Three-Dimensional Scaffolds for Intestinal Cell Culture: Fabrication, Utilization, and Prospects.
The intestine is a visceral organ that integrates absorption, metabolism, and immunity, which is vulnerable to external stimulus. Researchers in the fields such as food science, immunology, and pharmacology have committed to developing appropriate in vitro intestinal cell models to study the intestinal absorption and metabolism mechanisms of various nutrients and drugs, or pathogenesis of intestinal diseases. In the past three decades, the intestinal cell models have undergone a significant transformation from conventional two-dimensional cultures to three-dimensional (3D) systems, and the achievements of 3D cell culture have been greatly contributed by the fabrication of different scaffolds. In this review, we first introduce the developing trend of existing intestinal models. Then, four types of scaffolds, including Transwell, hydrogel, tubular scaffolds, and intestine-on-a-chip, are discussed for their 3D structure, composition, advantages, and limitations in the establishment of intestinal cell models. Excitingly, some of the in vitro intestinal cell models based on these scaffolds could successfully mimic the 3D structure, microenvironment, mechanical peristalsis, fluid system, signaling gradients, or other important aspects of the original human intestine. Furthermore, we discuss the potential applications of the intestinal cell models in drug screening, disease modeling, and even regenerative repair of intestinal tissues. This review presents an overview of state-of-the-art scaffold-based cell models within the context of intestines, and highlights their major advances and applications contributing to a better knowledge of intestinal diseases.


Particle Surface Modification in the Near-Electrode Region of an RF Discharge.
The results of a study on particles' surfaces after being exposed to the near-electrode region of a radio frequency (RF) discharge are presented. It was experimentally displayed that metal starts being deposited on the surface of particles levitating above the lower electrode of the discharge chamber after switching the RF discharge on. For melamine-formaldehyde (MF) particles, the appearance of an island metal coating is observed after 30 min of plasma exposure. Eroded electrodes and elements of the gas discharge chamber may serve as a source of deposited material. In addition, an analysis of the surface and composition of particles placed on the upper electrode after 6 h of plasma exposure is presented. We reveal that the composition and structure of the particle coating changes during the experiment. The MF particles under exposure become eroded, and needle-like structures containing metals are formed on their surface. We also observe the formation of columnar structures from the products of erosion of electrodes on particles with a metal coating.


Skull base chondrosarcomas: surgical treatment and results.
We describe our experience in the management of patients with skull base chondrosarcoma, an uncommon neoplasm of the skull base. Thirteen cases of surgically treated skull base chondrosarcomas were identified. The patients' follow-ups ranged from 7 to 86 months (mean, 47 months). The most common tumor locations were the jugular foramen (5 cases), the petrous apex (3 cases), and the petroclival region (3 cases). An infratemporal fossa type A approach was performed in 2 cases, and 2 patients underwent an infratemporal fossa type B approach. Two patients underwent a transotic approach, 1 patient underwent a petro-occipital transsigmoid approach, and a petro-occipital transsigmoid approach combined with a transotic approach was chosen in 1 case. One patient underwent an infratemporal fossa type C approach combined with a transotic approach, and 2 patients underwent an infratemporal fossa type B approach combined with a transotic approach. One patient underwent an infratemporal fossa type B approach combined with a transzygomatic approach, and the last patient underwent a transmastoid approach. Gross total tumor removal was achieved in all patients. Postoperative radiotherapy was performed in 7 cases. The most common complications were lower cranial nerve deficits. Two patients experienced recurrences, 36 months and 6 years after surgical removal. We believe that the primary treatment for chondrosarcomas of the skull base is gross total surgical resection. We usually do not recommend radiotherapy as the primary treatment for patients with skull base chondrosarcomas; however, radiotherapy may be considered as an alternative primary treatment in selected cases in which there are serious medical contraindications to surgery, as well as in elderly patients. We reserve postoperative radiotherapy for patients with histologically aggressive tumors (grade II or III), as well as for cases of subtotal resection or recurrent tumors.


Tumor-acidity and bioorthogonal chemistry-mediated construction and deconstruction of drug depots for ferroptosis under normoxia and hypoxia.
Mounting evidence shows that tumor hypoxia stress promotes tumor invasion and metastasis and induces therapeutic resistance. Oxygen-independent Fenton reaction, which refers to the iron-catalyzed conversion of endogenous hydrogen peroxide (H2O2) to hydroxyl radical (·OH), has been designed for ferroptosis therapy. Nevertheless, the treatment efficiency is compromised by limited H2O2 content and limited tumor retention and penetration of nanoparticles. Herein, we designed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots for tumor ferroptosis under normoxia and hypoxia. Briefly, the dendritic poly(amidoamine) (PAMAM, G4) was modified using cinnamaldehyde (CA) to deplete GSH and increase H2O2 levels, and ferrocene (Ferr) served as Fenton reaction catalyst to generate PFC. Subsequently, PFC was modified with maleic acid amide with slow pH-response rate and poly(2-azepane ethyl methacrylate) (PAEMA) with rapid pH-response rate, accompanied with highly efficient bioorthogonal chemistry to construct and deconstruct drug depots for enhanced tumor retention and penetration. The small-sized PFC potentially induced H2O2 self-supplied ferroptosis under normoxia and hypoxia. In sum, this work utilizes two tumoral acidity-responsive groups with different response rates and highly efficient bioorthogonal click chemistry, which paves a way for ferroptosis and provides a general drug delivery strategy with enhanced tumor retention and penetration. STATEMENT OF SIGNIFICANCE: Oxygen independent Fenton reaction refers to the conversion of endogenous H2O2 to ·OH which has been designed for ferroptosis therapy. Nevertheless, limited H2O2 level and abundant GSH in tumor cells could both compromise the treatment efficiency. Herein, we developed a tumor-acidity and bioorthogonal chemistry mediated construction and deconstruction of drug depots, which elevate the intracellular H2O2 level and deplete GSH for tumor ferroptosis under normoxia and hypoxia microenvironment. This work utilizes two tumoral acidity response groups with different response rates and highly efficient bioorthogonal click reactions, which paves a way for tumor cell ferroptosis and provides a general drug delivery strategy for enhanced tumor accumulation and penetration.


Developing a multidisciplinary complex wound care service.
This article will describe the development of a dedicated multidisciplinary complex/chronic wound care service. Using a recognized framework, the article will demonstrate how the needs of patients were first assessed and then addressed. The article will conclude that although more research is required, the results of this audit suggest that patients with long-standing complex/chronic wounds benefit from the care of a dedicated multidisciplinary wound care team. For the purpose of this article the term 'complex' is defined as any wound which is not progressing as expected despite the application of good quality standard wound care.


Electrokinetics at aqueous interfaces without mobile charges.
We theoretically consider the possibility of using electric fields in aqueous channels of cylindrical and planar geometry to induce transport in the absence of mobile ionic charges. Using the Navier-Stokes equation, generalized to include the effects of water spinning, dipole orientation and relaxation, we show analytically that pumping of a dipolar liquid through an uncharged hydrophobic channel can be achieved by injecting torque into the liquid, based on the coupling between molecular spinning and fluid vorticity. This is possible using rotating electric fields and suitably chosen interfacial boundary conditions or transiently by suddenly switching on a homogeneous electric field. A static electric field, however, does not induce a steady state flow in channels, irrespective of the geometry. Using molecular dynamics (MD) simulations, we confirm that static fields do not lead to any pumping, in contrast to earlier publications. The pumping observed in MD simulations of carbon nanotubes and oil droplets in a static electric field is tracked down to an imprudent implementation of Lennard-Jones interaction truncation schemes.


Risk Factors for and Effects of Persistent and Severe Hypophosphatemia Following Ferric Carboxymaltose.
Hypophosphatemia, osteomalacia, and fractures are complications of certain intravenous iron formulations. This study investigated risk factors for incident, severe, and persistent hypophosphatemia, and associated alterations in bone and mineral biomarkers following intravenous iron treatment. We analyzed data from the PHOSPHARE-IDA randomized clinical trials, comprising 245 patients aged 18 years or older with iron deficiency anemia at 30 outpatient clinics in the United States who received intravenous ferric carboxymaltose (FCM) or ferric derisomaltose (FDI). Outcome measures included serum phosphate, intact fibroblast growth factor-23 (iFGF23), 1,25-dihydroxyvitamin D (1,25(OH)2D), ionized calcium, parathyroid hormone (PTH), and alkaline phosphatase. FCM was the only consistent risk factor for incident hypophosphatemia (< 2.0 mg/dL; odds ratio vs FDI: 38.37; 95% CI: 16.62, 88.56; P < 0.001). Only FCM-treated patients developed severe hypophosphatemia (< 1.0 mg/dL; 11.3%; 13/115) or persistent hypophosphatemia (< 2.0 mg/dL at study end; 40.0%; 46/115). More severe hypophosphatemia associated with significantly greater increases in iFGF23, PTH, and alkaline phosphatase, and more severe decreases in 1,25(OH)2D and ionized calcium (all P < 0.05). Patients with persistent vs resolved hypophosphatemia demonstrated significantly greater changes in iFGF23, PTH, 1,25(OH)2D, and N-terminal procollagen-1 peptide levels (all P < 0.01), but alkaline phosphatase increased similarly in both groups. Treatment with FCM was the only consistent risk factor for hypophosphatemia. Patients who developed severe or persistent hypophosphatemia after FCM treatment manifested more severe derangements in bone and mineral metabolism. Changes in bone biomarkers continued beyond resolution of hypophosphatemia, suggesting ongoing effects on bone that may help explain the association of FCM with osteomalacia and fractures.


Illuminating an Invisible Epidemic: A Systemic Review of the Clinical and Economic Benefits of Early Diagnosis and Treatment in Inflammatory Disease and Related Syndromes.
Healthcare expenditures in the United States are growing at an alarming level with the Centers for Medicare and Medicaid Services (CMS) projecting that they will reach $5.7 trillion per year by 2026. Inflammatory diseases and related syndromes are growing in prevalence among Western societies. This growing population that affects close to 60 million people in the U.S. places a significant burden on the healthcare system. Characterized by relatively slow development, these diseases and syndromes prove challenging to diagnose, leading to delayed treatment against the backdrop of inevitable disability progression. Patients require healthcare attention but are initially hidden from clinician's view by the seemingly generalized, non-specific symptoms. It is imperative to identify and manage these underlying conditions to slow disease progression and reduce the likelihood that costly comorbidities will develop. Enhanced diagnostic criteria coupled with additional technological innovation to identify inflammatory conditions earlier is necessary and in the best interest of all healthcare stakeholders. The current total cost to the U.S. healthcare system is at least $90B dollars annually. Through unique analysis of financial cost drivers, this review identifies opportunities to improve clinical outcomes and help control these disease-related costs by 20% or more.


Orofacial functions and quality of life in children with unilateral cleft lip and palate.
This study aimed to evaluate the orofacial functions and oral health-related quality of life (OHRQoL) of children with unilateral cleft lip and palate (UCLP). This case-control study included patients with UCLP matched by sex and age with controls (children without UCLP), resulting in the inclusion of a total of 108 eight- to ten-year-old children. Orofacial functions and OHRQoL were evaluated using the Nordic Orofacial Test-Screening (NOT-S) and the Child Perceptions Questionnaire (CPQ 8-1 0 ), respectively. Data normality was assessed by the Kolmogorov-Smirnov test. Differences and correlations in NOT-S and CPQ 8-1 0 scores between and within the groups were evaluated using Mann-Whitney and Spearman´s correlation tests, respectively. The distribution of NOT-S and global ratings of CPQ 8-1 0 for each group were assessed by Chi-squared/Fisher's Exact tests. The UCLP group had a higher NOT-S total and examination scores than the controls. Dysfunctions related to breathing, facial symmetry/expression, and speech were more frequent in the UCLP patients than in the controls. The UCLP group had higher scores on the social well-being domain than the controls. There was a significant difference between the groups in their ratings in regards to the extent to which their oral condition affected their life overall, with controls perceiving it as somewhat better than patients. In both groups, NOT-S total and interview scores were positively correlated with CPQ 8-1 0 total and domain scores. The NOT-S examination score was only significantly correlated with social domain scores in the control group. The presence of UCLP was associated with clinical signs of orofacial dysfunctions related to breathing, facial symmetry/expression, and speech. Children with UCLP reported more orofacial dysfunctions and negative impacts on social well-being than controls.


Metasurface hologram for polarization measurement.
Polarization measurement is crucial for many optical applications in science and technology. Geometric metasurfaces have been used to develop polarization-sensitive holograms, providing a new opportunity for polarization measurement. We propose and experimentally demonstrate a hologram method to measure the polarization state of light. A reflective-type metasurface hologram is used to generate holographic images of graphene pattern. The ellipticity and helicity of the incident light are measured based on the intensities of the neighboring light spots, corresponding to two opposite circular polarization states. Benefiting from the advantages of reflective geometric metasurfaces, this device can operate in broadband.


The RNA-binding protein Staufen from rat brain interacts with protein phosphatase-1.
In mammalian neurones, homologues of the Drosophila RNA-binding protein Staufen are part of ribonucleoprotein complexes that move bidirectionally along dendritic microtubules and appear to regulate mRNA translocation and translation. In this study, putative components of Staufen granules were identified in a yeast two-hybrid screen of a rat brain cDNA library with a rat Staufen bait. Protein phosphatase-1 was found as an interacting partner. Binding appears to be mediated by a five amino acid residue sequence motif (R-K-V-T-F) in Staufen that is conserved in a number of proteins interacting with the phosphatase. A two amino acid residue mutation within this motif (R-K-V-G-A) disrupted the interaction. A cytoplasmic interaction of both proteins was shown by coimmunoprecipitation of rat Staufen and protein phosphatase-1 from the cytoplasm of transfected cells and rat brain homogenates. In mammalian brain, the phosphatase represents the first described endogenous interaction partner of Staufen. In primary hippocampal neurones, both proteins partially colocalize in somata and neuronal processes. Staufen does not modulate the in vitro protein phosphatase activity. These findings show that protein phosphatase-1 is a native component of Staufen particles. Cellular functions of Staufen may be regulated via phosphorylation or Staufen may recruite the phosphatase into specific ribonucleoprotein complexes.


What students bring to medical school: attitudes toward health promotion and prevention.
Health care providers' positive attitudes toward prevention and health promotion are important in achieving national health care goals. Limited studies of incoming medical students have been conducted that measure predictors of positive attitudes toward health promotion and prevention. Data were obtained from a 1993 curriculum evaluation survey of first-year students at five different medical schools in California. Attitudes toward health promotion and prevention were measured using a nine-question Prevention Attitude Scale (PAS). We developed 2 multivariate linear regression models using demographics, education choices, and personal social values and beliefs to predict PAS scores. We also performed bivariate analysis. Five hundred ninety-nine completed surveys were analyzed, with a response rate of 95%. Mean PAS score was 36.47 +/- 3.7 on a 0 to 44 scale. Female gender, Democratic party preference, and a planned specialty choice in preventive medicine or primary care predicted the highest PAS scores on bivariate analysis (p < 0.002). Significant correlation ( p < 0. 001) was shown between PAS scores and 2 additional scales regarding beliefs in associations of social factors and illness and in the importance of caring for the poor. Linear regression model using personal social values and beliefs explained 34% of the variance, as opposed to the demographic model that explained only 9% of the variance. In the schools studied, participating first-year medical students had moderately positive attitudes toward health promotion and prevention, as measured by PAS scores. In designing curriculum to improve medical students' attitudes toward health promotion and prevention, medical educators may need to consider other personal and social values held by medical students and to address the "political" aspects of health promotion and prevention. Future studies are needed to longitudinally follow medical student attitudes.


A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic-release oral system-methylphenidate in adults with attention-deficit/hyperactivity disorder.
We conducted a 3-phase, double-blind, placebo-controlled, parallel study design of osmotic-release oral system (OROS)-methylphenidate (MPH) in adults (19-60 years of age) with attention deficit/hyperactivity disorder as classified by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Phase 1 of the study was a 6-week, acute efficacy trial (n = 223), phase 2 was a 24-week, double-blind continuation study of responders (n = 96), and phase 3 was a double-blind, placebo-controlled, 4-week discontinuation study (n = 23). The mean daily dosage at phase 1 endpoint was 78.4 ± 31.7 mg (0.97 ± 0.32 mg/kg) OROS-MPH and 96.6 ± 26.5 mg (1.16 ± 0.19 mg/kg) placebo (P < 0.0001). Clinical response at phase 1 endpoint was significantly greater in the OROS-MPH group (62%, n = 67 vs 37%, n = 41; P < 0.001) and was maintained throughout 24 weeks of double-blind treatment. With double-blind, placebo-controlled discontinuation, however, there was no statistically significant difference in the rate of relapse between OROS-MPH responders randomized to placebo and those randomized to continue active treatment (18%, n = 2 vs 0%, n = 0; P = 0.1). As expected, decreased appetite, insomnia, being tense/jittery, mucosal dryness, and neurological symptoms were statistically significantly associated with OROS-MPH treatment. More work is needed to be conducted with larger samples being followed to study completion to better understand the long-lasting impact of pharmacotherapy for adult attention-deficit/hyperactivity disorder.


Types of opioid receptors: relation to antinociception.
The endogenous opioid peptides are derived from three large precursors. Pro-opiocortin and proenkephalin yield [Met]enkephalin, carboxy-extended [Met]enkephalins and [Leu]enkephalin. The fragments of prodynorphin are all carboxy-extended [Leu]enkephalins. Three approaches are of importance for an analysis of the physiological functions of the different endogenous opioid peptides. First, since these peptides interact with more than one of the mu-, delta- and kappa-binding sites and thus with their receptors, it is necessary to synthesize peptides or non-peptides, which bind to only one of the sites. As far as narcotic analgesics are concerned, morphine fulfils these conditions since it interacts almost exclusively with the mu-receptor. Secondly, antagonists are required that are selective for only one of the opioid receptors, even when used in high concentrations. Finally, it is important to find circumscribed areas in the nervous system that possess only one type of opioid receptor. It is now known that in the rabbit cerebellum the opioid receptors are almost exclusively of the mu-type whereas in the guinea-pig cerebellum they are almost exclusively of the kappa-type.


Two fluorescent Schiff base sensors for Zn(2+): the Zn(2+)/Cu(2+) ion interference.
Two simple and low cost 2,4-di-tert-butyl-6-[(1-hydroxycyclohexylmethylimino)methyl]phenol (L1) and 2-[{(1-hydroxycyclohexyl)methylimino}methyl]phenol (L2) Schiff base sensors exhibiting selectivity for Zn(2+) in water:methanol (95:5, v/v, 10 mM HEPES) are described. L1 and L2 display an "off-on" fluorescence effect forming the L1·Zn and L2·Zn complexes, respectively. In the case of L1·Zn, the emission response is quenched by the addition of Cu(2+) forming the respective L1·Cu complex; in spite of that, the fluorescence signal can be completely restored only by the addition of tartrate anions (C4H4O6(2-)) forming again L1·Znvia the "off-on" displacement approach. However, in the case of L2·Zn no Cu(2+) interference is observed, which is a typical problem for Zn(2+) sensors. Here we describe that a very subtle structural change in the ligand during transition from the enol-imine tautomer in L1 to the keto-enamine tautomer in L2 is enough to modulate the Zn(2+)/Cu(2+) selectivity. Also, the Zn(2+)vs. Cd(2+) discrimination for L1 and L2 is proved. Moreover, we found that the interaction between both L·Zn complexes and tartrate anions completely restored the free ligands by the ligand substitution mechanism even in a more efficient association than phosphate anions. Further, a second colorimetric response channel upon addition of Fe(2+) was observed for L1 and L2. Then, TD-DFT theoretical calculations were conducted in order to study the efficiency of the sensors to give different responses in the presence of such metal ions. Finally, the L2 sensor successfully detects Zn(2+) in Jurkat cells cultured with and without Zn(2+) enriched medium.


Effects of 17beta-oestradiol on rat detrusor smooth muscle contractility.
The aim of this study was to investigate the effect of 17beta-oestradiol (E(2)) on detrusor smooth muscle contractility and its possible neuroprotective role against ischaemic-like condition, which could arise during overactive bladder disease. The effect of E(2) was investigated on rat detrusor muscle strips stimulated with carbachol, KCl and electrically, in the absence or presence of a selective oestrogen receptor antagonist (ICI 182,780) and, by using confocal Ca(2+) imaging technique, measuring the amplitude (DeltaF/F(0)) and the frequency of spontaneous whole cell Ca(2+) flashes. Moreover, the effect of 1 and 2 h of anoxia-glucopenia and reperfusion (A-G/R), in the absence or presence of the hormone, was evaluated in rat detrusor strips perfused with Krebs solution which underwent electrical field stimulation to stimulate intrinsic nerves; the amplitude and the frequency of Ca(2+) flashes were also measured. 17beta-Oestradiol exhibited antispasmogenic activity assessed on detrusor strips depolarized with 60 mm KCl at two different Ca(2+) concentrations. 17beta-Oestradiol at the highest concentration tested (30 microm) significantly decreased detrusor contractions induced by all the stimuli applied. In addition, the amplitude and the frequency of spontaneous Ca(2+) flashes were significantly decreased in the presence of E(2) (10 and 30 microm) compared with control detrusor strips. In strips subjected to A-G/R, a significant increase in the amplitude of both spontaneous and evoked flashes was observed. 17beta-Oestradiol was found to increase the recovery of detrusor strips subjected to A-G/R. The ability of E(2) to suppress contraction in control conditions may explain its ability to aid recovery following A-G/R.


Genome-Wide Characterization of Salt-Responsive miRNAs, circRNAs and Associated ceRNA Networks in Tomatoes.
Soil salinization is a major environmental stress that causes crop yield reductions worldwide. Therefore, the cultivation of salt-tolerant crops is an effective way to sustain crop yield. Tomatoes are one of the vegetable crops that are moderately sensitive to salt stress. Global market demand for tomatoes is huge and growing. In recent years, the mechanisms of salt tolerance in tomatoes have been extensively investigated; however, the molecular mechanism through which non-coding RNAs (ncRNAs) respond to salt stress is not well understood. In this study, we utilized small RNA sequencing and whole transcriptome sequencing technology to identify salt-responsive microRNAs (miRNAs), messenger RNAs (mRNAs), and circular RNAs (circRNAs) in roots of M82 cultivated tomato and Solanum pennellii (S. pennellii) wild tomato under salt stress. Based on the theory of competitive endogenous RNA (ceRNA), we also established several salt-responsive ceRNA networks. The results showed that circRNAs could act as miRNA sponges in the regulation of target mRNAs of miRNAs, thus participating in the response to salt stress. This study provides insights into the mechanisms of salt tolerance in tomatoes and serves as an effective reference for improving the salt tolerance of salt-sensitive cultivars.


Prolongation of QTc interval due to increased parity and great grand multiparity.
Women are more prone to cardiac arrhythmias. Increased exposure to sex hormones may alter the ventricular repolarisation of the heart as the parity number increases. In this study, we aim to investigate the effect of parity number to electrocardiographic parameters. A total of 205 adult women were included for the study. Nulliparous (NP), primiparous (PP), multiparous (MP), grand multiparous (GMP) and great grand multiparous (GGMP) women constituted the study population. Increased parity has positive correlation with QTc interval (p=.000, r = 0.303). GGMP has significantly higher QTc compared to NP, PP, MP and GMP (p=.001, p=.000, p=.004 and p=.007, respectively). GGMP and parity have explanatory power on QTc (p=.019 and p=.020, respectively). Parity and GGMP affect cardiac repolarisation and prolong the QTc interval most probably due to repeated exposure to sex hormones. This study showed that GGMP and parity are independent risk factors for QTc interval prolongation.Impact StatementWhat is already known on this subject? Increased exposure to sex hormones may alter the ventricular repolarisation of the heart as the parity number increases. Previous studies showed that increased parity (up to 7) deteriorates ventricular diastolic functions, prolongs QTc interval and these conditions cause cardiovascular diseases.What do the results of this study add? In this study, we added great grand multiparity (10 or more parity) (GGMP) group that have never been studied before. We found that GGMP has much more impact on QTc prolongation than fewer parity groups and this result shows us that GGMP deteriorates ventricular functions more.What are the implications of these findings for clinical practice and/or further research? These results show us that women should be discouraged from having more delivery. Also, women with a pregnancy history of five and more (grand multiparity) should be evaluated with an electrocardiography and a cardiology consultation should be performed before re-conception. In the future, larger prospective studies are needed on this subject. In addition, other electrocardiographic parameters (QRS-T angle and Tpe/QTc in electrocardiography, etc.) that related with diastolic functions should be evaluated for comparison of GGMP and non-GGMP populations in future studies.


Defining the phenotype of PGAP3-congenital disorder of glycosylation; a review of 65 cases.
Biallelic pathogenic variants in PGAP3 cause a rare glycosylphosphatidyl-inositol biogenesis disorder, PGAP3-CDG. This multisystem condition presents with a predominantly neurological phenotype, including developmental delay, intellectual disability, seizures, and hyperphosphatemia. Here, we summarized the phenotype of sixty-five individuals including six unreported individuals from our CDG natural history study with a confirmed PGAP3-CDG diagnosis. Common additional features found in this disorder included brain malformations, behavioral abnormalities, cleft palate, and characteristic facial features. This report aims to review the genetic and metabolic findings and characterize the disease's phenotype while highlighting the necessary clinical approach to improve the management of this rare CDG.


The Peripherin Gene Regulates the Migration of Bone Marrow Mesenchymal Stem Cells in Wuzhishan Mini Pigs.
Increasing the migratory capacity of the implanted mesenchymal stem cells (MSCs) is a major challenge in developing successful cell transplantation therapies. Nevertheless, the regulatory factors involved in the migration of BMMSCs remain largely unknown. In this study, we studied the role of the peripherin (PRPH) gene in regulating the ability of Wuzhishan mini pig (WZSP) BMMSCs to migrate in vitro. Four different shRNA vectors directed against PRPH were designed and transfected into BMMSCs. The vector with the best interference effect was chosen to be used in the following experiments. The expression level of PRPH in BMMSCs was determined by quantitative real-time PCR and western blot analysis. The migration capacity of the BMMSCs was estimated using a scratch assay, a transwell in vitro migration model assay, and filamentous actin staining. The results showed that shRNA-mediated knockdown of the expression of the PRPH gene in BMMSCs reduced the ability of these cells to migrate. Overall, these results illustrate that the PRPH gene regulates the migration of BMMSCs in the WZSP.


Cultivation and characterization of limbal epithelial stem cells on contact lenses with a feeder layer: toward the treatment of limbal stem cell deficiency.
Limbal epithelial sheets are used to promote corneal surface reconstruction after the detection of limbal epithelial stem cell deficiency. The aim of this study was to evaluate a novel combination of limbal stem cells (LSCs) maintained on contact lenses (CLs) in the presence of a 3T3 feeder cell layer regarding preservation of stem cell phenotype and the potential use for future in vivo transplantation. Limbal epithelial cells were isolated from rabbit cornea and cultured with 3T3 cells on CLs. The preservation of LSC phenotype was determined using p63α and ABCG2 immunostaining, whereas epithelial differentiation was evaluated using CK3 and CK19. The colony-forming assay was used to determine the percentage of LSCs in cultures. Finally, CLs seeded with PKH26-labeled LSCs were transferred to rabbit eyes after performing a surgical keratectomy, and the transition and phenotype of labeled cells on the corneal surface were evaluated in whole-mount corneas. Proliferation of individual limbal cells was observed on CLs with a 3T3 feeder cell layer, showing holoclone formation and retention of viable stem or progenitor cell phenotype. Finally, a higher transition of cultivated cells after a dual sequential CL transplantation to the ocular surface was observed, showing the preservation of the LSC phenotype in the corneal surface. Limbal cells cultivated on a CL carrier overlaying a 3T3 feeder layer are mitotically active and retain the LSC phenotype. This novel technique of using CLs as a carrier offers an easily manipulable and nonimmunogenic method for transferring LSCs for ocular surface reconstruction in patients with limbal epithelial stem cell deficiency.


Signalling substitutions in the periplasmic domain of chemoreceptor Trg induce or reduce helical sliding in the transmembrane domain.
We used in vivo oxidative cross-linking of engineered cysteine pairs to assess conformational changes in the four-helix transmembrane domain of chemoreceptor Trg. Extending previous work, we searched for and found a fourth cross-linking pair that spanned the intrasubunit interface between transmembrane helix 1 (TM1) and its partner TM2. We determined the effects of ligand occupancy on cross-linking rate constants for all four TM1-TM2 diagnostic pairs in conditions that allowed the formation of receptor-kinase complexes for the entire cellular complement of Trg. Occupancy altered all four rates in a pattern that implicated sliding of TM2 relative to TM1 towards the cytoplasm as the transmembrane signalling movement in receptor-kinase complexes. Transmembrane signalling can be reduced or induced by single amino acid substitutions in the ligand-binding region of the periplasmic domain of Trg. We determined the effects of these substitutions on conformation in the transmembrane domain and on ligand-induced changes using the diagnostic TM1-TM2 cysteine pairs. Effects on rates of in vivo cross-linking showed that induced signalling substitutions altered the relative positions of TM1 and TM2 in the same way as ligand binding, and reduced signalling substitutions blocked or attenuated the ligand-induced shift. These results provide strong support for the helical sliding model of transmembrane signalling.


[Fecal elastase-1 determination in the diagnosis of chronic pancreatitis].
The diagnosis of chronic pancreatitis is based on morphological and functional data. To evaluate exocrine function, the secretin-cholecystokinin test is the gold standard but this is invasive and frequently unavailable. Recently, fecal elastase-1 determination has been investigated as an indirect test of pancreatic function. To evaluate the diagnostic value of fecal elastase-1 in chronic pancreatitis by comparing it with other indirect methods of evaluating pancreatic function such as the urine pancreolauryl test and fecal chymotrypsin determination. To do this, we analyzed the three diagnostic methods in four groups of patients: group I (14 patients with confirmed chronic pancreatitis); group II (5 patients with recurrent episodes of acute alcoholic pancreatitis; group III (9 patients with non-pancreatic diarrhea); group IV (8 patients with other gastrointestinal diseases). Compared with the control groups (groups III and IV), patients in groups I and II presented lower levels of fecal elastase-1 (groups I-II: 88 mcg/g, groups III-IV: 635 mcg/g, p < 0.0001), fecal chymotrypsin (4.3 U/g and 29.3 U/g, respectively, p < 0.0001), and pancreolauryl (14% and 54%, respectively, p < 0,001). In the diagnosis of confirmed chronic pancreatitis (group I) the fecal elastase-1 and pancreolauryl tests showed a sensitivity of 85.6% and 78.5%, respectively. However, in group II, the most sensitive test was the pancreolauryl test (80% versus 60% for the chymotrypsin test and only 40% for the fecal elastase-1 test). In contrast, the fecal elastase-1 test showed the highest specificity (94.1% versus 88.2% for the fecal chymotrypsin test and 81.3% for the pancreolauryl test). Fecal elastase-1 determination is an effective indirect method in the diagnosis of patients with advanced chronic pancreatitis. However, when the disease is in the early stages, its sensitivity is no greater than that of other indirect tests. The greatest advantage of this test is its high specificity.


Maximizing as satisficing: On pattern matching and probability maximizing in groups and individuals.
Distinguishing meaningful structure from unpredictable randomness is a key challenge in many domains of life. We examined whether collaborating three-person groups (n = 81) outperform individuals (n = 81) in facing this challenge with a two-part repeated choice task, where outcomes were either serially independent (probabilistic part) or fixed in a particular sequence (pattern part). Groups performed as well as the best individuals in the probabilistic part but groups' accuracy did not credibly exceed that of the average individual in the pattern part. Qualitative coding of group discussion data revealed that failures to identify existing patterns were related to groups accepting probability maximizing as a "good enough" strategy rather than expending effort to search for patterns. These results suggest that probability maximizing can arise via two routes: recognizing that probabilistic processes cannot be outdone (maximizing as optimizing) or settling for an imperfect but easily implementable strategy (maximizing as satisficing).


Physiological approach of beta receptor coupling to adenylate cyclase in rat airways: ontogenical modification and functional antagonism.
The relaxant effects of isoproterenol, forskolin and sodium nitroprusside were studied on tracheal pieces and lung parenchymal strips of Sprague-Dawley and Wistar rats according to age and functional antagonism with carbachol applied previously to induce the contraction. The beta receptor-related maximal relaxant effect of isoproterenol decreased from 4 to 11 weeks in Sprague-Dawley rat airways contracted with 10(-6) M carbachol. This maximal relaxant effect did not change with age in the Wistar strain. When lower carbachol concentrations were applied to Wistar trachea, the maximal relaxant effect of isoproterenol raised with a large decrease of the EC50 values. In the Sprague-Dawley strain, a similar diminution of carbachol concentration also allowed to increase the maximal amplitude of relaxation, but a smaller decrease of EC50 was observed as referred to the Wistar strain. These results suggest that the decrease with age of the maximal relaxation of Sprague-Dawley airways by isoproterenol might be linked to impaired functional antagonism between beta adrenergic and muscarinic stimulation in this rat strain. This hypothesis was strengthened by the observation of the effects of forskolin, an activator of adenylate cyclase, and sodium nitroprusside, a cyclic GMP-related relaxant drug, that did not show any modified effect in function of age in both rat strains. A modified regulation of adenylate cyclase complex with ontogenesis and with rat strain is suggested.


Test-trace-isolate-quarantine (TTIQ) intervention strategies after symptomatic COVID-19 case identification.
The test-trace-isolate-quarantine (TTIQ) strategy, where confirmed-positive pathogen carriers are isolated from the community and their recent close contacts are identified and pre-emptively quarantined, is used to break chains of transmission during a disease outbreak. The protocol is frequently followed after an individual presents with disease symptoms, at which point they will be tested for the pathogen. This TTIQ strategy, along with hygiene and social distancing measures, make up the non-pharmaceutical interventions that are utilised to suppress the ongoing COVID-19 pandemic. Here we develop a tractable mathematical model of disease transmission and the TTIQ intervention to quantify how the probability of detecting and isolating a case following symptom onset, the fraction of contacts that are identified and quarantined, and the delays inherent to these processes impact epidemic growth. In the model, the timing of disease transmission and symptom onset, as well as the frequency of asymptomatic cases, is based on empirical distributions of SARS-CoV-2 infection dynamics, while the isolation of confirmed cases and quarantine of their contacts is implemented by truncating their respective infectious periods. We find that a successful TTIQ strategy requires intensive testing: the majority of transmission is prevented by isolating symptomatic individuals and doing so in a short amount of time. Despite the lesser impact, additional contact tracing and quarantine increases the parameter space in which an epidemic is controllable and is necessary to control epidemics with a high reproductive number. TTIQ could remain an important intervention for the foreseeable future of the COVID-19 pandemic due to slow vaccine rollout and highly-transmissible variants with the potential for vaccine escape. Our results can be used to assess how TTIQ can be improved and optimised, and the methodology represents an improvement over previous quantification methods that is applicable to future epidemic scenarios.


Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice.
Berberine, an isoquinoline derivative alkaloid, has a wide range of pharmacological properties and is considered to have anti-inflammatory and neuroprotective effects. However, there are no reports about the effects and mechanisms of berberine in experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). Female C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with berberine at the day of disease onset and medication was administered daily until mice were sacrificed. Blood-brain barrier (BBB) permeability and the alteration of matrix metalloproteinase-2 (MMP-2, 72 kDa) and matrix metalloproteinase-9 (MMP-9, 92 kDa) in the brain and cerebrospinal fluid (CSF) of EAE mice were detected by quantitative measurement for Evan's blue (EB) content, Western blot and gelatin zymography respectively. The results showed that berberine attenuated clinical and pathological parameters of EAE, reduced the permeability of BBB, inhibited the activity and expression of MMP-9 but not MMP-2 in the CSF and brain of EAE mice. These findings suggest that berberine is effective to attenuate the clinical severity of EAE in C57 BL/6 mice by reducing the permeability of BBB, decreasing the expression and activity of MMP-9, and decreasing the inflammatory infiltration. We think that berberine might be a potential therapeutic agent for MS.


Utility-based quality of life in mothers of children with behaviour problems: A population-based study.
To examine the relationship between mothers' health-related quality of life (HRQoL) and child behaviour problems at age 2 years. To investigate whether the relationship between maternal HRQoL and child behaviour problems is independent of maternal mental health. Cross-sectional survey nested within a population-level, cluster randomised trial, which aims to prevent early child behaviour problems. One hundred and sixty mothers of 2-year-old children, in nine local government areas in Victoria, Australia. HRQoL was measured using the Assessment of Quality of Life 6D and child behaviour was measured using the child behaviour checklist (CBCL/1.5-5 years). Maternal mental health was measured using the Depression Anxiety Stress Scale. Data were collected at child age 2 years; demographic data were collected at child age 8 months. HRQoL was lower for mothers with children that had borderline/clinical behaviour problems compared to those with children without problems (mean difference -0.14, 95% confidence interval (CI): -0.16 to -0.12, P < 0.001). The finding did not markedly change when adjusting for household income, financial security, child gender, child temperament and intervention group status at child age 8 months (mean difference -0.12, 95% CI: -0.15 to -0.09, P < 0.001), but did attenuate when additionally adjusting for concurrent maternal mental health (mean difference -0.03, 95% CI: -0.05 to -0.02, P < 0.001). Child behaviour problems were associated with lower maternal HRQoL. Child behaviour problems prevention programmes could consider this association with maternal HRQoL and be designed to improve and report both mothers' and their child's health and wellbeing.


Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam.
The effect of erythromycin on the pharmacokinetics and pharmacodynamics of diazepam and flunitrazepam was investigated in two randomized, double-blind, cross-over studies. Healthy volunteers ingested erythromycin for one week 500 mg t.i.d. On the 4th day they ingested a single 5 mg dose of diazepam (6 subject, Study 1) or 1 mg dose of flunitrazepam (5 subjects, Study 2), respectively. Plasma drug concentrations and psychomotor effects were measured during 42 hr after the ingestion of diazepam or flunitrazepam. In Study 1 erythromycin increased the area under the diazepam plasma concentration-time curve [AUC (0-42 hr)] by 15% (P < 0.05) and the concentration of diazepam in plasma at 42 hr by 63% (P < 0.05). The median peak concentration (Cmax) and the half-life (t1/2) of diazepam were increased but they did not change significantly (P = 0.17 and 0.12, respectively). Plasma N-desmethyldiazepam concentrations were slightly reduced during erythromycin treatment up to 8 hr (P < 0.05). In Study 2 the AUC (0-42 hr) of flunitrazepam was increased by 25% (P < 0.05) during the erythromycin treatment. The t1/2 of flunitrazepam increased significantly (P < 0.05), but the Cmax remained unchanged. The psychomotor effects of diazepam or flunitrazepam were not changed significantly by erythromycin. These pharmacokinetic interactions can be explained by the reduced metabolic elimination of diazepam and flunitrazepam. The interactions of erythromycin with diazepam and flunitrazepam seem to be slight and of limited clinical significance only.


[The function of a face on person perception: the effect of the number of targets and degree of facial attractiveness].
The present study investigated how the influence and the function of a face on person perception might vary with the number of targets (one, two or four) and the degree of facial attractiveness (positive or negative). One hundred sixty-seven female undergraduates were tested. After studying behavioral descriptions and photographs of targets, each subject was asked to form impressions and recall the descriptions of the targets. The main results were as follows: (a) A face became more influential as the number of targets increased. (b) A positive face exerted greater influence than a negative face. (c) The effect of the number of targets was greater for negative faces.


Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide.
The XAD-2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5-fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose-response for CP was observed. There was a dose-response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with beta-glucuronidase allowed this type of source to be detected also.


Omnidirectional Walking Pattern Generator Combining Virtual Constraints and Preview Control for Humanoid Robots.
This paper presents a novel omnidirectional walking pattern generator for bipedal locomotion combining two structurally different approaches based on the virtual constraints and the preview control theories to generate a flexible gait that can be modified on-line. The proposed strategy synchronizes the displacement of the robot along the two planes of walking: the zero moment point based preview control is responsible for the lateral component of the gait, while the sagittal motion is generated by a more dynamical approach based on virtual constraints. The resulting algorithm is characterized by a low computational complexity and high flexibility, requisite for a successful deployment to humanoid robots operating in real world scenarios. This solution is motivated by observations in biomechanics showing how during a nominal gait the dynamic motion of the human walk is mainly generated along the sagittal plane. We describe the implementation of the algorithm and we detail the strategy chosen to enable omnidirectionality and on-line gait tuning. Finally, we validate our strategy through simulation experiments using the COMAN + platform, an adult size humanoid robot developed at Istituto Italiano di Tecnologia. Finally, the hybrid walking pattern generator is implemented on real hardware, demonstrating promising results: the WPG trajectories results in open-loop stable walking in the absence of external disturbances.


Percutaneous endoscopic gastrostomy and the evolution of contemporary long-term enteral access.
This paper is based on the opening lecture of the 23rd Congress of the European Society of Parenteral and Enteral Nutrition (ESPEN), given on September 9, 200l in Muenchen, Germany. The article relates the story of the origin and the evolution of the percutaneous endoscopic gastrostomy or PEG, based on the then-novel concept of sutureless approximation of a hollow viscus to the abdominal wall. It also provides a perspective of the clinical applications of PEG, in general, and the author's pediatric experience in particular. Additionally, it briefly describes the old and new expanded applications of the PEG concept. In this communication, the author of the procedure encourages young investigators to ask relevant questions in research and in clinical settings aimed at developing new ideas and concepts in the field of nutrition. He also stresses the need to carefully reflect upon the ethical and moral implications of new discoveries. The article contains pertinent illustrations and bibliographic references.


Structure of the outer membrane translocator domain of the Haemophilus influenzae Hia trimeric autotransporter.
Autotransporter proteins are defined by the ability to drive their own secretion across the bacterial outer membrane. The Hia autotransporter of Haemophilus influenzae belongs to the trimeric autotransporter subfamily and mediates bacterial adhesion to the respiratory epithelium. In this report, we present the crystal structure of the C-terminal end of Hia, corresponding to the entire Hia translocator domain and part of the passenger domain (residues 992-1098). This domain forms a beta-barrel with 12 transmembrane beta-strands, including four strands from each subunit. The beta-barrel has a central channel of 1.8 nm in diameter that is traversed by three N-terminal alpha-helices, one from each subunit. Mutagenesis studies demonstrate that the transmembrane portion of the three alpha-helices and the loop region between the alpha-helices and the neighboring beta-strands are essential for stability of the trimeric structure of the translocator domain, and that trimerization of the translocator domain is a prerequisite for translocator activity. Overall, this study provides important insights into the mechanism of translocation in trimeric autotransporters.


[Modernisation of the design of clinical trials for caries preventive agents].
In January 2002 the International Consensus Workshop on Caries Clinical Trials was organised in Scotland. The meeting was an initiative of both academic and industrial partners, in order to arrive at a consensus about ways to modernise the design of clinical trials for caries preventive agents (Caries Clinical Trials or CCTs). All presentations delivered at the workshop and the consensus statements formulated at the end of the workshop were published last year in a special issue of the Journal of Dental Research. In this paper some important aspects are highlighted and the workshop conclusions are presented.


A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells.
Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.


[Response of respiratory exchange ratio (R) to sinusoidal work load in humans].
An examination was made of the response of respiratory exchange ratio (R), carbon dioxide output (VCO2) and oxygen uptake (VO2) to sinusoidal work load with periods (T) of 1-16 min in six healthy men to determine whether R response is sinusoidal. The influence of the ratio of the amplitude of VCO2 to that of VO2 and the phase lag between them on R response was also studied by computer simulation. The results and conclusions obtained are as follows: 1) With decrease in the period, the amplitudes of VO2 and VCO2 dropped exponentially, becoming least at T of 1 min (T = 1 min). In contrast, the amplitude of R was largest at T = 4 min and subsequently decreased progressively. 2) The peak amplitude of R at T = 4 min can be explained by the larger phase lag and relatively low of amplitude of VCO2 to VO2. 3) The smallest amplitude of R at T = 1 min was due not to the ratio of amplitude or phase lag, but to remarkably smaller amplitudes of VO2 and VCO2. 4) The phase lag of VO2 to sinusoidal work load was smaller than that of VCO2. Phase lag of R was considerably larger than that of VO2 or VCO2. 5) The response curve of VO2 and VCO2 is a sinusoidal curve with the same period as exercise. However, the response of R is not a real sinusoidal but a deformed biphasic curve with a high crest and low trough. The deformity is determined by the phase lag between VO2 and VCO2 response and also the ratio of amplitude of VCO2 to that of VO2.


Vasoreactivity of Fluosol perfluorocarbon emulsion vs. Earl's balanced salt/albumin perfusates in the isolated perfused rat lung.
We compare the vasoreactive responses of Fluosol perfluorocarbon emulsion versus Earl's balanced salt+albumin solution as perfusates in an isolated perfused rat lung. Comparisons were made with three separate vasoconstrictive stimuli: norepinephrine, and prostaglandin F2 alpha dose-response analysis, and generation of hypoxic pulmonary vasoconstriction. The hypoxia experiments were also performed with N-nitro-arginine added to the perfusates to block production of endogenous nitric oxide prior to the application of hypoxic ventilation challenge. The vasoconstrictive effects of norepinephrine, PGF2 alpha and hypoxia were significantly depressed in the perfluorocarbon perfused versus salt/albumin solution perfused lungs. With the addition of NNA to the perfusates, hypoxic pulmonary vasoconstriction is enhanced in both Earl's/albumin perfused as well as in the fluorocarbon perfused lungs. We can conclude that the pulmonary vasoconstrictive effects of norepinephrine, PGF2 alpha, and hypoxia are depressed in perfluorocarbon emulsion perfused, compared to salt-albumin solution perfused lungs. It is possible that perfluorocarbon emulsions interfere with normal endothelial function. As such, these compounds may be useful in examination of normal and abnormal endothelial function in various research applications.


Effects of geometrical and energetic nonadditivity on the phase behavior of two-component symmetric mixtures.
Using Monte Carlo simulation methods in the grand-canonical ensemble, we have studied the phase behavior of three-dimensional symmetric binary mixtures of Lennard-Jones particles. We have also elucidated the effects of geometric and energetic nonadditivity on the phase behavior. Phase diagrams for several systems have been evaluated. We have demonstrated that in completely miscible mixtures the geometrical nonadditivity (negative as well as positive) stabilizes a liquid phase leading to a gradual increase of the critical temperature. The mechanism leading to such behavior is different when the system shows negative and positive geometrical nonadditivity. In the case of systems with negative energetic nonadditivity, which may exhibit demixing transition in the liquid phase, their phase behavior is also strongly affected by the geometric non-additivity. The systems with negative geometric nonadditivity have been demonstrated to show reentrant miscibility, while those with positive geometric nonadditivity show enhanced tendency toward mixing at sufficiently high temperatures. We have evaluated phase diagrams for several systems.


A Synthetic Route to Sodium α-Aminoalkanesulfinates and Their Application in the Generation of α-Aminoalkyl Radicals for Radical Addition Reactions.
The synthesis of sodium α-aminoalkanesulfinates and their synthetic utility as α-aminoalkyl radical precursors are reported. A variety of α-aminoalkanesulfinates were readily obtained from the reaction between the anions of N-Boc-protected alkylamines and 1,4-diazabicyclo[2.2.2]octanebis(sulfur dioxide). Treatment of sodium α-aminoalkanesulfinates with (diacetoxyiodo)benzene easily generated the corresponding α-aminoalkyl radicals under mild conditions, which were then applied in radical 1,2-addition to imines, radical 1,4-addition to electron-deficient olefins, and radical addition/cyclization to 2-isocyanobiphenyls.


The Application of Biological Feedback in the Rehabilitation of Patients after Ischemic Stroke.
Balance disorders are the main concern for patients after an ischemic stroke. They are caused by an abnormal force on the affected side or paresis, which causes uneven loading and visuospatial disorders. Minimizing the effects of stroke is possible through properly conducted rehabilitation. One of the known ways to achieve this objective is biological feedback. The lack of proper muscle tone on one side of the body is manifested by the uneven pressure of the lower extremities on the ground. The study and control groups were composed of two equal groups of 92 people each, in which the same set of kinesiotherapeutic exercises were applied. Patients in the study group, in addition to standard medical procedures, exercised five days a week on a Balance Trainer for four weeks. The examination and training with the device were recorded on the first day of rehabilitation, as well as after two and four weeks of training. The assessment was performed using the following functional tests and scales: Brunnström, Rankin, Barthel, Ashworth, and VAS. Patients in the control group started exercising on the Balance Trainer two weeks after the first day of rehabilitation using traditional methods. The study results reveal statistically significant reductions in the time the body's center of gravity (COG) spent in the tacks, outside the tracks and in the COG distance, lower COG excursions in all directions. Post-stroke patients that received biofeedback training presented significantly better results than patients that did not receive such training.


Allelotype analysis of esophageal adenocarcinomas: evidence for the involvement of sequences on the long arm of chromosome 4.
The incidence of esophageal adenocarcinoma has increased dramatically over the past 20 years. The causes for this change in incidence and the genetic defects that underlie tumorigenesis are unknown. We performed loss of heterozygosity (LOH) studies in esophageal adenocarcinomas in an effort to map the location of tumor suppressor genes involved in the initiation or progression of this cancer. A genome-wide search for LOH was undertaken using microsatellite repeat polymorphisms and a panel of 27 tumor and matched normal DNAs. This is the first report of an allelotype analysis of esophageal adenocarcinomas. We observed frequent loss of sequences on the short arm of chromosome 17 in the region of the TP53 gene. We also identified a region on 4q lost in more than half of the tumors investigated. The high rate of LOH for 4q sequences speaks to the involvement of an as yet unidentified tumor suppressor gene in esophageal adenocarcinoma tumorigenesis.


Environmental Control of Phosphoenolpyruvate Carboxylase Induction in Mature Mesembryanthemum crystallinum L.
Mesembryanthemum crystallinum L. plants shift the mode of carbon assimilation from C(3) to Crassulacean acid metabolism when stressed by high salinity. A prerequisite for Crassulacean acid metabolism induction is the synthesis of phosphoenolpyruvate carboxylase (PEPCase). A moderate increase in the abundance of PEPCase transcripts and activity is observed in 7-week-old, well-watered plants. This increase in PEPCase coincides in time with a decrease in the growth rate of the shoots. The steady-state level of PEPCase activity is uniform along the leaves of well-watered plants, as can be shown by comparing leaves of different age from individual 7-week-old plants. In contrast, the rate of induction in response to salt stress varies with the age of plants and to a lesser extent with the age of the leaves. Two-week-old seedlings induce PEPCase slowly under a moderate salt stress regimen, whereas older plants induce faster. When individual leaves from a seven-week-old plant are compared with respect to induction velocity, no clear-cut correlation with leaf age is apparent. The highest induction rate is observed in leaves from node five that are about 2 weeks old at the beginning of the experiment. PEPCase transcripts are readily down-regulated to minute levels when detached leaves are hydrated. The levels reached after 8 hours of rehydration are very similar, regardless of whether the leaves were cut from young or old plants or whether the plants were previously salt-stressed or well-watered. It is concluded that environmental rather than developmental factors are predominant in determining abundance of PEPCase activity and transcripts in leaves of mature M. crystallinum plants.


The risks of ankylosis of 89 avulsed human teeth stored in saliva prior to replantation-A re-evaluation of a long-term clinical study.
The survival of an avulsed tooth highly depends on the emergency management. The aim of this study was to evaluate the risk of ankylosis for avulsed human teeth stored in saliva preceded by various dry storage conditions prior to replantation. Data include 74 patients (54 male and 20 female) with 89 avulsed and replanted teeth (16 immature teeth, 73 mature teeth). Patient ages ranged from 6 to 36 years (median: 13.0 years). All teeth were stored in saliva before replantation. Treatment and follow-up were performed according to a standardized procedure. Follow-up periods ranged from 7 months to 20 years (mean 5.3 years). The risk of ankylosis over time was estimated by the Aalen-Johansen method in relation to the length of dry storage and the stage of root development. The effect of risk factors (root development and length of dry time) on the risk of ankylosis was analysed by Cox regression analysis. For mature teeth, dry storage for 5 min or less before saliva storage resulted in a 47.4% (95% confidence interval (CI): 32.8-60.7) ankylosis rate. When dry storage was >5 min and <20 min, the risk of ankylosis was 76.8% (95% CI: 45.7-91.5). When dry storage exceeded 20 min prior to saliva storage, ankylosis increased to 89.3% (95% CI: 68.0-96.7). Ankylosis also increased with increasing saliva storage time. Specifically, one additional minute of wet time increased the ankylosis hazard rate (HR) by approximately 1% (CI = [0%, 2%], p = .052). Teeth with mature root development were significantly more frequently affected by ankylosis than teeth with immature root development (HR: 2.4 (95% CI: 1.0-5.5), p = .04). Temporary storage in saliva should be encouraged if an avulsed permanent tooth cannot be immediately replanted or a suitable storage medium such as milk or saline is not immediately available at the place of the accident.


Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study.
In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p < 0.001). In comparison to age- and sex-matched peers, the proportion of problems in usual activities and anxiety/depression was significantly higher in MDS patients (p < 0.001). MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p < 0.001); in anxiety/depression in females and in younger people (p < 0.001); and in EQ-VAS in women and in persons older than 75 years (p < 0.05). Patients newly diagnosed with IPSS lower-risk MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.


[Episcleral single injection anesthesia in the caruncle for cataract surgery: report of 350 cases].
Episcleral single injection anesthesia in the caruncle ovoïds the rare but potentially dangerous complications and incidents of classic local anesthesia. Excellent motor and sensory block is obtained with a single injection in the anatomic marks are well defined. We have practiced this technique since February 1999 for cataract surgery in 350 cases. The different surgical techniques used were manual extracapsular extraction in 52% of cases, phacosection through tunnel incision in 38%, and phacoemulsification in 10%. Our preliminary results show good acceptance of the episcleral anesthesia for both patients and surgeons. Because it is effective and safe, this anaesthtic technique may be an alternative to classic anesthetic techniques in all cases where topical anesthesia is not indicated.


Hormonal treatments modulate pulsatile plasma growth hormone, gonadotrophin and osteocalcin levels in postmenopausal women.
Oestrogen plays a role in modulating growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin secretion in women. Indeed, the postmenopausal period is characterized by changes in plasma GH, LH, FSH and osteocalcin levels. The aim of the present study was to investigate the changes in the secretory patterns of these hormones in postmenopausal women under different therapeutic regimens. A total of 20 subjects took part in the study. They were subdivided into four groups comprising 5 untreated postmenopausal women (time since menopause 1-5 years), 5 postmenopausal women receiving steroid hormone replacement therapy, 5 postmenopausal women receiving salmon calcitonin and 5 fertile women with regular menstrual cycles. Blood samples were collected every 15 min for 4 h and hormone levels were measured by radioimmunoassay. Plasma GH levels fell in the postmenopausal women, but were restored under oestrogen-progestogen treatment. The pulsatile patterns of plasma LH and FSH did not show significant differences in the treated and untreated women. Plasma osteocalcin levels showed episodic fluctuations and mean levels decreased under steroid hormone or calcitonin treatment. No significant correlation was observed between plasma GH and osteocalcin or gonadotrophin levels or body mass index.


Optical zoom camera module using two poly-dimethylsiloxane deformable mirrors.
Miniaturization is an essential trend in the design of portable devices. Motor-driven lens technology is a traditional way to achieve autofocus and optical zoom functions. This approach usually requires considerable space and consumes significant power. Reflective optics is a methodology that not only can fold the optical path, but it has the advantage of low chromatic aberration. In this paper, we use a deformable mirror as a reflecting element in an optical zoom system. For its low Young's modulus and residual stress, we choose polydimethylsiloxane as a deformable membrane that can provide a large stroke. The optical zoom module consists of a pair of micromachined deformable mirrors. The thickness of this module is 10 mm, which enables 2× optical zoom. The smallest effective focal length is 4.7 mm at a full field angle of 52°, and the f-number is 4.4. The largest effective focal length of the module is 9.4 mm, and the f-number is 6.4.


Positive psychology interventions in breast cancer. A systematic review.
Positive psychology is an emerging area of empirical study, not only in clinical, but also in health psychology. The present systematic review aims to synthesize the evidence about the positive psychology interventions utilized in breast cancer. Relevant studies were identified via Pubmed, PsycINFO, Web of Science, Scopus, Cochrane, CINAHL, Wiley Online Library, TDX, and DIALNET databases (up to April 2013). Only those papers focused on interventions related to positive psychology and carried out on breast cancer patients were included. Of the 7266 articles found through databases, 16 studies were finally included in this review. Five groups of therapies were found: mindfulness-based approaches, expression of positive emotions, spiritual interventions, hope therapy, and meaning-making interventions. These specific interventions promoted positive changes in breast cancer participants, such as enhanced quality of life, well-being, hope, benefit finding, or optimism. However, the disparity of the interventions and some methodological issues limit the outcomes. Some studies provided relevant evidence about the clear development of positive aspects from the breast cancer experience. Positive interventions applied to patients and survivors of breast cancer were found to be able to promote positive aspects. A global consensus of a positive therapies classification is needed to take one more step in structuring positive psychology.


Morphological evaluation of maxillary second molars with fused roots: a micro-CT study.
To evaluate the internal and external morphologies of fused-rooted maxillary second molars by means of micro-computed tomography (micro-CT) analysis. A total of 100 fused-rooted maxillary second molars from a Brazilian subpopulation were divided into six groups according to the root morphology. The samples were scanned at a resolution of 19.6 μm and evaluated with regard to the external morphology of the roots, the root canal configuration, the percentage frequency of C-shaped canals and isthmuses, as well as the morphology of the root canal system at 1, 2 and 3 mm from the anatomical apex of the fused roots. The most prevalent root canal fusions were type 1, mesiobuccal root fused with distobuccal root (32%), followed by type 3, DB root fused with P root (27%), and type 4, MB root fused with DB root, and P root fused with MB or DB roots (21%). The prevalence of C-shaped root canal systems were 22%. Depending on the type of root fusion, the percentage frequency of isthmuses in the apical level varied from 9.3% to 42.8%, whilst the presence of apical deltas ranged from 18.5% to 57.1% of teeth. The root canal system of maxillary second molars with fused roots may have a high incidence of merging canals, isthmuses, apical deltas and C-shaped configurations.


Colonic adenoma with squamous metaplasia.
Squamous metaplasia arising within colon adenomas is a rare occurrence, with a 0.4% incidence noted predominantly in elderly males. A case of squamous metaplasia arising in a tubulovillous adenoma of the cecum, associated with adenocarcinoma, is described. Squamous metaplasia was immunoreactive for beta-catenin, but negative for cytokeratin 20, CDX2, p63, estrogen receptor, progesterone receptor, p16, and human papilloma virus. Squamous differentiation may serve as a precursor lesion for squamous neoplasia of the colorectum.


Accuracy of motor responses in subjects with and without control of antagonist muscle.
1. The aim of this study was to investigate the role of the antagonist muscle in determining the accuracy of fast, single-joint motor responses to a target. We recently found that C5/C6 tetraplegic subjects, who lacked voluntary control of their triceps muscle, were less accurate than control subjects in producing fast flexion movements to a target. 2. Two hypotheses are proposed to account for these larger errors: 1) the ability of tetraplegic subjects to compensate for errors arising early in the motor response is impaired because of the lack of antagonist muscle activation; or 2) tetraplegic subjects lack antagonist (braking) force, so they must use much smaller accelerative forces when they move, in order to avoid overshooting their target. Because studies have shown that low levels of force are produced with less relative accuracy than larger forces, this relative inaccuracy of force generation by the motor control system at low force levels is responsible for the inaccuracy of tetraplegics' movements. To test these two hypotheses, we compared the variability of "fast and accurate as possible" force pulses in four control subjects and four C5/C6 tetraplegic subjects to targets at 15, 30, and 45% of maximum voluntary contraction. Multiple regression analyses were performed to look for patterns of agonist or antagonist muscle activation consistent with compensatory adjustments for early trajectory errors in both groups of subjects. 3. Force rise time was significantly prolonged in tetraplegic subjects, although there was some overlap between groups. At similar levels of effort, there were no significant differences in constant and variable errors of control and tetraplegic subjects. We also found no consistent statistical evidence for the presence of compensatory electromyographic activity in either group of subjects. Subjects who lacked the ability to make corrections involving the triceps muscle performed as well as subjects with normal triceps strength. This suggests that a corrective mechanism involving the triceps must have a weak role, if any, in these experiments. 4. Together with our observation that lower force targets are indeed associated with larger relative variable errors, in both control and tetraplegic subjects, the above results lead us to conclude that the second hypothesis listed above is more likely correct. The antagonist muscle clearly enables the production of briefer force pulses. In addition, the antagonist indirectly contributes to the accuracy of isotonic movements because antagonist braking allows larger agonist forces to be used. These larger agonist forces are less variable, and produce more accurate movements, than the smaller forces used by tetraplegic subjects.


Pollen grains as a low-cost, green, alternative sorbent for hydrophilic solid-phase extraction.
Many natural products have demonstrated functionality as novel, green sorbents for organic compounds. However, only limited reports exist on the use of such green materials as solid-phase extraction (SPE) sorbents for select organic acids. In this study, we employed pollen grains as a hydrophilic sorbent and investigated the influence of various extraction parameters using a series of experimental designs. The chemical structure and surface properties of the prepared sorbent were investigated by Fourier-transform infrared spectroscopy and scanning electron microscopy. The Plackett-Burman design was used to experimentally screen for parameters that significantly influenced the extraction performance. Three selected parameters were then statistically optimized by applying a central composite design combined with a response surface methodology. Phenolic acid residues were determined and quantified using high performance liquid chromatography with ultraviolet detection; a mass spectrometric detector in the selected ion monitoring mode was also used for identification. As a practical example, phenolic acids in the soil were successfully separated by the developed pollen sorbent. These results therefore indicate that pollen grains can be considered as a sustainable, green, and safe alternative to bare silica for extraction and separation applications.


Pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure.
To ascertain the effects of chronic renal failure on the pharmacokinetics of 1R-cis 1'R-cis atracurium besylate (a stereoisomer, designated 51W89), we gave a bolus dose of 0.1 mg kg-1 (2 x ED95) to 17 patients with end-stage renal failure and to 15 patients with normal renal function undergoing elective surgery. All patients received thiopentone, fentanyl and midazolam i.v. and 70% nitrous oxide in oxygen. Blood samples were obtained over 8 h and plasma analysed for 51W89 and laudanosine concentration, using high pressure liquid chromatography. A two-compartment model was fitted to the 51W89 plasma concentration data using the NONMEM program, to estimate pharmacokinetic variables and to determine the influence of renal failure, age, weight and sex. Clearance of 51W89 was found to be reduced by 13% in renal failure. The typical value of T1/2 beta was 4.2 min longer in renal failure than in the healthy patients (34.2 vs 30.0 min, P < 0.005). In the healthy patients, clearance of 51W89 was greater in males, but it decreased with increasing age by approximately 1.5 ml min-1 yr-1. Mean plasma laudanosine concentrations were significantly higher in the renal failure group; nevertheless, they were approximately one-tenth of those reported after atracurium.


Developing Process Maps as a Tool for a Surgical Infection Prevention Quality Improvement Initiative in Resource-Constrained Settings.
Surgical infections cause substantial morbidity and mortality in low-and middle-income countries (LMICs). To improve adherence to critical perioperative infection prevention standards, we developed Clean Cut, a checklist-based quality improvement program to improve compliance with best practices. We hypothesized that process mapping infection prevention activities can help clinicians identify strategies for improving surgical safety. We introduced Clean Cut at a tertiary hospital in Ethiopia. Infection prevention standards included skin antisepsis, ensuring a sterile field, instrument decontamination/sterilization, prophylactic antibiotic administration, routine swab/gauze counting, and use of a surgical safety checklist. Processes were mapped by a visiting surgical fellow and local operating theater staff to facilitate the development of contextually relevant solutions; processes were reassessed for improvements. Process mapping helped identify barriers to using alcohol-based hand solution due to skin irritation, inconsistent administration of prophylactic antibiotics due to variable delivery outside of the operating theater, inefficiencies in assuring sterility of surgical instruments through lack of confirmatory measures, and occurrences of retained surgical items through inappropriate guidelines, staffing, and training in proper routine gauze counting. Compliance with most processes improved significantly following organizational changes to align tasks with specific process goals. Enumerating the steps involved in surgical infection prevention using a process mapping technique helped identify opportunities for improving adherence and plotting contextually relevant solutions, resulting in superior compliance with antiseptic standards. Simplifying these process maps into an adaptable tool could be a powerful strategy for improving safe surgery delivery in LMICs.


Middermal elastolysis. Report of a case and immunohistochemical studies on the dermal distribution of fibrillin, vitronectin and amyloid P component.
A 39-year-old woman with demarcated wrinkled areas, histologically characterized by absence of elastic fibers in the middle and upper reticular dermis, is described. Immunoreactivity of vitronectin and amyloid P component, present at the periphery of elastic fibers in normal skin in adults, was absent from the middermis of lesional skin as were orcein stained fibers. C9 neoantigen immunoreactivity, associated with elastic fibers in sun-exposed skin of middle-aged and elderly individuals, was present in conjunction with elastic fibers in papillary and lower reticular dermis in lesional skin but was absent in the middermis. In contrast, a fibrillin immunoreactive network was present throughout the dermis, indicating that the elastin-associated microfibrils are retained in the absence of amorphous elastin in lesional skin of middermal elastolysis.


Mentorship in Nuclear Medicine-Why and How?
Mentorship is a highly gratifying relationship that requires commitment from all involved parties. Several different mentorship models exist that can be modified to suit the requirements of the mentors and mentees, and be fine-tuned for individuals at different career levels. Our proposed framework can be deployed as a pilot design for the trainees and early-career faculty members in nuclear medicine with the scope of appropriate timely modifications based on user feedback.


Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: evaluation with rCBF-SPECT.
We treated five patients with hemispheric ischemic stroke with intravenous recombinant tissue plasminogen activator (rtPA), within 3-6 h after stroke onset. Regional cerebral blood flow was evaluated with single photon emission computed tomography (rCBF-SPECT) before and after treatment. One patient with aphasia and a moderately severe hemiparesis, who had a small flow deficit, was treated 5 h and 30 min after the onset of his stroke and had a prompt and complete recovery. The post treatment rCBF-SPECT showed normal flow. One patient with a very large flow deficit died of transtentorial herniation. In three other patient clinical condition remained unchanged, in one of them despite restoration of flow, demonstrated by transcranial doppler examination. In all these patients the rCBF-SPECT remained abnormal. rCBF-SPECT is a valuable tool in the explanatory analysis of fibrinolytic treatment in ischemic stroke.


Helicobacter pylori accelerates the biliary epithelial cell proliferation activity in hepatolithiasis.
Several authors have reported the presence of H. pylori in the human biliary tract. The aim of this study was to investigate the influence of the presence of H. pylori on the epithelial cell proliferation activity in the biliary tract with hepatolithiasis. A histopathological examination and polymerase chain reaction were used to detect the presence of H. pylori from fourteen patients with hepatolithiasis. The cell proliferation activity in the biliary epithelia was determined using proliferating cell nuclear antigen staining. A histopathological examination and polymerase chain reaction analysis demonstrated H. pylori to be detected in 5 (37%) and 4 (29%) out of 14 patients, respectively. The proliferating cell nuclear antigen labeling index was significantly higher in the H. pylori-positive patients (28.3%) than in the H. pylori-negative individuals (4.9%). H. pylori is present in the biliary tract of patients with hepatolithiasis, while H. pylori promotes the formation of stones in the biliary tract. The development of intrahepatic cholangiocarcinoma might therefore be linked to the presence of H. pylori because of the accelerated activity of cell kinetics in the epithelium of the biliary tract.


Histological classification of schistosomal egg induced polyps of colon and their clinical significance. An analysis of 272 cases.
272 cases of schistosomal egg induced polyps collected from mass-screening for colorectal carcinoma in Jiashan County were divided into 3 types: fibrous type (FT), mixed type (MT) and epithelial proliferative type (ET). The ET was characterized by crypt elongation, hypertrophy, variation in size, disorderly arrangement, as well as the high percentage of atypical hyperplasia (64.9%). The coexistence and transition between inflammatory reactive hyperplastic and neoplastic crypts were noticed. By HID/AB staining, sialomucins were increased in ET, CEA and PNA receptors detected by the ABC method were present in 18/20 and 6/18 of ET respectively. The mucin expression of ET was similar to that of adenomas. It is likely that a spectrum of ET, atypical hyperplasia and adenoma may exist. We suggest that the patients with ET, especially those with atypical hyperplasia, should be regarded as "risk group", and close follow-up is needed.


PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation.
PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas, macrocephaly, and mental deficiencies. We have used PTEN +/- mice to assess PTEN's role in subventricular zone (SVZ) precursor cells. For cultured SVZ neurosphere cells, haploinsufficiency for PTEN increases phosphorylation of Akt and forkhead transcription factor and slightly enhances proliferation. Based on a filter penetration assay, PTEN +/- cells are substantially more migratory and invasive than +/+ cells. The +/- cells also are more resistant to H(2)O(2)-induced apoptosis. Analysis of PTEN +/- and +/+ mice by BrdU labeling reveals no difference in the rate of cell proliferation in the SVZ. Exit of BrdU-labeled cells from the SVZ and radial migration to the outer layers of the olfactory bulb are more rapid for +/- cells. These observations indicate that PTEN regulates SVZ precursor cell function and is particularly important for migration and apoptosis in response to oxidative stress.


Tartary Buckwheat: A New Plant-Based Ingredient to Enrich Corn-Based Gluten-Free Formulations.
Tartary buckwheat is a pseudocereal receiving increasing attention as a minor crop interesting for agrobiodiversity conservation and sustainability. It is rich in bioactive substances which, however, may lead to sensory properties undesirable to the consumer, such as bitterness and astringency. The aim was to evaluate consumers' perception and overall liking of food products enriched with tartary or common buckwheat. A total of 120 consumers (56% women) aged 20-60 years (mean age ± SD: 38.8 ± 13.0 years) evaluated six samples of a corn-based gluten-free formulation enriched by increasing concentrations (20%, 30%, 40%) of either common (CB) or tartary buckwheat (TB) flour for overall liking and appropriateness of sensory properties. Results showed significant differences (p < 0.0001) in liking among samples. Considering all subjects, liking decreased with the increase of tartary buckwheat additions, although TB20 and TB30 samples were well accepted and comparable to all CB samples. TB40 was the least liked product. Two clusters of consumers showing opposite behaviours according to liking were found. One cluster (30%) showed an increased liking with the increasing amount of tartary buckwheat. These results show that by keeping the concentration of tartary buckwheat up to 30%, it is possible to develop new products accepted by consumers.


Mechanisms of inhibition of endothelial cell migration by taxanes.
Several antiangiogenic mechanisms have been proposed for the widely-used cancer chemotherapeutic drugs taxotere (docetaxel) and taxol (paclitaxel), but none has been definitively identified. We analyzed their effects at a range of concentrations on migration and mitosis of human umbilical vein endothelial cells (HUVECs) on microtubule and focal adhesion morphology and microtubule dynamic instability during migration. Both taxanes inhibited migration by inhibiting both maintenance of the forward direction of the cell and by slowing migration over the entire contorted path length. At low (but not all) taxane concentrations that inhibit HUVEC migration, the shortening rates and shortening lengths of microtubules at the leading edge were strongly inhibited; peripheral microtubules were reduced in number and fewer targeted focal adhesions; focal adhesions doubled in length and became ring-shaped, elongate, and reduced in number; and an increase in stabilized microtubules occurred centrally. HUVEC migration was 13-19-fold more sensitive to taxanes than was mitosis confirming that taxanes exhibit significant effects in addition to mitotic arrest that may contribute to their overall antitumor effects. No relationship was detected between centrosome position and migration characteristics. The data suggest that taxanes inhibit migration, at least in part, by inhibiting the dynamic instability of microtubules that possibly interact with guanine nucleotide exchange factors and thus with the focal adhesion-associated G-proteins that then lead to disruption of the regulated formation and turnover of focal adhesions. A mechanism is presented by which subcytotoxic concentrations of taxanes might stabilize dynamic instability of a few microtubules and thereby inhibit migration and angiogenesis.


Bioinformatics and Gene Network Analyses of the Swine Mammary Gland Transcriptome during Late Gestation.
We used the newly-developed Dynamic Impact Approach (DIA) and gene network analysis to study the sow mammary transcriptome at 80, 100, and 110 days of pregnancy. A swine oligoarray with 13,290 inserts was used for transcriptome profiling. An ANOVA with false discovery rate (FDR < 0.15) correction resulted in 1,409 genes with a significant time effect across time comparisons. The DIA uncovered that Fatty acid biosynthesis, Interleukin-4 receptor binding, Galactose metabolism, and mTOR signaling were among the most-impacted pathways. IL-4 receptor binding, ABC transporters, cytokine-cytokine receptor interaction, and Jak-STAT signaling were markedly activated at 110 days compared with 80 and 100 days. Epigenetic and transcription factor regulatory mechanisms appear important in coordinating the final stages of mammary development during pregnancy. Network analysis revealed a crucial role for TP53, ARNT2, E2F4, and PPARG. The bioinformatics analyses revealed a number of pathways and functions that perform an irreplaceable role during late gestation to farrowing.


Preliminary results of diode laser surgery for early glottic cancer.
To analyze the complications and preliminary oncologic results of microscopic diode laser surgery. Prospective research. Ankara Oncology Education and Research Hospital. This prospective study was conducted on a series of 64 patients with glottic carcinoma (Tis, T1, T2) treated with microscopic endolaryngeal diode laser surgery. Four patients had local recurrence (6.2%). Local control and larynx preservation rates were 93.8% and 100%, respectively, for all groups of patients. Two-year disease-free survival after primary surgery was 100% for the Tis group, 96.4% for the T1 group, and 89.7% for the T2 group. When considering anterior commissure involvement, 2-year disease-free survival after primary surgery was 100% for the AC0 group, 85.7% for the AC1 group, and 85.7% for the AC2 group. Our study of microscopic diode laser resection of Tis, T1, and T2 glottic tumors showed similar oncologic results to previous reports about CO2 laser surgery. In anterior commissure tumors, both techniques had high complication and recurrence rates.


Fingerfoods: a feasibility study to enhance fruit and vegetable consumption in Dutch patients with dementia in a nursing home.
Eating problems are highly prevalent in older patients with dementia and as a consequence, these patients are at greater risk of becoming malnourished. Fingerfoods, snacks that can be picked with thumb and forefinger, could be used to counteract malnutrition in patients with dementia. The aim of this feasibility study was to evaluate whether providing fruit and vegetable rich fingerfoods in the form of recognizable and familiar snacks on top of the normal intake was feasible for both patients with dementia and caregivers as a means to increase patients' nutritional status. Institutionalised patients with dementia (N = 15, 93% female, mean age = 85 years) were included in this feasibility study in the Netherlands. The residents received their regular diet supplemented with fingerfoods, comprising quiches and cakes rich in fruit or vegetables, for 6 weeks. Daily fingerfood consumption together with compensation behaviour at dinner of residents was administered with a checklist and food diaries at the start and end of the intervention as dose delivered. Furthermore, caregivers were asked to fill out a feedback form at the end of the intervention to measure fidelity and appreciation of the intervention. Patients consumed on average 1.4 pieces (70 g) of fingerfoods daily, containing 41 g of fruit and/or vegetables. Fruit and vegetable consumption increased during the provision of the fingerfoods and the residents seemed not to compensate this intake during the rest of the day. The intervention was generally positively received by the majority of caregivers, depending on the type of fingerfood and state of the resident. This feasibility study showed that providing recognizable fruit and vegetable rich fingerfoods to patients with dementia seems feasible for both patients and caregivers and could provide a pragmatic approach to enhance fruit and vegetable consumption and total food intake in institutionalized elderly. In an up-scaled study, effects of fingerfoods on nutritional status and quality of life should be investigated.


Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.
In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out in 1999 and 2001 to determine (i) whether faecal Escherichia coli resistance to co-trimoxazole in TB patients changed with time, and (ii) whether the resistance pattern was different in HIV-positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E. coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone) it was 62% (P < 0.001). The study shows a significant increase of E. coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E. coli and the Salmonella species, these findings could herald limitations on the short- and long-term benefits to be expected from the use of co-trimoxazole prophylaxis in preventing non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in Malawi.