Blood stem cell mobilization and collection in patients with chronic lymphocytic leukaemia: a nationwide analysis.
Some reports suggest that blood stem cell mobilization is difficult in a proportion of patients with CLL. We evaluated this issue in a large cohort of CLL patients. One hundred and twenty-eight patients with CLL underwent blood stem cell mobilization during 1995-2005 in Finland. Ninety-five percent of the patients had received fludarabine. The most common mobilization regimen was intermediate-dose CY plus G-CSF (90 patients, 70%). At least 2 x 10(6)/kg CD34+ cells were collected after the first mobilization attempt in 83 patients (65%), whereas 45 patients (35%) failed to reach this collection target. No differences were observed between these patient groups with regard to age, time from the diagnosis to mobilization, number of previous treatment lines, number of fludarabine courses, time from the last fludarabine-containing chemotherapy to mobilization, disease status or degree of marrow infiltration. Patients who failed collection had platelets <100 x 10(9)/l more commonly at the time of mobilization (30 vs 4%, P<0.001). A significant proportion of patients with CLL were difficult to mobilize. Adequate marrow function including platelet counts >100 x 10(9)/l seem to be important factors in terms of successful blood stem cell collection.


From Pathogenesis to Novel Therapeutics for Spinocerebellar Ataxia Type 3: Evading Potholes on the Way to Translation.
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a neurodegenerative disorder caused by a polyglutamine expansion in the ATXN3 gene. In spite of the identification of a clear monogenic cause 25 years ago, the pathological process still puzzles researchers, impairing prospects for an effective therapy. Here, we propose the disruption of protein homeostasis as the hub of SCA3 pathogenesis, being the molecular mechanisms and cellular pathways that are deregulated in SCA3 downstream consequences of the misfolding and aggregation of ATXN3. Moreover, we attempt to provide a realistic perspective on how the translational/clinical research in SCA3 should evolve. This was based on molecular findings, clinical and epidemiological characteristics, studies of proposed treatments in other conditions, and how that information is essential for their (re-)application in SCA3. This review thus aims i) to critically evaluate the current state of research on SCA3, from fundamental to translational and clinical perspectives; ii) to bring up the current key questions that remain unanswered in this disorder; and iii) to provide a frame on how those answers should be pursued.


MMP-10 Regulates Collagenolytic Activity of Alternatively Activated Resident Macrophages.
Matrix metalloproteinase-10 (MMP-10) is expressed by macrophages and epithelium in response to injury, but its functions in wound repair are unknown. We observed increased collagen deposition and skin stiffness in Mmp10(-/-) wounds, with no difference in collagen expression or reepithelialization. Increased collagen deposition in Mmp10(-/-) wounds was accompanied by less collagenolytic activity and reduced expression of specific metallocollagenases, particularly MMP-8 and MMP-13, where MMP-13 was the key collagenase. Ablation and adoptive transfer approaches and cell-based models demonstrated that the MMP-10-dependent collagenolytic activity was a product of alternatively activated (M2) resident macrophages. These data demonstrate a critical role for macrophage MMP-10 in controlling the tissue remodeling activity of macrophages and moderating scar formation during wound repair.


Heterogeneity in anticatalytic activity of antibody specific for horseradish peroxidase.
Rabbit antibodies specific for horseradish peroxidase are heterogeneous in their ability to inhibit enzyme activity. Heterogeneity was demonstrated by fractionation of the total antiperoxidase pool by differential ammonium sulfate precipitation and differential elution of antibody from enzyme affinity columns. Both fractionation methods yielded antibody subpopulations that differed in anticatalytic activity. Some antibody subpopulations decreased enzyme activity almost completely at low molar ratios of antibody to peroxidase. Other subpopulations were not effective inhibitors even at great molar excess. Admixture experiments demonstrated that inefficient antibody pools decreased the anticatalytic effect of highly inhibitory antibody. The degree of inhibition observed with unfractionated antiserum is a reflection of the interaction of various antibody subpopulations with the enzyme. No correlation was found between the immunoglobulin class of antiperoxidase and anticatalytic efficiency in analyses of numerous antisera. The determinant specificity of an antiperoxidase molecule determines its anticatalytic ability. A peptide fragment (mol. wt 22,500) of peroxidase prepared by partial tryptic digestion bount 60 to 70% of the total antiperoxidase in a number of antisera. However, the peptide did not bind inhibitory antibodies.


A simplified assay for the quantification of circulating activated protein C.
Available assays for circulating levels of activated protein C (APC) are either time-consuming or difficult to use in a routine laboratory, or have a detection limit above normal levels. We have developed a simplified assay that measures both the in vivo free APC and the in vivo APC complexed to PC inhibitor (PCI). We measured APC levels, with both assays, in 339 plasma samples, 165 from patients with venous thromboembolism (VTE) and 174 from healthy individuals. The mean APC level in the 339 samples was 0.038±0.010 nM, using a previous assay that measures only the in vivo APC level, and 0.041±0.010 nM with the present new assay. The coefficient of correlation between assays was r=0.954 (P<0.001). The mean APC level in VTE patients was 0.034±0.009 nM (previous assay) and 0.037±0.009 nM (new assay), significantly lower than those in controls (P<0.001). In both groups there was a significant correlation between the levels obtained by the two assays (P<0.001). These results show that both assays are equivalent, and confirm that the APC level is lower in VTE patients than in healthy individuals. Therefore, the new simplified assay, which measures the sum of circulating free APC and APC complexed to PCI, may be used to estimate the level of circulating APC, and will allow its use in routine laboratories.


Exploring increased hydraulic retention time as a cost-efficient way of valorizing residual biogas potential.
Effective substrate utilization with low residual methane yield in the digestate is crucial for the economy and sustainability of biogas plants. The composition and residual methane potential of 29 digestate samples from plants operating at hydraulic retention times of 13-130 days were determined to evaluate the economic viability of extended digestion. Considerable contents of fermentable fractions, such as cellulose (8-23%), hemicellulose (1-18%), and protein (13-22%), were present in the digestate dry matter. The ultimate residual methane yields varied between 55 and 236 ml/g of volatile solids and correlated negatively with the logarithm of the hydraulic retention time (r = -0.64, p < 0.05). Economic analysis showed that extending the retention time in 20 days would be viable for 18 systems if methane were sold for 1.00 €/m3, with gains up to 40 €/year/m3 of newly installed reactor capacity. The results show the importance of operating at sufficient hydraulic retention time.


Thermodynamic, structural, and nanomechanical properties of a fluorous biphasic material.
The dynamics of the amphiphilic semifluorinated F(CF2)12(CH2)12H (F12H12) alkane that undergoes two condensed phase transitions have been investigated by Brillouin light spectroscopy, shear rheometry, small- (SAXS) and wide-angle (WAXS) X-ray scattering, and thermodynamic PVT measurements. The solid (I)-solid (II) transition (Ts) is marked by a stronger temperature dependence of the sound velocity in phase II and by a 2 orders of magnitude drop of the shear modulus. Between the Ts and the melting transition (Tm), the presence of two phonons implies a coexistence of solid (II) and amorphous (liquid) regions in the submicrometer range at thermal equilibrium as revealed by the SAXS pattern of a single reflection superimposed on a very broad amorphous halo. This intriguing finding of a transient, very slow (over 10 h) solid/liquid coexistence within phase II is rationalized by a two-stage mechanism for melting of the smectic phase (II) of F12H12. A refinement of the known packing motifs for the two solid-state structures is proposed.


Thyroid dysfunction in the offspring of mothers with autoimmune thyroid diseases.
An integrated three-compartment thyroid model exists during gestation: pregnancy influences thyroid function in several ways, the placenta plays an active role in TRH-thyroid and iodide transport and metabolism, and the fetus develops its own hypothalamic-pituitary-thyroid axis. This commentary reviews some basic and new data, especially in the maternal-offspring relationship in the case of maternal autoimmune thyroid diseases. The careful control of maternal autoimmune thyroid disease is essential in order to avoid pathological changes in the offspring.


Investigating the internal system of defense of Gastropoda Aplysia depilans (Gmelin, 1791): Focus on hemocytes.
The internal defense system of mollusks represents an efficient protection against pathogens and parasites, involving several biological immune processes, such as phagocytosis, encapsulation, cytotoxicity, and antigenic recognition of self/non-self. Mollusks possess professional, migratory, and circulating cells that play a key role in the defense of the organism, the hemocytes. Several studies have been performed on hemocytes from different mollusks, but, to date, these cells are still scarcely explored. Different hemocyte populations have been found, according to the presence or absence of granules, size, and the species of mollusks studied. Our study aims to deepen the knowledge of the hemocytes of the gastropod Aplysia depilans using morphological techniques and light and confocal microscopy, testing Toll-like receptor 2, inducible nitric oxide synthetase, and nicotinic acetylcholine receptor alpha 7 subunit. Our results show two hemocyte populations distinguishable by size, and presence/absence of granules in the cytoplasm, strongly positive for the antibodies tested, suggesting for the first time the presence of these receptors on the surface of sea hare hemocytes by immunohistochemistry. These data help in the understanding of the immune system of this gastropod, providing additional data for comprehending the evolution of the defense response in metazoan phylogenesis.


[The extracellular matrix of optic nerve head in normal human adult].
To demonstrate the macromolecular components of extracellular matrix of lamina cribrosa from young human donors. Immunoperoxidase (ABC) staining method was used to investigate the distribution of collagen type IV, laminin and fibronectin in the lamina cribrosa of 7 pairs of normal human eyes. There was a large amount of collagen type IV and laminin in the cribrosa plates, but no positive staining of fibronectin in them. The positive staining of fibronectin only existed at the blood vessel region. The lamina cribrosa contains a specialized extracellular matrix of the central nerve system made up of plates of material resembling basement membrane.


Short-term morbidity and mortality of implantation of automatic implantable cardioverter-defibrillator.
Over the 3-year period from Jan. 1, 1986, through Dec. 31, 1988, we have implanted 101 automatic implantable cardioverter-defibrillators into patients with life-threatening ventricular arrhythmias. There were 82 male patients and 19 female patients. The mean age was 58 years with a range of 25 to 82 years. The indication for implantation was ventricular fibrillation in 89 patients and recurrent ventricular tachycardia in 12 patients. Seventy-seven patients had a history of prior myocardial infarction or coronary artery disease, or both. Eighteen patients had nonischemic cardiomyopathy. One patient had a prolonged QT syndrome and five patients had no evidence of preexisting structural heart disease. The mean injection fraction was 37% +/- 17%. Forty-one of the automatic implantable cardioverter-defibrillator implantations were associated with procedures necessitating cardiopulmonary bypass. The hospital mortality rate was 4% and the morbidity rate was 15%. The only statistical difference between those patients who did and did not have postoperative complications was a history of a prior myocardial infarction (90% versus 54%, p less than 0.05). Twenty percent of patients had new-onset postoperative atrial fibrillation after implantation of the device. Eleven percent of patients had sustained ventricular tachycardia postoperatively. Although there was a trend toward a higher complication/death rate in the patients whose automatic implantable cardioverter-defibrillator was inserted in association with cardiopulmonary bypass (24% versus 15%) and the occurrence of new-onset postoperative atrial fibrillation (27% versus 15%), these findings were not statistically significant. Automatic implantable cardioverter-defibrillator implantation with and without concomitant cardiopulmonary bypass is associated with a clinically important morbidity and mortality rate and development of postoperative arrhythmias.


Frequently missed diagnosis in geriatric psychiatry.
Older adults are an important segment of the population that has specific health care needs. Their unique biopsychosocial characteristics impact the presentation, evaluation, and management of psychiatric illnesses. This article describes how common psychiatric disorders present in an aging population. Research in this area is relatively new and much more information is still needed. Close attention should be paid to new knowledge as it emerges about this growing population.


[Polyketone Reaction in Biosynthetic Pathways of 2, 3, 5, 4'-Tetrahydroxy Stilhene-2-O-β-D-glucoside in Polygonum multiflorum by Biocatalysis].
2, 3, 5, 4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (THSG), the active ingredient of Polygonum multiflorum, its polyketone reaction in the biosynthesis pathways was studied by biocatalysis method. The substrates 4-coumaroyl-CoA and malonyl-CoA were catalyzed in vitro by the crude enzyme extracted from Polygonum multiflorum callus, then the products were verified by HPLC and LC-MS methods. And the crude enzyme was analyzed by ammonium sulfate precipitation method and SDS-PAGE. HPLC chromatogram showed the same retention time of both the product and resveratrol standards; LC-MS spectra showed that the m/z of product was 227, which was consistent with resveratrol standards under the mode of negative ion; Ammonium sulfate (AS) precipitation method showed AS of 40% - 70% had catalytic activity,and 50% - 60% was the optimum; SDS-PAGE showed protein bands were obviously different among different AS concentration between 20% - 80%, the protein band of 42 kDa was found in AS of 50% - 60%, which had the same molecular weight with stilbene synthase. The product of polyketone reaction in the biosynthesis of THSG is resveratrol rather than THSG, so it is speculated that THSG is the conversion product of resveratrol instead of the direct product of the polyketone reaction.


Discrepancy between in-vitro and in-vivo inductions of differentiation by retinoids of human acute promyelocytic leukemia cells in relapse.
In-vitro studies of leukemic cells with retinoic acid and a therapeutic clinical trial with its derivative, etretinate, in a 58 yr-old male patient with 15;17 translocation-positive acute promyelocytic leukemia (APL) in relapse are reported. Actinomycin D was used in combination. Bone marrow promyelocytes from the patient prior to etretinate and actinomycin D matured morphologically in the liquid culture with retinoic acid; 98% were matured myeloid cells after 6 days at a concentration of 10(-6) M of retinoic acid as compared with 2% in the control culture. Positive NBT reactions were seen in none of the cells in the latter but in 95% of the cells in the former. Actinomycin D, when added alone, only induced NBT positivity, but, when used in combination with retinoic acid, increased both NBT positivity and morphologically matured cells. The patient was treated daily with 2 micrograms/kg of actinomycin D (or 20 mg/m2 or 33 mg/m2 cytosine arabinoside after the 6th day) in 24-h infusions and per oral 90 mg/body of etretinate. No effectiveness was observed both morphologically and clinically. The patient expired 15 days after the initiation of etretinate. Thus, a discrepancy existed in the response of leukemic cells from this relapsed patient with APL to the in-vitro and in-vivo attempts to include differentiation by retinoids and actinomycin D.


Protective effects of melatonin in zymosan-activated plasma-induced paw inflammation.
The aim of the present study was to investigate the protective effect of the pineal hormone melatonin in a model of acute local inflammation (zymosan-activated plasma-induced paw oedema), in which oxyradicals, nitric oxide (NO) and peroxynitrite are known to play a crucial role in the inflammatory process. The intraplantar injection of zymosan-activated plasma elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration and increased levels of nitrite/nitrate in the paw exudate. The maximal increase in paw volume was observed at 3 h after administration (maximal in paw volume: 1.34 +/- 0.09 ml). At this time point, myeloperoxidase activity and lipid peroxidation were markedly increased in the zymosan-activated plasma-treated paw (226 +/- 10.2 mU/100 mg wet tissue, 31 +/- 2.1 mM/mg wet tissue, respectively). However, zymosan-activated plasma-induced paw oedema was significantly reduced in a dose-dependent manner by treatment with melatonin (given at 62.5 and 125 microg/paw) at 1, 2, 3, 4 h after injection of zymosan-activated plasma. Melatonin treatment also caused a significant reduction of the myeloperoxidase activity and lipid peroxidation and inhibited nitrite/nitrate levels in the paw exudate. The paw tissues were also examined immunohistochemically for the presence of nitrotyrosine (a marker of peroxynitrite formation). At 3 h following injection of zymosan-activated plasma, staining for nitrotyrosine was also found to be localised in the inflamed paw tissue. Treatment with melatonin (125 microg/paw) reduced the appearance of nitrotyrosine in the tissues. Our findings support the view that melatonin exerts anti-inflammatory effects.


Skeletal Class III correction in permanent dentition using reverse twin block appliance and fixed mechanotherapy.
The orthodontic management of patients with Class III malocclusion poses numerous prognostic and treatment challenges to the clinician. Various removable, orthopaedic, myofunctional and fixed appliances have been recommended for the correction of Class III malocclusion. The Reverse Twin Block (RTB) is a simple and well tolerated appliance which has often been used for the early management of such cases in mixed dentition. Cases reporting use of RTB in permanent dentition are however, limited. This article presents an insight into the encouraging results of reverse twin block (RTB) appliance used in conjunction with fixed mechanotherapy for the successful treatment of a 12-year-old patient presenting with skeletal Class III malocclusion and a concave facial profile. The RTB appliance helped establish a favourable environment for unrestricted maxillary growth, at the same time redirecting the mandibular growth to a clockwise direction and correcting the incisal relationship. The favourable treatment outcome and long-term stability achieved substantiates the feasibility of RTB appliance in mild to moderate skeletal Class III malocclusions in permanent dentition cases.


Expression of the envelope antigen of dengue virus in vaccine strains of Salmonella.
The envelope gene of dengue 4 virus (DEN) was cloned in a plasmid under the control of Escherichia coli expression signals. A clone that expressed 93% of the gene was found to be detrimental to the bacterial host. Another clone which carried only 76% of the E gene was found to be quite stable in vitro as well as in vivo. The killed recombinant bacteria induced antibodies in mice which recognized native DEN virus. Attenuated Salmonella typhimurium (SAL) strains carrying the DEN-E plasmid were tested for their efficacy as orally administered live vaccines. Protective immunization was assessed in a mouse model by immunizing three-week old BALB/c mice followed by challenge with DEN virus. It was found that these young mice were highly susceptible to the carrier SAL strains (M206 and aroA SL3261). Moreover, the SAL-infected mice were more susceptible to DEN virus challenge than control mice, suggesting that the SAL infection caused immunosuppression in these young mice.


Physical versus pharmacological counter-measures. Studies on febrile rabbits.
128 experiments were carried out on febrile rabbits at air temperatures of 8, 18, 24 and 30 degrees C in order to analyze the thermoregulatory effects and mechanisms of physical and/or pharmacological counter-measures. Fever was achieved by injection of 0.1 micrograms Salmonella typhi endotoxin (LPS)/kg into an ear vein. As the pharmacological counter-measure, injections of acetylsalicylic acid (ASA) into an ear vein were chosen. For the physical counter-measure, cooling thermodes (5 degrees C) were constructed for the abdominal skin, for the ear and for the rectum. ASA injections had no effect on the first fever maximum, even if applied 20 to 60 min before the LPS injection, but eliminated the second fever maximum. Of course, the additional hyperthermia observed at 30 degrees C ambient temperature could not be eliminated by the injections. On the other hand, cooling procedures can obviously not affect the pyrogen-induced temperature increase, but reduce the hyperthermic effect of a higher ambient temperature. Rectal cooling was more effective than ear or abdominal skin cooling. Abdominal cooling evoked an increase in metabolic heat production. Application of combined physical and pharmacological counter-measures achieved the strongest and quickest reduction of the second maximum, whereas the first maximum was not affected, as in all other experiments. The study emphasizes the necessity of taking into account the time course of the effector mechanisms in order to discriminate between hyperthermic and febrile components of temperature increase. In the initial phase cooling measures would evoke unwanted regulatory responses of the effectors, whereas during the second febrile maximum they would achieve a quicker reduction of core temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)


Stimulation of α2-adrenergic receptors in the central nucleus of the amygdala attenuates stress-induced reinstatement of nicotine seeking in rats.
Tobacco addiction is a chronic disorder that is characterized by craving for tobacco products, withdrawal upon smoking cessation, and relapse after periods of abstinence. Previous studies demonstrated that systemic administration of α2-adrenergic receptor agonists attenuates stress-induced reinstatement of drug seeking in rats. The aim of the present experiments was to investigate the role of noradrenergic transmission in the central nucleus of amygdala (CeA) in stress-induced reinstatement of nicotine seeking. Rats self-administered nicotine for 14-16 days and then nicotine seeking was extinguished by substituting saline for nicotine. The effect of the intra-CeA infusion of the α2-adrenergic receptor agonists clonidine and dexmedetomidine, the nonselective β1/β2-adrenergic receptor antagonist propranolol, and the α1-adrenergic receptor antagonist prazosin on stress-induced reinstatement of nicotine seeking was investigated. In all the experiments, exposure to footshocks reinstated extinguished nicotine seeking. The administration of clonidine or dexmedetomidine into the CeA attenuated stress-induced reinstatement of nicotine seeking. The administration of propranolol or prazosin into the CeA did not affect stress-induced reinstatement of nicotine seeking. Furthermore, intra-CeA administration of clonidine or dexmedetomidine did not affect operant responding for food pellets. This suggests that the effects of clonidine and dexmedetomidine on stress-induced reinstatement of nicotine seeking were not mediated by motor impairments or sedation. Taken together, these findings indicate that stimulation of α2-adrenergic receptors, but not blockade of α1 or β-adrenergic receptors, in the CeA attenuates stress-induced reinstatement of nicotine seeking. These findings suggest that α2-adrenergic receptor agonists may at least partly attenuate stress-induced reinstatement of nicotine seeking by stimulating α2-adrenergic receptors in the CeA.


Reliability of a urine dipstick in emergency department patients.
We conducted a study to examine whether a negative Chemstrip 9 result for leukocyte esterase and nitrite would reliably exclude an abnormal microscopic examination of the urine of emergency department patients. Three hundred urine specimens were subjected to Chemstrip 9 evaluations and full microscopic examinations in the microscopy laboratory. As the microscopy laboratory examination identified lower WBC and bacteria counts, increasing numbers of false-negative urine dipsticks results occurred. The results of our study reveal that the nitrite and leukocyte esterase assays miss significant microscopic findings with corresponding clinical pathology, with the nitrite examination being the less sensitive of the two tests. Based on our results, we believe it would not be prudent to use the Chemstrip 9 dipstick in the ED to exclude the presence of WBC and bacteria in the urine.


[A clinical investigation on the surgical approach and fixation in operative treatment zygomatic fractures].
To investigate the effect of soft tissue incision and rigid internal fixation in the treatment of zygomatic fracture. 70 cases with zygomatic fracture were entered into the study. The clinical data of 65 patients who were performed operations in the treatment were analyzed. The study focused on the incision, number and locations of Titanium plate. The facial contour, reduction,fixation, healing of incision, facial bisymmetry and complications of the operation were followed up 3 - 24 months after surgery. All the incisions were primary healing. Clinical and radiologic assessment of reduction was symmetric and stable in 91.5% of all cases, asymmetric in 8.5% of all cases. Subcutaneous hematoma happened in 5 cases, Ti plate exposure 1 in case, scalp scar width was more than 0.5 cm in 6 cases, frontal part or scalp paresthesia 8 cases. Coronal scalp incision has advantages such as good exposure, precise removal of the bone block and good symmetry of both sides. RIF can improve the stability of fracture, promotes fracture healing and guarantees the rehabilitation of zygomatic complex. direct reduction and rigid internal fixation with Titanium microplate or miniplate are satisfactory in zygomatic fracture.


Increased sensitivity of SPR assays in plasma through efficient parallel assay optimization.
The sensitivity of biosensor assays in complex media such as plasma or serum is often limited by non-specific binding. The degree of binding often varies between individuals and therefore a large number of different plasma samples have to be used during assay development. Some surface plasmon resonance (SPR) biosensors allow for parallel screening of several running buffer compositions, with a number of different immobilization levels for each buffer. These technical possibilities combined with statistical design of experiments (DoE) enable efficient parallel optimization of multiple assay conditions. In this paper we outline how to increase the sensitivity in SPR-based assays by minimizing background binding and variability from negative control plasma while retaining high signals from positive samples. To mimic immunogenicity studies of biotherapeutics we have used a model assay with anti-rituximab as an anti-drug antibody to be detected in plasma by binding to immobilized rituximab. Immobilization level and sodium chloride concentration were found to be the most important factors to optimize. There were also a number of significant interaction effects and strong non-linearites between the buffer composition/immobilization level and the assay performance, which necessitated DoE based optimization strategies. The applicability of the optimized conditions was verified with several assays (anti-erythropoietin, omalizumab, anti-IgE and anti-myoglobin) in spiked plasma samples resulting in detection levels in the range of 80-170 ng ml(-1). The buffer conditions presented in this paper can be used for other immunogenicity assays on biosensor platforms or as a good starting point for further assay development for new immunogenicity assays.


Difficulty of predicting the presence of lymph node metastases in patients with clinical early stage gastric cancer: a case control study.
The relationship between pathological factors and lymph node metastasis of pathological stage early gastric cancer has been extensively investigated. By contrast, the relationship between preoperative factors and lymph node metastasis of clinical stage early gastric cancer has not been investigated. The present study was to investigate discrepancies between preoperative and postoperative values. From January 2011 to December 2013, 1042 patients with clinical stage early gastric cancer who underwent gastrectomy with lymphadenectomy were enrolled. Preoperative and postoperative values were collected for subsequent analysis. Receiver operating characteristics curves were computed using independent predictive factors. Several discrepancies were observed between preoperative and postoperative values, including existence of ulcer, gross type, and histology (all McNemar p-values were <0.001). Multivariate analyses identified the following independent predictive factors for lymph node metastasis: postoperative values including age (p = 0.002), tumor size (p < 0.001), and tumor depth (p < 0.001); preoperative values including age (p = 0.017), existence of ulcer (p = 0.037), tumor size (p = 0.009), and prediction of the presence of lymph node metastasis in computed tomography scans (p = 0.002). These postoperative and preoperative independent predictive factors produced areas under the receiver operating characteristics curves of 0.824 and 0.660, respectively. Surgeons need to be aware of limitations in preoperative predictions of the presence of lymph node metastasis for clinical stage early gastric cancer.


Upper airway infections in preschool children--frequency and risk factors.
To estimate the frequency of upper respiratory tract infections (URTI) over a three month period and possible risk factors in the social surroundings, daily routines and health history. A retrospective epidemiological survey by means of questionnaires. Gardabaer, a small town, ten km south of Reykjavík, Iceland. All children in Gardabaer, six months to six years old (n = 555). Number of URTI and possible risk factors. The response rate was 81.8%. The most common infections were common cold (n = 345), acute otitis media (n = 82), sore throat (n = 75), and bronchitis (n = 13). The mean frequency of URTI during the previous three months was 2.2 in boys and 1.7 in girls (p < 0.01). Log-linear regression analysis showed that the predicted number of URTI was 1.9 higher if the child was attending day care, and that the number of URTI increased by 1.015 with each month until the age of 24 months, but decreased after that by 0.985. The major factors which affect the frequency of URTI are: age, sex, family history of frequent URTI, asthma, allergy, and the form of day care. Measures to reduce URTI could involve prospective intervention studies on the form of day care.


ABCD criteria to improve visual inspection with acetic acid (VIA) triage in HPV-positive women: a prospective study of diagnostic accuracy.
A simple system for visual inspection with acetic acid assessment, named ABCD criteria, has been developed to increase accuracy for triaging of high-risk human papillomavirus (HPV)-positive women. This study aimed to determine the accuracy of ABCD criteria for the detection of histologically confirmed cervical intraepithelial neoplasia grade two or worse (CIN2+) in HPV-positive women living in a low-resource setting. Prospective study of diagnostic accuracy. Cervical cancer screening programme based on a 3T-Approach (test, triage and treat) in the Health District of Dschang, West Cameroon. Asymptomatic non-pregnant women aged 30-49 years were eligible to participate. Exclusion criteria included history of CIN treatment, anogenital cancer or hysterectomy. A total of 1980 women were recruited (median age, 40 years; IQR 35-45 years), of whom 361 (18.4%) were HPV-positive and 340 (94.2%) completed the trial. HPV-positive women underwent a pelvic examination for visual assessment of the cervix according to ABCD criteria. The criteria comprised A for acetowhiteness, B for bleeding, C for colouring and D for diameter. The ABCD criteria results were codified as positive or negative and compared with histological analysis findings (reference standards). Diagnostic performance of ABCD criteria for CIN2+, defined as sensitivity, specificity, negative and positive predictive values. ABCD criteria had a sensitivity of 77.5% (95% CI 61.3% to 88.2%), specificity of 42.0% (95% CI 36.5% to 47.7%), positive predictive value of 15.1% (95% CI 10.8% to 20.8%), and negative predictive value of 93.3% (95% CI 87.6% to 96.5%) for detection of CIN2 +lesions. Most (86.7%) of the ABCD-positive women were treated on the same day. ABCD criteria can be used in the context of a single-visit approach and may be the preferred triage method for management of HPV-positive women in a low-income context. NCT03757299.


Evidence for a pathogenic role of BRCA1 L1705P and W1837X germ-line mutations.
BRCA1 L1705P (c.5114T>C) has been classified in the NCBI SNP database as the variant with uncertain significance and is absent in major BRCA1 databases. BRCA1 W1837X (c.5511G>A) results in a loss of only last 27 residues of BRCA1 protein, thus its pathogenic role still requires a confirmation. This report describes two breast cancer (BC) patients carrying BRCA1 L1705P and W1837X germ-line mutations, respectively. Significant evidence for BC-predisposing impact of the mentioned mutations have been obtained: (1) both index cases presented with the triple-negative receptor status of BC disease; (2) complete segregation with BRCA1-related cancers was observed in the families of these patients; (3) somatic loss of the remaining (wild-type) BRCA1 allele was detected in tumor tissues of the affected women. The results of this study have to be taken into account while providing genetic counseling to cancer patients and while considering the use of BRCA1-specific therapeutic compounds for BC treatment.


Zinc in the fetus and newborn.
The growing fetus and infant are at risk of becoming deficient of zinc, an adequate supply of which is essential for normal growth and development. Mild maternal zinc depletion was strongly associated with intrauterine growth retardation. Low levels of zinc in maternal plasma and poor placental perfusion reduced the materno-fetal transfer of zinc. Mean maternal dietary intake of zinc was 60% recommended daily allowance and mothers of small-for-gestational-age (SGA) babies consumed significantly less zinc than mothers of appropriate-for-gestational-age babies. In addition, iron/folate supplements, which are often routinely prescribed during pregnancy, despite dietary intakes of iron and folate being adequate, significantly decreased the oral bio-availability of zinc in pregnant women. Zinc supplementation may be beneficial to women at risk of delivering SGA babies. Zinc requirements and interactions are also important to consider when designing mineral supplements for preterm babies, infant formulae and food fortification in developing countries.


[Radiologic diagnosis of enterosalpingeal fistula complicating Crohn's disease].
Enterosalpingeal fistula is a rare complication of Crohn's disease which is rarely diagnosed preoperatively. We describe a new case of this complication suspected by CT scan and confirmed by hysterosalpingogram and contrast from the ileum. This case is about a 50-year-old woman suffering from ileal Crohn's disease diagnosed two years previously and actually complicated by stenosis and entero-salpingeal fistula. The treatment consisted on resection of the ileocaecal region with salpingectomy. Postoperative course was uneventful.


The treatment efficacy of pharmacotherapies for rapid eye movement sleep behavior disorder with polysomnography evaluation: A systematic review and meta-analysis.
Clonazepam and melatonin are commonly used as first-line medications for the treatment of rapid eye movement (REM) sleep behavior disorder (RBD), with other medications used in the clinic including pramipexole, ramelteon, and rotigotine. We performed a systematic review and meta-analysis of randomized and non-randomized controlled trials to assess the efficacy of these treatment options in RBD patients with polysomnography. We systematically retrieved results of randomized and non-randomized controlled trials using the PubMed, Embase, and Cochrane databases. Of the 454 studies identified, 13 were considered eligible for inclusion in the study. In comparison to baseline, clonazepam was found to significantly decrease the percentage of stage 2 sleep [4.00 (95% CI = 0.90 to 7.10)] in RBD patients. Melatonin was found to significantly improve patients' sleep efficiency [2.51(95% CI = 0.75 to 4.28)], significantly reduce the time spent in bed (TIB) [-11.71(95% CI = -23.05 to -0.37)], phasic activity[-25.79(95% CI = -42.13 to -9.46)] and tonic activity[-10.44(95% CI = -12.24 to -8.64)]. RWA[-5.87 (95% CI = -8.25 to -3.50)] significantly improve with the use of ramelteon. Pramipexole was found to significantly increase the total sleep time (TST) [27.17 (95% CI = 0.06 to 54.29)], and significantly reduce the periodic limb movements of sleep (PLMS) index [-11.42(95% CI = -21.38 to -1.47)]. We also found that pramipexole had different effects on idiopathic RBD (iRBD) and secondary RBD (sRBD). These results will help to guide the clinical use of medication in patients with RBD.


The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study.
Whether obesity is associated with a better prognosis in patients with type 2 diabetes mellitus is controversial. To investigate the association between body weight and prognosis in a large cohort of patients with type 2 diabetes followed for a prolonged period. Prospective cohort. National Health Service, England. Patients with diabetes. The relationship between body mass index (BMI) and prognosis in patients with type 2 diabetes without known cardiovascular disease at baseline was investigated. Information on all-cause mortality and cardiovascular morbidity (such as the acute coronary syndrome, cerebrovascular accidents, and heart failure) was collected. Cox regression survival analysis, corrected for potential modifiers, including cardiovascular risk factors and comorbid conditions (such as cancer, chronic kidney disease, and lung disease), was done. 10,568 patients were followed for a median of 10.6 years (interquartile range, 7.8 to 13.4). Median age was 63 years (interquartile range, 55 to 71), and 54% of patients were men. Overweight or obese patients (BMI >25 kg/m²) had a higher rate of cardiac events (such as the acute coronary syndrome and heart failure) than those of normal weight (BMI, 18.5 to 24.9 kg/m²). However, being overweight (BMI, 25 to 29.9 kg/m²) was associated with a lower mortality risk, whereas obese patients (BMI >30 kg/m²) had a mortality risk similar to that of normal-weight persons. Patients with low body weight had the worst prognosis. Data about cause of death were not available. In this cohort, patients with type 2 diabetes who were overweight or obese were more likely to be hospitalized for cardiovascular reasons. Being overweight was associated with a lower mortality risk, but being obese was not. National Institute for Health Research and University of Hull.


Binding of Cu2+ to Aβ1-29 causes aggregation and toxicity in SH-SY5Y cells.
The accumulation and aggregation of amyloid-β (Aβ) are critical factors in the pathogenesis of Alzheimer's disease (AD). Several studies have indicated that metal ions such as Cu2+and Zn2+ play a key role in the formation and stabilization of neurotoxic Aβ aggregates, however the molecular mechanisms underlying Aβ cytotoxicity have not yet been fully elucidated. Previously, we showed that the Aβ-derived fragment peptide (Aβ-FrP), Aβ1-19, altered conformation in the presence of Cu2+, inhibiting its digestion by metalloproteinase-7 (MMP-7). In this study we demonstrated that Aβ1-19 did not form aggregates in the presence of Cu2+. Therefore, we synthesized a new Aβ-FrP, Aβ1-29, which displayed Cu2+-dependent conformational conversion and aggregate formation. Aβ1-29 was cleaved by MMP-7, however this reaction was inhibited in the presence of Cu2+ in a similar way to Aβ1-19. Interestingly, Aβ1-29 showed conformational conversion and aggregate formation in the presence of Zn2+, however this did not confer resistance against MMP-7 cleavage. Moreover, Aβ1-29 induced the apoptotic cell death of neural SH-SY5Y cells in the presence of Cu2+ but not Zn2+. These results suggest that Cu2+, unlike Zn2+, may play an important role in the aggregation mechanism of Aβ and thus in the pathology of AD.


Development and characterization of a new potato starch/watermelon peel pectin composite film loaded with TiO2 nanoparticles and microencapsulated Lycium barbarum leaf flavonoids and its use in the Tan mutton packaging.
Reinforced edible film with active nanoparticles has been in increasing demand as a new technology to improve the quality and extend the shelf-life of muscle foods. The study aimed to fabricate and characterize a novel potato starch (Pst)/watermelon peel pectin (Wpp) composite film with the microencapsulated Lycium barbarum leaf flavonoids (MLF) and nano-TiO2 (Pst/Wpp/MLF/TiO2) and further apply the film in Tan mutton preservation. The moisture content, thickness and water vapor permeability (WVP) of the composite film were relatively increased with increasing the percentage of MLF, while nano-TiO2 had slight influence on the thickness, but leaded to a significantly decreased the moisture content and WVP. Also, the SEM images showed that the roughness and porosity were created on the film surface by adding MLF and nano-TiO2. FTIR revealed electrostatic and hydrogen bond interactions between the components in the film system. Meanwhile, MLF and nano-TiO2 effectively enhanced the mechanical strength, UV-barrier, controlled-release, thermal stability, antimicrobial and antioxidation properties of the Pst/Wpp film. Also, the composite film containing MLF and nano-TiO2 significantly inhibited the growth of microorganisms and chemical deterioration of mutton samples, which suggested that such film has potential as a prospective active packaging for preserving Tan mutton.


EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease.
Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-EphB4-RASA1 mutations, including those recently discovered in Vein of Galen malformation: the most common and severe brain arteriovenous malformation in neonates. We will also discuss emerging paradigms of the molecular and cellular pathophysiology of disease-causing ephrinB2-EphB4-RASA1 mutations, including the potential role of somatic mosaicism. These observations have potential diagnostic and therapeutic implications for patients with rare congenital cerebrovascular diseases and their families.


Insulin resistance as the underlying cause for the metabolic syndrome.
Classically, the metabolic syndrome is characterized as group of pathologies including visceral obesity, hypertension, dyslipidemia, and impaired glucose tolerance. It is now realized that insulin resistance plays a principal role in initiating and perpetuating the pathologic manifestations of the metabolic syndrome. A more in-depth understanding of the basic pathophysiologic mechanisms underlying insulin resistance may aid clinicians in treating and possibly delaying or even preventing the onset of the metabolic syndrome and its complications. This article outlines how abnormal insulin signaling and secretion, impaired glucose disposal, lipotoxicity, and proinflammatory cytokines exacerbate insulin resistance and result in the perturbations of the metabolic syndrome.


Growth enhancement of rice (Oryza sativa) by phosphate solubilizing Gluconacetobacter sp. (MTCC 8368) and Burkholderia sp. (MTCC 8369) under greenhouse conditions.
Two indigenous rhizospheric phosphate solubilizing isolates PSB 12 identified as Gluconacetobacter sp. (MTCC 8368) and PSB 73 identified as Burkholderia sp. (MTCC 8369) were examined for their growth enhancement potential of rice (Jyothi PTB 39) under pot culture assays. The results showed significant impact on microbial count and PSB population, phosphatase and dehydrogenase activity, available phosphorous in the soil, plant nutrient uptake and yield parameters. Gluconacetobacter sp. + RP60 treatment (30.96 µg PNP g-1 soil) retained highest phosphatase activity whereas Gluconacetobacter sp. + Burkholderia sp. + RP60 treatment recorded maximum dehydrogenase activity (38.88 µg TPF g-1 soil) after 60 days of treatment. The treatments Burkholderia sp. + RP60 and Gluconacetobacter sp. + RP60 produced comparable amount of P and these treatments were statistically at par throughout the growth period. Highest nutrient uptake and yield was noted in Gluconacetobacter sp. + Burkholderia sp. + RP60 treatment. A positive synergistic interaction between strains of Gluconacetobacter sp. and Burkholderia sp. has been noticed for their plant growth promotion activity. These strains could be of potential to develop as biofertilizers after testing their performance under field conditions either alone or as components of integrated nutrient management systems.


Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading.
Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor 1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/- ) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.


Erratum to "Bull fertility and semen quality are not correlated with dairy and production traits in Brown Swiss cattle" (JDS Commun. 3:120-125).
[This corrects the article DOI: 10.3168/jdsc.2021-0164.].


Evaluation of lignocellulosic wastes for production of edible mushrooms.
The degradation of lignocellulosic wastes such as paddy straw, sorghum stalk, and banana pseudostem was investigated during solid-state fermentation by edible mushrooms Pleurotus eous and Lentinus connotus. Biological efficiency of 55-65% was observed in paddy straw followed by sorghum stalk (45%) and banana pseudostem (33%) for both fungal species. The activity of extracellular enzymes, namely cellulase, polyphenol oxidase, and laccase, together with the content of cellulose, lignin, and phenols, was studied in spent substrates on seventh, 17th, and 27th days of spawning, and these values were used as indicators of the extent of lignocellulosic degradation by mushroom. Both the mushroom species proved to be efficient degraders of lignocellulosic biomass of paddy straw and sorghum stalk, and the extent of cellulose degradation was 63-72% of dry weight (d.w.), and lignin degradation was 23-30% of the d.w. In banana pseudostem, the extent of the degradation was observed to be only 15-22% of the d.w. for both lignin and cellulose. Preferential removal of cellulose during initial growth period and delayed degradation of lignin were observed in all three substrates. This is associated with decrease in activity of cellulase and polyphenol oxidase and increase in laccase activity with spawn aging in spent substrates. Thus, bioconversion of lignocellulosic biomass by P. eous and L. connotus offers a promising way to convert low-quality biomass into an improved human food.


Child-Directed Marketing, Health Claims, and Nutrients in Popular Beverages.
Fruit drinks are a major source of added sugar in children's diets. This study describes the associations between front-of-package child-directed marketing (i.e., sports, fantasy, or child-directed imagery; child-directed text) and (1) health-related claims and (2) nutrient content of fruit drinks, 100% juices, and flavored waters. Beverage purchase data from a national sample of 1,048 households with children aged 0-5 years were linked with front-of-package label and nutrition data to conduct a content analysis on fruit drinks (n=510), 100% juices (n=337), and noncarbonated flavored waters (n=40) in 2019-2020. Unstratified and stratified regression models assessed the differences in the prevalence of claims (macronutrient, micronutrient, natural/healthy, and fruit and juice), non-nutritive sweeteners, and nutrient content (calories, total sugar, and percent daily value of vitamin C) between drinks with and those without child-directed marketing in 2021. Fruit drinks with child-directed marketing were more likely to show front-of-package micronutrient claims (OR=2.1, 95% CI=1.5, 3.1) and contained more vitamin C (18.5% daily value, 95% CI=1.6, 35.5) than fruit drinks without child-directed marketing. 100% juices with child-directed marketing contained less vitamin C (-35.6% daily value, 95% CI= -57.5, -13.8) and 3.0 (95% CI= -5.5, -0.4) fewer grams of sugar than 100% juices without child-directed marketing. Flavored waters with child-directed marketing contained less vitamin C (-37.9% daily value, 95% CI= -68.1, -7.6) than flavored waters without child-directed marketing. The combination of child-directed marketing with health-related claims may mislead parents into believing that fruit drinks are healthy and appealing to their children, highlighting the need for government regulation of sugary drink marketing.


Prognostic value of changes in neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) for patients with cervical cancer undergoing definitive chemoradiotherapy (dCRT).
Peripheral NLR, PLR, and LMR have prognostic value in various malignancies as they are surrogates for inflammation. Recent studies have identified NLR, PLR, and LMR correlate with patient outcomes in cervical cancer patients however there remains uncertainty regarding the optimal time point for assessing these markers. We retrospectively reviewed cervical cancer patients underoing definitive chemoradiation therapy (dCRT). NLR, PLR, and LMR values were identified before, during, and after dCRT and both relative and absolute changes in these values were calculated and compared with patient outcmoes. Ninety-nine patients who met the includsion criteria were identified. NLR values before, during, and after dCRT correlated with progression free survival (PFS) and overall survival (OS). In addition, increasing NLR after treatment was associated with worse PFS and OS. LMR before and after treatment had a positive correlation with PFS however increasing LMR during dCRT was found to have a negative correlation with PFS and OS. NLR serves as a prognostic indicator irrespective of timing with response to dCRT. While higher LMR before treatment was a positive prognostic indicator, increasing LMR was found to negatively correlate with PFS and OS.


Risk factors for Alzheimer dementia in a community-based birth cohort at the age of 75 years.
Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25-3.48); (2) the epsilon 4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08-3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87-0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20-0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03-2.00). Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.


Editor's Choice - Timing of Carotid Intervention in Symptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis.
This review aimed to analyse the timing of carotid endarterectomy (CEA) and carotid artery stenting (CAS) after the index event as well as 30 day outcomes at varying time periods within 14 days of symptom onset. A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-analysis statement, comprising an online search of the Medline and Cochrane databases. Methodical quality assessment of the included studies was performed. Endpoints included procedural stroke and/or death stratified by delay from the index event and surgical technique (CEA/CAS). Seventy-one studies with 232 952 symptomatic patients were included. Overall, 34 retrospective analyses of prospective databases, nine prospective, three RCT, three case control, and 22 retrospective studies were included. Compared with CEA, CAS was associated with higher 30 day stroke (OR 0.70; 95% CI 0.58 - 0.85) and mortality rates (OR 0.41; 95% CI 0.31 - 0.53) when performed ≤ 2 days of symptom onset. Patients undergoing CEA/CAS were analysed in different time frames (≤ 2 vs. 3 - 14 and ≤ 7 vs. 8 - 14 days). Expedited CEA (vs. 3 - 14 days) presented a sampled 30 day stroke rate of 1.4%; 95% CI 0.9 - 1.8 vs. 1.8%; 95% CI 1.8 - 2.0, with no statistically significant difference. Expedited CAS (vs. 3 - 14 days) was associated with no difference in stroke rate but statistically significantly higher mortality rate (OR 2.76; 95% CI 1.39 - 5.50). At present, CEA is safer than transfemoral CAS within 2/7 days of symptom onset. Also, considering absolute rates, expedited CEA complies with the accepted thresholds in international guidelines. The ideal timing for performing CAS (when indicated against CEA) is not yet defined. Additional granular data and standard reporting of timing of intervention will facilitate future monitoring.


Effects of idebenone on lipid peroxidation and hemolysis in erythrocytes of stroke-prone spontaneously hypertensive rats.
Stroke-prone spontaneously hypertensive rats (SHRSP) were kept on a 1% NaCl solution as drinking water to shorten the onset-time of a stroke. The level of lipoperoxide (LPO) in the erythrocytes of SHRSP loaded with salt for 22 days was significantly higher than that of the controls. Idebenone treatment (30 mg/kg per day, p.o.) markedly decreased the LPO to the level of the controls. Hemolysis in SHRSP was accelerated by the salt-loading. Idebenone significantly inhibited the hemolysis in a dose-dependent manner. These results suggest that idebenone inhibits lipid peroxidation in erythrocytes and stabilizes the erythrocyte membrane.


The psychophysics of the pursuit oculomotor system.
When a fixation point moves under a row of identical targets at a speed of one target for each flash of a strobe, smooth apparent movement of the targets is seen (the "picket-fence illusion"). When the fixation point is removed, the eye continues to pursue the apparent target movement. Pursuit continues through small changes in target configuration, but is interrupted by a change to a very dissimilar target (such as 1 vs. x) in the middle of a row. This new method, the "pursuit-interruption method," showed that large differences in the number of pixels in a line did not interrupt tracking if the end points of the line were preserved. Pursuit interruption by changes in line orientation (such as /vs./) corresponded to the orientation bandwidth of orientation-sensitive cortical neurons. The maximum number of consecutive missing targets that does not interrupt pursuit depends on frequency of target presentation as well as on parameters of the pursuit system.


Bottle mix-up: Ethanol intoxication in an infant.
Alcohol intoxication is a common ingestion in pediatrics with close to 10,000 reports to poison control centers annually. Hypoglycemia, neurological depression (ataxia, coma, nystagmus, etc.) and unstable vitals (hypothermia, hypotension, bradycardia, and respiratory depression) are common presentations. The patient is a 3 month old female who was brought into the Emergency Department (ED) for one day of decreased oral intake and inconsolability. Vital signs were reassuring. Physical exam revealed gaze preference to the right with inability to look left, dysconjugate gaze, and hypotonia. Work-up including CT of the head, and urinalysis was unremarkable. Urine drug screen was found to be positive for ethanol with follow up serum ethanol at 162 mg/dL. With conservative management the patient returned to her baseline. On follow-up with her pediatrician, it was elicited that the mother inadvertently used a water bottle of vodka to mix the patient's formula. This case adds to the paucity of literature of abnormal presentations of alcohol intoxication in an infant.


Forensic usefulness of the silicone rubber cast of the cardiac vessels.
Adequate examination of the coronary arteries at forensic autopsy is often difficult. No matter whether the arteries are opened longitudinally or transversely, each method has its disadvantages. A technique making silicone rubber casts of the cardiac vessels providing simultaneous angiography is described. The method allows the three-dimensional precise assessment of stenotic lesions of the coronary arteries. It is concluded that the method examined could be useful for the forensic problems.


Magnetic resonance imaging in the evaluation and differentiation of uveal melanoma.
We evaluated 39 patients with intraocular disease by magnetic resonance imaging (MRI). Malignant uveal melanoma was considered the likely diagnosis in 25 patients. Seventeen patients underwent surgery, and the histopathologic diagnosis of melanoma was confirmed. The authors observed that uveal melanomas had characteristic MRI features consisting of a relatively high-signal intensity in T1-weighted images and a relatively low-signal intensity in T2-weighted images. These images reflected their inherently relative short T1 and T2 relaxation times. Choroidal lesions elevated more than 3 mm were well visualized on MRIs. MRI also proved valuable for differentiating uveal melanoma from associated subretinal effusion, choroidal hemangioma, choroidal metastasis, and hemorrhagic and serous choroidal detachments.


Prevention, diagnosis and treatment of carbon monoxide poisoning in an East-Slovakian ironworks.
The development of industry brings an increase in number of industrial poisonings by carbon monoxide. To treat these the East-Slovakian Ironworks has organised preventive measures. Instructive cases are illustrated. Measurement of carbon monoxide--haemoglobin in the laboratory gives an objective index for the degree of poisoning and the progress of treatment. The authors used cobaltous nitrate (0.13 mol/l) for control of the method. The best treatment was found to be hyperbaric oxygen in combination with multi-vitamin treatment. In some cases cardiorespiratory and antibiotic treatment is also necessary.


Useful to whom? Evaluation utilisation theory and boundaries for programme evaluation scope.
Programme evaluation is perpetually mandated in health professions education. Correspondingly, there has been an expansion in prescriptive methodological guides about 'how' to engage in various best practices in evaluation. However, what has gained less attention is an examination of the 'value' that different stakeholders seek to gain from programme evaluation. Evaluation utilisation theory and research can help us understand the diversity in both the driving forces for and the impact of programme evaluation. Awareness of the heterogeneity of evaluation utilisation priorities has implications for evaluation practices, including both methodological choices and understanding of the impact of programme evaluation in our field. In this article, I expound on the concept of evaluation utilisation by drawing on evaluation theory and research. 'Evaluation utilisation' refers to the application of programme evaluation processes and findings to influence thinking and action. Herein, different forms of 'evaluation utilisation' (including instrumental, conceptual, process and persuasive (symbolic and legitimative) utilisation) are discussed, as well as the related concept of 'evaluation misuse'. Furthermore, how the prioritisation of different forms of 'evaluation utilisation' can influence the scope and impact of evaluation scholarship are also discussed. Programme evaluation is a form of inquiry that requires more than the exercise of robust methodological techniques. Rather, it necessitates attention to the, sometimes divergent, priorities of different stakeholder groups. Although there is scant research on evaluation practices in health professions education, evaluation utilisation theory can inform critical examination of evaluation practices and impact in our field. Critically, understanding this body of work can help inform those engaged in evaluation about what they are (or should be) prioritising when they conduct programme evaluation, and better align evaluation methodologies with their scholarly, curricular and administrative intentions. Implications for future research and high-quality, transparent evaluation scholarship are presented.


Plasma fibrinogen and mortality in patients undergoing peritoneal dialysis: a prospective cohort study.
Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72-1.95, P = 0.51), 1.47 (95% CI, 0.93-2.33, P = 0.10), and 1.78 (95% CI, 1.15-2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86-1.68, P = 0.28), 1.29 (95% CI, 0.93-1.78, P = 0.13), and 1.53 (95% CI, 1.12-2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.


Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia.
Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol. To investigate whether combined therapy with omega-3 FA + policosanol offers benefits compared with omega-3 FA + placebo with respect to the lipid profile of patients with type II hypercholesterolaemia. This randomised, double-blind study was conducted in 90 patients with type II hypercholesterolaemia. After 5 weeks on a cholesterol-lowering diet, patients were randomised to omega-3 FA + placebo, omega-3 FA + policosanol 5 mg/day or omega-3 FA + policosanol 10 mg/day for 8 weeks. Omega-3 FA was supplied as 1g capsules (two per day); placebo and policosanol were provided in tablet form. Physical signs and laboratory markers were assessed at baseline and after 4 and 8 weeks on therapy. Drug compliance and adverse experiences (AEs) were assessed at weeks 4 and 8. The primary efficacy variable was LDL-C reduction; other lipid profile markers were secondary variables. After 8 weeks, omega-3 FA + policosanol 5 and 10 mg/day, but not omega-3 FA + placebo, significantly reduced LDL-C by 21.1% and 24.4%, respectively (both p < 0.0001). Omega-3 FA + policosanol 5 mg/day also significantly lowered TC (12.7%; p < 0.01) and TG (13.6%; p < 0.05), and significantly increased HDL-C (+14.4%; p < 0.001). Omega-3 FA + policosanol 10 mg/day significantly decreased TC (15.3%; p < 0.001) and TG (14.7%; p < 0.01), and significantly increased HDL-C (+15.5%; p < 0.0001). Omega-3 FA + placebo significantly reduced TG (14.2%; p < 0.05) but had no significant effect on other lipid profile variables. The proportion of randomised patients in the omega-3 FA + policosanol 5 or 10 mg/day groups that achieved LDL-C targets or reductions 15% was significantly greater than in the omega-3 FA + placebo group (p < 0.001). Combined therapy with omega-3 FA + policosanol 5 or 10 mg/day resulted in significantly greater changes in LDL-C, TC and HDL-C than treatment with omega-3 FA + placebo, but did not modify the TG response compared with the omega-3 FA + placebo group. Four patients (two in the omega-3 FA + placebo group and two in the omega-3 FA + policosanol 10 mg/day group) withdrew from the study; none of these withdrawals was due to AEs. Two patients reported mild AEs, namely nausea/headache (one in the omega-3 FA + placebo group) and heartburn (one in the omega-3 FA + policosanol 5 mg/day group). Policosanol 5 or 10 mg/day administered concomitantly with omega-3 FA 1 g/day improved LDL-C, TC and HDL-C, maintained the reduction in TG attributable to omega-3 FA monotherapy, and was well tolerated. Treatment with omega-3 FA + policosanol could be useful for regulating lipid profile in patients with type II hypercholesterolaemia, but further studies involving larger sample sizes are needed before definitive conclusions can be drawn.


Structural evidence that the activation peptide is not released upon thrombin cleavage of factor XIII.
The three-dimensional structure of the recombinant human factor XIII a2 dimer after cleavage by thrombin has been determined by X-ray crystallography. Factor XIII zymogen was treated with bovine alpha-thrombin in the presence of 3 mM CaCl2, and the cleaved protein was crystallized from Tris buffered at pH 6.5 using ethanol as the precipitating agent. Refinement of the molecular model of thrombin-cleaved factor XIII against diffraction data from 10.0 to 2.5 A resolution has been carried out to give a crystallographic R factor of 18.2%. The structure of thrombin-cleaved factor XIII is remarkably similar to that of the zymogen: there are no large conformational changes in the protein and the 37 residue amino terminus activation peptide remains associated with the rest of the molecule. This work shows that the activation peptide, upon thrombin cleavage, has the same conformation and occupies the same position with respect to the rest of the molecule as it does in the zymogen structure.


Senescence: does it all happen at the ends?
Over 60 years ago Barbara McClintock described the telomere and suggested that it protected the chromosome from illegitimate or end-to-end fusion, thus functioning to protect the genome. Since that time we have discovered that the telomere is a complex structure composed of both DNA and a growing list of associated proteins that together serve to regulate the length of the telomere and, as predicted by McClintock, protect genomic integrity. In addition to its protective role, the telomere has also been hypothesized to serve as a molecular clock that tallies the number of cell divisions and limits further divisions at a predetermined point. However, the precise role of telomeres in predicting and limiting cellular lifespan remains a matter of much debate. In this review, we highlight some of the salient points of basic telomere biology and relate them to the current controversies surrounding the role of telomeres and telomerase in cellular senescence.


Activation of protein kinase C modulates dihydroxycholecalciferol synthesis in rat renal tubules.
1,25(OH)2D3, the biologically active metabolite of vitamin D, is produced from 25(OH)D3 by the renal mitochondrial 25(OH)D3 1 alpha-hydroxylase. Several studies have implicated reversible phosphorylation and a possible role for protein kinase C (PKC) in acute regulation of 1,25(OH)2D3 production. In the experiments described here, we studied 1,25(OH)2D3 production in freshly isolated rat renal tubules treated with activators and inhibitors of PKC. In this mammalian system, TPA, but not its inactive analogue 4 alpha PDD, inhibited 1,25(OH)2D3 production in a dose-dependent fashion within 20 min. The acute inhibition of 1,25(OH)2D3 production by TPA exposure was preceded by an increase in membrane associated PKC activity, which was paralleled by a decrease in cytosolic PKC activity. Pre-incubation of tubules with staurosporine, a PKC inhibitor, abolished the inhibitory effect of TPA on 1,25(OH)2D3 production. Chronic (18 h) exposure of tubules to high dose TPA resulted in down regulation of both membrane and cytosolic PKC activity and re-exposure to TPA did not affect PKC translocation or 1,25(OH)2D3 production in down regulated tubules. Our data strongly suggest that modulation of renal PKC activity may be an important mechanism for acute regulation of 1,25(OH)2D3 production.


Measles-mumps-rubella vaccine and the development of autism.
The measles-mumps-rubella (MMR) vaccine has been postulated to cause a form of autism characterized by regression and bowel symptoms, and onset occurring shortly after vaccination. It is also claimed that, as a result, there has been a dramatic increase in autism prevalence. These hypotheses have now been tested in a number of epidemiologic studies that are reviewed in this article. None has found any evidence of the existence of a phenotypically distinct form of autism in children who received the MMR vaccine or of a clustering of onset symptoms in children who are autistic after receiving the MMR vaccine. There is no proof that the overall risk of autism is higher in children who were vaccinated with MMR or of an increase in autism prevalence associated with the use of the MMR vaccine. No epidemiologic evidence suggests an association between MMR vaccination and autism. Moreover, epidemiologic evidence against such an association is compelling.


Understanding prostaglandin metabolites and platelet-activating factor in the pathophysiology and treatment of the antiphospholipid syndrome.
As clinicians include an immunologic evaluation in their assessment of recurrent fetal loss among otherwise asymptomatic women, the diagnosis of PAPS will be uncovered with greater frequency. Our understanding of the underlying pathophysiology of PAPS is critical if we are to propose safe and rational therapies for these patients. It appears as though prostaglandin metabolites are implicated directly in the processes that culminate in this unique, localized vasculopathy; and research is actively progressing with this focus in mind. For the present, we should look critically at the available treatments to be sure that the rationale for use is consistent with current evidence and that the margin of fetal and maternal safety justifies their use. To date, only low-dose aspirin appears to alter prostaglandin metabolites favorably and is thus, emerging as our safest and most efficacious treatment.


Cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, inhibits proliferation and enhances therapeutic sensitivity in glioblastoma cells.
Glioblastoma (GB) is the most aggressive type of brain tumor. Rapid progression, active angiogenesis, and therapy resistance are major reasons for its high mortality. Elevated expression of members of the vascular endothelial growth factor (VEGF) family suggests that anti-VEGF therapies may be potent anti-glioma therapeutic approaches. Here, we evaluated the anti-tumor activity of cediranib, a pan inhibitor of the VEGF receptors, on GB cells. Anti-proliferative effects of cediranib were determined using MTT, crystal-violet staining, clonogenic and anoikis resistance assays. Apoptosis induction was assessed by Annexin V/PI staining and Western blot analysis and aggressive abilities of GB cells were investigated using cell migration/invasion assays and zymography. Small-interfering RNA (siRNA)-mediated Knockdown was used to study resistance mechanisms. The anti-proliferative and apoptotic effects of cediranib in combination with radiotherapy, temozolomide, bevacizumab were also evaluated using MTT, Annexin V/PI staining and Western blot analysis for cleaved PARP-1. Cediranib reduced GB cell proliferation, induced apoptotic cell death and inhibited the aggressive abilities of GB cells. Cediranib synergistically increased the anti-proliferative and apoptotic effects of radiotherapy and bevacizumab and augmented the sensitivity of GB cells to temozolomide chemotherapy. In addition, knockdown of MET and AKT potentiated cediranib sensitivity in cediranib-resistant GB cells. These findings suggest that cediranib, alone or in combination with other therapeutics, is a promising strategy for the treatment of GB and provide a rationale for further investigation of the therapeutic potential of cediranib for the treatment of this fatal malignancy.


Social cognition in schizophrenia.
Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder.


Synthesis, Application, and Antibacterial Activity of New Direct Dyes based on Chromene Derivatives.
This study aimed at synthesizing, analyzing, and utilizing two new direct dyes based on chromene derivatives as the chromophoric moiety in dyeing wool, silk, and cotton, with good color strength, light fastness, and other desirable features. New direct dyes with antimicrobial activities for Gram-positive, Gram-negative bacteria, and fungus are being developed. These dyes are used on cotton, silk, and wool materials, which have excellent light fastness, washing, rubbing, and perspiration fastness. All dyeing fabrics were tested for antibacterial activity. As a part of the experiment, parent structure 1 was previously synthesized. Then, diazotization and coupling reactions were used to prepare these dyes. P-Aminobenzenesulfonic acid (C1) and 4-Aminoazobenzene-3,4'-disulfonic acid (C2) were diazotized in hydrochloric acid with sodium nitrite and then coupled with compound 1 in a molar ratio of 1:1 at 25 °C until the pH was fixed at 5. Finally, the monoazo and diazo direct dyes (D1 and D2) were prepared. Wool, silk, and cotton materials benefit from the increased antibacterial activities and dyeing qualities (exhaustion and fixing) of synthetic dyes. Furthermore, they offer excellent fastness qualities (light, rubbing, and perspiration).


UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease.
The purpose of the study was to determine if UDP-glucuronosyltransferase (UGT) 2B7 allelic variants encoding for UGT2B7, primary enzyme responsible for morphine glucuronidation contribute to the variability in the hepatic clearance of morphine in sickle cell disease (SCD). Twenty-four hour PK study of morphine and UGT2B7 variants genotyping was performed in 20 SCD patients in a steady state of health. Presence of the -840G allele (GG and GA) was associated with lower morphine metabolites/morphine AUC ratio compared with AA genotype (1.8 +/- 0.5 vs. 3.0 +/- 1.8 for M6G/M and 10.1 +/- 2.7 vs. 15.7 +/- 9.4 for M3G/M) (P = 0.03). Presence of UGT2B7 -840G allele is associated with significantly reduced glucuronidation of morphine and thus contributes to the variability in hepatic clearance of morphine in SCD.


A high-performance liquid chromatography-tandem mass spectrometry method for quantification of perampanel in human plasma: Effect of concomitant anti-seizure medications on perampanel concentration in patients with epilepsy.
Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important. This study developed a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method to quantify perampanel in human plasma. Protein precipitation with acetonitrile was performed for sample preparation. Perampanel and perampanel-d5 (internal standard) were analyzed under gradient conditions using a C18 column. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.4 mL/min. Mass detection was performed using multiple reaction monitoring in the positive ionization mode. The proposed method was validated over a range of 0.5-500 ng/mL for perampanel. The linearity (r2 value) was higher than 0.999, and the linear equation was y = 0.00116x + 0.0116. The accuracy of the low-, middle-, and high-quality control samples was between 103% and 113%, and the intra- and inter-day precisions were below 6.81%. The quality of the proposed method was evaluated in accordance with the US Food and Drug Administration Bioanalytical Method Validation Guidance for Industry. The plasma concentrations of perampanel in 25 patients were successfully determined to be 38.7-577.7 ng/mL using the validated method.


Characterization of the novel HLA-DPB1*1299:01N allele by next-generation sequencing.
HLA-DPB1*1299:01N differs from HLA-DPB1*427:01 by one single nucleotide substitution and one nucleotide insertion.


Variation in use of targeted therapies for metastatic renal cell carcinoma: Results from a Dutch population-based registry.
For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS). Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008-2010 Cohort (n = 645) and a 2011-2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies. Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008-2010 Cohort; 35 % in the 2011-2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84-0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005). Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully.


Evaluation of dietary pattern stability and physical activity in three consecutive generations of women.
This study aimed to characterize major dietary patterns (DPs) in three consecutive generations and to delineate DP changes. Usual dietary intakes of 547 women from three generations were assessed using a validated dish-based Food Frequency Questionnaire. Factor analysis was performed to identify DPs, participants' scores for each DP were calculated and changes in DP scores and mean consumption of food groups were evaluated. Using Latent Class Analysis (LCA), participants were ranked according to their scores receiving for each DP. Three major DPs, defined as Traditional (TDP), Healthy (HDP), and Western (WDP) and the comparison of DP adherence between generations showed that TDP remained stable over time. WDP and HDP scores increased from Generation1 to the recent. Based on LCA, the "multifarious class" was similar in three generations. The "traditional class", "transitional class", and "health conscious class" were defined within the oldest, middle-aged, and younger generation, respectively. The younger women tended to have higher score for both WDP and HDP. This paradox may be as a result of health conscious behaviors parallel the unfavorable inevitable lifestyle changes.


An ultrastructural and cytochemical study of the interaction between latex particles and the haemocytes of the wax moth Galleria mellonella in vitro.
The plasmatocytes are the major phagocytic blood-cell type in the haemolymph of the wax-moth, Galleria mellonella. In the present study, these cells were allowed to attach to tissue culture dishes for 1 h, rinsed and then incubated with latex beads for up to 72 h. These cells were then fixed for routine transmission electron microscopy and acid phosphatase cytochemistry. Intracellular latex particles were found in tight, ill-defined phagosomes, which were often clearly associated with the Golgi complexes of the plasmatocytes. Fusion of both primary lysosomes and multivesicular bodies with the phagosomes occasionally occurred and this resulted in the accumulation of an acid phosphatase positive reaction product around the test particles. Subsequent experiments showed that this acid phosphatase activity was mainly associated with the primary lysosomes. The results of the lysosome/latex interactions are compared with those obtained from similar studies on the digestive mechanisms in other phagocytes.


Mobility changes in individuals with dysvascular amputation from the presurgical period to 12 months postamputation.
To describe changes in ambulation among individuals with lower-extremity amputation secondary to peripheral artery disease and/or diabetes prior to surgery through 12 months after surgery. To compare differences in ambulation by amputation level and to examine risk factors for change in ambulation over time. Prospective cohort study. Two Veterans Affairs medical centers, 1 university hospital, and a level I trauma center. Patients with peripheral artery disease or diabetes (N=239) undergoing a first unilateral major amputation were screened for participation between September 2005 and December 2008. Among these, 57% (n=136) met study criteria, and of these, 64% (n=87) participated. Standard of care at each facility. Ambulatory function measured using the Locomotor Capability Index-5. Seventy-five of the 87 (86%) subjects enrolled finished their 12-month follow-up interview. Ambulatory mobility declined during the period immediately prior to surgery (premorbid) and remained low at 6 weeks postsurgery. On average, ambulation improved after surgery but did not return to premorbid levels. In the final multivariate model, age and history of lower-extremity arterial reconstruction were significantly associated with a poorer ambulatory trajectory over time, while other factors, such as amputation level, prior alcohol use, and length of disability prior to amputation, were not. The findings highlight the importance of considering premorbid ambulatory function. Informing providers and patients about the trajectory and time course of changes in ambulation can enhance patient education, patient expectations, and treatment planning.


Early osseous abnormalities in Menkes' kinky hair syndrome.
Bone changes in a 4 m.o. infant with Menkes' Kinky Hair Syndrome, who also had a skeletal survey as a newborn, are reported. Whereas the late bone changes were diagnostic, the neonatal ones were similar to congenital rubella and cytomegalic virus infection. However the distribution of the metaphyseal changes were different.


Carbonate effects and pH-dependence of uranium sorption onto bacteriogenic iron oxides: kinetic and equilibrium studies.
The removal of U(VI) from groundwaters by adsorption onto bacteriogenic iron oxides (BIOS) has been investigated under batch mode. The adsorbent dosage, the uranium concentration, the concentration of carbonate and the use of a real groundwater spiked with uranium comprised the examined parameters. In addition, the effect of pH was examined in two different water matrixes, i.e., in distilled water and in real groundwater. Equilibrium studies were carried out to determine the maximum adsorption capacity of BIOS and the data correlated well with the Langmuir and Freundlich models. The presence of carbonate affected adversely the adsorption of U(VI) onto BIOS. The maximum adsorption capacity of BIOS was 9.25 mg g(-1) at 0.1mM carbonate concentration and decreased to 6.93 mg g(-1) at 0.5mM carbonate concentration, whereas at carbonate concentration of 2mM practically no adsorption occurred. The data were further analyzed using the pseudo-second order kinetic equation, which fitted best the experimental results. The initial adsorption rate (h) was found to increase with decreasing the concentration of carbonate in all cases. When experiments were accomplished in the absence of carbonate, the pH values did not have an effect on the adsorption of U(VI). However, the extent of U(VI) adsorption was strongly pH-dependent when the experiments were carried out in the real groundwater. The maximum adsorption capacity increased sharply as the pH decreased and optimum removal was obtained in the pH range 3.2-4.0, thus bacteriogenic iron oxides can found application in the removal of U(VI) by adsorption from low pH or low carbonate waters.


Aorta-pulmonary shunts in growing pigs. Functional and structural assessment of the changes in the pulmonary circulation.
Aorta-pulmonary shunts were produced in growing pigs, 4 to 12 weeks of age, by anastomosing the thoracic descending aorta to the pulmonary trunk, and the animals were followed for periods of 1 to 3 months. Correlation between the hemodynamic findings and the lung structure, analyzed by quantitative methods, showed that the young group (operated upon at 4 weeks of age) developed more severe pulmonary hypertension with increased muscularization of arteries of all sizes and reduction in the size of those running with respiratory bronchioli and beyond. Since this response is similar to that seen in cases of left-to-right shunt associated with congenital heart defects and pulmonary hypertension early in life, it seems that the present experiments reproduce the early response of the growing lung to such hemodynamic disturbance.


Tuberculosis case finding and preventive therapy in an HIV voluntary counseling and testing center in Uganda.
A large, urban human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) center in Kampala, Uganda. Tuberculosis (TB) is a leading cause of morbidity and mortality in persons with HIV infection in sub-Saharan Africa. Intensified TB case finding and use of isoniazid preventive therapy (IPT) for latent infection reduces the burden of TB, but few programs have been implemented due to concerns about feasibility. Retrospective evaluation of a TB case finding and IPT program. Over a 25-month period, 6305 patients newly diagnosed with HIV infection underwent evaluation: 293 (5%) had TB disease; 1955 (37%) patients were not eligible for preventive therapy because they lived > 20 km away, had advanced HIV disease, or had previously had TB. Of 3366 who had a tuberculin skin test (TST) placed, 2548 (76%) had the TST read; 894 (35%) of these were positive. Of 506 persons who started treatment, 335 (66%) completed it. This unique program was feasible, detected a high proportion of undiagnosed TB, and successfully treated persons with latent infection. Expanding access to HIV VCT as well as collaboration between HIV/ AIDS and TB programs can increase the proportion of HIV-infected persons who can benefit from these programs.


Stimulus novelty and cognitive-related ERP components of the infant brain.
This study recorded visual fixation performance and event-related brain potentials (ERPs) to examine processing of novel visual information in 6- to 7-mo.-old infants as well as to test attention- or memory-related hypotheses of the functional significance of the Nc-ERP component. Separate groups of infants were presented two versions of a novelty-probe task with three types of visual stimuli: (a) a frequent face on 70% of the trials, (b) an oddball face on 15% of the trials, and (c) novel probe stimuli on the remaining 15% of the trials. The novelty probes were faces in one group and irregular shapes in the second group. Analysis showed longer fixations and Nc responses of greater amplitude occurred to oddball and novel stimuli. It was concluded that Nc reflects a top-down, controlled processing mechanism that flexibly allocates attentional resources.


Perceiving emotions in visual stimuli: social verbal context facilitates emotion detection of words but not of faces.
Building on the notion that processing of emotional stimuli is sensitive to context, in two experimental tasks we explored whether the detection of emotion in emotional words (task 1) and facial expressions (task 2) is facilitated by social verbal context. Three different levels of contextual supporting information were compared, namely (1) no information, (2) the verbal expression of an emotionally matched word pronounced with a neutral intonation, and (3) the verbal expression of an emotionally matched word pronounced with emotionally matched intonation. We found that increasing levels of supporting contextual information enhanced emotion detection for words, but not for facial expressions. We also measured activity of the corrugator and zygomaticus muscle to assess facial simulation, as processing of emotional stimuli can be facilitated by facial simulation. While facial simulation emerged for facial expressions, the level of contextual supporting information did not qualify this effect. All in all, our findings suggest that adding emotional-relevant voice elements positively influence emotion detection.


Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces S1P effects on T cell proliferation and cytokine secretion without signaling migration.
Sphingosine 1-phosphate (S1P) has diverse effects on T cells that are mediated by the predominant S1P1 and S1P4 G protein-coupled receptors (GPCRs). S1P4 is expressed principally by leukocytes, but little is known of its T cell effects in immunity. Two approaches were used to investigate S1P4 signals in T cells. First, S1P4 was introduced into D10G4.1 mouse Th2 cells and EL4.IL-2 mouse T cells lacking endogenous S1P GPCRs. Second, mouse splenic CD4 T cells were treated with FTY720 to suppress S1P1 and leave S1P4 GPCRs as the only functionally relevant S1P receptor. Unlike S1P1, S1P4 failed to transduce chemotactic responses of any of the S1P4-only T cells to S1P or the phyto-S1P ligand selective for S1P4, or to suppress their chemotactic responses to chemokines. The S1P-S1P4 axis significantly inhibited T cell proliferation in each of the S1P4-only T cells activated by anti-CD3 and anti-CD28 MoAbs. Secretion of IL-4 by S1P4-D10G4.1 cells, IL-2 by S1P4-EL4.IL-2, and IFN-gamma by FTY720-treated CD4 T cells were significantly inhibited by S1P. In contrast, S1P enhanced secretion of IL-10 by stimulated S1P4-D10G4.1 T cells. Thus, S1P4 mediates immunosuppressive effects of S1P by inhibiting proliferation and secretion of effector cytokines, while enhancing secretion of the suppressive cytokine IL-10.


Beneficial effects of cornel iridoid glycoside on behavioral impairment and senescence status in SAMP8 mice at different ages.
The aim of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on behavioral changes and senescent status in senescence-accelerated mouse-prone 8 (SAMP8) mice at different ages (6, 10, and 14 months old). The learning and memory ability, the motor function and the aging conditions of SAMP8 mice were evaluated after CIG treatment in this study. Results showed that intragastrical administration of CIG (100 and 200mg/kg) for two months obviously improved the impaired cognitive ability of SAMP8 mice at the age of 6 months and 10 months, respectively. The treatment with CIG significantly increased the motor function of SAMP8 mice at 10 months and 14 months of age, respectively. CIG also evidently decreased the high grading score of senescence and increased the low surviving rate of SAMP8 mice at the age of 14 months. In addition, CIG treatment inhibited tau hyperphosphorylation in the hippocampus and striatum of SAMP8 mice at different ages. Together, these results indicate that CIG represent a potentially useful treatment for ameliorating the impaired cognitive ability, the motor dysfunction, aging conditions and hyperphosphorylation of tau in aging and age-related neurodegenerative diseases, such as Alzheimer's disease.


Memory and language in neurodegenerative diseases.
This article reviews recent studies concerning memory and language disorders in Alzheimer's disease and other neurodegenerative conditions. It shows how different memory and language subcomponents may differentially be impaired in different neurodegenerative diseases and at different stages of the same disease.