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Advancing the clinical perspective: a practice development project to develop the nurse practitioner role in an acute hospital trust.

AIMS: The aims of this project were to investigate awareness and foster understanding of the concept of the nurse practitioner and to facilitate and support the development of nurse practitioner roles within an acute hospital trust. BACKGROUND: A limited understanding of and minimal support for the development of the nurse practitioner (NP) role were identified within an acute hospital trust in the south of England. This was the impetus for pursuing the project outlined in this paper. THEORETICAL PERSPECTIVE: The project used practice development theory synonymously with action research methodology comprising of four action research cycles. METHOD: Data were collected in a variety of ways within the four overlapping cycles using formal and informal methods, which were analysed concurrently during the project. Techniques included questionnaires, semi-structured interviews, meetings, discussions and the project leader's field notes' diary. OUTCOMES: A better understanding of the concept and support for NP posts were enhanced across the trust. A Nurse Practitioner Development Group (NPDG) was established, which helped to facilitate the development of NP posts. An example of such a post was established within a NP-led gynaecology pre-operative assessment clinic, which was a pilot project and constituted Action Research cycle 3. CONCLUSION: It is concluded that the development of NP roles, with the support of a NPDG, within an agreed strategy offers a robust process for NP development within an acute hospital setting. RELEVANCE TO CLINICAL PRACTICE: This project demonstrated how practice development and action research might be used together as a systematic process for developing and supporting professional roles that aim to improve the quality of patient care and the effectiveness of health care services.

Acute Disease↗

[The general concepts of development and the principle of sustainable development].

A concept of the sustainable development principle proposed by the United Nations/International Committee on Environment and Development (ICED, 1987) and gained acceptance at the United Nations Conference on Environment and Development (Rio-de-Janeiro, 1992) lies not in the notion of a sustained character of the development but in an understanding of the development as a steadily and long existing and maintained process that is in advocating the stability of the development. It is known, that the state instability of open self-organizing and self-developing systems including the social ones is the the source of the development having a probabilistic, bifurcate and not quite predictable character. Such an understanding of the development should be well represented in the action initiated in the frame work of national and international state ecological policies.

Conservation of Natural Resources↗

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select disease areas and/or in clinically important drug-drug interaction studies. A tabular representation of select examples of analysis is provided covering areas of separation conditions, validation aspects and applicable conclusion. A limited discussion is provided on relevant aspects of the need for developing bioanalytical procedures for speedy drug discovery and development. Additionally, some key elements such as internal standard selection, likely issues of mass detection, matrix effect, chiral aspects etc. are provided for consideration during method development.

Animals↗

Golgi studies on Purkinje cell development in the frog during spontaneous metamorphosis. II. Details of dendritic development.

The development of Purkinje cell dendrites was studied in the bullfrog from premetamorphic tadpoles to 10-week-old postmetamorphic frog-lets by the Golgi-Kopsch method. In this species two distinct patterns of arbor formation may be seen, which appear to be related to differences in the timing of initial dendritic development. In Purkinje cells that begin development in early tadpole stages, the dendritic tree is elaborated by continuous and concomitant growth and branching, a process by which the developing arbor expands in both height and width. Arbor formation in Purkinje cells that begin development in metamorphosing tadpoles proceeds in two separate steps. Initially, dendrites of such cells elongate, but form only a few poorly developed branches; only when the arbor reaches near-adult height does branching become extensive. Additional differences present in Purkinje cells are reflected in the paucity of growth cones and filopodia in the tadpole, and numerous filopodia and growth cones in the metamorphic period. An interesting feature of dendritic development in this species is a tendency to alter the arboreal domain by the formation of extra-arboreal dendrites, and possibly by the occasional resorbtion of other partially formed dendrites. The pattern of dendritic development in the frog is different than in mammals and is difficult to interpret. Such unusual development may be due to disturbances in the timing of the formation of Purkinje cell dendrites and of the establishment of the external granular layer (EGL).

Animals↗

Structural and functional brain development and its relation to cognitive development.

Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development.

Adolescent↗

Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors.

The vitamin A metabolite, retinoic acid (RA), affects Th1 and Th2 development. The effect is partly exerted through the modulation of antigen-presenting cell functions, but it remains unclear whether RA directly exerts its effect on T cells to influence Th1/Th2 development. To clarify this problem, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two transient stimulations with defined combinations of ionomycin and phorbol myristate acetate followed by treatment with IL-2 and IL-4 and/or IL-12. In the second system, functional differentiation was induced in purified naive CD4 T cells from DO-11.10 TCR-transgenic and RAG-2-deficient mice with cytokines and antibodies to CD3 and CD28. In both systems, all-trans-RA at > or = 1 nM concentrations suppressed Th1 development, but enhanced Th2 development. 9-cis-RA elicited similar effects. The optimal enhancement of Th2 development in the second system, however, was achieved with a delayed addition of RA. The presence of RA during the initial stimulation period often suppressed Th2 development. The RA receptor (RAR) antagonists, LE540 and LE135, but not the retinoic X receptor (RXR) antagonist, PA452, inhibited the effect of RA on Th1/Th2 development. Accordingly, the RAR agonists, Am80 and Tp80, but not the RXR agonists, HX600 and TZ335, mimicked the effect of RA. The RXR agonists enhanced the effect of the RAR agonists only slightly, if at all. These results indicate that, via RAR, RA directly suppresses Th1 development and directly enhances Th2 development with its timely addition.

Alitretinoin↗

Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.

BACKGROUND: Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients. METHODS: Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets. RESULTS: When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules. CONCLUSIONS: Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

Antibodies↗

Organisational development in general practice: lessons from practice and professional development plans (PPDPs).

BACKGROUND: Improving the quality and effectiveness of clinical practice is becoming a key task within all health services. Primary medical care, as organised in the UK is composed of clinicians who work in independent partnerships (general practices) that collaborate with other health care professionals. Although many practices have successfully introduced innovations, there are no organisational development structures in place that support the evolution of primary medical care towards integrated care processes. Providing incentives for attendance at passive educational events and promoting 'teamwork' without first identifying organisational priorities are interventions that have proved to be ineffective at changing clinical processes. A practice and professional development plan feasibility study was evaluated in Wales and provided the experiential basis for a summary of the lessons learnt on how best to guide organisational development systems for primary medical care. RESULTS: Practice and professional development plans are hybrids produced by the combination of ideas from management (the applied behavioural science of organisational development) and education (self-directed adult learning theories) and, in conceptual terms, address the lack of effectiveness of passive educational strategies by making interventions relevant to identified system wide needs. In the intervention, each practice participated in a series of multidisciplinary workshops (minimum 4) where the process outcome was the production of a practice development plan and a set of personal portfolios, and the final outcome was a realised organisational change. It was apparent during the project that organisational admission to a process of developmental planning needed to be a stepwise process, where initial interest can lead to a fuller understanding, which subsequently develops into motivation and ownership, sufficient to complete the exercise. The advantages of introducing expert external facilitation were clear: evaluations of internal group processes were possible, strategic issues could be raised and explored and financial probity ensured. These areas are much more difficult to examine when only internal stakeholders are engaged in a planning process. CONCLUSIONS: It is not possible to introduce practice and professional development plans (organisational development and organisational learning projects) in a publicly funded health care system without first addressing existing educational and management structures. Existing systems are based on educational credits for attendance and emerging accountability frameworks (criteria checklists) for clinical governance. Moving to systems that are less summative and more formative, and based on the philosophies of continual quality improvement, require changes to be made in the relevant support systems in order achieve policy proposals.

Evidence-Based Medicine↗

The economics of follow-on drug research and development: trends in entry rates and the timing of development.

OBJECTIVES: The development of so-called 'me-too', or 'follow-on', drugs by the pharmaceutical industry has been viewed by some as duplicative and wasteful, while others have argued that these drugs often provide needed therapeutic options and inject some price competition into the marketplace. This study examines data on the trends in the speed with which competitive entry has occurred in the pharmaceutical marketplace and the competitive nature of the industry's development of these drugs. DATA AND METHODS: We examined data on the entry rates of drugs in a large number of therapeutic classes over time, as well as detailed survey information on the relative timing of the development of drugs in the classes. Classes were defined according to chemical structure or pharmacologic mode of action and similarity of clinical use. We determined average times to initial and subsequent entry in drug classes by period and examined the timing of development milestones achieved by what have turned out to be follow-on drugs in relation to the development and approval of the first drug in a class to be approved. RESULTS: We found that the period of marketing exclusivity that the breakthrough drug in a new class enjoys has fallen dramatically over time (a median of 10.2 years in the 1970s to 1.2 years for the late 1990 s). Approximately one-third of follow-on new drugs received a priority rating from the US FDA. The vast majority of the follow-on drugs for drug classes that were created in the last decade were in clinical development prior to the approval of the class breakthrough drug. CONCLUSIONS: The data suggest that entry barriers have fallen over time for new drug introductions. The increased competitiveness of the pharmaceutical marketplace was likely fueled by changes over time on both the supply and demand sides. The development histories of entrants to new drug classes suggest that development races better characterise new drug development than does a model of post hoc imitation. Thus, the usual distinctions drawn between breakthrough and 'me-too' drugs may not be very meaningful.

Drug Approval↗

Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3.

Transgenic and gene targeted mice have contributed greatly to our understanding of the mechanisms underlying B-cell development. We describe here a model system that allows us to apply molecular genetic techniques to the analysis of human B-cell development. We constructed a retroviral vector with a multiple cloning site connected to a gene encoding green fluorescent protein by an internal ribosomal entry site. Human CD34(+)CD38(-) fetal liver cells, cultured overnight in a combination of stem cell factor and interleukin-7 (IL-7), could be transduced with 30% efficiency. We ligated the gene encoding the dominant negative helix loop helix (HLH) factor Id3 that inhibits many enhancing basic HLH transcription factors into this vector. CD34(+)CD38(-) FL cells were transduced with Id3-IRES-GFP and cultured with the murine stromal cell line S17. In addition, we cultured the transduced cells in a reaggregate culture system with an SV-transformed human fibroblast cell line (SV19). It was observed that overexpression of Id3 inhibited development of B cells in both culture systems. B-cell development was arrested at a stage before expression of the IL-7Ralpha. The development of CD34(+)CD38(-) cells into CD14(+) myeloid cells in the S17 system was not inhibited by overexpression of Id3. Moreover, Id3(+) cells, although inhibited in their B-cell development, were still able to develop into natural killer (NK) cells when cultured in a combination of Flt-3L, IL-7, and IL-15. These findings confirm the essential role of bHLH factors in B-cell development and demonstrate the feasibility of retrovirus-mediated gene transfer as a tool to genetically modify human B-cell development.

Animals↗

Care of the frail elderly in developed and developing countries: the experience and the challenges.

Demographic and epidemiological changes will result in dramatic changes in the health needs of the world's populations. Everywhere there is a steep increase in the need for management of chronic diseases and for long-term care. Therefore, the search for effective policies to care for the frail elderly in general and long-term care (LTC) policies in particular, is one of the most pressing challenges facing modern society. There is no single converging paradigm and countries are experimenting with a number of different approaches. This section of the Monograph presents the experience in several developed and developing countries: Canada, United States, Italy, Germany, Sweden, Japan, Thailand and Chile. This effort is important because there is much to be learned from the experience of developed and developing countries in defining the range of policy options and in identifying successful and unsuccessful practices. In-depth understanding of the existing situations in developed and developing countries, and the nature of the variance among countries are important to provide insight for development of care policies by learning from what already exists. This article focuses on LTC, that is, on addressing the needs of the functionally disabled elderly. Our reflections are based on an international initiative to develop a decision-making framework for LTC policies launched by the World Health Organization (WHO) with the JDC-Brookdale Institute leading this effort.

Aged↗

Salmonellosis in children in developing and developed countries and populations.

PURPOSE OF REVIEW: The present review addresses recent developments that relate to the clinical management and prevention of childhood salmonellosis in developed and developing countries. RECENT FINDINGS: Invasive disease due to serovar Typhi as well as nontyphoidal salmonellae (NTS) is common in children younger than 5 years old in developing countries, and multidrug resistance is an increasingly difficult problem to manage. A new conjugate vaccine was found to be very effective in preventing typhoid fever in young Vietnamese children and was well tolerated, showing great promise for the future. Antibiotic use in the food animal industry is an important source of disease with multidrug resistant NTS strains in the developed world. Efforts for prevention are aimed at immunization of animals, control of antibiotic use in the food animal industry and careful monitoring of food-borne outbreaks. On the other hand, although the burden of NTS disease in children is far greater in developing countries, especially in tropical Africa, knowledge of even basic epidemiology is lacking. Importantly, it may be that, as spp. acquire increasing resistance, they also acquire increasing virulence that will lead to even greater morbidity and mortality. SUMMARY: Recent developments include a better knowledge of clinical aspects of invasive salmonellosis, an increasing response to the problem of multiple antibiotic resistance (including quinolones), and excellent results from the use of a recently developed conjugate vaccine for typhoid fever in children as young as 2 years old.

Anti-Bacterial Agents↗

Adherence to HAART: a systematic review of developed and developing nation patient-reported barriers and facilitators.

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) medication is the greatest patient-enabled predictor of treatment success and mortality for those who have access to drugs. We systematically reviewed the literature to determine patient-reported barriers and facilitators to adhering to antiretroviral therapy. METHODS AND FINDINGS: We examined both developed and developing nations. We searched the following databases: AMED (inception to June 2005), Campbell Collaboration (inception to June 2005), CinAhl (inception to June 2005), Cochrane Library (inception to June 2005), Embase (inception to June 2005), ERIC (inception to June 2005), MedLine (inception to June 2005), and NHS EED (inception to June 2005). We retrieved studies conducted in both developed and developing nation settings that examined barriers and facilitators addressing adherence. Both qualitative and quantitative studies were included. We independently, in duplicate, extracted data reported in qualitative studies addressing adherence. We then examined all quantitative studies addressing barriers and facilitators noted from the qualitative studies. In order to place the findings of the qualitative studies in a generalizable context, we meta-analyzed the surveys to determine a best estimate of the overall prevalence of issues. We included 37 qualitative studies and 47 studies using a quantitative methodology (surveys). Seventy-two studies (35 qualitative) were conducted in developed nations, while the remaining 12 (two qualitative) were conducted in developing nations. Important barriers reported in both economic settings included fear of disclosure, concomitant substance abuse, forgetfulness, suspicions of treatment, regimens that are too complicated, number of pills required, decreased quality of life, work and family responsibilities, falling asleep, and access to medication. Important facilitators reported by patients in developed nation settings included having a sense of self-worth, seeing positive effects of antiretrovirals, accepting their seropositivity, understanding the need for strict adherence, making use of reminder tools, and having a simple regimen. Among 37 separate meta-analyses examining the generalizability of these findings, we found large heterogeneity. CONCLUSIONS: We found that important barriers to adherence are consistent across multiple settings and countries. Research is urgently needed to determine patient-important factors for adherence in developing world settings. Clinicians should use this information to engage in open discussion with patients to promote adherence and identify barriers and facilitators within their own populations.

Antiretroviral Therapy, Highly Active↗

Conceptual framework underlying the development of a positive youth development program in Hong Kong.

The conceptual framework governing the development of a positive youth development program in Hong Kong is outlined. Based on a thorough literature review on: a) risk factors, protective factors and adolescent resilience; b) adolescent developmental assets; c) deficits-based and assets-based models on adolescent development; d) models on positive youth development programs and e) ecological models, 15 positive youth development constructs covered in this project are presented. The following assertions are maintained in the present positive youth development program: ecological assertion, change assertion, holistic assertion, developmental assets assertion, risk factors assertion, protective factors assertion, positive youth development assertion, positive youth development constructs assertion, integration assertion, and evidence-based assertion.

Adolescent↗

Fine-needle aspiration cytology: its origin, development, and present status with special reference to a developing country, India.

Fine-needle aspiration cytology (FNAC) was performed on a large scale at Memorial Hospital, New York, during the 1930s, but during the ensuing years, it did not gain much encouragement in United States. The technique had a resurgence in Scandinavia during the 1950s and 1960s, where it flourished before spreading to other parts of the world. It had also a revival in the United States, which contributed enormously to this tool in each and every aspect. The status of FNA during 1966-2002 was assessed through review of MEDLINE search data on FNA and its correlation with World Bank website data on classification of countries. A total of 849 journals published 5,609 articles on FNA over a period of 37 years. Both the number of publishing journals and the number of published articles on FNA were low during the 1960s (3.5 +/- 0.58 and 4.0 +/- 0.82, respectively) and 1970s (20.3 +/- 14.72 and 25.0 +/- 20.54, respectively), but their number increased sharply from the 1980s onward (78.2 +/- 25.65 and 147.2 +/- 66.89, respectively, during the 1980s, 126.2 +/- 11.94 and 301.4 +/- 35.99, respectively, during the 1990s, and 113.3 +/- 36.46 and 287.3 +/- 85.93, respectively, during the 2000s). The difference between the decades of 1960s-2000s, with respect to the number of publishing journals and published articles, was highly significant (P < 0.0001). Only 90 (10.6%) of the journals were from the arena of pathology and its branches. The remaining journals belonged to various other disciplines of medicine; a small fraction were even from the veterinary sciences. Ten journals, including three in the field of cytopathology, published 2,448 (43.6%) of the total articles on FNA. During 1987-2002, 46 (29.7%) of the 155 developing nations published articles on FNA, whereas 28 (52.8%) of the developed (high-income economies) countries did so, the difference being highly significant (P = 0.0044). The total number of publications from high-income economies was 3,124 (195.3 per year), as opposed to 772 (48.3 per year) from the developing world. The number of articles published from the developing nations (16.8 +/- 52.21) was significantly lower as compared with that from the high-income economies (111.6 +/- 242.03) (P = 0.005). Except for infectious diseases, the high-income economies had a definite edge over the developing nations in the absolute number of publications from each and every site/organ. However, when the frequency of publications on various organs/sites was compared between the two groups, it was found that the number of articles from high-income economies was significantly higher with respect to breast diseases (P < 0.001) and pancreatic lesions (P = 0.0158), whereas the developing nations published more frequently on small round cell tumors (excluding exclusive reports on lymphoma) and infectious diseases (P < 0.001). In India, FNAC was first introduced during the early 1970s and spread to different parts through formal teaching under the postgraduate curriculum in pathology and by conducting workshops and continuing medical education program for pathologists, surgeons/physicians, and radiologists. FNAC is now practiced in all medical colleges, in big public sector hospitals, and even in private clinics and laboratories. The number of centers practicing FNAC increased sharply during 1980s, as evident from the response of 69 laboratories in various parts of India to a questionnaire. As of 1998, 55.9% of the laboratories performed >/=1,000 cases of FNA per year. In 46% of the centers, pathologists alone performed the FNAC, whereas in 51%, they performed it in collaboration with radiologists and surgeons. Disposable syringes and needles were used in all the centers, but syringe holders were used in only in 61% of centers. In 86% of laboratories, two or more routine stains were used, and one or more ancillary techniques on fine-needle aspirates were adopted in 72.5% centers. Of the 772 publications from the developing world during 1987-2002, India alone contributed to 374 (48.4%). During 1975-2002, 154 articles on FNA were published needles were used in all the centers, but syringe holders were used in only in 61% of centers. In 86% of laboratories, two or more routine stains were used, and one or more ancillary techniques on fine-needle aspirates were adopted in 72.5% centers. Of the 772 publications from the developing world during 1987-2002, India alone contributed to 374 (48.4%). During 1975-2002, 154 articles on FNA were published in 15 indexed Indian journals.

Biopsy, Needle↗

Development studies of Aurelia (jellyfish) ephyrae which developed during the SLS-1 mission.

Aurelia polyps (scyphistomae) and ephyrae were exposed to microgravity for nine days aboard the space shuttle during the SLS-1 mission. During strobilation, polyps segment transversely and each segment develops into an ephyra. Polyps were induced to strobilate at 28 degrees C, using iodine or thyroxine, at L(Launch)-48h, L-24h, and L+8h. Ephyrae developed in the groups tested in space and on Earth. The number of ephyrae formed per polyp was slightly higher in the L+8h groups as compared with those induced at L-24h and L-48h. On Earth, iodine is used by jellyfish to synthesize jellyfish-thyroxine (Jf T4), needed for ephyra production. Since iodine-treated polyps strobilated and formed ephyrae in space, it appears that jellyfish can synthesize Jf-T4 in space. Indeed, two groups of polyps not given inducer formed ephyrae [correction of ephryae] in space, presumably due to enhanced Jf-T4 synthesis, utilization or accumulation. Some ephyrae that formed in space were also fixed in space on Mission Day (MD) 8; others were fixed post-flight. Examination of living ephyrae with the light microscope and fixed ones with the Scanning and Transmission Electron Microscopes revealed that those which developed in space were morphologically very similar to those which developed on Earth. Quantitation of arm numbers determined that there were no significant differences between space and Earth-developed ephyrae. Pulsing abnormalities, however, were found in greater numbers (18.3%) in space-developed ephyrae than in Earth-developed controls (2.9%). These abnormalities suggest abnormal development of the graviceptors, the neuromuscular system, or a defect in the integration between these systems in apparently microgravity-sensitive animals.

Animals↗

Drug discovery and developments in developing countries: bottlenecks and way forward.

Infectious and parasitic diseases continue to threaten the health of million of people throughout the world, with the major burden being in developing countries. Many of the currently available drugs for the treatment of these diseases face setbacks such as insufficient efficacy, increasing loss of effectiveness due to emergence of resistance, high levels of toxicity, inaccessibility and/or high costs. The driving force for drug discovery and development by pharmaceutical firms has been the foreseeable profit from drug sells. Since most infectious diseases prevail in developing countries and the fact that people living in these countries have poor purchasing power, the market for such drugs are unattractive to these firms. Thus, there has been reluctance for the pharmaceutical companies to engage in the development of drugs addressing diseases that mainly affect developing countries. Although a lot of research to discover new effective and cheap drugs is in progress in the disease endemic countries, it is not yet possible to fully develop leads and drug candidates from natural products, hence people in these countries continue to rely on traditional medicines. Poor economies and technological capabilities, lack of human resources and good management in these countries are the major constraints to progress in research and development work for new drugs. This paper discusses these major bottlenecks in drug discovery and development and suggests the way forward.

Communicable Diseases↗