Thrombocytopenia in pregnancy: diagnosis, pathogenesis and management.
Maternal thrombocytopenia is a common find during pregnancy. The rapid determination of its cause can often be difficult, with the diagnosis only being made in retrospect once the course of the platelet count is known. The majority of patients with thrombocytopenia in pregnancy will have incidental thrombocytopenia of pregnancy which is of no clinical significance.


Assessment of Physicochemical and Microbiological Quality of Public Swimming Pools in Addis Ababa, Ethiopia.
From swimming pools, bathers may acquire many potential pathogens or may be affected by the physicochemical characteristics of water used during bathing. Hence, this study aimed at assessing the physicochemical and microbiological quality of public swimming pools located at different hotels and recreation center in Addis Ababa, Ethiopia. A cross sectional study was carried out from February to May, 2016. Nine hotels and one recreation center which recognized to have public swimming services were included. A total of 60 swimming pool water samples from 10 swimming pools were collected at deeper, shallow and intake point twice on a weekly basis using a 250 ml sterile bottle containing sodium thiosulphate. PH, residual chlorine and temperature of samples were recorded at the time of collection. Sample containing bottles were transported in ice box to microbiological laboratory and analyzed on the same day. Standard cultural and biochemical methods were used for isolation and characterization of the main microbial groups. Total viable count, total coliform count, fecal coliform count and E. coli were determined. Data was analyzed using SPSS Version 20. Average PH and temperature of swimming pool water samples were 7.1 and 29oC respectively. Of all analyzed water samples, 58.4% (n=35/60) of them had PH range of 7.2-7.8, 58.3% (n=35/60) of samples had temperature in the range of 21oC-32oC and 25% (n=15/60) of water samples had residual chlorine in the range of 2-3mg/l. 73.3% (n=44/60) of the samples had a total viable count below 200 MPN/ml and 70% (n-42/60) of the samples had Total Coliform Count values less than 2 MPN/100 ml. Moreover, 66.7% (n=40/60) of the samples had fecal coliform counts falling below 1 MPN /100 ml. E. coli was absent in 70% (n=42/60) of the samples while it was present in 30% (n=18/60) of the samples. PH, residual chlorine and temperature value of majority of the swimming pools' water samples were within the acceptable limit. Regarding microbial quality, most swimming pools' water samples complied to the WHO standard. Swimming pools that did not comply to the standard both in physicochemical levels and microbial quality need improvement due to their significant health implication.


Interaction of antimalarial drugs with hemin.
Hemin (ferriprotoporphyrin IX) is shown to form complexes with the chloroquine class of antimalarial drugs. The Soret band of hemin becomes optically active upon the addition of chiral drugs. Results on the hemin-induced quenching of the fluorescence of chloroquine are consistent with the formation of a 2:1 hemin:drug complex with a formation constant of 1.4 x 10(7) at 298 K. Also a direct comparison of the drug-treated and drug-free parasites themselves, by the noninvasive photoacoustic spectroscopic method, reveals an in vivo interaction between endogenous hemin and the added drug.


The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia.
Mutations in ectodysplasin, the protein product of the EDA or ED1 gene, cause X-linked anhidrotic ectodermal dysplasia. From sixteen families we have identified thirteen mutations, of which nine were novel: a deletion of the entire exon 1, altered splicing site in intron 7 (IVS-2A-->G) and in intron 9 (IVS9+8 C-->G), deletion of 8 bp (1967-1974 nt), four missense mutations (G255C, G255D, W274G, C332Y) and nonsense mutation W274X. Previously identified and the novel mutations form four clusters: 1) at the junction of the transmembrane and extracellular domains, 2) at a putative protease recognition site, possibly affecting cleavage of ectodysplasin, 3) at the trimerizing collagen-like domain, and 4) at regions of high homology to tumor necrosis factor domains. Truncating and splice site mutations occur within the proximal two-thirds of the protein. Our data suggest the functional importance of specific ectodysplasin domains. Hum Mutat 17:349, 2001.


Should Benzodiazepines and Anticonvulsants Be Used During Electroconvulsive Therapy?: A Case Study and Literature Review.
This study aims to investigate the clinical effects of benzodiazepines or anticonvulsant use during a course of electroconvulsive therapy (ECT). A case report study of a patient who received ECT with and without concomitant flurazepam and pregabalin is presented. The literature on the use of benzodiazepines and anticonvulsants during ECT is reviewed. A woman with treatment resistant depression received a course of ECT while taking flurazepam and pregabalin, but seizures were of short duration and symptomatic improvement was minimal. After discontinuation of flurazepam and pregabalin, a course of right unilateral ultrabrief ECT was associated with adequate seizures and remission of depression and suicidal ideation. Our literature review suggests that benzodiazepines decrease seizure duration, but most evidence shows no association with increased seizure threshold. One prospective RCT and 3 large retrospective studies found that benzodiazepines compromise the efficacy of unilateral but not bilateral ECT. Regarding anticonvulsants, several studies had varied and contradictory results on their effect on seizure duration and seizure threshold. Of the 2 large retrospective studies and 3 RCTs, only 1 retrospective study showed that anticonvulsants decrease the efficacy of ECT. Judicious assessment of all medications used in combination with ECT is recommended. Overall, published studies suggest that benzodiazepines and anticonvulsants impact the clinical outcomes of ECT less than what would be expected given their pharmacologic effects. However, there are significant gaps in the literature, including a lack of study on suprathreshold stimulation of right unilateral ECT and the possibility of a greater effect with higher medication doses.


Clonal dominance. I. Restricted nature of the IgM antibody response to group A streptococcal carbohydrate in mice.
The IgM antibody response of mice to the streptococcal group A carbohydrate (GAC) was measured. With most strains tested, large amounts of IgM antibody were produced; in AKR mice, over 1% of the total nucleated spleen cells secreted IgM anti-GAC antibody after hyperimmunization. The relative avidity of the antibody was extimated by a modification of the Jerne plaque assay where spleen cells from individual mice were tested against erythrocytes with varying GAC epitope densitymthese studies showed that the earliest, as well as latest, IgM antibodies produced were highly restricted in avidity heterogeneity. No evidence of affinity maturation was seen upon hyperimmunization. These data favor the conclusion that the restricted IgG response seen in mice hyperimmunized to GAC is not the result of affinity driven competition for antigen among precursor cells.


Intrinsic subtype-associated changes in the plasma proteome in breast cancer.
Breast cancers are classified into five intrinsic subtypes: Luminal subtype A, Luminal subtype B, HER2+, Basal, and Normal-like. In this study, we compared the plasma proteome of patients with Luminal A, Luminal B, HER2+, and Basal subtype with plasma from healthy individuals. Protein changes were considered significant if q-value (false discovery rate) was less than 5%. The highest number of changes in the plasma proteome was observed in patients with Luminal type B followed by Basal type breast cancers. The plasma proteome of Luminal A and HER2+ breast cancer patients did not differ significantly from healthy individuals. In Basal breast cancer, a significant number of plasma proteins were downregulated compared with healthy individuals. Acute phase-response proteins α-glycoprotein orosomucoid 1 and serum amyloid protein P were specifically upregulated in the plasma of Luminal B breast cancer patients, suggesting prevalence of low-grade inflammation. Proteins involved in immune response and free radical scavenging were downregulated in the plasma of Luminal B patients, which is in agreement with defective immune system observed in cancer patients. These results reveal intrinsic subtype specific changes in the plasma proteome that may influence tumor progression as well as the systemic effects of cancer.


Spatiotemporal control of small GTPases with light using the LOV domain.
Signaling networks in living systems are coordinated through subcellular compartmentalization and precise timing of activation. These spatiotemporal aspects ensure the fidelity of signaling while contributing to the diversity and specificity of downstream events. This is studied through development of molecular tools that generate localized and precisely timed protein activity in living systems. To study the molecular events responsible for cytoskeletal changes in real time, we generated versions of Rho family GTPases whose interactions with downstream effectors is controlled by light. GTPases were grafted to the phototropin LOV (light, oxygen, or voltage) domain (Huala, E., Oeller, P. W., Liscum, E., Han, I., Larsen, E., and Briggs, W. R. (1997). Arabidopsis NPH1: A protein kinase with a putative redox-sensing domain. Science278, 2120-2123.) via an alpha helix on the LOV C-terminus (Wu, Y. I., Frey, D., Lungu, O. I., Jaehrig, A., Schlichting, I., Kuhlman, B., and Hahn, K. M. (2009). A genetically encoded photoactivatable Rac controls the motility of living cells. Nature461, 104-108.). The LOV domain sterically blocked the GTPase active site until it was irradiated. Exposure to 400-500nm light caused unwinding of the helix linking the LOV domain to the GTPase, relieving steric inhibition. The change was reversible and repeatable, and the protein could be returned to its inactive state simply by turning off the light. The LOV domain incorporates a flavin as the active chromophore. This naturally occurring molecule is incorporated simply upon expression of the LOV fusion in cells or animals, permitting ready control of GTPase function in different systems. In cultured single cells, light-activated Rac leads to membrane ruffling, protrusion, and migration. In collectively migrating border cells in the Drosophila ovary, focal activation of photoactivatable Rac (PA-Rac) in a single cell is sufficient to redirect the entire group. PA-Rac in a single cell also rescues the phenotype caused by loss of endogenous guidance receptor signaling in the whole group. These findings demonstrate that cells within the border cell cluster communicate and are guided collectively. Here, we describe optimization and application of PA-Rac using detailed examples that we hope will help others apply the approach to different proteins and in a variety of different cells, tissues, and organisms.


An evaluation of a competency tool (Niche) to develop nursing assistants.
As UK society changes, with people living longer and with chronic conditions, and less people available of working age to provide nursing care, there is a need to re-think how health-care is organized and delivered. This is likely to have an affect on the non-registered component of the health-care workforce. However, if patient safety is to be maintained, it is paramount that the competence of individuals taking on roles that were carried out by trained staff must be ensured. This pilot study of a competency tool, National Incremental Competencies in Healthcare Education (Niche), demonstrated that individuals could expand or change their role as a result of completing the educational package. The evaluation aims to examine the usefulness of this competency tool in preparing nursing assistants to take on new roles and meet patients' needs.


Embedding security into ferroelectric FET array via in situ memory operation.
Non-volatile memories (NVMs) have the potential to reshape next-generation memory systems because of their promising properties of near-zero leakage power consumption, high density and non-volatility. However, NVMs also face critical security threats that exploit the non-volatile property. Compared to volatile memory, the capability of retaining data even after power down makes NVM more vulnerable. Existing solutions to address the security issues of NVMs are mainly based on Advanced Encryption Standard (AES), which incurs significant performance and power overhead. In this paper, we propose a lightweight memory encryption/decryption scheme by exploiting in-situ memory operations with negligible overhead. To validate the feasibility of the encryption/decryption scheme, device-level and array-level experiments are performed using ferroelectric field effect transistor (FeFET) as an example NVM without loss of generality. Besides, a comprehensive evaluation is performed on a 128 × 128 FeFET AND-type memory array in terms of area, latency, power and throughput. Compared with the AES-based scheme, our scheme shows ~22.6×/~14.1× increase in encryption/decryption throughput with negligible power penalty. Furthermore, we evaluate the performance of our scheme over the AES-based scheme when deploying different neural network workloads. Our scheme yields significant latency reduction by 90% on average for encryption and decryption processes.


Differential cavitation, angiogenesis and wound-healing responses in injured mouse and rat spinal cords.
The vascular disruption, blood vessel loss and cavitation that occur at spinal cord injury (SCI) epicenters in mice and rats are different, but few studies have compared the acute SCI response in the two species. This is of interest since key elements of the rat SCI response are shared with humans. In this study, we investigated acute SCI responses and characterized changes in pro- and anti-angiogenic factors and matrix deposition in both species. Cavitation was absent in mouse but the area of the lesion site was 21- and 27-fold larger at 8 and 15 days post-lesion (dpl), respectively, in the rat compared to intact control. The absence of wound cavitation in the mouse was correlated with increased levels of immunoreactive pro-angiogenic, pro-matrix and pro-wound-healing factors, e.g. laminin, matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-A (VEGF-A) within the wound, which were 6.0-, 2.9-, and 2.8-fold, respectively, higher in the mouse compared to rats at 8 dpl. Increased axonal sparing was observed after dorsal column (DC) injury, detected by higher levels of neurofilament 200 (NF200) immunoreactivity in the dorsal column of mice compared to rats at both T7 and T9 spinal segments. Despite similar post SCI deficits in plantar heat tests at 2h after injury (1.4- and 1.6-fold lower than control mice and rats, respectively), by 7 days the magnitude of these responses were comparable to sham-treated controls in both species, while no post-SCI changes in Von Frey hair filament test response were observed in either species. We conclude that the more robust angiogenesis/wound-healing response in the mouse attenuates post-injury wound cavitation. Although the spinal cord functions that were monitored post-injury were similarly affected in both species, we suggest that the quality of the angiogenesis/wound-healing response together with the diminished lesion size seen after mouse SCI may protect against secondary axon damage and create an environment more conducive to axon sprouting/regeneration. These results suggest the potential therapeutic utility of manipulating the angiogenic response after human SCI.


Low-energy constraints on photoelectron spectra measured from liquid water and aqueous solutions.
We report on the effects of electron collision and indirect ionization processes, occurring at photoexcitation and electron kinetic energies well below 30 eV, on the photoemission spectra of liquid water. We show that the nascent photoelectron spectrum and, hence, the inferred electron binding energy can only be accurately determined if electron energies are large enough that cross sections for quasi-elastic scattering processes, such as vibrational excitation, are negligible. Otherwise, quasi-elastic scattering leads to strong, down-to-few-meV kinetic energy scattering losses from the direct photoelectron features, which manifest in severely distorted intrinsic photoelectron peak shapes. The associated cross-over point from predominant (known) electronically inelastic to quasi-elastic scattering seems to arise at surprisingly large electron kinetic energies, of approximately 10-14 eV. Concomitantly, we present evidence for the onset of indirect, autoionization phenomena (occurring via superexcited states) within a few eV of the primary and secondary ionization thresholds. These processes are inferred to compete with the direct ionization channels and primarily produce low-energy photoelectrons at photon and electron impact excitation energies below ∼15 eV. Our results highlight that vibrational inelastic electron scattering processes and neutral photoexcitation and autoionization channels become increasingly important when photon and electron kinetic energies are decreased towards the ionization threshold. Correspondingly, we show that for neat water and aqueous solutions, great care must be taken when quantitatively analyzing photoelectron spectra measured too close to the ionization threshold. Such care is essential for the accurate determination of solvent and solute ionization energies as well as photoelectron branching ratios and peak magnitudes.


Breath testing as a method for detecting lung cancer.
Early diagnosis of lung cancer is important due to high mortality in late stages of the disease. An ideal approach for population screening could be the breath analysis, due to its non-invasiveness, simplicity and cheapness. Using sensitive methods of analysis like gas chromatography/mass spectrometry in exhaled air of cancer patients were discovered some volatile organic compounds - possible candidates for cancer markers. However, these compounds were not specific for cancer cells. At the same time, integrative approaches used to analyze the exhaled breath have demonstrated high sensitivity and specificity of this method for lung cancer diagnosis. Such integrative approaches include detection of smell prints by electronic nose or integrated analysis of wide range of volatile organic compounds detected by gas chromatography/mass spectrometry or related methods. Modern statistical pattern recognition systems like logistic regression analysis, support vector machine or analysis by artificial neuronal network may improve diagnostic accuracy.


Cognitive content specificity in anxiety and depressive disorder symptoms: a twin study of cross-sectional associations with anxiety sensitivity dimensions across development.
The classification of anxiety and depressive disorders has long been debated and has important clinical implications. The present study combined a genetically sensitive design and multiple time points to investigate cognitive content specificity in anxiety and depressive disorder symptoms across anxiety sensitivity dimensions, a cognitive distortion implicated in both disorders. Phenotypic and genetic correlations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were examined at five waves of data collection within childhood, adolescence and early adulthood in two representative twin studies (n pairs = 300 and 1372). The physical concerns dimension of anxiety sensitivity (fear of bodily symptoms) was significantly associated with anxiety but not depression at all waves. Genetic influences on physical concerns overlapped substantially more with anxiety than depression. Conversely, mental concerns (worry regarding cognitive control) were phenotypically more strongly associated with depression than anxiety. Social concerns (fear of publicly observable symptoms of anxiety) were associated with both anxiety and depression in adolescence. Genetic influences on mental and social concerns were shared to a similar extent with both anxiety and depression. Phenotypic patterns of cognitive specificity and broader genetic associations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were similar at all waves. Both disorder-specific and shared cognitive concerns were identified, suggesting it is appropriate to classify anxiety and depression as distinct but related disorders and confirming the clinical perspective that cognitive therapy is most likely to benefit by targeting cognitive concerns relating specifically to the individual's presenting symptoms across development.


Comparative Proteomic Analysis of Slime from the Striped Pyjama Squid, Sepioloidea lineolata, and the Southern Bottletail Squid, Sepiadarium austrinum (Cephalopoda: Sepiadariidae).
Sepioloidea lineolata, the striped pyjama squid (family Sepiadariidae), is a small species of benthic bobtail squid distributed along the Southern Indo-Pacific coast of Australia. Like other sepiadariid squids, it is known to secrete large volumes of viscous slime when stressed. In order to identify key proteins involved in the function of sepiadariid slimes, we compared the slime proteome of Sepioloidea lineolata with that of a closely related species, Sepiadarium austrinum. Of the 550 protein groups identified in Sepioloidea lineolata slime, 321 had orthologs in Sepiadarium austrinum, and the abundance of these (iBAQ) was highly correlated between species. Both slimes were dominated by a small number of abundant proteins, and several of these were short secreted proteins with no homologues outside the class Cephalopoda. No mucins were identified within either species' slime, suggesting that it is structurally distinct from mucin polymer-based gels found in many vertebrate and echinoderm secretions. The extent of N-glycosylation in the slime of Sepioloidea lineolata was also studied via glycan cleavage with Peptide: N-glycosidase F (PNGase-F). Although very few (four) proteins showed strong evidence of N-glycosylation, we found that treatment with PNGase-F led to a slight increase in peptide identification rates compared with controls.


Hyperglycemia induces apoptosis of human pancreatic islet endothelial cells: effects of pravastatin on the Akt survival pathway.
Pancreatic islet microendothelium and beta cells exhibit an interdependent physical and functional relationship. In this study, we analyzed the effect of chronic hyperglycemia on human pancreatic islet microendothelial cells as well as the involvement of the phosphatidylinositol 3-kinase/Akt and nephrin pathways, interleukin-1beta, and nitric oxide production. In addition, whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors can reverse the response to high-glucose conditions was investigated. Proliferation of purified islet microendothelial cells cultured under hyperglycemic conditions (28 mmol/L glucose) decreased compared to that of normoglycemic cells (from 12.7% after 2 days to 47.7% after 30 days, P < 0.05). In parallel, apoptosis progressively increased from 7% after 2 days to 79% after 30 days in high glucose (P < 0.05) concomitant with an early increase of caspase-3 activity. Intermittent hyperglycemia induced greater apoptosis than sustained hyperglycemia. Apoptosis was accompanied by a reduced p-Akt/Akt ratio and inhibition of nephrin tyrosine phosphorylation. Pravastatin (1 mumol/L) decreased apoptosis induced by high glucose or oxidized LDL and increased Akt phosphorylation. Hyperglycemia significantly increased the production of the proinflammatory cytokine interleukin-1beta and stimulated the expression of inducible nitric oxide synthase and the production of nitric oxide, possibly relevant to beta cell mass and function. Thus, chronic hyperglycemia reduces islet microendothelial cell survival by inhibiting the serine-threonine kinase Akt pathway, and the effect of pravastatin on this pathway represents a potential tool to improve islet vascularization and, indirectly, islet function.


The Goldston syndrome: report of a case.
We present a case of the Goldston syndrome--that is, cystic renal dysplasia and the Dandy-Walker malformation. The condition was diagnosed by ultrasound in a 635 g fetus in the seventeenth week of gestation. Ultrasound studies showed the fetal head to be somewhat enlarged with slight dilatation of the lateral ventricles and marked dilatation of the fourth ventricle. The kidneys were symmetrically enlarged and multicystic. Autopsy revealed evidence of the oligohydramnios syndrome. The kidneys were typical of the Goldston syndrome as were the microscopic lesions in the liver. To our knowledge this is the first reported case in which this diagnosis was made during intrauterine life.


Tailoring Polymersome Shape Using the Hofmeister Effect.
Reshaping polymersomes remains a challenge for both size and shape control, methodology development, and mechanism understanding, which hindered their application in nanomedicine and nanomachine. Unlike liposome, polymersomes are capable of maintaining their shape due to their rigid and glassy membrane. Here we use the Hofmeister effect to guide the shape control of polymersome by tuning the ion type and concentration. Multiple morphologies such as ellipsoid, tube, disc, stomatocytes, and large compound vesicles are found. These results give evidence of demonstrating that the shape changes are not only induced by osmotic pressure, but also by the interaction with the polymersome membranes. Additionally, this methodology provides a general tool to tailor the shape of polymersome into various morphologies.


Compensatory changes in contralateral sympathetic neurons of the superior cervical ganglion and in their terminals in the pineal gland following unilateral ganglionectomy.
The sympathetic noradrenergic neurons of the rat superior cervical ganglia (SCGs) provide the major source of innervation to the pineal gland. The present study sought to determine if this sympathetic innervation can undergo collateral sprouting following partial denervation of the pineal by unilateral removal of the SCG (ganglionectomy), and whether such growth of axon terminals is associated with biochemical changes in the contralateral SCG. In the pineal gland following partial denervation, residual noradrenergic terminals underwent compensatory changes indicative of collateral sprouting, as evidenced by: a rapid reduction in tyrosine hydroxylase (TH) activity and in [3H]norepinephrine (NE) uptake, to about 50% of control by 2 days, which was followed by a gradual but sustained increase to levels of approximately 80% of control by 10 days and a reduction in the intensity and density but not in the distribution of fibers containing NE-induced fluorescence by 2 days, which was followed by a sustained increase. In the contralateral SCG, choline acetyltransferase (CAT) activity, a marker of cholinergic preganglionic terminals, was transiently increased to about 115% of control by 4 days and returned to control levels by 14 days after unilateral ganglionectomy; later, TH activity in noradrenergic cell bodies was gradually increased to about 140% of control by 10 days where it remained for up to 52 days. Unilteral ganglionectomy combined with decentralization of the contralateral SCG by preganglionic nerve cut prevented the compensatory changes in noradrenergic nerve terminals within the pineal.(ABSTRACT TRUNCATED AT 250 WORDS)


Carbon nanostructures in biology and medicine.
Carbon nanostructures have unique physical, chemical, and electrical properties, which have attracted great interest from scientists. They are being successfully implemented in sensing, biomedical and biological related studies. This review selectively analyzes current advances in the field of carbon nanostructure bioapplications. A very detailed review is presented on how carbon nanomaterials are currently exploited for biosensing and biomedical applications. To begin with, properties of carbon nanostructures will be discussed, involving their unusual structure, extraordinary electronic properties and fascinating electron transport. The next major section deals with the exciting progress related to carbon materials in electrochemistry, including electrochemical sensing, biomedical and biological applications. We classify biosensors developed so far by their signal generation strategy and provide a comprehensive overview of them. In addition, we offer insights into how the carbon nanostructures are used in each sensor system and how they improve the sensing performance. Finally, prospects and further developments in this exciting field of carbon materials are also suggested. In particular, the biofunctionalization of carbon nanostructures for biomedical applications, biosensor development by using carbon nanomaterials, and the investigation of carbon nanomaterials for living cell studies are summarized in more detail. Future perspectives and possible challenges in this rapidly developing area are also discussed.


Measuring shifts in function and evolutionary opportunity using variability profiles: a case study of the globins.
Variability profiles measured over a set of aligned sequences can be used to estimate evolutionary freedom to vary. Differences in variability profiles between clades can be used to identify shifts in function at the molecular level. We demonstrate such a shift between the alpha and beta subunits of hemoglobin. We also show that the variability profiles for myoglobin are different between whales and primates and speculate that the differences between the two clades may reflect a shift associated with the novel oxygen storage demands in the lineage leading to whales. We discuss the relationship between sequence variability and "evolutionary opportunity" and explore the utility of Maynard Smith's multidimensional evolutionary opportunity space metaphor for exploring functional constraints, genetic redundancy, and the context dependency of the genotype-phenotype map. This work has implications for quantitatively defining and comparing protein function. Supplementary data is available from bioinfo.mbb.yale. edu/align.


Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy.
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection caused by the JC virus that has no proven effective treatment. Although rare cases of PML have occurred with other anti-CD20 therapies, there had been no prior cases associated with ocrelizumab. To report the first ever case of PML occurring with ocrelizumab monotherapy in a patient with progressive multiple sclerosis without prior immunomodulation. This case was reported from an academic medical center. The patient had multiple sclerosis while receiving ocrelizumab monotherapy. Ocrelizumab monotherapy. A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient's symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy. In this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.


Artificial Turf Increases the Physical Demand of Soccer by Heightening Match Running Performance Compared with Natural Grass.
Modric, T, Esco, M, Perkovic, S, Basic, Z, Versic, S, Morgans, R, and Sekulic, D. Artificial turf increases the physical demand of soccer by heightening match running performance compared with natural grass. J Strength Cond Res 37(11): 2222-2228, 2023-This study aimed to determine differences in match running performance (MRP) of elite soccer players (n = 31) during matches played on artificial turf (AT) and natural grass (NG). The players' MRP (AT; 131 observations, NG; 135 observations) were collected during official matches (n = 32) using global positioning system and classified according to their playing positions as central defenders, central midfielders, fullbacks, forwards, and wingers. The MRP variables included total distance covered (TD), low-intensity running (LIR), moderate-intensity running (MIR), high-intensity running (HIR), total (Tacc) and high-intensity accelerations (Hacc), and total (Tdec) and high-intensity decelerations (Hdec). The influence of match outcome, location, and opponent quality was controlled for as contextual factors. Playing matches on AT resulted in (a) increased TD (Cohen's d (d) = 0.55, 0.61, and 0.28, respectively), MIR (d = 0.91, 0.79, and 0.49, respectively), and HIR (d = 0.67, 0.44, and 0.38, respectively) for central defenders, central midfielders, fullbacks; (b) increased Tacc (d = 0.38, 0.37, and 0.4, respectively) and Tdec (d = 0.31, 0.34, and 0.31, respectively) for central defenders, central midfielders, and wingers; and (c) decreased Hdec (d = -1.5) for forwards. These results show that playing on AT is more physically demanding for defensive and midfield players than playing on NG. Soccer coaches should consider implementing preparatory strategies that mitigate the increased demands of playing on AT for these players, especially before a competitive period when transitions between pitch surfaces routinely occur.


Molecular detection and characterization of highly pathogenic porcine reproductive and respiratory syndrome virus from a natural outbreak in wild pigs, Mizoram, India.
This study reports for the first time a natural outbreak of highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) caused by HP-PRRS virus (HP-PRRSV) in wild pigs characterized by sudden onset of depression, anorexia, respiratory distress, and high fever. The disease has caused severe haemorrhagic pneumonia, haemorrhagic lymphadenitis, enlarged spleen with areas of infarction, and petechial haemorrhages on the myocardium and on the surface of kidneys. HP-PRRSV was detected in representative tissue samples by reverse transcription-PCR, and the field strain was isolated in the MA104 cell line. The phylogenetic analyses based on the whole genome sequences and nucleotide sequences of open reading frame 5 (ORF5) gene showed close grouping with the subtype IV of lineage 8/8.7 of PRRSV II, which represents the HP-PRRSV strains that predominate in the pig population of China since 2010. The amino acid sequence analysis of the ORF5 gene revealed the replacement of leucine (L) at position 39 to isoleucine (I) in the primary neutralizing epitope. Among the four potential N glycosylation sites, the N34 was mutated and found to be restricted to only three N glycosylation sites. The present findings have indicated that HP-PRRSV can cause fatal outbreaks and may emerge as a major threat to the wild pig population.


Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease.
Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Aβ42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Aβ transporters: the low density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin (TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Aβ burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Aβ) and diminished secretion of TTR (less neuroprotection against cortical Aβ toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD.


Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells.
Cyclosporin A (CsA) may achieve its immunosuppressive effects by inhibiting the calcium- and calmodulin-dependent phosphatase calcineurin which is required for activation of target genes by members of the NFAT (nuclear factor of activated T cells) transcription factor family. Among these target genes is the gene encoding interleukin-2 (IL2), a cytokine facilitating progression through the G1 phase of the cell cycle. However, IL2 does not reverse CsA inhibition, suggesting that at least one other NFAT-sensitive gene may be involved. The human G0/G1 switch gene, G0S2, has potential NFAT-binding sites in the 5' flank and encodes a small basic potential phosphoprotein of unknown function. Using a sensitive, reverse transcription-polymerase chain reaction (RT-PCR) assay, G0S2 mRNA levels were assayed in cultured blood mononuclear cells. Freshly isolated cells contain high levels of G0S2 mRNA which rapidly decline. This "spontaneous stimulation" is also noted with some other G0S genes and has been attributed to some aspect of the isolation procedure. In cells that have been preincubated to lower mRNA levels, there is a transient increase in G0S2 mRNA, peaking between 1-2 h, in response to Concanavalin-A (ConA), or to the combination of phorbol ester (TPA), and the calcium ionophore, ionomycin. Both these responses are inhibited by CsA. Our results suggest that G0S2 expression is required to commit cells to enter the G1 phase of the cell cycle, and that, while not excluding other possible targets, early inhibition of G0S2 expression by CsA may be important in achieving immunosuppression. G0S2 may be of value as a reporter gene for analyzing the mechanism of action of CsA and its influence on the positive and negative selection of lymphocytes in response to self and not-self antigens.


Pain control in first-trimester surgical abortion: a systematic review of randomized controlled trials.
First-trimester abortions especially cervical dilation and suction aspiration are associated with pain despite various methods of pain control. Following the guidelines for a Cochrane review, we systematically searched for and reviewed randomized controlled trials comparing methods of pain control in first-trimester surgical abortion at less than 14 weeks gestational age using electric or manual suction aspiration. Outcomes included intra- and postoperative pain, side effects, recovery measures and satisfaction. We included 40 trials with 5131 participants. Because of heterogeneity, we divided studies into seven groups: Local anesthesia: Data were insufficient to show a clear benefit of a paracervical block (PCB) compared to no PCB. Reported mean pain scores (10-point scale) during dilation and aspiration were improved with carbonated lidocaine [weighted mean difference (WMD), -0.80; 95% confidence interval (CI), -0.89 to -0.71; WMD, -0.96; 95% CI, -1.67 to -0.25], deep injection (WMD, -1.64; 95% CI, -3.21 to -0.08; WMD, 1.00; 95% CI, 1.09 to 0.91), and with adding a 4% intrauterine lidocaine infusion (WMD, -2.0; 95% CI, -3.29 to -0.71; WMD, -2.8; 95% CI, -3.95 to -1.65). PCB with premedication: Ibuprofen and naproxen resulted in small reduction of intra- and postoperative pain. Conscious sedation: The addition of conscious intravenous sedation using diazepam and fentanyl to PCB decreased procedural pain. General anesthesia: Conscious sedation increased intraoperative but decreased postoperative pain compared to general anesthesia (GA) [Peto odds ratio (Peto OR) 14.77 (95%, CI 4.91-44.38) and Peto OR 7.47 (95% CI, 2.2-25.36) for dilation and aspiration, respectively, and WMD -1.00 (95% CI, -1.77 to -0.23) postoperatively). Inhalation anesthetics are associated with increased blood loss (p<0.001). GA with premedication: The cyclooxygenase (COX)-2 inhibitor etoricoxib; the nonselective COX inhibitors lornoxicam, diclofenac and ketorolac IM; and the opioid nalbuphine improved postoperative pain. Nonpharmacological intervention: Listening to music decreased procedural pain. No major complication was observed. Conscious sedation, GA and some nonpharmacological interventions decreased procedural and postoperative pain, while being safe and satisfactory to patients. Data on the widely used PCB are inadequate to support its use, and it needs to be further studied to determine any benefit.


Vasodilator drugs: systemic and regional considerations.
Therapeutic use of vasodilator drugs depends on the differential actions of these drugs on regional vascular beds. These differences include selective action on small and large arteries, differential potency on arterial and venous smooth muscle, and selectivity for autonomic receptors. The directly acting sodium nitroprusside and glyceryl trinitrate exemplify many of these differences as well as shared effects in the systemic, coronary and cerebral circulations.


Determination of allergenic egg proteins in food by protein-, mass spectrometry-, and DNA-based methods.
Egg allergy is one of the most common food allergies in both adults and children, and foods including eggs and their byproducts should be declared under food allergen labeling policies in industrial countries. Therefore, to develop and validate a sensitive and specific method to detect hidden egg allergens in foods, we compared immunochemical, DNA-based, and proteomic methods for detecting egg allergens in foods using egg allergen standards such as egg whole protein, egg white protein, egg yolk protein, ovomucoid, ovalbumin, ovotransferrin, lysozyme, and alpha-livetin. Protein-based immunochemical methods, including ELISA as an initial screening quantitative analysis and immunoblotting as a final confirmatory qualitative analysis, were very sensitive and specific in detecting potentially allergenic egg residues in processed foods in trace amounts. In contrast, the proteomics-based, matrix-assisted laser desorption/ionization time-of-flight MS and LC-tandem quadrupole time-of-flight MS methods were not able to detect some egg allergens, such as ovomucoid, because of its nondenaturing property under urea and trypsin. The DNA-based PCR method could not distinguish between egg and chicken meat because it is tissue-nonspecific. In further studies for the feasibility of these immunochemical methods on 100 real raw dietary samples, four food samples without listed egg ingredients produced a positive response by ELISA, but exhibited negative results by immunoblotting.


Comparative measurements of serum estriol, estradiol, and estrone in non-pregnant, premenopausal women; a preliminary investigation.
Little to no data exists in the literature for serum estriol values in non-pregnant, premenopausal women. The current medical community opinion holds that estriol has no significant role in non-pregnant women relative to the other estrogens. It is a possibility that estriol's primary function has yet to be discovered. Accordingly, the first step is to understand cycle-dependent serum estriol concentrations. We have made a preliminary investigation for serum estriol concentration of 26 women during the known cycle peaks of estrone and estradiol. Five of the women were also tested for serum estriol on various days throughout the cycle in order to develop a cycle-dependent concentration profile. The result of these experiments show that serum estriol was always significantly higher than the sum of estrone and estradiol and less fluctuating. We conclude that estriol is probably a significant estrogen component.


Identification of an extended N-acetylated sequence adjacent to the protein-linkage region of fibroblast heparan sulphate.
The distribution of N-sulphate groups within fibroblast heparan sulphate chains was investigated. The detergent-extractable heparan sulphate proteoglycan from adult human skin fibroblasts, radiolabelled with [3H]glucosamine and [35S]sulphate, was coupled to CNBr-activated Sepharose 4B. After partial depolymerization of the heparan sulphate with nitrous acid, the remaining Sepharose-bound fragments were removed by treatment with alkali. These fragments, of various sizes, but all containing an intact reducing xylose residue, were fractionated on Sephacryl S-300 and the distribution of the 3H and 35S radiolabels was analysed. A decreased degree of sulphation was observed towards the reducing termini of the chains. After complete nitrous acid hydrolysis of the Sepharose-bound proteoglycan, analysis of the proximity of N-sulphation to the reducing end revealed the existence of an extended N-acetylated sequence directly adjacent to the protein-linkage sequence. The size of this N-acetylated domain was estimated by gel filtration to be approximately eight disaccharide units. This domain appears to be highly conserved, being present in virtually all the chains derived from this proteoglycan, implying the existence of a mechanism capable of generating such a non-random sequence during the post-polymeric modification of heparan sulphate. Comparison with the corresponding situation in heparin suggests that different mechanisms regulate polymer N-sulphation in the vicinity of the protein-linkage region of these chemically related glycosaminoglycans.


Outcomes of silver nitrate use in perianal fistula: are perianal fistulas still a nightmare for surgeons?
In this study, we aimed to evaluate outcomes of % 20 silver nitrate (SNS) application in perianal fistula patients. All patients who received 20 % SNS treatment for intersphincteric and transsphincteric fistulas between January 2017 and December 2017 were included in our study. Patients were invited for control examinations after one week. Patients with continued discharges after single dose of SNS kept receiving solution six more times with one month intervals. Stopping of discharges were considered as finalization of the study. Cases with discharges after 6 episodes of SNS were described as insufficient healing. The patients were grouped according to healing status (healing patients in Group 1, non-healing patients in Group 2) .Gender, age, follow-up times, date of the complaint start, number of SNS application, type of fistula and frequency of fistula discharge were recorded. A total of 49 patients were included in this study. Forty-four (% 89.8) of them were male. The mean age was 44.9. Twenty-eight patients (57.1%) had intersphincteric fistulas, while twenty-two patients (42.9%) had intersfinteric fistulas. Mean number of SNS application was 4.1 (1-6). Patients in Group 1 had mean number of SNS therapy as 3.42 (1-6), whereas cases in Group 2 this number was 5.5 (3-6). Patients were observed approximately for 8.84 months (6-12). We were able to reach sufficient healing in 13 (%26) cases via 2 times and 20 (%40) cases via 3-6 times application of SNS. We were able to reach complete healing rates as % 67 with SNS application in perianal fistula. This is a non-invasive procedure and could be applied in out patient clinics, with low costs. Less complication rates enhances attraction. Patients will not loose chance of surgical treatment. Therefore, we believe SNS may be used as first line treatment in perianal fistulas. Follow-up, Perianal fistula, Silver nitrate.


[Z-plasty for valgus deformity in total knee arthroplasty].
Several options for treatment of valgus deformity in total knee arthroplasty (TKA) have been described. In 2002 the lateral approach to the valgus knee with Z-plasty of the articular capsule involving part of Hoffa's fat pad started to be used in our department. In this study the surgical technique, including steps for gradual deformity correction, is described and shortterm results are evaluated. A total of 1136 TKAs were carried out in the period from 1994 to 2004; of these 131 (11 %) were performed on valgus knee. After a visit to the Schulthess Klinik and personal communication with Dr. med. T. Drobny, we began to use the lateral approach to the valgus knee, with Z-plasty of the articular capsule and involvement of Hoffa's fat pad. Forty-two patients (35 women and 7 men) were treated by this technique. The average age of this group was 71 years, and the average preoperative valgus deformity was 20.5 degrees. A skin incision is made along the midline and, in its lower part, it is led toward the lateral border of the tibial tubercle. The joint capsule is incised in the superficial layer at about 2 cm lateral to the patella. Dissection of the superficial and deep layers of the capsule is made laterally, extending up to 4 cm. After joint exposure, the fat pad is separated from the medial attachment and preserved, on a lateral pedicle, with the patellar ligament. If needed, this flap can be used to close a defect in the distal articular capsule. By including both parts of the joint capsule produced by Z-plasty, medial transposition of the patella is achieved after suture. The deformity is corrected in a sequential manner according to its severity and the effect of release in each step, as follows: 1) Point incisions of the iliotibial band at a 5-cm distance above the articular fissure (piecrusting). 2) Subperiosteal elevation of the iliotibial band attachment from Gerdy's tubercle. 3) Release of the posterolateral capsule. 4) Subperiosteal release of the femoral attachment of the lateral collaterall ligament and dissection of the popliteal muscle. 5) Release of the lateral head of the gastrocnemius muscle. The evaluation of patients was based on the Knee Society Clinical Rating System. Using this surgical technique, correction of deformity was achieved in all patients. The knee axis after surgery improved to 6.6 degrees on the average. The more extensive dissection of lateral structures resulted in larger blood losses, which were on average 1150 ml, and the procedure also required a longer tourniquet application (55 min). The patients were followed up on average for 22 months. The Knee Score assessment in the whole group (42 knees) was on average 90.6 points, with 92.0, 93.3 and 87.9 for rating system categories A, B and C, respectively. The average range of motion was 0 to 118 degrees , and none of the patients reported femoropatellar problems. Revision surgery for hematoma was performed in one patient and puncture of the knee joint had to be done in several patients. Redress for postoperative motion restriction was carried out in three patients and one patient underwent repeat surgery for infection. The lateral approach with Z-plasty of the capsule and fat pad involvement provides maximal release of and access to the lateral structures, reduces the risk of insufficient blood supply of the patella and also resolves patellar subluxation. This technique thus allows us to reduce the probability of developing femoropatellar problems that are frequently responsible for poor TKA outcomes in the valgus knee. The technique described here is an effective approach to the valgus knee requiring total replacement. It provides good access to exposed lateral structures and, with the use of Z-plasty, permits correct alignment and tracking of the patella. In addition, it minimally interferes with blood supply to the patella and completely avoids problems associated with suture of the articular capsule.


Environmental stress increases variability in the expression of dental cusps.
Teeth are an important model for developmental studies but, despite an extensive literature on the genetics of dental development, little is known about the environmental influences on dental morphology. Here we test whether and to what extent the environment plays a role in producing morphological variation in human teeth. We selected a sample of modern human skulls and used dental enamel hypoplasia as an environmental stress marker to identify two groups with different stress levels, referred to as SG ("stressed" group) and NSG ("nonstressed" group). We collected data on the occurrence and the relative development of 15 morphological traits on upper molars using a standard methodology (ASU-DAS system) and then we compared the frequencies of the traits in the two groups. Overall, the results suggest that (a) stressors like malnutrition and/or systemic diseases have a significant effect on upper molar morphology; (b) stress generates a developmental response which increases the morphological variability of the SG; and (c) the increase in variability is directional, since individuals belonging to the SG have more developed and extra cusps. These results are consistent with the expectations of the current model of dental development.


Impact of Point-of-Care Ultrasound Examination on Triage of Patients With Suspected Cardiac Disease.
Complementing the physical examination with a point-of-care ultrasound study (POCUS) can improve patient triage. We aimed to study the impact of POCUS on the diagnosis and management of outpatients and hospitalized patients with suspected cardiac disease. In this multicenter study, a pocket-sized device was used to perform POCUS when the diagnosis or patient management was unclear based on anamnesis, physical examination, and basic diagnostic testing. Eighteen physicians (cardiac fellows 49%, cardiologists 30%, and echocardiographers 21%) performed physical examinations extended by POCUS on 207 patients (inpatients 83% and outpatients 17%). POCUS findings resulted in a change in the primary diagnosis in 14% of patients. In patients whose diagnosis remained unchanged, POCUS results reinforced the initial diagnosis in 48% of the cases. In 39% of the patients, the diagnostic plan was altered, including referral (16%) or deferral (23%) to other diagnostic techniques. Alteration in medical treatment (drug discontinuation or initiation) occurred in 11% of the patients, and in 7% POCUS results influenced the decision whether to perform a therapeutic procedure. Hospitalization or discharge was determined after POCUS in 11% of the patients. In conclusion, during patient triage, extension of the physical examination by POCUS can cause physicians to alter their initial diagnosis, resulting in an immediate change of diagnostic and therapeutic procedures. Based on POCUS results, physicians altered the diagnostic plan either by avoiding or referring patients to other diagnostic procedures in almost half of the studied population.


Measuring Physical Activity in Juvenile Idiopathic Arthritis: Activity Diary Versus Accelerometer.
(1) To determine convergent validity of an activity diary (AD) and accelerometer (Actical brand/Phillips-Respironics) in measuring physical activity (PA) in children with juvenile idiopathic arthritis (JIA). (2) To determine how many days give reliable results. (3) To analyze effects of correcting accelerometer data for non-wear. Patients with JIA (8-13 yrs) were recruited from 3 Dutch pediatric rheumatology centers. PA was assessed for 7 days with an AD and accelerometer, and was expressed as mean min/day of rest, light PA (LPA), moderate to vigorous PA (MVPA), and PA level (PAL). To analyze convergent validity, intraclass correlation coefficients (ICC) were calculated and paired sample Student t tests were performed. The required number of days to achieve reliable results was calculated using the Spearman-Brown prophecy formula. Convergent validity between AD and accelerometer was moderate for rest and PAL (ICC 0.41). ICC for LPA and MVPA were < 0.24. AD overestimated PAL and MVPA compared with the accelerometer. Wearing the accelerometer 7-19 days gave reliable PA estimates on group and individual levels. For the AD, 13-36 days were needed. Adjusting accelerometer data for non-wear resulted in a clinically relevant higher mean number of min/day spent in LPA (effect size 1.12), but not in MVPA (effect size 0.44). Convergent validity between AD and accelerometer is moderate to poor. In children with JIA, 1-week assessment with an accelerometer is sufficient to measure PA (all levels) reliably. On an individual level and for clinical use, 3 weeks are required. Additional use of AD enables correction for non-wear of accelerometer data.


Developmental Origins of Chronic Physical Aggression: A Bio-Psycho-Social Model for the Next Generation of Preventive Interventions.
This review describes a bio-psycho-social approach to understanding and preventing the development of chronic physical aggression. The debate on the developmental origins of aggression has historically opposed genetic and environmental mechanisms. Recent studies have shown that the frequency of physical aggression peaks in early childhood and then decreases until old age. Molecular genetic studies and twin studies have confirmed important genetic influences. However, recent epigenetic studies have highlighted the important role of environments in gene expression and brain development. These studies suggest that interrelated bio-psycho-social channels involved in the development of chronic physical aggression are generally the product of an intergenerational transmission process occurring through assortative mating, genetic inheritance, and the inheritance of physical and social environmental conditions that handicap brain functioning and support the use of physical aggression to solve problems. Given these intergenerational mechanisms and physical aggression onset in infancy, it appears clear that preventive interventions should start early in pregnancy, at the latest.


An examination of the relationship between personality patterns and symptom/mood patterns.
Relationships between various personality styles measured by the basic and pathological personality scales of the Millon Clinical Multiaxial Inventory (MCMI) and mood or symptom states measured by the Profile of Mood State scales were examined. The MCMI personality scale-POMS symptom/mood scale relationships found in this study are compared with MCMI personality scale-MMPI and SCL-90 symptom/mood scale relationships reported in the MCMI manual. Consistent associations of moderate strength were found between: (a) the MCMI Compulsive-Conforming and Passive-Aggressive (Negativistic) scales (negative and positive associations, respectively) and various measures of depression, anxiety and hostility; (b) the MCMI Avoidant, Schizotypal and Borderline-Cycloid scales and various measures of depression and anxiety; (c) the MCMI Schizoid-Asocial scale and various measures of depression; and (d) the Histrionic-Gregarious scale and various measures of high energy-activity. These MCMI personality scale-symptom/mood scale relationships are generally consistent both with the underlying theory of personality and psychopathology upon which the MCMI is based and with the personality-symptom scale relationships found within the MCMI.


Cardiac valvulopathy associated with pergolide use.
To review the risk of pergolide associated cardiac valvulopathy in patients with Parkinson's disease. MEDLINE, Embase, and the Cochrane Library. Reference lists were reviewed and librarians were consulted to identify additional trials. All studies and case reports in the English literature on pergolide and cardiac valvulopathy. Demographics of patients, study duration, dose and duration of pergolide use, echocardiogram results, length of follow-up, and clinical outcome. Twenty-two published articles were identified. There were no randomized controlled trials. Follow-up time varied between a few months and four years. Three case reports and four studies (three case control and one observational) assessed 246 patients. Evidence for valvulopathy was found in all studies. Variable methods were used to assess the degree of valvular regurgitation making comparisons between studies difficult. Little clinical correlation is available for echocardiogram results. Variable improvement was shown in the few patients in whom the drug was stopped. There is insufficient data to determine whether dose and duration or other comorbities have an effect on the risk of developing cardiac valvulopathy. Pergolide therapy is associated with an increased risk of developing cardiac valvulopathy but the true incidence and importance of this remains unknown. Further prospective studies are needed with standardized assessments of echocardiograms.


Evaluation of the frequency of putative prostate cancer stem cells in primary and metastatic prostate cancer.
Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+ve and express high levels of alpha2beta1 integrin. In this study we have, for the first time, assessed matched primary and bone marrow biopsies from prostate cancer patients for the distribution of cells carrying these and a number of other putative stem cell markers. Eleven matched (primary and bone metastasis) specimens from prostate cancer patients were assessed for the presence of cd133, cd44, alpha2beta1 integrin, CXCR4, c-met, alpha6 integrin, and nestin using immunohistochemistry and stain intensity and distribution scored. In the bone metastases, tumor cells staining positively for cd133 were detected at low frequency in approximately 50% of samples. Staining for nestin was confined to endothelium. Positive staining of tumor cells for the other antigens was present at variable frequency in >70% of metastases with the exception of CXCR4 which was absent from all but 2 specimens. Where positive staining of tumor cells was present in the metastasis, cells staining for each antigen were present in the matched primary with the exception of cd44 which was absent in all but 2/11 matched primary tissues. In established metastases no single or combination of marker expression profiles identify the established metastatic phenotype, although cd44 expression was shown to be more frequent in metastases that in primary cancers.


Analysis of Genetic Diversity and Population Structure of Sesame Accessions from Africa and Asia as Major Centers of Its Cultivation.
Sesame is an important oil crop widely cultivated in Africa and Asia. Understanding the genetic diversity of accessions from these continents is critical to designing breeding methods and for additional collection of sesame germplasm. To determine the genetic diversity in relation to geographical regions, 96 sesame accessions collected from 22 countries distributed over six geographic regions in Africa and Asia were genotyped using 33 polymorphic SSR markers. Large genetic variability was found within the germplasm collection. The total number of alleles was 137, averaging 4.15 alleles per locus. The accessions from Asia displayed more diversity than those from Africa. Accessions from Southern Asia (SAs), Eastern Asia (EAs), and Western Africa (WAf) were highly diversified, while those from Western Asia (WAs), Northern Africa (NAf), and Southeastern Africa (SAf) had the lowest diversity. The analysis of molecular variance revealed that more than 44% of the genetic variance was due to diversity among geographic regions. Five subpopulations, including three in Asia and two in Africa, were cross-identified through phylogenetic, PCA, and STRUCTURE analyses. Most accessions clustered in the same population based on their geographical origins. Our results provide technical guidance for efficient management of sesame genetic resources in breeding programs and further collection of sesame germplasm from these different regions.


Changes in ovarian expression of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 messenger ribonucleic acids during ovulation in rat.
We investigated the time course and localization of ovarian tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) expression during the ovulatory period in rat by RNase protection assay and in situ hybridization. Immature female Wistar rats were injected with 25 IU pregnant mare serum gonadotropin (PMSG), followed 50 h later by 25 IU human chorionic gonadotropin (hCG). Levels of tPA mRNA were low before hormone treatment and after PMSG treatment. After hCG treatment, tPA mRNA levels increased rapidly, the first peak at 4 h after hCG treatment and reached a maximum just prior to ovulation, 12 h later, before declining again. PAI-1 mRNA was barely detectable before hormone treatment but was transiently induced by hCG treatment, reaching peak levels after 4 h. Subsequently, PAI-1 mRNA levels decreased until early luteinization. The expression of tPA mRNA 4 h after hCG treatment occurred mainly in the follicular thecal-interstitial cells, but was barely detectable in the granulosa cells, whereas 12 h after hCG treatment it was maximal in the granulosa cells of the large follicles destined to ovulate. PAI-1 mRNA was expressed mainly in ovarian stromal tissue and in the thecal external interstitial cells encapsulating the follicles at 4 h after hCG treatment. These results suggest that the temporal regulation of tPA biosynthesis after hCG induction depends on the cell types and size classes in the various ovarian compartments. PAI-1 may be produced by the stormal tissue and the thecal external interstitial cells and is perhaps implicated in structural changes during follicular growth, ovulation and luteinization.


Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori.
Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large amounts of Tipα, which are incorporated into gastric cancer cells by directly binding to nucleolin on the cell surface, which is a receptor of Tipα. The binding complex induces expression of TNF-α and chemokine genes, and activates NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). To understand the mechanisms of Tipα in tumor progression, we looked at numerous effects of Tipα on human gastric cancer cell lines. Induction of cell migration and elongation was found to be mediated through the binding to surface nucleolin, which was inhibited by the nucleolin-targeted siRNAs. Tipα induced formation of filopodia in MKN-1 cells, suggesting invasive morphological changes. Tipα enhanced the phosphorylation of 11 cancer-related proteins in serine, threonine and tyrosine, indicating activation of MEK-ERK signal cascade. Although the downregulation of E-cadherin was not shown in MKN-1 cells, Tipα induced the expression of vimentin, a significant marker of the epithelial-mesenchymal transition (EMT). It is of great importance to note that Tipα reduced the Young's modulus of MKN-1 cells determined by atomic force microscopy: This shows lower cell stiffness and increased cell motility. The morphological changes induced in human gastric cancer cells by Tipα are significant phenotypes of EMT. This is the first report that Tipα is a new inducer of EMT, probably associated with tumor progression in human gastric carcinogenesis.


Comparative risk assessment studies estimating the hazard posed by long-term consumption of PPCPs in river water.
This study assesses the risk due to Emerging Contaminants (ECs), present in Indian rivers - Ganga (650 million inhabitants), Yamuna (57 million inhabitants), and Musi (7,500,000 inhabitants), 13 ECs in total, have been used for risk assessment studies. Their concentrations (e.g., Fluconazole: 236950 μg/l, Ciprofloxacin: 31000 μg/l, Caffeine: 21.57 μg/l, etc.) were higher than the threshold concentrations for safe consumption (e.g. Fluconazole allowable level is 3.8 μg/l, and Ciprofloxacin allowable level is 0.51 μg/l). Three different pathways of emerging contaminants (ECs) transfer (oral water ingestion, oral fish ingestion, and dermal water contact) have been considered and the study is carried out in 2 ways: (i) deterministic and (ii) probabilistic approaches (using Monte Carlo iterative methods with 10000 simulations) with the aid of a software - Risk (version 7.5). The risk value, quantified by Hazard Quotient (HQ) is higher than the allowable limit of 1 for several compounds in the three rivers like Fluconazole (HQ = 18276.713), Ciprofloxacin (HQ = 278.675), Voriconazole (HQ = 14.578), Cetirizine (HQ = 1006.917), Moxifloxacin (HQ = 8.076), Caffeine (HQ = 55.150), and Ibuprofen (HQ = 9.503). Results show that Fluconazole and Caffeine pose the maximum risk in the rivers via the "oral pathway" that allows maximum transfer of the ECs present in the river (93% and 82% contribution to total risk). The risk values vary from nearly 25 times to 19000 times the United States Environmental Protection Agency (USEPA) threshold limit of 1 (e.g., Caffeine Infant Risk = 25.990 and Fluconazole Adult Risk = 18276.713). The most susceptible age group, from this study, is "Adults" (19-70 years old), who stand the chance of experiencing the adverse health hazards associated with prolonged over-exposure to the ECs present in the river waters. Musi has the maximum concentration of pollutants and requires immediate remediation measures. Further, both methods indicate that nearly 60-70% of the population in all the three study areas are at risk of developing health hazards associated with over-exposure to ECs regularly, making the areas inhabitable.


Organisational impact: Definition and assessment methods for medical devices.
Health technology assessment (HTA) is a rapidly developing area and the value of taking non-clinical fields into consideration is growing. Although the health-economic aspect is commonly recognised, evaluating organisational impact has not been studied nearly as much. The goal of this work was to provide a definition of organisational impact in the sector of medical devices by defining its contours and exploring the evaluation methods specific to this field. Following an analysis of the literature concerning the impact of technologies on organisations as well as the medical literature, and also after reviewing the regulatory texts in this respect, the group of experts identified 12 types of organisational impact. A number of medical devices were carefully screened using the criteria grid, which proved to be operational and to differentiate properly. From the analysis of the practice and of the methods described, the group was then able to derive a few guidelines to successfully evaluate organisational impact. This work shows that taking organisational impact into consideration may be critical alongside of the other criteria currently in favour (clinically and economically). What remains is to confer a role in the decision-making process on this factor and one that meets the economic efficiency principle.


Therapeutic angiogenesis/arteriogenesis in the chronic ischemic rabbit hindlimb: effect of venous basic fibroblast growth factor retroinfusion.
Therapeutic induction of angiogenesis has been shown in experimental hindlimb ischemia. An alternative to targeting the ischemic hindlimb tissue via the severely stenosed or occluded artery consists in the intact venous system, e.g., by retroinfusion. We tested whether basic fibroblast growth factor (bFGF) enhances angiogenesis induction. Therefore, we applied bFGF retrogradely as compared to intramuscular application. Furthermore, we assessed whether bFGF-induced angiogenesis was enhanced by low-dose VEGF coapplication. Chronic hindlimb ischemia in rabbits was established by excision of the femoral artery at day 0 (d0). At d7, baseline collateral number in the ischemic limb and collateral flow velocity of contrast agent (frame count score) were assessed. Thereafter, saline solution (control group) or bFGF (20 microg/kg) with or without VEGF (10 microg/kg) was retroinfused through the femoral vein. Alternatively, bFGF (20 microg/kg) was injected into thigh and calf muscles. At d35, collateral growth and flow velocity were quantified, and tissue samples were analyzed for capillary density. In the untreated control group, capillary/muscle fiber (C/FM) ratio of the ischemic limb was 0.87 +/- 0.12, and collateral number as well as frame count score at -d35 did not change compared to d7 (107% +/- 7% and 109% +/- 10% of baseline, respectively). Retrograde application of bFGF induced capillary and collateral growth (C/FM ratio 1.56 +/- 0.19 and frame count 161% +/- 29% of baseline), resulting in enhanced flow velocity (143% +/- 13%), similar to the intramuscular application of bFGF. Additional low-dose VEGF retroinfusion did not further increase capillary/collateral growth (1.49 +/- 0.08 and 172% +/- 26%) nor perfusion velocity (149% +/- 7%). The authors conclude that bFGF retroinfusion is a feasible approach of inducing angiogenesis and arteriogenesis in an ischemic hindlimb, resulting in increased blood perfusion, which was not further extended by additional low-dose VEGF coapplication.


[Ultrasound-guided insertion and the proportion of catheter-associated thrombosis].
Central venous accesses are of great importance in daily medical practice. Insertion into the jugular vein is common due to its accessibility. Catheter-associated venous thrombosis is a relatively common medium-term complication. The use of ultrasound to guide catheterization offers multiple advantages and promises to make vascular access installation a safer technique. To compare the proportion of catheter-associated jugular thrombosis when an anatomical landmark technique is used with respect to the ultrasound-guided technique. An observational, cross-sectional, and analytical study that compares the frequency of thrombosis when the ultrasound-guided technique was used concerning anatomical reference technique in patients in an intensive care unit. A total of 91 patients were studied: in 44 an ultrasound-guided technique was used, and in 47 anatomical references. A single case of mural thrombosis (2.7%) was observed in the ultrasound-guided insertion group vs. 11 cases (23.4%) in the other group, resulting in a significant association between the anatomical reference insertion technique and thrombosis. Chi squared (1, n = 91) = 8.86, p = 0.004. The proportion of catheter-associated jugular thrombosis is greater when an anatomical reference technique is used compared to the ultrasound-guided technique.


MiR-218 promotes apoptosis of U2OS osteosarcoma cells through targeting BIRC5.
Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is a member of apoptosis inhibition family which suppresses caspase activity. Osteosarcoma tissues have significantly higher BIRC5 and lower microRNA-218 (miR-218) level than adjacent tissues, indicating tumor suppressor role of miR-218 in osteosarcoma. Bioinformatics analysis showed satisfactory targeting correlation between miR-218 and 3'-UTR of BIRC5 mRNA. This study, thus, investigated if dysregulation of miR-218 and BIRC5 affected apoptosis of osteosarcoma cells U2OS. A total of 42 osteosarcoma patients were collected for tumor and adjacent tissues to compare miR-218 and BIRC5 expressions. Dual-luciferase reporter gene assay examined targeted regulation between miR-218 and BIRC5. In vitro cultured U2OS cells were treated with miR-218 mimic and/or si-BIRC5. Caspase-3 activity was measured by spectrometry while flow cytometry was used to test cell apoptosis, plus protein expression assay by Western blot assay. Compared to adjacent tissues, osteosarcoma tissues had significantly depressed miR-218 expression and elevated BIRC5 expression (p<0.05). miR-21 targeted 3'-UTR of BIRC5 to suppress its expression. The elevation of miR-218 and/or silencing BIRC5 significantly depressed BRIC5-induced inhibition on caspase-5, and facilitated U2OS cell apoptosis (p<0.05). We observed that miR-218 was significantly down-regulated in osteosarcoma tissues, which had elevated BIRC5 expression. MiR-218 targeted and inhibited BIRC5 expression, weakened caspase-5 inhibition by BIRC5, and facilitated U2OS osteosarcoma cell apoptosis.


The relationship between social, policy and physical venue features and social cohesion on condom use for pregnancy prevention among sex workers: a safer indoor work environment scale.
This study aims to report on a newly developed Safer Indoor Work Environmental Scale that characterises the social, policy and physical features of indoor venues and social cohesion; and using this scale, longitudinally evaluate the association between these features on sex workers' (SWs') condom use for pregnancy prevention. Drawing on a prospective open cohort of female SWs working in indoor venues, a newly developed Safer Indoor Work Environment Scale was used to build six multivariable models with generalised estimating equations (GEE), to determine the independent effects of social, policy and physical venue-based features and social cohesion on condom use. Of 588 indoor SWs, 63.6% used condoms for pregnancy prevention in the last month. In multivariable GEE analysis, the following venue-based features were significantly correlated with barrier contraceptive use for pregnancy prevention: managerial practices and venue safety policies (adjusted OR (AOR)=1.09; 95% CI 1.01 to 1.17), access to sexual and reproductive health services/supplies (AOR=1.10; 95% CI 1.00 to 1.20), access to drug harm reduction (AOR=1.13; 95% CI 1.01 to 1.28) and social cohesion among workers (AOR=1.05; 95% CI 1.03 to 1.07). Access to security features was marginally associated with condom use (AOR=1.13; 95% CI 0.99 to 1.29). The findings of the current study highlight how work environment and social cohesion among SWs are related to improved condom use. Given global calls for the decriminalisation of sex work, and potential legislative reforms in Canada, this study points to the critical need for new institutional arrangements (eg, legal and regulatory frameworks; labour standards) to support safer sex workplaces.


Conditions for the Successful Implementation of Computer-Aided Drug Monitoring From Registered Nurses' Perspective-A Case Site Analysis.
This research addressed the introduction of a computerized decision support system for drug monitoring to be used by registered nurses in nursing homes. The system was introduced, and its effects were evaluated over the period of 1 year; however, at the end of 1 year, the implementation was not successful in all the participating settings. The aim of this study was to identify the conditions needed for the successful implementation of a computerized decision support system from the registered nurses' perspective. Two case sites were purposively selected based on the implementation's success in one nursing home, but not in the other. Focus group discussions were performed, one in each setting, with eight registered nurses. An inductive thematic analysis was conducted. The findings revealed six themes illustrating the registered nurses' views about the conditions needed: need to see benefits, have the time and take the time, curb administrative hassle, collaboration at all levels, stated responsibility, and requirements set from managerial positions. The most outstanding findings, when compared with the previous implementations of nursing informatics, involved collaboration and the view of drug monitoring responsibility in relation to themselves and the physicians.


A new, long-term daily satellite-based rainfall dataset for operational monitoring in Africa.
Rainfall information is essential for many applications in developing countries, and yet, continually updated information at fine temporal and spatial scales is lacking. In Africa, rainfall monitoring is particularly important given the close relationship between climate and livelihoods. To address this information gap, this paper describes two versions (v2.0 and v3.0) of the TAMSAT daily rainfall dataset based on high-resolution thermal-infrared observations, available from 1983 to the present. The datasets are based on the disaggregation of 10-day (v2.0) and 5-day (v3.0) total TAMSAT rainfall estimates to a daily time-step using daily cold cloud duration. This approach provides temporally consistent historic and near-real time daily rainfall information for all of Africa. The estimates have been evaluated using ground-based observations from five countries with contrasting rainfall climates (Mozambique, Niger, Nigeria, Uganda, and Zambia) and compared to other satellite-based rainfall estimates. The results indicate that both versions of the TAMSAT daily estimates reliably detects rainy days, but have less skill in capturing rainfall amount-results that are comparable to the other datasets.


Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable animal model for human toxoplasmosis.
Toxoplasma gondii causes toxoplasmosis, a worldwide disease. Experimentation with pigs is necessary for the development of new therapeutic approaches to human diseases. BR-1 mini pigs were intramuscularly infected with T. gondii with tachyzoites (RH strain) or orally infected with cysts (ME-49 strain). Haematology and serum biochemistry were analysed and buffy coat cells were inoculated in mice to determine tachyzoite circulation. No alterations were observed in erythrocyte and platelet values; however, band neutrophils increased seven days after infection with ME-49. Serology of the mice inoculated with pig blood leucocytes revealed circulating ME-49 or RH strain tachyzoites in the pigs' peripheral blood at two and seven or nine days post-infection. The tachyzoites were also directly observed in blood smears from the infected pigs outside and inside leucocytes for longer periods. Alanine-aminotransferase was high at days 21 and 32 in the RH infected pigs. After 90 days, the pigs were euthanised and their tissue samples were processed and inoculated into mice. The mice serology revealed the presence of parasites in the hearts, ileums and mesenteric lymph nodes of the pigs. Additionally, cysts in the mice were only observed after pig heart tissue inoculation. The infected pigs presented similar human outcomes with relatively low pathogenicity and the BR-1 mini pig model infected with ME-49 is suitable to monitor experimental toxoplasmosis.


Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)
To evaluate relationships of serum carotenoids, alpha-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the case's diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum beta-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. A marginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of alpha- and beta-carotene, alpha-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids beta-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.


Indium-111 platelet scintigraphy for the diagnosis of acute venous thrombosis.
Platelets labeled with indium-111 have been used successfully as a marker of active thrombosis in man. To establish the diagnostic accuracy of platelet scintigraphy in comparison to contrast venography in the diagnosis of acute lower limb venous thrombosis, we evaluated 103 consecutive patients divided into two groups. Platelets were labeled by the indium-111 oxine method. Patients from group I (n = 73, 56 had venograms) were asymptomatic and underwent platelet scintigraphy 1.1 +/- 0.6 days (mean +/- 1 SD) after a major orthopedic procedure. Patients from group II (n = 30, all had venograms) were symptomatic and underwent platelet scintigraphy 1.2 +/- 1.7 days after venography. In group II, 15 patients with positive findings on contrast venography were treated with intravenous heparin; five others with positive venograms did not receive heparin until platelet scintigraphy was completed. Both platelet scintigraphy and contrast venography were evaluated by two blinded observers. Only studies with blinded agreement of both platelet scintigraphy and contrast venography were included in the analysis. Sensitivity and specificity of platelet scintigraphy for the whole limb were 93% and 97% in group I and 42% and 67% in group II. The lower sensitivity in group II was most likely attributable to therapy with heparin. These results demonstrate that platelet scintigraphy, a test that permits imaging for up to five days after a single injection, correlates favorably with contrast venography in patients who have not received heparin and may be used as a surveillance test in high-risk patients. The role of platelet scintigraphy in acutely symptomatic patients requires further evaluation.


Is the adhesive material secreted by sea urchin tube feet species-specific?
Sea urchin adoral tube feet are highly specialized organs that have evolved to provide efficient attachment to the substratum. They consist of a disk and a stem that together form a functional unit. Tube foot disk tenacity (adhesive force per unit area) and stem mechanical properties (e.g., stiffness) vary between species but are apparently not correlated with sea urchin taxa or habitats. Moreover, ultrastructural studies of sea urchin disk epidermis pointed out differences in the internal organization of the adhesive secretory granules among species. This prompted us to look for interspecific variability in the composition of echinoid adhesive secretions, which could explain the observed variability in adhesive granule ultrastructure and disk tenacity. Antisera raised against the footprint material of Sphaerechinus granularis (S. granularis) were first used to locate the origin of adhesive footprint constituents in tube feet by taking advantage of the polyclonal character of the generated antibodies. Immunohistochemical assays showed that the antibodies specifically labeled the adhesive secretory cells of the disk epidermis in the tube feet of S. granularis. The antibodies were then used on tube foot histological sections from seven other sea urchin species to shed some light on the variability of their adhesive substances by looking for antibody cross-reactivity. Surprisingly, no labeling was observed in any of the species tested. These results indicate that unlike the adhesive secretions of asteroids, those of echinoids do not share common epitopes on their constituents and thus would be "species-specific." In sea urchins, variations in the composition of adhesive secretions could therefore explain interspecific differences in disk tenacity and in adhesive granule ultrastructure.


Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.
A six week course of cimetidine (1 g/day) healed peptic ulcers in 20 of 23 patients (14 with duodenal ulcer, nine with gastric ulcer). Reduction of basal acid output by 73% and peak acid output by 36% led to a rise in concentrations of intragastric aerobic bacteria and nitrate-reducing bacteria. While the mean intragastric concentration of nitrate was unchanged by treatment, there were statistically significant rises in nitrite and N-nitrosamine concentrations. The conversion from nitrates to nitrites was closely related to the occurrence of nitrate-reducing bacteria. In three patients the intragastric milieu had returned to normal two months after cimetidine treatment had been discontinued. Mean nitrite and N-nitrosamine concentrations did not return to pre-treatment levels in the group of eight patients who remained on maintenance cimetidine (0.4 g at night-time) for three months after the full dose treatment. This study shows that cimetidine treatment can create an intragastric milieu resembling that of atrophic gastritis. Large scale and long-term studies are necessary to establish whether these findings have any clinical significance.


Perspectives on artificial joint design.
Due to poor interdisciplinary communication, many artifical joint designs fail to account for some features that normally allow bones to survive for life. In part, these features concern modeling drifts and remodeling basic multicellular units (BMUs), the microdamage thresholds of bone, its load-grain alignment and shear lock properties, load focusing and defocusing, mechanical usage/strain thresholds for controlling the biological mechanisms, and the regional acceleratory phenomenon. This article reviews briefly some major aspects of these features and suggests how implant design might account for them.


Superior limbic keratoconjunctivitis associated with soft contact lens wear.
Four cosmetic soft contact lens wearers experienced lens intolerance and mild irritative symptoms. All four displayed changes suggestive of those seen in superior limbic keratoconjunctivitis with papillary hypertrophy and inflammation of the upper tarsus, superior tarsal and bulbar conjunctival fluorescein staining, superior limbal hypertrophy, and upper corneal punctate staining. Three of the four conditions resolved with discontinuance of lens wear alone; the fourth improved, but there was persistence of mild upper bulbar conjunctival and corneal staining for two years. No common causative contact lens-related factors were obvious in the four. Three of the patients were subsequently able to resume lens wear on a modified basis.


Electronic spectroscopy of transient species in solid neon: the indene-motif polycyclic hydrocarbon cation family C9Hy(+) (y = 7-9) and their neutrals.
In this Perspective the development and application of a mass-selective matrix isolation approach, employed with success over the last two decades in the spectroscopic characterization of numerous ions and neutral reactive species, is illustrated with original data for hydrocarbon cations and neutrals with a six- and a five-membered carbon ring fused. The setup allows for the electronic and vibrational assessment of these isolated molecules and ions in the inert neon environment. The transient species of interest are chosen due to their astrophysical relevance, and the role they play in flames, plasmas, combustion, organic reactions and atmospheric chemistry. Electronic absorption and fluorescence spectra of indene-related polycyclic aromatic hydrocarbon derivatives, C9Hy(+) (y = 7-9) cations, are presented. The ions were produced in a discharge source and investigated by means of absorption and emission spectroscopies after selectively trapping them in 6 K neon matrices. Photoconversion between the two C9H8(+) indenylium isomers and, upon irradiation, H2 loss from C9H9(+) were observed. Corresponding neutral species C9Hy are identified by photobleaching the matrices containing the cations.


Hyperphagia in intestinal disease.
Six patients with hyperphagia (ingestion of 5-11 000 Kcals/day) associated with severe malabsorption and steatorrhoea are described. The cause of the malabsorption was coeliac disease in three patients, Crohn's disease with ileal resection in two, and carcinoma of the pancreas in one patient. There was no evidence of neurological or endocrine disease (apart from mild diabetes mellitus in the patient with carcinoma of the pancreas) but three patients suffered from severe depression. This association may be commoner than previously realized and be revealed in patients with steatorrhoea of unexplained severity by careful dietary assessment. Its detection has therapeutic implications since restriction of caloric and fat intake decreased steatorrhoea without weight loss in several of the patients described.


Novel aggregative adherence fimbria variant of enteroaggregative Escherichia coli.
Enteroaggregative Escherichia coli (EAEC) organisms belong to a diarrheagenic pathotype known to cause diarrhea and can be characterized by distinct aggregative adherence (AA) in a stacked-brick pattern to cultured epithelial cells. In this study, we investigated 118 EAEC strains isolated from the stools of Danish adults with traveler's diarrhea. We evaluated the presence of the aggregative adherence fimbriae (AAFs) by a multiplex PCR, targeting the four known major subunit variants as well as their usher-encoding genes. Almost one-half (49/118) of the clinical isolates did not possess any known AAF major fimbrial subunit, despite the presence of other AggR-related loci. Further investigation revealed the presence of an AAF-related gene encoding a yet-uncharacterized adhesin, termed agg5A. The sequence of the agg5DCBA gene cluster shared fimbrial accessory genes (usher, chaperone, and minor pilin subunit genes) with AAF/III, as well as the signal peptide present in the beginning of the agg3A gene. The complete agg5DCBA gene cluster from a clinical isolate, EAEC strain C338-14, with the typical stacked-brick binding pattern was cloned, and deletion of the cluster was performed. Transformation to a nonadherent E. coli HB101 and complementation of the nonadherent C338-14 mutant with the complete gene cluster restored the AA adhesion. Overall, we found the agg5A gene in 12% of the 118 strains isolated from Denmark, suggesting that this novel adhesin represents an important variant.


Effects of a video guided T'ai Chi group intervention on center of balance and falls efficacy: a pilot study.
This pilot study evaluated effects of a video-guided T'ai Chi group intervention on center of balance (COB) and falls efficacy, using a one arm, pre/post design. Thirty-two participants began the study, 17 completed pre- and post-testing and 15 were lost to follow-up. Outcomes were compared for the 17 participants who completed pre- and post-testing and subgroups based on session attendance. Irrespective of session attendance, participant COB scores improved. There was a significant negative correlation between number of sessions attended and pre and post scores on the fall efficacy (fear of falling) measure, indicating those with higher fear of falling were less likely to complete the study. Older participants were also less likely to continue participation. Findings indicate potential benefits of T'ai Chi in improving COB (a fall risk factor) among community-dwelling older adults. However, those with greater potential benefit (higher fear scores, older participants) were less likely to continue participation.


Clinical experience with misonidazole: high dose fractions versus daily low doses.
In April 1976 clinical experience with misonidazole began at the University Clinic for Radiotherapy and Radiobiology of Vienna. Initially the drug was given mainly in four to six divided large doses ranging from 50 to 80 mg/kg (2.1-3.1 g/m2). Since October 1977 daily low doses in the range of 1-2g (0.45-1.3 g/m2) were used. So far over 100 patients with advanced tumor stages have been under investigation. Serum levels for the different treatment schedules are reviewed and sensitizer enhancement ratios larger than 1.3 may be expected even with daily low doses of misonidazole. Neurological side effects are analyzed and related to the cumulative dose (in g/m2) and overall treatment time. Depending on the overall time of drug administration the total dose of misonidazole can be adjusted to avoid undersirable side effects. It is our impression that normal tissue reactions are unchanged by the use of misonidazole. Preliminary results of a randomized clinical trial in patients with high-grade astrocytomas appear to be favorable for the sensitizer group. Als some impressive clinical results were seen in patients when using daily low doses of misonidazole.