Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1.
Plumbagin, a natural quinonoid constituent isolated from the root of medicinal plant Plumbago zeylanica L, has exhibited anti-tumor and anti-proliferative activities in various tumor cell lines as well as in animal tumor models. However, its anticancer effects and the mechanisms underlying its suppression of glioma cell growth have not been elucidated. Oncogenic transcription factor Forkhead Box M1 (FOXM1) has garnered particular interest in recent years as a potential target for the prevention and/or therapeutic intervention in glioma, nevertheless, less information is currently available regarding FOXM1 inhibitor. Here, we reported that plumbagin could effectively inhibit cell proliferation, migration and invasion and induce apoptosis of glioma cells. Cell cycle assay showed that plumbagin induced G2/M arrest. Interestingly, we found that plumbagin decreased the expression of FOXM1 both at mRNA level and protein level. Plumbagin also inhibited the transactivation ability of FOXM1, resulting in down-regulating the expression of FOXM1 downstream target genes, such as cyclin D1, Cdc25B, survivin, and increasing the expression of p21(CIP1) and p27(KIP1). Most importantly, down-regulation of FOXM1 by siFOXM1 transfection enhanced plumbagin-induced change in viability. On the contrary, over-expression of FOXM1 by cDNA transfection reduced plumbagin-induced glioma cell growth inhibition. These results suggest that plumbagin exhibits its anticancer activity partially by inactivation of FOXM1 signaling pathway in glioma cells. Our findings indicate that plumbagin may be considered as a potential natural FOXM1 inhibitor, which could contribute to the development of new anticancer agent for therapy of gliomas.


Idiopathic thrombocytopenia, initial illness and long term follow up.
One hundred and eighty one children with thrombocytopenia for which no cause could be found have been studied. One patient died with severe bleeding possibly from disseminated intravascular coagulation and one developed cerebral haemorrhage, both within two weeks of onset. Ninety one per cent of the 135 with acute disease but only 36% of those with chronic disease remitted spontaneously. Twenty per cent of spontaneous remission occurred more than one year after onset. Six patients have run an intermittent course for 10 to 20 years. Four patients have had symptomless thrombocytopenia for between 10 and 30 years. Of 32 children treated by splenectomy 24 maintained normal platelet values thereafter. One boy died from pneumococcal septicaemia two years after splenectomy but he had not received prophylactic penicillin. One hundred and fifty eight patients were followed up 3 to 37 years (mean 16.4 years) after onset. None who recovered spontaneously or after splenectomy had had further bleeding problems. No patient nor immediate relative had developed other autoimmune disease. We consider that a short course of corticosteroids immediately after diagnosis is justified in all cases even though we cannot produce proof that it influences the course of the disease. We do not accept any place for long term immunosuppressant treatment.


The chaperonin GroEL binds a polypeptide in an alpha-helical conformation.
Chaperones facilitate folding and assembly of nascent polypeptides in vivo and prevent aggregation in refolding assays in vitro. A given chaperone acts on a number of different proteins. Thus, chaperones must recognize features present in incompletely folded polypeptide chains and not strictly dependent on primary structural information. We have used transferred nuclear Overhauser effects to demonstrate that the Escherichia coli chaperonin GroEL binds to a peptide corresponding to the N-terminal alpha-helix in rhodanese, a mitochondrial protein whose in vitro refolding is facilitated by addition of GroEL, GroES, and ATP. Furthermore, the peptide, which is unstructured when free in aqueous solution, adopts an alpha-helical conformation upon binding to GroEL. Modification of the peptide to reduce its intrinsic propensity to take up alpha-helical structure lowered its affinity for GroEL, but, nonetheless, it could be bound and took up a helical conformation when bound. We propose that GroEL interacts with sequences in an incompletely folded chain that have the potential to adopt an amphipathic alpha-helix and that the chaperonin binding site promotes formation of a helix.


The Role of the Right Hemisphere White Matter Tracts in Chronic Aphasic Patients After Damage of the Language Tracts in the Left Hemisphere.
The involvement of the right hemisphere (RH) in language, and especially after aphasia resulting from left hemisphere (LH) lesions, has been recently highlighted. The present study investigates white matter structure in the right hemisphere of 25 chronic post-stroke aphasic patients after LH lesions in comparison with 24 healthy controls, focusing on the four cortico-cortical tracts that link posterior parietal and temporal language-related areas with Broca's region in the inferior frontal gyrus of the LH: the Superior Longitudinal Fasciculi II and III (SLF II and SLF III), the Arcuate Fasciculus (AF), and the Temporo-Frontal extreme capsule Fasciculus (TFexcF). Additionally, the relationship of these RH white matter tracts to language performance was examined. The patients with post-stroke aphasia in the chronic phase and the healthy control participants underwent diffusion tensor imaging (DTI) examination. The aphasic patients were assessed with standard aphasia tests. The results demonstrated increased axial diffusivity in the RH tracts of the aphasic patients. Patients were then divided according to the extent of the left hemisphere white matter loss. Correlations of language performance with radial diffusivity (RD) in the right hemisphere homologs of the tracts examined were demonstrated for the TFexcF, SLF III, and AF in the subgroup with limited damage to the LH language networks and only with the TFexcF in the subgroup with extensive damage. The results argue in favor of compensatory roles of the right hemisphere tracts in language functions when the LH networks are disrupted.


Reframing HIV Stigma and Fear : Considerations from Social-ecological and Evolutionary Theories of Reproduction.
HIV stigma and fears surrounding the disease pose a challenge for public health interventions, particularly those that target pregnant women. In order to reduce stigma and improve the lives of vulnerable populations, researchers have recognized a need to integrate different types of support at various levels. To better inform HIV interventions, the current study draws on social-ecological and evolutionary theories of reproduction to predict stigma and fear of contracting HIV among pregnant women in South India. The aims of this study were twofold: compare the social-ecological model to a modified maternal-fetal protection model and test a combined model that included strong predictors from each model. The study took place in 2008-2011 in Mysore District, Karnataka, India. Using data from a cross-sectional survey and biological indicators of health, we statistically modeled social-ecological variables representing individual, interpersonal, and community/institutional levels. Participants were 645 pregnant women. The social-ecological and combined models were the best-fitting models for HIV-related stigma, and the combined model was the best fit for HIV-related fear. Our findings suggest that combining reproductive life history factors along with individual, interpersonal, and community/institutional factors are significant indicators of HIV-related stigma and fear. Results of this study support a multifaceted approach to intervention development for HIV-related stigma and fear. The combined model in this study can be used as a predictive model for future research focused on HIV stigma and fear, with the intent that dual consideration of social-ecological and evolutionary theories will improve public health communication efforts.


[Genetic counseling and instruction for deaf couples directed by genetic testing].
To analyze the molecular pathogenesis of deaf couples by means of genetic testing. To provide accurate genetic counseling and instruction for deaf couples with different etiology based upon results of genetic testing. Four deaf families from July 2005 to May 2006. Each subject was with moderate to profound hearing loss. Genomic and mitochondrial DNA (mtDNA) of each subject were extracted from whole blood. Genetic testing of GJB2, SLC26A4 (PDS) and mtDNA A1555G mutation were offered to each individuals. The husband from family 1 didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation while his wife was confirmed to carry compound SLC26A4 mutations. The possibility of their offspring's to be SLC26A4 single mutation carrier was 100%. The couple from family 2 both didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation. The possibility of their offspring's having hereditary deafness caused by GJB2, SLC26A4 and mtDNA A1555G mutation was excluded. The husband from family 3 was confirmed to carry homozygous GJB2 mutations and a single SLC26A4 mutation while his wife who was diagnosed with enlarged vestibular aqueduct syndrome (EVAS) by CT scan was proven to carry a single SLC26A4 mutation. The risk of their offspring's suffering EVAS was 50%. The husband from family 4 was mtDNA A1555G positive while his wife who was diagnosed with cochlear malformation by CT scan didn't carry GJB2, SLC26A4 and mtDNA A1555G mutation. The risk of their offspring's having hereditary deafness caused by GJB2, SLC26A4 and mtDNA A1555G mutation was excluded. Genetic testing could be applied to offer the more accurate genetic counseling and instruction to deaf couples.


Estimation of chlorophyll-a concentration in Turbid Lake using spectral smoothing and derivative analysis.
As a major indicator of lake eutrophication that is harmful to human health, the chlorophyll-a concentration (Chl-a) is often estimated using remote sensing, and one method often used is the spectral derivative algorithm. Direct derivative processing may magnify the noise, thus making spectral smoothing necessary. This study aims to use spectral smoothing as a pretreatment and to test the applicability of the spectral derivative algorithm for Chl-a estimation in Taihu Lake, China, based on the in situ hyperspectral reflectance. Data from July-August of 2004 were used to build the model, and data from July-August of 2005 and March of 2011 were used to validate the model, with Chl-a ranges of 5.0-156.0 mg/m3, 4.0-98.0 mg/m3 and 11.4-35.8 mg/m3, respectively. The derivative model was first used and then compared with the band ratio, three-band and four-band models. The results show that the first-order derivative model at 699 nm had satisfactory accuracy (R2 = 0.75) after kernel regression smoothing and had smaller validation root mean square errors of 15.21 mg/m3 in 2005 and 5.85 mg/m3 in 2011. The distribution map of Chl-a in Taihu Lake based on the HJ1/HSI image showed the actual distribution trend, indicating that the first-order derivative model after spectral smoothing can be used for Chl-a estimation in turbid lake.


Anion-Exchange Properties of Plant Root Surfaces.
Anion-exchange properties of plant root surfaces were demonstrated by using negatively charged anion dyes. The site of the positive charges may be amino groups which become positively charged in the presence of hydrogen ions but are neutralized under alkaline conditions.


In vitro activity of zinc salts against human rhinoviruses.
The antiviral activity of zinc salts against rhinovirus types 1A and 39 was assayed by yield reduction and inhibition of cytopathic effect in cell culture. The findings indicate that the zinc salts tested have low in vitro therapeutic indices and suggest that the possible beneficial effects of zinc lozenges in reducing cold symptoms may not be related to selective antirhinovirus activity.


Amide bond formation with a new fluorous carbodiimide: separation by reverse fluorous solid-phase extraction.
A new fluorous carbodiimide is introduced along with a convenient procedure for amide coupling reactions. Reactions of acids and amines under standard conditions for carbodiimide couplings, followed by simple reverse fluorous solid-phase extraction (FSPE) over standard silica gel, provide the target amide products in good yields and purities. The use of HFE-7100 as a fluorous solvent is crucial for the success of the reverse FSPE.


Roles of T-cells in the development of allergic conjunctival diseases.
Massive infiltration of eosinophils is the typical histopathologic feature of severe forms of allergic conjunctival diseases (ACDs) such as vernal keratoconjunctivitis. Although ACD is an antigen (Ag)-specific disease, eosinophils lack Ag-specific receptors. Therefore, my group studied the likely roles of immunocompetent cells bearing Ag-specific receptors in inducing conjunctival eosinophil infiltration in ACDs. To induce experimental conjunctivitis (EC), Brown Norway rats and C57BL/6 and Balb/c mice were passively immunized by the transfer of Ag-specific or primed IgE, splenocytes, or purified T-cells and then challenged with Ag in eyedrops. The transfer of Ag-primed splenocytes or T-cells, but not of Ag-specific IgE, induced conjunctival eosinophil infiltration. We also showed that soon after EC induction by T-cell transfer, activated Ag-specific T-cells infiltrated the conjunctiva. Moreover, when EC-developing animals were topically treated with the T-cell-specific immunosuppressants cyclosporin A and FK506, conjunctival eosinophil infiltration was abrogated. In addition, only the transfer of Ag-specific type 2 helper T-cells (TH2 cells), but not of type 1 helper T-cells or CD8 T-cells, could induce conjunctival eosinophil infiltration. Our data show that Ag-specific TH2 cells play a crucial role in inducing conjunctival eosinophil infiltration during the development of EC. It is necessary to elucidate the roles that conjunctival residential cells and immunocompetent cells other than T-cells play in the conjunctival eosinophil infiltration of EC.


Neuroimaging studies of social cognition in schizophrenia.
Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology.


Comparison of Ocular Ultrasound Versus SD-OCT for Imaging of the Posterior Vitreous Status in Patients With DME.
To assess the percentage of vitreous adherence to the posterior pole in patients with diabetic macular edema (DME) with ocular ultrasonography (US) and establish a comparison with spectral-domain optical coherence tomography (SD-OCT). Cross-sectional consecutive analysis of patients followed in a diabetic retinopathy consultation. Vitrectomized eyes and patients with epiretinal membranes were excluded. A comparison between macular SD-OCT 20 × 20°, SD-OCT 55 × 35°, and ocular US for the vitreous status was performed. A subanalysis of the percentage of eyes with thickened posterior hyaloid and focal vitreous macular adhesion (VMA) was determined with SD-OCT 20 × 20° and SD-OCT 55 × 35°. From 78 eyes of 39 patients, 55 eyes were included. All patients had type 2 diabetes mellitus with a median duration of 20 years (range: 3 to 40 years); 60% were phakic, and 61.8% were male. Previous treatments included intravitreal injections in 54.5% eyes, macular laser in 67.3%, and panretinal photocoagulation in 56.4%. All eyes had a non-posterior vitreous detachment (PVD) status on US. The 55 × 35° SD-OCT detected a non-PVD status in 96.4% (100% in video display mode) and a VMA in 87.3%. The 20 × 20° SD-OCT only detected a VMA in 43.6% of cases, with a thickened posterior hyaloid in 40% and a focal VMA in 18.2%. In the authors' DME patients, vitreous adherence to the posterior pole was highly prevalent, with a total agreement between US and SD-OCT 55 × 35° video display mode. SD-OCT 20 × 20° is not an accurate method to diagnose VMA compared to SD-OCT 55 × 35°. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S50-S53.].


[Status quo of and challenges for research on rust disease in medicinal plants].
Medicinal plants are beneficial to human health. However,most of the major producing regions of medicinal plants suffer from rust disease,which threatens the yield and quality of Chinese medicinal materials,thus causes huge economic loss,and hinders the sustainable development of the Chinese medicine industry. By the end of 2020,rust disease had been reported in medicinal plants of 76 species and 33 families. In the 76 species,79 rust pathogens were detected. The majority of these pathogens belonged to Puccinia( 33,39. 24%),Coleosporium( 14,15. 19%),and Aecidium( 11,13. 92%). Of these 79 rust pathogens,10 were autoecious and 13 were heteroecious. Through literature research,this study reviewed the symptoms,pathogen species,severity and distribution,prevalence and occurrence conditions,and control measures of rust disease in medicinal plants,and thereby summarized the research status of rust disease in medicinal plants and the gap with other plants,which is expected to serve as a reference for further research on rust disease in medicinal plants.


Investigation of Azimuth Multichannel Reconstruction for Moving Targets in High Resolution Wide Swath SAR.
The azimuth multichannel imaging scheme with the large receive antenna divided into multiple sub-apertures usually leads to azimuth non-uniform sampling, and echoes from all azimuth channels should be reconstructed based on the signal model before conventional SAR imaging. Unfortunately, the multichannel signal model of a moving target is different from that of a fixed target. This paper analyzes the multichannel signal model of the moving target and the effect of the target velocity on azimuth multichannel reconstruction. Based on the multichannel signal mode of the moving target, a new multichannel signal reconstruction algorithm is proposed. Furthermore, the slant range velocity is estimated by computing signal energy distribution. Simulation results on point targets validate the proposed approach.


Impact of serial measurements of tricuspid annular plane systolic excursion on mortality and morbidity after heart transplantation.
The impact of right ventricular (RV) dysfunction on long-term post-HTx outcomes remains uncertain. We assessed the impact of serial measurements of Tricuspid Annular Plane Systolic Excursion (TAPSE) on post-HTx mortality and morbidity. This two-center retrospective cohort study included consecutive adult HTx recipients (2000-2017). We used multivariable extended hazard regression models to evaluate the association between TAPSE and left ventricular ejection fraction (LVEF), entered as time-dependent variables, and all-cause mortality, cardiac allograft vasculopathy (CAV), acute cellular rejection (ACR), and chronic kidney disease (CKD). TAPSE was modelled using cubic splines. We included 485 HTx recipients (9461 TAPSE measurements), median (25th- 75th percentile) 19 (10-27) mm; median age was 52 (41-59) years, and 71.3% were male. During a follow-up of 6.7 (3.0-10.8) years, 92 patients died, 225 had ACR >2R, 234 CAV, and 91 CKD. By multivariable analysis, for each 1-mm decrease in patients with a TAPSE value <15mm, mortality increased by 22% (P<.001). For the average HTx recipient with a TAPSE of 15mm, 10mm, and 6mm, 1-year mortality was 3%, 7%, and 17%, and 5-year mortality was 8%, 20%, and 43%, respectively. Reduced TAPSE was significantly associated with increased CAV but notACR and CKD. A decrease in TAPSE below 15mm represents clinically significant graft dysfunction, warranting close monitoring.


[Prostitution, the state, and society in Spain. The regulation of prostitution under the monarchy of Isabel II (1854-1868)].
After two centuries of official abolition, regulated prostitution came back during the reign of Isabella II and particularly from the Progresist period onwards (1854-1856). After recalling the origins of such regulations (1845-1847) and the rules applied in Madrid, which are worth noting because of their importance and influence, we are presenting the different decrees enforced in some regions of Spain (and particularly in the province of Cadiz), in a chronological way which enables the reader to understand the formation, administrative and medical, of these regulations. Instead of putting the prostitute in a house of correction or expelling her from the town as done before, these regulations would put her in a brothel, pretending that she would not move freely and that she would regularly be controlled concerning sexually transmitted diseases. The tolerance of prostitution confirmed as well the space and role of brothels in the social life of the main Spanish towns.


Biological activities of purified harpin(Xoo) and harpin(Xoo) detection in transgenic plants using its polyclonal antibody.
Many harpins have been found in plant pathogen bacteria that can elicit disease and insect resistance in plants, and promote plant growth. In this work, we overexpressed and purified Xanthomonas oryzae pv. oryzae harpin, harpin(Xoo), in Escherichia coli BL21/pGEX-hpa1. Harpin(Xoo) was fused to the C-terminus of glutathione S-transferase (GST) and purified using the Bulk GST purification module and thrombin cleavage capture kit. Purified harpin(Xoo) protein was sensitive to protease K and stable to heat treatment, and could not induce a hypersensitive response after treatment with various plant metabolic inhibitors; these characteristics were similar to harpin(Ea) of Erwinia amylovora. The purified harpin(Xoo) showed a similar ability to induce tobacco mosaic virus resistance in tobacco as harpin(Ea). Its antibody worked well in detecting the purified harpin(Xoo), harpin(Xoo) in the total protein of E. coli BL21/pGEX-hpa1 and an hpa1 transgenic rice.


[Relationship between epicardial adipose tissue and clinical prognosis of patients with coronary heart disease after percutaneous coronary intervention].
Objective: To further evaluate the clinical value of epicardial adipose tissue volume (EATV) in predicting the prognosis of coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: From July 2013 to July 2016 in TEDA International Cardiovascular Disease Hospital, a total of 474 patients diagnosed with CHD were included in this study.According to the result of EATV, patients were divided into three groups, group A (EATV≤75 ml), group B (75 ml<EATV<150 ml), and group C (EATV≥150 ml). Then the level of body mass index (BMI), hypersensitive c-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were tested for all the three groups.All the patients were followed up for 1 year for major adverse cardiovascular events (MACE). The clinical value of EATV in predicting the occurrence of MACE events was evaluated. Results: The BMI, level of hs-CRP, TNF-α in group B were higher than group A, group C were significantly higher than group B, with statistically significant difference across all the comparisons (P<0.05). Spearman correlation analysis showed EATV was positively correlated with hs-CRP, IL-6, TNF-α (r=0.675-0.700, P<0.01). The incidence of MACE in the three groups were 8.50% in group C, 5.26% in group B, 3.13% in group A, and the differences were all significant (P<0.01). ROC curve showed the cut-off value of EATV level was 120.39 ml to predict MACE (area under cure: 0.751, 95%CI: 0.634-0.868, P<0.01), and the sensitivity was 72.7%, the specificity was 61%.EATV>120.39 ml can be used as an independent risk factor for predicting the occurrence of MACE. Conclusion: The level of EATV is closely related to the occurrence of MACE events, and EATV>120.39 ml is an independent risk factor for MACE in patients with CHD after PCI.


Rsf-1/HBXAP overexpression is independent of gene amplification and is associated with poor outcome in patients with urinary bladder urothelial carcinoma.
Urothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive genes. Rsf-1, a subunit of ATP-dependent chromatin-remodelling complexes that mediates ATPase-dependent chromatin remodelling, confers tumour aggressiveness in certain carcinomas. The authors evaluate the Rsf-1 gene and expression status and its associations with clinicopathological features and survival in their UCUB collection. Immunohistochemistry was used to assess the Rsf-1 expression profile in 295 UCUB specimens, and was found to correlate with clinicopathological data. Real-time RT-PCR and fluorescence in situ hybridisation were used to detect RSF-1 mRNA expression and gene dosage in 20 independent cases. Western blot analysis was used to evaluate Rsf-1 protein expression in human urothelial cell lines. Rsf-1 overexpression was demonstrated in 101 cases (34.2%), and was significantly associated with advanced primary tumour (p<0.001), nodal metastasis (p=0.004), higher histological grades (p=0.001) and frequent mitoses (p<0.001). Moreover, it was predictive in disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p<0.0001 for both). Although RSF-1 gene amplification can be barely detected, its mRNA expression is significantly enhanced in tumours with higher primary tumour (p=0.041) and positive nodal statuses (p=0.010), respectively. Rsf-1 protein was abundant in invasive urothelial carcinoma cells but was not benign. Overexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome. The current study by the authors suggests gene amplification-independent mechanisms driving Rsf-1 overexpression during UCUB tumour progression.


A Rare Case of Intramural Müllerian Adenosarcoma Arising from Adenomyosis of the Uterus.
Müllerian adenosarcomas usually arise as polypoid masses in the endometrium of post-menopausal women. Occasionally, these tumors arise in the cervix, vagina, broad and round ligaments, ovaries and rarely in extragenital sites; these cases are generally associated with endometriosis. We experienced a rare case of extraendometrial, intramural adenosarcoma arising in a patient with adenomyosis. A 40-year-old woman presented with sudden-onset suprapubic pain. The imaging findings suggested leiomyoma with cystic degeneration in the uterine fundus. An ill-defined ovoid tumor with hemorrhagic degeneration, measuring 7.5 cm in diameter, was detected. The microscopic findings showed glandular cells without atypia and a sarcomatous component with pleomorphism and high mitotic rates. There was no evidence of endometrial origin. To recognize that adenosarcoma can, although rarely, arise from adenomyosis is important to avoid overstaging and inappropriate treatment.


Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice.
T cells are required for normal host defense against fungal infection, and individuals with T cell-deficiency syndromes are highly susceptible to fungal pathogens. Interleukin (IL)-17A is a proinflammatory cytokine that interconnects myeloid and lymphoid host defense. The role of murine (m) IL-17A/mIL-17A receptor (R) interactions was evaluated in a murine model of systemic candidiasis. In response to systemic challenge with Candida albicans, expression of mIL-17A was induced, and IL-17AR knockout (IL-17AR(-/-)) mice had dose-dependent, substantially reduced survival. Fungal burden in the kidneys of IL-17AR(-/-) mice was dramatically increased (25-fold at 96 h). In IL-17AR(-/-) mice, both mobilization of peripheral neutrophils and their influx to infected organs were significantly impaired and delayed. In vivo expression of mIL-17A protected normal mice from a lethal dose of C. albicans (100% at day 7 and 65% at day 42). The data suggest that the mIL-17A/mIL-17AR system is required for normal fungal host defense in vivo. IL-17A could have potential as a therapeutic cytokine for systemic C. albicans infections in immunocompromised patients with cancer or advanced acquired immunodeficiency syndrome.


Antimicrobial surveillance in idiopathic parkinsonism: indication-specific improvement in hypokinesia following Helicobacter pylori eradication and non-specific effect of antimicrobials for other indications in worsening rigidity.
Following Helicobacter pylori eradication in a placebo-controlled trial, the hypokinesia of idiopathic parkinsonism improved but flexor rigidity worsened. We surveyed the effect of all antimicrobial prescriptions in 66 patients with idiopathic parkinsonism over a median of 1.9 (interquartile range 0.4, 3.5) years. Initial Helicobacter screening was followed (where positive) by gastric biopsy. Serial lactulose hydrogen breath tests (364 tests) for small intestinal bacterial overgrowth monitored the need to encourage fluid intake and bulk/osmotic laxatives. We measured hypokinesia (401 assessments of mean stride length at free walking speed in 58 patients) and upper limb flexor rigidity (396 assessments in 49). Following successful H. pylori eradication (12 cases) but not failed (2), stride increased in entire group (including those receiving levodopa), core group (those receiving only longer-t½ antiparkinsonian medication or untreated) and untreated (p = .001 each case). The effect was greater with less antiparkinsonian medication (19 (95% CI, 14, 25) cm/year in untreated). Flexor rigidity was unchanged. Following antimicrobials for other indications (75 courses), hypokinesia was unchanged. However, flexor rigidity increased cumulatively. It increased in core group only after a first course (by (10 (0, 20)%/year, p = .05)), but then in entire, core and untreated after a second course (18 (6, 31), 33 (19, 48) and 29 (12, 48)%/year respectively; p = .002, .001 and .001) and further still after a third (17 (2, 34), 23 (8, 41) and 38 (15, 65)%/year; p = .02, .003 and .001). Initially, 40/66 were lactulose hydrogen breath test positive. Odds for positivity fell with time (by 59 (46, 75)%/year, p = .001) and tended to be lower with Helicobacter positivity (28 (8, 104)%, p = .06), but were unrelated to other antimicrobial interventions. Improved hypokinesia following antimicrobials appeared unique to Helicobacter eradication. Rigidity increased following successive antimicrobial exposures for other indications, despite diminishing lactulose hydrogen breath test positivity.


Increased erythrocyte glutathione peroxidase activity and serum tumor necrosis factor-alpha in HIV-infected patients: relationship to on-going prothrombotic state.
A condition of oxidative stress, due to perturbation of oxidant/antioxidant balance, has been suggested to play a role not only in the pathogenesis of human immunodeficiency virus (HIV) infection, but also in the promotion of a thrombophilic condition. Because various hemostatic dysfunctions usually considered as risk factors for thrombotic events were reported in HIV infection, this study was undertaken to investigate whether the oxidative phenomenon could promote a prothrombotic state in such condition. Erythrocyte glutathione peroxidase (GSH-Px), the major free-radical scavenger enzyme, and serum tumor necrosis factor-alpha (TNF-alpha) were evaluated in 33 consecutive HIV-infected out-patients and 35 matched HIV-negative healthy controls at a distance of any acute episode. Thrombin generation was explored by measuring the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), whereas fibrin degradation products (D-dimer) and plasminogen activator inhibitor (PAI-1) activity were evaluated as indices of plasmin activity and fibrinolytic derangement. The anticoagulant pathway was investigated by measuring the plasma levels of antithrombin and protein C. Erythrocyte GSH-Px activity and serum TNF-alpha were significantly higher in HIV-infected patients when compared to controls. F1 + 2, D-dimer, and PAI-1 activity were increased in HIV-infected patients by comparison with controls. Normal antithrombin, but decreased protein C, was instead detected in HIV-infected patients. In the latter patients, serum TNF-alpha negatively correlated with both erythrocyte GSH-Px activity and plasma D-dimer. On the other hand, a positive correlation was shown between F1 + 2 and D-dimer and between D-dimer and GSH-Px activity. Furthermore, a trend toward increasing levels of GSH-Px with increasing PAI-1 activity was reported. These findings suggest a relationship between erythrocyte oxidative stress and the hypercoagulable condition during HIV infection.


Intraoperative systemic lidocaine inhibits the expression of HMGB1 in patients undergoing radical hysterectomy.
Surgery stressors trigger inflammatory response and excessive inflammatory response leads to organ failure or even septic shock. HMGB1 as a later inflammatory cytokines and a critical mediator of severe sepsis is always associated with the aggravation of organ failure. Previous study shows that lidocaine can inhibit the expression of HMGB1 in macrophage of septic rats and protect animals from organ failure. The present study sought to determine whether intraoperative systemic lidocaine could attenuate the level of HMGB1 by inhibiting it expression in PBMC from patients underwent radical hysterectomy. Thirty patients were recruited and divided randomly into two groups according to the difference of study medicine. Patients in lidocaine group received an intravenous bolus infusion of 1.5 mg/kg of lidocaine followed by a continuous infusion of 1.5 mg/kg/h till discharged from operating room, and those in the control group received normal saline. Peripheral blood sample was drawn at pre-surgery, discharge from operating room and 48 h post-surgery. Monocytes were isolated and cultured with medium alone or with LPS. HMGB1 protein in serum or in supernatant of PBMC was detected with ELISA, while the HMGB1 mRNA in PBMC was determined by real-time quantitative PCR. The result showed that lidocaine not only attenuated the level of HMGB1 protein in serum and supernatant, but inhibited the transcription of HMGB1 mRAN in PBMC. The present study of us demonstrated that intraoperative systemic lidocaine can attenuate the level of HMGB1 and inhibit its expression in PBMC from patients underwent radical hysterectomy. Therefore, lidocaine may play an important role in many other clinical diseases by inhibiting HMGB1.


Autophagic control of listeria through intracellular innate immune recognition in drosophila.
Autophagy, an evolutionally conserved homeostatic process for catabolizing cytoplasmic components, has been linked to the elimination of intracellular pathogens during mammalian innate immune responses. However, the mechanisms underlying cytoplasmic infection-induced autophagy and the function of autophagy in host survival after infection with intracellular pathogens remain unknown. Here we report that in drosophila, recognition of diaminopimelic acid-type peptidoglycan by the pattern-recognition receptor PGRP-LE was crucial for the induction of autophagy and that autophagy prevented the intracellular growth of Listeria monocytogenes and promoted host survival after this infection. Autophagy induction occurred independently of the Toll and IMD innate signaling pathways. Our findings define a pathway leading from the intracellular pattern-recognition receptors to the induction of autophagy to host defense.


Diastereoselective imino-aldol condensation of chiral 3-(p-Tolylsulfinyl)-2-furaldimine and ester enolates.
(Ss)-3-(p-Tolylsufinyl)-2-furaldimine was synthesized, and condensation of the chiral furaldimine with lithium ester enolates has been examined. The product distribution of the reaction is dependent upon reaction conditions and on the kind of the substituent placed on the esters. Disubstituted ester enolate resulted in the exclusive formation of (4R)-beta-lactam, while unsubstituted, tert-butyl ester enolate preferentially gave (3R)-beta-amino ester. With the monosubstituted ester enolates, the condensation afforded (4R)-beta-lactams and/or (3R)-beta-amino esters as major products. This method has been applied to an efficient route to chiral furyl beta-lactams.


Molecular cloning, expression, and characterization of dnaK in Streptococcus pneumoniae.
DnaK is known to be highly conserved in all species and is a major immunogen in Streptococcus pneumoniae. To elucidate the role of dnaK in S. pneumoniae, dnaK was cloned in Escherichia coli using a homologous dnaK probe generated by PCR. The His-tagged DnaK was overexpressed in soluble form and purified from E. coli. Alignment of the deduced DnaK amino acid sequence from nucleotide sequences of the cloned dnaK revealed high homology with DnaK analogs in E. coli (53%) and Staphylococcus aureus (73%). However, anti-pneumococcal DnaK antiserum did not crossreact with DnaK analogs in E. coli, S. aureus and human cells suggesting that pneumococcal DnaK might be a good candidate as a vaccine.


CO2 capture and electrochemical conversion using superbasic [P66614][124Triz].
The ionic liquid trihexyltetradecylphosphonium 1,2,4-triazolide, [P66614][124Triz], has been shown to chemisorb CO2 through equimolar binding of the carbon dioxide with the 1,2,4-triazolide anion. This leads to a possible new, low energy pathway for the electrochemical reduction of carbon dioxide to formate and syngas at low overpotentials, utilizing this reactive ionic liquid media. Herein, an electrochemical investigation of water and carbon dioxide addition to the [P66614][124Triz] on gold and platinum working electrodes is reported. Electrolysis measurements have been performed using CO2 saturated [P66614][124Triz] based solutions at -0.9 V and -1.9 V on gold and platinum electrodes. The effects of the electrode material on the formation of formate and syngas using these solutions are presented and discussed.


New insights into the meaning and usefulness of principal component analysis of concatenated trajectories.
A comparison between different conformations of a given protein, relating both structure and dynamics, can be performed in terms of combined principal component analysis (combined-PCA). To that end, a trajectory is obtained by concatenating molecular dynamics trajectories of the individual conformations under comparison. Then, the principal components are calculated by diagonalizing the correlation matrix of the concatenated trajectory. Since the introduction of this approach in 1995 it has had a large number of applications. However, the interpretation of the eigenvectors and eigenvalues so obtained is based on intuitive foundations, because analytical expressions relating the concatenated correlation matrix with those of the individual trajectories under consideration have not been provided yet. In this article, we present such expressions for the cases of two, three, and an arbitrary number of concatenated trajectories. The formulas are simple and show what is to be expected and what is not to be expected from a combined-PCA. Their correctness and usefulness is demonstrated by discussing some representative examples. The results can be summarized in a simple sentence: the correlation matrix of a concatenated trajectory is given by the average of the individual correlation matrices plus the correlation matrix of the individual averages. From this it follows that the combined-PCA of trajectories belonging to different free energy basins provides information that could also be obtained by alternative and more straightforward means.


Olea europaea L. Leaf Extract Alleviates Fibrosis Progression and Oxidative Stress Induced by Bleomycin on a Murine Model of Lung Fibrosis.
In this study, we aim to investigate the effect of industrial Olea europaea L. leaf extract (OLE) against bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Male Wistar rats were treated with a single intratracheal injection of BLM (4 mg/kg) and a daily intraperitoneal injection of OLE (10, 20, and 40 mg/kg) for 4 weeks. Results of HPLC and LC-MS analysis revealed a large amount of oleuropein (15.43%/DW) in OLE. BLM induced apparent damage of lung architecture with condensed collagen bundles, increased lipid peroxidation which has been deduced from malondialdehyde (MDA) levels: (.9 ± .13 vs .25 ± .12 nmol/mg protein) and hydroxyproline content (.601 ± .22 vs .154 ± .139 mg/g of lung tissue) and decreased catalase (CAT) (5.93.10-5 ± 4.23.10-5 vs 6.41.10-4 ± 2.33.10-4 μmol/min/mg protein) and superoxide dismutase (SOD) (28.73 ± 3.34 vs 50.13 ± 2.1 USOD/min/mg protein) levels compared to the control. OLE treatment (40 mg/kg) stabilized MDA content (.32 ± .15 and .27 ± .13 vs .9 ± .13 nmol/mg protein), normalized SOD (61.27 ± 13.37 vs 28.73 ± 3.34 USOD/min/mg protein), and CAT (5.2.10-4 ±1.8.10-4 vs 5.93.10-5 ± 4.23.10-5 μmol/min/mg protein) activities and counteracted collagen accumulation and hydroxyproline content (.222 ± .07 vs .601 ± .22 mg/g of lung tissue) in the lung parenchyma. Finally, OLE might have a potent protective effect against PF by regulating oxidative parameters and attenuating collagen deposition, due to the existence of large amount of bioactive phenolic molecules.


Real-Time User Identification and Behavior Prediction Based on Foot-Pad Recognition.
In the IoT (Internet of things)-based smart home, the technology for recognizing individual users among family members is very important. Although research in areas such as image recognition, biometrics, and individual wireless devices is very active, these systems suffer from various problems such as the need to follow an intentional procedure or own a specific device. Furthermore, with a centralized server system for IoT service, it is difficult to guarantee real-time determinism with high accuracy. To overcome these problems, we suggest a method of recognizing users in real time from the foot pressure characteristics measured as a user steps on a footpad. The proposed model in this paper uses a preprocessing algorithm to determine and generalize the angle of foot pressure. Based on this generalized foot pressure angle, we extract nine features that can distinguish individual human beings, and employ these features in user-recognition algorithms. Performance evaluation of the model was conducted by combining two preprocessing algorithms used to generalize the angle with four user-recognition algorithms.


[Correlation of intravesical prostatic protrusion with clinical evaluation parameters in BPH patients].
To investigate the correlation of the degrees of intravesical prostatic protrusion (IPP) measured by transabdominal ultrasound with the clinical evaluation parameters in BPH patients. We measured the length of IPP in the mid-sagittal section by transabdominal ultrasound in 275 BPH outpatients with lower urinary tract symptoms, and analyzed the correlations of the degree of IPP with the age, prostatic volume (PV), international prostatic symptom score (IPSS), maximum uroflow rate (Qmax), and postvoid residual urine volume (PVR) of the patients. The degree of IPP was correlated positively with the age (r = 0.210, P < 0.01), PV (r = 0.534, P < 0.01) and PVR (r = 0.314, P < 0.01), but negatively with the Qmax (r = -0.364, P < 0.01) of the BPH patients. There was no significant correlation between the degree of IPP and IPSS (r = 0.064, P = 0.299). The degree of IPP may be associated with the age and prostatic volume of BPH patients. Transabdominal ultrasound measurement of IPP is a useful noninvasive method to assess the presence and severity of bladder outlet obstruction in BPH patients.


[Osteonecrosis of the jaws associated with bisphosphonates: five cases].
Bisphosphonates have been recently associated with bone necrosis of jaws. Five patients were treated, two males and three females. All patients received bisphophonates and chemotherapeutic agents, two for multiple myeloma and three for breast cancer with bone metastasis. Bisphophonates were discontinued. None of the patients had received radiotherapy to the head and neck. The localization was mandibular in four patients and the maxillary area in one with oro-antral fistula. Histological and microbiological studies were performed. Histopathology demonstrated osteonecrosis and ruled out detectable neoplastic disease of the jaws. Four biopsies showed Actinomycosis. Four patients underwent sequestrectomy, but the mucosa did not heal. Two mechanisms are involved: the antiangiogenic effect of bisphophonates has recently been described in vivo; as bone mineralization increases, accumulation of microdamage is observed in animals studies. Only the jaws are affected by bone necrosis, suggesting a possible trophism for bisphosphonate uptake? Other risks factors have been found: cancer, use of chemotherapeutic agents or corticosteroids, renal failure, Actinomycosis infection. The only effective treatment is dental prevention before starting treatment.


Development and Validation of Spectrophotometric Methods for the Determination of Canagliflozin or Gliclazide and Metformin in the Presence of Metformin Impurity (1-Cyanoguanidine).
Background: Quantitative multicomponent analysis is considered an analytical goal to save time and cost in analysis. Objective: This work aimed to provide sensitive and selective [successive ratio subtraction coupled with constant multiplication (SRS-CM) and chemometric] methods for the determination of coformulated antidiabetic drugs, namely canagliflozine and metformin or gliclazide and metformin in presence of metformin degradation product, 1-cyanoguanidine. Methods: SRS-CM method was developed for the determination of canagliflozin and metformin at 292 and 237 nm, respectively, using 14 μg/mL canagliflozin as a divisor in the first step to cancel the spectrum of canagliflozin. Then, 18 μg/mL metformin was used as a divisor in the second step to cancel the spectrum of metformin. Finally, we obtained the spectrum of cyanoguanidine. Chemometric method was applied for the determination of the gliclazide and metformin mixture in a 225-235 nm range. Sample enrichment technique was used to increase the concentration of canagliflozin or gliclazide to allow its simultaneous determination with metformin without prior separation. Results: Validation parameters according to the International Conference on Harmonization guidelines were satisfactory over the concentration ranges of 5 to 16 μg/mL for canagliflozin and metformin as well as 2.5 to 12.5 and 6 to 24 μg/mL for gliclazide and metformin, respectively. Conclusions: The method provides sufficient selectivity and accuracy to be applied for routine analysis and quality control in laboratories for the cited drugs. Highlights: This work shows two examples to how to select a suitable UV spectrophotometric method to overcome the spectral overlap.


De novo, systemic, deleterious amino acid substitutions are common in large cytoskeleton-related protein coding regions.
Human mutagenesis is largely random, thus large coding regions, simply on the basis of probability, represent relatively large mutagenesis targets. Thus, we considered the possibility that large cytoskeletal-protein related coding regions (CPCRs), including extra-cellular matrix (ECM) coding regions, would have systemic nucleotide variants that are not present in common SNP databases. Presumably, such variants arose recently in development or in recent, preceding generations. Using matched breast cancer and blood-derived normal datasets from the cancer genome atlas, CPCR single nucleotide variants (SNVs) not present in the All SNPs(142) or 1000 Genomes databases were identified. Using the Protein Variation Effect Analyzer internet-based tool, it was discovered that apparent, systemic mutations (not shared among others in the analysis group) in the CPCRs, represented numerous deleterious amino acid substitutions. However, no such deleterious variants were identified among the (cancer blood-matched) variants shared by other members of the analysis group. These data indicate that private SNVs, which potentially have a medical consequence, occur de novo with significant frequency in the larger, human coding regions that collectively impact the cytoskeleton and ECM.


The role of PSMA PET/CT to predict upgrading in patients undergoing radical prostatectomy for ISUP grade group 1 prostate cancer.
To investigate the additive role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) independent from multiparametric magnetic resonance imaging (mpMRI) and clinical-pathological parameters to predict pathological upgrading in patients with ISUP grade group (GG) 1 prostate cancer (PCa) at prostate biopsy. A total of 41 patients who underwent robotic radical prostatectomy (RP) for GG1 disease at prostate biopsy with preoperative PSMA PET/CT and mpMRI images available for central review were included in the study. Univariate and multivariate logistic regression analyses were performed to determine the independent predictors of pathological upgrading (GG ≥ 2). Final RP pathology revealed upgrading in 26 patients (65.9%); to GG 2 disease in 25 cases and GG 4 disease in one case. International Society of Urological Pathology (ISUP) upgrading rates for prostate imaging-reporting and data system (PIRADS)-5, PIRADS-4, and PIRADS ≤ 3 lesions were 78%, 74%, and 38%, respectively. Fourteen out of 15 (93.3%) patients with an SUVmax ≥ 5.6 and all patients with an SUVmax ≥ 6.5 (n = 10) had pathological upgrading. The upgrading rate in patients with SUV < 5.6 was 46.2% (12/26). Intraprostatic SUVmax ≥ 5.6 was found as the only independent predictor of pathological upgrading in multivariate analysis. High prostatic PSMA uptake was found to be a very reliable predictor of pathological upgrading, but low PSMA uptake cannot exclude pathological upgrading. Intraprostatic PSMA uptake along with previously known mpMRI and biopsy-related parameters should be considered when making a treatment decision in patients with GG1 PCa at prostate biopsy.


[Effectiveness of influenza vaccination in healthy adults--a fourfold decrease in influenza morbidity during one influenza season].
Despite the existence and availability of effective and safe influenza vaccines, influenza still remains an important cause of morbidity and mortality worldwide, incl. all economic consequences and the increased number of days of work incapacity. Vaccination against influenza is an effective method of prevention of the disease and its complications. Nevertheless many people still do not trust the effectiveness of anti-influenza vaccination, incl. many physicians, nurses and other health professionals. The objective of the present study is to evaluate the effectiveness of vaccination against influenza in healthy adults aged 18-60 years, vaccinated with one of the five commonly available vaccines. The evaluation is based on notifications of influenza and influenza--like diseases. The trial comprised 375 subjects vaccinated against influenza during a given season, as a control group served 340 non-vaccinated subjects. Both groups of volunteers were investigated for six months. During this period the incidence of influenza or influenza--like diseases was recorded, the presence of local and general influenza symptoms, the number of days of work incapacity and the number of visits to the doctor. These data were obtained by the postal correspondence method. In the group of 375 vaccinated subjects 17 (4.5%) became ill. In the group of non-vaccinated subjects 65 (19.1%) became ill. The difference in the incidence of influenza was statistically significant. In subjects vaccinated against influenza a 73-76% effectiveness of vaccination was achieved. Subjects in the non-vaccinated group reported more than a fourfold incidence of influenza as compared with vaccinated subjects. The symptoms of the disease did not differ significantly in the two groups. The most frequent symptom of the disease which was recorded in both groups was fever higher than 38 degrees C, pain in the joints, myalgia and finally cough. More than two thirds of the sick volunteers visited their doctor while ill. From the results of the study it is obvious that vaccination against influenza in healthy adults significantly reduces the incidence of influenza, reduces the number of days of work incapacity and leads to a diminution of the number of medical examinations. Vaccination against influenza is effective in the prevention of the disease and is beneficial also for healthy non-risk population groups.


Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.
This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.


Medical library services in Kuwait: history and future prospects.
Despite immense resources and a growing interest in education and libraries, library development in Kuwait has been restricted by the problems common to all developing countries. These include an overdose of bureaucracy, lack of trained librarians, and little perception of the library's importance in the educational system. Medical librarianship is virtually a new field. The only medical library of any significance in the country is the Faculty of Medicine Library established in 1974 to serve the newly organized Faculty of Medicine of Kuwait University. In recent years, the Faculty of Medicine Library has gone through several reassessments and many changes. It has expanded its collection, begun computerized searching, and recruited several professional librarians. Now semiautonomous from the university's Libraries Department and housed in a new, modern building, the library has the potential to become the main medical library in the Persian Gulf area.


Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study.
Sodium valproate enteric-coated tablets were used in this double-blind, randomized, cross-over study of 16 patients with juvenile myoclonic epilepsy comparing 1000 mg and 2000 mg VPA daily in b.i.d. administration with 6 months of observation on each dose. Myoclonic, absence, and generalized tonic-clonic seizures were registered separately. Subjective side-effects were monitored, and a computerized neuropsychologic test battery was performed on each dose. There was no significant difference in seizure frequency between the two doses. Only 25% of the patients were seizure free throughout the study despite concentrations well within the normally proposed therapeutic range for VPA. During the higher dose, 37.5% of the patients had an improved seizure control, but 25% of the patients had an increase in seizure frequency compared to the lower dose. However, there was no correlation between VPA concentrations and subjective side-effects or neuropsychologic test results. Our observations point out the possibility that the common strategy of increasing plasma levels in difficult-to-treat patients until side effects occur should perhaps be reconsidered, but this suggestion needs further confirmation.


Target cells for interferon induction by BL-20803.
The role of certain cells of the reticuloendothelial system in the interferon response of mice to the low-molecular-weight compound 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazola-3,4-b-quinoline dihydrochloride (BL-20803) was studied. Mouse spleen adherent cells cultured in vitro with subtoxic concentrations of BL-20803 produced interferon. Adherent cells isolated from peritoneal washes were unresponsive to the compound. Treatment of mice with rabbit antiserum to mouse adherent cells suppressed interferon production by at least 65%, wheras antisera to thymocytes or to nonadherent spleen cells failed to suppress the interferon response. Pretreatment of mice with zymosan resulted in the appearance of circulating interferon in mice given 100 mg of the inducer/kg (a dosage to which they are normally unresponsive). No potentiation of the interferon response to the drug occured in immunized mice actively making a humoral or delayed-type hypersensitivity immune response. It is concluded that a specific type of cell in the mouse, the so-called "fixed macrophage," may be a major target for interferon induction by BL 20803.


Exploiting Natural Variation to Uncover an Alkene Biosynthetic Enzyme in Poplar.
Alkenes are linear hydrocarbons with one or more double bonds. Despite their potential as biofuels and precursors for specialty chemicals, the underlying biochemistry and genetics of alkene biosynthesis in plants remain elusive. Here, we report on a screen of natural accessions of poplar (Populus trichocarpa), revealing that the leaf cuticular waxes are predominantly composed of alkanes and alkenes. Interestingly, the accumulation of alkenes increases with leaf development, is limited to the abaxial side of the leaf, and is impaired in a few accessions. Among other genes, a β-ketoacyl CoA synthase gene (PotriKCS1) was downregulated in leaves from non-alkene-producing accessions. We demonstrated biochemically that PotriKCS1 elongates monounsaturated fatty acids and is responsible for the recruitment of unsaturated substrates to the cuticular wax. Moreover, we found significant associations between the presence of alkenes and tree growth and resistance to leaf spot. These findings highlight the crucial role of cuticular waxes as the first point of contact with the environment, and they provide a foundation for engineering long-chain monounsaturated oils in other species.


Modifications of sleep structure induced by increasing levels of acoustic perturbation in normal subjects.
In each non-REM (NREM) sleep stage, the aggregation of the arousal-related phasic events permits identification of periods of arousal fluctuation (cyclic alternating pattern or CAP) and periods of long-lasting arousal stability (non-CAP or NCAP). As the ratio CAP time to NREM sleep time (CAP/NREM) measures the instability of arousal during sleep, any perturbing event determines an increase of CAP/NREM. On the basis of these premises, 6 healthy volunteers underwent 5 sleep recordings at increasing intensities of sound pressure level (basal condition followed by continuous white noise at 45 dBA, 55 dBA, 65 dBA and 75 dBA, respectively). Besides a remarkable enhancement of CAP/NREM (P less than 0.00001), acoustic perturbation induced a significant linear increase of waking time after sleep onset, stage 2, NREM sleep, stage shifts and a significant linear decrease of stage 4, deep sleep, REM sleep and total sleep time. At each step of environmental disturbance, the values of the CAP ratio were consistent with the gradual changes of sleep organization. Although the Multiple Sleep Latency Test was unremarkable during the day following the sleep recording, CAP/NREM was significantly correlated with the personal evaluation of sleep quality (P less than 0.01). Through this model of transient situational insomnia it was possible to outline different degrees of subjective complaint depending on 3 ranges of CAP/NREM. A crucial role of CAP in the pathophysiological mechanisms of clinical insomnia is hypothesized.


The home as a framework for health care.
The past two or three decades have witnessed a steep rise in the cost of health and social services. It is anticipated that this uphill climb will continue and bring these systems to a complete collapse within a few decades. The prevention of this crisis depends on the elimination of some of the causes of the rise: (a) we do not want to save costs by sacrificing the quality of our services; (b) we have no control over the quantity of clients utilizing these services, or the seriousness of their problems; (c) we can, however, replace part of the expensive institutional care by the more natural and cost-effective home care, supplied by volunteers, strengthened by human and technological services. These principles guided an Israeli organization called Yad Sarah, whose leadership in the supply of home and community care enables thousands of ill, elderly and disabled people to remain at home and thus save the high cost of institutionalization.


Differential control of cardiac and sympathetic vasomotor activity from the dorsomedial hypothalamus.
1. The dorsomedial hypothalamus (DMH) plays a crucial role in mediating the cardiovascular responses to different stressors, including acute psychological stress and cold stress. Activation of neurons in the DMH evokes increases in arterial pressure and in the activity of sympathetic nerves innervating the heart, blood vessels and brown adipose tissue. The descending pathways from the DMH to the spinal sympathetic outflow include synapses with neurons in medullary nuclei and possibly other brain stem regions. 2. Recent studies from our and other laboratories have indicated that neurons in the rostral ventrolateral medulla (RVLM) and in the region of the raphe pallidus (RP) in the medulla are important components of the descending pathways that mediate the cardiovascular response to activation of the DMH. Neurons in the RP primarily mediate the sympathetic cardiac components of the DMH-evoked response, whereas the RVLM neurons primarily mediate the sympathetic vasomotor component. 3. Activation of DMH neurons not only increases heart rate and sympathetic vasomotor activity, but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure. 4. Activation of 5-hydroxytryptamine 5-HT(1A) receptors in the medulla oblongata leads to a selective suppression of cardiac and sympathetic vasomotor components of the DMH-evoked response, but does not affect sympathetic reflex responses evoked from baroreceptors or chemoreceptors. Thus, central 5-HT(1A) receptors modulate cardiovascular responses evoked from the DMH in a highly potent but selective fashion.


CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation.
SPG76 is one of the rare forms of hereditary spastic paraplegia (HSP) which causes by mutations in the CAPN1 gene. The mode of inheritance of SPG76 is autosomal recessive (AR) and so far, only 24 families and 25 mutations in this gene have been reported worldwide. These mutations have been associated with a spectrum of disorders from pure HSP to spastic ataxia. HSP genetically is one of the most heterogeneous neurological disorders and to date, 79 types of HSP (SPG1-SPG79) have been identified, however, it has been suggested that many HSP-genes, particularly in AR-HSPs, remained unknown. AR-HSPs clinically overlap with other neurodegenerative disorders, making an accurate diagnosis of the disease difficult. Therefore, in addition to clinical examination, a high throughout genetic method like whole exome sequencing (WES) may be necessary for the diagnosis of this type of neurodegenerative disorders. Herein, we present the clinical features and results of WES in the first Iranian family with a novel CAPN1 variant, c.C853T:p.R285* and pure HSP. Some of the previous studies have mentioned that the "spasticity-ataxia phenotype might be conducted to the diagnosis of SPG76" but recently the number of pure HSP patients with CAPN1 mutation is increasing. The present study also expands the mutation spectrum of pure CAPN1-related SPG76; emphasizing that CAPN1 screening is required in both pure HSP and spasticity-ataxia phenotypes. As noted in some other literature, we suggest the clinical spectrum of this disorder to be considered as "CAPN1-associated neurodegeneration".


Metastatic head and neck cancer to the percutaneous endoscopic gastrostomy exit site: a case report and review of the literature.
Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure and is an important supportive treatment adjunct for patients with head and neck cancer. We report a case in which squamous cell carcinoma of the larynx implanted at a PEG exit site. This was resected for cure. In this case, and in five others reviewed in the literature, the PEG placement method was the "pull" technique. It is unknown whether other methods of PEG placement may reduce metastatic implants at the PEG exit site, but the possibility of this complication must be considered.


Effects of lipase, lipoxygenase, peroxidase, and rutin on quality deteriorations in buckwheat flour.
To investigate the effects of changes in lipase, lipoxygenase, peroxidase (POX), and rutin concentrations on the quality of buckwheat flour, 14 buckwheat varieties were stored for 0, 4, 10, and 30 days at 5 or 20 degrees C. During the storage period, lipase activity correlated to pH (significantly negative) and water-soluble acid (WSA) (significantly positive). The lipoxygenase 1 protein concentration had a negative correlation to WSA (significant at 0 and 4 storage days at 5 degrees C and at 0 and 10 storage days at 20 degrees C). POX had significant correlation to pH and peroxide value (POV) at 5 degrees C, whereas it was not significant at 20 degrees C. The rutin concentration had negative correlations to WSA (significant at 30 days of storage at 5 degrees C and at 4 days of storage at 20 degrees C). Thus, lipase activity plays an important role that relates to lipid degradation in quality deterioration of buckwheat flour.


Human keratinocytes express HLA-DR antigens in the tuberculin reaction.
The cellular response in the human skin tuberculin reaction was studied with immunohistochemical double-staining techniques in frozen sections of skin biopsies taken 6 h to 8 days after intradermal PPD injections. Cell infiltrates were observed from day 2 onwards and increased in size up to 4 days. Most of the infiltrating cells reacted with anti-Leu 3a (T 'helper/inducer' phenotype) antibodies. In contrast to normal epidermis, not only Langerhans cells but also keratinocytes expressed HLA-DR antigens from day 4 onwards. The induction of HLA-DR antigens on keratinocytes may be secondary to T-cell activation. Since the HLA-DR expression on keratinocytes appeared late in the tuberculin reaction, the function may be to suppress rather than enhance the immune response.


Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheumatoid arthritis patients.
The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.


The clinical and histological response of HIV-associated kidney disease to antiretroviral therapy in South Africans.
Little is known about the progression of kidney disease in HIV-infected patients in developing countries in the era of antiretroviral therapy (ART). HIV-infected patients were screened for kidney disease. Kidney biopsies were performed before and after initiation of ART to assess the clinical and histological response to treatment. Data were collected from all participants in accordance with the study protocol. The mean follow-up was 2.4 patient years on ART. There was a rapid immunological and renal response to ART. The renal response was reflected by a significant rise in the estimated glomerular filtration rate (eGFR) and rapid regression of proteinuria. The histological patterns were highly variable, ranging from non-specific lesions such as mesangial hyperplasia and interstitial nephritis to HIV-immune complex disease (HIV-ICD) with or without features of HIV-associated nephropathy (HIVAN). In the follow-up biopsies, the histological response to treatment was variable with a combination of no change, progression or regression of lesions. This study demonstrated a spectrum of renal histological lesions in HIV-associated kidney disease. Initiation of ART produced a rapid and sustained clinical renal response in all participants, irrespective of the histology. Follow-up biopsies showed an inconsistent histological response of lesions to treatment. In lesions that regressed, there appeared to be a discrete lag in histological response when compared with the rapid clinical response.


Assessing interprofessional competence using a prospective reflective portfolio.
The assessment of interprofessional competence or capability following interprofessional education (IPE) remains essential if we are to ensure future practitioners who are able to work in teams and collaborate for improved health outcomes. Any IPE curriculum must design and describe its theoretical stance and this also applies to how learning will be assessed. This article reports on a study of the use of an IPE portfolio by students across 10 professions as a flexible framework for students to demonstrate their learning. Using a qualitative approach, the completed portfolios of a proportion of students from medicine, social work, and speech and language therapy were read, and a sub-set of students were interviewed to gain their perceptions of this assessment process. The findings are discussed in the light of the value of reflection for learning to consolidate interprofessional understanding. The study highlights how emotional and cognitive learning triggers lead to new understandings for collaborative practice reached only because students were able to reflect on their experiences. The portfolio is now summative and includes other assessment components.


A naturalistic test of Peplau's theory in home visiting.
Nurse-client relationships have been considered the foundation of successful home-visiting programs for vulnerable families. Even though nurse-client relationships are important when working with multiproblem families, relationship theory has not been used to guide interventions in home visiting. Identification of a fitting theory could provide direction for tailoring interventions to families at a "dose" individualized to meet their needs. This article reports a small study that tested the applicability of Peplau's theory of interpersonal relations in nursing (Peplau, 1952/1991) in the context of home visiting. Five prenatal clients and public health nurses participated in the study. Home visits were observed and audio-recorded beginning with the first prenatal home visit and ending in the early postpartum period. Audiotapes were transcribed and analyzed using a start list of codes based on Peplau's theory. Changes in the percentage of interaction assigned to the relationship phases along with a rating from the Relationship Form were compared over time to determine whether relationships progressed as predicted by Peplau. Findings of this study supported Peplau's theory. Implications for nursing practice and research are discussed.


[GTPases of translational apparatus].
Protein biosynthesis is a complex biochemical process. It integrates multiple steps where different translation factors specifically interact with the ribosome in a precisely defined order. Among the translation factors one can find multiple GTP-binding or G-proteins. Their functioning is accompanied by GTP hydrolysis to the GDP and inorganic phosphate ion Pi. Ribosome stimulates the GTPase activity of the translation factors, thus playing a role analogues to GTPase-activating proteins (GAP). Translation factors--GTPases interact with the ribosome at all stages of protein biosynthesis. Initiation factor 2 (IF2) catalyse initiator tRNA binding to the ribosomal P-site and subsequent subunit joining. Elongation factor Tu (EF-Tu) is responsible for the aminoacyl-tRNA binding to the ribosomal A-site, while elongation factor G (EF-G) catalyses translocation of mRNA in the ribosome by one codon, accompanied by tRNA movement between the binding sites. In its turn, release factor 3 (RF3) catalyse dissociation of the ribosomal complex with release factors 1 or 2 (RF1 or RF2) following the peptide release. This review is devoted to the functional peculiarities of translational GTPases as related to other G-proteins. Particularly, to the putative GTPase activation mechanism, structure and functional cycles.


The prevalence of neuroleptic malignant syndrome in learning disability.
No information has been published on the incidence of neuroleptic malignant syndrome in learning disability. However, some studies of individuals who have developed neuroleptic malignant syndrome have suggested that individuals with learning disabilities may be over represented. This study aims to identify the association between learning disability and neuroleptic malignant syndrome. A retrospective case-note analysis was performed with psychiatric case notes for clients with learning disability, in two geographical catchment areas. It was recorded whether clients had been exposed to neuroleptics, and whether any neurological symptoms had subsequently developed which could have been suggestive of neuroleptic malignant syndrome. It was found that 301 individuals had been exposed to neuroleptics, out of 570 case notes examined. Only one case of neuroleptic malignant syndrome was identified, giving a lifetime prevalence rate of 0.3%. This study failed to demonstrate a higher than expected prevalence of neuroleptic malignant syndrome in clients with learning disability exposed to neuroleptics.


Improving the performance of methylalumoxane: a facile and efficient method to trap "free" trimethylaluminum.
The presence of "free" trimethylaluminum (TMA) in methylalumoxane (MAO) solutions can be highly detrimental to the performance of metallocene and "post-metallocene" olefin polymerization catalysts. The most used strategy to remove "free" TMA is to evaporate MAO solutions to dryness, until a free-flowing white powder ("solid MAO") is left. This procedure is tedious and potentially hazardous, because in some cases the distillate is a concentrated hydrocarbon solution of TMA. Moreover, "solid MAO" is poorly soluble in common polymerization media, and once in solution it can regenerate TMA to some extent. This communication reports on a facile alternative, which consists in the controlled addition of a sterically hindered phenol, such as 2,6-di-tert-butylphenol, effectively trapping "free" TMA. We show here that 2,6-di-tert-butylphenol/MAO solutions activate equally well the dichloro-precursors of well-known zirconocene and bis(phenoxyimine)Ti catalysts, and that their use in propene polymerization results in a substantially higher productivity, polymer stereoregularity, and/or average molecular mass compared with activation by MAO alone.


[Intracellular survival and replication of legionella pneumophila within host cells].
Legionella pneumophila is a facultative intracellular pathogen which replicates within macrophages and monocytes and finally cause a severe pneumonia known as Legionnaires' disease. An important hallmark of the pathogenesis of this bacterium is their ability to manipulate host cell processes, creating a specified replicative niche within host cells. An L. pneumophila-containing phagosome (LCP) is allowed to associate sequentially with smooth vesicles, mitochondria, and the rough endoplasmic reticulum (RER) to form a compartment called a replicative phagosome. LCPs are biologically characterized by delayed acidification and a low tendency to fuse with lysosomes. The establishment of these specialized phagosomes is mediated by the Icm/Dot Type IV secretion system, which is essential for the intracellular growth of L. pneumophila. L. pneumophila utilizes the Icm/Dot system to inject bacterial effector molecules into the host cell cytosol to survive and replicate in the intracellular compartment through modulation of phagosome biogenesis. This review focuses on our studies on specific aspects of L. pneumophila infection to host cells and bacterial factors which regulates its intracellular growth. We found several characteristic phenomena leading to L. pneumophila infection, which is dependent on LCP formation: active bacterial protein synthesis in L. pneumophila within macrophages, specific exclusion of actin-binding protein p57/Coronin-1 from LCP, and suppression of reactive oxygen species (ROS) production by macrophages upon infection with L. pneumophila. Furthermore, we identified a novel bacterial factor, PmiA, which is involved in multiplication within both protozoa and macrophages. Our recent study has begun to reveal that the biological function of PmiA is closely associated with that of the Icm/Dot type IV secretion system.


Hydrodynamic trapping of molecules in lipid bilayers.
In this work we show how hydrodynamic forces can be used to locally trap molecules in a supported lipid bilayer (SLB). The method uses the hydrodynamic drag forces arising from a flow through a conical pipette with a tip radius of 1-1.5 μm, placed approximately 1 μm above the investigated SLB. This results in a localized forcefield that acts on molecules protruding from the SLB, yielding a hydrodynamic trap with a size approximately given by the size of the pipette tip. We demonstrate this concept by trapping the protein streptavidin, bound to biotin receptors in the SLB. It is also shown how static and kinetic information about the intermolecular interactions in the lipid bilayer can be obtained by relating how the magnitude of the hydrodynamic forces affects the accumulation of protein molecules in the trap.


Prey and Pollen Food Choice Depends on Previous Diet in an Omnivorous Predatory Mite.
The time allocated by omnivorous predators to consuming prey versus plant-provided foods (e.g., pollen) directly influences their efficacy as biocontrol agents of agricultural pests. Nonetheless, diet shifting between these two very different food sources remains poorly understood. We hypothesized that previous diet composition influences subsequent choice of prey and plant food types. We tested this hypothesis by observing the foraging choices of Amblyseius swirskii (Athias-Henriot) mites (Mesostigmata: Phytoseiidae), which were first maintained on either prey (broad mites) or corn pollen, and then offered familiar and unfamiliar foods. A. swirskii exhibited strong fidelity to familiar food, whether prey or pollen, suggesting there are physiological or behavioral costs involved in shifting between such different foods. Results illustrate the importance of previous diet for subsequent pest consumption by omnivorous natural enemies.


Rehabilitation Interventions to modify endocrine-metabolic disease risk in Individuals with chronic Spinal cord injury living in the Community (RIISC): A systematic review and scoping perspective.
Endocrine-metabolic disease (EMD) risk following spinal cord injury (SCI) is associated with significant multi-morbidity (i.e. fracture, diabetes, heart disease), mortality, and economic burden. It is unclear to what extent rehabilitation interventions can modify EMD risk and improve health status in community-dwelling adults with chronic SCI. To characterize rehabilitation interventions and summarize evidence on their efficacy/effectiveness to modify precursors to EMD risk in community-dwelling adults with chronic SCI. Systematic searches of MEDLINE PubMed, EMBASE Ovid, CINAHL, CDSR, and PsychInfo were completed. All randomized, quasi-experimental, and prospective controlled trials comparing rehabilitation/therapeutic interventions with control/placebo interventions in adults with chronic SCI were eligible. Two authors independently selected studies and abstracted data. Mean differences of change from baseline were reported for EMD risk outcomes. The GRADE approach was used to rate the quality of evidence. Of 489 articles identified, 16 articles (11 studies; n=396) were eligible for inclusion. No studies assessed the effects of rehabilitation interventions on incident fragility fractures, heart disease, and/or diabetes. Individual studies reported that exercise and/or nutrition interventions could improve anthropometric indices, body composition/adiposity, and biomarkers. However, there were also reports of non-statistically significant between-group differences. There was very low-quality evidence that rehabilitation interventions can improve precursors to EMD risk in community-dwelling adults with chronic SCI. The small number of studies, imprecise estimates, and inconsistency across studies limited our ability to make conclusions. A high-quality longitudinal intervention trial is needed to inform community-based rehabilitation strategies for EMD risk after chronic SCI.


Retinoic acid differentially modulates triiodothyronine and retinoic acid receptors in rat liver according to thyroid status.
Triiodothyronine (T3) receptors (TRs) and retinoic acid (RA) receptors (RARs) exert their effects on growth, differentiation and cellular homeostasis by acting as transcription factors. The binding characteristics of these receptors have been studied in liver of hypothyroid and hyperthyroid rats, with or without treatment with T3, RA or T3 + RA together. The changes in binding induced by RA treatment depended on the hormonal status of the rat. In hypothyroid rats the T3 binding capacity was unaltered by administration of T3 or RA alone but increased by 48% after treatment with T3 and RA together. In these rats administration of RA, T3 or T3 + RA increased the RAR binding capacity by 45, 79 and 112%, respectively. In hyperthyroid rats the administration of RA reduced the TR and RAR binding capacities by 22 and 37%, respectively. We found also that the affinity constants of TRs and RARs were reduced in hypothyroid rats after treatment with T3 or T3 + RA. It is suggested that this change of the properties of receptors is related to a ligand-dependent conformational change in these receptors.


Hemifacial asymmetry in emotion expressions.
We examined asymmetry in posed facial expression of emotions: happy and sad. Hemifacial composite photographs, left-left and right-right, were prepared, and subjects rated these for intensity of expressed emotion. Overall, left-left composites were judged to have expressed emotions relatively more intensely than the right-right composites. The significant Sex x Emotion interaction revealed that female expressors were judged as more expressive than male expressors in expressing sad facial emotion. Sex difference in expression of happy facial emotion was not significant.


Prolactinemia in exercising male athletes.
8 male collegial athletes were submitted at random to three (55, 70 and 85% of VO2 max) ergocycle exercises of 20-min duration. Venous blood samples were obtained before, during and after ergocycling sessions by antecubital catheterization. Serum prolactin was measured by RIA using specific antiserum. The exercise treatments induced a blood prolactin response proportional to the intensity of the work loads.


Thermotolerant coral symbionts modulate heat stress-responsive genes in their hosts.
Some corals may become more resistant to bleaching by shuffling their Symbiodiniaceae communities toward thermally tolerant species, and manipulations to boost the abundance of these symbionts in corals may increase resilience in warming oceans. However, the thermotolerant symbiont Durusdinium trenchii may reduce growth and fecundity in Caribbean corals, and these tradeoffs need to be better understood as this symbiont spreads through the region. We sought to understand how D. trenchii modulates coral gene expression by manipulating symbiont communities in Montastraea cavernosa to produce replicate ramets containing D. trenchii together with paired ramets of these same genets (n = 3) containing Cladocopium C3 symbionts. We then examined differences in global gene expression between corals hosting Durusdinium and Cladocopium under control temperatures, and in response to short-term heat stress. We identified numerous transcriptional differences associated with symbiont identity, which explained 2%-14% of the transcriptional variance. Corals with D. trenchii upregulated genes related to translation, ribosomal structure and biogenesis, and downregulated genes related to extracellular structures, and carbohydrate and lipid transport and metabolism, relative to corals with Cladocopium. Unexpectedly, these changes were similar to those observed in Cladocopium-dominated corals in response to heat stress, suggesting that thermotolerant D. trenchii may cause corals to increase expression of heat stress-responsive genes, explaining both the increased heat tolerance and the associated energetic tradeoffs in corals containing D. trenchii. These findings provide insight into the ecological changes occurring on contemporary coral reefs in response to climate change, and the diverse ways in which different symbionts modulate emergent phenotypes of their hosts.


Cystectomy in women.
The technique for radical cystectomy in women is described, with special consideration given to the pelvic anatomy, and the urethra- and nerve-sparing approach in female patients. Advances in understanding female pelvic anatomy, following detailed animal, cadaveric and clinical studies, merged to give a better intraoperative identification of the sphincteric apparatus and neurovascular structures. Respecting the oncological premises, cystectomy in female patients can be done with a nerve-sparing technique. In rare cases the entire inner genitalia, including the anterior vaginal wall, can be preserved, which might lead to improved functional results with greater patient satisfaction. However, the oncological result should never be endangered by organ preservation.


[Left atrial myxoma with extramedullary hematopoiesis and ossification].
A 65-year-old female with palpitation was referred to our hospital for a further examination. Trans-esophageal and thoracic echocardiogram demonstrated a left atrial tumor with a patchy calcification, arising from the lower portion of the interatrial septum. It was completely extirpated together with its sessile pedicle and the related disc of interatrial septum. The tumor showed the extensive extramedullary hematopoiesis and ossification around scanty clusters of myxoma cells on light microscopy. These findings indicated further support to the belief that the primitive mesenchymal cell is the origin in cardiac myxoma.


Clinical Applications of Interleukin-37: A Key Player in the Immunopathogenesis of Immune Disorders.
Recently, the era of medicine has been encountered with the exponential growth of special seroimmunobiomarkers in clinical trials. Lately, Interleukin-37 (IL-37) has attracted a wide range of basic medical scientists' attention due to its controversial functions in physiologic or pathologic microenvironments. In this research, an updated overview of immunobiological functions and clinical applications of IL-37 in a wide range of diseases, are discussed in order to highlight the role of recent laboratory-based results of IL-37. Data of this systematic review article were collected from initial 237 articles in Google Scholar search engine, Science Direct, PubMed, Scopus, and Embase databases. Eventually, 134 total articles were considered from March 2000 to June 2019 time interval, by using 5 keywords. Relevant English articles, abstracts and conference papers all were included. No restrictions of methods and type of the article were imposed. As one of the newly immunotherapeutic based approaches, clinical applications of cytokines are promisingly taken into account for diagnosis and treatment of multiple diseases. Various evidence suggests that IL-37 has notable roles in the regulation of acute and chronic inflammatory responses. Also, IL-37 has been studied in pregnancy, obesity, infectious, cardiovascular, neurologic, autoimmune, and metabolic diseases. Also, the protective functions of IL-37 against multiple cancers, are disputably related to the type and stage of cancer as well as the IL-37 variant. The broad spectrum of IL-37 and its receptors in diseases, seem to be a potential candidate with pivotal effects for immunomodulation and immune gene therapy of various pathologic states.


The diagnosis of dementias of the Alzheimer type.
There are a large number of people with primary degenerative dementia of the Alzheimer type throughout the world. This number will continue to increase during the next century, and will represent a major health problem for future generations. The diagnosis of the dementia is based on the presence of disturbances in higher cortical functions, cognition, language or behaviour, and the presence of apraxia and agnosia. To determine the etiology of the dementia, a number of investigations are required; these include neurological examination, use of diagnostic criteria, assessment instruments and measurement of mental functions, electroencephalography, and imaging techniques. Diagnosis is generally obvious in the middle stages of the disorder, but may be difficult or even hazardous in the early stages. This is a major handicap for research investigations. At present, emission tomography is the only technique which identifies abnormalities in the early stages of the disorder and which differentiates primary degenerative dementia from multi-infarct dementia. For the time being, this technique is still too sophisticated and costly to be used on a regular basis, but it will prove indispensable in the identification, understanding and early treatment of dementia.


Neuropathologic analysis of Lewy-related α-synucleinopathy in olfactory mucosa.
We analyzed the incidence and extent of Lewy-related α-synucleinopathy (LBAS) in the olfactory mucosa, as well as the central and peripheral nervous systems of consecutive autopsy cases from a general geriatric hospital. The brain and olfactory mucosa were immunohistochemically examined using antibodies raised against phosphorylated α-synuclein. Thirty-nine out of 105 patients (37.1%) showed LBAS in the central or peripheral nervous systems. Seven patients presented LBAS (Lewy neurites) in the olfactory lamina propria mucosa. One out of the seven cases also showed a Lewy neurite in a bundle of axons in the cribriform plate, but α-synuclein deposits were not detected in the olfactory receptor neurons. In particular, high incidence of α-synuclein immunopositive LBAS in the olfactory mucosa was present in the individuals with clinically as well as neuropathologically confirmed Parkinson's disease and dementia with Lewy bodies (6/8 cases, 75%). However, this pathologic alteration was rare in the cases with incidental or subclinical Lewy body diseases (LBD) (one out of 31 cases, 3.2%). In the olfactory bulb, the LBAS was usually present in the glomeruli and granular cells of most symptomatic and asymptomatic cases with LBD. Our studies further confirmed importance of the olfactory entry zone in propagation of LBAS in the human aging nervous system.


Long-term effect of sildenafil on echocardiographic parameters in dogs with asymptomatic myxomatous mitral valve degeneration.
Sildenafil is a selective phosphodiesterase-5 inhibitor that has been demonstrated to delay ventricular remodeling in humans and experimental animals. The aim of this prospective study was to assess the chronic effects of sildenafil administration on echocardiographic indices and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in dogs with naturally occurring, asymptomatic myxomatous mitral valve degeneration. Thirty client-owned dogs with ACVIM class B1 or B2 were enrolled. Dogs were randomly assigned to treatment (sildenafil 1-3 mg/kg, PO, BID for 180 days) or control groups. A total of 12 dogs completed the 180 days trial in the sildenafil group, whereas 10 dogs remained in control group. When comparing the difference from baseline values obtained over time between groups, the stroke volume (SV) at day 30 was significantly higher in the sildenafil group (P=0.038). The LA/Ao and the MR jet area were significantly lower beginning at day 30 (only MR jet area; P=0.006), day 90 (P=0.006 and P=0.027, respectively) and day 180 (P=0.029 and P=0.032, respectively). The 2D-LA was significantly lower at day 90 when compared with control group (P=0.028). The differences of NTproBNP from baseline were significantly lower when compared with control group at the same timepoint (D90, P=0.017 and D180, P=0.013). In conclusion, this study suggested that long-term treatment with sildenafil prevented aggravation of disease progression as suggested by several echocardiographic indices (i.e. SV, LA/Ao, MR jet area, 2D-LA) and reduced NTproBNP level at the indicated timepoints in dogs with asymptomatic mitral valve degeneration.


TBT causes regime shift in shallow lakes.
Tributyltin (TBT) is an organotin compound used since the early 1960s as a biocide in boat antifouling paints. Its use has been linked to a host of negative effects in marine ecosystems including malformations and imposex in Mollusca and acute toxicity in many other aquatic animals. Yet, the consequences of TBT use in freshwaters are largely unknown. Here, for the first time we reveal that TBT may have caused hitherto unsuspected damage to freshwater ecosystems. Through an analysis of dated sediment cores collected from a system of recreationally boated, shallow lakes, we show that first evidence of TBT is associated with a dramatic loss of submerged vegetation and associated diverse animal communities. Cause and effect are difficult to unravel in our study. However, we hypothesize that TBT, through reducing populations of grazing organisms in lakes already affected by eutrophication, promoted the replacement of macrophytes by phytoplankton, ultimately leading to a regime shift in the ecosystem. Our findings may have parallels in freshwater ecosystems all over the world.


Direct and short construction of the ACDE ring system of daphenylline.
Daphenylline, a novel daphniphyllum alkaloid, boasts a fused and bridging ring system coupled with six stereogenic centers. Here we present a direct and short construction of the ACDE ring system of daphenylline from the known 3-(2-bromophenyl)propanal in 10 steps and 17 % overall yield. The synthesis features an iron(III)-catalyzed aza-Cope-Mannich reaction, a self-terminating 6-exo-trig aryl radical-alkene cyclization and an intramolecular Friedel-Crafts acylation.


[Preparation and study of phytotoxicity of N-arylalkyl substituted amides. I. Benzylamides].
A series of N-benzyl substituted amides (substances I-CV) have been prepared and tested for phytotoxicity. Preliminary tests were carried out on various common plants using both pre- and post-emergence tests at doses of 6 kg/ha. Further tests using doses of 4 and 2 kg/ha were carried out on the most interesting compounds. Some of the compounds tested showed marked phytotoxic activity. This activity appears clearly different as regards mechanism from that of homologous anilides. The amides studied appear to be quite inactive as inhibitors of the Hill reaction.