Whole genome scan identifies several chromosomal regions linked to equine sarcoids.
Despite the evidence for a genetic predisposition to develop equine sarcoids (ES), no whole genome scan for ES has been performed to date. The objective of this explorative study was to identify chromosome regions associated with ES. The studied population was comprised of two half-sibling sire families, involving a total of 222 horses. Twenty-six of these horses were affected with ES. All horses had been previously genotyped with 315 microsatellite markers. Quantitative trait locus (QTL) signals were suggested where the F statistic exceeded chromosome-wide significance at P < 0.05. The QTL analyses revealed significant signals reaching P < 0.05 on equine chromosome (ECA) 20, 23 and 25, suggesting a polygenic character for this trait. The candidate regions identified on ECA 20, 23 and 25 include genes regulating virus replication and host immune response. Further investigation of the chromosome regions associated with ES and of genes potentially responsible for the development of ES could form the basis for early identification of susceptible animals, breeding selection or the development of new therapeutic targets.


Tolerosome-induced oral tolerance is MHC dependent.
Oral administration of a protein antigen generates a serum factor that induces tolerance when transferred into naïve recipients. This serum factor has been described in rats as consisting of exosome-like structures or tolerosomes, which express major histocompatibility complex class II molecules (MHCII) and mediate antigen-specific tolerance. In this study, we investigated the functions of serum-derived tolerosomes both in vivo and in vitro. Tolerosomes were purified from the 100,000 g pellet fraction of serum from ovalbumin (OVA)-fed mice. When transferred into naïve recipient mice, the tolerosomes mediated OVA-specific tolerance. We also found that tolerosomes from OVA-fed mice induced the activation of OVA-specific T cells both in vivo and in vitro. The inoculation of severe combined immunodeficiency (SCID) mice with an interferon-gamma-producing cell line normalized the expression of MHCII in the intestinal epithelial cells and restored their ability to generate tolerosomes. Syngeneic but not allogeneic transfer of tolerosomes from OVA-fed donors induced tolerance in the recipients. Our results show that tolerosomes can be isolated from mouse serum, that tolerosome-induced oral tolerance requires MHCII expression in intestinal epithelial cells, and that tolerosomes are functional only in syngeneic recipients.


Potential use of monoclonal antibodies in the diagnostic distinction of gynecomastia from breast carcinoma in men.
Immunohistochemical (IHC) assays using the monoclonal antibodies (MoAbs) B72.3 and B6.2, recognizing two distinct and independently expressed breast tumor-associated antigens (BTAAs), recently have been shown to significantly improve the accuracy of cytodiagnosis of breast nodules by fine-needle aspiration (FNA). To evaluate whether the same method may be useful diagnostically in distinguishing gynecomastia from breast cancer in men, a retrospective avidin-biotin immunoperoxidase assay study was performed on 50 cases of gynecomastia and 30 cases of breast carcinoma in men, using a panel of five MoAbs known to recognize different BTAAs. The results of this study demonstrated that MoAbs B1.1, HMFG2, and MBr1 displayed a strong reactivity with gynecomastia and carcinoma, but MoAbs B72.3 and B6.2 separated benign and malignant lesions in a high percentage of cases. When used in combination, the latter two reagents reacted with 96% of the carcinomas that were analyzed but labeled only 67% of gynecomastia cases. Thus, the conjoint use of these two reagents may enhance the use of FNA biopsy as a valuable tool in the presurgical diagnosis of breast nodules in men.


Synthesis and Study of a New Type of Nonanionic Demulsifier for Chemical Flooding Emulsion Demulsification.
The application of chemical flooding improves the stability of the produced emulsion, which reduces the demulsification efficiency of conventional demulsifiers. To improve the demulsification effect, in this paper, a new multibranched nonanionic polyether demulsifier, FYJP, was prepared by grafting carboxylate based on a nonionic demulsifier. The FYJP demulsifier could generate an initiator through p-tert-butylphenol, triethylenetetramine, and methanol, which was polymerized with ethylene oxide (EO) and propylene oxide (PO) to produce a nonionic polyether demulsifier. Sodium chloroacetate was used to modify the polyether demulsifier to obtain a new type of nonanionic polyether demulsifier. The FYJP polyether demulsifier was characterized by the hydrophilic-lipophilic balance (HLB) value, relative solubility (RSN), and surface activity of the demulsifier, and the demulsification mechanism was analyzed by a microscopic demulsification process test, and the effect of demulsifier dosage on the demulsification effect was discussed. Meanwhile, a dehydration test was carried out. The experimental results showed that the highest dehydration rate of the demulsifier was 94.7% at 85 °C, 100 ppm demulsifier dosage, 50 mL of a W/O emulsion, and 120 min demulsification time. The abovementioned studies show that FYJP is an effective demulsifier for chemical flooding emulsions, and this work promises to provide a reference for future demulsifier research.


Energy Expenditure, Protein Oxidation and Body Composition in a Cohort of Very Low Birth Weight Infants.
The nutritional management of preterm infants is a critical point of care, especially because of the increased risk of developing extrauterine growth restriction (EUGR), which is associated with worsened health outcomes. Energy requirements in preterm infants are simply estimated, so the measurement of resting energy expenditure (REE) should be a key point in the nutritional evaluation of preterm infants. Although predictive formulae are available, it is well known that they are imprecise. The aim of our study was the evaluation of REE and protein oxidation (Ox) in very low birth weight infants (VLBWI) and the association with the mode of feeding and with body composition at term corrected age. Indirect calorimetry and body composition were performed at term corrected age in stable very low birth weight infants. Urinary nitrogen was measured in spot urine samples to calculate Ox. Infants were categorized as prevalent human milk (HMF) or prevalent formula diet (PFF). Fifty VLBWI (HMF: 23, PFF: 27) were evaluated at 36.48 ± 0.85 post-conceptional weeks. No significant differences were found in basic characteristics or nutritional intake in the groups at birth and at the assessment. No differences were found in the REE of HMF vs. PFF (59.69 ± 9.8 kcal/kg/day vs. 59.27 ± 13.15 kcal/kg/day, respectively). We found statistical differences in the protein-Ox of HMF vs. PFF (1.7 ± 0.92 g/kg/day vs. 2.8 ± 1.65 g/kg/day, respectively, p < 0.01), and HMF infants had a higher fat-free mass (kg) than PFF infants (2.05 ± 0.26 kg vs. 1.82 ± 0.35 kg, respectively, p < 0.01), measured with air displacement plethysmography. REE is similar in infants with a prevalent human milk diet and in infants fed with formula. The HMF infants showed a lower oxidation rate of proteins for energy purposes and a better quality of growth. A greater amount of protein in HMF is probably used for anabolism and fat-free mass deposition. Further studies are needed to confirm our hypothesis.


Plant pre-mRNA splicing in fission yeast, Schizosaccharomyces pombe.
Pre-mRNA splicing or the removal of introns from precursor messenger RNAs depends on the accurate recognition of intron sequences by the splicing machinery. We have analyzed various aspects of intron sequence and structure in relation to splice site selection and splicing efficiency of a plant gene AmA1 in Schizosaccharomyces pombe. Earlier, we reported the cloning of AmA1, a seed albumin gene from Amaranthus hypochondriacus [A. Raina, A. Datta, Proc. Natl. Acad. Sci. USA 89 (1992) 11774]. In the absence of an in vitro splicing system for plants, the expression of AmA1 genomic clone in S. pombe has been used to analyze splicing of intron constructs. We aim to focus on S. pombe as a possible alternative and examined its effectiveness as a host for plant gene splicing. The results show here that pre-mRNA transcripts of AmA1 gene underwent splicing in S. pombe.


Implementation of Intranasal Midazolam for Prolonged Seizures in a Child Neurology Practice.
Currently, evidence supports the use of intranasal midazolam as an effective, and in many cases, preferable treatment option for prolonged seizures in children. Despite this knowledge, intranasal midazolam is not routinely found as a standard of care. The goal of this project was to implement the use of intranasal midazolam as a rescue medication for prolonged seizures within a child neurology practice and, in doing so, create a model for implementation that would be replicable for other practice sites. This project focused on the development of a process to make intranasal midazolam available as a treatment option and then the creation of an educational intervention for providers within a child neurology practice. Provider surveys analyzed provider attitudes toward intranasal midazolam and its frequency of use. Because of this project, a dramatic increase in the prescribing of intranasal midazolam was observed within a child neurology practice.


[A computerized method for detection of acute cerebral infarction on CT images].
This paper proposes a computerized method for automated detection of acute cerebral infarction (ACI) on CT images. This method is based on the difference value of image features in the two regions-of-interests (ROIs) selected at symmetrical positions. In our computerized method, first, we segmented the brain parenchyma by the thresholding technique after correction of inclination of the midsagittal plane with translation and rotation of the image. Then we selected the middle cerebral artery (MCA) region of the brain parenchyma. Moreover, many ROIs with a 32×32 matrix size were selected in the MCA region. In addition, image features in each ROI were determined from the statistical analysis, the co-occurrence matrix and the run length matrix. Finally, ROIs with ACI were classified by using a linear discriminant analysis with difference values of image features in two ROIs at symmetrical positions. Nineteen cases with ACI and normal 14 cases were employed in this study. As a result of our experiments, the sensitivity of detection of ACI was 88.0% with an average number of false positives of 4.6 per case. Our computerized method provided a relatively high performance for detection of ACI. Therefore, we believe this method would be useful for an algorithm of a computer-aided diagnosis to detect ACI on CT images.


Minibodies and Multimodal Chromatography Methods: A Convergence of Challenge and Opportunity.
This case study describes early phase purification process development for a recombinant anticancer minibody produced in mammalian cell culture. The minibody did not bind to protein A. Cation-exchange, anion-exchange, hydrophobic-interaction, and hydroxyapatite (eluted by phosphate gradient) chromatographic methods were scouted, but the minibody coeluted with BSA to a substantial degree on each. Hydroxyapatite eluted with a sodium chloride gradient separated BSA and also removed a dimeric contaminant, but BSA consumed so much binding capacity that this proved impractical as a capture tool. Capto MMC media proved capable of supporting adequate capture and significant dimer removal, although both loading and elution selectivity varied dramatically with the amount of supernatant applied to the column. An anion-exchange step was included to fortify overall virus and DNA removal. These results illustrate the value of multimodal chromatography methods when affinity chromatography methods are lacking and conventional alternatives prove inadequate.


Gastrointestinal, hepatobiliary, pancreatic, and iron-related diseases in long-term survivors of allogeneic hematopoietic cell transplantation.
Gastrointestinal and hepatobiliary problems in the second year after allogeneic hematopoietic cell transplant (HCT) are usually a continuation of symptoms of protracted acute graft-versus-host disease (GVHD), chronic GVHD, medication side effects, and infection related to immune suppression. As time passes, as tolerance develops, and as immunity improves, the frequency and severity of these problems wane, but new problems involving the gut and liver may arise, sometimes insidiously and sometimes decades after the transplant. Examples are esophageal strictures related to chronic GVHD, gallstones, cirrhosis caused by chronic hepatitis C, secondary malignancy, and rare cases of pancreatic atrophy. One very common complication of transplantation, iron overload, is often associated with substantial iron accumulation in the liver; however, the most troublesome complications are not hepatic but cardiac and endocrine-related.


Use of the AB5000 ventricular assist device in cardiogenic shock after acute myocardial infarction.
The mortality rate of patients experiencing acute myocardial infarction (AMI) complicated by cardiogenic shock remains high. After conventional therapies have failed, ventricular assist devices (VADs) have been used to bridge patients to recovery or transplantation. A voluntary US registry was established to track all patients implanted with the AB5000 VAD. We report the results of the first 100 patients in the registry with the indication of AMI cardiogenic shock. Data were retrospectively reviewed for demographics, preimplant condition, surgical techniques, and outcomes. Survival was assessed at 30 days after VAD explant or at discharge. Myocardial recovery (subset of survival) was defined as satisfactory unassisted native cardiac function for 30 days after VAD explant or at discharge. Forty patients (40%) survived to 30 days after VAD explant or discharge of the first 100 patients. Of the survivors, 63% (n = 25) experienced myocardial recovery. Patients who recovered required an average of 25 +/- 22 days of VAD support. The estimated survival after explant for the recovery patients at 2 years after VAD explant was 78%. Results from this nationwide registry suggest that VADs can restore normal hemodynamics and support recovery of native cardiac function in the majority of survivors when conventional therapies fail. However, a longer duration of support than previously recognized may be required. In the absence of clinical guidelines, early aggressive use of VAD support in AMI complicated by cardiogenic shock may improve outcomes, and recovery of native cardiac function should always be the primary goal.


Conduction block in hereditary neuropathy with susceptibility to pressure palsies.
Slow nerve conduction velocities, temporal dispersion of action potentials and conduction block occur in polyneuropathies with segmental demyelination. Conduction block has been reported in focal compressive neuropathies and in acute and chronic autoimmune polyneuropathy but not in hereditary motor and sensory demyelinating neuropathy. We report conduction block in five nerves of four patients from two families with a hereditary neuropathy with susceptibility to pressure palsies and pathologic changes of segmental demyelination and tomaculous swellings. Conduction block that may be long lasting is a feature of this type of hereditary neuropathy, which should be considered in the differential diagnosis of this electrophysiologic finding.


Hemopexin as an Inhibitor of Hemolysis-Induced Complement Activation.
Hemopexin is the main plasmatic scavenger of cell-free heme, released in the context of intravascular hemolysis or major cell injury. Heme is indispensable for the oxygen transport by hemoglobin but when released outside of the erythrocytes it becomes a danger-associated molecular pattern, contributing to tissue injury. One of the mechanisms of pro-inflammatory action of heme is to activate the innate immune complement cascade. Therefore, we hypothesized that injection of hemopexin will prevent hemolysis-induced complement activation. Human plasma-derived hemopexin is compatible with the heme clearance machinery of the mice. 100 or 500 mg/kg of hemopexin was injected in C57Bl/6 mice before treatment with phenylhydrazine (inducer of erythrocytes lysis) or with PBS as a control. Blood was taken at different timepoints to determine the pharmacokinetic of injected hemopexin in presence and absence of hemolysis. Complement activation was determined in plasma, by the C3 cleavage (western blot) and in the kidneys (immunofluorescence). Kidney injury was evaluated by urea and creatinine in plasma and renal NGAL and HO-1 gene expression were measured. The pharmacokinetic properties of hemopexin (mass spectrometry) in the hemolytic mice were affected by the target-mediated drug disposition phenomenon due to the high affinity of binding of hemopexin to heme. Hemolysis induced complement overactivation and signs of mild renal dysfunction at 6 h, which were prevented by hemopexin, except for the NGAL upregulation. The heme-degrading capacity of the kidney, measured by the HO-1 expression, was not affected by the treatment. These results encourage further studies of hemopexin as a therapeutic agent in models of diseases with heme overload.


Influence of antibiotics on some intestinal microflora associated characteristics.
Intestinal functions related to the presence of microbes in host organisms are normally heavily influenced by administration of antimicrobial drugs. We have investigated the effect of several antibiotics in man and rat, on some MACs (Microflora Associated Characteristics). A MAC is defined as the recording of any anatomical structure, biochemical or physiological function in the host organism which is influenced by microflora. When functional, active microbes are absent as in germfree animals, healthy newborns, or in relation to antimicrobial therapies, a MAC defined as a GAC (Germfree Animal Characteristic). Faecal samples have been collected prior to, during and up to several weeks after the antimicrobial administration in order to investigate different MAC/GAC patterns. Microbial conversion of cholesterol to coprostanol, bilirubin to urobilinogen and 7-alpha-dehydroxylation of cholic acid have been investigated to evaluate hepatic/intestinal co-functions, and degradation of intestinal mucin in order to evaluate the integrity in the intestinal mucosa. Furthermore, degradation of the dietary derived beta-aspartylglycine, the level of faecal trypsin and production of short chain fatty acids were investigated to evaluate dietary/intestinal co-functions. It is concluded that each antimicrobial drug creates its own profile, both with regard to duration and function.


Interventional management for benign airway tumors in relation to location, size, character and morphology.
To select minimally stressful methods for patients with benign bronchial tumors, and evaluate interventional strategies in relation to location, size, character and morphology. We reviewed the indications and efficacy of various interventional bronchology techniques at our institution, including individual or combined laser resection, electrocautery, argon plasma coagulation and high radiofrequency snaring for the treatment of various types of benign bronchial tumors. It is essential to treat endoscopically that the tumor is visible and has a stalk and not invade beyond bronchial wall. By using combined techniques, no complications or recurrences were encountered. Interventional bronchology techniques for benign bronchial tumors can be simple and safe, and therapeutic strategies should be designed in relation to location, size, character and morphology of tumors.


The origins of Better Jobs Better Care.
Better Jobs Better Care was the nation's largest single initiative created to reduce the high vacancy and turnover rates of direct care workers and improve workforce quality through both policy and practice changes. In this article, we describe the important role and key characteristics of direct care workers, what motivated the unique partnership between a provider association and a direct care worker advocacy organization to create this initiative, and how the initiative was designed to respond to the key challenges through applied research and demonstration projects. We conclude by discussing how BJBC has influenced providers, policy makers, and direct care workers to think about these frontline caregivers, who are the crux of the long-term care workforce.


The Synapse Diversity Dilemma: Molecular Heterogeneity Confounds Studies of Synapse Function.
Recent studies have shown an unexpectedly high degree of synapse diversity arising from molecular and morphological differences among individual synapses. Diverse synapse types are spatially distributed within individual dendrites, between different neurons, and across and between brain regions, producing the synaptome architecture of the brain. The spatial organization of synapse heterogeneity is important because the physiological activation of heterogeneous excitatory synapses produces a non-uniform spatial output of synaptic potentials, which confounds the interpretation of measurements obtained from population-averaging electrodes, optrodes and biochemical methods that lack single-synapse resolution. Population-averaging measurements cannot distinguish between changes in the composition of populations of synapses and changing synaptic physiology. Here we consider the implications of synapse diversity and its organization into synaptome architecture for studies of synapse physiology, plasticity, development and behavior, and for the interpretation of phenotypes arising from pharmacological and genetic perturbations. We conclude that prevailing models based on population-averaging measurements need reconsideration and that single-synapse resolution physiological recording methods are required to confirm or refute the major synaptic models of behavior.


Nitric oxide regulates ovarian blood flow in the rat during the periovulatory period.
The aim of this study was to characterize the roles of nitric oxide (NO) on the rat ovarian blood flow (OBF) during the preovulatory period. Immature Sprague-Dawley rats were primed with pregnant mares' serum gonadotrophin (PMSG, 15 IU) and given hCG (15 IU) 48 h later. The ovary was exposed 48-56 h after PMSG, a laser Doppler probe was attached to the ovarian surface and OBF was measured at two time periods: preovulatory (PO) 48 h after PMSG and ovulatory (OV) 6-8 h after hCG. A non-selective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), was injected i.v. (4 and 10 mg/kg) or intrabursally (1 mg/kg). Intravenous administration of L-NAME to OV rats rapidly increased blood pressure and reduced OBF by 30%, which returned to the pretreatment level within 30 min. L-NAME given into the ovarian bursa of both PO and OV rats did not affect blood pressure and reduced OBF by nearly 40%, which remained low throughout the experiment. Intravenous injection of hCG to PO rats increased OBF to 116.1% at 5 min and 133.5% at 30 min in relation to the pretreatment level. When L-NAME was given intrabursally, subsequent hCG injection was without effect. These results indicate that locally produced NO is important for the maintenance and increase of rat OBF during the preovulatory period.


Views of adolescent female youth on physical activity during early adolescence.
Early adolescence is a time when a transition away from sport and physical activity participation is at its highest level among female youth (Hedstrom & Gould, 2004). This has led to the identification of barriers and facilitators of physical activity participation for adolescent females. Consequently there have been calls to overcome barriers and augment facilitators via the creation of gender-relevant programming. Despite these calls and efforts, a gender disparity remains, and a detailed understanding of how girls experience and interpret physical activity within the context of their lives is still lacking. The current project aimed to gain further insight into the foregoing using tenets of Interpretive Phenomenology to further understand the lived physical activity experiences of females during early adolescence, delineating their barriers to participation and the factors enabling participation. Five themes were identified and made into vignettes to facilitate understanding from adolescent females' perspectives: friends or don't know anyone, good or not good enough, fun or not fun; good feeling or gross; and peer support or peer pressure. The physical activity promotion implications for female youth are discussed within the context of these themes.


Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha phosphorylation pathway.
Inhibition of protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result of the activation of a family of kinases in response to various forms of stress. Although some consequences of eIF2alpha phosphorylation are cytoprotective, phosphorylation of eIF2alpha by RNA-dependent protein kinase (PKR) is largely proapoptotic and tumor suppressing. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is a tumor suppressor protein that is mutated or deleted in various human cancers, with functions that are mediated through phosphatase-dependent and -independent pathways. Here, we demonstrate that the eIF2alpha phosphorylation pathway is downstream of PTEN. Inactivation of PTEN in human melanoma cells reduced eIF2alpha phosphorylation, whereas reconstitution of PTEN-null human glioblastoma or prostate cancer cells with either wild-type PTEN or phosphatase-defective mutants of PTEN induced PKR activity and eIF2alpha phosphorylation. The antiproliferative and proapoptotic effects of PTEN were compromised in mouse embryonic fibroblasts that lacked PKR or contained a phosphorylation-defective variant of eIF2alpha. Induction of the pathway leading to phosphorylation of eIF2alpha required an intact PDZ-binding motif in PTEN. These findings establish a link between tumor suppression by PTEN and inhibition of protein synthesis that is independent of PTEN's effects on phosphoinositide 3'-kinase signaling.


Selective doping of silicon nanowires by means of electron beam stimulated oxide etching.
Direct patterning of silicon dioxide by means of electron beam stimulated etching is shown, and a full characterization of exposure dose is presented. For its high dose, this technique is unsuitable for large areas but can be usefully employed like a precision scalpel for removing silicon dioxide by well-localized points. In this work, this technique is applied to the definition of windows through the oxide surrounding top down fabricated n-doped silicon nanowires. These windows will be employed for a selective doping of the nanowire by boron diffusion. In this way, pn junctions can be fabricated in well-localized points in the longitudinal direction of the nanowire, and an electrical contact to the different junctions can be provided. Electrical I-V characteristics of a nanowire with pn longitudinal junctions are reported and discussed.


Short-course chemotherapy of tuberculosis: the harsh realities.
Recent studies have indicated that it is possible to successfully treat even far-advanced tuberculosis with a variety of chemotherapy regimens ranging in duration from 4.5 to 9 months. Furthermore, much or all of some regimens can be given twice-weekly. However, three major barriers remain to widespread success: (1) Noncompliance with prescribed treatment; (2) increasing prevalence of drug resistance; and, (3) sorely limited resources in impoverished segments of the third world. While noncompliance is responsible for a greater number of treatment failures, increasing levels of drug resistance pose a greater long-term threat due to a protracted carrier-vector state, soaring costs for adequate drug regimens, and--ultimately--the conversion of an imminently treatable infection into an unmanageable scourge--the resurrection of the "White Plague."


High throughput adjustable 96-well plate assay for androgen receptor binding: a practical approach for EDC screening using the chimpanzee AR.
The issue as to whether natural and man-made chemicals interfere with endocrine function has raised concerns. This interference could be biologically significant even at very low doses if the chemicals interact deleteriously with hormone receptors at low concentrations. Therefore, the United States Environmental Protection Agency (USEPA) Office of Coordination and Policy (OSCP) requested that a nonhuman mammalian androgen receptor binding assay be developed for possible use in their Endocrine Disruptor Screening Program (EDSP). Ideally, this assay would be high throughput, not use animals as a source of receptor protein, easily deployed throughout the scientific community, utilize reagents available to both the public and private sector, and have the potential for future automation. We developed a highly modified 96-well plate assay which meets these criteria. It employs a baculovirus expressed recombinant primate androgen receptor which is publically available and exploits the unique ability of some mammalian androgen receptors to remain biologically active after guanidine hydrochloride (GdnHCl) solubilization. This GdnHCl treated receptor remains soluble and requires no additional purification prior to use. We provide a very detailed description of the assay protocol itself, and similarly detailed method for producing and solubilizing the receptor.


Comparison of critically ill COVID-19 and influenza patients with acute respiratory failure.
Coronavirus disease 2019 (COVID-19) is one of the biggest pandemic causing acute respiratory failure (ARF) in the last century. Seasonal influenza carries high mortality, as well. The aim of this study was to compare features and outcomes of critically-ill COVID-19 and influenza patients with ARF. Patients with COVID-19 and influenza admitted to intensive care unit with ARF were retrospectively analyzed. Fifty-four COVID-19 and 55 influenza patients with ARF were studied. Patients with COVID-19 had 32% of hospital mortality, while those with influenza had 47% (P=0.09). Patients with influenza had higher Eastern Cooperative Oncology Group, Clinical Frailty Scale, Acute Physiology and Chronic Health Evaluation II and admission Sequential Organ Failure Assessment (SOFA) scores than COVID-19 patients (P<0.01). Secondary bacterial infection, admission acute kidney injury, procalcitonin level above 0.2 ng/ml were the independent factors distinguishing influenza from COVID-19 while prone positioning differentiated COVID-19 from influenza. Invasive mechanical ventilation (odds ratio [OR], 42.16; 95% confidence interval [CI], 9.45-187.97), admission SOFA score more than 4 (OR, 5.92; 95% CI, 1.85-18.92), malignancy (OR, 4.95; 95% CI, 1.13-21.60), and age more than 65 years (OR, 3.31; 95% CI, 0.99-11.03) were found to be independent risk factors for hospital mortality. There were few differences in clinical features of critically-ill COVID-19 and influenza patients. Influenza cases had worse performance status and disease severity. There was no significant difference in hospital mortality rates between COVID-19 and influenza patients.


Isolation and characterization of a novel gene expressed in multiple cancers.
Using differential display method, we have isolated and characterized a novel gene, N8, encoding an approximately 24 kDa protein. It is located on human chromosome 8q13 region. N8 gene is expressed at high levels in tumor derived cell lines from multiple cancers. It is also expressed at higher levels in lung tumors than normal lung tissue. N8 is also differentially expressed in fetal and adult tissues. In adult, N8 is expressed at high levels in brain, kidney, prostate, pancreas and intestine and at very low levels in lung, liver, hematopoietic cells and gonads. During murine embryonic development N8 is expressed in the epithelium of the intestine, stomach, olfactory epithelium, neuronal layers of retina, kidney and salivary gland. Taken together, these results suggest that N8 may play different roles during embryogenesis and in the adult animals.


HBx-K130M/V131I Promotes Liver Cancer in Transgenic Mice via AKT/FOXO1 Signaling Pathway and Arachidonic Acid Metabolism.
Chronic hepatitis B viral (HBV) infection remains a high underlying cause for hepatocellular carcinoma (HCC) worldwide, while the genetic mechanisms behind this remain unclear. This study elucidated the mechanisms contributing to tumor development induced by the HBV X (HBx) gene of predominantly Asian genotype B HBV and its common HBx variants. To compare the potential tumorigenic effects of K130M/V131I (Mut) and wild-type (WT) HBx on HCC, the Sleeping Beauty (SB) transposon system was used to deliver HBx Mut and WT into the livers of fumarylacetoacetate hydrolase (Fah)-deficient mice and in the context of transformation related protein 53 (Trp53) deficiency. From our results, HBx Mut had a stronger tumorigenic effect than its WT variant. Also, inflammation, necrosis, and fibrosis were evident in HBx experimental animals. Reduction of forkhead box O1 (FOXO1) with increased phosphorylation of upstream serine/threonine kinase (AKT) was detected under HBx Mut overexpression. Thus, it is proposed that HBx Mut enhances disease progression by reducing FOXO1 via phosphorylation of AKT. At the metabolomic level, HBx altered the expression of genes that participated in arachidonic acid (AA) metabolism, as a result of inflammation via accumulation of proinflammatory factors such as prostaglandins and leukotriene in liver. Taken together, the increased rate of HCC observed in chronic hepatitis B patients with K130M/V131I-mutated X protein, may be due to changes in AA metabolism and AKT/FOXO1 signaling. IMPLICATIONS: Our findings suggested that HBx-K130M/V131I-mutant variant promoted HCC progression by activating AKT/FOXO1 pathway and inducing stronger inflammation in liver via AA metabolism.


Optical refrigeration to 119 K, below National Institute of Standards and Technology cryogenic temperature.
We report on bulk optical refrigeration of Yb:YLF crystal to a temperature of ~124 K, starting from the ambient. This is achieved by pumping the E4-E5 Stark multiplet transition at ~1020 nm. A lower temperature of 119±1 K (~-154C) with available cooling power of 18 mW is attained when the temperature of the surrounding crystal is reduced to 210 K. This result is within only a few degrees of the minimum achievable temperature of our crystal and signifies the bulk solid-state laser cooling below the National Institute of Standards and Technology (NIST)-defined cryogenic temperature of 123 K.


Religiosity predicts negative attitudes towards science and lower levels of science literacy.
Past research suggests that religion and science may conflict on which is a better tool for explaining the world. This conflict implies that religiosity might negatively impact both attitudes toward science and science knowledge. However, past research has focused mostly on religious affiliation and has not consistently identified such a relation using a general religiosity measure that assesses religious beliefs and religious practice. Using two large, nationally representative datasets as well as two original datasets, and controlling for relevant demographic variables, four studies (N = 9,205) showed that general measures of religiosity are negatively associated with science knowledge, a relation that was partially mediated by an association between religiosity and negative attitudes toward science. Study 2 also showed that parents' reports about their religiosity and its role in their children's upbringing predicted, some 20 years later, their children's attitudes toward science. The studies are correlational but the longitudinal relations in Study 2 suggests that religiosity might undermine science literacy.


Stereocontrolled photodimerization with congested 1,8-bis(4'-anilino)naphthalene templates.
Suzuki cross-coupling of a 1,8-dihalonaphthalene with 4-methoxy-3-methylphenylboronic acid or 4-acetamidophenylboronic acid and subsequent functional group transformation gave 1,8-bis(3'-methyl-4'-anilino)naphthalene, 16, and 1,8-bis(4'-anilino)naphthalene, 21, in 65% and 90% overall yield, respectively. These congested compounds exhibit two cofacial aniline rings that favor a proximate, parallel arrangement of covalently attached cinnamoyl units suitable for stereoselective photodimerization. The [2 + 2]cycloaddition was found to proceed with high yield and exclusive formation of cis,trans,cis-cyclobutane-1,2-dicarboxylic acids. Amide formation with cinnamoyl chloride and template 21 followed by photochemical dimerization and acidic hydrolysis gave β-truxinic acid, 10, in 69% overall yield. Coupling of 21 and (E)-3-(3,4-dimethylphenyl)acrylic acid in the presence of EDC, UV irradiation, and cleavage gave cis,trans,cis-3,4-bis(3,4-dimethylphenyl)cyclobutane-1,2-dicarboxylic acid, 26, in 60% yield. In both cases, the template was quantitatively recovered.


Vitamin D status, bone metabolism and bone mass in patients with alcoholic liver cirrhosis.
Osteoporosis is seen in some 12-50 % patients with liver cirrhosis. Detrimental effects of alcohol are exerted directly on the bone cells and indirectly on hormones. Vitamin D is involved in osteoblast differentiation, bone matrix synthesis and bone mineralization, as well as in its decomposition. Vitamin D deficiency has been reported in about 2/3 patients with liver cirrhosis. Determination of vitamin D status, bone metabolic activity and bone mass in patients with alcoholic liver cirrhosis (ALC). Thirty male patients with ALC were investigated in the period October 2011- March 2012. Total vitamin D, parathormone, osteocalcin and CrossLaps were determined by the ECLIA method (electrochemiluminiscence immunoassay) using Elecsys 2010 analyzer. Bone mineral density was measured by means of dual-energy x-ray absorptiometry (DXA) using the Lunar Prodigy. Result analysis was performed using descriptive statistics and hypothesis testing, as well as nonparametric one-way analysis of variance, Kruskal-Wallis test, Mann-Whitney U-test, Pearson correlation coefficient. Deficiency in vitamin D (< 50 nmol/l) was noted in 66.66 % patients, with highest prevalence in Child-Pugh C class patients (chi-square = 5.878, p < 0.05). Osteocalcin levels were below the lower limit of normal in 86.7 % patients. CrossLaps was increased in only 20 % patients, but a significant increase was noted in Child-Pugh C class patients. Osteoporosis was diagnosed in 20 % of patients, with no correlation with disease severity and vitamin D status. Vitamin D deficiency is present in patients with ALC. Decrease in bone formation and bone mass is most probably multicausal (Tab. 2, Fig. 1, Ref. 30).


Cyclooxygenase-2 inhibitors attenuate increased blood pressure in renovascular hypertensive models, but not in deoxycorticosterone-salt hypertension.
COX-2 is an inducible cyclooxygenase (COX) that has been reported to be expressed in the macula densa and surrounding cortical thick ascending limb in normotensive rats. The present study assessed the contribution of COX-2 in three different rat models of hypertension, each characterized by a different activation of the renal renin-angiotensin system. Mean blood pressure (MBP) in the rat 2 kidney-1 clip (2K1C) model was significantly reduced with a COX-2 selective inhibitor, NS-398 (10 mg/kg, p.o., twice a day) (vehicle-administered rats (n = 8): 154 +/- 6 mmHg; NS-398-administered rats (n = 5): 128 +/- 10 mmHg). By contrast, a COX-1 selective inhibitor, mofezolac, did not lower MBP. Increased plasma renin activity (23 +/- 8 ng/kg/h (n = 6) vs. sham operation, 2.4 +/- 0.9 ng/kg/h (n = 4)) was markedly reduced to 6.8 +/- 2.7 ng/ml/h (n = 5) by NS-398, but not by mofezolac. The development of 1 kidney-1 clip (1K1C) hypertension was also inhibited by NS-398 (vehicle (n = 12): 133 +/- 1 mmHg; NS-398 (n = 7): 122 +/- 3 mmHg) accompanied by a reduction in plasma renin activity (3.0 +/- 0.3 ng/ml/h, n = 4) to 1.0 +/- 0.2 ng/ml/h (n = 5). The COX-2 inhibitor increased urinary excretions in the 1K1C model, but not in the 2K1C model. In a deoxycorticosterone acetate (DOCA)-salt model, plasma renin activity was markedly suppressed to less than 0.3 ng/ml/h. The COX-2 inhibitor caused no significant changes in MBP, plasma renin activity, or urinary excretion, suggesting that COX-2 made a lesser contribution in this model. Increased expression of COX-2 mRNA and protein was observed in the kidneys of 1K1C and 2K1C rats, but not in DOCA-salt rats. These results suggest that COX-2 plays a significant role in the development of 2K1C and 1K1C renovascular hypertension, in addition to making a substantial contribution to the diuretic effect in the 1K1C model.


Smart Ternary Strategy in Promoting the Performance of Polymer Solar Cells Based on Bulk-Heterojunction or Layer-By-Layer Structure.
Although the rapid development of polymer solar cells (PSCs) has been achieved, it is still a great challenge to explore efficient ways for improving power conversion efficiency (PCE) of PSCs from materials and device engineering. Ternary strategy has been confirmed as an efficient way to improve PCE of PSCs by employing three kinds of materials. In this work, one polymer donor PM6, and two non-fullerene materials N3 and MF1 are selected to prepare ternary PSCs with layer-by-layer (LbL) or bulk-heterojunction (BHJ) structure. The LbL and BHJ-PSCs exhibit PCEs of 16.75% and 16.76% with 15 wt% MF1 content in acceptors, corresponding to over 5% or 4% PCE improvement compared with N3-based binary PSCs with LbL or BHJ structure. The PCE improvement is mainly attributed to the fill factor enhancement from 73.29% to 76.95% for LbL-PSCs or from 74.13% to 77.51% for BHJ-PSCs by employing the ternary strategy. This work indicates that ternary strategy has great potential in preparing highly efficient LbL-PSCs via simultaneously optimizing molecular arrangement and the thickness of each layer.


Myrmecridium hiemale sp. nov. from snow-covered alpine soil is the first eurypsychrophile in this genus of anamorphic fungi.
Myrmecridium hiemale sp. nov. was isolated from snow-covered alpine bare soil and is described as the first eurypsychrophilic species of this genus of filamentous fungi. Colony growth temperature experiments were carried out in the range 4-37 °C. Morphological characteristics and colony appearance were in accordance with characteristics typical for Myrmecridium, but M. hiemale does not grow at temperatures of 25 °C and above. Sequence analyses of the internal transcribed spacer and LSU rRNA D1/D2 regions indicated that the strain in question represents a distinct taxon within the genus Myrmecridium (Myrmecridiaceae, Sordariomycetes, Ascomycota). The type strain of M. hiemale is CBS 141017T(=JMRC 12083T). A morphological description is provided, and a key is presented for the currently known taxa of Myrmecridium, a group of interesting fungi that are either saprobes or plant endophytes.


Development and characterization of a GC-enabled QLT-Orbitrap for high-resolution and high-mass accuracy GC/MS.
We detail the development and characterization of a GC/QLT-Orbitrap hybrid mass spectrometer capable of high resolution (up to 100,000 at m/z 400) and sub-parts-per-million mass accuracy GC/MS. A high-duty cycle, innovative scan type, the nested scan, was implemented to synchronize the Orbitrap acquisition rate and the time scale of gas chromatography (up to 6.5 Hz at resolution 7500). We benchmark this instrument's key figures of merit, including resolution, mass accuracy, linear dynamic range, and spectral accuracy, and demonstrate its performance for two challenging applications: the determination of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) in environmental samples and the profiling of primary metabolites in Arabidopsis thaliana extracts.


Tumor targeting HPMA-porphyrin-99mTc copolymer molecular imaging agent.
Porphyrins typically show preferential uptake and retention by tumor tissues via receptor-mediated endocytosis of low-density lipoproteins. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific targeting porphyrin HPMA [HPMA: N-(2-hydroxypropyl)methacrylamide] copolymer tracer poly(HPMA)-porphyrin-DTPA-(99m)Tc (DTPA: diethylenetriaminepentaacetic acid), nonspecific targeting HPMA copolymer tracer poly(HPMA)-DTPA-(99m)Tc, and nontargeting tracer DTPA-(99m)Tc are described in this study. The results showed that the cellular accumulation of poly(HPMA)-porphyrin-DTPA-(99m)Tc complex was found to be time-dependent. The uptake of poly(HPMA)-porphyrin-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that uptake of the poly(HPMA)-porphyrin-DTPA-(99m)Tc was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that uptake of the poly(HPMA)-DTPA-(99m)Tc was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-porphyrin-DTPA-(99m)Tc (5.18 ± 0.50% ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03% ID/g). Moreover, higher T/B for poly(HPMA)-porphyrin-DTPA-(99m)Tc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(HPMA)-porphyrin-DTPA-(99m)Tc is a potential macromolecular tumor targeting molecular agent.


Cathepsin S generates soluble CX3CL1 (fractalkine) in vascular smooth muscle cells.
CX3CL1 chemokine (fractalkine) is highly expressed by vascular smooth muscle cells (VSMCs) in atherosclerotic lesions. Its membrane-bound form promotes cell-cell interactions, whereas the soluble form induces chemotaxis of CX3CR1- expressing leukocytes. We show that the cysteine protease cathepsin S, expressed by VSMCs, is able to cleave membrane-anchored CX3CL1, releasing a 55-kDa fragment to the medium, thus regulating the adhesion of VSMCs and the capture of monocytes to the sites of atherogenesis. Moreover, strong co-localization of cathepsin S and CX3CL1 with a recycling endosome marker Rab11a suggests a processing of CX3CL1 in recycling endosomes during its redistribution to the plasma membrane.


The impact of expanded Medicaid eligibility on access to naloxone.
Federal, state and local US governments have sought interventions to reduce deaths due to opioid overdoses by increasing the availability of naloxone. The Affordable Care Act (ACA) expanded Medicaid coverage to low-income, childless adults, potentially giving this group financial access to naloxone. The aims of this paper are: (1) to describe the changes in the amount of Medicaid-covered naloxone used between 2009 and 2016 and (2) to quantify the differential change in the amount of dispensed naloxone between states that expanded their Medicaid programs and states that did not. A quasi-experimental approach based on states' ongoing choice to expand their Medicaid program to all adults with incomes between 100 and 138% of the federal poverty line (FPL), starting in 2014. As of 2018, 37 states had expanded and 14 states had not. Estimation of the policy impact relies on a difference-in-difference method. US state Medicaid programs. Data are from the Medicaid Drug Rebate Program and include all dispensed prescriptions of naloxone through the Medicaid program. State/quarters with fewer than 10 prescriptions are suppressed; n = 1632. Prior to Medicaid expansion, the number of Medicaid-covered naloxone prescriptions was very similar in expansion and non-expansion states. On average, states that expanded Medicaid had 78.2 (95% confidence interval = 16.0-140.3, P = 0.02) more prescriptions per year for naloxone compared with states that did not expand Medicaid coverage, a nearly 10 increase over the pre-expansion years. Medicaid expansion contributed to this growth in Medicaid-covered naloxone more than other state-level naloxone policies. Medicaid accounts for approximately a quarter of naloxone sales. Medicaid expansion generated 8.3% of the growth in naloxone units from 2009 to 2016, holding other factors constant.


Measurements of catecholamine-mediated apoptosis of immunocompetent cells by capillary electrophoresis.
Single cell analysis with capillary electrophoresis, a technique capable of detecting zeptomole quantities (10(-21) mole) of neurochemical species, has been used to demonstrate that lymphocytes are capable of active synthesis of dopamine and norepinephrine. Exposure of lymphocytes to catecholamines at concentrations as low as 10 nM leads to decreased proliferation and differentiation, e.g. interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and immunoglobulin (Ig). In addition, both inhibition of dopamine uptake with nomifensine and inhibition of packing of catecholamines into vesicles with tetrabenazine, results in significantly lower levels of dopamine and norepinephrine (p < 0.01 and p < 0.05, respectively). The catecholamine-dependent inhibition of T- and B-lymphocyte activity is mediated via an induction of a Bcl-2/Bax and Fas/FasL involved apoptosis. These findings indicate a novel mechanism for regulation of lymphocyte activity in the central nervous system, whereby elevated regional levels of catecholamines might lead to the immunoprivilege of the brain.


Renal bone disease: radiological investigation.
The bone disease associated with chronic renal impairment is complex and multifactorial, and has changed over past decades. Whereas originally features of vitamin D deficiency (rickets/osteomalacia) and secondary hyperparathroidism (erosions, osteosclerosis, brown cysts) predominated, improvement in management and therapy have resulted in such readiographic features being present in a minority of patients. Metastatic calcification and "adynamic" bone develop as a complication of disease (phosphate retention) and treatment (phosphate binders). New complications (amyloid deposition, noninfective spondyloarthropathy, osteonecrosis) are now seen complicating long-term hemodialysis and/or renal transplantation. Radiographs remain the most important imaging technique, but occasionally other imaging and quantitative techniques (CT, MRI, bone densitometry) are relevant to diagnosis and management.


Fibro-osseous lesions of craniofacial bones. The role of imaging.
Fibro-osseous lesions of the craniofacial structures are a group of pathologic conditions that are somewhat difficult to classify. Fibro-osseous lesions of the jaw may be divided into two categories: fibrous dysplasia, a developmental lesion characterized by the development of swelling, which consists of proliferating fibrous tissue that replaces normal bone; and those that have been postulated to originate from the periodontal ligament. This article describes the imaging characteristics of fibrous dysplasia and other fibro-osseous lesions of oral bones, including ossifying fibroma, periapical cemental dysplasia, cemento-ossifying fibroma, and florid osseous dysplasia.


Mixed colony formation composed of erythroblasts and myeloblasts by leukemic blast progenitors in patients with erythroleukemia.
To determine the clonal origin and growth requirement of leukemic blast progenitors in erythroleukemia, acute myelogenous leukemia (AML) M6, T cell-depleted mononuclear cells obtained from 5 erythroleukemia patients were cultured in methylcellulose media. Although plating efficiency did not significantly differ from those in the other AML subtypes, the morphology of colonies in erythroleukemia was distinct. Two types of colonies were formed; one was composed of myeloblasts, and the other consisted of erythroblasts and myeloblasts. The "mixed" colony formation was not stimulated by interleukin-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor or erythropoietin. Both types of colonies were formed spontaneously in the absence of supplemented growth-stimulatory factor when cultured at high density. The results suggest that leukemic blast progenitors in erythroleukemia originated at the stage of bipotent hematopoietic precursor capable of differentiating into erythroid and myeloid lineages. The formation of mixed colonies composed of erythroblasts and myeloblasts in the absence of erythropoietin or colony-stimulating factor may indicate the deranged hematopoiesis in erythroleukemia.


Investigation of heme distortions and heme-protein coupling in the isolated subunits of oxygenated human hemoglobin by resonance Raman dispersion spectroscopy.
To probe the distortions of the heme groups resulting from heme-apoprotein interaction in the isolated subunits of oxygenated human hemoglobin (i.e., alpha SH-oxyHbA and beta SH-oxyHbA), the dispersion of the depolarization ratio of the Raman lines at 1375 cm-1 (nu 4) and 1638 cm-1 (nu 10) was measured at various pHs. The data were analyzed in terms of vibronic coupling parameters which depend on symmetry-classified normal distortions of the heme groups. In the alpha-chain the nu 10 mode is not affected by symmetry-lowering distortions. In the beta-chain, however, this mode is significantly influenced by asymmetric B1g and B2g distortions. This was interpreted in terms of different interactions between the peripheral substituents and the porphyrin macrocycle in the respective chains. The nu 4 mode of both chains is subject to B1g (B2g) and A2g distortions, which are more pronounced in beta SH-oxyHbA. This is most probably due to differences in the repulsive interactions between the proximal imidazole and the pyrrole. While the depolarization ratio of both lines investigated is pH-independent in alpha SH-oxyHbA, it exhibits a significant pH dependence in beta SH-oxyHbA. This parallels the finding that the isolated beta-chains exhibit a Bohr effect whereas the alpha-chains do not. Consequently, the pH dependence of the coupling parameters and the Bohr effect of beta SH-oxyHbA could be rationalized in terms of the very same proton binding processes.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects on small airway obstruction of long-term treatments with beclomethasone/formoterol hydrofluoroalkane (metered-dose inhaler) versus fluticasone/salmeterol (dry-powder inhaler) in asthma: a preliminary study.
New formulations of extrafine particles of long-acting beta-2 agonists plus inhaled corticosteroids (LABA + ICS) have been shown to reach peripheral regions of the lung. The aim of the study was to assess the effect on small airway obstruction of long-term treatments with two different LABA + ICS formulations in asthma. Ten subjects with moderate persistent asthma were enrolled. After a 4-week washout period they were treated in a randomized crossover design for 24 weeks with formoterol, 12 micrograms, and beclomethasone, 200 micrograms, hydrofluoroalkane (HFA; by metered-dose inhaler) b.i.d. (FB) or salmeterol, 50 micrograms, and fluticasone, 250 micrograms (by dry-powder inhaler), b.i.d. (SF). At baseline and at the end of each period subjects underwent an Asthma Control Test (ACT) and Pulmonary Function Testing. The N(2) phase III slope and closing volume (CV) during single-breath washout test and difference between the maximal expiratory flow rates with air and heliox at isovolume corresponding to 50% [Delta(heliox-air)MEF(50%)] were measured to assess changes on peripheral airways function. Two subjects dropped out and eight completed the study. After SF and FB, forced expiratory volume at 1 second (FEV(1); p < 0.01) and FEV(1)/forced vital capacity (FVC; p < 0.01 for SF and p < 0.05 for FB) increased when compared with baseline. Although both FB and SF treatments slightly increased delta(heliox-air)MEF(50% isovolume) versus baseline, only after FB the N(2) phase III slope and CV decreased from 1.61 ± 0.61%/L to 1.35 ± 0.49 N(2)%/L (p = 0.054) and from 0.98 ± 0.56 L to 0.88 ± 0.58 L (p < 0.05), respectively. ACT score raised from 19 ± 5 (baseline) to 23 ± 1 after FB (p < 0.02) and 23 ± 2 after SF (p < 0.05). When compared with baseline and in contrast to SF (50/250 micrograms b.i.d.), FB HFA (12/200 micrograms b.i.d.) significantly improved functional parameters reflecting small airway obstruction in asthmatic patients. Registered in the public trial registry at www.ClinicalTrials.gov identifier: NCT01255579.


SIX1 Predicts Poor Prognosis and Facilitates the Progression of Non-small Lung Cancer via Activating the Notch Signaling Pathway.
Background: Many transcription factors involved in embryonic development and reactivated in tumors are considered potential prognostic biomarkers and novel therapeutic targets in various cancers. Sine oculis homeobox homolog 1 (SIX1), a developmentally restricted transcriptional regulator, plays a critical role during tumor initiation and development. However, the prognostic value and biological function of SIX1 in non-small cell lung cancer (NSCLC) remain unclear. Methods: Bioinformatic analyses were conducted to investigate the expression of SIX1 in cancer and adjacent normal tissues of NSCLC and further explore the correlations between SIX1 expression and clinical outcomes. Western blotting and RT-PCR analysis were performed to detect of SIX1 expression level in NSCLC cell lines and normal bronchial epithelial cell. EdU, CCK-8, clonal formation assay, wound healing and transwell assay were performed to explore the effects of gain- or loss-of-function of SIX1 on cellular proliferation, migration and invasion in vitro. Gene set enrichment analysis (GSEA) was used to identify the potential signaling pathways involved in SIX1 mediated biological function and the correlation was confirmed by western blotting and RT-PCR analysis. In vivo experiment was conducted to further validate the tumor-promoting effects of SIX1. Results: Bioinformatic analysis indicated that SIX1 was markedly upregulated in NSCLC tissues of and positively correlated with poor prognosis of patients with NSCLC. Ectopic expression of SIX1 facilitated proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. On the contrary, knocking down SIX1 exhibited the opposite effects. Mechanistic studies suggested that SIX1 activated the Notch pathway to promote the malignant biological behaviors of NSCLC, which could be reversed by inhibiting the Notch signaling with γ-secretase inhibitor. Conclusions: SIX1 could facilitate multiple malignant biological behaviors by activating the Notch signaling pathway and function as a promising prognostic biomarker.


Differential processing of part-to-whole and part-to-part face priming: an ERP study.
We provide electrophysiological evidence supporting the hypothesis that part and whole face processing involve distinct functional mechanisms. We used a congruency judgment task and studied part-to-whole and part-to-part priming effects. Neither part-to-whole nor part-to-part conditions elicited early congruency effects on face-specific ERP components, suggesting that activation of the internal representations should occur later on. However, these components showed differential responsiveness to whole faces and isolated eyes. In addition, although late ERP components were affected when the eye targets were not associated with the prime in both conditions, their temporal and topographical features depended on the latter. These differential effects suggest the existence of distributed neural networks in the inferior temporal cortex where part and whole facial representations may be stored.


Iron Release from the Siderophore Pyoverdine in Pseudomonas aeruginosa Involves Three New Actors: FpvC, FpvG, and FpvH.
Siderophores are iron chelators produced by bacteria to access iron, an essential nutriment. Pyoverdine (PVDI), the major siderophore produced by Pseudomonas aeruginosa PAO1, consists of a fluorescent chromophore linked to an octapeptide. The ferric form of PVDI is transported from the extracellular environment into the periplasm by the outer membrane transporter, FpvA. Iron is then released from the siderophore in the periplasm by a mechanism that does not involve chemical modification of the chelator but an iron reduction step. Here, we followed the kinetics of iron release from PVDI, in vitro and in living cells, by monitoring its fluorescence (as apo PVDI is fluorescent, whereas PVDI-Fe(III) is not). Deletion of the inner membrane proteins fpvG (PA2403) and fpvH (PA2404) affected 55Fe uptake via PVDI and completely abolished PVDI-Fe dissociation, indicating that these two proteins are involved in iron acquisition via this siderophore. PVDI-Fe dissociation studies, using an in vitro assay, showed that iron release from this siderophore requires the presence of an iron reducer (DTT) and an iron chelator (ferrozine). In this assay, DTT could be replaced by the inner membrane protein, FpvG, and ferrozine by the periplasmic protein, FpvC, suggesting that FpvG acts as a reductase and FpvC as an Fe2+ chelator in the process of PVDI-Fe dissociation in the periplasm of P. aeruginosa cells. This mechanism of iron release from PVDI is atypical among Gram-negative bacteria but seems to be conserved among Pseudomonads.


Mucosal patterns of Helicobacter pylori-related gastritis without atrophy in the gastric corpus using standard endoscopy.
To identify the mucosal patterns of Helicobacter pylori (H. pylori)-related gastritis in the gastric corpus using standard endoscopy and to evaluate their reproducibility. A total of 112 consecutive patients underwent upper gastrointestinal endoscopy. The endoscopists classified the endoscopic findings into 4 patterns. In the second part of the study, 90 images were shown to 3 endoscopists in order to evaluate the inter-observer and intra-observer variability in image assessment. The mucosal patterns of the gastric body were categorized into 4 types. Type 1 pattern was defined as cleft-like appearance, type 2 as regular arrangement of red dots, type 3 pattern as the mosaic mucosal pattern and type 4 pattern as the mosaic pattern with a focal area of hyperemia. Type 1 and type 2 mucosal patterns were statistically significant in predicting H. pylori-negative status as compared with other mucosal types (chi(2) = 12.79 and 61.25 respectively, P < 0.01). Type 3 and type 4 mucosal patterns were statistically significant in predicting a H. pylori-positive status as compared with other mucosal types (chi(2) = 21.22 and 11.02 respectively, P < 0.01). Furthermore, the sensitivity, specificity, positive and negative predictive values of type 3 plus type 4 patterns for predicting H. pylori-positive gastric mucosa were 100%, 86%, 94%, and 100%, respectively. The mean kappa values for inter- and intra-observer agreement in assessing the various endoscopic patterns were 0.808 (95% CI, 0.678-0.938) and 0.826 (95% CI, 0.727-0.925) respectively. Our study suggests that mucosal patterns in H. pylori-infected gastric mucosa without atrophy can be reliably identified using standard endoscopy in the gastric corpus.


When neural crest and placodes collide: interactions between melanophores and the lateral lines that generate stripes in the salamander Ambystoma tigrinum tigrinum (Ambystomatidae).
A prominent element of the early larval pigment pattern in the salamander Ambystoma tigrinum tigrinum (family Ambystomatidae) is a horizontal stripe over the lateral surface of the myotomes where otherwise abundant, neural crest-derived melanophores are not found. This study examines the formation of this "melanophore-free region". When the trunk lateral lines were ablated (by removing cranial lateral line placodes), the melanophore-free region did not form; instead, melanophores populated the middle of the flank and the distribution of yellow, neural chest-derived zanthophores was perturbed. Time-lapse videomicrography demonstrated that during normal development, the melanophore-free region is established because melanophores retreat from the midbody lateral line primordium as it migrates caudally along the inner side of the epidermis. Melanophores do not repopulate the middle of the flank after primordium migration and heterochronic grafting experiments suggest that extracellular factors contribute to maintaining the melanophore-free region during these later stages. Finally, photographic series, microsurgical manipulations, electron microscopy, and staining for molecules of the extracellular matrix (peanut agglutinin-binding components, tenascin, chondroitin sulfate proteoglycans, fibronectin, laminin) suggest that several factors contribute to establishing and maintaining the melanophore-free region, including steric effects of the lateral lines, interactions between melanophores and xanthophores, lateral line-dependent alterations of the subepidermal basement membrane, and a general elaboration of the extracellular matrix. Lateral line effects on melanophores are inferred to be a shared, ancestral feature of pigment pattern development for the families Ambystomatidae and Salamandridae (D.M. Parichy, Dev. Biol. 174, 265-282. 1996). The results of this study thus provide insights into a phylogenetically primitive mechanism for stripe formation, and a context for interpreting evolutionary innovations in pattern-forming mechanisms.


[Study on synthesis, structure characterization and fluorescence of europium complexes of 2-(4-fluorobenzoyl) benzoic acid].
The present paper reports three new europium complexes, EuL3(H2O)6, EuL3Phen(H2O)4 and EuL3 (TPPO) (H2O)5, synthesized with Eu(NO3)3 x 6H2O, 2-(4-fluorobenzoyl) benzoic acid, Phen and TPPO(L = 2-(4-fluorobenzoyl) benzoic acid, Phen = 1, 10-phenanthroline, TPPO = triphenyl phosphine oxide). Their composition and chemical structures were characterized by elemental analysis, IR and 1H NMR spectroscopy. The IR spectra indicated that all complexes exhibited the characteristic peaks of carboxylate, asymmetric stretching vibration (vas (CO2(- and symmetric stretching vibration (vs (CO2(- peaks; the C = O stretching band at 1,692 cm(-1) of COOH and the O--H stretching band around 2,500-3,200 cm(-1) disappeared. All these complexes had a smaller Deltav(vas (CO2(-))-vs(CO2(- value than that of NaL, so the carboxylate groups coordinated with the europium ion in the form of bridging bidentate. In 1HNMR, the signals of hydrogen in 2-(4-fluorobenzoyl) benzoic acid became wide and shifted upfield, and those in Phen, TPPO shifted downfield. The excitation and emission spectra were recorded at room temperature. The excitation spectra showed that the optimum excitation peaks of these three complexes, EuL3 (H2O)6, EuL3Phen(H2O)5 and EuL3(TPPO)(H2O)5, were at 353.0, 355.0 and 357.0 nm, respectively. All these three complexes showed Eu3+ ion characteristic emission bands, the electron-dipole transition 5D0 --> 7F2 and magnetism dipole transition 5D0 --> 7F1; their emission peaks were at 596.0, 617.0; 596.0, 619.0; 595.0, 620.0 nm, and the relative intensities were 1.1, 8.6; 15.2, 100.0; 3.6, 23.2, respectively. The intensity of 5D0 --> 7F2 was stronger than that of 5D0 --> F1, which indicated that europium ions were at asymmetric center. The emission intensities of europium ions were greatly sensitized by Phen.


Polymorphic variants of the IL2RA gene and susceptibility to type 1 diabetes in the Polish population.
Polymorphic variants of the IL2RA gene, which encodes high-affinity alpha subunit (CD25) of the interleukin-2 receptor, were recently found to affect the risk of several autoimmune disorders. This study was aimed to investigate the association of selected IL2RA polymorphisms (rs11594656, rs3118470, rs2104286 and rs7093069) with type 1 diabetes (T1D) in a Polish cohort comprising 445 patients and 671 healthy control subjects. The minor A allele at rs11594656 was found significantly less frequently among T1D subjects, compared with the control group [P = 0.011; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.629-0.942]. In contrast, the minor C allele at rs3118470 appeared to be significantly associated with the occurrence of T1D (P = 0.003; OR = 1.30; 95% CI = 1.094-1.550). Two other IL2RA single nucleotide polymorphisms (SNPs) did not show significant differences among investigated groups. In conclusion, the study confirms the association of the IL2RA locus with T1D in the Polish population.


Investigation of the μ- and κ-opioid receptor activation by eight new synthetic opioids using the [35 S]-GTPγS assay: U-47700, isopropyl U-47700, U-49900, U-47931E, N-methyl U-47931E, U-51754, U-48520, and U-48800.
In 2009, new synthetic opioids appeared on the new psychoactive substances market. This class of new psychoactive substances generally poses a health risk due to the high affinity and potency of most of these compounds for the opioid receptors. It is known that overdoses can lead to respiratory depression and result in death. However, for many new synthetic opioids, data on toxicological and toxicokinetic properties are scarce. In the present study, eight U-opioids were investigated for their structure activity relationships at the μ- and κ-opioid receptors using a [35 S]-GTPγS assay. The potencies of the investigated U-opioids were lower than those of the reference compounds (μ-opioid receptor: hydromorphone, fentanyl; κ-opioid receptor: U-69593, U-50488). At the μ-opioid receptor, U-47700 showed the highest potency with an EC50 value of 111 nM, and at the κ-opioid receptor, U-51754 was found to be the most potent compound with an EC50 value of 120 nM. The following structural features were advantageous for activating the μ-opioid receptor: two chlorine substituents in 3,4-position at the aromatic ring, the absence of the methylene group between the amide group and the aromatic ring, a methyl group at the amide nitrogen, and/or a dimethylamine residue at the amine nitrogen of the cyclohexane ring. Further, the following structural features were beneficial for κ-opioid receptor activation: a methylene group between the amide group and the aromatic ring, a pyrrolidine residue at the amine nitrogen of the cyclohexane ring, a methyl group at the amide nitrogen, and/or a chlorine substitution at the 3,4-position of the aromatic ring.


Acquired esotropia: subjective and objective outcomes.
The measurement of outcomes of pediatric therapy will be increasingly important to third-party payers as they allocate health care resources. We undertook this study to assess the effectiveness of treatment of acquired esotropia, as measured subjectively by parents and objectively by examination. A chart review was used to gather objective clinical data from all patients presenting between 1994 and 1995 with esotropia after their first birthday. Parents' impressions of the quality and impact of treatment were tabulated by using a telephone questionnaire. Of 48 patients studied (mean age, 3.8 years; 44 months' follow-up), the 26 with amblyopia were effectively treated in 81% of cases. Mean esotropic angles decreased, with glasses and/or surgery, from 33.1 to 4.9 PD at distance and from 40.0 to 11.4 PD at near. The average estimated cost of care was 547 dollars per patient per year. Parents considered treatment "extremely important" to their child's future happiness and success in 90% of cases. Our experience has shown that treatment of acquired esotropia in childhood, while relatively inexpensive, is highly effective, both objectively and subjectively.


Internal mammary vessels as recipients for free TRAM breast reconstruction: aesthetic and functional considerations.
The utilisation of the internal mammary vessels (IMVs) as recipient vessels for free TRAM reconstruction of the breast is well established. To gain adequate access to the IMVs, a medial segment of the ipsilateral third costal cartilage is usually excised. Concern has been expressed regarding potential complications specific to use of this site, including pneumothorax, intercostal neuralgia, chest wall herniae and contour defects. We present a retrospective study of our experience with free TRAM breast reconstruction, using the IMVs as recipient vessels, to ascertain the incidence of such complications. Twenty-five consecutive cases were studied. The clinical notes were analysed for information regarding immediate and late complications. All the patients were recalled and underwent assessment and examination by the authors. There were no cases of haemo- or pneumothorax on the side of the reconstruction. There were no complaints of chest pain suggestive of intercostal neuralgia. No discernible contour defects at the site of rib excision were found and no thoracic herniae were demonstrated. We suggest that internal mammary vessels can safely be used as recipients for free TRAM reconstruction of the breasts with no added aesthetic or functional morbidity.


Complete Regression of Rhabdomyosarcoma in an Adult Secondary to Postoperative Wound Infection Following Limb Salvage Surgery: A Case Report.
A 33-year old man presented with a 25-cm lower extremity embryonal rhabdomyosarcoma with presumed extensive nodal metastasis on positron emission topography scan. Neoadjuvant chemotherapy and radiation provided minimal response. Following limb salvage resection and flap coverage, a prolonged postoperative infection occurred requiring intravenous antibiotics and wound care over 5 months. Given the infection, no postoperative radiation or chemotherapy was administered. Eight months following surgery, positron emission topography scan showed complete regression of local and nodal disease. The patient has remained in complete remission for more than 4 years. Postoperative wound infection leading to complete regression of embryonal rhabdomyosarcoma has not been reported. Stimulation of the innate and adaptive immune system through infectious elements is an area of ongoing immunotherapy research to improve sarcoma treatment outcomes.


Molecular Skin Surface-Based Transformation Visualization between Biological Macromolecules.
Molecular skin surface (MSS), proposed by Edelsbrunner, is a C2 continuous smooth surface modeling approach of biological macromolecules. Compared to the traditional methods of molecular surface representations (e.g., the solvent exclusive surface), MSS has distinctive advantages including having no self-intersection and being decomposable and transformable. For further promoting MSS to the field of bioinformatics, transformation between different MSS representations mimicking the macromolecular dynamics is demanded. The transformation process helps biologists understand the macromolecular dynamics processes visually in the atomic level, which is important in studying the protein structures and binding sites for optimizing drug design. However, modeling the transformation between different MSSs suffers from high computational cost while the traditional approaches reconstruct every intermediate MSS from respective intermediate union of balls. In this study, we propose a novel computational framework named general MSS transformation framework (GMSSTF) between two MSSs without the assistance of union of balls. To evaluate the effectiveness of GMSSTF, we applied it on a popular public database PDB (Protein Data Bank) and compared the existing MSS algorithms with and without GMSSTF. The simulation results show that the proposed GMSSTF effectively improves the computational efficiency and is potentially useful for macromolecular dynamic simulations.


The influence of chronic pancreatitis on carcinogenesis: an experimental study in rats.
The literature contains many controversial or unclearly defined opinions about the risk of development of carcinoma of the exocrine part of the pancreas in patients with chronic pancreatitis. This and our own clinical observations based on analysis of patients with chronic pancreatitis treated surgically (anastomotic and resectional procedures) formed the background to an experimental study to define the risk of carcinogenesis in the course of chronic pancreatitis in rats. In Wistar rats with chronic pancreatitis induced by etionine and then exposed to carcinogenic action of azaserine, proliferation, adenomas and acinic cell carcinomas of the exocrine part of the pancreas were diagnosed; the carcinomas were transplantable. In rats treated with azaserine only, benign proliferative lesions and adenomas were found. The presence of the p53 mutation protein was observed in carcinomatous pancreatic cells in malignant lesions of the pancreas in primary and transplantable cancers, but was not detected in benign proliferative lesions and adenomas. Chronic pancreatitis in Wistar rats predisposes the exocrine part of pancreas to malignant transformation. Growth of cancers of the exocrine part of the pancreas in male rats, but not in female rats, suggests hormonal determination of experimental pancreatic cancer. Results demonstrate that chronic pancreatitis in rats predisposes to malignant proliferative lesions, including acinic cell carcinoma. Expression of the protein product of p53 gene mutations correlated with neoplastic transformation of pancreas preceded by chronic pancreatitis, and was also detected in transplantable tumours.


Specialization of the DNA-cleaving activity of a group I ribozyme through in vitro evolution.
In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group I ribozyme to obtain individuals with a 10(5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approximately 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiments confirmed the selective advantage of two covarying mutations within the catalytic core of the ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average of 28 mutations relative to the wild-type that are responsible for the altered phenotype.


Channel Scaling Dependent Photoresponse of Copper-Based Flexible Photodetectors Fabricated Using Laser-Induced Oxidation.
Copper (Cu) oxide compounds (CuxO), which include cupric (CuO) and cuprous (Cu2O) oxide, have been recognized as a promising p-channel material with useful photovoltaic properties and superior thermal conductivity. Typically, deposition methods or thermal oxidation can be used to obtain CuxO. However, these processes are difficult to apply to flexible substrates because plastics have a comparatively low glass transition temperature. Also, additional patterning steps are needed to fabricate applications. In this work, we fabricated a metal-semiconductor-metal photodetector using laser-induced oxidation of thin Cu films under ambient conditions. Raman spectroscopy, scanning electron microscopy-energy-dispersive X-ray spectroscopy, and atomic force microscopy were used to study the composition and morphology of our devices. Moreover, the photoresponse of this device is reported herein. We performed an in-depth analysis of the relationship between the channel size and number of carriers using scanning photocurrent microscopy. The carrier transport behaviors were identified; the photocurrent decreased as the length and width of the channel increased. Furthermore, we verified the suitability of the device as a flexible photodetector using a variety of bending tests. Our in-depth analysis of this Cu-based flexible photodetector could play an important role in understanding the mechanisms of other flexible photovoltaic applications.


Systemic treatment of advanced pancreatic cancer.
Pancreatic cancer belongs to the most malignant gastrointestinal cancers and, in its advanced stage, remains a deadly disease for nearly all affected patients. Treatment of metastatic adenocarcinoma of the pancreas not only involves chemotherapy and targeted therapy, but also requires attention to accompanying comorbidities as well as frequently intensive supportive treatment and psychosocial support. Gemcitabine-based combinations with fluoropyrimidines and platin analogs have essentially failed to provide a substantial prolongation of survival and may constitute a treatment option only in patients with a good performance status. Among targeted therapies, only the EGFR tyrosine kinase inhibitor erlotinib has shown activity which is marginal in the overall population, but clinically relevant in patients developing skin rash. New avenues of polychemotherapy are presently explored since the gemcitabine-free FOLFIRINOX-regimen (infusional 5-fluorouracil/folinic acid plus irinotecan and oxaliplatin) was shown to be markedly superior to gemcitabine in selected good-performance patients. Pancreatic cancer is notably characterized as a hypovascular tumor rich in desmoplastic stromal tissue. An innovative approach to treatment therefore focuses on peritumoral fibroblasts and aims to induce a depletion of the stroma either by inhibition of the hedgehog pathway or by targeting SPARC (secreted protein acidic and rich in cysteine) via application of albumin-bound paclitaxel.


Effect of telehealth interventions on anxiety and depression in cancer patients: A systematic review and meta-analysis of randomized controlled trials.
Cancer patients not only experience a variety of problems associated with the treatment of their disease but also a range of psychological problems such as anxiety and depression, which may lead to reduced adherence to treatment and a lower quality of life for cancer patients. Telehealth interventions are widely used for cancer patients, and their effectiveness in improving anxiety and depression in cancer patients is variable and still contradictory. Embase, Pubmed, Web of Science, PsycINFO, CINAHL Complete, and the Cochrane Central Register of Controlled Trials were searched from inception to 19 April 2022. Data synthesis was conducted using STATA 15.0, and scores for anxiety and depression were calculated using standardized mean differences and 95% confidence intervals. A total of 13125 cancer patients from 68 randomized controlled trials were included in the systematic evaluation. The meta-analysis showed that the telehealth intervention had a significant effect on anxiety (standardized mean differences = -0.40, 95% confidence intervals: -0.6 to 0.2, p < 0.001) and depression (standardized mean differences = -0.48, 95% confidence intervals: -0.67 to 0.28, p < 0.001) in patients with cancer. Telehealth interventions significantly improved anxiety and depression levels in cancer patients compared to traditional care interventions. Breast cancer patients most often received telehealth interventions; electronic device-based and application-based telehealth interventions were more effective than online interventions; short-term interventions were more effective than medium-term and long-term interventions, and different outcome measurement tools led to different intervention outcomes. More high-quality research is needed to explore the effects of telehealth interventions.


Test procedures for obtaining representative extracts suitable for reliable in vitro toxicity assessment of paper and board intended for food contact.
This paper describes the use of a suite of extraction procedures applicable to the assessment of the in vitro toxicity of paper/board samples intended for food-contact applications. The sample is extracted with ethanol, water, or exposed to modified polyphenylene oxide (Tenax) for fatty, non-fatty and dry food applications, respectively. The water extracts are directly suitable for safety assessment using in vitro bioassays. The ethanol extracts of the paper/board and of the exposed Tenax require pre-concentration to give acceptable sensitivity. This is because the in vitro bioassays can tolerate only a small percentage of added organic solvent before the solvent itself inhibits. The extraction procedures have been selected such that they mimic the foreseeable conditions of use with foods and that they are also fully compatible with the battery of in vitro biological assays for the safety assessment of the total migrate. The application of the extraction protocols is illustrated by the results for one of the many paper/board samples provided by the BIOSAFEPAPER project industrial platform members. The assessment indicated that this sample should not be considered as suitable for use with fatty foodstuffs but was suitable for dry and non-fatty foods. Information subsequently received from the manufacturer revealed that this was a non-food-grade product included in the project to test the capabilities of the bioassay procedures. The selection criteria for the test conditions and the suite of methods developed have been prepared in Comité Européen de Normalisation (CEN) format and is currently being progressed by CEN/TC172 as a European Standard.


Acinetobacter peritoneal dialysis peritonitis: a changing landscape over time.
Acinetobacter species are assuming an increasingly important role in modern medicine, with their persistent presence in health-care settings and antibiotic resistance. However, clinical reports addressing this issue in patients with peritoneal dialysis (PD) peritonitis are rare. All PD peritonitis episodes caused by Acinetobacter that occurred between 1985 and 2012 at a single centre were retrospectively reviewed. Clinical features, microbiological data, and outcomes were analysed, with stratifications based upon temporal periods (before and after 2000). Acinetobacter species were responsible for 26 PD peritonitis episodes (3.5% of all episodes) in 25 patients. A. baumannii was the most common pathogen (54%), followed by A. iwoffii (35%), with the former being predominant after 2000. Significantly more episodes resulted from breaks in exchange sterility after 2000, while those from exit site infections decreased (P = 0.01). The interval between the last and current peritonitis episodes lengthened significantly after 2000 (5 vs. 13.6 months; P = 0.05). All the isolates were susceptible to cefepime, fluoroquinolone, and aminoglycosides, with a low ceftazidime resistance rate (16%). Nearly half of the patients (46%) required hospitalisation for their Acinetobacter PD-associated peritonitis, and 27% required an antibiotic switch. The overall outcome was fair, with no mortality and a 12% technique failure rate, without obvious interval differences. The temporal change in the microbiology and origin of Acinetobacter PD-associated peritonitis in our cohort suggested an important evolutional trend. Appropriate measures, including technique re-education and sterility maintenance, should be taken to decrease the Acinetobacter peritonitis incidence in PD patients.


Laparoscopic trans teres vault suspension, a new laparoscopic method of treatment of female genital prolapse - a preliminary report.
Pelvic organ prolapse (POP) is treated with a great variety of procedures and none is fully satisfactory. The aim of the study was to introduce and evaluate the effectives of laparoscopic trans teres vault suspension (LTTVS) technique as a new method for POP treatment. In the years 2013-2014, eight symptomatic women with grades II-IV POP underwent LTTVS procedure. The mean age of patients was 65.25 years (range from 52 to 76 years). The surgery encompassed total hysterectomy, suturing the vagina and fixation of uterosacral ligaments to the vaginal stump, fixation of stumps of round ligaments to the vaginal stump, and fixation of the vaginal stump to the anterior rectus fascia. Mean follow-up was 17.75 months (range from 6 to 27 months). Eight patients were successfully operated. The symptoms of POP resolved after surgery and subjective quality of life increased. In one case a complication such as common fibular nerve injury appeared; however, it resolved after one month of physiotherapy. The other patient reported radiating pain down the leg after three months. No recurrence of vaginal stump prolapse was observed during the follow-up. LTTVS is a promising method for POP treatment. Due to repair with the use of native tissues, physiological placement of vaginal stump, and high efficacy it can be considered as an alternative to other POP surgeries. The method requires additional research on larger groups of patients.


Doxycycline-encapsulated solid lipid nanoparticles as promising tool against Brucella melitensis enclosed in macrophage: a pharmacodynamics study on J774A.1 cell line.
Brucellosis is a zoonotic disease caused by Brucella species. It has been estimated that more than 500,000 new cases of Brucellosis occur annually all around the world. Relapse of the disease is one of the most important challenges. The most important reason for the relapse of brucellosis is the survival of the bacteria inside the macrophages, which makes them safe from the immune system and disrupts drug delivery mechanism. The present study was performed to assess the effects of Doxycycline-loaded Solid Lipid Nanoparticles (DOX-SLN) on the Brucella melitensis inside macrophages. DOX-SLN was prepared using double emulsion method. The technological characterization of DOX-SLN, including particle size, zeta potential, polydispersity index (PDI), drug loading and encapsulation efficiency were used. Fourier-transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC) were used to assess the interactions between Nanoparticles (NPs) components and crystalline form of doxycycline. Moreover, the effect of DOX-SLN on the bacteria were compared with that of the doxycycline using various methods, including well diffusion, Minimum Inhibitory Concentration (MIC), and investigation of their effects on murine macrophage-like cells cell line J774A.1. The means of particle size, zeta potential, PDI, drug loading and encapsulation efficiency were 299 ± 34 nm, - 28.7 ± 3.2 mV, 0.29 ± 0.027, 11.2 ± 1.3%, and 94.9 ± 3.2%, respectively. The morphology of NPs were spherical with a smooth surface. No chemical reaction was occurred between the components. Doxycycline was located within NP matrix in its molecular form. The DOX-SLN significantly decreased the microbial loading within macrophages (3.5 Log) in comparison with the free doxycycline. Since the DOX-SLN showed better effects on B. melitensis enclosed in macrophages than the free doxycycline, it is recommended to use it for treating brucellosis and preventing relapse.


Endotoxin- and inflammation-induced depression of the hepatic drug metabolism in rats.
Carrageenan-induced inflammation and exposure to endotoxin considerably decreased the content of cytochrome P-450 and activities of ethylmorphine N-demethylase and meperidine N-demethylase, but did not decrease the activities of aniline hydroxylase or NADPH-cytochrome c reductase, compared with the respective activities in rats treated with carrageenan alone. These results suggest that under these experimental conditions, the two host-related environmental factors interact and enhance a decrease in rat hepatic microsomal drug metabolizing enzymes depending on the substrate used.


[Expression of intermediate filaments in cutaneous cylindroma].
Using different monoclonal anti-cytokeratin antibodies (broad spectrum, cytokeratin 7, 8, 18, 19) and the antibody A55-A/A9 until now characterized only by immunohistology the staining of ductal structures and some cells within the lobulae of dermal cylindromata was demonstrated. In regard to the cytokeratin polypeptide patterns of the adnexes in uninvolved skin an exact histogenetic correlation by our findings is not possible, but the pattern is consistent with the conception of the glandular origin of the tumours.


Combined single-port and endoluminal technique for laparoscopic anterior resection.
To determine the technical feasibility and clinical outcomes of laparoscopic anterior resection using combined single-port and endoluminal technique. A single port was placed at the umbilicus. Sigmoid colon was retracted using transabdominal sutures. After adequate mobilization, the colon was stapled distal to the lesion using noncutting endostapler, and the rectum was opened distal to the staple line. The transanal endoscopic operation device was placed transanally and the anvil of a circular stapler was then delivered through the device into the peritoneal cavity. The anvil was placed intraluminally through a colotomy made proximal to the lesion; after this, the colon was transected above the colotomy site. The specimen was next delivered transanally through the transanal endoscopic operation device. Finally, the rectum was closed with endostapler and intracorporeal side-to-end colorectal anastomosis was constructed using the circular stapler. This technique was attempted in an 80-year-old woman with a 3 cm sessile polyp in the distal sigmoid. Laparoscopic anterior resection was arranged as the polyp was not amenable to endoscopic removal. The operative time was 150 minutes. There was no intraoperative complication. The patient was discharged on postoperative day 6, with a maximum pain score of 3. Laparoscopic anterior resection using this combined single-port and endoluminal technique is feasible for small lesions in the sigmoid colon or upper rectum. The technique avoids multiple trocar incisions and a minilaparotomy for specimen retrieval.


Natural incidence of Fusarium species and fumonisins B1 and B2 associated with maize kernels from nine provinces in China in 2012.
Fusarium species, which can produce mycotoxins, are the predominant pathogens causing maize ear rot, a disease that results in severe economic losses and serves as a potential health risk for humans and animals. A survey was conducted in 2012 to investigate the contamination of maize by Fusarium species and fumonisins B1 and B2. A total of 250 maize samples were randomly collected from nine provinces (Hebei, Shanxi, Inner Mongolia, Yunnan, Sichuan, Guizhou, Heilongjiang, Liaoning and Ningxia) in China. Fusarium species were isolated and identified using morphological (electron microscope) and molecular methods (polymerase chain reaction (PCR) and sequencing). Fumonisins B1 and B2 were analysed using high-performance liquid chromatography with fluorescence detection (HPLC-FLD) with OPA (2-Mercaptoethanol, o-phthaldialdehyde) post-column derivatisation. A total of 2321 Fusarium isolates (20.7%) were obtained from all the samples. These isolates included nine Fusarium species, namely, F. graminearum, F. verticillioides, F. subglutinans, F. proliferatum, F. temperatum, F. oxysporum, F. equiseti, F. meridionale and F. chlamydosporum. The incidence of occurrence of Fusarium species in Guizhou was the highest, while in Inner Mongolia it was the lowest. F. verticillioides was the dominant species of maize ear rot in Liaoning, Sichuan, Hebei and Ningxia. F. graminearum was the dominant species in Yunnan, Guizhou and Shanxi. F. subglutinans was the dominant species in Heilongjiang. F. verticillioides and F. graminearum percentages were the same in Inner Mongolia. The incidence of fumonisins in Liaoning was high (up to 81.0%) and in Heilongjiang low (up to 10.3%). Except Shanxi, more than 50% of maize samples from other provinces were contaminated with fumonisins, with concentrations less than 500 ng g(-1). About 33% of maize samples from Yunnan were contaminated with high levels of fumonisins, and average of fumonisin levels were 5191 ng g(-1). Fusarium species causing maize ear rot in different areas in China were highly diverse and such areas with exposure to high levels of fumonisin contamination have a potential health risk for human and animals.


[Comparison of effects of preoperative stenting for obstructing colorectal cancers according to the location of the obstructing lesion].
With the development of self-expanding metallic stents, colonic obstruction can be relieved without the need for surgery. The results of preoperative placement of stents for malignant colorectal obstruction might be different according to the obstructing lesion. The objective of this study was to compare clinical improvement rates and operative results after preoperative placement of stents for malignant colorectal obstruction according to the location of the obstructing lesion. This is a retrospective study including 57 patients who underwent self-expanding metallic stent insertion for obstructing resectable colorectal cancers. Patients were classified into three groups according to the location of the lesion as follows: proximal to the sigmoid colon (Group A), sigmoid colon (Group B), and rectum (Group C). The number of patients in A, B, and C groups was 13, 22, and 22, respectively. No significant differences in age, gender, stent type, and accompanying diseases among the three groups were observed. There were no significant differences in stent-related complications, clinical improvement rates, and one-stage resection rates among the three groups. The postoperative complications, the requirement rate of ICU care, the period of ICU stay, postoperative hospital stay, and hospital mortality did not significantly differ among the three groups. Clinical improvement rates and operative results after successful placement of stents for obstructing resectable colorectal cancers are not different according to the location of the obstructing lesion, suggesting that preoperative stenting for one-stage curative resection is useful, irrespective of the location of lesion.