[Correction of ametropia following early surgery of congenital cataract].
Variants of an approach towards choosing the means for aphakia correction after an early surgery for congenital cataract, made during the first life year of infant, are presented in the case study. The main requirements, which must be applicable to a correction method under the mentioned conditions, are substantiated. The key advantages of contact lenses are shown, from such stand point, versus other correction methods, including spectacles, intraocular lenses and refractive epikeratoplasty. Unstable anatomic-and-optic ocular parameters in the first-year life infants are the principle obstacle for the primary IOL implantation. The issue on a secondary IOL implantation must be individually decided at the age of 10 to 12.


Aspects of treatment. The anatomical basis for portal decompressive surgery.
Definitive surgical techniques used in the treatment of portal hypertension all aim to achieve portal venous decompression. The historic development of the various procedures currently employed provides a broad repertoire of surgical operations. Each of the procedures merits consideration and may be specifically indicated in a given situation. Description of the operative steps emphasizes the importance of the anatomical relationships of the various structures.


Euthanasia tactics: patterns of injustice and outrage.
Struggles over euthanasia can be examined in terms of tactics used by players on each side of the issue to reduce outrage from actions potentially perceived as unjust. From one perspective, the key injustice is euthanasia itself, especially when the person or relatives oppose death. From a different perspective, the key injustice is denial of euthanasia, seen as a person's right to die. Five types of methods are commonly used to reduce outrage from something potentially seen as unjust: covering up the action; devaluing the target; reinterpreting the action, including using lying, minimising consequences, blaming others and benign framing; using official channels to give an appearance of justice; and using intimidation. Case studies considered include the Nazi T4 programme, euthanasia in contemporary jurisdictions in which it is legal, and censorship of Exit International by the Australian government. By examining euthanasia struggles for evidence of the five types of tactics, it is possible to judge whether one or both sides use tactics characteristic of perpetrators of injustice. This analysis provides a framework for examining tactics used in controversial health issues.


The Effects of Different Forms of Caffeine Supplement on 5-km Running Performance.
Caffeine is frequently used by athletes as an ergogenic aid. Various alternate forms of caffeine administration are available, which may produce different effects. This investigation compares the effects of different forms of caffeine supplementation on 5-km running performance, and the relationship between athlete ability and degree of enhancement attained. Fourteen amateur runners completed a series of self-paced outdoor time trials following unknown ingestion of a placebo (P) or one of 3 alternate forms of caffeine supplement. Trials were randomized in a crossover design with caffeine (approximately 3-4.5 mg·kg-1) administered 15 minutes before each trial via chewing gum (CG), dissolvable mouth strips (CS), or tablet (CT). Compared with P, all caffeine supplements led to worthwhile enhancements in running performance with a mean (±95% confidence limit) overall effect across all supplements of 1.4% ± 0.9%. Individual caffeine treatment effects (CG = 0.9% ± 1.4%, CS = 1.2% ± 1.0%, and CT = 2.0% ± 1.1%) were not significantly different (P > .05) from each other; however, CT trials produced the largest gain and was significantly different (P = .02) compared with P. There was no significant difference in heart rate or rate of perceived exertion across the performance trials. The magnitude of caffeine enhancement was also strongly correlated (r = .87) with no-treatment performance time. The findings showed that irrespective of delivery form, moderate dose of caffeine supplementation produces worthwhile gains in 5-km running performance compared with a P. Furthermore, the magnitude of caffeine enhancement is highly individualized, but it appears related to athlete performance ability.


Fusarium head blight development and deoxynivalenol accumulation in wheat as influenced by post-anthesis moisture patterns.
Mist chamber experiments were conducted to quantify and model the effects of post-anthesis moisture on Fusarium head blight (FHB) index (IND) and deoxynivalenol (DON). Four mist treatments, one daily and three intermittent, were applied during an 8-day window immediately after anthesis, plus an untreated check. All intermittent mist treatments received moisture on 4 of the 8 days, but the distribution of the supplemental moisture during the treatment window varied among the treatments. Separate sets of spikes in each treatment were either spray or point inoculated with a spore suspension of Fusarium graminearum. Based on results from linear mixed-model analyses, mist treatment had a significant effect on arcsine-square root-transformed IND (arcIND) and log-transformed DON (logDON) in spray-inoculated spikes but only a marginal effect on DON in point-inoculated spikes. The daily mist treatments (Mist1) consistently had the highest mean IND and DON but several of the 4-day intermittent mist treatments were not significantly different, particularly for point inoculations. Only Mist1 and one of the intermittent mist treatments (Mist2; 2 days of mist at the beginning and end of the treatment window) had significantly higher infection efficiency (estimated diseased spikelets per spore) than the check; however, none of the treatments increased the rate of disease spread within the spike (based on visual symptoms) relative to the check. For all treatments, there was a significant, positive linear relationship between IND and logDON, with estimated mean regression slopes (rates of logDON increase per unit increase in IND) of 0.04 and 0.02 logDON %(-1) IND for the point- and spray-inoculated experiments, respectively. Mist treatment did not have a significant effect on the slope but had a significant effect on the intercept. The height of the regression line (logDON after adjusting for IND) was consistently higher for Mist2 than for Mist1 for both point- and spray-inoculated spikes. Estimated mean back-transformed DON at a fixed level of IND was 4.9 and 2.9 ppm higher for Mist2 than Mist1 in the spray- and point-inoculation experiments, respectively. Generalized linear mixed models were used to estimate the risk of IND and DON exceeding critical thresholds, showing similar results among treatments in terms of estimated probabilities. The estimated probabilities of IND≥10% at 20 days after inoculation and DON≥2, 5, and 10 ppm were not significantly different between Mist1 and Mist2. These results suggest that post-anthesis moisture patterns may play a role in DON exceeding critical thresholds even when FHB level are relatively low.


Affective systems induce formal thought disorder in early-stage psychosis.
Although formal thought disorder (FTD) has been described since early conceptualizations of psychosis, its underlying mechanisms are unclear. Evidence suggests FTD may be influenced by affective and cognitive systems; however, few have examined these relationships-with none focusing on early-stage psychosis (EP). In this study, positive FTD and speech production were measured in sex- and race-matched EP (n = 19) and healthy control (n = 19) groups by assessing "reactivity"-a change in experimental compared with baseline conditions-across baseline, affective, and cognitive conditions. Relationships with functioning were also examined within each group. Three key findings emerged: (a) the EP group displayed large differences in positive FTD and speech production, (b) those with EP exhibited affective reactivity for positive FTD, and (c) positive FTD and affective reactivity were linked with poor real-world functioning in EP and these relationships did not considerably change when controlling for positive symptom (e.g., delusions, hallucinations) severity. Our findings provide preliminary evidence that affective, but not cognitive, systems play a critical role in positive FTD. Affective reactivity, in particular, may aid in predicting those with EP who go on to develop serious social impairments. Future work should focus on whether affective systems differentially influence those at separate points on the psychosis-spectrum in an effort to establish evidence-based treatments for FTD. (PsycINFO Database Record


Hypernatremia in the intensive care unit.
Hypernatremia is a relatively frequent electrolyte disorder seen in critically ill patients. As many as 27% of patients in intensive care units (ICUs) develop hypernatremia of variable severity during an ICU stay. Debate among specialists often ensues as to whether to correct hypernatremia or not. Some practitioners, particularly intensivists, believe that correction of hypernatremia with fluids may cause expansion of the extracellular fluid volume (ECFV) thereby worsening ventilation and impeding extubation. Other practitioners, including many nephrologists, do not expect correction of hypernatremia to lead to clinically apparent ECFV expansion, and fear other deleterious effects of hypernatremia. In this review we address the controversy regarding appropriate practice. There are no randomized, clinical trials (RCTs) to guide the administration of electrolyte-free fluid administration in hypernatremic patients. However, there are associations, demonstrated in the literature, suggesting that hypernatremia of any severity will increase the mortality and length of stay in these patients. These associations generally support the practice of correction of hypernatremia. In addition, our knowledge of the distribution of total body water influences us towards correcting hypernatremia as an appropriate therapy. We do not expect that adequate RCTs addressing this question will be performed. Allowing persistence of any degree of hypernatremia is associated with increased mortality, length of stay (LOS) and postdischarge mortality. We expect that proper use of electrolyte-free water intake will avoid adverse outcomes.


Electrically driven green, olivine, and amber color nanopyramid light emitting diodes.
We report the fabrication and studies of electrically driven green, olivine, and amber color nanopyramid GaN light emitting diodes (LEDs). InGaN/GaN multiple quantum wells (MQWs) were grown on the nanopyramid semipolar facets. Compared with the commonly used (0001) c-plane MQWs, the semipolar facet has lower piezoelectric field, resulting in much faster radiative recombination efficiency. This is important for high In content MQWs. The measured internal quantum efficiencies for green, olivine, and amber color LED are 30%, 25%, and 21%, respectively. The radiative and non-radiative lifetime of the semipolar MQWs are also investigated.


Mutational analysis of the MECP2 gene in Tunisian patients with Rett syndrome: a novel double mutation.
Rett syndrome is a severe disorder characterized by loss of acquired skills after a period of normal development in infant girls. It is caused mainly by mutations in the MECP2 gene. In this study, we reported mutations in the MECP2 gene in 7 Tunisian patients with classic Rett syndrome. The results showed the presence of a double mutation in 1 patient: p.R306C and c.1461+98insA, which create a new hypothetical polyadenylation site in the 3(')UTR of the MECP2 gene. We also detected in another patient a new variant c.1461+92C>G in the 3(')UTR located previous to 34 bp from the polyadenylation site with a score of 4.085. This variation is located in a hypothetical splicing enhancer with a score of 1.96277 according to the ESE finder program. In the remaining 5 patients, we found 2 common mutations: p.T158M in 4 individuals and p.R168X in only 1 girl.


Magnetic resonance imaging in the diagnosis of malignant tumors of the maxillofacial region.
Magnetic resonance imaging (MRI) is a radiological imaging method that has not yet found routine application in the detection and assessment of malignant tumors of the maxillofacial region. The aim of this study was to evaluate MRI in the detection, diagnosis and differential diagnosis of malignant tumors of the maxillofacial region. This prospective study included 42 patients with clinically confirmed malignant tumors of the maxillofacial region. All patients were examined by MRI. This imaging method was evaluated for the ability to detect tumor location and to analyze dimensions and structure of the tumor, bone involvement, effect on neurovascular structures and extension to soft tissues. MRI results were compared with histopathologic and intraoperative findings as the 'gold standard' methods. MRI identified all of the clinically confirmed tumors. The sensitivity for tumor location was 94.4%, tumor necrosis 93%, hemorrhage 93.3% and bone involvement 91.4%. The specificity for tumor location was 84%, tumor necrosis 92.8%, hemorrhage 92.8% and bone involvement 85.7%. In the evaluation of soft tissue tumor extension to bone structures, MRI sensitivity and specificity was 94.4% and 88.2%, respectively. The sensitivity for perineural infiltration and tumor involvement of vascular structures was 91% and 91.6%, respectively. The specificity for perineural infiltration was 96.7% and for tumor involvement of vascular structures 88%. MRI sensitivity and specificity for intracranial extension, intraorbital propagation, extension to pterygopalatine fossa and other surrounding anatomic spaces was 93.5% and 90.9%, respectively. MRI proved advantageous for the ability to distinguish neurovascular structures from adjacent soft tissues without the use of intravenous contrast media. Study results demonstrated MRI to provide valuable information in the analysis of tumor structure, bone involvement and extension to soft tissues of malignant tumors of the maxillofacial region.


B cell tolerance in mice transgenic for anti-CD8 immunoglobulin mu chain.
To analyze in vivo the induction of B cell tolerance against a T cell surface antigen, we generated transgenic mice expressing an anti-CD8.2 mu heavy chain gene. We show that self-specific B cells are efficiently tolerized if they express the membrane-bound form of the transgenic mu chain on their surface but that they can escape tolerization if they express only the secreted form. In the latter, we find an enhanced expression of anti-CD8.2 antibodies after polyclonal B cell activation. As a result, transgenic anti-CD8.2 antibodies bind to the CD8+ T cells but they did not induce their elimination. Furthermore, we observed the preferential expression of a limited subset of endogenous light chains with the transgenic mu chain. This suggests a positive or negative selection for particular heavy and light chain combinations in B lymphocytes.


Prevention of lumbar reherniation by the intraoperative use of a radiofrequency bipolar device: A case-control study.
The most common complication after lumbar discectomy is reherniation. Although many studies have investigated factors that may increase the reherniation risk, few are agreed upon all. It has been suggested that limited nucleus removal is associated with higher reherniation risk, while more aggressive nucleus removal can result in increased disc degeneration. Here, we assessed the efficacy of a coblation-assisted microdiscectomy in adult patients undergoing single-level disc surgery. We prospectively compared the reherniation rate in 75 patients (Group 1) undergoing single-level lumbar disc surgery completed with the radiofrequency bipolar system Aquamantys® (Medtronic, Minneapolis, MN, USA) to that of a historical control group (n = 75) matched for variables related to herniation level and characteristics (Group 2). Patients were followed up to 4 years. Reherniations were assessed, pain and function were monitored throughout, and imaging was performed at annual follow-up. The overall symptomatic reherniation rate was 4%. In particular, one case (1.3%) was observed in Group 1 and five (6.7%) in Group 2 (P < 0.05). Magnetic resonance imaging identified a total of 4 (2.7%) asymptomatic reherniations at 12 months, 6 (4%) at 24 and 36 months, and 7 (4.7%) at 48 months. Overall, Group 1 contained one (1.3%) asymptomatic reherniation case, while six (8%) were observed in Group 2 (P < 0.05). The low reherniation rate in patients treated by the coblation-assisted microdiscectomy suggests that this technique may reduce the reherniation risk. Clinical outcomes for pain and function at 4 years follow-up compared favorably with literature data. Randomized controlled trial could confirm these results.


Air quality assessment and pollution forecasting using artificial neural networks in Metropolitan Lima-Peru.
The prediction of air pollution is of great importance in highly populated areas because it directly impacts both the management of the city's economic activity and the health of its inhabitants. This work evaluates and predicts the Spatio-temporal behavior of air quality in Metropolitan Lima, Peru, using artificial neural networks. The conventional feedforward backpropagation known as Multilayer Perceptron (MLP) and the Recurrent Artificial Neural network known as Long Short-Term Memory networks (LSTM) were implemented for the hourly prediction of [Formula: see text] based on the past values of this pollutant and three meteorological variables obtained from five monitoring stations. The models were validated using two schemes: The Hold-Out and the Blocked-Nested Cross-Validation (BNCV). The simulation results show that periods of moderate [Formula: see text] concentration are predicted with high precision. Whereas, for periods of high contamination, the performance of both models, the MLP and LSTM, were diminished. On the other hand, the prediction performance improved slightly when the models were trained and validated with the BNCV scheme. The simulation results showed that the models obtained a good performance for the CDM, CRB, and SMP monitoring stations, characterized by a moderate to low level of contamination. However, the results show the difficulty of predicting this contaminant in those stations that present critical contamination episodes, such as ATE and HCH. In conclusion, the LSTM recurrent artificial neural networks with BNCV adapt more precisely to critical pollution episodes and have better predictability performance for this type of environmental data.


Methods for improving thermal tolerance in military personnel prior to deployment.
Acute exposure to heat, such as that experienced by people arriving into a hotter or more humid environment, can compromise physical and cognitive performance as well as health. In military contexts heat stress is exacerbated by the combination of protective clothing, carried loads, and unique activity profiles, making them susceptible to heat illnesses. As the operational environment is dynamic and unpredictable, strategies to minimize the effects of heat should be planned and conducted prior to deployment. This review explores how heat acclimation (HA) prior to deployment may attenuate the effects of heat by initiating physiological and behavioural adaptations to more efficiently and effectively protect thermal homeostasis, thereby improving performance and reducing heat illness risk. HA usually requires access to heat chamber facilities and takes weeks to conduct, which can often make it impractical and infeasible, especially if there are other training requirements and expectations. Recent research in athletic populations has produced protocols that are more feasible and accessible by reducing the time taken to induce adaptations, as well as exploring new methods such as passive HA. These protocols use shorter HA periods or minimise additional training requirements respectively, while still invoking key physiological adaptations, such as lowered core temperature, reduced heart rate and increased sweat rate at a given intensity. For deployments of special units at short notice (< 1 day) it might be optimal to use heat re-acclimation to maintain an elevated baseline of heat tolerance for long periods in anticipation of such an event. Methods practical for military groups are yet to be fully understood, therefore further investigation into the effectiveness of HA methods is required to establish the most effective and feasible approach to implement them within military groups.


Calcium channel blocker-related periperal edema: can it be resolved?
Calcium channel blocker (CCB)-related edema is quite common in clinical practice and can effectively deter a clinician from continued prescription of these drugs. Its etiology relates to a decrease in arteriolar resistance that goes unmatched in the venous circulation. This disproportionate change in resistance increases hydrostatic pressures in the precapillary circulation and permits fluid shifts into the interstitial compartment. CCB-related edema is more common in women and relates to upright posture, age, and the choice and dose of the CCB. Once present it can be slow to resolve without intervention. A number of strategies exist to treat CCB-related edema, including switching CCB classes, reducing the dosage, and/or adding a known venodilator such as a nitrate, an angiotensin-converting enzyme inhibitor, or an angiotensin-receptor blocker to the treatment regimen. Angiotensin-converting enzyme inhibitors have been best studied in this regard. Diuretics may alter the edema state somewhat, but at the expense of further reducing plasma volume. Traditional measures such as limiting the amount of time that a patient is upright and/or considering use of graduated compression stockings are useful adjunctive therapies. Discontinuing the CCB and switching to an alternative antihypertensive therapy will resolve the edema.


[Hepatic portoenterostomy and primary liver transplantation in the treatment of biliary atresia].
Results show that the use of sequential surgical treatment, employing Kasai portoenterostomy in infancy, followed by selective liver transplantation for children with progressive hepatic deterioration yields improved overall survival. All children with successful Kasai portoenterostomy procedures who do not require orthotopic liver transplantation are survivors. Using newer transplant techniques, the 5-year survival rate for children who receive transplants with a primary diagnosis of biliary atresia was 82%. This yields an overall survival rate of 86% in this entire study population. Limited donor availability and increased complications after liver transplantation in infants less than 1 year of age mitigate against the use of primary liver transplantation without prior portoenterostomy for infants with biliary atresia. At present, these two operative procedures should be used as sequential and complementary modes of treatment rather than as competitive procedures. When biliary atresia is not recognized in infancy and established cirrhosis has resulted, primary transplantation should be offered as the initial surgical treatment.


Genetic diversity and divergence at the Arbutus unedo L. (Ericaceae) westernmost distribution limit.
Mediterranean forests are fragile ecosystems vulnerable to recent global warming and reduction of precipitation, and a long-term negative effect is expected on vegetation with increasing drought and in areas burnt by fires. We investigated the spatial distribution of genetic variation of Arbutus unedo in the western Iberia Peninsula, using plastid markers with conservation and provenance regions design purposes. This species is currently undergoing an intense domestication process in the region, and, like other species, is increasingly under the threat from climate change, habitat fragmentation and wildfires. We sampled 451 trees from 15 natural populations from different ecological conditions spanning the whole species' distribution range in the region. We applied Bayesian analysis and identified four clusters (north, centre, south, and a single-population cluster). Hierarchical AMOVA showed higher differentiation among clusters than among populations within clusters. The relatively low within-clusters differentiation can be explained by a common postglacial history of nearby populations. The genetic structure found, supported by the few available palaeobotanical records, cannot exclude the hypothesis of two independent A. unedo refugia in western Iberia Peninsula during the Last Glacial Maximum. Based on the results we recommend a conservation strategy by selecting populations for conservation based on their allelic richness and diversity and careful seed transfer consistent with current species' genetic structure.


Programmed chromosome fragmentation in ciliated protozoa: multiple means to chromosome ends.
SUMMARYCiliated protozoa undergo large-scale developmental rearrangement of their somatic genomes when forming a new transcriptionally active macronucleus during conjugation. This process includes the fragmentation of chromosomes derived from the germline, coupled with the efficient healing of the broken ends by de novo telomere addition. Here, we review what is known of developmental chromosome fragmentation in ciliates that have been well-studied at the molecular level (Tetrahymena, Paramecium, Euplotes, Stylonychia, and Oxytricha). These organisms differ substantially in the fidelity and precision of their fragmentation systems, as well as in the presence or absence of well-defined sequence elements that direct excision, suggesting that chromosome fragmentation systems have evolved multiple times and/or have been significantly altered during ciliate evolution. We propose a two-stage model for the evolution of the current ciliate systems, with both stages involving repetitive or transposable elements in the genome. The ancestral form of chromosome fragmentation is proposed to have been derived from the ciliate small RNA/chromatin modification process that removes transposons and other repetitive elements from the macronuclear genome during development. The evolution of this ancestral system is suggested to have potentiated its replacement in some ciliate lineages by subsequent fragmentation systems derived from mobile genetic elements.


Phylogenomic data reveal three new families of poorly studied Solifugae (camel spiders).
The systematics of the arachnid order Solifugae have been an enigma, owing to challenges in interpreting morphology, a paucity of molecular phylogenetic studies sampling across the group, and a dearth of taxonomic attention for many lineages. Recent work has suggested that solifuge families largely exhibit contiguous distributions and reflect patterns of vicariance, with the exception of three families: Melanoblossidae, Daesiidae and Gylippidae. Morphological studies have cast doubt on their existing circumscriptions and the present composition of these taxa renders their distributions as disjunct. We leveraged ultraconserved elements (UCEs) to test the phylogenetic placement of three key lineages of Solifugae that cause these anomalous distributions: Dinorhax rostrumpsittaci (putative melanoblossid), Namibesia (putative daesiid), and Trichotoma (putative gylippid). Phylogenetic placement of these three genera based on UCEs rendered the families that harbor them as para- or polyphyletic, recovering instead relationships that better accord with a biogeographic history driven by vicariance. Toward a stable and phylogenetically informed classification of Solifugae, we establish three new families, Dinorhaxidae new rank, Namibesiidae new rank and Lipophagidae new rank.


TRANSPLANTATION TOLERANCE INDUCED IN ADULT MICE BY PROTEIN OVERLOADING OF DONORS.
Treatment of donor animals with unrelated antigens can regularly inhibit reactivity of spleen cells against the host, with subsequent induction of specific immune tolerance in the recipient animals if the barrier to histocompatibility is weak. Mice made tolerant in this way accept skin grafts from donor strain animals. In the case of strong differences (in H(2) locus) or heterologous (rat-mouse) combinations, the inhibition of the reactivity of the transferred lymphoïd cells against the host is partial, and the skin-graft survival time is significantly prolonged.


Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies.
The association between fruit and vegetable intake and colorectal cancer risk has been investigated by many studies but is controversial because of inconsistent results and weak observed associations. We summarized the evidence from cohort studies in categorical, linear, and nonlinear, dose-response meta-analyses. We searched PubMed for studies of fruit and vegetable intake and colorectal cancer risk that were published until the end of May 2010. We included 19 prospective studies that reported relative risk estimates and 95% confidence intervals (CIs) of colorectal cancer-associated with fruit and vegetable intake. Random effects models were used to estimate summary relative risks. The summary relative risk for the highest vs the lowest intake was 0.92 (95% CI: 0.86-0.99) for fruit and vegetables combined, 0.90 (95% CI: 0.83-0.98) for fruit, and 0.91 (95% CI: 0.86-0.96) for vegetables (P for heterogeneity=.24, .05, and .54, respectively). The inverse associations appeared to be restricted to colon cancer. In linear dose-response analysis, only intake of vegetables was significantly associated with colorectal cancer risk (summary relative risk=0.98; 95% CI: 0.97-0.99), per 100 g/d. However, significant inverse associations emerged in nonlinear models for fruits (Pnonlinearity<.001) and vegetables (Pnonlinearity=.001). The greatest risk reduction was observed when intake increased from very low levels of intake. There was generally little evidence of heterogeneity in the analyses and there was no evidence of small-study bias. Based on meta-analysis of prospective studies, there is a weak but statistically significant nonlinear inverse association between fruit and vegetable intake and colorectal cancer risk.


Intracranial aneurysms treated with coil placement: test characteristics of follow-up MR angiography--multicenter study.
To determine the test characteristics of magnetic resonance (MR) angiography in the assessment of occlusion of aneurysms treated with coil placement. This was an ethics committee-approved multicenter study. written informed consent was obtained in 311 patients with 343 aneurysms, who had been treated with coil placement and were scheduled for routine follow-up with intraarterial digital subtraction angiography (DSA). Thirty-five patients participated two or three times. Either 3.0- or 1.5-T time-of-flight (TOF) and contrast material-enhanced MR angiography were performed in addition to intraarterial DSA. Aneurysm occlusion was evaluated by independent readers at DSA and MR angiography. The test characteristics of MR angiography were assessed by using DSA as the standard. The area under the receiver operating characteristic curve (AUC) was calculated for 3.0- versus 1.5-T MR angiography and for TOF versus contrast-enhanced MR angiography, and factors associated with discrepancies between MR angiography and DSA were assessed with logistic regression. Aneurysm assessments (n = 381) at DSA and MR angiography were compared. Incomplete occlusion was seen at DSA in 88 aneurysms (23%). Negative predictive value of MR angiography was 94% (95% confidence interval [CI]: 91%, 97%), positive predictive value was 69% (95% CI: 60%, 78%), sensitivity was 82% (95% CI: 72%, 89%), and specificity was 89% (95% CI: 85%, 93%). AUCs were similar for 3.0- (0.90 [95% CI: 0.86, 0.94]) and 1.5-T MR (0.87 [95% CI: 0.78, 0.95]) and for TOF MR (0.86 [95% CI: 0.81, 0.91]) versus contrast-enhanced MR (0.85 [95% CI: 0.80, 0.91]). A small residual lumen (odds ratio, 2.1 [95% CI: 1.1, 4.3]) and suboptimal projection at DSA (odds ratio, 5.5 [95% CI: 1.5, 21.0]) were independently associated with discordance between intraarterial DSA and MR angiography. Documentation of good diagnostic performance of TOF MR angiography at both 1.5 and 3.0 T in the current study represents an important step toward replacing intraarterial DSA with MR angiography in the follow-up of patients with aneurysms treated with coils.


Corticosteroid use in viral pneumonia: experience so far and the dexamethasone breakthrough in coronavirus disease-2019.
Dexamethasone was shown to decrease the mortality in coronavirus disease-2019 (COVID-19) recently. Use of corticosteroids was harmful in other coronavirus infections previously. WHO recommended against routine use of corticosteroids in COVID-19. In view of these, we reviewed the evidence about the use of corticosteroids in virus-induced acute respiratory distress syndrome (ARDS). Corticosteroids are beneficial in ARDS regardless of etiology. However, they increased the mortality rate in influenza-associated ARDS. In SARS and the Middle East respiratory syndrome, corticosteroids increased the mortality, delayed the viral clearance and increased the length of hospital stay. In the case of COVID-19, the available evidence from retrospective and observational studies is inconclusive about the corticosteroid use. Low-dose therapies appear to be effective. Evidence from a randomized control study found dexamethasone is effective in decreasing mortality in severe COVID-19 cases. More studies are needed to validate the benefit of corticosteroids in COVID-19.


Cerebral hemorrhage in recipients of renal transplantation.
The causes and circumstances of intracerebral hematoma after kidney transplantation have been poorly studied. No data are available on its impact on outcome after a successful renal grafting. We used the Mayo Clinic medical diagnostic index to identify the patients with a diagnosis of intracerebral hematoma among the 1573 patients who received a renal transplant at the Mayo Clinic between 1966 and 1998. Ten intracranial hematomas occurred in 9 patients and were the cause of death in 6 (1%) of the 530 patients known to have died. The interval from renal transplantation to intracranial hematoma ranged from 12 to 114 months (average, 57 months). All patients with intracranial hemorrhage had poorly controlled hypertension. Intracranial hematoma was more frequently and significantly associated with autosomal dominant polycystic kidney disease (4/146 [2.7%]; P<.01) and with diabetes mellitus (3/410 [0.7%]; P<.01) than with other underlying causes of renal failure (2/1017 [0.2%]). In this preliminary study, the risk of cerebral hemorrhage may have increased 10-fold in patients with autosomal dominant polycystic kidney disease and 4-fold in patients with diabetes mellitus, when compared with the population of patients having other causes of renal failure. Most cerebral hemorrhages were catastrophic and fatal but appeared to be responsible for only 1% of the deaths after renal transplantation.


Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma.
Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.


Synthesis, spectral characterization, crystal structure, cytotoxicity and apoptosis-Inducing activity of two derivatives of 2-hydroxy-1,4-naphthaquinone.
A phenaxazone compound [5H-Benzo[a]phenoxazin-5-one (BP)] along with an aminoquinone[2-[(o-hydroxyphenyl)amino]-1,4-naphthaquinone (HAN)] derivatives were synthesized from lawsone using ultrasound irradiation technique. The structure of the compounds were characterized by elemental analysis and various spectral studies. Optoelectronic properties were studied using Schrodinger material science suit (2015). The compounds exhibit fluorescence emission in longer wave length it may find applications in photodynamic therapy. Single crystal X-ray diffraction studies reveals that the compound BP crystallizes in monoclinic space group. The antioxidant activity of HAN and BP were determined using DPPH radical scavenging assay and the results indicate that both the compounds have good antioxidant capacity, HAN having more scavenging activity than BP. Lead molecules were identified using in silico molecular docking studies as a green chemistry approach. iGEMDOCK, GOLD and Schrödinger softwares were used for these studies. The docking studies reveal that the structural modification of the parent compound gave more active compounds making them promising lead molecules. The lead molecules were subjected to in vitro studies. The cytotoxicity of BP and HAN was studied using human breast cancer (SKBR3) cell lines. The IC50 value of HAN was found to be 19.8μM while BP was found to have cell viability, less than 10% even at 25μM concentration. The chemotherapeutic agents kill the cancer cells mainly through apoptosis. HAN and BP were subjected to apoptosis studies. BP was found to more active than HAN. Thus it can be suggested that the mechanism of cell death may be through apoptosis.


Intrinsic regulation of enteroendocrine fate by Numb.
How terminal cell fates are specified in dynamically renewing adult tissues is not well understood. Here we explore terminal cell fate establishment during homeostasis using the enteroendocrine cells (EEs) of the adult Drosophila midgut as a paradigm. Our data argue against the existence of local feedback signals, and we identify Numb as an intrinsic regulator of EE fate. Our data further indicate that Numb, with alpha-adaptin, acts upstream or in parallel of known regulators of EE fate to limit Notch signaling, thereby facilitating EE fate acquisition. We find that Numb is regulated in part through its asymmetric and symmetric distribution during stem cell divisions; however, its de novo synthesis is also required during the differentiation of the EE cell. Thus, this work identifies Numb as a crucial factor for cell fate choice in the adult Drosophila intestine. Furthermore, our findings demonstrate that cell-intrinsic control mechanisms of terminal cell fate acquisition can result in a balanced tissue-wide production of terminally differentiated cell types.


The use of biological fluids in microfluidic paper-based analytical devices (μPADs): Recent advances, challenges and future perspectives.
The use of microfluidic paper-based analytical devices (μPADs) for aiding medical diagnosis is a growing trend in the literature mainly due to their low cost, easy use, simple manufacturing, and great potential for application in low-resource settings. Many important biomarkers (proteins, ions, lipids, hormones, DNA, RNA, drugs, whole cells, and more) and biofluids are available for precise detection and diagnosis. We have reviewed the advances μPADs in medical diagnostics have achieved in the last few years, focusing on the most common human biofluids (whole blood/plasma, sweat, urine, tears, and saliva). The challenges of detecting specific biomarkers in each sample are discussed, along with innovative techniques that overcome such limitations. Finally, the difficulties of commercializing μPADs are considered, and future trends are presented, including wearable devices and integrating multiple steps in a single platform.


Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.
Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.


Skeletal muscle vasodilation during electrical stimulation of the preoptic recess.
Transverse (3rd-order) arterioles (diam 12 +/- 2 micron, n = 6) in rat spinotrapezius muscle were observed with video microscopy during electrical stimulation of preoptic recess in periventricular region of hypothalamus (AV3V region) to test whether active skeletal muscle vasodilation was mediated by a beta-adrenergic mechanism. Bipolar wire electrodes were implanted in AV3V 3-7 days before an experiment. Continuous superfusion of propranolol (10(-5) M) caused steady-state reduction (3 +/- 1 microns) in arteriolar diameter and reduced steady-state vasodilation (26 +/- 2 vs. 11 +/- 2 microns) caused by a continuous superfusion of isoproterenol (10(-6) M). Six arterioles were observed with and without propranolol during four frequencies of AV3V stimulation (8-15 V, 0.2-0.5 ms pulse duration; 10, 15, 20, and 25 Hz; 1 min stimulus duration). Stimulation caused frequency-related reductions in arterial blood pressure (10-20 mmHg), which were sustained and not altered by propranolol. Transient peak diameters were observed after 30 +/- 7 s; the time was not related to stimulus frequency or affected by propranolol. Peak diameters averaged 14-17 microns during vehicle and 11-12 micron during propranolol (maximum diam 32 +/- 3). Peak vasodilations were significant but identical with vehicle or propranolol (avg 3 +/- 1 microns) and not related to stimulus frequency. Diameters stabilized at steady-state values above base line only during 15 and 20 Hz with vehicle and only during 20 Hz with propranolol. We conclude that AV3V stimulation causes transient vasodilation in spinotrapezius muscle that is probably not mediated by beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of the eicosapentaenoic acid synthesis gene cluster from Shewanella sp. in a transgenic marine cyanobacterium, Synechococcus sp.
The eicosapentaenoic acid (EPA) synthesis gene cluster isolated from a marine bacterium, Shewanella putrefaciens strain SCRC-2738, was cloned and expressed in the marine cyanobacterium Synechococcus sp. A broad-host-range cosmid vector, pJRD215 (10.2 kb, Smr Kmr), was used to clone a 38 kb insert, pEPA, containing the EPA synthesis gene cluster, creating plasmid pJRDEPA (approx. 48 kb). This plasmid was transferred to the cyanobacterial host at a frequency of 2.2 x 10(-7). Cyanobacterial transconjugants grown at 29 degrees C produced 0.12 mg EPA (g dry weight)-1, whereas those grown at 23 degrees C produced 0.56 mg EPA (g dry weight)-1. The yield was further improved to 0.64 mg (g dry weight)-1 by incubation for 1 d at 17 degrees C. This is believed to be the first successful cloning and expression of such a large heterologous gene cluster in a marine cyanobacterium.


Factors that influence advance directives completion amongst terminally ill patients at a tertiary hospital in Kenya.
An advance directive (AD) is a written or verbal document that legally stipulates a person's health care preference while they are competent to make decisions for themselves and is used to guide decisions on life-sustaining treatment in the event that they become incapacitated. AD can take the form of a living will, a limitation of care document, a do-not-resuscitate order, or an appointment of a surrogate by durable power of attorney. The completion rate of AD varies from region to region, and it is influenced by multiple factors. The objectives of this study were to determine the proportion of terminally ill patients with AD and to identify the factors that influence the completion of AD amongst terminally ill patients at a tertiary hospital in Kenya. The study was a retrospective survey. All available records of terminally ill patients seen at Aga Khan University Hospital, Nairobi, between July 2010 and December 2015, and that met the inclusion criteria were included in the study. In total, 216 records of terminally ill patients were analyzed: 89 records were of patients that had AD and 127 records were of patients that did not have AD. The proportion of terminally ill patients that had completed AD was 41.2%. The factors that were associated with the completion of AD on bivariate analysis were history of ICU admission, history of endotracheal intubation, functional status of the patient, the medical specialty taking care of the patient, patient's caregiver discussing the AD with the patient, and a palliative specialist review. On multivariate regression analysis, discussion of AD with a caregiver and patient's functional impairment were the factors with statistically significant association with completion of AD. The proportion of terminally ill patients that had AD in their medical records was significant. However, most terminally ill patients did not have AD. Our data, perhaps the first on the subject in East Africa, suggest that most of the factors associated with AD completion mirrored those seen in other regions of the world. Discussion between patient and their physician and patient's functional impairment were the factors independently associated with completion of AD. Therefore, physicians need to be aware of the importance of discussions of AD with their patients.


Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes.
Interleukins (IL)-17A and -22 are involved in the patho-genesis of psoriasis. Cathelicidin LL37 serves as not only antimicrobial peptide but also as autoinflammatory mediator. 1,25-Dihydroxyvitamin D3 analogues, such as calcipotriol, are used as topical treatment for psoriasis. However, the effect of calcipotriol on the mRNA expression/production of human cathelicidin antimicrobial protein (hCAP18) and LL37 peptide by IL-17A/IL-22-stimulated keratinocytes remains controversial. To evaluate the modulatory action of calcipotriol on the production of hCAP18 and LL37, we analysed hCAP18 mRNA expression and hCAP18/LL37 peptide production in IL-17A/IL-22-stimulated cultured human keratinocytes by real-time qPCR, ELISA, western blotting, and immunocytostaining. By western blotting, hCAP18 protein was detected in keratinocytes cultured for 72 h with IL-17/IL-22. Calcipotriol increased hCAP18 mRNA expression in IL-17/IL-22-stimulated keratinocytes. However, LL37 peptide in the culture supernatants was reduced by calcipotriol. Immunostaining revealed that the overproduced LL37 resides within the cells. LL37 promotes psoriasis via interaction with extracellular DNA, but may suppress psoriasis by interfering cytosolic DNA.


Facilitation of antagonist motor output through short-latency sensory pathways during postnatal development in the mouse.
Reciprocal inhibition of motor neurons via Ia inhibitory interneurons recruited by stimulation of proprioceptive afferents supplying antagonist muscles has been well described. Changes in the efficacy of inhibition, and sometimes even a switch from inhibition to facilitation, have been reported in the literature after disruption of descending pathways. We sought to test whether such facilitation could be expressed in normal animals by evaluating the presence of facilitation in acute preparations from uninjured animals. Using an isolated spinal cord preparation from neonatal mice, changes in the monosynaptic stretch reflex response in knee flexor motor neurons (posterior biceps semitendinosus; PBST) were monitored following conditioning stimulation of proprioceptive sensory afferents in other muscle nerves. As expected for reciprocal inhibition, conditioning by stimulation of quadriceps (knee extensors and PBST antagonists) sensory afferents resulted in inhibition of the stretch reflex response. Facilitation, however, of the stretch reflex response by quadriceps conditioning stimulation was observed when the glycinergic reciprocal inhibitory pathway was blocked by application of strychnine. Facilitation was elicited by low-threshold proprioceptive afferents and occurred at latencies consistent with a disynaptic circuit. The magnitude of facilitation was larger at birth than at one week postnatal. Our results also suggest reciprocal facilitation is restricted to antagonist muscle pairs, as facilitation of PBST responses was not observed when conditioned with the obturator nerve supplying the adductor muscles. Overall, these data suggest the efficacy of facilitation is modulated during the first postnatal week, while the specificity of facilitation is already established by birth.


Studies of alloxan toxicity on the beta cell.
The ability of sugars to protect the beta cell from alloxan diabetes is highly stereospecific. The alpha anomer, which is present in equilibrium in both glucose and 3-O-methyl glucose (3-OMG) at approximately 34 per cent, provides greater protection than the beta anomer. The greater protection of the alpha anomer of glucose is present fifteen seconds between its administration and alloxan, but there is no difference in protection following a thirty-second interval. The nonmetabolized analogue, 3-OMG, provides even greater protection than glucose, and this higher affinity is expressed both by the lower dose necessary to provide protection, as well as by the higher dose of mannoheptulose needed to remove thr protection. Mannoheptulose not only removes the protection provided by exogenous glucose but sensitizes the beta cell to the toxic effects of alloxan in the fasting state, probably by inhibiting the protection provided by endogenous glucose. Mannoheptulose is able to remove glucose protection before, with, or after the administration of glucose prior to alloxan injection. Finally, the protective effect of both glucose and 3-OMG is time-related, and the protection not only is due to absolute concentration but also appears to be affected by a changing concentration.


Three decades of lung cancer in Christchurch.
The hospital admission rate and management of bronchogenic carcinoma over a period of three decades has been studied by reviewing admissions to the acute general hospitals in Christchurch, using five year samples. Although there was an improvement in the management of the disease between the first and second decades, this plateaued between the second and third. In the first five year period, (1952-6), 97 (47%) out of 208 patients were dead within a month of diagnosis and six patients lived for more than three years. In 1962-66 (21%) out of 328 patients were dead within a month of diagnosis and 25 patients lived longer than three years. In the last five year period (1972-6) 75 patients (16.8%) out of 707 were dead within one month of diagnosis and 46 survived for more than three years. Twenty-six patients remained alive and well seven to eleven years after diagnosis, a long term survival rate of 3.6%.


Effect of berberine on expression of hepatocyte nuclear factor-4alpha in rats with fructose-induced insulin resistance.
The effects of berberine on the expression of hepatocyte nuclear factor-4alpha (HNF-4alpha) in liver of rats with fructose-induced insulin resistance and the molecular mechanism of berberine preventing insulin resistance were investigated. The experimental animals were divided into two groups of 16 animals each. The control group received a control routine diet containing 60% carbohydrate, and the study group a high-fructose diet containing 60% fructose as the sole source of carbohydrate. At the end of 6 weeks these were each subdivided into two groups. One was administered with berberine [187.5 mg/(kg x d) in 5 g/L carboxymethyl cellulose] by intragastric intubation and the other group was treated with a vehicle (5 g/L carboxymethyl cellulose). The rats were fed on the same dietary regimen for the next 4 weeks. After the experimental period of 10 weeks, plasma glucose, insulin and triglyceride levels were measured. HOMA insulin resistance index (HOMA-IR) was assayed. Immunohistochemistry, semiquantitative RT-PCR and western blot were used to detect the expression of HNF-4alpha in liver. Compared with control diet, fructose feeding induced hyperinsulinemia, HOMA-IR and increased triglyceride (all P<0.01). Berberine prevented the rise in plasma insulin (P<0.01), HOMA-IR (P<0.01) and triglyceride (P<0.05) in the fructose-fed rats. No change in plasma glucose was seen among these groups. The mRNA and protein expression of HNF-4alpha was decreased in the fructose-fed rats, but berberine could promote its expression. It was concluded that berberine could prevent fructose-induced insulin resistance in rats possibly by promoting the expression HNF-4alpha in liver.


[The European schizophrenia outpatient health outcomes (SOHO) study: baseline findings of the Spanish sample].
To describe the baseline findings and study population of the Spanish sample of the Schizophrenia Outpatient Health Outcomes (SOHO) Study. The SOHO study is an ongoing, large, prospective, long-term observational study of schizophrenia treatment in 10 European countries. The study population consists of outpatients who initiate therapy or change to a new antipsychotic. A total of 86 investigators enrolled 2,020 in Spain (10,972 patients in Europe). 64 % of patients were men and the mean age was 38.7 years. The Spanish SOHO study sample had considerable functional impairment at baseline. The main reason for change of therapy was lack effectiveness followed by intolerability. Patients included in the study and those receiving their first antipsychotic for schizophrenia are most likely to receive an atypical agent. The Spanish SOHO study population appears to represent the Spanish outpatients with schizophrenia in whom a treatment decision is required. Baseline findings reflect Spanish clinical practice with respect to patients treated with individual antipsychotics.


An unusual case of multifocal central serous chorioretinopathy with low serum cortisol managed using eplerenone.
In this report, we describe a rare case of a 44-year-old Asian male with acute central serous chorioretinopathy (CSC) with bullous exudative retinal detachment. Endocrinology evaluation revealed hypothalamic-pituitary-adrenal axis suppression with low serum cortisol. Furthermore, neuroimaging revealed the presence of a pituitary microadenoma. He was treated with systemic eplerenone and hydrocortisone. After 12 weeks, bullous detachment completely resolved. Our case is a unique description of acute CSC with underlying low serum cortisol levels that responded to treatment with mineralocorticoid antagonist. This case highlights the various endocrine abnormalities other than the raised serum cortisol that can occur in patients with CSC.


Brain natriuretic peptide as a surrogate marker for cardioembolic stroke with paroxysmal atrial fibrillation.
Cardioembolic stroke generally results in severer disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic from noncardioembolic stroke (atherothrombotic and lacunar stroke), whenever ischemic stroke patients have sinus rhythm at the time of presentation. In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic or noncardioembolic stroke and assessed whether this could provide a basis for differentiating cardioembolic stroke (especially due to paroxysmal atrial fibrillation) from noncardioembolic stroke. Our patient cohort consisted of 99 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005, to December 31, 2006. We excluded 23 patients with valve disease, heart failure, myocardial infarction or chronic renal failure. The mean age of the remaining 76 patients (51 males, 25 females) was 70.0 +/- 10.1 years. Thirty-six patients had cardioembolic stroke with atrial fibrillation (including permanent and paroxysmal atrial fibrillation); the remaining 40 had noncardioembolic stroke. The plasma brain natriuretic peptide was evaluated on the first morning after admission in all patients. In cardioembolic stroke with atrial fibrillation (permanent and paroxysmal atrial fibrillation), the plasma brain natriuretic peptide, ratio of peak early filling velocity to peak atrial systolic velocity (E/A) and left atrial diameter were significantly increased (p < 0.001), and the left atrial appendage flow was significantly decreased (p < 0.001), compared with noncardioembolic stroke. Analyzed in those 4 factors, cardioembolic stroke was strongly predicted with >95% accuracy assessed by plasma brain natriuretic peptide and left atrial appendage flow. From our results, it was suggested that the first-day brain natriuretic peptide and left atrial appendage flow measurements would be helpful in differentiating cardioembolic stroke with atrial fibrillation from noncardioembolic stroke.


Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates.
Bronchopulmonary dysplasia (BPD) remains an important cause of mortality and morbidity in preterm infants and inflammation plays a significant role in its pathogenesis. The use of inhaled corticosteroids may modulate the inflammatory process without concomitant high systemic steroid concentrations and less risk of adverse effects. This is an update of a review published in 2012 (Shah 2012). We recently updated the related review on "Inhaled versus systemic corticosteroids for treating bronchopulmonary dysplasia in ventilated very low birth weight preterm neonates". To determine the effect of inhaled versus systemic corticosteroids started within the first 7 days of life on preventing death or BPD in ventilated very low birth weight infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 1), MEDLINE via PubMed (1966 to 23 February 2017), Embase (1980 to 23 February 2017), and CINAHL (1982 to 23 February 2017). We searched clinical trials registers, conference proceedings and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Randomised or quasi-randomised controlled trials comparing inhaled versus systemic corticosteroid therapy (irrespective of dose and duration) starting in the first seven days of life in very low birth weight preterm infants receiving assisted ventilation. Clinical outcomes data were extracted and analysed using Review Manager. When appropriate, meta-analysis was performed using typical relative risk (RR), typical risk difference (RD) and weighted mean difference (WMD). Meta-analyses were performed using typical relative risk, typical risk difference (RD), and weighted mean difference with their 95% confidence intervals (CI). If RD was statistically significant, the number needed to benefit or the number needed to harm was calculated. We assessed the quality of evidence was evaluated using GRADE principles. We included two trials that involved 294 infants. No new studies were included for the 2017 update. The incidence of death or BPD at 36 weeks' postmenstrual age was not statistically significantly different between infants who received inhaled or systemic steroids (RR 1.09, 95% CI 0.88 to 1.35; RD 0.05, 95% CI -0.07 to 0.16; 1 trial, N = 278). The incidence of BPD at 36 weeks' postmenstrual age among survivors was not statistically significant between groups (RR 1.34, 95% CI 0.94 to 1.90; RD 0.11, 95% CI -0.02 to 0.24; 1 trial, N = 206). There was no statistically significant difference in the outcomes of BPD at 28 days, death at 28 days or 36 weeks' postmenstrual age and the combined outcome of death or BPD by 28 days between groups (2 trials, N = 294). The duration of mechanical ventilation was significantly longer in the inhaled steroid group compared with the systemic steroid group (typical MD 4 days, 95% CI 0.2 to 8; 2 trials, N = 294; I² = 0%) as was the duration of supplemental oxygen (typical MD 11 days, 95% CI 2 to 20; 2 trials, N = 294; I² = 33%).The incidence of hyperglycaemia was significantly lower with inhaled steroids (RR 0.52, 95% CI 0.39 to 0.71; RD -0.25, 95% CI -0.37 to -0.14; 1 trial, N = 278; NNTB 4, 95% CI 3 to 7 to avoid 1 infant experiencing hyperglycaemia). The rate of patent ductus arteriosus increased in the group receiving inhaled steroids (RR 1.64, 95% CI 1.23 to 2.17; RD 0.21, 95% CI 0.10 to 0.33; 1 trial, N = 278; NNTH 5, 95% CI 3 to 10). In a subset of surviving infants in the United Kingdom and Ireland there were no significant differences in developmental outcomes at 7 years of age. However, there was a reduced risk of having ever been diagnosed as asthmatic by 7 years of age in the inhaled steroid group compared with the systemic steroid group (N = 48) (RR 0.42, 95% CI 0.19 to 0.94; RD -0.31, 95% CI -0.58 to -0.05; NNTB 3, 95% CI 2 to 20).According to GRADE the quality of the evidence was moderate to low. Evidence was downgraded on the basis of design (risk of bias), consistency (heterogeneity) and precision of the estimates.Both studies received grant support and the industry provided aero chambers and metered dose inhalers of budesonide and placebo for the larger study. No conflict of interest was identified. We found no evidence that early inhaled steroids confer important advantages over systemic steroids in the management of ventilator-dependent preterm infants. Based on this review inhaled steroids cannot be recommended over systemic steroids as a part of standard practice for ventilated preterm infants. Because they might have fewer adverse effects than systemic steroids, further randomised controlled trials of inhaled steroids are needed that address risk/benefit ratio of different delivery techniques, dosing schedules and long-term effects, with particular attention to neurodevelopmental outcome.


SNP mining porcine ESTs with MAVIANT, a novel tool for SNP evaluation and annotation.
Single nucleotide polymorphisms (SNPs) analysis is an important means to study genetic variation. A fast and cost-efficient approach to identify large numbers of novel candidates is the SNP mining of large scale sequencing projects. The increasing availability of sequence trace data in public repositories makes it feasible to evaluate SNP predictions on the DNA chromatogram level. MAVIANT, a platform-independent Multipurpose Alignment VIewing and Annotation Tool, provides DNA chromatogram and alignment views and facilitates evaluation of predictions. In addition, it supports direct manual annotation, which is immediately accessible and can be easily shared with external collaborators. Large-scale SNP mining of polymorphisms bases on porcine EST sequences yielded more than 7900 candidate SNPs in coding regions (cSNPs), which were annotated relative to the human genome. Non-synonymous SNPs were analyzed for their potential effect on the protein structure/function using the PolyPhen and SIFT prediction programs. Predicted SNPs and annotations are stored in a web-based database. Using MAVIANT SNPs can visually be verified based on the DNA sequencing traces. A subset of candidate SNPs was selected for experimental validation by resequencing and genotyping. This study provides a web-based DNA chromatogram and contig browser that facilitates the evaluation and selection of candidate SNPs, which can be applied as genetic markers for genome wide genetic studies. The stand-alone version of MAVIANT program for local use is freely available under GPL license terms at http://snp.agrsci.dk/maviant. Supplementary data are available at Bioinformatics online.


Proportional hazards regression for the analysis of clustered survival data from case-cohort studies.
Case-cohort sampling is a commonly used and efficient method for studying large cohorts. Most existing methods of analysis for case-cohort data have concerned the analysis of univariate failure time data. However, clustered failure time data are commonly encountered in public health studies. For example, patients treated at the same center are unlikely to be independent. In this article, we consider methods based on estimating equations for case-cohort designs for clustered failure time data. We assume a marginal hazards model, with a common baseline hazard and common regression coefficient across clusters. The proposed estimators of the regression parameter and cumulative baseline hazard are shown to be consistent and asymptotically normal, and consistent estimators of the asymptotic covariance matrices are derived. The regression parameter estimator is easily computed using any standard Cox regression software that allows for offset terms. The proposed estimators are investigated in simulation studies, and demonstrated empirically to have increased efficiency relative to some existing methods. The proposed methods are applied to a study of mortality among Canadian dialysis patients.


Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: a population-based study in southern Europe.
The authors evaluated the risk of venous thromboembolism associated with hormone replacement therapy in a cohort of 265,431 women aged 45-79 years who did not have major risk factors for venous thromboembolism. Through review of hospital charts, 171 cases were confirmed (pulmonary embolism = 77; deep venous thrombosis = 94). Ten thousand controls were randomly sampled. The risk of venous thromboembolism among nonusers of hormone replacement therapy was 1.3 per 10,000 women per year. Current users of hormone replacement therapy had 2.3 times higher risk of venous thromboembolism (95 percent confidence interval 1.0-5.3) compared with nonusers. The increased risk was restricted to the first year of treatment.


Safety of ferumoxytol in children undergoing cardiac MRI under general anaesthesia.
Ferumoxytol, an "off-label" contrast agent, allows for better cardiac MRI quality as compared with gadolinium-based contrast agents. However, hypotension has been reported with the use of ferumoxytol for indications other than cardiac MRI. The purpose of our investigation was to evaluate the safety of ferumoxytol in children undergoing general anaesthesia for cardiac MRI. Medical records of children undergoing general anaesthesia for cardiac MRI were reviewed. Baseline demographic and medical characteristics, as well as imaging and anaesthetic duration and technique, were collected. The incidence of hypotension or other adverse events', need for vasoactive support, or airway intervention throughout the anaesthetic, was recorded. A total of 95 patients were identified, 61 received ferumoxytol and 34 received gadolinium. There were no significant differences between groups with respect to age, weight, or baseline blood pressure. The incidence of low blood pressure - systolic or mean - after contrast administration did not differ between groups, and there was no difference in sustained hypotension or use of vasopressors between groups. One patient who received ferumoxytol had possible anaphylaxis. The image acquisition time (45 versus 68 min, p=0.002) and anaesthesia duration (100 versus 132 min, p=0.02) were shorter in the ferumoxytol group. Transient low blood pressure was common in children undergoing cardiac MRI with anaesthesia, but the incidence of hypotension did not differ between ferumoxytol and gadolinium groups. The use of ferumoxytol was associated with significantly shorter scan time and anaesthesia duration, as well as a decreased need for airway intervention.


Photoreceptor waveguides and effective retinal image quality.
Individual photoreceptor waveguiding suggests that the entire retina can be considered as a composite fiber-optic element relating a retinal image to a corresponding waveguided image. In such a scheme, a visual sensation is produced only when the latter interacts with the pigments of the outer photoreceptor segments. Here the possible consequences of photoreceptor waveguiding on vision are studied with important implications for the pupil-apodization method commonly used to incorporate directional effects of the retina. In the absence of aberrations, it is found that the two approaches give identical predictions for an effective retinal image only when the pupil apodization is chosen twice as narrow as suggested by the traditional Stiles-Crawford effect. In addition, phase variations in the retinal field due to ocular aberrations can delicately alter a waveguided image, and this may provide plausible justification for an improved visual sensation as compared with what should be expected on the grounds of a retinal image only.


[The metabolic therapy of ischemic stroke: the use of nootropil].
54 patients were treated by notropil (pyracetam). The results of therapy were evaluated statistically according to a number of clinical scales and neurophysiologic indices (EEG and evoked potentials with mapping of bioelectric activity). The results were compared with the data about 56 patients of the control group which were treated by traditional method without application of notropil. Notropil was applied by two ways: small doses (4-12 g daily) during 5 days or high doses (10-12 g daily) during 30 days from the moment when the patient admitted to the hospital. Intravenous injections of the drug were used in all cases as well as its internal administration. It was showed either efficiency of the drug, especially in high doses, in early beginning of the treatment and its duration for at least 30 days or good tolerance of the drug. Authors supposed that application of pyracetam is not adequate in strokes with severe disorders of consciousness and cerebral edema.


Bilateral surgical removal of impacted lower third molar teeth as a model for drug evaluation: a test with ibuprofen.
It was considered that double-blind crossover studies of therapeutic efficacy after acute injury could well be done in patients who required surgical removal of impacted wisdom teeth from both sides of the lower jaw. In the present trial 24 healthy patients received either placebo or ibuprofen (Brufen: 400 mg three times daily), a non-steroidal anti-inflammatory agent, for 5 days commencing the day before surgery. Treatments were given on the two occasions when impacted wisdom teeth were to be removed from one side or other of the lower jaw. A number of objective and subjective parameters were recorded for paired comparison of the post-operative courses, including swelling, trismus and pain. A mechanical device which allows simple and accurate measurement of cheek swelling is described. On the 1st, 3rd and 5th post-operative days in the ibuprofen group the measured swelling averaged 93, 89 and 82%, respectively, of that in the placebo group; the corresponding alpha-values were 0.35, 0.06 and 0.07. Patients with less swelling after ibuprofen were not always those with a high serum concentration of the drug. Ibuprofen significantly reduced pain on the day of the operation. This may at least partly account for less trismus and the preference of the patients for their post-operative courses with ibuprofen. Examination of various haematological parameters did not reveal any significant difference between the two operations. Subjective scores indicated that neither wound-healing nor bleeding was affected by ibuprofen, nor were any side effects detected.


Doxorubicin Drug-Eluting Embolic Chemoembolization of Hepatocellular Carcinoma: Study of Midterm Doxorubicin Delivery in Resected Liver Specimens.
This study evaluated the midterm delivery of doxorubicin in liver specimens from patients (N = 4) with hepatocellular carcinoma treated with drug-eluting embolic (DEE) transarterial chemoembolization. The patients had surgical resection 57, 79, 80 and 105 days after doxorubicin DEE chemoembolization. Doxorubicin concentrations inside embolic particles and in surrounding tissues were assessed by infrared microspectroscopy and microspectrofluorimetry, respectively. Embolic particles still contained doxorubicin and provided sustained drug delivery within targeted tissues 80 days after chemoembolization. Doxorubicin was undetectable after 105 days. In addition, aggregation of embolic particles inside vessel lumina was associated with slower doxorubicin elution and higher tissue concentrations when the number of aggregated embolic particles increased.


Probability-Based Rejection of Decoding Output Improves the Accuracy of Locomotion Detection During Gait.
Prosthetic users need reliable control over their assistive devices to regain autonomy and independence, particularly for locomotion tasks. Despite the potential for myoelectric signals to reflect the users' intentions more accurately than external sensors, current motorized prosthetic legs fail to utilize these signals, thus hindering natural control. A reason for this challenge could be the insufficient accuracy of locomotion detection when using muscle signals in activities outside the laboratory, which may be due to factors such as suboptimal signal recording conditions or inaccurate control algorithms.This study aims to improve the accuracy of detecting locomotion during gait by utilizing classification post-processing techniques such as Linear Discriminant Analysis with rejection thresholds. We utilized a pre-recorded dataset of electromyography, inertial measurement unit sensor, and pressure sensor recordings from 21 able-bodied participants to evaluate our approach. The data was recorded while participants were ambulating between various surfaces, including level ground walking, stairs, and ramps. The results of this study show an average improvement of 3% in accuracy in comparison with using no post-processing (p-value < 0.05). Participants with lower classification accuracy profited more from the algorithm and showed greater improvement, up to 8% in certain cases. This research highlights the potential of classification post-processing methods to enhance the accuracy of locomotion detection for improved prosthetic control algorithms when using electromyogram signals.Clinical Relevance- Decoding of locomotion intent can be improved using post-processing techniques thus resulting in a more reliable control of lower limb prostheses.


Suppression of immunoglobulin G synthesis as a result of antibody-mediated suppression of immunoglobulin M synthesis in chickens.
Development of heterogeneity of immunoglobulin classes has been investigated in the chicken by studying the effects of antibody-mediated suppression of IgM synthesis. Treatment of 13-day embryos with purified goat antibodies to IgM resulted in the elimination of IgM-containing cells from the bursa of Fabricius of 16- and 19-day embryos. When combined with bursectomy at hatching, administration of anti-IgM in ovo suppressed the synthesis not only of IgM but also of IgG. A number of experimental birds lacked detectable circulating immunoglobulins, plasma cells, and germinal centers when killed at 10 weeks of age. Contrasting results were obtained when IgM synthesis was suppressed after bursectomy at hatching. Birds so treated produced little or no IgM but synthesized normal amounts of IgG. The results suggest that, within the bursal environment, IgG-producing cells arise exclusively from cells that previously synthesized IgM. A model for generation of antibody variability is presented.


Winter at the alpine timberline causes complex within-tree patterns of water potential and embolism in Picea abies.
Winter temperatures at the alpine timberline cause ice formation in the xylem of conifers blocking water uptake as well as water shifts within the axes system. This amplifies drought stress that, in combination with freeze-thaw events, causes embolism. This study focussed on within-tree patterns of water potential (psi) and embolism in Norway spruce [Picea abies (L.) Karst.]. At five sampling dates in midwinter, psi was determined at numerous positions in the crown of three trees, and at the end of March, the extent of embolism in representative sections of the axes system was analysed. Until 14 March, mean psi decreased to -3.77 +/- 0.11 MPa with less negative psi in exposed crown parts. On 30 March, psi was -1.60 +/- 0.06 MPa, while loss of conductivity reached up to 100%. Conductivity losses increased with exposition and were highest in the smallest tree. The observed complex within-tree patterns of psi and embolism were caused by ice blockages and differences in stress intensities within the xylem. High conductivity losses despite moderate psi in exposed crown parts indicated freeze-thaw events to be a major inducer of winter embolism. Tree size may play a critical role for winter water relations as trees profit from water stored in the stem and in crown parts below the snow cover.


[Thermodynamic studies of triple-helical structures of the collagen type in oligotripeptides during study of molecular chain elongation].
The conformational transition collagen-like triple helix in equilibrium with chains of oligotripeptides Z-(Gly-Pro-Pro)n-OMe with n = 6, 7, 8 in water by variation of solution temperature and sample concentration has been studied using IR-, CD-spectroscopy and microcalorimetry methods. The straight line correlation between the obtained value of the transition enthalpy and entropy and the number of the triplets (3n - 2), involved in the interpeptide set of hydrogen bonds was revealed. Evidently the effect of terminal groups is really weak in this case, and the interpeptide bonds of the triple helix may be regarded as equivalent one another. The estimated cooperative block of nucleation corresponds in length to the one full turn of the superhelix. The state diagrams of the oligotripeptides with n = 6, 7, 8 in aqueous solution are presented.


A Bayesian experimental autonomous researcher for mechanical design.
While additive manufacturing (AM) has facilitated the production of complex structures, it has also highlighted the immense challenge inherent in identifying the optimum AM structure for a given application. Numerical methods are important tools for optimization, but experiment remains the gold standard for studying nonlinear, but critical, mechanical properties such as toughness. To address the vastness of AM design space and the need for experiment, we develop a Bayesian experimental autonomous researcher (BEAR) that combines Bayesian optimization and high-throughput automated experimentation. In addition to rapidly performing experiments, the BEAR leverages iterative experimentation by selecting experiments based on all available results. Using the BEAR, we explore the toughness of a parametric family of structures and observe an almost 60-fold reduction in the number of experiments needed to identify high-performing structures relative to a grid-based search. These results show the value of machine learning in experimental fields where data are sparse.


BaCO3 mesocrystals: new morphologies using peptide-polymer conjugates as crystallization modifiers.
Nanocrystal superstructures of barium carbonate (BaCO(3)) which exhibit unusual morphologies are obtained by the carbon dioxide vapor diffusion technique in the presence of poly(ethylene oxide)-block-eicosa aspartate (PEO-b-Asp(20)). The highly effective bioconjugate acts as a crystal growth modifier over a broad range of concentrations. Instead of commonly observed branched needles, the morphology can be systematically varied along different twinned growth patterns towards well-defined branched dumbbells. Detailed analysis of the crystal substructures with high resolution scanning electron microscopy (HRSEM) and dynamic light scattering (DLS) discloses a potential growth mechanism of the superstructures and reveals the role of the polymeric bioconjugate therein.


Pilot evaluation of black cohosh for the treatment of hot flashes in women.
Hot flashes cause significant morbidity in postmenopausal women, including women with breast cancer. We undertook a pilot study to estimate the effectiveness of black cohosh to reduce hot flashes. Women who reported significant hot flashes (> or = 14 per week) were enrolled. Black cohosh was given in the form of the commercial product Remifemin. The first week was a no-treatment baseline period, and therapy was given for the subsequent 4 weeks. Hot flash data were collected by daily questionnaires during baseline and treatment weeks. Adverse effects were recorded. Twenty-one women completed the study. Their mean age was 56 years (range, 38-80). Thirteen patients had a history of breast cancer. Six patients were taking tamoxifen or raloxifene. Patients reported an average of 8.3 hot flashes per day during the baseline week. The reduction in mean daily hot flash frequency was 50% (95% CI, 34%-65%), while weekly hot flash scores were reduced 56% (95% CI, 40%-71%) at completion of the study. Overall, patients reported less trouble with sleeping, less fatigue, and less abnormal sweating. No patients stopped therapy because of adverse effects. Black cohosh appeared to reduce hot flashes and had a low toxicity. The efficacy found in this trial seems to be more than would be expected by a placebo effect (20%-30% hot flash reduction in previous trials). These results suggest that further evaluation of this black cohosh preparation with a phase III randomized trial is indicated.


Effect of sodium intake on brain angiotensin-converting enzyme activity in spontaneously hypertensive rat.
The effect of sodium intake on angiotensin-converting enzyme activity in five areas of the brain (the cerebral cortex, midbrain, striatum, thalamus and hypothalamus) was studied in normotensive, spontaneously hypertensive and stroke-prone spontaneously hypertensive rats. The enzyme activity was significantly higher in the hypothalamus than in other areas of the brain of spontaneously hypertensive rats. Sodium intake resulted in a significant rise of the enzyme activity in the midbrain of spontaneously hypertensive rats and also in the midbrain and the striatum of stroke-prone spontaneously hypertensive rats. In normotensive rats, however, there was no significant difference in the enzyme activity in any area of brain between the control and the salt-treated group. It is likely therefore that a high circulating sodium level increases angiotensin-converting enzyme content of the brain in spontaneously hypertensive rats, and it is suggested that the increased converting-enzyme activity may play a role in development of hypertension induced by sodium loading.


A two-centre validation study of sterility test of corneal storage media with elimination of interfering antimicrobials in compliance with the European Pharmacopoeia.
The purpose of this study was to validate the sterility test of corneal culture and deswelling/transport media using a device for removal of antimicrobials before incubation in BACTEC™ automated system in two Italian Eye Banks. Corneal culture medium, TISSUE-C, and deswelling/transport medium, CARRY-C, were inoculated with 10-100 cfu of six European Pharmacopoeia (EP) reference strains and either treated with medical device RESEP for removal of antimicrobials (RESEP+ group) or left untreated (RESEP- group) before injection into the BACTEC Plus bottles. The same steps were repeated in the absence of inocula with tryptone soy broth samples as negative controls, and the inocula were also directly injected in the BACTEC™ bottles as growth controls. All the samples were incubated in BACTEC™ automated system for 7 days, and the time to detection of microbial growth was recorded automatically. At both the Eye Banks, in the RESEP+ groups, microbial growth was detected in 100% of samples. In the RESEP- group, the method sensitivity ranged from 66.7 ± 21.1 to 88.9 ± 6.4% for TISSUE-C samples while for CARRY-C samples the method sensitivity ranged from 94.5 ± 5.1 to 100%. The method specificity corresponded to 100% for all the groups at both Eye Banks. This two-centre validation study showed that the use of RESEP increased the sensitivity of sterility test using BACTEC™ automated system up to 100% and, consequently, allowed validation of the method for sterility testing of corneal storage and deswelling/transport media according to the EP requirements. The test could not be validated without the use of RESEP.


The effects of mannitol on the transport of ciprofloxacin across respiratory epithelia.
Inhalation of antibiotics and mucolytics is the most important combination of inhaled drugs for chronic obstructive lung diseases and has become a standard part of treatment. However, it is yet to be determined whether the administration of a mucolytic has an effect on the transport rate of antibiotics across the airway epithelial cells. Consequently, the aim of this study was to investigate the effects of inhalation dry powder, specifically mannitol, on ciprofloxacin transport using a Calu-3 air-interface cell model. Transport studies of ciprofloxacin HCl were performed using different configurations including single spray-dried ciprofloxacin alone, co-spray-dried ciprofloxacin with mannitol, and deposition of mannitol prior to ciprofloxacin deposition. To understand the mechanism of transport and interactions between the drugs, pH measurements of apical surface liquid (ASL) and further transport studies were performed with ciprofloxacin base, with and without the presence of ion channel/transport inhibitors such as disodium cromoglycate and furosemide. Mannitol was found to delay absorption of ciprofloxacin HCl through the increase in ASL volume and subsequent reduction in pH. Conversely, ciprofloxacin base had a higher transport rate after mannitol deposition. This study clearly demonstrates that the deposition of mannitol prior to ciprofloxacin on the air-interface Calu-3 cell model has an effect on its transport rate. This was also dependent on the salt form of the drug and the timing and sequence of formulations administered.


Impact of contact sensitization in chronic spontaneous urticaria.
Patch testing is performed to diagnose allergic contact dermatitis to avoid exposure to the revealed contact allergens. Nevertheless, patch testing is not routinely performed in the evaluation of patients with chronic idiopathic (spontaneous) urticaria (CIU). The objective of this study was to determine the frequency of sensitization to patch test allergens in severe CIU and assess a role of the allergen avoidance in CIU remission. The cases of patients with severe CIU were retrospectively studied. The patients were patch tested using T.R.U.E. TEST. Three groups were studied: CIU with positive patch test group; CIU with negative patch test group and control group, which included the cases of not patch-tested patients with CIU. The groups were followed up monthly to assess changes in Chronic Urticaria Severity Score (CUSS) after allergen avoidance. Forty-three subjects with severe CIU were patch tested. Nickel sulphate was positive in 4 (9.3%) cases, potassium dichromate in 2 (4.7%) cases, cobalt, balsam of Peru, paraphenylene diamine, fragrance mix and epoxy resin were positive in 1 (2.3%) case. Their baseline CUSS (5.4 ± 0.5) improved significantly after 1 month of allergen avoidance (3.2 ± 1.1; P < 0.001); but similar improvement of CUSS (5.3 ± 0.5) was seen in 34 patients with CIU with negative patch test (3.2 ± 1.3; P < 0.001) and in 49 patients with CIU of control group (5.2 ± 0.4 to 3.4 ± 1.3; P < 0 < 0.001) after 1 month. There is no relationship between avoidance of contact allergens and the course of CIU.


[Scanning electron microscopy studies of human lenses].
In order to better understand the mechanism of tearing of the human lens capsule during circular capsulorhexis, scanning electron microscopic (SEM) examinations were made particularly of the rhexis edge. Anterior segments from cornea donor eyes, as well as capsular pieces extracted during cataract surgery, were studied after fixation in glutaraldehyde, critical point drying, and sputtering with gold. The edges of the capsulorhexis were found to be very regular even in the area of zonular attachment. Neither the surface of the lens capsule nor the edge of the rhexis itself indicated any morphological influence on the direction of tearing. From the results we conclude that the rhexis of the lens capsule is only directed by the forces applied and not by particular morphological structures. To avoid radial tears, a deep anterior chamber, resulting in a relief of the anterior zonular portion seems most important. This minimizes radial forces on the anterior lens capsule, which provides the best condition for a safe rhexis.


Factors associated with future dental care utilization among low-income smokers overdue for dental visits.
Smokers are at increased risk of oral disease. While routine dental care can help prevent and treat oral health problems, smokers have far lower rates of dental care utilization compared with non-smokers. We sought to better understand which factors may facilitate or hinder dental care utilization among low-income smokers participating in a randomized intervention trial in order to inform future intervention planning. This is a secondary analysis of data collected between 2015 and 2017 as part of the OralHealth4Life trial. Participants were eligible callers to the Louisiana, Nebraska, and Oregon state tobacco quitlines who had no dental appointment in the prior or upcoming six months. We examined the association between participants' baseline characteristics and their receiving professional dental care between baseline and the 6-month follow-up survey. Participants were racially diverse (42% non-White) and two-thirds had an annual household income under $20,000. Most (86.7%) had not had a dental cleaning in more than one year. Commonly cited barriers to dental care included cost (83.7%) and no dental insurance (78.1%). Those with dental insurance were more likely to see a dentist at follow-up (RR 1.66). Similarly, those reporting a dental insurance barrier to care were less likely to see a dentist at follow-up (RR 0.69); however, there was no significant utilization difference between those reporting a cost barrier vs. those who did not. After controlling for these financial factors, the following baseline characteristics were significantly associated with a higher likelihood of dental care utilization at 6 months: higher motivation (RR 2.16) and self-efficacy (RR 1.80) to visit the dentist, having a disability (RR 1.63), having a higher education level (RR 1.52), and having perceived gum disease (RR 1.49). Factors significantly associated with a lower likelihood of dental care utilization included being married (RR 0.68) and not having a last dental cleaning within the past year (RR 0.47). Our findings provide important insight into factors that may facilitate or deter use of professional dental care among low-income smokers. This information could inform the development of future interventions to promote dental care utilization. ClinicalTrials.gov : NCT02347124 ; registered 27 January 2015.


A review of decision support, risk communication and patient information tools for thrombolytic treatment in acute stroke: lessons for tool developers.
Tools to support clinical or patient decision-making in the treatment/management of a health condition are used in a range of clinical settings for numerous preference-sensitive healthcare decisions. Their impact in clinical practice is largely dependent on their quality across a range of domains. We critically analysed currently available tools to support decision making or patient understanding in the treatment of acute ischaemic stroke with intravenous thrombolysis, as an exemplar to provide clinicians/researchers with practical guidance on development, evaluation and implementation of such tools for other preference-sensitive treatment options/decisions in different clinical contexts. Tools were identified from bibliographic databases, Internet searches and a survey of UK and North American stroke networks. Two reviewers critically analysed tools to establish: information on benefits/risks of thrombolysis included in tools, and the methods used to convey probabilistic information (verbal descriptors, numerical and graphical); adherence to guidance on presenting outcome probabilities (IPDASi probabilities items) and information content (Picker Institute Checklist); readability (Fog Index); and the extent that tools had comprehensive development processes. Nine tools of 26 identified included information on a full range of benefits/risks of thrombolysis. Verbal descriptors, frequencies and percentages were used to convey probabilistic information in 20, 19 and 18 tools respectively, whilst nine used graphical methods. Shortcomings in presentation of outcome probabilities (e.g. omitting outcomes without treatment) were identified. Patient information tools had an aggregate median Fog index score of 10. None of the tools had comprehensive development processes. Tools to support decision making or patient understanding in the treatment of acute stroke with thrombolysis have been sub-optimally developed. Development of tools should utilise mixed methods and strategies to meaningfully involve clinicians, patients and their relatives in an iterative design process; include evidence-based methods to augment interpretability of textual and probabilistic information (e.g. graphical displays showing natural frequencies) on the full range of outcome states associated with available options; and address patients with different levels of health literacy. Implementation of tools will be enhanced when mechanisms are in place to periodically assess the relevance of tools and where necessary, update the mode of delivery, form and information content.


Algorithms for radiological image registration and their clinical application.
This paper reviews recent work in radiological image registration and provides a classification of image registration by type of transformation and by methods employed to compute the transformation. The former includes transformation of 2D images to 2D images of the same individual, transformation of 3D images to 3D images of the same individual, transformation of images to an atlas or model, transformation of images acquired from a number of individuals, transformations for image guided interventions including 2D to 3D registration and finally tissue deformation in image guided interventions. Recent work on computing transformations for registration using corresponding landmark based registration, surface based registration and voxel similarity measures, including entropy based measures, are reviewed and compared. Recently fully automated algorithms based on voxel similarity measures and, in particular, mutual information have been shown to be accurate and robust at registering images of the head when the rigid body assumption is valid. Two approaches to modelling soft tissue deformation for applications in image guided interventions are described. Validation of complex processing tasks such as image registration is vital if these algorithms are to be used in clinical practice. Three alternative validation strategies are presented. These methods are finding application outside the original domain of radiological imaging.


Depleting syndecan-4+ T lymphocytes using toxin-bearing dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand: a new opportunity for treating activated T cell-driven disease.
Because syndecan-4 (SD-4) is expressed by some (but not all) T cells following activation and serves as the exclusive ligand of dendritic cell-associated heparan sulfate proteoglycan-dependent integrin ligand (DC-HIL), we envisioned the DC-HIL/SD-4 pathway to be a therapeutic target for conditions mediated by selectively activated T cells. We conjugated soluble DC-HIL receptor with the toxin saporin (SAP; DC-HIL-SAP) and showed it to bind activated (but not resting) T cells and become internalized by and deplete SD-4(+) T cells. In hapten-sensitized mice, DC-HIL-SAP injected i.v. prior to hapten challenge led to markedly suppressed contact hypersensitivity responses that lasted 3 wk and were restricted to the hapten to which the mice were originally sensitized. Such suppression was not observed when DC-HIL-SAP was applied during sensitization. Moreover, the same infusion of DC-HIL-SAP produced almost complete disappearance of SD-4(+) cells in haptenated skin and a 40% reduction of such cells within draining lymph nodes. Our results provide a strong rationale for exploring use of toxin-conjugated DC-HIL to treat activated T cell-driven disease in humans.