Peak performance singing requires daily vocal exercise in songbirds.

Vocal signals mediate much of human and non-human communication. Key performance traits - such as repertoire size, speed and accuracy of delivery - affect communication efficacy in fitness-decisive contexts such as mate choice and resource competition 1 . Specialized fast vocal muscles 2,3 are central to accurate sound production 4 , but it is unknown whether vocal, like limb muscles 5,6 , need exercise to gain and maintain peak performance 7,8 . Here, we show that for song development in juvenile songbirds, the closest analogue to human speech acquisition 9 , regular vocal muscle exercise is crucial to achieve adult peak muscle performance. Furthermore, adult vocal muscle performance reduces within two days of abolishing exercise, leading to downregulation of critical proteins transforming fast to slower muscle fibre types. Daily vocal exercise is thus required to both gain and maintain peak vocal muscle performance, and if absent changes vocal output. We show that conspecifics can detect these acoustic changes and females prefer the song of exercised males. Song thus contains information on recent exercise status of the sender. Daily investment in vocal exercise to maintain peak performance is an unrecognized cost of singing and could explain why many birds sing daily even under adverse conditions 10 . Because neural regulation of syringeal and laryngeal muscle plasticity is equivalent, vocal output may reflect recent exercise status in all vocalizing vertebrates.

Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: Results of the BROADEN study: Volanesorsen in FPLD; The BROADEN Study.

BACKGROUND: Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations. OBJECTIVE: The present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes. METHODS: BROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open-label extension and post-treatment follow-up periods. Patients received weekly subcutaneous volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides at 3 months. Secondary endpoints included relative percent change in hepatic fat fraction (HFF), visceral adiposity, and glycated hemoglobin levels. RESULTS: Forty patients (11 men, 29 women) were enrolled, majority of whom were aged <65 years (mean, 47 years) and White. Least squares mean (LSM) percent change in triglycerides from baseline to 3 months was -88% (95% CI, -134 to -43) in the volanesorsen group versus -22% (95% CI, -61 to 18) in the placebo group, with a difference in LSM of -67% (95% CI, -104 to -30; P=0.0009). Volanesorsen induced a significant LSM relative reduction in HFF of 53% at month 12 versus placebo (observed mean [SD]: 9.7 [7.65] vs. 18.0 [8.89]; P=0.0039). No statistically significant changes were noted in body volume measurements (fat, liver, spleen, visceral/subcutaneous adipose tissue) or glycated hemoglobin. Serious adverse events in patients assigned to volanesorsen included 1 case each of sarcoidosis, anaphylactic reaction, and systemic inflammatory response syndrome. CONCLUSION: In BROADEN, volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD.

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk.

AIMS: Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200-500 mg/dL (2.26-5.65 mmol/L). Patients received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6-12 months. The primary endpoint was the percent change in fasting triglyceride levels from baseline to Month 6 of exposure. Baseline median (interquartile range) fasting triglyceride levels were 262 (222-329) mg/dL [2.96 (2.51-3.71) mmol/L]. Treatment with olezarsen resulted in mean percent triglyceride reductions of 23% with 10 mg every 4 weeks, 56% with 15 mg every 2 weeks, 60% with 10 mg every week, and 60% with 50 mg every 4 weeks, compared with increase by 6% for the pooled placebo group (P-values ranged from 0.0042 to <0.0001 compared with placebo). Significant decreases in apoC-III, very low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were also observed. There were no platelet count, liver, or renal function changes in any of the olezarsen groups. The most common adverse event was mild erythema at the injection site. CONCLUSION: Olezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at high risk for or with established cardiovascular disease. TRIAL REGISTRATION NUMBER: NCT03385239.

Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Volanesorsen is an antisense oligonucleotide that targets hepatic apolipoprotein C-III synthesis and reduces plasma triglyceride concentration. The aim of this study was to explore the safety and efficacy of volanesorsen in patients with multifactorial chylomicronaemia syndrome. METHODS: The COMPASS trial was a randomised, placebo-controlled, double-blind, phase 3 study done at 38 international clinical sites in Canada, France, Germany, the Netherlands, UK, and USA. Eligible patients were aged 18 years or older with multifactorial severe hypertriglyceridaemia or familial chylomicronaemia syndrome, who had a BMI of 45 kg/m2 or less and fasting plasma triglyceride of 500 mg/dL or higher. Patients were randomly assigned (2:1) with an interactive response system using an allocation sequence and permuted block randomisation to receive subcutaneous volanesorsen (300 mg) or a matched volume of placebo (1·5 mL) once a week for 26 weeks. After 13 weeks of treatment, dosing was changed to 300 mg of volanesorsen or placebo every 2 weeks for all patients, except those who had completed 5 months or more of treatment as of May 27, 2016. Participants, investigators, sponsor personnel, and clinical research staff were all masked to the treatment assignments. The primary outcome was percentage change from baseline to 3 months in fasting triglyceride in the full analysis set (all patients who were randomly assigned and received at least one dose of study drug and had a baseline fasting triglyceride assessment). This trial is registered with ClinicalTrials.gov, NCT02300233 (completed). FINDINGS: Between Feb 5, 2015, and Jan 24, 2017, 408 patients were screened for eligibility. 294 were excluded and 114 randomly assigned to receive either volanesorsen (n=76) or placebo (n=38). One patient in the volanesorsen group discontinued before receiving the study drug. The total number of dropouts was 28 (four in the placebo group and 24 in the treatment group). Volanesorsen reduced mean plasma triglyceride concentration by 71·2% (95% CI -79·3 to -63·2) from baseline to 3 months compared with 0·9% (-13·9 to 12·2) in the placebo group (p<0·0001), representing a mean absolute reduction of fasting plasma triglycerides of 869 mg/dL (95% CI -1018 to -720; 9·82 mmol/L [-11·51 to -8·14]) in volanesorsen compared with an increase in placebo of 74 mg/dL (-138 to 285; 0·83 mmol/L [-1·56 to 3·22]; p<0·0001). In the key safety analysis, five adjudicated events of acute pancreatitis occurred during the study treatment period, all in three of 38 patients in the placebo group. The most common adverse events were related to tolerability and included injection-site reactions (average of 24% of all volanesorsen injections vs 0·2% of placebo injections), which were all mild or moderate. One participant in the volanesorsen group had a platelet count reduction to less than 50 000 per µL and one patient had serum sickness, both of which were regarded as serious adverse events. INTERPRETATION: Volanesorsen significantly reduced triglyceride concentrations in patients with multifactorial chlyomicronaemia and might reduce acute pancreatitis events in these patients. FUNDING: Ionis Pharmaceuticals and Akcea Therapeutics.

Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy.

INTRODUCTION: AKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients. METHODS/DESIGN: Approximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life-Diabetic Neuropathy questionnaire. CONCLUSION: NEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCT04136184) and EudraCT (2019-001698-10).

Hereditary transthyretin amyloidosis with peripheral neuropathy (hATTR-PN for short) is a rare inherited condition. In hATTR-PN, a protein called transthyretin (TTR for short) builds up and damages nerves throughout the body. This neuropathy causes symptoms such as weakness, loss of sensation, and pain. Currently available medicines can slow disease progression, but researchers are looking for more effective treatments with fewer side effects. AKCEA-TTR-L_Rx is an investigational treatment for hATTR-PN. AKCEA-TTR-L_Rx prevents the liver from making TTR, reducing the amount that causes disease progression. It is similar to an existing treatment called inotersen, but designed for better delivery to the liver and is more potent. This article describes the NEURO-TTRansform study that will evaluate how effective AKCEA-TTR-L_Rx is for treating hATTR-PN. Around 140 adults with hATTR-PN from the USA, Canada, and Europe will be able to take part in this study. The study treatment period will be 85 weeks long. People will receive injections underneath the skin of either: AKCEA-TTR-L_Rx every 4 weeks, or Inotersen once a week for 35 weeks, followed by a switch to AKCEA-TTR-L_Rx every 4 weeks. People may continue to receive AKCEA-TTR-L_Rx after the study treatment period ends. In this study, researchers will compare results from people who received AKCEA-TTR-L_Rx to results from people who received no active ingredients (called placebo) in a similar study (called NEURO-TTR). Researchers will measure the differences in peoples': Neuropathy symptoms. Quality of life. TTR protein levels in the blood.

Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia.

AIMS: Loss-of-function mutations in ANGPTL3 are associated with beneficial effects on lipid and glucose metabolism and reduced risk of coronary artery disease. Vupanorsen (AKCEA-ANGPTL3-L Rx ) is an N-acetyl galactosamine-conjugated antisense oligonucleotide targeted to the liver that selectively inhibits angiopoietin-like 3 (ANGPTL3) protein synthesis. METHODS AND RESULTS: This was a double-blind, placebo-controlled, dose-ranging, Phase 2 study. Patients (N =105) with fasting triglycerides >150 mg/dL (>1.7 mmol/L), type 2 diabetes, and hepatic steatosis were treated for 6 months with 40 or 80 mg every 4 weeks (Q4W), or 20 mg every week (QW) of vupanorsen, or placebo given subcutaneously. The primary efficacy endpoint was per cent change in fasting triglycerides from baseline at 6 months. Median baseline triglycerides were 2.84 mmol/L (252 mg/dL). Significant reductions in triglycerides of 36%, 53%, 47%, and in ANGPTL3 of 41%, 59%, 56%, were observed in the 40 mg Q4W, 80 mg Q4W, and 20 mg QW groups, respectively, compared with 16% reduction in triglycerides and 8% increase in ANGPTL3 in placebo. Compared with placebo, vupanorsen 80 mg Q4W reduced apolipoprotein C-III (58%), remnant cholesterol (38%), total cholesterol (19%), non-high-density lipoprotein cholesterol (HDL-C; 18%), HDL-C (24%), and apolipoprotein B (9%). There was no improvement in glycaemic parameters, or hepatic fat fraction. Treatment with vupanorsen was not associated with clinically significant changes in platelet counts, and the most common adverse events were those at the injection site, which were generally mild. CONCLUSION: Vupanorsen results in a favourable lipid/lipoprotein profile and provides a potential strategy for residual cardiovascular risk reduction.

Differentiating Familial Chylomicronemia Syndrome From Multifactorial Severe Hypertriglyceridemia by Clinical Profiles.

CONTEXT: Differentiation between familial chylomicronemia syndrome (FCS, type 1 hyperlipoproteinemia), a rare metabolic disorder, and the more common multifactorial severe hypertriglyceridemia (sHTG, type 5 hyperlipoproteinemia) is challenging because of their overlapping symptoms but important in patient management. OBJECTIVE: To assess whether readily obtainable clinical information beyond triglycerides can effectively diagnose and differentiate patients with FCS from those with sHTG, based on well-curated data from two intervention studies of these conditions. METHODS: The analysis included 154 patients from two phase 3 clinical trials of patients with sHTG, one cohort with genetically confirmed FCS (n = 49) and one with multifactorial sHTG (n = 105). Logistic regression analyses were performed to determine the ability of variables (patient demographics, medical history, and baseline lipids, individually or in sets) to differentiate the patient populations. Receiver operating characteristics were used to determine the variable sets with the highest accuracy (percentage of times actual values matched predicted) and optimal sensitivity and specificity. RESULTS: The primary model diagnosed 45 of 49 patients with FCS and 99 of 105 patients with sHTG correctly. Optimal sensitivity for all available parameters (n = 17) was 91.8%, optimal specificity was 94.3%, and accuracy was 93.5%. Fasting low-density lipoprotein cholesterol (LDL-C) provided the highest individual predictability. However, a three-variable set of ultracentrifugally measured LDL-C, body mass index, and pancreatitis history differentiated the diseases with a near similar accuracy of 91.0%, and adding high-density lipoprotein cholesterol and very low-density lipoprotein cholesterol for a five-variable set provided a small incremental increase in accuracy (92.2%). CONCLUSIONS: In the absence of genetic testing, hypertriglyceridemic patients with FCS and sHTG can be differentiated with a high degree of accuracy by analyzing readily obtainable clinical information.

Conservation Research Is Not Happening Where It Is Most Needed.

Target 19, set by the Convention on Biological Diversity, seeks to improve the knowledge, science base, and technologies relating to biodiversity. We will fail to achieve this target unless prolific biases in the field of conservation science are addressed. We reveal that comparatively less research is undertaken in the world's most biodiverse countries, the science conducted in these countries is often not led by researchers based in-country, and these scientists are also underrepresented in important international fora. Mitigating these biases requires wide-ranging solutions: reforming open access publishing policies, enhancing science communication strategies, changing author attribution practices, improving representation in international processes, and strengthening infrastructure and human capacity for research in countries where it is most needed.

Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.

CONTEXT: Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis. OBJECTIVE: This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis. DESIGN: Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 µg, or teriparatide, 20 µg. A 24-week extension was also performed in a subset of subjects. PARTICIPANTS: Postmenopausal women with osteoporosis (n = 222). MAIN OUTCOME MEASURES: BMD by dual-x-ray absorptiometry and biochemical markers of bone turnover. RESULTS: At 24 weeks, lumbar spine BMD increased by 2.9, 5.2, and 6.7% in the abaloparatide, 20-, 40-, and 80-µg groups, respectively, and 5.5% in the teriparatide group. The increases in the 40- and 80-µg abaloparatide groups and the teriparatide group were significantly greater than placebo (1.6%). Femoral neck BMD increased by 2.7, 2.2, and 3.1% in abaloparatide, 20-, 40-, and 80-µg groups, respectively, and 1.1% in the teriparatide group. The increase in femoral neck BMD with abaloparatide, 80 µg was significantly greater than placebo (0.8%). Total hip BMD increased by 1.4, 2.0, and 2.6% in the abaloparatide, 20-, 40-, and 80-µg groups, respectively. The total hip increases in the 40- and 80-µg abaloparatide groups were greater than both placebo (0.4%) and teriparatide (0.5%). CONCLUSIONS: Compared with placebo, 24 weeks of daily sc abaloparatide increases BMD of the lumbar spine, femoral neck, and total hip in a dose-dependent fashion. Moreover, the abaloparatide-induced BMD increases at the total hip are greater than with the marketed dose of teriparatide. These results support the further investigation of abaloparatide as an anabolic therapy in postmenopausal osteoporosis.

Life after lower extremity amputation in diabetics / La vida tras la amputación de las extremidades inferiores por diabetes

Lower limb amputees typically have reduced mobility which affects their ability to perform daily tasks and to successfully reintegrate into community life. A major goal of rehabilitation for amputees is to improve quality of life (QOL). This study therefore focussed on QOL and functional independence for persons with lower limb amputations secondary to diabetes. OBJECTIVE: To determine the QOL and functional independence of lower limb diabetic amputees one to three years post amputation, using variables such as age, gender and amputation level. METHOD: A total of 87 participants were selected from the 2006-2009 physiotherapy records at the St Ann's Bay Hospital. These participants completed the World Health Organization Quality of Life Scale (WHO QOL-BREF) and the Functional Independence Measure (FIM). Data were analysed using SPSS (version 12) and the mean values for QOL and functional independence were calculated. Relationships between the variables: age, gender and level of amputation with QOL and functional independence were analysed using descriptive and inferential statistical techniques. RESULTS: Among the 35 males and 52 females participating in the study, below knee amputees recorded higher scores for QOL (p < 0.05) and functional independence (p < 0.0001) compared to the above knee amputees. The result also showed that females had a significantly higher average score than males among the four domains for QOL. Similar results were obtained from the FIM where women again had significantly higher scores than males (p < 0.0001). The majority of females across the age groups reported average to high QOL (p < 0.0001) compared to the males. A positive correlation (r = 0.5999, p < 0.0001) was found between functional independence and quality of life of all participants. CONCLUSION: The results showed that below knee amputees functioned better than those with above knee amputations and that females were more likely to cope and function with the disability than males.

Los amputados de las extremidades inferiores enfrentan el cuadro típico de la reducción de su movilidad, lo cual afecta su capacidad para realizar las tareas cotidianas y reintegrarse con éxito a la vida de la comunidad. Uno de los objetivos principales de la rehabilitación de los amputados es mejorar la calidad de vida (CDV). En concordancia con ello, este estudio centra su atención en la CDV y la independencia funcional de personas con amputación de las extremidades inferiores a consecuencia de diabetes secundaria. OBJETIVO: Determinar la CDV y la independencia funcional de diabéticos amputados de las extremidades inferiores, de uno a tres años tras la amputación, a partir de variables tales como la edad, el género, y el nivel de amputación. MÉTODO: Un total de 87 participantes fueron seleccionados de los archivos de fisioterapia de 2006- 2009 en el Hospital Saint Ann Bay. Estos participantes completaron las evaluaciones de la Escala de Calidad de Vida de la Organización Mundial de la Salud (WHO QOL-BREF) y la Medida de Independencia Funcional (MIF). Se analizaron los datos usando SPSS (versión 12) y se calcularon los valores promedios de la CDV y la independencia funcional. Las relaciones entre las variables - edad, género y nivel de amputación - con respecto a la CDV y la independencia funcional, fueron analizadas usando técnicas estadísticas descriptivas e inferenciales. RESULTADOS: Entre los 35 varones y 52 hembras que participaron en el estudio, los amputados por debajo de la rodilla registraron puntuaciones más altas para la CDV (p < 0.05) y la independencia funcional (p < 0.0001) en comparación con los amputados por arriba de la rodilla. El resultado también mostró una puntuación promedio significativamente más alta en las hembras que en los varones, en los cuatro dominios de la CDV. Se obtuvieron resultados similares del MIF, en los que de nuevo las mujeres tenían puntuaciones significativamente más altas que los varones (p < 0.0001). La mayoría de las hembras en todos los grupos etarios reportaron desde una CDV promedio a una CDV alta (p < 0.0001) en comparación con los varones. Se halló una correlación positiva (r = 0.5999, p < 0.0001) entre la independencia funcional y la calidad de vida de todos los participantes. CONCLUSIÓN: Los resultados mostraron que los amputados por debajo de las rodillas funcionaban mejor que aquéllos con amputaciones por encima de la rodilla, y que las mujeres presentaban una mayor probabilidad de lidiar y funcionar exitosamente con la discapacidad en comparación con los hombres.

Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140.

This report describes the discovery of RAD140, a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). The characterization of RAD140 in several preclinical models of anabolic androgen action is also described.

Life after lower extremity amputation in diabetics.

UNLABELLED: Lower limb amputees typically have reduced mobility which affects their ability to perform daily tasks and to successfully reintegrate into community life. A major goal of rehabilitation for amputees is to improve quality of life (QOL). This study therefore focussed on QOL and functional independence for persons with lower limb amputations secondary to diabetes. OBJECTIVE: To determine the QOL and functional independence of lower limb diabetic amputees one to three years post amputation, using variables such as age, gender and amputation level. METHOD: A total of 87 participants were selected from the 2006-2009 physiotherapy records at the St Ann's Bay Hospital. These participants completed the World Health Organization Quality of Life Scale (WHO QOL-BREF) and the Functional Independence Measure (FIM). Data were analysed using SPSS (version 12) and the mean values for QOL and functional independence were calculated. Relationships between the variables: age, gender and level of amputation with QOL and functional independence were analysed using descriptive and inferential statistical techniques. RESULTS: Among the 35 males and 52 females participating in the study, below knee amputees recorded higher scores for QOL (p < 0.05) and functional independence (p < 0.0001) compared to the above knee amputees. The result also showed that females had a significantly higher average score than males among the four domains for QOL. Similar results were obtained from the FIM where women again had significantly higher scores than males (p < 0.0001). The majority of females across the age groups reported average to high QOL (p < 0.0001) compared to the males. A positive correlation (r = 0.5999, p < 0.0001) was found between functional independence and quality of life of all participants. CONCLUSION: The results showed that below knee amputees functioned better than those with above knee amputations and that females were more likely to cope and function with the disability than males.

Recombinant human luteinizing hormone, lutropin alfa, for the induction of follicular development and pregnancy in profoundly gonadotrophin-deficient women.

OBJECTIVE: To provide evidence of efficacy and safety for use of lutropin alfa in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency. DESIGN: An open-label, noncomparative extension of a randomized, double-blind, placebo-controlled study PATIENTS: A total of 31 hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in 23 medical centres in four countries were studied. INTERVENTIONS: Lutropin alfa 75 IU and follitropin alfa (75-225 IU), individually based on each patient's response as is consistent with usual medical practice. MEASUREMENTS: Follicular development as defined by (i) at least one follicle >or= 17 mm; (ii) preovulatory serum oestradiol level >or= 109 pg/ml on the day of hCG administration; and (iii) midluteal phase P(4) level >or= 7.9 ng/ml. Pregnancy and over-response leading to cycle cancellation were considered treatment successes. Pregnancy rates were assessed. RESULTS: In a total of 54 cycles, 27 of 31 (87.1%) profoundly gonadotrophin-deficient patients achieved follicular development within three cycles. Twenty of 27 patients (74.1%) who achieved follicular development and received hCG became pregnant; 16 (59.3%) continued to clinical pregnancy. One patient was hospitalized for severe ovarian hyperstimulation syndrome. Lutropin alfa was well tolerated. CONCLUSIONS: Coadministration of lutropin alfa 75 IU and follitropin alfa is safe and effective in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in a setting consistent with established medical practice.

Aspects histopathologiques de tumeurs vasculaires cervico faciales en orl au CNHU de Cotonou (1985-2005) / Histopathological aspects of cervico-facial vascular tumors in ENT at the CNHU of Cotonou (1985-2005)

Dans une étude rétrospective entre le 1er janvier 1985 et le 30 juin 2005, vingt six (26) cas de tumeurs vasculaires avec confirmation histopathologique ont été recensées en ORL au CNHU de Cotonou. Les sujets de 0 à 20 ans ont constitué 57,6% de la série. La prédominance a été masculine 57,6%. Les motifs de consultation les plus enregistrés ont été la tuméfaction de la face 53,9% et celle du cou 30,9%. L'histopathologie a révélé 88,5% de tumeurs bénignes et 11,6% de tumeurs malignes. Les principales étiologies retrouvées ont été : l'hémangiome 65,3%, le lymphangiome 19,2% et l'hémangio-endothéliome malin 7,6%.

Characterization and Ultrastructural Localization of Chitinases from Metarhizium anisopliae, M. flavoviride, and Beauveria bassiana during Fungal Invasion of Host (Manduca sexta) Cuticle.

Extracellular chitinases have been suggested to be virulence factors in fungal entomopathogenicity. We employed isoelectric focusing and a set of three fluorescent substrates to investigate the numbers and types of chitinolytic enzymes produced by the entomopathogenic fungi Metarhizium anisopliae, Metarhizium flavoviride, and Beauveria bassiana. Each species produced a variety of N-acetyl-(beta)-d-glucosaminidases and endochitinases during growth in media containing insect cuticle. M. flavoviride also produced 1,4-(beta)-chitobiosidases. The endochitinases could be divided according to whether they had basic or acidic isoelectric points. In contrast to those of the other two species, the predominant endochitinases of M. anisopliae were acidic, with isoelectric points of about 4.8. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the acidic chitinases of M. anisopliae into two major bands (43.5 and 45 kDa) with identical N-terminal sequences (AGGYVNAVYFY TNGLYLSNYQPA) similar to an endochitinase from the mycoparasite Trichoderma harzianum. Use of polyclonal antibodies to the 45-kDa isoform and ultrastructural immunocytochemistry enabled us to visualize chitinase production during penetration of the host (Manduca sexta) cuticle. Chitinase was produced at very low levels by infection structures on the cuticle surface and during the initial penetration of the cuticle, but much greater levels of chitinase accumulated in zones of proteolytic degradation, which suggests that the release of the chitinase is dependent on the accessibility of its substrate.