Prognostic impact of molecular markers in a series of 220 primary glioblastomas.
In contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival. A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers. Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main predictors of outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P = .01) and EGFR amplification with good prognosis on multivariate analysis (P = .02). Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.


Bisphosphonates: from grandparents to grandchildren.
Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption by their action on osteoclasts. Bisphosphonates have been extensively used in the elderly with primary and secondary osteoporosis, Paget's disease, and hypercalcemia of malignancy. In recent years, bisphosphonates have been used to treat children acutely for resistant hypercalcemia and chronically for various metabolic bone diseases. The theoretical concerns of possible adverse effects of these drugs on the growing skeleton have not been proven to be true. In the present review, we have critically analyzed the available literature on bisphosphonate therapy in both adult and pediatric clinical trials. Although not yet approved by the FDA for use in children, bisphosphonates, from published experience, demonstrate benefit to the child with no serious adverse effects. Based on the literature analysis the review furnishes detailed recommendations and practical guidelines regarding the use of oral and intravenous bisphosphonates in children. Bisphosphonates might be the first agents to provide the pediatrician with an opportunity to treat mineral and bone disorders of childhood, which until recently did not have satisfactory therapy.


The effect of fluoride treatment on bone mineral in rabbits.
Fluoride therapy has been used clinically for many years, but its use remains controversial and many basic questions remain unanswered. Accordingly, this study returns to an animal model to study the effects of high doses of fluoride on bone mineral in rabbits. Twelve rabbits, aged 3(1/2) months at the start of the study, received drinking water fluoridated at 100 ppm while their 12 control counterparts drank distilled water. All rabbits were sacrificed after 6 months. Fluoride was readily incorporated into femoral cortical bone (7473 +/- 966 ppm F versus 1228 +/- 57 ppm in controls; P < 0.00005). Fluoride therapy led to increased mineralization, as measured by density fractionation (P < 0.0005 for the distributions). The bone mineral itself was altered, with a significant increase in the width of crystals (66.2 +/- 2.0 A versus 61.2 +/- 0.9 A; P < 0.01). The microhardness of both cortical and cancellous bone in the femoral head of fluoride-treated rabbits was greater than that in the controls (P < 0.05). The phosphate, calcium, and carbonate contents in the bone was the same in both groups. Finally, fluoride administration did not affect the architecture or connectivity of cancellous bone in the femoral head. Previously published data [1] indicated that the mechanical properties of bone were adversely affected; this suggests that the effect of high doses of fluoride on the strength and stiffness of bone may be mediated by its effect on bone mineral.


Asymmetry in body composition in female hockey players.
The aim of the study was to determine if a sport in which one side of the body is dominant, like field hockey, influences regional body composition and bone mineral density (BMD) distribution in particular body segments, and whether the sporting level is a determining factor. Dual energy X-ray absorptiometry (DXA) method (Lunar Prodigy Advance; General Electric, Madison, USA) with the whole body scan was used to measure bone mineral density, fat mass and lean mass in 31 female field hockey players divided according to their sporting level. The morphological asymmetry level was assessed between two body sides and body segments in athletes from the National Team (n=17) and from the Youth Team (n=14) separately and between groups. Bone mineral density in the lower extremity and of the trunk was significantly asymmetric in favor of the left side in the National Team. In the case of the Youth Team, only the trunk BMD indicated clear left-right difference with left side dominance. Both the lean mass and fat mass values were relatively higher on the left side of all body segments and it related to both analyzed groups of athletes. The present study shows that playing field hockey contributes to laterality in body composition and BMD and that the sporting level is a determining factor. In most cases the left side dominated. A greater asymmetry level was observed in more experienced female field hockey players.


Wavelength dependence of the scattering loss in fluoride optical fibers.
Scattering losses as low as 0.025 dB/km at 2.55 microm have been measured in short lengths of fluoride-glass optical fiber.These measurements were made on several 5-7-cm lengths of fiber. Measurements were also made at various wavelengths to determine the wavelength dependence of the optical loss.


Can laparoscopic antireflux surgery improve the quality of life in children with neurologic and neuromuscular handicaps?
Children with neurologic and neuromuscular handicaps frequently have various symptoms related to gastroesophageal reflux (GER) disease. The long-term efficacy of antireflux surgery remains controversial in such children with GER. The clinical results of such patients who underwent laparoscopic fundoplication were examined in the current study. Between 1997 and 2003, laparoscopic fundoplication was performed in 56 handicapped children (mean age, 6 years), and gastrostomy was performed concurrently in 52. The main symptoms were emesis/hematemesis in 40 and respiratory symptoms, including repeated respiratory infection and distress, in 31. There were no severe postoperative complications or operative mortality. Emesis/hematemesis was controlled adequately in those without recurrence. Respiratory symptoms were controlled unsuccessfully in 16 patients (52%), 8 of whom required further respiratory care including nasal airway tube, tracheostomy, and laryngotracheal separation. Recurrence of GER disease occurred in 10 patients, 7 of whom underwent a second Nissen fundoplication successfully. Thirteen died within the median follow-up period of 14 months. Laparoscopic fundoplication is effective in controlling emesis/hematemesis, but its efficacy is limited in terms of respiratory problems in handicapped children. Further refinements in diagnostic and treatment strategies are mandatory to improve the quality of life in such patients.


A novel PHKA2 gross deletion mutation in a Korean patient with X-linked liver glycogenosis type I.
X-linked liver glycogenosis (XLG) is caused by a mutation in the PHKA2 gene which encodes the alpha subunit of phosphorylase kinase (PHK). Although XLG is not a rare disease, there have been no reports of PHKA2 mutations in Koreans. A 5-year-old boy presented with easy fatigability and hepatomegaly. Liver enzymes were increased and liver histology revealed deposition of glycogen. The PHK activity was markedly decreased compared to control. No amplification was observed at exon 8 of the PHKA2 gene, as a result of the deletion of exon 8. Sequence analysis revealed a hemizygous deletion in the region of exon 8 (c.717+781_864+225del1626). The patient was diagnosed as having XLG I. To the best of our knowledge, this is the first report of XLG I in Koreans.


Radioimmunotherapy for treatment of B-cell lymphomas and other hematologic malignancies.
Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. Recent data suggest that radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. The safety and efficacy of radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define radioimmunotherapy's role in the treatment of lymphomas.


Neuroimmune pharmacology as a component of pharmacology in medical school curriculum.
An introduction to the discipline of pharmacology is a standard part of the scientific foundation of medical school curricula. Neuroimmune pharmacology is a new subtopic that integrates fundamental concepts of neuroscience, immunology, infectious disease, and pharmacology. The integration of these areas is important to medical training in view of the growing concern over neurodegenerative diseases and cognitive disorders. This article introduces a submodule and concomitant syllabus for inclusion of neuroimmune pharmacology as a component of a pharmacology curriculum. The introductory lectures of neuroimmune pharmacology will concentrate on the role of the immune system in (1) schizophrenia and major depression; (2) neurodegenerative disorders; and (3) drug addiction. Emphasis will be placed on the competencies of critical thinking, problem solving, learning interest, and effectiveness of medical students. Problem-based learning and case study discussions will also be applied.


Comparative study of thin sectional anatomical images from Chinese visible human data set and computed tomography images of superior mediastinum.
The structures of superior mediastinum and their spatial relationships are complex and difficult to master. This study aimed to compare visualization of the superior mediastinum based on computed tomography (CT) images and on the thin sections of the Chinese visible human (CVH) data set to provide a sectional anatomical basis for diagnostic imaging of superior mediastinal pathology. CVH sections of the mediastinum of a 35-year old male were compared with plain and enhanced CT images of a 45-year old male without apparent abnormalities in the upper chest. In addition, a three-dimensional model based on the CVH sections was compared with a model based on CT images. Although CT imaging is noninvasive and can be carried out in many individuals, its weakness is clearly the visualization of small soft tissue structures. In this respect, the sectional anatomical approach of the CVH images is complementary, as it visualizes these small soft tissue structures due to the higher resolution in the plain of sectioning and the color of the different structures in the section. Three-dimensional surface and volume rendering of reconstructions of the CVH data set can help medical students and less experienced thoracic surgeons to familiarize themselves with the topographic anatomy of the superior mediastinal structures and their spatial relationships, and thus with interpreting CT images of patients.


Anandamide and other N-acylethanolamines in mouse peritoneal macrophages.
N-acyl phosphatidylethanolamine (N-acyl PE) and free N-acylethanolamine (NAE) in mouse peritoneal macrophages were identified and quantified by gas chromatography-mass spectrometry (GC-MS) of tertbutyldimethylsilyl derivatives in the presence of internal standards synthesized from [1,1,2,2-2H4]ethanolamine. N-acyl PE was present at a level of 123-187 pmol/mumol lipid P (521-768 pmol/10(8) cells), with arachidonic acid making up about 3-4% of the N-acyl moieties. NAE, on the other hand, was present at a level of only 17-30 pmol/mumol lipid P (70-121 pmol/10(8) cells), with N-arachidonoylethanolamine (anandamide) making up less than 1% of total NAE. Use of deuterium labeled internal standards and optimization of GC-MS conditions makes it possible to detect as little as 0.1 ng of saturated and 1 ng (3 pmol) of polyunsaturated NAEs in a lipid extract. The present method can be used to determine agonist-induced changes in the levels and compositions of N-acyl PE and NAE.


Aldosterone regulation in primary aldosteronism: differences between adenoma and bilateral hyperplasia.
1. The diurnal patterns of plasma aldosterone, plasma renin activity (PRA), cortisol and adrenocorticotrophic hormone (ACTH) in the supine and in the upright position have been studied in fourteen patients with primary aldosteronism, five with adenoma and nine with bilateral hyperplasia. Blood samples were drawn at intervals from 6 h to 30 min. 2. Supine patients with an adenoma showed marked diurnal variations of aldosterone, with maximal values at 08.00 hours and minimal values of 18.00 hours and secretory spurts beginning after 02.00 hours. Plasma cortisol paralleled aldosterone, and ACTH seemed to anticipate aldosterone and cortisol variations; PRA remained unchanged. In patients with hyperplasia, aldosterone was significantly lower than in the adenoma group at 08.00 hours, and its decline during the day was less marked; fluctuations rather than secretory episodes were seen. 3. After patients assumed the upright posture, aldosterone remained unchanged or decreased in patients with adenoma, whereas it significantly increased in hyperplasia; PRA remained low, although a slight increment was seen in the latter group. The different response of aldosterone in the two groups was not modified by the administration of propranolol, apparently excluding a renin-dependent mechanism. On the other hand, dexamethasone seemed to affect the response of aldosterone to the upright posture in both groups; in adenoma there was a slight but significant increase, and in hyperplasia the usual rise was partially suppressed. 4. It is concluded that ACTH has a predominant role in regulating aldosterone secretion in primary aldosteronism due to adenoma, whereas its action in bilateral hyperplasia is only permissive.


Diabetes-induced accelerated atherosclerosis in swine.
Patients with diabetes are at higher risk for atherosclerotic disease than nondiabetic individuals with other comparable risk factors. Studies examining mechanisms underlying diabetes-accelerated atherosclerosis have been limited by the lack of suitable humanoid animal models. In this study, diabetes was superimposed on a well-characterized swine model of atherosclerosis by injection of the beta-cell cytotoxin streptozotocin (STZ), resulting in a >80% reduction in beta-cells and an increase in plasma glucose to diabetic levels. Animals were maintained without exogenous insulin for up to 48 weeks. Plasma glucose and cholesterol levels and lesion extent and severity were quantified in swine with diabetes and hyperlipemia alone and in combination compared with controls. Diabetes had no effect on plasma cholesterol levels, but diabetic/hyperlipemic (D-HL) swine developed hypertriglyceridemia and showed a doubling in aortic sudanophilia over nondiabetic/hyperlipemic (N-HL) swine as early as 12 weeks (47.25 +/- 4.5 vs. 24.0 +/- 4.6%). At 20 weeks, coronary artery stenosis was significantly greater in D-HL than in N-HL animals (86 +/- 10 vs. 46 +/- 8%). Coronary lesions predominantly arose in the first 2-3 cm of the vessels and displayed humanoid morphology. Aortic lesions in D-HL swine had double the cholesterol content of those in N-HL swine, and incorporation of oleate into cholesteryl ester was significantly greater in grossly normal aortic areas of D-HL swine compared with N-HL and was attributed to similar elevated incorporation in monocytes. This large study demonstrates that a model of diabetes with humanoid characteristics, including hypertriglyceridemia and severe, accelerated atherosclerosis can be reproducibly induced and maintained in swine. This model should potentially be of great value in elucidating mechanisms underlying the accelerated atherosclerosis seen in human diabetic individuals.


Acquired hypertrichosis lanuginosa associated with malignancy.
A patient is described with acquired hypertrichosis lanuginosa associated with malignancy; the case history and pathologic findings are described. The literature, consisting of 35 cases, is analyzed in respect to the hormonal and pathologic findings, and the age and sex of the patients. No definite hormonal cause is as yet assignable to this syndrome.


Mercury toxicity, molecular response and tolerance in higher plants.
Mercury (Hg) contamination in soils has become a great concern as a result of its natural release and anthropogenic activities. This review presents broad aspects of our recent understanding of mercury contamination and toxicology in plants including source of Hg contamination, toxicology, tolerant regulation in plants, and minimization strategy. We first introduced the sources of mercury contamination in soils. Mercury exists in different forms, but ionic mercury (Hg(2+)) is the predominant form in soils and readily absorbed by plants. The second issue to be discussed is the uptake, transport, and localization of Hg(2+) in plants. Mercury accumulated in plants evokes severe phytotoxicity and impairs numerous metabolic processes including nutrient uptake, water status, and photosynthesis. The mechanisms of mercury-induced toxicology, molecular response and gene networks for regulating plant tolerance will be reviewed. In the case of Hg recent much progress has been made in profiling of transcriptome and more importantly, uncovering a group of small RNAs that potentially mediates plant tolerance to Hg. Several newly discovered signaling molecules such as nitric oxide and carbon monoxide have now been described as regulators of plant tolerance to Hg. A recently emerged strategy, namely selection and breeding of plant cultivars to minimize Hg (or other metals) accumulation will be discussed in the last part of the review.


Passive role of articular chondrocytes in quinolone-induced arthropathy in guinea pigs.
The role of articular chondrocytes and matrix degrading enzymes such as collagenase and neutral protease in the pathogenesis of quinolone-induced cartilage degeneration was investigated in immature guinea pigs. Articular cartilage from nalidixic acid (NA) treated guinea pigs was examined for the presence of protease activity or the ex vivo synthesis of collagenase at various times post-treatment. Histologic evaluation of knee joints confirmed the presence of degenerative changes in the matrix, but increased collagenase synthesis or protease activity were not detected. A separate group of animals was used to determine the importance of articular chondrocytes in the lesion generation. These cells were killed by intra-articular injection of the glycolysis inhibitor iodoacetic acid (IA) prior to treatment of the animals with NA. Typical "blister-like" their presence was not required for lesion development. Cartilage exposed to IA only did not exhibit "blister-like" lesions indicating that chondrocyte death and proteoglycan loss in conjunction with frictional forces associated with load-bearing were not sufficient to induce major matrical disruptive changes during the period of this study. These results indicate that articular chondrocytes are not actively involved in inducing the degenerative changes and provide no evidence for involvement of collagenase or neutral protease in the pathogenesis of the lesion.


[The effect of transverse dental compensation of camouflaged treatment in adult skeletal Class Ⅲ patients with width discrepancy using cone-beam CT].
To investigate the effect of buccolingual inclination and width of molars and their alveolar ridge height in skeletal Class III patients with width discrepancy by camouflaged treatment using cone-beam CT (CBCT). Sixteen adult patients (5 males, 11 females) with mild to moderate skeletal Class III were treated with camouflaged method in the Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University from 2014 to 2015. CBCT scans were performed before and after treatment. Dicom data were calibrated and reconstructed using the software Simplant 16.0. Fifty-nine landmarks and two reference planes were located and measured in three coordinated dimensions. The data was processed using SPSS 17.0 software package. The buccolingual inclination of the maxillary first and second molars were increased, while the mandibular ones were decreased significantly after treatment (P＜0.05). The inter-molar width was increased in the upper arch while decreased in the lower arch. The buccal alveolar ridge height of maxillary molars was decreased significantly (P＜0.05). No significant difference of alveolar ridge height was found in the lingual side of maxillary molars or either side of mandibular molars. Camouflaged treatment deteriorated the transverse compensation in skeletal Class Ⅲ patients with width discrepancy, accompanied with maxillary buccal alveolar bone resorption. When camouflaged treatment is planned, the potential of molar compensation in transverse dimension should be clearly defined. Appropriate pre-adjusted appliance or surgery-assisted expansion should be considered to avoid periodontal risks.


Alteration of affective Theory of Mind in amnestic mild cognitive impairment.
The concept of amnestic mild cognitive impairment (aMCI) concerns a population of older individuals at high risk of developing probable Alzheimer's disease (AD). Impairments of the cognitive component of Theory of Mind (ToM), that is the inference about other people's beliefs, have been well documented in AD; on the contrary, controversial findings have been reported on the affective component of ToM (inference about other's feelings), a process mainly based on medial portions of the prefrontal cortex. The current study aimed at evaluating the affective component of ToM in aMCI subjects. Twenty aMCI subjects and 20 age-matched healthy controls (HC) underwent a standard neuropsychological assessment and the assessment of affective ToM with the full 36-item version of reading the mind in the eyes (RME). Although aMCI subjects had formal impaired performances only in memory tasks, HC outperformed aMCI subjects in several cognitive tasks, including also the RME (mean RME scores 21.7 ± 3.0 vs. 17.0 ± 3.8%; 60.3% of correct answers vs. 47.2%). The lower RME performance of aMCI patients provides the first empirical evidence that aMCI may be associated with difficulties in tasks of affective ToM, in accordance with recent findings of early difficulties of aMCI patients in other processes that are mainly dependent on the medial prefrontal cortex, such as reversal learning and decision making under ambiguity. Findings of the current study need further empirical confirmation in larger samples of aMCI patients and also the investigation of other MCI subtypes is needed.


Atrial gland cells synthesize a family of peptides that can induce egg laying in Aplysia.
Endogenous peptides induce egg laying in the marine mollusc Aplysia in two ways: egg-laying hormone (ELH) from the neuroendocrine bag cells acts directly, causing the release of eggs from the ovotestis; peptides A and B from the atrial gland act indirectly, activating the bag cells to release ELH. Another atrial gland peptide (egg-releasing hormone; ERH) is a structural and functional hybrid of ELH and peptides A and B; it can act both directly and indirectly to induce egg laying. Atrial glands were incubated in a mixture of 3H-amino acids for 18 h, and the biosynthetically labelled peptides isolated using sequential Sephadex G-50 column chromatography and isoelectric focusing. Radiolabelled peaks were localized and bioassayed in intact animals. Bioactive peaks were then characterized functionally using two additional assays: egg laying in bag cell-less animals (ELH-like peptides) and in vitro induction of bag cell discharge (A- and B-like peptides). ERH-like molecules are active in both assays. Homogeneity of bioactive IEF peaks was assessed by SDS-PAGE. Sephadex G-50 gel filtration of biosynthetically labelled atrial gland extracts reveals two major peptide peaks. Peak D (apparent Mr 6,000) is strongly radiolabelled and contains most of the egg-laying activity, but has a low absorbance at 274 nm. Peak E (apparent Mr 3,500) is weakly labelled and contains a small proportion of the total egg-laying activity, but has a large absorbance at 274 nm. Isoelectric focusing of radiolabelled peptides in peak D reveals seven distinct ELH-like species (pI 5.5, 7.5, 8.5, 8.7, 8.9, 9.1, 9.4), and two peaks (pI 5.9, 8.1) that have both ELH-like and A-/B-like activity. The pI 8.1 peak may result from the comigration of peptide A with ERH or with an unidentified ELH-like peptide. It is not yet clear whether the pI 5.9 activity results from comigration of distinct peptides or from the presence of a previously uncharacterized ERH-like molecule. Isoelectric focusing of radiolabelled peptides in peak E reveals five distinct ELH-like species (pI 7.3, 8.5, 8.7, 9.1, 9.4), and one peak (pI 8.9) with both ELH-like and A-/B-like activity. The pI 8.9 peak may result from the comigration of an ELH-like peptide with peptide B. Three of the ELH-like peptides (pI 8.5, 8.9, 9.1) found in peak E are probably identical to the ELH-like peptides found at the same pI's in peak D.(ABSTRACT TRUNCATED AT 400 WORDS)


Intensification of sodium hydroxide pretreatment of corn stalk using magnetic field in a fluidic system.
To promote NaOH pretreatment of corn stalk (CS), a continuous processing system uniting magnetic field and millimeter-scaled channel flow was established. First, four comparative pretreatments were conducted: (I) CS was pretreated with NaOH under traditional agitation; (II) CS was pretreated with NaOH in a flowing state inside the millimeter-scaled channel; (III) CS was pretreated with NaOH in a flowing state and under a static magnetic field; or (IV) CS was pretreated with NaOH in a flowing state and under a rotating magnetic field. By comparison, the highest pentose (121.22mg/g dry CS) and hexose (287.04mg/g dry CS) yields were obtained in the shortest pretreatment time with Pretreatment IV (8h). Accordingly, the key parameters of Pretreatment IV were optimized as 6.71Hz frequency, 0.50L/min flow rate, and 1.02% NaOH concentration. Under these conditions, 439.24mg sugars were released by 1g dry CS during pretreatment and enzymatic hydrolysis.


Parental factors in dominance of lateral buds on rhizomes of Agropyron repens (L.) beauv.
A mixture of 1-naphthylacetic acid and 6-benzylaminopurine was found to be an effective substitute for the rhizome apex of attached rhizomes, when the plants were not at anthesis. The same mixture was not effective, however, when the plants were at anthesis. The same growth-regulators applied to the apical end of detached multi-node rhizome fragments did not maintain correlative inhibition unless growth-regulators were simultaneously applied to the basal end. Various interactions between apical and basal applications are discussed with regard to their role as a parental factor in apical dominance.


Massive localized lymphedema: a clinicopathologic study of 46 patients with an enrichment for multiplicity.
Massive localized lymphedema is a monstrous tumefactive pseudosarcoma seen in middle-aged morbidly obese adults. Since its initial description in 1998, the etiology remains unknown, although associations with trauma, surgeries, and hypothyroidism have been reported. Herein, we report the largest study of massive localized lymphedema and expand upon its clinicopathologic features. Fifty-four cases from 46 patients were retrospectively identified from the institutional archives of The Ohio State University Wexner Medical Center between 2002 and 2015. Forty-six patients (21 males and 25 females, mean age 50 years) presented with large masses developing over a 5-60-month period. The majority of patients were Caucasian (n=39). All patients were obese with a mean weight of 384.7 lb and a mean body mass index of 59.6 kg/m(2). Thirty-six patients had a history of atherosclerotic cardiovascular disease and diabetes mellitus type 2 was present in 22 patients. Eight patients had multifocal massive localized lymphedema. The sites included thigh (n=33), abdomen (n=17), suprapubic region (n=1), mons pubis (n=6), scrotum (n=2), perianal region (n=1), and right flank (n=1). Mostly, the clinical impression was benign processes, including pannus or lymphedema pseudotumor. Grossly, the mean weight was 8237 g and the mean size was 53.2 cm. Histologically, eight cases showed a unique pattern of dystrophic calcifications mimicking hyperchromatic, atypical nuclei that might lead to misdiagnosis of liposarcoma, four cases showed focal metaplastic ossification, and three cases showed multinucleated cells in addition to prototypic features of massive localized lymphedema. We report that this is the largest series of massive localized lymphedema. This is a lesion mostly seen in morbidly obese patients and the thigh is the most common site of involvement. We note a marked racial predilection for Caucasians and a tendency towards multiplicity. We suggest that obesity itself and the related metabolic syndrome have an important role in its pathogenesis.


Regulation of Na+/H+ and Cl-/HCO3- antiports in Vero cells.
The effect of serum, phorbol-12-myristate-13-acetate (TPA), and forskolin on the activity Na+/H+ antiport and the Na(+)-coupled and Na(+)-independent Cl-/HCO3- antiport was studied in Vero cells by measuring 22Na+ and 36Cl- fluxes and changes in cytosolic pH (pHi). The Na(+)-independent Cl-/HCO3- antiport, which acts as an acidifying mechanism, is strongly pH-sensitive. In serum-starved cells it is activated at alkaline cytosolic pH, with a half-maximal activity at pHi approximately 7.20. Incubation with serum increased the activity of the Na(+)-independent Cl-/HCO3- antiport at pHi values from 6.8 to 7.2. Thus serum appeared to alter the pHi sensitivity of this antiporter such that the threshold value for activation of the antiport was shifted to a more acidic value. Na+/H+ antiport was somewhat stimulated initially by addition of serum, but further incubation with serum (greater than 45 min) decreased its activity. The activity of the Na(+)-coupled Cl-/HCO3- antiport, which is the major alkalinizing antiport in Vero cells, was not altered by short-term incubation with serum (less than 10 min) but decreased after prolonged incubation (greater than 45 min). Our findings with TPA and forskolin indicate that the effect of serum is partly mediated by the protein kinase C pathway, whereas the cyclic adenosine monophosphate pathway does not appear to play an important role. The net effect of serum on the pHi-regulating antiports was a slight decrease in intracellular pH.


Low-dose-rate brachytherapy for prostate cancer in renal transplant recipients.
Prostate cancer (PCa) is the most common malignancy among men and one of the most common neoplasms affecting renal transplant recipients (RTRs). The available treatments for localized PCa among the general population (GP), surgery and external beam radiotherapy, carry a risk of damage to the transplanted kidney, the ureters, and the bladder and therefore tend to be avoided by most groups. The objective of this study was to assess the efficacy and feasibility of low-dose-rate brachytherapy (LDR-BT) for PCa in RTRs. We carried out a retrospective review on all RTRs diagnosed of PCa who had undergone LDR-BT at our institution between 2000 and 2015. Nine patients met these criteria, but 1 did not fulfill the followup. Hence, we analyzed 8 patients. We reviewed all clinical data for PCa and graft function in these patients and compared the results with the GP. Mean baseline prostate-specific antigen was 6.8 ± 1.9 ng/mL. All PCa had a Gleason score of 6 and were classified as low risk according the Europe Association of Urology guidelines. Mean followup after seed implantation was 48 ± 12.8 months. All 8 patients remain free of prostate-specific antigen failure. Five-year progression-free survival, cancer-specific survival, and overall survival rates were 100%, 100%, and 62.5%. There was no specific toxicity associated with LDR-BT, and there were no acute adverse events affecting the graft. LDR-BT is a feasible and acceptable treatment for localized PCa in RTRs. Oncological outcomes are similar to the GP, and there is minimal toxicity to the renal graft.


Influence of lactate and acetate salt adaptation on Salmonella Typhimurium acid and heat resistance.
The aim of the present study was to determine the survival of Salmonella Typhimurium adapted with sodium lactate (NaL), potassium lactate/sodium acetate mixture (KL/NaA) or sodium acetate (NaA) in simulated gastric fluid (SGF) and during heat treatment. NaL-, KL/NaA- and NaA-adapted cells were prepared by incubating in tryptic soy broth (TSB) containing these salts at 5, 5 and 3% (w/v) concentration levels, respectively, for 24 h at 37 °C. The Baranyi model was used to compare the growth kinetic parameters of adapted cells. The acid and heat resistance of adapted cells were determined by incubating in SGF (pH 2.04) at 37 °C and in TSB at 55.8, 57.8 and 59.8 °C, respectively. Adapted cells had significantly (P < 0.05) longer lag phase duration (LPD) and slower maximum growth rate (MGR) than non-adapted cells. The acid resistance of KL/NaA-adapted cells was not significantly (P > 0.05) different from that of non-adapted cells. NaL-adapted cells were more susceptible to the low pH environment, whereas NaA-adapted cells showed enhanced acid resistance compared to non-adapted and other adapted cells. Unlike acid resistance, both NaL- and NaA-adapted cells showed enhanced heat resistance with increased D-values, regardless of treatment temperatures. Thus, this study indicates that adaptation of S. Typhimurium to 5% NaL or 3% NaA could enhance their ability to survive thermal processes or in the human stomach, possibly increasing the risk of Salmonella outbreaks.


An ultra-high throughput screening approach for an adenine transferase using fluorescence polarization.
We have developed a novel assay for measuring the activity of an enzyme that transfers multiple adenine-containing groups to an acceptor protein. The assay is based on fluorescence polarization (FP) technology in a 1536-well plate format. In the assay, a long wavelength fluorescence tracer, Texas Red (Rhodamine), was covalently conjugated to adenine of the donor substrate through a C(6) spacer arm. As a result of the transfer of the adenine-containing moieties to the acceptor protein substrate, the rotational correlation time of the Texas Red conjugate increased, hence increasing the degree of fluorescence polarization. The pharmacological profile and kinetics of the enzyme measured according to the FP method were consistent with those determined previously by conventional analysis. We have successfully executed a 250,000-compound high throughput screening program based on the FP assay method. The quality and validity of the assay were verified by a variety of statistical analyses.


α-Synuclein Spontaneously Adopts Stable and Reversible α-Helical Structure in Water-Less Environment.
A highly stable, spontaneous, and reversible α-helical-structure formation in recombinant and chemically modified α-synuclein protein is demonstrated for the first time in a water-less (1.5 % w/w H2 O) polymer surfactant environment. Using a combination of circular dichroism and ATR-FTIR spectroscopy, we show that whilst native α-synuclein in aqueous solution shows a predominant unordered conformation (≈64 %), mixing with polyethylene glycol based anionic polymer surfactant (PS) and removing water reveals a 25 % unordered, 25 % α-helical, and 27 % β-sheet structure. Interestingly, bioconjugation of native α-synuclein with a diamine molecule, to increase the positive charge on the protein chain, and subsequent electrostatic coupling with the PS forms a conjugate with a retained unordered structure. Removal of water from this system provides a highly stable α-helical (≈74 %) water-less liquid system. Surprisingly, the α-helical-to-unordered state transition is completely reversible and is achieved at ≈25-30 w/w% of water in the system. Moreover, the α-helix shows an extraordinary temporal stability (>6 months) in a waterless environment.


Nonlinear antiresonant ring interferometer.
A beam-splitter ring-mirror configuration employing a Kerr-like nonlinear medium, that is, a nonlinear antiresonant ring interferometer, is proposed for several optical functional devices. The basic idea behind the configuration is derived from the formation of a nonlinear refractive-index grating in a Kerr-like medium inside the unbalanced ring.


Quantitative and compositional study of cardiolipin in platelets by electrospray ionization mass spectrometry: application for the identification of Barth syndrome patients.
The concentration of cardiolipin (CL) in cultured skin fibroblasts is a useful indicator of Barth syndrome (BTHS; MIM 302060), but the sampling and culturing of fibroblasts are burdensome and time-consuming procedures. We investigated whether the analysis of CL in platelets might help to identify BTHS in patients suspected of having this condition. We used HPLC and online electrospray ionization mass spectrometry (HPLC-ESI-MS) to quantify CL molecular species. The CL content of platelets was studied in blood samples of BTHS and non-BTHS patients. Control blood samples drawn from healthy adults were collected and analyzed within 24 h (n = 10) and 48 h (n = 10) to characterize any effect of sample shipping time on the CL content in platelets. Samples were collected from children 1-10 years of age who were not affected by BTHS (n = 6) and from BTHS patients (n = 4) and analyzed within 24 h. Results for all four groups were compared by a Student t-test for all individual analyses. We found different CL molecular species, e.g., (C18:2)(4)-CL. BTHS patients had a specific decrease of tetralinoleyl-CL concentrations in platelets (0.1-0.5 nmol/mg of protein; n = 4) compared with all control groups (2.3-5.5 nmol/mg of protein; n = 26). Only minor differences were observed among the different control groups. Quantitative and compositional analyses of CL in platelets by the proposed method allow identification of BTHS patients more rapidly than gene analysis or analysis of CL in cultured skin fibroblasts. The abnormality of CL may explain the abnormal mitochondrial function observed in BTHS. The differences between the control groups did not cause any complication.


[Prevalence erectile dysfunction in patients with hypertension].
Erectile dysfunction (ED), defined as the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance, is closely associated with hypertension. We assessed the prevalence of ED in patients with hypertension at the primary care level. We analyzed factors associated with ED in these patients. We also worked out the relationship between cardiovascular disease risks and ED. This transversal multicenter study was carried out in educational primary care centers. A total of 512 patients with hypertension completed the International Index of Erectile Function in its abridged form (IIEF-5). Their known cardiovascular risk factors, comorbidity, toxic habits and hypertension history were taken form their medical records. Of 512 patients, 5 were not included in the study because of incomplete data in the IIEF-5 questionnaire. Mean age was 63.36 years (range 30 to 86). The prevalence of erectile dysfunction was 46.5%. Correlation of ED with age [OR = 1.05 (1.028-1.075)], diabetes mellitus [OR = 2.06 (1.247-3.406)] and ischemic heart disease [OR = 3.15 (1.429-6.947)] did reach statistical significance (p < 0.05). A linkage with cardiovascular disease risks, as worked out by the Framingham study, was not found. We observe a high prevalence of ED in patients with hypertension.


[The effect of hemodilution and autotransfusion on diagnostic levels of digoxin in serum of patients operated on with extracorporeal circulation].
In many patients operated on for valvular heart diseases indications are present to digitalis administration in the preoperative period. During extracorporeal circulation fluctuations occur of blood potassium concentration which increase the risk for toxic effect of digitalis. In the work, digoxin concentration was studied in the serum of patients operated on in extracorporeal circulation in whom administration of this drug was discontinued 48 hours before the operation. The first digoxin dose (0.5 mg) was given directly after withdrawal of extracorporeal circulation, and another 0.5 mg was given after 4 hours. Digoxin concentrations were determined by fluorescence-polarization-immunological method using TD* Abbott device. The digoxin concentration increased rapidly and reached its peak after 6 hours (1.9 ng/ml), decreasing after 12 hours to 0.9 ng/ml and persisted at this therapeutic level in further samples. The present studies demonstrated that digoxin administration directly after withdrawal of extracorporeal circulation and within 24 hours after the operation in commonly accepted doses provided therapeutic concentration of the drug and caused no increase of the risk for toxic reaction development.


Comparative Cost-Effectiveness Analysis of Modified 1-Layer versus Formal 2-Layer Vasovasostomy Technique.
Approximately 2% to 6% of men undergoing vasectomy will ultimately have it reversed. Cost is a major consideration for patients and providers with regard to vasovasostomy. Opportunities for cost savings for vasectomy reversal lie in the reduction of variable costs, namely operative time and materials used. In this study we determine the cost benefits of a modified 1-layer vasovasostomy compared to a formal 2-layer vasovasostomy. A retrospective analysis was performed of a single surgeon experience of vasectomy reversals performed from 2010 to 2015. The cohort consisted of men who underwent bilateral vasovasostomy using a formal 2-layer or modified 1-layer technique. The primary end points of the analysis were total operative time; number, cost and type of suture used; and patency/postoperative semen analysis. Bivariate analysis was performed for these continuous variables using the Wilcoxon rank test and the chi-square test was used for categorical variables. Of the 106 men who underwent bilateral vasovasostomy 81.1% (86) had a formal and 18.9% (20) had a modified 1-layer repair. The modified 1-layer closure resulted in a significantly shorter operative time, lower microsuture cost and lower overall operative cost compared to formal repair (all p <0.05). There were no statistically significant differences in semen parameters between the 2 techniques at the first postoperative visit. The modified 1-layer vasovasostomy resulted in shorter operative times and lower costs compared to formal repair without compromising postoperative patency. In this era of cost containment the modified repair provides the opportunity to perform vasectomy reversal at a lower cost to patients and providers.


A unique bFGF-responsive transcriptional element.
The mitogen-regulated protein/proliferin (mrp/plf) genes encode closely related proteins that stimulate cell proliferation and angiogenesis. Basic fibroblast growth factor (bFGF) increases mrp/plf mRNA and protein production by 3T3 cells. Although the three cloned mrp/plf gene promoters are over 97% identical, only mrp3 is transcriptionally activated by bFGF. A series of truncated mrp3 promoter sequences were tested to determine the minimal promoter sequence necessary for bFGF-responsive transcription. Within the minimal bFGF-responsive mrp3 promoter fragment, a putative FGF-regulatory element (FRE) was identified. Nuclear factors that bind the FRE are present in 3T3 cells. When present upstream of a thymidine kinase basal promoter, the FRE exhibits high transcriptional activity and responds to bFGF. Thus, the FRE is a strong transcriptional element that is regulated by bFGF and that may participate in regulating the mrp3 gene and perhaps other FGF-regulated genes.


Tilting-filter measurements in dayglow rocket photometry.
A rocket-borne photometer containing two tilting-filter channels for the measurement of the [OI] lambdalambda6300-A and 5577A emission lines in the day airglow is described. The results of one flight substantiate the employment of tilting filters to determine accurate corrections for background continuum and provide reliable height profiles of emission intensity down to approximately 90 km. Discussions on the calibration of the instrument and its baffling against sunlight are also presented.


Kras mutations and p53 overexpression in pseudomyxoma peritonei: association with phenotype and prognosis.
Little information exists on Kras mutations and p53 overexpression in pseudomyxoma peritonei (PMP). These genetic alterations are associated with poorer prognoses in colorectal cancer. We postulated that these mutations might be more frequent in high-grade (HG) PMP (peritoneal mucinous carcinomatosis) versus low-grade (LG) PMP (disseminated peritoneal adenomucinosis/peritoneal mucinous carcinomatosis), for which survival differences are well documented. We collected data retrospectively on patients with PMP of appendiceal origin tested for Kras mutation (commercial assay) and p53 overexpression (immunohistochemistry). We used Fisher's exact test, chi-square test, and Kaplan-Meier survival curves for analysis. Of 64 cases with Kras mutations, 25 were classified as LG and 39 as HG PMP. Median age at diagnosis was 53 ± 11.5 y. We detected Kras mutations in 37 of 64 patients (57.8%). In LG PMP, 15 of 25 (60%) were Kras mutant versus 22 of 39 (56.4%) in HG PMP (P=0.80). Nearly 89% of mutations were seen in codon 12. We noted overexpression of p53 in 44.3% (86 of 194) of patients overall, which was significantly different between LG PMP and HG PMP: 35.5% (37 of 104) versus 54.4% (49 of 90), respectively (P=0.009). Kras mutations did not affect prognosis. Overexpression of p53 was associated with a worse outcome. Kras mutation and p53 overexpression rates are comparable to those of colorectal adenomas and mucinous colorectal cancer. Codon 12 mutations may be associated with mucin production. Kras mutation status is not prognostic for overall survival. Overexpression of p53 was significantly correlated with female sex, higher-grade disease, and worse survival.


Excess weight at time of presentation of myocardial infarction is associated with lower initial mortality risks but higher long-term risks including recurrent re-infarction and cardiac death.
To evaluate the influence of elevated body mass index (BMI) on short- and long-term survival following acute myocardial infarction (AMI). Recent studies suggest an obesity survival paradox in individuals undergoing percutaneous coronary intervention with better 30-day and 1-year outcomes in obese relative to normal weight patients. We tested a similar obesity paradox hypothesis following acute myocardial infarction. Short- and long-term all-cause mortality, and risk of recurrent AMI were evaluated according to BMI status in 894 consecutive survivors of AMI <80 years of age admitted to the Mayo Clinic Coronary Care Unit between January 1, 1988 and April 16, 2001. Normal weight, overweight and obesity were defined as BMI <25, 25-29.9, and >30 kg/m(2), respectively. Overall mortality following hospital discharge was significantly lower in overweight and obese patients and was mostly attributable to lower 6-month mortality (adjusted HR = 0.47, P = 0.01 for BMI >25 kg/m(2)) relative to normal weight patients, while long-term mortality among 6-month survivors was similar in all 3 groups. The risk of recurrent AMI was higher in patients with BMI >25 kg/m(2) (adjusted HR = 2.30, P = 0.01). Overweight and obese patients were significantly more likely to die from cardiac rather than non-cardiac causes (P < 0.01). Following AMI, overweight and obese individuals although paradoxically protected from short-term death have a long-term mortality risk that is similar to normal weight individuals. Younger age at the time of initial infarction and fewer non-cardiovascular comorbidities presumably explain the short-lived obesity survival paradox following myocardial infarction.


Proteomics analysis of sensitive and tolerant barley genotypes under drought stress.
Drought is a severe environmental constraint to plant productivity and an important factor limiting barley yield. To investigate the initial response of barley to drought stress, changes in protein profile were analyzed using a proteomics technique. Three-day-old barley seedlings of sensitive genotype 004186 and tolerant genotype 004223 were given two treatments, one with 20 % polyethylene glycol and the second with drought induced by withholding water. After 3 days of treatments, proteins were extracted from shoots and separated by 2-dimensional polyacrylamide gel electrophoresis. Metabolism related proteins were decreased in the sensitive genotype under drought; however, they were increased in the tolerant genotype. Photosynthetic related proteins were decreased and increased among the three sensitive and three tolerant genotypes, respectively. In addition, amino acid synthesis and degradation related proteins were increased and decreased among the three tolerant genotypes. These results suggest that chloroplastic metabolism and energy related proteins might play a significant role in the adaptation process of barley seedlings under drought stress.


[The effect of thyroparathyroidectomy, parathyroid hormone and calcitonin on plasma strontium in rats].
The effect of thyroparathyroidectomy (TPTX) on the plasmatic Sr concentrations in rats previously supplemented with this element, has been studied, as well as its effect on the treatment of TPTX rats with hormonal combinations and, finally, the one presenting hormonal excess or defect of the phosphocalcium metabolism regulating hormones: parathormone (PTH) and calcitonin (CT). Twenty four hours after TPTX, the plasmatic Sr concentrations show a pattern similar to those of Ca and Mg and contrary to Pi. The subsequent evolution is different, as the plasmatic concentrations increase, probably due to the maintenance of Sr supplementation. The administration of this element to TPTX rats and the treatment with a hormonal combination with two of the following hormones: PTH, CT and T4 antagonize the hormonal effect on the restoration of the plasmatic concentrations of the elements analyzed. The PTH excess and defect (TPTX treated with CT + T4) show plasmatic increases in Sr; the CT excess provokes decreases while the defect (administration of PTH + T4) causes increases. The T4 administration reproduces the CT effects, but inconsistently. These results suggest that CT may be the hormone that plays a regulating role in the plasmatic Sr concentrations.


Development of an ease-of-use remote healthcare system architecture using RFID and networking technologies.
The study aims to provide an ease-of-use approach for senior patients to utilize remote healthcare systems. An ease-of-use remote healthcare system (RHS) architecture using RFID (Radio Frequency Identification) and networking technologies is developed. Specifically, the codes in RFID tags are used for authenticating the patients' ID to secure and ease the login process. The patient needs only to take one action, i.e. placing a RFID tag onto the reader, to automatically login and start the RHS and then acquire automatic medical services. An ease-of-use emergency monitoring and reporting mechanism is developed as well to monitor and protect the safety of the senior patients who have to be left alone at home. By just pressing a single button, the RHS can automatically report the patient's emergency information to the clinic side so that the responsible medical personnel can take proper urgent actions for the patient. Besides, Web services technology is used to build the Internet communication scheme of the RHS so that the interoperability and data transmission security between the home server and the clinical server can be enhanced. A prototype RHS is constructed to validate the effectiveness of our designs. Testing results show that the proposed RHS architecture possesses the characteristics of ease to use, simplicity to operate, promptness in login, and no need to preserve identity information. The proposed RHS architecture can effectively increase the willingness of senior patients who act slowly or are unfamiliar with computer operations to use the RHS. The research results can be used as an add-on for developing future remote healthcare systems.


Synthetic studies and biosynthetic speculation on marine alkaloid chartelline.
Synthetic studies and biosynthetic speculation on chartelline inspired by an unexpected reaction are described.


[Risk of hepatitis C virus infection in medical occupations].
Following the introduction of sensitive and specific tests for the detection of hepatitis C virus (HCV) infection studies could be performed to determine the risk to acquire a HCV infection in medical professions. The aim of this report is to summarize the knowledge in this field, especially regarding the risk of transmission of HC virus by injuries with infected material, such as needles. The risk to acquire a HCV infection following needlestick injuries was found to be markedly lower than the risk for transmission of hepatitis B virus infection. In 7 studies from different countries this risk has been found to be between zero to a maximum of 10% (average 2%). When the frequency of HCV infection was studied in occupational groups in hospital (nurses, technical assistants, doctors), it did not differ significantly compared to the prevalence in general population. These and other findings concerning the risk of transmission of HCV infections (between spouses, mother/newborns) clearly show that the risk of transmission of HCV infection is markedly lower than that of HBV infection. These facts should be considered in judging of applications for the recognition of HCV infection as occupational disease.


Lymphocyte transformation induced by autologous cells. X. Soluble factors that generate cytotoxic T lymphocytes.
Cytotoxic T lymphocytes (CTL) were not generated in an autologous mixed lymphocyte reaction (MLR) in the presence of human AB serum. No CTL were generated in cultures that contained T cells and irradiated autologous, allogenetic, or hapten-modified autologous T lymphocytes. However, when allogeneic T lymphocytes or hapten-modified autologous T lymphocytes were added to an autologous MLR, specific CTL were generated. Furthermore, supernatant medium from an autologous MLR allowed the generation of specific CTL in T cell cultures to which allogeneic T cells or hapten-modified autologous T cells were added.


Neurological and mental outcome after severe head injury in childhood: a long-term follow-up of 318 children.
Identification of prognostic risk factors in paediatric head injury. Long-term follow-up of 318 children with severe head injuries with a mean follow-up period of 8 years and 9 months. The neurological and mental outcome was classified by the Glasgow Outcome Scale and the Frankfurt Mental Outcome Scale. Prognostic risk factors were a primary post-traumatic vigilance disturbance longer than 24 hours, less than seven points on the Glasgow Coma Scale, an increased intracranial pressure with cerebral perfusion pressure below 50 mmHg, age at accident younger than 2 years, physical abuse and the development of post-traumatic epilepsy. The infant brain is more vulnerable to lasting deficits and is more prone to post-traumatic seizure development. Post-traumatic epilepsy itself causes a deterioration in outcome because of the developmental disturbance at epilepsy onset and often unfavourable course. Physically abused children with their often multiple and repeated head injuries are predestined for poor outcome.


Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta.
Among the endocrine factors associated with breast cancer, estrogens are considered to play a central role in human breast carcinogenesis. Breast cancer risks are increased by long-term exposure to estrogens. Zeranol (Ralgro) is a nonsteroidal agent with estrogenic activity that is used as a growth promoter in the U.S. beef and veal industry. To determine whether zeranol and estradiol-17beta play a role in the neoplastic transformation of human breast and to compare the estrogenic potency of zeranol to that of estradiol-17beta in human breast, we treated human breast epithelial cell MCF-10A with different doses of zeranol or estradiol-17beta for 10 repeated treatment cycles. By utilizing the doubling time assay, soft agar assay, and reverse transcriptase polymerase chain reaction (RT-PCR) assay, we showed that 10 repeated estradiol-17beta or zeranol treatment cycles to MCF-10A cells decrease the doubling time of the cells by 30 to 40% and stimulate colony formation in soft agar and induce estrogen receptor beta (ER-beta) mRNA expression, all of which are not dose related in our tested dose range. Furthermore, we show that zeranol and estradiol-17beta have a similar potency in the stimulation and inhibition of gene expressions in human breast cancer cell line MCF-7 by RT-PCR. These results indicate that both zeranol and estradiol-17beta can induce human breast epithelial cell neoplastic transformation with similar potency in the long-term exposure through the oxidation-reduction (redox) pathway and/or ER-beta-mediated pathway.


PEI conjugated gold nanoparticles: efficient gene carriers with visible fluorescence.
Low molecular weight polyethyleneimines were conjugated onto gold nanoparticles to form Au-PEI conjugates. Au-PEI is the first reported gene carrier which has both high transfection efficiency and strong fluorescence. Au-PEI showed higher transfection efficiency and it can be used for bioimaging because it can be detected by confocal laser scanning microscopy and in vivo bioimaging system.


[Ultrastructural findings of the muscles around lip clefts].
Our electron microscopic observations show alterations of the muscles near the cleft margins confirming the theory resulting from light microscopic and immunohistochemical findings that the myogenic structures surrounding cleft margins are inferior tissue that is capable neither of regeneration nor of normal function. The clinical implication derived from these observations is that the tissue in the vicinity of the clefts should be generously excised when doing cheiloplasties.


Rupture of the posterior tibial tendon associated with closed ankle fracture.
Rupture of the posterior tibial tendon has rarely been associated with closed ankle fractures. All previous cases have been in association with pronation-external rotation type fractures in which the medial malleolus has been fractured. This case represents the first such report of a severed posterior tibial tendon in the absence of a medial malleolar fracture and reemphasizes the importance of critically evaluating intraoperative radiographs following the open reduction and internal fixation of closed ankle fractures to assess the possibility of soft tissue interposition. In the event of an acute rupture of the posterior tibial tendon, the authors recommend primary tendon repair.


Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons.
The tetrodotoxin-resistant (TTX-R) voltage-gated Na(+) channels Na(v)1.8 and Na(v)1.9 are expressed by a subset of primary sensory neurons and have been implicated in various pain states. Although recent studies suggest involvement of TTX-R Na(+) channels in sensory synaptic transmission and spinal pain processing, it remains unknown whether TTX-R Na(+) channels are expressed and function presynaptically. We examined expression of TTX-R channels at sensory synapses formed between rat dorsal root ganglion (DRG) and spinal cord (SC) neurons in a DRG/SC co-culture system. Immunostaining showed extensive labeling of presynaptic axonal boutons with Na(v)1.8- and Na(v)1.9-specific antibodies. Measurements using the fluorescent Na(+) indicator SBFI demonstrated action potential-induced presynaptic Na(+) entry that was resistant to tetrodotoxin (TTX) but was blocked by lidocaine. Furthermore, presynaptic [Ca(2+)](i) elevation in response to a single action potential was not affected by TTX in TTX-resistant DRG neurons. Finally, glutamatergic synaptic transmission was not inhibited by TTX in more than 50% of synaptic pairs examined; subsequent treatment with lidocaine completely blocked these TTX-resistant excitatory postsynaptic currents. Taken together, these results provide evidence for presynaptic expression of functional TTX-R Na(+) channels that may be important for shaping presynaptic action potentials and regulating transmitter release at the first sensory synapse.


Antitumor activity of TZT-1027 (Soblidotin).
TZT-1027 (Soblidotin), a newly synthesized dolastatin 10 derivative that depolymerizes microtubules, has potent antitumor activity. Cell-killing kinetic analysis was performed by the colony-forming assay and the kinetics of TZT-1027 were compared with those of neocarzinostatin, adriamycin and vincristine, known to be typical concentration-, AUC- and time-dependent agents, respectively. DNA fragmentation was detectable by electrophoresis, cytotoxicity was evaluated by MTT assay and antitumor activity was examined by measuring the tumor weight after treatment. TZT-1027 exhibited its cytocidal and apoptosis-inducing activity in a time-dependent manner. Its growth-inhibitory effect was less affected by overexpression of P-glycoprotein than that of other tubulin inhibitors and was not affected by the overexpression of breast cancer resistance protein or multidrug resistance-associated protein. TZT-1027 exhibited potent antitumor activities in an in vivo tumor model in which vincristine and docetaxel failed to show effectiveness. Because its growth-inhibitory and antitumor activities were superior to those of the other drugs tested, including the tubulin inhibitors paclitaxel, docetaxel and vincristine, TZT-1027 should be useful in the chemotherapy of tumors that are not responsive to other tubulin inhibitors.


Investigation on distal femoral strength and reconstruction failure following curettage and cementation: In-vitro tests with finite element analyses.
Cement augmentation following benign bone tumor surgery, i.e. curettage and cementation, is recommended in patients at high risk of fracture. Nonetheless, identifying appropriate cases and devices for augmentation remains debatable. Our goal was to develop a validated biomechanical tool to: predict the post-surgery strength of a femoral bone, assess the precision and accuracy of the predicted strength, and discover the mechanisms of reconstruction failure, with the aim of finding a safe biomechanical fixation. Tumor surgery was mimicked in quantitative-CT (QCT) scanned cadaveric human distal femora, and subsequently tested in compression to measure bone strength (FExp). Finite element (FE) models considering bone material non-homogeneity and non-linearity were constructed to predict bone strength (FFE). Analyses of contact, damage, and crack initiation at the bone-cement interface (BCI) were completed to investigate critical failure locations. Results of paired t-tests did not show a significant difference between FExp and FFE (P > 0.05); linear regression analysis resulted in good correlation between FExp and FFE (R2 = 0.94). Evaluation of the models precision using linear regression analysis yielded R2 = 0.89, with the slope = 1.08 and intercept = -324.16 N. FE analyses showed the initiation of damage and crack and a larger cement debonding area at the proximal end and most interior part of BCI, respectively. Therefore, we speculated that devices that reinforce critical failure locations offer the most biomechanical advantage. The QCT-based FE method proved to be a reliable tool to predict distal femoral strength, identify some causes of reconstruction failure, and assist in a safer selection of fixation devices to reduce post-operative fracture risk.


Simple mucin-type carbohydrate antigens in major salivary glands.
Simple mucin-type carbohydrate antigens Tn, sialosyl-Tn and T are often markers of neoplastic transformation and have very limited expression in normal tissues. We performed an immunohistological study of simple mucin-type carbohydrate antigens, including H and A variants, with well-defined monoclonal antibodies (MAb) on frozen and paraffin-embedded normal salivary gland tissue from 22 parotid, 14 submandibular, six sublingual, and 13 labial glands to elucidate the simple mucin-type glycosylation pattern in relation to cyto- and histodifferentiation. The investigated carbohydrate structures were predominantly observed in the cell cytoplasm, most often in the supranuclear area, suggesting localization to the Golgi region, whereas ductal contents were unstained. Mucous acinar cells expressed Tn, sialosyl-Tn, and H and A antigens, regardless of glandular location. Serous acinar cells, on the other hand, expressed A, H, and inconstantly sialosyl-T, Tn, and sialosyl-Tn antigens in major salivary glands, whereas serous cells of minor (labial) salivary glands expressed H exclusively, Tn and sialosyl-T antigens inconstantly, but never sialosyl-Tn and A antigens. The difference may be related to a more simple cytodifferentiation of serous cells of minor (labial) salivary glands as compared with major salivary glands. Duct cells in major salivary glands expressed A, H, and inconstantly T, sialosyl-T, and Tn antigens, whereas minor (labial) salivary glands ducts exclusively expressed H, T and sialosyl-T antigens, differences that may be related to dissimilarities in the duct system. Myoepithelial cells and basal cells exclusively expressed T and sialosyl-T antigens, which may prove useful in studies of salivary gland tumors, since these cells are known to play a key role in the histological characteristics of some salivary gland tumors. The results indicate a similar glycosylation pattern in the different major salivary glands, whereas minor (labial) salivary gland differ slightly in serous and duct cells. The limited and exclusive intracellular expression of the immature Tn, sialosyl-Tn, and T antigens indicates that these structures may be of value as markers of salivary gland tumors.


Agency and facial emotion judgment in context.
Past research showed that East Asians' belief in holism was expressed as their tendencies to include background facial emotions into the evaluation of target faces more than North Americans. However, this pattern can be interpreted as North Americans' tendency to downplay background facial emotions due to their conceptualization of facial emotion as volitional expression of internal states. Examining this alternative explanation, we investigated whether different types of contextual information produce varying degrees of effect on one's face evaluation across cultures. In three studies, European Canadians and East Asians rated the intensity of target facial emotions surrounded with either affectively salient landscape sceneries or background facial emotions. The results showed that, although affectively salient landscapes influenced the judgment of both cultural groups, only European Canadians downplayed the background facial emotions. The role of agency as differently conceptualized across cultures and multilayered systems of cultural meanings are discussed.


Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.
Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.


Electrical stimulation of different retinal components and the effect of asymmetric pulses.
High resolution electrical stimulation of neural tissue is a fundamental challenge in applications such as deep brain stimulation and artificial vision. In artificial vision, achieving and validating local selective epi-retinal stimulation of different layers in the retina is particularly challenging owing to plurality of retinal cell types and delocalized wiring. Strong selectivity and non-localized responses to epi-retinal stimulation, over a wide range of realistic stimulation parameters, was achieved and validated using asymmetric pulses. The reported method consists of multi electrode array (MEA) stimulation and recording from a developing chick retina combined with calcium imaging. Data show direct and indirect neuronal activation in the chick retina model. In particular, axonal activation, orientation and conduction velocity are derived, and the non-local nature of the responses to direct axonal stimulation is demonstrated. Some of the previous research with mammalian retinas demonstrated local responses around the stimulating electrode, revealing little as to axonal activation. Recent studies showed activation along the nerve fibers and studied the effect of pulse duration to improve stimulation localization (Twyford and Fried, 2016; Weitz et al., 2015). The chick retina offers a straight forward mapping of axonal activation. Here we demonstrate that the chick retina, combined with MEA recording and stimulation along with calcium imaging is a powerful tool to study retinal activation and in particular the effect of asymmetry on axonal activation. MEA recording and stimulation from the chick retina is exceptionally powerful in distinguishing between direct and indirect responses. This method facilitates comparison between different stimulation strategies. We show that asymmetric electrical stimulations allow control over the intensity of direct activation.


Microautoradiographic studies on distribution of 5 alpha-dihydrotestosterone, cyproterone acetate and oestradiol-17 beta in human prostatic hyperplasia tissue transplanted to juvenile rats.
While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to new born rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radio-active androgen 5 alpha-dihydrotestosterone (5 alpha-DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17 beta (E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3: 1 and 1.5: 1 for epithelium to stroma after administration of [3H] 5 alpha-DHT and [3H]CA administration respectively and 0.5: 1 after [3H]E2. The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5 alpha-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [3H] 5 alpha-DHT and [3H]CA administration both in the epithelium and stroma suggest that an antagonism may also exist in the stroma.


Natural radioactivity determination in samples of Peperomia pellucida commonly used as a medicinal herb.
The concentration of (238)U, (232)Th, (230)Th, (226)Ra, (228)Ra and (210)Pb were determined in samples of Peperomia pellucida and in the surrounding soil, by alpha spectrometry and gross alpha and beta counting. The radionuclide activity concentrations ranged from 4.3 to 38 Bq kg(-1), 1.7-124 Bq kg(-1), 2.1-38 Bq kg(-1), 8.5-37 Bq kg(-1), 3.2-46 Bq kg(-1), 39-93 Bq kg(-1), respectively. In the plant extractions and infusions as used for consumption, the mean recoveries were from 23% to 60% in maceration and 24-75% in infusion.


Hovk 1 and the Middle and Upper Paleolithic of Armenia: a preliminary framework.
The territory of present day Armenia is a geographic contact zone between the Near East and the northern Caucasus. Armenian Middle and Upper Paleolithic records are both few and patchy as a result of the historical paucity of systematic archaeological research in the country. Consequently, it is currently difficult to correlate the Armenian Middle and Upper Paleolithic records with those from other neighboring regions. We present new archaeological and chronometric data (luminescence, U-Th, and 14C) from our ongoing research at Hovk 1 Cave in northeast Armenia. We discuss in particular two activity phases in Hovk 1 Cave for which we have outline chronometric data: (1) an early Middle Paleolithic occupational phase, dated by optically stimulated luminescence (OSL) to 104+/-9.8 ka BP(OSL); and (2) a Paleolithic occupational phase characterized by microlithic flakes dated by AMS 14C to 39,109+/-1,324 calibrated years BP(Hulu). The two phases are separated by a hiatus in hominin occupation corresponding to MIS 4 and an episode in early MIS 3. These chronometric data, taken together with the preliminary paleoenvironmental reconstruction of the Hovk 1 Cave and environment, suggest that these activity phases represent short-lived and seasonal use of the cave presumably by small groups of hunters during episodes of mild climate. Neither tool manufacture nor butchery appears to have taken place within the cave, and consequently, the archaeological record included, for the most part, finished tools and blanks. We address the chronology and techno-typological aspects of Hovk 1 lithics in relation to: (1) the Paleolithic records of Armenia, and (2) the broader interregional context of early Middle Paleolithic hominin occupation and the Middle-Upper Paleolithic transition in the Caucasus.


Hyperspectral imaging performance of a TeO2 acousto-optic tunable filter in the ultraviolet region.
A compact UV hyperspectral imager can be designed with an acousto-optic tunable filter (AOTF) installed in front of an enhanced CCD camera. Tellurium dioxide (TeO2) is the most commonly used crystal for AOTFs from 0.4 to 4 microm. We conducted an experiment to determine the UV spectral response of an imaging TeO2 AOTF in tandem with a known KDP AOTF and obtained good-quality hyperspectral images by using the TeO2 filter down to 365 nm. We compared the performance of the TeO2 filter-based hyperspectral imager with an imager based on a KDP filter because currently the latter is the best available material for the UV, and we found the performance of the TeO2 imager in the range 355-480 nm to be superior to that of a KDP imager. We present our experiments and the results obtained.


Novel sites of expression of functional angiotensin II receptors in the late gestation fetus.
In the adult, the peptide hormone angiotensin II (AII) is primarily known as a regulator of circulatory homeostasis, but recent evidence also suggests a role in cell growth. This study of AII in late gestation rat fetuses revealed the unexpected presence of receptors in skeletal muscle and connective tissue, in addition to those in recognized adult target tissues. The AII receptors in this novel location decreased by 80 percent 1 day after birth and were almost undetectable in the adult. Studies in fetal skin fibroblasts showed that the receptors were coupled to phospholipid breakdown, with concomitant increases in inositol phosphate and cytosolic calcium. The abundance, timing of expression, and unique localization of functional AII receptors in the fetus suggest a role for AII in fetal development.


Nutritional problems in end-stage liver disease: contribution of impaired gastric emptying and ascites.
To evaluate gastric emptying before and after paracentesis in patients with cirrhosis. Patients with ascites often report early satiety. The effect of paracentesis on gastric emptying has not been studied previously. Twelve patients who required therapeutic paracentesis were studied (mean age, 57 years; range, 47-69 years). Gastric emptying was performed with radionuclide scintigraphy. Satiety was evaluated with a visual analogue scale. Wilcoxon signed-rank tests were used for comparison between pre-and poststudies. The causes of cirrhosis included alcohol (seven patients), a combination of alcohol and hepatitis C (two), chronic hepatitis C only (one), primary biliary cirrhosis (one), and cryptogenic (one). The median volume of ascitic fluid removed at paracentesis was 5,450 mL (range, 2,500-7,200 mL). Median 2-hour gastric emptying was 65.5% before paracentesis and 61.5% after ( p > 0.05). Median 4-hour gastric emptying was 92.5% before paracentesis and 96.5% after ( p > 0.05). Both satiety score and caloric intake were significantly improved after paracentesis ( p < 0.05). Although satiety and calorie intake improve after large-volume paracentesis in patients with cirrhosis, these changes do not seem to correspond with improved gastric emptying. Therefore, other mechanisms most likely contribute to satiety.


Multicentric reticulohistiocytosis: assessment of pulmonary disease by gallium-67 scintigraphy.
We present a case of multicentric reticulohistiocytosis with pulmonary involvement. Scintigraphic evaluation with gallium-67 citrate demonstrated bilateral hilar uptake on 2 occasions. Possible mechanisms for gallium avidity are discussed. Gallium scintigraphy has a potential role for assessing systemic involvement in this disease.


No impact of an extensive social intervention program on return to work and quality of life after acute cardiac event: a cluster-randomized trial in patients with negative occupational prognosis.
To examine the effectiveness of extensive social therapy intervention during inpatient multi-component cardiac rehabilitation (CR) on return to work and quality of life in patients with low probability of work resumption after an acute cardiac event. Patients after acute cardiac event with negative subjective expectations about return to work or unemployment (n = 354) were included and randomized in clusters of 3-6 study participants. Clusters were randomized for social counseling and therapy led by a social worker, six sessions of 60 min each in 3 weeks, or control group (usual care: individual counseling meeting by request). The return to work (RTW) status and change in quality of life (QoL, short form 12: Physical and Mental Component Summary PCS and MCS) 12 months after discharge from inpatient CR were outcome measures. The regression model for RTW showed no impact of the intervention (OR 1.1, 95% CI 0.6-2.1, P = 0.79; n = 263). Predictors were unemployment prior to CR as well as higher anxiety values at discharge from CR. Likewise, QoL was not improved by social therapy (linear mixed model: ΔPCS 0.3, 95% CI - 1.9 to 2.5; P = 0.77; n = 177; ΔMCS 0.7, 95% CI - 1.9 to 3.3; P = 0.58; n = 215). In comparison to usual care, an intensive program of social support for patients during inpatient cardiac rehabilitation after an acute cardiac event had no additional impact on either the rate of resuming work or quality of life.


Hemodynamic properties and arterial structure in male rat offspring with fetal hypothyroidism.
Thyroid hormones (THs) play a crucial role in the development of different systems during fetal life; fetal hypothyroidism (FH) is associated with reduced cardiac function and dimensions in neonates. The aim of this study is to determine whether TH deficiency during fetal life is associated with arterial structural and hemodynamic changes during adulthood. Hypothyroidism was induced by adding 0.025% 6-propyl-2-thiouracil in drinking water throughout pregnancy, while controls consumed only tap water. Hemodynamic parameters, cross-sectional area, intima-media thickness (IMT), and density of nuclei of smooth muscle cells and endothelial cells (ECs) in the aorta and mesenteric arteries were measured. Compared to controls, in the FH group, baseline systolic blood pressure (105.7 ± 3.1 vs. 87.9 ± 3.3 mm Hg, p < 0.01), diastolic blood pressure (64.4 ± 1.7 vs. 53.2 ± 2.1 mm Hg, p < 0.05), and mean arterial pressure (80.9 ± 2.1 vs. 67.1 ± 2.1 mm Hg, p < 0.01) were significantly lower. In addition, in the FH group, intensity and latency of response to phenylephrine were significantly lower and longer, respectively, as were the IMT and density of ECs in the aorta and superior mesenteric arteries. In conclusion, this study showed that TH deficiency during fetal life can have long-lasting functional and histological effects, which can compromise cardiovascular function during adulthood.


To compare the efficacy and safety of nifedipine sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phenomenon in South Korea; Korean Raynaud study (KOARA study).
This study examined the efficacy and safety of nifedipine sustained release (nifedipine SR) compared with Ginkgo biloba extract as treatment for primary Raynaud's phenomenon (RP) in Korea. Primary RP were screened and assigned to either the nifedipine SR group (Group N) or the Ginkgo biloba extract group (Group G) in the ratio of 2:1. After a run-in period of 2 weeks, patients received treatment for 8 weeks. We observed the percent improvement of the RP attack rate between before and after the 8-week treatment. Ninety-three subjects were randomly assigned. The percent improvement in Group N was 50.1% at 8 weeks after treatment, while it was 31.0% in Group G (p = 0.03). No serious adverse events occurred, and almost adverse events were mild and improved without specific treatment. nifedipine SR was more effective than Ginkgo biloba extract for treatment of primary RP in Korean patients. Both drugs were tolerable with primary RP patients.


Predictive models for mortality and length of hospital stay in an Egyptian burns centre.
Our aim was to obtain a statistical profile of survivors and deaths among burn victims and to develop predictive models for mortality and length of hospital stay. All patients admitted to the Burns Unit of Alexandria Main University Hospital over a 1-year period were included. Of 533 cases, mean length of hospital stay was 15.5 +/- 21.6 days and the mortality rate was 33%. Total surface area burnt, inhalation burns, age, sex, depth and degree of burn wounds were the significant independent predictors of mortality in multiple logistic regression analysis. The significant independent predictors of the length of hospital stay were clothing ignition, total surface area burnt, sex, degree and depth of burn and inhalation burns.


Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users.
Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals. Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression. The incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and <100 cells/µL: RR, 7.4 [95% CI, 6.87-8.02]). The risk of IPD declined over time, although this was not the case for IDUs where the risk remained unchanged. The incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.


Utility of next-generation sequencing methods to identify the novel HLA alleles in potential stem cell donors from Chinese Marrow Donor Program.
The human leucocyte antigen (HLA) is the most polymorphic region of the human genome. Compared with Sanger-sequencing-based typing (SBT) methods, next-generation sequencing (NGS) has significantly higher throughput and depth sequencing characteristics, having dramatic impacts on HLA typing in clinical settings. Here, we performed NGS technology with Ion Torrent S5 platform to evaluate the potential four novel HLA alleles detected in five donors from Chinese Marrow Donor Program (CMDP, Shaanxi Province) during routine Sanger SBT testing. We also predicted the highest estimated relative frequency novel allele-bearing haplotypes according to their phenotypes and HaploStats database. NGS assays, as it provided the phase-defined and complete sequencing information, undoubtedly increase novel allele identification which will greatly enrich HLA database and provide more information for donor selection.


The impact of antipsychotics as a risk factor for thromboembolism.
Patients with schizophrenia are predisposed toward developing cardiovascular disease. Although neuroleptics affect the cardiovascular system, it is also important to consider the consequences of the disease itself such as lower physical activity due to living on disability pension, inadequate nutrition, and/or nicotine addiction, being more common among patients with schizophrenia versus the general population. All these factors combined lead to an increased risk of death caused by cardiovascular conditions in schizophrenic patients. Individuals receiving typical antipsychotic drugs have been reported to have elevated concentrations of antiphospholipid antibodies, including anticoagulants and anticardiolipin antibodies. The presence of both antibodies is associated with an increased risk for thromboembolism. It is also likely that mental illness is accompanied by increased procoagulant activity. Patients with acute psychosis have been shown to have a statistically significant increase in the concentrations of D-dimer, P-selectin, and in the expression of platelet glycoprotein IIb/IIIa receptors. Learning about causes and mechanisms of venous thromboembolism could help to reduce or neutralize the adverse effects of antipsychotic treatment and facilitate the identification of appropriate markers necessary to monitor changes and provide preventive care against hazardous and potentially fatal complications such as deep venous thrombosis and pulmonary embolism. Before atypical neuroleptic treatment is administered to hospitalized patients, all possible risk factors for thromboembolism should be considered to allow the application of lower risk drugs. Also, other preventive measures should be taken into account, including hydration, compression stockings, regular exercise of lower extremities, and low-molecular-weight heparin injections.


Carols in the wind.
To compare mood and emotional responses to music played on pipe organs and pipeless (digital) organs. A two-organ (pipe v. digital) crossover study. St Theodore's Anglican Church, Adelaide. 43 non-musician volunteers. Changes in mood and emotions measured by the Profile of Mood States. Both instruments produced significant reductions in the emotions commonly experienced during the Christmas season: tension-anxiety, depression-rejection, anger-hostility and fatigue. There were no significant changes for vigour or confusion-bewilderment, and no significant differences between the mood-altering effects of the two instruments. Pipeless organs are as effective as pipe organs in inducing beneficial mood changes.


Pneumocystis jiroveci pneumonia in patients receiving dasatinib treatment.
Dasatinib may cause various adverse effects such as myelosuppression and pleural effusion. It is well known that dasatinib may affect cellular immunity, which leads to the subsequent risk of a myriad of infections and viral reactivations, especially cytomegalovirus. Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection that typically occurs in immunocompromised hosts. Although pneumonia is not uncommon among dasatinib-treated patients, dasatinib-associated PJP has been reported only once in the literature, without a description of the clinical details. We report herein two cases of PJP in patients receiving treatment containing dasatinib. One patient developed PJP at 7 months following dasatinib in combination with chemotherapy for the treatment of acute lymphoblastic leukemia. The other patient developed pleural effusion and PJP at 2 years following dasatinib treatment for chronic myeloid leukemia. Both patients recovered well after management with sulfamethoxazole/trimethoprim. Our experience illustrates that PJP is a potentially important complication of dasatinib-based treatment. Raising clinical awareness is important as prompt diagnosis and timely management are the cornerstones of successful treatment.


Erotic transference and a threatened sense of self.
In this study of erotic transference the phenomenon is defined in the manner of Freud (1915) and Blum (1973). It involves a circumscribed behaviour which consists of an erotic preoccupation with the therapist which often has the quality of an obsession. It is prolonged, usually for months or years, is relatively immutable, and can be seen as a milder variant of de Clerembault's syndrome. It is suggested that the psychic purpose of the preoccupation is to maintain a threatened sense of self. The erotic content of the preoccupation is likely to be a consequence of the sexualization of the early relationship with caregivers, which was impingeing and disruptive of self-development. In an illustrative case, the disturbance of this development was considered to include an impediment to the development of the transitional field, the mother herself replacing the transitional object.


E-cadherin and alpha-catenin expression in normal, hyperplastic and neoplastic endometrium.
The aim of this study was to determine whether modulation of expression of cell adhesion molecules may occur in neoplastic transformation of endometrial epithelium. E-Cadherin and α-catenin protein expression were evaluated by immunohistochemistry in 124 biopsies representative of normal, hyperplastic and neoplastic endometrium. In normal endometrium (proliferative, secretive and atrophic endometrium) strong homogeneous, E-cadherin and α-catenin reactivity was found; 58.3% and 66.6% of biopsies representative of simple hyperplastic endometrium were homogeneously positive for E-cadherin and α-catenin, respectively, whereas no samples representative of atypical hyperplasia showed evidence of homogeneous E-cadherin or α-catenin expression. No expression of homogeneous E-cadherin was seen in endometrial adenocarcinomas; α-catenin homogeneous immunostaining was observed in 2 G1 and 2 G2 out of 22 adenocarcinoma samples (18.2%). A homogeneous co-expression of both molecules was seen only in normal (70%) and simple hyperplastic (46%) endometrium. These results suggest that E-cadherin and α-catenin down-regulation might be associated with neoplastic transformation of endometrial tissues.


Different characteristics in chick embryos of two broiler lines differing in susceptibility to ascites.
1. The relationship between the length of incubation, hatching, hypoxic condition, thyroid hormones and the occurrence of ascites were studied in embryos of 2 broiler lines differing in susceptibility to the ascites syndrome. 2. Both the time of external pipping (ep) and hatching of embryos from the ascites-resistant (AR) broiler line was earlier compared to the ascites-sensitive line (AS). The interval between internal pipping (ip) and ep was the same between the lines, but the interval between ep and hatching was shorter in the resistant line. 3. The T3 and T4 concentrations in plasma of the AS line were lower compared to the AR line. 4. Analyses of partial pressures of oxygen (pO2) and carbon dioxide (pCO2) in the air cell of the egg revealed that at day 18 the AS embryos had lower pO2 and higher pCO2 concentrations compared to the AR embryos. 5. The delay in hatching of the AS embryos might induce a more pronounced and/or extended hypoxic environment, thereby creating an environment that evokes ascites.


The effects of ambient solar UV radiation on alkaloid production by Erythroxylum novogranatense var. novogranatense.
Truxillines are alkaloids produced by Erythroxylum species and are thought to be derived from the UV-driven dimerization of cinnamoylcocaines. This study was conducted to determine the effects of ambient UV radiation on the production of truxillines in Erythroxylum novogranatense var. novogranatense. Field plants were grown under shelters covered with plastic filters that were transparent to UV radiation, filtered UV-B, or both filtered UV-B and UV-A radiation. The treatments had no significant effect on plant biomass or specific leaf weight. Absorption values in the UV-C and UV-A region of acidified-methanol leaf extracts were higher for plants exposed to UV radiation compared to the no UV radiation treatment. There was a trend in decreasing levels of trans-cinnamoylcocaine and a statistically significant decrease in levels of cis-cinnamoylcocaine in the leaves of plants exposed to UV radiation compared to the no UV radiation treatment. Truxilline levels increased in leaves from plants exposed to UV radiation compared to the no UV radiation treatment. Most significantly, the ratio of truxillines to total cinnamoylcocaines in the leaves was affected by UV, increasing with increased UV exposure. The results support the hypothesis that UV radiation is involved in the formation of truxillines from cinnamoylcocaines.