Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement, relapsing soon after primary treatment with fludarabine-rituximab.
Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.


DPC in acute-phase inpatient hospital care. Visualization of amount of nursing care provided and accessibility to nursing care.
The purpose of this study was to improve accessibility to nursing care by clarifying the relationship between patient characteristics and the amount of nursing care for the Diagnosis Procedure Combination system (DPC). The subjects included 528 lung cancer patients; 170 gastric cancer patients; and 91 colon cancer patients, who were hospitalized from July 1, 2008, to March 31, 2010, at a university hospital. The patients were categorized into groups according to factors that could affect the amount of nursing care. Next, the relationship between the patient characteristics and the amount of nursing care was analyzed. Then the results from this study were used to classify patient characteristics according to the patient type and the amount nursing care required. The patient characteristics, which affected the amount of nursing care, varied according to each DPC code. The major factors affecting the amount of nursing care were whether the patient had received a surgical (under general anesthetics) treatment or a non-surgical treatment and the level of activities of daily living (ADL) of the hospitalized patients. For those who had received a surgical operation for colon cancer, the patient's age also affected the amount of nursing care. The findings show that the method for the visualization of the amount of nursing care based on the classification of patient characteristics can be implemented into the electronic health record system. This method can then be used as a management tool to assure appropriate distribution of nursing resources.


Frontiers of nursing in the twenty-first century: development of models and theories on the concept of nursing.
Theories and models on the concept of nursing are reviewed briefly and their contribution then assessed in terms of their potential to advance the scientific basis of nursing practice. The constructs are acknowledged to have moved the focus of nursing from disease to patient need and provided different ways of looking at the nurse's contribution. Yet, despite this advance, the constructs have not been put to the rigours of scientific testing and so remain at the level of speculation. Therefore, towards the developments for the twenty-first century it is proposed that these ideas should be put to the test to establish their relevance in the real world of nursing care. This requires: a framework from which the nature, extent and purpose of care can be specified; independent criteria which can be used to judge effectiveness of care; knowledge as it relates to the different and varied core concepts underlying the practice of nursing; and a working definition of need. In addition, the extent of care for the community needs to be made explicit through research. Together, this represents a challenge to develop theories which are logically related to single core concepts which themselves represent specific areas of actual nursing practice.


Light-Induced In Situ Transformation of Metal Clusters to Metal Nanocrystals for Photocatalysis.
In situ transformation of glutathione-capped gold (Aux) clusters to gold (Au) nanocrystals under simulated solar light irradiation was achieved and utilized as a facile synthetic approach to rationally fabricate Aux/Au/TiO2 ternary and Au/TiO2 binary heterostructures. Synergistic interaction of Aux clusters and Au nanocrystals contributes to enhanced visible-light-driven photocatalysis.


Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection.
Using our gp120/41-expressing, NK cell activity-resistant CEM.NKR cell clones as targets in HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) assays, we demonstrate here that the serum titers of anti-HIV-1 ADCC antibodies bear a significant (P < 0.05) positive correlation with the peripheral blood CD4+ T cell counts and a negative one with the number of copies of HIV-1 RNA in the plasma of HIV-infected individuals. These findings underscore the importance of these antibodies as a protective immune parameter in these infections.


Sutureless Lichtenstein: first results of a prospective randomised clinical trial.
Inguinal hernia repair, according to Lichtenstein, is very popular due to its minimal invasiveness (local anaesthesia), easy and reproducible technique, low recurrence rate, and low morbidity. However, recent publications demonstrate an elevated rate of chronic irritations and pain, probably due to tension or nerve compression by the fixing sutures. We, therefore, established a concept to avoid these sutures by attaching the prosthesis with glue. After a pilot study, a randomised prospective trial was started. The aim of our study was to compare the results of the classical Lichtenstein repair (group 1) vs the "Sutureless Lichtenstein" (group 2) in terms of postoperative complications and recurrences. Operative access and management of the hernial sac was equal to Lichtenstein for both groups. In group 1, we sutured the mesh with PDS 2/0; in group 2, the mesh was glued with n-butyl-cyanoacrylate. In both groups, the operation was then completed according to Lichtenstein, and unrestricted activity was allowed after 2 weeks. A total of 46 patients have been operated on. The follow-up results at 3 weeks and [3 months] were: group 1 ( n=24) vs group 2 ( n=22): recurrences 0 [0] vs 0 [0], minor pain 8 [4] vs 4 [1], local numbness 14 [10] vs 10 [6]. No adhesive-related complications were seen. Patients will be followed for 2 years. The results in group 2 were excellent, and there was no difference vs group 1. Furthermore, there was a tendency for better results in group 2. These results are very promising and justify a continuation of the study.


Percutaneous central gray stimulation for cancer pain.
Electrical stimulation of the periventricular and periaqueductal gray matter via a percutaneous electrode appears to be a useful method for relieving cancer pain with midline and bilateral distribution. Due to the nondestructive character and the minor surgical risks involved in this procedure it may be tried before considering bilateral cordotomy or myelotomy. A possible mechanism of action or at least a contributive factor to the pain relief is the activation of endorphins.


Evidence of Altered Habenular Intrinsic Functional Connectivity in Pediatric ADHD.
The habenula is a small region in the epithalamus that contributes to the regulation of midbrain dopaminergic circuits implicated in attention-deficit hyperactivity disorder (ADHD). This investigation aims to evaluate the intrinsic functional connectivity (iFC) of the habenula in children with ADHD. A total of 112 children (5-9 years; 75 ADHD, 37 healthy comparisons) completed anatomical and resting-state functional magnetic resonance imaging (MRI) scans. Habenula regions of interest (ROIs) were identified individually on normalized T1-weighted anatomical images. Seed-based iFC analyses and group comparisons were conducted for habenula ROIs, as well as thalamic ROIs to test the specificity of habenula findings. Children with ADHD exhibited reduced habenula-putamen iFC compared with healthy comparisons. Group differences in thalamic iFC showed no overlap with habenular findings. These preliminary findings suggest that habenula-putamen iFC may be disrupted in children with ADHD. Further work is needed to confirm and elucidate the role of this circuit in ADHD pathophysiology.


Serotonin inhibits voltage-gated sodium current by cyclic adenosine monophosphate-dependent mechanism in bullfrog taste receptor cells.
We have investigated the effect of 5-hydroxytryptamine (serotonin) (5-HT) on the membrane properties of bullfrog taste receptor cells (TRCs) using patch-clamp technique. External application of 5-HT reversibly suppressed the voltage-gated Na(+) current (I(Na)) in about half of the TRCs sampled. The magnitude of suppression of peak I(Na) was dependent on the holding potential of the cell. Forskolin and cyclic adenosine monophosphate (cAMP) mimicked the suppressive effect of 5-HT on I(Na), but an internal protein kinase A-inhibitor potentiated I(Na). These results suggest that 5-HT suppresses I(Na) of bullfrog TRCs via protein kinase A-dependent phosphorylation, resulting in suppression of the excitability of bullfrog TRCs.


Neurobehavioral Cognitive Status Examination: its use with unilateral stroke patients in a rehabilitation setting.
The Neurobehavioral Cognitive Status Examination (NCSE) was administered to 12 patients with right unilateral stroke and 12 with left unilateral stroke and to 12 orthopedic, non-brain-dysfunctional patients who were matched in age and education, for the purpose of studying its usefulness in characterizing cognitive deficits in a stroke rehabilitation population. MANOVA demonstrated significant differences (Phillai's trace, p = .007) between the stroke groups and the controls, but not between the unilateral stroke groups. Significant univariate Fs (F[2,3], p less than .05) occurred between the stroke groups and the controls in comprehension, naming, constructions, memory, and similarities. Correlations revealed strong relationships among the scales; little relationship to age was found. Education correlated with attention, comprehension, repetition, and similarities. The number of medications patients were taking did not correlate with either individual scale scores or an overall score on the NCSE. The test was found to be sensitive to cognitive effects of stroke, although there was little discrimination between left-sided and right-sided strokes. The correlational structure of the test's scales provided general support for an attention/concentration dimension, at least one general language dimension, and a general memory dimension. Further factor analytic study was recommended to more definitively assess the test's factorial dimensions. Individual descriptive data suggested that the screen and the last item of the constructions scale were too difficult. It was suggested that the item be changed or that a clue be offered to the patient.


3-(Benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.
Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole, [18F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer. Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied. In vivo behavior, in normal mice and on AD mice models, were also analyzed. [18F]-IND1 was obtained in good radiochemical yield, was stable for at least 2 h in different conditions, and had adequate lipophilicity for blood-brain barrier penetration. Biodistribution studies, in normal mice, showed that [18F]-IND1 was retained in the brain after 1 h. In vivo tacrine-blocking experiments indicated this uptake could be specifically due to AChE interaction. Studies in transgenic AD mice showed differential, compared with normal mice, binding in many brain regions. [18F]-IND1 can be used to detect AChE changes in AD patients.


The predictive value and the management of cycles with low initial estradiol levels.
This study was undertaken to examine the predictive value of low estradiol (E2) after 5 days of human menopausal gonadotropin (hMG) stimulation response to therapy in that cycle. We further examined whether the outcome of such cycles can be improved by increasing the hMG dose. When 18 cycles in which day 8 E2 was less than or equal to 50 pg/mL were compared with 48 cycles with corresponding E2 levels of 51 to 150 pg/mL, the former showed a significantly worse response to subsequent hMG therapy. To determine the effect of an increase in hMG dose we studied 48 cycles with day 8 E2 of 51 to 150 pg/mL. In 32 cycles hMG dose was increased from three to a mean of five ampules a day, after 5 days of therapy. In 16 cycles it was kept constant at three ampules per day. Although a tendency towards lower fertilization rate was observed in the higher hMG groups, no significant differences were observed in the results between the two groups. We thus conclude that very low E2 levels after 5 days of gonadotropin therapy are predictive of low response in that cycle, and that in cycles with day 8 E2 of 51 to 150 pg/mL, increasing the dosage of hMG on day 8 and beyond does not alter the course of the cycle.


Intraprocedural reconstruction of the left atrium and pulmonary veins as a single navigation tool for ablation of atrial fibrillation: a feasibility, efficacy, and safety study.
Pulmonary vein (PV) isolation is a technically challenging intervention. For this reason, integration of three-dimensional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) in order to enhance effectiveness and safety has been widely adopted. A novel imaging approach--intraprocedural rotational angiography and reconstruction of the left atrium and PVs--is feasible and provides high anatomic accuracy. The purpose of this study was to prove the feasibility, safety, and efficacy of this imaging approach as a single navigation tool for PV isolation. Forty-four patients (25 men and 19 women; age 57 +/- 11 years) with atrial fibrillation (AF) who presented for PV isolation were studied. Rotational angiography during adenosine-induced ventricular asystole was performed under sedation with propofol. The left atrium and PVs were reconstructed by three-dimensional atriography using specialized software (EP navigator prototype, Philips Medical Systems). Three-dimensional atriography was used as a single navigation tool for guiding PV isolation. Of 176 PVs, 174 (99%) were isolated. Total procedural and fluoroscopy times were 192 +/- 46 minutes and 44 +/- 12 minutes, respectively. During follow-up of 6 +/- 3 months, 31 (70%) patients were free of symptoms and had no evidence of AF without any antiarrhythmic medication. MRI examination of 41 patients at 3-month follow-up excluded PV stenosis. No major complications occurred. Three-dimensional atriography is a novel intraprocedural three-dimensional imaging technique that is based on rotational angiography. It can be safely and effectively used as a single navigation tool for performing PV isolation.


Clinical practices in neonatal oxygenation: where have we failed? What can we do?
Oxygen is among the most frequently used therapies in neonates worldwide. Nevertheless, many times it is used unnecessarily. Neonatal practices have changed over the last several years; treatments originally believed to be beneficial have been discarded. Oxygen utilized 'just in case' or 'prophylactically' can lead to great damage previously ignored and/or unseen by healthcare providers. It is imperative to improve education on neonatal oxygenation and saturation monitoring. It is also important not to depend on old assumptions, which were not based on evidences. The potential for unseen damage at the cellular and tissue levels cannot be ignored. Therapies that prove to be outdated or even dangerous must be eliminated while further research and confirmation of the best practices are determined. Freedom to choose can come at a price.


Soft tissue sarcomas in adolescents and young adults: a comparison with their paediatric and adult counterparts.
Survival outcomes for adolescent and young adult patients with soft tissue sarcomas lag behind those of children diagnosed with histologically similar tumours. To help understand these differences in outcomes, we discuss the following issues with regard to the management of these patients with soft tissue sarcomas: delays in diagnosis, trial availability and participation, aspects of the organisation of care (with an emphasis on age-specific needs), national centralisation of sarcoma care, international consortia, and factors related to tumour biology. Improved understanding of the causes of the survival gap between adolescents and young adults with sarcomas will help drive new initiatives to improve final health outcomes in these populations. In this Review, we specifically focus on embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and adult soft tissue sarcomas diagnosed in adolescents and young adults, and discuss the age-specific needs of these patients.


Computer-assisted volumetric stereotactic neurosurgery: present methodology and future directions.
Classic craniotomy for biopsy or resection of intra-axial brain tumors usually employed large skin flaps and craniotomy openings. These were necessary so that surgeons could be certain that a subcortical tumor could be localized and that the extent of the lesion lay somewhere beneath and within the limits of the craniotomy. Localization methods for classic resection methods were qualitative and imprecise.


Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-kappaB, suppresses IkappaBalpha ubiquitination and modulates innate immune responses.
Salmonella enterica translocates virulent factors into host cells using type III secretion systems to promote host colonization, intracellular bacterial replication and survival, and disease pathogenesis. Among many effectors, the type III secretion system encoded in Salmonella pathogenicity island 2 translocates a Salmonella-specific protein, designated Salmonella secreted factor L (SseL), a putative virulence factor possessing deubiquitinase activity. In this study, we attempt to elucidate the mechanism and the function of SseL in vitro, in primary host macrophages and in vivo in infected mice. Expression of SseL in mammalian cells suppresses NF-kappaB activation downstream of IkappaBalpha kinases and impairs IkappaBalpha ubiquitination and degradation, but not IkappaBalpha phosphorylation. Disruption of the gene encoding SseL in S. enterica serovar typhimurium increases IkappaBalpha degradation and ubiquitination, as well as NF-kappaB activation in infected macrophages, compared with wild-type bacteria. Mice infected with SseL-deficient bacteria mount stronger inflammatory responses, associated with increased production of NF-kappaB-dependent cytokines. Thus, SseL represents one of the first bacterial deubiquitinases demonstrated to modulate the host inflammatory response in vivo.


Mechanisms of alcohol tolerance.
Functional tolerance to ethanol can be prolonged by administration of the neuropeptide arginine vasopressin (AVP), which acts at specific CNS receptors. AVP receptors in brain (lateral septum) have been shown to be localized, in part, presynaptically, and the mechanism of action of AVP may thus involve modulation of neurotransmitter release. AVP has also been found to increase the levels of mRNA for the cellular proto-oncogene, c-fos, in the septum and hippocampus. This response to AVP, which may be direct or indirect, may underlie the long-term neuroadaptive effects of the peptide. Studies with vasopressin antagonists have indicated a role for endogenous AVP in modulation of ethanol tolerance, and measurement of hypothalamic vasopressin mRNA by Northern blot analysis and in situ hybridization indicates that chronic ethanol ingestion may alter AVP synthesis. Tolerance to the aversive effects of ethanol has been postulated to influence alcohol drinking behavior in some individuals. Elucidation of the mechanism by which AVP affects ethanol tolerance may eventually lead to pharmacological means to modulate tolerance and, consequently, alcohol intake patterns.


Management of severe chest injuries.
Anoxia and haemorrhage are the causes of early death in patients with severe chest injuries. Early recognition with prompt resuscitation is the cornerstone of their management. Intensive care and a cohesive multidisciplinary approach to patients with associated multiple injuries are important.


[Construction of recombinant adenoviral vector to coexpress human neurotrophin3 and EGFP gene and its conduction efficiency to rat cochlea in vitro].
To construct an adenoviral vector that codes for both human NT3 and EGFP, to confirm the transduction efficiency in rat cochlear cultures and to assess the protection of NT3 on SGNs survival. PAdeasy-1 and pAdTrack CMV were used to constructed Ad/NT3 adenovirus and then to transfer postnatal day 3 rat cochlear cultures. The transduction efficiency was determined by microscope observation. The amounts of SGNs were counted to evaluated protection of Ad/NT3 on SGNs survival. EGFP positive cells were observed in all cochlear turns. There was approximately 49% in outer sulcus cells and 27% in the interdental cells; less than 2% of the hair cells and SGN. The amounts of SGN of treated Ad/NT3 adenovirus are more than cochlea SGN only Ad/EGFP adenovirus after cultured for 15 days. Ad/NT3 adenovirus could transduce EGFP and NT3 in large number of supporting cells, but few hair cells or SGNs. The putative release of NT3 from these supporting cells could enhance cell survival and promote neurite outgrowth from SGNs.


Counselor skill influences outcomes of brief motivational interventions.
The aim of this study was to estimate the influence of counselor skills during brief motivational interventions (BMIs) on patient alcohol use 12 months later. Ninety-five BMIs delivered by five counselors of similar background and training were recorded and coded using the Motivational Interviewing Skills Code (MISC). Baseline alcohol measures and sociodemographics of patients did not differ across counselors, whereas MISC scores and outcome at 12 months did. Multilevel models showed that counselors with better motivational interviewing (MI) skills achieved better outcomes overall and maintained efficacy across all levels of an important predictor (patient ability to change), whereas counselors with poorer MI skills were effective mostly at high levels of ability to change. Findings indicated that avoidance of MI-inconsistent skills was more important than frequency of using MI-consistent skills and that training and selection of counselors should be based more on the overall MI-consistent gestalt than on particular MI techniques.


Rhodococcus equi--an emerging human pathogen in immunocompromized hosts: a report of four cases from Malaysia.
Rhodococcus equi, a recognized pathogen in horses, is emerging as a human opportunistic pathogen, especially in immunocompromized hosts. We describe four immunocompromized patients who had serious R. equi infections with an overall mortality of 75%. The natural habitat of R. equi is soil, particularly soil contaminated with animal manure. Necrotizing pneumonia is the commonest form of infection but extrapulmonary infections, such as wound infections and subcutaneous abscess, have also been described in humans. R. equi is cultured easily in ordinary non-selective media. Large, smooth, irregular colonies appear within 48 hours. It is a facultative, intracellular, nonmotile, non-spore forming, gram-positive coccobacillus, which is weakly acid-fast staining and bears a similarity to diphtheroids. It forms a salmon-colored pigment usually after 48 hours incubation. A particular characteristic of this organism is that it undergoes synergistic hemolysis with some bacteria on sheep blood agar. R. equi may be misidentified as diphtheroids, Mycobacterium species, or Nocardia. In vitro R. equi is usually susceptible to erythromycin, ciprofloxacin, vancomycin, aminoglycosides, rifampin, imipenem and meropenem. The organism can be difficult to eradicate, making treatment challenging. Increased awareness of the infection may help with early diagnosis and timely treatment.


AACAP 2001 research forum: challenges and recommendations regarding recruitment and retention of participants in research investigations.
Clinical research depends on the participation of representative samples. At the 2001 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Workgroup on Research conducted a research forum with the purpose of improving recruitment and retention of children and adolescents in research protocols. An interdisciplinary group of participants focused on (1) consumers and families, (2) communities, (3) professionals and health care delivery systems, (4) regulatory bodies, and (5) alternative research designs. Obstacles and challenges were identified and solutions were discussed. Key recommendations include the following: Investigators must become involved with community stakeholders and more explicitly communicate with families about research procedures, risks, and benefits; budgets should include explicit items for case management and referrals to families who do not meet entry criteria; the culture of clinical settings must incorporate research conducted by clinicians; regulatory bodies must streamline and coordinate protocols and procedures; designs emphasizing flexible treatment strategies and adaptive treatments should be encouraged; and health care systems should consider changing incentives for research participation, including the radical notion that reimbursement be made in terms of improvement rather than service units. An integrated approach is recommended, requiring direct involvement of investigators in communities where research is to be conducted.


catena-Poly[bis(trimethylphenylammonium) [hexa-mu-chlorido-dichloridotricuprate(II)]]: an alternating zigzag chain of CuCl(4) and Cu(2)Cl(6) complexes.
The title compound, {(C(9)H(14)N)(2)[Cu(3)Cl(8)]}(n), consists of parallel chains of alternating quasiplanar Cu(2)Cl(6) and planar CuCl(4) complexes separated by trimethylphenylammonium cations. Both inorganic complexes possess inversion symmetry. Pairs of neighboring chloride ions of the CuCl(4) complex each form a symmetric bridge and an asymmetric bridge to Cu(2)Cl(6) complexes on either side. The Cu(2)Cl(6) complex contains two symmetric chloride bridges between the copper cations with a terminal chloride bound to each five-coordinated Cu(II) ion. The CuCl(4) complex completes its coordination environment by forming two long semicoordinate contacts to the bridging chloride ions of neighboring Cu(2)Cl(6) complexes. The use of the bridging rather than the terminal chloride ions to form semicoordinate contacts generates a new zigzag chain structure that differs from the straight chain structures found for other A(2)Cu(3)Cl(8) compounds. The zigzag chain structure is adopted so as to conform to the shorter repeat distance dictated by stacking of the organic cations.


Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group.
This report provides follow-up progression-free survival (PFS) and median survival data for women who achieved clinical complete remission (cCR) from stage III ovarian cancer after first-line therapy and were treated with altretamine consolidation therapy. Patients who enrolled in the SWOG 9326 study from September 1993 to July 1997 were required to have documented cCR from stage III ovarian cancer following front-line platinum-based therapy. Treatment consisted of 6 months of oral altretamine at 260 mg/m(2)/day for 14 consecutive days of a 28-day cycle. Ninety-seven of 112 enrolled patients were evaluable for efficacy. This report presents median 6.2-year follow-up, dating from study registration. Median PFS was 28 (95% CI: 19-43) months. Median PFS for patients with optimal disease was 45 (95% CI: 27-48) months and for patients with suboptimal disease was 17 (95% CI: 12-26) months. Twenty-six of 61 (43%) patients with optimally debulked lesions and 5 of 36 (14%) patients with suboptimally debulked lesions remained disease free. Median survival of patients with optimally debulked disease has not been reached; median survival of patients with suboptimally debulked disease was 39 (95% CI: 19-51) months. No treatment-related adverse events were reported during the follow-up period. Consolidation therapy with oral altretamine was generally well tolerated and associated with prolonged progression-free and overall survival in the Phase II setting.


Mechanisms of target recognition and destruction in macrophage-mediated tumor cytotoxicity.
Macrophages can be activated to kill neoplastic cells selectively and efficiently. Recent studies from his laboratory on mechanisms of target recognition and injury operative in such lysis have centered on the binding of tumor targets to the secretion of a cytolytic protease (cytolytic factor (CF]) by activated murine macrophages. Activated macrophages selectively and extensively bind neoplastic cells; nonselective binding of a low degree is seen between numerous cell pairs. The selective binding of three nonadherent tumors, which is much firmer than the nonselective binding, appears to depend on shared recognition structures contained within plasma membranes of the three tumors. Activated macrophages also secrete a potent, cytolytic, serine protease of molecular weight approximately 40,000. Secretion of CF is closely correlated with activation for cytolysis, and specific protease inhibitors of CF block macrophage-mediated cytotoxicity. Binding of tumor cells to activated macrophages triggers augmented secretion of CF. Several lines of evidence indicate that the capacity for selective binding and the capacity for secreting CF are separate and independently regulated functions of activated macrophages and that each is necessary but not sufficient for completion of macrophage-mediated tumor cytotoxicity. Analysis of the complete lytic interaction between activated macrophages and tumor cells suggests that binding and then secretion of CF are sequentially involved. These data have been integrated into a minimal hypothetical model, which suggests that macrophage-mediated tumor cytotoxicity is a multistep event encompassing 1) selective binding of tumor cells to the surface of activated macrophages and 2) secretion of multiple lytic effector substances, including CF, from the activated macrophages.


Phylogeography of Buddleja crispa (Buddlejaceae) and its correlation with drainage system evolution in southwestern China.
Southwestern China is an area of active tectonism and erosion, yielding a dynamic, deeply eroded landscape that is hypothesized to have influenced the genetic structure of the resident populations of plants and animals. However, few studies have been conducted to examine the influence of changing river channels, particularly in the Yarlung Tsangpo area, on genetic distributions in plants. We here examine the population structure of Buddleja crispa, a dominant element of the dry, warm/hot river-valley communities, seeking to delimit the current population genetic structure and its relation to past changes in the courses of the major rivers in this area. • Two chloroplast DNA fragments were used to estimate the genetic variation and phylogeographic structure of the populations, and to infer nested clades, of the species. • We detected low intrapopulational haplotype diversity and higher overall population haplotype diversity (h(S) = 0.085, h(T) = 0.781). Molecular variance was mainly observed between groups (81.42%). Robust population genetic structure were detected by AMOVA (F(ST) = 0.967), coinciding with three nested clades (identified by NCPA) and five phylo-groups linked with paleo-drainage systems (identified by SAMOVA). No support for extensive spatial or demographical expansion was obtained. • A general pattern of genetic isolation by vicariance was inferred, and detected disjunct patterns strongly indicate that currently discontinuous drainage systems were historically linked. Most importantly, population subdivisions and genetic variation perfectly reflect the putative Paleo-Red-River drainage pattern, and Yarlung Tsangpo populations are closely related to Central Yunnan Plateau populations, indicating that they were previously connected by ancient river courses. Divergence times between these river systems estimated by molecular dating (in the Pleistocene) agree with previous findings.


Thermal behaviors, nonisothermal decomposition reaction kinetics, thermal safety and burning rates of BTATz-CMDB propellant.
The composite modified double base (CMDB) propellants (nos. RB0601 and RB0602) containing 3,6-bis (1H-1,2,3,4-tetrazol-5-yl-amino)-1,2,4,5-tetrazine (BTATz) without and with the ballistic modifier were prepared and their thermal behaviors, nonisothermal decomposition reaction kinetics, thermal safety and burning rates were investigated. The results show that there are three mass-loss stages in TG curve and two exothermic peaks in DSC curve for the BTATz-CMDB propellant. The first two mass-loss stages occur in succession and the temperature ranges are near apart, and the decomposition peaks of the two stages overlap each other, inducing only one visible exothermic peak appear in DSC curve during 350-550 K. The reaction mechanisms of the main exothermal decomposition processes of RB0601 and RB0602 are all classified as chemical reaction, the mechanism functions are f(alpha)=(1-alpha)(2), and the kinetic equations are dalpha/dt = 10(19.24)(1-alpha)(2)e(-2.32x10(4)/T) and dalpha/dt = 10(20.32)(1-alpha)(2)e(-2.32x10(4)/T). The thermal safety evaluation on the BTATz-CMDB propellants was obtained. With the substitution of 26% RDX by BTATz and with the help of the ballistic modifier in the CMDB propellant formulation, the burning rate can be improved by 89.0% at 8 MPa and 47.1% at 22 MPa, the pressure exponent can be reduced to 0.353 at 14-20 MPa.


Feedback and facilitation in the adrenocortical system: unmasking facilitation by partial inhibition of the glucocorticoid response to prior stress.
Previously stressed animals remain responsive to subsequent stressors, despite secreting an adequate corticosteroid signal during the first stress which should act to damp the response to a second stress. We have previously postulated that stress acts to facilitate subsequent responses in the adrenocortical system, and that this facilitation is balanced by the corticosteroid feedback signal. To test this hypothesis directly, we treated young male rats with cyanoketone (CK) to partially block the adrenal capacity to synthesize corticosterone (B). Subsequently, groups of CK- or vehicle (VEH)-treated rats were exposed to the FIRST stress of 30-min restraint with small blood samples collected at 0, 15, and 30 min. The FIRST stress was given to subgroups of rats 12, 9, 6, or 3 h before lights off (12 h) or lights on (24 h). At 12 or 24 h, rats were again restrained with blood samples at 0 ("basal") and 30 min (SECOND stress). Control groups were stressed for the first time when the experimental groups received their SECOND stress. Plasma ACTH and B concentrations were measured. Although in the absence of stress, basal B concentrations were normal in CK-treated compared to VEH-treated rats throughout the day, the B response to the FIRST stress was reduced by 60% in the CK- compared to the VEH-treated group. When the FIRST stress was performed during the time of lights on, "basal" plasma ACTH was elevated in CK groups at 12 h (lights off) compared to levels in both previously stressed VEH groups and unstressed CK controls. There was no difference at this time of day in the magnitude of the ACTH response to the SECOND stress in CK rats compared to that in CK rats receiving their only stress (controls) or that in VEH-treated rats receiving the SECOND stress. When first stress was performed during the time of lights off, "basal" plasma ACTH at 24 h (lights on) in CK and VEH rats were not different compared to levels in their respective unstressed controls. The ACTH response to the SECOND stress at 24 h was elevated in all previously stressed CK groups compared to that in either CK control or VEH groups. At neither time of day were SECOND stress ACTH concentrations in VEH rats different from those in control VEH rats. At 12 h (lights off), but not at 24 h (lights on), "basal" ACTH was significantly elevated in VEH rats above the unstressed VEH control values.(ABSTRACT TRUNCATED AT 400 WORDS)


Factors influencing the autologous mixed leukocyte reaction in normal subjects.
The proliferative response of T cells to autologous non-T cells (autologous mixed leukocyte reaction, AMLR) varies with the duration of incubation as well as the concentration and nature of the stimulator cells. The peak response was generally found on days 6, 7 or 8 of incubation, but with unseparated non-T cells, as well as varying in different individuals this varied in the same individual on different days. Removal of adherent cells from the stimulator population increased the magnitude of the peak response and improved day-to-day consistency both in size of peak response and in the duration of incubation required. Adherent cells were poor stimulators. Some of the variability in AMLR in normals and the differences between normal and disease subjects may relate to inclusion of an adherent cell population in the test and to the use of a fixed time period for incubation.


Effects of ionic strength and temperature on adsorption of atrazine by a heat treated kerolite.
The adsorption of 6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine (atrazine) on a heat treated kerolite sample at 600 degrees C (K-600) from pure water solution at 10 degrees C, 25 degrees C and 40 degrees C has been studied. The influence of the presence of 0.1 M KCl in the medium was also investigated for a better understanding of variables affecting the adsorption of this herbicide. The experimental adsorption data points were fitted to the Langmuir equation in order to calculate the adsorption capacities (Xm) of the samples; Xm values range from 2.3x10(3) mg kg-1 (pure water solution at 40 degrees C) up to 15.2x10(3) mg kg-1 (0.1 M KCl solution at 10 degrees C). The adsorption data were also fitted to the Freundlich equation in order to clarify the influence of the presence of 0.1 M KCl on atrazine adsorption. The parameter K10 obtained from this equation (adsorption capacity at an equilibrium solution concentration of atrazine equal to 10 mg l-1) shows clearly that the presence of 0.1 M KCl in the medium tends to increase the adsorption of atrazine in the range of temperature studied. The adsorption experiment also showed that the lower temperature, the more effective the adsorption of atrazine from both, pure water and 0.1 M KCl solutions. The values of the removal efficiency (R) obtained ranged from 39% at 40 degrees C (pure water solution) up to 93% at 10 degrees C (0.1 M KCl solution).


Influence of alterations in meal frequency on lipogenesis and body fat content in the rat.
Rats were allowed to eat only 2 hr per day (meal-fed) or were fed ad libitum (nibbler) for 12 wk; another group of animals was meal-fed for 3 wk and then fed ad libitum (converted I) while the fourth group of rats (converted II) was meal-fed for 3 wk, allowed to nibble for the next 3 wk, meal-fed from the 6th to 9th wk and then returned to ad libitum feeding for the last 3 wk. Body fat gain and food efficiency was increased in converted I rats. The lipogenic capacity of adipose tissue from meal-fed rats was greater than observen meal-fed rats were reverted to ad libitum feeding whereas lipogenic activity increased rapidly when ad libitum fed rats were switched to meal-feeding.


A computational framework for the statistical analysis of cardiac diffusion tensors: application to a small database of canine hearts.
We propose a unified computational framework to build a statistical atlas of the cardiac fiber architecture from diffusion tensor magnetic resonance images (DT-MRIs). We apply this framework to a small database of nine ex vivo canine hearts. An average cardiac fiber architecture and a measure of its variability are computed using most recent advances in diffusion tensor statistics. This statistical analysis confirms the already established good stability of the fiber orientations and a higher variability of the laminar sheet orientations within a given species. The statistical comparison between the canine atlas and a standard human cardiac DT-MRI shows a better stability of the fiber orientations than their laminar sheet orientations between the two species. The proposed computational framework can be applied to larger databases of cardiac DT-MRIs from various species to better establish intraspecies and interspecies statistics on the anatomical structure of cardiac fibers. This information will be useful to guide the adjustment of average fiber models onto specific patients from in vivo anatomical imaging modalities.


Between-register and within-register variability in event-finding and rates in the MONICA-France Project.
The 1985 and 1986 coronary event data from the three French MONICA Registers in Haute-Garonne (Toulouse), Bas-Rhin (Strasbourg) and the Urban Community of Lille (UCL) are used to compare the sources of information, the distribution of events in different diagnostic categories, and their possible effects on event rates. All three registers follow the MONICA protocol, and use the "cold pursuit" method, with data abstracted retrospectively from medical files or from the doctors establishing the causes of death. The health system and medical background are similar in the three centers. The distribution of the sources of information (in-hospital and out-of-hospital) and the distribution of events by diagnostic categories are different among centres. The possible effects of these differences on rates of definite myocardial infarction or possible coronary death are estimated between registers and within registers during a 2-year period. Cross-sectional comparisons are questionable, and possible false trends in event rates require special attention.


CD4+CD25- T cells in aged mice are hyporesponsive and exhibit suppressive activity.
Studies on humans and rodents have established that functional deterioration of CD4 T cells occurs with aging. We report in this study that approximately 70% of CD4(+)CD25(-) T cell preparations from individual 24-mo-old mice are hyporesponsive to in vitro stimulation with anti-CD3 Ab. The remaining 30% of CD4(+)CD25(-) T cell preparations showing the intermediate or normal responsiveness in the primary stimulation also exhibit the hyporesponsive properties after primary stimulation. Both of these hyporesponsive aged CD4(+)CD25(-) T cells could inhibit the proliferation of cocultured CD4(+)CD25(-) T cells from young mice, like CD4(+)CD25(+) T cells, which have recently been demonstrated as an immune regulator in young mice. Another experiment revealed that hyporesponsive aged CD4(+)CD25(-) T cells arrest the cell division of cocultured young CD4(+)CD25(-) T cells. The suppressive activity observed in aged CD4(+)CD25(-) T cells is aging-dependent, not mediated by humoral factors, cell-contact dependent, and broken by the addition of IL-2 or anti-GITR Ab, but not by anti-CTLA-4 Ab. These studies show that aging not only leads to a decline in the ability to mount CD4(+)CD25(-) T cell responses, but at the same time, also renders these aged CD4(+)CD25(-) T cells suppressive.


[The peculiarities of deposition of foreign particles in the skin region experimentally damaged by the electrical saw cutting element].
The objective of the present study was to detect the deposition of foreign particles and other introduced objects in the human skin region damaged by the electrical saw cutting elements and to use the data thus obtained for the estimation of the speed and the type of the instrument, the main characteristics of the cutter covering and/or composition of its surface. The experiments included the sawing of the skin fragments using the small steel saws differing in the type of the surface cover, such as the uncoated (steel), stained, nickel- or chromium-plated, blue-finished saws with the movement speed of the cutting element 500, 1000, 2500, 2,000, and 3,000 revolutions per minute. The study provided information about the peculiarities of deposition of foreign particles and other introduced objects in the damaged regions of the human skin that allow not only to establish the fact of using the electrical saw with a high-speed back-and-forth movements of the cutting element but also the type of the instrument and the main characteristics of its cover and/or the composition of its surface.


Standards for Clinical Trials in Male and Female Sexual Dysfunction: IV. Unique Aspects of Clinical Trials in Female Sexual Dysfunction.
The focus of this article, the fourth in the series, Standards for Clinical Trials in Male and Female Sexual Dysfunction, is on aspects of clinical trial design and measurement that are specific to clinical trials for treatments of female sexual dysfunction. Challenges in this area include the limited extent of treatment development and clinical trial research across the spectrum of female sexual dysfunctions, changing regulatory considerations, changing diagnostic criteria for female sexual dysfunction, and the need to articulate assessment procedures to these changes. Discussion focuses on approaches to addressing these challenges in clinical trials in female sexual dysfunction.


Electrochemical immunoassay for lactalbumin based on the use of ferrocene-modified gold nanoparticles and lysozyme-modified magnetic beads.
The authors describe a method for electrochemical determination of the breast cancer biomarker α-lactalbumin (α-LA) using disposable screen-printed carbon electrodes (SPCEs). Lysozyme-conjugated Fe3O4 nanoparticles (Lys-Fe3O4NPs) were used to capture α-LA on the surface of the SPCEs which then is trapped in an immunosandwich using secondary antibodies labeled with ferrocene-modified gold nanoparticles. The amperometric response of ferrocene (recorded at +0.1 V vs. silver pseudo-reference electrode) as well as the electrocatalytic activity of gold nanoparticles on the hydrogen evolution reaction (recorded at -1.0 V Vs Ag pseudo-reference electrode) was exploited to sense α-LA. A sensitive voltammetric response is observed, with (a) a sensitivity of 0.8789 μA·nM-1.cm-2, (b) a detection limit (LOD, at S/N = 3) as low as 0.07 ng·mL-1, and (c) linear response in the 0.75 to 630 ng mL-1 α-LA concentration range. The assay is selective and reproducible, and the SPCEs have good storage stability. The SPCEs were applied (a) to the analysis of (spiked) maternal milk, (b) of spiked serum from healthy and pregnant persons, and (c) of serum of patients suffering from breast cancer. Graphical abstract Schematic presentation of a sensitive electrochemical immunoassay platform based on ferrocene modified gold nanoparticles and lysozyme modified magnetic beads for the determination of alpha lactalbumin in human sera and breast milk by the amperometric response of ferrocene and hydrogen evolution reaction.


Perirhinal N-methyl-D-aspartate and muscarinic systems participate in object recognition in rats.
To determine the possible involvement of N-methyl-d-aspartate (NMDA) and muscarinic activation of the perirhinal cortex in object recognition, an NMDA antagonist (d,l-2-amino-5-phosphonopentanoic acid (AP5)) and a muscarinic antagonist (scopolamine) were injected into the perirhinal cortex of rats. A high dose of AP5 (60 mM) and two doses of scopolamine (20 and 80 mM), but not a low dose of AP5 (30 mM) alone, significantly impaired discrimination between novel and familiar objects in a spontaneous object recognition task, which is one of the recognition memory tasks. These results suggest that activation of both NMDA and muscarinic receptors in the perirhinal cortex contributes to object recognition.


[Protective effect on dentin of acid etching using prepolymerization of an enamel-dentinal adhesive (SEM study)].
In this report the Authors examined the protective action obtained on the dentin by using a varnish before acid etching. Sectional surfaces of twelve extracted teeth were observed by SEM, analysing the cover, the polymerization and the efficiency of dentine protection. The result show the effectiveness of the applied technique.


Provision of food and water in rodent whole body plethysmography safety pharmacology respiratory studies - Impact on animal welfare and data quality.
We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. Male Han Wistar rats or CD1 mice (n=8) were placed in WBP chambers and respiratory parameters recorded for approximately 6h on four separate occasions. On each occasion the animals were exposed to a different plethysmography chamber environment using a randomised design: no food/water (the standard conditions), water bottle, hydrating gel and wet food. In a further session, rats (n=8) were administered theophylline, or vehicle and respiratory parameters measured in the plethysmography chamber containing wet food. Respiratory parameters of rats were not significantly altered by the provision of water or food. Providing wet food resulted in reduced body weight loss. Administration of theophylline caused the expected increase in respiratory rate. When mice were given access to hydrating gel or wet food the respiratory parameters were significantly affected; respiratory rate and tidal volume were increased. Providing wet food resulted in reduced bodyweight loss. The provision of food and water did not impact on respiratory parameters in rats placed in WBP chambers. When provided with wet food, rats lost less bodyweight. Therefore, to improve welfare conditions for rats during WBP respiratory studies wet food should be provided when appropriate to the study design. In mice, provision of food and water led to changes in respiratory parameters, therefore these improvements in welfare conditions are not suitable for mice.


Artificial erection in diagnosis and treatment of impotence.
The use of artificial erection (AE) for the diagnosis and treatment of erectile failure was studied in 180 impotent males selected from a group of 440 men who underwent a complete multidisciplinary approach including nocturnal penile tumescence (NPT), arterial, neurologic, hormonal, and psychologic studies. Five groups were identified: (1) nonorganic (15.3%) impotence considered as a control group for AE normal values; (2) arterial (26.6%); (3) neurologic (12.2%); (4) arterial and neurologic (19.4%); and (5) a group of 47 remaining patients (26.1%) with abnormal NPT and normal arterial and neurologic studies who had the highest flow to obtain and maintain erection and were classified as "venous incompetence." Results of AE flows of patients of groups 2, 3, 4, and 5 are presented and discussed in the focus of erectile physiology, pathophysiology of erectile failure, and surgery. Patients of groups 2 and 4 with normal flows had a 26.6 per cent rate of improvement due to AE. Results and comments indicate that AE ranks as a major procedure in the diagnosis and treatment of impotence.


Modified fluid gelatin. An alternative macromolecular agent for centrifugal leukapheresis.
We studied a French modified fluid gelatin (MFG), substituting it for hydroxyethyl starch (HES) in leukapheresis procedures using three currently available blood cell separators, and observing its effects on the function of platelets and granulocytes. As a cell-collecting agent, we found MFG to be as effective as HES with intermittent flow centrifugation (Haemonetics), and slightly less so with one continuous flow device (IBM 2997). MFG was clearly less effective than HES with the Fenwal CS-3000 continuous flow separator, although we have reason to believe it would be possible to improve efficiency with this machine by changing the operating variables. Tests of platelet and granulocyte function showed negligible alteration with either agent and no difference between them. MFG disappears much more rapidly from the circulation than HES (after a single injection, it is undetectable by the third day). Reaction frequency with MFG was about the same as that of HES, with perhaps somewhat more frequent allergic manifestations.


Enhancement of catalytic performance of porcine pancreatic lipase immobilized on functional ionic liquid modified Fe3O4-Chitosan nanocomposites.
Magnetic chitosan nanocomposites were designed and fabricated by combining the magnetic nanoparticles Fe3O4 and chitosan covalently modified by imidazole-based ionic liquids with various functional groups, to be utilized as a support matrix for immobilization of porcine pancreatic lipase (PPL). Ionic liquids modified chitosan was characterized with nuclear magnetic resonance (NMR) and the nanocomposites were characterized with Fourier transform infrared spectroscopy (FTIR), vibrating-sample magnetometer (VSM), thermogravimetry analysis (TGA), Transmission electron microscope (TEM) and Scanning electron microscopy (SEM). The enzymatic properties of PPL were significantly improved by immobilization onto all thus prepared nanocomposites, and among the supports, modified with ionic liquids bearing hydroxyl group exhibited relatively enhanced performance. Particularly, the MCS-IL(8C)-OH-PPL exhibited the highest specific activity which was 6.68 times that of free PPL, and the residual activity of MCS-IL(8C)-OH-PPL remarkably maintained 91.5% of its initial activity even after 10 repeated cycles. The residual activity of MCS-IL(8C)-OH-PPL retained 55.8% after incubated in 6 M urea solution for 1 h and maintained the noticeable initial activity of 75.5% after incubated in phosphate buffer at 50 °C with pH 7.5 for 6 h. In conclusion, the study demonstrated that Fe3O4@Chitosan nanocomposites modified with functional ionic liquids could be utilized as a novel nanosupport for enzyme immobilization.


Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms.
The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.


Employment arrangements and mental health in a cohort of working Australians: are transitions from permanent to temporary employment associated with changes in mental health?
We investigated whether being in temporary employment, as compared with permanent employment, was associated with a difference in Short Form 36 mental health and whether transitions from permanent employment to temporary employment were associated with mental health changes. We used fixed-effects regression in a nationally representative Australian sample with 10 waves of data collection (2001-2010). Interactions by age and sex were tested. Two forms of temporary employment were studied: "casual" (no paid leave entitlements or fixed hours) and "fixed-term contract" (a defined employment period plus paid leave). There were no significant mental health differences between temporary employment and permanent employment in standard fixed-effects analyses and no significant interactions by sex or age. For all age groups combined, there were no significant changes in mental health following transitions from stable permanent employment to temporary employment, but there was a significant interaction with age (P = 0.03) for the stable-permanent-to-casual employment transition, because of a small transition-associated improvement in mental health for workers aged 55-64 years (β = 1.61, 95% confidence interval: 0.34, 2.87; 16% of the standard deviation of mental health scores). Our analyses suggest that temporary employment is not harmful to mental health in the Australian context and that it may be beneficial for 55- to 64-year-olds transitioning from stable permanent employment to casual employment.


Detection of Vaccinia Virus in Milk: Evidence of a Systemic and Persistent Infection in Experimentally Infected Cows.
Bovine vaccinia (BV) is a zoonosis caused by Vaccinia virus (VACV), which affects lactating cows and milkers. VACV DNA and infectious particles have been detected in milk of naturally infected cows. However, the period and pattern of VACV shedding in milk is unknown, as is whether the presence of VACV in milk is due to a localized or a systemic infection. To address those questions, eight lactating cows were inoculated with VACV in previously scarified teats. The experiment was divided in two phases. In Phase 1, milk samples were collected daily for 33 days, and in Phase 2, four animals from the first phase were immunosuppressed. In both phases, milk was collected with a sterile catheter on even days and by hand milking on odd days. All animals showed typical BV lesions in the inoculated teats. All milk samples were subjected to nested polymerase chain reaction (PCR) and real-time quantitative PCR to detect VACV DNA. PCR-positive samples were subjected to virus isolation. VACV DNA was intermittently detected in milk in both phases and infectious viral particles could be detected only in phase 2, on the 69th, 73rd, 74th, 77th, 79th, and 81st days postinfection. Despite the possibility of propagation of VACV through milk, it is known that milk continues to be drawn and marketed normally during outbreaks of the disease. The detection of both VACV DNA and infectious particles in milk samples draws attention to the potential public health risk associated with the consumption of milk from BV outbreaks. Detection of VACV in the milk from noninfected teats demonstrated that VACV shedding in milk might be related to a systemic infection. Moreover, it was shown that VACV DNA and viral infectious particles could be detected in milk even after healing of the lesions, demonstrating that VACV may cause a persistent infection in cattle.


Risks for obesity.
Whether or not obesity per se is an independent risk factor remains controversial. However, a variety of studies have shown that obesity precipitates certain well-known risk factors, such as glucose intolerance, hyperlipidemia, hyperestrogenemia, hypertension, and left ventricular hypertrophy. Distribution of adipose tissue also seems to influence cardiovascular risk; patients with predominantly male-pattern obesity exhibit more profound risk for cardiovascular disease.


Maximum entropy method for magnetoencephalography.
Simulations show that the maximum entropy method is a promising technique for image reconstruction in magnetoencephalography. An algorithm based on the work of Skilling and Bryan [1] and an appropriately modified expression for the "entropy" is shown to provide high-quality reconstructions of both isolated and dense distributions of neural current "dipoles", neglecting return currents. In particular the results are substantially superior to those obtained with the well-known minimum norm procedure.


Inside-out medial meniscus suture: an analysis of the risk of injury to the popliteal neurovascular bundle.
To assess the risk of damage to the popliteal neurovascular structures when inserting the needle through the posterior aspect of the knee during inside-out suture of the posterior horn of the medial meniscus. The first stage of our study consisted of simulating a virtual meniscal suture during magnetic resonance imaging by tracing a line from 3 different points (located medially [MP], centrally [CP], and laterally [LP] to the patellar tendon) to the posterior horn of the medial meniscus. This procedure was undertaken both at rest and with valgus stress. The next phase involved the suture of the posterior horns of medial menisci taken from cadaveric specimens, the needle being inserted through 3 separate locations (again located medially [MP], centrally [CP], and laterally [LP] to the patellar tendon). Finally, the distance from each suture thread to the aforementioned neurovascular bundle was measured. During the magnetic resonance imaging study, the measured distances at rest were 26.4 mm for MP, 28.8 mm for CP, and 31 mm for LP, whereas those recorded with valgus stress were 21.7 mm for MP, 23.6 mm for CP, and 26 mm for LP. In the second phase of the study (cadaveric specimen suture), the distances obtained were 22.6 mm for MP, 27.6 mm for CP, and 33 mm for LP. Our results indicate that when the needle is inserted through the 3 points investigated into the posteromedial region of the knee (10 mm from the posterior horn of the internal meniscus) during inside-out suture, it is far enough from the popliteal neurovascular bundle for the maneuver to be performed with a reasonable safety margin. However, this margin can be increased further still if the needle is inserted into the joint through a point located laterally to the patellar tendon. Inside-out suture performed 10 mm from the posterior horn of the internal meniscus through the portals studied offers a sufficient margin of safety to avoid damage to the popliteal neurovascular bundle.


Stabilization of insulin receptor subunit structure by glutathione-insulin transhydrogenase.
A partially purified insulin receptor preparation from rat liver was incubated at 37 degrees C with and without the protein-disulfide interchange enzyme, glutathione-insulin transhydrogenase (thiol: protein-disulfide oxidoreductase/isomerase, EC 1.8.4.2/5.3.4.1). Insulin-binding activity was then assessed by crosslinking receptor-125I-insulin complexes and subjecting them to electrophoresis on SDS-polyacrylamide gels in the absence and presence of reductant followed by autoradiography. Prior incubation of the receptor at 37 degrees C in the absence of the enzyme markedly decreased the subsequent binding of 125I-insulin to the holoreceptor (Mr 350 000) and to its subunits (Mr 180 000 and 130 000), while addition of the enzyme to the preincubation medium served to substantially prevent this decrease. The loss in binding at 37 degrees C was not restored by subsequent addition of the enzyme, nor was the loss prevented by any of the several known inhibitors of proteolysis. The apparent stabilization of receptor by transhydrogenase, as evidenced by the increase in binding above control levels, was proportional to both the enzyme concentration and the duration of incubation. These effects seem to be specific for transhydrogenase, since several other disulfide-containing proteins were found to be ineffective. These data suggest that the stabilization of the subunit structure of the insulin receptor at physiological temperatures may take place via a disulfide interchange reaction catalyzed by glutathione-insulin transhydrogenase.


Effects of cyclosporin A withdrawal on renal function and renal stimulation in liver transplant patients treated with triple-drug immunosuppression for over 2 years.
The influence of CsA withdrawal on the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) was prospectively studied in nine stable liver transplant recipients. Before CsA withdrawal (test 1), and 6 months thereafter (test 2) the renal function was determined by measuring GFR and the ERPF with 125I-iothalamate and 131I-hippuran respectively. The renal function was also stimulated with dopamine, with an amino-acid infusion and a combination of both. After CsA withdrawal the GFR increased, median from 74 ml min-1 to 90 ml min-1, (P < 0.04). The ERPF also increased, median from 310 ml min-1 to 380 ml min-1, (P < 0.03). In test 1 as well as in test 2 the renal function could be stimulated, especially with dopamine. GFR and ERPF improved, even after more than 2 years of CsA treatment. These results suggest that long-term CsA treatment impairs the renal function, though in these liver transplant patients CsA treatment did not prevent afferent and efferent arteriolar vasodilatation after renal stimulation. This reversible intrarenal vasoconstriction during CsA treatment may predict renal improvement after CsA withdrawal.


Comparison of early outcome from transperitoneal versus transhepatic percutaneous cholecystostomy.
To determine whether there is a statistically significant difference in the short-term clinical outcome in patients undergoing percutaneous cholecystostomy based on the anatomic route of gallbladder puncture that is, transhepatic versus transperitoneal. Our population consisted of 132 patients who: 1) presented with acute cholecystitis, 2) were at high risk for surgery because of comorbid conditions, 3) underwent percutaneous cholecystostomy either using computed tomography guidance or ultrasound guidance and whose anatomic route was known: the transhepatic percutaneous cholecystostomy group comprised 59 patients, the transperitoneal group 73 patients. Demographic characteristics and clinical parameters of the groups were compared statistically, as were postprocedure hospital course, complications and time to hospital discharge. The two groups were similar in demographic characteristics. There was a statistically significant tendency for computed tomography-guided percutaneous cholecystostomy to be transhepatic, and for ultrasound-guided percutaneous cholecystostomy to be transperitoneal. There were no differences in short-term postprocedure complications between the two groups. There was a tendency for shorter time to hospital discharge following transperitoneal percutaneous cholecystostomy. Transperitoneal and transhepatic percutaneous cholecystostomy are similar in short-term safety, with no significant difference in complication rate. The interventional radiologist can feel secure in performing percutaneous cholecystostomy using either approach.


Gypsy homologous sequences in Drosophila subobscura (gypsyDS).
Characterization of sequences homologous to the Drosophila melanogaster gypsy transposable element was carried out in Drosophila subobscura (gypsyDS). They were found to be widely distributed among natural populations of this species. From Southern blot and in situ analyses, these sequences appear to be mobile in this species. GypsyDS sequences are located in both euchromatic and heterochromatic regions. A complete gypsyDS sequence was isolated from a D. subobscura genomic library, and a 1.3-kb fragment which aligns with the ORF2 of the D. melanogaster gypsy element was sequenced. Comparisons of this sequence in three species (D. subobscura, D. melanogaster, and D. virilis) indicate that there is greater similarity between the D. subobscura-D. virilis sequences than between D. subobscura and D. melanogaster. Molecular divergence of gypsy sequences between D. virilis and D. subobscura is estimated at 16 MY, whereas the most likely divergence time of these two species is more than 60 MY. These data strongly suggest that gypsy sequences have been horizontally transferred between these species.


Chronic ethanol exposure during adolescence through early adulthood in female rats induces emotional and memory deficits associated with morphological and molecular alterations in hippocampus.
There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus.


Imbalance of G and C contents influences the sensitivity of single-strand conformation polymorphism.
After analyzing chicken ATPase6 by single-strand conformation polymorphism (SSCP), we observed two band species. But based on the sequencing results, we found two mutations, and one of them was not detected by SSCP. The primer P2 was designed to detect the additional mutation site, which was not detected by the original primer. And the P2 SSCP results then agreed with the sequencing data. Analysis of the percent of G and C bases and secondary structures indicated that it might be caused by a similar secondary structure which might be resulting from serious imbalance of G and C contents.


Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference.
A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline.


Transcobalamin II expression is regulated by transcription factor(s) binding to a hexameric sequence (TGGTCC) in the promoter region of the gene.
Transcobalamin II (TCII) is a plasma protein that transports cobalamin to tissues for cellular uptake by receptor-mediated endocytosis. Human umbilical vein endothelial cells (HUVEC) in culture constitutively express TCII. However, in other cell lines, TCII expression is dependent on high cell density. ECV304, a cell line with some properties of HUVEC, expresses TCII only when seeded at high density. An electrophoretic mobility-shift assay using nuclear extract from such high-density-seeded ECV 304 cells shifted a 24-bp oligonucleotide probe to generate an unique slow moving band that was competed out by unlabeled probe. This unique band was not observed with nuclear extract from low-density-seeded ECV304 cells. A 3(') sequence, 5(')-TGGTCC-3('), in the 24-bp oligonucleotide was identified as the binding site for the nuclear protein(s) because this band was not competed out when the hexameric sequence was scrambled to 5(')-CTTCTT-3('). Binding of a transcription factor(s) to this hexamer, that is located 121bp upstream of the transcription start site, appears to be essential for the regulated or constitutive expression of TCII.


Construction of transgenic swine with induced expression of Cre recombinase.
Miniature pigs have been recognized as valuable experimental animals in medical research. However, porcine models related to gene knockout of human diseases are not widely available. The objective of this study was to establish Mx1-Cre pigs using somatic cell nuclear transfer. In this study, we created transgenic pigs using somatic cell nuclear transfer (SCNT). Transfer of 210, 230, 250 and 215 zygotes to four surrogates produced 10 piglets. The Cre recombinase expression in transgenic pigs was studied using reverse transcriptase (RT)-PCR and immunohistochemistry. Mx1-Cre swine were shown to harbor the Cre gene in their genomic DNA using the PCR. In conclusion, Mx1-Cre transgenic piglets were successfully produced by SCNT. These transgenic swine, in conjunction with inducible systems for controlling Cre expression and function, are likely to have a profound impact on the study of human diseases.


Crystal structure of the human ecto-5'-nucleotidase (CD73): insights into the regulation of purinergic signaling.
In vertebrates ecto-5'-nucleotidase (e5NT) catalyzes the hydrolysis of extracellular AMP to adenosine and represents the major control point for extracellular adenosine levels. Due to its pivotal role for activation of P1 adenosine receptors, e5NT has emerged as an appealing drug target for treatment of inflammation, chronic pain, hypoxia, and cancer. Crystal structures of the dimeric human e5NT reveal an extensive 114° conformational switch between the open and closed forms of the enzyme. The dimerization interface is formed by the C-terminal domains and exhibits interchain motions of up to 13°. Complex structures with adenosine and AMPCP indicate that structural control of the domain movement determines the selectivity for monophosphate nucleotides. Binding modes of nucleotide-derived and flavonoid-based compounds complexed to the C-terminal domain in the open form reveal an additional binding pocket of ∼210 Å(3) that might be explored to design more potent inhibitors.


[Management of malaria in Togolese communities].
The objective of this study was to collect community basis data on prevention and home management of malaria for the future assessment of "Roll Back Malaria", the new world strategy of fighting against malaria. The study was carried out in 3 districts in Togo. Mothers were questioned about the quality of home management of uncomplicated malaria on 951 children aged under 5. Fathers were questioned about the use of mosquito bed nets in 597 households, and 246 women were interviewed about the prevention of malaria during pregnancy. Home management of children under treatment was correct in only 38.1% of cases and the drug observance was followed by only 35.4% of patients. Mosquito nets were used in 30.5% of households and only 16.5% were treated with insecticides. Only 22.7% of children under 5 slept under mosquito nets. 80% women made at least one antenatal visit and 74.4% received regular malaria chemoprophylaxis. Many efforts should be made in Togo to increase the quality of home management of malaria and the use of insecticide-treated bed nets.


Preferences of Israeli adolescents in regard to health services: a pilot study.
This pilot study surveyed Israeli adolescents' preferences regarding health services as a preliminary step for a national survey. A total of 444 students filled a questionnaire including demographics, personal health data, and preferences regarding 31 statements on health care, based on a Philadelphia questionnaire. Factors of most significant impact in seeking health care were cleanliness, integrity, respectfulness, knowledge, and competence. The 10 top statements important to Israeli teens included 9 of the 11 top statements of the Philadelphia teens. Future research may demonstrate change in outcome if adolescents' desires were attended based on a cultural adapted questionnaire.


Sterol binding by OSBP-related protein 1L regulates late endosome motility and function.
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols and cholesterol, and characterize a mutant, ORP1L Δ560-563, defective in oxysterol binding. While wild-type ORP1L clusters LE, ORP1L Δ560-563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT motif, suggesting that it is due to enhanced LE-ER interactions. Endosome motility is reduced upon overexpression of ORP1L. Both wild-type ORP1L and the Δ560-563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [(3)H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid transport are regulated by ORP1L.


Malignant lymphoma in northern Iraq: a retrospective analysis of 270 cases according to the World Health Organization classification.
Based on the World Health Organization (WHO) classification, the distribution of various subtypes of malignant lymphoma (ML) appears to differ by geographical region. studying the patterns of ML retrospectively in a previously uncharted country (Iraq) and to compare it with patterns observed regionally and worldwide. Two hundred and seventy lymphoma patients referred to two major histopathology referral centers in Northern Iraq, were categorized according to the WHO classification, using morphology and appropriate immunohistochemistry. There were 205 (76%) non-Hodgkin lymphomas (NHL) and 65 (24%) Hodgkin lymphomas (HL). Of the NHL, 91% were B-cell and 9% T-cell. The most common NHL was Diffuse large B-cell lymphoma (DLBCL) which comprised 52.2% of NHL, followed by Burkitt's lymphoma (BL) at 14.6%. The latter were mostly intestinal primaries. While follicular lymphomas (FL) were infrequent constituting 2.9 % of NHL. Extranodal primaries were found in 48.3% of NHL. Hodgkin's lymphoma (HL) included 48% nodular sclerosis (NS) and 37% mixed cellularity (MC). All HL were nodal primaries. Among NHL, the high frequencies of DLBCL, extra nodal primaries and intestinal BL, and the infrequency of FL in northern Iraq, is similar to reports from nearby countries but differs considerably from the West and Far East, indicating a shared regional Middle East influence on non-Hodgkin lymphoma patterns. In contrast to earlier Iraqi and regional studies on HL, NS has surpassed MC as the most frequent histological subtype in Northern Iraq. This trend probably reflects the increasing urbanization that has taken place in this region.


Validation and use of an indirect enzyme-linked immunosorbent assay for detection of antibodies to West Nile virus in American Alligators (Alligator mississippiensis) in Florida.
In October 2002, West Nile virus (WNV) was identified in farmed American alligators (Alligator mississippiensis) in Florida showing clinical signs and having microscopic lesions indicative of central nervous system disease. To perform seroepidemiologic studies, an indirect enzyme-linked immunosorbent assay (ELISA) was developed to determine exposure of captive and wild alligators to WNV. To validate the test, a group of WNV-seropositive and -seronegative alligators were identified at the affected farm using hemagglutination inhibition (HAI) and the plaque reduction neutralization test (PRNT). The indirect ELISA utilized a rabbit anti-alligator immunoglobulins polyclonal antibody as the secondary antibody, and inactivated WNV-infected Vero cells were used as the coating antigen. For all samples (n=58), the results of the ELISA were consistent with the HAI and PRNT findings. Plasma was collected from 669 free-ranging alligators from 21 sites across Florida in April and October 2003. Four samples collected in April and six in October were positive for WNV antibodies using HAI, PRNT, and the indirect ELISA. This indicated that wild alligators in Florida have been exposed to WNV. These findings can be used as a baseline for future surveys.


Chest CT of unresectable lung cancer.
A major role of CT in lung cancer patients is to spare those with unresectable lesions unnecessary surgery. Here the CT findings of inoperable lesions (Stages IIIB and IV in the new International Staging System) are illustrated.


Long-term predictive factors of the morphology based outcome in bare platinum coiled intracranial aneurysms: Evaluation by pre- and post-contrast 3D time-of-flight MR angiography.
Our aim was to identify long-term predictive factors of the morphology-based outcome (MBO) of bare platinum coiled intracranial aneurysms. A retrospective analysis of 96 bare platinum coiled intracranial aneurysms followed up from 1997 to 2016 using pre- and post-contrast 3D time-of-flight MR angiography (MRA) was performed. Logistic regression analysis was used to identify factors associated with a positive history of surrounding coil mass enhancement (SCME) and poor MBO. Spearman's rank correlation test was used to analyze the relationship between the initial angiographic result (IAR) class, sequential change of the SCME category, and MBO grade. Factors independently associated with poor MBO were incomplete IAR (OR=14.94, 95%CI: 2.46, 289.21, P=0.002) and a history of SCME (OR=4.13, 95% CI: 1.05, 18.65, P=0.043). The MBO grade strongly correlated with the IAR class (correlation coefficient [r]=0.84, P<0.0001). MBO grade correlated with sequential change of the SCME category (r=0.56, P<0.0001). The sequential change of the SCME category correlated with IAR class (r=0.53, P<0.0001). Although IAR and its class were strong long-term predictive factors of MBO, a history of SCME and upgrading of sequential change of SCME category were also long-term predictive factors of the MBO of bare platinum coiled intracranial aneurysms.


Gold Nanoclusters@Ru(bpy)₃²⁺-Layered Double Hydroxide Ultrathin Film as a Cathodic Electrochemiluminescence Resonance Energy Transfer Probe.
Herein, it is the first report that a cathodic electrochemiluminescence (ECL) resonance energy transfer (ERET) system is fabricated by layer-by-layer (LBL) electrostatic assembly of CoAl layered double hydroxide (LDH) nanosheets with a mixture of blue BSA-gold nanoclusters (AuNCs) and Ru(bpy)3(2+) (denoted as AuNCs@Ru) on an Au electrode. The possible ECL mechanism indicates that the appearance of CoAl-LDH nanosheets generates a long-range stacking order of the AuNCs@Ru on an Au electrode, facilitating the occurrence of the ERET between BSA-AuNC donors and Ru(bpy)3(2+) acceptors on the as-prepared AuNCs@Ru-LDH ultrathin films (UTFs). Furthermore, it is observed that the cathodic ECL intensity can be quenched efficiently in the presence of 6-mercaptopurine (6-MP) in a linear range of 2.5-100 nM with a detection limit of 1.0 nM. On the basis of these interesting phenomena, a facile cathodic ECL sensor has successfully distinguished 6-MP from other thiol-containing compounds (e.g., cysteine and glutathione) in human serum and urine samples. The proposed sensing scheme opens a way for employing the layered UTFs as a platform for the cathodic ECL of Ru(bpy)3(2+).


The role of routine pre-operative bedside echocardiography in detecting aortic stenosis in patients with a hip fracture.
The prevalence and severity of aortic stenosis in unselected patients admitted with a hip fracture is unknown. Derriford Hospital operates a routine weekday, pre-operative, targeted bedside echocardiography examination on all patients admitted with a hip fracture. We carried out a prospective service evaluation for 13 months from October 2007 on all 501 admissions, of which 374 (75%) underwent pre-operative echocardiography. Of those patients investigated, 8 (2%) had severe, 24 (6%) moderate and 113 (30%) had mild aortic stenosis or aortic sclerosis. Eighty-seven of 278 (31%) patients with no murmur detected clinically on admission had aortic stenosis on echocardiography and of the 96 patients in whom a murmur was heard pre-operatively, 30 (31%) had a normal echocardiogram. Detection of a murmur does not necessarily reflect the presence of underling aortic valve disease. However, if a murmur is heard then the likelihood of the lesion's being moderate or severe aortic stenosis is increased (OR 8.5; 95% CI 3.8-19.5). Forty-four (12%) of our unselected patients with fractured femur had either moderate or severe aortic stenosis (with or without moderate or severe left ventricular failure), or mild stenosis with moderately or severely impaired left ventricular function.


Multiple-trait genomic evaluation of linear type traits using genomic and phenotypic data in US Holsteins.
Currently, the USDA uses a single-trait (ST) model with several intermediate steps to obtain genomic evaluations for US Holsteins. In this study, genomic evaluations for 18 linear type traits were obtained with a multiple-trait (MT) model using a unified single-step procedure. The phenotypic type data on up to 18 traits were available for 4,813,726 Holsteins, and single nucleotide polymorphism markers from the Illumina BovineSNP50 genotyping Beadchip (Illumina Inc., San Diego, CA) were available on 17,293 bulls. Genomic predictions were computed with several genomic relationship matrices (G) that assumed different allele frequencies: equal, base, current, and current scaled. Computations were carried out with ST and MT models. Procedures were compared by coefficients of determination (R(2)) and regression of 2004 prediction of bulls with no daughters in 2004 on daughter deviations of those bulls in 2009. Predictions for 2004 also included parent averages without the use of genomic information. The R(2) for parent averages ranged from 10 to 34% for ST models and from 12 to 35% for MT models. The average R(2) for all G were 34 and 37% for ST and MT models, respectively. All of the regression coefficients were <1.0, indicating that estimated breeding values in 2009 of 1,307 genotyped young bulls' parents tended to be biased. The average regression coefficients ranged from 0.74 to 0.79 and from 0.75 to 0.80 for ST and MT models, respectively. When the weight for the inverse of the numerator relationship matrix (A(-1)) for genotyped animals was reduced from 1 to 0.7, R(2) remained almost identical while the regression coefficients increased by 0.11-0.26 and 0.12-0.23 for ST and MT models, respectively. The ST models required about 5s per iteration, whereas MT models required 3 (6) min per iteration for the regular (genomic) model. The MT single-step approach is feasible for 18 linear type traits in US Holstein cattle. Accuracy for genomic evaluation increases when switching ST models to MT models. Inflation of genomic evaluations for young bulls could be reduced by choosing a small weight for the A(-1) for genotyped bulls.


Augmentation of the neurochemical effects of cocaine in the ventral striatum and medial prefrontal cortex following preexposure to amphetamine, but not nicotine: an in vivo microdialysis study.
This study assessed the ability of cocaine to increase synaptic levels of dopamine (DA) in the ventral striatum (VS) and medial prefrontal cortex (mPFC) following repeated daily exposure to amphetamine or nicotine. In vivo microdialysis was used to assay DA levels in the awake freely moving male Sprague-Dawley rats. Three days following guide cannula implantation, subjects received 9 daily preexposure injections of amphetamine (1.0 mg/kg salt weight, IP), nicotine (0.6 mg/kg base weight, SC), or vehicle. Probes were then inserted and perfused with Ringer's solution overnight. Once stable baseline levels of DA were established, the subjects received a cocaine (15 mg/kg, IP) challenge injection and dialysate samples were collected every 20 minutes. Subjects preexposed to vehicle exhibited a 200% increase in DA levels in the VS and a 170% increase in the mPFC following the cocaine injection. DA recovery was significantly augmented in both regions in amphetamine-preexposed subjects with 450% and 285% increases above baseline levels observed in the VS and mPFC, respectively. In contrast, cocaine-induced DA levels in nicotine-preexposed subjects did not differ significantly from vehicle-preexposed controls in either brain region. Data are discussed in terms of alterations in the locomotor activating and reinforcing effects of cocaine following similar preexposure procedures.


The relationship of health care transition readiness to disease-related characteristics, psychosocial factors, and health care outcomes: preliminary findings in adolescents with chronic kidney disease.
The current study utilized the Disability-Stress-Coping Model to conceptualize how disease-related risk factors (disease severity, age of diagnosis, and disease burden) and psychosocial resilience factors (coping efficacy, family cohesion, and quality of life) influence health care transition (HCT) readiness when controlling for age and disease severity [1]. Additionally, the impact of low HCT readiness on emergency room visits and medication adherence was examined. The sample was comprised of 41 adolescents with chronic kidney disease (CKD) who ranged in age from 13 to 18 years (Mean=15.7). Multiple regression analyses were conducted. None of the disease-related factors were associated with HCT readiness. Of the psychosocial factors, only family cohesion was a significant predictor and accounted for 10% unique variance. Transition readiness was significantly related to both the number of self-reported emergency room visits and medication adherence such that high readiness was related to fewer visits to the emergency room and better medication adherence; these variables accounted for 6.4% and 14.9% of the unique variance respectively. These findings suggest that disease-related risk factors may be less critical to predicting transition readiness than resilience factors such as family cohesion. Additionally, when adolescents have low transition readiness they are likely to experience significant negative health outcomes.


Augmentation of natural killer (NK) cell activity by a streptococcal preparation, OK-432, in patients with malignant tumors.
Recently, a streptococcal preparation, OK-432 has been used successfully as an immunopotentiator for immunotherapy in patients with malignant tumors in Japan. In this paper, we report that the administration of OK-432 augments the cytotoxic activity of peripheral blood lymphoid cells against a natural killer (NK) cell-sensitive erythroleukemic cell line, K562, in tumor patients. In patients before or after surgery, sufficient amounts of OK-432 strongly augmented the cytotoxic activity within 3 days after the initial administration of OK-432. Thereafter the levels of cytotoxicity declined rapidly. The administration of a lower dose of OK-432 gave a lower increase in cytotoxicity. Enhanced cytotoxicity occurred with the reintroduction of OK-432 but remained at lower levels of activity. Characterization and fractionation of OK-432-induced effector cells revealed that the augmented cytotoxicity seemed to be carried mainly by NK cells. A low titer of interferon was detected in 3 of 10 patients within 72 hr after the first inoculation of the agent. Furthermore, we discuss the potency of OK-432 for the induction of interferon in detail.


Hypereosinophilia and acute bilateral facial palsy: an unusual presentation of a common disease.
A 60-year-old man presented with an acute, pruritic, erythematous rash associated with marked hypereosinophilia (2.34×10(9)/l (0.04-0.40)). There was eosinophilic infiltration on hepatic, bone marrow and lymph node biopsies, with multiple lung nodules and mild splenomegaly. However, extensive investigation excluded parasitic or bacterial causes, specific allergens or the Fip1L1 mutation seen in myeloproliferative hypereosinophilia. Six months into the illness, he developed an acute, left, complete lower motor neurone facial palsy over hours, and an acute right lower motor neurone facial palsy 2 weeks later, without recovery. Over the subsequent 3 months, he developed complex partial seizures, a transient 72-h non-epileptic encephalopathy and episodic vertigo with ataxia. Further investigation showed bilateral enhancement of the VII nerves and labyrinthis on gadolinium-enhanced MR brain scan, cerebrospinal fluid lymphocytosis and neurophysiological evidence of polyradicolopathy. His eosinophil count fell with corticosteroids, hydroxycarbamide, imatinib and ultimately mepolezumab, but without symptomatic improvement. Repeat lymph node biopsy showed Kaposi's sarcoma, leading to a diagnosis of HIV-1 infection with a modestly reduced CD4 count of 413×10(6)/l (430-1690). Hypereosinophila and eosinophilic folliculitis are recognised features of advanced HIV infection, and transient bilateral facial palsy occasionally occurs at the time of seroconversion. This is the first report of a chronic bilateral facial palsy likely due to primary HIV infection, not occurring during seroconversion and in association with hypereosinophilia. This case emphasises the protean manifestations of HIV infection and the need for routine testing in atypical clinical presentations.


Treatment with and without initial stabilizing surgery for primary traumatic patellar dislocation. A prospective randomized study.
There is no consensus about the management of acute primary traumatic patellar dislocation in young physically active adults. The objective of this study was to compare the clinical outcomes after treatment with and without initial stabilizing surgery for primary traumatic patellar dislocation in young adults. Forty young adults, thirty-seven men and three women with a median age of twenty years (range, nineteen to twenty-two years), who had an acute primary traumatic patellar dislocation were randomly allocated to be treated with initial surgical stabilization (eighteen patients, with each receiving one of two types of initial stabilizing procedures) or to be managed with an orthosis (twenty-two patients, including four who had osteochondral fragments removed arthroscopically). After a median of seven years, thirty-eight patients returned for a follow-up examination. Redislocations, subjective symptoms, and functional limitations were evaluated. Radiographs and magnetic resonance images were obtained at the time of randomization, and twenty-nine (76%) patients underwent magnetic resonance imaging at the time of final follow-up. A hemarthrosis as well as injuries of the medial retinaculum and the medial patellofemoral ligament were found on magnetic resonance imaging in all patients at the time of randomization. During the follow-up period, six of the twenty-one nonoperatively treated patients and none of the seventeen patients treated with surgical stabilization had a redislocation (p = 0.02). Four nonoperatively treated patients and two patients treated with surgical stabilization reported painful patellar subluxation. The median Kujala scores were 91 points for the surgically treated patients and 90 points for the nonoperatively treated patients. Thirteen patients in the surgically treated group and fifteen in the nonoperatively treated group regained their former physical activity level. At the time of follow-up, a full-thickness patellofemoral articular cartilage lesion was detected on magnetic resonance imaging in eleven patients; the lesions were considered to be unrelated to the form of treatment. In a study of young, mostly male adults with primary traumatic patellar dislocation, the rate of redislocation for those treated with surgical stabilization was significantly lower than the rate for those treated without surgical stabilization. However, no clear subjective benefits of initial stabilizing surgery were seen at the time of long-term follow-up.