Development and characterization of 79 nuclear markers amplifying in viviparous and oviparous clades of the European common lizard.

The European common lizard (Zootoca vivipara) is a widely distributed species across Europe and Asia exhibiting two reproductive modes (oviparity/viviparity), six major lineages and several sublineages. It has been used to tackle a large variety of research questions, nevertheless, few nuclear DNA sequence markers have been developed for this species. Here we developed 79 new nuclear DNA sequence markers using a clonation protocol. These markers were amplified in several oviparous and viviparous specimens including samples of all extant clades, to test the amplification success and their diversity. 49.4% of the markers were polymorphic and of those, 51.3% amplified in all and 94.9% amplified in 5-7 of the extant Z. vivipara clades. These new markers will be very useful for the study of the population structure, population dynamics, and micro/macro evolution of Z. vivipara. Cross-species amplification in four lizard species (Psammodromus edwardsianus, Podarcis muralis, Lacerta bilineata, and Takydromus sexlineatus) was positive in several of the markers, and six makers amplified in all five species. The large genetic distance between P. edwardsianus and Z. vivipara further suggests that these markers may as well be employed in many other species.

Phytotoxic and antimicrobial activity of volatile and semi-volatile organic compounds from the endophyte Hypoxylon anthochroum strain Blaci isolated from Bursera lancifolia (Burseraceae).

AIMS: To evaluate the phytotoxic, antifungal and antioomycete activity; and, determine the chemical composition of the volatile organic compounds (VOCs) and semi-volatile metabolites produced by the endophyte Hypoxylon anthochroum strain Blaci isolated from Bursera lancifolia. METHODS AND RESULTS: Based on its macro- and micro-morphological features, the strain Blaci was identified as Nodulisporium sp.; partial analysis of its ITS1-5.8-ITS2 ribosomal gene sequence revealed the identity of the teleomorphic stage of the fungus as H. anthochroum. Phytotoxic and antimicrobial activities of VOCs, and culture medium and mycelium organic extracts from H. anthochroum Blaci were determined by simple and multiple antagonism bioassays, and gas phase and agar dilution bioassays respectively. The volatile and semi-volatile metabolites were identified by gas chromatography-mass spectrometry. VOCs from a 5-day H. anthochroum strain Blaci culture caused the inhibition of seed germination, root elongation and seedling respiration on Amaranthus hypochondriacus, Panicum miliaceum, Trifolium pratense and Medicago sativa. In addition, extracts, phenylethyl alcohol and eucalyptol main compounds present in the VOCs and extract displayed a high phytotoxic activity, inhibiting the three physiological processes on the four test plants in a concentration-dependent manner. CONCLUSIONS: The results revealed that H. anthochroum strain Blaci produces a mixture of VOCs. These VOCs showed a strong phytotoxic activity on seed germination, root elongation, and seedling respiration of four plants and slightly affected the growth of phytopathogenic fungi and oomycetes. Also, the culture medium and mycelium extracts of H. anthochroum showed a high phytotoxic activity on the four test plants and, generally, the culture medium extract was more phytotoxic than the mycelium extracts. SIGNIFICANCE AND IMPACT OF THE STUDY: This work firstly reports the phytotoxic activity of volatile and semi-volatile compounds produced by the endophyte H. anthochroum strain Blaci on seed germination, root elongation, and seedling respiration of four different plants; consequently, these compounds could be useful in biocontrol of weeds and plant pathogens.

Clinical, functional and radiological results of Achilles tenorraphy surgically treated with mini-open technique.

AIM: The aim of this paper was to report clinical, functional and radiological results of 80 patients surgically treated with a combined mini-open and percutaneous surgical repair as proposed by Kakiuchi. METHODS: All patients were evaluated with a physical examination, evaluation scales, a functional test (Ergo-jump Bosco System), and an ultrasonographic exam along with Power Doppler Ultrasonography (PDU) (S/S). RESULTS: At a mean follow-up of 58 months no cases of rerupture were detected. VISA-A evaluation scale showed an excellent score in 63 patients (78.75%), a good score in 14 patients (17.5%), a fair score in two patients (2.5%), and a poor score in one patient (1.25%). Hannover scale showed an excellent score in 63 patients (78.75%), and a good score in 17 patients (21.25%). Ergo-Jump evaluation showed a 2.07% mean deficit of the affected limb at the Squatting Jump test, a 3.26% mean deficit at the Counter Movement Jump test, and a 0.0062% mean improvement at the Repetitive Jump test. Ultrasonographic exam showed in all cases a satisfactory recovery of the integrity of the operated tendon. The mean AP and LL widths showed a significant increase of 7.13±2.97 mm (+56.1%) and of 4.01±2.36 mm (+43.81%) respectively. According to the modified Öhberg score scale, PDU exam showed a grade +1 in 16 patients (20%) and a grade +2 in seven cases (8.7%). CONCLUSION: The absence of rerupture cases, the satisfactory functional and ultrasonographic results of the patients included in this study cause us to consider this technique as reliable and effective even in young high-demand patients.

Association between digoxin use and gastrointestinal bleeding in contemporary continuous flow left ventricular assist device support.

BACKGROUND: Assess the association between digoxin use and gastrointestinal bleeding (GIB) in a multicenter continuous flow left ventricular assist device (LVAD) cohort. METHODS: Patients implanted with continuous flow LVADs with data on GIB and digoxin use from two centers were included in the analysis (n = 649). GIB events were captured up to 2 years of follow-up. Digoxin use was defined as digoxin prescribed at discharge or within the first 3 months after LVAD implantation. A negative binomial regression model was performed to determine the association between digoxin use and number of GIB events over the follow-up period. RESULTS: Mean age of the cohort was 57 years (±14) and 45% (293/649) were bridge to transplant (BTT). Digoxin was prescribed in 33% of patients. Digoxin use was associated with an unadjusted 32% reduction in the incidence of rate of all cause GIB (IRR 0.68, 95% CI 0.46-0.99, p = 0.049). After adjusting for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile, renal function, and implanting center there was still a 34% reduction in the incidence rate (IRR 0.67, 95% CI 0.45-0.99, p = 0.048). When limiting the analysis to those with likely arteriovenous malformation associated GIB, the association strengthened (unadjusted: IRR 0.48, 95 % CI 0.26-0.89, p = 0.02, adjusted: IRR 0.47, 95 % CI 0.25-0.9, p = 0.022). CONCLUSIONS: In this multicenter study, inclusive of contemporary devices, digoxin use was associated with reduced GIB events. Prospective data will be required to confirm this association.

Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial.

BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). RESULTS: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.

Unprecedented simultaneous enhancement in damage tolerance and fatigue resistance of zirconia/Ta composites.

Dense (>98 th%) and homogeneous ceramic/metal composites were obtained by spark plasma sintering (SPS) using ZrO2 and lamellar metallic powders of tantalum or niobium (20 vol.%) as starting materials. The present study has demonstrated the unique and unpredicted simultaneous enhancement in toughness and strength with very high flaw tolerance of zirconia/Ta composites. In addition to their excellent static mechanical properties, these composites also have exceptional resistance to fatigue loading. It has been shown that the major contributions to toughening are the resulting crack bridging and plastic deformation of the metallic particles, together with crack deflection and interfacial debonding, which is compatible with the coexistence in the composite of both, strong and weak ceramic/metal interfaces, in agreement with predictions of ab-initio calculations. Therefore, these materials are promising candidates for designing damage tolerance components for aerospace industry, cutting and drilling tools, biomedical implants, among many others.

Molecular lysis of synovial lining cells by in vivo herpes simplex virus-thymidine kinase gene transfer.

Herpes simples virus thymidine kinase (HSV-TK) expression plasmid DNA was injected into the joint space of rabbits with antigen-induced arthritis (AIA). Purified plasmid DNA was able to mediate transfection of synovial lining cells and transient overexpression of HSV-TK in the context of active synovial inflammation. The pharmacodynamic distribution of intraarticular expression plasmid DNA was confined to the joint space. Arthritic rabbits treated with intraarticular expression plasmid DNA followed by intravenous ganciclovir (GCV, 5 mg/kg) twice daily for 3 days showed histologic evidence of synovial lining layer cytolysis when articular tissues were examined 21 days posttreatment. There was also a reduction in joint swelling in the TK-treated knees. No untoward clinical effects were observed in the rabbits and no evidence of cytolytic damage specific to the TK-GCV gene therapy was observed either in the articular cartilage or bone. The application of TK-GCV intraarticular gene therapy using purified expression plasmid DNA for the induction of synovial cytolysis may be applicable to the treatment of human inflammatory arthritis.

The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence.

We have investigated membrane interactions and perturbations induced by NH(2)-DKWASLWNWFNITNWLWYIK-COOH (HIV(c)), representing the membrane interface-partitioning region that precedes the transmembrane anchor of the human immunodeficiency virus type-1 gp41 fusion protein. The HIV(c) peptide bound with high affinity to electrically neutral vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1), and induced vesicle leakage and lipid mixing. Infrared spectra suggest that these effects were promoted by membrane-associated peptides adopting an alpha-helical conformation. A sequence representing a defective gp41 phenotype unable to mediate both cell-cell fusion and virus entry, was equally unable to induce vesicle fusion, and adopted a non-helical conformation in the membrane. We conclude that membrane perturbation and adoption of the alpha-helical conformation by this gp41 region might be functionally meaningful.

Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]-phenyl]methanone, methanesulfonic acid salt.

Acylation of the sodio anion of beta-tetralone with phenyl anisoate, followed by a Grignard reaction of the resultant 4 with 4-methoxyphenylmagnesium bromide, gave rise to two novel dihydronaphthalene isomers 5 and 6. Regioselective demethylation of either 5 or 6 by NaSEt produced [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone (7). Etherification of the phenolic group of 7 by N-(2-chloroethyl)pyrrolidine and subsequent methanesulfonate salt formation provided [3,4-dihydro-2-(4-methoxyphenyl)-1-maphthalenyl]]4-]2-(1-pyrrolidinyl)ethoxy]phenyl]methanone, methane sulfonic acid salt (3). Potent antiestrogenic activity of 3 was demonstrated by both oral and subcutaneous administration to rats and mice. In vitro binding studies with rat uterine cytosol estrogen receptors indicate compound 3 has a very high binding affinity which exceeds that of estradiol.

Antiestrogens. 3. Estrogen receptor affinities and antiproliferative effects in MCF-7 cells of phenolic analogues of trioxifene, [3,4-dihydro-2-(4- methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]- phenyl]methanone.

Benzothiophenes 3 and 4, derived from the acrylophenone antiestrogen trioxifene (2), are characterized by high estrogen receptor (ER) affinity and low residual estrogenicity compared to tamoxifen (1a). In order to characterize further the growth suppression mechanism for these structural types we have prepared structural variants of 2 bearing hydroxy groups positioned to maximize ER affinity. Thus, dihydronaphthalenes 5 and 6 and benzofluorenes 7 and 8 were prepared and studied in MCF-7 human breast cancer cells, in comparison with 3 and 4. All compounds were powerful suppressants of cell growth, with 50% inhibition ranging from 4.5 to 160 nM. Greatest potency was seen with diphenols 6 and 8. These compounds had intracellular ER affinities ranging from 0.2 to 4.1% of that of estradiol, suggestive of a potential for partial agonist effects. Simultaneous exposure of cells to 0.1 microM concentrations of estradiol and 3 or 4 did not affect the degree of growth inhibition seen with 0.1 microM 3 or 4 alone. Partial reversal of inhibition occurred when 0.1 microM 5-8 were each accompanied by 0.1 microM estradiol. Under these conditions complete reversal of growth inhibition has been found with 1a, 1b, and other triarylethylenes. Calmodulin, a putative target for triarylethylenes, and which is antagonized by 1a, was shown to interact weakly with 7 and 8 and not at all with 3-6. These results suggest that MCF-7 cell growth suppression by 3-8 may be due to interaction with unidentified receptors besides ER and extend earlier findings indicating that events occurring after interaction of these compounds with ER differ from those of triarylethylene antiestrogens.

Health literacy and health-related knowledge among persons living with HIV/AIDS.

BACKGROUND: Functional health literacy is associated with illness-related knowledge, understanding, and treatment perceptions for several chronic illnesses. This study examined health literacy in relation to knowledge and understanding of HIV/AIDS. METHODS: Persons living with HIV/AIDS recruited from AIDS service organizations and HIV clinics completed the Test of Functional Health Literacy for Adults (TOFHLA) reading comprehension scale and measures of health status, knowledge and understanding of health status, perceptions of primary care givers, and perceptions of anti-HIV treatments. RESULTS: Eighteen percent of the sample scored below the cutoff for marginal functional health literacy on the TOFHLA. Controlling for years of education, persons of lower health literacy were significantly less likely to have an undetectable HIV viral load, somewhat less likely to know their CD4 cell count and viral load, and lower health-literacy persons who knew their CD4 count and viral load were less likely to understand their meaning. Lower health literacy was also related to misperceptions that anti-HIV treatments reduce risks for sexually transmitting HIV and beliefs that anti-HIV treatments can relax safer-sex practices. CONCLUSIONS: Poor health literacy creates barriers to fully understanding one's health, illness, and treatments. Misperceptions of treatment in the case of HIV infection creates danger for potentially transmitting treatment-resistant strains of HIV. These results have implications for patient education and treatment programming for people who have poor health-literacy skills and are living with HIV/AIDS.

Calcium channel blockers in systemic hypertension.

Alterations in transmembrane flux of calcium ions may be playing a role in the pathophysiology of systemic hypertension. Calcium channel blockers have been shown to be effective antihypertensive drugs with excellent safety profiles. They are efficacious in the long term treatment of systemic hypertension in all population subgroups, and have special applicability for treating patients with hypertensive urgencies and individuals with concomitant diseases such as angina pectoris and arrhythmias.

Hydrophobic-at-interface regions in viral fusion protein ectodomains.

In this chapter we shall describe how to apply the hydrophobicity-at-interface scale, as proposed by Wimley and White [Wimley, W. C. and White, S. H. (1996) Nature Struct. Biol. 3:842-848], to the detection of amino acid sequences of viral envelope glycoproteins putatively engaged in interactions with the target membranes. In addition, a new approach will be briefly introduced to infer the bilayer location at equilibrium of membrane-partitioning sequences. The use of these new procedures may be important in describing the molecular mechanism leading to the formation of a fusion pore by viral glycoproteins.

Early intervention: why, for whom, how, and at what cost?

When the concept of intervention is applied to human development, the goal is usually to enhance functioning or to prevent some unwanted condition. During the past 20 years, the United States has committed itself to an early intervention position for young children who are socio-economically, educationally, or physically disadvantaged. This article summarizes the knowledge base concerning early educational interventions and to recommend actions concerning public policy and associated research.

[Biology of Anopheles (Kerteszia) neivai H., D. & K., 1913 (Diptera: Culicidae) from the Pacific coast of Colombia. IV. Age structure and malaria transmission]. / Biología de Anopheles (Kerteszia) neivai H., D. & K, 1913 (Diptera: Culicidae) en la Costa Pacífica de Colombia. IV - Estructura etárea y transmisión de malaria.

With the aim of determining the dynamics of malaria transmission in the village of Charambirá (Chocó), Colombia, studies on the age structure of Anopheles neivai (a known vector on the Pacific Coast) were undertaken, based on its gonadotrophic status. Mosquitoes were captured indoors at sunset using human bait and bucal aspirators and then maintained in cylindrical cardboard boxes, with damp paper and feeding dispensaries, until dissection on the following day. Of the 200 specimens dissected during September-October 1986, 68 (34%) showed traces of less than two ovipositions, while the rest (66%) evidenced at least three ovipositions. The difference between the first group considered as "non-infective" and the second group considered as "potentially infective" was highly significant (X2 = 10.68; P = 0.001). The study showed that 1.5% of the dissected A. neivai had traces of ten ovipositions demonstrating high longevity and multiple bloodfeedings. The results suggest that there is a considerable risk of contracting malaria in Charambirá at dusk.

[Intraventricular neurocytoma. Report of 2 cases and analysis of the therapeutic possibilities]. / Neurocitoma intraventricular. Reporte de dos casos y análisis de posibilidades terapéuticas.

Intraventricular or central neurocytoma is a recently described unusual benign cerebral tumor. Common features include: predominant occurrence in young adults, septum pellucidum and fornix localization, and signs of intracranial hypertension due to obstructive hydrocephalus. Histopathologically, this tumor is characterized by a uniform neoplastic cell population with features of neuronal differentiation. Radiologic findings such as calcification, well-circumscribed tumor mass and confinement to the lateral and third ventricles are common. An anterior transcallosal neurosurgical approach yielded good outcomes. Radiotherapy should be considered for residual and recurrent neurocytomas. However, the radiation sensitivity of intraventricular neurocytoma has not been established and further studies are required to determine susceptibility to irradiation.

[Non-Hodgkin's lymphoma of the parotid gland: 2 cases]. / Linfoma no Hodgkin en parótida: dos casos.

We report two cases of bilateral parotid swelling at initial clinical assessment of non-Hodgkin lymphoma. The swelling was not associated with other symptoms. They both were stage IV and were treated by chemotherapy. We have reviewed the literature about first manifestations of the disease, clinical diagnosis and incidence. The importance of early biopsy of such lesions is emphasised.

[Experience with the HME-Provox Stomafilter in laryngectomized patients]. / Experiencia con el uso del HME-Provox Stomafilter en pacientes laringuectomizados.

Respiratory symptoms after total laryngectomy are both frequent and troublesome. Previous studies have demonstrated the positive effect of a heat and moisture exchanger (MHE) on the respiratory system in patients after total laryngectomy. In the present study we analyze the opinion of 40 total laryngectomized patients regarding the use of the MHE-Provox Stomafilter kit. Focus has been directed to speech function parameters and pulmonary symptoms. Benefits in phonatory parameters--intelligibility, fluency, pressure and telephone intelligibility, have been over 70%. Reduction in pulmonary symptoms--coughing, sputum production, forced expectoration, stoma cleaning--have also been significant. Our results support the use of MHE Provox Stomafilter for minimizing and preventing respiratory problems and increasing the quality of the voice through the tracheoesophageal puncture system.

[Recurrence after removal of a vocal cord for laryngeal fissure]. / Recidivas tras cordectomía por laringofisura.

The evolution of 39 patients undergoing cordectomy by laryngofissure between 1980 and 1995 was analyzed. All patients were male. There were 33 (84.6%) T1a and 6 T1b (15.4%). Cause specific survival at 3, 5 and 10 years was 92.3, 89.7 and 89.7%, with an overall survival of 89.7, 84.3 and 65.8% at 3, 5 and 10 years respectively. Positive margins were found in two patients. Local recurrences were present in 4 patients (10.2%), loco-regional in 1 patient (2.5%), and paratracheal in 1 patient (2.5%). Salvage therapy included total laryngectomy in four patients (10.2%) and partial surgery in one patient. Correct evaluation of tumor extension and adequate free margin analysis are the essentials to avoid local recurrence after cordectomy, a well establish option for treatment of early glottic carcinoma.

[Nevus comedonicus]. / El nevo comedónico.

Nevus comedonicus is and uncommon abnormality. Clinical and histopathologic characteristics are described. Also the histogenesis is discussed. Eleven new cases are reported. A tretinoin solution or cream produced excellent improvement.