Pilot-scale production of murine monoclonal antibodies in agitated, ceramic-matrix or hollow-fiber cell culture systems.
The purpose of this research was to compare three bioreactor systems for the pilot-scale production of monoclonal antibodies (MAbs). We needed to produce gram quantities of murine MAbs against human prostatic acid phosphatase for use in fragmentation, radiolabeling and in vivo radio-imaging studies. The stable hybridoma cell line secreting IgG1 antibodies was chosen for production. Of the available bioreactor systems, we chose to test an agitating 30-liter bioreactor in repeated batch mode, a ceramic-matrix bioreactor in both repeated batch and continuous perfusion modes and a hollow-fiber bioreactor in continuous perfusion mode. The highest cultured MAb yield, 151 +/- 126 mg/day (mean +/- SD, n = 22), was achieved in the 30-liter bioreactor in repeated batch mode with the MAb being harvested in a large volume of medium, giving a reactor productivity of 4.3 +/ 3.4 mg/liter/day (mean +/- SD, n = 22). The most concentrated MAb was harvested from the continuously perfused hollow-fiber bioreactor, which had the highest reactor productivity, 307 +/ 142 mg/liter/day (mean +/- SD, n = 47) and an average rate of MAb production of 55.3 +/- 25.7 mg/day (mean +/- SD, n = 47). Taking the use of serum into consideration, the cost of MAb production was lowest in the continuously fed and harvested ceramic-matrix and hollow-fiber cell culture systems. A compact blood glucose meter proved to be a novel and suitable device for the rapid monitoring of glucose concentrations in hybridoma cultures.


The Use of Mycophenolate Mofetil in the Treatment of Bullous Pemphigoid.
The first-line treatment for patients with bullous pemphigoid (BP), the most common autoimmune blistering disease, is systemic glucocorticoids, which are associated with numerous side effects. Mycophenolate mofetil (MMF) may be beneficial in BP as a steroid-sparing alternative; however, evidence is limited. To evaluate the efficacy and safety of MMF in patients with BP. In this retrospective chart review, records of patients with BP treated with MMF alone or in combination with prednisone, who presented between 2013 and 2017, were analyzed. Twenty-six patients were included. Twelve patients were treated with MMF alone (monotherapy) and fourteen were treated with MMF and prednisone concomitantly at some point during their treatment course (dual therapy). Improvement in BP was observed in 26 (100%) patients with MMF therapy. Mean time to improvement was 0.8 months. Twenty-five (96.2%) patients [11/12 (91.7%) on monotherapy and 14/14 (100%) on dual therapy] achieved complete control of their disease. Mean time to complete control amongst all patients was 5.6 months. Twelve (46.2%) patients [4/12 (33.3%) on monotherapy and 8/14 (57.1%) on dual therapy] experienced disease remission with no subsequent flares for up to 15 months after MMF was discontinued. Twelve mild adverse effects were reported with one individual discontinuing therapy due to gastrointestinal symptoms. No serious adverse effects were reported. MMF is a safe and effective therapy for BP and can yield improvement and complete response in most patients and remission in some. J Drugs Dermatol. 2022;21(2):151-155. doi:10.36849/JDD.6042.


Statistical techniques for comparing measurers and methods of measurement: a critical review.
1. Clinical and experimental pharmacologists and physiologists often wish to compare two methods of measurement, or two measurers. 2. Biostatisticians insist that what should be sought is not agreement between methods or measurers, but disagreement or bias. 3. If measurements have been made on a continuous scale, the main choice is between the Altman-Bland method of differences and least products regression analysis. It is argued that although the former is relatively simple to execute, it does not distinguish adequately between fixed and proportional bias. Least products regression analysis, although more difficult to execute, does achieve this goal. There is almost universal agreement among biostatisticians that the Pearson product-moment correlation coefficient (r) is valueless as a test for bias. 4. If measurements have been made on a categorical scale, unordered or ordered, the most popular method of analysis is to use the kappa statistic. If the categories are unordered, the unweighted kappa statistic (K) is appropriate. If the categories are ordered, as they are in most rating scales in clinical, psychological and epidemiological research, the weighted kappa statistic (K(w)) is preferable. But K(w) corresponds to the intraclass correlation coefficient, which, like r for continuous variables, is incapable of detecting bias. Simple techniques for detecting bias in the case of ordered categorical variables are described and commended to investigators.


Occurrence of Powdery Mildew Caused by Blumeria graminis f. sp. poae on Poa pratensis in China.
Poa pratensis, known as bluegrass, is a perennial grass and one of the best varieties with highly valued pasture and turf grass uses. It is widely grown on golf courses and used for lawns in squares and parks (Luo et al. 2020). During April and May 2020, powdery mildew-like signs and symptoms were observed on leaves of P. pratensis in Muye Park, Xinxiang city (35.3°N; 113.9°E), Henan Province, China. White or grayish powdery masses in spots- or coalesced lesions were abundant on the adaxial surfaces of leaves and covered up to 90 % of the leaf area. Some of the mildew-infested leaves appeared chlorotic or began senescence. Mildew-infested leaves were collected to microscopically observe the morphological characteristics of this pathogen. Conidiophores were composed of foot cells, followed by one or two cells, and conidia. The ellipsoid- shaped conidia (n = 50) were 25 - 36 × 10 - 15 μm (length × width), on average 30 × 13 μm, with a length/width ratio of 2.3. Foot-cells (n = 15) were 30 - 44 μm long and 7 - 15 μm wide. On leaf surfaces, germinated conidia produced a short primary germ tube and then a long secondary germ tube that finally differentiated into a hooked appressorium. Chasmothecia were not found. Based on these morphological characteristics, the pathogen was initially identified as B. graminis f. sp. poae, the known forma specialis (f. sp.) of B. graminis on P. pratensis (Braun and Cook 2012; Troch et al. 2014). Mycelia of the pathogen were scraped from infected leaves and total genomic DNA was isolated using the method described previously (Zhu et al. 2019). The rDNA internal transcribed spacer (ITS) region was amplified applying primer pairs ITS1/ITS4 (White et al. 1990). The amplicon was cloned and sequenced by Invitrogen (Shanghai, China). The obtained sequence for the pathogen was deposited into GenBank under Accession No. MT892956 and was 100 % identical (549/549 bp) to B. graminis on P. pratensis (AB273530) (Inuma et al. 2007). In addition, the phylogenetic analysis clearly showed that the identified fungus and B. graminis f. sp. poae were clustered in the same branch. To perform pathogenicity analysis, leaf surfaces of eight healthy plants were inoculated by dusting fungal conidia from diseased leaves. Eight non-inoculated plants served as a control. The non-inoculated and inoculated plants were separately maintained in two growth chambers (humidity, 60 %; light/dark, 16 h/8 h; temperature, 18 ℃). Twelve to fourteen days after inoculation, B. graminis signs were visible on inoculated leaves, while control plants remained healthy. The pathogenicity assays were repeated twice and showed same results. Therefore, based on the morphological characteristics and molecular analysis, the pathogen was identified and confirmed as B. graminis f. sp. poae. This pathogen has been reported on P. pratensis in Switzerland and Japan (Inuma et al. 2007). This is, to our best knowledge, the first disease note reporting B. graminis on P. pratensis in China. Because the hybridization of B. graminis formae speciales (ff. spp.). allow the pathogens to adapt to new hosts, P. pratensis may serve as a primary inoculum reservoir of B. graminis to threaten other species, including cereal crops (Klingeman et al. 2018; Menardo et al. 2016). In addition, powdery mildew may negatively affect the yield and quality of grasses. Our report expands the knowledge of B. graminis f. sp. poae and provides the fundamental information for future powdery mildew control.


Homozygosity for a nonsense mutation in the alpha-tropomyosin slow gene TPM3 in a patient with severe infantile nemaline myopathy.
The nemaline myopathies are muscle disorders of variable severity and age of onset, with characteristic nemaline bodies in the sarcoplasm. Genes for dominant (NEM1) and recessive (NEM2A) nemaline myopathy have been localised to chromosomes one and two, respectively. A missense mutation in the alpha-tropomyosin gene (TPM3) has been associated with NEM1 in one family. Probands from 76 other nemaline myopathy families have now been screened for TPM3 mutations. One proband, who was not noted to have any weakness neonatally, but who died at 21 months of age, was shown to be homozygous for a single strand conformation polymorphism (SSCP) in skeletal-muscle-specific exon 1 of TPM3. Sequencing revealed homozygosity for a nonsense mutation at codon 31 (CAG to TAG). The patient should have no functioning alpha-tropomyosin slow protein. The nemaline bodies in this patient were exclusively in type one fibres, consistent with the expression of TPM3 only in type one fibres.


Universality in lattice models of dynamic arrest: introduction of an order parameter.
We introduce an order parameter for dynamical arrest. Dynamically available volume (unoccupied space that is available to the motion of particles) is expressed as holes for the simple lattice models we study. Near the arrest transition the system is dilute in holes, so we expand dynamical quantities in a series of hole density. Unlike the situation when presented in particle density, all cases of simple models that we examine have a quadratic dependence of the diffusion constant on hole density. This observation implies that in certain regimes ideal dynamical arrest transitions may possess a hitherto unnoticed degree of universality.


Trend in cerebral palsy birth prevalence in eastern Denmark: birth-year period 1979-86.
To investigate changes in cerebral palsy birth prevalence and perinatal mortality rate by different gestational age groups, 1979-86, cerebral palsy cases in eastern Denmark were identified from the Danish Cerebral Palsy Register, and information on birth and mortality rates was sought in the Danish Medical Birth Register. From 1979-82 to 1983-86, the birth prevalence of cerebral palsy increased from 2.6 to 3.0 per 1000 (P < 0.05). The rate for infants of 31 weeks' gestation or more did not change, whereas a significant increase was observed in infants below 31 weeks (85-123 per 1000, P < 0.05). In the same periods, perinatal mortality in eastern Denmark decreased significantly from 8.6 to 7.8 per 1000. The decrease in stillbirth rate was significant in all subgroups of gestational ages except in those of 28-30 weeks' gestation. The early neonatal mortality rate decreased significantly only in infants below 31 weeks (282-239 per 1000, P < 0.05). Thus, in eastern Denmark, cerebral palsy birth prevalence has increased from birth-year period 1979-82 to 1983-86 because of an increased rate in preterm infants below 31 weeks, who at the same time had a reduced risk of early neonatal death.


Improved cycling time-trial performance after ingestion of a caffeine energy drink.
Not all athletic competitions lend themselves to supplementation during the actual event, underscoring the importance of preexercise supplementation to extend endurance and improve exercise performance. Energy drinks are composed of ingredients that have been found to increase endurance and improve physical performance. The purpose of the study was to investigate the effects of a commercially available energy drink, ingested before exercise, on endurance performance. The study was a double-blind, randomized, crossover design. After a 12-hr fast, 6 male and 6 female trained cyclists (mean age 27.3 +/- 1.7 yr, mass 68.9 +/- 3.2 kg, and VO2 54.9 +/- 2.3 ml x kg-1 x min-1) consumed 500 ml of either flavored placebo or Red Bull Energy Drink (ED; 2.0 g taurine, 1.2 g glucuronolactone, 160 mg caffeine, 54 g carbohydrate, 40 mg niacin, 10 mg pantothenic acid, 10 mg vitamin B6, and 10 microg vitamin B12) 40 min before a simulated cycling time trial. Performance was measured as time to complete a standardized amount of work equal to 1 hr of cycling at 70% Wmax. Performance improved with ED compared with placebo (3,690 +/- 64 s vs. 3,874 +/- 93 s, p < .01), but there was no difference in rating of perceived exertion between treatments. b-Endorphin levels increased during exercise, with the increase for ED approaching significance over placebo (p = .10). Substrate utilization, as measured by open-circuit spirometry, did not differ between treatments. These results demonstrate that consuming a commercially available ED before exercise can improve endurance performance and that this improvement might be in part the result of increased effort without a concomitant increase in perceived exertion.


Double-pass excimer laser photorefractive keratectomy: treatment in 62 eyes with high myopia.
To evaluate the efficacy and safety of Excimer Laser Photorefractive Keratectomy (PRK) on the correction of high myopia, we performed planned double-pass PRK procedure at the same session on 62 eyes of 55 patients with myopia ranging from -6.30D to -15.25D (mean, -9.94D). In the first pass, a myopic correction of -6.00D with a 4.5 millimeter ablation zone was performed, and immediately after, a second correction of remaining myopia with a 5.0 millimeter ablation zone was performed. Attempted correction ranged from -6.30D to -9.50D (mean, -8.70D). The eyes were divided into two groups which were -10.50D or less (group A), and higher than -10.50D (group B). All the eyes received topical corticosteroid therapy postoperatively. One year after double-pass PRK, uncorrected visual acuity in group A and B improved to 20/40 or better in 84.0%, and 73.3% of the eyes and to 20/30 or better in 75.0% and 33.3% of the eyes respectively. The mean refractive errors at 12 months after PRK were -0.3 +/- 1.6D in group A, and -1.5 +/- 2.1D in group B. The percent of achieved correction within +/- 1.0D were 70.8% in group A, and 46.7% in group B 12 months after surgery. The epithelium healed by three days and there were no corneal erosions. Corneal haze (Grade 2 or more) was seen in 9.0% in group A and 36.4% in group B at 12 months after PRK. A planned double-pass PRK is a promising approach to correct high myopia (up to -10.50D), but long-term follow up will be required.


Observation of Efimov Molecules Created from a Resonantly Interacting Bose Gas.
We convert a strongly interacting ultracold Bose gas into a mixture of atoms and molecules by sweeping the interactions from resonant to weak. By analyzing the decay dynamics of the molecular gas, we show that in addition to Feshbach dimers it contains Efimov trimers. Typically around 8% of the total atomic population is bound into trimers, identified by their density-independent lifetime of about 100 μs. The lifetime of the Feshbach dimers shows a density dependence due to inelastic atom-dimer collisions, in agreement with theoretical calculations. We also vary the density of the gas across a factor of 250 and investigate the corresponding atom loss rate at the interaction resonance.


Outcome of therapy in the conservative management of temporomandibular pain dysfunction disorder.
The present study considered predictors of the outcome of treatment for temporomandibular pain dysfunction disorder (TMPD). Thirty-seven patients were assessed with objective and self-report measures of physiological and psychosocial aspects of this disorder at initial assessment and at 6-month follow-up subsequent to conservative physical therapy. Patients were subdivided into slow and rapid responders to conservative physical therapy based on self-reported level of improvement. Measures employed included the Temporomandibular Pain Dysfunction Disorder Questionnaire and the Temporomandibular Pain Dysfunction Disorder Clinical Form. Eighty-one per cent of patients showed a 50% or greater improvement in pain severity at follow-up, with minimal differential changes across the two groups found in the physiological symptoms, while the rapid responding group showed greater improvement in terms of psychosocial factors. These findings indicated that psychosocial factors, particularly coping strategies and illness behaviour, cannot be ignored in the management of TMPD.


DR-positive maternal engrafted T cells in a severe combined immunodeficiency patient without graft-versus-host disease.
A 2 1/2-year-old male infant with severe combined immunodeficiency was documented by HLA typing and the presence of a female karyotype in the few spontaneously dividing cells to have an intrauterine-derived maternal lymphocyte graft. The presence of DR antigens on the engrafted maternal E rosette-forming T cells was demonstrated by both cytotoxicity and immunofluorescence techniques using both conventional and monoclonal antihuman DR antisera. These DR antigens were of the same allospecificity, DR4, as the mother's peripheral blood B cells. The patient's B cells and monocytes expressed DR alloantigens DR4 and DR3, corresponding to his genotype. Although fresh maternal lymphocytes react strongly in vitro against patient non-T cells, the engrafted maternal T lymphocytes no longer show this activity. Furthermore, clinical evidence suggesting mild graft-versus-host disease was completely resolved by the end of his first year. The presence of the DR-positive maternal cells may reflect the survival of a group of activated suppressor cells mediating graft tolerance of host tissue.


Histopathological changes of the skin in hens infested with Dermanyssus gallinae.
Studies were carried out on dead hens from a commercial farm of layer hens. Sections of skin from the region of the breast and under the wings with changes following mite bites were taken for histopathological examinations. In the histopathological preparations hyperkeratosis of epidermis and pachydermatosis were ascertained. Numerous lymphocytic cells focally infiltrated the connective tissue and were present under the epidermis. Subcutaneous connective tissue was oedematous. Furthermore, excessive desquamation of the corneal layer of the epidermis and small epidermoidal cysts in dermis occurred, containing callous cells and amorphous protein substances.


GRIN'91: gradient-index optical systems.
The Ninth Topical Meeting on Gradient-Index Optical Systems was held in Monterey, Calif., 8-9 April 1991. In this Introduction we define the scope of the contributions published in this feature issue.


Identification of Clostridium difficile Immunoreactive Spore Proteins of the Epidemic Strain R20291.
Clostridium difficile infections are the leading cause of diarrhea associated with the use of antibiotics. During infection, C. difficile initiates a sporulation cycle leading to the persistence of C. difficile spores in the host and disease dissemination. The development of vaccine and passive immunization therapies against C. difficile has focused on toxins A and B. In this study, an immunoproteome-based approach to identify immunogenic proteins located on the outer layers of C. difficile spores as potential candidates for the development of immunotherapy and/or diagnostic methods against this devastating infection is used. To identify potential immunogenic proteins on the surface of C. difficile R20291, spore coat/exosporium extracts are separated by 2D electrophoresis (2-DE) and analyzed for reactivity against C. difficile spore-specific goat sera. Finally, the selected spots are in-gel digested with chymotrypsin, peptides generated are separated by nanoUPLC followed by MS/MS using Quad-TOF-MS, corroborated by Ultimate 3000RS-nano-UHPLC coupled to Q-Exactive-Plus-Orbitrap MS. The analysis identify five immunoreactive proteins: spore coat proteins CotE, CotA, and CotCB; exosporium protein CdeC; and a cytosolic methyltransferase. This data provides a list of spore surface protein candidates as antigens for vaccine development against C. difficile infections.


Affinity chromatography using trypanocidal arsenical drugs identifies a specific interaction between glycerol-3-phosphate dehydrogenase from Trypanosoma brucei and Cymelarsan.
A 36-kDa protein was isolated by affinity chromatography using Cymelarsan, an arsenical drug currently used in African trypanosomiasis treatment, as ligand. This protein was identified as glycerol-3-phosphate dehydrogenase. Trypanosomal glycerol-3-phosphate was bound covalently, whereas its counterpart from rabbit muscle bound by ionic interaction. Arsenical drugs inhibit the enzyme in a dose-dependent manner. Oxidation of cysteine residues protects against inactivation without significantly diminishing enzymic activity. Drug concentrations giving 50% inhibition of the dehydrogenase activity were determined for the enzyme from both Trypanosoma brucei and rabbit and indicate a higher sensitivity of the trypanosomal enzyme to arsenical drugs and thiol reagents. MS was used to identify residues of glycerol-3-phosphate dehydrogenase bound by Cymelarsan; they are not conserved in the mammalian enzyme.


Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial.
Immunomodulator therapy is effective for patients with Crohn's disease (CD) but has not been shown to affect disease progression, presumably because it is given too late after diagnosis. We compared the efficacy of early treatment (within 6 months after diagnosis) with azathioprine versus conventional management of patients at high risk for disabling disease. We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease. From July 2005 to November 2010, patients at 24 French centers were randomly assigned to treatment with azathioprine (2.5 mg ∙ kg(-1) ∙ day(-1), n = 65) or conventional management (azathioprine only in cases of corticosteroid dependency, chronic active disease with frequent flares, poor response to corticosteroids, or development of severe perianal disease) (n = 67). The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion. During the 3-year follow-up period, 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy. Forty-one patients in the conventional management group required immunosuppressant therapy (61%; median time to first prescription, 11 months). In the azathioprine group, a median 67% of trimesters were spent in remission (interquartile range, 11%-85%) compared with 56% in the conventional management group (interquartile range, 29%-73%) (P = .69). Among secondary outcomes, a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group (96% ± 3% and 82% ± 6% at month 36, respectively; P = .036). The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups. Based on results from a clinical trial, administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission. Clinicaltrials.gov, Number NCT00546546.


Immunochemical Assay for Satratoxin G and other Macrocyclic Trichothecenes Associated with Indoor Air Contamination by Stachybotrys chartarum.
Although satratoxin G (SG) is the primary macrocyclic trichothecene produced by Stachybotrys chartarum, a fungus frequently associated with outbreaks of indoor air illness, little is known about the actual quantities of this mycotoxin in suspect or normal building environments. Using antibodies produced against an SG hemisuccinate-bovine serum albumin conjugate, we devised an enzyme-linked immunosorbent assay that enabled the detection of as little as 100 pg/mL of SG and that could also detect other members of the satratoxin family. Detection by this assay of satratoxins in methanolic extracts of S. chartarum in rice cultures was comparable to that of high-performance liquid chromatography, indicating that this assay will be useful in detecting SG and other satratoxins in environmental samples.


Actin-related proteins.
Actin-related proteins (Arps) participate in a diverse array of cellular processes. They modulate assembly of conventional actin, contribute to microtubule-based motility catalyzed by dynein, and serve as integral components of large protein complexes required for gene expression. We highlight here recent work aimed at understanding the roles played by Arps in each of these processes.


Synthesis of 1,3-Dioxepine-Fused (Tricyclic) Bispyrazoles Involved with Pyrazolone Derivatives and Dichloromethane.
A simple and novel method for the synthesis of novel 1,3-dioxepine-fused (tricyclic) bispyrazoles is described. It involves a Cs2CO3-mediated O-alkylation of readily available pyrazolone derivatives with dichloromethane as the methylene source followed by PhI(OAc)2-mediated intramolecular oxidative biheteroaryl coupling under mild conditions. This scalable protocol was applied for the preparation of valuable and novel 1,3-dioxepine-fused (tricyclic) bispyrazoles that could find applications in medicinal or material chemistry.


[Quality of life of older people living in Antofagasta, Chile].
As basic needs of older people are covered, the concern about the determinants of their quality of life becomes preeminent. To evaluate the relationship between self-reported quality of life and related variables. The Quality of Life Survey for older people developed by the World Health Organization (WHOQOL-Old), the reduced scale of Ryff Psychological Well Being, the Functional Social Support Questionnaire, the SF-12 and GHQ12 general health surveys were applied to 406 older adults aged 71 ± 7 years (83% women), that were members of older people organizations and lived in Antofagasta, Chile. Older people that perceived themselves as sick had significantly lower quality of life scores. Self-acceptance, social support, autonomy and having a purpose in life also influenced the perception of quality of life. Health issues and the sense of self efficacy are determinants of the quality of life of these older subjects.


Vitronectins produced by human cirrhotic liver and CCl4-treated rats differ in their glycosylation pattern and tissue remodeling activity.
Liver cirrhosis (LC) is a disease characterized by pathological accumulation and alteration of extracellular matrix (ECM) proteins; the interaction between two such proteins, collagen and vitronectin (VN), is considered to be the key to controlling ECM remodeling in liver cirrhosis. If it is possible to control the modification of oligosaccharides on VN, it may be possible to retard progression of liver cirrhosis. In this study, we examined the relationship between changes in VN glycosylation and activity related to the remodeling of hepatic tissue in human LC and a rat model of LC generated using carbon tetrachloride (CCl4). Plasma concentrations of VN in human LC declined to approximately two-thirds that in normal plasma, but the ratio of active VN, which has collagen-binding activities, increased 2.8 times in LC plasma. In contrast, purified LC-VN exhibited similar binding activities toward type I, IV, and V collagens to those of normal VN. Lectin reactivities and carbohydrate analyses of LC-VN revealed that branching, fucosylation, and sialylation of N-glycans were higher than those of normal VN. On the other hand, the plasma level of rat CCl4-VN increased and the ratio of active molecules to collagen in plasma decreased. Increased fucosylation of LC-VN was not detected in carbohydrates of CCl4-VN. The changes in rat VN due to CCl4 treatment did not correspond to the changes in plasma levels of human VN caused by LC, the ratio of active molecules, or carbohydrate composition, thereby indicating that CCl4-treated rats are not an appropriate model for studying VNs in human LC. Glycosidase treatment of VNs supported the hypothesis that the collagen-binding activity of VN is modulated by alterations of glycosylation during LC, which may contribute to (a) the matrix incorporation of VN and (b) tissue fibrosis.


Recurrence of DiGeorge syndrome: prenatal detection by FISH of a molecular 22q11 deletion.
We report on a prenatal diagnosis by FISH of a familial 22q11 deletion associated with DiGeorge syndrome (DGS). The deletion was seen in the proband with symptoms of full DGS, in the physically normal father, and in a subsequent pregnancy. After birth this child showed hypocalcaemia, a T cell deficit, and a right sided aortic arch.


Increased Complications in Octogenarians Undergoing Same-Day Discharge following Total Knee Arthroplasty: A Matched Cohort Analysis.
Same-day discharge pathways in total knee arthroplasty (TKA) are gaining popularity as a means to increase patient satisfaction and reduce overall costs, but these pathways have not been thoroughly evaluated in potentially at-risk populations, such as in patients ≥80 years old. The purpose of this study was to compare 90-day complications and mortality following same-day discharge after primary TKA in patients ≥80 years old and those <80 years old. Patients who underwent unilateral primary TKA, were discharged on postoperative day 0, and had a minimum 90-day follow-up were identified in a national insurance claims database (PearlDiver Technologies) using Current Procedural Terminology code 27447. These patients were stratified into two cohorts based upon age: (1) nonoctogenarians (<80 years old) and (2) octogenarians (≥80 years old). These cohorts were propensity matched based upon sex, Charlson comorbidity index, and obesity status. Univariate analysis was performed to determine differences in 90-day complications and mortality between the two cohorts. In total, 1,111 patients were included in each cohort. Both cohorts were successfully matched, with no observed differences in matched parameters for demographics or comorbidities. There was no significant difference in 90-day mortality between the two cohorts (p = 0.896). However, octogenarians were at significantly increased risk of postoperative atrial fibrillation (20.8 vs. 10.4%; p < 0.001), nonatrial fibrillation arrhythmias (8.4 vs. 5.6%; p = 0.009), pneumonia (4.5 vs. 2.2%; p = 0.002), stroke (3.1 vs. 1.7%; p = 0.037), heart failure (10.5 vs. 7.5%; p = 0.012), and urinary tract infection (UTI; 14.3 vs. 9.4%; p < 0.001) compared with the nonoctogenarian cohort. Relative to matched controls, octogenarians were at significantly increased risk of numerous 90-day medical complications following same-day primary TKA, including cardiopulmonary complications, stroke, and UTI. Clinicians should be cognizant of these complications and counsel patients appropriately when electing to perform same-day TKA in the octogenarian population.


Different effects of aliskiren and losartan on fibrinolysis and insulin sensitivity in hypertensive patients with metabolic syndrome.
The aim of this study was to compare the effect of aliskiren and losartan on fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic syndrome. After 2-week placebo period, 76 outpatients with mild to moderate hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1 antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of treatment. At the end of each treatment period patients performed an euglycemic hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both aliskiren and losartan induced a significant and similar SBP/DBP reduction (-15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both drugs decreased PAI-1 antigen and activity after 2 weeks of treatment; subsequently, only the decreasing effect of aliskiren was sustained throughout the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1 increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs. aliskiren)]. The tPA activity showed no significant change with aliskiren and a decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs. aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01 vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs. baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of patients, despite similar BP reduction, aliskiren improved the fibrinolytic balance as well as IS, while losartan worsened the fibrinolytic balance and did not affect IS. The clinical relevance of these different effects remains to be clarified.


A staged decompression of right ventricle allows growth of right ventricle and subsequent biventricular repair in patients with pulmonary atresia and intact ventricular septum.
To achieve the growth of right-sided heart structures, our choice of the first palliation for patients with pulmonary atresia and intact ventricular septum (PA-IVS) includes a modified Blalock-Taussig shunt (BTS) with pulmonary valvotomy. We sought to analyse the impact of the first palliation on the growth of right-sided heart structures and factors associated with a choice of definitive surgical procedure. Fifty patients with PA-IVS who underwent a staged surgical approach from 1991 to 2012 were retrospectively reviewed. Right ventricular (RV)-coronary artery fistulas were seen in 42% of patients at the time of birth. All 50 patients had a modified BTS with pulmonary valvotomy. Six patients died after the first palliation or inter-stage. Thirty patients achieved a biventricular repair (BVR group), 6 patients had a 1 + 1/2 ventricular repair (1 + 1/2V group) and 5 patients had a Fontan completion (Fontan group). After modified BTS with pulmonary valvotomy, tricuspid valve z-score did not increase in any of the group (BVR: pre -2.79 vs post -2.24, 1 + 1/2V: pre -5.25 vs post -6.69, Fontan: pre -6.82 vs post -7.94). Normalized RV end-diastolic volume increased only in BVR group after modified BTS with pulmonary valvotomy (BVR: pre 32% vs post 64%, 1 + 1/2V: pre 43% vs post 42%, Fontan: pre 29% vs post 32%). Major RV-coronary artery fistula was a strong factor with proceeding single-ventricle palliation [BVR: 4/30 (13%) patients, 1 + 1/2V: 1/6 (17%) and Fontan: 4/5 (80%)]. Tricuspid valve growth was not obtained by modified BTS with pulmonary valvotomy; therefore, tricuspid valve size at birth appeared to be a predictor for achieving BVR. Proportionate RV growth was seen only in patients who achieved BVR. However, RV growth was not seen in patients having 1 + 1/2 ventricular repair. Major RV-coronary artery fistula was a strong predictor for proceeding single-ventricle palliation.


Cost of malaria control in Sri Lanka.
The study provides estimates of the cost of various malaria control measures in an area of North-Central Province of Sri Lanka where the disease is endemic. We assumed that each measure was equally effective. In these terms, impregnating privately purchased bednets with insecticide was estimated to cost Rs 48 (US(40.87) per individual protected per year, less than half the cost of spraying houses with residual insecticides. Larviciding of vector breeding sites and especially the elimination of breeding habitats by flushing streams through seasonal release of water from upstream reservoirs was estimated to be cheaper than other preventive measures (Rs 27 (US$ 0.49) and Rs 13 (US$ 0.24) per individual protected, respectively). Inclusion of both operational and capital costs of treatment indicates that the most cost-effective intervention for the government was a centrally located hospital with a relatively large catchment area (Rs 71 (US$ 1.29) per malaria case treated). Mobile clinics (Rs 153 (US$ 2.78) per malaria case treated) and a village treatment centre (Rs 112 (US$ 2.04)) per malaria case treated) were more expensive options for the government, but were considerably cheaper for households than the traditional hospital facilities. This information can guide health planners and government decision-makers in choosing the most appropriate combination of curative and preventive measures to control malaria. However, the option that is cheapest for the government may not be so for the householders, and further studies are needed to estimate the effectiveness of the various preventive measures.


Derivatized dextran inhibition of smooth muscle cell proliferation.
Proliferation of vascular smooth muscle cells is postulated to be one of the key events in the pathogenesis of atherosclerosis or during the development of focal glomerular sclerosis. Several studies have suggested that the antiproliferative effects of heparin appear to be regulated by different structural determinants. Our experiments show that dextrans substituted with carboxylic and benzylamide sulphonate groups markedly inhibit the growth of smooth muscle cells in vitro. Studies on the structure-function relationships of these products to their effect on rat aorta smooth muscle cells are reported. The antiproliferative capacity is similar to that of heparin.


The relevance of associate degree nursing education: past, present, future.
Associate degree nursing education remains a relevant choice for students entering the nursing profession. Since its introduction fifty years ago, associate degree nursing education has had a significant impact on the registered nursing population in the United States. The climate for a new type of nurse was created by a nursing shortage, the growth of community and junior colleges, and government and consumer interest. Evaluation of initial programs revealed that desired outcomes were met. A proliferation of associate degree nursing programs followed with there currently being more than 800 associate degree nursing programs in the nation. Controversy regarding associate degree nursing as an entry level for registered nurses has been evolving since its inception. Issues related to technical nursing versus professional nursing titles and roles, and differentiated roles have been divisive for the nursing profession. Current demographics reveal that associate degree nursing continues to make a positive impact on the registered nurse population, providing almost 60% of entry level graduates each year, and attracting a greater percentage of minority groups and males. Associate degree nursing representatives should be involved in defining the future of nursing. Societal needs for health care and individual rights for access to education should be considered. Collaborative efforts among the nursing organizations are essential to promoting recruitment and retention efforts.


Factors affecting the success rate of the Quickert and Wies procedures for lower lid entropion.
Many different surgical procedures have been described for the treatment of involutional lower lid entropion. Two commonly performed operations, namely, the Wies and Quickert procedures were analysed to assess the success rates and the factors responsible for their failures. The failure rates were 26% and 5% for the Wies and Quickert procedures, respectively. Most of the failures in these procedures were attributed to untreated lid laxity and the mean time of recurrence was 8 months. We therefore stress the importance of careful lid examination, in particular for horizontal lid laxity, as this will influence the choice of surgical procedure and ultimately the success of treatment.


Sparfloxacin in the treatment of drug resistant tuberculosis or intolerance of first line therapy.
Patients with multiresistant tuberculosis (TB) and patients with intolerance of first line antituberculosis drugs present a major treatment problem. Sparfloxacin is highly active against mycobacteria, but the use is restricted by side effects and the contribution to antituberculosis therapy is unclear. A prospective study has therefore been performed to analyse the efficacy and tolerability of sparfloxacin in cases of resistant TB or intolerance of first line therapy. Between April 1993 and April 1999, 30 TB patients (28 with pulmonary TB and two with lymph node TB) were treated with combinations of sparfloxacin and at least two other drugs at the Chest Hospital Heckeshorn, Berlin. Sixteen patients were infected by resistant mycobacteria (one single drug resistance (SDR), one polyresistance, and 14 multidrug resistances (MDR); 14 males (age range 23-53 yrs), 2 females (68-74 yrs)). Twelve patients (11 males, one female, 27-80 yrs) had not tolerated first line antituberculosis drugs. Two additional male patients had continuous proof of Mycobacterium tuberculosis in sputum without resistance during therapy The duration of sparfloxacin therapy during hospitalization ranged 2.5-4 months. Twenty-five patients completed therapy and were cured according to this study's definition. Although sparfloxacin was generally well tolerated, five mild phototoxic reactions and six moderate prolongations of the electrocardiographic QT-interval (30-40 ms compared to baseline < or = 450 ms) were registered without clinical symptoms in the patient group. In summary, sparfloxacin proved an effective and safe alternative antituberculosis drug for complicated tuberculosis.


Superpotent [Dmt¹] dermorphin tetrapeptides containing the 4-aminotetrahydro-2-benzazepin-3-one scaffold with mixed μ/δ opioid receptor agonistic properties.
Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both μ- and δ-opioid receptors but no detectable affinity for the κ-opioid receptor. Measurements of cAMP accumulation, phosphorylation of extracellular signal-regulated kinase (ERK1/2) in HEK293 cells stably expressing each of these receptors individually, and functional screening in primary neuronal cultures confirmed the potent agonistic properties of these peptides. The most potent ligand H-Dmt-NMe-d-Ala-Aba-Gly-NH(2) (BVD03) displayed mixed μ/δ opioid agonist properties with picomolar functional potencies. Functional electrophysiological in vitro assays using primary cortical and spinal cord networks showed that this analogue possessed electrophysiological similarity toward gabapentin and sufentanil, which makes it an interesting candidate for further study as an analgesic for neuropathic pain.


Primary pulmonary hyalinizing spindle cell tumor with giant rosettes: A clinicopathological and immunohistochemical study of 2 cases.
Two cases of primary intrapulmonary hyalinizing spindle cell tumor with giant rosettes are presented. The patients are one woman and one man ages 37 and 42 years respectively. Both patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging revealed the presence of an intrapulmonary mass. One tumor was located in the left lower lobe while the other tumor was in the right upper lobe. Both patients underwent lobectomy. The tumors ranged from 2.4 to 3.0 cm in greatest dimension and were characterized by the presence of a bland spindle cell proliferation with areas of hyalinization and the presence of the so-called giant rosettes. Immunohistochemical stains were performed and the spindle cell component show positive staining for vimentin and negative staining for Bcl-2, CD34, STAT6, p40. Keratin immunohistochemical stain highlighted the entrapped alveolar epithelium while S-100 protein showed weak focal staining in the spindle cells. Both patients have remained alive and well without evidence of recurrence or metastasis for a period of 6 to 14 months post-surgical resection. The cases herein presented highlight the ubiquitous distribution of this tumor and underscores the importance of keeping this particular tumor in the differential diagnosis of spindle cell tumors of the lung.


[Normothermal extracorporeal perfusion of the liver].
In view of providing hepatic assistance, and for conservation aims in attempts at transplantation conditions have been investigated for achieving extracorporeal normothermal perfusion of the liver isolated from pig and dog. A total of 33 experiments have been performed. The preparations and the devices used allow to apply the method in a patient only after stabilisation of the perfusion, and frees the medical team from a series of technical problems. The duration and the quality of the perfusion are especially influenced by the collecting technique. In the dog the liver should be removed 3--5 hours, and in the pig 7--8 hours before perfusion is started. The functional condition of the liver can be assessed at 45 minutes after the start of the perfusion by evaluating the following criteria: the macroscopic aspect of the liver, the blood flow, the biliary flow, the ascitis fluid, TGP and oxygen consumption. Adequate installations and a permanent involvement of the laboratory team are essential conditions for the application of this method to the treatment of acute severe hepatic failure.


Quality of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal in pediatric intensive care: a systematic review protocol.
Inadequate management of pain and sedation in critically ill children can cause unnecessary suffering and agitation, but also delirium and iatrogenic withdrawal. It is, therefore, important to address these four interrelated conditions together. Some clinical practice guidelines (CPGs) are available for the management of pain and sedation, and a few for delirium and iatrogenic withdrawal in the paediatric intensive care unit; none address the four conditions altogether. Critical appraisal of the quality of CPGs is necessary for their recommendations to be adopted into clinical practice. The aim of this systematic review is to identify and appraise the quality of CPGs and recommendations for management of either pain, sedation, delirium and iatrogenic withdrawal. Researchers will conduct a systematic review in electronic databases (Medline ALL (Ovid), Embase.com, CINAHL with Full Text (EBSCO), JBI EBP Database (Ovid)), guideline repositories and websites of professional societies to identify CPGs published from 2010 to date. They will then combine index and free terms describing CPGs with pain, sedation, delirium and withdrawal. The researchers will include CPGs if they can be applied in the paediatric intensive care population (newborns to 18 years old) and include recommendation(s) for assessment of at least one of the four conditions. Two independent reviewers will screen for eligibility, complete data extraction and quality assessments using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the AGREE Recommendation Excellence instruments. Researchers will report characteristics, content and recommendations from CPGs in tabulated forms. Ethical approval is not required for this systematic review. Results will be published in a peer-reviewed journal. CRD42021274364.


Imperfect supercritical bifurcation in a three-dimensional turbulent wake.
The turbulent wake of a square-back body exhibits a strong bimodal behavior. The wake randomly undergoes symmetry-breaking reversals between two mirror asymmetric steady modes [reflectional symmetry-breaking (RSB) modes]. The characteristic time for reversals is about 2 or 3 orders of magnitude larger than the natural time for vortex shedding. Studying the effects of the proximity of a ground wall together with the Reynolds number, it is shown that the bimodal behavior is the result of an imperfect pitchfork bifurcation. The RSB modes correspond to the two stable bifurcated branches resulting from an instability of the stable symmetric wake. An attempt to stabilize the unstable symmetric wake is investigated using a passive control technique. Although the controlled wake still exhibits strong fluctuations, the bimodal behavior is suppressed and the drag reduced. This promising experiment indicates the possible existence of an unstable solution branch corresponding to a reflectional symmetry preserved (RSP) mode. This work is encouraging to develop a control strategy based on a stabilization of this RSP mode to reduce mean drag and lateral force fluctuations.


Forgotten partners of international assignments: development and test of a model of spouse adjustment.
The authors developed and tested a model of spouse adjustment to international assignments in a sequence of qualitative and quantitative investigations. From in-depth interviews with expatriate spouses, half of whom had either positive or negative experiences living abroad, the authors identified several potentially important sources of adjustment. These constructs were integrated with others from identity theory and earlier research on expatriates to develop a conceptual model of spouse adjustment. The model was tested by collecting multisource questionnaire data from 221 international assignee couples working in 37 countries. Correlation and regression analyses revealed several important relationships between individual, interpersonal relationship, and environmental sources of identity, and the adjustment of expatriate spouses.


Template-Triggered Emergence of a Self-Replicator from a Dynamic Combinatorial Library.
Self-assembly of a specific member of a dynamic combinatorial library (DCL) may lead to self-replication of this molecule. However, if the concentration of the potential replicator in the DCL fails to exceed its critical aggregation concentration (CAC), then self-replication will not occur. We now show how addition of a template can raise the concentration of a library member-template complex beyond its CAC, leading to the onset of self-replication. Once in existence, the replicator aggregates promote further replication also in the absence of the template that induced the initial emergence of the replicator.


[Claude syndrome caused by mesencephalic infarction: 2 cases].
Paramedian midbrain infarcts limited to the oculomotor nerve fibers are uncommon. We studied 2 cases where the clinical syndrome included a third cranial nerve palsy and a contralateral cerebellar ataxia. The CT scan disclosed a paramedian midbrain tegmental infarct, so that it is possible to term our two cases Claude's syndrome. The oculomotor nerve fascicular palsies were complete in one case and limited to the extraocular muscles in the second case. The selective involvement of oculomotor function suggests intraaxial fascicular organisation of the third cranial nerve in the brainstem.


Leukotriene receptor antagonists and related compounds.
Leukotrienes (LTs), lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past year and a half, the development of three new drugs that modulate the LT pathway has been completed. The first subclass of these drugs, leukotriene receptor antagonists (LTRA) (zafirlukast and montelukast), blocks the interaction of the cysteinyl form of the LTs with the cell type bearing the receptor. The second subclass, the 5-lipoxygenase (5-LO) inhibitors (zileuton) inhibits the 5-LO enzyme, which prevents the formation of both cysteinyl LTs and LTB4. The LT modulators have shown efficacy in inhibiting the physiological changes occurring after allergen, acetylsalicylic acid and exercise challenge in asthmatics. In addition, they have shown efficacy in improving symptoms, beta-agonist use and forced expiratory volume in 1 s (FEV1) in chronic, 'day-to-day' asthma in patients with mild disease. Comparison studies with low doses of inhaled corticosteroids suggest that LT modulators may have similar effects on symptom scores and beta-agonist use, but have lesser effects on FEV1. Finally, emerging data suggest that these drugs are beneficial in decreasing the dose of inhaled corticosteroids necessary to control more moderate to severe asthma. While long term studies will be helpful in determining the 'disease modifying' effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients.


Molecular cytogenetic analysis in mouse sperm of chemically induced aneuploidy: studies with topoisomerase II inhibitors.
The ability of two topoisomerase II (topo II) inhibitors, etoposide (VP-16) and merbarone (MER), to induce meiotic delay and aneuploidy in mouse spermatocytes was investigated. The progression from meiotic divisions to epididymal sperm was determined by injecting male mice with 5-bromo-2'-deoxyuridine (BrdU) and treating the animals 13 days later with the test chemicals. At 20-24 days after treatment, BrdU-containing sperm were identified with a FITC-labelled anti-BrdU antibody and green fluorescent sperm were scored with a laser scanning cytometer (LSC). It was found that VP-16 (50mg/kg) treatment induced a meiotic delay of about 24h. A significant reduction of BrdU-labelled sperm was observed at 22 days compared to the controls (VP-16 group: 14.20%; controls: 41.10%, P<0.001). At 23 and 24 days, there were no significant differences between the VP-16 and the control groups. MER (80 mg/kg) treatment did not cause meiotic delay. To determine the frequencies of hyperhaploid and diploid sperm, male mice were treated with 12.5, 25 and 50mg/kg VP-16 or 15, 30 and 60 mg/kg MER. Sperm were sampled from the Caudae epididymes 24 days after VP-16 treatment or 22 days after MER treatment. Significant increases above the concurrent controls in the frequencies of total hyperhaploid sperm were found after treatment with 25, 50mg/kg VP-16 (0.074 and 0.122% versus 0.052%) and after treatment with 60 mg/kg MER (0.098% versus 0.044%). Furthermore, significant increases in the frequencies of diploid sperm were found after treatment of mice with all three doses of VP-16 (0.024, 0.032 and 0.056% versus 0.004 and 0.00%, respectively) and with 30 and 60 mg/kg MER (0.022 and 0.05% versus 0.004 and 0.002%, respectively). All dose responses could be expressed by linear equations. The results indicate that cancer patients may stand transient risk for siring chromosomally abnormal offspring after chemotherapy with these topo II inhibitors.


Correlation between Clinical and Arthroscopic Findings in Meniscal Tear of Knee.
The meniscus is the most commonly injured structure in the knee joint. Carefully performed clinical examination can give better diagnosis of meniscal tear. The aim of this study was to find out the correlation between clinical and arthroscopic findings in meniscal tear of knee. This cross sectional observational study was conducted in the Department of Orthopaedic Surgery, BSMMU, Dhaka from July 2012 to June 2014. Thirty patients of meniscal tear were selected as per inclusion and exclusion criteria. After proper evaluation and clinical examination of these patient arthroscopic examinations was done under spinal anesthesia. A total number of 30 patients were recruited in this study. Twenty seven (90%) patients were male and only 3(10%) were female. Mean±SD of age was 26.00±5.55 and range was 17-34 years. Out of 30 patients 19(63.3%) had right knee affected and the rest 11(36.7%) had left knee affected. It was found from clinical diagnosis that most of the patients had MM injury (73.4%) and LM injury was in 26.6% patients. From arthroscopic diagnosis we found most of the patients had multiple types of injury (40.0%) followed by 26.7% patents had isolated MM injury, 16.6% patients had isolated LM injury, 10.0% patients had other injuries like ACL, PCL or MCL and rest 6.7% patients had no injury at all. Sensitivity, specificity, PPV, NPV and accuracy of clinical diagnosis in diagnosis of MM injury were 94.4%, 58.3%, 77.3%, 87.5% and 80.0% respectively. Sensitivity, specificity, PPV, NPV and accuracy of clinical diagnosis in diagnosis of LM injury were 85.7%, 91.3%, 75.0%, 95.5% and 90.0% respectively. Clinical evaluation may diagnose meniscal tear accurately.


MS2 and Qβ bacteriophages reveal the contribution of surface hydrophobicity on the mobility of non-enveloped icosahedral viruses in SDS-based capillary zone electrophoresis.
SDS is commonly employed as BGE additive in CZE analysis of non-enveloped icosahedral viruses. But the way by which SDS interacts with the surface of such viruses remains to date poorly known, making complicate to understand their behavior during a run. In this article, two related bacteriophages, MS2 and Qβ, are used as model to investigate the migration mechanism of non-enveloped icosahedral viruses in SDS-based CZE. Both phages are characterized by similar size and surface charge but significantly different surface hydrophobicity (Qβ > MS2, where '>' means 'more hydrophobic than'). By comparing their electrophoretic mobility in the presence or not of SDS on both sides of the CMC, we show that surface hydrophobicity of phages is a key factor influencing their mobility and that SDS-virus association is driven by hydrophobic interactions at the surface of virions. The CZE analyses of heated MS2 particles, which over-express hydrophobic domains at their surface, confirm this finding. The correlations between the present results and others from the literature suggest that the proposed mechanism might not be exclusive to the bacteriophages examined here.


[Evaluation of 18 epididymo-orchitis cases].
Eighteen patients with epididymo-orchitis were reviewed clinically, microbiologically and serologically. While there were positive urine culture in 5 patients before treatment, only one of them had positive culture in the epididymal aspirate. The epididymo-orchitis in two patients was the complications of the brucellosis. Ofloxacin or doxycycline was used in the treatment of 16 patients for 2-3 weeks and all, except one patient were recovered completely. The cases secondary to the brucellosis were treated with rifampicin plus doxycycline combination for 6 weeks. After treatment, no positive urine cultures were noted in all patients. As a result the epididymal aspiration to clarify etiological agent is not necessarily needed and empirical treatment may be generally curative.


Continuous-wave single-frequency laser with dual wavelength at 1064 and 532 nm.
A continuous-wave high-power single-frequency laser with dual-wavelength output at 1064 and 532 nm is presented. The dependencies of the output power on the transmission of the output coupler and the phase-matching temperature of the LiB(3)O(5) (LBO) crystal are studied. An output coupler with transmission of 19% is used, and the temperature of LBO is controlled to the optimal phase-matching temperature of 422 K; measured maximal output powers of 33.7 W at 1064 nm and of 1.13 W at 532 nm are obtained with optical-optical conversion efficiency of 45.6%. The laser can be single-frequency operated stably and mode-hop-free, and the measured frequency drift is less than 15 MHz in 1 min. The measured Mx2 and My2 for the 1064 nm laser are 1.06 and 1.09, respectively. The measured Mx2 and My2 for the 532 nm laser are 1.12 and 1.11, respectively.


A rapid in vitro method of identifying contact allergens and irritants.
A rapid in vitro method has been developed to screen skin allergens and irritants. It has been shown by others that allergens induce the secretion of interleukin (IL)-1 betaby dendritic cells and macrophages, which are known antigen-presenting cells present in blood, and that irritants induce the secretion of IL-1 alphaby the same cells. We have shown that the allergens nickel, chromium, isoeugenol, and dinitrofluoro benzene induce the secretion of IL-1 betaat levels that are two- to threefold higher than those of controls and that the nonallergens and irritants sodium dodecyl sulfate, Tween-20, acetic acid, sodium hydroxide, and dimethyl sulfoxide fail to induce such a response. All the chemical allergens tested induced the secretion of IL-1 alphaat concentrations two- to fivefold higher than those of controls, depending on the concentration and the particular irritant. Allergen-induced T-cell proliferation has also been demonstrated by the expression of IL-2 as well as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide reduction (MTT) assay (10-50% more than control). All the allergens and irritants caused cytotoxicity at higher doses, as indicated by the release of lactate dehydrogenase. This method can be used to differentiate the allergens from the irritants in a simple and convenient manner.


Nickel Catalysis Enables Oxidative C(sp(2) )-H/C(sp(2) )-H Cross-Coupling Reactions between Two Heteroarenes.
Nickel can be used to promote oxidative C(sp(2) )-H/C(sp(2) )-H cross-coupling between two heteroarenes. The reaction scope can be extended to aromatic carboxamides as the coupling partner. The reaction exhibits high functional-group compatibility and broad substrate scope. The silver oxidant can be recycled to reduce costs and waste, which is very useful for practical applications.


[Impact of HER2, EGFR, IGF-1R, and VEGFR expressions on the outcome of chemotherapy for advanced gastric cancer].
We aimed to elucidate the clinical significance of the expressions of HER2, epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGF-1R), and vascular endothelial growth factor receptor 1, 2, 3 (VEGF-R1, VEGF-R2, and VEGF-R3) in gastric cancer. The study group comprised 57 patients who had undergone gastrectomy at the National Cancer Center Hospital and subsequently received first-line chemotherapy (S-1 monotherapy [n=29] or irinotecan+cisplatin [n=28]) for recurrent or residual tumors. We performed immunohistochemical analysis of formalin-fixed paraffinembedded specimens of surgically removed primary tumors to determine the expressions of HER2, EGFR, IGF-1R, and VEGFR1 in tumor cells and the expressions of VEGF-R1, VEGF-R2, and VEGF-R3 in tumor stromal vessels. The expressions of HER2 (p=0.017) and IGF-1R (p=0.025) were significantly more common in intestinal type tumors than in diffuse type. The protein expressions did not correlate with tumor response in either chemotherapy-regimen group. Among the patients who underwent S-1 monotherapy, those with cytoplasmic VEGF-R1-positive tumors had significantly shorter progression-free survival (logrank, p=0.017). In the survival analysis of all the patients, coexpression of membranous IGF-1R and VEGF-R3 in stromal vessels was the most significant predictor of poor survival (hazard ratio, 1.82; 95% CI, 1.31-2.63; p<0.001). The results of our study will facilitate more efficient use of molecular targeted agents in patients with gastric cancer.


Finasteride as a chemopreventive agent in prostate cancer: impact of the PCPT on urologic practice.
Prostate cancer chemoprevention involves the use of natural and/or synthetic agents that inhibit or reverse the development of precancerous lesions or delay progression of these lesions to invasive disease. The recent completion of the first Phase III trial for prostate cancer prevention, the Prostate Cancer Prevention Trial (PCPT) using the drug finasteride, has provided the urologic community with the first evidence that a chemopreventive agent can reduce the risk of developing prostate cancer. The enthusiasm for the clear relative risk reduction in the finasteride arm of the trial has been tempered by the observation that the incidence of high-grade tumors was higher in men receiving finasteride compared to those on placebo. A question remains about whether the observed higher incidence in high-grade tumors is real or whether it is related to a pathologic or sampling artifact. The PCPT has instigated a great deal of debate, resulting in the larger urologic community being reluctant to recommend the widespread use of finasteride as a chemopreventive agent. This review summarizes the PCPT, analyzes its controversial results, and describes future prostate cancer chemoprevention studies.


Ethanolic extract of the Goldenseal, Hydrastis canadensis, has demonstrable chemopreventive effects on HeLa cells in vitro: Drug-DNA interaction with calf thymus DNA as target.
This study tested chemotherapeutic potential of Hydrastis canadensis (HC) extract in HeLa cells in vitro, with emphasis on its drug-DNA interaction and apoptosis induction ability. Nuclear uptake of HC by DAPI, Ao/Eb staining and internucleosomal DNA damage by comet assay was studied through fluorescence microscopy. Possible changes in MMP and apoptotic signalling events were critically analyzed. Cell cycle progression studied through FACS and fragmented DNA through "TUNEL" assay were critically analyzed. RT-PCR studies were conducted for analyzing Cyt-C and Bax translocation in mitochondrial and cytosolic extracts, and Caspase 3 in whole cell lysate. Role of p53-mediated regulation of NF-κβ and TNF-α was elucidated by Western blot analysis. Data of CD and Tm profile of CT-DNA were analyzed. Overall results indicated anti-cancer potential of HC through its ability to induce apoptosis, and interaction with CT-DNA that changed structural conformation of DNA, proving HC to be a promising candidate for chemoprevention.


Heterogeneity of the internal structure of PDR1, a family of Ty1/copia-like retrotransposons in pea.
We characterised the extent of heterogeneity among PDR1 elements, a Ty1/copia-like retrotransposon family in pea, by restriction mapping and PCR with primers designed to amplify four functional domains. The data suggest that two main subfamilies of PDR1 differ in the size of their 5'-region. There are also sequence variants and rearranged copies which include a wide range of deletions of different sizes and deletions combined with insertions of host DNA, or inversions of various regions of the retrotransposon. A deletion hotspot has been found at nucleotide position 394, where buffer sequences of 26 bp and 38 bp containing microsatellite motifs have been generated. There is more heterogeneity in the gag domain of PDR1 than in other functional domains, and the extent and pattern of this diversity was assessed among 56 Pisum accessions. We found a higher rate of rearrangement and sequence variation within the gag domain of PDR1 in P. fulvum and P. abyssinicum accessions than would be expected from the degree of insertion site polymorphism. A neighbour-joining phylogenetic tree constructed for gag sequences has a similar branching pattern to the equivalent insertion site tree, implying that the PDR1 family and its gag domain have coevolved with the pea genome. Combining both trees revealed clear and distinct subgroups among the Pisum ssp.


Real-time monitoring of tumor progression and drug responses in a preclinical mouse model of prostate cancer.
Monitoring disease progression through imaging is playing an increasingly important role in the treatment of prostate cancer. Here, we report that primary mouse prostate cancer cell lines stably expressing luciferase and tumor biomarkers can be monitored through bioluminescence imaging along with assays of serum biomarkers and immune function. Tumorigenesis in immunocompetent C57BL/6 mice can be monitored in by collecting samples from the dorsal flank, dorsolateral prostate, and tail vein to obtain real-time subcutaneous, orthotopic, and metastasis indicators, respectively. We used this technique to confirm the therapeutic effect of immune checkpoint blockade. Our findings suggest the presented indicators are ideally suited for real-time tracking of drug responses, tumor progression and immune function.


Unilamellar nanosheet of layered manganese cobalt nickel oxide and its heterolayered film with polycations.
The exfoliation of layered Li[Mn(1/3)Co(1/3)Ni(1/3)]O(2) into individual monolayers could be achieved through the intercalation of quaternary tetramethylammonium (TMA(+)) ions into protonated metal oxide. An effective exfoliation occurred when the TMA(+)/H(+) ratio was 0.5-50. Reactions outside this range produced no colloidal suspension, but all the manganese cobalt nickel oxides precipitated. Atomic force microscopy and transmission electron microscopy clearly demonstrated that exfoliated manganese cobalt nickel oxide nanosheets have a nanometer-level thickness, underscoring the formation of unilamellar nanosheets. The maintenance of the hexagonal atomic arrangement of the manganese cobalt nickel oxide layer upon the exfoliation was confirmed by selected area electron diffraction analysis. According to diffuse reflectance ultraviolet--visible spectroscopy, the exfoliated manganese cobalt nickel oxides displayed distinct absorption peaks at approximately 354 and approximately 480 nm corresponding to the d-d transitions of octahedral metal ions, which contrasted with the featureless spectrum of the pristine metal oxide. In the light of zeta potential data showing the negative surface charge of manganese cobalt nickel oxide nanosheets, a heterolayered film of manganese cobalt nickel oxide and conductive polymers could be prepared through the successive coating process with colloidal suspension and polycations. The UV--vis and X-ray diffraction studies verified the layer-by-layer ordered structure of the obtained heterolayered film, respectively.


EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen.
Chordoma is a rare malignant bone tumour with a poor prognosis and limited therapeutic options. We undertook a focused compound screen (FCS) against 1097 compounds on three well-characterized chordoma cell lines; 154 compounds were selected from the single concentration screen (1 µm), based on their growth-inhibitory effect. Their half-maximal effective concentration (EC50 ) values were determined in chordoma cells and normal fibroblasts. Twenty-seven of these compounds displayed chordoma selective cell kill and 21/27 (78%) were found to be EGFR/ERBB family inhibitors. EGFR inhibitors in clinical development were then studied on an extended cell line panel of seven chordoma cell lines, four of which were sensitive to EGFR inhibition. Sapitinib (AstraZeneca) emerged as the lead compound, followed by gefitinib (AstraZeneca) and erlotinib (Roche/Genentech). The compounds were shown to induce apoptosis in the sensitive cell lines and suppressed phospho-EGFR and its downstream pathways in a dose-dependent manner. Analysis of substituent patterns suggested that EGFR-inhibitors with small aniline substituents in the 4-position of the quinazoline ring were more effective than inhibitors with large substituents in that position. Sapitinib showed significantly reduced tumour growth in two xenograft mouse models (U-CH1 xenograft and a patient-derived xenograft, SF8894). One of the resistant cell lines (U-CH2) was shown to express high levels of phospho-MET, a known bypass signalling pathway to EGFR. Neither amplifications (EGFR, ERBB2, MET) nor mutations in EGFR, ERBB2, ERBB4, PIK3CA, BRAF, NRAS, KRAS, PTEN, MET or other cancer gene hotspots were detected in the cell lines. Our findings are consistent with the reported (p-)EGFR expression in the majority of clinical samples, and provide evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Predictors of Posthospital Transitions of Care in Patients With Advanced Cancer.
Purpose Patients with advanced cancer experience potentially burdensome transitions of care after hospitalizations. We examined predictors of discharge location and assessed the relationship between discharge location and survival in this population. Methods We conducted a prospective study of 932 patients with advanced cancer who experienced an unplanned hospitalization between September 2014 and March 2016. Upon admission, we assessed patients' physical symptoms (Edmonton Symptom Assessment System) and psychological distress (Patient Health Questionnaire-4). The primary outcome was discharge location (home without hospice, postacute care [PAC], or hospice [any setting]). The secondary outcome was survival. Results Of 932 patients, 726 (77.9%) were discharged home without hospice, 118 (12.7%) were discharged to PAC, and 88 (9.4%) to hospice. Those discharged to PAC and hospice reported high rates of severe symptoms, including dyspnea, constipation, low appetite, fatigue, depression, and anxiety. Using logistic regression, patients discharged to PAC or hospice versus home without hospice were more likely to be older (odds ratio [OR], 1.03; 95% CI, 1.02 to 1.05; P < .001), live alone (OR, 1.95; 95% CI, 1.25 to 3.02; P < .003), have impaired mobility (OR, 5.08; 95% CI, 3.46 to 7.45; P < .001), longer hospital stays (OR, 1.15; 95% CI, 1.11 to 1.20; P < .001), higher Edmonton Symptom Assessment System physical symptoms (OR, 1.02; 95% CI, 1.003 to 1.032; P < .017), and higher Patient Health Questionnaire-4 depression symptoms (OR, 1.13; 95% CI, 1.01 to 1.25; P < .027). Patients discharged to hospice rather than PAC were more likely to receive palliative care consultation (OR, 4.44; 95% CI, 2.12 to 9.29; P < .001) and have shorter hospital stays (OR, 0.84; 95% CI, 0.77 to 0.91; P < .001). Patients discharged to PAC versus home had lower survival (hazard ratio, 1.53; 95% CI, 1.22 to 1.93; P < .001). Conclusion Patients with advanced cancer who were discharged to PAC facilities and hospice had substantial physical and psychological symptom burden, impaired physical function, and inferior survival compared with those discharged to home. These patients may benefit from interventions to enhance their quality of life and care.


A low cost, home-made, reverse-line blot hybridisation assay for rapid detection of rifampicin resistance in Mycobacterium tuberculosis.
Cetrangolo Hospital, Vicente Lopez, Argentina, 1995-1999. To describe a home-made reverse-line blot hybridisation assay for the detection of rifampicin resistance-associated mutations in the rpoB gene of Mycobacterium tuberculosis, and to evaluate the usefulness of this rifampicin oligonucleotide, or 'RIFO' assay, to predict rifampicin resistance. A total of 135 M. tuberculosis isolates from the Cetrangolo Hospital were tested using the RIFO assay, the proportion method and the Mycobacterial Growth Indicator Tube (MGIT 960). In addition, 120 drug-susceptible isolates from the Netherlands were included. The results obtained with the proportion method and the MGIT 960 system were in full agreement. In the RIFO assay, 90 of the 97 rifampicin-resistant isolates were correctly identified (sensitivity 92.8%, positive predictive value 100%). All of the drug-susceptible isolates were correctly predicted by the RIFO assay. With this home-made molecular test, rifampicin resistance in M. tuberculosis can be predicted in colonies isolated in culture in only 1 day, and can therefore shorten the laboratory turn around time for rifampicin susceptibility testing by weeks. In principle the test can also be applied directly to Zichl-Neelsen slides and clinical material, as has been demonstrated for another reverse-line blot-based assay for M. tuberculosis, spoligotyping.


Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage.
Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO2 nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO2 nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO2 nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO2. And Se@SiO2 has few interference to the therapeutic effect of DOX. Particularly, Se@SiO2 significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO2 in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO2 nanocomposite in the clinical use of DOX.


Gal-Gal binding and hemolysin phenotypes and genotypes associated with uropathogenic Escherichia coli.
To determine whether uropathogenic strains of Escherichia coli exhibit a distinctive constellation of phenotypes, we examined 44 urinary isolates from women with radiologically normal urinary tracts and pyelonephritis, cystitis, or asymptomatic bacteriuria and 73 fecal isolates from healthy control subjects. The strains were characterized by their O serogroup, by their binding specificity (as determined by adhesins), and by their production of hemolysin and colicin V. In addition, the strains were assessed for homologous gene sequences by means of DNA-hybridization probes prepared from cistrons that encode hemolysin and the Gal-Gal binding adhesin--two determinants of virulence, which cause tissue injury and promote bacterial colonization of uroepithelia, respectively. In contrast to most isolates from normal feces and from the urine of patients with asymptomatic bacteriuria, pyelonephritis strains belong to a small number of O serogroups; all express the Gal--Gal binding adhesin and 75 per cent are hemolytic. A gene probe for the Gal--Gal binding adhesin, derived from the chromosome of one strain from a patient with pyelonephritis, hybridized with the DNA of all other pyelonephritis strains. The probe for the hemolysin gene hybridized with DNA from all other hemolytic strains. These data indicate that most cases of pyelonephritis are due to a small number of pathogenic clones that express critical determinants of virulence, and that the nucleotide sequences for hemolysin and the Gal--Gal binding adhesin in heterologous strains share homology. We are tempted to speculate that the gene products of these shared regions of the genome might form the basis for a vaccine against pyelonephritis.


Combined effects of hydralazine and nitrate on serum biochemistry and left ventricular remodeling in chronic heart failure patients.
To investigate the effects of hydralazine combined with nitrate on serum levels of Adropin and brain natriuretic peptide (BNP), left ventricular remodeling and prognosis in patients with chronic heart failure (CHF). 126 CHF patients were divided into control group (n=13, sodium nitroprusside) and combined treatment group (n=63, sodium nitroprusside ± hydralazine). Serum Adropin and BNP levels and left ventricular mass index (LVMI) of patients before treatment and 10 days after treatment were recorded, so did patient's end-point events. It was found that compared with those before treatment, the serum levels of Adropin, BNP, and LVMI in combined group and control group after 10 days of treatment were lower (P<0.05). The end-point event rate in the combined group was 19.05% (12/63). The serum levels of Adropin, BNP, and LVMI in the combined group with end-point events were higher than those of patients without end-point events (P<0.05). Spearman correlation analysis showed that serum levels of Adropin and BNP were positively correlated with LVMI and the end-point events rate (P<0.05). To sum up, hydralazine combined with sodium nitroprusside treatment can effectively reduce serum Adropin and BNP levels, and the risk of left ventricular remodeling and poor prognosis in patients with CHF.


Dissociated Development of Speech and Limb Sensorimotor Learning in Stuttering: Speech Auditory-motor Learning is Impaired in Both Children and Adults Who Stutter.
Stuttering is a neurodevelopmental disorder of speech fluency. Various experimental paradigms have demonstrated that affected individuals show limitations in sensorimotor control and learning. However, controversy exists regarding two core aspects of this perspective. First, it has been claimed that sensorimotor learning limitations are detectable only in adults who stutter (after years of coping with the disorder) but not during childhood close to the onset of stuttering. Second, it remains unclear whether stuttering individuals' sensorimotor learning limitations affect only speech movements or also unrelated effector systems involved in nonspeech movements. We report data from separate experiments investigating speech auditory-motor learning (N = 60) and limb visuomotor learning (N = 84) in both children and adults who stutter versus matched nonstuttering individuals. Both children and adults who stutter showed statistically significant limitations in speech auditory-motor adaptation with formant-shifted feedback. This limitation was more profound in children than in adults and in younger children versus older children. Between-group differences in the adaptation of reach movements performed with rotated visual feedback were subtle but statistically significant for adults. In children, even the nonstuttering groups showed limited visuomotor adaptation just like their stuttering peers. We conclude that sensorimotor learning is impaired in individuals who stutter, and that the ability for speech auditory-motor learning-which was already adult-like in 3-6 year-old typically developing children-is severely compromised in young children near the onset of stuttering. Thus, motor learning limitations may play an important role in the fundamental mechanisms contributing to the onset of this speech disorder.


Application of region-of-interest imaging techniques to neurointerventional radiology.
To reduce radiation exposure to patients and staff during neurointerventional procedures, region-of-interest (ROI) techniques were used with fluoroscopy, road mapping, and digital subtraction angiography in 19 patients. ROI filters, made of multiple layers of gadolinium, were attached to the collimators. Patient skin exposure was reduced by a factor of 3.3-10.0 across 85% of the field of view, and exposures were reduced to below thresholds for skin effects.


[Usefulness of p53 in the clinical management of bladder tumors].
The antioncogene p53 has been the subject of many studies in the field of bladder cancer, for many years and there appears to be a good correlation between p53 protein overexpression and pejorative clinicopathological factors, but contradictory results have been reported concerning its prognostic value. These discordances can be partly explained by the various immunohistochemical methods used in published series. Standardization of a highly sensitive and specific immunohistochemical method for the detection of p53 alterations now appears to be essential in order to accurately determine the value of p53 in the clinical management of bladder cancer.


Recent trends in financing long-term care.
There has been dramatic change in the financing of long-term care in the last few years. Major private insurance carriers have introduced long-term care insurance policies to meet some of the custodial care needs of a variety of consumer groups, including old and young retirees as well as current employees. Newer policies are tying coverages more closely to a measure of disability that reflect the ability of persons to live independently. Insurers, consumer groups, and policymakers have come to understand the importance of developing innovative financing mechanisms that emphasize prefunding and cash accumulation to make policies more affordable and more desirable to a broader spectrum of the aged and nonaged population.


Structural analysis of the cysteine-containing peptides from the major 3-methylcholanthrene-induced isozyme of cytochrome P-450 (P-450c) in rat liver microsomes.
Cytochrome P-450c, the major 3-methylcholanthrene-inducible isozyme of cytochrome P-450 in rat liver microsomes, was subjected to proteolytic digestion after S-carboxymethylation of the protein, and the peptides were resolved by high-pressure liquid chromatography. Since it is now recognized that cytochromes P-450 contain a thiolate as the axial fifth ligand of the heme, seven peptides containing eight cysteines were subjected to microsequence analysis. One cysteine-containing peptide (Tsa-56) was shown to possess 46-69% homology with a common peptide found in five other cytochromes P-450 but is not anticipated to be the heme-binding segment on the basis of X-ray crystallographic results obtained with Pseudomonas putida cytochrome P-450cam. Analysis of the other cysteine-containing peptides in cytochrome P-450c revealed two peptides (Tsa-54 and T-46) of only limited homology with the highly conserved region of cytochromes P-450cam, P-450LM2, P-450b, and P-450e that are all presumed to contain the heme-binding cysteine. Another peptide that contained two cysteines and a stretch of hydrophobic residues (Tsa-47) had limited sequence homology with a similar peptide found in several other cytochromes P-450. This domain is located a short distance from the proposed heme-binding cysteine in other cytochromes P-450. Sequence analysis of a cysteine-containing peptide (T-30) from another 3-methylcholanthrene-inducible rat liver cytochrome P-450 (cytochrome P-450d) revealed 91% homology with peptide T-46 from cytochrome P-450c, but this peptide shows no significant homology with any of the cysteine-containing peptides from other cytochromes P-450.(ABSTRACT TRUNCATED AT 250 WORDS)


Modes of heart rate compensations during exercise ECG test.
Heart rate (HR) compensation of electrocardiographic (ECG) parameters is not an unique concept. However, in the detection of coronary artery disease (CAD) ST-segment plotted as a function HR has been studied extensively during the last 20 years. In clinical practice quantitative methods are evolved for the exercise phase of the exercise test and post-exercise recovery phase has not been studied as extensively. Quantitative parameters, as ST/HR hysteresis, which represents the average difference in ST depressions between the exercise and recovery phases at an identical HR up to three minutes of recovery, has been shown to improve the detection of CAD. Furthermore, the ST/HR parameters have been demonstrated to be very competent in a prediction of mortality.


An obesity dietary quality index predicts abdominal obesity in women: potential opportunity for new prevention and treatment paradigms.
Background. Links between dietary quality and abdominal obesity are poorly understood. Objective. To examine the association between an obesity-specific dietary quality index and abdominal obesity risk in women. Methods. Over 12 years, we followed 288 Framingham Offspring/Spouse Study women, aged 30-69 years, without metabolic syndrome risk factors, cardiovascular disease, cancer, or diabetes at baseline. An 11-nutrient obesity-specific dietary quality index was derived using mean ranks of nutrient intakes from 3-day dietary records. Abdominal obesity (waist circumference >88 cm) was assessed during follow-up. Results. Using multiple logistic regression, women with poorer dietary quality were more likely to develop abdominal obesity compared to those with higher dietary quality (OR 1.87; 95% CI, 1.01, 3.47; P for trend = .048) independent of age, physical activity, smoking, and menopausal status. Conclusions. An obesity-specific dietary quality index predicted abdominal obesity in women, suggesting targets for dietary quality assessment, intervention, and treatment to address abdominal adiposity.


Ovarian Cancer: Differentially Expressed microRNAs in Tumor Tissue and Cell-Free Ascitic Fluid as Potential Novel Biomarkers.
Ovarian cancer is the deadliest gynecologic cancer. The large-scale microRNA (miRNA) expression profiling and individual miRNA validation was performed to find potential novel biomarkers for ovarian cancer. The most consistent overexpression of miRs-200b-3p, 135 b-5p and 182-5p was found in both ascitic fluid and tumors and suggests their potential as oncogenes. miR-451a was consistently underexpressed so may be a tumor suppressor. Results were inconsistent for miR-204-5p, which was overexpressed in ascitic fluid but underexpressed in tumor tissue. miR-203a-3p was generally overexpressed but this failed to be proved in independent sample set in tissue validation.


Anti-amyloidogenic indolizino[3,2-c]quinolines as imaging probes differentiating dense-core, diffuse, and coronal plaques of amyloid-β.
Abnormal deposition of amyloid-β (Aβ) is a major biomarker that is often used to diagnose Alzheimer's disease (AD). The Aβ plaque levels in the cortex and hippocampus are measured by either brain histology or positron emission tomography. Although cerebral plaques are found in several phenotypes, such as dense-core, diffuse, and coronal, imaging probes differentiating these plaques are currently unavailable. Here, we report that fluorescent indolizino[3,2-c]quinoline derivatives (YIQ) distinguish Aβ plaque phenotypes in brains of 5XFAD Alzheimer transgenic mice. We synthesized and screened 64 YIQ compounds through a series of in vitro and ex vivo Aβ staining assays. We found 20 compounds that could stain the Aβ phenotypes, 10 for dense-core plaques, eight for both dense-core and diffuse plaques, and two for solely visualizing only the coronal plaques while leaving the centric core unstained. Among the 20 imaging candidates, five YIQs displaying anti-Aβ aggregation efficacy were confirmed by thioflavin T assays and electrophoretic analyses.


Two new tools: multi-purpose cloning vectors that carry kanamycin or spectinomycin/streptomycin resistance markers.
We have constructed two new multi-purpose cloning vectors, pJKKmf(-) and pJKSp/Smf(-), that carry resistance to kanamycin (Km) and spectinomycin/streptomycin (Sp/Sm), respectively. These plasmids are based on pGEM3Zf(-) and therefore contain a pUC-vector-derived multiple cloning site for 13 restriction sites flanked by T7 and SP6 RNA polymerase promoters, the alpha-peptide coding region of beta-galactosidase for blue/white colony screening and the bacteriophage f1 origin of replication for production of single-stranded DNA in the presence of a helper phage. We have used these vectors to reclone sequences from a maize genomic library, to produce radiolabeled RNA probes and to make single-stranded DNA.


[CD40 ligandization promotes IL-6 and Flt3 ligand production of bone marrow stromal cells].
To analyze the expression of the CD(40) and its ligand (CD(40)L) on bone marrow stromal cells (BMSC), and investigate interleukin-3 (IL-3), IL-6, Flt3 ligand (FL) and stem cell factor (SCF) production of BMSC after stimulated with CD(40) agonistic monoclonal antibody (5C11) and its role in the regulation of hematopoiesis. BMSC were freshly isolated from adult bone marrow. The expression of CD(40) on these cells was determined with flow cytometry, the concentrations of IL-3, IL-6, FL and SCF in the supernatant at 24, 48 and 72 hours after BMSC cultured with 5C11 at a dose of 20 micro g/ml were determined by the ELISA assay. After BMSC incubated with 5C11 for 24 hours, the supernatant was collected and cultured with purified cord blood CD(34)(+) cells for 7 days under 37 degrees C in a fully humidified atmosphere supplement with 5% CO(2). Colony formation assay and Annexin V assay were employed to determine the proliferation and apoptosis of the CD(34)(+) cells. BMSC expressed CD(40) and the production of IL-6 and FL increased after stimulated with 5C11 while IL-3 and SCF had no change. The supernatant collected from the stimulated BMSC promoted proliferation of CD(34)(+) cells, increased the CFU-GM yields and had anti-apoptosis effects. CD(40) ligandization on BMSC increased the production of IL-6 and FL and promoted the proliferation of CD(34)(+) cells. The couple CD(40)/CD(40)L may be involved in the control of hematopoiesis via modulation of the cytokine network in the bone marrow.


[Statistic determination of release limits of a finished product active principle compared to drug specification at peremption and eventually at the end of its after reconstitution].
At manufacturing, finished dosage forms must meet the 75/318/EEC Directive particularly the criteria defining the potency registered limits i.e. +/- 5% variation of their nominal contents in general except some cases where sound justification can be provided on the basis of experimental results obtained at 95% confidence level. The described statistical method allows calculation of release limits of potency of any dosage form and applies to any parameter for which the rate of change with time is predictably uniform and linear. Assurance is then provided at 95% confidence level that any lot showing a mean release assay result within the calculated release limits will remain within registered limits at any subsequent time within its shelf-life. On the basis of real quality profiles including dozens of lots, the authors explains that the use of this statistical method leads to an efficient retrospective validation technic by means of chemical analysis.


Timely septation requires SNAD-dependent spindle pole body localization of the septation initiation network components in the filamentous fungus Aspergillus nidulans.
In the filamentous fungus Aspergillus nidulans, cytokinesis/septation is triggered by the septation initiation network (SIN), which first appears at the spindle pole body (SPB) during mitosis. The coiled-coil protein SNAD is associated with the SPB and is required for timely septation and conidiation. We have determined that SNAD acted as a scaffold protein that is required for the localization of the SIN proteins of SIDB and MOBA to the SPB. Another scaffold protein SEPK, whose localization at the SPB was dependent on SNAD, was also required for SIDB and MOBA localization to the SPB. In the absence of either SEPK or SNAD, SIDB/MOBA successfully localized to the septation site, indicating that their earlier localization at SPB was not essential for their later appearance at the division site. Unlike their functional counterparts in fission yeast, SEPK and SNAD were not required for vegetative growth but only for timely septation. Furthermore, down-regulation of negative regulators of the SIN suppressed the septation and conidiation phenotypes due to the loss of SNAD. Therefore, we conclude that SPB localization of SIN components is not essential for septation per se, but critical for septation to take place in a timely manner in A. nidulans.


Stages of change as a correlate of mental health symptoms in abused, low-income African American women.
The current study aims to further our understanding of the applicability of the transtheoretical model (TM) to intimate partner violence (IPV), with particular focus on mental health symptoms (depression, posttraumatic stress disorder symptomatology, suicidal ideation) in a sample of low-income African American women seeking medical services at an inner city emergency department. Results revealed that of the 121 abused African American women, the majority (95%) were in the precontemplation and contemplation stages of the change process. Further, contrary to predictions, bivariate analyses revealed those at further stages of change endorsed more severe mental health symptoms. However, a multivariate analysis of variance examining differences in level of mental health symptoms between women high and low on stages of change was inconclusive due to the small number of women at the higher stages of the TM model. These findings contribute to the growing body of literature supporting the TM as applied to IPV. Results are discussed in terms of applicability to intervention design.


Train the Brain: Novel Electroencephalography Data Indicate Links between Motor Learning and Brain Adaptations.
EEG differences were examined between part and whole practice in the learning of a novel motor task. Recording was done at 4 sites (i.e., O1, O2, C3, and C4) on 30 participants who performed a novel mirror star tracer task. Individuals were randomly assigned to 3 groups: whole practice, part practice, and control (no practice). Whole practice is defined as practicing a skill in its entirety. Part practice is defined as practicing separate, independent parts of the skill, and gradually combining those parts with parts that are dependent on one another. Each group was assessed during a pretest and posttest. EEG data was analyzed using a 2×2×2×3 (trials×hemisphere×site×practice) repeated measures mixed model ANOVA for each of the wave bands (lower alpha, upper alpha, lower beta, upper beta). All participants performed the task faster as no practice effect was found across the three groups; however the part practice group exhibited a significant decrease in errors. Reduced activation in the occipital and central sites was observed for lower alpha in the posttest compared to the pretest, for all participants. Hemispheric differences were present for all wavebands, with greater activation in the left hemisphere independent of practice type. The results of our study indicate that task learning was likely associated with the observed changes in the lower alpha waveband. Further, a concomitant behavior between the hemispheric lateralization of alpha and beta waveforms was observed. These results have implications for athlete training and rehabilitation. They indicate the utility of EEG for learning assessment in athletes. They also indicate learning strategies with a partial movement focus may be a beneficial strategy to support the development of complex sport skills training and rehabilitation strategies focused on reacquisition of skills prior to sport reintegration.