The Hemileia vastatrix effector HvEC-016 suppresses bacterial blight symptoms in coffee genotypes with the SH 1 rust resistance gene.

A number of genes that confer resistance to coffee leaf rust (SH 1-SH 9) have been identified within the genus Coffea, but despite many years of research on this pathosystem, the complementary avirulence genes of Hemileia vastatrix have not been reported. After identification of H. vastatrix effector candidate genes (HvECs) expressed at different stages of its lifecycle, we established an assay to characterize HvEC proteins by delivering them into coffee cells via the type-three secretion system (T3SS) of Pseudomonas syringae pv. garcae (Psgc). Employing a calmodulin-dependent adenylate cyclase assay, we demonstrate that Psgc recognizes a heterologous P. syringae T3SS secretion signal which enables us to translocate HvECs into the cytoplasm of coffee cells. Using this Psgc-adapted effector detector vector (EDV) system, we found that HvEC-016 suppresses the growth of Psgc on coffee genotypes with the SH 1 resistance gene. Suppression of bacterial blight symptoms in SH 1 plants was associated with reduced bacterial multiplication. By contrast, HvEC-016 enhanced bacterial multiplication in SH 1-lacking plants. Our findings suggest that HvEC-016 may be recognized by the plant immune system in a SH 1-dependent manner. Thus, our experimental approach is an effective tool for the characterization of effector/avirulence proteins of this important pathogen.

Cervico-Mental Angle Suspensory Ligament: The Keystone to Understand the Cervico-Mental Angle and the Ageing Process of the Neck.

The authors performed cadaveric dissections to investigate the existence of an anatomical structure creating and maintaining the cervical mental angle, aiming to understand the anatomical bases of the cervico-mental angle and its modifications over time. Six fresh cadaver dissections were performed; four were done in the Caen University anatomy laboratory one in Paris XV University and one in the Coventry University hospital, England. At the end of this investigation, the authors were able to demonstrate the existence of an anatomical structure in the neck, the cervico-mental angle suspensory ligament. This ligament that fixates the platysma and skin to deeper structures originated from the second branchial arch and seems to play a key role in the formation of the cervico-mental angle and in the anatomical alterations in the ageing process. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Predisposing risk factors for cleft lip and palate in an Amazonian population by focusing on nutritional factors: A case-control study.

BACKGROUND: Orofacial clefts (OFC) are the most common congenital malformation of the craniofacial skeleton. Attempts have been made to correlate the components of maternal diet as triggers for the development or prevention of OFC. OBJECTIVE: To analyze nutritional status as a predictive factor for the development of cleft lip and palate in an Amazonian population. METHODS: A total of 152 mothers within 3 months of delivery were interviewed for comparison: 51 mothers of children with nonsyndromic cleft lip and palate (CLP) (study group) and 101 mothers of children without OFC (control group). A food frequency questionnaire was used to assess maternal nutrition and to analyze the influence of macro- and micronutrients on the possible predisposition or protection for CLP. RESULTS: The study group showed higher percentage of lipid intake than did the control group (p = 0.01). Among the participants with no family history of OFC, the study group had a higher percentage of lipid intake (p = 0.002) and lower vegetable intake (p = 0.037). Maternal micronutrient intake among the participants with a positive family history was lower in the study group for vitamins B2 (p = 0.03), B5 (p = 0.036), E (p = 0.03), and folate (p = 0.022). CONCLUSIONS: Nutritional analysis indicated that higher maternal lipid intake increased the likelihood of having offsprings with nonsyndromic CLP. Moreover, families with a history of OFC and low maternal folate intake showed heightened risk of nonsyndromic CLP in their offsprings.

Cardiac mitochondrial respiration following a low-carbohydrate, high-fat diet in apolipoprotein E-deficient mice.

Low-carbohydrate diets are considered to be an effective approach to weight loss and have, subsequently, grown in popularity. Despite the apparent health benefits that these diets may provide for insulin resistance, hypertension, and dyslipidemia, their implications on cardiomyocyte oxidative capacity have yet to be investigated. To evaluate the adaptations induced by a 6-week low-carbohydrate, high-fat (LCHF) diet on mitochondrial respiration, two groups of male mice were investigated: Apolipoprotein E-deficient mice on a LCHF diet (L-DIET) and apolipoprotein E-deficient mice on a regular rodent diet (CON). Heart tissue was extracted and used for high-resolution respirometry (HRR), while immunoblotting was performed to quantify mitochondrial density and complexes. The results demonstrate increased expression of all five mitochondrial subunits in the L-DIET group compared to control condition. Furthermore, HRR revealed increased efficiency of substrate consumption, implying augmented oxidative capacity in the L-DIET group. These findings further support the notion that cardiomyocytes prefer lipids as a primary fuel source, by demonstrating that the shift in metabolism caused by a LCHF diet facilitates such an environment. This provides important information regarding the effects of a LCHF on cardiomyocytes, especially when considering free radical production and heart dysfunction.

Diuretic activity and neuropharmacological effects of an ethanol extract from Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae).

Ethnopharmacological relevance Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a shrub empirically used as diuretic, and for the treatment of neurological disorders. These pharmacological effects have not been previously evaluated. AIM OF THE STUDY: To evaluate the diuretic and CNS effects of a standardized ethanol extract of Senna septemtrionalis aerial parts (SSE). MATERIALS AND METHODS: Gas chromatography mass spectrometry was used to perform a chemical analysis with SSE. In all tests, SSE was evaluated from 10 to 100 mg/kg p.o. The diuretic activity of SSE was assessed in mice individually placed in metabolic cages. After 6 h, the urine volume and the electrolyte excretion (Na and K) were measured. The role of prostaglandins and nitric oxide was assessed administrating mice with indomethacin and N(ω)-nitro-L-arginine methyl ester (L-NAME), prior the administration of 100 mg/kg SSE. The sedative effects of SSE were analyzed with the pentobarbital-induced sleeping time test. The effects of SSE on motor coordination in mice were evaluated with the rotarod test. The antidepressant-like activity of SSE was analyzed with the forced swimming test (FST) and the tail suspension test (TST). The role of 5-HT2 receptor, α1-and α2-adrenoceptors, or muscarinic receptors was assessed administrating mice with cyproheptadine, prazosin, yohimbine, and atropine, respectively, prior the administration of 100 mg/kg SSE in the FST. The anxiolytic-like activity of SSE (10-100 mg/kg p.o.) was assessed using the light-dark test (LDB), the elevated plus maze test (EPM), the cylinder exploratory test, and the open field test (OFT). The anticonvulsant effect of SSE (1-100 mg/kg) was evaluated in mice administered with different convulsant agents: strychnine, pentylenetetrazol (PTZ), isoniazid (INH) or yohimbine. RESULTS: The main compound found in SSE was D-pinitol (42.2%). SSE (100 mg/kg) increased the urinary volume (2.67-fold), as well as the excretion of Na (5.60-fold) and K (7.2-fold). The co-administration of SSE with L-NAME or indomethacin reverted the diuretic activity shown by SSE alone. SSE lacked sedative effects and did not affect motor coordination in mice. SSE (100 mg/kg) showed higher and similar antidepressant-like effect, compared to 20 mg/kg fluoxetine, in the FST and TST, respectively. The co-administration of SSE with yohimbine reverted the antidepressant-like activity shown by SSE alone. SSE (100 mg/kg) showed anxiolytic-like activity in the four models of anxiety, with similar activity with 1.5 mg/kg clonazepam. The seizure-protective effect of SSE was ED50 = 73.9 ±â€¯8.4 mg/kg (INH) and 40.4 ±â€¯5.2 mg/kg (yohimbine). CONCLUSION: The diuretic effects of SSE involve the possible contribution of prostaglandins and nitric oxide. SSE showed moderate anxiolytic and anticonvulsant effects, whereas the participation of α2-adrenoceptors is probably associated in the antidepressant-like effects of SSE.

Benzodioxoles: novel cannabinoid-1 receptor inverse agonists for the treatment of obesity.

The application of the evolutionary fragment-based de novo design tool TOPology Assigning System (TOPAS), starting from a known CB1R (CB-1 receptor) ligand, followed by further refinement principles, including pharmacophore compliance, chemical tractability, and drug likeness, allowed the identification of benzodioxoles as a novel CB1R inverse agonist series. Extensive multidimensional optimization was rewarded by the identification of promising lead compounds, showing in vivo activity. These compounds reversed the CP-55940-induced hypothermia in Naval Medical Research Institute (NMRI) mice and reduced body-weight gain, as well as fat mass, in diet-induced obese Sprague-Dawley rats. Herein, we disclose the tools and strategies that were employed for rapid hit identification, synthesis and generation of structure-activity relationships, ultimately leading to the identification of (+)-[( R)-2-(2,4-dichloride-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholin-4-yl-methanone ( R)-14g . Biochemical, pharmacokinetic, and pharmacodynamic characteristics of ( R)-14g are discussed.

Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases.

A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound ( 5) was found during a high-throughput screening campaign. Structure-activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds ( R)- 58 and ( R)- 71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.

Facial Reanimation in the Seventh and Eighth Decades of Life.

BACKGROUND: Treatment of facial paralysis in the older population is often relegated to static rather than dynamic reanimation for fear of poor outcomes. This pervasive approach lacks physiologic foundation and is not evidence based. Thus, the authors present an extensive literature review demonstrating weak evidence supporting this misguided concept, followed by detailed outcomes from three centers of the largest reported series to date of patients older than 60 years after reanimation performed using three techniques-lengthening temporalis myoplasty, free functional muscle, and nerve transfers. METHODS: A PubMed search spanning over 40 years identified all reports on reanimation in patients older than 60 years. In addition, detailed demographics, surgical techniques, and outcomes of 30 patients older than 60 years were analyzed. RESULTS: Of 629 articles, only 45 patients were identified, described in case reports or small series, lacking details or consistent long-term follow-up. In the clinical series, average age, preoperative House-Brackmann score, and comorbidities were similar among the groups. Highest excursion was observed in the free functional muscle group, followed by nerve transfer and temporalis myoplasty, averaging 10.4, 6.8, and 3.1 mm, respectively. The most notable philtral deviation correction was in the lengthening temporalis myoplasty group, followed by the free muscle and nerve transfer groups, averaging 5.6, 2.2, and 1.13 mm, respectively. Complication rates were highest in the free functional muscle group. CONCLUSIONS: Facial palsy patients should not be denied dynamic restoration based on age alone. Although surgical technique may vary based on duration of palsy, surgeon experience, and preference, with each presenting advantages and disadvantages, dynamic restoration is feasible regardless of age. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Pre-clinical and clinical evaluation of solution and soft gelatin capsule formulations for a BCS class 3 compound with atypical physicochemical properties.

R1481 is a sub-type selective muscarinic receptor antagonist with the potential treatment of overactive bladder. R1481 presents two challenges for drug development. The first is the viscous semi-solid nature of the active pharmaceutical ingredient (API). The second challenge is the poor oral bioavailability of this water soluble, metabolically stable compound due to low intestinal permeability, and the P-glycoprotein (P-gp) efflux mechanism. Vitamin E TPGS is reported by others to enhance bioavailability by increasing the solubility of active compounds and by inhibiting P-gp in the intestine. In this report, compatibility of R1481 in Capmul MCM-based formulations with and without vitamin E TPGS is summarized. Review of accelerated stability studies of oral formulations led to the identification of a soft gelatin capsule formulation using neat Capmul MCM as an acceptable formulation for Phase 1 clinical studies. Soft gelatin capsules (5 mg strength) were manufactured with and without the addition of vitamin E TPGS. Clinical data show that vitamin E TPGS does not improve systemic exposure of R1481 in humans.

Ritidoplastia e paralisia facial: como lidar? / Facelift and Facial nerve injury: how to deal with?

Não é novidade para os cirurgiões plásticos, especialmente aos que se dedicam à cirurgia de face, que o nervo facial pode ser lesado virtualmente em qualquer cirurgia de ritidoplastia. Porém, apesar da importância contida nesse tema, não é tarefa simples encontrar na literatura artigos que abordem de forma objetiva a correlação entre lesão do nervo facial e cirurgia facial. Paralisias faciais, sejam elas completas ou não, podem se tornar situações potencialmente conflituosas na relação médicopaciente. Este artigo, portanto, visa propor de forma clara e sucinta, baseada na experiência dos autores, um guia de como evitar, identificar e tratar uma potencial lesão do nervo facial no contexto de uma cirurgia de face, em especial a ritidoplastia.

Is largely known that the facial nerve virtually can be injured in every facial lift. Even though its importance, it is difficult to find in the literature articles related to this theme. Complete or incomplete facial paralysis after a facial procedures, may become a very uncomfortable situation between the patient and the surgeon, that is why we propose in this article a guide which intends to help avoid, identify and manage a facial nerve injury in the event of a face lift. Identifying Facial palsy before the surgery: Intending to make the pre-op facial assessment as simple as possible, we suggest a systematic approach examination. Avoiding facial nerve injury during face lifting: Several technical details are discussed along the text aiming to minimize the risk of nerve damage during the surgical procedure. What to in the event of a post-operative facial palsy: The authors propose a logical approach to the facial palsy, suggesting a planning for diagnosis, classification of the lesion and a rational treatment for the injury. Conclusion: This article presents a guide showing some safe technical options to avoid nerve damage during rythidoplasty, how to identify the lesion and treat it if necessary.

Political activities of social workers: addressing perceived barriers to political participation.

This article reviews the literature on political participation of social workers and the variables that promote or impede political advocacy. Early research in the 1980s and 1990s most often reported education, feelings of efficacy, having a macro-type job, and being a member of a national association as factors that determine greater political participation. Since the late 1990s, organizational and legal issues have surfaced more prominently as barriers to political participation by social workers. This article addresses barriers to participation, such as not feeling competent to perform policy-related tasks and perceived legal barriers.It then analyzes the actual restrictions that nonprofit 501(c)(3) organizations and publicly employed social workers face in lobbying and partisan politics. The article summarizes the activities that are legally allowed in these areas and concludes that social workers can be more politically active than they often realize.

Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification.

Replacement of the N-butyl side-chain of lead 5-HT4 receptor antagonist 2 with propanesulfonylpiperidinyl, morpholinyl, and piperazinyl groups led to higher affinity analogs 4-6. In vitro drug metabolism screens and cassette pharmacokinetic studies in the dog led to identification of the N-methylpiperazinyl analog (6b), which displayed pharmacokinetic, selectivity, and safety parameters sufficient for advancement to the clinic for the treatment of urinary incontinence.

Managed care and mental health: personal realities.

A review of the literature revealed mixed reviews on the impact of managed care on mental health service delivery. Research supports that managed care contributes to a reduction in inpatient costs and an increase in outpatient service use. Other studies suggest that there are problems with access and quality of care. An additional issue is whether or not, and to what extent, mental health services are "carved out" from physical health for patients. This study discusses the findings of a qualitative analysis of Medicaid managed care recipients on the barriers and enabling factors to obtaining mental health services in a full carve-out managed care model. Results indicate that reduced access, quality of care problems, and a lack of integration of care exist. Additionally, recipients' interactions with managed care, service providers, and caseworkers affect their mental health care. The results also report on the tactics used by recipients to cope with service problems. Implications for social work practice and research are discussed and recommendations for service delivery and evidence-based education are delineated.

O que há de novo na profilaxia da endocardite bacteriana. Deve-se mudar a conduta atual? / What?s new in the prophylaxis of bacterial endocarditis. We must change our current practice?

JUSTIFICATIVA E OBJETIVOS: A endocardite é uma doença em que agentes infecciosos invadem as superfícies endocárdicas, produzindo inflamação e lesões. Sendo muito discutida após a publicação das diretrizes da American Heart Association de 2007. Tais diretrizes têm causado muitas controvérsias na literatura atual, com reflexo na decisão quanto à conduta a ser adotada para sua profilaxia. Dessa forma, este estudo teve por objetivo contribuir na prática clínica, no tocante a real indicação e custo efetividade da profilaxia antimicrobiana para a prevenção da endocardite bacteriana. CONTEÚDO: Este estudo versa sobre a profilaxia da endocardite bacteriana, através de uma revisão da literatura e seus conceitos mais relevantes, discutindo o consenso americano e sua aplicabilidade na realidade brasileira. Para tanto foram feitas duas pesquisas na base de dados da PubMed, Sociedade Brasileira de Cardiologia e Sociedade Brasileira de Odontologia. CONCLUSÃO: A escolha da profilaxia antibiótica deve levar em conta os aspectos atuais de nossa população, bem como a classificação de risco para endocardite e a evolução clínica de cada paciente na prática diária, para uma correta indicação do antibiótico e melhora de seu custo efetividade.

Derrame pleural: abordagem diagnóstica / Pleural apoplexy: diagnostic approach

Derrame pleural é o acúmulo anormal de líquido no espaço entre as pleuras parietal e visceral. Para tanto, deve haver um descompasso entre a produção e a reabsorção do líquido pleural, normalmente presente nesse espaço (cavidade pleural), com a finalidade de facilitar o deslizamento pulmonar e, finalmente as trocas gasosas. Nesse artigo, os autores fazem uma abordagem simplificada e diagnóstica dos diferentes tipos de derrame pleural.

Tomografia computadorizada e ressonância magnética no estadiamento do câncer de colo do útero / Computed tomography and magnetic resonance imaging in the staging of cancer of the cervix

Os autores fazem uma revisão sobre o uso da tomografia computadorizada e da ressonância magnética no estadiamento do câncer de colo do útero.