Guide to the topics system

TOPICS is a system for computer-based information exchange among a network of people who share certain areas of interest. The system supports simultaneous discussion of many topics at once by allowing members to raise brief, pointed topics/inquiries and then to enter responses to those inquiries. The responses are shared with all members who express an interest in each topic by selecting it. The system is designed to facilitate the flow of inquiries and responses without overloading members with irrelevant or uninteresting information. Nested within the Electronic Information Exchange System (EIES), this tailored communication system written in the INTERACT programming language helps regulate the flow of information by allowing network members to select those topics of interest after receiving the brief topic-raising inquiries. Members receive responses only for those topics which they select, and thus most of the irrelevant information is filtered out by the computer. As new topics are raised, they are delivered to members who are given the option of selecting them or not. In addition, each topic is assigned keywords by its author. An alphabetic index of these keywords is kept up to date by the computer so that members can scan it or search it for specific keywords to find particular topics, even old ones that were not interesting when first raised. Furthermore, if many responses are waiting to be delivered to a user who is in a hurry or otherwise wants to see those on a specific topic only, the system will deliver responses by keyword or topic number, if desired. Finally, through its membership and access structure, the information flow in the system can be tailored to meet differing needs of specific groups. Topics and members are organized into separate exchanges so that a particular group of people can exchange among themselves while other groups do likewise in other areas without overlap. Within an exchange, topics may be open to all or directed to specific people only. Furthermore, members may be grouped and topics directed to only specific groups of members. Membership in an exchange is available to regular EIES members as well as holders of EIES sub-account memberships who are using a multi-user account

The evolution of a tailored communications structure : the topics system

A computer-based human communication system should be designed for people\u27s use, in response to their perceived needs and communications styles; no single system can meet the needs of all groups and individuals. It might seem that a general electronic mail or computerized conferencing system with a standard set of features should be able to meet most communications needs, in much the same way that the telephone system meets the needs of a wide range of users. However, there are many communications structures found in everyday life, ranging from one-to-many news broadcasts, to the many-to-many patterns of town meetings, from the unstructured and informal gatherings at the local pub, to highly structured meetings using Robert\u27s Rules of Order. Each of these is an example of a specific communications structure appropriate in some circumstances and quite inappropriate in others. Within a flexible computerized conferencing system such as the Electronic Information Exchange System (EIES), it is possible to tailor the features of the system to the needs of the users, rather than forcing them to adapt their communications behaviors to the system and its limitations. Current concepts and structures such as electronic mail and conferencing will be supplemented in the next decade by an ever-increasing array of specially designed structures to meet specific needs. Hiltz and Turoff (1978) discuss some of the promises and potentials for how human communication via computer will transform the ways we work, play, learn, and govern ourselves. They also discuss in some detail a variety of communications structures designed for group problem-solving and decision-making. The major question addressed here is how these communications structures evolve. How are they initiated? Where do they lead? What forces govern their evolution? For a structure to be effective, it must meet the needs of the group using it. However, the perceived needs of a group may (and probably will) change over time. This means that as a group\u27s needs change, either as it learns more about the medium or as its situation changes, the communications structure must EVOLVE to match those needs. Thus, the process of designing and implementing a communications structure becomes an ongoing process. Since it is generally recognized that the microelectronics and telecommunications wave of change we are now beginning to experience (Toffler, 1980) will transform the very fabric of our society, and since the communications procedures and structures we use in this electronic medium are going to evolve very rapidly in the next two decades, an understanding of the process of this evolution seems critical for our successful transition to a post-industrial, communications-era society. A model of the ongoing process or design of these structures is introduced in Johnson-Lenz (1980c). Included there is the concept or GROUPWARE—the integrated, systemic whole made up of a group\u27s processes and procedures, PLUS software to support those processes and procedures. Most specific software structures can be used in a variety of ways, depending on the characteristics of the group and its perceived needs for process. Thus, the system which evolves is not only the computer software but also the process and procedures followed by the group to achieve its purposes, with or without software support; hence the term GROUPWARE. This paper traces the evolution or a particular communications structure, the TOPICS system, as well as the evolution of several groups using that system, each with its own unique and evolving groupware supported by the TOPICS software, and each contributing its own unique set or needs to the evolution or the software. The TOPICS system, resident on EIES, was designed and developed by the authors, in collaboration with the groups using it

How to Use Electronic Information Exchange System

This booklet is an introduction to the use of EIES, Electronic Information Exchange System. EIES (pronounced eyes ) is a very powerful computerized system that allows you to communicate with others on the system in a number of different ways. The intent of this booklet is to teach you the simpler parts of the system and to make you comfortable with using the one-page User\u27s Guide For Electronic Information Exchange System. Later on, as you gain more experience with EIES, you may want to learn some of the more advanced features and tricks. EIES has been designed so that you have to learn only what you need. It\u27s just about impossible to learn how to use a computer system from a booklet without some direct experience with the machine itself. So, don\u27t be discouraged if some of the parts of this booklet seem confusing or hard to understand at first reading. The best way to learn about EIES is to use the instructions in this booklet and try them yourself to see what happens. EIES has been designed to be forgiving ; that is, if you make a mistake, nothing serious happens. You can\u27t hurt the system, so don\u27t be shy about trying new things. After reading through this booklet, plan to spend thirty minutes to an hour practicing logging on and learning to send messages. Try to find a time when you will be uninterrupted, if possible. After this beginning practice session, and with the help of this booklet, you should know enough to begin messaging other people and participating in any conference to which you belong. This booklet contains sections on: using your terminal TELENET getting into EIES sending messages message sending shortcuts text editing the EIES directory finding others in the directory participating in conferences getting printouts shortcuts for getting printouts special roles on EIES etiquette and hints for using this new communications form EIES terminology and jargon EIES checklist advanced features selected references If all you want to do is learn how to get into EIES and send a message, read only the first four sections. Save the rest for later. Read what you need

Scenario adjustment in stated preference research

AbstractPoorly designed stated preference (SP) studies are subject to a number of well-known biases, but many of these biases can be minimized when they are anticipated ex ante and accommodated in the study's design or during data analysis. We identify another source of potential bias, which we call “scenario adjustment,” where respondents assume that the substantive alternative(s) in an SP choice set, in their own particular case, will be different from what the survey instrument describes. We use an existing survey, developed to ascertain willingness to pay for private health-risk reduction programs, to demonstrate a strategy to control and correct for scenario adjustment in the estimation of willingness to pay. This strategy involves data from carefully worded follow-up questions, and ex post econometric controls, for each respondent's subjective departures from the intended choice scenario. Our research has important implications for the design of future SP surveys

Users\u27 manual for the Electronic Information Exchange System

The purpose of this manual is to teach you the simpler parts of the system and make you comfortable with using the one-page User\u27s Guide. As you gain more experience with the system, you may wish to learn some of the advanced features available. But EIES (pronounced eyes ) has been designed so that you don\u27t need to learn more than meets your needs. Since the best way to learn how to use a computer system is by direct experience, don\u27t be discouraged if some of this manual is confusing at first. The most effective way to learn is to try the instructions and see what happens. EIES has been designed to be forgiving : that is, nothing terrible will happen if you make a mistake. Since you can\u27t hurt the system, or easily lose anything, be brave about trying new things! Anyone can become proficient sending messages and participating in conferences after experimenting with the system for two to four hours, and EIES users have ranged in age from 8 to 90. After reading this manual, plan to spend about thirty minutes to an hour practicing logging on and learning to send messages. You\u27ll then know enough to begin messaging other people and participating in conferences. This manual is only an introduction to the simpler parts of EIES, which is a rich and evolving communications system that can be customized and tailored to the specific needs of individuals and groups. Feel free to contact the User Consultants (HELP,110) if you have needs not covered here, since there are a large and growing number of advanced and specialized features available

A hipotalamikus neuronális energiaszint szabályozásának vizsgálata: Az NTPDázok, mint lehetséges energia-regulátorok szerepe a pozitív gonadotropin feedback során. = Regulation of neuronal energy levels in the hypothalamus: NTPDases as possible energy regulators of the positive gonadotrophin feedback.

Pályázatunk fő célja, hogy a serkentő idegi működéshez szükséges celluláris energiaszint „korlátozó”, vagy éppen „megengedő” szerepét vizsgáljuk. A hypothalamicus (HT) NTPDáz3 ATP-szabályzó szerepét a tervezettnél szélesebb spektrumban vizsgáltuk, valamint figyelembe vettük, hogy a HT egyszerre több homeosztatikus funkció idegi központja. Ezért figyelembe vettük az érintett homeosztatikus folyamatokat szabályzó idegi struktúrák átfedéseit és a közös mechanizmusokat. A kísérletek két, egymással szorosan összefüggő folyamat elemzésére terjedtek ki, melyek eredményei a következők szerint foglalhatók össze: 1. A mitokondriális metabolizmus, beleértve az NTPDáz3 aktivitását is, valamint a hypothalamus O2 ellátása, az ösztrusz ciklushoz, illetve annak egyes fázisaihoz igazodó hullámzó tendenciát mutatott; Ez a hullámzó tendencia az állatok több mint 80 %-ában a hypothalamusnak csak az egyik féltekéjében mutatkozott, míg az ellenoldali félteke mitokondriális metabolizmusa a ciklus minden fázisában egyenletes, kiegyenlített tendenciát mutatott. 2. Az ADP-függő 3-as típusú mitokondriális légzés korrelál a korábbi kísérleteink szerint leírt gyors ütemű, nagyszámú hypothalamicus excitatórikus szinapszis létrejöttének és aktivitásának idejével, ami az ösztrusz ciklus proösztrusz-korai ösztrusz fázisainak idejére esik. 3. Az 1-5-ös típusú mitokondriális légzés elemzése azt valószínűsíti, hogy a mitokondriális NTPDáz3 blokkolása átfogóan lassítja a mitokondrium metabolizmusát. | The project’s main goal was to examine the limiting/permissive role of the cellular energy levels in hypothalamic (HT) excitatory neuronal activity. Considering that the HT is the regulatory center of more than one homeostatic systems, investigations on the ATP-regulating activity of hypothalamic NTPDase3 were more detailed than originally outlined. Hypothalamic structural and functional overlaps were considered. Studies included two major lines of experiments with result summarized as follows: 1.) The mitochondrial metabolism, including the NTPDase3 activity, and the hypothalamic O2 supply showed a fluctuating pattern corresponding to the phases of the estrous cycle. This phenomenon could only be observed in either the left or right hypothalamic hemispheres in cca. 80 percent of the animals, while the contralateral hemishere showed no such fluctuations. 2.) The ADP-dependent State 3 (St3) mitochondrial respiration correlates with the rapid generation and function of excitatory synapses during late proestrus and early estrus. 3.) Analysis of St1-5 data imply that inhibition of mitochondrial NTPDase3 function leads to overall down-regulation of mitochondrial metabolism

Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) is a broad-spectrum antibiotic used to prevent opportunistic infections in patients with HIV infection. Primary prophylaxis with co-trimoxazole has been shown to decrease hospitalisation, morbidity and mortality among people living with HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, Pneumocystis pneumonia, toxoplasmosis and severe bacterial infections.[1-4] Co-trimoxazole is inexpensive and widely available. In standard adult treatment guidelines and essential medicine lists in South Africa (SA), the current recommendation is that co-trimoxazole should be provided for HIV-infected patients with a CD4+ count ˂200 cells/μL, HIV/tuberculosis (TB) co-infection and/or advanced HIV disease (World Health Organization (WHO) stage 3 or 4). Because of expanded access and progression towards initiation of antiretroviral treatment (ART), the WHO issued updated guidelines for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend co-trimoxazole prophylaxis for adults (including pregnant women) with severe or advanced HIV clinical disease (WHO stage 3 or 4) and/or with a CD4+ count ≤350 cells/μL. In settings with a high prevalence of malaria and/or severe bacterial infections, prophylaxis is recommended for all patients regardless of WHO clinical stage or CD4+ cell count. However, the timing of discontinuation of co-trimoxazole prophylaxis may vary and is dependent on the malarial/ bacterial infection burden in different settings.[5] Therefore, the current WHO guidance should be adapted in the context of a country-specific epidemiological profile and priorities. The impact and benefit of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected patients with a CD4+ count ≤350 cells/μL in regions with high infectious disease burdens (irrespective of CD4+ count) have been shown in a good-quality systematic review and meta-analysis that included both randomised controlled trials (RCTs) and observational cohort studies.[6] This extensive systematic review by Suthar et al.[6] showed that co-trimoxazole prophylaxis reduced the rate of death when initiated at CD4+ counts ≤350 cells/μL with ART in populations in Africa and Asia. Co-trimoxazole prophylaxis in ART-naive patients with CD4+ counts >350 cells/μL reduced the rate of death and malaria, and continuation of prophylaxis after ART-induced recovery with CD4+ counts >350 cells/μL reduced hospital admission, pneumonia, malaria and diarrhoea in African populations (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] While this review largely informed the 2014 WHO guideline update, the findings need to be interpreted in the context of studies included and the varied epidemiological profile across middle- and low-income countries. There were only 2 relatively small RCTs with very few events of key endpoints; therefore, the finding of non-significance was likely (e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 2 studies was unblinded, and the follow-up in the other study was only 4 months. Ongoing co-trimoxazole prophylaxis was better than discontinuation of the drug at CD4+ counts >200 cells/μL for 3 endpoints with an adequate number of events (pneumonia, diarrhoea and malaria). Furthermore, 8 of 9 studies were conducted in countries with a high burden of malaria and bacterial and parasitic diseases, which is generalisable to the SA context.[9] Although seasonal malaria occurs in the north-eastern parts of SA, the incidence of malaria mortality and morbidity has declined remarkably over time (˂10 000 cases annually for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed cases of malaria were reported in the public health sector in 2015.[9] In this review, further stratification of the impact of co-trimoxazole prophylaxis at CD4+ counts ˂200 cells/μL v. 200 - 350 cells/μL was not available. Lower bacterial resistance to co-trimoxazole is possible among populations included in this review, while resistance to co-trimoxazole in SA is common in patients with community-acquired bacterial infections.[11-13] This potential risk of resistance compounded by the lack of long-term toxicity data needs to be weighed against recommending prophylaxis in populations where benefit has not been established. Local observational studies suggest no benefit of co-trimoxazole prophylaxis with a CD4+ count >200 cells/μL or in patients who were not WHO clinical stage 3 or 4.[14,15] In an observational cohort of patients attending the adult HIV clinics at the University of Cape Town, SA, the effect of prophylactic low-dose co-trimoxazole on survival and morbidity was examined over a 5-year follow-up period. Co-trimoxazole reduced the hazards of mortality by ~44% and the incidence of severe HIV-related illnesses by ~48% in patients with evidence of advanced immunosuppression (WHO stage 3 or 4) or laboratory measurement of total lymphocyte count ˂1 250 × 106/L or CD4+ count ˂200 cells/μL. However, no beneficial effect was seen in patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/μL. A potential limitation of this study was that the sample size of patients with a CD4+ count 200 - 500 cells/μL receiving co-trimoxazole was small and may have been underpowered to observe a significant benefit. In this study, patients on ART were excluded.[14] In another SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole effectiveness in reducing mortality risk during ART among persons with a CD4+ count >200 cells/μL and varying WHO clinical stages, overall co-trimoxazole prophylaxis reduced mortality by 36% across all CD4+ count strata. Analysis stratified by baseline CD4+ count showed a similar reduction in mortality risk among persons with a CD4+ count ˂200 cells/μL, but no statistically significant association was found between co-trimoxazole prophylaxis and survival in the subgroup of persons with a CD4+ count >200 - 350 cells/μL, CD4+ count >350 cells/μL and WHO stage 1 or 2 disease. However, the findings of this study need to be interpreted cautiously for the following reasons: the group with a CD4+ count >350 cells/μL was small (n=917) and might not have had enough events to draw inferences; the study population was a cohort of miners and might not have been potentially representative of the SA population; and, being a non-randomised study, residual confounding might have been a potential limitation. An earlier Cochrane review established the benefit of initiating prophylaxis at a CD4+ count ˂200 cells/μL in those with stage 2, 3 or 4 HIV disease (including TB), and discontinuation once the CD4+ count was >200 cells/μL for >6 months.[16] There was a reduction of ~31% in mortality, 27% in morbid events and 55% in hospitalisation. Significant reductions were also detected for bacterial and parasitic infections and for Pneumocystis jirovecii pneumonia. Considering the above-mentioned evidence gaps and lack of generalisability of studies to SA, the current National Essential Medicines List Committee and Adult Hospital-Level Technical Sub-committee do not support the implementation of the updated guidance by the WHO for co-trimoxazole prophylaxis among adult HIV-infected patients. Efforts should be directed towards exploring several research gaps. The impact of co-trimoxazole prophylaxis on morbidity and mortality at higher CD4+ counts in low-malariaburden areas needs to be investigated further. More data are needed on timing of co-trimoxazole cessation in HIV and TB co-infection in our context

Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five bestknown peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake

Comparative analysis and functional implications of ligand dependent changes in estrogen- and thyroid hormone receptor expression in the developing cerebellum

Abstract Trophic hormones are important regulators of CNS development and function. In particular, estrogen (E2) and thyroid hormones (THs) regulate cell migration, differentiation, proliferation and synaptogenesis/network formation during cerebellar development. These hormone-regulated events involve the binding of hormone ligands to their cognate receptors that function as transcription factors to activate relevant genes for the adequate orchestration of developmental processes. Recent reports implicate a complex mechanism through which E2 and THs influence the expression levels of each other’s receptors (ERs and TRs) to precisely mediate developmental signals. Here we examined the effects of the presence or absence of E2 and THs on the expression levels of their receptor mRNAs and proteins. Cerebellar granule cell cultures were treated with either E2, T3, T4 or a combination of these hormones, and resulting receptor expression levels were determined by quantitative PCR and Western blot techniques. Results were compared to non-treated controls and to samples obtained from 14-day-old in situ cerebella. Additionally, we determined the effects that glial cells might have on the regulation of ER-TR expression levels. Results show that: (i) ER and TR expression levels depend on the individual or combined presence/absence of E2 and THs; (ii) glial cells are important mediators in the hormonal regulation of neuronal ER-TR expression, and (iii) loss of tissue integrity results in characteristic changes in ER-TR expression levels. These observations suggest that both E2 and THs are required for the precise orchestration of cerebellar development and that alterations in the tissue concentration of either of the hormones may influence signaling mechanisms that are driven by both E2 and THs. Comparison of data from in vitro and in situ samples also revealed a shift in receptor expression levels after loss of tissue integrity, likely indicating possible adjusting/regenerative mechanisms after cerebellar tissue injury