Cardiovascular efficacy and safety of bococizumab in high-risk patients

BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin– kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of −56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of –59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients. (Funded by Pfizer; SPIRE-1 and SPIRE-2 ClinicalTrials.gov numbers, NCT01975376 and NCT01975389.

Avaliação de Trichogramma spp. para o controle de Trichoplusia ni.

Resumo O objetivo deste trabalho foi avaliar as características biológicas dos parasitoides Trichogramma acacioi, T. atopovirilia, T. marandobai, T. demoraesi, T. exiguum (duas linhagens) e T. pretiosum (seis linhagens), criados em ovos de Trichoplusia ni. O experimento foi conduzido em delineamento inteiramente casualizado, com 15 repetições. As características biológicas avaliadas foram: parasitismo, viabilidade, razão sexual e número de indivíduos por ovo. A percentagem de parasitismo variou entre 7,66 e 53%, com maior valor observado para a linhagem Tspd de Trichogramma pretiosum, e o menor para a linhagem Trecife de T. pretiosum. Não houve diferença significativa dessa espécie quanto à viabilidade, que ficou acima de 85%. A razão sexual variou de 0,75 a 1, e a linhagem Tspd apresentou o menor valor. O número de parasitoides por ovo variou entre 2,39 para T. marandobai (linhagem Tm1) e 1,34 para T. exiguum (linhagem Te1). A espécie que apresentou o melhor desempenho em laboratório foi T. pretiosum (Tspd), com os maiores valores observados na percentagem de parasitismo e na emergência. Termos para indexação: Brassicaceae, controle biológico, lagarta mede?palmo, parasitismo, parasitoide de ovos

Validity of self-reported weight: a study of urban brazilian adults

Para avaliar a validade do peso auto-referido em inquéritos de prevalência de obesidade, o mesmo foi comparado com o peso medido de 659 adultos, residentes em Porto Alegre, RS, Brasil, em 1986-87. Ambos os pesos foram obtidos por entrevistador, na casa do participante, na mesma ocasião. A média das diferenças entre peso auto-referido e peso medido foi pequena (-0,06 +/-3,16 kg; média +/- desvio padrão) e a correlação entre eles alta (r=0,97). Sessenta e dois por cento dos participantes referiram seu peso com erro < 2 kg, 87% com erro menor do que 4 kg e 95% com erro < 6 kg. Indivíduos de baixo peso hiperestimaram seu peso, o oposto ocorrendo com indivíduos obesos (p; 30) por peso referido, foi de 10% e a por peso medido, de 11%. Concluindo, a validade do peso auto-referido é aceitável para inquéritos de prevalência realizados em contextos similares.In order to evaluate the validity of self-reported weight for use in obesity prevalence surveys, self-reported weight was compared to measured weight for 659 adults living in the Porto Alegre county, RS Brazil in 1986-87, both weights being obtained by a technician in the individual's home on the same visit. The mean difference between self-reported and measured weight was small (-0.06 +/- 3.16 kg; mean +/- standard deviation), and the correlation between reported and measured weight was high (r=0.97). Sixty-two percent of participants reported their weight with an error of < 2 kg, 87% with an error of < 4 kg, and 95% with an error of < 6 kg. Underweight individuals overestimated their weight, while obese individuals underestimated theirs (p; 30) by reported weight was 10%, by measured weight 11%. Thus, the validity of reported weight is acceptable for surveys of the prevalence of ponderosity in similar settings

What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood disorder with international prevalence estimates of 5 % in childhood, yet significant evidence exists that far fewer children receive ADHD services. In many countries, ADHD is assessed and diagnosed in specialist mental health or neuro-developmental paediatric clinics, to which referral by General (Family) Practitioners (GPs) is required. In such ‘gatekeeper’ settings, where GPs act as a filter to diagnosis and treatment, GPs may either not recognise potential ADHD cases, or may be reluctant to refer. This study systematically reviews the literature regarding GPs’ views of ADHD in such settings. Methods: A search of nine major databases was conducted, with wide search parameters; 3776 records were initially retrieved. Studies were included if they were from settings where GPs are typically gatekeepers to ADHD services; if they addressed GPs’ ADHD attitudes and knowledge; if methods were clearly described; and if results for GPs were reported separately from those of other health professionals. Results: Few studies specifically addressed GP attitudes to ADHD. Only 11 papers (10 studies), spanning 2000–2010, met inclusion criteria, predominantly from the UK, Europe and Australia. As studies varied methodologically, findings are reported as a thematic narrative, under the following themes: Recognition rate; ADHD controversy (medicalisation, stigma, labelling); Causes of ADHD; GPs and ADHD diagnosis; GPs and ADHD treatment; GP ADHD training and sources of information; and Age, sex differences in knowledge and attitudes. Conclusions: Across times and settings, GPs practising in first-contact gatekeeper settings had mixed and often unhelpful attitudes regarding the validity of ADHD as a construct, the role of medication and how parenting contributed to presentation. A paucity of training was identified, alongside a reluctance of GPs to become involved in shared care practice. If access to services is to be improved for possible ADHD cases, there needs to be a focused and collaborative approach to training

Biology of Telenomus pachycoris (Hymenoptera: Scelionidae), a parasitoid of eggs of Pachycoris torridus (Hemiptera: Scutelleridae): the effects of egg age, exposure time, and temperature.

Made available in DSpace on 2017-10-07T10:28:38Z (GMT). No. of bitstreams: 1 DoriPaperFloridaEntomologist.pdf: 219472 bytes, checksum: 9814666d8e2039e5f1c7bd30493944ce (MD5) Previous issue date: 2017-10-06bitstream/item/164722/1/Dori-Paper-Florida-Entomologist.pd

Identification of midgut membrane proteins from different instars of Helicoverpa armigera (Lepidoptera: Noctuidae) that bind to Cry1Ac toxin.

Helicoverpa armigera is a polyphagous pest sensitive to Cry1Ac protein from Bacillus thuringiensis (Bt). The susceptibility of the different larval instars of H. armigera to Cry1Ac protoxin showed a significant 45-fold reduction in late instars compared to early instars. A possible hypothesis is that gut surface proteins that bind to Cry1Ac differ in both instars, although higher Cry toxin degradation in late instars could also explain the observed differences in susceptibility. Here we compared the Cry1Ac-binding proteins from second and fifth instars by pull-down assays and liquid chromatography coupled to mass spectrometry analysis (LC-MS/MS). The data show differential protein interaction patterns of Cry1Ac in the two instars analyzed. Alkaline phosphatase, and other membrane proteins, such as prohibitin and an anion selective channel protein were identified only in the second instar, suggesting that these proteins may be involved in the higher toxicity of Cry1Ac in early instars of H. armigera. Eleven Cry1Ac binindg proteins were identified exclusively in late instar larvae, like different proteases such as trypsin-like protease, azurocidin-like proteinase, and carboxypeptidase. Different aminopeptidase N isofroms were identified in both instar larvae. We compared the Cry1Ac protoxin degradation using midgut juice from late and early instars, showing that the midgut juice from late instars is more efficient to degrade Cry1Ac protoxin than that of early instars, suggesting that increased proteolytic activity on the toxin could also explain the low Cry1Ac toxicity in late instars

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

Periodontal disease has been associated with elevations of blood cytokines involved in atherosclerosis in systemically healthy individuals, but little is known about this association in stable cardiovascular patients. The aim of this study was to assess the association between periodontal disease (exposure) and blood cytokine levels (outcomes) in a target population of patients with stable coronary artery disease (CAD). Material and Methods This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. Results CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). Conclusion Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients

Bacillus Thuringiensis: diversidade gênica em isolados Lepidoptera-específicos.

O presente trabalho teve como objetivo caracterizar geneticamente 1.073 isolados de Bacillus thuringiensis, de três coleções brasileiras, provenientes da UNESP, Jaboticabal, ESALQ - Piracicaba e da EMBRAPA. Sete Lagoas, analisando os tipos de genes cryl apresentados pelos isolados. Para isso, foram elaborados oligonucleotídeos iniciadores a partir de 16 regiões conservadas e 4 regiôes não conservadas das seqüências de cada uma das 16 subclasses do gene cryl. Essas seqüências foram amplificadas por PCR e a presença de amplicons para cada subclasse foi calculada em porcentagem por gene e por coleção. Nessa análise, 55,7'?u dos isolados apresentaram amplificação para o gene cryl, e as subclasses cryl Aa, cryl Al>, cryl Ac. cryl Ad, cryl Ac, cryl Af, cryl 1 Ag, l e cryl 1 Bj; cryl Ca e cryl Fa estão presentes em ai ta proporção de isolados, variando de 43,4 % a 54, 9'?u. Verificou-se que existe uma distribuição das subclasses dentro do banco de isolados de B. thuringiensis em estudo, com maior porcentagem de isolados portadores dos genes cryl Al> (42,12%) e com menor porcentagem de representantes da subclasse cryl D/1 (0,6%). A variabilidade gênica, nas coleções analisadas, destaca as coleções de Jaboticabal e Piracicaba como fontes de isolados promissores para uso em programas de Controle Biológico de pragas da ordem Lepidoptera. A coleção de Sete Lagoas, na qual as freqüências das subclasses estudadas foram reIativamente baixas (a baixo de 20%), destaca somente o gene cryl A/1, presente em 38,5% dos isolados desta coleção

Adult feeding and mating effects on the biological potential and parasitism of Trichogramma pretiosum and T. acacioi (Hym.: Trichogrammatidae).

ABSTRACT: This work was carried out to study the effects of adult feeding and mating on the biological potential and parasitism of Trichogramma pretiosum and T. acacioi (Hymenoptera: Trichogrammatidae) to improve their use in biological control programs. Both species presented higher parasitism and longevity whenever adults were fed. Fed and unmated T. pretiosum females led to low parasitism whereas T. acacioi females did not present parasitism whatsoever. Egg viability of T. pretiosum was similar for fed and mated individuals, but T acacioi showed lower values for this parameter when unfed and without mating. Unmated females produced only males while mated ones had more than 60% female descendents for both Trichogramma species. Therefore, mated and fed female parasitoids should be released in crop systems to increase the biological control. RESUMO: Os efeitos do acasalamento e alimentação no potencial biológico e parasitismo de Trichogramma pretiosum e Trichogramma acacioi (Hymenoptera: Trichogrammatidae), foram estudados objetivando-se aprimorar o uso dessas espécies no controle biológico. O parasitismo e longevidade dos adultos de ambas as espécies foram maiores para fêmeas alimentadas e o parasitismo foi nulo e baixo para fêmeas acasaladas e não-alimentadas de T. acacioi e T. pretiosum, respectivamente. A viabilidade de ovos parasitados por T. pretiosum foi semelhante entre os tratamentos, mas para T. acacioi houve uma menor viabilidade do parasitismo realizado por fêmeas sem acasalamento e sem alimento. Descendentes de T. pretiosum e T. acacioi sem acasalamento produziram apenas machos, enquanto fêmeas acasaladas tiveram mais de 60% dos descentes fêmeas para as duas espécies de Trichogramma. Portanto, fêmeas acasaladas e alimentadas devem ser liberadas para o controle biológico

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)