Distribution of certain types of occlusal anomalies among Saudi Arabian adolescents in Jeddah city.
To assess the distribution of certain types of occlusal anomalies in a sample of Saudi adolescents aged 13-15 years in Jeddah city. Across-sectional study. Clinical examination of Saudi adolescents was carried out in the screening clinics, Faculty of Dentistry, King Abdul-Aziz University. Occlusal anomalies were recorded according to Björk and Co-workers (1964). 1,024 adolescents aged 13-14 years (608 males and 416 females) were randomly selected from ten intermediate schools. Participants were invited to dental school during the "Annual Dental Health Week" as a part of collaborative efforts between King Abdul-Aziz University and Ministry of Education. Distribution of post-normal occlusion, pre-normal occlusion, bimaxillary protrusion, overjet, overbite, midline deviation and maxillary and mandibular crowding were calculated for the examined subjects. Only 9% of the examined adolescents had normal occlusion. Post-normal occlusion, pre-normal occlusion and bimaxillary protrusion represented 21%, 15% and 8% of the studied sample respectively. Moderate and severe overjet and overbite accounted for 24% & 5% and 27% & 13%, respectively. Midline deviation was detected in 24% of the students. Mild, moderate and severe maxillary and mandibular crowding represented 9%, 26% & 4% and 11%, 38% & 9%, respectively. All the studied occlusal parameters except bimaxillary protrusion were statistically higher in females. Ninety one percent of the surveyed subjects exhibited some occlusal anomalies. These anomalies were generally higher among adolescent girls.


Detection of small numbers of immature cells in the blood of healthy subjects.
To determine the frequency of immature haemopoietic cells in the peripheral blood of healthy persons. Cytocentrifuge preparations were made using mononuclear leucocytes separated by a Ficoll-Hypaque density gradient. The slides were stained by May-Grünwald-Giemsa. The combination with immunoperoxidase technique allowed immunotyping of uncommon blood cells. Blast cells expressing the progenitor cell marker CD34 represented 0.11 (0.06) per cent (mean (SD)) of the total mononuclear leucocyte count; these were the haemopoietic progenitor cells in the peripheral blood. Dark blue cells expressing CD38, CD45, HLA-DR, CD4, CD11a, CD29, CD49d, CD50, and CD54 represented 0.30 (0.21) per cent of the mononuclear leucocytes; most of these cells did not express T, B, NK, myelomonocytic, progenitor cell, proliferation, activation, blood dendritic cell, or follicular dendritic cell markers. These were dendritic cell precursors in the peripheral blood. Very small numbers of cells expressing CD83 were found. Blast-like cells expressing CD45, HLA-DR, CD11a, and CD50 represented 0.15 (0.10) per cent of the mononuclear leucocytes; morphology and immunotyping supported the conclusion that these cells were poorly differentiated monocytes. Morphological investigation of mononuclear leucocytes in peripheral blood of healthy persons can be used to detect small numbers of blasts, dark blue cells, and blast-like cells. The immunoperoxidase technique can then be used for immunotyping of these cells. This simple method may be helpful in diagnosing haematological disorders.


Psychometric properties of the portuguese version of the Kansas City cardiomyopathy questionnaire in dilated cardiomyopathy with congestive heart failure.
Several studies have shown that patients with congestive heart failure (CHF) have a compromised health-related quality of life (HRQL), and this, in recent years, has become a primary endpoint when considering the impact of treatment of chronic conditions such as CHF. To evaluate the psychometric properties of the Portuguese version of a new specific instrument to measure HRQL in patients hospitalized for CHF: the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ was applied to a sample of 193 consecutive patients hospitalized for CHF. Of these, 105 repeated the assessment 3 months after admission, with no events during this period. Mean age was 64.4 +/- 12.4 years (21-88), and 72.5% were 72.5% male. CHF was of ischemic etiology in 4% of cases. This version of the KCCQ was subjected to statistical validation, with assessment of reliability and validity, similar to the American version. Reliability was assessed by the internal consistency of the domains and summary scores, which showed similar values of Cronbach alpha (0.50-0.94). Validity was assessed by convergence, sensitivity to differences between groups and sensitivity to changes in clinical condition. We evaluated the convergent validity of all domains related to functionality, through the relationship between them and a measure of functionality, the New York Heart Association (NYHA) classification. Significant correlations were found (p < 0.01) for this measure of functionality i patients with CHF. Analysis of variance between the physical limitation domain, the summary scores and NYHA class was performed and statistically significant differences were found (F = 23.4; F = 36.4; F = 37.4, p = 0.0001) in the ability to discriminate severity of clinical condition. A second evaluation was performed on 105 patients at the 3-month follow-up outpatient appointment, and significant changes were observed in the mean scores of the domains assessed between hospital admission and the clinic appointment (differences from 14.9 to 30.6 on a scale of 0-100), indicating that the domains assessed are sensitive to changes in clinical condition. The correlation between dimensions of quality of life in the KCCQ is moderate, suggesting that the dimensions are independent, supporting the multifactorial nature of HRQL and the suitability of this measure for its evaluation. The KCCQ is a valid instrument, sensitive to change and a specific measure of HRQL in a population with dilated cardiomyopathy and CHF.


Mylohyoid bridging in South Indian mandibles.
The incidence of the bony bridging of the mylohyoid groove of the mandible was studied in a collection of two hundred and twenty five south Indian mandibles. The bony bridging was noticed in 6.39% of the mandibles studied. The incidence of this trait shows a wide range of variation among the different population groups of India. The bony bridging of the mylohyoid may be useful as a non-metric trait in population studies when used in combination of other non-metric traits.


Tibial interference screw fixation in anterior cruciate ligament reconstruction with and without autograft bone augmentation.
Because tibial fixation of soft-tissue grafts in anterior cruciate ligament (ACL) reconstruction is problematic, this study aimed to develop a means of delivering bone graft evenly around tendon autograft and define any mechanical, radiologic, or histologic benefit using an ovine model. A device to deliver bone graft evenly throughout the tibial tunnel was developed. Forty mature sheep underwent simulated quadruple hamstring tendon-ACL reconstruction by use of a bioresorbable interference screw, either with or without bone graft augmentation of the tibial tunnel. Endpoint data were derived at time 0 and after 6 weeks in vivo. Radiostereometric analysis provided quantitation of the translational characteristics; computed tomography evaluated tunnel volume, and measures of yield strength and stiffness were obtained. Sequential fluorochrome administration assessed bone formation, and light microscopy surveyed the biological response. Radiostereometric analysis highlighted differences in the translational characteristics of ACL-deficient knees when compared with intact knees. Reconstructed knees (with or without autograft) showed significantly greater translation when compared with unoperated knees at 6 weeks; autograft bone augmentation provided no benefit. Neither tunnel volume nor yield strength nor stiffness was improved with the addition of autograft bone. No untoward histologic responses were observed. Bone apposition rates were similar between treatment groups. An even distribution of bone graft throughout the tunnels was observed. This model has confirmed the ability of the bone graft-delivery system to evenly distribute bone graft throughout the tunnels. However, the study has failed to show improvement in stability or fixation strength after augmentation with autograft bone. The autograft bone-delivery system may provide a means of establishing an osteoconductive/inductive environment. At this early juncture (6 weeks), no benefit could be defined. Its use in combination with bone morphogenetic proteins or stem cells may provide more rapid fixation, rehabilitation, and reconstitution of bone volume within the tunnel.


Genetic tools to enhance the study of gene function and regulation in Staphylococcus aureus.
The bursa aurealis transposon has been used to create transposon insertion libraries of Bacillus anthracis and Staphylococcus aureus. To provide a set of genetic tools to enhance the utility of these libraries, we generated an allelic-exchange system that allows for the replacement of the transposon with useful genetic markers and fluorescent reporter genes. These tools were tested in the Nebraska Transposon Mutant Library (NTML), containing defined transposon insertions in 1,952 nonessential S. aureus genes. First, we generated a plasmid that allows researchers to replace the genes encoding green fluorescent protein (GFP) and erythromycin resistance in the transposon with a noncoding DNA fragment, leaving a markerless mutation within the chromosome. Second, we produced allelic-exchange plasmids to replace the transposon with alternate antibiotic resistance cassettes encoding tetracycline, kanamycin, and spectinomycin resistance, allowing for the simultaneous selection of multiple chromosomal mutations. Third, we generated a series of fluorescent reporter constructs that, after allelic exchange, generate transcriptional reporters encoding codon-optimized enhanced cyan fluorescent protein (ECFP), enhanced yellow fluorescent protein (EYFP), DsRed.T3(DNT), and eqFP650, as well as superfolder green fluorescent protein (sGFP). Overall, combining the NTML with this allelic-exchange system provides an unparalleled resource for the study of S. aureus.


Occupational dermatoses among office personnel.
As offices have become more complex environments, the number of skin problems among office workers has increased. Among the agents implicated are carbonless copy paper, duplicating machines, formaldehyde, video display terminals, and rubber bands. Accurate diagnosis can be difficult but usually results in complete cure.


Activities of antennal and ocellar interneurones in the protocerebrum of the honey-bee.
1. Unit responses to olfactory and mechanical stimuli of the antennae, and illumination of the ocelli, were recorded extracellularly in the protocerebrum of the honey-bee. 2. Bimodal units responded both to antennal and to ocellar stimuli; antennal units responded to the former and the ocellar units to the latter. Some antennal units responded to olfactory stimuli (olfactory units), and others responded to mechanical stimuli (mechanical units). 3. Ocellar units in the brain showed phasic responses at the start and/or cessation of illumination. Six types of responses were found. 4. About two-thirds of the bimodal units showed the same type of response to stimulation of the antennae as to stimulation of the ocelli. Most of them showed excitation by each stimulus. 5. Bimodal units were distributed around the alpha-lobe in the protocerebral lobe, whereas the antennal and the ocellar units were widely distributed. 6. By turning off the ocellar illumination, background discharge frequency, and the pattern and magnitude of responses to antennal stimuli, were changed. The activities of the ocellar units were altered by inputs from the antenna. 7. It was postulated that antennal and ocellar inputs converge and interact with each other in the protocerebral lobe of the honey-bee.


[Transient complete AV block as a sequela of Borrelia myocarditis].
A 49-year-old man suddenly developed dyspnoea, sweating, fever (up to 38.5 degrees C), vertigo and angina. After emergency admittance to hospital the ECG showed 3 degrees A-V block, requiring temporary pacemaker insertion. The patient reported that a month before he had been bitten, probably by a tick. Serological tests demonstrated a recent Borrelia infection (rise of IgG antibody titre to 1:2048, IgM antibody titre to 1:128). Coronary angiography excluded any haemodynamically significant coronary heart disease as a cause of the conduction disorder. Myocardial biopsy showed changes pointing to a past myocarditis. This suggested Borrelia infection as the cause of the complete A-V block. Under treatment with broad-spectrum antibiotics for 15 days the fever subsided and the ECG became normal. Shortly before discharge, an elevated pulmonary wedge pressure on 150 W exercise indicated persistence of mild left-ventricular failure.


Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer.
Ovarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer. We applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy. We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo. This study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.


Beta-amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor alpha and NMDA receptors.
Although abundant reactive microglia are found associated with beta-amyloid (Abeta) plaques in Alzheimer's disease (AD) brains, their contribution to cell loss remains speculative. A variety of studies have documented the ability of Abeta fibrils to directly stimulate microglia in vitro to assume a neurotoxic phenotype characterized by secretion of a plethora of proinflammatory molecules. Collectively, these data suggest that activated microglia play a direct role in contributing to neuron death in AD rather than simply a role in clearance after plaque deposition. Although it is clear the Abeta-stimulated microglia acutely secrete toxic oxidizing species, the identity of longer-lived neurotoxic agents remains less defined. We used Abeta-stimulated conditioned media from primary mouse microglia to identify more stable neurotoxic secretions. The NMDA receptor antagonists memantine and 2-amino-5-phosphopetanoic acid as well as soluble tumor necrosis factor alpha (TNFalpha) receptor protect neurons from microglial-conditioned media-dependent death, implicating the excitatory neurotransmitter glutamate and the proinflammatory cytokine TNFalpha as effectors of microglial-stimulated death. Neuron death occurs in an oxidative damage-dependent manner, requiring activity of inducible nitric oxide synthase. Toxicity results from coincident stimulation of the TNFalpha and NMDA receptors, because stimulations of either alone are insufficient to initiate cell death. These findings suggest the hypothesis that AD brains provide the appropriate microglial-mediated inflammatory environment for TNFalpha and glutamate to synergistically stimulate toxic activation of their respective signaling pathways in neurons as a contributing mechanism of cell death.


Retinal structural changes in patients receiving tamoxifen therapy by spectral-domain optical coherence tomography.
Purpose: To evaluate choroidal thickness, ganglion cell complex (GCC) and photoreceptor outer segment (PROS) length were measured in patients with breast cancer undergoing tamoxifen therapy, using spectral-domain optical coherence tomography (SD-OCT); results were compared with those for normal eyes.Materials and methods: Forty-four patients with breast cancer, undergoing tamoxifen therapy, and 41 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500, 1000, 1500 μm), and temporal (temporal distance to fovea 500, 1000, 1500 μm) choroidal thickness measurements were performed using the enhanced depth imaging mode of SD-OCT. Using an Early Treatment Diagnostic Retinopathy Study (ETDRS) circle at the macular level, the automated retinal segmentation software was applied to determine the thickness of the GCC. PROS length was determined manually, as the distance from the inner surface of the ellipsoid zone to the inner surface of retina pigment epithelium.Results: The mean choroidal thickness was statistically greater in the tamoxifen group than controls in all quadrants (p < 0.001 for all quadrants). Of all tamoxifen users (44 eyes of 44 patients), 33 eyes (75%) had uncomplicated pachychoroid (UCP). Pachychoroid pigment epitheliopathy (PPE) was detected in five tamoxifen-group patients (11.3%). Patients with PPE in one eye had UCP in the fellow eye. Central serous chorioretinopathy findings were observed in one patient. Tamoxifen users had statistically lower GCC thickness in all inner rings of the ETDRS inlay and in the nasal outer ring only (p = 0.027, 0.002, 0.002, 0.001, and 0.030, respectively). No statistically significant difference in mean subfoveal PROS length was found between the groups.Conclusions: SD-OCT provides valuable information for identifying structural changes and evaluating ocular findings in patients receiving tamoxifen therapy. Increased choroidal thickness, PPE and thinning GCC were detected in tamoxifen users. These OCT findings may be an early indicator of retinal toxicity for patients undergoing tamoxifen therapy in the follow-up period.


Prostatic acid phosphatase in serum of patients with prostatic cancer is a specific phosphotyrosine acid phosphatase.
We developed an assay to measure at acid pH the phosphotyrosine phosphatase activity in sera from patients with prostatic cancer. The method used quantifies the inorganic phosphate liberated from phosphotyrosine after incubation with serum, followed by the deproteinization of the reaction mixture. A high acid phosphatase (EC 188.8.131.52) activity towards phosphotyrosine was observed in all sera from patients with increased activity of prostatic acid phosphatase. This activity represented 96% of prostatic acid phosphatase and 77% of total acid phosphatase activities. Moreover, it was correlated (r = 0.91) with the amount of serum prostatic acid phosphatase determined by radioimmunoassay. When serum acid phosphatase activity was measured on several phosphorylated substrates, preferential hydrolysis was demonstrated for those in which the phosphate group was esterified on an aromatic ring rather than those presenting an aliphatic chain. Among phosphoamino acids, only phosphotyrosine was a good substrate, with little or no activity observed with phosphoserine and phosphothreonine. Human seminal plasma and partially purified prostatic acid phosphatase, tested for their activity on some of these substrates, gave similar results. On the other hand, sera from patients with above-normal alkaline phosphatase activity and no prostatic disease showed little or no activity on phosphotyrosine at both acid and alkaline pH values. Evidence is presented that the prostatic acid phosphatase in serum is a specific phosphotyrosine acid phosphatase.


SMARCB1-deficient Vulvar Neoplasms: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 14 Cases.
Loss of expression of the SMARCB1 (INI1/BAF47/SNF5) tumor-suppressor protein, originally identified in pediatric malignant rhabdoid tumors, has been noted in significant percentages of epithelioid sarcomas of classical and proximal-type and in myoepithelial carcinomas. Epithelioid sarcoma and myoepithelial carcinoma are very rare in the vulvar region, and few of these cases have been evaluated for SMARCB1 protein loss by immunohistochemistry (IHC) or for SMARCB1 gene alterations by molecular genetic techniques. We studied the clinicopathologic, IHC, and molecular genetic features of 14 SMARCB1-deficient vulvar neoplasms. All available routinely stained sections were reexamined, and IHC analysis for wide-spectrum cytokeratins, high-molecular weight cytokeratins, epithelial membrane antigen, S100 protein, CD34, smooth muscle actin, desmin, and SMARCB1 was performed. Multiplex ligation-dependent probe amplification and DNA sequencing of the SMARCB1 gene was performed on 12 cases with sufficient available tissue. The 14 vulvar tumors occurred in adult women (mean age 46 y, range 22 to 62 y) and measured 1.1 to 8.8 cm in size (mean 4.7 cm). Tumors were classified as classical-type epithelioid sarcoma (N=1), proximal-type epithelioid sarcoma (N=6), myoepithelial carcinoma (N=4), and "SMARCB1-deficient vulvar sarcoma, not otherwise specified" (N=3) on the basis of combined histopathologic and IHC findings. One myoepithelial carcinoma showed divergent rhabdomyoblastic differentiation. All tested cases showed partial or complete SMARCB1 deletions (homozygous: 9 cases; heterozygous: 3 cases). One case with a heterozygous deletion also showed a c.528delC mutation in exon 5. Fluorescence in situ hybridization for EWSR1 rearrangement was performed for 3 cases classified as myoepithelial carcinoma and was negative. Follow-up (13 patients, range 5 to 72 mo, mean 31 mo) data showed 3 patients dead of disease, 1 alive with unresectable metastatic disease, 1 alive with radiographic evidence of extensive lymph nodal disease, and 8 alive without disease. We conclude that SMARCB1-deficient vulvar neoplasms chiefly comprise epithelioid sarcoma and myoepithelial carcinoma, although some defy easy classification. No association was seen between clinical behavior and the type of SMARCB1 alteration.


TGF-β and CTGF are Mitogenic Output Mediators of Wnt/β-Catenin Signaling in Desmoid Fibromatosis.
Desmoid fibromatosis is a locally aggressive clonal fibroblastic proliferation with high recurrence rates and no metastatic potential. Implicated molecular aberrations occur within the Wnt/β-catenin pathway (APC and β-catenin gene mutations). Transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) are profibrotic growth factors, downstream from nuclear translocation of β-catenin, that lead to increased fibrogenesis. CTGF (a downstream effector of TGF-β) is a matricellular protein that modulates the activity of growth factors, adhesion molecules, integrins, and extracellular matrix thus playing a central role in tissue remodeling and fibrosis. Recently there has been growing interest in use of extracellular matrix inhibitors for treatment of various fibrogenic diseases. Desmoid fibromatosis samples (n=15) were evaluated for expression of β-catenin, TGF-β, and CTGF using immunohistochemistry on formalin paraffin-embedded material. A control group comprising scar tissue and adjacent normal skin (n=10) were simultaneously immunostained with above mentioned markers. Real-time polymerase chain reaction was performed on frozen specimens of desmoid fibromatosis (n=6) and normal skin (n=2). All 15 desmoid tumors were positive for β-catenin (surrogate marker of Wnt/β-catenin pathway dysregulation) which was negative in control normal skin and scar samples. TGF-β and CTGF were negative in 9 of 10 normal skin controls. TGF-β and CTGF were positive in all cases of scar tissue. All 15 cases of desmoid tumors were positive for TGF-β and CTGF. The real-time polymerase chain reaction showed higher expression levels of TGF-β and CTGF in desmoid fibromatosis compared with normal skin. The high constitutive expression of β-catenin downstream effectors; TGF-β, CTGF has the potential for enabling targeted therapy.


Enhancing Selectivity of Protein Biopharmaceuticals in Ion Exchange Chromatography through Addition of Organic Modifiers.
Charge heterogeneity among therapeutic monoclonal antibodies (mAbs) is considered an important critical quality attribute and requires careful characterization to ensure safe and efficacious drug products. The charge heterogeneity among mAbs is the result of chemical and enzymatic post-translational modifications and leads to the formation of acidic and basic variants that can be characterized using cation exchange chromatography (CEX). Recently, the use of mass spectrometry-compatible salt-mediated pH gradients has gained increased attention to elute the proteins from the charged stationary phase material. However, with the increasing antibody product complexity, more and more selectivity is required. Therefore, in this study, we set out to improve the selectivity by using a solvent-enriched mobile phase composition for the analysis of a variety of mAbs and bispecific antibody products. It was found that the addition of the solvents to the mobile phase appeared to modify the hydrate shell surrounding the protein and alter the retention behavior of the studied proteins. Therefore, this work demonstrates that the use of solvent-enriched mobile phase composition could be an attractive additional method parameter during method development in CEX.


Air pollution and activation of implantable cardioverter defibrillators in London.
Air pollution may increase the incidence of ventricular cardiac arrhythmias. We investigated this in patients with implantable cardioverter defibrillators attending London clinics. We explored associations between dates of activation of defibrillators and daily concentrations of various metrics of particulate matter and of pollutant gases at lags from 0 to 5 days, using a fixed-stratum case-crossover analysis controlling for confounding factors. Over an average of 1200 days of observation, 705 patients experienced 5462 activation days. Of 11 pollutants considered, we found positive associations with particle sulfate, particulate matter with aerodynamic diameter less than 10 microm and less than 2.5 microm, ozone, and sulfur dioxide. Only the association for particle sulfate was not easily explainable by chance (for 1 microg/m, lag 0-1 day, odds ratio = 1.025 [95% confidence interval = 1.003 to 1.047]). There was little or no evidence of associations with markers of primary vehicle emissions (particle number concentration, black smoke, nitrogen oxides, and carbon monoxide). There was little evidence of interactions with clinical factors such as ischemic heart disease, frequency of activation, or cardiac drugs. Overall there was little evidence of an association between air pollution and activation of implantable cardioverter defibrillators. The pollutants with positive associations tended to be those of secondary origin with a regional distribution, rather than primary pollutants emitted from transport sources.


The Pinocchio effect and the Cold Stress Test: Lies and thermography.
We applied the use of thermography to cognitive neuropsychology, particularly as an objective marker of subjective experiences, in the context of lying. We conducted three experiments: (a) An important lie was invented by the participants in 3 min, and it was recounted by phone to a significant person while they were recorded by the thermographic camera, obtaining a face and hands map of the lie. (b) A similar methodology was carried out, but adding the Cold Stress Test (CST) of the dominant hand during the phone call, obtaining a second physiologic marker (the percentage of thermal recovery) to detect the lie. Further, it established a control condition where it generated anxiety in the participants using IAPS images with negative valence and high arousal, which were described by phone to a loved one. We obtained results that showed significant correlations between changes in body temperature and mental set. Of particular interest was the temperature of the nose and hand, which tended to decrease during lying (Experiment 1). The participants also showed a lower recovery of the temperature after the CST when they were lying (Experiment 2). (c) Experiment 3 is a replication of Experiment 2 but with a different type of lie (a more ecological task) in a different scenario (following the ACID interview, with the use of the phone eliminated and participants motivated to lie well). The main pattern of results was replicated. We obtained an accuracy of 85% in detection of deception with 25% of false alarms.


Development of SRAP, SRAP-RGA, RAPD and SCAR markers linked with a Fusarium wilt resistance gene in eggplant.
Fusarium wilt (Fusarium oxysporum Schlecht. f. sp. melongenae) is a vascular disease of eggplant (Solanum melongena L.). The objectives of this work were (1) to confirm the monogenic inheritance of fusarium wilt resistance in eggplant, (2) to identify molecular markers linked to this resistance, and (3) to develop SCAR markers from most informative markers. We report the tagging of the gene for resistance to fusarium wilt (FOM) in eggplant using SRAP, RGA, SRAP-RGA and RAPD markers. Analysis of segregation data confirmed the monogenic inheritance of resistance. DNA from F(2) and BC(1) populations of eggplant segregating for fusarium wilt resistance was screened with 2,316 primer combinations to detect polymorphism. Three markers were linked within 2.6 cM of the gene. The codominant SRAP marker Me8/Em5 and dominant SRAP-RGA marker Em12/GLPL2 were tightly linked to each other and mapped 1.2 cM from the resistance gene, whereas RAPD marker H12 mapped 2.6 cM from the gene and on the same side as the other two markers. The SRAP marker was converted into two dominant SCAR markers that were confirmed to be linked to the resistance gene in the F(2,) BC(1) and F(2) of BC(3) generations of the same cross. These markers provide a starting point for mapping the eggplant FOM resistance gene in eggplant and for exploring the synteny between solanaceous crops for fusarium wilt resistance genes. The SCAR markers will be useful for identifying fusarium wilt-resistant genotypes in marker-assisted selection breeding programs using segregating progenies of the resistant eggplant progenitor used in this study.


Effect of Clinical Geriatric Assessments and Collaborative Medication Reviews by Geriatrician and Family Physician for Improving Health-Related Quality of Life in Home-Dwelling Older Patients Receiving Polypharmacy: A Cluster Randomized Clinical Trial.
Polypharmacy and inappropriate drug regimens are major health concerns among older adults. Various interventions focused on medication optimization strategies have been carried out, but the effect on patient-relevant outcomes remains uncertain. To investigate the effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician (FP) on health-related quality of life and other patient-relevant outcomes in home-dwelling older patients receiving polypharmacy. Cluster randomized, single-blind, clinical trial. Norwegian FPs were recruited from March 17, 2015, to March 16, 2017, to participate in the trial with their eligible patients. Participants were home-dwelling patients 70 years or older, using at least 7 medications regularly, and having their medications administered by the home nursing service. Patients in the control group received usual care. Randomization occurred at the FP level. A modified intent-to-treat analysis was used. The intervention consisted of 3 main parts: (1) clinical geriatric assessment of the patients combined with a thorough review of their medications; (2) a meeting between the geriatrician and the FP; and (3) clinical follow-up. The primary outcome was health-related quality of life as assessed by the 15D instrument (score range, 0-1; higher scores indicate better quality of life, with a minimum clinically important change of ±0.015) at week 16. Secondary outcomes included changes in medication appropriateness, physical and cognitive functioning, use of health services, and mortality. Among 174 patients (mean [SD] age, 83.3 [7.3] years; 67.8% women; 87 randomized to the intervention group and 87 randomized to the control [usual care] group) in 70 FP clusters (36 intervention and 34 control), 158 (90.8%) completed the trial. The mean (SD) 15D instrument score at baseline was 0.708 (0.121) in the intervention group and 0.714 (0.113) in the control group. At week 16, the mean (SD) 15D instrument score was 0.698 (0.164) in the intervention group and 0.655 (0.184) in the control group, with an estimated between-group difference of 0.045 (95% CI, 0.004-0.086; P = .03). Several secondary outcomes were also in favor of the intervention. There were more drug withdrawals, reduced dosages, and new drug regimens started in the intervention group. This study's findings indicate that, among older patients exposed to polypharmacy, clinical geriatric assessments and collaborative medication reviews carried out by a geriatrician in cooperation with the patient's FP can result in positive effects on health-related quality of life. ClinicalTrials.gov identifier: NCT02379455.


[The population's knowledge concerning dengue fever, vectors, and control measures in São José do Rio Preto, São Paulo state]
Educational campaigns to inform the population about dengue fever, vectors, and related control measures have been carried out since 1985 by health services. In order to assess knowledge levels in São José do Rio Preto, São Paulo, a household survey was performed with a sample of 537 households in the urban area of São José do Rio Preto, São Paulo, in April and May 1995, where the same number of women were interviewed with questions about dengue fever, vectors, and control measures. Knowledge as displayed was satisfactory, except for that concerning hemorrhagic dengue. However, acquisition of knowledge was not followed by adoption of necessary control measures was insufficient to decrease infestation rates for dengue vectors in the city.


An 18S rRNA Workflow for Characterizing Protists in Sewage, with a Focus on Zoonotic Trichomonads.
Microbial eukaryotes (protists) are important components of terrestrial and aquatic environments, as well as animal and human microbiomes. Their relationships with metazoa range from mutualistic to parasitic and zoonotic (i.e., transmissible between humans and animals). Despite their ecological importance, our knowledge of protists in urban environments lags behind that of bacteria, largely due to a lack of experimentally validated high-throughput protocols that produce accurate estimates of protist diversity while minimizing non-protist DNA representation. We optimized protocols for detecting zoonotic protists in raw sewage samples, with a focus on trichomonad taxa. First, we investigated the utility of two commonly used variable regions of the 18S rRNA marker gene, V4 and V9, by amplifying and Sanger sequencing 23 different eukaryotic species, including 16 protist species such as Cryptosporidium parvum, Giardia intestinalis, Toxoplasma gondii, and species of trichomonad. Next, we optimized wet-lab methods for sample processing and Illumina sequencing of both regions from raw sewage collected from a private apartment building in New York City. Our results show that both regions are effective at identifying several zoonotic protists that may be present in sewage. A combination of small extractions (1 mL volumes) performed on the same day as sample collection, and the incorporation of a vertebrate blocking primer, is ideal to detect protist taxa of interest and combat the effects of metazoan DNA. We expect that the robust, standardized methods presented in our workflow will be applicable to investigations of protists in other environmental samples, and will help facilitate large-scale investigations of protistan diversity.


Lithography for imprinting colored patterns with quantum dots.
In this article, we report a new form of lithography that involves a reaction between a gas and an ion embedded in a polymer film. The principle is based on a combination of top-down and bottom-up approaches in which a transmission electron microscope grid is placed on a poly(vinylpyrrolidone) film containing Cd2+ ions, which is then exposed to H2S gas. This leads to the generation of a fluorescent yellow pattern due to the formation of CdS nanoparticles on exposed parts of the film. Also, we have used the same method to generate patterns in two colors by starting with a green fluorescent dye incorporated into the film and following the same procedure in which patterned yellow-orange CdS nanoaparticles are distributed over the background fluorescence of the dye. We have used fluorescence microscopy, UV-vis and fluorescence spectroscopy, transmission electron microscopy, atomic force microscopy, and X-ray diffraction methods for the characterization of the products and patterns. This method could possibly be a fairly general method of generating patterned materials on 2D and 3D substrates.


The role of dietary and plasma lipids in childhood atherogenesis.
Maria Daria Haust, MD, has made many significant contributions to our understanding of atherogenesis in children, particularly in associating the earliest lesions (fatty spots and streaks) with the normal growth and remodeling of arteries. It is my privilege to link her early work to more recent findings which show that the early lesions seen in the arteries of children before puberty bear no relationship to the risk of atherosclerosis in later life. Furthermore, present evidence supports the view that intervening in childhood (2-15 years) with low-fat low-cholesterol diets or even worse, lipid-lowering drugs to prevent atheroslerotic plaques in adulthood is wasted effort. Overzealous parents may unwittingly induce malnutrition in their children and many children with restricted access to palatable foods, will yearn for them even more as they become older leading to over weightness. Pediatricians from various scientific bodies around the world vary in their advice to mothers regarding diets for children. The program adopted by Health Canada on the advice of pediatricians in that country, which is also supported by the European Society of Pediatrics, Gastroenterology and Nutrition, recommends that the fat content of diets for children should be tapered gradually from 40% of energy at 2 years of age to 30% of energy at the conclusion of linear growth (late adolescence).


Potential correlation between menopausal status and the clinical course of orbital cavernous hemangiomas.
To evaluate the clinical course of radiologically diagnosed orbital cavernous hemangiomas in the setting of presumed changes in estrogen/progesterone levels. An institutional review board-approved retrospective cohort chart review of patients from January 1, 1983, to January 1, 2013, was undertaken searching both outpatient ophthalmology diagnoses and radiologic diagnoses, identifying 32 orbital cavernous hemangiomas, which were subsequently divided into group 1, presumed to have stable levels of estrogen/progesterone, and group 2, presumed to have decreasing levels of estrogen/progesterone. Patients were then categorized as having short-term, mid-range, or long-term follow up. Serial imaging studies were evaluated and graded as having increased, decreased, or remained stable in size. In group 1, no lesions decreased in size, 69% remained stable, and 31% increased in size. In group 2, no lesions increased in size, 45% remained stable, and 55% decreased in size. When evaluating only those patients with long-term follow up, many masses in group 1 increased in size, while the majority in group 2 decreased in size. In this study evaluating orbital cavernous hemangiomas over a span of 30 years, the authors found that in postmenopausal women with assumed decreasing levels of circulating estrogen/progesterone, the vast majority of lesions either remained stable or decreased in size, suggesting the effect of hormone levels on such vascular lesions and supporting the role for observation in asymptomatic individuals in this patient population.


Betulinic acid enhances 1alpha,25-dihydroxyvitamin D3-induced differentiation in human HL-60 promyelocytic leukemia cells.
Betulinic acid (BA) is a pentacyclic triterpene found in a number of medicinal plants and has been shown to cause apoptosis in a number of cell lines. We report here that BA may also have an effect on HL-60 cell differentiation. BA was cytotoxic to HL-60 cells with an IC50 of 5.7 microM after a 72-h treatment. Flow cytometry analysis showed that after exposure to 1-12 microM of BA for 72 h, approximately 10% of viable cells were in the sub-G1, presumably apoptotic, phase. At the same time differentiation was induced in approximately 10% (at 1 microM BA) to a maximum of 20% (at 6 microM BA) of cells as judged by the NBT-reduction test, and the expression of membrane markers CD11b and CD14. On the other hand, at 1 and 5 nM, 1alpha,25-dihydroxyvitamin D3 (DHD3) induced differentiation in approximately 10 and 70% of cells, respectively. At 1 nM DHD3, the addition of 1 microM BA increased differentiated cells from 10 to 43% and with 3 microM BA the increase was to 80%. BA also enhanced the effects of DHD3 in the expansion of the G1 cell population with a concomitant decrease of S phase cells. The effects of DHD3 and BA on CD11b and CD14 expression were inhibited by PD98059, a MEK inhibitor. Our results suggest that BA may enhance the effect of DHD3 in inducing mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase-mediated HL-60 cell differentiation.


Reproductive suppression of giraffe (Giraffa camelopardalis) under managed care using a GnRH immunological product.
Giraffe present unique contraception challenges as males persistently pursue females during estrus. Year-round pursuit during frequent recurring estrus can pose significant risk under slippery conditions. Complete ovarian suppression is a useful tool in giraffe because it eliminates estrous behavior, interest from the male, and controls reproduction. Effective reproduction control in giraffes has been achieved with porcine zona pellucida, oral melengestrol acetate, and depot medroxy-progesterone acetate. However, these methods allow some degree of folliculogenesis and estrous behavior. Improvest® is a gonadotropin releasing hormone (GnRH) immunological product that elicits antibodies against GnRH and abrogates the effects of endogenous GnRH. This study evaluated the efficacy of Improvest® for gonadal suppression in seven females and one male giraffe by monitoring steroid hormones. Seven female giraffe were treated intramuscularly with an initial dose, a booster at 4 weeks and maintenance boosters at 3-month intervals (600 µg/dose) for 12 months. Six females were on supplemental contraception during the induction phase because separation from males was not possible. In the male (treated with 400 µg), testosterone concentrations decreased after the second injection. However, even with low serum testosterone concentrations, mounting (of nontreated females) behavior was still observed occasionally. Ovarian activity was suppressed in all treated females and interest by the males stopped; supplemental contraceptives (during the induction phase) did not impede the effect of Improvest®. After 15.3 months (seven doses), Improvest® was discontinued in three females which no longer needed contraception. In these females, ovarian activity was noted approximately 90 days after the last dose.


Swine-origin influenza virus (SOIV) in Louisiana, 2009.
Since the new flu strain--named A(H1N1) or Swine Origin Influenza Virus (SOIV) to differentiate it from the seasonal H1N1--first emerged in Mexico and the United States in April, it has spread to 74 countries around the globe. The objectives of this article are to describe the initial stages of the epidemic in Louisiana and to draw some epidemiologic lessons for the future, which could be particularly useful if the pandemic continues during the winter season 2009-2010. Between April 22, 2009 (date when the first specimen was collected) to May 31, 2009, a six week period, there were 133 cases of SOIV infection detected in Louisiana. Cases were diagnosed in late April in several regions of the state, showing that when the first cases had been identified in Mexico and California, the infection was already widespread in Louisiana. The most affected age group was between the ages of five and 25.


Rat donor lung quality deteriorates more after fast than slow brain death induction.
Donor brain death (BD) is initiated by an increase in intracranial pressure (ICP), which subsequently damages the donor lung. In this study, we investigated whether the speed of ICP increase affects quality of donor lungs, in a rat model for fast versus slow BD induction. Rats were assigned to 3 groups: 1) control, 2) fast BD induction (ICP increase over 1 min) or 3) slow BD induction (ICP increase over 30 min). BD was induced by epidural inflation of a balloon catheter. Brain-dead rats were sacrificed after 0.5 hours, 1 hour, 2 hours and 4 hours to study time-dependent changes. Hemodynamic stability, histological lung injury and inflammatory status were investigated. We found that fast BD induction compromised hemodynamic stability of rats more than slow BD induction, reflected by higher mean arterial pressures during the BD induction period and an increased need for hemodynamic support during the BD stabilization phase. Furthermore, fast BD induction increased histological lung injury scores and gene expression levels of TNF-α and MCP-1 at 0.5 hours after induction. Yet after donor stabilization, inflammatory status was comparable between the two BD models. This study demonstrates fast BD induction deteriorates quality of donor lungs more on a histological level than slow BD induction.


Diadenosine polyphosphates: postulated mechanisms mediating the cardiac effects.
Diadenosine polyphosphates (Ap(n)A) are naturally occurring molecules which have been identified in human and guinea-pig cardiac tissue and whose physiological role is being established. They are stored in platelet dense granules in a metabolically inactive form. Ap(n)A form a class of dinucleotides, including diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) which have vasopressor actions in some tissues and vasodilator actions in others. Ap(n)A have been reported to interact with receptors distinct from P1 and P2-purinoceptors, and the presence of a unique Ap4A receptor has been demonstrated in isolated ventricular myocytes. Despite the identification of this receptor, other studies suggest that some of the cardiovascular effects are mediated by purinoceptors. Ap(n)A are released from platelet dense granules into the circulation during the platelet release reaction where they can reduce heart rate. The existence of Ap(n)A in myocardial tissue and platelet granules as well as their effects on coronary artery tone and myocardial function suggests a regulatory role for these compounds in the heart. This review describes the effects of Ap(n)A in terms of their coronary vasomotor and cardiac electrophysiological effects. The mechanism responsible for these effects is reviewed; including the involvement of purinergic receptors, the effects of alterations in extracellular pH and the contribution of nitric oxide and prostanoids. Potential pro-arrhythmogenic effects of diadenosine polyphosphates during myocardial ischaemia are also discussed as these compounds could contribute to inhomogeneities of repolarization in ischaemic myocardium.


Pore-Forming Monopeptides as Exceptionally Active Anion Channels.
We describe here a unique family of pore-forming anion-transporting peptides possessing a single-amino-acid-derived peptidic backbone that is the shortest among natural and synthetic pore-forming peptides. These monopeptides with built-in H-bonding capacity self-assemble into an H-bonded 1D columnar structure, presenting three types of exteriorly arranged hydrophobic side chains that closely mimic the overall topology of an α-helix. Dynamic interactions among these side chains and membrane lipids proceed in a way likely similar to how α-helix bundle is formed. This subsequently enables oligomerization of these rod-like structures to form ring-shaped ensembles of varying sizes with a pore size of smaller than 1.0 nm in diameter but sufficiently large for transporting anions across the membrane. The intrinsic high modularity in the backbone further allows rapid tuning in side chains for combinatorial optimization of channel's ion-transport activity, culminating in the discovery of an exceptionally active anion-transporting monopeptide 6L10 with an EC50 of 0.10 μM for nitrate anions.


Proteoglycans and catabolic products of proteoglycans present in ligament.
The aim of the present study was to characterize the proteoglycans and catabolic products of proteoglycans present in the tensile region of ligament and explant cultures of this tissue, and to compare these with those observed in the tensile region of tendon. Approx. 90% of the total proteoglycans in fresh ligament was decorin, as estimated by N-terminal amino acid sequence analysis. Other species that were detected were biglycan and the large proteoglycans versican (splice variants V(0) and/or V1 and/or V2) and aggrecan. Approx. 23% of decorin detected in the matrix was degraded. Intact decorin and decorin fragments similar to those observed in the matrix that retained the N-terminus were also observed in the medium of ligament cultures. Intact biglycan core protein was detected in the matrix and medium of ligament cultures, and two fragments originating from the N-terminal region of biglycan were observed in the matrix of cultured ligament. Versican and versican fragments that retained the N-terminus of versican core protein were detected in fresh matrix and medium of tendon cultures. Approx. 42% of versican present in the fresh ligament was degraded. Aggrecan catabolites appearing in the culture medium were derived from aggrecanase cleavage of the core protein. An intact link protein and a degradation product from the N-terminal region of type XII collagen were also detected in the medium of the ligament explant.


3D intestinal organoids in metabolic research: virtual reality in a dish.
The advent of near physiological organoid technology has produced a step change in our understanding of stem cells and has provided the research community with a powerful new cell based tool to model human physiology and disease. We review the pros and cons of intestinal organoid culture systems. The molecular and genetic tools to manipulate them and how they are being used to answer fundamental questions in metabolic research, including the function of enteroendocrine cells in health and disease.


Quantum Information and Algorithms for Correlated Quantum Matter.
Discoveries in quantum materials, which are characterized by the strongly quantum-mechanical nature of electrons and atoms, have revealed exotic properties that arise from correlations. It is the promise of quantum materials for quantum information science superimposed with the potential of new computational quantum algorithms to discover new quantum materials that inspires this Review. We anticipate that quantum materials to be discovered and developed in the next years will transform the areas of quantum information processing including communication, storage, and computing. Simultaneously, efforts toward developing new quantum algorithmic approaches for quantum simulation and advanced calculation methods for many-body quantum systems enable major advances toward functional quantum materials and their deployment. The advent of quantum computing brings new possibilities for eliminating the exponential complexity that has stymied simulation of correlated quantum systems on high-performance classical computers. Here, we review new algorithms and computational approaches to predict and understand the behavior of correlated quantum matter. The strongly interdisciplinary nature of the topics covered necessitates a common language to integrate ideas from these fields. We aim to provide this common language while weaving together fields across electronic structure theory, quantum electrodynamics, algorithm design, and open quantum systems. Our Review is timely in presenting the state-of-the-art in the field toward algorithms with nonexponential complexity for correlated quantum matter with applications in grand-challenge problems. Looking to the future, at the intersection of quantum information science and algorithms for correlated quantum matter, we envision seminal advances in predicting many-body quantum states and describing excitonic quantum matter and large-scale entangled states, a better understanding of high-temperature superconductivity, and quantifying open quantum system dynamics.


Determination of the Relationship between Expression and Functional Activity of Multidrug Resistance-Associated Protein 1 using Scanning Electrochemical Microscopy.
Cancer cells can develop multidrug resistance (MDR) after prolonged exposure to chemotherapeutic drugs, which is a severe impediment to successful treatment. MDR is typically associated with transmembrane proteins mediating efflux of administered drugs, thereby keeping their intracellular concentration below the threshold required to kill cells. Although expression assays based on flow cytometry and immunostaining have shown that multidrug resistance-associated protein 1 (MRP1) is prevalent in many cancer types, the functional activity of this efflux pump is more difficult to elucidate, especially at the single-cell level. Herein, we report the measurement of MRP1 functional activity in individual cancer cells using scanning electrochemical microscopy (SECM). Cells were cultured onto plastic substrates containing selective adhesion sites. Optical microscopy and SECM revealed that cells adapt to the underlying surface, while MRP1 functional activity increases once the dimensions of the adhesive islands become smaller than those of the cell itself. Time-lapse SECM imaging revealed a suitable window of 30 min to complete each measurement before the cell undergoes blebbing, which is associated with a considerable increase in functional activity. Distinct cell populations were produced by performing a doxorubicin drug challenge on two parental cell lines (e.g., wild-type HeLa cells and MRP1-overexpressing HeLa-R cells). Expression and functional activity of MRP1 were determined using flow cytometry and SECM, and our findings show that these parameters do not directly correlate. This suggests that functional activity may represent a powerful indicator of a cancer cell's response to chemotherapeutic treatment and should improve our understanding of efflux mechanisms based on MRP1.


Ten-Year Experience with Percutaneous Cryoablation of Renal Tumors: Tumor Size Predicts Disease Progression.
Introduction: Percutaneous cryoablation (PCA) has emerged as an alternative to extirpative management of small renal masses (SRMs) in select patients, with a reduced risk of perioperative complications. Although disease recurrence is thought to occur in the early postoperative period, limited data on long-term oncologic outcomes have been published. We reviewed our 10-year experience with PCA for SRMs and assessed predictors of disease progression. Materials and Methods: We reviewed our prospectively maintained database of patients who underwent renal PCA from March 2005 to December 2015 (n = 308). Baseline patient and tumor variables were recorded, and postoperative cross-sectional imaging was examined for evidence of disease recurrence. Disease progression was defined as the presence of local recurrence or new lymphadenopathy/metastasis. Results: Mean patient age was 67.2 ± 11 years, mean tumor size was 2.7 ± 1.3 cm, and mean nephrometry score was 6.8 ± 1.7. At mean follow-up of 38 months, local recurrence and new lymphadenopathy/metastasis occurred in 10.1% (31/308) and 6.2% (19/308) of patients, respectively. Excluding patients with a solitary kidney and/or von Hippel-Lindau, local recurrence and new lymphadenopathy/metastasis occurred in 8.6% (23/268) and 1.9% (5/268) of cases, respectively. Kaplan-Meier estimated disease-free survival was 92.5% at 1 year, 89.3% at 2 years, and 86.7% at 3 years post-PCA. Increasing tumor size was a significant predictor of disease progression (hazard ratio 1.32 per 1-cm increase in size, p = 0.001). Conclusions: PCA is a viable treatment option for patients with SRMs. Increasing tumor size is a significant predictor of disease progression following PCA.


Differential proliferative index of cancer stem-like cells in primary and recurrent medulloblastoma in human.
Medulloblastoma is the most common malignant primitive neuroectodermal tumor found in children. It has a tendency to recur at a primary or distant site. The mechanism underlying the regulation of the recurrence of medulloblastoma remains largely unknown. Recently, several reports have described that cancer stem-like cells (CSCs) can be identified and isolated in medulloblastoma. The authors therefore attempted to demonstrate the correlation between the biological features of medulloblastoma's CSCs and its recurrence. The data used were obtained in five consecutive patients with medulloblastomas who subsequently experienced tumor recurrence from 2004 to 2007. The authors performed the immunohistochemical assays to analyze the expression of CSC markers, proliferation features, and proliferative status of CSCs in primary and recurrent medulloblastoma. Of the five patients, two had recurrence at the primary site and three had a distant recurrence. CSC markers such as CD133(Prominin-1), DCX, PSA-NCAM, TUC-4, and nestin were expressed regardless of primary or recurrent medulloblastoma. All the five tumor specimens had a high proliferation index (PI). The PI was even higher in the group of patients after recurrence at a distant site (p<0.05), while the PI remained almost the same after primary recurrence. The Ki67/nestin-, Ki67/DCX-, and Ki67/TUC-4-positive cells were significantly increased in recurrent medulloblastoma at both the primary and distant sites, whereas CSCs in primary medulloblastoma showed much lower proliferative features (p<0.05). Our data suggest that tumorigenesis of medulloblastomas and their recurrence might be related to CSCs. More proliferating CSCs in medulloblastomas denote worse prognosis.


[Ampicillin concentration in the blood when administered by jet injection and needle-syringe methods].
The studies were carried out on 50 persons. Ampicillin was administered with the help of a jet injector B1-2 and needle syringe in doses of 250 or 500 and 500 mg respectively. When the drug was administered by infusion, its maximum blood levels were achieved earlier than after needle-syringe administration of the drug and were higher (22.83+/-4.10 and 6.3+/-0.09 gamma/ml respectively). Even when ampicillin was administered with the help of the injector in a dose of 250 mg its blood levels were much higher than those after needle-syringe administration in a dose of 500 mg. After jet infusion the prolongation of the drug retention time in the blood at therapeutical levels was observed as compared to the needle-syringe administration.


Adaptive compressed sensing for the fast terahertz reflection tomography.
In this paper, an adaptive compressed sensing is proposed in order to enhance the performance of fast tetrahertz reflection tomography. The proposed method first acquires data at random measurement points in the spatial domain, and estimates the regions in each tomographic image where much degradation is expected. Then, it allocates additional measurement points to those regions, so that more data are acquired adaptively at the regions prone to degradation, thereby improving the quality of the reconstructed tomographic images. The proposed method was applied to the T-ray reflection tomography system, and the image quality enhancement by the proposed method, compared to the conventional method, was verified for the same number of measurement points.


[In vivo restriction of Escherichia coli-transforming DNA by endonuclease R.M.EcoRI].
Transformation of Escherichia coli K-12 for various chromosomal markers was accomplished by using AB1157 recBC+ strain as a recipient. The yield of transformants was reduced 10-fold, as compared with that obtained in JC7623 recBC sbcB recipient. Elimination of transformation has been obtained for arg, pro, his markers in AB1157 (pSA14) harbouring the R.M.EcoRI coding plasmid. Production of restriction endonuclease in this strain did not affect the efficiency of transformation for thr, leu markers. The presence of pSA25 which is isogenic to pSA14 but devoid of R.M.EcoRI genes has been irrelevant to transformation for leu, arg, pro, his, thr markers. Correlation between the restriction of transformed markers in vivo and in vitro is discussed.


Toll-like receptors, inflammation, metabolism and obesity.
Obesity is a highly prevalent health problem in Western countries that leads to many important diseases such as type 2 diabetes and metabolic syndrome being now considered an inflammatory chronic disease. Adipocytes are no longer considered passive cells storing fat since they are major producers of inflammatory cytokines during obesity. Adipocytes and macrophages share many biological properties including the synthesis of similar molecules regulating inflammation. Fatty acid levels are elevated in obesity and induce inflammatory pathways by yet a mostly unknown mechanism, leading to the development of insulin and leptin resistance. Recent studies suggest that these effects could be mediated through the activation of toll-like receptors (TLR). TLR signalling pathways might contribute to the development of obesity-associated insulin resistance, thus representing a connection between innate immunity and metabolism. Here, we summarize the recent evidence for the important role that TLRs play in adipose tissue, obesity and insulin resistance.


Tumor necrosis factor-alpha promoter variants and iron phenotypes in 785 hemochromatosis and iron overload screening (HEIRS) study participants.
We sought to determine if TNF promoter variants could explain iron phenotype heterogeneity in adults with previous HFE genotyping. HEIRS Study participants genotyped for C282Y and H63D were designated as high transferrin saturation (TS) and/or serum ferritin (SF) (high TS/SF), low TS/SF, or controls. We grouped 191 C282Y homozygotes as high TS/SF, low TS/SF, or controls, and 594 other participants by race/ethnicity as high TS/SF or controls. Using denaturing high-performance liquid chromatography (DHPLC), we screened the TNF promoter region in each participant. We performed multiple regression analyses in C282Y homozygotes using age, sex, HEIRS Study Field Center, and positivity for TNF -308G-->A and -238G-->A to determine if these attributes predicted ln TS or ln SF. DHPLC analyses were successful in 99.3% of 791 participants and detected 9 different variants; TNF -308G-->A and -238G-->A were the most prevalent. Most subjects positive for variants were heterozygous. The phenotype frequencies of each variant did not differ significantly (p<0.05) across subgroups of C282Y homozygotes, or across white, black, Hispanic, and Asian non-C282Y homozygotes subgrouped as high TS/SF phenotypes and controls. TNF -308G-->A positivity was a significant predictor of initial screening ln TS but not ln SF; TNF -238G-->A predicted neither ln TS nor ln SF. We conclude that TNF promoter variants have little, if any, effect on initial screening SF values in adults with or without C282Y homozygosity. We cannot exclude a possible association of homozygosity for TNF promoter variants on TS and SF values.


Skeletal effects of parathyroid hormone infusion in ovariectomized rats with or without estrogen repletion.
We employed skeletally matured rats to study changes in biochemical markers of bone turnover, bone mineral density (BMD), and bone biomechanics produced by continuous elevation of parathyroid hormone (PTH) in estrogen-deplete and -replete rodents. Ninety-six 7-month-old virgin female rats were divided randomly into 12 groups (n = 8) and treated as follows. One group was killed on the day of surgery. The remaining groups were either bilaterally ovariectomized (Ovx) or sham-operated and left untreated for 8 weeks, at which point, two groups, one sham and one Ovx, were killed. The remaining nine groups were treated for 2 weeks or 4 weeks. One sham and two Ovx groups received subcutaneous implants of Alzet miniosmotic pumps with vehicle for PTH. Two Ovx groups were given pumps with vehicle as well as a subcutaneous implant of 17beta-estradiol, which delivered 10 microg/kg per day. Two Ovx groups were implanted with rat PTH(1-34) in Alzet miniosmotic pumps, which delivered 30 microg PTH/kg per day. Two Ovx groups were implanted with both estradiol pellets and PTH-loaded pumps. One group of Ovx animals from each treatment was killed after 2 weeks and the other after 4 weeks. Biochemical markers of bone turnover, serum osteocalcin and urinary free pyridinoline, BMD, and mechanical strength of excised bones were measured. As expected, there was a significant increase in N-terminal PTH and serum calcium levels in all PTH infusion groups. Both serum osteocalcin and urinary pyridinoline showed a rapid increase within the first 2 weeks of the PTH infusion and remained elevated at week 4. In estrogen-replete groups, osteocalcin increased by week 2 of PTH infusion but pyridinoline did not increase until week 4. BMD of the distal and proximal femur showed the expected decrease 8 weeks after ovariectomy but did not exhibit any further changes during the 4 weeks of treatment with vehicle. Four weeks of PTH infusion in Ovx animals resulted in BMD loss at the midshaft, distal, and proximal regions of the femur. Estrogen repletion by itself, beginning 8 weeks after ovariectomy, produced no change in BMD at any site when compared with from Ovx vehicle-treated rats. Estrogen repletion in PTH-infused Ovx animals resulted in significant improvements of BMD comparable with sham-operated animals at all three femoral regions. The indentation test at the cancellous bone of the distal femur, three-point bending test at the midshaft femur, and cantilever bending test at the femoral neck showed that the changes in mechanical strength in these sites were consistent to the changes found in BMD. Our results showed that (1) continuously elevated levels of PTH induced additional loss of BMD in estrogen-deficient animals beyond the rapid bone loss phase associated with ovariectomy, (2) estrogen repletion, given by implant, to PTH-infused Ovx animals, reversed these BMD changes increasing BMD to levels comparable with estrogen-sufficient rats, and (3) these changes were reflected in the mechanical strength determined at these sites. These results lend experimental support that hormone replacement therapy may benefit bone health in postmenopausal women with primary hyperparathyroidism (PHPT). In addition, it raises the possibility that a continuous elevation of PTH could exert anabolic effects on skeletal tissue if its catabolic component can be minimized.


Stability of serrated gold coil markers in prostate localization.
We investigated the stability of serrated gold coils (Visicoil) implanted within the prostate glands of patients undergoing definitive external beam radiotherapy for prostate cancer. Radiopaque Visicoils of diameter 0.75 mm and median length 3 cm (range 2-4 cm) were implanted, one into each lobe of the prostate glands of 30 patients planned for external beam treatment. The coils were visualized on CT simulation and again after 25 fractions of treatment (5 WK). Data from 30 patients were studied, of whom 19 also received androgen ablation therapy. The average change in the distance between the two coils over five weeks of treatment was 0.8mm (± 0.6 mm), with a maximum of 2.5 mm in one patient. Average residual errors (standard deviations) for the positions of individual coil segments after five weeks of therapy were only 0.7 mm LAT, 0.6 mm AP, and 0.4 mm SI. The average change in distance between the coils over five weeks compared favorably with published data regarding marker seed stability. Overall, less than a 2 mm margin (i.e., 2 standard deviations) would adequately compensate for positioning uncertainty of the coils in more than 95% of cases.


Multidetector CT of the liver and hepatic neoplasms: effect of multiphasic imaging on tumor conspicuity and vascular enhancement.
Our aim was to determine which of three contrast-enhanced phases (early arterial, late arterial, or portal venous) was optimal for achieving maximal enhancement of the celiac artery, portal vein, and hepatic parenchyma. We also wanted to learn which phase provided the maximal tumor-to-parenchyma difference when using multidetector CT (MDCT) with fixed timing delays. Fifty-two patients with suspected or known hepatic tumors underwent multiphasic contrast-enhanced MDCT using double arterial (early and late arterial) and venous phase acquisitions with fixed timing delays. All patients were administered 150 mL of IV contrast material at an injection rate of 4 mL/sec. Images were acquired at 20 sec for the early arterial phase, 35 sec for the late arterial phase, and 60 sec for the portal venous phase. Attenuation measurements of the celiac artery, portal vein, normal hepatic parenchyma, and the hepatic tumor were compared. Three reviewers independently and subjectively rated tumor conspicuity for each of the three phases. Ratings were compared using kappa statistics. Late arterial phase images showed maximal celiac axis attenuation, whereas portal venous phase images revealed the highest portal vein and normal hepatic parenchymal attenuation. Maximal tumor-to-parenchyma differences for hypovascular tumors was superior in the portal venous phase, but we found no significant differences in maximal tumor-to-parenchyma differences for hypervascular tumors among the evaluated phases. On subjective analysis, interobserver agreement was moderate to very good for the three phases. All three reviewers graded both hypovascular and hypervascular tumor conspicuity as superior in either the late arterial phase or the portal venous phase in most patients. In only one patient was the early arterial phase graded as superior to the late arterial and portal venous phases (by two of the three reviewers). When MDCT of the liver is performed using fixed timing delays, maximal vascular and hepatic parenchymal enhancement is achieved on either late arterial phase or portal venous phase imaging. In most patients, early arterial phase imaging does not improve tumor conspicuity by either quantitative or subjective analysis.


Impairment of rapid movement in Huntington's disease.
Patients with Huntington's disease (HD) and relatives at risk were examined with respect to their capacity to produce rapid voluntary motor activity. For this purpose, the fastest possible self-paced single isometric forefinger extensions and the fastest alternating forefinger movements were tested. In addition to these fastest voluntary performances, the time course of spontaneous hyperkinetic finger movements and the peak frequency of finger and hand tremor were analysed as a measure of the temporal characteristics of involuntary movements. Comparison of these parameters in HD patients and individuals at risk with age and sex-matched normal controls revealed a significant slowing of all types of contractions or movements in the majority (up to 95%) of the patients and in up to 40% of the relatives at risk. Reaction times were only slightly prolonged, and the abnormalities of the movement parameters showed no correlation with detailed psychometric data. Hence it is unlikely that the disturbance in the execution of rapid motor acts is due to dementia. Tremor was also slower than normal and the hyperkinesias were still slower than the fastest voluntary contractions. It appears from this study that slowness of motor performance is not only evident in Parkinson's disease but may represent a more general dysfunction in basal ganglia disease.


[Expression of matrix Gla protein and bone morphogenetic protein 2 in renal papillary tissues in patients with calcium oxalate kidney stones].
To compare expression levels of matrix Gla protein (MGP) and bone morphogenetic protein 2 (BMP-2) in Randall's plaque of renal papillary tissues in patients with calcium oxalate kidney stones and the underlying mechanism for stone formation. Methods: A total of 30 samples of Randall's plaque in renal papillary tissues from patients with calcium oxalate kidney stones were collected from the Department of Urology of Xiangya Hospital of Central South University from April, 2015 to December, 2015 and served as an experimental group. Ten samples of renal papillary tissues in patients undergone renal tumor nephrectomy were collected from the same hospital and served as a control group. The expressions of MGP and BMP-2 mRNA and protein were detected by quantitative real-time PCR and Western blot.Meanwhile, immunohistochemical technique was used to observe the expressions of MGP and BMP-2 in different parts of renal papillary tissues in the 2 groups. Results: 1) The mRNA expression levels of MGP in the experimental group and the control group were 0.760±0.804 and 1.365±0.348, respectively, with significant difference between them (P<0.05). Them RNA levels of BMP-2 in the experimental group and the control group were 2.500±0.725 and 1.485±0.870, respectively, with significant difference between them (P<0.05). The expression levels of MGP protein in the experimental group and the control group were 0.130±0.424 and 0.202±0.704, respectively, with no significant difference between them (P>0.05). The expression levels of BMP-2 protein in the experimental group and the control group were 0.885±0.220 and 0.682±0.272, respectively, with significant difference between them (P<0.05). The immunohistochemistry showed that the protein expression of MGP in the experimental group was lower than that in the control group, while the protein expression of BMP-2 in the experimental group was higher than that in the control group (both P<0.05). Conclusion: The BMP-2 expression is increased while MGP expression is decreased in renal papillary tissues in patients with calcium oxalate kidney stones, and the formation of calcium oxalate kidney stone might be a kind of osteogenetic reaction or ectopic calcification.


Is there a blood pressure lowering effect of MRAs in heart failure? An overview and meta-analysis.
Although mineralocorticoid antagonists (MRAs) have been proposed as effective fourth-line blood pressure (BP) lowering agents in resistant hypertension, this effect in heart failure is undetermined. In this synthesis of heart failure randomized controlled trials (RCTs), we evaluated the extent of BP lowering following MRA treatment against placebo. We searched Medline and the Cochrane Collaboration Library databases from 1991 to September 2016 for RCTs, in which MRAs were compared with placebo. The quality of RCTs was assessed with Cochrane risk of bias tool. Outcomes were the extent of systolic and diastolic BP lowering. We included seven studies (13,354 patients, 65.8% males, mean age of 66.3 years, mean follow-up period of 9.4 months, mean baseline BP of 123.5/75.0 mmHg) of MRAs compared with placebo. MRAs were not significantly associated with systolic - 1.8 (95% CI: - 8.0, 4.4) mmHg or diastolic - 0.3 (95% CI: - 3.4, 2.7) mmHg, BP reduction. Although systolic BP was not lowered by spironolactone, diastolic BP was lowered by - 3.0 (95% CI: - 3.4, - 2.6) mmHg. Eplerenone treatment did not significantly lowered systolic [- 0.04 (95% CI: - 4.4, 4.3) mmHg], but it was associated with minimal diastolic BP increase [1.0 (95% CI: 0.5, 1.53) mmHg]. MRAs were not associated with systolic and diastolic BP reduction in heart failure patients. This finding suggests that MRAs should be used according to their indications in heart failure independently of initial BP levels.


Passage of CD18- and CD18+ bovine neutrophils into pulmonary alveoli during acute Pasteurella haemolytica pneumonia.
CD18 is a subunit for three beta 2 integrin molecules (Mac-1, p150, 95, LFA-1), which are expressed on the plasma membrane of neutrophils. These molecules mediate passage of neutrophils into sites of infection. In children and animals that lack CD18 expression, neutrophil infiltration is impaired in most tissues. However, in lung, CD18- neutrophils have been identified in the airway spaces during spontaneous episodes of pneumonia. To determine whether CD18 is vital for passage through the pulmonary alveolar wall, lung lobes of cattle with neutrophils that were deficient in CD18 expression (CD18-) and cattle with normal CD18 expression (CD18+) were inoculated with Pasteurella haemolytica by fiberoptic bronchoscopy; control lobes were inoculated with pyrogen-free saline (PFS). Neutrophil passage into alveolar lumina at 4 and 6 hours postinoculation was measured by computerized image analysis. Blood levels of neutrophils for CD18- cattle ranged from 12- to 26-fold higher than for CD18+ cattle prior to inoculation, and counts in both groups rose slightly postinoculation. In P. haemolytica-inoculated lobes, total numbers of neutrophils in alveolar lumina of the two groups were similar. An increase in the number of neutrophils in the alveolar wall was fourfold greater in CD18- cattle than in CD18+ cattle. In PFS-inoculated lobes, the number of neutrophils in the alveolar wall was sixfold higher in CD18 cattle than in CD18+ cattle. This work shows that by 4 and 6 hours, CD18- neutrophils enter the alveolar lumen at a rate similar to that in CD18+ cattle. Higher numbers of CD18- neutrophils are present in the alveolar wall of control (PFS) and bacteria-inoculated lobes. Thus, the CD18- cells are increased in the walls of alveoli and numbers of neutrophils that enter the alveolar lumen are similar in CD18+ and CD18- cattle.


Macular cone abnormalities in retinitis pigmentosa with preserved central vision using adaptive optics scanning laser ophthalmoscopy.
To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.


The Diagnostic, Therapeutic and Prognostic Relevance of Neutrophil Extracellular Traps in Polytrauma.
Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research.


Islet β-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model.
Type 1 diabetes is preceded by islet β-cell dysfunction, but the mechanisms leading to β-cell dysfunction have not been rigorously studied. Because immune cell infiltration occurs prior to overt diabetes, we hypothesized that activation of inflammatory cascades and appearance of endoplasmic reticulum (ER) stress in β-cells contributes to insulin secretory defects. Prediabetic nonobese diabetic (NOD) mice and control diabetes-resistant NOD-SCID and CD1 strains were studied for metabolic control and islet function and gene regulation. Prediabetic NOD mice were relatively glucose intolerant and had defective insulin secretion with elevated proinsulin:insulin ratios compared with control strains. Isolated islets from NOD mice displayed age-dependent increases in parameters of ER stress, morphologic alterations in ER structure by electron microscopy, and activation of nuclear factor-κB (NF-κB) target genes. Upon exposure to a mixture of proinflammatory cytokines that mimics the microenvironment of type 1 diabetes, MIN6 β-cells displayed evidence for polyribosomal runoff, a finding consistent with the translational initiation blockade characteristic of ER stress. We conclude that β-cells of prediabetic NOD mice display dysfunction and overt ER stress that may be driven by NF-κB signaling, and strategies that attenuate pathways leading to ER stress may preserve β-cell function in type 1 diabetes.


Decrements in hippocampal activity with item repetition during continuous recognition: an fMRI study.
fMRI (1.5 mm isotropic voxels) was employed to investigate the relationship between hippocampal activity and memory strength in a continuous recognition task. While being scanned, subjects were presented with colored photographs that each appeared on four occasions. The requirements were to make one response when an item was presented for the first or the third time and to make a different response when an item appeared for the second or the fourth time. Consistent with prior findings, items presented for the first time elicited greater hippocampal and parahippocampal activity than repeated items. The activity elicited by repeated items declined linearly as a function of number of presentations ("graded" new > old effects). No medial-temporal lobe regions could be identified where activity elicited by repeated items exceeded that for new items or where activity elicited by repeated items increased with number of presentations. These findings are inconsistent with the proposal that retrieval-related hippocampal activity is positively correlated with memory strength. We also identified graded new > old effects in several cortical regions outside the medial-temporal lobe, including the left retrosplenial/posterior cingulate cortex and the right lateral occipito-temporal cortex. By contrast, graded old > new effects were evident in bilateral mid-intraparietal sulcus and precuneus.


Advancing the application of systems thinking in health: analysing the contextual and social network factors influencing the use of sustainability indicators in a health system--a comparative study in Nepal and Somaliland.
Health systems strengthening is becoming a key component of development agendas for low-income countries worldwide. Systems thinking emphasizes the role of diverse stakeholders in designing solutions to system problems, including sustainability. The objective of this paper is to compare the definition and use of sustainability indicators developed through the Sustainability Analysis Process in two rehabilitation sectors, one in Nepal and one in Somaliland, and analyse the contextual factors (including the characteristics of system stakeholder networks) influencing the use of sustainability data. Using the Sustainability Analysis Process, participants collectively clarified the boundaries of their respective systems, defined sustainability, and identified sustainability indicators. Baseline indicator data was gathered, where possible, and then researched again 2 years later. As part of the exercise, system stakeholder networks were mapped at baseline and at the 2-year follow-up. We compared stakeholder networks and interrelationships with baseline and 2-year progress toward self-defined sustainability goals. Using in-depth interviews and observations, additional contextual factors affecting the use of sustainability data were identified. Differences in the selection of sustainability indicators selected by local stakeholders from Nepal and Somaliland reflected differences in the governance and structure of the present rehabilitation system. At 2 years, differences in the structure of social networks were more marked. In Nepal, the system stakeholder network had become more dense and decentralized. Financial support by an international organization facilitated advancement toward self-identified sustainability goals. In Somaliland, the small, centralised stakeholder network suffered a critical rupture between the system's two main information brokers due to competing priorities and withdrawal of international support to one of these. Progress toward self-defined sustainability was nil. The structure of the rehabilitation system stakeholder network characteristics in Nepal and Somaliland evolved over time and helped understand the changing nature of relationships between actors and their capacity to work as a system rather than a sum of actors. Creating consensus on a common vision of sustainability requires additional system-level interventions such as identification of and support to stakeholders who promote systems thinking above individual interests.


Vertical Bone Augmentation Using Ring Technique with Three Different Materials in the Sheep Mandible Bone.
The purpose of this study was to examine the volumetric alterations and osseointegration properties in the augmented area of the ring technique using different types of bone graft material in sheep mandible bone. Three different materials (columnar forms, 7-mm diameter, 3-mm height) were stabilized using dental implants with a turned surface in the mandible bone of Finnish Dorset cross-bred sheep: group A, autogenous bone; group B, bovine bone; group C, biphasic bone substitute. Animals were euthanized after 5 weeks (N = 6). Three-dimensional image data by digital oral scanner were taken at the surgery and sacrifice, and the volume alteration of the material was calculated. The bone samples were fixed in formalin and dehydrated in ethanol. Resin-embedded samples were subjected to non-decalcified ground sectioning, and histologic and histomorphometric analysis (bone and material area alteration, bone-to-implant contact [BIC]) were done. In three-dimensional (3D) image analysis, group A showed a statistically higher percentage of remaining materials compared with groups B and C. The histologic observation showed no new bone formations around the implants in all groups, especially at the maxillary site of the implant in the augmented area. In histomorphometric analysis, group A showed a statistically higher percentage of bone area (BA) compared with groups B and C; however, in all groups, bone-to-implant contact (BIC) showed low values, and there were no statistical differences between groups. The results of this study suggested that the autogenous bone maintained bone volume around the dental implant using the ring technique, and the impact of surface properties was of some importance; osseointegration with the turned surface in the augmented area showed low BIC values in all groups.


Aerial Imagery Analysis - Quantifying Appearance and Number of Sorghum Heads for Applications in Breeding and Agronomy.
Sorghum (Sorghum bicolor L. Moench) is a C4 tropical grass that plays an essential role in providing nutrition to humans and livestock, particularly in marginal rainfall environments. The timing of head development and the number of heads per unit area are key adaptation traits to consider in agronomy and breeding but are time consuming and labor intensive to measure. We propose a two-step machine-based image processing method to detect and count the number of heads from high-resolution images captured by unmanned aerial vehicles (UAVs) in a breeding trial. To demonstrate the performance of the proposed method, 52 images were manually labeled; the precision and recall of head detection were 0.87 and 0.98, respectively, and the coefficient of determination (R 2) between the manual and new methods of counting was 0.84. To verify the utility of the method in breeding programs, a geolocation-based plot segmentation method was applied to pre-processed ortho-mosaic images to extract >1000 plots from original RGB images. Forty of these plots were randomly selected and labeled manually; the precision and recall of detection were 0.82 and 0.98, respectively, and the coefficient of determination between manual and algorithm counting was 0.56, with the major source of error being related to the morphology of plants resulting in heads being displayed both within and outside the plot in which the plants were sown, i.e., being allocated to a neighboring plot. Finally, the potential applications in yield estimation from UAV-based imagery from agronomy experiments and scouting of production fields are also discussed.


Brewer's asthma due to malt contamination.
We describe a case of a 28 year old brewery worker who developed asthma whilst grinding malt. Lung function measurements demonstrated deterioration and improvement in lung function associated with work and absence from work. Inhalation challenge with ground malt from the brewery was positive but with ground malt from another source was negative suggesting a contaminant of the malt was responsible. Culture of the brewery malt showed heavy contamination with Aspergillus niger, but A. niger skin test was negative and aspergillus-specific IgG was not detected in the patients serum. Removal of the subject from the grinding room resulted in resolution of symptoms and normal lung function. We discuss the role of A. niger as an aetiological agent for occupational asthma with reference to the above case.


Inside-to-outside growth and turnover of the wall of gram-positive rods.
Gram-positive, rod-shaped bacteria, given a pulse of peptidoglycan precursors, first exhibit a lag before the second or turnover phase of peptidoglycan commences. This is because new material is inserted on the inner face of the wall and gradually displaced through the wall. Based on this experimental observation, a mathematical model was constructed and compared with experimental data obtained in several laboratories for the first and second phases of wall turnover of Bacillus subtilis. The model allows the parameters of the process to be estimated for experiments with any labeling time. According to the surface stress theory the wall which is layed down immediately outside the cytoplasmic layer is in an unextended conformation. As subsequent additions of murein occur, the wall moves outward, becomes stretched, and bears the stress due to hydrostatic pressure. Ultimately, peptide and glycosyl bonds become cleaved. At the end of the lag phase the cleavage becomes so extensive that wall fragments are liberated into the medium. This strategy permits rod-shaped growth. In some experimental situations the half-life of wall radioactivity in this second phase roughly equals the doubling time; consequently, the exponential release probably does not represent random turnover but instead is the result of expansion of the underlying wall that continues to create strain which favors autolysis action. The slower turnover of the third phase, where there is a much slower loss, is also included in the analysis.


Dural adhesion to porous cranioplastic implant: A potential safety concern.
Patient-specific implants are used for cranioplastic skull reconstruction when large bone flaps must be replaced or where there are complex or critical contours, especially near the face. These implants have a low complication rate, with poor fit and postoperative infection being the most common complications. We report here a potentially serious hazard that may arise from the use of porous implants. A 45-year-old woman sustained severe head trauma in a motor vehicle accident that required urgent surgical intervention. Because of progressive resorption of her native bone flap, she underwent replacement of her native flap with a hard tissue replacement/patient-matched implant cranioplasty. Eight years later, she sustained a traumatic laceration over her vertex that necessitated removal of her cranioplastic implant because of persistent local infection. Intraoperatively, the dural flap was ingrowing and firmly adherent to the inside surface of the porous cranioplasty. After several failed attempts to remove the whole implant piecemeal, we attempted to dissect the dural flap from the brain surface to remove it together with the cranioplastic implant but exposure of the extensive cortical adhesions between the brain surface and the dural flap was compromised by the hard overlying cranioplastic implant. Despite our meticulous attempts to cut off these cortical adhesions, a perisylvian blood vessel was avulsed, resulting in intraparenchymal hemorrhage. In this case, dural adhesion and ingrowth to the underside of the cranioplasty implant led to disastrous bleeding when the implant needed to be removed years after initial implantation.


The early auditory gamma-band response is heritable and a putative endophenotype of schizophrenia.
Reduced power and phase locking of the early auditory gamma-band response (EAGBR) have been reported in schizophrenia, but findings are equivocal. Further, little is known about genetic (heritability) and environmental influences on the EAGBR or its potential as an endophenotype of schizophrenia. The present study used a twin design to examine whether EAGBR power and phase locking are heritable and reduced in schizophrenic patients and their unaffected co-twins and thus putative endophenotypes of schizophrenia. The study sample included a total of 194 individuals, consisting of 15 monozygotic [MZ] twin pairs concordant for schizophrenia, 9 MZ twin pairs discordant for schizophrenia, and 42 MZ and 31 dizygotic (DZ) control pairs. Evoked power and phase-locking factor of the EAGBR were computed on Morlet wavelet-transformed electroencephalogram responses to standard tones during an auditory oddball target detection task. Structural equation modeling was applied to estimate heritability and genetic and environmental correlations with schizophrenia for the EAGBR measures. Both evoked power and phase-locking phenotypes were heritable traits (power: h(2) = 0.65; phase locking: h(2) = 0.63). Impaired EAGBR measures were significantly associated with schizophrenia. Patients with schizophrenia and their unaffected identical co-twins exhibited significantly reduced EAGBR power compared with control subjects. In each phenotype, shared genetic factors were likely the source of the observed associations with schizophrenia. Our results support EAGBR measures as putative endophenotypes of schizophrenia, likely reflecting an ubiquitous local cortical circuit deficit.