Quantitative ethnopharmacological documentation and molecular confirmation of medicinal plants used by the Manobo tribe of Agusan del Sur, Philippines.

BACKGROUND: The Philippines is renowned as one of the species-rich countries and culturally megadiverse in ethnicity around the globe. However, ethnopharmacological studies in the Philippines are still limited especially in the most numerous ethnic tribal populations in the southern part of the archipelago. This present study aims to document the traditional practices, medicinal plant use, and knowledge; to determine the relative importance, consensus, and the extent of all medicinal plants used; and to integrate molecular confirmation of uncertain species used by the Agusan Manobo in Mindanao, Philippines. METHODS: Quantitative ethnopharmacological data were obtained using semi-structured interviews, group discussions, field observations, and guided field walks with a total of 335 key informants comprising of tribal chieftains, traditional healers, community elders, and Manobo members of the community with their medicinal plant knowledge. The use-report (UR), use categories (UC), use value (UV), cultural importance value (CIV), and use diversity (UD) were quantified and correlated. Other indices using fidelity level (FL), informant consensus factors (ICF), and Jaccard's similarity index (JI) were also calculated. The key informants' medicinal plant use knowledge and practices were statistically analyzed using descriptive and inferential statistics. RESULTS: This study enumerated the ethnopharmacological use of 122 medicinal plant species, distributed among 108 genera and belonging to 51 families classified in 16 use categories. Integrative molecular approach confirmed 24 species with confusing species identity using multiple universal markers (ITS, matK, psbA-trnH, and trnL-F). There was strong agreement among the key informants regarding ethnopharmacological uses of plants, with ICF values ranging from 0.97 to 0.99, with the highest number of species (88) being used for the treatment of abnormal signs and symptoms (ASS). Seven species were reported with maximum fidelity level (100%) in seven use categories. The correlations of the five variables (UR, UC, UV, CIV, and UD) were significant (rs ≥ 0.69, p < 0.001), some being stronger than others. The degree of similarity of the three studied localities had JI ranged from 0.38 to 0.42, indicating species likeness among the tribal communities. Statistically, the medicinal plant knowledge among respondents was significantly different (p < 0.001) when grouped according to education, gender, social position, occupation, civil status, and age but not (p = 0.379) when grouped according to location. This study recorded the first quantitative ethnopharmacological documentation coupled with molecular confirmation of medicinal plants in Mindanao, Philippines, of which one medicinal plant species has never been studied pharmacologically to date. CONCLUSION: Documenting such traditional knowledge of medicinal plants and practices is highly essential for future management and conservation strategies of these plant genetic resources. This ethnopharmacological study will serve as a future reference not only for more systematic ethnopharmacological documentation but also for further pharmacological studies and drug discovery to improve public healthcare worldwide.

Screening for rheumatic heart disease: is a paradigm shift required?

This focused review presents a critical appraisal of the World Heart Federation criteria for the echocardiographic diagnosis of rheumatic heart disease (RHD) and its performance in African RHD screening programmes. It identifies various logistical and methodological problems that negatively influence the current guideline's performance. The authors explore novel RHD screening methodology that could address some of these shortcomings and if proven to be of merit, would require a paradigm shift in the approach to the echocardiographic diagnosis of subclinical RHD.

Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure.

We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa Although 65% of isolates were multiple-drug resistant, therapeutic options were available, as all were susceptible to ≥1 antibiotic. A total of 92% of patients received active antimicrobial therapy, but only 57% received early active therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt bacteremia score (P = 0.046) and delayed active therapy (P = 0.027) were predictive of death and microbiologic failure, respectively.

Clinical Appraisal of Fosfomycin in the Era of Antimicrobial Resistance.

Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum ß-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician-diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent.

Doripenem MICs and ompK36 porin genotypes of sequence type 258, KPC-producing Klebsiella pneumoniae may predict responses to carbapenem-colistin combination therapy among patients with bacteremia.

Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 µg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 µg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.

Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials.

The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome inhibitor bortezomib (Velcade) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique ß-lactone-γ-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.

Development of pharmacotherapies for drug addiction: a Rosetta stone approach.

Current pharmacotherapies for addiction represent opportunities for facilitating treatment and are forming a foundation for evaluating new medications. Furthermore, validated animal models of addiction and a surge in understanding of neurocircuitry and neuropharmacological mechanisms involved in the development and maintenance of addiction - such as the neuroadaptive changes that account for the transition to dependence and the vulnerability to relapse - have provided numerous potential therapeutic targets. Here, we emphasize a 'Rosetta Stone approach', whereby existing pharmacotherapies for addiction are used to validate and improve animal and human laboratory models to identify viable new treatment candidates. This approach will promote translational research and provide a heuristic framework for developing efficient and effective pharmacotherapies for addiction.

Views of mental illness and mental health care in Thailand: a report of an ethnographic study.

This paper reports some of the findings of an ethnographic study carried out in Thailand over a 2-year period. Interviews were conducted with three clinical nurses, three student nurses, 14 nurse educators, one psychiatrist, one Buddhist monk and two lay people (n = 24) about their views of mental health and mental health care in Thailand. Data (comprising field notes and interview transcripts) were analysed with the aid of Atlas.ti. Data were also collected through observation and conversation. This paper reports only the findings from the interviews. Findings emerged under the following headings: Causes of mental illness; Status of the mentally ill; Karma; Merit making; Kwan; Treatment and care; Reasons for becoming a mental health nurse. A range of causes, including the effects of ghosts and spirits, were identified under the first heading. The stigma of mental illness was noted under the second. Karma and merit making are Buddhist concepts and were discussed by many respondents as was the animist concept of kwan. Treatment and care seemed to include both 'modern' and 'traditional' approaches. These findings are discussed and some tentative 'rules' that appear to exist within the culture are mooted. The study is descriptive in nature and the findings cannot be generalized; however, it is hoped that they go some way to illuminate aspects of Thai culture as they relate to the mental health and mental health nursing fields.

Synthesis of a novel family of diterpenes and their evaluation as anti-inflammatory agents.

The synthesis and biological evaluation of a new family of diterpenes, represented by structures 2 and 3, is presented. These compounds constitute isomeric analogues of acanthoic acid (1) and were examined as potent anti-inflammatory agents. Among them, methyl ester 12 exhibited a low non-specific cytotoxicity, inhibited TNF-alpha synthesis and displayed good specificity in suppressing cytokine expression.

Filosofía y medicina en la antigua Grecia: modelos de conocimiento y sus repercusiones

En este trabajo se investigan algunas de las complejidades de la relación entre la filosofía y la medicina en la antigua Grecia. Algunos filósofos citan la medicina como análoga de la filosofía, por ejemplo en conexión con la afirmación de que puede haber expertos objetivos a quienes los meros profanos deben someterse. Algunos médicos, sin embargo, ponen objecciones a lo que representan como líneas dogmáticas, apriorísticas, de la indagación filosófica, y desarrollan una epistemología y una metodología alternativas de carácter empírico. El recuerdo y la experiencia se invocan de formas llamativamente divergentes porque el debate se desarrollaba dentro de y entre diferentes tradiciones filosóficas y médicas (AU)

6-hydroxydopamine lesion of rat nigrostriatal dopaminergic neurons differentially affects nicotinic acetylcholine receptor subunit mRNA expression.

Nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in the rat substantia nigra (SN) was assayed by semiquantitative RT-PCR following 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal dopaminergic neurons. Six months after unilateral injection of 6-OHDA or saline into the SN, total RNA was isolated from ipsilateral and contralateral tissue samples. RT-PCR amplifications were performed with template titration using primers specific for sequences encoding 1. nAChR alpha 2-alpha 7 and beta 2-beta 4 subunits 2. Glutamic acid decarboxylase 3. Glyceraldehyde 3-phosphate dehydrogenase for normalization of template mass. PCR products specific for alpha 3, alpha 4, alpha 5, alpha 6, alpha 7, beta 2, beta 3, and glutamic acid decarboxylase were detected in the reactions containing SN RNA. This is the first evidence that alpha 7 may be expressed in the SN. alpha 2 and beta 4 PCR products were not detected in SN reactions, although they were observed in hippocampus and thalamus control reactions. A comparison of ipsilateral and contralateral SN RT-PCR reaction products showed substantial decreases in alpha 5, alpha 6, and beta 3 product yields following 6-OHDA, but not sham treatment. Neither the SN of sham-lesioned rats nor the thalamus of 6-OHDA-lesioned rats yielded similar results, indicating that the effects observed in 6-OHDA-treated SN were not caused by local mechanical damage or a nonspecific response, respectively. Effects of 6-OHDA treatment on alpha 3, alpha 4, alpha 7, beta 2, or glutamic acid decarboxylase product yields from SN samples were small or undetectable. The results suggest that alpha 5, alpha 6, and beta 3 subunit-encoding mRNAs are expressed at substantially higher levels in dopaminergic than in nondopaminergic cell bodies in the SN.

Computerised biofeedback games: a new method for teaching stress management and its use in irritable bowel syndrome.

OBJECTIVES: To develop and test a computer biofeedback game designed to teach deep relaxation to patients with a stress related disorder and to assess whether relaxation can improve symptomatic episodes. STUDY DESIGN AND SETTING: An open, prospective, single centre study. Department of Gastroenterology, Royal Free Hospital, London. SUBJECTS: Forty patients with irritable bowel syndrome refractory to conventional medical treatment. MAIN OUTCOME MEASURES: Development of a computer aided biofeedback apparatus directed at the gut for teaching relaxation to patients with irritable bowel syndrome. The patients' ability to complete a computer game involving biofeedback modulated by a physiological loop that related changes in stress (monitored by electrodermal activity) to animated computer graphics. The degree to which deep relaxation was achieved was measured numerically by a progressive reduction in the sensitivity level of the biofeedback loop. The success of relaxation in ameliorating physical symptoms of irritable bowel syndrome was assessed by daily diaries in which global and weighted bowel symptom scores were entered. RESULTS: A computer biofeedback game based on animated gut imagery was successfully developed. Most patients learned to achieve progressively deeper levels of relaxation after four 30 minute biofeedback sessions (mean difference in sensitivity level 2.0 (95% confidence interval 0.96 to 2.93), p < 0.001). Use of 'dosed' relaxation when bowel symptoms were troublesome was helpful in 50% of patients. It reduced the global symptom score (mean difference 0.5 (0.02 to 0.32), p < 0.04) and the bowel symptom score (mean difference 0.8 (0.04 to 1.58), p < 0.04). At long term follow up, 64% of patients who had been helped by dosed relaxation continued to use the technique, although they had had no further contact with the hospital. CONCLUSIONS: This computer biofeedback game taught deep relaxation rapidly and effectively. Half the patients with refractory irritable bowel syndrome found the technique helpful on most occasions on which it was used. Computer biofeedback games may offer a simple, inexpensive strategy for managing other stress related medical disorders.

A method for increasing the surface details of resin embedded viruses using Congo/Crimean haemorrhagic fever virus as a model.

The surface details of resin embedded viruses can be greatly enhanced by the use of uranyl acetate block staining. The virions are embedded in agar immediately after fixation and block stained with 3% uranyl acetate in methanol during dehydration. This technique allows those particles outside their host cells to show clearly the spikes normally seen only by the separate use of negative staining.

The treatment of social phobia. Real-life rehearsal with nonprofessional therapists.

Sixteen socially phobic outpatients underwent a 4-week course of social skills training that attempted to maximize rehearsal in real-life settings. The therapy was largely conducted by nonprofessional volunteers after a 2-hour training workshop. It consisted of multiple role-played practice in the clinic, followed immediately by rehearsal in a real-life setting in the company of a nonprofessional therapist and a fellow patient. Subsequently, patients were randomly paired to perform further rehearsals between sessions. Drug therapy was controlled by double blind assignment to propranolol or inert placebo throughout the course of treatment. Measures of specific fears, generalized social anxiety, self-image, and global tension and anxiety were administered 1 month before treatment, immediately before and after treatment, and at 6 months follow-up. During a 4-week drug-free period prior to active treatment no improvement was noted on any measures. After the 4-week treatment period significant improvement had occurred on all outcome measures. Propranolol and placebo subgroups showed very similar results. Treatment gains were sustained at follow-up. It was concluded that repeated behavior rehearsal, both in the clinic and in real life is a cost-effective treatment procedure for many social phobias. The approach is straightforward and can be applied by nonprofessionals, including the patients themselves, after limited training and with minimal supervision.

The general practitioner and changes in obstetric practice.

Compared with the 1960s fewer general practitioners today are obtaining a postgraduate diploma in obstetrics, and the future more stringent criteria for practitioners wishing to undertake this will probably restrict the numbers of family doctors wishing to practise in this field. More deliveries are being performed in institutions--either in consultant or general-practitioner units. Morever, within a decade probably few G.P.s will attend during normal labour or delivery, which can and should be conducted by midwives. In future, therefore, G.P.s should have a new role in obstetrics, being responsible for some antenatal supervision and postnatal care, including postnatal examinations, taking a cervical smear, and advice on birth control.