Incidence and impact of skin mottling over the knee and its duration on outcome in critically ill patients.
Skin mottling is frequent and can be associated with an increased mortality rate in ICU patients with septic shock. Its overall incidence in ICU and its impact on outcome is unknown. We aimed to assess the incidence of skin mottling over the knee among all critically ill patients admitted in ICU and its role on their outcome. An observational study over a 1-year period in a 15-bed medical ICU of a teaching hospital. Skin mottling over the knee was prospectively and qualitatively assessed by trained nurses. Incidence of skin mottling was 29% (230 of 791 patients) in overall, and 49% (32 of 65 patients) in the subset of patients admitted for septic shock. Skin mottling was present on the day on admission in 65% of patients and persisted more than 6 h in 59% of cases. In-ICU mortality was 8% in patients without mottling, 30% in patients with short skin mottling and 40% in patients with persistent skin mottling (p < 0.01 between all groups). In the overall population, skin mottling over the knee was associated with in-ICU mortality independently from SAPS II (aOR 3.29 [95% CI, 2.08-5.19], p < 0.0001). Among patients with skin mottling over the knee, persistence of skin mottling remained associated with increased in-ICU mortality independently of organ dysfunctions at the mottling onset (OR 2.77 [95% CI, 1.34-5.72], p = 0.004). Skin mottling is frequent in the general population of patients admitted in ICU. Occurrence and persistence of skin mottling are independently associated with in-ICU mortality.


Lung transplantation for idiopathic pulmonary fibrosis.
Outcomes of lung transplantation for idiopathic pulmonary fibrosis (IPF) are thought to be worse than those for other indications, although the reasons are unknown. In addition, the choice of single versus double lung transplantation is unclear. To guide decision-making, we (1) compared survival of patients receiving transplantation for IPF with survival of patients receiving transplantation for non-IPF diagnoses, (2) identified risk factors for mortality after transplantation for IPF, and (3) ascertained whether double lung transplantation for IPF confers a survival advantage. From February 1990 to November 2005, 469 patients underwent lung transplantation, 82 for IPF. Multiphase hazard modeling was used to identify risk factors, and propensity matching was used to compare survival of IPF and non-IPF patients and to assess the effect of single versus double lung transplantation. Survival estimates after transplantation for IPF were 95%, 73%, 56%, and 44% at 30 days and 1, 3, and 5 years, somewhat worse than for matched non-IPF patients (p = 0.03). Risk factors for mortality were earlier date of transplantation (p = 0.07), single lung transplantation (p = 0.03), and higher wedge pressure (p = 0.003). Survival for double versus single lung transplantation was 81% versus 67% at 1 year and 55% versus 34% at 5 years; however, among matched non-IPF patients, corresponding survivals were 88% versus 71% at 1 year and 72% versus 48% at 5 years (p = 0.3). Survival after lung transplantation for IPF is worse than after other indications for transplantation when multiple clinical variables are accounted for. Survival may be improved by double lung transplant.


Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA.
Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital Sequencing™ is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient's cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing.


Tracheal Bronchus With Difficult Lung Isolation: A Case Report.
Tracheal bronchus (TB) occurs in 0.1-3% of the population as an accessory bronchus that originates in the trachea, typically supplying the right upper lobe. The presence of a TB can pose unique airway challenges, particularly during procedures that require lung isolation. Here, we describe a case of TB with difficult lung isolation. Careful examination with fiberoptic bronchoscopy permitted double lumen tube positioning without obstruction of the TB. A second case is presented where the presence of TB did not affect anesthetic management. Implications of TB for airway management and strategies for successful one-lung ventilation are discussed.


Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exercise.
The present study was undertaken to test the hypothesis that the contraction mode of action [static-isometric (Iso), shortening-concentric (Con), or lengthening-eccentric (Ecc)] used to stress the muscle provides a differential mechanical stimulus eliciting greater or lesser degrees of anabolic response at the initiation of a resistance training program. We performed an acute resistance training study in which different groups of rodents completed four training sessions in either the Iso, Con, or Ecc mode of contraction under conditions of activation and movement specifically designed to elicit equivalent volumes of force accumulation. The results of this experiment indicate that the three modes of contraction produced nearly identical cell signaling, indicative of an anabolic response involving factors such as increased levels of mRNA for IGF-I, procollagen III alpha1, decreased myostatin mRNA, and increased total RNA concentration. The resulting profiles collectively provide evidence that pure mode of muscle action, in and of itself, does not appear to be a primary variable in determining the efficacy of increased loading paradigms with regard to the initiation of selected muscle anabolic responses.


[Neurodevelopmental schizophrenia: the concept of developmental origins of certain forms of schizophrenia].
This article presents the concept of neurodevelopmental schizophrenia and reviews the studies that contributed to its formulation. According to this concept some forms of schizophrenia (early onset, with predominating negative symptoms) are conditioned by distorted CNS development, probably in prenatal period. Such pathogenesis of certain forms of the disease is suggested by the following results of the studies on the CNS structure and function in schizophrenia: 1) structural abnormalities on in vivo brain imaging and postmortem studies 2) cytoarchitectural distortions in some brain regions, suggestive of disruption of cell migration during the CNS developmental processes 3) co-occurrence of the CNS congenital anomalies, minor physical anomalies and schizophrenia 4) neurological defects and psychosocial childhood dysfunction in individuals with adult onset schizophrenia. Genetical conditions, viral infections in prenatal period, obstetric complications or combination of the mentioned factors are considered as the factors disturbing the CNS developmental processes.


Monophasic versus biphasic cardiac stimulation: mechanism of decreased energy requirements.
The purpose of the present study was to examine the effects of monophasic and biphasic stimulation under conditions of full and incomplete repolarization in an in vivo dog model and in an in vitro rabbit ventricular single cell model. Strength-interval curves were constructed with monophasic cathodal stimulation and biphasic subthreshold anodal followed by cathodal stimulation in dogs prior to and late after left anterior descending coronary artery occlusion. At the monophasic absolute refractory period plus 10 msec, less cathodal current was required for biphasic compared to monophasic stimulation (P = 0.04). Moreover, the biphasic absolute ventricular refractory period (116 +/- 8 msec) was significantly shorter than the monophasic absolute ventricular refractory period (136 +/- 15 msec) (P less than 0.02). At coupling intervals greater than 30 msec after the monophasic absolute ventricular refractory period, there was no distinction between monophasic and biphasic stimuli. Similarly enhanced excitability was observed with biphasic stimuli in infarcted hearts. Voltage clamp measurements mimicking conditions of the in vivo studies demonstrated that when repolarization is incomplete, a hyperpolarizing prepulse reactivates additional sodium current resulting in enhanced excitability. In conclusion, biphasic stimulation consisting of a hyperpolarizing anodal prepulse followed by a cathodal pulse decreases the current required for excitation compared to cathodal monophasic stimulation in a critical zone near the ventricular absolute refractory period.


Frequent LOH at hMLH1, a highly variable SNP in hMSH3, and negligible coding instability in ovarian cancer.
Molecular alterations such as DNA microsatellite instability (MSI/RER), single nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) can occur throughout the genome and be associated with different types of cancer. In the present study, we aimed at detecting molecular alterations within the mismatch DNA repair genes in ovarian cancer (OC), using a sensitive, accurate and reliable protocol we have developed. A combination of high-resolution GeneScan software analysis and automated DNA cycle sequencing was used. Negligible coding MSI was observed in selected sequences of mismatch DNA repair genes in our series of sixty-two ovarian tumors and matched blood DNAs. Unlike MSI, loss of one hMLH1 allele was scored in almost half (47%) of the informative cases. In addition, an SNP in hMSH3/intron 5 was found to be highly variable in OC patients. 1) Coding DNA instability is likely to be a very rare event in OC and, therefore, may not significantly contribute to the development of OC, and 2) the high frequency of LOH at hMLH1 observed in our ovarian tumors suggests that further investigation is needed to determine if such a trend exists in other mismatch DNA repair and/or critical genes.


Investigation of surface plasmon resonance in gold/alumina composite films prepared by rf-sputtering.
Alumina films containing gold nanoparticles (NPs) were grown by magnetron radio frequency (rf) sputtering technique. They were investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD) and optical absorption spectroscopy. It is suggested that the increase of the contrast of surface plasmon resonance band after annealing is connected with increasing of electron free mean path in Au NPs rather than with change in particle size distribution. The absorption spectra of the nanocomposites have been modelled taking into account a correction of the dielectric constant for electron mean free path limitation.


AIDS, drought, and child malnutrition in southern Africa.
To investigate trends in child malnutrition in six countries in southern Africa, in relation to the HIV epidemic and drought in crop years 2001/2 and 2002/3. Epidemiological analysis of sub-national and national surveys with related data. Data from Lesotho, Malawi, Mozambique, Swaziland, Zambia and Zimbabwe, compiled and analysed under UNICEF auspices. Secondary data: children 0-5 years for weight-for-age; HIV prevalence data from various sources especially antenatal clinic surveillance. Child nutritional status as measured by prevalence of underweight deteriorated from 2001 onwards in all countries except Lesotho, with very substantial increases in some provinces/districts (e.g. from 5 to 20% in Maputo (Mozambique, 1997-2002), 17 to 32% in Copperbelt (Zambia, 1999-2001/2) and 11 to 26% in Midlands province (Zimbabwe, 1999-2002)). Greater deterioration in underweight occurred in better-off areas. Areas with higher HIV/AIDS prevalences had (so far) lower malnutrition rates (and infant mortality rates), presumably because more modern areas--with greater reliance on trade and wage employment--have more HIV/AIDS. Areas with higher HIV/AIDS showed more deterioration in child nutrition. A significant area-level interaction was found of HIV/AIDS with the drought period, associated with particularly rapid deterioration in nutritional status. First, the most vulnerable may be households in more modern areas, nearer towns, to whom resources need to be directed. Second, the causes of this vulnerability need to be investigated. Third, HIV/AIDS amplifies the effect of drought on nutrition, so rapid and effective response will be crucial if drought strikes again. Fourth, expanded nutritional surveillance is now needed to monitor and respond to deteriorating trends. Finally, with or without drought, new means are needed of bringing help, comfort and assistance to the child population.


Atomic and molecular parity nonconservation and sum frequency generation solutions to the ozma problem.
Two Ozma problems are defined. Parity nonconservation is necessary for their solutions. Both problems may be solved by beta decay or atomic optical activity. Atomic and molecular sum frequency generation is chosen, as it supplies rich methods of effecting "gedanken" solutions to the Ozma problems. A new method of measuring a parameter manifesting molecular parity violations is advanced.


[A clinical cohort study of split and whole liver transplantations].
Objective: To investigate the surgical efficacy of split liver transplantation. Methods: Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group (n=60) and whole liver transplantation group (n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results: Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time(M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours,U=6.608,P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours,U=2.825,P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes,U=1.048,P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml,U=0.966,P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U,U=1.732,P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days,U=2.677,P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days,U=2.237,P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51),χ2=3.935,P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days,U=1.607,P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group(P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively(P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion: Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.


Correlates of picky eating and food neophobia in young children: a systematic review and meta-analysis.
Picky eating behavior is prevalent among toddlers and may negatively impact their growth and development. This article summarizes the correlates of picky eating and food neophobia in young children, which were identified using a socio-ecological framework. A literature search was conducted in 4 electronic databases. Inclusion criteria were English-language peer-reviewed publications that investigated correlate(s) of picky eating or food neophobia in children aged ≤30 months. Correlates were categorized into 4 levels: cell, child, clan (family), and community/country. Thirty-two studies, which examined 89 correlates, were identified from the keyword searches of the databases and manual searches of the reference lists of included articles. The most examined correlates were characteristics related to the child (sex, weight, and dietary intake) and parent (feeding beliefs and practices). A meta-analysis estimated the prevalence of picky eating to be 22%. Each additional month of a child's age was associated with a 0.06 U increase in the Children's Eating Behavior Questionnaire food fussiness score. This review highlights the importance of investigating child-parent dyads and bidirectional feeding interactions and draws attention to the lack of picky eating research at the level of the cell and the community/country.


Quench-flow experiments combined with mass spectrometry show apomyoglobin folds through and obligatory intermediate.
Folding of apomyoglobin is characterized by formation of a compact intermediate that contains substantial helicity. To determine whether this intermediate is obligatory or whether the protein can fold directly into the native state via an alternate parallel pathway, we have combined quench-flow hydrogen-exchange pulse labeling techniques with electrospray ionization mass spectrometry. The mass spectra of apomyoglobin obtained at various refolding times suggest that apomyoglobin indeed folds through a single pathway containing an obligatory intermediate with a significant hydrogen-bonded secondary structure content.


Epigenetic Mechanism and Therapeutic Implications of Atrial Fibrillation.
Atrial fibrillation (AF) is the most common arrhythmia attacking 1. 5-2.0% of general population worldwide. It has a significant impact on morbidity and mortality globally and its prevalence increases exponentially with age. Therapies like catheter ablation or conventional antiarrhythmic drugs have not provided effective solution to the recurrence for AF over the past decades. Over 100 genetic loci have been discovered to be associated with AF by Genome-wide association studies (GWAS) but none has led to a therapy. Recently potential involvement of epigenetics (DNA methylation, histone modification, and non-coding RNAs) in the initiation and maintenance of AF has partly emerged as proof-of-concept in the mechanism and management of AF. Here we reviewed the epigenetic features involved in AF pathophysiology and provided an update of their implications in AF therapy.


[Evaluation of dopaminergic activity of the hypothalamus in patients with polycystic ovarian syndrome].
To evaluate the hypothalamic dopaminergic activity in patients with polycystic ovary syndrome (PCOS), we studied the PRL, TSH, LH and FSH responses to i.m. administration of sulpiride in five euthyroid women affected by PCOS and in five normal women. The mean basal PRL and TSH plasma levels resulted significantly higher (p less than 0.01) in PCOS subjects with respect to normal subjects. The incremental area under PRL and TSH profiles, after sulpiride administration, were significantly lower (p less than 0.05) in PCOS patients than in the control group; no significant variation of LH and FSH plasma levels resulted. Our data suggest a decrease dopaminergic activity in PCOS.


Eight-Electron Silver and Mixed Gold/Silver Nanoclusters Stabilized by Selenium Donor Ligands.
The first atomically and structurally precise silver-nanoclusters stabilized by Se-donor ligands, [Ag20 {Se2 P(Oi Pr)2 }12 ] (3) and [Ag21 {Se2 P(OEt)2 }12 ]+ (4), were isolated by ligand replacement reaction of [Ag20 {S2 P(Oi Pr)2 }12 ] (1) and [Ag21 {S2 P(Oi Pr)2 }12 ]+ (2), respectively. Furthermore, doping reactions of 4 with Au(PPh3 )Cl resulted in the formation of [AuAg20 {Se2 P(OEt)2 }12 ]+ (5). Structures of 3, 4, and 5 were determined by single-crystal X-ray diffraction. The anatomy of cluster 3 with an Ag20 core having C3 symmetry is very similar to that of its dithiophosphate analogue 1. Clusters 4 and 5 exhibit an Ag21 and Au@Ag20 core of Oh symmetry composed of eight silver capping atoms in a cubic arrangement and encapsulating an Ag13 and Au@Ag12 centered icosahedron, respectively. Both ligand exchange and heteroatom doping result in significant changes in optical and emissive properties for chalcogen-passivated silver nanoparticles, which have been theoretically confirmed as 8-electron superatoms.


Relationship between gastric mucosal IL-8 levels and histological gastritis in patients with Helicobacter pylori infection.
To determine the role of host immune responses in H. pylori infection, we examined the relationship between gastric mucosal IL-8 levels and histological gastritis in patients with H. pylori infection. Biopsy tissue obtained from 99 patients were homogenizedand mucosal IL-8 levels measured by ELISA. The gastric mucosal IL-8 levels in both the antrum and corpus were higher in patients with H. pylori than in H. pyloi negativepatients. IL-8 levels in the corpus but not the antrum correlated with the severity of the atrophy. The IL-1B polymorphism had no influence on the degree of IL-8 production. These findings indicate that IL-8 production is independent of IL-1B polymorphisms and IL-8 may play an important role in the development of atrophic gastritis.


Protocatechuic Acid, a Phenolic from Sansevieria roxburghiana Leaves, Suppresses Diabetic Cardiomyopathy via Stimulating Glucose Metabolism, Ameliorating Oxidative Stress, and Inhibiting Inflammation.
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera of T2D rats revealed the occurrence of hyperlipidemia and diabetic pathophysiology. A significantly (p < 0.01) high levels of serum C-reactive protein and pro-inflammatory mediators revealed the establishment of inflammatory occurrence in T2D rats. Besides, significantly high levels of troponins in the sera revealed the establishment of cardiac dysfunctions in T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly reverse the changes in serum biochemical parameters related to cardiac dysfunctions. Molecular mechanism studies demonstrated impairment of signaling cascade, IRS1/PI3K/Akt/AMPK/p 38/GLUT4, in glucose metabolism in the skeletal muscle of T2D rats. Significant (p < 0.01) activation of polyol pathway, enhanced production of AGEs, oxidative stress and up-regulation of inflammatory signaling cascades (PKC/NF-κB/PARP) were observed in the myocardial tissue of T2D rats. However, protocatechuic acid (50 and 100 mg/kg, p.o.) treatment could significantly (p < 0.05-0.01) stimulate glucose metabolism in skeletal muscle, regulated glycemic and lipid status, reduced the secretion of pro-inflammatory cytokines, and restored the myocardial physiology in T2D rats near to normalcy. Histological assessments were also in agreement with the above findings. In silico molecular docking study again supported the interactions of protocatechuic acid with different signaling molecules, PI3K, IRS, Akt, AMPK PKC, NF-κB and PARP, involved in glucose utilization and inflammatory pathophysiology. In silico ADME study predicted that protocatechuic acid would support the drug-likeness character. Combining all, results would suggest a possibility of protocatechuic acid to be a new therapeutic agent for DC in future.


ERK/PP1a/PLB/SERCA2a and JNK pathways are involved in luteolin-mediated protection of rat hearts and cardiomyocytes following ischemia/reperfusion.
Luteolin has long been used in traditional Chinese medicine for treatment of various diseases. Recent studies have suggested that administration of luteolin yields cardioprotective effects during ischemia/reperfusion (I/R) in rats. However, the precise mechanisms of this action remain unclear. The aim of this study is to confirm that luteolin-mediated extracellular signal regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways are responsible for their cardioprotective effects during I/R. Wistar rats were divided into the following groups: (i) DMSO group (DMSO); (ii) I/R group (I/R); (iii) luteolin+I/R group (Lut+I/R); (iv) ERK1/2 inhibitor PD98059+I/R group (PD+I/R); (v) PD98059+luteolin+I/R group (PD+Lut+I/R); and (vi) JNK inhibitor SP600125+I/R group (SP+I/R). The following properties were measured: contractile function of isolated heart and cardiomyocytes; infarct size; the release of lactate dehydrogenase (LDH); the percentage of apoptotic cells; the expression levels of Bcl-2 and Bax; and phosphorylation status of ERK1/2, JNK, type 1 protein phosphatase (PP1a), phospholamban (PLB) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Our data showed that pretreatment with luteolin or SP600125 significantly improved the contraction of the isolated heart and cardiomyocytes, reduced infarct size and LDH activity, decreased the rate of apoptosis and increased the Bcl-2/Bax ratio. However, pretreatment with PD98059 alone before I/R had no effect on the above indexes. Further, these consequences of luteolin pretreatment were abrogated by co-administration of PD98059. We also found that pretreatment with PD98059 caused a significant increase in JNK expression, and SP600125 could cause ERK1/2 activation during I/R. In addition, we are the first to demonstrate that luteolin affects PP1a expression, which results in the up-regulation of the PLB, thereby relieving its inhibition of SERCA2a. These results showed that luteolin improves cardiomyocyte contractile function after I/R injury by an ERK1/2-PP1a-PLB-SERCA2a-mediated mechanism independent of JNK signaling pathway.


[Ultrasound Examination and Management of Twin Pregnancy.]
Twin pregnancies are found in about 3 % of all pregnancies and 2/3 are dizygotic and 1/3 are monozygotic. In the last 30 years after the introduction of assisted conception and increasing maternal age the rate of twin pregnancies dramatically increased. Compared to singletons, twins have more complications such as intrauterine demise, intrauterine selective fetal growth reStriction, congenital anomalies, miscarriage and preterm labour. Monochorionic twins are at high risk for unique complications because of blood exchange through vascular communications in the shared placenta. Twin pregnancies should be considered as a high risk pregnancies and the well-being of the two fetuses should be taken into account with a strict protocol for follow up and management options. Ultrasound examination olavs a maior role in fetal surveillance.


Characterization of a peptide endothelium-derived constricting factor EDCF.
Endothelium regulates vascular tone by the release of dilator and constrictor mediators. Among the latter, besides endothelin, an 'endothelium derived constricting factor' EDCF sensitive to cyclooxygenase-inhibitors has been described. The aim of this study was to clarify the nature of this EDCF. Eluate from porcine aortic segments or supernatants (crude extracts) of porcine aortic segments were each tested for vascular effects in a bioassay system consisting of two endothelium-denuded acceptor vessels (rabbit abdominal aorta) before or after treatment with trypsin. The donor vessels were incubated with physiological saline solution with or without treatment with cycloheximide, quinacrine or indomethacine. Ultrafiltrates and fractions of a gelfiltration of the supernatants were also tested and compared with SDS-PAGE of these extracts. Finally, porcine aortic endothelial cells (PAEC) were cultured and the supernatant compared with that of the native aortae. A vasoconstrictive factor was released from the luminal surface of the porcine aortic segments, which if infused into the rabbit aortas induced two succeeding vasoconstrictions of 15-20 min duration each (the first 20 min after the first of extract-infusion, the second after 50 min) reaching 7% amplitude of a 0.2 mumol 1(-1) norepinephrine-induced constriction. These constrictions were enhanced if the crude extract of the porcine aortae was concentrated. This constricting factor was a protein with an approximative molecular weight of 9.000 Da. The release of this factor was insensitive to cycloheximide pretreatment indicating no de novo synthesis. However, the release of the factor could be markedly (50%) depressed by pretreatment with either quinacrine or indomethacine. The factor was not released from cultured PAEC. From these results, we conclude, that besides endothelin, endothelium luminally can release another endothelium-derived constricting factor named EDCF, a peptide with a molecular weight of 9.000 Da, which is not identical to endothelium and can induce long lasting vasoconstrictions. The release or synthesis of that EDCF seems to depend on cyclooxygenase and phospholipase A2 activity. We, thus, propose the name PLA2-sensitive EDCF for that factor.


Polymyxin resistance of Pseudomonas aeruginosa phoQ mutants is dependent on additional two-component regulatory systems.
Pseudomonas aeruginosa can develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistant phoQ mutant defined 41 novel loci required for resistance, including two regulatory systems, ColRS and CprRS. Deletion of the colRS genes, individually or in tandem, abrogated the polymyxin resistance of a ΔphoQ mutant, as did individual or tandem deletion of cprRS. Individual deletion of colR or colS in a ΔphoQ mutant also suppressed 4-amino-L-arabinose addition to lipid A, consistent with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion of colRS or cprRS in the ΔphoQ mutant or individual deletion of cprR or cprS failed to suppress 4-amino-L-arabinose addition to lipid A, indicating that this modification alone is not sufficient for PhoPQ-mediated polymyxin resistance in P. aeruginosa. Episomal expression of colRS or cprRS in tandem or of cprR individually complemented the Pm resistance phenotype in the ΔphoQ mutant, while episomal expression of colR, colS, or cprS individually did not. Highly polymyxin-resistant phoQ mutants of P. aeruginosa isolated from polymyxin-treated cystic fibrosis patients harbored mutant alleles of colRS and cprS; when expressed in a ΔphoQ background, these mutant alleles enhanced polymyxin resistance. These results define ColRS and CprRS as two-component systems regulating polymyxin resistance in P. aeruginosa, indicate that addition of 4-amino-L-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate that colRS and cprS mutations can contribute to high-level clinical resistance.


Antigen processing for presentation to T lymphocytes: function, mechanisms, and implications for the T-cell repertoire.
Antigen processing encompasses the metabolic events that a protein antigen must undergo in or on the antigen-presenting cell before it can be recognized by the T lymphocyte. It appears that a primary goal of these events is to unfold the protein to expose residues that are buried in the native conformation, which is designed to be soluble in water. The APC usually accomplishes this task by proteolytic cleavage of the protein, but we have found that artificial unfolding without proteolysis is sufficient. The purpose of unfolding may be to allow different faces of the antigenic site to bind simultaneously to the T-cell receptor and the MHC molecule on the APC, or to interact with other structures on the membrane of the APC. This requirement for unfolding appears to apply to everything from small peptides to large multimeric proteins. We have found that the way the antigen is processed and the structure of the fragments produced can greatly affect the availability of antigenic sites. For instance, some antigenic sites are not recognized when the native protein is used as immunogen, despite the fact that immunization with a small peptide corresponding to that site reveals both the ability of the site to bind to MHC molecules of the animal in question and the presence of a T-cell repertoire specific for that site. The antigenic site is not destroyed by processing, since it can be presented by the same F1 APC to T cells of another MHC type. Similarly, cross-reactivity between homologous epitopes of related proteins may occur at the peptide level even though the native proteins do not crossreact for the same T-cell clone. Since these events occur with monoclonal T cells, they cannot be due to suppressor cells specific for other sites on the native molecule. The best explanation is that the products of natural processing of the protein are larger than the peptides corresponding to the minimal antigenic sites, and contain hindering structures that interfere with binding to some MHC molecules and not others, or to some T-cell receptors and not others. Thus, antigen processing is a third factor that can lead to apparent Ir gene defects - in addition to MHC specificity and holes in the T-cell repertoire - and can significantly influence which antigenic sites are immunodominant.(ABSTRACT TRUNCATED AT 400 WORDS)


Subglottic web: A rare cause of respiratory distress in neonate.
A full term male neonate presented with stridor and respiratory distress at birth. Direct laryngoscopy after tracheostomy and patient stabilization revealed a subglottic web with a very small hole at 6 o'clock position. The patient was managed by cauterization of web using Bugbee electrode with resultant normal lumen post operatively.


Fractalkine and apoptotic/anti-apoptotic markers in granulosa cells of women with polycystic ovarian syndrome.
Owing to the role of fractalkine in regulating cellular apoptosis/proliferation, we investigated fractalkine effects on apoptosis/proliferation signaling of granulosa cells in polycystic ovarian syndrome (PCOS) patients through in vitro and in vivo experiments. In vivo, granulosa cells were collected from 40 women undergoing oocyte retrieval (20 controls and 20 PCOS). The expression levels of fractalkine, BAX, Bcl2, Bcl2-XL, Bad, and TNF-α were assessed using RT-PCR. In vitro, we determined the effect of different doses of fractalkine on the expression of the above mentioned genes in GCs of both groups. We found that the expression levels of fractalkine and Bcl-2 were significantly lower in the GCs of PCOS patients compared to the control group (p < 0.05). In contrast, the expression levels of TNF-α and BAX were higher in the patient's group than in the control group. The results suggested that expression levels of fractalkine were negatively and positively correlated with the number of oocytes and fertilized oocytes respectively. Moreover, fractalkine could dose-dependently increase fractalkine and decrease BAD, BAX, Bcl-xl, and TNF-α expressions in the control GCs. In contrast, GCs collected from PCOS patients revealed an increase in expression of BAD, BAX, and Bcl-xl following fractalkine treatment. Our findings indicated that insufficient expression of fractalkine in PCOS patients is related with elevated apoptotic and inflammatory markers and reduced anti-apoptotic genes in the GCs.


Dimension reduction methods for microarrays with application to censored survival data.
Recent research has shown that gene expression profiles can potentially be used for predicting various clinical phenotypes, such as tumor class, drug response and survival time. While there has been extensive studies on tumor classification, there has been less emphasis on other phenotypic features, in particular, patient survival time or time to cancer recurrence, which are subject to right censoring. We consider in this paper an analysis of censored survival time based on microarray gene expression profiles. We propose a dimension reduction strategy, which combines principal components analysis and sliced inverse regression, to identify linear combinations of genes, that both account for the variability in the gene expression levels and preserve the phenotypic information. The extracted gene combinations are then employed as covariates in a predictive survival model formulation. We apply the proposed method to a large diffuse large-B-cell lymphoma dataset, which consists of 240 patients and 7399 genes, and build a Cox proportional hazards model based on the derived gene expression components. The proposed method is shown to provide a good predictive performance for patient survival, as demonstrated by both the significant survival difference between the predicted risk groups and the receiver operator characteristics analysis. R programs are available upon request from the authors. http://dna.ucdavis.edu/~hli/bioinfo-surv-supp.pdf.


Type of intracranial hemorrhage after endovascular stroke treatment: association with functional outcome.
Intracranial hemorrhage (ICH) is a frequent complication after endovascular stroke treatment. To assess the association of the occurrence and type of ICH after endovascular treatment (EVT) with functional outcome. We analyzed data from the MR CLEAN-NO IV and MR CLEAN-MED trials. Both trials included adult patients with ischemic stroke with a large vessel occlusion in the anterior circulation, who were eligible for EVT. ICH was classified (1) as asymptomatic or symptomatic (concomitant neurological deterioration of ≥4 points on the NIHSS, or ≥2 points on 1 NIHSS item), and (2) according to the Heidelberg Bleeding Classification. We used multivariable ordinal logistic regression analyses to assess the association of the occurrence and type of ICH with the modified Rankin Scale score at 90 days. Of 1017 included patients, 331 (33%) had an asymptomatic ICH, and 90 (9%) had a symptomatic ICH. Compared with no ICH, both asymptomatic (adjusted common OR (acOR)=0.76; 95% CI 0.58 to 0.98) and symptomatic (acOR=0.07; 95% CI 0.04 to 0.14) ICH were associated with worse functional outcome. In particular, isolated parenchymal hematoma type 2 (acOR=0.37; 95% CI 0.14 to 0.95), combined parenchymal hematoma with hemorrhage outside infarcted brain tissue (acOR=0.17; 95% CI 0.10 to 0.30), and combined hemorrhages outside infarcted brain tissue (acOR=0.14; 95% CI 0.03 to 0.74) were associated with worse functional outcome than no ICH.Strength of the association of ICH with functional outcome depends on the type of ICH. Although the association is stronger for symptomatic ICH, asymptomatic ICH after EVT is also associated with worse functional outcome.


Treatment outcomes in spontaneous intracranial hypotension: do epidural blood patches stop the leaks?
Spontaneous intracranial hypotension (SIH) is a postural headache syndrome unrelated to dural puncture. Because of the increasing failure of epidural blood patch (EBP) to relieve headache in SIH, we retrospectively investigated the epidemiological features and treatment outcomes in 55 cases of SIH. The study population was stratified by age and sex; continuous variables were compared for differences by t-tests; categorical variables were compared by Chi-squared analysis or Fisher exact tests. Significant differences were identified by P values of 0.05 or less. The mean age of the study population was 44 +/- 12 years with a female to male ratio of 1.3:1.0. Men presented with subdural hematomas (P = 0.001) more often than women. Meningeal enhancement on contrast magnetic resonance imaging (MRI) was the most consistent radiographic finding. Radionuclide cisternography (RC) demonstrated thoracolumbar dural leaks in 16 of 22 patients. EBP failures were more common in patients aged 40 and younger than in older patients (P = 0.003). Postural headache from SIH was not uniformly responsive to EBP, and had significant comorbidities, especially in men. The management of postural headache in SIH by other techniques to restore brain position and cerebrospinal fluid dynamics should be investigated.


No evidence for GM-CSF receptor alpha chain gene mutation in AML-M2 leukemias which have lost a sex chromosome.
Sixty-five percent of acute myeloid leukemias subtype M2 (AML-M2), displaying a translocation between chromosomes 8 and 21 (t8;21) have also lost one or other copy of the sex chromosomes (XO). This finding has led to the hypothesis that a recessive oncogene may be present in the DNA common to both sex chromosomes, that is the pseudoautosomal region. The alpha chain of the receptor for the hemopoietic growth factor GM-CSF has recently been mapped to the human pseudoautosomal region and, given the role of this molecule in the control of normal hemopoiesis, it is thought to be a good candidate gene. This paper examines the structure, expression, and sequence of the GM-CSF receptor alpha chain gene (GMR alpha) in three primary AML-M2,XO samples and one AML-M2,XO cell line. Results of this work show no gross rearrangement or loss of the remaining allele of GMR alpha, detectable expression of its transcript and protein, and no changes at the nucleotide sequence level. Thus, we find no evidence to support a role for the GM-CSF receptor alpha chain molecule in the development of AML-M2,XO leukemias.


[DUODENAL PEPTIC ULCER TREATMENT BY H. PYLORI ERADICATION: CONTROLED RANDOMIZED STUDY]
As Helicobacter pylori infection represents a very important causal factor in the development of duodenal peptic ulcer, several therapeutic trials have been developed in order to obtain an efficient eradication of the microorganism. The aim of our study has been to evaluate, in patients with duodenal peptic ulcer, the effect of double antibiotic short therapy associated to famotidine on the eradication of Helicobacter pylori, cicatrization of ulcerous lesion and the histological changes after the treatment. Forty patients with duodenal ulcer and Helicobacter pylori infection were distributed al random in two groups (I and II). Group I received tetracycline 2 gr per day plus furazolidone 400 mg per day for a week, and famotidine 40 mg per day for four weeks. Group II received just famotidine 40 mg per day for six weeks. Al the initial endoscopy, four biopsies were taken from the gastric antrurn for histological study and determination of Helicobacter pylori. The endoscopy was repeated between 6 and 8 weeks after the beginning of the antibiotic treatment, when four biopsies were taken again from the gastric antrum with the same purpose, and the results were compared. Twenty-eight patients completed the study, 14 in group I and 14 in group II. Helicobacter pylori eradication was obtained in 85,7% of patients in group I and 0% in group II (p=0.00002). Ulcer cicatrization was obtained in 100% of patients of group I compared to 85,7% of patients of group II (p=0.48). The histological degree of gastritis significantly diminished after the treatment in patients of Group I, in relation to the histological parameters of severity (p=0,002), activity (p=0,00002) and presence of lymphoid follicles (p=0.02). These changes were not significantly observed in group II. Two patients of group I had mild sideeffects (14,3%), and none of them was observed in group II (p=0.48). We concluded that the treatment used (tetracycline + furazolidone) was highly efficacious in the eradication of Helicobacter pylori, as well as in the cicatrization, reduction of antral gastric mucous inflammation, and a low rate of side-effects.


Effect of Electrochemical Pre-Lithiation on Layered Oxide Cathodes for Anode-Free Lithium-metal Batteries.
Due to high energy density and lower manufacturing cost, anode-free lithium-metal batteries (AFLMBs) are attracting increasing attention. The challenges for developing them lie in inferior Coulombic efficiency and short cycle life due to the highly reactive lithium metal. Herein, an electrochemical pre-lithiation strategy is applied to layered oxide cathodes, specifically LiNiO2 and LiCoO2 , aiming to provide an additional lithium source and understand the effect on the cathode structure for AFLMBs. The mechanism for accommodating the excess Li depends on the structural stability of the cathodes where LiNiO2 forms lithiated Li2 NiO2 with the excess lithium in the crystalline lattice while the excess lithium in LiCoO2 forms a Li2 O phase. More importantly, an optimal amount of Li excess is necessary to maintain decent cycle stability and specific capacity in AFLMB, with 40% excess Li for LiNiO2 and 150% for LiCoO2 . While the pre-lithiation process causes particle pulverization depending on the amount of Li excess, LiCoO2 offers a much better cycle performance than LiNiO2 with a promising capacity retention of 80% after 300 cycles in AFLMB (vs 76% after 100 cycles for 40% Li excess in LiNiO2 ). This study provides a promising avenue for developing tailor-made layered oxide cathodes for AFLMBs.


Facile synthesis of tetrafluorotyrosine and its application in pH triggered membrane lysis.
"Smart" peptides that lyse membranes in response to biological stimuli are of considerable interest. Herein, we report a facile synthesis of L-tetrafluorotyrosine (L-f(4)Y) and its utilization as a pH sensing element. The synthetic route affords gram quantities of L-f(4)Y within two days. Incorporation of this unnatural amino acid into magainin 2 gives a peptide that turns on its membrane-lytic activity upon mild acidification.


Fluid overload and outcomes in critically ill children: A single center prospective cohort study.
To prospectively evaluate the association between fluid overload (FO) and clinical outcomes, mortality, mechanical ventilation (MV), and duration and length of stay in a pediatric intensive care unit (PICU). Over a 12-month period, patients who were on MV for >24h or vasoactive support were prospectively included. Demographic and clinical data were recorded. Daily FO was calculated as [(fluid in-fluid out)/admission weight]×100%. Multivariate stepwise logistic regression analysis was used to determine predictors of survival. 224 patients were included; median age was 3.3 (IQR 0.7, 9.9) years, mortality was 15.6%. The median peak FO (PFO) was 12.5% (IQR 5, 25), PFO>10% was present in 55.8% of patients, and PFO>20% was present in 33%. The PFO in non-survivors was 17.8% (IQR 8, 30) and 11% (IQR 4, 23) in survivors (p=0.028). A survival analysis showed no association between PFO and mortality. A multivariate analysis identified vasoactive support, >3 organ failures and acute kidney injury (AKI) but not FO as independent risk factors for mortality. FO was associated with MV duration and PICU length of stay. FO is frequent in a general PICU population, but PFO is not an independent risk factor for mortality. Future studies of FO should focus on patients with AKI and multiorgan failure for better classification of severity and potential interventions.


The decoupling of Smoothened from Galphai proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning.
The Hedgehog (Hh) signal is transmitted by two receptor molecules, Patched (Ptc) and Smoothened (Smo). Ptc suppresses Smo activity, while Hh binds Ptc and alleviates the suppression, which results in activation of Hh targets. Smo is a seven-transmembrane protein with a long carboxyl terminal tail. Vertebrate Smo has been previously shown to be coupled to Galpha(i) proteins, but the biological significance of the coupling in Hh signal transduction is not clear. Here we show that although inhibition of Galpha(i) protein activity appears to significantly reduce Hh pathway activity in Ptc(-/-) mouse embryonic fibroblasts and the NIH3T3-based Shh-light cells, it fails to derepress Shh- or a Smo-agonist-induced inhibition of Gli3 protein processing, a known in vivo indicator of Hh signaling activity. The inhibition of Galpha(i) protein activity also cannot block the Sonic Hedgehog (Shh)-dependent specification of neural progenitor cells in the neural tube. Consistent with these results, overexpression of a constitutively active Galpha(i) protein, Galpha(i2)QL, cannot ectopically specify the neural cell types in the spinal cord, whereas an active Smo, SmoM2, can. Thus, our results indicate that the Smo-induced Galpha(i) activity plays an insignificant role in the regulation of Gli3 processing and Shh-regulated neural tube patterning.


Daily life negative mood and exhaled nitric oxide in asthma.
Psychosocial stress and negative affect have been linked to asthma exacerbations, but longitudinal studies demonstrating a daily life association between negative affect and airway nitric oxide are missing. The longitudinal association between negative mood fluctuations, exhaled nitric oxide, and lung function in asthma was examined. Self-assessments of the fraction of exhaled nitric oxide (FeNO), spirometry (forced expiratory volume in the first second, FEV1), negative mood, and daily activities were obtained from 20 patients with asthma for 2 months, resulting in 1108 assessments for the analyses (approximately 55 per patient). Concurrent and prospective associations between FeNO, FEV1, and negative mood were analyzed using mixed effects regression models for longitudinal data. Negative mood was positively associated with changes in FeNO during the same day, and to a stronger extent when prior day negative mood was included in the prediction. FeNO and negative mood were positively associated with same-day FEV1, with the latter relation being partially mediated by changes in FeNO. Associations between FeNO and FEV1 were stronger in younger patients, with earlier onset of asthma, or with lower asthma control. Findings were not changed when controlling for physical activity, medication, cold symptoms, air pollution, and hours spent outside. Daily life changes of negative mood in asthma are positively associated with FeNO changes and FeNO increases are associated with a mild bronchodilation. These findings indicate that psychological influences need to be considered when using FeNO as indicator of airway inflammation and guide for treatment decisions.


Topical tacrolimus therapy of resistant cutaneous lesions in lupus erythematosus: a possible alternative.
To determine the efficacy of tacrolimus ointment 0.1% on resistant cutaneous lesions in patients with lupus erythematosus. Twelve patients with skin manifestations were studied. Six had discoid lupus (DL), four subacute cutaneous lupus erythematosus (SCLE) and two systemic lupus erythematosus (SLE). All patients had extensive skin lesions refractory to previous treatment. Patients received topical tacrolimus 0.1% for a minimum of 6 weeks and response was evaluated by physicians' and patients' assessment and documented with photographs at baseline and at the end of the treatment. Eleven of 12 patients completed the therapy. One patient with DL discontinued because of side--effects-peeling and a burning sensation. Six patients were clearly improved, one patient had a minor remission of his face lesion while in four the rashes remained the same. Two patients with SCLE had significant regression of their lesions while the other two had no improvement. In DL, two had certain improvement, one minor improvement and two were without response. The patients with SLE had significant amelioration of their extensive photosensitive rash. Tacrolimus ointment 0.1% may be an effective alternative in patients with severe resistant cutaneous manifestations in lupus erythematosus.


Investigation of factors enhancing droplets spreading on leaves with burrs.
Spread effect is one of the aspects on deposition quality evaluation of pesticide droplets. It could be affected by many factors such as the microstructure of the target plant leaf surface, physical features of the droplets, and the concentration of spray additives. In this study, using a high-speed photography system, 2.3% glyphosate ammonium salt solution with different concentration of the additive was applied to investigate the impact process of single droplet deposition on the plant leaf surface with burrs. Effect of droplet sizes and velocities on spreading area and dynamic deposition procedure was analyzed using image processing programs. The diffusion factor in the process of droplet spreading was changed over time. The occurrence of bubbles in the droplets was observed in the results. With the bubble generation, the droplet diameter expands and a better diffusion effect is obtained. As a result, better spreading effect was obtained as the droplet diameter was expanded with the generation of bubbles. The significant effects of each physical property of droplets on droplet spreading and the interaction effects between the influencing factors were analyzed. A significant correlation was found between additive concentration, droplet impact velocity, droplet diameters and droplet spreading area. All interactions of concentration:velocity, concentration:diameter, velocity:diameter, and concentration:velocity:diameter had a significant effect on the spreading area of droplets. The study of the factors influencing the process of pesticide droplet impact on the leaf surface contributes to the efficient use of pesticides. Thus, the consumption of pesticides and the resulting impact on the environment can be reduced.


Natural Halloysites-Based Janus Platelet Surfactants for the Formation of Pickering Emulsion and Enhanced Oil Recovery.
Janus colloidal surfactants with opposing wettabilities are receiving attention for their practical application in industry. Combining the advantages of molecular surfactants and particle-stabilized Pickering emulsions, Janus colloidal surfactants generate remarkably stable emulsions. Here we report a straightforward and cost-efficient strategy to develop Janus nanoplate surfactants (JNPS) from an aluminosilicate nanoclay, halloysite, by stepwise surface modification, including an innovative selective surface modification step. Such colloidal surfactants are found to be able to stabilize Pickering emulsions of different oil/water systems. The microstructural characterization of solidified polystyrene emulsions indicates that the emulsion interface is evenly covered by JNPS. The phase behaviors of water/oil emulsion generated by these novel platelet surfactants were also investigated. Furthermore, we demonstrate the application of JNPS for enhanced oil recovery with a microfluidic flooding test, showing a dramatic increase of oil recovery ratio. This research provides important insights for the design and synthesis of two-dimensional Janus colloidal surfactants, which could be utilized in biomedical, food and mining industries, especially for circumstances where high salinity and high temperature are involved.


Fatty acid synthase mediates high glucose-induced EGFR activation in oral dysplastic keratinocytes.
Recent studies point to the epidermal growth factor receptor (EGFR) as a critical mediator of type 2 diabetes mellitus (T2DM)-induced renal, cardiac, and ocular complications. T2DM is considered a systemic contributing factor in oral carcinogenesis. Similarly, increased EGFR gene copy number and protein expression strongly predict tumor progression. Yet, the impact of hyperglycemia on EGFR activity in oral potentially malignant disorders remains unclear. We recently reported that fatty acid synthase (FASN), a key de novo lipogenic enzyme, mediates EGFR activation in nicotine-treated oral dysplastic keratinocytes. While in non-malignant tissues FASN expression is extremely low, it is frequently upregulated in several cancers, including oral squamous cell carcinoma. The present study was carried out to investigate whether high glucose conditions trigger pro-oncogenic responses in oral dysplastic keratinocytes via FASN-mediated EGFR activation. Cell viability and migration of oral dysplastic keratinocytes were evaluated when exposed to normal (5 mM) or high (20 mM) glucose conditions in the presence of FASN and EGFR inhibitors. Western blotting was also performed to assess changes in FASN protein expression and EGFR activation. Oral dysplastic keratinocytes exposed to high glucose led to EGFR activation in a FASN-dependent manner. Likewise, high glucose significantly enhanced cell viability and migration in a FASN/EGFR-mediated fashion. Notably, EGFR inhibition by the anti-EGFR monoclonal antibody cetuximab significantly reduced the proliferation of FASN-overexpressing oral dysplastic keratinocytes. These novel findings suggest that FASN may act as a key targetable metabolic regulator of glucose-induced EGFR oncogenic signaling in oral potentially malignant disorders.


Recent progress in studies on cell-mediated immune responsiveness in insects.
Comparative immunologists have been engaged in a search for the origins of cell-mediated immunity for a long time. One group of invertebrates that have been receiving increasing attention has been the insects. These animals not only serve as good experimental models, but are of great interest because of their evolutionary success. Several studies have shown that insects generally respond to particular foreign material by mounting an encapsulation reaction. On a more specific level, insects have also been found to be capable of quickly rejecting integumentary xenografts. A basic enigma however, has been the reported inability of insects to respond to integumentary allografts. Recent work from our lab indicates that if one concentrates on the fate of the soft tissue component of the integument, one can readily demonstrate allograft reactivity in these animals. We have now confirmed this by yet another system which monitors the loss of 3H-thymidine from labeled allo- and autografts. Thus, future studies promise to unravel some long sought after questions concerning the evolution of cellular defense mechanisms.


Mechanistic insights on spider neurotoxins.
In physiology research, animal neurotoxins historically have served as valuable tools for identification, purification, and functional characterization of voltage-dependent ion channels. In particular, toxins from scorpions, sea anemones and cone snails were at the forefront of work aimed at illuminating the three-dimensional architecture of sodium channels. To date, at least six different receptor binding sites have been identified and--most of them--structurally assigned in terms of protein sequence and spatial disposition. Recent work on Australian funnel-web spiders identified certain peptidic ingredients as being responsible for the neurotoxicity of the crude venom. These peptides, termed delta-atracotoxins (delta-ACTX), consist of 42 amino acids and bind to voltage-gated sodium channels in the same way as classical scorpion alpha-toxins. According to the 'voltage-sensor trapping model' proposed in the literature, delta-ACTX isoforms interact with the voltage sensor S4 transmembrane segment of alpha-subunit domain IV, thereby preventing its normal outward movement and concurrent conformational changes required for inactivation of the channel. As consequence prolonged action potentials at autonomic or somatic synapses induce massive transmitter release, resulting in clinical correlates of neuroexcitation (e.g., muscle fasciculation, spasms, paresthesia, tachycardia, diaphoresis, etc.). On the other hand, the major neurotoxin isolated from black widow spiders, alpha-latrotoxin (alpha-LTX), represents a 132 kDa protein consisting of a unique N-terminal sequence and a C-terminal part harboring multiple ankyrin-like repeats. Upon binding to one of its specific presynaptic receptors, alpha-LTX has been shown to tetramerize under physiological conditions to form Ca2+-permeable pores in presynaptic membranes. The molecular model worked out during recent years separates two distinguishable receptor-mediated effects. According to current knowledge, binding of the N terminus of alpha-LTX at one of its specific receptors either triggers intracellular signaling cascades, resulting in phospholipase C-mediated mobilization of presynaptic Ca2+ stores, or leads to the formation of tetrameric pore complexes, allowing extracellular Ca2+ to enter the presynaptic terminal. Alpha-LTX-triggered exocytosis and fulminant transmitter release at autonomic synapses may then provoke a clinical syndrome referred to as 'latrodectism', characterized by local and incapacitating pain, diaphoresis, muscle fasciculation, tremor, anxiety, and so forth. The present review aims at providing a short introduction into some of the exciting molecular effects induced by neurotoxins isolated from black widow and funnel-web spiders.


The frequency of genes encoding exotoxin A and exoenzyme S in Pseudomonas aeruginosa strains isolated from burn patients.
Pseudomonas aeruginosa infections have emerged as a major infectious disease threat in recent decades with infection particularly in immunocompromised hosts. P. aeruginosa possesses several virulence factors with involvement in pathogenesis. The aim of this study was to examine the prevalence of virulence genes of toxA and toxS and to analyze their relation to antimicrobial resistance of the isolates. In total 185 clinical isolates of P. aeruginosa were collected from burn patients. Antimicrobial susceptibility testing was done by disk diffusion method. PCR amplification was performed on extracted DNA from the isolates and the presence of encoding genes for exotoxin A (toxA) and exoenzyme S (toxS) were investigated by using specific primers. In disk diffusion method, the isolates showed high sensitivity to colistin sulfate (100%) followed by imipenem (41.9%). The most prevalent resistance was seen against ceftazidime (90.5%) and gentamicin (88.5%). Multidrug resistance (MDR) demonstrated in 113 isolates (76.35%). According to PCR amplification, 133 (89.8%) and 127 (85.8%) isolates possessed toxA and toxS genes respectively. The frequencies of genes among MDR strains were 102 (76.6%) for toxA and 98 (77.1%) for toxS. Eighty five MDR isolates possessed both genes (73.9%). The non-MDR strains (23.65%), harbored lower prevalence of simultaneous toxA and toxS genes (26%) compared to MDR strains. The present study established a higher frequency of MDR among P. aeruginosa isolates from burn patients. It was found that the frequency of both toxA &S genes were significantly higher in MDR strains P. aeruginosa strains.


Laparoscopic surgery of the liver and biliary tract.
Laparoscopic treatment of liver and biliary tract disease is growing in popularity but requires extensive experience. Among the lesions now managed with minimally invasive methods are simple cysts, polycystic liver disease, hydatid cysts, biliary stones, and benign solid tumors. Patient selection, surgical techniques, and outcomes are described.


Dual-cured etch-and-rinse adhesive systems increase the bond durability of direct coronal dentin restorations.
This study aimed to evaluate the bond durability of dentin restorations bonded with light- or dual-cured etch-and-rinse adhesive systems. A three-step adhesive system (Scotchbond Multipurpose Plus), an acetone-based two-step adhesive system (Prime & Bond 2.1), and an ethanol-based two-step adhesive system (Excite) were tested. Both the light- and the dual-cured versions were evaluated. High C-factor dentin cavities were prepared on 120 bovine incisors, which were then restored with resin composite (n=10). The samples were stored in water for 24 hours, and half of them were subjected to additional degradation with 10% NaOCl for five hours. The push-out bond strength test was performed in a universal testing machine until failure. Failure modes were evaluated by scanning electron microscopy. Data were analyzed by three-way analysis of variance and Tukey tests (p<0.05). The dual-cured adhesive system presented a higher immediate bond strength and durability than those that were light cured. The three-step adhesive system produced the highest values, whereas the acetone-based adhesive system produced the lowest result. Therefore, the use of dual-cured etch-and-rinse adhesive systems can induce increased bond durability to direct coronal dentin restorations.


SEX-RATIO MANIPULATION IN RESPONSE TO HOST SIZE BY THE PARASITOID WASP SPALANGIA CAMERONI: A LABORATORY STUDY.
The prediction of Charnov et al.'s (1981) host-size model that there should be a negative relationship between host size and wasp sex ratio (proportion sons) was supported for Spalangia cameroni, a solitary parasitoid wasp. The relationship was shown to be a result of offspring sex manipulation by females in response to host size rather than a result of differential mortality of the sexes. A major assumption of the host-size model is that host size has a greater effect on the ultimate reproductive success of emerging female wasps than of males. This assumption was not supported. Host size had a positive effect on the size of both male and female S. cameroni. However, neither host size nor wasp size affected longevity, production of offspring by females, or ability of males to compete for mates. Host size may differentially affect the reproductive success of female and male wasps through effects on other aspects of reproductive success. Tests of the assumptions of offspring sex-ratio manipulation hypotheses are scarce but critical, not only for parasitoid wasps, but also for other organisms.


The intestinal proteome of diabetic and control children is enriched with different microbial and host proteins.
In this study, the intestinal microbial proteome of children with established type 1 diabetes (T1D) was compared with the proteome of healthy children (Control) with the aim to identify differences in the activity of the intestinal microbiota that not only will contribute to a deeper knowledge of the functionality of the gut in these children but also may provide new approaches to improve the control of the disease. Faecal protein extracts collected from three T1D children (aged 9.3±0.6 years) and three Control children (aged 9.3±1.5 years) were analysed using a combination of 2D gel electrophoresis and spectral counting. The results evidenced markedly differences between the intestinal proteome of T1D children and the Control. The T1D microbial intestinal proteome was enriched with proteins of clostridial cluster XVa and cluster IV and Bacteroides. In contrast, the Control proteome was enriched with bifidobacterial proteins. In both groups, proteins with moonlight function were observed. Human proteins also distinguished the two groups with T1D children depleted in exocrine pancreatic enzymes.


Therapy for relapsed multiple myeloma.
Despite significant progress in our understanding and the development of novel therapies, most patients with multiple myeloma will experience relapse of their disease. Therapy of relapsed myeloma has improved due to the availability of novel agents that are highly active against the disease. However, the selection of therapy can be challenging due to the emergence of toxicities, comorbidities and frailty. In the following we discuss our approach to the treatment of the patient with relapsed myeloma.


Dentistry and the Law Conference, November 9, 1990.
Dr. Guaccio was the only general dentist invited to present material on dental implants at the 3rd Annual Dentistry and the Law Conference held in conjunction with the Loyola School of Law and Randall K. Berning & Associates on November 9, 1990, in Chicago. The presentation was made before a group composed mainly of persons with degrees in both law and dentistry as well as individuals from dental schools and department chairpersons. Representatives from the various specialty organizations were also in attendance. The presentation made by Dr. Guaccio brings to light several of the problems facing the dental profession as it attempts to come to grips with legal issues surrounding dental implant care.


BIVM, a novel gene widely distributed among deuterostomes, shares a core sequence with an unusual gene in Giardia lamblia.
A novel gene, BIVM (for basic, immunoglobulin-like variable motif-containing), has been identified using an electronic search based on the conservation of short sequence motifs within the variable region of immunoglobulin (Ig) genes. BIVM maps to human chromosome 13q32-q33 and is predicted to encode a 503-amino-acid protein with a pI of 9.1. The 5' untranslated region of BIVM is encoded in two exons; the coding portion is encoded in nine exons. BIVM is tightly linked (41 bp) and in the opposite transcriptional orientation to MGC5302 (also known as KDEL1 and EP58) in human. The ubiquitous expression of BIVM in normal tissues and the presence of a 5' CpG island suggest that BIVM is a housekeeping gene. Characterization of BIVM in representative species demonstrates significant conservation throughout deuterostomes; no sequence with significant identity to BIVM has been detected in proteostomes. However, an unusual gene has been identified in the protozoan pathogen Giardia lamblia that is similar to the core sequence of BIVM, suggesting the possibility of a horizontal gene transfer.


Evidence from transgenic mice that glucose transport is rate-limiting for glycogen deposition and glycolysis in skeletal muscle.
A line of transgenic mice was constructed in which the human Glut1 glucose transporter is overexpressed in skeletal muscle. Overexpression of Glut1 protein was evident in epitrochlearis, extensor digitorum longus (EDL), and quadriceps muscles, and resulted in 6.6-7.4-fold elevations in basal glucose transport activity as measured in isolated muscles in vitro. The elevated glucose transporter activity in the skeletal muscles of transgenic mice was associated with a 10-fold increase in glycogen concentration in EDL and quadriceps muscles that was not due to an increase in muscle glycogen synthase activity or a decrease in glycogen phosphorylase activity. The increased glucose transport activity also resulted in a 2-fold increase in muscle lactate concentration, with no increase in muscle glucose 6-phosphate. Despite a slight (10%) increase in muscle hexokinase activity, there was a 4-fold increase in total muscle free glucose in transgenic mice, indicating that hexokinase becomes rate-limiting for glucose uptake when the rate of glucose transport is very high. These results demonstrate that the muscle glycogen content can be dramatically elevated by increasing the muscle Glut1 protein level and that glucose transport is a rate-limiting step for muscle glucose disposal in normal, resting mice.


Calciphylaxis with peau d'orange induration and absence of classical features of purpura, livedo reticularis and ulcers.
Calciphylaxis is an ill-defined syndrome that is commonly associated with chronic renal failure. Its heterogeneous clinical features include painful livedo reticularis-like purpuric patches and plaques, vesicles, irregularly shaped ulcers, and black eschars. Despite demonstration of extensive vascular arteriolar calcification in this syndrome, its exact pathogenesis remains unknown. Here, we report a case of calciphylaxis presenting with indurated plaques without the usual clinical picture of livedo reticulate purpura, ulcers or necrotic eschars. This case provides an opportunity to review the clinical spectrum of calciphylaxis and to discuss the therapeutic approaches and pathogenesis of this syndrome from deep intra-wall vascular calcification to the resulting infarctions of adjacent tissues.


Post-traumatic hydrocephalus - incidence, risk factors, treatment, and clinical outcome.
Post-traumatic hydrocephalus (PTH) is well-known after traumatic brain injury (TBI), but there is limited evidence regarding patient selection for ventriculo-peritoneal (VP)-shunt treatment. In this study, we investigated the incidence and risk factors for PTH and the indication for and outcome after shunt treatment. In this retrospective study, 836 TBI patients, treated at our neurointensive care (NIC) unit at Uppsala university hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiology, treatments, and outcome variables were evaluated. Post-traumatic ventriculomegaly occurred in 46% of all patients at NIC discharge. Twenty-nine (3.5%) patients received a VP-shunt. Lower GCS M at admission, greater amount of subarachnoid hemorrhage, meningitis, decompressive craniectomy (DC), and ventriculomegaly at NIC discharge were risk factors for receiving a VP-shunt. Fourteen of the PTH patients showed impeded recovery or low-pressure hydrocephalus symptoms, of whom 13 experienced subjective clinical improvement after shunt treatment. Five PTH patients showed deterioration in consciousness, of whom four improved following shunt treatment. Five DC patients received a shunt due to subdural hygromas (n =2) or external brain herniation (n = 3), of whom two patients improved following treatment. Five patients were vegetative with concurrent ventriculomegaly and these patients did not have any positive shunt response. Altogether, 19 (66%) PTH patients improved after shunt surgery. Post-traumatic ventriculomegaly was common, but few developed symptomatic PTH and received a VP-shunt. Patients with low-pressure hydrocephalus symptoms had the best shunt response, whereas patients with suspected vegetative state exhibited a minimal shunt response.


Cutaneous melanocytic lesions: do not miss the invisible gorilla.
Of all pathology fields, the analysis of melanocytic lesions has one of the highest rates of review for legal reasons, particularly regarding the distinction between nevus and melanoma. Among the most frequently involved are desmoplastic melanoma, nevoid melanoma, and Spitz nevus versus spitzoid melanoma. Therefore, it follows that pathologists and dermatopathologists should pay special attention when dealing with such type of lesions. This review article will emphasize a number of clinical, histologic, and immunohistochemical features we believe are essential when evaluating lesions whose differential diagnosis includes melanoma/nevus. Furthermore, we want to stress the importance of examining the entire slide within the context of all available information in order to not miss the invisible gorilla in the slide. Regarding this apparently bizarre choice to illustrate these problems (to not miss an invisible gorilla), we request the reader to continue reading this article to find out why.


Exploring the Landscape of the PP7 Virus-like Particle for Peptide Display.
Self-assembling virus-like particles (VLPs) can tolerate a wide degree of genetic and chemical manipulation to their capsid protein to display a foreign molecule polyvalently. We previously reported the successful incorporation of foreign peptide sequences in the junction loop and onto the C-terminus of PP7 dimer VLPs, as these regions are accessible for surface display on assembled capsids. Here, we report the implementation of a library-based approach to test the assembly tolerance of PP7 dimer capsid proteins to insertions or terminal extensions of randomized 15-mer peptide sequences. By performing two iterative rounds of assembly-based selection, we evaluated the degree of favorability of all 20 amino acids at each of the 15 randomized positions. Deep sequencing analysis revealed a distinct preference for the inclusion of hydrophilic peptides and negatively charged amino acids (Asp and Glu) and the exclusion of positively charged peptides and bulky and hydrophobic amino acid residues (Trp, Phe, Tyr, and Cys). Within the libraries tested here, we identified 4000 to 22,000 unique 15-mer peptide sequences that can successfully be displayed on the surface of the PP7 dimer capsid. Overall, the use of small initial libraries consisting of no more than a few million members yielded a significantly larger number of unique and assembly-competent VLP sequences than have been previously characterized for this class of nucleoprotein particle.


Peroneal nerve compression secondary to an anomalous biceps femoris muscle in an adolescent athlete.
Common peroneal nerve compression is a well-recognized entity that can cause severe debilitating clinical manifestations. The current literature describes numerous locations and mechanisms of compression, including both structural and systemic causes. Anatomical variants should be considered part of the differential diagnosis in peroneal nerve impingement. We present the case of a 14-year-old basketball player with footdrop secondary to compression of the common peroneal nerve from an accessory biceps femoris muscle, which was treated by neurolysis. In addition, we review the systematic workup of patients with nerve compression.


From HIV Abandonment to Adoption: Case study of New Life Home for abandoned babies, Kenya.
The number of orphaned and vulnerable children (OVC) worldwide has increased as a result of the Human Immunodeficiency Virus (HIV) pandemic. New Life Home (NLH) specialises in the care of infants who have been orphaned or abandoned, often because of their exposure to HIV and places them for adoption. This paper documents the lessons learnt from the Home's first 8.5 years of existence. This retrospective study analyses the pattern of the 490 infants admitted at NLH. The characteristics of the infants' stay are analysed: bio-data, weight, HIV exposure, referring organisation/agent and outcome. This study ceased to follow infants after adoption, death, transferral to other homes, or reunion with own family. The infants came via health facilities (58%), local authorities (15%), good Samaritans (2%), and other children's homes (25%). At the end of the study period, 425 (92%) of babies were still alive. Of those who died, 80% were less than 6 months old (p<0.003) and 45% were HIV positive. A child mortality rate of 77.6/1000 was demonstrated with the key associated factors being HIV exposure (p <0001), and weight at admission (p=0.002). The mortality rate for the HIV exposed was 71/1000 at 6 months, 94.7/1000 at 12 months and 100.6/1000 at 18 months, while for those not exposed to the virus it was 43.3/1000 at 6 months and 46.7/1000 at 12 months. The major cause of death in the HIV exposed was pneumonia (56%) and septicaemia (22%). The majority of infants, 323 (67%) were adopted, some were reabsorbed into their biological families 31(6.3%) and a minority 7(1.4%) transferred to other children's homes which cater for older children. NLH demonstrates a possible model of care for OVC as majority of vulnerable child can have the opportunity to be adopted and thereby a 'second lease' of life. This strategy is worth studying and duplicating in the mitigation of the OVC dilemma in HIV high prevalence countries in sub-Saharan Africa.


Existential issues in the management of the demented elderly patient.
Four major existential themes are explored, as they relate to the predicament of the relative supporting a demented elderly dependent at home. These issues, namely, death, isolation, freedom, and meaning are discussed with respect to their dynamic impact on the stressed supporter as well as their implications for anxiety management.


Solitary delayed contralateral testicular metastasis from renal cell carcinoma.
We report a 60 year old male presenting with contralateral testicular metastasis 7 years following radical nephrectomy for renal cell carcinoma. Testicular metastases from renal cell carcinoma reported in literature are predominantly ipsilateral and invariably on the left side. Usually these are present simultaneously with the renal primary or precede the diagnosis of renal tumors. Delayed contralateral testicular metastatic has not been reported to the best of our knowledge. The case highlights the unique behaviour of renal cell carcinoma with an unusual site of recurrence. The clinical presentation, pathogenesis and management of this rare presentation along with review of recent literature are discussed.


Comparison of human retinal pigment epithelium gene expression in macula and periphery highlights potential topographic differences in Bruch's membrane.
To describe gene expression differences between healthy, young human retinal pigment epithelium (RPE) cells from the macular area and RPE cells from two locations in the retinal periphery. RPE cells from six human donor eyes, ages 17-36, without histopathological abnormalities, were dissected by laser and isolated from cryosections. Total RNA was isolated, amplified, and hybridized to a custom made oligonucleotide array containing 22,000 genes. Bioinformatic analysis was carried out using the computer programs Rosetta Resolver and the webtools EASE/David and GoStat. Confirmatory real time PCR (RT-PCR) and immunohistochemistry were performed according to standard protocols. Microarray and statistical analysis yielded 438 genes that were differentially expressed between macular RPE, and at least one out of two peripheral RPE locations. Out of these genes, 33 that showed fold changes of four, or higher, were selected for RT-PCR confirmation. For 17 genes (51%), a significant differential expression was found, while 11 additional genes (33%) showed a similar trend. Immuno-staining of one target (WFDC1) confirmed its differential expression on the protein level. Functional annotation and overrepresentation analysis independently defined extracellular matrix (ECM) genes as a statistically overrepresented class of genes in our RPE dataset. In total, 33 ECM genes were differentially expressed between macular and peripheral RPE regions. A subset of proteins corresponding to these genes is known to be present in Bruch's membrane. Our data showed that consistent topographical gene expression differences in the human RPE constitute around 1-5% of the RPE transcriptome. These changes may underlie topographical differences in RPE physiology, and pathology and may reflect local differences in the molecular composition and turnover of Bruch's membrane.


Arabidopsis thaliana ethylene-responsive element binding protein (AtEBP), an ethylene-inducible, GCC box DNA-binding protein interacts with an ocs element binding protein.
Ocs elements are a group of promoter sequences required for the expression of both pathogen genes in infected plants and plant defense genes. Genes for ocs element binding factors (OBFs), belonging to a specific class of basic-region leucine zipper (bZIP) transcription factors, have been isolated in a number of plants. Using protein-protein interaction screening with OBF4 we have isolated AtEBP, an Arabidopsis protein that contains a novel DNA-binding domain, the AP2/EREBP domain. One class of proteins that contain this domain are the tobacco ethylene-responsive element binding proteins (EREBPs). The EREBPs bind the GCC box that confers ethylene responsiveness to a number of pathogenesis related (PR) gene promoters. AtEBP expression is inducible by exogenous ethylene in wild-type plants and AtEBP transcripts are increased in the ctr1-1 mutant, where ethylene-regulated pathways are constitutively active. Electrophoretic mobility-shift assay and DNase I footprint analysis revealed that AtEBP can specifically bind to the GCC box. Interestingly, the highest level of AtEBP expression was detected in callus tissue, where ocs elements are very active. Synergistic effects of the GCC box with ocs elements or the related G-box sequence have been previously observed, for example, in the ethylene-induced expression of a PR gene promoter. Our results suggest that cross-coupling between EREBP and bZIP transcription factors occurs and may therefore be important in regulating gene expression during the plant defense response.


[Immediate results of the surgical treatment of aneurysms of the ascending aorta associated with aortic insufficiency].
Experience with surgical treatment of ascending-artery aneurysms with concomitant aortic insufficiency is summed up. Forty-four patients were operated on, 30 of those having dissecting aneurysm of the ascending aorta. There were 6 operations where coronary arterial openings were isolated and stitched into a valve-containing conduit and 8 supracoronary resections with prosthetic aortic valve implantation. Hospital mortality rate was 78.6%. Thirty patients underwent Bentall-De Bono operation or Cabrol's operation. Hospital mortality was 26.6%. As surgical techniques and corrective methods improved, hospital mortality could be considerably reduced (to 7.7%).


Classification of breast cancer histopathological images using interleaved DenseNet with SENet (IDSNet).
In this study, we proposed a novel convolutional neural network (CNN) architecture for classification of benign and malignant breast cancer (BC) in histological images. To improve the delivery and use of feature information, we chose the DenseNet as the basic building block and interleaved it with the squeeze-and-excitation (SENet) module. We conducted extensive experiments with the proposed framework by using the public domain BreakHis dataset and demonstrated that the proposed framework can produce significantly improved accuracy in BC classification, compared with the state-of-the-art CNN methods reported in the literature.


Diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer.
The study contained herein was undertaken to review and summarize the current literature on diagnostic and therapeutic applications of monoclonal antibodies in colorectal cancer. Limitations of traditional imaging techniques have encouraged development of targeted imaging strategies using radiolabeled monoclonal antibodies. Diagnostic immunoscintigraphy can detect lesions not identified by conventional imaging modalities, although it has not proven useful in the management of primary colorectal cancers and in hepatic metastases. Immunoscintigraphy shows promise in cases of local recurrence and rising carcinoembryonic antigen values; however, the impact of immunoscintigraphy on clinical outcomes and cost-effectiveness remains unproven. Radioimmunoguided surgery has been advocated as a method of more accurately detecting tumor extension and accomplishing radical resection. The technique remains controversial, and its use is not widespread. With respect to therapeutic applications, immunotherapy has most often been investigated in the setting of advanced stage disease. Results in this setting have been poor. In contrast, adjuvant immunotherapy after resection of Dukes C carcinoma has achieved convincing results, with improvements in survival comparable with that of adjuvant chemotherapy. Adjuvant trials are now under way to examine the effectiveness of monoclonal antibodies in the postoperative treatment of early-stage (II) tumors and the combination of monoclonal antibodies and chemotherapy in advanced-stage (III) tumors. Bispecific antibodies, or immunoconjugates with cytokines or toxins, represent additional areas of interest and future investigations. At present, immunoscintigraphy is not sufficient to determine, by itself, resectability of colorectal tumor and has limited usefulness in select cases of recurrent cancer and possibly in cases of rising carcinoembryonic antigen values. Immunotherapy with monoclonal antibodies as a postoperative adjuvant treatment shows promise and is currently being investigated in national trials.


Performance of immobilized Zymomonas mobilis 31821 (pZB5) on actual hydrolysates produced by Arkenol technology.
By applying the Arkenol process using highly concentrated sulfuric acid, various biomass feedstocks, including cedar tree, rice straw, newspaper, and bagasse, were successfully processed and converted into glucose and xylose for fermentation usage in a flash fermentation reactor in which the performance of National Renewable Energy Laboratory's patented rec-Zymomonas mobilis 31821 (pZB5) after immobilization was investigated. The immobilization medium is a photocrosslinked resin made from polyethylene glycols or polypropylene glycols. Recombinant or rec-Z. mobilis used in the study has been shown to efficiently ferment glucose and xylose at a relatively high concentration (12-15%), that is a typical hydrolysate produced from cellulosic feedstocks. The application of immobilized rec-Z. mobilis and flash fermentation technology, together with concentrated acid technology producing a high concentration sugar solution, promises to speed the development of the cellulose-to-ethanol industry.


The miR-383-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer.
To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC). We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383. The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines. Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.


Perforating calcifying epithelioma of Malherbe with a rapid evolution.
A very rare case of calcifying epithelioma of Malherbe (CEM) with a rapid evolution and perforation of the epidermis is reported. Clinical appearance was atypical and did not suggest any diagnosis. Histopathologic examination shows a picture of CEM with some peculiar findings. Furthermore, in the upper dermis there are epithelial strands of shadow cells, partially calcified, tending to come in contact with the perforated epidermis and to be eliminated through it. The acute form of CEM and the mechanism of epidermal perforation in perforating dermatoses are discussed.


The replacement of the chair, stand and phoropter by subjective autorefraction--a candid evaluation.
With all the competition from outside of professional optometry, it is imperative that the doctor of optometry offer the patient a service that is superior. Keep in mind that I am no better than or different from other doctors, but my patients see me that way. That is an important ingredient in a successful practice. My experience demonstrates that the Humphrey Over-refraction System can function with great efficiency as the primary and indeed the only subjective refraction device in a busy solo practice. It can also take a mediocre practice and help to put it on the map. Some may not have confidence in automation. Others may feel that the methods described herein are maverick or financially risky. If you are skeptical, whatever the reason, you will obviously stick with traditional refractive methods. If, on the other hand, you are dissatisfied with traditional methods and the fruits of your labor, automation is a solid alternative as long as sound management guidelines are followed.


Cell type-dependent HIF1 α-mediated effects of hypoxia on proliferation, migration and metastatic potential of human tumor cells.
Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions. Importantly, HT168-M1 human melanoma cells with high baseline migration capacity showed increased HIF-1α and small GTPases expression, RhoA activation and migration under hypoxia. These activities were blocked by anti- HIF-1α shRNA. Moreover, the in vivo metastatic potential was promoted by hypoxia mimicking CoCl2 treatment and reduced upon inhibition of HIF-1α in a spleen to liver colonization experiment. In contrast, HT29 human colon cancer cells with low migration capacity showed limited response to in vitro hypoxia. The expression of the small G-proteins decreased both at mRNA and protein levels and the RhoA activation was reduced. Nevertheless, the number of lung or liver metastatic colonies disseminating from orthotopic HT29 grafts did not change upon CoCl2 or chetomin treatment. Our data demonstrates that the hypoxic environment induces cell-type dependent changes in the levels and activation of small GTPases and results in varying migratory and metastasis promoting responses in different human tumor cell lines.


Termination of early gestation with (15S)-15-methyl prostaglandin F2 alpha methyl ester vaginal suppositories.
Vaginal suppositories containing (15S)-15-methyl prostaglandin F2 alpha methyl ester were administered to 40 subjects, in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects received a 3-mg suppository followed in 3 hours by a 1 mg suppository, ten subjects received the 1-mg suppository followed in 3 hours by a 3-mg suppository, and twenty subjects received the 3-mg suppository followed in 1 hour by the 1-mg suppository. Twenty-four subjects (60%) had a successful termination of their pregnancy using the two vaginal prostaglandin suppository regimen. All subjects who aborted had 10 percent or less of their pretreatment levels of beta-hCG 7 to 22 days after therapy. Sixteen subjects (40%) did not abort. One of the subjects who failed treatment refused the second suppository due to gastrointestinal side effects and uterine cramping following the insertion of the 1-mg suppository. A second subject had an incomplete abortion and developed mild endometritis. Sixteen subjects reported side effects which included nausea, emesis, diarrhea, uterine cramping requiring analgesia, restlessness, shakiness, and dizziness. The addition of the second vaginal suppository containing this particular prostaglandin analogue did not significantly increase the overall abortifacient activity of this method.


Children with cochlear implants: the communication journey.
Cochlear implantation is now a well-established procedure for profoundly deaf children providing access to speech through hearing for many of them. Much attention has focused on which communication mode to adopt with this group of children but very little work has looked at the choices that parents make before and after cochlear implantation. This study, following on from two earlier studies, looked in depth at the experiences of 12 families. It finds that parents choose the most effective way of communicating with their child but retain as their goal, the development of oral communication skills. For many this is a journey in which different approaches are utilised at various stages in the child's development.