Circannual Alterations in the Circadian Rhythm of Melatonin Secretion

To determine if a circadian rhythm known to be functionally related to the reproductive axis varies on a circannual basis, we monitored the circadian secretion of melatonin at monthly intervals for 2 years in four ovariectomized, estradiol-implanted ewes held in a constant short-day photoperiod. Prior to the study, ewes had been housed in a short-day (8L:16D) photoperiod for 4 years and were exhibiting circannual reproductive rhythms as assessed by serum luteinizing hormone (LH) levels. Three of the four sheep showed unambiguous deviations from the expected nocturnal melatonin secretion at two different times approximately 1 year apart. Nocturnal rises in melatonin, which usually last the duration of the dark phase, were delayed by 3-14 h or were missing. Altogether, five of the seven melatonin alterations observed in these three ewes occurred during the nadir of the circannual LH cycle. In the remaining ewe, we did not observe an altered melatonin secretory pattern during this period, and this ewe also failed to show a high amplitude circannual cycle of LH. The results provide evidence for a circannual change in the circadian rhythm of melatonin secretion. This alteration in melatonin secretion may serve as a "functional" change in daylength, and thereby may influence the expression of the circannual reproductive rhythm of sheep held in a fixed photoperiod for an extended time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68029/2/10.1177_074873049501000104.pd

Does Seasonal Reproductive State Affect the Neuroendocrine Response of the Ewe to a Long-Day Pattern of Melatonin?

This study examined whether or not the reproductive response of female sheep to photoperiod varies with seasonal reproductive state. The specific objective was to test the hypothesis that the reproductive response to a long-day pattern of melatonin varies with the reproductive state of the ewe. The response examined was the synchronization of reproductive neuroendocrine induction (rise in serum luteinizing hormone, or LH) following nocturnal infusion of melatonin into pinealectomized ewes for 35 consecutive nights. This infusion restored a pattern of circulating melatonin similar to that in pineal-intact ewes maintained in a long photoperiod (LD 16:8). The ewes had been pinealectomized and without melatonin replacement for 16-25 months prior to the study. They were in differing reproductive states at the start of the infusion, as their endogenous reproductive rhythm had become desynchronized among individuals and with respect to time of year. Noninfused pinealectomized ewes served as controls. Regardless of the reproductive state at the start of the 35-day infusion of the long-day pattern of melatonin, all treated ewes exhibited the same reproductive neuroendocrine response after the infusion was ended. This consisted of a synchronized rise in LH some 6-8 weeks after the infusion was terminated, the maintenance of a high level of serum LH for some 15 weeks, and a subsequent precipitous fall in LH to a very low level. These results provide evidence that a long-day pattern of melatonin can synchronize reproductive neuroendocrine induction in the ewe, regardless of reproductive condition, and thus do not support the hypothesis that this response differs with seasonal reproductive state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66625/2/10.1177_074873049200700101.pd

Influenza surveillance in 15 countries in Africa, 2006-2010

BACKGROUND: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa. METHODS: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI) or severe acute respiratory infections (SARI) and virologic data. RESULTS: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Influenza was detected in 22% of ILI cases and 10% of SARI cases. Children 0-4 years accounted for 48% all ILI and SARI cases of which 20% and 10 respectively were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial co-circulation of influenza A and B occurred most years. CONCLUSIONS: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.The work presented in this manuscript was funded completely or in part by host governments, Institute Pasteur, and cooperative agreements with the U.S. Centers for Disease Control and Prevention and/or the U.S. Department of Defense.http://www.journals.uchicago.edu/toc/jid/currenthb2013ay201

Photoperiodic synchronization of the annual reproductive rhythm of the ewe.

Many long lived species have endogenous circannual rhythms. The annual cycle of daylength synchronizes endogenous rhythms so that rhythms are appropriately phased with the seasons, occur synchronously among conspecifics and have a period of one year. The purpose of this thesis is to investigate the photoperiodic requirements for synchronization of the circannual reproductive rhythm of sheep. An experimental system was employed in which specific photoperiodic signals were replaced in a physiological and reversible manner to pinealectomized ewes that could not otherwise perceive photoperiod. Specific photoperiodic cues were restored via infusion of circadian patterns of melatonin, the pineal hormone that transduces photoperiodic information to the neuroendocrine axis. In this manner, the effects of specific photoperiodic signals on the circannual reproductive rhythm were monitored. The experimental findings demonstrate that the annual reproductive rhythm can be generated in the absence of the pineal gland. Pinealectomized ewes exhibited asynchronous circannual reproductive cycles, which were out of phase with the seasons and which usually had a period less than one year. In addition, the results of these studies demonstrate that the pineal gland mediates synchronization of the annual reproductive cycle via its circadian pattern of melatonin secretion. Significant new findings of these studies are that the circannual reproductive rhythm can be synchronized by exposure to information about just one discrete segment of the photoperiodic year and not all segments of the photoperiodic year provide equally effective synchronizing signals. Specifically, cues associated with the longer photoperiods perceived around the summer solstice are the most effective in synchronizing rhythms with the seasons and among ewes. Furthermore, these studies provide evidence that, in the sheep, the specific characteristics of the photoperiodic signal, rather than the stage of the reproductive rhythm when the signal is perceived, play the major role in synchronizing the rhythm with the environment. Findings were incorporated into a conceptual model to describe how discrete segments of the photoperiodic year synchronize circannual rhythms so they are appropriately phased with the seasons, occur synchronously among conspecifics and have a period of one year.Ph.D.PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105310/1/9116326.pdfDescription of 9116326.pdf : Restricted to UM users only

Patient retention, clinical outcomes and attrition-associated factors of HIV-infected patients enrolled in Zimbabwe's National Antiretroviral Therapy Programme, 2007-2010.

Since establishment of Zimbabwe's National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored.To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART.A retrospective review of abstracted patient records of adults ≥ 15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition.Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1-1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1-2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4-2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1-11.2).Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention

Retention of patients after 6, 12, 24, and 36 months.

<p>Note: These analyses are not based on imputed data.</p

Median CD4 T-cell count (cells/µL) gains during ART stratified by gender.

<p>Note: These analyses are not based on imputed data.</p

Median weight gains (kilograms) during ART stratified by gender.

<p>Note: These analyses are not based on imputed data.</p