OBJECTIVE

To determine incidence, severity, characteristics, and causes of anemia and transfusion requirements in medical intensive care patients.

METHODS

Open prospective clinical study in a 24-bed medical intensive care unit in a tertiary-care university hospital.

METHODS

Patients (N = 96) treated in the intensive care unit for >3 days.

METHODS

None.

METHODS

Parameters of erythropoiesis and red blood cell metabolism, including hemoglobin, reticulocyte counts, serum iron, transferrin, ferritin, haptoglobin, vitamin B12, folic acid, and erythropoietin concentrations were determined serially. Diagnostic blood loss and red blood cell transfusions were recorded, and the total blood loss was estimated from changes in hemoglobin concentrations and the amount of hemoglobin transfused.

RESULTS

The median hemoglobin concentration was 12.1 g/dL at admission and 11.2 g/dL at the end of the intensive care unit stay. A total of 74 patients (77%) suffered from anemia and received 257 red blood cell units, approximately half of which were given within the first 5 days. Three patients who received 19 red blood cell units were admitted with acute gastrointestinal bleeding, but in the remainder, a median total blood loss of 128 mL/d was not (n = 60) or not solely (n = 11) a result of overt bleeding. Diagnostic blood loss declined from a median of 41 mL on day 1 to <20 mL after 3 wks and contributed 17% (median) to total blood loss. Acute renal failure, fatal outcome, and simplified acute physiology score >38 on admission were associated with a 5.8-, 7.0-, and 2.8-fold increase in total blood loss. Reticulocyte counts and erythropoietin concentrations were inappropriately low for the degree of anemia, and plasma transferrin saturation was mostly <20%.

CONCLUSIONS

Anemia is frequent and results in a high requirement for red blood cell transfusions in the medical intensive care setting. A major proportion of blood loss is not caused by overt bleeding or diagnostic blood sampling but, rather, may result from various other reasons, e.g., occult gastrointestinal bleeding and renal replacement therapy. The erythropoietic response to anemia is blunted, probably as a consequence of an inappropriate increase in erythropoietin production and diminished iron availability. (Crit Care Med 1999; 27:2630-2639)

OBJECTIVE

To allow fast and high-quality reconstruction of clinical accelerated multi-coil MR data by learning a variational network that combines the mathematical structure of variational models with deep learning.

UNASSIGNED

Generalized compressed sensing reconstruction formulated as a variational model is embedded in an unrolled gradient descent scheme. All parameters of this formulation, including the prior model defined by filter kernels and activation functions as well as the data term weights, are learned during an offline training procedure. The learned model can then be applied online to previously unseen data.

RESULTS

The variational network approach is evaluated on a clinical knee imaging protocol for different acceleration factors and sampling patterns using retrospectively and prospectively undersampled data. The variational network reconstructions outperform standard reconstruction algorithms, verified by quantitative error measures and a clinical reader study for regular sampling and acceleration factor 4.

CONCLUSIONS

Variational network reconstructions preserve the natural appearance of MR images as well as pathologies that were not included in the training data set. Due to its high computational performance, that is, reconstruction time of 193 ms on a single graphics card, and the omission of parameter tuning once the network is trained, this new approach to image reconstruction can easily be integrated into clinical workflow. Magn Reson Med 79:3055-3071, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND

There have been few systematic reviews and no meta-analyses of the clinical benefits of nutritional support in patients with, or at risk of developing, pressure ulcers. Therefore, this systematic review and meta-analysis was undertaken to address the impact of enteral nutritional support on pressure ulcer incidence and healing and a range of other clinically relevant outcome measures in this group.

METHODS

Fifteen studies (including eight randomised controlled trials (RCTs)) of oral nutritional supplements (ONS) or enteral tube feeding (ETF), identified using electronic databases (including Pub Med and Cochrane) and bibliography searches, were included in the systematic review. Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of life, complications, mortality, anthropometry and dietary intake were recorded, with the aim of comparing nutritional support versus routine care (e.g. usual diet and pressure ulcer care) and nutritional formulas of different composition. Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with routine care could be included in a meta-analysis of pressure ulcer incidence.

RESULTS

Meta-analysis showed that ONS (250-500 kcal, 2-26 weeks) were associated with a significantly lower incidence of pressure ulcer development in at-risk patients compared to routine care (odds ratio 0.75, 95% CI 0.62-0.89, 4 RCTs, n=1224, elderly, post-surgical, chronically hospitalised patients). Similar results were obtained when a combined meta-analysis of ONS (4 RCT) and ETF (1 RCT) trials was performed (OR 0.74, 95% CI 0.62-0.88, 5 RCTs, n=1325). Individual studies showed a trend towards improved healing of existing pressure ulcers with disease-specific (including high protein) versus standard formulas, although robust RCTs are required to confirm this. Although some studies indicate that total nutritional intake is improved, data on other outcome measures (quality of life) are lacking.

CONCLUSIONS

This systematic review shows enteral nutritional support, particularly high protein ONS, can significantly reduce the risk of developing pressure ulcers (by 25%). Although studies suggest ONS and ETF may improve healing of PU, further research to confirm this trend is required.

OBJECTIVE

To determine whether parents are receiving anticipatory guidance, whether they could use more information on anticipatory guidance topics, and how receipt of anticipatory guidance relates to satisfaction with care.

METHODS

Analysis of data from a telephone interview of 2017 respondents between July 1995 and January 1996. A stratified random-digit dialing design was used to obtain a nationally representative sample of parents with children between 0 and 3 years old.

METHODS

Discussions with a physician or nurse about 6 anticipatory guidance topics and whether parents could use more information on these topics. Willingness of parents to pay extra to discuss these topics and receive additional care. Ratings of how well clinicians provide health care.

RESULTS

The percentage of parents who had not discussed each subject with a clinician varied by topic: newborn care (< 3 months old), 38%; crying, 65%; sleep patterns, 59%; encouraging learning, 77%; discipline (ages 6-36 months), 75%; and toilet training (ages 18-36 months), 66%. Thirty-seven percent of parents had not discussed any of these topics. Among parents who had not discussed a particular issue, the percentage who reported that they could use more information ranged from 22% for both newborn care and crying to 55% for encouraging learning; similar percentages who had discussed the topics could also use more information. Parents who had discussed more of these topics with a clinician were more likely to report excellent care. Parents who could use more information on a larger number of topics were much more willing to pay for additional care.

CONCLUSIONS

Although anticipatory guidance is considered an important component of well-child care, the majority of parents reported that they had not discussed most standard topics with a clinician. Many parents could use more information on these topics. Effort is required to provide parents with the information they need to take good care of their children. Arch Pediatr Adolesc Med. 2000;154:1191-1198.

OBJECTIVE

To develop novel orthotopic xenograft models of medulloblastoma in severe combined immunodeficient mice and to evaluate the in vivo antitumor efficacy of valproic acid.

METHODS

Orthotopic xenografts were developed by injecting 10(3) to 10(5) tumor cells from four medulloblastoma cell lines (D283-MED, DAOY, MHH-MED-1, and MEB-MED-8A) into the right cerebellum of severe combined immunodeficient mice. Animals were then examined for reproducibility of tumorigenicity, cell number-survival time relationship, and histopathologic features. Tumor growth was monitored in vivo by serially sectioning the xenograft brains at 2, 4, 6, and 8 weeks postinjection. Valproic acid treatment, administered at 600 microg/h for 2 weeks via s.c. osmotic minipumps, was initiated 2 weeks after injection of 10(5) medulloblastoma cells, and treated and untreated animals were monitored for differences in survival. Changes in histone acetylation, proliferation, apoptosis, differentiation, and angiogenesis in xenografts were also evaluated.

RESULTS

Tumorigenicity was maintained at 100% in D283-MED, DAOY, and MHH-MED-1 cell lines. These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas. Animal survival time was inversely correlated with injected tumor cell number. Treatment with valproic acid prolonged survival time in two (D283-MED and MHH-MED-1) of the three models and was associated with induction of histone hyperacetylation, inhibition of proliferation and angiogenesis, and enhancement of apoptosis and differentiation.

CONCLUSIONS

We have developed intracerebellar orthotopic models that closely recapitulated the biological features of human medulloblastomas and characterized their in vivo growth characteristics. Valproic acid treatment of these xenografts showed potent in vivo anti-medulloblastoma activity. These xenograft models should facilitate the understanding of medulloblastoma pathogenesis and future preclinical evaluation of new therapies against medulloblastoma.

Quantification of blood oxygen saturation on the basis of a measurement of its magnetic susceptibility demands knowledge of the difference in volume susceptibility between fully oxygenated and fully deoxygenated blood (Δχ(do) ). However, two very different values of Δχ(do) are currently in use. In this work we measured Δχ(do) as well as the susceptibility of oxygenated blood relative to water, Δχ(oxy) , by MR susceptometry in samples of freshly drawn human blood oxygenated to various levels, from 6 to 98% as determined by blood gas analysis. Regression analysis yielded 0.273 ± 0.006 and -0.008 ± 0.003 ppm (cgs) respectively, for Δχ(do) and Δχ(oxy) , in excellent agreement with previous work by Spees et al. (Magn Reson Med 2001;45:533-542).

This study intended to investigate the possibility of magnetic resonance (MR) to characterize the acute plaque due to multiple sclerosis (MS). To obtain information, in vivo measurements of relaxation processes were performed in 10 patients with known acute MS plaques, using a whole-body superconductive MR-scanner, operating at 1.5 T. The measurements were repeated several times, from onset of the disease and during remission by use of six-point partial saturation inversion recovery and 32-echo multiple spin-echo sequences, giving T1 and T2, respectively. We also focused on the issue, whether T1 and T2 relaxation processes in fact were monoexponential. The results of the first T1 and T2 measurements of the acute plaques were not clearly different from T1 and T2 of presumably chronic plaques obtained in a group of chronic MS patients previously (H.B.W. Larsson, J. Frederiksen, L. Kjär, O. Hendriksen, and J. Olesen, Magn. Reson. Med. 7, 43 (1988)). In some of the acute plaques a slight initial increase in T1 and T2 was seen, when the measurement was repeated in about 10 days. Thereafter T1 decreased slowly in all but one patient as a function of days. In all cases the T1 relaxation process followed a monoexponential course. The T2 relaxation process was a monoexponential function in the acute plaques, when measured within 20 days from onset of disease. After an average of 78 days, however, the T2 relaxation process clearly became biexponential in all but two patients. Later some of the relaxation curves changed back toward monoexponentiality. Thus, the study shows that it is possible to detect significant changes in MR parameters during the evolution of the disease, and these changes are discussed in relation to knowledge of pathoanatomical events in MS.

Previous epidemiological and feeding studies have observed that adherence to Mediterranean diet (Med-Diet) is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In two sub-studies of the PREDIMED (PREvencion con DIeta MEDiterranea) trial, we analyzed the effects at 3 months of two Med-Diet interventions supplemented with either virgin olive oil (VOO) or nuts compared with a control low-fat diet (LFD). Both Med-Diets showed an anti-inflammatory effect reducing serum C-reactive protein, interleukin-6 (IL6) and endothelial and monocytary adhesion molecules and chemokines (P<0.05; all), whereas these parameters increased after the LFD intervention (P<0.05; all). In another substudy, we evaluated the long-term (1 year) effects of these interventions on vascular risk factors in 516 high-risk subjects, as well as the effect of different Med-Diet components in the reduction of these biomarkers. At 1 year, the Med-Diet groups had significant decreases in the plasma concentrations of IL6, tumor necrosis factor receptor (TNFR) 60 and TNFR80 (P<0.05), while intercellular adhesion molecule 1 (ICAM-1), TNFR60 and TNFR80 concentrations increased in the LFD group (P<0.002). In addition, those allocated in the highest tertile of VOO and vegetables consumption had a significant diminution of plasma TNFR60 concentration compared with those in tertile 1 (P<0.02). In conclusion, Med-Diet exerts an anti-inflammatory effect on cardiovascular system since it down-regulates cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk.

A novel method for detecting neural activity in functional magnetic resonance imaging (fMRI) data is introduced. It is based on canonical correlation analysis (CCA), which is a multivariate extension of the univariate correlation analysis widely used in fMRI. To detect homogeneous regions of activity, the method combines a subspace modeling of the hemodynamic response and the use of spatial relationships. The spatial correlation that undoubtedly exists in fMR images is completely ignored when univariate methods such as as t-tests, F-tests, and ordinary correlation analysis are used. Such methods are for this reason very sensitive to noise, leading to difficulties in detecting activation and significant contributions of false activations. In addition, the proposed CCA method also makes it possible to detect activated brain regions based not only on thresholding a correlation coefficient, but also on physiological parameters such as temporal shape and delay of the hemodynamic response. Excellent performance on real fMRI data is demonstrated. Magn Reson Med 45:323-330, 2001.

The degree to which antioxidant loss occurs in human skin after UV irradiation is unknown, as is the cascade of events that might occur. We have, therefore, evaluated a tissue culture model of human skin for its usefulness for studying oxidative injury by UV-irradiation. Human skin equivalents, a tissue culture model, were irradiated using a full solar UV spectrum (UVA and UVB, 280-400 nm) (0 to 16.8 J/cm2, 0-12 minimal erythemal dose, MED), then incubated from 1 to 24 h. Ubiquinol was the most UV-light sensitive antioxidant and was depleted by 2.1 J/cm2 (1.5 MED, p < .004); ubiquinone decreased with 4.2 J/cm2 (3 MED, p < .0007). A linear decrease in alpha-tocopherol occurred--approximately 1.7 pmol tocopherol/cm2 surface were destroyed per J/cm2 UV-light. Urate was depleted by irradiation with 8.4 J/cm2 (6 MED), while ascorbate was depleted by 16.8 J/cm2 (12 MED). Cellular protein carbonyls and lactic dehydrogenase (LDH) leakage into the medium were only increased at 1 h incubation following exposure to 16.8 J/cm2 (12 MED). At 24 h incubation, PGE2 was increased in the medium of cells exposed to UV-irradiation at 0.35 J/cm2 (0.25 MED) compared with sham-exposed cells (p < .04); higher UV exposures lead to significant increases in both PGE2 (p < .001) and LDH (p < .001) in the medium. In conclusion, human skin equivalents respond to suberythemal levels of UV-irradiation by increasing production of PGE2; higher levels of UV-irradiation (at least 1 MED) were needed to deplete cellular antioxidants and induce immediately detectable oxidative damage.

S.A.AR86 and Girdwood S.A., two South African Sindbis-like arboviruses, are closely related antigenically to the Swedish isolate, Ockelbo82 [Lundström, J. O., Vene, S., Saluzzo, J. F., and Niklasson, B. (1993) Am. J. Trop. Med. Hyg. 49(5), 531-537]. Each of these viruses is associated with human disease, and Girdwood S.A. was isolated from a human case. In addition, S.A.AR86 is unique among Sindbis-like viruses in that adult mice remain sensitive to lethal infection with S.A.AR86. The complete genomic sequences of S.A.AR86 and Girdwood S.A. were determined. The S.A.AR86 RNA genome contained 11,663 nucleotides, excluding the 5' CAP structure and 3' poly(A) tail. In comparison to the consensus sequence of the prototype Egyptian Sindbis strain AR339, S.A.AR86 differed at 5.57% of the nucleotides, including a 54-nucleotide deletion, two insertions of 6 nucleotides each, and a 3-nucleotide insertion in the 3' terminal one-third of the S.A.AR86 nsP3 gene. S.A.AR86 is one of only three alphaviruses sequenced to date that does not have an opal termination codon between the nsP3 and the nsP4 genes. These genes are separated by a cysteine codon in the S.A.AR86 genome. The genome of Girdwood S.A. was 11,717 nucleotides in length, excluding the 5' CAP and 3' poly(A) tail. Girdwood S.A. contained an opal termination codon between nsP3 and nsP4 and did not have the large 54-nucleotide deletion in nsP3, although Girdwood S.A. did contain the remaining insertions and deletions characteristic of S.A.AR86. S.A.AR86 was more closely related to Girdwood S.A. than to the Egyptian isolate, and the South African isolates as a group were more closely related to the Swedish isolate. Comparison of the S.A.AR86 sequence to that of Ockelbo82, Girdwood S.A., and Sindbis virus AR339 revealed several codons where S.A.AR86 differed from the conserved amino acid encoded by the other three viruses. These changes may be related to the ability of S.A.AR86 to initiate a lethal central nervous system infection in adult mice. To fulfill a prerequisite for testing this hypothesis, a full-length cDNA clone of S.A.AR86 was constructed from which infectious genomic RNA replicas could be derived. The sequence of this clone differed from the S.A.AR86 genomic RNA sequence at four translationally silent positions, and virus derived from the clone reproduced the adult mouse neurovirulence phenotype of its biological progenitor.

Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5'-triphosphate agonists at P2Y(1), P2Y(2), P2Y(4), and P2Y(11) receptors, but not P2Y(6) receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208-218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y(1) or human P2Y(1) and P2Y(2) receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC(50) at the hP2Y(1) receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5'-diphosphate. 2-Cl-(N)-methanocarba-ATP and its N(6)-Me analogue were also highly selective, full agonists at P2Y(1) receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y(1) receptors, while the corresponding ribosides were inactive. Although beta,gamma-methylene-ATP was inactive at P2Y receptors, beta,gamma-methylene-(N)-methanocarba-ATP was a potent hP2Y(1) receptor agonist with an EC(50) of 160 nM and was selective versus hP2Y(2) and hP2Y(4) receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5'-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y(1) receptors.

We have previously shown that the MED-1,2 divergent GATA factors act apparently zygotically to specify the fates of the MS (mesoderm) and E (endoderm) sister cells, born at the 7-cell stage of C. elegans embryogenesis. In the E cell, MED-1,2 activate transcription of the endoderm-promoting end-1 and end-3 genes. We demonstrate by in situ hybridization that med transcripts accumulate both in the EMS cell and in the maternal germline in a SKN-1-dependent manner. Removal of zygotic med function alone results in a weakly impenetrant loss of endoderm. However, med-1,2(-) embryos made by mothers in which germline med transcripts have been abrogated by transgene cosuppression fail to make endoderm 50% of the time, similar to the phenotype seen by RNAi. We also find that reduction of Med or End activity results in aberrant numbers of intestinal cells in embryos that make endoderm. We further show that regulation of the paralogous end-1 and end-3 genes consists of both shared and distinct inputs, and that END-3 activates end-1 expression. Our data thus reveal three new properties of C. elegans endoderm specification: both maternal and zygotic activities of the med genes act to specify endoderm, defects in endoderm specification also result in defects in gut cell number, and activation of the paralogous end-1 and end-3 genes differs qualitatively in the relative contributions of their upstream regulators.

Purkinje and cerebellar nuclear neurons both have Na currents with resurgent kinetics. Previous observations, however, suggest that their Na channels differ in their susceptibility to entering long-lived inactivated states. To compare fast inactivation, slow inactivation, and open-channel block, we recorded voltage-clamped, tetrodotoxin-sensitive Na currents in Purkinje and nuclear neurons acutely isolated from mouse cerebellum. In nuclear neurons, recovery from all inactivated states was slower, and open-channel unblock was less voltage-dependent than in Purkinje cells. To test whether specific subunits contributed to this differential stability of inactivation, experiments were repeated in Na(V)1.6-null (med) mice. In med Purkinje cells, recovery times were prolonged and the voltage dependence of open-channel block was reduced relative to control cells, suggesting that availability of Na(V)1.6 is quickly restored at negative potentials. In med nuclear cells, however, currents were unchanged, suggesting that Na(V)1.6 contributes little to wild-type nuclear cells. Extracellular Na(+) prevented slow inactivation more effectively in Purkinje than in nuclear neurons, consistent with a resilience of Na(V)1.6 to slow inactivation. The tendency of nuclear Na channels to inactivate produced a low availability during trains of spike-like depolarization. Hyperpolarizations that approximated synaptic inhibition effectively recovered channels, suggesting that increases in Na channel availability promote rebound firing after inhibition.

BACKGROUND

Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients with CFS.

METHODS

Patients with CFS and matched sedentary control subjects performed a maximal test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed using univariate and multivariate statistical methods.

RESULTS

The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed.

CONCLUSIONS

When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances. Arch Intern Med. 2000;160:3270-3277.

BACKGROUND

Recently, rapid improvements in technology and decrease in sequencing costs have made RNA-Seq a widely used technique to quantify gene expression levels. Various normalization approaches have been proposed, owing to the importance of normalization in the analysis of RNA-Seq data. A comparison of recently proposed normalization methods is required to generate suitable guidelines for the selection of the most appropriate approach for future experiments.

RESULTS

In this paper, we compared eight non-abundance (RC, UQ, Med, TMM, DESeq, Q, RPKM, and ERPKM) and two abundance estimation normalization methods (RSEM and Sailfish). The experiments were based on real Illumina high-throughput RNA-Seq of 35- and 76-nucleotide sequences produced in the MAQC project and simulation reads. Reads were mapped with human genome obtained from UCSC Genome Browser Database. For precise evaluation, we investigated Spearman correlation between the normalization results from RNA-Seq and MAQC qRT-PCR values for 996 genes. Based on this work, we showed that out of the eight non-abundance estimation normalization methods, RC, UQ, Med, TMM, DESeq, and Q gave similar normalization results for all data sets. For RNA-Seq of a 35-nucleotide sequence, RPKM showed the highest correlation results, but for RNA-Seq of a 76-nucleotide sequence, least correlation was observed than the other methods. ERPKM did not improve results than RPKM. Between two abundance estimation normalization methods, for RNA-Seq of a 35-nucleotide sequence, higher correlation was obtained with Sailfish than that with RSEM, which was better than without using abundance estimation methods. However, for RNA-Seq of a 76-nucleotide sequence, the results achieved by RSEM were similar to without applying abundance estimation methods, and were much better than with Sailfish. Furthermore, we found that adding a poly-A tail increased alignment numbers, but did not improve normalization results.

CONCLUSIONS

Spearman correlation analysis revealed that RC, UQ, Med, TMM, DESeq, and Q did not noticeably improve gene expression normalization, regardless of read length. Other normalization methods were more efficient when alignment accuracy was low; Sailfish with RPKM gave the best normalization results. When alignment accuracy was high, RC was sufficient for gene expression calculation. And we suggest ignoring poly-A tail during differential gene expression analysis.

BACKGROUND

This review presents the current in vitro and in vivo animal and human research on the roles of IL-8 in ocular inflammatory diseases.

METHODS

Data sources were a literature review using Pub Med, Medline, and ISI databases (from 1990 to 2011). Search items included interleukine-8 (IL-8), CXCL8, chemokines, cytokines, alone or in combination with the, serum, aqueous, vitreous, eye, ocular, ocular tissues, ophthalmic, and review.

RESULTS

IL-8 may be involved in primary or secondary ocular inflammations. Ocular effects of IL-8 differ based on the source of the secretion and site of the action. The most important effects of IL-8 in the eyes are angiogenic activities and induction of ocular inflammation.

CONCLUSIONS

IL-8 plays important roles in ocular inflammation and angiogenesis in conjunctiva, cornea, iris, retina, and orbit. Anti-IL-8 targeted immunotherapy has been introduced as an important treatment modality, provided that IL-8 signal blocking takes place in desired areas and tissues.

The multi-subunit, human CRSP coactivator-also known as Mediator (Med)-regulates transcription by mediating signals between enhancer-bound factors (activators) and the core transcriptional machinery. Interestingly, different activators are known to bind distinct subunits within the CRSP/Med complex. We have isolated a stable, endogenous CRSP/Med complex (CRSP/MedMedMedMedMedMedMedMedMedMed occurs normally. Thus, it appears that CRSP/Med may be regulated by a combinatorial assembly mechanism that allows promoter-selective function upon exchange of specific coactivator targets.

OBJECTIVE

Evidence-based treatment guidelines have been unable to provide evidence-based guidance on the effects of acupuncture for irritable bowel syndrome (IBS) because the only previous systematic review included only small, heterogeneous, and methodologically unsound trials. We conducted a new systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effects of acupuncture for treating IBS.

METHODS

MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Cumulative Index to Nursing and Allied Health, and the Chinese databases Sino-Med, CNKI, and VIP were searched through November 2011. Eligible RCTs compared acupuncture with sham acupuncture, other active treatments, or no (specific) treatment, and evaluated acupuncture as an adjuvant to another treatment. Our outcomes were overall IBS symptom severity and health-related quality of life. Dichotomous data were pooled to provide a relative risk (RR) of substantial improvement after treatment, and continuous data were pooled to provide a standardized mean difference (SMD) in post-treatment scores between groups.

RESULTS

A total of 17 RCTs (N=1,806) were included. We found no evidence of an improvement with acupuncture relative to sham acupuncture on symptom severity (SMD=-0.11, 95% confidence interval (95% CI): -0.35 to 0.13; 4 RCTs) or quality of life (SMD=-0.03, 95% CI: -0.27 to 0.22; 3 RCTs). Because of the homogeneity of the results of the sham-controlled trials, results were unaffected by restriction to the four sham-controlled RCTs that used adequate randomization, blinding, and had few withdrawals/dropouts. Among RCTs that did not use a placebo control, acupuncture was more effective than pharmacological therapy (RR of symptom improvement=1.28, 95% CI: 1.12 to 1.45; 5 RCTs) and no (specific) treatment (RR = 2.11, 95% CI: 1.18 to 3.79; 2 RCTs). There was no difference between acupuncture and Bifidobacterium (RR=1.07, 95% CI: 0.90 to 1.27; 2 RCTs) or between acupuncture and psychotherapy (RR=1.05, 95% CI: 0.87 to 1.26; 1 RCT). Acupuncture as an adjuvant to another Chinese medicine treatment was statistically significantly better than the other treatment alone, in trials with a high risk of bias (RR=1.17, 95% CI: 1.02 to 1.33; 4 RCTs).

CONCLUSIONS

Sham-controlled RCTs have found no benefits of acupuncture relative to a credible sham acupuncture control on IBS symptom severity or IBS-related quality of life. In comparative effectiveness Chinese trials, patients reported greater benefits from acupuncture than from pharmacological therapies. Future trials may help clarify whether or not these reportedly greater benefits of acupuncture relative to pharmacological therapies are due entirely to patients' preferences for acupuncture or patients' greater expectations of improvement on acupuncture relative to drugs.

The pannier (pnr) gene encodes a GATA transcription factor and acts in several developmental processes in Drosophila, including embryonic dorsal closure, specification of cardiac cells and bristle determination. We show that pnr is expressed in the mediodorsal parts of thoracic and abdominal segments of embryos, larvae and adult flies. Its activity confers cells with specific adhesion properties that make them immiscible with non-expressing cells. Thus there are two genetic domains in the dorsal region of each segment: a medial (MED) region where pnr is expressed and a lateral (LAT) region where it is not. The homeobox gene iroquois (iro) is expressed in the LAT region. These regions are not formed by separate polyclones of cells, but are defined topographically. We show that ectopic pnr in the wing induces MED thoracic development, indicating that pnr specifies the identity of the MED regions. Correspondingly, when pnr is removed from clones of cells in the MED domain, they sort out and apparently adopt the LAT fate. We propose that (1) the subdivision into MED and LAT regions is a general feature of the Drosophila body plan and (2) pnr is the principal gene responsible for this subdivision. We argue that pnr acts like a classical selector gene but differs in that its expression is not propagated through cell divisions.

BACKGROUND

Treatment decisions in clinical cardiology are directed by results from randomized clinical trials (RCTs). We studied the appropriateness of the use and interpretation of subgroup analysis in current therapeutic cardiovascular RCTs.

METHODS

We reviewed main reports of phase 3 cardiovascular RCTs with at least 100 patients, published in 2002 and 2004, and from major journals (Circulation, J Am Coll Cardiol, Am Heart J, Am J Cardiol, N Engl J Med, Lancet, JAMA, BMJ, Ann Intern Med). Information on subgroups included prespecification, number, interaction test use, significant subgroups found, and emphasis on findings. We examined appropriateness of reporting and differences according to sample size, overall trial result, and CONSORT adoption.

RESULTS

We selected 63 RCTs, with a median of 496 (range 100-15,245) patients. Thirty-nine RCTs were reported with subgroup analyses and 26 with>> 5 subgroups. No trial was specifically powered to detect subgroup effects, and only 14 RCTs were reported with fully prespecified subgroups. Only 11 RCTs were reported with interaction tests. Furthermore, 21 RCTs were reported with claims of significant subgroups and 15 with equal or more emphasis to subgroups than to the overall results. Subgroup analyses in large RCTs >> 500 patients) were reported more often than in small ones (24/30 vs 15/33, P = .005). No differences were found according to overall result (positive/negative) or CONSORT adoption.

CONCLUSIONS

Subgroup analyses in recent cardiovascular RCTs were reported with several shortcomings, including a lack of prespecification and testing of a large number of subgroups without the use of the statistically appropriate test for interaction. Reporting of subgroup analysis needs to be substantially improved because emphasis on these secondary results may mislead treatment decisions.

We tested the use of a deep learning algorithm to classify the clinical images of 12 skin diseases-basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, actinic keratosis, seborrheic keratosis, malignant melanoma, melanocytic nevus, lentigo, pyogenic granuloma, hemangioma, dermatofibroma, and wart. The convolutional neural network (Microsoft ResNet-152 model; Microsoft Research Asia, Beijing, China) was fine-tuned with images from the training portion of the Asan dataset, MED-NODE dataset, and atlas site images (19,398 images in total). The trained model was validated with the testing portion of the Asan, Hallym and Edinburgh datasets. With the Asan dataset, the area under the curve for the diagnosis of basal cell carcinoma, squamous cell carcinoma, intraepithelial carcinoma, and melanoma was 0.96 ± 0.01, 0.83 ± 0.01, 0.82 ± 0.02, and 0.96 ± 0.00, respectively. With the Edinburgh dataset, the area under the curve for the corresponding diseases was 0.90 ± 0.01, 0.91 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. With the Hallym dataset, the sensitivity for basal cell carcinoma diagnosis was 87.1% ± 6.0%. The tested algorithm performance with 480 Asan and Edinburgh images was comparable to that of 16 dermatologists. To improve the performance of convolutional neural network, additional images with a broader range of ages and ethnicities should be collected.

BACKGROUND

Acupuncture has been applied to relieve low back pain (LBP) in many countries. However, a bibliometric analysis of the global use of acupuncture for LBP is rare.

OBJECTIVE

The aim of this study was to demonstrate the state of the art and trends concerning the global use of acupuncture for LBP in recent 20 years.

METHODS

Literature relating to acupuncture for LBP from 1997 to 2016 was retrieved from Web of Science. CiteSpace was used to analyze country/institution, cited journals, authors/cited authors, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers.

RESULTS

A total of 958 references were obtained, and the total number of publications continually increased over the investigated period. Journal articles (662) were the most frequently occurring document type. The most productive country and institution in this field was the USA (342) and Harvard University (47), respectively. The J Altern Complem Med (69) was the most productive journal, and Pain (636) was the most cocited journal, which reflected the nature of the research. The Haake's (2007) article (cocitation counts: 130) and the Cherkin's (2001) article (centrality: 0.59) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. Cherkin was the most influential author, with the highest number of publications of 25 and a cocitation number of 226. The four hot topics in acupuncture for LBP were research method, evaluation, economy, and comprehensive therapy. The three frontier topics were intervention, test reliability, and prevalence.

CONCLUSIONS

This study provides an insight into acupuncture for LBP and valuable information for acupuncture researchers to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers.

In this paper we discuss the dualism of gene networks and their role in systems biology. We argue that gene networks (1) can serve as a conceptual framework, forming a fundamental level of a phenomenological description, and (2) are a means to represent and analyze data. The latter point does not only allow a systems analysis but is even amenable for a direct approach to study biological function. Here we focus on the clarity of our main arguments and conceptual meaning of gene networks, rather than the causal inference of gene networks from data. WIREs Syst Biol Med 2011 3 379-391 DOI: 10.1002/wsbm.134 For further resources related to this article, please visit the WIREs website.