Clinicians' knowledge and attitudes towards patient reported outcomes in colorectal cancer care - insights from qualitative interviews.
Patient-reported outcomes (PROs) can be used in cancer care to monitor patients' disease-related symptoms and functional status. However, successful implementation of such instruments is only possible if clinical staff are convinced of the clinical benefits. It is therefore crucial to investigate the attitudes of clinical staff to PROs in routine cancer care. Semi-structured, guideline-based interviews were held with 12 clinicians working in certified colorectal cancer centers in Germany who are taking part in an observational study on PROs (five surgeons, two oncologists, one psycho-oncologist, two oncological care nurses, one stoma therapist, and one physician assistant) in order to investigate firstly, how clinicians describe PRO instruments ("wording"); and secondly, the clinicians' general attitude toward PROs. A qualitative content analysis according to Kuckartz was performed. The wording used to describe PROs was not consistent. Statements on attitudes toward PROs were very heterogeneous and were therefore categorized into "(rather) positive" and "(rather) negative." The principal advantages of PROs mentioned by participants included broader, structured knowledge about patients and treatment, as well as relevance for patients. Subcategories for (rather) negative attitudes included statements expressing doubts about the questionnaires and "no need for PROs." The clinicians participating mainly expressed fairly positive attitudes toward PROs. However, they had little knowledge about PROs in general and the interviews therefore mainly reflect their expectations and assumptions about them. These initial impressions may be regarded as providing a basis for future implementation strategies and for training of clinicians on how to use PROs in routine cancer care.


Behavior and fate of microcystin-LR in soils amended with biochar and peat.
Activities such as irrigation with cyanobacteria-polluted water can lead to microcystins (MCs) migration from soil surface to the deeper layers, which could pose a potential risk to ground drinking water safety. The present study evaluated the sorption, degradation and leaching behavior of microcystin-LR (MC-LR) in two different soils amended with biochar and peat. Results showed that both biochar and peat could significantly increase MC-LR sorption in both soils. The Freundlich unit capacity coefficient (Kf) of 2% biochar treatment were 2-3 times higher than those of the control treatment. Amendment of 2% peat greatly boosted the biodegradation of MC-LR, whereas amendment of 2% biochar significantly reduced the biodegradation of MC-LR in both soils. The half-lives of MC-LR were 4.99 d (Control), 5.59 d (2% Biochar) and 3.50 d (2% Peat) in soil A and 6.66 d (Control), 6.93 d (2% Biochar) and 5.13 d (2% Peat) in soil B, respectively. All the amendments, except treatment 1% Peat, could significantly reduce the recovery rates of MC-LR in the leachate of columns with both soils. Amendment of 2% biochar and 2% peat reduced the recovery rates of MC-LR by 15.87% and 8.6% in soil A and 18.4% and 10.3% in soil B, compared with the controls. This work provides a better understanding of the environmental behavior of MC-LR in soils with different amendments, which is also meaningful for groundwater protection in cyanobacterial-polluted areas.


Effect of different residential settings on gait kinematic parameters in older adults with cognitive impairment.
To compare the parameters of gait kinematics of older adults with cognitive impairment who live in community dwellings or those living or spending most of the time in non-family environment settings. The sample was composed of 33 older adults of both sexes with cognitive impairment. Participants were separated into three groups: a community-dwelling older adult group comprised of 11 subjects; a semi-institutionalized older adult group comprised of 10 older adults attended in a geriatric daycare institution; and an institutionalized older adult group comprised of 12 older adults living in long-term institutions. Gait kinematics were recorded by pressure sensors (footswitches). Fifty gait cycles at self-selected pace were analyzed to obtain: gait speed, stride length, stance, swing, and stride time. The variability of these parameters was also analyzed. MANCOVA identified the main effect of groups (p < 0.001). Gait speed of older adults living in long-term institutions and older adults attended in geriatric daycare institutions was slower than community-living older adults (p < 0.001 and p = 0.04, respectively). Swing and stride time variability was higher in older adults living in long-term institutions (p = 0.003 and p = 0.001) and in older adults attended in geriatric daycare institutions (p = 0.02 and p = 0.001) than in community-dwelling older adults. The most important finding was that older adults with cognitive impairment who need non-family residential setting care had higher gait kinematics abnormalities, which may increase the risk of falls, compared to those who live in the community.


Spontaneous emphysematous osteomyelitis of the spine: A case report.
Spontaneous emphysematous osteomyelitis of the spine is a very rare but severe condition caused by gas-forming microorganisms. We present the case of a 41-year-old obese male patient presenting at the Emergency Department with diabetic ketoacidosis, fever, and difficulty in walking. computed tomography and magnetic resonance imaging of the spine revealed bone marrow edema and intraosseous gas collections at the level of the fourth and fifth lumbar metameres, suggesting an osteomyelitis sustained by gas-forming microorganisms, which was then confirmed by the isolation of Klebsiella pneumonia in blood culture. Imaging plays a central role for the diagnosis of emphysematous osteomyelitis: the presence of multiple intraosseous gas collections of variable size, especially in patients with specific risk factors, is highly suggestive of an infection caused by gas-forming pathogens. Being familiar with this peculiar neuroradiological appearance is essential to ensure an early diagnosis and a timely antimicrobial therapy, which can considerably ameliorate the prognosis.


Importance of PI3-kinase pathway in response/resistance to aromatase inhibitors.
Endocrine therapy has been the most effective treatment modality for hormone receptor positive breast cancer. However, its efficacy has been limited by either de novo or acquired resistance. Recent data indicates that activation of the phosphatidylinositol 3-kinase (PI3K) signaling is associated with the poor outcome luminal B subtype of breast cancer and accompanied by the development of endocrine therapy resistance. Importantly, inhibition of PI3K pathway signaling in endocrine resistant breast cancer cell lines reduces cell survival and improves treatment response to endocrine agents. Interestingly, mutations in PIK3CA, the alpha catalytic subunit of the class IA PI3K, which renders cells dependent on PI3K pathway signaling, is the most common genetic abnormality identified in hormone receptor positive breast cancer. The synthetic lethality observed between estrogen deprivation and PI3K pathway inhibition in estrogen receptor positive (ER+) breast cancer cell lines provides further scientific rational to target both estrogen receptor and the PI3K pathway in order to improve the outcome of ER+ breast cancer.


Amnion responses to intrauterine inflammation and effects of inhibition of TNF signaling in preterm Rhesus macaque.
Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal inflammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm Rhesus macaque model of IUI induced by lipopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA sequencing (RNA-seq) amnion transcriptomic profiles were remarkably similar in both Rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on nuclear factor κB (NF-κB) signaling and reversed by the anti-tumor necrosis factor (TNF) antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immunohistology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.


Cost-benefit analysis simulation of a hospital-based violence intervention program.
Violent injury is a major cause of disability, premature mortality, and health disparities worldwide. Hospital-based violence intervention programs (HVIPs) show promise in preventing violent injury. Little is known, however, about how the impact of HVIPs may translate into monetary figures. To conduct a cost-benefit analysis simulation to estimate the savings an HVIP might produce in healthcare, criminal justice, and lost productivity costs over 5 years in a hypothetical population of 180 violently injured patients, 90 of whom received HVIP intervention and 90 of whom did not. Primary data from 2012, analyzed in 2013, on annual HVIP costs/number of clients served and secondary data sources were used to estimate the cost, number, and type of violent reinjury incidents (fatal/nonfatal, resulting in hospitalization/not resulting in hospitalization) and violent perpetration incidents (aggravated assault/homicide) that this population might experience over 5 years. Four different models were constructed and three different estimates of HVIP effect size (20%, 25%, and 30%) were used to calculate a range of estimates for HVIP net savings and cost-benefit ratios from different payer perspectives. All benefits were discounted at 5% to adjust for their net present value. Estimates of HVIP cost savings at the base effect estimate of 25% ranged from $82,765 (narrowest model) to $4,055,873 (broadest model). HVIPs are likely to produce cost savings. This study provides a systematic framework for the economic evaluation of HVIPs and estimates of HVIP cost savings and cost-benefit ratios that may be useful in informing public policy decisions.


Body mass index and lifetime healthcare utilization.
Overweight and obesity is a major global public health challenge, and understanding the implications for healthcare systems is essential for policy planning. Past studies have typically found positive associations between obesity and healthcare utilization, but these studies have not taken into consideration that obesity is also associated with early mortality. We examined associations between body mass index (BMI, reported as kg/m2) and healthcare utilization with and without taking BMI-specific survival into consideration. We used nationally representative data on 33 882 adults collected between 2002 and 2015. We computed BMI- and age-specific primary and secondary care utilization and multiplied the estimated values with gender-, age-, and BMI-specific probabilities of surviving to each age. Then, we summed the average BMI-specific utilization between 18 and 85 years. During a survival-adjusted lifetime, males with normal weight (BMI: 18.5-24.9) had, on average, 167 primary care, and 77 secondary care contacts. In comparison, males with overweight (BMI: 25.0-29.9), category I obesity (BMI: 30.0-34.9), and category II/III obesity (BMI ≥35.0) had 11%, 41%, and 102% more primary care, and 14%, 29%, and 78% more secondary care contacts, respectively. Females with normal weight had, on average, 210 primary care contacts and 91 secondary care contacts. Females with overweight, category I obesity, and category II/III obesity had 20%, 34%, and 81% more primary care contacts, and 26%, 16%, and 16% more secondary care contacts, respectively. The positive association between BMI and healthcare utilization was reduced, but not offset, when BMI-specific survival was taken into consideration. Our findings underpin previous research and suggest that interventions to offset the increasing prevalence of overweight, and especially obesity, are warranted.


Quantification of particle sizes with metal replication under standard freeze-etching conditions: a gold ball standard for calibrating shadow widths was used to measure freeze-etched globular proteins.
The real size of platinum-carbon (Pt-C) replicated particles is not directly equivalent to either its metal-coated diameter or its shadow width. This paper describes two indirect methods, shadow widths and coated particle diameters, for determining a particle's actual size beneath a Pt-C replication film. Both produce equivalent measurements using the same standardized conditions: 2.3 nm Pt-C films deposited at a 45 degree angle on an approximately -100 degrees C surface in a 10(-6) torr vacuum. For the first method, gold balls nucleated in a partial pressure of helium and deposited on flat indirect carbon films (root mean square roughness of 0.8 nm) on 400 mesh grids were used as test particles for calibrating shadow widths as a function of particle size. The gold ball test specimens were replicated, and a distribution of Pt-C shadow widths orthogonal to the Pt-C deposition direction was measured and averaged for gold balls 1.5 +/- 0.25 nm, 2.0 +/- 0.25 nm, etc. The diameter of each gold ball was measured within the Pt-C film along with its shadow width because the Pt-C did not obscure or adhere well to the gold. The shadow width distributions for each gold size do not differ significantly from log normal. Two proteins, the lactose repressor and the mitochondrial ATPase, F1, were also used as replication test objects. Negative staining of both proteins was conducted to measure their average diameters. In the second method, a distribution of Pt-C-coated lac repressor diameters perpendicular to the shadow direction was measured. The Pt-C film thickness measured on the quartz crystal monitor was subtracted from the average metal-coated protein diameter to obtain the lac repressor's diameter. The Pt-C-coated particle diameter distributions also did not differ significantly from log normal. While doing this work it was discovered that outgassing the Pt-C electron gun greatly affected Pt-C film granularity: 19 sec produced a high contrast, granular Pt-C film, whereas 120 sec yielded a low contrast, less granular Pt-C film. Both gold balls and protein particles were subjected in separate experiments to either 19 or 120 sec of outgassing of the Pt-C gun prior to Pt-C replication. Outgassing had a profound effect on the average size of the Pt-C shadow widths on both gold and protein particles. The Pt-C gun outgassing procedure also determined the smallest replicated particle that could be resolved. The frequency of some smaller gold ball sizes detected after replication was reduced disproportionately with 19 sec vs. 120 sec outgassing. However, Pt-C gun outgassing did not affect the average measured diameter of the Pt-C-coated protein particles. The "geometric assumption" that each metal-coated particle creates a shadow width the same size as the metal-coated particle diameter was tested using a globular protein. Pt-C replication of protein particles at a 45 degree and 20 degree angle could not confirm the geometric assumption because an average shadow width was always significantly larger than its average Pt-C-coated particle diameter. A model for how the large shadow widths are formed is presented. Gold balls were also replicated at a 45 degree angle with current high resolution conditions at a substrate temperature of -185 degrees C, and the results of these replicas were compared to the results reported here at approximately -100 degrees C.


Immunogenic and reactogenic efficacy of Covaxin and Covishield: a comparative review.
SARS-CoV-2 is an RNA virus that was identified for the first time in December 2019 in Wuhan, China. The World Health Organization (WHO) labeled the novel coronavirus (COVID-19) outbreak a worldwide pandemic on March 11, 2020, due to its widespread infectivity pattern. Because of the catastrophic COVID-19 outbreak, the development of safe and efficient vaccinations has become a key priority in every health sector throughout the globe. On the 13th of January 2021, the vaccination campaign against SARS-CoV-2 was launched in India and started the administration of two types of vaccines known as Covaxin and Covishield. Covishield is an adenovirus vector-based vaccine, and Covaxin was developed by a traditional method of vaccine formulation, which is composed of adjuvanted inactivated viral particles. Each vaccine's utility or efficiency is determined by its formulation, adjuvants, and mode of action. The efficacy of the vaccination depends on numeral properties like generation antibodies, memory cells, and cell-mediated immunity. According to the third-phase experiment, Covishield showed effectiveness of nearly 90%, whereas Covaxin has an effectiveness of about 80%. Both vaccination formulations in India have so far demonstrated satisfactory efficacy against numerous mutant variants of SARS-CoV-2. The efficacy of Covishield may be diminished if the structure of spike (S) protein changes dramatically in the future. In this situation, Covaxin might be still effective for such variants owing to its ability to produce multiple antibodies against various epitopes. This study reviews the comparative immunogenic and therapeutic efficacy of Covaxin and Covishield and also discussed the probable vaccination challenges in upcoming days.


Involvement of Peroxiredoxin-3, Thioredoxin-2, and Protein Deglycase-1 in Cypermethrin-Induced Parkinsonism.
Owing to its lipophilic nature, cypermethrin makes entry into the brain through the blood-brain barrier and causes severe damage to the nigrostriatal dopaminergic neurons after prolonged exposure. Following substantial accrual in the brain, cypermethrin induces the abnormal expression and accumulation of α-synuclein. Besides, cytochrome P450 2E1 (CYP2E1) causes free radical generation leading to lipid peroxidation in toxicant-induced parkinsonism. Conversely, 4-hydroxynonenal (4-HNE), a byproduct of lipid peroxidation, is known to contribute to neuronal damage. The current investigation aimed to explicate the participation of endogenous redox-sensitive proteins in cypermethrin-induced cellular and animal models of parkinsonism. The qualitative and quantitative expressions of selected redox-sensitive proteins were evaluated employing the standard procedures. Cypermethrin reduced the expression of peroxiredoxin 3 (Prx3), thioredoxin 2 (Trx2), and protein deglycase-1 (DJ-1). Knocking down of Prx3, Trx2, or DJ-1 further reduced the level of expression in the cypermethrin-treated group. Reduction in the expression of Prx3, Trx2, or DJ-1 was found to be associated with overexpression of α-synuclein and 4-HNE modification of proteins. Besides, cypermethrin increased the expression of CYP2E1, which was not altered after Prx3 or Trx2 knockdown. However, knocking down the DJ-1 augmented the level of CYP2E1 both in the cypermethrin-treated group and its respective control. The outcomes of the study demonstrate that cypermethrin reduces the level of Prx3, Trx2, and DJ-1 proteins. While the reduction in the expression of selected redox-sensitive proteins leads to α-synuclein overexpression and 4-HNE modification of proteins, DJ-1 attenuation is also linked with increased CYP2E1 expression, which in turn could lead to oxidative stress-mediated neuronal damage.


CT-derived radiomic analysis for predicting the survival rate of patients with non-small cell lung cancer receiving radiotherapy.
Radiomics provides an opportunity to minimize adverse effects and optimize the efficacy of treatments noninvasively. This study aims to develop a computed tomography (CT) derived radiomic signature to predict radiological response for the patients with non-small cell lung cancer (NSCLC) receiving radiotherapy. Total 815 NSCLC patients receiving radiotherapy were sourced from public datasets. Using CT images of 281 NSCLC patients, we adopted genetic algorithm to establish a predictive radiomic signature for radiotherapy that had optimal C-index value by Cox model. Survival analysis and receiver operating characteristic curve were performed to estimate the predictive performance of the radiomic signature. Furthermore, radiogenomics analysis was performed in a dataset with matched images and transcriptome data. Radiomic signature consisting of three features was established and then validated in the validation dataset (log-rank P = 0.0047) including 140 patient, and showed a significant predictive power in two independent datasets totaling 395 NSCLC patients with binary 2-year survival endpoint. Furthermore, the novel proposed radiomic nomogram significantly improved the prognostic performance (concordance index) of clinicopathological factors. Radiogenomics analysis linked our signature with important tumor biological processes (e.g. Mismatch repair, Cell adhesion molecules and DNA replication) associated with clinical outcomes. The radiomic signature, reflecting tumor biological processes, could noninvasively predict therapeutic efficacy of NSCLC patients receiving radiotherapy and demonstrate unique advantage for clinical application.


[Diagnostic value of determining carcino-embryonic antigens in the aqueous humor (author's transl)].
Diagnostic tapping of the anterior chamber to determine the CEA count in aqueous humor is discussed. Taking the serum aqueous humor barrier (filtration index) into account, it is possible to determine how much of this tumor antigen is produced locally. A case report illustrates the relevance of the method in a case of bilateral metastases of breast cancer in the choroid.


Correlation effects on the doped triangular lattice in view of the physics of sodium-rich NaxCoO2.
The peculiar correlation effects on the triangular lattice are studied by means of the rotationally invariant slave boson method in a cellular cluster approach. Hence nonlocal correlations are included in a short-range regime. Their impact for the single-band Hubbard model is studied at half filling, i.e., on the Mott transition, and with doping. Using the realistic band structure of NaxCoO2, we may also shed light on the cobaltate physics for x > or = 1/3, with the in-plane transition from antiferromagnetic tendencies towards the onset of ferromagnetism for a finite Hubbard U.


The interglenoid tubercle of the atlas is ancestral to lissamphibians.
Lissamphibians, represented today by frogs, salamanders, and caecilians, diverged deep in the tetrapod tree of life. Extensive morphological adaptations to disparate lifestyles have made linking extant lissamphibians to one another and to their extinct relatives difficult and controversial. However, the discovery of a feature on the atlas of the frog Xenopus laevis, may add to the small set of osteological traits that unite lissamphibians. In this study, we combine our observations of atlas development in X. laevis with a deep examination of atlantal interglenoid tubercle (TI) occurrence in fossil taxa. The TI is shown herein to occur transiently on the ossifying atlas of roughly one-third of X. laevis tadpoles but is absent in adults of this species. In ancestral character state estimations (ACSE), within the evolutionary context of lissamphibians as dissorophoid temnospondyls, this feature is found to be ancestrally shared among lissamphibians, its presence is uncertain in stem batrachians, and then the TI is lost in extant caecilians and frogs. However, our data suggests apparent TI loss around the origin of frogs may be explained by its ontogenetically transient nature. The only nonamphibian tetrapods with a TI are "microsaurs," and this similarity is interpreted as one of many convergences that resulted from convergent evolutionary processes that occurred in the evolution of "microsaurs" and lissamphibians. The TI is thus interpreted to be ancestral to lissamphibians as it is found to be present in some form throughout each extant lissamphibian clade's history.


Incidence and risk factors of the intraoperative localization failure of nonpalpable breast lesions by radio-guided occult lesion localization: a retrospective analysis of 579 cases.
The radio-guided occult lesion localization (ROLL) technique allows the identification of nonpalpable breast lesions by means of the preoperative, intratumoral injection of a radiotracer. Our study aimed to determine the incidence and risk factors of ROLL failure. We collected data about all women who underwent ROLL in our department from 2002 to 2009, focusing on patient characteristics such as breast size and density, lesion size, localization, histology, radiologist, and surgeon experience. Data were analyzed using R v2.10.1, considering p < 0.05 significant. A total of 579 ROLLs were performed on 555 women with a mean age of 58.7 (± 10.96) years. Incidence of ROLL failure at the first intervention was 4 % (23/579). Through monovariate analysis, ROLL failure was significantly influenced by stereotactic mammography-guided procedure, invasive tumors, pathological and radiological lesion size ≤ 5 mm, and the lesion's location in the central or upper breast quadrants. Through multivariate analysis, the most predictive factors for ROLL failure were as follows: lesion localization in the central quadrant, lesion radiological size ≤ 5 mm, and radiologist inexperience. The main risk factors for ROLL failure were the radiologist's inexperience, lesion size ≤ 5 mm, and its localization in the central subareolar quadrant, probably due to an unfavorable radiological and surgical reaching of the breast area.


A virus that can take the heat.
Foot-and-mouth disease virus shows remarkable thermal lability, a property that is a particular problem for vaccine preparations. In this issue of Structure, Rincón and colleagues show that electrostatic repulsion within the capsid is responsible for this lability, and they present rationally designed mutants with increased thermostability.


Elevation of oxygen release by nitroglycerin without an increase in blood flow in the hepatic microcirculation.
The effect of nitroglycerin on oxygen (O2) release in the microcirculation was investigated by examining single, unbranched hepatic sinusoids of rats using dual-spot microspectroscopy. Nitroglycerin significantly increased O2 release from erythrocytes flowing in the sinusoids. Differences in O2 saturation of hemoglobin per unit length of the sinusoid were significantly enhanced, while there were no significant changes in erythrocyte velocity, hemoglobin concentration or oxyhemoglobin flow into the sinusoids, or in regional hepatic blood flow measured with a laser tissue blood flow meter. No change was noted for hepatic O2 consumption measured in isolated liver perfused with hemoglobin-free oxygenated buffer. Isosorbide dinitrate showed a similar but slower effect. These findings suggest that nitroglycerin and isosorbide dinitrate enhance O2 release from erythrocytes without significantly increasing tissue blood flow.


Cloning and amplified expression in Streptomyces lividans of a gene encoding extracellular beta-lactamase from Streptomyces albus G.
A 4.9-kb DNA fragment containing the bla gene for the extracellular beta-lactamase (BLA) of Streptomyces albus G was cloned in Streptomyces lividans using the conjugative, low-copy-number plasmid pIJ61 as vector. No expression of bla was observed when this DNA fragment was introduced into Escherichia coli HB101 on a plasmid vector. A 1.5-kb PstI-SstI fragment containing the bla gene was cloned in S. lividans on the nonconjugative, high-copy-number plasmid pIJ702. A tenfold higher yield of BLA was obtained from S. lividans carrying this plasmid than from S. albus G grown under optimal production conditions. The BLA from the clone reacts with beta-iodopenicillanate according to a branched pathway which is characteristic of the original S. albus G BLA enzyme.


Esophageal stent placement for the treatment of acute intrathoracic anastomotic leak after esophagectomy.
Anastomotic leak after intrathoracic esophagogastrostomy remains a dreaded complication of esophagectomy. Traditional therapy has most often consisted of reoperative repair or observation and drainage, each prolonging hospitalization and the initiation of oral nutrition. This investigation summarizes our experiences treating these patients using an occlusive, removable esophageal stent. Over a 4-year period, patients found to have an acute, significant intrathoracic anastomotic leak after esophagectomy for benign or malignant disease undergoing surgery at or transferred to a single institution were offered endoluminal esophageal stent placement as initial therapy. Stents were placed endoscopically utilizing general anesthesia and fluoroscopy. Leak occlusion was confirmed by esophagram. Patients were followed until their stent was removed and their anastomotic leak had resolved. Seventeen patients had an esophageal stent placed for an anastomotic leak during the study period. Leak occlusion occurred in all 17 patients. One patient was found to also have a perforation of the gastric conduit and underwent operative repair. Fourteen patients (82%) were able to initiate oral nutrition within 72 hours of stent placement. Stent migration occurred in 3 patients (18%), requiring repositioning in 2 and replacement in 1. All stents were removed at a mean of 17±9 days after placement. Endoluminal esophageal stent placement is a safe and effective method for the treatment of an intrathoracic anastomotic leak after esophagectomy. This treatment resulted in rapid leak occlusion, provided the opportunity for earlier oral nutrition, and avoided the potential morbidity of reoperative repair or esophageal diversion.


Quantitative autoradiographic distribution and pharmacological characterization of (3H)buspirone binding to sections from rat, bovine and marmoset brain.
(3H)Buspirone binds with high affinity (KD = 11 nM) to sections from rat striatum. Spiroperidol, chlorpromazine, (+)-butaclamol and apomorphine are the most potent inhibitors of (3H)buspirone binding. Ketanserin, SCH 23390, serotonin and phentolamine are clearly less active. The regional distribution of (3H)buspirone binding in rat and marmoset brain is characterized by high silver grain densities in the olfactory tubercle, nucleus accumbens and striatum. In the hypophysis, the pars intermedia is strongly labeled. Within the hippocampal formation, slightly higher binding site densities are found in the dentate gyrus. The distribution pattern of binding sites in the dentate gyrus varies according to the species investigated. The data presented in this study permit the conclusion that (3H)buspirone binds with high affinity to dopamine 2 receptors but do not exclude additional binding to other types of receptors, e.g. 5-HT1 receptors. The interaction of buspirone with dopamine 2 receptors may be mainly responsible for its pharmacological profile.


What have we known so far about microplastics in drinking water treatment? A timely review.
Microplastics (MPs) have been widely detected in drinking water sources and tap water, raising the concern of the effectiveness of drinking water treatment plants (DWTPs) in protecting the public from exposure to MPs through drinking water. We collected and analyzed the available research articles up to August 2021 on MPs in drinking water treatment (DWT), including laboratory- and full-scale studies. This article summarizes the major MP compositions (materials, sizes, shapes, and concentrations) in drinking water sources, and critically reviews the removal efficiency and impacts of MPs in various drinking water treatment processes. The discussed drinking water treatment processes include coagulation-flocculation (CF), membrane filtration, sand filtration, and granular activated carbon (GAC) filtration. Current DWT processes that are purposed for particle removal are generally effective in reducing MPs in water. Various influential factors to MP removal are discussed, such as coagulant type and dose, MP material, shape and size, and water quality. It is anticipated that better MP removal can be achieved by optimizing the treatment conditions. Moreover, the article framed the major challenges and future research directions on MPs and nanoplastics (NPs) in DWT.


The reaction of Helix photosensitive neurons to light and cyclic GMP.
The effect of light and cyclic nucleotides (cGMP and cAMP) on a group of identified photosensitive neurons in Helix pomatia left parietal ganglion was examined. The onset of light induces in these cells a slow inward current shift associated with decrement of slope conductance. The reversal potential (Erev) of the light induced current (IL) and its changes due to altered extracellular concentration of potassium support the assumption that (IL) is due to suppression of K+ conductance. Elevation of intracellular concentration of cyclic GMP by adding 8-bromo-cGMP into the bathing solution or by injecting the nucleotide into the cell mimics, in all cases, the effect of light: it produces an inward current accompanied by decrement of slope conductance. The effect of elevation of cAMP was inconsistent. The I-V relations of IL and IcGMP follow a similar course and have a common Erev. The assumption that 3',5'-cyclic GMP is increased by light is also supported by comparing the effect of light and the cyclic nucleotide on the action potential. Both light and 8-bromo-cGMP broaden the action potential by increasing the voltage-dependent Ca2+ current.


Stimulation of osteoclast formation and bone resorption by glucocorticoids: Synergistic interactions with the calcium regulating hormones parathyroid hormone and 1,25(OH)2-vitamin D3.
Osteoporosis is a significant health problem, with skeletal fractures increasing morbidity and mortality. Excess glucocorticoids (GC) represents the leading cause of secondary osteoporosis. The first phase of glucocorticoid-induced osteoporosis is increased bone resorption. In this Chapter, in vitro studies of the direct glucocorticoid receptor (GR) mediated cellular effects of GC on osteoclasts to affect bone resorption and indirect effects on osteoblast lineage cells to increase the RANKL/OPG ratio and stimulate osteoclastogenesis and bone resorption are reviewed in detail, together with detailed descriptions of in vivo effects of GC in different portions of the skeleton in research animals and humans. Brief sections are devoted to contrasting functions of GC in osteonecrosis, vitamin D formation, in vitro and in vivo bone resorptive actions dependent on vitamin D receptor and vitamin D toxicity, as well as the molecular basis of GR action. Included are also more detailed assessments of the interactions of GC with the major calcium regulating hormones, 1,25(OH)2-vitamin D3 and parathyroid hormone, describing the in vitro increases in RANKL/OPG ratios, osteoclastogenesis and synergistic bone resorption that occurs when GC is combined with either 1,25(OH)2-vitamin D3 or parathyroid hormone. Additionally, a molecular basic for the synergistic interaction of GC with 1,25(OH)2-vitamin D3 is provided along with a suggested molecular basic for the interaction between GC and parathyroid hormone.


6-Mercapto-FAD and 6-thiocyanato-FAD as active site probes of phenol hydroxylase.
Recently, the synthesis and properties of several 6-substituted flavins as active site probes for flavoproteins have been reported (Ghisla, S., Massey, V., and Yagi, K. (1986) Biochemistry 25, 3282-3289). Here, we report results of experiments in which 6-thiocyanato-FAD and 6-mercapto-FAD have been substituted for the native flavin of phenol hydroxylase. The 6-SCN-FAD enzyme was converted spontaneously to the 6-mercaptoflavin form probably due to dissociation of flavin, followed by attack of external protein thiols. The pK alpha values of uncomplexed and phenol-bound 6-mercapto-FAD enzyme were determined. Both the spontaneously formed 6-mercapto-FAD enzyme and the enzyme reconstituted with preformed 6-mercapto-FAD were treated with a variety of thiol-specific reagents, and reaction rates were followed by spectroscopic means. Comparison with the corresponding rates found with free flavin suggested a high degree of accessibility to the flavin 6-position. Accessibility was somewhat decreased in the presence of phenol. Upon treatment with low concentrations of methyl methanethiosulfonate or N-ethylmaleimide (NEM), extremely rapid spectral changes were apparent. The former reaction, however, was reversed spontaneously within 2 h. Reaction with NEM was biphasic, with spectral changes consistent with the mechanism previously proposed (Steenkamp, D. J., McIntire, W., and Kenney, W. C. (1978) J. Biol. Chem. 253, 2818-2824), followed by a small absorbance decrease due to protein conformational changes. The NEM reaction is unusual, being easily reversed by addition of excess dithiothreitol.


DKK3, Downregulated in Invasive Epithelial Ovarian Cancer, Is Associated with Chemoresistance and Enhanced Paclitaxel Susceptibility via Inhibition of the β-Catenin-P-Glycoprotein Signaling Pathway.
Dickkopf-3 (DKK3), a tumor suppressor, is frequently downregulated in various cancers. However, the role of DKK3 in ovarian cancer has not been evaluated. This study aimed to assess aberrant DKK3 expression and its role in epithelial ovarian carcinoma. DKK3 expression was assessed using immunohistochemistry with tissue blocks from 82 patients with invasive carcinoma, and 15 normal, 19 benign, and 10 borderline tumors as controls. Survival data were analyzed using Kaplan-Meier and Cox regression analysis. Paclitaxel-resistant cells were established using TOV-21G and OV-90 cell lines. Protein expression was assessed using Western blotting and immunofluorescence analysis. Cell viability was assessed using the MT assay and 3D-spheroid assay. Cell migration was determined using a migration assay. DKK3 was significantly downregulated in invasive carcinoma compared to that in normal, benign, and borderline tumors. DKK3 loss occurred in 56.1% invasive carcinomas and was significantly associated with disease-free survival and chemoresistance in serous adenocarcinoma. DKK3 was lost in paclitaxel-resistant cells, while β-catenin and P-glycoprotein were upregulated. Exogenous secreted DKK3, incorporated by cells, enhanced anti-tumoral effect and paclitaxel susceptibility in paclitaxel-resistant cells, and reduced the levels of active β-catenin and its downstream P-glycoprotein, suggesting that DKK3 can be used as a therapeutic for targeting paclitaxel-resistant cancer.


Meta-analysis on the use of the Heartstring anastomotic device to prevent stroke in patients undergoing off-pump coronary artery bypass grafting.
Postoperative stroke is the Achilles' heel of coronary artery bypass surgery compared with percutaneous coronary intervention. In this meta-analysis, we sought to determine the efficacy of the Heartstring proximal anastomotic device to reduce the risk of postoperative stroke after off-pump coronary artery bypass grafting (OPCAB). Studies on the Heartstring device were identified by searching PubMed, Cochrane Library and Scopus up to November 2010. The results were expressed as pooled proportions (%) with 95% confidence interval (95% CI). Heterogeneity across the studies was evaluated by the I(2) test and a random effects model was used. Eighteen articles were pertinent with this issue and we were able to retrieve data on the Heartstring anastomotic device in OPCAB from eight studies. Three studies were prospective and routine epi-aortic ultrasound was used in three studies. A total of 819 patients were enrolled in these eight studies and six of them suffered stroke postoperatively. Cumulative analysis showed a pooled rate of immediate postoperative stroke after OPCAB with the use of Heartstring of 1.9% (95% CI 0.8-4.5, I(2)=23%). Sensitivity analysis including the only three studies evaluating patients with diseased ascending aorta as detected at epi-aortic ultrasound showed that a pooled rate of stroke was 3.2% (95% CI 0.8-11.9, I(2)=0%). Six studies reported on immediate postoperative mortality and the pooled mortality rate was 1.9% (95% CI 0.1-3.4). The results of this meta-analysis suggest that the risk of stroke after OPCAB may not be markedly reduced by the use of Heartstring device. On the other hand, a rather low rate of stroke was observed among patients with diseased ascending aorta indicating its potential value in these patients. Most of studies included in this meta-analysis were of poor methodological quality, and properly conducted prospective studies are needed to get more conclusive results on the safety and efficacy of Heartstring anastomosis device.


How longitudinal data can contribute to our understanding of host genetic effects on the gut microbiome.
A key component of microbiome research is understanding the role of host genetic influence on gut microbial composition. However, it can be difficult to link host genetics with gut microbial composition because host genetic similarity and environmental similarity are often correlated. Longitudinal microbiome data can supplement our understanding of the relative role of genetic processes in the microbiome. These data can reveal environmentally contingent host genetic effects, both in terms of controlling for environmental differences and in comparing how genetic effects differ by environment. Here, we explore four research areas where longitudinal data could lend new insights into host genetic effects on the microbiome: microbial heritability, microbial plasticity, microbial stability, and host and microbiome population genetics. We conclude with a discussion of methodological considerations for future studies.


Intestinal enzyme activity in lambs chronically infected with Trichostrongylus colubriformis: effect of anthelmintic treatment.
After twenty weeks of continuous dosing with Trichostrongylus colubriformis larvae substantial, but declining, numbers of worms had persisted in most of the lambs examined, although there were wide inter-individual variations. Mucosal lesions were found in the proximal small intestines of all the infected animals, their severity being directly related to worm burden. Representative brush border enzyme activities analysed in intestinal mucosal extracts from the same lambs showed differing responses. Alkaline phosphatase and glycyl-L-leucine dipeptidase were significantly depleted, whereas maltase activity was only marginally reduced, and leucine aminopeptidase activity was normal. Mucosal acetylcholinesterase activity was significantly elevated in the parasitised animals and, interestingly in view of the postulated role of this enzyme in nematode pathogenicity, the level of activity was directly correlated with individual worm burdens. Intestinal trypsin and chymotrypsin activities were unaffected and the level of superoxide dismutase, an enzyme associated with the inflammatory response, was normal. There were also no consistent changes in the mucosal activities of several enzymes including lactic dehydrogenase, creatine phosphokinase, aldolase, and glutamic oxaloacetate transaminase, whose leakage from damaged or necrotic tissues has been well defined in terms of the concomitant increase in their activity in the circulation. Lambs treated orally with fenbendazole five and/or ten weeks before slaughter either in the presence or absence of continued larval intake, had negligible worm burdens, and showed little evidence of intestinal damage at post mortem. Brush border enzyme levels, with the exception of alkaline phosphatase and, in two cases dipeptidase, were normal in these animals. The activity of alkaline phosphatase was approximately double that in the continuously infected, untreated lambs, but remained markedly lower than in the uninfected controls. The activities of the other enzymes studied, including acetylcholinesterase, were within the control range. In summary, in chronic trichostrongylosis even relatively low nematode burdens were associated with marked pathological and biochemical damage in the intestine with both lesion severity and mucosal acetylcholinesterase activity being directly related to worm numbers. Although morphological integrity was completely restored after anthelmintic treatment, the persistent low activity of brush border alkaline phosphatase coupled with the enzymological findings in untreated, infected animals suggests that recovery of the full functional capability of the intestinal mucosa may take longer.


Treatment with a spore-based probiotic containing five strains of Bacillus induced changes in the metabolic activity and community composition of the gut microbiota in a SHIME® model of the human gastrointestinal system.
MegaSporeBiotic™ is an oral, spore-based probiotic comprised of five Bacillus spp. (Bacillus indicus HU36, Bacillus subtilis HU58, Bacillus coagulans SC208, Bacillus licheniformis SL307, and Bacillus clausii SC109). The effects of MegaSporeBiotic™ on gut microbiota activity and community composition were evaluated for the first time using an in vitro model of the human gastrointestinal tract, the simulator of the human intestinal microbial ecosystem (SHIME®), under healthy conditions. Following a stabilization period and a control period (2 weeks each), the reactor feed was supplemented with daily MegaSporeBiotic™ for 3 weeks (treatment period). Changes in microbial community activity and composition between the control and treatment periods were evaluated for each colon compartment (ascending [AC], transverse [TC], and descending colon [DC]). Propionate levels increased significantly in the TC (week 2, P = 0.02; week 3, P = 0.0019) and DC (week 2, P = 0.03) with treatment while lactate levels significantly decreased in the TC (week 3, P = 0.03). Ammonium levels were significantly decreased during the final week of treatment (TC, P = 0.02; DC, P = 0.03). Overall, Akkermansia muciniphila, Bifidobacteria spp., and Firmicutes increased with treatment while Lactobacillus spp. and Bacteroidetes decreased. The Firmicutes:Bacteroidetes ratio increased with treatment in the AC compartment. MegaSporeProbiotic™ treatment resulted in changes in metabolism and increased bacterial diversity.


Phase II evaluation of diaziquone (CI-904, AZQ) in the treatment of human malignant glioma.
Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22-69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m2 I.V. (10 min.) X 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: greater than 50%, 4: 25-50%), and 1 disease stabilization (less than 25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma.


Left atrial myxoma in a child with unique presentation: chest pain.
We present a 16-year-old girl who presented with chest pain. Given her obesity and positive family history, she was felt to have atherosclerotic heart disease. However, an echocardiogram showed an atrial myxoma, which prompted surgical excision. This case supports the routine use of echocardiography and widened differential diagnosis when presented with pediatric chest pain.


Rolling hairpin model for replication of parvovirus and linear chromosomal DNA.
A novel, quasicircular scheme is proposed for the replication of parvovirus DNA. Daughter strands are initiated after the copying and rearrangement of a terminal palindromic sequence, a process termed 'hairpin transfer'. Such a process may be involved in the replication of other viruses and host cell DNA.


Domestic violence in the coronavirus disease 2019 era: Insights from a survivor.
Amid the coronavirus disease 2019 (COVID-19) pandemic, there has been an alarming rise in domestic violence worldwide. Factors believed to be fueling this escalation in domestic violence include increasing social confinement at home during lockdowns and mounting stress levels from unemployment that have resulted from the economic uncertainties of these times. This contribution explores some of the challenges faced by physicians in clinically assessing victims of domestic violence during the COVID-19 era. One such challenge is the increased reliance on telemedicine during the pandemic, a medium of communication that offers a narrower clinical view of patients than is what is usually provided by an in-person examination. In this contribution, we offer suggestions on how best to screen for domestic violence, whether through telemedicine or during an in-person encounter. The history and physical findings that suggest domestic violence are reviewed along with recommendations on how to make the clinical examination more sensitive and compassionate to the needs of the victims. One of the authors of this contribution (L.C.H.) is herself a survivor of domestic violence and has courageously shared, in these pages, details of her harrowing near murder by an abusing husband. From this case history, it is hoped that readers will gain wider insights into what domestic violence means from the perspective of a victim and how we can better help save victims from this widespread and devastating social problem.


Abscess after a laparoscopic appendectomy presenting as low back pain in a professional athlete.
A professional baseball player presented to the orthopaedic clinic for a preseason assessment because of continued lumbar spine and flank pain. He had a laparoscopic appendectomy for a perforated appendix 8 months before his presentation. He was able to finish the previous season with only mild limitation. He presented with back pain that limited his activity. His examination was nonlocalizing, but subsequent computed tomography revealed a hepatic abscess. The abscess was drained; he was treated with intravenous antibiotics; and his symptoms resolved.


A quantitative in-vivo MR imaging study of brain dehydration in diabetic rats and rats treated with peptide hormones.
The main aim of the study was to evaluate the combination of quantitative diffusion, T2 and Magnetisation Transfer Imaging of brain water homeostasis using untreated diabetes as an animal model of brain dehydration. In addition, experimental groups of diabetic rats treated with insulin and insulin-like growth factor (IGF-I) and normal rats treated with IGF-I and growth hormone were studied using the same MR imaging protocol. Untreated diabetes caused weight reduction and an increase in water intake, indicating a general body dehydration linked to chronic blood hyperosmolarity. In the investigated cortical gray matter untreated diabetes caused a significant reduction in the apparent diffusion coefficient of water (ADC) and an increase in T2 relaxtivity (R2) when compared to a control group. No significant changes were observed for the calculated magnetisation transfer parameters Kfor and T1sat. Both ADC and R2 normalized after appropriate insulin treatment whereas only ADC was normalized after IGF-I treatment. IGF-I treatment of normal rats caused significantly higher rate of increase in body weight compared to normal controls. There were, however, no significant changes in ADC, R2 nor the magnetisation transfer parameters measured in the cortical gray matter of the IGF-I treated normal rats. In conclusion, we found that changes in brain water homeostasis during diabetes were detected by quantitative MR imaging, and that the dehydration induced by diabetes was normalized by insulin treatment but not by IGF-I.


Characterization of Pediococcus acidilactici postbiotic and impact of postbiotic-fortified chitosan coating on the microbial and chemical quality of chicken breast fillets.
This study was carried out to characterize antioxidant activity, total phenolic content, and the phenolic and flavonoids profile of postbiotic of Pediococcus acidilactici and to evaluate the effects of postbiotics (10% and 50%) alone and in combination with chitosan coating (1%) on the microbial and chemical quality of chicken breast fillets during storage at 4 °C. Antioxidant activity and total phenolic content of the postbiotics were found to be 1291.02 ± 1.5 mg/L TEAC and 2336.11 ± 2.36 mg/L GAE, respectively. The most abundant phenolic was vanillic acid, followed by t-caffeic, gallic, and caftaric acids. The postbiotic-chitosan (50% + 1%) combination decreased L. monocytogenes and S. Typhimurium counts by 1.5 and 2.1 log10 CFU/g, respectively, compared to the control (P < 0.05). This combination decreased the total viable count (TVC), lactic acid bacteria (LAB), and psychrotrophic bacteria count compared to the control (P < 0.05). No differences were found in thiobarbituric acid (TBA) values among the samples during storage (P > 0.05). Postbiotic treatment did not significantly change the pH values and color properties of the breast fillets (P > 0.05). Postbiotic-chitosan combinations extended the shelf-life by up to 12 days compared to the control. In conclusion, the postbiotic-chitosan combination can be used to preserve and improve the microbial quality of chicken meat products.


The use of differential scanning calorimetry to study drug-membrane interactions.
Differential-scanning calorimetry is a thermodynamic technique widely used for studying drug-membrane interactions. This chapter provides practical examples on this topic, highlighting the caution to be taken in analyzing thermal data as well as scientific information that can be derived by the proper use of the technique. An example is given using model bilayers containing high concentration of the anesthetic steroid alphaxalone. It is shown that the breadth of the phase transitions and the maximum of the phase-transition temperature of the bilayer depend on the equilibration conditions before acquiring the thermal scan. In addition, the quality of the thermo-gram depends on its perturbation and incorporation effects; for dissecting these effects, a complementary technique such as solid-state nuclear magnetic resonance spectroscopy is necessary. Differential-scanning calorimetry is a useful technique to study the interdigitation effect of a drug by monitoring DeltaH changes. Cholesterol, a main constituent of membrane bilayers, appears to disrupt the interdigitating effect. In general, the thermal effects of the drug incorporated into a membrane bilayer depends on the drug stereoelectronic properties.


Residue-Specific Force Field Improving the Sample of Intrinsically Disordered Proteins and Folded Proteins.
Intrinsically disordered proteins and regions (IDPs and IDRs) have attracted increasing interest with their abundance in the human proteome and critical roles in various human diseases. However, the characterization of structural dynamics of IDPs presents a challenge to general experimental methods due to their highly heterogeneous ensembles. Molecular dynamics (MD) simulation has been an alternative method with recent advances in computation power. Nevertheless, it is imperative that eligible predictions are determined by a highly precise force field, but traditional force fields sometimes give a collapsed disorder structure and overestimate the stability of IDPs. Here, we present a novel residue-specific force field, OPLSIDPSFF, to correct backbone dihedral terms for all 20 natural amino acids based on OPLS-AA/L. Extensive tests of 11 IDPs and two short peptides show that the simulated chemical shifts and J-coupling with the OPLSIDPSFF force field are in quantitative agreement with those from NMR experimental observables and are more accurate than the base generic force field. The influences of solvent models were also investigated, and it was found that TIP4P-D water had positive effects on limited observables. Furthermore, OPLSIDPSFF can still be used to model structural and dynamic properties of two tested folded proteins and fast-folding proteins. These findings confirm that the newly developed residue-specific force field OPLSIDPSFF can improve the conformer sampling of intrinsically disordered and folded proteins.


Middle-low-temperature oxidation and adsorption of arsenic from flue gas by Fe-Ce-based composite catalyst.
Fe-Ce-based composite catalysts were prepared and used for As2O3 catalytic oxidation and adsorption. They were characterized by XRD, BET, H2-TPR, Raman, SEM and XPS. The results suggests Fe, La and Zr can be partially doped into CeO2 lattice to form solid solutions. Compared with pure Fe2O3, the composite catalysts have stronger low-temperature reducibility, especially La3+ doping is beneficial to the formation of more low-temperature active sites. Raman and XPS measurements disclose the presence of oxygen vacancy and surface adsorbed oxygen in composite catalysts and these are more prominent in FeCeLaO. Ce3+ ratio increases to 18.30% after reaction, which confirms part of Ce4+ can participate in As2O3 oxidation and be reduced to Ce3+. The oxidation and adsorption capacity for As2O3 were investigated at different temperatures and O2 concentrations. The results show FeCeLaO exhibits excellent activity at middle-low-temperatures of 200-400 °C, the oxidation efficiency of As2O3 can reach 100%, the total adsorbed arsenic at 400 °C reaches 583.7 μg/g, which is 1.8 times of pure Fe2O3 at 600 °C. As2O3 oxidation mechanism over FeCeLaO with/without O2 was proposed through the Mars-Maessen theory with the aid of surface-active oxygen. The abundant oxygen vacancy defects and active chemisorbed oxygen play important roles and guarantee an efficient As2O3 oxidation, which is also the essential reason why the composite catalysts can effectively oxidize and adsorb As2O3 at middle-low-temperature of 200-400 °C, while pure Fe2O3 can only be at high temperature of 600-700 °C.


Decreased indoleamine 2,3-dioxygenase expression in dendritic cells and role of indoleamine 2,3-dioxygenase-expressing dendritic cells in immune thrombocytopenia.
Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO(+) DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO(+) DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO(+) DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.


Item to decision mapping in rapid response learning.
Repeated classification of a visually presented stimulus rapidly leads to a form of response learning that bypasses the original evaluation in favor of a more efficient response mechanism. In two experiments, we examined the level of input and output representations that make up this form of learning. In Experiment 1, alterations in the finger mapping of the output response had no effect on the expression of response learning, demonstrating that a classification decision, not motor output, is associated with repeated items. In Experiments 2A and 2B, we tested whether response learning would transfer across different visual exemplars of a studied item. There was no evidence of transfer to different visual exemplars, even when these exemplars were judged to be highly visually similar. Taken together, these results indicate that response learning consists of the formation of an association between a specific visual representation and a classification decision.


Surgical repair of superoinferior ventricles: experience with 3 patients.
Superoinferior ventricles are a rare anomaly characterized by a horizontal ventricular septum and a hypoplastic right ventricular sinus localized anterosuperiorly to the left ventricle. This anomaly frequently is accompanied by malformation of the atrioventricular valves. A large ventricular septal defect is always present, and anomalies of the ventriculoarterial relations are common. The results of surgical repair of this complex lesion have been poor. Our recent surgical experience with 3 patients, 2 of whom are well 36 and 38 months postoperatively, suggests a hopeful outcome for the repair of this complex anomaly. The surgical approach was different in each of the 3 patients, demonstrating the need for a precise echocardiographic and angiocardiographic preoperative description of the cardiac anatomy to appropriately repair the multiple variants of this complex anomaly.


Concentrations of selected essential and non-essential elements in arctic fox (Alopex lagopus) and wolverines (Gulo gulo) from the Canadian Arctic.
Arctic fox (Alopex lagopus) and wolverine (Gulo gulo) tissues were collected in the Canadian Arctic from 1998 to 2001 and analyzed for various essential and non-essential elements. Several elements (Ag, Al, As, B, Ba, Be, Co, Cr, Mo, Ni, Sb, Sn, Sr, Tl, U and V) were near or below the detection limits in >95% arctic fox and wolverine samples. Concentrations of Cd, Cu, Fe, total Hg (THg), Mn, Pb, Se and Zn were quantifiable in >50% of the samples analyzed and reported herein. Hepatic elemental concentrations were not significantly different among arctic foxes collected at Ulukhaqtuuq (Holman), NT (n=13) and Arviat, NU (n=50), but were significantly greater than concentrations found in wolverine liver from Kugluktuk (Coppermine), NU (n=12). The mean (+/-1 S.E.) concentrations of Cd in kidney were also significantly greater in arctic fox (1.08+/-0.19 microg g(-1) wet wt.) than wolverine (0.67+/-0.18 microg g(-1) wet wt.). However, mean hepatic Cu concentrations (Ulukhaqtuuq: 5.5+/-0.64; Arviat: 7.1+/-0.49 microg g(-1) wet wt.) in arctic foxes were significantly lower than in wolverines (32+/-3.3 microg g(-1) wet wt.). Hepatic total Hg (THg) concentrations in arctic fox from this study were not significantly different from specimens collected in 1973, suggesting that THg concentrations have not changed dramatically over the past 30 years. The mono-methylmercury (MeHg) concentrations in selected (n=10) arctic fox liver samples from Arviat (0.14+/-0.07 microg g(-1) wet wt.) comprised 14% of THg. While the molar concentrations of THg were correlated with Se in arctic foxes and wolverines, the hepatic Hg/Se molar ratios were consistently lower than unity; suggesting that Se-mediated detoxification pathways of Hg are not overwhelmed at current exposure.


Magnetization filters: applications to NMR imaging of elastomers.
The general Fourier scheme for parameter selective imaging is subdivided into three periods: A preparation period for application of magnetization filters, an evolution period for space encoding, and a detection period for acquisition of the spectroscopic dimension. Depending on sample requirements and available time, the first and the last period can be omitted. Preparation of the initial magnetization for space encoding by appropriate filters is a powerful and time-saving way to introduce parameter-selective image contrast. This is illustrated by filters of molecular dynamics, which are sensitive to segmental motion in different time windows for contrast enhancement in composite and aged elastomers. Further contrast amplification is achieved by computing the difference of images acquired with different filter settings.


Phylogeny and taxonomy of the genera of Erysiphaceae, part 5: Erysiphe (the "Microsphaera lineage" part 1).
In this contribution, we offer the fifth installment of a series focusing on the phylogeny and taxonomy of powdery mildews. This paper is the second segment evaluating the genus Erysiphe. The first treatment of Erysiphe focused on phylogenetically basal species in the "Uncinula lineage." This research presents a phylogenetic-taxonomic assessment of species that form the group previously referred to as the "Microsphaera lineage." Given the size of the group, we split the treatment of this lineage of Erysiphe species into two parts based on their phylogenetic placement. Phylogenetic trees based on ITS+28S data are supplemented by sequences of additional markers (CAM, GADPH, GS, RPB2, and TUB). Included in the analysis of the Microsphaera lineage is the "Erysiphe aquilegiae complex" (group, clade, cluster), which encompasses sequences obtained from an assemblage of Erysiphe species with insufficient resolution in rDNA analyses. Attempts have been made to resolve this group at the species level by applying a multilocus approach. A detailed discussion of the "Erysiphe aquilegiae complex" is provided. Sequences are provided for the first time for several species, particularly North American species, such as Erysiphe aggregata, E. erineophila, E. parnassiae, and E. semitosta. Ex-type sequences for Microsphaera benzoin and M. magnusii have been retrieved. Alphitomorpha penicillata, Microsphaera vanbruntiana, and M. symphoricarpi are epitypified with ex-epitype sequences. The new species Erysiphe alnicola, E. deutziana, E. cornigena, E. lentaginis, and E. sambucina are described, the new combinations E. lauracearum, E. passiflorae, and E. sambucicola are introduced, and the new name E. santali is proposed.


Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission.
Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency.In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments.Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis.Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated.For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved.Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course.


Optimisation of a TALE nuclease targeting the HIV co-receptor CCR5 for clinical application.
Disruption of the C-C-Chemokine-receptor-5 (CCR5) gene induces resistance towards CCR5-tropic HIV. Here we optimised our previously described CCR5-Uco-TALEN and its delivery by mRNA electroporation. The novel variant, CCR5-Uco-hetTALEN features an obligatory heterodimeric Fok1-cleavage domain, which resulted in complete abrogation of off-target activity at previously found homodimeric as well as 7/8 in silico predicted, potential heterodimeric off-target sites, the only exception being highly homologous CCR2. Prevailing 18- and 10-bp deletions at the on-target site revealed microhomology-mediated end-joining as a major repair pathway. Notably, the CCR5Δ55-60 protein resulting from the 18-bp deletion was almost completely retained in the cytosol. Simultaneous cutting at CCR5 and CCR2 induced rearrangements, mainly 15-kb deletions between the cut sites, in up to 2% of T cells underlining the necessity to restrict TALEN expression. We optimised in vitro mRNA production and showed that CCR5-on- and CCR2 off-target activities of CCR5-Uco-hetTALEN were limited to the first 72 and 24-48 h post-mRNA electroporation, respectively. Using single-cell HRMCA, we discovered high rates of TALEN-induced biallelic gene editing of CCR5, which translated in large numbers of CCR5-negative cells resistant to HIVenv-pseudotyped lentiviral vectors. We conclude that CCR5-Uco-hetTALEN transfected by mRNA electroporation facilitates specific, high-efficiency CCR5 gene-editing (30%-56%) and it is highly suited for clinical translation subject to further characterisation of off-target effects.


A low-cost gradient system for high-performance liquid chromatography. Quantitation of complex pharmaceutical raw materials.
A device is described that makes use of an eight-port motor valve to generate step gradients on the low-pressure side of a piston pump with a low dead volume. Such a gradient device with an automatic control unit, which also permits repetition of previous steps, can be built for about half the cost of a gradient system with two pumps. Applications of this gradient unit to the separation of complex mixtures of glycosides and alkaloids are discussed and compared with separations systems using two high-pressure pumps. The gradients that are used on reversed-phase material with solvent mixtures of water and completely miscible organic solvents are suitable for quantitative routine control of pharmaceutical products. The reproducibility of retention data is excellent over several months and, with the use of loop injectors, major components can be determined quantitatively with a reproducibility of better than 2% (relative standard deviation). The step gradient selector valve can also be used as an introduction system for very large sample volumes. Up to 11 can be injected and samples with concentrations of less than 1 ppb can be determined with good reproducibilities.


Sequence analysis of the ADE2 gene coding for phosphoribosylaminoimidazole carboxylase in Schwanniomyces occidentalis.
We have determined the nucleotide sequence of a 3.3 kb fragment containing the gene (ADE2) encoding phosphoribosylaminoimidazole carboxylase (AIRC) from the yeast Schwanniomyces occidentalis. Translation of a 1671 bp open reading frame predicts a protein of 557 amino acids which has significant homology to AIRC from Saccharomyces cerevisiae and Schizosaccharomyces pombe. The 5' untranslated region of the S. occidentalis gene contains a sequence corresponding to the consensus binding site of the S. cerevisiae transcription regulatory proteins GCN4, BAS1 and BAS2.


Changes in steroidogenic enzyme and steroidogenic acute regulatory protein messenger RNAs in ovarian follicles during ovarian development of rainbow trout (Oncorhynchus mykiss).
In salmonid fishes, estradiol-17beta (E2) and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) are the major steroid hormones controlling oocyte growth (vitellogenesis) and final maturation (resumption of meiosis). The aim of this study was to determine changes in mRNAs encoding ovarian steroidogenic enzymes and steroidogenic acute regulatory protein (StAR) during ovarian development in female rainbow trout. We analyzed the levels of mRNAs encoding the enzymes P450 side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17alpha-hydroxylase/C17-C20 lyase (P450c17), aromatase (P450arom), and carbonyl reductase-like 20beta-hydroxysteroid dehydrogenase (20beta-HSD), and StAR in developing ovarian follicles of rainbow trout by Northern blot, in relation to the pattern of serum E2 and 17,20beta-P levels. Serum E2 levels were elevated during vitellogenesis and decreased prior to an ovulatory increase in 17,20beta-P. Transcripts for P450scc and P450c17 increased in late vitellogenic follicles, then decreased in post-ovulatory follicles. In contrast, P450arom transcripts were abundant during vitellogenesis and then declined as vitellogenesis was completed and were barely detectable in post-ovulatory follicles. 3beta-HSD mRNA levels increased in late vitellogenic follicles and were maintained at high levels in post-ovulatory follicles. 20beta-HSD and StAR mRNA levels were very low during vitellogenesis, and then strongly increased during late vitellogenesis to a peak in post-ovulatory follicles. These results indicate that the expression of genes encoding steroidogenic enzymes and StAR change dynamically, dependent on the developmental stages of rainbow trout follicles. The acquisition of the ability of later stage follicles to rapidly produce large quantities of 17,20beta-P appears to be supported by a preparatory increase in mRNAs encoding StAR and other steroidogenic enzymes.


Accelerating the self-pay revenue cycle through e-billing and e-payment.
As consumers assume a larger percentage of their healthcare costs, electronic payment systems can provide time savings on the front end and reduce bad consumer debt on the back end. Proponents say the systems increase staff efficiency and add a "green element to paper-strewn offices.


Association between neighbourhood socioeconomic characteristics and high-risk injection behaviour amongst injection drug users living in inner and other city areas in Montréal, Canada.
Area-level socioeconomic conditions are associated with epidemic rates of viral hepatitis and HIV amongst urban injection drug users (IDUs), but whether specific socioeconomic markers are uniformly related to IDU outcomes across different urban environments is unclear. We evaluated whether injection behaviour is differentially related to neighbourhood socioeconomic characteristics for IDUs in inner city vs. surrounding urban areas. The study population was 468 active IDUs on the Island of Montréal. Neighbourhoods were represented as 500m radius buffers around individual IDU dwelling places. High-risk injection behaviour (HRIB) was defined dichotomously. Relations between neighbourhood socioeconomic disadvantage (percentage households below low-income cutoff), neighbourhood educational attainment (percentage adults with university degree), and HRIB were assessed using multivariate logistic regression. Stratified analyses were conducted for inner city IDUs (n=219), and those in surrounding areas (n=249). Similar proportions of IDUs in inner city and surrounding areas reported HRIB. Neighbourhood socioeconomic characteristics were not associated with HRIB for IDUs in surrounding areas. For inner city IDUs, those in socioeconomically disadvantaged neighbourhoods were more likely to practice HRIB (OR 4.34; 95% CI 1.15-16.35). Conversely, inner city IDUs residing in lower educational attainment neighbourhoods had a lower odds of HRIB (OR 0.41; 95% CI 0.21-0.80). HRIB did not vary according to urban environment but for inner-city IDUs was differentially related to socioeconomic markers. Associations between HRIB and neighbourhood socioeconomic disadvantage and lower educational attainment, positive and negative, respectively, indicate that adverse socioeconomic circumstances are not related to a uniformly greater likelihood of HRIB.


Molecular analysis of GALT gene in Argentinian population: Correlation with enzyme activity and characterization of a novel Duarte-like allele.
Classical galactosemia is an autosomal recessive inherited metabolic disorder caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. GALT enzyme deficiency leads to the accumulation of galactose-1-phosphate in various organs, causing hepatic, renal and cerebral impairment. Over 300 mutations have been reported in the GALT gene. The aim of this study was to describe molecular characterization of GALT gene in Argentinian patients with decreased GALT activity, and to correlate molecular results with enzyme activity. 37 patients with enzyme activity below 6.3 μmol/h/g Hb (35% of normal value) were included. GALT activity was measured on red blood cells. DNA was extracted from peripheral blood. p.Gln188Arg mutation was studied by PCR-RFLP and, on samples negative or heterozygous, GALT gene was sequenced. In vivo splicing analysis of the GALT gene was performed on RNA extracted from leukocytes of one patient. 14 different sequence variations were identified among 72 unrelated alleles. The two most common disease-causing mutations were p.Gln188Arg (24/72) and p.Lys285Asn (9/72). Three novel mutations were detected. One of them, c.688G>A, caused partial skipping of exon 9 of the GALT gene. Enzyme activity correlated with GALT genotype in 36 of the 37 patients. This is the first report of sequence variations in the GALT gene in the Argentinian population. This study highlights the contribution of the molecular analysis to the diagnosis of Galactosemia and reveals c.688G>A as a novel Duarte-like variant, with a high prevalence in our population.


Thoracoscopic partial pericardiectomy in the diagnosis and management of pericardial effusion.
An effort was made to present our experience with thoracoscopy in the diagnosis and management of pericardial effusions. Twenty-two partial pericardiectomies were performed with the thoracoscopic approach in patients with pericardial effusions, the etiology of which was uremic (n = 7), neoplastic (n = 8), idiopathic (n = 5), septicemia (n = 1), and postpericardiotomy (n = 1). All cases had grade III-IV/IV radiological cardiomegaly and ultrasonographic confirmation of the effusion. We found hemodynamic compromise in 17 patients. The operation, requiring the insertion of three trocars, enabled us to remove a large part (approximately 6 x 10 cm) of the left anterolateral side of the pericardium and aspirate the effusion contents for diagnostic and therapeutic purposes. In five cases we found coexisting pleural effusions. The pericardial effusion had a mean volume of 817 ml, which was serous in 11 cases, hematic in six, serohematic in four, and purulent in one. Cytology of the pericardial effusion was positive for neoplasia in four cases (one pulmonary neoplasia, two breast carcinomas, and one lymphoma). We observed conversion to grade I/IV cardiomegaly in 16 cases and a return to normality in the other six, with the absence of ultrasonographic effusion in all cases. There was no recurrence during the mean follow-up period of 20.5 months (range: 2-47). The thoracoscopic management of pericardial effusions is a simple and effective technique that allows us to create a large pericardial window that drains the effusion definitively, determines its etiology, and explores and treats coexisting pleural lesions, all without recurrences.


Mucin histochemistry of virus-induced duodenal adenomas in guinea fowl.
The type of mucoproteins in virus-induced duodenal adenomas in guinea fowl were compared with those in the normal duodenal mucosa. The mucin-producing cells in the latter contained a mixture of acid and neutral mucins. Neutral and sulphomucins prevailed in the crypts and in the lower part of the villi, while the amount of the sialomucins increased progressively toward the tip of the villi. In the adenomas, goblet cells were more numerous and were unevenly distributed. In their mucin profile the deeply located tumor glandular structures resembled normal crypts and lower parts of the villi and superficial portions of the adenomas were similar to the upper part of the villi. Qualitative changes in the mucin secretion with deviation from the normal vertical distribution of mucin types were rarely observed. The histochemical study carried out supplemented the histological characterization of the virus-induced duodenal adenomas and contributed to the elucidation of some aspects of their histogenesis.


Indomethacin treatment of eighteen patients with Sweet's syndrome.
The standard treatment for Sweet's syndrome (acute febrile neutrophilic dermatosis) is oral corticosteroids. Despite a good initial response, the disease is characterized by frequent relapses. Our purpose was to test the therapeutic effect of the nonsteroidal antiinflammatory drug indomethacin on Sweet's syndrome. All patients with Sweet's syndrome observed during a 4-year period were given indomethacin, 150 mg/day for the first week and 100 mg/day for two additional weeks. The therapeutic response was assessed on days 4, 7, 14, 30, and 180. Seventeen of 18 patients had a good initial response; fever and arthralgias were markedly attenuated within 48 hours and eruptions cleared between 7 and 14 days. The remaining patient's cutaneous lesions continued to develop and were successfully treated with prednisone (1 mg/kg/day). The only side effect of indomethacin treatment was epigastric pain in two patients. No patient had a relapse after discontinuation of indomethacin (mean followup, 20.1 months). Indomethacin is a safe and effective treatment for Sweet's syndrome.


The association of clinical variables and filter design with carotid artery stenting thirty-day outcome.
Patient and device selection are important for the success of carotid artery stenting (CAS). We hypothesize that distal protection filter (DPF) design characteristics that minimize blood flow resistance and maximize capture efficiency are associated with the absence of transient ischemic attack (TIA), stroke and neurologic-related death after 30 days. Records from 208 patients were reviewed retrospectively. Filter design characteristics were quantified previously in our laboratory. The association between risk factors and design characteristics with 30-day outcome was quantified using univariate analysis. The 30-day all-cause stroke and death rate was 8.7% (asymptomatic: 7.7%, symptomatic: 10.6%). Five DPFs were used in the study: Accunet (41.3%), Angioguard (33.2%), FilterWire (24%), Emboshield (1%), and Spider (.5%). Diabetes (P = .04) and prior carotid endarterectomy (CEA, P = .03) were associated with adverse outcome. Prior stroke (P = .01) and prior CEA (P = .04) were significant for peri-procedural stroke. Design characteristics such as capture efficiency were associated with favorable outcomes. Patients with prior CEA or stroke are more likely to have unfavorable CAS outcomes after 30 days. Filters with high capture efficiency may yield the best clinical results. Analysis of the effect of design characteristics on CAS outcome should aid the design of future devices.


Virtual surgical planning and 3D printing in pediatric musculoskeletal oncological resections: a proof-of-concept description.
Patient-specific models may have a role in planning and executing complex surgical procedures. However, creating patient-specific models with virtual surgical planning (VSP) has many steps, from initial imaging to finally realizing the three-dimensional printed model (3DPM). This manuscript evaluated the feasibility and potential benefits of multimodal imaging and geometric VSP and 3DPM in pediatric orthopedic tumor resection and reconstruction. Twelve children with Ewing's sarcoma, osteosarcoma, or chondrosarcoma were studied. Computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) were acquired as the standard-of-care. Bony and soft tissue components of the tumor and the adjacent bone were segmented to create a computer-generated 3D model of the region. VSP used the computer-generated 3D model. The Objet350 Stratasys™ polyjet printer printed the final physical model used for pre-surgical planning, intraoperative reference, and patient education. Clinical impact, the utility of the model, and its geometric accuracy were assessed. Subjectively, using the patient-specific model assisted in preoperative planning and intra-operative execution of the surgical plan. The mean difference between the models and the surgical resection was -0.09 mm (range: -0.29-0.45 mm). Pearson's correlation coefficient (r) of the cross-sectional area was -0.9994, linear regression r2 = 0.9989, and the Bland Altman plot at 95% confidence interval showed all data within boundaries. We studied the geometric accuracy, utility and clinical impact of VSP and 3DPM produced from multi-modal imaging studies and concluded 3DPM accurately represented the patients' tumor and proved very useful to the surgeon in both the preoperative surgical planning, patient and family education and operative phases. Future studies will be planned to evaluate surgery procedure duration and other outcomes.


Expression analysis of circulating miR-146a and miR-155 as novel biomarkers related to effective immune responses in human cystic echinococcosis.
Cystic echinococcosis, an important zoonotic disease, is caused by Echinococcus granulosus. MicroRNAs are a small group of single-stranded noncoding RNAs, which play an effective role in biological processes. This study aimed at comparing the expression levels of miR-146a and miR-155 in the plasma of patients with hydatidosis and healthy individuals. A group of 20 patients with hydatid cyst formed a study group and 20 healthy individuals with no known chronic diseases formed a control group. Plasma samples were collected from hydatidosis patients as well as sex- and age-matched healthy volunteers. After that, RNA extraction and cDNA synthesis were done and the expression levels of miR-146a and miR-155 were determined by quantitative real-time polymerase chain reaction (PCR) for both groups. The results indicated that the level of miR-146a increased in all patients with hydatidosis compared to the control group. Also, the level of miR-155 increased in all hydatidosis patients, but no correlation was observed in the level of miR-155 between the two groups. The results also revealed that miR-146a and miR-155 upregulation in the plasma leads to the development of novel biomarkers for echinococcosis. One of the reasons for the increase of miRNAs in hydatidosis may be their role in modulating the immune system. These miRNAs are likely to be considered as one of the most important biomarkers in determining the severity of hydatidosis.


[Our indications in surgical treatment of supra-condylar fractures of the femur].
The treatment of supracondylar fractures of the femur should be surgical. The authors consider the requirements of a strict technic of osteosynthesis. The use for this purpose: either a plate and strip, or a plate and screw, and justify their respective indications.


Characterization of abnormal free glycophosphatidylinositols accumulating in mutant lymphoma cells of classes B, E, F, and H.
Several mutant lymphoma lines are unable to add glycophosphatidylinositol membrane anchors to proteins. Some of them accumulate abnormal glycolipids which can be labeled by tritiated myo-inositol, mannose, or ethanolamine and which are not present in the corresponding parental cell lines. The [3H]myo-inositol-labeled abnormal lipids were isolated and characterized using hydrofluoric acid dephosphorylation, nitrous acid deamination, acetolysis, and exoglycosidase treatments alone or in combination. This partial characterization suggests that the class F mutant EL-4-f contains 3 abnormal glycolipids containing 3, 2, or 1 mannose residues, the headgroups of which are Man alpha 1,2Man alpha 1,6(X-->)Man alpha-GlcN-acylinositol, Man alpha 1,6(X-->)Man alpha-GlcN-inositol, and (X-->)Man alpha-GlcN-acylinositol where X represents a charged, hydrofluoric acid-sensitive substituent. A fourth, minor abnormal lipid with a Man alpha 1,6(X-->)Man alpha-GlcN-inositol headgroup but a different lipid moiety is also found. The substituent X is likely to consist of phosphoethanolamine since hydrofluoric acid releases [3H]ethanolamine from the [3H]ethanolamine-labeled version of these lipids. Pulse-chase experiments indicate that the abnormal glycophosphatidylinositols of class F mutants are very long-lived. The class B mutant S1A-b has previously been shown to contain an abnormal Man alpha 1,6(phosphoethanolamine-->)Man alpha-GlcN-acylinositol-P-lipid intermediate. Here we show that S1A-b also accumulates a more polar but less abundant lipid which has the identical headgroup structure but lacks the acyl group on the inositol residue. The class E mutant BW5147-e accumulates a hydrophobic glycolipid with the headgroup structure GlcN-acylinositol. All the abnormal glycolipids except those of EL-4-f are heterogeneous with regard to their lipid moiety since base-resistant as well as base-sensitive lipids are present. This suggests that the base-resistant alkylglycerols typical of mammalian anchors can get integrated into anchors at early stages of glycophosphatidylinositol formation.


Ubiquitin family modifications and template switching.
Homologous recombination plays an important role in the maintenance of genome integrity. Arrested forks and DNA lesions trigger strand annealing events, called template switching, which can provide for accurate damage bypass, but can also lead to chromosome rearrangements. Advances have been made in understanding the underlying mechanisms for these events and in elucidating the factors involved. Ubiquitin- and SUMO-mediated modification pathways have emerged as key players in regulating damage-induced template switching. Here I review the biological significance of template switching at the nexus of DNA replication and recombination, and the role of ubiquitin-like modifications in mediating and controlling this process.


[The postoperative mortality rate in paediatric surgery (author's transl)].
In the German Democratic Republic a well balanced network of paediatric surgical departments is serving the people. With the help of these specialised institutions the mortality rate of infants and children suffering from surgical diseases could be lowered decisively.


[Methodological views on the SF-36 summary scores based on the adult German population].
The SF-36 is a widely used instrument to measure health-related quality of life that provides a profile of eight scales [Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE) and Mental Health (MH)]. To reduce the dimension of the profile, a principal component analysis with the data of the US SF-36 Survey was undertaken. As a result, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) were gained by weighting and summing up of the original scales of the SF-36. The weights were assumed to be country specific. Comparing the weights from the representative samples of nine European countries with those from the USA it has been suggested that the weights gained from the US sample could be applied to all datasets for purposes of comparability and simplicity. In this paper, for a new representative German population sample completed in 1998, the calculation results are compared with those for the older German population sample from 1994. PCS and MCS are calculated using the weights from the new German population sample as well as using the American weights. In this paper, the calculations for the 1998 representative population sample were repeated based on the US weights developed in 1994. The German weights were also calculated based on the 1998 sample. The results were compared and the pro and cons of using the American weights are discussed. In essence, the American weights continue to be acceptable for international comparisons. The separate evaluation of physical and mental health for men and women allows additional insight into gender-specific changes. In this paper, the summary scales for the 1998 German normative population are calculated gender specific. The weights to be used in future studies are also published. With respect to gender mainstreaming, this approach should be taken into consideration in quality of life research. Regarding the methodological and factorial difficulties, the questions arise if the summary scales should be applied instead of the original scales of the SF-36 questionnaire.