Perceptions and evaluations of front-line health workers regarding the Brazilian National Program for Improving Access and Quality to Primary Care (PMAQ): a mixed-method approach

Although it is well known that a successful implementation depends on the front-liners’ knowledge and participation, as well as on the organizational capacity of the institutions involved, we still know little about how front-line health workers have been involved in the implementation of the Brazilian National Program for Improving Access and Quality to Primary Care (PMAQ). This paper develops a contingent mixed-method approach to explore the perceptions of front-line health workers - managers, nurses, community health workers, and doctors - regarding the PMAQ (2nd round), and their evaluations concerning health unit organizational capacity. The research is guided by three relevant inter-related concepts from implementation theory: policy knowledge, participation, and organizational capacity. One hundred and twenty-seven health workers from 12 primary health care units in Goiânia, Goiás State, Brazil, answered semi-structured questionnaires, seeking to collect data on reasons for adherence, forms of participation, perceived impact (open-ended questions), and evaluation of organizational capacity (score between 0-10). Content analyses of qualitative data enabled us to categorize the variables “level of perceived impact of PMAQ” and “reasons for adhering to PMAQ”. The calculation and aggregation of the means for the scores given for organizational capacity enabled us to classify distinct levels of organizational capacity. We finally integrated both variables (Perceived-Impact and Organizational-Capacity) through cross-tabulation and the narrative. Results show that nurses are the main type of professional participating. The low organizational capacity and little policy knowledge affected workers participation in and their perceptions of the PMAQ

Pengaruh Kepemimpinan Kepala Sekolah Dan Supervisi Terhadap Kinerja Guru Pada Sma Kristen Barana’ (Studi Kasus Di SMA Kristen Barana Kabupaten Toraja Utara)

Tujuan penelitian ini adalah untuk mengetahui :1) pengaruh kepemimpinan kepala sekolah terhadap kinerja guru pada SMA Kristen Barana’, 2) pengaruh supervisi kepala sekolah terhadap kinerja guru pada SMA Kristen Barana’, 3)pengaruh kepemimpinan kepala sekolah dan supervise secara bersama-sama terhadap kinerja guru pada SMA Kristen Barana’. Metode penelitian yang digunakan dalam penelitian ini adalah metode penelitian kuantitatif deskriptif. Jenis dari penelitian diskriptif yang peneliti gunakan adalah penelitian korelasi sebab akibat. Sampel diperoleh dengan menggunakan sampling jenuh (sensus) yaitu semua guru SMA Kristen Barana yang berjumlah 39 orang. Data diperoleh melalui instrumen penelitian berupa kuesioner. Hasil penelitian menunjukkan bahwa: (1) terdapat pengaruh yang positif dan signifikan kepemimpinan kepala sekolah terhadap kinerja guru, dengan uji- t diperoleh nilai signifikansi 0,000 < 0,05 (2) terdapat pengaruh yang positif dan signifikan supervisi kepala sekolah terhadap kinerja guru, dengan uji-t diperoleh nilai signifikansi 0,007 < 0,05, (3) terdapat pengaruh positif dan signifikan kepemimpinan dan supervisi kepala sekolah terhadap kinerja guru dengan uji F diperoleh nilai signifikansi 0,000 < 0,05 dengan kontribusi kepemimpinan dan supervisi kepala sekolah terhadap kinerja guru sebesar 62,5%

Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria

<p>Abstract</p> <p>Background</p> <p>The six organic solvent extracts of <it>Artemisia nilagirica </it>were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains.</p> <p>Methods</p> <p>The agar disk diffusion method was used to study the antibacterial activity of <it>A. nilagirica </it>extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC) of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 μg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in <it>A. nilagirica</it>.</p> <p>Results</p> <p>All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for <it>Klebsiella pneumoniae, Enterococcus faecalis </it>and <it>Staphylococcus aureus</it>. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 μg/ml and the methanol extract exhibited a higher inhibition activity against <it>Escherichia coli, Yersinia enterocolitica, Salmonella typhi</it>, <it>Enterobacter aerogenes</it>, <it>Proteus vulgaris</it>, <it>Pseudomonas aeruginosa </it>(32 μg/ml), <it>Bacillus subtilis </it>(64 μg/ml) and <it>Shigella flaxneri </it>(128 μg/ml). The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids.</p> <p>Conclusion</p> <p>All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the <it>A. nilagirica </it>extracts. Hence, the isolation and purification of therapeutic potential compounds from <it>A. nilagirica </it>could be used as an effective source against bacterial diseases in human and plants.</p

Association between the ACCN1 Gene and Multiple Sclerosis in Central East Sardinia

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3′ untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3′ UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS

Broadening the phenotype of TARDBP mutations: the TARDBP Ala382Thr mutation and Parkinson’s disease in Sardinia

Mutations in the TARDBP gene are a cause of autosomal dominant amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration (FTLD), but they have not been found so far in patients with Parkinson’s disease (PD). A founder TARDBP mutation (p.Ala382Thr) was recently identified as the cause of ~30% of ALS cases in Sardinia, a Mediterranean genetic isolate. We studied 327 consecutive Sardinian patients with clinically diagnosed PD (88 familial, 239 sporadic) and 578 Sardinian controls. One family with FTLD and parkinsonism was also included. The p.Ala382Thr heterozygous mutation was detected in eight unrelated PD patients (2.5%). The three patients from the FTLD/parkinsonism family also carried this mutation. Within the control group, there were three heterozygous mutation carriers. During follow-up, one of these individuals developed motoneuron disease and another, a rapidly progressive dementia; the third remains healthy at the age of 79 but two close relatives developed motoneuron disease and dementia. The eight PD patients carrying the p.Ala382Thr mutation had all sporadic disease presentation. Their average onset age was 70.0 years (SD 9.4, range 51–79), which is later but not significantly different from that of the patients who did not carry this mutation. In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD

Usefulness of real time PCR for the differentiation and quantification of 652 and JP2 Actinobacillus actinomycetemcomitans genotypes in dental plaque and saliva

BACKGROUND: The aim of our study is to describe a fast molecular method, able to distinguish and quantize the two different genotypes (652 and JP2) of an important periodontal pathogen: Actinobacillus actinomycetemcomitans. The two genotypes show differences in the expression of an important pathogenic factor: the leukotoxin (ltx). In order to evidence this, we performed a real time PCR procedure on the ltx operon, able to recognize Aa clinical isolates with different leukotoxic potentials. METHODS: The specificity of the method was confirmed in subgingival plaque and saliva specimens collected from eighty-one Italian (Sardinian) subjects with a mean age of 43.9, fifty five (68 %) of whom had various clinical forms of periodontal disease. RESULTS: This procedure showed a good sensitivity and a high linear dynamic range of quantization (10(7)-10(2 )cells/ml) for all genotypes and a good correlation factor (R2 = 0.97–0.98). Compared with traditional cultural methods, this real time PCR procedure is more sensitive; in fact in two subgingival plaque and two positive saliva specimens Aa was only detected with the molecular method. CONCLUSION: A low number of Sardinian patients was found positive for Aa infections in the oral cavity, (just 10 positive periodontal cases out of 81 and two of these were also saliva positive). The highly leukotoxic JP2 strain was the most representative (60 % of the positive specimens); the samples from periodontal pockets and from saliva showed some ltx genotype for the same patient. Our experience suggests that this approach is suitable for a rapid and complete laboratory diagnosis for Aa infection

Involvement of EphB1 Receptors Signalling in Models of Inflammatory and Neuropathic Pain

EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy. In sensory systems, they play a role in both the onset of inflammatory and neuropathic pain, and in the establishment of central sensitisation, an NMDA-mediated form of synaptic plasticity thought to underlie most forms of chronic pain. We studied wild type and EphB1 knockout mice in a range of inflammatory and neuropathic pain models to determine 1), whether EphB1 expression is necessary for the onset and/or maintenance of persistent pain, regardless of origin; 2), whether in these models cellular and molecular changes, e.g. phosphorylation of the NR2B subunit of the NMDA receptor, increased c-fos expression or microglial activation, associated with the onset of pain, are affected by the lack of functional EphB1 receptors. Differences in phenotype were examined behaviourally, anatomically, biochemically and electrophysiologically. Our results establish firstly, that functional EphB1 receptors are not essential for the development of normal nociception, thermal or mechanical sensitivity. Secondly, they demonstrate a widespread involvement of EphB1 receptors in chronic pain. NR2B phosphorylation, c-fos expression and microglial activation are all reduced in EphB1 knockout mice. This last finding is intriguing, since microglial activation is supposedly triggered directly by primary afferents, therefore it was not expected to be affected. Interestingly, in some models of long-term pain (days), mechanical and thermal hyperalgesia develop both in wild type and EphB1 knockout mice, but recovery is faster in the latter, indicating that in particular models these receptors are required for the maintenance, rather than the onset of, thermal and mechanical hypersensitivity. This potentially makes them an attractive target for analgesic strategies

Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors

The clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer. By studying EGFR inhibitor-resistant patients treated with a combination of an EGFR inhibitor and a drug targeting the putative resistance-causing fusion oncogene, we identify patients who benefit and those who do not from this treatment approach. Through evaluation including RNA-seq of potential drug resistance-imparting fusion oncogenes in 504 patients with EGFR mutant lung cancer, we identify only a minority of them as functional, potentially capable of imparting EGFR inhibitor resistance. We further functionally validate fusion oncogenes in vitro using CRISPR-based editing of EGFR mutant cell lines and use these models to identify known and unknown drug resistance mechanisms to combination therapies. Collectively, our results partially reveal the complex nature of fusion oncogenes as potential drug resistance mechanisms and highlight approaches that can be undertaken to determine their functional significance.</p