Intraocular Pressure Calculation in Myopic Patients After Laser-Assisted In Situ Keratomileusis.
Corneal refractive surgery is widely used worldwide. Myopia is the most common reason for laser-assisted corneal refractive surgery (LASIK) and one of the risk factors for glaucoma. Intraocular pressure (IOP) measurement becomes variable postoperatively as the results are affected by the decrease in corneal thickness and biomechanics. This prospective clinical case study attempted to establish a simple correction formula for the calculation of IOP in post-LASIK myopic patients. This study included 300 eyes of 150 patients with myopia and myopic astigmatism as a refractive error who underwent LASIK. IOP was measured preoperatively and 6 months postoperatively. Preoperative and postoperative corneal thickness as well as ablation depth were measured. Statistical analysis was performed to detect the relationship between ablation depth and change in IOP. An attempt was made to construct a correction formula for the calculation of post-LASIK IOP. The age of the patients ranged between 18 and 50 (mean ± SD 34.78±8.8) years. The spherical equivalent of refractive error ranged between -1.5 and -10 diopters. The mean IOP decreased significantly from 15.72±2.37 mmHg preoperatively to 11.71±2.24 mmHg postoperatively, with a mean difference of 4±1.75 mmHg (p˂0.001). A positive correlation was detected between corneal thickness and IOP difference among patients both preoperatively and postoperatively (p˂0.001). A positive correlation was identified between ablation depth and IOP change (p˂0.001). The correction formula for IOP was established: Real IOP=4+0.7(preoperative IOP)-0.3(ablation depth). IOP measurements change after corneal refractive surgery with LASIK. A corrected formula may be a good option for the proper calculation of post-LASIK IOP.


Climate change and health in Southeast Asia - defining research priorities and the role of the Wellcome Trust Africa Asia Programmes.
This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.


Substrate supply for calcite precipitation in Emiliania huxleyi: assessment of different model approaches.
Over the last four decades, different hypotheses of Ca(2+) and dissolved inorganic carbon transport to the intracellular site of calcite precipitation have been put forth for Emiliania huxleyi (Lohmann) Hay & Mohler. The objective of this study was to assess these hypotheses by means of mathematical models. It is shown that a vesicle-based Ca(2+) transport would require very high intravesicular Ca(2+) concentrations, high vesicle fusion frequencies as well as a fast membrane recycling inside the cell. Furthermore, a kinetic model for the calcification compartment is presented that describes the internal chemical environment in terms of carbonate chemistry including calcite precipitation. Substrates for calcite precipitation are transported with different stoichiometries across the compartment membrane. As a result, the carbonate chemistry inside the compartment changes and hence influences the calcification rate. Moreover, the effect of carbonic anhydrase (CA) activity within the compartment is analyzed. One very promising model version is based on a Ca(2+) /H(+) antiport, CO2 diffusion, and a CA inside the calcification compartment. Another promising model version is based on an import of Ca(2+) and HCO3 (-) and an export of H(+) .


Hydraulic and oncotic pressure measurements in inner medulla of mammalian kidney.
The vasa recta are thought to play an important role in the transfer of water andsolutes within the renal medulla. Hydraulic pressures were measured in vasa recta onthe surface of the exposed papilla in young Munich Wistar rats, and blood was collected from these microvessels for determination of total protein concentration and calculation of colloid oncotic pressure. In descending vasa recta at the base of the exposed papilla, mean hydraulic pressure was 9.2 plus or minus 0.4 (SE) mmHg and plasma protein concentration averaged 7.1 plus or minus 0.4 g/100 ml. Corresponding valuesin ascending vasa recta at the same level were 7.8 plus or minus 0.4 mmHg and 5.6 plusor minus 0.3 g/100 ml. respectively. The protein concentrations correspond to calculated oncotic pressures of 26 and 18 mmHg in descending and ascending vasa recta, respectively. We interpret these findings as evidence for net water uptake by the vasa recta in the renal inner medulla for which the driving forces are the transcapillary hydraulic and oncotic pressure differences.


Energetics of strand-displacement reactions in triple helices: a spectroscopic study.
DNA triple helices offer exciting new perspectives toward oligonucleotide-directed inhibition of gene expression. Purine and GT triplexes appear to be the most promising motifs for stable binding under physiological conditions compared to the pyrimidine motif, which forms at relatively low pH. There are, however, very little data available for comparison of the relative stabilities of the different classes of triplexes under identical conditions. We, therefore, designed a model system which allowed us to set up a competition between the oligonucleotides of the purine and pyrimidine motifs targeting the same Watson-Crick duplex. Several conclusions may be drawn: (i) a weak hypochromism at 260 nm is associated with purine triplex formation; (ii) delta H degree of GA, GT and TC triplex formation (at pH 7.0) was calculated as -0.1, -2.5 and -6.1 kcal/mol per base triplet, respectively. This unexpectedly low delta H degree for the purine triple helix formation implies that its delta G degree is nearly temperature-independent and it explains why these triplexes may still be observed at high temperatures. In contrast, the pyrimidine triplex is strongly favoured at lower temperatures; (iii) as a consequence, in a system where two third-strands compete for triplex formation, displacement of the GA or GT strand by a pyrimidine strand may be observed at neutral pH upon lowering the temperature. This original purine-to-pyrimidine triplex conversion shows a significant hypochromism at 260 nm and a hyperchromism at 295 nm which is similar to the duplex-to-triplex conversion in the pyrimidine motif. Further evidence for this triplex-to-triplex conversion is provided by mung bean-nuclease foot-printing assay.


[Engagement anomalies of the patella].
Among the patellar instabilities, the authors have singled out the anomaly of engagement. Occurring accidentally in the first 30 degrees of knee flexion, it causes a dynamic derangement. The sole logical treatment appears to be wide resection of the lateral retinaculum and a heightening and shortening suture of the medial retinaculum.


The weave technique for nipple reconstruction.
Traditional nipple reconstruction relies on local flap techniques. However, there are several problems associated with local flap reconstruction including loss of projection, widening of the base width, and difficulty working around the mastectomy scar. This study presents a variation of traditional local flap nipple reconstruction, which is termed the weave technique. Rather than using two flaps to create base width, the weave technique uses one. By controlling the base width, this may serve to sustain long-term projection. Second, filling the inside of the nipple with the second flap may contribute to longer term projection. Because there is no third flap, it is easier to orient the nipple with respect to the mastectomy scar. To date, the senior author has used this method to reconstruct 55 nipples in 40 patients, with 415 days (range 191-733) mean follow-up time. This includes 45 (82%) nipple reconstructions after tissue expander-implant reconstruction. The use of this technique has produced excellent aesthetic results with nipple projection and site healing. The majority of patients have been satisfied with their nipple reconstruction. Three patients had wound healing difficulties, including two (3.6%) that healed with conservative wound care and one (1.8%) in a radiated patient requiring surgical revision. There were no other revisions necessary and no infections. In summary, the weave technique is a suitable modification to the popular C-V technique that maintains the benefits and simplicity of the aforementioned flap while potentially reducing projection loss, conserving base width, and allowing greater flexibility for nipple placement.


Prolactin and progesterone receptors in pregnancy-dependent mammary tumors in GR/A mice.
In this study, cellular prolactin receptors and cytosolic progesterone receptors were examined and compared in pregnancy-dependent mammary tumors (PDMT) and in normal mammary glands of pregnant GR/A mice. PDMT and normal mammary glands were examined in the same animal, thus assuring an identical hormonal environment. The PDMT cells had a larger capacity to bind prolactin or the synthetic progesterone, R5020, than did the normal mammary gland. While the dissociation constant (Kd) value for prolactin binding to normal mammary epithelial cells was similar to that of PDMT cells, PDMT cells had 2.2 times more prolactin receptors than the normal cells. Progesterone binding activity was detected only in PDMT, but not in the normal mammary cells. The receptor concentration and the Kd value for progesterone binding of PDMT were 606 fmol/mg protein and 3.53 nM, respectively. It appears, therefore, that normal regulation of these receptors may be altered within the PDMT cells. The increased growth responsiveness of PDMT to the hormones of pregnancy, especially prolactin, progesterone, and placental lactogen, may be a function of a sharp increase in the level of cellular receptors for these mammotropic hormones.


Induction of Autophagy by Pterostilbene Contributes to the Prevention of Renal Fibrosis via Attenuating NLRP3 Inflammasome Activation and Epithelial-Mesenchymal Transition.
Chronic kidney disease (CKD) is recognized as a global public health problem. NLRP3 inflammasome activation has been characterized to mediate diverse aspect mechanisms of CKD through regulation of proinflammatory cytokines, tubulointerstitial injury, glomerular diseases, renal inflammation, and fibrosis pathways. Autophagy is a characterized negative regulation mechanism in the regulation of the NLRP3 inflammasome, which is now recognized as the key regulator in the pathogenesis of inflammation and fibrosis in CKD. Thus, autophagy is undoubtedly an attractive target for developing new renal protective treatments of kidney disease via its potential effects in regulation of inflammasome. However, there is no clinical useful agent targeting the autophagy pathway for patients with renal diseases. Pterostilbene (PT, trans-3,5-dimethoxy-4-hydroxystilbene) is a natural analog of resveratrol that has various health benefits including autophagy inducing effects. Accordingly, we aim to investigate underlying mechanisms of preventive and therapeutic effects of PT by reducing NLRP3 inflammasome activation and fibrosis through autophagy-inducing effects. The renal protective effects of PT were evaluated by potassium oxonate (PO)-induced hyperuricemia and high adenine diet-induced CKD models. The autophagy induction mechanisms and anti-fibrosis effects of PT by down-regulation of NLRP3 inflammasome are investigated by using immortalized rat kidney proximal tubular epithelial NRK-52E cells. To determine the role of autophagy induction in the alleviating of NLRP3 inflammasome activation and epithelial-mesenchymal transition (EMT), NRK-52E with Atg5 knockdown [NRK-Atg5-(2)] cells were applied in the study. The results indicated that PT significantly reduces serum uric acid levels, liver xanthine oxidase activity, collagen accumulation, macrophage recruitment, and renal fibrosis in CKD models. At the molecular levels, pretreatment with PT downregulating TGF-β-triggered NLRP3 inflammasome activation, and subsequent EMT in NRK-52E cells. After blockage of autophagy by treatment of Atg5 shRNA, PT loss of its ability to prevent NLRP3 inflammasome activation and EMT. Taken together, we suggested the renal protective effects of PT in urate nephropathy and proved that PT induces autophagy leading to restraining TGF-β-mediated NLRP3 inflammasome activation and EMT. This study is also the first one to provide a clinical potential application of PT for a better management of CKD through its autophagy inducing effects.


Augmentation of human leukemic cell invasion by activation of a small GTP-binding protein Rho.
The functions of a small GTP-binding protein, Rho, in human leukemic cell invasion was investigated in vivo and in vitro. Human leukemic KM3 and Reh cells (derived from B-cell-type common acute lymphoid leukemias) were inoculated into severe combined immundeficiency (SCID) mice. Alteration of invasion in SCID mice inoculated with KM3 cells that were introduced with the expression vector for Rho Val14 (Rho V14), an activated mutant form of Rho, was observed. SCID mice inoculated with KM3 and Reh cells developed paraplegia 21 days after inoculation. All died by day 26-27. The leukemic cells were localized to bone marrow and around the spinal cord, with no infiltration into peripheral blood, spleen, liver, thymus, or lymph nodes. SCID mice inoculated with Rho V14-transfected KM3 cells showed a 5-day reduction in the time to paraplegia and death compared with SCID mice inoculated with hygromycin-resistance gene-transfected KM3 (hyg(r)) cells. In addition, the mice inoculated with Rho V14 cells showed leukemic cell infiltration, not only into bone marrow and around the spinal cord but also into peripheral blood, liver, and spleen. There were no in vitro or in vivo differences in growth rates of Rho V14 and hyg(r) cells. However, the Rho V14 cells showed markedly increased cell adhesion compared to the hyg(r) cells. Results suggest that Rho activation accelerates human leukemic cell invasion via augmentation of cell adhesion.


Study on the levels of glycosylated lipoprotein in patients with coronary artery atherosclerosis.
The main risk factors for atherosclerosis patients are not fully explicated. The aim of this study was to analyze the levels of blood lipid and glycosylated lipoprotein in patients with coronary artery atherosclerosis and healthy individuals and to study the relationship between the glycosylated lipoprotein and atherosclerosis. The study involved 200 patients diagnosed with myocardial infarction caused by coronary atherosclerosis as case group and 230 healthy individuals as control group. We analyzed and contrasted the levels of blood lipid and glycosylated lipoprotein between the different groups. In addition, we investigated the correlation between glycosylated low-density lipoprotein (G-LDL) and glucose levels. There is no statistical difference between the level of TG in case group and control group. The level of CHOL, HDL-C, and LDL-C in case group is significantly lower than that in control group (3.90 [3.23, 4.42] vs 5.16 [4.86, 5.77] [mmol/L]; 1.09 [0.83, 1.38] vs 1.46 [1.15, 1.80] [mmol/L]; 2.22 [1.68, 2.81] vs 2.95 [2.60, 3.27] [mmol/L]) (P < 0.05). The level of GLU, HbA1c, G-HDL, and G-LDL in case group is significantly higher than that in control group (7.10 [5.68, 9.27] vs 4.84 [4.68, 5.07] [mmol/L]; 6.8 [6.3, 7.4] vs 5.9 [5.6, 6.1] [%]; 30.08 [25.04, 40.17] vs 22.95 [18.14, 27.06] [ng/mL], 6.26 [4.95, 7.50] vs 3.61 [2.66, 5.15] [ng/mL]) (p < 0.05). The level of G-LDL in patients with coronary atherosclerosis was relevant with the level of GLU and HbA1c (r = 0.625, 0.706, P < 0.05), and there was no relevance with LDL-C (r = 0.331, P > 0.05). Hyperlipidemia is not an important cause of coronary atherosclerosis. High glucose levels and glycosylated lipoprotein are of high importance in the development and progression of coronary atherosclerosis.


[Improvement in the diagnosis of opisthorchiasis by fecal egg count].
Chemical sedimentation method of coproovoscopic diagnosis of trematodoses was modified: sodium nitrate was replaced by sodium nitrite (this increased the helminthic egg membrane hydrophilia) and the optimal ratio of sodium nitrite to acetic acid solution volumes was experimentally selected. This improved the method sensitivity twofold (p less than 0.001). Three series of investigations of the sensitivities of the modified chemical sedimentation method, microscopy of the native smear, Kato's, Hein's, Kalantaryan's, Stoll's methods, and ether-formalin sedimentation of helminthic eggs were carried out with the material from opisthorchiasis patients with invasion of low intensity. The modified technique proved to be the most sensitive (p less than 0.01) and productive (p less than 0.001). It is recommended for screening the population at endemic regions and for control analyses after etiotropic therapy of trematodosis patients.


[Alopecia areata in children].
Alopecia areata is a hair disease of unknown origin characterized by the sudden appearance of one or more bald patches. This disorder may develop in adults as well as in children. In childhood there is often an association with atopy. Most investigators feel that alopecia areata is an auto-immune phenomenon with heterogeneous aetiology. This article deals with hypotheses for the development of alopecia areata stressing also the psychosomatic aspects. Different therapy modalities have been propagated in alopecia areata, though complete satisfactory effects have been achieved by none. In childhood application of dithranol and locally applied corticosteroids are the only suitable therapeutic possibilities. Insufficient insight into the pathogenesis and associations of this disorder in childhood warrants further investigations.


Gut peptide receptors in pancreata of azaserine-treated and normal control rats.
Gut peptides are involved in the growth and carcinogenesis of the exocrine pancreas of rats after treatment with azaserine. However, little is known about the influence of azaserine on expression of gut peptide receptors in the pancreas of the rat. Cholecystokinin, bombesin, somatostatin, secretin, and vasoactive intestinal peptide receptors were therefore visualized and quantified by storage phosphor autoradiography in pancreata of either saline control or azaserine-treated rats. As expected, putative preneoplastic lesions were formed in the pancreata of the azaserine-treated but not in the control animals. The pancreata of control rats contained receptors for cholecystokinin, bombesin, somatostatin, secretin, and vasoactive intestinal peptide. Cholecystokinin receptors were of the A-type and showed, in contrast to the other receptors, a heterogeneous expression due to variability of the high-affinity receptors. In the pancreata of azaserine-treated animals a significantly increased binding capacity of high-affinity receptors fro cholecystokinin was found not only in atypical acinar cell nodules but also in non-nodular pancreas when compared to pancreas of control rats (P < 0.05). Neither atypical acinar cell nodules nor non-nodular pancreas of rats treated by azaserine were shown to possess receptors for the other four types of gut peptide receptors. The spectrum of peptide receptors in pancreas of control and azaserine-treated rats in this study may help to understand the mechanism whereby gut hormones may modulate pancreatic carcinogenesis.


Pinellia ternata agglutinin expression in chloroplasts confers broad spectrum resistance against aphid, whitefly, Lepidopteran insects, bacterial and viral pathogens.
Broad spectrum protection against different insects and pathogens requires multigene engineering. However, such broad spectrum protection against biotic stress is provided by a single protein in some medicinal plants. Therefore, tobacco chloroplasts were transformed with the agglutinin gene from Pinellia ternata (pta), a widely cultivated Chinese medicinal herb. Pinellia ternata agglutinin (PTA) was expressed up to 9.2% of total soluble protein in mature leaves. Purified PTA showed similar hemagglutination activity as snowdrop lectin. Artificial diet with purified PTA from transplastomic plants showed marked and broad insecticidal activity. In planta bioassays conducted with T0 or T1 generation PTA lines showed that the growth of aphid Myzus persicae (Sulzer) was reduced by 89%-92% when compared with untransformed (UT) plants. Similarly, the larval survival and total population of whitefly (Bemisia tabaci) on transplastomic lines were reduced by 91%-93% when compared with UT plants. This is indeed the first report of lectin controlling whitefly infestation. When transplastomic PTA leaves were fed to corn earworm (Helicoverpa zea), tobacco budworm (Heliothis virescens) or the beet armyworm (spodoptera exigua), 100% mortality was observed against all these three insects. In planta bioassays revealed Erwinia population to be 10,000-fold higher in control than in PTA lines. Similar results were observed with tobacco mosaic virus (TMV) challenge. Therefore, broad spectrum resistance to homopteran (sap-sucking), Lepidopteran insects as well as anti-bacterial or anti-viral activity observed in PTA lines provides a new option to engineer protection against biotic stress by hyper-expression of an unique protein that is naturally present in a medicinal plant.


Challenges of Implementing an Effective Primary Health Care Accreditation Program: a qualitative study in Iran.
Accreditation is a prerequisite for scientific management of the health system, owing to its numerous benefits on health centres' performance. The current study examined Iran's primary healthcare accreditation program to ascertain the challenges to its successful implementation. This qualitative study examined the perspectives of 32 managers and staff members in the pilot accreditation program (from the Ministry of Health and Medical Education, Semnan University of Medical Sciences, and Aradan District Health Network). Three in-depth group interviews were conducted using a semi-structured questionnaire, and the data obtained were assessed using thematic analysis. As a result of this investigation identified six themes, 29 sub-themes, and 218 codes as challenges to the successful accreditation of primary health care in Iran. Six main themes, including "organisational culture", "motivational mechanisms", "staff workload", "training system", "information systems", and "macro-executive infrastructure", were identified as the main domain of challenges, with seven, five, two, four, three, and eight sub-themes respectively. Accreditation of PHC in Iran faces significant challenges and obstacles that, if ignored, can jeopardise the program's success and effectiveness. By identifying challenges and obstacles and making practical suggestions for overcoming them, the findings of this study can aid in the program's successful implementation and achievement of desired outcomes.


[The mechanisms of interdependent influence of prefrontal cortex, hippocampus and amygdala on the basal ganglia functioning and selection of behaviour].
The hypothetical mechanism of functioning of neural networks that include limbic structures, neocortex and basal ganglia is proposed. A hypothesis is based on known data that the hippocampus, amygdala and prefrontal cortex interreact with each other, that their efferents converge on spiny cells of nucleus accumbens, that these inputs are topically organised and could be modified. Since GABAergic spiny cells of nucleus accumbens innervate neurons in the output basal ganglia nuclei which inhibit excitatory transmission through the thalamic nuclei into limbic structures and neocortex, the degree of activation of neurones in mentioned structures and, hence, a behaviour selection essentially depends on the character of responses of spiny cells. A summation of excitation of spiny cells and amplification of their responses during simultaneous firing of neurons of a limbic structure and neocortex, ultimately will lead to rising in neocortical activity and increase of its influence on a behaviour selection. If two structures are excited with temporary shift, activation of neurons of that structure which has firstly been strongly excited can be additionally increased due to a disinhibition of thalamic nuclei through the basal ganglia, whereas activity of neurons in other structure can be depressed if responses of spiny cells evoked by excitation arriving from this structure are decreased. Such suppression can be a consequence of heterosynaptic depression which is based on potentiation of efficacy of excitatory inputs from the different structures converging on inhibitory interneurons in the nucleus accumbens and basolateral amygdala. As a result, the behaviour choice will be determined by that structure which has been involved in activity firstly. A damage of different inputs into the nucleus accumbens from limbic structures must result in various behaviour disorders owing to the topical organisation of these inputs.


Activation of a keratinocyte phospholipase A2 by bradykinin and 4 beta-phorbol 12-myristate 13-acetate. Evidence for a receptor-GTP-binding protein versus a protein-kinase-C mediated mechanism.
The release of arachidonic acid from cellular phospholipids and its subsequent conversion to eicosanoids is the common early response of skin keratinocytes to a wide variety of exogenous or endogenous agonists including irritant skin mitogens such as the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate (PMA) or the inflammatory peptide bradykinin. In mouse keratinocytes labeled with [14C]arachidonic acid, both PMA and bradykinin induced the release of the fatty acid in a dose-dependent and time-dependent manner. Three lines of evidence indicate phospholipase A2 activity to be involved in arachidonic acid release: (a) its inhibition by mepacrine, (b) the concomitant generation of lysophosphatidylcholine from [3H]choline-labeled cells and (c) an increase in arachidonic acid release from 14C-labeled phosphatidylcholine in particulate fractions from PMA-treated and bradykinin-treated keratinocytes. Inhibition or down regulation of protein kinase C (PKC) led to a suppression of PMA-induced but not bradykinin-induced arachidonic acid release, indicating a critical involvement of this kinase in phorbol-ester-induced activation of epidermal phospholipase A2 activity. Bradykinin-induced activation of phospholipase A2 was however, shown to be mediated by specific B2 receptors coupled to GTP-binding proteins (G protein). In support of this mechanism it was demonstrated that the bradykinin-induced phospholipase A2 activity was increased in the presence of non-hydrolysable GTP but decreased upon addition of non-hydrolysable GDP analogues. Moreover, cholera toxin stimulated both basal and bradykinin-induced phospholipase A2 activity in a cAMP-independent manner, whereas pertussis toxin was found to be inactive in this respect. The data suggest that epidermal phospholipase A2 activity can be stimulated by bradykinin via a B2 receptor-G-protein-dependent pathway, which is independent of PKC and a PKC-dependent pathway which is activated by phorbol esters such as PMA.


Opening a can of worms: a test of the coinfection facilitation hypothesis.
Parasitic infections are a global occurrence and impact the health of many species. Coinfections, where two or more species of parasite are present in a host, are a common phenomenon across species. Coinfecting parasites can interact directly, or indirectly via their manipulation of (and susceptibility to) the immune system of their shared host. Helminths, such as the cestode Schistocephalus solidus , are well known to suppress immunity of their host (threespine stickleback, Gasterosteus aculeatus ), potentially facilitating other parasite species. Yet, hosts can evolve a more robust immune response (as seen in some stickleback populations), potentially turning facilitation into inhibition. Using wild-caught stickleback from 21 populations with non-zero S. solidus prevalence, we tested an a priori hypothesis that S. solidus infection facilitates infection by other parasites. Consistent with this hypothesis, individuals with S. solidus infections have 18.6% higher richness of other parasites, compared to S. solidus -uninfected individuals from the same lakes. This facilitation-like trend is stronger in lakes where S. solidus is particularly successful but is reversed in lakes with sparse and smaller cestodes (indicative of stronger host immunity). These results suggest that a geographic mosaic of host-parasite coevolution might lead to a mosaic of between-parasite facilitation/inhibition effects.


The effects of progesterone treatment on nuchal translucency in women with threatened miscarriage.
This study aims to investigate the effects of progesterone on the possible changes in nuchal translucency (NT) levels for patients diagnosed with threatened miscarriage. The study group was composed of 125 patients diagnosed with threatened miscarriage and taking 400 mg/day micronized orally progesterone at least for two weeks, the control group was composed of 160 healthy pregnant women not taking any progesterone. Crown rump length (CRL) NT thickness, Pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (Beta-HCG) levels of patients were measured for assessment of aneuploidy risk. Both of the groups were divided into four subgroups to determine the relationship between thickness of NT and progesterone use for specific CRL measurements. CRL in the first, second, third and fourth group was 45-55 mm, 55-65 mm, 65-75 mm, 75-84 mm, respectively. The two groups were age and BMI matched. In all groups of CRL there were no significant difference in Mom levels of NT thickness, PAPP-A and free Beta-HCG between the study and control groups. There havent been any relation between NT thickness and progesterone use.IMPACT STATEMENTWhat is already known about this subject? Recently some studies have claimed that progesterone use might have caused atypical blood flow pattern on foetal circulation, which could possibly increase NT. If the NT thickness is affected by the use of progesterone, then the false positive rate of detecting Down Syndrome screening tests would increase.What the results of this study add? In this study we did not found any relation between NT thickness and progesterone use.What the implications are of these findings for clinical practice and/or further research? Using orally progesterone due to threatened miscarriage do not change NT thickness levels. Further studies have to be done with a large number of participants.


Large-area soft-imprinted nanowire networks as light trapping transparent conductors.
Using soft-imprint nanolithography, we demonstrate large-area application of engineered two-dimensional polarization-independent networks of silver nanowires as transparent conducting electrodes. These networks have high optical transmittance, low electrical sheet resistance, and at the same time function as a photonic light-trapping structure enhancing optical absorption in the absorber layer of thin-film solar cells. We study the influence of nanowire width and pitch on the network transmittance and sheet resistance, and demonstrate improved performance compared to ITO. Next, we use P3HT-PCBM organic solar cells as a model system to show the realization of nanowire network based functional devices. Using angle-resolved external quantum efficiency measurements, we demonstrate engineered light trapping by coupling to guided modes in the thin absorber layer of the solar cell. Concurrent to the direct observation of controlled light trapping we observe a reduction in photocurrent as a result of increased reflection and parasitic absorption losses; such losses can be minimized by re-optimization of the NW network geometry. Together, these results demonstrate how engineered 2D NW networks can serve as multifunctional structures that unify the functions of a transparent conductor and a light trapping structure. These results are generic and can be applied to any type of optoelectronic device.


[A possible principle of kinesthetic compensation].
The movement of the cat forelimb was studied under the conditions of complete transection of the classical somatosensory pathways from the limb to the cortex of the contralateral hemisphere. It was demonstrated that in animals with the intact system of the somatosensory (kinesthetic) feedback, the parameters of the same memorized movement varied widely from response to response whereas the exclusion of lemniscus projections from the control system led to the poor movement pattern and to the appearance of motor stereotypy. The hypothesis is advanced that deficit of kinesthetic information in this case is compensated for not only by the other intact connections of the kinesthetic analyzer but also due to the conversion of the nervous system to the central-programmed level control which itself demands less participation of the somatosensory feedback. The non-crossed projections of the kinesthetic analyzer are capable of forming and correcting this program and of ensuring the effect afferentation as well. The same principle of the functioning may take place in any compensatory reconstructions in the CNS.


Biologic imaging of head and neck cancer: the present and the future.
While anatomic imaging (CT and MR imaging) of HNC is focused on diagnosing and/or characterizing the disease, defining its local extent, and evaluating distant spread, accurate assessment of the biologic status of the cancer (cellularity, growth rate, response to nonsurgical chemoradiation therapy, and so forth) can be invaluable for prognostication, planning therapy, and follow-up of lesions after therapy. The combination of anatomic and biologic imaging techniques can thus provide a more comprehensive evaluation of the patient. The purpose of this work was to review the present and future clinical applications of advanced biologic imaging techniques in HNC evaluation and management. As part of the biologic imaging array, we discuss MR spectroscopy, diffusion and perfusion MR imaging, CTP, and FDG-PET scanning and conclude with exciting developments that hold promise in assessment of tumor hypoxia and neoangiogenesis.


Apoptosis in Living Animals Is Assisted by Scavenger Cells and Thus May Not Mainly Go through the Cytochrome C-Caspase Pathway.
Because billions of cells die every day in their bodies, animals have evolutionarily developed apoptosis to preserve the tissue environment from adverse effects of dead cells, a process achieved via phagocytosis of the cell corpses by professional or amateur phagocytes that are collectively referred to as scavengers. Hence, apoptosis is a merger of two procedures separately occurring inside the dying and the scavenger cells, respectively. The task of apoptosis research is to study how these death procedures occur without hurting the host tissues, and recruitment of in vitro system into the study must be justified for this purpose. Cells in culture have no motivation to preserve the environment, and their death does not involve corpse clearance by scavengers. Therefore, programmed cell death in culture should be redefined, for example as stress-induced cell death, to avoid many sources of confusions, since the word "apoptosis" had already been defined, prior to the era of cell culture, as a silent and beneficial cell suicide with corpse clearance as a distinctive hallmark. We should start over again on apoptosis research by determining whether different physiological apoptotic procedures in animals involve the cytochrome c-caspase pathway, since it has been established from cultured cells as a central mechanism of "apoptosis" but whether it overarches any physiological apoptotic procedure in animals is still unclear. Probably, cells in living animals are programmed to use scavengers to assist their apoptosis but cells in culture have no scavengers to help and thus need to go mainly through the cytochrome c-caspase pathway.


[The value of early exercise testing in patients with myocardial infarction complicated by evolving left ventricular aneurysm].
The values of an early exercise test limited by criteria for test termination were compared with coronaro- and ventriculographic measurements made 2-3 days after the test in 51 males of working age who suffered from transmural myocardial infarction complicated by local aneurysm in 12 cases and by overall left ventricular aneurysm in 39. The exercise test performed in the early periods was found to substantially increased its sensitivity. The isolated ST-dominant segment elevation in patients with local aneurysm and isolated coronary artery lesion indicated that the patients had a favourable prognosis. On the contrary, the combination of two criteria or more of a positive test in patients with global aneurysm and multivessel disease suggests that the patients with temporary disability should be followed up. The presence of T-dominant ST-segment elevation, anginal pain concurrent with an inadequate BP elevation shows that there is a high risk for postinfarction complications.


Functional colloidal micro-sieves assembled and guided above a channel-free magnetic striped film.
Colloidal inclusions in lab-on-a-chip devices can be used to perform analytic operations in a non-invasive fashion. We demonstrate here a novel approach to realize fast and reversible micro-sieving operations by manipulating and transporting colloidal chains via mobile domain walls in a magnetic structured substrate. We show that this technique allows one to precisely move and sieve non-magnetic particles, to tweeze microscopic cargos or to mechanically compress highly dense colloidal monolayers.


Geographic and Socioeconomic Determinants of Full Coverage COVID-19 Vaccination in Peru: Findings from a National Population-Based Study.
Despite the fact that vaccination coverage against COVID-19 has made great progress in Peru, there is still a quarter of the population that has not been fully vaccinated. This study aims to determine the factors associated with complete vaccination in Peruvian adults. An analysis of the National Household Survey 2022 in Peru was performed. Prevalence ratios with their 95% confidence intervals (95% CI) were estimated to assess the factors associated with vaccination with three or more doses of the COVID-19 vaccine. A total of 58,471 participants were included in the study and 75.8% of the surveyed population were found to have received full vaccination. Significant differences in complete coverage were observed according to sex, age, educational level, ethnicity, poverty status, and geographic location. In the adjusted analysis, individuals aged 60 years or older, those with higher educational attainment, the non-poor, and those living in urban areas were more likely to be fully vaccinated. Native individuals and people who live in households without media are less likely to be fully covered. These results highlight the importance of considering demographic and socioeconomic factors when analyzing COVID-19 vaccination coverage. Additional strategies are needed to address vaccination gaps and ensure better vaccination coverage.


Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices.
Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates.


Access to New Zealand Sign Language interpreters and quality of life for the deaf: a pilot study.
This paper aims to: (1) explore usage and accessibility of sign language interpreters, (2) appraise the levels of quality of life (QOL) of deaf adults residing in New Zealand, and (3) consider the impact of access to and usage of sign language interpreters on QOL. Sixty-eight deaf adults living in New Zealand participated in this study. Two questionnaires were employed: a 12-item instrument about access and use of New Zealand sign language interpreters and the abbreviated version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF). The results showed that 39% of this sample felt that they were unable to adequately access interpreting services. Moreover, this group scored significantly lower than a comparable hearing sample on all four WHOQOL-BREF domains. Finally, the findings revealed that access to good quality interpreters were associated with access to health services, transport issues, engagement in leisure activities, gaining more information, mobility and living in a healthy environment. These findings have consequences for policy makers and agencies interested in ensuring that there is an equitable distribution of essential services for all groups within New Zealand which inevitably has an impact on the health of the individual.


Interplay between connexin40 and nitric oxide signaling during hypertension.
Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.


Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature.
Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT.


Erectile function following brachytherapy, external beam radiotherapy, or radical prostatectomy in prostate cancer patients.
For localized prostate cancer, treatment options include external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT). Erectile dysfunction (ED) is a common side-effect. Our aim was to evaluate penile erectile function (EF) before and after BT, EBRT, or RP using a validated self-administered quality-of-life survey from a prospective registry. Analysis included 478 patients undergoing RP (n = 252), EBRT (n = 91), and BT (n = 135) with at least 1 year of follow-up and EF documented using IIEF-5 scores at baseline, 6 weeks, 6 months, 1 year, and annually thereafter. Differences among treatments were most pronounced among patients with no or mild initial ED (IIEF-5 ≥ 17). Overall, corrected for baseline EF and age, BT was associated with higher IIEF-5 scores than RP (+ 7.8 IIEF-5 score) or EBRT (+ 3.1 IIEF-5 score). EBRT was associated with better IIEF-5 scores than RP (+ 4.7 IIEF-5 score). In patients undergoing EBRT or RP with bilateral nerve sparing (NS), recovery of EF was observed and during follow-up, the differences to BT were not statistically significant. Overall age had a negative impact on EF preservation (corrected for baseline IIEF). In our series, EF was adversely affected by each treatment modality. Considered overall, BT provided the best EF preservation in comparison to EBRT or RP.


Hydatid cysts of the lung.
Cystic hydatid disease is a zoonosis caused by infection with the larval cysts of Echinococcus granulosus. Cysts commonly develop in the liver and lungs. Diagnosis in non-endemic regions is often delayed due to a failure to consider hydatidosis. This results from a non-specific presentation and a failure to record an accurate geographical history. The diagnosis requires integrating an appropriate index of suspicion with correct interpretation of imaging and serological tests. In our case, a 44-year-old woman of Yemeni origin presented to a UK hospital with chest pain, pruritus and weight loss. Following detection of pulmonary nodules, a CT-guided biopsy was carried out to exclude malignancy. Iatrogenic cyst rupture precipitated an acute eosinophilic pleurisy. Cystic hydatid disease was subsequently diagnosed following strongly positive hydatid serological tests. This case illustrates the importance of considering diagnoses appropriate to an individual's geographical history particularly in the context of rising immigration and foreign travel.


A new porcine model of reperfusion injury after lung transplantation.
Rodent models have been described to investigate lung preservation and reperfusion injury but have significant disadvantages. In large animals single lung transplant studies are probably optimal but problems remain over the ability to rigorously separate the lungs for assessment while promoting medium to long-term animal survival for meaningful investigation. Our aim was to develop a novel and refined large animal model to assess reperfusion injury in the transplanted lung, overcoming the difficulties associated with existing models. Specifically, small animal models of lung transplantation usually have short perfusion times (often one hour) and include extracorporeal circuits while larger animal models often require the contralateral lung to be excluded after transplantation-an unphysiological situation under which to evaluate the graft. A porcine model of left lung allotransplantation was developed in which native and donor lungs are individually ventilated. Sampling catheters placed within the graft lung allowed specimen withdrawal without mixing of blood from the contralateral lung after reimplantation. The model permits a variety of clinical scenarios to be simulated with the native lung supporting the animal irrespective of function in the graft. This model has been used in over 60 transplant procedures with a postoperative survival time of 12 h being readily achieved. The mean operating time was 2.6 h. The mortality rate is 4% in our series. We have found the model to be reliable, reproducible and flexible. We propose this model as an adaptable investigation for evaluating lung reperfusion injury and preservation.


Spatial ecology and conservation of leatherback turtles (Dermochelys coriacea) nesting in Bioko, Equatorial Guinea.
Bioko Island (Equatorial Guinea) hosts important nesting habitat for leatherback sea turtles, with the main nesting beaches found on the island's southern end. Nest monitoring and protection have been ongoing for more than two decades, although distribution and habitat range at sea remains to be determined. This study uses satellite telemetry to describe the movements of female leatherback turtles (n = 10) during and following the breeding season, tracking them to presumed offshore foraging habitats in the south Atlantic Ocean. Leatherback turtles spent 100% of their time during the breeding period within the Exclusive Economic Zone (EEZ) of Equatorial Guinea, with a core distribution focused on the south of Bioko Island extending up to 10 km from the coast. During this period, turtles spent less than 10% of time within the existing protected area. Extending the border of this area by 3 km offshore would lead to a greater than threefold increase in coverage of turtle distribution (29.8 ± 19.0% of time), while an expansion to 15 km offshore would provide spatial coverage for more than 50% of tracking time. Post-nesting movements traversed the territorial waters of Sao Tome and Principe (6.4%of tracking time), Brazil (0.85%), Ascension (1.8%), and Saint Helena (0.75%). The majority (70%) of tracking time was spent in areas beyond national jurisdiction (i.e. the High Seas). This study reveals that conservation benefits could be achieved by expanding existing protected areas stretching from the Bioko coastal zone, and suggests shared migratory routes and foraging space between the Bioko population and other leatherback turtle rookeries in this region.


The effects of bone marrow stem and progenitor cell seeding on urinary bladder tissue regeneration.
Complications associated with urinary bladder augmentation provide the motivation to delineate alternative bladder tissue regenerative engineering strategies. We describe the results of varying the proportion of bone marrow (BM) mesenchymal stem cells (MSCs) to CD34 + hematopoietic stem/progenitor cells (HSPCs) co-seeded onto synthetic POC [poly(1,8 octamethylene citrate)] or small intestinal submucosa (SIS) scaffolds and their contribution to bladder tissue regeneration. Human BM MSCs and CD34 + HSPCs were co-seeded onto POC or SIS scaffolds at cell ratios of 50 K CD34 + HSPCs/15 K MSCs (CD34-50/MSC15); 50 K CD34 + HSPCs/30 K MSCs (CD34-50/MSC30); 100 K CD34 + HSPCs/15 K MSCs (CD34-100/MSC15); and 100 K CD34 + HSPCs/30 K MSCs (CD34-100/MSC30), in male (M/POC; M/SIS; n = 6/cell seeded scaffold) and female (F/POC; F/SIS; n = 6/cell seeded scaffold) nude rats (n = 96 total animals). Explanted scaffold/composite augmented bladder tissue underwent quantitative morphometrics following histological staining taking into account the presence (S+) or absence (S-) of bladder stones. Urodynamic studies were also performed. Regarding regenerated tissue vascularization, an upward shift was detected for some higher seeded density groups including the CD34-100/MSC30 groups [F/POC S- CD34-100/MSC30 230.5 ± 12.4; F/POC S+ CD34-100/MSC30 245.6 ± 23.4; F/SIS S+ CD34-100/MSC30 278.1; F/SIS S- CD34-100/MSC30 187.4 ± 8.1; (vessels/mm2)]. Similarly, a potential trend toward increased levels of percent muscle (≥ 45% muscle) with higher seeding densities was observed for F/POC S- [CD34-50/MSC30 48.8 ± 2.2; CD34-100/MSC15 53.9 ± 2.8; CD34-100/MSC30 50.7 ± 1.7] and for F/SIS S- [CD34-100/MSC15 47.1 ± 1.6; CD34-100/MSC30 51.2 ± 2.3]. As a potential trend, higher MSC/CD34 + HSPCs cell seeding densities generally tended to increase levels of tissue vascularization and aided with bladder muscle growth. Data suggest that increasing cell seeding density has the potential to enhance bladder tissue regeneration in our model.


STEM undergraduates' perspectives of instructor and university responses to the COVID-19 pandemic in Spring 2020.
We examined undergraduate STEM students' experiences during Spring 2020 when universities switched to remote instruction due to the COVID-19 pandemic. Specifically, we sought to understand actions by universities and instructors that students found effective or ineffective, as well as instructor behaviors that conveyed a sense of caring or not caring about their students' success. In July 2020 we conducted 16 focus groups with STEM undergraduate students enrolled in US colleges and universities (N = 59). Focus groups were stratified by gender, race/ethnicity, and socioeconomic status. Content analyses were performed using a data-driven inductive approach. Participants (N = 59; 51% female) were racially/ethnically diverse (76% race/ethnicity other than non-Hispanic white) and from 32 colleges and universities. The most common effective instructor strategies mentioned included hybrid instruction (35%) and use of multiple tools for learning and student engagement (27%). The most common ineffective strategies mentioned were increasing the course workload or difficulty level (18%) and use of pre-recorded lectures (15%). The most common behaviors cited as making students feel the instructor cared about their success were exhibiting leniency and/or flexibility regarding course policies or assessments (29%) and being responsive and accessible to students (25%). The most common behaviors cited as conveying the instructors did not care included poor communication skills (28%) and increasing the difficulty of the course (15%). University actions students found helpful included flexible policies (41%) and moving key services online (e.g., tutoring, counseling; 24%). Students felt universities should have created policies for faculty and departments to increase consistency (26%) and ensured communication strategies were honest, prompt, and transparent (23%). To be prepared for future emergencies, universities should devise evidence-based policies for remote operations and all instructors should be trained in best practices for remote instruction. Research is needed to identify and ameliorate negative impacts of the pandemic on STEM education.


Benzodiazepine inhibition of the calcium-calmodulin protein kinase system in brain membrane.
Benzodiazepines inhibit Ca2+-calmodulin-stimulated membrane protein phosphorylation. The effects of the benzodiazepines on protein phosphorylation are stereospecific and produced by membrane-bound benzodiazepine. The potency of benzodiazepine kinase inhibition is correlated with the ability of the benzodiazepines to inhibit electric shock-induced convulsions. These findings provide evidence that some of the anticonvulsant and neuronal stabilizing effects of benzodiazepines may be modulated by the Ca2+-calmodulin protein kinase system and indicate that this calmodulin-kinase system represents an identifiable benzodiazepine receptor in brain that is distinquishable by several criteria from the previously described high affinity benzodiazepine receptor.


[Current aspects of the pathology and differentiation of extranodal marginal zone B-cell lymphoma, MALT-Type, and gastrointestinal diffuse large B-cell lymphoma].
The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell lymphoma which is predominantly localised in the stomach with a typical morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a composite lymphoma (ComL) and represents a fascinating model of lymphoma progression. In this review we focus on current aspects regarding the molecular characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual relationships.


Temporal trend analysis of nurses' knowledge about implantable cardioverter defibrillators.
Although crucial, research on nurses' knowledge on the use of implantable cardioverter defibrillators (ICDs) is scant. The aims of the study were to investigate (i) the level of nurses' knowledge on care of patients with ICDs, (ii) whether knowledge level is related to education and type of hospital where nurses practice and (iii) whether knowledge level changes among nurses over time. We developed a questionnaire comprising 27 items in four parts: (1) Sociodemographics, (2) Technical facts about ICDs, (3) Daily life challenges and (4) Self-evaluation of knowledge. After validation, surveys were conducted during 1-week cardiac educational courses in 2003-2010. In total, 463 nurses working in cardiology-related areas participated, yielding a response rate of 91%. Practical and technical knowledge about ICDs was lacking. Nurses were unaware or did not know that mobile phones can affect the device (80%), that patients are restricted from driving heavy vehicles (69%), and that ICDs can deliver unintended shock therapy (73%). However, they were aware that ICD patients can resume sexual (87%) and physical activity (85%). There were few significant differences with regard to education and type of hospital where nurses practiced, but significant time trends in correct answers regarding kitchen appliances, resumption of physical activity and shock delivery. Over an 8-year period, despite the increased usage of ICDs, overall nurses had a lack of knowledge in relation to specific key clinical issues on the care of ICD patients. As a consequence, these patients may fail to receive qualified care. Future research should assess knowledge of other health care professionals and focus on interventions that increase and maintain an appropriate knowledge level in care of ICD patients. Relevance to clinical practice The level of nurses' knowledge on care of patients with ICDs needs to be systematically raised in order to ensure appropriate counselling and nursing care.


An extracytoplasmic function sigma factor cotranscribed with its cognate anti-sigma factor confers tolerance to NaCl, ethanol and methylene blue in Azospirillum brasilense Sp7.
Azospirillum brasilense, a plant-growth-promoting rhizobacterium, is exposed to changes in its abiotic environment, including fluctuations in temperature, salinity, osmolarity, oxygen concentration and nutrient concentration, in the rhizosphere and in the soil. Since extra-cytoplasmic function (ECF) sigma factors play an important role in stress adaptation, we analysed the role of ECF sigma factor (also known as RpoE or σ(E)) in abiotic stress tolerance in A. brasilense. An in-frame rpoE deletion mutant of A. brasilense Sp7 was carotenoidless and slow-growing, and was sensitive to salt, ethanol and methylene blue stress. Expression of rpoE in the rpoE deletion mutant complemented the defects in growth, carotenoid biosynthesis and sensitivity to different stresses. Based on data from reverse transcriptase-PCR, a two-hybrid assay and a pull-down assay, we present evidence that rpoE is cotranscribed with chrR and the proteins synthesized from these two overlapping genes interact with each other. Identification of the transcription start site by 5' rapid amplification of cDNA ends showed that the rpoE-chrR operon was transcribed by two promoters. The proximal promoter was less active than the distal promoter, whose consensus sequence was characteristic of RpoE-dependent promoters found in alphaproteobacteria. Whereas the proximal promoter was RpoE-independent and constitutively expressed, the distal promoter was RpoE-dependent and strongly induced in response to stationary phase and elevated levels of ethanol, salt, heat and methylene blue. This study shows the involvement of RpoE in controlling carotenoid synthesis as well as in tolerance to some abiotic stresses in A. brasilense, which might be critical in the adaptation, survival and proliferation of this rhizobacterium in the soil and rhizosphere under stressful conditions.


Magnetic resonance-guided high-intensity focused ultrasound treatment of locally advanced pancreatic adenocarcinoma: preliminary experience for pain palliation and local tumor control.
The purpose of this study was to evaluate the feasibility of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for pain palliation and local tumor control in selected patients with unresectable primary pancreatic adenocarcinoma. After providing dedicated informed consent, 7 patients with histologically proven unresectable pancreatic adenocarcinoma underwent MRgFUS treatment on a dedicated 3-T unit featuring a dedicated ablation system. All lesions were evaluated for device accessibility before the treatment. Procedures of MRgFUS were performed with the patients under general anesthesia with constant controlled respiration. Clinical assessment included evaluation of symptom severity using a visual analog scale before and after the treatment. Imaging follow-up, including both computed tomographic and magnetic resonance examinations, was performed immediately after the treatment and at 3 and 6 months to evaluate the effects of MRgFUS on the targeted tumor and the occurrence, if any, of procedure-related complications. The MRgFUS ablation was successfully performed in 6 patients; no adverse events were observed during or after the procedure. In a single patient, lesion accessibility was limited at treatment time, and the procedure was suspended. The visual analog scale score decreased in all patients from a mean (SD) of 7 (1) to 3 (1) after the treatment. Follow-up imaging results revealed negligible (n = 1) or no (n = 5) tumor regrowth within the ablation area. One patient died because of a metastatic disease 13 months after the treatment, whereas the other 5 are nonprogressing survivors at 6 and 8 months after the treatment. Our preliminary clinical experience suggests that MRgFUS is a feasible and repeatable ablative technique in selected patients with unresectable and device-accessible pancreatic adenocarcinoma.


Executive control functions in simulated driving.
Teenage novice drivers have elevated crash rates compared with more experienced drivers. This study examined the hypothesis that driving accidents in young adults are associated with individual and developmental differences in prefrontally-mediated executive control functions. High-school students completed a simulated driving task and six experimental tasks that tapped three basic components of executive functioning (response inhibition, working memory updating, and mental shifting). Individual differences in executive functioning were related to simulated driving performance, and these effects were selective in that the updating component of executive functioning was the primary predictor of driving performance. Furthermore, the observed effects were accentuated in participants with minimal experience of computer games, suggesting that computer game skills compensated for inefficient working memory functions. The results of this study suggest that individual and developmental differences in executive functions contribute to driving accidents in young adults.


Chromosome analysis of spleen and/or lymph nodes of patients with chronic myeloid leukemia (CML).
Origin and spread of the chromosomally abnormal cells that appear in chronic myeloid leukemia (CML) after transformation are unknown. Spleen and lymph node may be involved. In 16 patients with CML splenectomy and/or adenectomy were performed before or during the blastic crisis of the disease, followed by a chromosomal analysis of the cells from the removed organ. At the same time, the chromosomes of the blood cell and of the bone marrow were also analyzed. Analyses were done with R banding. The results show that an extramedullary clonal development with duplication of the Ph1 chromosome and other features occurred. From a cytogenetic standpoint, acute blastic phase of CML is frequently characterized by an increased number of chromosomes owing to preferential gain of additional chromosomes. This, then, would clearly point to extamedullary acute transition in CML.


Falling off track during the transition to high school: what we know and what can be done.
Ninth grade, observes Ruth Curran Neild, marks a critical juncture in American schooling. Students who manage the academic demands of the transition to high school have a high probability of graduating four years later. But those who do not-who fail to earn as many credits as they should during ninth grade-face a substantially elevated risk of dropping out of high school. Neild examines four theories about why ninth grade poses difficulties for some students. The first is that ninth grade coincides with life-course changes, such as reduced parental supervision and increased peer influence. The second is that in moving to a new school, students must break the bonds they have formed with their middle-school teachers and peers. The third is that some students are inadequately prepared for high school. The final theory is that the organization of some high schools is itself a major source of students' difficulty. Each theory, says Neild, suggests a particular type of policy response. The strongest evidence, observes Neild, points to inadequate preparation for high school and the organization of high schools. Reform efforts thus far have tended to address high school organization, with or without a focus on instructional quality or helping students to catch up on academic skills. Evaluations of these reforms, says Neild, suggest that both school organization and instructional improvement are necessary to keep ninth graders on track to graduation. Neild notes that school districts and state departments of education also are addressing the problem. In addition to supporting comprehensive school reform with a focus on ninth graders, districts have created accountability indicators of how well high schools are keeping ninth graders on track. States are helping districts to develop their capacity to maintain and analyze data on ninth-grade progress, including "early warning indicator systems" that identify students who are falling off track to graduation.


Association between Liver Fibrosis and Serum PSA among U.S. Men: National Health and Nutrition Examination Survey (NHANES), 2001-2010.
To evaluate the association of liver fibrosis scores with PSA level among U.S. adult men overall and by race/ethnicity. Data from the National Health and Nutrition Examination Survey (NHANES), 2001-2010, were used. Males ages ≥40 years without a prostate cancer diagnosis and who had serum PSA, liver enzymes, albumin, and platelet counts measured as part of NHANES protocol were included. Liver fibrosis was measured using three scores: aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 index (FIB-4), and NAFLD fibrosis score (NFS). We assessed overall and race/ethnicity-stratified geometric mean PSA by fibrosis score using predictive margins by linear regression, and the association of abnormal fibrosis scores (APRI > 1, FIB-4 > 2.67, NFS > 0.676) and elevated PSA (>4 ng/mL) by logistic regression. A total of 6,705 men were included. Abnormal liver fibrosis scores were present in 2.1% (APRI), 3.6% (FIB-4), and 5.6% (NFS). Men with higher fibrosis scores had lower geometric mean PSA (all P trend < 0.02). Men with abnormal APRI had a lower odds of PSA > 4 ng/mL [adjusted OR (aOR) = 0.33; 95% confidence interval (CI), 0.11-0.96]. Compared with men with 0 abnormal scores, those with 2 or 3 abnormal fibrosis scores had a lower odds of PSA > 4 ng/mL (aOR = 0.55; 95% CI, 0.33-0.91). The patterns were similar by race/ethnicity. Men of all race/ethnicities with higher liver fibrosis scores had lower serum PSA, and men with advanced fibrosis scores had a lower odds of an elevated PSA. These findings support further research to inform the likelihood of delay in prostate cancer detection in men with abnormal liver function.


Skin cancer screening in organ transplant centres in the United Kingdom: a national survey.
Organ transplant recipients (OTRs) have up to 500-fold increased risk of keratinocyte skin cancer (KSC). International guidelines recommend at least annual skin cancer screening for OTRs. To explore the current skin cancer surveillance practice in UK transplant centres across all solid organs and the barriers to surveillance. An online survey was sent to all 59 transplant centres in the UK specialising in kidney (n = 24), pancreas (n = 10), heart and/or lung (n = 13), liver (n = 8) and intestine (n = 4) transplants. Fifty-one (86%) transplant centres responded. Twenty-eight (55%) centres provided skin cancer surveillance post-transplantation, of which 18 (64%) had a non-skin cancer specialist providing screening. Only 21 (41%) units performed a full skin examination. Eight units (29%) screened at least bi-annually in the first five years post-transplantation. Of the 23 (45%) centres that did not provide skin cancer surveillance, limitations included: reliance on patient-reported lesions (48%), lack of skin surveillance training (30%), lack of funding (48%), not a requirement in all patients (17%) and time restraints in the clinic (30%). In the UK, many transplant units do not provide skin surveillance. Collaboration between skin cancer and transplant specialists would improve surveillance rates and reduce morbidity and mortality.


Three-dimensional structure of the modiolus. A computerized reconstruction study.
Modiolus is a dense, compact, mobile fibromuscular structure, reachable by the dissection of buccolabial musculature. We undertook this study to provide detailed information about the macroscopic and microscopic anatomy of modiolus and its 3-dimensional (3-D) shape. Fifteen micrometer thick serial sections were taken from the fixed cadaveric tissue samples and then stained with hematoxylin and eosin, and Massons' trichrome stain. Stained sections were photographed digitally and images were transferred to computer medium to perform 3-D reconstruction. The study was carried out in the dissection lab of the Anatomy Department of Hacettepe University, Ankara, Turkey between 2002 and 2003. The modiolus appears to be a tortuous, blunt conelike structure, extending vertically from the buccal mucosa to the dermis of the skin. The base of the cone is adjacent to the mucosa. As the structure has great clinical importance, and satisfactory complete 3-D analysis of the subject is not yet available; we believe that our study presenting the histological and 3-D description of the modiolus will be of great help to surgeons for satisfactory esthetic and functional results during surgical operations related to the oral commissure.


Role of islet structure and cellular interactions in the control of insulin secretion.
Close cellular proximity and correct anatomical arrangement within islets are essential for normal patterns of insulin secretion. Thus, segregation of islets into single cells is associated with a dramatic decline in stimulus secretion-coupling and glucose-induced insulin release. Generation of pseudoislets from clonal islet cell lines provides a useful model to examine islet cell interactions and insulin secretion. Such studies have highlighted the functional importance of cell adhesion molecules and connexins. Pseudoislets comprising insulin-secreting cell lines have been shown to closely mimic primary islets in both size and morphology, displaying a significantly enhanced response to glucose, nutrients and drugs over equivalent monolayer cultures. Here, we consider the influence of islet structure and cellular interactions in the control of insulin secretion. The functional characteristics of pseudoislets derived from clonal beta-cell lines or a combination of alpha-, beta- and delta-cell lines are discussed in light of normal islet function and possible therapeutic application.


Gastric ulcers and swollen kidneys: a rare diagnosis complicating Crohn's disease.
We present a case of a 48-year-old woman with Crohn's colitis admitted with abdominal pain and fever. She had been started on azathioprine 6 months before presentation and had received three doses of infliximab. Abdominal CT scan revealed a liver abscess. Azathioprine was stopped and antibiotics started. She was subsequently discharged with follow-up imaging planned. She presented 3 weeks later with haematemesis. Gastroscopy revealed multiple gastric ulcers. A repeat CT scan showed bilateral renal masses and a renal biopsy was arranged. Gastric and renal biopsies were consistent with B cell lymphoma. Chemotherapy was started and resulted in improvement in CT scan findings as well as ulcer healing.


Worthless donations: male deception and female counter play in a nuptial gift-giving spider.
In nuptial gift-giving species, benefits of acquiring a mate may select for male deception by donation of worthless gifts. We investigated the effect of worthless gifts on mating success in the spider Pisaura mirabilis. Males usually offer an insect prey wrapped in silk; however, worthless gifts containing inedible items are reported. We tested male mating success in the following experimental groups: protein enriched fly gift (PG), regular fly gift (FG), worthless gift (WG), or no gift (NG). Males that offered worthless gifts acquired similar mating success as males offering nutritional gifts, while males with no gift experienced reduced mating success. The results suggest that strong selection on the nuptial gift-giving trait facilitates male deception by donation of worthless gifts. Females terminated matings faster when males offered worthless donations; this demonstrate a cost of deception for the males as shorter matings lead to reduced sperm transfer and thus give the deceiving males a disadvantage in sperm competition. We propose that the gift wrapping trait allows males to exploit female foraging preference by disguising the gift content thus deceiving females into mating without acquiring direct benefits. Female preference for a genuine prey gift combined with control over mating duration, however, counteracts the male deception.


[Druggists of Aalst during the 18th century].
Our previous research and the recent edition of the regesta of the scabinal records of the city of Aalst (Alost, Occidental Flanders Province, Belgium), gave us the opportunity to write here for the very first time a prosopography of the apothecaries of that city during the 18th century. Additional information about medical doctors and surgeons are also included.


TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury.
Acute lung injury (ALI) is characterized by endothelial barrier disruption and associated inflammatory responses, and transient receptor potential cation channel 6 (TRPC6)-mediated Ca2+ influx is critical for endothelial hyperpermeability. In this study, we investigated the role of TRPC6 in LPS-induced ALI, analyzed gene expression in WT and TRPC6-/- lungs using RNA sequencing, and explored the effects of TRPC6 in the LPS-induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) to elucidate the underlying mechanisms. Intratracheal instillation of LPS caused edema in the mouse lungs. Deletion of TRPC6 reduced LPS-induced lung edema and decreased cell infiltration. RNA sequencing analysis suggested that downregulated cell adhesion molecules in TRPC6-/- lungs may be responsible for their resistance to LPS-induced injury. In addition, downregulation of TRPC6 significantly alleviated the LPS-induced decrease in eNOS expression in lung tissue as well as in HUVECs. Moreover, inhibition of TRPC6 with the channel antagonist larixyl led to a decrease in LPS-induced hyperpermeability and ROS production in HUVECs, which could be reversed by blocking eNOS. Our findings suggest that inhibition of TRPC6 ameliorates LPS-induced ALI, which may be achieved by acting on the cell adhesion molecule signaling pathway and participating in the regulation of eNOS levels in endothelial cells.


Feasibility of telephone-administered interviews to evaluate long-term outcomes of trauma patients in urban Ethiopia.
Little is known about long-term functional outcomes of trauma patients in low-income and middle-income countries. In sub-Saharan Africa most studies of injury only collect data through emergency department disposition or hospital discharge, and methods of collecting long-term data are subject to significant bias. With the recent increase in access to mobile telephone technology, we hypothesized that structured, telephone-administered interviews now offer a feasible means to collect data about the long-term functional outcomes of trauma patients in urban Ethiopia. We piloted a telephone-administered interview tool based on the Glasgow Outcome Scale-Extended. Using departmental logbooks, 400 consecutive patients presenting to two public referral hospitals were identified retrospectively. Demographics, injury data, and telephone numbers were collected from medical records. When a telephone number was available, patients or their surrogates were contacted and interviewed 6 months after their injuries. We were able to contact 47% of subjects or their surrogates, and 97% of those contacted were able and willing to complete an interview. At 6-month follow-up, 22% of subjects had significant persistent functional disability. Many injuries had an ongoing financial impact, with 17% of subjects losing or changing jobs, 18% earning less than they had before their injuries, and 16% requiring ongoing injury-related medical care. Lack of documented telephone numbers and difficulty contacting subjects at recorded telephone numbers were the major obstacles to data collection. Language barriers and respondents' refusal to participate in the study were not significant limitations. In urban Ethiopia, many trauma patients have persistent disability 6 months after their injuries. Telephone-administered interviews offer a promising method of collecting data about the long-term trauma outcomes, including functional status and the financial impact of injury. These data are invaluable for capacity building, quality improvement efforts, and advocacy for injury prevention and trauma care. III, retrospective cohort study.


alpha-thrombin inhibits interleukin-6-induced Stat3 signaling and gp130 gene expression in primary cultures of human lung fibroblasts.
Exposure of primary human lung fibroblasts (HLF) to interleukin-6 (IL-6) rapidly induced Stat3 (signal transducers and activators of transcription 3) tyrosine phosphorylation. In these cells, alpha-thrombin did not induce tyrosine phosphorylation of Stat3; however, it potently induced its serine phosphorylation. Interestingly, a short pretreatment of cells with alpha-thrombin significantly inhibited IL-6-induced tyrosine phosphorylation of Stat3. The inhibition by alpha-thrombin was attenuated if cells were pretreated with U0126, a specific inhibitor of the mitogen-activated protein (MAP) kinase kinase 1 (MAPKK1). Exposure of HLF cells to IL-6 induced a twofold increase in gp130 mRNA levels; however, alpha-thrombin inhibited this IL-6-induced response almost to control levels. These results demonstrate, for the first time, that in HLF cells alpha-thrombin inhibits IL-6-induced Stat3 signaling via activation of MAPKK1 and that this cross-talk regulates IL-6-induced gp130 gene expression.


Critical appraisal skills training for health care professionals: a randomized controlled trial [ISRCTN46272378].
Critical appraisal skills are believed to play a central role in an evidence-based approach to health practice. The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aimed at health care professionals. This prospective controlled trial randomized 145 self-selected general practitioners, hospital physicians, professions allied to medicine, and healthcare managers/administrators from the South West of England to a half-day critical appraisal skills training workshop (based on the model of problem-based small group learning) or waiting list control. The following outcomes were assessed at 6-months follow up: knowledge of the principles necessary for appraising evidence; attitudes towards the use of evidence about healthcare; evidence seeking behaviour; perceived confidence in appraising evidence; and ability to critically appraise a systematic review article. At follow up overall knowledge score [mean difference: 2.6 (95% CI: 0.6 to 4.6)] and ability to appraise the results of a systematic review [mean difference: 1.2 (95% CI: 0.01 to 2.4)] were higher in the critical skills training group compared to control. No statistical significant differences in overall attitude towards evidence, evidence seeking behaviour, perceived confidence, and other areas of critical appraisal skills ability (methodology or generalizability) were observed between groups. Taking into account the workshop provision costs and costs of participants time and expenses of participants, the average cost of providing the critical appraisal workshops was approximately pound 250 per person. The findings of this study challenge the policy of funding 'one-off' educational interventions aimed at enhancing the evidence-based practice of health care professionals. Future evaluations of evidence-based practice interventions need to take in account this trial's negative findings and methodological difficulties.


Development of an infection-resistant, bioactive wound dressing surface.
Trauma, whether caused by an accident or in an intentional manner, results in significant morbidity and mortality. The goal of this study was to develop a novel biomaterial surface in vitro and ex vivo that provides both localized infection resistance nd hemostatic properties. Our hypothesis is that a combination of specific surface characteristics can be successfully incorporated into a single biomaterial. Functional groups were created with woven Dacron (Cntrl) material via exposure to ethylenediamine (C-EDA). The antibiotic ciprofloxacin (Cipro) was then applied to the C-EDA material using pad/autoclave technique (C-EDA-AB) followed by surface immobilization of the coagulation cascade enzyme thrombin (C-EDA-AB-Thrombin). Antimicrobial activity by the C-EDA-AB surface persisted for 5 days compared with Cntrl and dipped controls, which lasted <1 h. C-EDA-AB-Thrombin surfaces had 2.6- and 105-fold greater surface thrombin activity compared with nonspecifically bound thrombin and Cipro-dyed surfaces, respectively. Surface thrombus formation ex vivo was evident after 1 min of exposure, with thrombus organization evident by 2.5 min. In contrast, C-EDA-AB and Cntrl segments showed only blood protein adsorption on the fibers. Thus, this study demonstrated that Cipro and thrombin can be simultaneously incorporated onto a biomaterial surface while maintaining their respective biological activities.


Substrate recognition drives the evolution of serine proteases.
A method is introduced to identify amino acid residues that dictate the functional diversity acquired during evolution in a protein family. Using over 80 enzymes of the chymotrypsin family, we demonstrate that the general organization of the phylogenetic tree and its functional branch points are fully accounted for by a limited number of residues that cluster around the active site of the protein and define the contact region with the P1-P4 residues of substrate.


Introduction.
The OSA 2005 Special Topical Meeting on "Adaptive Optics: Analysis and Methods" was held in Charlotte, North Carolina, on June 8th and 9th of that year. The papers presented during those two days provided an overview of recent progress in the theory and application of adaptive optics (AO) for real-time atmospheric turbulence compensation. This Focus Issue is devoted to a further exploration of seven of these topics, ranging from formal analytical treatments of optimal estimation and control methods for AO, to recent field tests of wave front sensing and reconstruction using multiple laser guide stars.


Tests of noninferiority via rate difference for three-arm clinical trials with placebo.
In assessing a noninferiority trial, the investigator intends to show efficacy by demonstrating that a new experimental drug/treatment is not worse than a known active control/reference by a small predefined margin. If it is ethically justifiable, it may be advisable to include an additional placebo group for internal validation purpose. This constitutes the well-known three-arm clinical trial with placebo. In this paper, we study two asymptotic statistical methods for testing of noninferiority in three-arm clinical trials with placebo for binary outcomes based on rate difference. They are sample-based estimation method and restricted maximum likelihood estimation method, respectively. We investigate the performance of the proposed test procedures under different sample size allocation settings via a simulation study. Both methods perform satisfactorily under moderate to large sample settings. However, the restricted maximum likelihood estimation method usually possesses slightly smaller actual type I error rates, which are relatively close to the prespecified nominal level, while the sample-based method can be expressed in a simple closed-form format. Real examples from a pharmacological study of patients with functional dyspepsia and a placebo-controlled trial of subjects with acute migraine are used to demonstrate our methodologies.


Hardware-based rendering of full-parallax synthetic holograms.
We present a method for efficiently calculating the interference of complex-valued two-dimensional wave patterns that is useful during the generation of synthetic holograms. These patterns are represented as a special kind of images (textures), and the interference is calculated in a computer graphics rendering process. This enables us to leverage hardware support for holographic imaging that is implemented in many state-of-the-art computer workstations. Using this approach, we gain a speedup of a factor of 60-90 compared with conventional calculation methods for interfering wave patterns. Our method is evaluated numerically, examples are shown, and the program code is outlined.


Segmenting health maintenance organizations to study productivity and profitability.
As the decade ended, health maintenance organizations (HMOs) were increasing in popularity as a means of health care delivery. These groups take many forms, so it is important for the analyst to see if the efficiency and financial results for these different forms vary. The four major forms are profit vs. not-for-profit, chain vs. non-chain, group/staff vs. individual practice association (IPA), and federally qualified vs. non-federally qualified. Using a nationwide database of all the HMOs in the United States, the article compares liquidity rates, leverage ratios, profitability ratios, marketing, and per member ratios across the four groups using paired t tests. The two classifications that showed the most differences were group/staff vs. IPA and federally qualified vs. non-federally qualified. IPAs have a better liquidity position and lower leverage ratios than group/staff but their administrative costs are higher and the time to receive payments and to pay debts is higher. Non-federally qualified have somewhat higher liquidity ratios and higher profitability ratios. These significant differences in financial outcomes indicate that studies of HMOs should segment different major forms of organizations and study them separately before trying to show the effects of different policies on HMO efficiency and effectiveness.


Comparative compositional and functional analyses of Bothrops moojeni specimens reveal several individual variations.
Snake venoms are complex protein mixtures with different biological activities that can act in both their preys and human victims. Many of these proteins play a role in prey capture and in the digestive process of these animals. It is known that some snakes are resistant to the toxicity of their own venom by mechanisms not yet fully elucidated. However, it was observed in the Laboratory of Herpetology of Instituto Butantan that some Bothrops moojeni individuals injured by the same snake species showed mortalities caused by envenoming effects. This study analyzed the biochemical composition of 13 venom and plasma samples from Bothrops moojeni specimens to assess differences in their protein composition. Application of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed distinct venom protein profiles, but very homogeneous plasma profiles. Western Blotting (WB) was performed with plasma samples, which were submitted to incubation with the respective venom. Some individuals showed an immunorecognized band zone around 25 kDa, indicating interaction between the same individual plasma and venom proteins. Crossed-WB assay using non-self-plasma and venom showed that this variability is due to venom protein composition instead of plasma composition. These venoms presented higher caseinolytic, collagenolytic and coagulant activities than the venoms without these regions recognized by WB. Mass spectrometry analyses performed on two individuals revealed that these individuals present, in addition to higher protein concentrations, other exclusive proteins in their composition. When these same two samples were tested in vivo, the results also showed higher lethality in these venoms, but lower hemorrhagic activity than in the venoms without these regions recognized by WB. In conclusion, some Bothrops moojeni specimens differ in venom composition, which may have implications in envenomation. Moreover, the high individual venom variability found in this species demonstrates the importance to work with individual analyses in studies involving intraspecific venom variability and venom evolution.


Progress towards construction of a total restriction fragment map of a human chromosome.
We present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human inserts were isolated by hybridisation to a human Alu sequence. DNAs from ninety-six randomly chosen cosmids were digested with either EcoRI or HindIII, end-labelled with 35S-dATP and analysed using agarose gel electrophoresis. Comparison of the restriction fragment patterns revealed two pairs of overlapping clones, that were confirmed by cross-hybridization of the overlapping fragments. The two pairs of cosmids both mapped to human chromosome 17, as shown by hybridization to a panel of somatic cell hybrids. These data demonstrate that the generation of an overlapping cosmid map along a human chromosome is feasible, representing an intermediate step towards the complete sequencing of a human chromosome.


[A food cognition questionnaire].
Many authors evoke the role of cognition in the persistence of symptoms or in relapse. In pathology the cognitions produced by the patients are called dysfunctional or erroneous. The content of the cognitions are words or images issued from the treatment of information. In emotional disorders, the structure of thoughts named dysfunctional "schemata" involves a biased treatment of information and leads to erroneous cognitions. Several studies have attempted to elicit the most specific cognitions of different diseases. In this field, Hollon and Kendall found 36 cognitions specific to depression gathered in the automatic thoughts questionnaire (ATQ). In the same spirit, Beck et al. gathered 14 cognitions of anxiety and 12 depressed cognitions in the cognition check list (CCL). In the etiology and maintenance of eating disorders the cognitions take a large place. Around 1980 cognitive dysfunctioning was described and concerned food, interpersonal relationship and body shape. A few years later, some experimental studies explored these processes. The Stroop test, a categorization task, showed specific cognitive impairment in with patients eating disorders versus normal control subjects. It was then established that cognitive errors were based on food cognitions in restrictive patients, whereas they were based on body shape cognitions in bulimic patients. In several famous papers, Garner described typical cognitions of eating disorder patients and distinguished food-cognitions, eating-cognitions using case reports. As far as we know there is no clinical tool concerning such cognitions in France. That is the main motivation of the authors. The aim of this paper was to determine the characteristic cognitions of anorexic, anorexic-bulimic and bulimic patients and to compare them with those of normal control subjects. The goal of the study was to create a food cognition questionnaire. FIRST STEP METHODS: In the first step, food cognitions were collected among female eating disorder patients and normal female control subjects during systematic investigation. Ninety-two women were assessed and provided more than 3 000 food cognitions. Two independent psychologists identified the most frequent cognition per group and thus retained 115 food items. These items were randomly assigned. This provided the questionnaire. To illustrate the latter, here are the first five items: 1) Apricots are good for the health because they are rich in vitamins. 2) Pears are big fruit, difficult to digest. 3) Canned fruit is soaked with sugar. 4) Banana is a fruit which makes one put on weight. 5) White coloured food give the impression that it is not alive... The list of possible answers was: never, rarely, sometimes, often enough, often, always. SECOND STEP METHODS: In the second step, the food cognition questionnaire was proposed to 217 women including 131 eating disorder patients (53 anorexic, 50 anorexic bulimic, 28 bulimic) and 86 normal control subjects. The values of body mass index and the eating attitude test differed when we compared the two groups, and the mean age was close to 26 years in both groups. The statistic analysis highlighted six discriminative variables: two clinical criteria (weight and height) and four food-items given below: Q24: When I see food being fried, I feel the grease all over my body. Q76: When I start a cookie packet, I eat it up. Q102: When I feel anxious, I crave for food to fill my body. Q106: Eating pastry gives me heart-burn and makes me belch. The statistical model allowed us to differentiate eating disorder patients from normal control subjects. The content of the four food items is in agreement with experimental and clinical data. All these items included some aspects of the quality or quantity of food and also the negative consequences of food consumption on the body. To conclude, the model can help clinicians identify the patients and then initiate treatment. We also insist on the fact that this study is new and empirical, and should be extended by determining some food items for example, which would clarify the difference of behaviour between anorexics and bulimics.


Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance.
The most common BCR-ABL transcripts in chronic myeloid leukemia (CML) are e13a2(b2a2) and e14a2(b3a2). Other transcripts such as e1a2 are rare and their outcome with tyrosine kinase inhibitors (TKI) therapy is undefined. We analyzed 1292 CML patients and identified 14 with only e1a2 transcripts, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Of the CP, 4 achieved complete hematologic response (CHR); 2, complete cytogenetic response (CCyR); 2, partial cytogenetic response (PCyR), and 1 did not respond to imatinib. Five patients progressed to myeloid BP (3), lymphoid BP (1), or AP (1). The AP patient received various TKIs sequentially and achieved only CHR. BP patients received hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone) plus imatinib/dasatinib or idarubicin plus cytarabine (Ara-C); 2 did not respond, 1 had CCyR, and 1 short-lasting complete molecular response (CMR). Overall, cytogenetic responses lasted 3 to 18 months; only 2 achieved major molecular response (MMR) on TKI. P190(BCR-ABL) CML is rare and is associated with an inferior outcome to therapy with TKI. These patients need to be identified as high-risk patients.