Diversity trapped in cages: Revision of Blumenavia Möller (Clathraceae, Basidiomycota) reveals three hidden species.
Basidiomata of Phallales have a diversified morphology with adhesive gleba that exudes an odor, usually unpleasant that attracts mainly insects, which disperse the basidiospores. The genus Blumenavia belongs to the family Clathraceae and, based on morphological features, only two species are currently recognized: B. rhacodes and B. angolensis. However, the morphological characters adopted in species delimitations within this genus are inconsistent, and molecular data are scarce. The present study aimed to review and identify informative characters that contribute to the delimitation of Blumenavia species. Exsiccates from America and Africa were analyzed morphologically, and molecularly, using ITS, LSU, ATP6, RPB2 and TEF-1α markers for Maximum Parsimony, Bayesian and Maximum likelihood analyses, and also for coalescent based species delimitations (BP&P), as well as for bPTP, PhyloMap, Topo-phylogenetic and Geophylogenetic reconstructions. According to our studies, seven species can be considered in the genus: B. rhacodes and B. angolensis are maintained, B. usambarensis and B. toribiotalpaensis are reassessed, and three new species are proposed, B. baturitensis Melanda, M.P. Martín & Baseia, sp. nov., B. crucis-hellenicae G. Coelho, Sulzbacher, Grebenc & Cortez, sp. nov., and B. heroica Melanda, Baseia & M.P. Martín, sp. nov. Blumenavia rhacodes is typified by selecting a lectotype and an epitype. Macromorphological characters considered informative to segregate and delimit the species through integrative taxonomy include length of the basidiomata, color, width and presence of grooves on each arm as well as the glebifer position and shape. These must be clearly observed while the basidiomata are still fresh. Since most materials are usually analyzed after dehydration and deposit in collections, field techniques and protocols to describe fugacious characters from fresh specimen are demanded, as well as the use of molecular analysis, in order to better assess recognition and delimitation of species in Blumenavia.


Beta3 integrin activation improves alphavbeta3-mediated retraction of fibrin matrices.
Integrins are heterodimeric transmembrane glycoproteins that mediate cell interactions with the extracellular matrix. In vivo, integrin affinity can be modulated by intracellular signaling events. This can be simulated by a point mutation (D723R) in the cytoplasmic tail of the beta3 integrin subunit which results in constitutive activation. The effects of beta3 integrin activation on the function of alphavbeta3, an integrin which is important to the adhesive events of multiple cell types, were addressed using Chinese hamster ovary cells expressing either the wild-type alphavbeta3 integrin or the mutant alphavbeta3(D723R). The interactions of these cell lines with fibrin matrices were compared. Receptor expression levels were confirmed by FACS analyses using a monoclonal anti-alphavbeta3 antibody. Cell attachment to fibrin-coated dishes was determined after 1 h by fixation and crystal violet staining followed by elution of the dye and OD measurement. Fibrin clot retraction was measured by culturing cells in fibrin clots for 24 h. The clots were detached from the dish and the surface area was calculated at individual time points. CHO alphavbeta3(D723R) cells displayed a greater than twofold increase in attachment to fibrinogen or to fibrin matrices when compared to wild-type transfectants. Further, CHO alphavbeta3(D723R) cell retraction of fibrin matrices was significantly greater at nearly all time points. Activation of the beta3 integrin subunit significantly improves the interaction of alphavbeta3 with fibrin and may play a role in the integrin-mediated signaling events which occur following vascular injury.


Chemical exposures in the synthetic rubber industry and lymphohematopoietic cancer mortality.
This study evaluated the association between exposure to several chemicals and mortality from lymphohematopoietic cancer (LHC) among 16,579 synthetic rubber industry workers who were followed up from 1943 to 1998. Poisson regression analyses examined LHC rates in relation to butadiene, styrene, and DMDTC exposure. Models provided maximum likelihood estimates of the relative rate for the contrast between categories of one agent, adjusting for other agents and for additional potential confounders. Cumulative exposure to 1,3-butadiene was associated positively with all leukemia (relative rates of 1.0, 1.4, 1.2, 2.9, and 3.7, respectively, for exposures of 0, >0 to <33.7, 33.7 to <184.7, 184.7 to <425.0, and 425.0+ ppm-years), chronic myelogenous leukemia and to a lesser extent with chronic lymphocytic leukemia. Adjusting for styrene and DMDTC attenuated these associations. After controlling for butadiene, neither styrene nor DMDTC displayed a consistent exposure-response trend with all leukemia, chronic myelogenous leukemia, or chronic lymphocytic leukemia. This study found a positive association between butadiene and leukemia that was not explained by exposure to other agents examined.


[Risk factors associated with reinfection of Schistosoma japonicum].
To explore the risk factors of Schistosoma japonicum reinfection after chemotherapy in a hilly endemic area. In a hilly endemic area of S. japonica, data on contact to contaminated water and the rates of reinfection after mass praziquantel treatment were collected from residents who participated in a prospective cohort study on S. japonica. An unconditional logistic regression analysis was performed to identify the risk factors associated with the reinfection of S. japonicum. Logistic regression analysis data showed that three factors were associated with S. japonicum reinfection: eggs per gram stool (EPG) prior to chemotherapy (OR = 2.066, 95% CI: 1.173 - 3.639), gender (OR = 4.260, 95% CI: 1.275 - 14.235) and average degree of exposure (Index B) from April to October (OR = 1.138, 95% CI: 1.045 - 1.240). Interaction between gender and average exposure Index B from April to October was identified (OR = 0.875, 95% CI: 0.817 - 0.982). Eggs per gram stool (EPG) prior to chemotherapy, level of exposure to infected water and gender were risk factors for reinfection with S. japonicum after chemotherapy. In addition, there appeared an antagonism between gender and level of exposure to infected water.


Induction of antibodies directed against self and altered-self determinants by a synthetic adjuvant, muramyl dipeptide and some of its derivatives.
In a serum free, 2-mercaptoethanol supplemented culture medium muramyl dipeptide (MDP) is able to increase the number of plaque-forming cells (PFC) directed against syngeneic, bromelain-treated red blood cells (br-MRBC) and against an autoantigen, mouse albumin. The non-specific stimulation of anti-br-MRBC PFC by MDP, as by bacterial lipopolysaccharide (LPS), can be observed in spleen cell populations depleted of adherent and phagocytic cells, and in nu/nu spleen cell cultures. However, the kinetics of the induction of anti-br-MRBC PFC in murine spleen cell cultures in presence of LPS or of MDP are not identical. Moreover, MDP is able to stimulate C3H/He Orl (LPS low-responder strain) cells. Thus, the mechanisms of non-specific stimulation by MDP or by LPS could be different. Experiments done with thirteen structural analogues of MDP showed that there exists a good correlation between the adjuvant activity and the ability to induce anti-br-MRBC PFC.


Intercellular adhesion molecule-1 is required for the early formation of granulomas and participates in the resistance of mice to the infection with the fungus Paracoccidioides brasiliensis.
The migration of leukocytes to inflammatory sites elicited by Paracoccidioides brasiliensis is supposed to be coordinated by cytokines and chemokines. Here, we investigated the role of intercellular adhesion molecule-1 (ICAM-1) in recruiting inflammatory cells to lungs of mice infected with P. brasiliensis and in determining the outcome of the disease. Expression of ICAM-1 was up-regulated on T lymphocytes after infection with the fungus, and its expression was dependent on interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. Moreover, the absence of ICAM-1 resulted in high susceptibility to the infection and delayed formation of granulomatous lesions. In addition, the absence of ICAM-1 resulted in increased growth and dissemination of fungus, decreased number of CD3+CD4+ and CD3+CD8+ T cells, and increased production of interleukin-4 in the inflammatory site. The organization of a granulomatous reaction in mice deficient of ICAM-1 was delayed, starting only on day 60 after infection, whereas in wild-type mice it was complete on day 30 of infection. These data show that ICAM-1 is effectively involved in cellular migration and in the organization of the granulomatous lesion caused by the fungus P. brasiliensis.


Characterization of hair follicles induced in implanted, cultured rat keratinocyte sheets.
Cultured rat keratinocyte sheets form hair follicles in combination with rat vibrissa dermal papillae when they are transplanted subcutaneously in syngeneic rats and athymic mice. In the present study, the histologic details of these induced follicles were analyzed by preparing cultured sheets mixed with normal rat keratinocytes and green fluorescent protein (GFP)-transgenic rat keratinocytes. Histologic examination demonstrated that some induced follicles maintained their size and morphology for at least 18 weeks, whereas others decreased in size and others totally differentiated into cornified structures between 3 and 6 weeks. The percentage of the grafts with GFP-positive cells decreased during the same period. This finding suggests that some GFP-positive cells were transient-amplifying cells that turned into terminally differentiated cells and were lost during this period. Some large follicles and some small follicles maintained their hair-producing ability and the proliferative activity in their hair matrix for 18 weeks. In addition, one 6-week-old follicle contained label-retaining cells in the outer root sheath. Seven of 25 follicles induced from chimera epithelium contained both GFP-positive cells and GFP-negative cells. These results suggest that stem cells are present in the induced follicle and the induced follicle consists of polyclonally derived cells. The presence of early anagen-like large follicles at week 6 and 9 and a telogen-like small follicle at week 18 also suggests that hair-growth cycle phases proceeded in the induced follicles. In conclusion, the follicles induced in the cultured keratinocyte sheets maintained hair-producing ability and proliferative activity for at least 18 weeks. This and the presence of label-retaining cells suggest that there are stem cells in the induced follicles, which seem to have a hair-growth cycle.


How to Enter a Bacterium: Bacterial Porins and the Permeation of Antibiotics.
Despite tremendous successes in the field of antibiotic discovery seen in the previous century, infectious diseases have remained a leading cause of death. More specifically, pathogenic Gram-negative bacteria have become a global threat due to their extraordinary ability to acquire resistance against any clinically available antibiotic, thus urging for the discovery of novel antibacterial agents. One major challenge is to design new antibiotics molecules able to rapidly penetrate Gram-negative bacteria in order to achieve a lethal intracellular drug accumulation. Protein channels in the outer membrane are known to form an entry route for many antibiotics into bacterial cells. Up until today, there has been a lack of simple experimental techniques to measure the antibiotic uptake and the local concentration in subcellular compartments. Hence, rules for translocation directly into the various Gram-negative bacteria via the outer membrane or via channels have remained elusive, hindering the design of new or the improvement of existing antibiotics. In this review, we will discuss the recent progress, both experimentally as well as computationally, in understanding the structure-function relationship of outer-membrane channels of Gram-negative pathogens, mainly focusing on the transport of antibiotics.


Molecular and Morpho-Agronomical Characterization of Root Architecture at Seedling and Reproductive Stages for Drought Tolerance in Wheat.
Water availability is a major limiting factor for wheat (Triticum aestivum L.) production in rain-fed agricultural systems worldwide. Root architecture is important for water and nutrition acquisition for all crops, including wheat. A set of 158 diverse wheat genotypes of Australian (72) and Indian (86) origin were studied for morpho-agronomical traits in field under irrigated and drought stress conditions during 2010-11 and 2011-12.Out of these 31 Indian wheat genotypes comprising 28 hexaploid (Triticum aestivum L.) and 3 tetraploid (T. durum) were characterized for root traits at reproductive stage in polyvinyl chloride (PVC) pipes. Roots of drought tolerant genotypes grew upto137cm (C306) as compared to sensitive one of 63cm with a mean value of 94.8cm. Root architecture traits of four drought tolerant (C306, HW2004, HD2888 and NI5439) and drought sensitive (HD2877, HD2012, HD2851 and MACS2496) genotypes were also observed at 6 and 9 days old seedling stage. The genotypes did not show any significant variation for root traits except for longer coleoptiles and shoot and higher absorptive surface area in drought tolerant genotypes. The visible evaluation of root images using WinRhizo Tron root scanner of drought tolerant genotype HW2004 indicated compact root system with longer depth while drought sensitive genotype HD2877 exhibited higher horizontal root spread and less depth at reproductive stage. Thirty SSR markers were used to study genetic variation which ranged from 0.12 to 0.77 with an average value of 0.57. The genotypes were categorized into three subgroups as highly tolerant, sensitive, moderately sensitive and tolerant as intermediate group based on UPGMA cluster, STRUCTURE and principal coordinate analyses. The genotypic clustering was positively correlated to grouping based on root and morpho-agronomical traits. The genetic variability identified in current study demonstrated these traits can be used to improve drought tolerance and association mapping.


Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels.
The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1), a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272), p22phox (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked to key actions involved in the fibrinolytic process.


Bacterial translocation and intestinal morphological findings in jaundiced rats.
The susceptibility to sepsis in obstructive jaundice may be related to bacterial translocation (BT) from the gastrointestinal tract. We evaluated BT to visceral organs and morphological changes of the intestinal mucosa in a rat model of obstructive jaundice. Animals were randomly divided into two groups: in group A the common bile duct was tied and divided, while group B had the bile duct mobilized but not tied. After seven days, peritoneal swabs and liver, spleen, pancreas, lung, mesenteric lymph nodes (MLN), cecum, and terminal ileum biopsies were obtained for cultures. Light and electron microscopy were performed on intestinal samples. The TUNEL assay was performed to detect apoptosis. Data were analyzed using Fisher exact test and Student t test. Bile duct obliteration resulted in an increased incidence of BT. Seven days after duct obliteration, BT to the peritoneal cavity was evident in 37.5% of the animals in group A and 25% in group B. The respective BT rates for the two groups were: 42.8% vs 37.5% to MLN, 71.4% vs 25% to liver, 42.8% vs 12.5% to spleen, 28.6% vs 0% to pancreas and 14.3% vs 0% to lungs. Despite a trend, this was not statistically significant. Cecal counts did not differ statistically among the groups, while ileal counts were significantly higher in jaundiced rats (P < 0.05). Structural and ultrastructural abnormalities were evident only in the mucosa of the terminal ileum of jaundiced rats. Apoptosis was significantly increased in the terminal ileum of jaundiced rats (P < 0.002). This study suggests the possible association of biliary obstruction and BT. The nonspecific physical injury observed may contribute to breakdown of gastrointestinal barrier function thus promoting BT.


Evaluation of the VITEK 2 Gram-negative (GN) microbial identification test card: collaborative study.
A collaborative study was conducted to evaluate the performance of the VITEK 2 Gram-negative (GN) Identification card for use with the VITEK 2 automated microbial identification system. The GN test card is used in the identification of fermenting and nonfermenting Gram-negative bacilli, including the select agent organisms Brucella melitensis, Francisella tularensis, Burkholderia mallei, B. pseudomallei, and Yersinia pestis. The VITEK 2 GN card is based on 47 biochemical tests measuring carbon source utilization, inhibition and resistance, and enzymatic activities. A total of 20 laboratories representing government, industry, and private testing facilities throughout the United States participated. In this study, 720 Gram-negative inclusivity isolates were analyzed by the GN Identification method. Of the 720 well-characterized isolates, 707 were identified correctly, 0 were misidentified, 0 were unidentified, and 13 were not characterized as a Gram-negative organism. Additionally, 120 isolates exclusive of fermenting and nonfermenting Gram-negative bacilli were screened by Gram stain. A total of 117 isolates were correctly excluded. Three organisms were incorrectly characterized by Gram stain procedures, resulting in incorrect analysis and misidentification by VITEK 2 GN. The VITEK 2 GN identification method is an acceptable automated method for the rapid identification of Gram-negative bacteria.


Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum.
Natural compounds often have complex molecular structures and unknown molecular targets. These characteristics make them difficult to analyse using a classical pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a complex molecule possessing wide-ranging biological activities, cellular mechanisms and roles in potential therapeutic treatment, including Alzheimer's disease and cancer. Here, we investigate the physiological effects and molecular targets of curcumin in Dictyostelium discoideum We show that curcumin exerts acute effects on cell behaviour, reduces cell growth and slows multicellular development. We employed a range of structurally related compounds to show the distinct role of different structural groups in curcumin's effects on cell behaviour, growth and development, highlighting active moieties in cell function, and showing that these cellular effects are unrelated to the well-known antioxidant activity of curcumin. Molecular mechanisms underlying the effect of curcumin and one synthetic analogue (EF24) were then investigated to identify a curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB). Using in silico docking analysis, we then showed that curcumin might function through direct binding to a key regulatory region of PsrA. These findings reveal novel cellular and molecular mechanisms for the function of curcumin and related compounds.


Heterogeneous rate of protein evolution in serotonin genes.
Serotonin (5-hydroxytryptamine) is a neurotransmitter crucial for cardiovascular, gastrointestinal, and brain function. It is also involved in several aspects of behavior and associated with a variety of personality disorders in humans. Its dual role as a crucial element in vital physiological functions (strictly evolutionary conserved) and in traits that differ substantially across species makes the evolution of serotonin function particularly interesting. We studied the evolution of serotonin function through the identification of the selective forces shaping the evolution of genes in its functional pathway in primates and rodents. Serotonin genes are highly conserved and show no signals of positive selection, suggesting functional constraint as the main force driving their evolution. They show, nevertheless, considerable differences in constraint between primates and rodents, with some genes showing dramatic differences between the 2 groups. These genes most likely represent cases of functional divergence between primates and rodents and point out to the relevance of using closely related species in gene-based evolutionary studies to avoid the effect of unrecognized functional differences between distant species. Within each group (rodents or primates), genes also show heterogeneity in evolution. Genes from the same gene family (with structure and function alike) tend to evolve at a similar rate, but this is not always the case. A few serotonin genes show substantial differences in constraint with the rest of members of their family, suggesting the presence of important and unrecognized functional differences among the genes, which may be involved in species-specific evolution.


Management of Discoloured Anterior Teeth With Radicular Cyst: A Case Report.
Dental trauma often has tooth discoloration and periapical lesion as its sequelae. Intracoronal bleaching restores the aesthetics, while a retrograde approach is required for non-healing lesions. A patient with discolored teeth, draining sinus, tenderness and a periapical lesion on the radiograph was treated initially with conventional root canal therapy and walking bleach technique. After four months, the sinus tract reappeared and on cone-beam computed tomography (CBCT) examination, a large periapical lesion with loss of buccal cortical plate was seen. A minimally invasive retrograde cystic enucleation, apicectomy, and filling with biodentine were then performed. The defect area was filled with synthetic nanocrystalline hydroxyapatite granules combined with platelet-rich-fibrin. Follow-ups after one, three, and six months were taken. The six-month CBCT revealed complete bone healing. Non-vital bleaching yields acceptable cosmetic results. Additionally, if the conventional procedures are not successful in treating radicular cyst, apical surgery must be the ultimate choice.


Lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction: from physiology to clinical aspects.
Erectile dysfunction, prostatic hyperplasia and lower urinary tract symptoms hare important pathogenetic links. Endothelial dysfunction and hormonal alterations represent the main aspects. The present article examines the anatomical, physiological, and pathophysiological characteristics of this association, finalizing the text to an interpretation of the clinical management of these patients based on these functional considerations.


Calcium antagonists and deep gingival pockets in the population-based SHIP study.
Gingival overgrowth is a common undesired side-effect in patients taking calcium channel blockers. Different reports have suggested that the drug-induced gingival hyperplasia may aggravate inflammatory periodontal disease. However, representative epidemiological data are lacking. We investigated the association between the intake of calcium antagonists and periodontitis in a population-based analysis including the most important risk factors of periodontitis. In a cross-sectional epidemiological investigation involving 4290 subjects aged 20-80 years, we recorded periodontal risk factors and identified participants using calcium antagonists. Periodontal parameters, attachment loss, probing depth and number of teeth were assessed. In a subgroup analysis with matched pairs, 456 subjects using calcium antagonists and 456 without were compared for periodontal status. Subjects treated with calcium antagonistic drugs had significantly deeper gingival pockets than their drug-free counterparts. This was observed in the total population of 4290 and confirmed by logistic regression analyses (P < 0.001) controlled for the known risk factors of periodontitis (age, sex, smoking, education). In the matched-pair analysis only the probing depth was increased: extent probing depth > or = 4 mm median 23.5 vs. 17.0% (P < 0.001); mean probing depth 3.0 +/- 0.8 vs. 2.7 +/- 0.9 mm (P < 0.001). No differences were found in extent and severity of clinical attachment loss and in the number of teeth. The risk of gingival overgrowth was aggravated in smokers. In the general population, treatment with calcium antagonists leads to gingival overgrowth without an aggravation of periodontal disease. Interaction with smoking indicates the multifactorial background of the undesired effect of calcium antagonists.


Tissue biotype and its relation to the underlying bone morphology.
Tissue biotypes have been linked to the outcomes of periodontal and implant therapy. The purpose of this study is to determine the dimensions of the gingiva and underlying alveolar bone in the maxillary anterior region and to establish their association. Tissue biotypes of 22 fresh cadaver heads were assessed clinically and radiographically with cone-beam computed tomography (CBCT) scans. Maxillary anterior teeth were atraumatically extracted. The thickness of both soft tissue and bone were measured using a caliper to the nearest 0.1 mm by two calibrated examiners. Probing depths and gingival recession were measured at two points (mid-labial and mid-palatal). Clinical and CBCT measurements of both soft tissue and bone thickness were subsequently compared and correlated. No statistically significant differences were observed between the clinical and CBCT measurements of both soft tissue and bone thickness except the palatal soft tissue measurements. The labial gingival thickness was moderately associated with the underlying bone thickness measured with CBCT (R = 0.429; P <0.05). Gingival recession was not associated with the thickness of both labial gingiva and bone. CBCT measurements were an accurate representation of the clinical thickness of both labial gingiva and bone. In addition, the thickness of the labial gingiva had a moderate association with the underlying bone radiographically.


Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review.
The hypothesis of preimplantation genetic diagnosis (PGS) was first proposed 20 years ago, suggesting that elimination of aneuploid embryos prior to transfer will improve implantation rates of remaining embryos during in vitro fertilization (IVF), increase pregnancy and live birth rates and reduce miscarriages. The aforementioned improved outcome was based on 5 essential assumptions: (i) Most IVF cycles fail because of aneuploid embryos. (ii) Their elimination prior to embryo transfer will improve IVF outcomes. (iii) A single trophectoderm biopsy (TEB) at blastocyst stage is representative of the whole TE. (iv) TE ploidy reliably represents the inner cell mass (ICM). (v) Ploidy does not change (i.e., self-correct) downstream from blastocyst stage. We aim to offer a review of the aforementioned assumptions and challenge the general hypothesis of PGS. We reviewed 455 publications, which as of January 20, 2017 were listed in PubMed under the search phrase < preimplantation genetic screening (PGS) for aneuploidy>. The literature review was performed by both authors who agreed on the final 55 references. Various reports over the last 18 months have raised significant questions not only about the basic clinical utility of PGS but the biological underpinnings of the hypothesis, the technical ability of a single trophectoderm (TE) biopsy to accurately assess an embryo's ploidy, and suggested that PGS actually negatively affects IVF outcomes while not affecting miscarriage rates. Moreover, due to high rates of false positive diagnoses as a consequence of high mosaicism rates in TE, PGS leads to the discarding of large numbers of normal embryos with potential for normal euploid pregnancies if transferred rather than disposed of. We found all 5 basic assumptions underlying the hypothesis of PGS to be unsupported: (i) The association of embryo aneuploidy with IVF failure has to be reevaluated in view how much more common TE mosaicism is than has until recently been appreciated. (ii) Reliable elimination of presumed aneuploid embryos prior to embryo transfer appears unrealistic. (iii) Mathematical models demonstrate that a single TEB cannot provide reliable information about the whole TE. (iv) TE does not reliably reflect the ICM. (v) Embryos, likely, still have strong innate ability to self-correct downstream from blastocyst stage, with ICM doing so better than TE. The hypothesis of PGS, therefore, no longer appears supportable. With all 5 basic assumptions underlying the hypothesis of PGS demonstrated to have been mistaken, the hypothesis of PGS, itself, appears to be discredited. Clinical use of PGS for the purpose of IVF outcome improvements should, therefore, going forward be restricted to research studies.


Echolocation signal structure in the Megachiropteran bat Rousettus aegyptiacus Geoffroy 1810.
Rousettus aegyptiacus Geoffroy 1810 is a member of the only genus of Megachiropteran bats to use vocal echolocation, but the structure of its brief, click-like signal is poorly described. Although thought to have a simple echolocation system compared to that of Microchiroptera, R. aegyptiacus is capable of good obstacle avoidance using its impulse sonar. The energy content of the signal was at least an order of magnitude smaller than in Microchiropteran bats and dolphins (approximately 4 x 10(-8) J m(-2)). Measurement of the duration, amplitude and peak frequency demonstrate that the signals of this animal are broadly similar in structure and duration to those of dolphins. Gabor functions were used to model signals and to estimate signal parameters, and the quality of the Gabor function fit to the early part of the signal demonstrates that the echolocation signals of R. aegyptiacus match the minimum spectral spread for their duration and amplitude and are thus well matched to its best hearing sensitivity. However, the low energy content of the signals and short duration should make returning echoes difficult to detect. The performance of R. aegyptiacus in obstacle avoidance experiments using echolocation therefore remains something of a conundrum.


A multilevel model of the effects of equal opportunity climate on job satisfaction in the military.
To date, minimal work has explored associations between equal opportunity (EO) climate and employee work attitudes, and no known research has investigated the effects of EO climate beyond the individual level. We address these gaps in the literature by testing a multilevel structural equation model in which effects of EO climate are considered at both the individual and unit levels. At the individual level, we predicted that psychological EO climate would be directly associated with job stress and job satisfaction, as well as indirectly related to job satisfaction via stress. In addition, cross-level associations between unit EO climate and job stress and job satisfaction were hypothesized to be mediated by cohesion. Findings supported the proposed model; hypothesized relations were supported at both levels of analysis. We conclude with a discussion of the findings, study limitations, and directions for future EO climate research.


Hemorrhage, phenobarbital, and fluctuating cerebral blood flow velocity in the neonate.
Fifty-one sequential intubated babies with birth weights of less than 1,751 were evaluated by serial Doppler ultrasound during the first three days of life. These babies were part of a phenobarbital prophylaxis trial cohort study. Subependymal-intraventricular hemorrhage developed in 17 of the babies. Infants with subependymal-intraventricular hemorrhage, whether or not they received pancuronium or phenobarbital, had coefficients of variation comparable to those of babies without hemorrhage. Coefficient of variation values of the right were comparable to values obtained from the left anterior cerebral artery complex and did not appear to be consistently altered by the presence of subependymal-intraventricular hemorrhage. Coefficient of variation values appeared to be consistently greatest on day 1 and lowest on day 2. In addition, the values overall increased as the number of waves used to determine the coefficient of variation enlarged from five to 20. This phenomena, however, was not seen among pancuronium recipients and suggests that movement artifact may be a determinant of coefficient of variation values. We conclude that, when the best 20 waves are chosen to evaluate the coefficient of variation, no association exists between coefficient of variation values and development of subependymal-intraventricular hemorrhage or administration of phenobarbital.


Delayed-onset endophthalmitis associated with conjunctival filtering blebs.
The purpose of the study is to evaluate the causative organisms, treatment methods, and visual acuity outcomes of patients treated for delayed-onset endophthalmitis associated with conjunctival filtering blebs. The medical records of 32 patients with conjunctival filtering bleb-associated endophthalmitis treated at the Bascom Palmer Eye Institute between 1989 and 1995 were reviewed retrospectively. Bleb-associated endophthalmitis was diagnosed at 1 month or more after surgery in all patients. Patients with bleb infections only but without, signs of intraocular infection were excluded from this series. Previous antimetabolite therapy was used in 20 patients, including mitomycin C in 14 and 5-fluorouracil in 6. Streptococcal species were the most frequently cultured organisms occurring in 15 (47%) of 32 eyes. Of the 32 patients, 30 received intraocular antibiotics. The initial treatment included a pars plana vitrectomy in 18 patients and a vitreous tap without vitrectomy in 12 patients. Two of three patients who presented with no light perception vision were treated by evisceration. Overall, 15 (47%) of 32 patients achieved a final visual acuity of 20/400 or better. Of those patients with Streptococcal species cultured from the eye, 6 (40%) of 15 had a visual acuity of 20/400 or better compared to 9 (52%) of 17 in patients with non-Streptococcal species. Delayed-onset endophthalmitis associated with conjunctival filtering blebs is a current and future concern, especially with increasing use of mitomycin C. The Streptococcal species are a common causative organism. Despite current treatment of these patients, the visual acuity outcomes generally are worse than in patients with acute-onset endophthalmitis after cataract surgery.


Segmented mirror polishing experiment.
An experiment was conducted to demonstrate the capability of polishing segmented mirrors. A mirror segment was figured with the computer controlled polisher using special software and tooling. This process rapidly reduced surface figure errors and produced a good figure to the segment's edges.


[Purification of the heparin-binding haemagglutinin adhesin of Mycobacterium tuberculosis and its application in diagnosis of tuberculosis].
To investigate the application of heparin-binding haemagglutinin adhesin (HBHA) in tuberculosis (TB) diagnosis. We prepared native HBHA from cultivated Mycobacterium Bovis Calmetta Guerin (BCG) in Suton liquid medium. After BCG grew to the stationary status, native HBHA was acquired by specific CL-6B chromatography column binding heparin. At the same time, we cloned hbhA gene from Mycobacterium tuberculosis into PET-32alpha (+) expression vector. Recombinant HBHA from E. coli was obtained. Based on the native HBHA and recombinant HBHA, we chose 4 groups of pulmonary TB, extra-pulmonary TB, PPD (-) and PPD (+) healthy control with 47 in each group and conducted ELISA from serum for specific HBHA antibody level. At last we calculated the sensitivity and specificity in TB diagnosis by detection of anti-HBHA antibody level. The native HBHA could be diluted and purified with the PBS containing the 375 mmol/L NaCl by specific CL-6B chromatography column binding heparin; There was no significant difference in experimental result based on the natural and recombinant HBHA protein, also no difference between PPD (-) and PPD (+) healthy control groups. Serum antibody level by ELISA could distinguish pulmonary TB and ertra-pulmonary TB (t = 12.224, P< 0.05). The antibody level of the TB groups (pulmonary TB and ertra-pulmonary TB) was higher than the healthy control groups [PPD (+) and PPD (-) healthy control] (t =25.909, P<0.05). Both recombinant and native HBHA can be used as immunological diagnosis in TB. It can be used in TB and especially extra-pulmonary TB diagnosis.


Combined transrectal ultrasonography and urodynamics in the evaluation of detrusor-sphincter dyssynergia.
Thirty-one combined transrectal ultrasonographic and urodynamic studies were performed in 24 patients with spinal cord lesions at different levels between C4 and T12. Ultrasonography provided accurate real-time imaging of the bladder neck, prostatic urethra and external sphincter during the bladder filling phase as well as during the voiding phase. Bladder and rectal pressures, sphincter EMG and uroflow were recorded simultaneously. Transrectal ultrasonography contributed significantly to the accuracy of diagnosing detrusor-sphincter dyssynergia. Sphincter contractions were clearly visualised with ultrasonographic video monitoring. This imaging method was especially helpful in sorting out the problems of 3 patients with poor emptying of bladder after endoscopic sphincterotomy. One had a urethral stricture and the other 2 had sphincters that opened adequately but bladders that emptied poorly because of detrusor hypocontractility. Other problems, such as benign prostatic hyperplasia and false passage, were also easily recognised. Transrectal ultrasonography not only provides accurate information but also involves no exposure to radiation and thus precludes the need for costly lead-shielded examination rooms.


Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline.
Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit cancer-special proteasome and induce cell death in human cancer cells. However, the involved molecular mechanism is not known yet. We therefore synthesized three copper complexes and investigated their abilities on inhibiting proteasome activity and inducting apoptosis in human breast cancer cells. Furthermore, we employed molecular dockings to analyze the possible interaction between the synthetic copper complexes and the β5 subunit of proteasome which only reflects the chymotrypsin-like activity. Our results demonstrate that three Cu(II) complexes possess potent proteasome inhibition capability in a dose-dependent and time-dependent manner in MDA-MB-231 human breast cancer cells. They could bind to the β5 subunit of the 20S proteasome, which consequently cause deactivation of the proteasome and tumor cell death. The present study is significant for providing important theoretical basis for design and synthesis of anticancer drugs with low toxicity, high efficiency and high selectivity.


Is there a reentrant glass in binary mixtures?
By employing computer simulations for a model binary mixture, we show that a reentrant glass transition upon adding a second component occurs only if the ratio alpha of the short-time mobilities between the glass-forming component and the additive is sufficiently small. For alpha approximately 1, there is no reentrant glass, even if the size asymmetry between the two components is large, in accordance with the two-component mode-coupling theory. For alpha<<1, on the other hand, the reentrant glass is observed and reproduced only by an effective one-component mode-coupling theory.


Insulin potentiating factor and chromium content of selected foods and spices.
An unidentified factor that potentiates the action of insulin in glucose metabolism was investigated in selected foods and spices. Chromium content of these foods and spices was also determined. Foods and spices were extracted with 0.1N NH4OH (1:20, w/v) and the supernatants assayed for insulin potentiation activity in the rat epididymal fat cell assay. Among the selected foods, tuna fish, peanut butter, and vanilla ice cream had some insulin potentiating activity. Among the spices, apple pie spice, cinnamon, cloves, bay leaves, and turmeric potentiated insulin activity more than three-fold. Chromium concentration of foods ranged from 1 to 145 ng/g, and spices ranged from 4 to 1818 ng/g. Insulin potentiating activity of foods and spices did not correlate with total chromium. Spices are generally used for flavor and taste in food preparations, but cinnamon, cloves, bay leaves, and turmeric may have an additional role in glucose metabolism.


Factors affecting the production and composition of Egyptian buffalo milk.
The data comprise 254 first and 150 second 305-day lactation records of buffaloes and their dams at Mahalet Mousa Experimental Station. These records were used for the evaluation of the effect of various factors upon 305-day milk yield. The average daily milk yield and percentage constituents were measured on 58 lactation records. Samples were taken on the seventh, fourteenth and thirtieth day post-partum and at 30 day intervals throughout the lactation. The parameters studied were: age at first calving, 305-day milk yield and butter fat, protein and total solids contents percentages. Average age at first calving was 42.9 and 40.9 months for heifers and their dams, respectively. Average 305-day milk yield was 1,004.3 kg and 1,552.7 for first and second lactations, respectively. The later age at which buffalo cows produce their first calf, the greater the milk production in first lactation. Buffaloes that calve in summer produce more milk than those which calve in winter months. Average fat, protein and total solids percentages were 6.59, 4.11 and 16.52 respectively, in the first lactation and 6.63, 3.99 and 16.48 respecitvely in the second lactation. Phenotypic correlations between milk yield and yields of constituents were high and positive. Those among constituent percentages were positive and moderate. In general, correlations between milk yield and constituents content were negative. Milk yield increased after calving towards a peak ranging between 30 and 90 days for the first and second lactations, respectively. Constituent percentages were high at the beginning, declining thereafter as milk yield increased, followed by a gradual rise till the end of lactation.


Seizures in children with supratentorial astroglial neoplasms.
We reviewed the records of 98 consecutive patients, 18 years of age or younger, with pathologically confirmed supratentorial astroglial neoplasms at the Children's Hospital, Boston, to evaluate the importance of seizures in their presentation and natural history. Tumors were diagnosed using the WHO criteria as pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas, glioblastomas, giant cell glioblastomas, oligoastrocytomas and gangliogliomas. Our results were as follows. (1) Fifty percent of children had seizures as part of their presentation and 30% had seizures as their only presenting phenomenon. (2) The seizures varied in nature, but complex (55%) or simple (28%) partial seizures were by far the most common types, occurring in 77% of cases. (3) Preoperative electroencephalography (EEG) accurately lateralized to the tumor side in 88% of the cases and localized to the correct lobe in 56%. (4) Tumors involving cerebral cortex significantly correlated with seizures at presentation as compared to noncortical locations; 59% of patients with cortical tumors presented with seizures, and only 15% of patients with noncortical tumors experienced seizures. Lesions in the temporal and frontal lobes had the highest incidence of seizures. (5) Patients with gangliogliomas and oligoastrocytomas had the highest incidence of seizures, 88 and 86%, respectively, whereas patients with anaplastic astrocytoma had the lowest incidence, 21%. (6) Histopathologic calcification was associated with seizures at presentation approaching significance (p = 0.06). (7) Seizures at presentation were significantly associated with good prognosis (p = 0.02).


Transforming laboratory test results to improve clinical outcome predictions in HIV patients. Swiss HIV Cohort Study.
Transforming natural units of laboratory markers of HIV disease may improve their ability to predict clinical outcomes. The authors examined this issue within a prospective study of 394 patients enrolled in the Swiss HIV Cohort Study (SHCS) between 1991 and 1993. Baseline predictors included CD4+ and CD8+ cell counts, HIV RNA levels, beta2-microglobulin, and age. Outcomes were death and clinical progression. A range of power transformations was applied to each predictor, and the goodness-of-fit of the corresponding proportional hazards models was assessed. The prognostic value of all laboratory variables could be improved on by power transformations. To predict either outcome variable, the "best" transformation of HIV RNA copies and CD8+ cell counts was the logarithm; for beta2-microglobulin, it was power -2. For CD4+ cell counts, the best transformation depended on the outcome variable: it was power 0.2 when predicting survival, and power 0.4 when predicting clinical progression. The single best predictor variable was the ratio of HIV RNA copies per CD4+ cell, for both death (logarithmic transformation) and clinical progression (power -0.1 transformation). Natural units of laboratory variables are not optimal for the prediction of clinical events in HIV-infected patients. Which transformation is best depends on the predictor under consideration.


Examine the Moderating Role of Teacher's Self-Efficacy in the Relationship Between the Job Satisfaction and Professional Learning Community in China.
The study aimed in examining the impact of the professional learning community, and teachers' self-efficacy on the job satisfaction of teachers. Additionally, the study has also examined the moderating role of teachers' self-efficacy in the relationship between the professional learning community (PLC) and job satisfaction. The SEM-PLS is employed for the data analysis. The response rate of the study is 50%. The study is carried out on the primary teachers in China. Three research questions were developed in the current study. The questions were related to the job satisfaction level of PE teachers, which was far beyond the level of satisfaction. As a result, teachers of PE classes had low performance. It was found by the study that professional learning community, job satisfaction of teachers, and self-efficacy are linked with each other. However, the results are inconclusive because of the limitation of the sample. The study has several implications among researchers, practitioners, and teachers. The study is among the few earlier studies on the issues related to Job Satisfaction and the professional learning community in China. The study has highlighted an important issue related to the Job Satisfaction and professional learning community in China.


Cumulative associations between midlife health behaviors and physical functioning in early old age: a 17-year prospective cohort study.
To examine cumulative associations between midlife health behaviors and walking speed and upper-limb strength in early old age. Prospective cohort study. Whitehall II Study. Individuals (mean age 49.1 ± 5.9 in 1991-93) with health behavior data for at least two of the three assessments (1991-93, 1997-99, 2002-04) and physical functioning measures in 2007-09 (mean age 65.9 ± 5.9) (N = 5,671). A trained nurse assessed walking speed and upper-limb strength. Unhealthy behaviors were defined as current or recent smoking, nonmoderate alcohol consumption (abstinence or heavy drinking), fruit and vegetable consumption less than twice per day, and physical inactivity (<1 h/wk of moderate and <1 h/wk of vigorous physical activity). For each unhealthy behavior, a cumulative score was calculated as the number of times a person reported the behavior over the three assessments divided by 3. The score ranged between 0 (never) and 1 (all three times). In linear regression models adjusted for age, sex, education, marital status, and height, all unhealthy behaviors in 1991-93 were associated with slower walking speed in 2007-09, with differences ranging from 0.10 (nonmoderate alcohol consumption) to 0.25 (physical inactivity) of a standard deviation between participants with and without the unhealthy behavior (Pt-test <.001). For walking speed, the accumulation-of-risk model provided the best fit for unhealthy diet (β for a 1-point increment in the low fruit and vegetable consumption score = -0.29, 95% confidence interval (CI) = -0.36 to -0.22) and physical inactivity (β = -0.37, 95% CI = -0.45 to -0.29). For smoking and nonmoderate alcohol consumption, a cumulative effect was also observed, but partial F-tests did not suggest that it provided a better fit than models with behaviors in 1991-93, 1997-99, or 2002-04. All behavioral scores except smoking were associated with grip strength, but F-tests supported the accumulation-of-risk hypothesis only for physical inactivity. These findings highlight the importance of duration of unhealthy behaviors, particularly for diet and physical activity, when examining associations with physical functioning.


Conformational Effects of the A21G Flemish Mutation on the Aggregation of Amyloid β Peptide.
Among the various hereditary mutants of amyloid β (Aβ) in familial Alzheimer's disease (AD), the A21G Flemish-type mutant has unique properties showing a low aggregation propensity but progressive deposition in vascular walls. Moreover, in contrast to other familial AD cases that show extensive Aβ1-42 deposition in the brain, patients with Flemish AD predominantly exhibit the deposition of the Aβ1-40 isoform. Here we report the structural characterization of the Flemish-type mutant (A21G) in comparison with the wild-type Aβ1-40 peptide to examine the possible effects of the A21G mutation on the conformation of the Aβ1-40 isoform. The kinetic analysis of the aggregation of the peptides monitored by thioflavin T fluorescence measurement indicates that the mutation precludes the initial nucleation process of amyloid fibril formation by Aβ1-40. Spectroscopic data indicate that the Flemish-type mutant bound to aqueous micelles composed of lyso-GM1, in which the mobile N-terminal segment is tethered through the C-terminal helical segment, has reduced α-helical structure compared to the wild-type peptide. Our findings suggest that the mutational perturbation to the membrane binding properties is coupled with the changes in nucleation behavior of Aβ during its fibril formation.


Anthropometric measurements in 126 microtia reconstructions.
Due to its complex, three-dimensional morphology, auricular reconstruction remains one of the most challenging procedures in reconstructive surgery. A subject that remains controversial, however, is the question of the growth potential of the cartilaginous framework. This study explored the anthropometric changes of the reconstructed auricle and the contralateral normal ear in a series of Asian patients. The records of 126 unilateral microtia patients in three age groups who underwent autogenous costal cartilage auricular reconstruction between 2007 and 2010 were reviewed. The average age was 14 years, and the average follow-up was 2.5 years. The auricular height was measured as the distance from the supra-auricle to the subauricle, and the width was measured as the distance from preauricle to the postauricle. Measurements of the height and width of the reconstructed auricle and the contralateral normal side were taken at implantation and at the final follow-up. Comparisons between the three age groups were performed using a paired Student t test to examine the mean auricular heights and widths for significant interval changes in size. The measurements showed average width increases of 1.24 mm (3.68%) and 1.35 mm (3.91%) in the reconstructed auricles of children and adolescents, respectively, but we did not find obvious changes in the adult group. No significant differences were found in the height measurement of the reconstructed auricle in the three groups. The mature size of the normal ear was reached by age 12, with slowing as patients entered adolescence and adulthood. Comparison of the reconstructed auricle and the contralateral normal ear revealed a very similar growth rate in the adult group. There were average height decreases of 0.77 mm (1.3%) and 1.3 mm (2.09%) in the reconstructed auricles of children and adolescents compared with the normal side. The results showed an average width increase of 1.13 mm (3.15%) in the adolescent group but not in the child or adult groups. The results of this study have generated some useful parameters for the study of growth of the reconstructed auricle and contralateral normal ear. This information serves to clarify the issue of auricular framework fabrication in terms of proper size, especially for Asian patients. Further investigation and analysis are necessary to provide further proof of the graft change.


Cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm.
We developed and evaluated a novel system for guiding radiofrequency catheter ablation therapy of ventricular tachycardia. This guidance system employs an inverse solution guidance algorithm (ISGA) using a single equivalent moving dipole (SEMD) localization method. The method and system were evaluated in both a saline tank phantom model and in vivo animal (swine) experiments. A catheter with two platinum electrodes spaced 3 mm apart was used as the dipole source in the phantom study. A 40-Hz sinusoidal signal was applied to the electrode pair. In the animal study, four to eight electrodes were sutured onto the right ventricle. These electrodes were connected to a stimulus generator delivering 1-ms duration pacing pulses. Signals were recorded from 64 electrodes, located either on the inner surface of the saline tank or on the body surface of the pig, and then processed by the ISGA to localize the physical or bioelectrical SEMD. In the phantom studies, the guidance algorithm was used to advance a catheter tip to the location of the source dipole. The distance from the final position of the catheter tip to the position of the target dipole was 2.22 ± 0.78 mm in real space and 1.38 ± 0.78 mm in image space (computational space). The ISGA successfully tracked the locations of electrodes sutured on the ventricular myocardium and the movement of an endocardial catheter placed in the animal's right ventricle. In conclusion, we successfully demonstrated the feasibility of using an SEMD inverse algorithm to guide a cardiac ablation catheter.


Ending cervical cancer: A call to action.
The outlook for elimination of the scourge of cervical cancer is bright, because we now have the tools to achieve this goal. In recent years human papillomavirus (HPV) vaccination in high-income countries has resulted in dramatic decreases in HPV infection and associated cervical disease. If all countries with a substantial burden of disease introduce the vaccine nationally, we can protect the vast majority of women and girls most at risk. For women who are beyond the vaccination target age, progress has been made in screening and treatment for cervical precancer, but we must accelerate this momentum to reduce incidence and mortality worldwide to the very low rates found in wealthier countries. Human and financial resources must be increased and directed to programs that follow best practices and reach all women, including the marginalized or disadvantaged. Seven key actions are recommended. Now is the time for action at national, regional, and global levels.


Risk factors for predicting mortality in elderly patients with COVID-19: A review of clinical data in China.
While elderly patients are at high risk of fatality, research concerning COVID-19 has largely been done on clarifying the clinical features. As such, the present work aims to identify risk factors for mortality in elderly patients with COVID-19. Given that single-centre studies are less likely informative as elderly remains a minority in the total Chinese population, the present study reviewed the clinical data of geriatric COVID-19 patients gathered from different sources in the public domain. Based on the data of 154 individuals from 26 provinces, age remained a key mortality risk factor among geriatric patients of different ages. While dyspnoea and chest pain/discomfort were more commonly seen in deceased patients as they represented severe pneumonia, fever was more prominent in surviving patients. This was likely due to the lower baseline body temperature observed in elderly which translated to a lower maximum temperature of fever. However, lowering the threshold temperature for fever is not recommended in surveillance. Instead, baseline body temperature measured on a regular basis should be used to define the threshold temperature for fever. Against mixed results, more research should be done on identifying comorbidities associated with mortality in geriatric patients.


Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation.
Acute lymphoblastic leukemia (ALL) is a challenging disease with a growing genetic landscape, even though there is substantial gap between developed and non-developed countries when it comes to availability of such new technologies. This manuscript reports a 5-year retrospective cohort of newly diagnosed ALL patients and their genetic findings and outcomes. An expanded genetic evaluation by using FISH and RT-PCR was implemented, aiming to identify Ph-like alterations. Patients were treated according to our local protocol, which allocated patients according to age and Philadelphia-chromosome status. A total of 104 patients was included, with median age of 37.5 years. Philadelphia chromosome was detected in 33 cases of B-lineage. Among 45 Ph-negative B-lineage, after excluding KMT2A or TCF3-PBX1 cases, we identified 9 cases with Ph-like fusion. Ph-positive and Ph-like patients had higher initial WBC (p = 0.06). Out of 104 cases, two cases did not start chemotherapy and an early death rate of 10.8% was found. Allogeneic transplantation was performed in 18 cases, being ten performed in first CR. Three-year overall survival (OS) and 3-year event-free survival were 42.8% and 30.8%, respectively. For patients treated with a pediatric regimen, 3-year OS was 52.5%. Extramedullary disease (HR 0.42) and platelet counts (HR 0.9) were independently associated with OS. We still face excessive non-relapse mortality that compromises our results. Alternative strategies implementing FISH and RT-PCR are feasible and able to identify Ph-like fusions. Delays in allogeneic transplantation, as well as the unavailability of new agents, impact long-term survival. Measures to decrease early infection are desirable.


Characteristic CT and MR imaging findings of cerebral paragonimiasis.
The early diagnosis of cerebral paragonimiasis (CP) is essential for a good prognosis. We seek to provide references for early diagnosis by analyzing the imaging characteristics of cerebral paragonimiasis. Images of 27 patients with CP (22 males and 5 females; median age 20.3 years; range: 4 to 47 years) were retrospectively evaluated. All patients underwent head computed tomography (CT) scans; 22 patients underwent conventional magnetic resonance imaging (MRI) sequences, including contrast-enhanced MRI for 20 patients and diffusion-weighted-imaging (DWI) for 1 patient. The diagnosis was confirmed based on a positive antibody test using enzyme-linked immunosorbent assay (ELISA) for paragonimiasis in the serum. The most common imaging findings of CP were isodense or hypodense lesions combined with extensive hypodense areas of perilesional edema on CT scans and a large mass composed of multiple ring-shaped lesions with surrounding edema on MRI images. The conglomeration of multiple ring-shaped lesions (n=11 patients), "tunnel signs" (n=12 patients) and worm-eaten signs (n=5 patients) were characteristic of most CP images. In 14 patients, contrast-enhanced MRI showed varying degrees of contrast enhancement combined with adjacent meningeal enhancement (n=10). A large mass comprising multiple ring-shaped lesions of different sizes, "tunnel signs" and worm-eaten signs with surrounding edema are the most characteristic features of CP. Extensive invasions of the adjacent meninges and ventricular wall (19 patients), multiple intracerebral lesions, bilateral hemispheric involvement, and lesion migration are other noteworthy imaging characteristics.


[Erythematotelangiectatic skin--diagnostic difficulties].
Erythematotelangiectatic skin is a common cosmetic and medical problem. Flushing or persistent erythema, teleangiectasias, and occasionally other inflammatory skin lesions can be caused by internal or environmental factors. Certain physiologic reactions and systemic or dermatologic diseases represent internal conditions leading to visible skin flushing in the blush area. Erythematotelangiectatic skin is found in body areas which are particularly exposed to various environmental factors and perform important esthetic functions at the same time. Determination of the main etiopathologic factor responsible for flushing in the blush area precedes the selection of an adequate method of care, correction or treatment of the erythematotelangiectatic skin. The main aim of this study was to analyze fundamental mechanisms of flushing or persistent erythema and their sequellae basing on the literature. Another aim was to review current diagnostic options useful in examining the etiology and severity of erythematotelangiectatic skin symptoms.


How to lead departments outside your clinical competence.
Leading departments outside your clinical competence takes a special set of skills. Follow these approaches and enhance your transferable leadership skills to succeed.


Effect of long-term ethanol consumption on the rat ventricle.
The chronic ingestion of alcohol has been correlated with cardiac dysfunction. This study looked at the effect of chronic ethanol ingestion on the rat ventricle. The studies were carried out on hearts from male Long-Evans hooded rats, pair-fed on ethanol (E) or normal (N) liquid diet. The E rats received 35-39% of calories as ethanol. The studies were carried out after 40 weeks on the diet. The data show the E rats had reduced papillary muscle function, and increased incidence of isoproterenol induced extra beats and failure. There was no difference in responsiveness to isoproterenol, alpha, beta, or muscarinic receptor number or agonist binding characteristics between hearts from E and N rats. The cardiac dysfunction in the E group is thought to be due to possible membrane structural changes, or to changes in the characteristics of the autonomic receptor system beyond the receptor level.


Medical emergency department attendance of under 16-year-olds with dental problems.
Medical emergency departments (MED) are under increasing pressure in the UK with suggestions that unnecessary attendances to MED, which may include dental problems, are to blame. The aim of this cross-sectional study was to examine the period prevalence of under 16-year-olds attendance to medical emergency departments (MED) with oral and dental problems over a 5-year period and investigate reason for attendance. This cross-sectional study was carried out as part of a service evaluation at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Retrospective data were collected between 1 January 2012 and 31 December 2016 from the MED database using coding and a free text search of all paediatric attendances. The data were then analysed using descriptive statistics. Over the 5-year period, 135 760 under 16-year-olds attended the MED. Of these, 868 (0.6%) attended for dental problems. The most common dental reasons for attendance were as follows: Candida accounted for 22.6% of the 0- to 5-year-olds; dental trauma accounted for 29.5% of 6- to 11-year-olds; and mandibular fractures accounted for 18.9% of the 12- to 16-year-olds. Of those who attended the MED for dental problems, 28.5% resided in areas with an Index of Multiple Deprivation decile of 1, the areas of highest deprivation in the UK. Many of the diagnoses may have been appropriately managed elsewhere in the community, which may result in improved treatment provision and tailored care pathways, as well as reducing strain on the MED. Further research is needed to investigate why patients attend MED with dental problems.


Histology of the perforated tympanic membrane and its muco-epithelial junction.
A histological study was performed on total human tympanic membranes with a central perforation. The specimens originated from 30 consecutive and unselected operations in which a total myringectomy was performed prior to reconstruction by means of a tympanic allograft. Beside excessive thickening of the tympanic membrane in 73%, all membranes showed other histological abnormalities: inflammation (97%), excessive fibrosis (97%), tympanosclerosis (80%), hyperkeratosis (83%), rete riges (43%) and epithelial inclusions (6%). Histological localisation of the muco-epithelial junction showed a medial position in 30%, with extensive middle ear invasion by squamous epithelium in 7%. The surgeon performing myringoplasty should keep these findings in mind and he should closely examine the medial side of the perforated tympanic membrane in order to remove any ingrowing epithelium that otherwise would be trapped.


Compact superconducting ring at ritsumeikan university.
A compact superconducting storage ring (0.575 GeV and 300 mA) with a racetrack microtron injection system was installed at Ritsumeikan University and has been operated successfully since April 1996. As the radius of the circular electron orbit is small (0.5 m), it is possible to use a radiation beam of relatively high photon flux at a short distance from the source point. Beamlines have been constructed including those for XAFS, soft X-ray spectroscopy, VUV spectroscopy, fluorescent X-ray analysis, soft X-ray microscopy, X-ray diffraction/scattering and photoelectron spectroscopy; the photoelectron spectrometer is combined with an ion-beam-scattering spectrometer to obtain information both on the electronic states and on the atomic arrangements of a solid surface. In addition there are two beamlines, one for LIGA exposure and the other for synchrotron radiation ablation, which are devoted to producing new devices and materials. The synchrotron radiation facility is open not only to users in the University but also to researchers in industry, governmental institutions and other universities.


New bimetallic compounds based on the bis(thiosemicarbazonato) motif.
Zinc and copper bis(thiosemicarbazonato) complexes containing more than one metal centre have been prepared with a view to examining their application for molecular imaging. The zinc complexes are fluorescent with excitation and emission at relatively long wavelengths. The dinuclear copper complex undergoes two sequential, quasi-reversible reductions.


Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high-throughput screening.
The production of engineered nanomaterials (ENMs) is a scientific breakthrough in material design and the development of new consumer products. While the successful implementation of nanotechnology is important for the growth of the global economy, we also need to consider the possible environmental health and safety (EHS) impact as a result of the novel physicochemical properties that could generate hazardous biological outcomes. In order to assess ENM hazard, reliable and reproducible screening approaches are needed to test the basic materials as well as nanoenabled products. A platform is required to investigate the potentially endless number of biophysicochemical interactions at the nano/bio interface, in response to which we have developed a predictive toxicological approach. We define a predictive toxicological approach as the use of mechanisms-based high-throughput screening in vitro to make predictions about the physicochemical properties of ENMs that may lead to the generation of pathology or disease outcomes in vivo. The in vivo results are used to validate and improve the in vitro high-throughput screening (HTS) and to establish structure-activity relationships (SARs) that allow hazard ranking and modeling by an appropriate combination of in vitro and in vivo testing. This notion is in agreement with the landmark 2007 report from the US National Academy of Sciences, "Toxicity Testing in the 21st Century: A Vision and a Strategy" (http://www.nap.edu/catalog.php?record_id=11970), which advocates increased efficiency of toxicity testing by transitioning from qualitative, descriptive animal testing to quantitative, mechanistic, and pathway-based toxicity testing in human cells or cell lines using high-throughput approaches. Accordingly, we have implemented HTS approaches to screen compositional and combinatorial ENM libraries to develop hazard ranking and structure-activity relationships that can be used for predicting in vivo injury outcomes. This predictive approach allows the bulk of the screening analysis and high-volume data generation to be carried out in vitro, following which limited, but critical, validation studies are carried out in animals or whole organisms. Risk reduction in the exposed human or environmental populations can then focus on limiting or avoiding exposures that trigger these toxicological responses as well as implementing safer design of potentially hazardous ENMs. In this Account, we review the tools required for establishing predictive toxicology paradigms to assess inhalation and environmental toxicological scenarios through the use of compositional and combinatorial ENM libraries, mechanism-based HTS assays, hazard ranking, and development of nano-SARs. We will discuss the major injury paradigms that have emerged based on specific ENM properties, as well as describing the safer design of ZnO nanoparticles based on characterization of dissolution chemistry as a major predictor of toxicity.


Measuring the composition-curvature coupling in binary lipid membranes by computer simulations.
The coupling between local composition fluctuations in binary lipid membranes and curvature affects the lateral membrane structure. We propose an efficient method to compute the composition-curvature coupling in molecular simulations and apply it to two coarse-grained membrane models-a minimal, implicit-solvent model and the MARTINI model. Both the weak-curvature behavior that is typical for thermal fluctuations of planar bilayer membranes as well as the strong-curvature regime corresponding to narrow cylindrical membrane tubes are studied by molecular dynamics simulation. The simulation results are analyzed by using a phenomenological model of the thermodynamics of curved, mixed bilayer membranes that accounts for the change of the monolayer area upon bending. Additionally the role of thermodynamic characteristics such as the incompatibility between the two lipid species and asymmetry of composition are investigated.


A retrospective study and gene analysis of canine sterile panniculitis.
In this study, a retrospective analysis was conducted to assess the current aspects and predisposing factors of canine sterile panniculitis. Miniature dachshund, neutered, and younger dogs appeared to be predisposed. In addition, histories of previous surgery and injection were associated in 46.5% of the cases, with several types of surgical suture materials used. About 88% of the dogs had multifocal lesions, frequently with signs of systemic illnesses. Whereas systemic immunosuppressive therapy was effective in most dogs, surgical excision of lesions was rarely curative. In order to prevent recurrences, over 65% of the cases required prolonged immunosuppressive therapy. Polymorphism of canine alpha(1)AT gene was investigated as a candidate gene for sterile panniculitis. Eight polymorphisms were discovered in seven Miniature dachshunds by direct nucleotide sequencing, which included a 12-bp deletion, three non-synonymous single nucleotide polymorphisms, and four silent substitutions. Genotyping of the two polymorphisms, c.109_120del12 and c.483A>C, which identified at high incidence in the dachshunds, was conducted in 83 dogs of 6 popular breeds. The frequencies of neither polymorphism differed between Miniature dachshunds and other breeds, suggesting that neither is responsible for developing panniculitis.


Chemically modified, immobilized trypsin reactor with improved digestion efficiency.
Tryptic digestion followed by identification using mass spectrometry is an important step in many proteomic studies. Here, we describe the preparation of immobilized, acetylated trypsin for enhanced digestion efficacy in integrated protein analysis platforms. Complete digestion of cytochrome c was obtained with two types of modified-trypsin beads with a contact time of only 4 s, while corresponding unmodified-trypsin beads gave only incomplete digestion. The digestion rate of myoglobin, a protein known to be rather resistant to proteolysis, was not altered by acetylating trypsin and required a buffer containing 35% acetonitrile to obtain complete digestion. The use of acetylated-trypsin beads led to fewer interfering tryptic autolysis products, indicating an increased stability of this modified enzyme. Importantly, the modification did not affect trypsin's substrate specificity, as the peptide map of myoglobin was not altered upon acetylation of immobilized trypsin. Kinetic digestion experiments in solution with low-molecular-weight substrates and cytochrome c confirmed the increased catalytic efficiency (lower K(M) and higher k(cat)) and increased resistance to autolysis of trypsin upon acetylation. Enhancement of catalytic efficiency was correlated with the number of acetylations per molecule. The favorable properties of the new chemically modified trypsin reactor should make it a valuable tool in automated protein analysis systems.


Genetic trend for milk yield from doe evaluations in the northeast United States.
Milk production records of 306 Alpine, 72 LaMancha, 170 Nubian, 84 Saanen, and 235 Toggenburg does born in the Northeast from 1972 through 1979 were used to estimate trends of additive genetic value. Estimated transmitting abilities were doubled and averaged for all does born in each year to obtain yearly estimates of genetic value. Genetic trends from regression of yearly mean genetic value on year of birth for Alpine, LaMancha, Nubian, Saanen, and Toggenburg averaged 11.4, -7.9, 1.9, 14.6, and 11.7 kg per year. Genetic trends were less than theoretically possible, indicating that more effective selection schemes are needed, although because of the limited number of does, the trends may not represent actual trends.


Health Technology Assessment (HTA) Case Studies: Factors Influencing Divergent HTA Reimbursement Recommendations in Australia, Canada, England, and Scotland.
To evaluate the national regulatory, health technology assessment (HTA), and reimbursement pathways for public health care in Australia, Canada, England, and Scotland, to compare initial Canadian national HTA recommendations with the initial decisions of the other HTA agencies, and to identify factors for differing national HTA recommendations between the four HTA agencies. Information from the public domain was used to develop a regulatory process map for each jurisdiction and to compare the HTA agencies' reimbursement recommendations. Medicines that were reviewed by all four agencies and received a negative recommendation from only one agency were selected as case studies. All four countries have a national HTA agency. Their reimbursement recommendations are guided by both clinical efficacy and cost-effectiveness, and the necessity for patient input. Their activities, however, vary because of different mandates and their unique political, social, and population needs. All have an implicit or explicit quality-adjusted life-year threshold. The seven divergent case studies demonstrate examples in which new medicine-indication pairs have been rejected because of uncertainties surrounding a range of factors including cost-effectiveness, comparator choice, clinical benefit, safety, trial design, and submission timing. The four HTA agencies selected for inclusion in this study share common factors, including a focus on clinical efficacy and cost-effectiveness in their decision-making processes. The differences in recommendations could be considered to be due to an individual agency's approach to risk perception, and the comparator choice used in clinical and cost-effectiveness studies.


Mesenteric cryptococcal granuloma in a dog caused by Cryptococcus neoformans var. grubii.
Although cryptococcosis is usually associated with respiratory and neurologic signs in domestic species (such as sneeze, cough, nasal discharge, seizures, ataxia), clinical manifestations of the disease may be more subtle and nonspecific. A 3-year-old male castrated Boxer dog presented with a history of chronic vomiting, diarrhea, weight loss, and lethargy. At no time had respiratory or neurologic signs been noted by the owners or the primary care veterinarian. Palpation of an abdominal mass revealed an atypical lesion location: a large (16 × 9 × 7 cm) mass at the root of the mesentery. Diagnosis was achieved through cytology of this mass and a positive serologic Cryptococcus capsular antigen titer; polymerase chain reaction was utilized for speciation of the abdominal isolate as Cryptococcus neoformans variety grubii. The animal was euthanized due to poor prognosis. After necropsy and histopathologic analysis, the mesenteric mass and associated lymph nodes were identified as large fungal granulomas. This is a rare manifestation of cryptococcosis, involving several visceral organs, with no remaining evidence of the route of entry of the organism. As prompt diagnosis of mycotic illness is paramount to successful management, this case indicates that cryptococcal infection should be considered as a differential diagnosis in dogs with gastrointestinal signs and lymphadenopathy. The protean nature of cryptococcosis is discussed within the context of a brief review of emerging and unresolved issues in pathogenesis.


The perioperative effects of chronic preoperative opioid use on shoulder arthroplasty outcomes.
Chronic opioid therapy is an increasingly used modality for the treatment of osteoarthritis-associated pain. We hypothesized that chronic opioid use would be associated with adverse outcomes in shoulder arthroplasty. A retrospective analysis of patients undergoing elective anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (rTSA) at a single institution from 2012-2015 was performed. Patients were stratified by preoperative opioid use (nonusers, short-acting opioid users, and long-acting opioid users), and their postoperative clinical outcomes were assessed. We identified 262 patients (170 rTSA and 92 anatomic TSA), of whom 138 were using opioids preoperatively (82% short acting and 18% long acting). When non-opioid users, short-acting opioid users, and long-acting opioid users were compared, mean total milligrams of morphine equivalents administered during postoperative hospitalization was significantly higher for those with preoperative opioid use (66.9 mg, 111.4 mg, and 208.3 mg, respectively; P < .001). In addition, postoperative visual analog scale pain scores were higher on postoperative day 0 (2.6, 3.2, and 3.9, respectively; P = .007), day 1 (4.0, 4.9, and 6.0, respectively; P < .001), and day 2 (3.0, 3.9, and 5.1, respectively; P < .001). Opioid use was not associated with a significantly increased hospital length of stay, complications, or readmission rates. For patients who completed 2-year follow-up, both the opioid user and non-opioid user groups demonstrated similarly improved postoperative American Shoulder and Elbow Surgeons shoulder scores. A preoperative history of opioid use before shoulder arthroplasty was associated with significantly higher perioperative opioid consumption and visual analog scale scores. However, unlike in patients undergoing total knee or hip arthroplasty, preoperative opioid use was not associated with increased hospital length of stay, perioperative complications, or 90-day readmission rates for shoulder arthroplasty.


Diagnosis and Outcome of Periosteal Chondrosarcoma in Two Cats.
Two cats, both over 10 yr old, were presented for evaluation of non-painful bony proliferations on the appendicular skeleton. These proliferations were identifiable via palpation. Radiographs showed a smooth, proliferative bony lesion of the distal femur (case 1) and tarsus (case 2) with mild soft tissue swelling. Surgical debulking with incomplete resection was performed in each cat. Subsequent histopathology resulted in a diagnosis of periosteal chondrosarcoma (PC). Although both cats have experienced local recurrence, both are still alive more than 2.5 yr after mass debulking. Periosteal chondrosarcoma is a differential diagnosis in proliferative cortical bony lesions near an articular surface in older cats. Partial resection of these masses can lead to an excellent quality of life, and proper diagnosis can avoid amputation or even euthanasia.


Broadband dielectric spectroscopy of a nematic liquid crystal in benzene.
Broadband dielectric spectroscopy has been used to analyze the temperature, frequency, and concentration dependences of the molecular dynamics of a nematic liquid crystal (5CB) mixed with the nonpolar solvent benzene. Differential scanning calorimetry measurement has been also performed to confirm the phase transitions of 5CB/benzene mixtures. The phase transition temperatures (crystalline to isotropic phases) thus obtained have been described very accurately from the temperature-dependent relaxation strength, the relaxation time, and the symmetric shape parameter of the relaxation function obtained from the fitting procedure. Two relaxation processes reflecting overall rotations around the short and long molecular axes are observed in both the nematic and isotropic phases. In the crystalline phase, the former process with the longer relaxation time disappeared, and latter process with shorter relaxation time shows a discontinuity at the freezing temperature. The relaxation process with shorter relaxation time obtained in the crystalline phase is larger than that obtained in the nematic phase because of the large restrictions in the crystalline phase. For the first time, we have precisely explained the molecular mechanism and structure of liquid crystalline materials as a function of concentration, temperature, and frequency.


Theoretical model for laser ablation outcome predictions in brain: calibration and validation on clinical MR thermometry images.
Neurosurgical laser ablation is experiencing a renaissance. Computational tools for ablation planning aim to further improve the intervention. Here, global optimisation and inverse problems are demonstrated to train a model that predicts maximum laser ablation extent. A closed-form steady state model is trained on and then subsequently compared to N = 20 retrospective clinical MR thermometry datasets. Dice similarity coefficient (DSC) is calculated to provide a measure of region overlap between the 57 °C isotherms of the thermometry data and the model-predicted ablation regions; 57 °C is a tissue death surrogate at thermal steady state. A global optimisation scheme samples the dominant model parameter sensitivities, blood perfusion (ω) and optical parameter (μeff) values, throughout a parameter space totalling 11 440 value-pairs. This represents a lookup table of μeff-ω pairs with the corresponding DSC value for each patient dataset. The μeff-ω pair with the maximum DSC calibrates the model parameters, maximising predictive value for each patient. Finally, leave-one-out cross-validation with global optimisation information trains the model on the entire clinical dataset, and compares against the model naïvely using literature values for ω and μeff. When using naïve literature values, the model's mean DSC is 0.67 whereas the calibrated model produces 0.82 during cross-validation, an improvement of 0.15 in overlap with the patient data. The 95% confidence interval of the mean difference is 0.083-0.23 (p < 0.001). During cross-validation, the calibrated model is superior to the naïve model as measured by DSC, with +22% mean prediction accuracy. Calibration empowers a relatively simple model to become more predictive.


Compaction simulator studies of a new drug substance: effect of particle size and shape, and its binary mixtures with microcrystalline cellulose.
The compaction characteristics of a new drug substance with two crystal habits and particle size fractions as well as its binary mixtures with microcrystalline cellulose were studied using an integrated compaction research system under 300 and 450 MPa pressures. The results indicate that the drug substance has poor intrinsic compaction properties. The three-dimensional hexagonal crystal habit or smaller particle size consistently produced a slightly higher total work of compaction as compared with the cubic brick habit or larger particle size, respectively. However, neither crystal habit produced a coherent compact. The compactability of the drug substance was improved by the inclusion of microcrystalline cellulose, and the crushing strength of the compacts increased as the amount of microcrystalline cellulose in the binary mixture was increased. Such correlation was not observed when the compaction data were evaluated using either the Heckel equation or the percentage porosity change as a function of applied pressure.


Protective effect of posterior cerebral circulation on carotid body ischemia.
Carotid Bodies (CB) are fed mainly by External Carotid Artery (ECA) and rarely by Internal Carotid Artery (ICA). We aimed to investigate the effect of Bilateral Common Carotid Artery ligation and BCCAL plus bilateral external carotid artery ligation on CB. This study has been conducted on 30 hybrid male rabbits. Normal CB analyses were made in six of these animals and others divided into two groups. BCCAL has been applied to the 1st group, and the 2nd group has undergone bilateral ECA ligation in addition to BCCAL. After sacrificing the animals, both sides CB were histopathologically observed. Normal and ischemic cells were counted. Bilateral Common Carotid Artery ligation did not cause total atrophy in CB. Partial reversible atrophy of CB was seen in group I, but that atrophy was found to be irreversible and all animals died within one week after ligation in group II. Retrograde blood flow mechanisms and collateral circulation impede the oligemic CB atrophy after BCCAL. But bilateral ECA ligation, in addition to BCCAL, causes both sides irreversible CB atrophy and death of animals within one week of ligation. The CB are parasympathetic paraganglia. They are chemoreceptors and located at the bifurcation zone of common carotid arteries. They are fed mainly by ECA or by its branches and rarely by ICA. As a consequence of this, BCCAL and/or ligation of external branches of common carotid artery may lead to an ischemic impairment of CB. In order to analyse the effect of carotid stenosis on CB, CB were directly examined in 6 of 30 hybrid rabbits. BCCAL was applied to twelve rabbits (group I) with ligation of both ECA in addition to BCCAL were made to the others (group II). Animals were followed up four months in group I; but all of the animals in group II died within one week. From both sides the CB were taken including the carotid bifurcation and histopathological changes were evaluated. As a result, it has been observed that incomplete ischemic lesions have developed in the CB because of retrograde blood flow from posterior circulation to the ECA providing blood for the CB. But in the second group these changes were irreversible and on both sides CB complete atrophy developed in those whose ECA were also ligated bilaterally.


Physical limits of acuity and hyperacuity.
An ideal detector is derived for the discrimination of arbitrary stimuli in the two-alternative forced-choice paradigm. The ideal detector's performance is assumed to be limited only by quantal fluctuations, the optics of the eye, and the size and spacing of the receptors in the retinal mosaic. Detailed predictions are presented for two-point acuity and hyperacuity tasks. The ideal detector's two-point resolution, over a wide range of luminances, is approximately 10 times worse than its two-point vernier acuity or separation discrimination. Furthermore, two-point resolution is shown to vary in proportion to the -1/4 power of spot intensity, but vernier acuity and separation discrimination vary in proportion to the -1/2 power of spot intensity. It is shown that this ideal detector can be implemented by the use of appropriately shaped receptive fields. The derivation provides a simple way to determine the shapes of these optimal receptive fields for arbitrary stimuli. The sensitivities of real (human) and ideal detectors are compared.


Fractures of the posterolateral tibial plateau.
We reviewed the clinical records and operative notes of 28 patients with fractures of the posterolateral tibial plateau seen at our institution from 1949 to 1982. Five of the 28 patients had chronic depressions of the posterolateral tibial plateau after initial treatment elsewhere. All five were disabled because of significant functional instability when the knee was in flexion. There were 23 acute fractures, of which 4 were initially nondisplaced and treated nonoperatively. One nonoperative patient was lost to followup; the remaining three were rated as having had good or excellent results. Nineteen patients had acute depressed fractures and were treated operatively with open reduction, elevation of the depressed area, and bone grafting, with or without internal fixation. All patients treated operatively at the time of injury were seen for followup from 24 to 145 months postoperatively, with a mean followup of 59 months. One patient was lost to followup; the other 18 were rated using both objective and subjective criteria. Seventeen (94%) achieved a final rating of excellent or good; one patient (6%) achieved a rating of fair. We have observed these fractures occurring in a younger population and producing significant disability in activities requiring a stable knee in flexion. The depressed posterolateral tibial plateau fracture is best assessed by AP, lateral, and 45 degrees internal oblique views on radiographic examination. Because of continued disability caused by chronic, depressed fractures of this type, we recommend open reduction and bone grafting in acute cases to eliminate instability in flexion. This procedure produces good or excellent results in most cases.


Free and protein-bound plasma estradiol-17 beta during the menstrual cycle.
Methods are described for the measurement of the estradiol-binding capacity of TeBG and of the free, TeBG-bound, and non-specifically protein-bound fractions of plasma estradiol. Each determination used undiluted plasma at 37 C, and a total volume of less than 2.0 ml of plasma was required to complete all the assays. The measurement of the per cent of free estradiol was affected by changes in plasma dilution. The measurement of the other fractions of estradiol was not influenced by changes in either the dilution or the volume of plasma. The distribution of plasma estradiol was determined daily throughout 5 individual menstrual cycles. The per cent of free, the per cent of TeBG-bound, and the TeBG binding capacity of estradiol remained constant throughout the cycle with mean values of 2.21 +/- 0.04% (SE), 38.4 +/- 0.7%, and 16.6 +/- 0.43 ng/ml, respectively. The mean association constant of TeBG for estradiol was 6.58 +/- 0.25 x 10(7)M-1. The concentration of the free and non-specifically protein-bound fractions of estradiol paralleled the total plasma concentration of estradiol. The results show that biologic events related to normal cyclic changes of plasma estradiol may be attributed to fluctuations in the free estradiol and to estradiol which is bound with low affinity to non-specific plasma proteins.


Risk of venous thromboembolism with drospirenone in combined oral contraceptive products.
To review primary literature regarding the risk of venous thromboembolism (VTE) in users of combined oral contraceptives (COCs) containing drospirenone compared to COCs containing other progestins. A literature search of MEDLINE and EMBASE (1950-January 2010) was conducted using the following search terms: VTE, thrombosis, thromboembolism, COC, combined hormonal contraceptives, drospirenone, Yasmin, and Yaz. Additional references were retrieved from reference citations. All English-language primary literature studies were evaluated for relevance. Five studies were identified for evaluation: 1 prescription event monitoring study, 2 prospective postmarketing cohort studies, 1 validation study, and 1 retrospective cohort study. Use of a COC is associated with a 3- to 6-fold increase in VTE risk compared to nonuse. This risk may vary among different oral contraceptives due to the progestin component. Studies evaluated showed that women utilizing a drospirenone-containing COC did not have a higher risk of VTE when compared to women utilizing other progestins. The crude incidence rate ratio for VTE in women taking a COC containing drospirenone compared to a COC containing other progestins ranged from 0.9 to 1.7 (95% CI 0.5 to 2.4). While the studies evaluating VTE risk were mostly large and long term, most failed to consider important risk factors for VTE such as prolonged immobility, obesity, smoking history, and family history of VTE (which could suggest a genetic predisposition to thrombotic events). It was also unclear with some of the studies whether equivalent estrogen doses were used in the comparisons. Several studies have evaluated the risk of VTE in users of COC-containing drospirenone compared with other progestins, and none were able to show a significantly increased risk of VTE with drospirenone. The recent media attention regarding VTE risk and drospirenone-containing COCs does not seem to be well supported by the research currently available.


Tribenzylphosphine oxide.
The title compound, (C(6)H(5)CH(2))(3)PO, is an organic tertiary phosphine oxide. The molecule has threefold symmetry, with the P-O bond along the threefold axis. Main dimensions include P-O 1.488 (4), P-C 1.823 (3) A and O-P-C 114.7 (1) degrees. The crystals were accidentally obtained when preparing complexes of nickel(II) with dibenzylphosphine.