Association between fetal fraction on cell-free DNA testing and first-trimester markers for pre-eclampsia.
To evaluate the association between fetal fraction on cell-free DNA (cfDNA) testing and first-trimester markers for pre-eclampsia, and to investigate the possible association of low fetal fraction with increased risks for pre-eclampsia (PE) and fetal growth restriction (FGR). This was a retrospective cohort study including all women with a singleton pregnancy who had risk calculation for PE and FGR between 11 + 0 and 13 + 6 weeks' gestation and who also had cfDNA as a primary or secondary screening test for chromosomal abnormalities at any gestational age at two fetal medicine clinics in Sydney and Melbourne, Australia, between March 2013 and May 2017. Logarithmically transformed fetal fraction results were adjusted for gestational age and maternal characteristics. Associations with mean arterial pressure (MAP), mean uterine artery pulsatility index (UtA-PI), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), and risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks were analyzed using correlation analysis and univariable and multivariable linear regressions. In total, 4317 singleton pregnancies that underwent cfDNA testing with fetal fraction reported were included. Significant prediction of fetal fraction was provided by gestational age, conception by in-vitro fertilization, maternal age, body mass index, chronic hypertension, diabetes mellitus, South Asian ethnicity and being parous without history of PE or FGR. Fetal fraction was associated inversely with MAP and UtA-PI and associated positively with PAPP-A and PlGF. The lower the fetal fraction, the higher were the risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks (P < 0.001 for all). There is a significant association between fetal fraction result and first-trimester markers for adverse pregnancy outcome. Low fetal fraction is associated with an increased risk for pregnancy complication, but its capacity to act an as independent first-trimester marker in an algorithm for screening for PE and FGR requires further research. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Decreased amount of the Rh antigen D in hereditary spherocytosis (HS).
This study was done to determine whether hereditary spherocytosis (HS) red blood cells (RBC) have decreased amounts of Rh antigens. Initially we studied the RBC of five members of one family, two of whom had HS. Using automated quantitative haemagglutination tests, we demonstrated that HS RBC agglutinated less with Rh antisera of four specificities than did normal RBC, indicating that Rh antigens are decreased on HS RBC. In this family, the strength of other blood group antigens on HS RBC was estimated by manual titres and agglutination scores. No appreciable differences in the agglutination of HS and normal RBC were observed with non-Rh antisera. To assess the strength of the D antigen more accurately, the number of D sites was quantitated on the RBC of 19 individuals with HS and 11 of their healthy relatives. HS RBC had 9209 +/- 4084 (mean +/- SD) D sites, whereas the normal RBC had 15 394 +/- 5763 D sites. These two means were significantly different (P less than 0.01). HS RBC were also compared to normal RBC of unrelated individuals who had the same Rh phenotype. These analyses showed that HS RBC had about half of the normal number of D sites. Our data indicate that HS red cells have decreased amount of the Rh antigen D and probably also of other Rh antigens.


Robertsonian translocations in wheat arise by centric misdivision of univalents at anaphase I and rejoining of broken centromeres during interkinesis of meiosis II.
The mechanism of origin of Robertsonian translocations was investigated in plants monosomic for chromosome 1A of wheat and 1H(t) of Elymus trachycaulus by GISH. Chromosomes 1A and 1H(t) stayed univalent in all metaphase I cells analyzed, suggesting that Robertsonian translocations do not originate from meiotic recombination in centromeric regions with shared DNA sequence homology. At ana-/telophase I, the 1H(t) and 1A univalents underwent either chromosome or chromatid segregation and misdivided in 6-7% of the pollen mother cells. None of the ana-/telophases I analyzed had Robertsonian translocations, which were only observed in 2% of the "half tetrads" at ana-/telophase II. The frequency of Robertsonian translocations observed at ana-/telophase II corresponds well with the number of Robertsonian translocations (1-4%) detected in progenies derived from plants monosomic for group-1 chromosomes of wheat (1A, 1B, and 1D) and 1H(t) of E. trachycaulus. Our data suggest that Robertsonian translocations arise from centric misdivision of univalents at ana-/telophase I, followed by segregation of the derived telocentric chromosomes to the same nucleus, and fusion of the broken ends during the ensuing interkinesis.


The effectiveness of using co-dominant polymorphic allelic series for (1) checking pedigrees and (2) distinguishing full-sib pair members.
Formulae express the effectiveness of parentage exclusion tests and differences separating full-sib pairs by compounding genotypic information on discrete examples of co-dominant alleles segregating at gene loci on different autosomes. Such polymorphisms occur among structural genes and polymorphic DNA sequences. Two general formulae state the theoretical effectiveness of using co-dominant alleles for (1) testing parentage and (2) distinguishing sibs. The formula for parentage exclusion tates the probability (PE) that a given series of co-dominant alleles of known frequency should detect a falsely recorded father (or mother). The other formula describes how genetic polymorphism can distinguished closely related individuals. It states the probability (PS) that alleles distinguish the members of full-sib pairs, dizygotic twins and tissue chimeras. To derive the two general formulae, particular formulae were calculated for n = 2, 3 and 4 co-dominant alleles. By increasing the numbers of alleles, the formulae were seen to contain recurrent patterns which were then expressed in the two general formulae for n alleles. Some examples demonstrate applications of the two formulae in problems concerning parentage and sibship.


Improvement of progressive systemic sclerosis (PSS) with estriol treatment.
Two female patients suffering from progressive systemic sclerosis (PSS) of generalized type were treated with estriol for 10 months. Although complete cure was not achieved, considerable beneficial effects were observed in these patients, but no serious side effects. Thus, skin softening was observed on all involved parts of these patients, which was accompanied by increased mobility of large or medium-sized joints and improved pigmentation and cyanotic redness on fingers and extremities. However, no apparent improvement of internal organ involvement could be detected. Histopathologically, a drastic reduction of homogenization of collagen bundles in the dermis of affected forearms was seen in these patients following estriol treatment. To our knowledge this is the first report of estriol therapy for PSS.


A systematic review of the use of simulated patient methodology in pharmacy practice research from 2006 to 2016.
Simulated patient (SP) methodology (mystery shopping) is used increasingly to assess quality of pharmacy services, and evaluate impact of interventions. Our objective was to review papers reporting on the use of SP methodology in pharmacy practice research 2006-2016 in community pharmacies worldwide. We searched EMBASE and MEDLINE for papers reporting on the use of mystery shopping in pharmacy settings, using a wide range of terms for SPs, based on previous review. We removed irrelevant papers, duplicates, papers not written in English, and review papers and reviewed remaining papers. Two reviewers carried out data abstraction, using the same tool as the previous review and inserting data into Excel, focusing on how the SP methodology is used. A total of 148 papers from 52 countries from all regions of the world were included in the review. A wide range of terms described the method, and simulated patient was the most common (49 papers). Most studies were cross-sectional (124), and most investigated only community pharmacies (115). The most common aim was to evaluate some aspect of pharmacists' or other staff's advice and counselling (94). Number of visits is 2-7785. Many papers did not cover details, such as number of visits planned, and carried out, scenario used, training and background of SPs, and ethical approval for the study. The use of SP methodology has increased substantially in the field of pharmacy over the past decade. This is a useful method in a wide range of countries and settings. Greater detail is required in reporting.


Autolysis of isolated adipocytes by endogenously produced fatty acids.
Isolated rat adipocytes, in which lipolysis was maximally stimulated by isoproterenol, continued to produce fatty acids in excess of the high-affinity binding capacity of the fatty acid acceptor bovine serum albumin in the incubation medium. At an average of 17 mol fatty acids/mol serum albumin, there was a burst of lactate dehydrogenase activity recovered in the incubation medium, indicating cell lysis. It is concluded that endogenously produced fatty acids will cause autolysis of adipocytes in vitro. Actively lipolysing adipocytes were more fragile than resting cells, since increasing amounts of lactate dehydrogenase activity was recovered in the medium during active lipolysis.


Imitation and action in autism: a critical review.
This article considers the evidence for an imitative deficit in autism and for the possible role of deficiencies in the representation of actions. An argument is developed for the claim that the imitation problem is diagnostic of a basic information-processing rather than a social dysfunction. Reviews are offered of the empirical literature on gestural imitation in autism (and other developmental disorders) and the more anecdotal evidence for problems in the domain of action development in autism. An account that may help to integrate these areas is suggested, as are directions for future research.


Metabolic analysis of mouse brains that have compromised iron storage.
Iron is a critical component of the CNS that must be tightly regulated; too little iron can result in energy insufficiency and too much iron can result in oxidative stress. The intracellular iron storage protein ferritin is central to the regulation of iron. In this study, we determined the neurochemical profile of brains of animals deficient in heavy-chain ferritin (H-ferritin) using high-resolution magic angle spin proton magnetic resonance spectroscopy (HR-MAS (1)H MRS). Spectra of 2 mm-thick coronal tissue punches ( approximately 4 mg) were obtained using a CPMG pulse sequence on Bruker Avance 500 and quantified (nmol/mg tissue) using customized LCModel software (16 metabolites). In H-ferritin deficient mice, we found significant increases in striatal glutamate, hippocampal choline, and N-acetyl-aspartyl-glutamate in both the cortex and the hippocampus (t-test, p < 0.05). Neurochemical profiling with principal component analysis (PCA) revealed increased glutamate in the hippocampus, striatum, and ventral tegmental area (VTA) in H-ferritin deficient animals as compared to wild-type. While lactate was increased in the VTA of deficient animals, it was decreased in the striatum. Also, GABA was increased in both cortical and striatal regions of deficient mice. These changes reveal the importance of proper iron management for maintaining neurochemical balance and provide new evidence for region specific differences in neurochemical profiles as a result of compromised ability of neurons to store iron while overall iron status is normal. Because H-ferritin is predominantly expressed in neurons, the neurochemical profile is suggestive of neuronal iron deficiency and may have relevance to the functional consequences associated with brain iron deficiency.


Interaction of the anticancer p28 peptide with p53-DBD as studied by fluorescence, FRET, docking and MD simulations.
The p28 peptide, derived from the blue copper protein Azurin, exerts an anticancer action due to interaction with the tumor suppressor p53, likely interfering with its down-regulators. Knowledge of both the kinetics and topological details of the interaction, could greatly help to understand the peptide anticancer mechanism. Fluorescence and Förster resonance energy transfer (FRET) were used to determine both the binding affinity and the distance between the lone tryptophan (FRET donor) of DNA Binding Domain (DBD) of p53 and the Iaedens dye (FRET acceptor) bound to the p28 peptide. Docking, Molecular Dynamic simulations and free energy binding calculations were used to single out the best complex model, compatible with the distance measured by FRET. Tryptophan fluorescence quenching provided a 105 M-1 binding affinity for the complex. Both FRET donor fluorescence quenching and acceptor enhancement are consistent with a donor-acceptor distance of about 2.6 nm. Docking and molecular dynamics simulations allowed us to select the best complex, enlightening the contact regions between p28 and DBD. p28 binds to DBD partially engaging the L1 loop, at the same region of the p53 down-regulator COP1, leaving however the DNA binding site available for functional interactions. Elucidation of the DBD-p28 complex gets insights into the functional role of p28 in regulating the p53 anticancer activity, also offering new perspectives to design new drugs able to protect the p53 anticancer function.


Histochemical study on 5'-nucleotidase in the cerebrovascular system in stroke-prone spontaneously hypertensive rats.
5'-Nucleotidase activity in the cerebrovascular system in stroke-prone spontaneously hypertensive rats was histochemically investigated. In the hypertensive rats, an enhancement of 5'-nucleotidase activity was observed already in the early stage of hypertension and the enzyme activity increased with advancing age. The enzyme activity appeared earlier and stronger in the larger arteries in the basal portion than the pial arteries in the convexity of the brain and arterioles in the brain parenchyma. The activity in the arterial walls proved to be particularly strong in the thickened parts showing cellular hyperplasia, mainly at the branching portions. The reaction products localized along the plasma membrane, and also in the cytoplasma in some parts where the activity was strong. Relationship between the increased 5'-nucleotidase activity and aging of the cells composing the cerebrovasculature resulted from an accelerated or repeated cell proliferation was discussed.


Hypothalamic amenorrhea in a Camurati-Engelmann disease--a case report.
A case report of a patient diagnosed with Camurati-Engelmann Disease (CED) in association with the functional hypothalamic amenorrhea disturbances. CED is a very rare genetically determined disorder classified as a type of bone dysplasia. Case report. Department of Gynecological Endocrinology, 3rd grade Medical University Hospital. Twenty-one years old female patient with CED admitted to the hospital because of primary amenorrhea. Her history revealed skeletal deformities and hearing impairment. Clinical examination, ultrasound, laboratory evaluations (including serum gonadotropins (FSH, LH) at basal state and after stimulation with gonadotropin-releasing hormone, serum basal estradiol) radiological studies (X-ray of the head, the lumbar spine and lower extremities; a computed tomography of the head), G-banding karyotype, polymerase chain reaction and DNA sequencing. Hormonal serum evaluations were made using an enzyme-linked immunosorbent assay. The exon 4 of the transforming growth factor beta 1 gene was amplified by a polymerase chain reaction and the product was directly sequenced. The hormonal analysis was characteristic for the hypogonadotropic hypogonadism. Radiological and molecular analyses confirmed CED diagnosis. The hypothalamic amenorrhea in a patient with CED may be explained as a consequence of fat hypotrophy and very low body mass index. Therefore, impairment within hypothalamic-pituitary axis in patients with CED should be treated with special attention.


Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation.
Familial hyperaldosteronism type 1 is an autosomal dominant disorder attributed to a chimeric CYP11B1/CYP11B2 gene (CG). Its prevalence and manifestation in the pediatric population has not been established. We aimed to investigate the prevalence of familial hyperaldosteronism type 1 in Chilean hypertensive children and to describe their clinical and biochemical characteristics. We studied 130 untreated hypertensive children (4 to 16 years old). Blood samples for measuring plasma potassium, serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. The detection of CG was performed using long-extension PCR. We found 4 (3.08%) of 130 children with CG who belonged to 4 unrelated families. The 4 patients with CG had very high aldosterone/renin ratio (49 to 242). In addition, we found 4 children and 5 adults who were affected among 21 first-degree relatives. Of the 8 affected children, 6 presented severe hypertension, 1 presented prehypertension, and 1 presented normotension. High serum aldosterone levels (>17.7 ng/dL) were detected in 6 of 8 subjects (range: 18.6 to 48.4 ng/dL) and suppressed plasma renin activity (≤0.5 ng/mL per hour) and high aldosterone/renin ratio (>10) in 8 of 8 children (range: 49 to 242). Hypokalemia was observed in only 1 of 8 children. We demonstrated that the prevalence of familial hyperaldosteronism type 1 in a pediatric hypertensive pediatric population was surprisingly high. We found a high variability in the clinical and biochemical characteristics of the affected patients, which suggests that familial hyperaldosteronism type 1 is a heterogeneous disease with a wide spectrum of presentations even within the same family group.


Use of 5-BrdUrd/313 nm light technique for identification of cells in initial S-phase within GM-CFCc compartment.
Long-term, low-level, BrdUrd infusion identifies two subpopulations of GM-CFCc with quite dissimilar sensitivities to 313 nm light. The responses of these two GM-CFCc subpopulations to hydroxyurea indicate that both are rapidly proliferating at the time of the assay. However, the absolute UV-light sensitivity of the S-phase components and the effects of increasing BrdUrd concentration indicate that the two GM-CFCc subpopulations passed through the previous cell cycle at widely disparate rates. Further, those GM-CFCc originating from a parental cell with a slow turnover are associated with a lower buoyant density than those GM-CFCc that have been in rapid cycle for at least two generations. These results indicate that the resistance to 313 nm-light irradiation, shown by S-phase cells in the first cell cycle of the BrdUrd labeling, may provide evidence of the proliferative history of the cell being assayed.


Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder.
Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder.


Purification and characterization of the cold-active alkaline protease from marine cold-adaptive Penicillium chrysogenum FS010.
An extracellular cold-active alkaline serine protease from Penicillium chrysogenum FS010 has been purified. The purification procedure involved: ammonium sulfate precipitation, DEAE ion-exchange chromatography and sephadex G-100 gel chromatography. SDS-PAGE of the purified enzyme indicated a molecular weight of 41,000 +/- 1,000 Da. The protease is stable in a pH range of 7.0-9.0 and has a maximum activity at pH 9.0. Compared with other industrial proteases, the enzyme shows a high hydrolytic activities at lower temperatures and a high sensitivity at a temperature over 50 degrees C. The isoelectric point of the enzyme is approximate to 6.0. Enzymatic activity is enhanced by the addition of divalent cations such as Mg(2+) and Ca(2+) and inhibited by addition of Cu(2+)and Co(2+). PMSF and DFP are its specific inhibitors. The application of the cold-active alkaline protease is extremely extensive, and widely used in detergents, feed, food, leather and many other industries.


Using feature generation and feature selection for accurate prediction of translation initiation sites.
Correct prediction of the translation initiation site (TIS) is an important issue in genomic research. We show that feature generation together with correlation based feature selection can be used with a variety of machine learning algorithms to give highly accurate translation initiation site prediction. Only very few features are needed and the results achieve comparable accuracy to the best existing approaches. Our approach has the advantage that it does not require one to devise a special prediction method; rather standard machine learning classifiers are shown to give very good performance on the selected features. The raw and generated features which we have found to be important are the following: positions -3 and -1 in the sequence; upstream k-grams for k=3, 4, and 5; stop-codon frequency; downstream in-frame 3-gram; and the distance of ATG to the beginning of the sequence. The best result, with an overall accuracy of 90%, is obtained by selecting only seven features from this set. The same features retrained with the use of a scanning model achieves an overall accuracy of 94% on this dataset.


The rabbit as an experimental animal for tracheal surgery.
The circumferential resection of the trachea with end-to-end anastomosis is a well-established clinical procedure. Still, some problems remain to be solved, such as the choice of optimal suture material. Dogs are primarily used for experimental work in this field, but are difficult to obtain. This operation was performed on nine rabbits, eight of whom survived to the preplanned date of sacrifice. Two of the survivors were found to have severe stricture at the anastomosis. This study indicates that the rabbit is a suitable experimental animal for circumferential resection and anastomosis of the trachea.


A psychometric comparison of the Beck Depression Inventory-II in English and Spanish.
The Beck Depression Inventory-II (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996) is a widely used measure of depressive symptomatology originally authored in English and then translated to Spanish. However, there are very limited data available on the Spanish translation. This study compared the psychometric characteristics of the BDI-II in Spanish and English in a sample of 895 college students. The instrument was administered twice with a 1-week interval, either in the same language on both occasions or in a different language on each occasion. Results show strong internal consistency and good test-retest reliability in both languages. Confirmatory factor analysis demonstrated that the published English-language factor structure showed good fit with data from the Spanish instrument. Among bilingual participants who took the BDI-II in both languages, there was no significant language effect. These data provide initial evidence of comparable reliability and validity between the English and Spanish BDI-II in a nonclinical sample.


Suppression of Caco-2 and HEK-293 cell proliferation by Kigelia africana, Mimusops zeyheri and Ximenia caffra seed oils.
Animal-derived oils and purified fatty acids, but not indigenous fruit-tree-derived seed oils, have been used to study cell growth and differentiation. In this study, we determined the effects of the Kigelia africana, the Mimusops zeyheri and the Ximenia caffra seed-oil on cell proliferation in culture. Human colon adenocarcinoma (Caco-2) and human embryonic kidney (HEK-293) cells were maintained and treated with various concentrations (0, 20, 40, 80, 100 and 120 mg/l) of K. africana, M. zehyeri and X. caffra seed oil. The trypan blue dye exclusion method was used to determine cell growth 48-hours after oil treatment. All three tree seed oils suppressed both Caco-2 and HEK-293 cell growth in a dose-dependent manner. Importantly, the tree seed oils did not cause increased cell death as the number of dead cells remained unchanged under control and oil-treated conditions. K. africana oil significantly suppressed Caco-2 cell growth compared to HEK-293 cell growth at all oil concentrations, whereas M. zeyheri and X. caffra seed oils significantly suppressed HEK-293 and Caco-2 cell growth, only at a concentration of 80 mg/l. The suppression of Caco-2 and HEK-293 cell proliferation by K. africana, M. zeyheri and X. caffra seed oils suggest a potential antiproliferative effect of these tree seed oils on the two cell lines.


Patterns of alcohol use and associated physical and lifestyle characteristics according to new Australian guidelines.
To describe the pattern of alcohol consumption and associated physical and lifestyle characteristics in a population-based sample of Australian men. A community-based age-stratified random sample of 1420 men (median age 56 years, range 20-93) participating in the Geelong Osteoporosis Study, an epidemiological study set in south-eastern Australia. Daily alcohol intake was ascertained from a detailed food frequency questionnaire and categorized according to the Australian National Health and Medical Research Council 2009 guidelines (non-drinkers, greater than zero but ≤ 2 drinks per day, > 2 drinks per day), with a standard drink equivalent to 10 g of ethanol. Anthropometry was measured and lifestyle factors self-reported. Body composition was determined using dual energy absorptiometry. Socio-economic status was categorized according to the Australian Bureau of Statistics data. Results were age standardized to the Australian male population figures. The median daily ethanol consumption was 12 g (IQR 2-29) per day with a range of 0-117 g/day. The age-standardized proportion of non-drinkers was 8.7%, 51.5% consumed up to two drinks per day (≤ 20 g ethanol/day), and 39.9% exceeded 2 standard drinks per day (> 20 g ethanol/day). Alcohol consumption was positively associated with cigarette smoking, weight, higher SES and inversely with age and physical activity. Approximately, 40% of Australian men consume alcohol at levels in excess of current recommendations, which in combination with other risk factors may adversely impact upon health.


Ecophysiology of Amaranthus palmeri, a sonoran desert summer annual.
Basic photosynthetic and water relations characteristics in relation to soil water availability were investigated in Amaranthus palmeri, a common C4 summer annual of the Sonoran Desert. Under conditions of high soil water availability, photosynthetic capacity exceeded 70 μmol CO2 m-2 s-1 at a leaf temperature optimum of 42°C, and photosynthesis was not light saturated at an irradiance of 2.0 mmol m-2 s-1 (400-700 nm). Leaves of A. palmeri exhibited diaheliotropic movements, allowing them to take advantage of their high photosynthetic capacity. In response to a long term drought cycle, both photosynthetic rate and leaf conductance to water vapor decreased, reaching minima at an approximate leaf water potential of-2.9 MPa. Active leaf osmotic adjustment appeared to play an important role in allowing leaves to maintain gas exchange activities down to these low leaf water potentials. The photosynthetic rate became light saturated at the lower leaf water potentials. Although the two parameters decreased in concert, the decreased photosynthetic rate was not due to increased stomatal diffusion limitations, since intercellular CO2 concentrations remained constant over the range of leaf water potentials. Instead it appeared that during the drought cycle, both intrinsic photosynthetic capacity and leaf protein content decreased as well. These results suggested a coordination of gas exchange parameters during long term drought such that the intercellular CO2 concentration remained constant.


The school nurse's role in treatment of the student with autism spectrum disorders.
Some healthcare concerns have been found to be commonly associated with Autism Spectrum Disorders (ASD). Identification and treatment of these medical issues can improve the functioning of the child with ASD. This article will offer practical suggestions for the school nurse. As a "front-line" medical professional in the schools, the school nurse is positioned to provide guidance on implementing interventions for the student with ASD. By being knowledgeable about current research and treatment options for the various associated medical conditions, the school nurse can help the student achieve academic success in the school setting.


Grey water treatment in UASB reactor at ambient temperature.
In this paper, the feasibility of grey water treatment in a UASB reactor was investigated. The batch recirculation experiments showed that a maximum total-COD removal of 79% can be obtained in grey-water treatment in the UASB reactor. The continuous operational results of a UASB reactor treating grey water at different hydraulic retention time (HRT) of 20, 12 and 8 hours at ambient temperature (14-24 degrees C) showed that 31-41% of total COD was removed. These results were significantly higher than that achieved by a septic tank (11-14%), the most common system for grey water pre-treatment, at HRT of 2-3 days. The relatively lower removal of total COD in the UASB reactor was mainly due to a higher amount of colloidal COD in the grey water, as compared to that reported in domestic wastewater. The grey water had a limited amount of nitrogen, which was mainly in particulate form (80-90%). The UASB reactor removed 24-36% and 10-24% of total nitrogen and total phosphorus, respectively, in the grey water, due to particulate nutrients removal by physical entrapment and sedimentation. The sludge characteristics of the UASB reactor showed that the system had stable performance and the recommended HRT for the reactor is 12 hours.


Trials define anti-tumor effects of anti-resorptive agents: denosumab ahead of zoledronate 2 to 1.
New data presented at the 2010 meeting of the American Society of Hematology (ASH), at the 33rd San Antonio Breast Cancer Symposium (SABCS), and released by Amgen are beginning to define the anti-tumor effects of Amgen's denosumab (Xgeva™) and Novartis's zoledronate (Zometa®) in multiple myeloma, breast cancer, and prostate cancer. Just prior to the ASH meeting, Amgen received approval of denosumab for oncology indications. The antibody against RANK ligand, already approved as Prolia® for osteoporosis, will need to demonstrate advantages over its primary competitor zoledronate, a bisphosphonate. Multiple myeloma data presented at the ASH meeting defined zoledronate's ability to slow progression of disease as well as promote bone health, giving zoledronate a clear advantage over denosumab in myeloma. However, zoledronate failed to show an anti-tumor effect in the AZURE trial (Adjuvant Zoledronic Acid to Reduce Recurrence) presented at the SABCS, while denosumab data presented at the meeting suggested slightly greater efficacy than zoledronate in breast cancer. Finally, top-line results from the '147 trial (Study on Prolonging Bone Metastasis-Free Survival in Men With Hormone Refractory Prostate Cancer) suggest that denosumab can help prevent bone metastases in prostate cancer, an ability not yet shown by zoledronate.


Thermohydrogel Containing Melanin for Photothermal Cancer Therapy.
Melanin is an effective absorber of light and can extend to near infrared (NIR) regions. In this study, a natural melanin is presented as a photothermal therapeutic agent (PTA) because it provides a good photothermal conversion efficiency, shows biodegradability, and does not induce long-term toxicity during retention in vivo. Poloxamer solution containing melanin (Pol-Mel) does not show any precipitation and shows sol-gel transition at body temperature. After irradiation from 808 nm NIR laser at 1.5 W cm-2 for 3 min, the photothermal conversion efficiency of Pol-Mel is enough to kill cancer cells in vitro and in vivo. The tumor growth of mice bearing CT26 tumors treated with Pol-Mel injection and laser irradiation is suppressed completely without recurrence postirradiation. All these results indicate that Pol-Mel can become an attractive PTA for photothermal cancer therapy.


[Ultrasound skin findings in HIV infection by imaging with 7.5 MHz linear transducers].
Sonography is an important tool in aiding the diagnosis of tumor-like and cystic findings in the skin and soft tissues. This is also true in patients with HIV infection and AIDS. While sonography of the skin often is performed with 20-MHz transducers, also lower-frequency devices which are more readily available contribute substantially to dermatologic diagnoses. The domain of skin sonography are tumors; in the special context of AIDS, Kaposi's sarcoma and lymphomas are of major interest. The characteristic appearance of Kaposi's tumors is a spindle-shaped outline with low echogenicity and relative homogenicity. The tumor volume is easily established using measurements in two directions. Shrinkage of the volume after therapy, e.g. chemotherapy, may be documented in a more objective manner as compared to subjective rating of nodularity. Several characteristic images of Kaposi's sarcoma, lymphoma, lymph nodes, lipoma, and cysts are demonstrated in the paper.


Peritoneal and retroperitoneal anatomy and its relevance for cross-sectional imaging.
It is difficult to identify normal peritoneal folds and ligaments at imaging. However, infectious, inflammatory, neoplastic, and traumatic processes frequently involve the peritoneal cavity and its reflections; thus, it is important to identify the affected peritoneal ligaments and spaces. Knowledge of these structures is important for accurate reporting and helps elucidate the sites of involvement to the surgeon. The potential peritoneal spaces; the peritoneal reflections that form the peritoneal ligaments, mesenteries, and omenta; and the natural flow of peritoneal fluid determine the route of spread of intraperitoneal fluid and disease processes within the abdominal cavity. The peritoneal ligaments, mesenteries, and omenta also serve as boundaries for disease processes and as conduits for the spread of disease.


Training-induced alterations in muscle glycogen utilization in fibre-specific types during prolonged exercise.
Using the glycogen depletion technique, we have examined utilization of specific fibre types during prolonged submaximal exercise to investigate the recruitment pattern employed by the central nervous system to sustain force generation in the face of a progressive glycogen depletion. Six male subjects (Vo2 max, 52.8 +/- 2.5 mL.kg-1.min-1, mean +/- SE) cycled at 59% of pretraining Vo2 max (the same absolute power output) for 99.5 +/- 6 min on two occasions, before training and after 10-12 days of intensive training, involving 2 h of cycling per day. Prior to the training, glycogen concentration during exercise in the type I and type IIA fibres of the vastus lateralis muscle as measured by microphotometric techniques was progressively reduced during exercise. The pattern of depletion in both of these fibre types was parallel and showed an early marked depletion amounting to 51 (p less than 0.05) and 35% (p less than 0.05) in the type I and type IIA fibres, respectively, during the first 15 min of exercise. At the end of exercise, glycogen levels in type I and type IIA fibres were reduced to 9 and 44% of initial levels, respectively. In contrast, glycogen concentration in type IIB fibres was not significantly (p less than 0.05) altered throughout the exercise. Following training, a pronounced glycogen sparing occurred that was conspicuous in only the type I and type IIA fibres, which was most pronounced during the first 15 min of the exercise. Similar to pretraining, glycogen concentrations in type IIB fibres were unaffected by either exercise or training.(ABSTRACT TRUNCATED AT 250 WORDS)


[Kinetics of the response of native skin tissue to electric stimulation using polarizing electrodes].
Response kinetics of skin tissue to electric current stimulation was studied. A simple method is proposed which permits to separate the response into the electrically active and electrically passive components--inner potential and resistance. The evidence obtained is discussed.


The Evidence for Lifestyle Modification in Lowering Blood Pressure in the Elderly.
Lifestyle modifications are a safe, effective treatment option for hypertension, yet are widely underutilized by clinicians, particularly in the elderly population. This review outlines the nonpharmacologic approaches to the treatment and prevention of hypertension, and discusses their applicability to the elderly population. Accepted recommendations include weight loss, regular exercise, decreased alcohol consumption, and dietary modifications. Each of these changes has been shown to independently reduce blood pressure in elderly individuals, as well as reduce the incidence and severity of comorbid conditions which potentiate cardiovascular risk. The safety of these recommendations equals or exceeds that of pharmacologic therapy, and few contraindications to their implementation exist. A simple, safe, and effective plan appropriate and acceptable to the geriatric patient is described, offering primary care physicians a guideline to follow when prescribing lifestyle modifications to the elderly hypertensive patient. (c) 2000 by CVRR, Inc.


[Experience in the treatment of severe forms of sepsis by extracorporeal therapy and hyperbaric oxygenation].
The results of multiple modality treatment of 81 patients with sepsis complicated by multiple organ failure are assessed. In 40 patients the traditional therapy of sepsis was supplemented with extracorporeal methods (hemoperfusion, autotransfusion of UV-exposed blood, and perfusion of xenospleen slices) and hyperbaric oxygenation (HBO) sessions. In the patients treated traditionally the mortality was 94%, whereas addition of extracorporeal treatment and HBO decreased this value to 40%. Hence, extracorporeal treatment and HBO are recommended for the treatment of sepsis.


Decolorization and phytotoxicity reduction in an innovative anaerobic/aerobic photobioreactor treating textile wastewater.
The potential of a novel anaerobic/aerobic algal-bacterial photobioreactor for the treatment of synthetic textile wastewater (STWW) was here assessed. Algal-bacterial symbiosis supported total organic carbon, nitrogen and phosphorous removal efficiencies of 78 ± 2%, 47 ± 2% and 26 ± 2%, respectively, at a hydraulic retention time (HRT) of 8 days. A decrease in the HRT from 8 to 4 and 2 days resulted in a slight decrease in organic carbon and phosphate removal, but a sharp decrease in nitrogen removal. Moreover, an efficient decolorization of 99 ± 1% and 96 ± 3% for disperse orange-3 and of disperse blue-1, respectively, was recorded. The effective STWW treatment supported by the anaerobic/aerobic algal-bacterial photobioreactor was confirmed by the reduction in wastewater toxicity towards Raphanus sativus seed germination and growth. These results highlighted the potential of this innovative algal-bacterial photobioreactor configuration for the treatment of textile wastewater and water reuse.


Experiences with high dose radiopeptide therapy: the health physics perspective.
One of the new, promising areas of nuclear medicine involves radiolabeled low-molecular-weight peptides for the diagnosis and management of cancer. Somatostatin analogous peptides bind to membrane receptors on tumors with high specificity. These analogues, when radiolabeled with 123I, 131I, 99mTc, or (111)In, allow for external scintigraphic imaging or radioguided surgical resection of tumors. Somatostatin analogues with high tumor binding affinity have also been used for high-dose radiotherapy at the Medical Center of Louisiana since 1994. Although we had extensive prior experience with relatively high-dose 131I administration for thyroid ablation, our personnel protection, contamination control, and other safety techniques required significant modification to ensure effective contamination and radiation exposure control. As therapy with radiolabeled peptides becomes more widely utilized, the controls developed at our institution may be implemented by others to maintain exposures ALARA.


Assessment of estrogenic and anti-androgenic activities of the mycotoxin zearalenone and its metabolites using in vitro receptor-specific bioassays.
Zearalenone (ZEN) is a well-known mycotoxin present in numerous agricultural products. Humans and animals are therefore at a risk of exposure to zearalenone through consumption of contaminated food. After intake, ZEN is reduced to α- and β-zearalenol (α-ZEL and β-ZEL), zearalanone (ZAN), and α- and β-zearalanol (α-ZAL and β-ZAL). Although their estrogenicity has been well characterized, much less is known about their interaction with other nuclear receptors. This study was undertaken to investigate interactions of ZEN and its five metabolites, with the human androgen receptor (hAR) and estrogen receptor alpha (hERα). Their ability to induce hAR-mediated reporter gene expression was examined in androgen-sensitive PALM cells, whereas the effects on hERα function were assessed in MCF-7 cells using the E-Screen bioassay. We confirm that ZEN and its metabolites are full agonists for hERα and demonstrate that all six compounds tested possess hAR-mediated antagonistic activity in PALM cells, in which ZAN, α-ZAL, and β-ZAL were the most effective hAR antagonists. Overall, the observed estrogenic and anti-androgenic potencies of ZEN and its metabolites suggest that these compounds may interfere with the endocrine system by various modes of action and that further investigation is warranted into their role as endocrine disrupters in animals and humans.


Some observations on the trace element concentrations in human dental enamel.
The concentration of trace elements has been measured for dental enamel from 86 healthy human teeth using particle-induced X-ray emission (PIXE). The majority of the teeth (n = 70) were collected from dentists in the county of Oxfordshire in the United Kingdom, although a smaller group (n = 16) were collected from Cornwall. The elements K, Ca, Mn, Fe, Co, Ni, Cu, Zn, Sr, Pb, and Hg have been detected and statistically analyzed by grouping according to sex, age, and geographical location. The concentrations of Fe and Cu were found to be lower in the teeth from female donors (P < 5%) and are believed to result from the continued burden of blood loss during menstruation. Strong positive correlations (P < 0.1%) were found between Ca, Co, Ni, and Zn for all groups; these elements were also found to exhibit a negative correlation (P < 1%) with age for teeth from female donors. This is believed to be related to decalcification during the menopause. Pb was found to exhibit a positive correlation (P < 5%) with age for both sexes, and is believed to substitute for Ca in the Ca hydroxy apatite (HAP) within the dental enamel.


Primary intracranial plasma-cell granuloma. Case report.
The authors report the fourth case of primary intracranial plasma-cell granuloma. The patient was a 16-year-old girl who presented with loss of vision as the major clinical feature. The tumor resembled a meningioma both preoperatively and grossly at surgery. Because the tumor did not respond to steroid treatment following subtotal surgical excision, radiation therapy was administered to the affected area. Major considerations in the differential diagnosis of this neoplasm are discussed.


Reperfusion for acute ischemic stroke: arterial revascularization and collateral therapeutics.
Reperfusion of the ischemic territory forms the basis of most acute stroke treatments. This overview of the literature relating to reperfusion in acute ischemic stroke published within the last year provides a snapshot of a rapidly evolving aspect of cerebrovascular disease. Arterial revascularization from systemic thrombolysis to combination endovascular procedures to achieve recanalization has proliferated. Stroke imaging continues to discern features of critical pathophysiology that may influence tissue fate and clinical outcome. Balancing the risk of hemorrhagic transformation against the therapeutic aim to salvage the ischemic penumbra remains a formidable challenge. Collateral therapeutics that enhance perfusion outside the ischemic core present novel dimension to acute stroke therapy, focused on ischemia and not just the clot or plaque. These timely findings illustrate the essential role of reperfusion in acute stroke, delineating aspects of arterial revascularization and collateral therapeutics to be refined in coming years.


[Lumbar epidural veins (anatomic study apropos of 31 cases)].
Using 31 corrosion preparations with fortacryl-minium, a new systematization of lumbar internal vertebral veins is suggested. The classical posterior longitudinal vein was not found. An anterior-lateral venous flow, composed of an anterior-internal venous canal and of an anterior-external venous canal was described. These venous canals jointly progress along internal face of the pedicle and leave a wider space between them in front of the exit foramina, to allow the passage of roots. The authors then study the transversal veins, the junction of the lumbar column with the sacral column and veins of the exit foramina.


Numerical study and topology optimization of 1D periodic bimaterial phononic crystal plates for bandgaps of low order Lamb waves.
The optimum topology of bimaterial phononic crystal (PhCr) plates with one-dimensional (1D) periodicity to attain maximum relative bandgap width of low order Lamb waves is computationally investigated. The evolution of optimized topology with respect to filling fraction of constituents, alternatively stiff scattering inclusion, is explored. The underlying idea is to develop PhCr plate structures with high specific bandgap efficiency at particular filling fraction, or further with multiscale functionality through gradient of optimized PhCr unitcell all over the lattice array. Multiobjective genetic algorithm (GA) is employed in this research in conjunction with finite element method (FEM) for topology optimization of silicon-tungsten PhCr plate unitcells. A specialized FEM model is developed and verified for dispersion analysis of plate waves and calculation of modal response. Modal band structure of regular PhCr plate unitcells with centric scattering layer is studied as a function of aspect ratio and filling fraction. Topology optimization is then carried out for a few aspect ratios, with and without prescribed symmetry, over various filling fractions. The efficiency of obtained solutions is verified as compared to corresponding regular centric PhCr plate unitcells. Moreover, being inspired by the obtained optimum topologies, definite and easy to produce topologies are proposed with enhanced bandgap efficiency as compared to centric unitcells. Finally a few cases are introduced to evaluate the frequency response of finite PhCr plate structures produced by achieved topologies and also to confirm the reliability of calculated modal band structures. Cases made by consecutive unitcells of different filling fraction are examined in order to attest the bandgap efficiency and multiscale functionality of such graded PhCr plate structures.


Light-induced photoreceptor apoptosis in vivo requires neuronal nitric-oxide synthase and guanylate cyclase activity and is caspase-3-independent.
Apoptosis is the mode of photoreceptor cell death in inherited and induced retinal degeneration. However, the molecular mechanisms of photoreceptor cell death in human cases and animal models of retinal dystrophies remain undefined. Exposure of Balb/c mice to excessive levels of white light results in photoreceptor apoptosis. This study delineates the molecular events occurring during and subsequent to the induction of retinal degeneration by exposure to white light in Balb/c mice. We demonstrate an early increase in intracellular calcium levels during photoreceptor apoptosis, an event that is accompanied by significant superoxide generation and mitochondrial membrane depolarization. Furthermore, we show that inhibition of neuronal nitric-oxide synthase (nNOS) by 7-nitroindazole is sufficient to prevent retinal degeneration implicating a key role for neuronal nitric oxide (NO) in this model. We demonstrate that inhibition of guanylate cyclase, a downstream effector of NO, also prevents photoreceptor apoptosis demonstrating that guanylate cyclase too plays an essential role in this model. Finally, our results demonstrate that caspase-3, frequently considered to be one of the key executioners of apoptosis, is not activated during retinal degeneration. In summary, the data presented here demonstrate that light-induced photoreceptor apoptosis in vivo is mediated by the activation of nNOS and guanylate cyclase and is caspase-3-independent.


Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.
The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.


Manpower supply and demand in pathology.
Recently physicians, the federal government, and medical specialty societies have shown increasing interest in manpower needs in medicine and in the medical specialties. Since 1976 the Joint Task Force on Pathology Manpower of the American Society of Clinical Pathologists, the College of American Pathologists, and the Association of Pathology Chairmen has completed and published three reports on pathology manpower supply and demand. The results of these studies agree with a recently completed study by a federally mandated commission. These studies show pathology manpower in the early 1980s is in good balance between supply and demand. They also indicate this equilibrium will continue until 1990 unless unanticipated changes in supply and demand take place.


[Establishment of an HBV chronic hepatitis B infection mouse model by vivo transduction of HBV cccDNA].
To generate a mouse model of chronic hepatitis B (CHB) infection by performing in vivo transduction of hepatitis B virus (HBV) covalently closed circular (ccc)DNA. Nude mice were injected with HBV cccDNA at doses of 1.5, 1.0 or 0.5 mug/ml. A control group was generated by giving equal injection volumes of physiological saline. The serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) on post-injection days 1 and 3, weeks 1-6, 8 and 10 were assayed by reflection immunoassay. At post-injection week 10, all animals were sacrificed and liver tissues were collected. Copies of HBV DNA in serum and liver tissue were detected by real-time PCR. HBV antigens in liver tissue were detected of by immunohistochemistry. Pathological analysis of liver tissue carried out with hematoxylin-eosin staining. Linear correlation of data was determined by statistical analysis. HBsAg and HBeAg were detected in sera from all three groups of cccDNA-injected mice staring at post-injection day 1 and lasting through week 10. The levels of HBsAg over the 10-week period showed two patterns of increase-decrease;the lowest level was detected at week 4 and the highest level was detected at week 8. In contrast, the levels of HBeAg over the 10-week period showed three patterns of increase-decrease; the lower levels were detected at weeks 2 and 4 and the higher levels at weeks 3 and 6. HBV DNA copies in liver tissues showed a cccDNA dose-dependent descending trend over the 10-week study period (1.5 mug/ml:1.14E+07 ± 6.51E+06 copies/g, 1.0 mug/ml:9.81E+06 ± 9.32E+06 copies/g, and 0.5 mug/ml:3.72E+06 ± 2.35E+06 copies/g; Pearson's r =0.979). HBV DNA copies in sera showed the pattern of 1.0 mug/ml cccDNA more than 1.5 mug/ml cccDNA more than 0.5 mug/ml cccDNA, and in general were higher than those detected in the liver tissues. Liver tissues from all cccDNA-injected mice showed positive immunohistochemistry staining for both HBsAg and HBeAg. HE staining showed that the liver tissues of all cccDNA-injected mice had severe fatty and vacuolar degeneration and less obvious structure of liver lobules (compared to the liver tissues from control mice). The CHB mouse model successfully established in this study by in vivo transduction of HBV cccDNA may represent a useful tool to study the pathogenic mechanisms and potential antiviral treatments of human CHB.


Treatment of infants with lymphoblastic leukaemia: results of the UK Infant Protocols 1987-1999.
One hundred and twenty-six infants with acute lymphoblastic leukaemia (ALL) were treated on two consecutive protocols, Infant 87 (n = 40) and Infant 92 (n = 86), in an attempt to improve the poor prognosis of this disease. Both included intensive induction and consolidation with intrathecal and high-dose systemic therapy for central nervous system (CNS) protection. Intensification therapy was modified and high-dose chemotherapy with bone marrow transplantation in first remission was permitted in Infant 92. Four-year event-free survival was superior in Infant 92 (33%; 95% CI 23-44%) compared with Infant 87 (22.5%; 95% CI 12-37%) (P = 0.04) and survival at 4 years was also superior, 46% (95% CI 35-57%) c.f. 32.5% (95% CI 20-48%) (P = 0.01), largely as a result of a significant reduction in remission deaths. Twelve patients in Infant 92 underwent bone marrow transplantation (BMT) in first remission, but their survival was no better than that of patients receiving chemotherapy. Multivariate analysis of prognostic factors showed the adverse influence of younger age, CNS involvement at diagnosis and a high initial leucocyte count, but not of CD10 expression. Cytogenetic analysis, available in 93% of patients in Infant 92, showed that 67% had chromosomal rearrangements involving 11q23 of which 39% had the translocation t(4;11) (q21;q23). There was no significant difference in event-free survival between cytogenetic subgroups, although no children under 6 months of age with 11q23 abnormalities, other than the t(4;11), survived. In conclusion, infants with lymphoblastic leukaemia remain a high-risk group, but it is unclear whether their adverse prognosis can be attributed to unfavourable cytogenetics alone. The role of high-dose therapy and BMT in first remission remains uncertain.


Factors affecting provision of successful monitoring in home Telehealth.
To investigate acceptance and usage issues in relation to Telehealth products as used by frail older clients of the Transition Care Program and their carers. The study design was a quasi-randomised controlled clinical trial. A stratified random sample of participants was allocated to one of five groups using a random number table. Study participants who were already in possession of a pendant alarm provided by the study service provider at study commencement, or were assessed as needing a pendant alarm, were allocated to the first number out of 1 (control group), 4 or 5 (home Telehealth monitoring with a pendant alarm up to 12 or 24 weeks) on the random number table list. If they were in possession of a pendant alarm that was not from the study service provider they were automatically allocated to the control group. If they were assessed as not needing a pendant alarm they were allocated to the first number on the list out of 2 or 3 (home Telehealth monitoring up to 12 or 24 weeks). In all instances, when a participant was allocated to the first applicable number on the list, that number was crossed off the list. A total of 43 participants who commenced the study used Telehealth equipment. There was a 13% Telehealth reading failure rate. There was no significant difference between clients with and clients without carers for the reading failure rate. This non-significant difference was consistent across all of the identified reasons for why readings failed including staff not following up, participant non-compliance (with and without carer), equipment failure, participants not returning a call from the staff investigating non-reading and user error. If the health of the client requires high reading rate reliability, the fact that the client has a carer to assist them cannot be assumed to increase the safe usage of the Telehealth equipment for reading rate reliability. As such staff should ensure that they are diligent in monitoring in-home Telehealth regardless of the presence or absence of a carer.


Experimental investigation of the immunoregulatory and anti-inflammatory effects of the traditional Chinese medicine "Li-Yan Zhi-Ke Granule" for relieving chronic pharyngitis in rats.
Chronic pharyngitis, a chronic inflammation of the pharyngeal mucous membrane and submucous lymphoid tissues, is often caused by unsatisfactory treatment of acute pharyngitis or repeated occurrences of upper respiratory tract infection and is related to a high-dust environment. Traditional herbal pharmacotherapy is well known for combining plant species to create complex phytochemical mixtures in the attempt to ameliorate pathophysiological processes. The aim of current study is to investigate the effect of immunoregulation and anti-inflammation with the traditional Chinese medicine (TCM) "Li-Yan Zhi-Ke Granule" in rats. Determination of serum hemolysin and the carbon particle clearance test were performed. The results demonstrate that administration of the TCM "Li-Yan Zhi-Ke Granule" may improve the effect of phagocytosis by mononuclear macrophages and immune function in rats, and may also increase the immunoregulatory and anti-inflammatory responses of rats with chronic pharyngitis. This traditional drug could relieve the symptoms of sore throat and cough in rats with chronic pharyngitis.


Impact of care pathways for in-hospital management of COPD exacerbation: a systematic review.
In-hospital management of COPD exacerbation is suboptimal, and outcomes are poor. Care pathways are a possible strategy for optimizing care processes and outcomes. The aim of the literature review was to explore characteristics of existing care pathways for in-hospital management of COPD exacerbations and to address their impact on performance of care processes, clinical outcomes, and team functioning. A literature search was conducted for articles published between 1990 and 2010 in the electronic databases of Medline, CINAHL, EMBASE, and Cochrane Library. Main inclusion criteria were (I) patients hospitalized for a COPD exacerbation; (II) implementation and evaluation of a care pathway; (III) report of original research, including experimental and quasi experimental designs, variance analysis, and interviews of professionals and patients about their perception on pathway effectiveness. Four studies with a quasi experimental design were included. Three studies used a pre-post test design; the fourth study was a non randomized controlled trial comparing an experimental group where patients were treated according to a care pathway with a control group where usual care was provided. The four studied care pathways were multidisciplinary structured care plans, outlining time-specific clinical interventions and responsibilities by discipline. Statistic analyses were rarely performed, and the trials used very divergent indicators to evaluate the impact of the care pathways. The studies described positive effects on blood sampling, daily weight measurement, arterial blood gas measurement, referral to rehabilitation, feelings of anxiety, length of stay, readmission, and in-hospital mortality. Research on COPD care pathways is very limited. The studies described few positive effects of the care pathways on diagnostic processes and on clinical outcomes. Though due to limited statistical analysis and weak design of the studies, the internal validity of results is limited. Therefore, based on these studies the impact of care pathways on COPD exacerbation is inconclusive. These findings indicate the need for properly designed research like a cluster randomized controlled trial to evaluate the impact of COPD care pathways on performance of care processes, clinical outcomes, and teamwork.


Mass extinction in a dynamical system of evolution with variable dimension.
Introducing the effect of extinction into the so-called replicator equations in mathematical biology, we construct a general model where the diversity of species, i.e., the dimension of the equation, is a time-dependent variable. The system shows very different behavior from the original replicator equation, and leads to mass extinction when the system initially has high diversity. The present theory can serve as a mathematical foundation for the paleontologic theory for mass extinction. This extinction dynamics is a prototype of dynamical systems where the variable dimension is inevitable.


Expression of TAK1, a mediator of TGF-beta and BMP signaling, during mouse embryonic development.
TGF-beta activated kinase 1 (TAK1) is a MAP kinase kinase kinase (MAPKKK) that has been shown to function downstream of BMPs and TGF-beta (J. Biol. Chem. 275 (2000) 17647; EMBO J. 17 (1998) 1019; Science 270 (1995) 2008), as well as in the interleukin-1 (IL-1) signaling pathway (J. Biol. Chem. 276 (2001) 3508; Nature 398 (1999) 252). Using immunohistochemistry (IHC), we demonstrate that TAK1 is expressed ubiquitously during early development. At mid-gestation, TAK1 expression becomes more restricted, with high levels seen specifically during development of diverse organs and tissues including the nervous system, testis, kidney, liver and gut. Additionally, TAK1 expression is seen in the developing lung and pancreas. Our results suggest that TAK1 may play multiple roles in mouse development.


Splenic marginal lymphoma and glomerulonephritis: case report and review of the literature.
Malignant lymphomas can affect kidneys in several ways. They may precipitate acute renal failure by causing ureteral or renal vascular obstruction, or by direct renal parenchymal infiltration. Furthermore, they may insult renal function via paraneoplastic mechanisms such as hypercalcemia. Lymphomas only rarely can cause glomerulonephritis (GN). We report a case of a 72-year-old male who presented with mild renal function impairment, proteinuria, and microscopic hematuria, suggesting active glomerulonephritis, and pancytopenia of immune origin. A bone marrow biopsy led to a diagnosis of splenic marginal zone lymphoma. Although a kidney biopsy was not performed, glomerulonephritis was attributed to the lymphoma and splenic marginal zone lymphoma-related glomerulonephritis was the final diagnosis. The course of splenic marginal zone lymphoma is extremely indolent. The first manifestation in some patients can be immune cytopenia or other autoimmune phenomena. These patients may respond well to corticosteroids. Therefore, our patient was started on prednisolone resulting in a good hematologic response. Renal function also improved and proteinuria and hematuria disappeared, suggesting a lymphoma-related origin of the GN. Two years after full steroids withdrawal, the patient remained stable with a good renal function and daily protein excretion less than 300 mg. Lymphomas rarely are the cause of secondary glomerulonephritis; however, with a lack of an apparent cause, the clinician should be aware of them, particularly in the elderly with autoimmune manifestations.


Bioequivalent or nonbioequivalent?
The current tests for bioequivalence are based on assumptions that are not valid in general; this paper shows why it is necessary to use a method that does not depend upon assumptions that cannot, and need not, be proved in general.


Effect of measles-virus infection and interferon treatment on invasiveness of Shigella flexneri in HEp2-cell cultures.
The influence of measles-virus infection on the invasiveness of Shigella flexneri in HEp2-cell cultures was studied. Bacterial invasiveness was significantly enhanced in cell cultures incubated with virus before bacterial inoculation. This effect was a function of time after introduction of virus to the cell cultures and of the concentration of virus. The increase in bacterial invasiveness was observed before production of infectious virus particles and before a cytopathic effect was evident. A similar enhancement of invasiveness was demonstrated when cell cultures were pretreated with UV-inactivated measles virus. Pretreatment of cells with interferon did not influence invasiveness, although it reduced the effect of measles-virus infection.


Neural regulation of the ovary: evidence for hypothalamic asymmetry in endocrine control.
The effects of hypothalamic hemi-islands on ovarian compensatory hypertrophy (OCH) were determined in prepubertal female rats. In animals with hypothalamic hemi-islands on the left side, OCH was blocked in rats hemi-ovariectomized on the ipsi- but not the contralateral side. A potential asymmetrical involvement of the hypothalamus in OCH was suggested by the further observation that this phenomenon could not be demonstrated in rats given hypothalamic hemi-islands on the right side and hemi-ovariectomized on the ipsi- or contralateral side. These data suggest that in addition to a possible direct neural contribution to endocrine feedback, the two-halves of the hypothalamus may differ in terms of their sensitivity to various components of endocrine control.


Protein Cysteinyl-S-Nitrosylation: Analysis and Quantification.
The thiol moiety of cysteine residues can undergo a number of biologic modifications including oxidation, sulfenylation, nitrosylation, persulfidation, metalation, and other modifications. These modifications can control biological function, including gain as well as loss of function. Herein, we focus attention on the proteomic analysis of S-nitrosylation in health and disease. We describe a novel quantitative approach that combines accurate, sensitive fluorescence modification of cysteinyl-S-nitrosylation that leaves electrophoretic mobility unaffected (SNOFlo), and introduce unique concepts for measuring changes in S-nitrosylation status relative to protein abundance. We present several studies where suitability of this approach for investigating endogenous S-nitrosylation is addressed.


Enhanced oxidative burst without interleukin 1 production by normal human polymorphonuclear leukocytes primed with muramyl dipeptides.
Purified polymorphonuclear (PMN) cells were obtained from human blood leukocytes by centrifugation on colloidal silica gradients. PMNs could be primed for PMA-triggered oxidative burst by muramyl peptide molecules (MDP) and two of its adjuvant active nonpyrogenic derivatives. The priming effect of MDP could be demonstrated after a 1-h incubation period, whereas monocytes needed an 18-h incubation to produce an enhanced response in the NBT reduction test. Only the monocyte-enriched population was able to produce IL-1 activity after muramyl peptide stimulation. Under such conditions, PMNs neither produced nor secreted IL-1-like activity, and no IL-1 inhibitor was present in the supernatant fluids. In conclusion, muramyl peptides were able to prime PMNs for oxidative burst but not to stimulate IL-1-like factor production.


Men cross America faster than women--the "Race Across America" from 1982 to 2012.
The sex difference in ultraendurance performance has been investigated in swimmers, runners, and triathletes but not in cyclists. The purpose of this study was to examine the sex difference in the longest ultra-cycling race in the world, the Race Across America (RAAM). Cycling speed of female and male finishers in the RAAM between 1982 and 2012 was compared. A total of 452 athletes including 404 men (89.4%) and 48 women (10.6%) finished. Mean cycling speed was 19.4 ± 2.0 km/h for men and 17.5 ± 2.0 km/h for women. Men were riding 1.9 ± 2.0 km/h (10.9%) faster than women. The fastest cycling speed ever was 24.77 km/h for men and 21.27 km/h for women, with a sex difference of 14.2%. Between 1982 and 2012, cycling speed was 22.7 ± 1.1 km/h for the annual fastest men and 18.4 ± 1.6 km/h for the annual fastest women, with an unchanged sex difference of 19.4% ± 7.3% (P > .05). For the annual top 3 men, cycling speed was 21.8 ± 0.9 km/h with no change across years (P > .05). The annual top 3 women achieved a cycling speed of 16.6 ± 1.0 km/h with no change over time (P > .05). The sex difference of 24.6% ± 3.0% showed no change across years (P > .05). In the last 30 y, men crossed America faster than women, and it seems unlikely that women will overtop men in the near future in the RAAM. However, the sex difference was only 14-15% among top competitors. Future studies need to analyze anthropometric, psychological, and physiological characteristics of successful female and male ultracyclists.


Many-particle dynamics and intershell effects in Wigner molecules.
We apply classical molecular dynamics within the velocity Verlet algorithm to examine the formation dynamics of Wigner crystals in two-dimensional harmonic oscillators. Using a large ensemble of initial conditions as well as different freezing mechanisms, we obtain reliable information on the energies and probabilities of stable and metastable configurations, their formation dynamics, and their stability. Wigner-crystal configurations of up to 30 particles are presented and the dynamics of transition processes, e.g., intershell effects, are analyzed.


[Cancer risk by family history--a cohort study in Kanagawa Prefecture].
Cancer family history was studied for 43,117 subjects aged 35-79 at the occasion of stomach cancer mass screening and were followed up for 5 years. 376 cases of cancer were notified out of them by the linkage with records of population based cancer registry covering the prefecture. Significantly elevated risk among those with family history was found only for breast cancer (observed 3, expected 0.82).


Drawing and the cerebral hemispheres: bilateral EEG alpha.
Bilateral EEG alpha (alpha) was measured during several cognitive tasks in two experiments. EEG alpha was suppressed relative to baseline in both hemispheres during every drawing and writing task. In addition, there were task-related EEG alpha asymmetries. Differences in left-hemisphere, but not right-hemisphere EEG alpha activity, were responsible for EEG alpha asymmetry differences between writing and drawing tasks. There was no difference in bilateral EEG alpha during drawing an upright versus an inverted drawing stimulus; failing to support Edward's (1977, 1979) 'cognitive shift' approach to drawing instruction.


Preparation, characterization and application of urease nanoparticles for construction of an improved potentiometric urea biosensor.
The nanoparticles (NPs) aggregates of commercial urease from jack beans (Canavalia ensiformis) were prepared by desolvation and glutaraldehyde crosslinking and functionalized by cysteamine dihydrochloride. These enzyme nanoparticles (ENPs) were characterized by transmission electron microscopy (TEM), UV and Fourier transform infrared (FTIR) spectroscopy. The TEM images of urease NPs showed their size in the range, 18-100nm with an average of 51.2nm. The ENPs were more active and stable with a longer shelf life than native enzyme molecules. The ENPs were immobilized onto chitosan (CHIT) activated nitrocellulose (NC) membrane via glutaraldehyde coupling with 32.22% retention of initial activity of free ureaseNPs with a conjugation yield of 1.63mg/cm2. This NC membrane was mounted at the lower/sensitive end of the ammonium ion selective electrode (AISE) with O-ring and then electrode was connected to a digital pH meter to construct a potentiometric urea biosensor. The biosensor exhibited optimum response within 10s at pH 5.5and 40°C. The biosensor was employed for measurement of potentiometric determination of urea in sera of apparently healthy and persons suffering from kidney disorders. The biosensor displayed a low detection limit of 1µM/L with a wide working range of 2-80µM/L (0.002-0.08mM) and sensitivity of 23mV/decade. The analytical recovery of added urea in serum was 106.33%. The within and between-batch coefficient of variations (CVs) of present biosensor were 0.18% and 0.32% respectively. There was a good correlation (r = 0.99) between sera urea values obtained by reference method (Enzymic colorimetric kit method) and the present biosensor. The biosensor had negligible interference from Na+,K+,NH+4 and Ca2+ but Mg2+,Cu2+ and ascorbic acid but had slight interference, which was overcome by specific ion selective electrode. The ENPs bound NC membrane was used maximally 8-9 times per day over a period of 180 days, when stored in 0.01M sodium acetate buffer pH 5.5 at 4°C.


External ventricular drain practice variations: results from a nationwide survey.
OBJECTIVE While guidelines exist for many neurosurgical procedures, external ventricular drain (EVD) insertion has yet to be standardized. The goal of this study was to survey the neurosurgical community and determine the most frequent EVD insertion practices. The hypothesis was that there would be no standard practices identified for EVD insertion or methods to avoid EVD-associated infections. METHODS The American Association of Neurological Surgeons membership database was queried for all eligible neurosurgeons. A 16-question, multiple-choice format survey was created and sent to 7217 recipients. The responses were collected electronically, and the descriptive results were tabulated. Data were analyzed using the chi-square test. RESULTS In total, 1143 respondents (15.8%) completed the survey, and 705 respondents (61.6%) reported tracking EVD infections at their institution. The most common self-reported infection rate ranged from 1% to 3% (56.1% of participants), and 19.7% of respondents reported a 0% infection rate. In total, 451 respondents (42.7%) indicated that their institution utilizes a formal protocol for EVD placement. If a respondent's institution had a protocol, only 258 respondents (36.1%) always complied with the protocol. Protocol utilization for EVD insertion was significantly more frequent among residents, in academic/hybrid centers, in ICU settings, and if the institution tracked EVD-associated infection rates (p < 0.05). A self-reported 0% infection rate was significantly more commonly associated with a higher level of training (e.g., attending physicians), private center settings, a clinician performing 6 to 10 EVD insertions within the previous 12 months, and prophylactic continuous antibiotic utilization (p < 0.05). CONCLUSIONS This survey demonstrated heterogeneity in the practices for EVD insertion. No standard practices have been proposed or adopted by the neurosurgical community for EVD insertion or complication avoidance. These results highlight the need for the nationwide standardization of technique and complication prevention measures.


Alcohol consumption and self-reported drinking-related problem behaviors as related to sex, work environment, and level of education.
This study examined the relation of sex, work environment, and level of education to self-reported alcohol-related problem behaviors and estimates of weekly consumption. 216 employees of various establishments located in the eastern United States participated in the study, which involved answering a 17-item questionnaire. It was hypothesized that men would report more problems and greater consumption than women, college educated individuals more than people with no college background, and employees of alcohol-related environments more than those of nonalcohol-related environments. The results confirmed the predictions for environment and sex. There were also significant interactions between sex and environment and for sex and education concerning consumption. The triple interaction was also significant for the consumption variable. Further investigation is needed to determine the ramifications for both employers and employees of alcohol-related areas.


Neuromuscular mechanisms of primary peristalsis.
Primary peristalsis of the esophagus is initiated by the act of swallowing. Control of the orderly contraction must take into account coordination of the activity in the esophageal body with the sphincters at either end, integration of activity between the striated and smooth muscle portions of the esophagus, and the central and peripheral neural and muscular control mechanisms present. Peristalsis in the striated section is directed by sequential vagal excitation arising in a brainstem "Central Program Generator." Peristalsis in the smooth muscle section involves the interaction of central and peripheral neural mechanisms and probably the interaction between these neural mechanisms and smooth muscle properties. Coordination of activity between the striated and smooth muscle portions has similar multifaceted neural and mechanical components. In the smooth muscle, 2 main neural mechanisms, a cholinergic excitatory one and a nonadrenergic, noncholinergic (NANC) inhibitory one interact together and with central and local influences to regulate the amplitude, velocity, and direction of propagation of the peristaltic contraction.


Patients' perceptions of information received about medication prescribed for bipolar disorder: implications for informed choice.
Previous research suggests that patients are dissatisfied with information provided about medication prescribed for mental illness, but has not identified which aspects of information provision are unsatisfactory. 223 members of the Manic Depression Fellowship (MDF) completed the Satisfaction with Information about Medicines Scale (SIMS), a validated measure of patients' satisfaction with various aspects of information provision. Patients reported highest dissatisfaction with information about potential problems associated with medication; over 60% of participants reported dissatisfaction with information about the risks of side effects and whether the medication would affect their sex lives. Participants were significantly less satisfied with information about potential problems associated with their medication than people prescribed medication for HIV in a previously reported study (p<.01). Those reporting low adherence to medication had significantly lower satisfaction with information scores than those reporting high adherence (p<.05). The sample could be prone to selection bias; participants were members of an organisation for people affected by bipolar disorder, whilst the comparator group was a NHS HIV clinic sample. Furthermore, the objective amount and type of information provided was not assessed, therefore the cause of patients' dissatisfaction is not known. Perceived satisfaction with information is low, particularly in relation to possible drug side-effects. Health practitioners need to elicit individuals' information requirements and tailor information to meet their needs, in order to facilitate informed choice and adherence to treatment. Moreover, they need to provide information in a manner appropriate for a patient's cognitive functioning at different illness phases.


Taphonomy of the early Miocene flora, Hiwegi Formation, Rusinga Island, Kenya.
A fossil flora was collected in situ from early Miocene deposits at site R117 in the Hiwegi Formation of Rusinga Island contemporaneous with and in close proximity to the sites from where the anthropoid primates were recovered. The flora exhibits a spatially and temporally patchy distribution of fruits and seeds, mixed with twigs of various sizes, fragments of wood, bark, and leaves, all with random orientations and very low depositional dips. There has been minimal transport and the flora evidently accumulated as in situ litter beneath local vegetation. Based on Nearest Living Relatives (NLR) of fruits and seeds, the vegetation represented is a deciduous broad-leaved woodland with continuous canopy, with trees, shrubs, lianas, and climbers, reminiscent of the structure of the modern vegetation in the steep-sided protected valleys in the Laetoli-Endulen area. The interpretation of the vegetation is supported by the presence of twigs, wood, and bark fragments from larger diameter axes. Climbers are represented by twining stem fragments as well as by a wide variety of distinctive fruits and seeds. The proportion of fossilised thorny twigs represents only 3% of the twig collections, and there are no unequivocal forest trees amongst the NLR. No grasses were present; monocotyledons are only represented by a single date palm stone. No conifer seeds or cones have been recovered, and there are no coniferous leafy shoots.


Conformational preferences in the Ser133-phosphorylated and non-phosphorylated forms of the kinase inducible transactivation domain of CREB.
Phosphorylation of Ser133 within the kinase inducible transactivation domain (KID) of the transcription factor CREB potentiates interaction with the KIX domain of coactivator CBP. Heteronuclear NMR spectroscopic analyses reveal that the KID domain is largely unstructured except for residues that comprise the alphaA helix in the pKID-KIX complex, which populate helical conformations to a significant extent (>50%). The helical content in the alphaB region is very small in the non-phosphorylated form (approximately 10%) although a small increase is detected upon Ser133 phosphorylation. The intrinsic bias towards helical conformations probably facilitates folding of the KID domain upon binding to KIX while the principal role of the phosphate group appears to be largely in mediating the intermolecular interactions in the pKID-KIX complex.


HD-MB03 is a novel Group 3 medulloblastoma model demonstrating sensitivity to histone deacetylase inhibitor treatment.
Medulloblastomas are the most common malignant brain tumors in childhood. Emerging evidence suggests that medulloblastoma comprises at least four distinct diseases (WNT, SHH, Group 3 and 4) with different biology, clinical presentation, and outcome, with especially poor prognosis in Group 3. The tight connection of biology and clinical behavior in patients emphasizes the need for subgroup-specific preclinical models in order to develop treatments tailored to each subgroup. Herein we report on the novel cell line HD-MB03, isolated from tumor material of a patient with metastasized Group 3 medulloblastoma, and preclinical testing of different histone deacetylase inhibitors (HDACis) in this model. HD-MB03 cells grow long term in vitro and form metastatic tumors in vivo upon orthotopic transplantation. HD-MB03 cells reflect the original Group 3 medulloblastoma at the histological and molecular level, showing large cell morphology, similar expression patterns for markers Ki67, p53, and glial fibrillary acidic protein (GFAP), a gene expression profile most closely matching Group 3 medulloblastomas, and persistence of typical molecular alterations, i.e., isochromosome 17q [i(17q)] and MYC amplification. Protein expression analysis of HDACs 2, 5, 8, and 9 as well as the predictive marker HR23B showed intermediate to strong expression, suggesting sensitivity to HDACis. Indeed, treatment with HDACis Helminthosporium carbonum (HC)-toxin, vorinostat, and panobinostat revealed high sensitivity to this novel drug class, as well as a radiation-sensitizing effect with significantly increased cell death upon concomitant treatment. In summary, our data indicate that HD-MB03 is a suitable preclinical model for Group 3 medulloblastoma, and HDACis could represent a therapeutic option for this subgroup.


Antibacterial compounds from the Australian native plant Eremophila glabra.
Recent reports of Eremophila glabra (R.Br.) Ostenf. (Scrophulariaceae) displaying antibacterial activity has led us to investigate the bioactive secondary metabolites responsible for this activity. Bioassay-directed fractionation of solvent extracts prepared from the leaves of E. glabra led to the isolation of seven serrulatane diterpenes, three flavonoids and the caffeoyl ester disaccharide verbascoside. Among these, four serrulatanes, namely 18-acetoxy-8, 20-dihydroxyserrulat-14-en-19-oic acid (14), 18,20-diacetoxy-8-hydroxyserrulat-14-en-19-oic acid (16), 8,18,20-triacetoxyserrulat-14-en-19-oic acid (17) and 18-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (18) are described for the first time, while 8,20-diacetoxyserrulat-14-en-19-oic acid (3), 8,18,20-trihydroxyserrulat-14-en-19-oic acid (5) and 20-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (19) were previously reported. All three flavonoids hispidulin (12), jaceosidin (13) and cirsimaritin (15) are known but reported for the first time in E. glabra. All compounds were tested in an agar diffusion antimicrobial assay against Staphylococcus aureus (NCTC 10442) and Staphylococcus epidermidis (ATCC 14990). Compounds 12, 13, 17, 18 and 19 exhibited moderate activity, with minimum inhibitory concentrations (MICs) ranging from 32 to 512μg/mL. Compound 19 demonstrated the highest activity against S. epidermidis ATCC 14990 with MIC of 32μg/mL, while 13 demonstrated the highest activity against S. aureus NCTC 10442 with MIC of 128μg/mL.


The role of hydroxychloroquine in the treatment of lichen planopilaris: A retrospective case series and review.
A variety of systemic agents are used to treat lichen planopilaris (LPP) with a limited evidence base. The aim of our study was to retrospectively review the response rate to and tolerability of hydroxychloroquine in a cohort of patients with LPP in an effort to add to the evidence base for its use. Twenty-three patients with a clinical and histopathological diagnosis of LPP who had been treated with hydroxychloroquine for their disease in a single center were identified. A retrospective review of these patients' medical records was performed and physician rated response was documented. Complete response was observed in 61% of our patients, and a further 9% of patients demonstrated partial response. Thirteen percent of patients withdrew from treatment because of suspected adverse effects. Our sample size was small, and data was collected retrospectively. We found hydroxychloroquine to be a reasonable therapeutic choice in LPP.


Mechanism for the origin and the evolutionary significance of heterochronia.
Using material on the evolution of the fundus of the oral cavity in amphibians, four principles were established for the origin of heterochronia: efficiency of ontogenesis; adaptability of an earlier (than in ancestors) beginning for functioning of traits; loss of the adaptive significance of a trait at a previous stage, but a preservation of it at a subsequent stage; and, a prolongation of the adaptive significance of a trait at later stages. The origin of heterochronia is associated with changes in the succession of the functioning of genes, with reorganization of systems of morphogenetic correlations, and with change in the traits themselves that undergo heterochronia. The uniqueness of heterochronia as an adaptation consists of an increase in the evolutionary flexibility of specific stages of ontogenesis.


Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma.
The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRI nu/nu mice with a combination of the hyaluronic-acid-cleaving enzyme hyaluronidase (HYase) and vinblastine is a very effective therapeutic procedure. In three out of four melanoma models (SK-MEL-2, -3, -5) the weekly peritumoral administration of high-dose HYase (100,000 IU/kg) 4 h prior to the injection of 0.3 mg/kg vinblastine in the vicinity of the tumor (seven weekly therapeutic cycles) caused marked antitumor effects, while HYase and vinblastine were inactive when given alone. The pretreatment with HYase, which is well tolerated by the test animals, prevented local inflammation reactions commonly seen after subcutaneous vinblastine administration. Tumor growth and metastatic behavior of the melanomas used were neither increased nor reduced by HYase after peritumoral administration without subsequent vinblastine injection. The curative activity of the regional chemotherapy with HYase/vinblastine could be demonstrated on the SK-Mel-3 melanoma. After an observation time of 18 weeks, tumor cells could no longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evidence of previously growing tumors. In contrast to the controls, no metastases could be observed in the axillary lymph nodes of the test animals.


The effects of instructional interventions related to street crossing and individuals with disabilities.
Adequate street crossing skills reduce the risk of injury and increase the functional independence of individuals with disabilities. This paper reviews research involving instructional interventions for street crossings with individuals with disabilities. Eight studies were included. There was evidence individuals could be taught street crossings using classroom based interventions, roadside instruction, or virtual reality technology. Classroom based methods were successful when involving strategies which promoted generalization of skills. Task analysis found the steps involved in street crossing included: stopping at the curb, looking left and right, walking quickly, walking within the crosswalk, and continuing to look left and right. A variety of instructional strategies were used, but the small body of literature did not allow clear identification of superior strategies.


A [+18RGD] protamine variant for nontoxic and effective reversal of conventional heparin and low-molecular-weight heparin anticoagulation.
Protamine sulfate reversal of heparin anticoagulation causes adverse side effects. Additionally, protamine sulfate is relatively ineffective at reversing factor Xa inhibition caused by low-molecular weight heparin (LMWH, Enoxaparin). Previously, a +18 compound partially reversed heparin and LMWH with minimal toxicity. In the present study, a new +18 protamine-like variant, [+18RGD], with an added RGD sequence [acetyl-EA(R2A2R2A)4R2GRGDSPA-amide], was compared to a previously developed compound, [+18BE,Acetyl-EAA-(K2A2K2A)4K2-Amide] and standard protamine [Prot +21] regarding the reversal of conventional unfractionated heparin (Hep) and LMWH. These three agents were given at 1 mg per 100 IU activity of Hep or LMWH rapidly over 10 sec. Hemodynamic toxicity was based on maximum declines in blood pressure, heart rate, cardiac output, and oxygen consumption over the first 5 min after reversal (calculated as a total toxicity score, TTS). The more negative the TTS, the more toxic the agent. Degrees of toxicity (TTS) of [+18RGD], [+18BE],and[Prot +21] for reversal of Hep were -1.19, -2.00, and -7.32, respectively; and for reversal of LMWH they were -2.85, -3.98,and -6.17, respectively. These differences were significant for Hep (P < 0.01) and approached significance for LMWH (P = 0.07). Maximum hemodynamic perturbations paralleled the TTS pattern. [+18RGD] provided equal reversal efficacy to [Prot +21] for Hep, with a statistically significant (P < 0.05) lessening of platelet count declines (Plt 27, -46, and -55%, respectively). [+18RGD] improved reversal efficacy for LMWH, at 3, 10, and 30 min following its administration. At 3 min, antifactor Xa reversal was 72, 40, and 30%, respectively, for [+18RGD], [+18BE], and [Prot +21]; [+18RGD] effects were significantly better (P < 0.01). [+18RGD] reversed both Hep and LMWH anticoagulation with minimal toxicity. Such a compound should decrease clinical complications attending the use of standard protamine for reversal of conventional heparin or LMWH anticoagulation.


Combined C-11 methionine and F-18 FDG PET imaging in a case of neurosarcoidosis.
PET scanning of the brain with F-18 FDG and C-11 methionine (MET) is useful for characterizing brain lesions discovered at MRI or CT. Most positive PET scans indicate malignancy. However, this case report demonstrates positive F-18 FDG and C-11 MET PET scans in a patient with a nonmalignant condition, neurosarcoidosis. We detail the history and evaluation of a 59-year-old woman who presented with ataxia. The patient's evaluation included a contrast-enhanced MRI followed by PET scanning of the brain with C-11 MET and of the brain and trunk with F-18 FDG. The patient subsequently underwent biopsy of a lesion as directed by MRI and PET. The MRI demonstrated multiple enhancing leptomeningeal lesions consistent with metastatic disease. PET with F-18 FDG and C-11 MET demonstrated lesions in both cerebellar hemispheres with F-18 FDG accumulation in the mediastinum and left hilum. Biopsy of a brain lesion directed by MRI and PET revealed sarcoidosis. In evaluating brain lesions, PET with F-18 FDG and C-11 MET can help localize the lesion best suited for biopsy. However, not all lesions that have increased uptake on C-11 MET or F-18 FDG PET are malignant. Granulomatous inflammatory diseases such as neurosarcoidosis should also be considered in the differential diagnosis.


Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study.
Increases in resting-state heart rate and decreases in its variability are associated with substantial morbidity and mortality, yet contradictory findings have been reported for the effects of the mood and anxiety disorders and of antidepressants. The authors investigated heart rate and heart rate variability in a large cohort from Brazil, using propensity score weighting, a relatively novel method, to control for numerous potential confounders. A total of 15,105 participants were recruited in the Brazilian Longitudinal Study of Adult Health. Mood and anxiety disorders were ascertained using the Portuguese version of the Clinical Interview Schedule-Revised. Heart rate and its variability were extracted from 10-minute resting-state electrocardiograms. Regressions weighted by propensity scores were carried out to compare participants with and without depressive or anxiety disorders, as well as users and non-users of antidepressants, on heart rate and heart rate variability. Use of antidepressants was associated with increases in heart rate and decreases in its variability. Effects were most pronounced for the tricyclic antidepressants (Cohen's d, 0.72-0.81), followed by serotonin and norepinephrine reuptake inhibitors (Cohen's d, 0.42-0.95) and other antidepressants (Cohen's d, 0.37-0.40), relative to participants not on antidepressants. Only participants with generalized anxiety disorder showed robust, though small, increases in heart rate and decreases in its variability after propensity score weighting. The findings may, in part, underpin epidemiological findings of increased risk for cardiovascular morbidity and mortality. Many factors that have an adverse impact on cardiac activity were controlled for in this study, highlighting the importance of cardiovascular risk reduction strategies. Further study is needed to examine whether, how, and when such effects contribute to morbidity and mortality.