assess the capability of an automated system to improve the efficiency of field expedient tests that may help predict injury risk and provide corrective strategies for deficits identified. The field expedient tests include survey questions and measures of movement quality, balance, trunk stability, power, mobility, and foot structure and mobility. Data entry for these tests was automated using handheld computers, barcode scanning, and netbook computers. An automated algorithm for injury risk stratification and mitigation techniques was run on a server computer. Without automation support, subjects were assessed in 84.5 ± 9.1 minutes per subject compared with 66.8 ± 6.1 minutes per subject with automation and 47.1 ± 5.2 minutes per subject with automation and process improvement measures (p < 0.001). The average time to manually enter the data was 22.2 ± 7.4 minutes per subject. An additional 11.5 ± 2.5 minutes per subject was required to manually assign an intervention strategy. Automation of this injury prevention screening protocol using handheld devices and netbook computers allowed for real-time data entry and enhanced the efficiency of injury screening, risk stratification, and prescription of a risk mitigation strategy.


[Comparative study on image quality of third-generation dual-source CT pulmonary angiography combined with advanced modeled iterative reconstruction].
Objective: To quantitatively evaluate the quality of advanced modeled iterative reconstruction (ADMIRE) combined with 70 kVp and linear blending images in low dose dual energy (70 kVp/sn150 kVp) pulmonary angiography. Methods: A total of 74 cases with normal BMI underwent dual-source CT dual-energy pulmonary angiography with small amount of contrast medium (30 ml) from 2015 to 2017 from the First Affiliated Hospital of Zhengzhou University were randomly assigned to protocol Ⅰ(100 kVp/sn140 kVp) or protocol Ⅱ(70 kVp/sn150 kVp). 70 kVp+ ADMIRE (group 1), linear blending+ ADMIRE (group 2), 100 kVp+ SAFIRE (group 3) images were obtained. CT value and noise standard deviation (SD) of pulmonary arteries were measured in pulmonary trunk artery, left pulmonary artery and left superior pulmonary artery, then SNR and CNR were calculated. Radiation dose parameters (CTDIvol, DLP) were recorded. Results: CT values of pulmonary artery of group 1 were significantly higher than those in group 2 and 3 (both P<0.05). In group 2, SD value of pulmonary artery was lower than that of group 1 and 3(both P<0.05). SD value of pulmonary trunk and left pulmonary artery in group 1 was higher than that in group 3 (P<0.05), SD value of left superior pulmonary artery had no significant difference between group 1 and group 3 (P>0.05). SNR and CNR value in group 1 and group 2 had no statistical difference, but they were both higher than that in group 3 (both P<0.05). The effective dose of protocolⅠwas 46% lower than protocol Ⅱ. Conclusion: ADMIRE combined with 70 kVp and linear blending images are better than SAFIRE combined with 100 kVp images, and radiation dose is reduced.70 kVp/sn150 kVp with small amount of contrast medium (30 ml) is a feasible dual energy pulmonary artery scanning protocol.


[Use of external local low pressure to improve blood flow in children with infantile cerebral palsy].
Cardiovascular system was studied in 16 children with spastic quadriplegic infantile cerebral palsy (ICP) aged 3-10 years. It was found at rheography that hemodynamics of ICP children differs from normal, in particular arterial tonicity and peripheral resistance were increased. The children were exposed to external local low pressure. This treatment reduced vascular tonicity, peripheral resistance and increased arterial elasticity. The effect is most noticeable on rheoencephalograms.


Comparison of regional fat mass measurement by whole body DXA scans and anthropometric measures to predict insulin resistance in women with polycystic ovary syndrome and controls.
Polycystic ovary syndrome (PCOS) is characterized by obesity and insulin resistance. Measures of regional obesity may be used to predict insulin resistance. In the present study we compared fat distribution in patients with PCOS vs. controls and established the best measure of fat mass to predict insulin resistance in patients with PCOS. The study was cross-sectional in an academic tertiary-care medical center with 167 premenopausal women with PCOS and 110 controls matched for ethnicity, BMI and age. Total and regional fat and lean body mass were assessed by whole body dual-energy X-ray absorptiometry (DXA) scans. Anthropometric measures (BMI, waist) and fasting metabolic analyses [insulin, glucose, lipids, Homeostasis model assessment (HOMA-IR), lipid accumulation product, and visceral adiposity index] were determined. Trial registration numbers: NCT00451568, NCT00145340. Women with PCOS had higher central fat mass (waist, waist-hip ratio, and upper/lower fat ratio) compared with controls. In bivariate associations, the strongest associations were found between HOMA-IR and the fat mass measures trunk fat (r = 0.59), waist (r = 0.57) and BMI (r = 0.56), all p < 0.001. During multiple regression analyses, trunk fat, waist and BMI were the best predictors of HOMA-IR (R2 = 0.48, 0.49, and 0.47, respectively). Women with PCOS were characterized by central obesity. Trunk fat, waist and BMI were the best predictors of HOMA-IR in PCOS, but only limited information regarding insulin resistance was gained by whole body DXA scan.


Light modulation of histidine-kinase activity in bacterial phytochromes monitored by size exclusion chromatography, crosslinking, and limited proteolysis.
Phytochromes are photoreceptors that have been found in plants, bacteria, and fungi. Most bacterial and fungal phytochromes are histidine kinases and, for several bacterial phytochromes, light regulation of kinase activity has been demonstrated. Typical histidine kinases are homodimeric proteins in which one subunit phosphorylates the substrate histidine residue of the other subunit; dimerization is an intrinsic property of the histidine kinase itself. Truncated phytochromes which lack the histidine kinase can also form dimers, but the interaction between subunits is modulated by light. This light-dependent dimerization can give a clue to the intramolecular signal transduction of phytochromes which modulates the histidine kinase activity. Size exclusion chromatography, limited proteolysis, and protein crosslinking can be used to study light-induced conformational changes and the interaction of subunits within the homodimer.


Temporary regression during language acquisition: a linguistic analysis of a 2 1/2-year-old child with epileptic aphasia.
A 2 1/2-year-old child suffered a brief and temporary regression of speech, with complete recovery, on two separate occasions. During the second episode, clinical evaluation and electroencephalographic data led to the diagnosis of epileptic aphasia. The child's conversations at home were tape-recorded by the mother during the acute phase of the disorder and the recovery period, and transcripts of the conversations were analysed by means of a linguistic profile. These analyses confirmed the clinical improvement in the child's language abilities, which occurred within a few days. This case illustrates the remarkably specialised and localised cerebral function which underlies speech production at an early age. It indicates that this function can be interfered with selectively and temporarily, without any significant effect on general behaviour.


Advances in Monte Carlo Simulation for Light Propagation in Tissue.
Monte Carlo (MC) simulation for light propagation in tissue is the gold standard for studying the light propagation in biological tissue and has been used for years. Interaction of photons with a medium is simulated based on its optical properties. New simulation geometries, tissue-light interaction methods, and recording techniques recently have been designed. Applications, such as whole mouse body simulations for fluorescence imaging, eye modeling for blood vessel imaging, skin modeling for terahertz imaging, and human head modeling for sinus imaging, have emerged. Here, we review the technical advances and recent applications of MC simulation.


Fracture resistance and marginal adaptation of conventionally cemented fiber-reinforced composite three-unit FPDs.
This in vitro study investigated the marginal adaptation and fracture resistance of three-unit fiber-reinforced composite fixed partial dentures (FPD) luted with two different resin-modified glass-ionomers. A total of 48 FPDs were constructed from the glass fiber-reinforced materials FibreKor/Sculpture, Vectris/Targis, or the polyethylene fiber system BelleGlass/Connect (n = 16 for each brand). The reconstructions were conventionally luted on human molars using resin-modified ProTecCEM or Fuji Plus and then exposed to thermocycling and mechanical loading. During thermocycling and mechanical loading, cementation failed in seven of eight FibreKor or BelleGlass FPDs and in one of eight Vectris/Targis FPDs luted with ProTecCEM. All Fuji Plus-cemented FPDs showed no signs of damage or cementation loss. The fracture resistance of the remaining FPDs was as follows: Vectris/Targis-ProTecCem 1,361 +/- 360 N, Vectis/Targis-Fuji Plus 923 +/- 207 N, BelleGlass/Connect 940 +/- 155 N, and FibreKor/Sculpture 524 +/- 202 N. The marginal adaptation of the cement-tooth interface deteriorated by 13% to 21% for all reconstructions after stress application, which was not statistically significant. The crown-cement interface had a significantly greater marginal gap only with the combination of FibreKor and Fuji Plus after stress simulation (change 33%). Conventional cementation of fiber-reinforced FPDs can lead to cementation loss. The marginal adaptation and fracture resistance deteriorated in comparison to adhesively cemented reconstructions.


Adolescent-onset anorexia nervosa: 18-year outcome.
The long-term outcome of anorexia nervosa is insufficiently researched. To study prospectively the long-term outcome and prognostic factors in a representative sample of people with teenage-onset anorexia nervosa. Fifty-one people with anorexia nervosa, recruited by community screening and with a mean age at onset of 14 years were compared with 51 matched comparison individuals at a mean age of 32 years (18 years after disorder onset). All participants had been examined at ages 16 years, 21 years and 24 years. They were interviewed for Axis I psychiatric disorders and overall outcome (Morgan-Russell assessment schedule and the Global Assessment of Functioning). There were no deaths. Twelve per cent (n=6) had a persisting eating disorder, including three with anorexia nervosa. Thirty-nine per cent of the anorexia nervosa group met the criteria for at least one psychiatric disorder. The general outcome was poor in 12%. One in four did not have paid employment owing to psychiatric problems. Poor outcome was predicted by premorbid obsessive-compulsive personality disorder, age at onset of anorexia nervosa and autistic traits. The 18-year outcome of teenage-onset anorexia nervosa is favourable in respect of mortality and persisting eating disorder.


Health care utilization among young adult injection drug users in Harlem, New York.
This cross-sectional study investigated the predictors for and patterns of health care utilization among young adult injection drug users (IDUs). The subjects were 206 IDUs, ages 18-29, who were street-recruited from Harlem, New York. Participants were interviewed about their drug use, health conditions, and use of services such as health care, needle exchange programs (NEPs), and drug treatment in the preceding 6 months. Data were analyzed using logistic regression. Health insurance was associated with use of health care both among NEP users [AOR (adjusted odds ratio) 10.66] and non-NEP users (AOR 2.45). Use of health care was independently associated with drug treatment (AOR 2.58), being gay/bisexual (AOR 3.86), and negatively associated with injecting cocaine (AOR 0.56). Half the participants (49%) had used health care in the previous 6 months; 48% were uninsured. Many participants who did not use health services reported a condition that would have warranted medical care. Health insurance was strongly associated with use of health care, particularly among those who attend NEPs. Young adult IDUs may benefit from increased efforts to help them arrange and maintain health insurance coverage, potentially at NEPs. NEPs may be connecting young IDUs with health insurance to medical care through referrals.


Phase reconstruction from reflectivity in fiber Bragg gratings.
It is shown that a recently proposed phase-retrieval technique for Bragg gratings [Opt. Lett. 22, 93 (1997); J. Lightwave Technol. 15, 1314 (1997)] is not well suited for gratings with imperfections. The reconstructed group delay is in many cases not a more accurate estimate than the simulated group delay of the perfect, designed grating, independently of how small the errors in the grating structure are. The error in the group delay may be especially large near the zeros in the reflection spectrum.


Stable antibody expression at therapeutic levels using the 2A peptide.
Therapeutic monoclonal antibodies (mAbs) are currently being developed for the treatment of cancer and other diseases. Despite clinical success, widespread application of mAb therapies may be limited by manufacturing capabilities. In this paper, we describe a mAb delivery system that allows continuous production of a full-length antibody at high-concentrations in vivo after gene transfer. The mAb is expressed from a single open reading frame by linking the heavy and light chains with a 2A self-processing peptide derived from the foot-and-mouth disease virus. Using this expression system, we generated a recombinant adeno-associated virus vector encoding the VEGFR2-neutralizing mAb DC101 (rAAV8-DC101). A single dose of rAAV8-DC101 resulted in long-term expression of >1,000 microg/ml of DC101 in mice, demonstrating significant anti-tumor efficacy. This report describes the first feasible gene therapy approach for stable delivery of mAbs at therapeutic levels, which may serve as an attractive alternative to direct injection of mAbs.


Dyschezia in dogs with discrete erosive anal disease and histological lesions suggestive of mucocutaneous lupus erythematosus.
Eight dogs suffered chronic defecation problems characterised by severe dyschezia, manifested by signs of fear and vocalisation on defecation. One or more depigmented, discrete erosions, easily bleeding on palpation, were found in the perineal region. Histopathological changes included interface dermatitis, apoptotic keratinocytes, focal hydropic degeneration of basal epidermal cells, focal thickening of the basement membrane zone and dermal lichenoid infiltrations with mononuclear and plasma cells. A diagnosis of cutaneous or discoid lupus erythematosus was made on the basis of these clinical, physical and specific histopathological changes. The dogs were treated systemically with immunomodulating drugs and good results were obtained.


On the effects of substitution, intercalation, non-stoichiometry and block layer concept in TiS2 based thermoelectrics.
TiS2 based layered sulfides have recently received increasing interest from the thermoelectric community. Due to its layered structure, the TiS2 compound with its enormous capacity for chemical substitution and intercalation offers different means to optimize the thermoelectric response through concomitant tuning of carrier concentration and decrease of the lattice thermal conductivity. In this review, we first discuss and summarize the crystal structures and physical/chemical properties of TiS2 based layered sulfides. Then, the approaches that successfully enhanced the thermoelectric performances in the TiS2 ceramic samples densified by Spark Plasma sintering are outlined, which include intercalation, non-stoichiometry, cationic substitution, and the block layer concept.


Pick's disease: selective occurrence of apolipoprotein E-immunoreactive Pick bodies in the limbic system.
We carried out immunohistochemical examination of apolipoprotein E (apoE) in brains from two patients with Pick's disease. In these cases 1 and 2, the APOE genotypes were epsilon 3/4 and epsilon 3/3, respectively. In both cases, numerous argyrophilic globular intraneuronal inclusions, Pick bodies (PBs), were distributed widely throughout the brain, and immunohistochemically were occasionally positive for apoE. Interestingly, such apoE-immunoreactive PBs were virtually restricted to neurons in the limbic system; in the dentate gyrus, the proportion of apoE-immunoreactive PBs relative to the total number of argyrophilic PBs was 5.0% in case 1 and 2.7% in case 2, whereas in the frontal and temporal neocortices it was less than 0.1% in both cases. Diffuse cytoplasmic immunoreactivity for apoE was found in only a few limbic system neurons without PBs in both cases. In conclusion, it is considered that apoE may not be positively involved in the process of PB formation and that the preferential distribution of apoE-immunoreactive PBs in the limbic system may reflect the presence of certain regional factors associated with the synthesis or metabolism of apoE in this particular system.


Highly fluorescent core-shell hybrid nanoparticles templated by a unimolecular star conjugated polymer for a biological tool.
Highly fluorescent core-shell hybrid nanoparticles were readily fabricated from the soft template of a unimolecular star conjugated polymer (HCP-star-PDMAEMA). Since the hyperbranched conjugated polymer (HCP) core was isolated by a silicon dioxide (SiO(2)) shell, HCP@SiO(2) with excellent optical properties was retained in the aqueous solution for potential application in biological imaging.


Etodolac induces apoptosis and inhibits cell adhesion to bone marrow stromal cells in human myeloma cells.
Cyclooxygenase-2 (COX-2) is reported to regulate apoptosis and to be an important cellular target for therapy. We examined whether etodolac, meloxicam, and thalidomide inhibited proliferation and induced apoptosis in myeloma cell lines (RPMI 8226 and MC/CAR cells). Etodolac induced apoptosis more strongly compared with thalidomide or meloxicam. Etodolac induced down-regulation of Bcl-2 protein and mRNA, activation of Caspase-9, -7 and -3, cIAP-1 and Survivin, and loss of mitochondrial membrane potential in a dose-dependent manner. In addition, when myeloma cells were coincubated with 50 microM etodolac on bone marrow stromal cells (BMSCs), myeloma cell adhesion to BMSCs was significantly inhibited compared with thalidomide or meloxicam coincubation, and the adhesion molecules VLA-4, LFA-1 (CD11a), CXCX4, and CD44 were suppressed on myeloma cells treated with etodolac. Moreover, 50-100 microM racemate of etodolac significantly inhibited the proliferation of myeloma cells compared to 100 microM R-etodolac or S-etodolac. Etodolac induced loss of mitochondrial membrane potential and apoptosis via a COX-2-independent pathway, suppressed the expression of adhesion molecules, and inhibited myeloma cell adhesion to BMSCs compared with thalidomide or meloxicam. The activities of etodolac potentially extend to the treatment of patients with myeloma resistant to standard chemotherapy, including thalidomide.


Pharmacokinetics of high-dose oral CCNU in bone marrow transplant patients.
CCNU (lomustine) and other nitrosourea compounds are rapidly metabolized to alkylating moieties, which are active against various malignancies. In humans, CCNU undergoes biotransformation to the geometric isomers of 4'-hydroxyCCNU. The pharmacokinetics of trans-and cis-4'-hydroxyCCNU were determined in five patients with Hodgkin's or non-Hodgkin's lymphoma receiving sequential doses of CCNU (15 mg/kg), etoposide (60 mg/kg) and cyclophosphamide (100 mg/kg) prior to autologous bone marrow transplantation. Plasma concentrations of the isomeric forms of the metabolites were determined by high-performance liquid chromatography. Data were analysed using noncompartmental pharmacokinetic methods. Formation of the trans-isomer predominated over that of the cis-isomer, with an average exposure ratio of 1.4 (range 1.0-2.1). Peak plasma concentrations occurred between 1 and 4.1 h postdosing and averaged 1.56 mg/l for the trans-isomer and 1.10 mg/l for cis isomer. Peak plasma concentrations and systemic exposures varied approximately six- and ninefold, respectively, reflecting significant interindividual variability in alkylating activity after high doses of CCNU. Plasma half-lives of the metabolites were 3.1 h (range 1.1-4.5 h) for the trans-isomer and 3.5 h (range 1.3-6.4 h) for the cis- isomer, and varied linearly with increasing patient body weight. There was no significant difference in plasma half-lives after high-dose CCNU administration observed in this study and those reported previously after the administration of substantially lower doses of CCNU. Despite linearity in the pharmacokinetics of the isomeric forms of 4'-hydroxyCCNU at high doses, large interindividual variability in exposure to the CCNU metabolites was observed. Potential saturation of metabolic pathways to the isomers at these doses may manifest as toxic symptoms since alkylating moieties formed directly from the parent, CCNU, may be associated with greater toxicity than those formed from the isomeric forms of the 4'-hydroxylated metabolite.


Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cell.
Involvement of GTP-binding proteins in angiotensin II-induced mobilization of calcium has been examined in adrenal glomerulosa cells by using pertussis toxin. Pretreatment of glomerulosa cells with pertussis toxin abolishes angiotensin II-induced calcium influx without blocking inositol trisphosphate production. These results suggest a role of the pertussis toxin-sensitive GTP-binding protein in transducing angiotensin II-receptor occupancy into opening of calcium channel.


Development and evaluation of an experimental model of cutaneous columnaris disease in koi Cyprinus carpio.
A reproducible, experimental model of columnaris disease was developed to study the pathogenesis of cutaneous disease associated with Flavobacterium columnare infection in koi (Cyprinus carpio). In experimental infections, lesions were usually restricted to skin and fins; gill necrosis was not a consistent finding. Cytologic and histopathologic examinations provided a presumptive diagnosis of columnaris disease. Specific detection of F. columnare was done using the polymerase chain reaction and DNA in situ hybridization (ISH). Polymerase chain reaction allowed the detection of F. columnare in fresh biological material and in formalin-fixed, paraffin-embedded tissues. The DNA ISH technique allowed the identification and localization of F. columnare in formalin-fixed, paraffin-embedded tissues. Using these molecular techniques, F. columnare was readily detected in skin specimens from infected fish; however, the bacterium was infrequently detected in specimens of liver, kidney, and spleen. These observations suggest that columnaris disease generally presents as a cutaneous disease that is unassociated with systemic infection in koi. Hematologic studies indicated that most infected koi developed microcytic, normochromic, nonregenerative anemia and leukopenia characterized by lymphopenia, mild neutrophilia, and monocytosis. Biochemical changes in diseased fish included significant hyperglycemia, hyponatremia, and hypochloridemia.


Cognitive-behavioural intervention for depression after stroke: five single case studies on effects and feasibility.
The purpose of the study was to investigate whether or not a cognitive-behavioural intervention for depression after stroke has an effect and is feasible. A single-subject quasi experimental design (SSED) was used with an AB design and follow-up. The participants were five first episode stroke patients attending outpatient rehabilitation in a rehabilitation centre in The Netherlands. Mood and quality of life were measured on four occasions over four weeks (baseline phase A). During the eight week intervention phase (B) a visual analogue measure of mood was administered three times a week. Immediately after the intervention, and one and three months later, the baseline measures were repeated. The intervention (phase B) was based on cognitive-behavioural principles: recognising negative thoughts and challenging them, learning principles of relaxation, and planning of pleasurable activities. Following intervention three patients reported they had improved, three patients reported a minor improvement in quality of life, and four patients reported a more positive mood. Three months later three patients reported fewer depressive symptoms. Both patients and therapist were positive about the intervention and three months later, in daily life, all patients still applied the strategies. It was concluded that despite some ambiguous results, it seems that the cognitive-behavioural intervention has an effect on patients' mood. The intervention was rated as feasible by both patients and therapists.


Mouse mutants lacking the type 2 IGF receptor (IGF2R) are rescued from perinatal lethality in Igf2 and Igf1r null backgrounds.
The cation-dependent and cation-independent mannose 6-phosphate receptors (CD- and CI-MPRs) bind the phosphomannosyl recognition marker of lysosomal hydrolases, but in mammals the latter also interacts with insulin-like growth factor II (IGF-II). While IGF signaling is mediated by the type 1 IGF receptor (IGF1R), the type 2 receptor (IGF2R/CI-MPR) serves IGF-II turnover. Mouse mutants inheriting maternally a targeted disruption of the imprinted Igf2r gene, which is normally expressed only from the maternal allele, have increased serum and tissue levels of IGF-II and exhibit overgrowth (135% of normal birthweight) and generalized organomegaly, kinky tail, postaxial polydactyly, heart abnormalities, and edema. These mutants usually die perinatally, but a small minority can survive depending on genetic background and can occasionally reproduce, except for some females characterized by an imperforate vagina and hydrometrocolpos. Consistent with the hypothesis that lethality in the absence of IGF2R-mediated turnover is caused by excess of IGF-II overstimulating IGF1R, Igf2r mutants are completely rescued when they carry a second mutation eliminating either IGF-II or IGF1R. Normal embryonic development of the Igf1r/Igf2r double mutants, which differ from wild-type siblings only in the pattern of postnatal growth, appears to occur by signaling of IGF-II, being in excess, through a genetically identified unknown receptor, since triple mutants lacking IGF1R, IGF2R, and IGF-II are nonviable dwarfs (30% of normal size). In contrast with the Igf2r/Igf2 double mutants, mice lacking IGF2R/CI-MPR and CD-MPR survive in an IGF-II null background at a very low frequency and only for a few postnatal weeks, indicating that the mannose 6-phosphate-mediated lysosomal enzyme trafficking is essential for viability.


A parents' group in the management of anorexia nervosa.
Recent reports have suggested that family therapy is useful in the treatment of anorexia nervosa. There are, however, recognized contraindications to family therapy. As we were seeing patients with anorexia nervosa for whom family therapy was not possible, we predicted that the formation of a group for the parents would provide benefit through education, support and insight. The present study was designed to develop and evaluate such a group. We selected parents of ten anorectic patients for whom family therapy was contraindicated. There were two therapists, the unit social worker and a former patient who had successfully overcome the symptoms of anorexia nervosa. After an 18-month period, the ten couples were sent anonymous questionnaires assessing the group's value. Six indicated positive feelings about the group and felt they had benefited. One couple reported dissatisfaction. Most perceived the group as an important part of the overall treatment.


Enhanced patency of small-diameter, externally supported Dacron iliofemoral grafts seeded with endothelial cells.
Fourteen adult foxhounds underwent bilateral iliofemoral bypasses with externally supported, knitted Dacron grafts measured 4 mm in internal diameter and 10 cm in length. These conduits were preclotted with 10 ml of blood mixed with 0.5 ml of culture medium. Autologous endothelial cells, enzymatically derived from external jugular veins, were added to blood and medium used to preclot one graft in each dog. The other, unseeded graft served as a control. Grafts were anastomosed, end to end, to the iliac and femoral arteries. All dogs received dipyridamole, 50 mg twice a day for 4 days preoperatively, and aspirin, 5 grains four times a day for 1 day preoperatively. Both drugs were continued 14 days after operation. Grafts were removed from three dogs at 2 and 4 weeks and from four dogs at 8 and 16 weeks. All grafts were patent at 2 weeks during drug administration. Cumulative patency rates beyond 2 weeks were 73% in 11 seeded grafts and 27% in 11 control grafts, a statistically significant difference (P = 0.03). Seeded grafts were completely surfaced with a monolayer of endothelium between 2 and 4 weeks. Small-graft patency appeared related to evolution of endothelial surfaces, the development of which was clearly facilitated by seeding with autologous endothelium.


The federal response to the AIDS epidemic.
The response of the U.S. government to the AIDS epidemic is reviewed within the context of health policy making in the U.S.A. in general and the reduced role of the federal government in domestic social programs in particular. This review involves multiple levels of government, the relationship of government to the private sector, the diffusion of authority within a federal system, the long delays in policy implementation because of the absence of mechanisms to deal with emergency situations, the tendency to fund the response to AIDS from reallocation of appropriated funds, thereby creating financial distress for existing programs. The federal response to AIDS is considered uncoordinated, insufficient and inadequate in particular with respect to the support of public health education and the financing of health care for AIDS patients. These are needed while a vaccine may still be years away.


Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi--a rodent malaria model.
We describe here a rodent malaria model using cloned lines of Plasmodium chabaudi chabaudi in inbred CBA/Ca mice that exhibits both clonal antigenic variation in late stage-specific surface antigens, and deep vascular schizogony in the liver. We show that both these features are modulated by the spleen, and that surface antigen expression is crucially involved in the sequestering phenotype. Surface antigens are variant in chronic infection, and host protective immune responses can distinguish between these variants. Splenectomy abolishes this difference. The acute infection with non-sequestering cloned lines is kinetically indistinguishable from sequestering clones, but parasites unable to express variant sequestration-associated antigen do not form a chronic recrudescing infection. Another clone, able to re-express this antigen in the presence of the spleen, undergoes typical chronic recrudescence. In this model, the biological significance of sequestration-associated variant antigen seems to enable the establishment of chronic infection in the presence of a primed spleen.


Cluster modelling of disease incidence via RJMCMC methods: a comparative evaluation. Reversible jump Markov chain Monte Carlo.
The spatial modelling of small area health data has, for some time, included spatial autocorrelation as a random effect. This effect is non-specific and global and does not address the location of clusters of disease (a specific task). This paper addresses the need for specific and non-specific random effects within spatial epidemiology. In addition, individual frailty is also considered important and a computational algorithm based on reversible jump Markov chain Monte Carlo (RJMCMC) methods is described.


Daily Life Satisfaction in Older Adults as a Function of (In)Activity.
This 14-day daily diary study tested the between-person and within-person associations between sedentary behavior, physical activity, and life satisfaction in community-dwelling older adults. Older adults (n = 100) wore ActivPAL3 activity monitors for 14 days and, at the end of each day, answered questions regarding their health behaviors and life satisfaction. Separate multilevel models were tested for self-reported and objectively measured behavioral data. In the model using objectively measured behavioral data, life satisfaction was (a) negatively associated with sedentary behavior at the within-person level and unassociated with sedentary behavior at the between-person level and (b) unassociated with physical activity at either the between-person or within-person level. In the model using self-reported behavioral data, life satisfaction was (a) unassociated with sedentary behavior at either the between-person or within-person level and (2) positively associated with physical activity at the within-person, but not at the between-person, level. Results indicated that daily deviations in objectively measured sedentary behavior and self-reported physical activity have implications for older adults' well-being. Interventions designed to enhance well-being and quality of life in older adults should consider targeting daily changes in total sedentary behavior and daily changes in the volume or frequency of physical activity.


The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling.
The innate immune system deploys a variety of sensors to detect signs of infection. Nucleic acids represent a major class of pathogen signatures that can trigger robust immune responses. The presence of DNA in the cytoplasm of mammalian cells is a danger signal that activates innate immune responses; however, how cytosolic DNA triggers these responses remained unclear until recently. In this review, we focus on the mechanism of DNA sensing by the newly discovered cGAS-cGAMP-STING pathway and highlight recent progress in dissecting the in vivo functions of this pathway in immune defense as well as autoimmunity.


Whole-genome prediction of fatty acid composition in meat of Japanese Black cattle.
Because fatty acid composition influences the flavor and texture of meat, controlling it is particularly important for cattle breeds such as the Japanese Black, characterized by high meat quality. We evaluated the predictive ability of single-step genomic best linear unbiased prediction (ssGBLUP) in fatty acid composition of Japanese Black cattle by assessing the composition of seven fatty acids in 3088 cattle, of which 952 had genome-wide marker genotypes. All sires of the genotyped animals were genotyped, but their dams were not. Cross-validation was conducted for the 952 animals. The prediction accuracy was higher with ssGBLUP than with best linear unbiased prediction (BLUP) for all traits, and in an empirical investigation, the gain in accuracy of using ssGBLUP over BLUP increased as the deviations in phenotypic values of the animals increased. In addition, the superior accuracy of ssGBLUP tended to be more evident in animals whose maternal grandsire was genotyped than in other animals, although the effect was small.


Computer-aided learning--a solution for the training needs of users & maintainers of medical equipment.
It can be argued that the strategic role of training and assessment in the use and maintenance of medical equipment for the delivery of safe and efficient healthcare is underestimated. While there has been frequent comment on this issue, the resources provided for this activity are most often insufficient. New methods are required to deliver regular, cost-effective training within the working environment, at the time and place of need. Similarly, the administrative workload has to be automated--and thus reduced--if training is to improve in both frequency and content. Computer-aided learning has had increasing and diverse application in education and training over the past few decades. The sophistication of software tools and the reduced cost of the necessary hardware makes this a viable and appropriate method for application in the field of Clinical Engineering. However, this technology has not yet been fully exploited to provide instruction in the use and maintenance of equipment. In this paper, it is proposed that computer-based training packages should not only be a source of interactive instruction and assessment, but also act as rapidly accessible reference materials or simulators of the actual device for the purpose of fault finding or troubleshooting. Brief details of a sample package are given for training in the use and maintenance of the Siemens Elema Servo Ventilator 900C.


An assessment of statin safety by neurologists.
The National Lipid Association's (NLA) Statin Safety Task Force charged the Neurology Expert Panel with the task of reviewing the scientific evidence related to adverse effects with statins and providing assessments and advice regarding the safety of statins. The evidence included key adverse reaction statin literature identified via a Medline search by the Task Force and Panel members and the commissioned reviews and research presented in this supplement. Panel members were asked to use this evidence to independently form explicit answers to a series of questions posed by the Task Force. Panelists were asked to grade the type of literature and the confidence they had in it in forming their answers using prescribed scales. Panelists were encouraged to seek the highest level of evidence available to answer their questions and to concentrate on literature involving humans. In addition, the Neurology Expert Panel was asked to propose recommendations to regulatory authorities, health professionals, patients, researchers, and the pharmaceutical industry to address statin safety issues.


Bone marrow nucleated cell concentrate autograft in temporomandibular joint degenerative disorders: 1-year results of a randomized clinical trial.
to assess the reliability of bone marrow nucleated cell (BMNc) intra-articular injection in patients with degenerative temporomandibular joint disorders (TMDs), and to compare its efficacy with that of hyaluronic acid (HA). this study was designed as a randomized, controlled trial of parallel groups. Patients affected by degenerative joint mandibular disorders were enrolled in this prospective clinical trial and randomly divided into two groups. The HA group underwent temporomandibular joint (TMJ) arthrocentesis and HA injection, whilst patients in the BMNc group were inoculated with BMNc inside the joint after lavage. Outcome measures were: assessing pain at rest and during motion, joint noises, chewing efficiency, and maximum interincisal opening. A postoperative MRI scan was performed and compared with the preoperative one, while examining for cartilage regeneration. Clinical and radiological data were collected from baseline to 12 months follow-up. Thirty patients, 15 for each group, complaining of different degrees of unilateral TMD with internal derangement, were enrolled and treated. In both groups, significant clinical improvements were detected after the procedure up to 1 year postoperatively. The BMNc group presented significantly better pain relief than the HA group after 6 months (p = 0.028) and 12 months (p = 0.000). No significant differences were observed in terms of joint noises. In terms of chewing efficiency, the BMNc group showed positive significant differences after 12 months (p = 0.000). Maximum interincisal opening presented significantly better values in the BMNc group after 6 months (p = 0.001) and 12 months (p = 0.000). No MRI evidence of cartilage regeneration was reported. intra-articular TMJ BMNc injection improved clinical outcomes in TMD treatment. The Results of this first human-model study are promising but further studies are needed to determine whether BMNc can represent the best treatment for TMDs.


Mitochondria from the lamprey (Lampetra fluviatilis). Oxidative phosphorylation and related processes.
1. High efficiency of oxidative phosphorylation and a good respiratory control in liver, heart and somatic muscle mitochondria of the lamprey (Lampetra fluviatilis) were observed when the particles were isolated in a complex sucrose medium containing EDTA, heparin and nicotinamide. The coupling properties of these mitochondria were further improved by including serum albumin in the incubation medium. 2. The content of total adenine nucleotides in lamprey mitochondria was between 4 and 6 nmoles/mg protein. The translocation of these nucleotides across mitochondrial membrane was stimulated by serum albumin. 3. Lamprey mitochondrial phospholipids contain a large proportion (64-72%) of polyunsaturated fatty acids. 4. Electron micrographs of mitochondria from lamprey liver, heart and somatic muscle are presented.


[Diet as a determinant of central nervous system development: role of essential fatty acids].
Nervous system is second to adipose tissue in containing the highest lipid concentration. Membrane phospholipids possess a high content of long chain polyunsaturated fatty acids (LCPUFA) of the n-3 and n-6 families, derived from the corresponding essential fatty acids. Docosahexaenoic acid (22:6n-3) is found in the highest concentrations in the gray matter and the photoreceptors of the retina. n-3 LCPUFA deficiency in infants, mainly if born preterm, modifies neural functions causing learning disabilities and visual function abnormalities. The adequate lipid nutrition of the mother before and during pregnancy and in breast feeding determine the lipid transfer of fatty acids to the fetus and infant, respectively. LCPUFA are conditionally essential in preterm infants, born with lower lipid depots. The formulation of infant formulas, mainly for preterm babies, should include adequate proportions of n-3 and n-6 LCPUFA.


Human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease.
Specific monocyte and macrophage subsets have been implicated in atherosclerosis, with intermediate monocytes proportionally elevated in cardiovascular disease and M1 macrophages abundant in unstable atherosclerotic plaques. While several studies have shown altered proportions of these subsets in atherosclerosis, studies examining functional and phenotypic subset alterations remain scarce. We used whole blood flow cytometry to investigate the expression of M1 (CD86) and M2 (CD163) markers on monocyte subsets of atherosclerotic patients and controls. Atherosclerotic patients had a more inflammatory monocyte profile than controls, indicated by increased intermediate subset proportions, a higher classical monocyte CD86/CD163 ratio, and elevated serum M1-related chemokines. A more inflammatory profile appeared to correlate with atherosclerotic risk, as in controls classical monocyte CD86/CD163 ratio was negatively correlated with HDL and apolipoprotein A1, and positively correlated with interleukin-1β. We conclude that monocyte subsets show functional and phenotypic changes in cardiovascular disease and such changes are likely to contribute to atherosclerotic progression.


[Ultrasound techniques in anesthesiology--guided vascular access using sonography].
In anaesthetic practise ultrasound can facilitate cannulation of veins and arteries not only in adults but also in children. It is the main advantage and safety feature of this technique, that the targeted vessels and the surrounding anatomical structures are visualized and that the needle is advanced under continuous observation. Moreover, its systematic use can reduce the rate of unsuccessful cannulation attempts, which can be caused by anatomical variations or thrombi, occluding the targeted vessel. Ultrasound guided vascular cannulation can decrease complication rates and might improve patients safety e.g. by avoiding puncture of the carotid artery. However, in order to pass on these potential benefits to the patient and justify the increased expenses related to the purchasing of preferably portable ultrasound systems, it is mandatory to offer an appropriate ultrasound training programs for physicians using this technique.


Designing Drug Conjugates Based on Sugar Decorated V-Shape and Star Polymethacrylates: Influence of Composition and Architecture of Polymeric Carrier.
Amphiphilic ethylenediamine (EDA)-functionalized V-shape and star copolymers with centrally placed methyl-α,D-glucopyranoside were designed as nanocarriers. Anticancer doxorubicin (DOX) was conjugated in water via amine groups in copolymers to form ketimine linkers. Variations of arm length and number (40-65 units per arm and 2 vs 3 vs 4 arms), DOX feed amount, and conjugation site content (50-160 units of EDA groups), as responsible for efficiency of drug attachment (10-60 units of conjugated DOX) and its release at various pH (5.0 vs 7.4), were studied to demonstrate potential for drug delivery. Size of conjugate particles (10-195 nm) formed in aqueous solution was strongly dependent on the polymer composition and topology. The broad range of drug amounts (25-95%) were detected by the precipitation method, showing pH sensitivity by some polymeric conjugates with faster DOX release in acidic conditions.


The use of long-acting contraceptives in adolescents.
DMPA and implants have played an important role in the attempt to prevent teenage pregnancies. Adolescent health care providers should provide continued counseling to girls using DMPA or implants and should promptly address any concern associated with these methods. Future studies are warranted to explore ways to prevent or reduce the side effects of DMPA and implants, as well as to develop new, optimal, long-acting contraceptives. Detailed baseline information should be obtained in every future study that explores the presence of side effects during the use of long-acting contraceptives.


A prospective study of ankle injury risk factors.
Many factors are thought to cause ankle ligament injuries. The purpose of this study was to examine injury risk factors prospectively and determine if an abnormality in any one or a combination of factors identifies an individual, or an ankle, at risk for subsequent inversion ankle injury. We examined 145 college-aged athletes before the athletic season and measured generalized joint laxity, anatomic foot and ankle alignment, ankle ligament stability, and isokinetic strength. These athletes were monitored throughout the season. Fifteen athletes incurred inversion ankle injuries. Statistical analyses were performed using both within-group (uninjured versus injured groups) data and within-subject (injured versus uninjured ankles) data. No significant differences were found between the injured (N = 15) and uninjured (N = 130) groups in any of the parameters measured. However, the eversion-to-inversion strength ratio was significantly greater for the injured group compared with the uninjured group. Analysis of the within-subject data demonstrated that plantar flexion strength and the ratio of dorsiflexion to plantar flexion strength was significantly different for the injured ankle compared with the contralateral uninjured ankle. Individuals with a muscle strength imbalance as measured by an elevated eversion-to-inversion ratio exhibited a higher incidence of inversion ankle sprains. Ankles with greater plantar flexion strength and a smaller dorsiflexion-to-plantar flexion ratio also had a higher incidence of inversion ankle sprains.


Thiorphan and analogs: lack of correlation between potency to inhibit "enkephalinase A" in vitro and analgesic potency in vivo.
The potencies of the R and S isomers of thiorphan and rigid analogs of thiorphan to produce analgesia in a mouse hot-plate assay have been compared with their potencies to inhibit enkephalin degradation by rat brain "enkephalinase A." The R and S isomers of thiorphan were equipotent as enzyme inhibitors (IC50 approximately 10(-9) M) but had significantly different analgesic profiles when injected i.c.v. Rigid analogs of thiorphan were less potent enzyme inhibitors (IC50 values of 10(-7) - 10(-4) M) but produced analgesia and potentiated Tyr-D-Ala-Gly-Phe-Met-NH2 induced analgesia at doses (i.c.v.) comparable to thiorphan. These observations suggest that inhibitors of enkephalinase A produce analgesia through a pharmacological mechanism which is not directly related to inhibition of enkephalin degradation.