Cervical cancer screening decentralized policy adaptation: an African rural-context-specific systematic literature review.

BACKGROUND: Worldwide, nearly 570,000 women are diagnosed with cervical cancer each year, with 85% of new cases in low- and middle-income countries. The African continent is home to 35 of 40 countries with the highest cervical cancer mortality rates. In 2014, a partnership involving a rural region of Senegal, West Africa, was facing cervical cancer screening service sustainability barriers and began adapting regional-level policy to address implementation challenges. OBJECTIVE: This manuscript reports the findings of a systematic literature review describing the implementation of decentralized cervical cancer prevention services in Africa, relevant in context to the Senegal partnership. We report barriers and policy-relevant recommendations through Levesque's Patient-Centered Access to Healthcare Framework and discuss the impact of this information on the partnership's approach to shaping Senegal's regional cervical cancer screening policy. METHODS: The systematic review search strategy comprised two complementary sub-searches. We conducted an initial search identifying 4272 articles, then applied inclusion criteria, and ultimately 19 studies were included. Data abstraction focused on implementation barriers categorized with the Levesque framework and by policy relevance. RESULTS: Our findings identified specific demand-side (clients and community) and supply-side (health service-level) barriers to implementation of cervical cancer screening services. We identify the most commonly reported demand- and supply-side barriers and summarize salient policy recommendations discussed within the reviewed literature. CONCLUSIONS: Overall, there is a paucity of published literature regarding barriers to and best practices in implementation of cervical cancer screening services in rural Africa. Many articles in this literature review did describe findings with notable policy implications. The Senegal partnership has consulted this literature when faced with various similar barriers and has developed two principal initiatives to address contextual challenges. Other initiatives implementing cervical cancer visual screening services in decentralized areas may find this contextual reporting of a literature review helpful as a construct for identifying evidence for the purpose of guiding ongoing health service policy adaptation.

Peer intervention in case management practice.

Using peers as case managers in dealing with current and chronic public health problems such as substance abuse, gang violence, or the HIV/AIDS crisis has been shown to improve outreach efforts, monitoring, and outcomes in hard-to-reach populations. This article focuses on a case management strategy that uses peer modeling interventions to assist people in renegotiating their present life circumstances. Peer modeling engages peers of the client population as case managers and employs group-mediated, social control intervention strategies in the community to bring about positive changes in lifestyle and living conditions. The peer approach is an enhanced version of case management, utilizing the core activities of outreach, assessment, planning, linking, monitoring, and advocacy but adding peer-led, skill-based training activities, coupled with a system of positive incentives designed to encourage a more healthful lifestyle. To clarify this enhanced approach to case management, the authors present a matrix to illustrate how key case management activities might be enhanced through peer modeling interventions. We conclude by suggesting the circumstances in which an organization responsible for service delivery might consider using peer modeling in addressing difficult public health problems, and we discuss the advantages and disadvantages of such a strategy.

Changing dose of progesterone results in sudden changes in frequency of luteinizing hormone pulses and secretion of 17 beta-estradiol in bovine females.

The aim of the present study was to elucidate the time course according to which changes in circulating concentrations of progesterone influence pulsatile secretion of LH and secretion of 17 beta-estradiol. Our working hypothesis was that changing the dose of progesterone would result in changes in frequency of LH pulses and secretion of 17 beta-estradiol within 72 h. Five days after behavioral estrus, thirty-three cows were randomly assigned to one of five groups: 1) control, no treatment (CONT, n = 5); 2) treatment with two progesterone-releasing intravaginal devices (PRIDs) for 11 days (2PRID, 5-6 ng/ml plasma progesterone, n = 7); 3) treatment with a 0.5 PRID for 11 days (0.5PRID, 1-2 ng/ml plasma progesterone, n = 7); 4) treatment with 2 PRIDs for 8 days followed by treatment with a 0.5 PRID for 3 days (2-0.5PRID, n = 7); and 5) treatment with a 0.5 PRID for 8 days followed by treatment with 2 PRIDs for 3 days (0.5-2PRID, n = 7). Cows subject to PRID treatments received injections of prostaglandin F2 alpha on Days 1 and 2 (Day 0 = day of initiation of PRID treatments, fifth day of the estrous cycle in CONT cows) to lyse the existing corpus luteum. Cows were bled for 12 h at 15-min intervals on Day 7.5 of the treatment period (twelfth day of the estrous cycle in CONT cows). The dose of progesterone was changed on Day 8 in cows that were assigned to the 2-0.5PRID and 0.5-2PRID groups, and blood collections continued an additional 72 h to characterize profiles of circulating concentrations of LH and 17 beta-estradiol. Cows treated with a 0.5 PRID had a greater (p < 0.05) number of LH pulses and higher (p < 0.05) concentrations of 17 beta-estradiol throughout the entire blood collection period than cows in the 2PRID and CONT groups. An increase in the number of LH pulses was detected within 6 h after the change from the high to the low dose of progesterone (2-0.5PRID), and frequency of LH pulses was similar to that of cows in the 0.5PRID group for the remainder of the period of blood collection. LH pulse frequency declined within 6 h after the shift from the low to the high dose of progesterone (0.5-2PRID) and was similar to that of cows in the 2PRID group by 12 h after the dose was changed. Within 6 h after the dose of progesterone was changed, circulating concentrations of 17 beta-estradiol increased (p < 0.05) in cows shifted from the high to low dose (2-0.5PRID) and declined (p < 0.05) after the dose of progesterone was changed from low to high (0.5-2PRID). We conclude that changing the circulating concentrations of progesterone concurrently affects frequency of pulsatile LH release and secretion of 17 beta-estradiol within 6-24 h.

Dosage of the synthetic progestin, norgestomet, influences luteinizing hormone pulse frequency and endogenous secretion of 17 beta-estradiol in heifers.

The objective of this study was to determine whether there were doses at which the synthetic progestin, norgestomet, could mimic midluteal phase concentrations of progesterone in regulating the secretion of LH and 17 beta-estradiol in bovine females. Heifers were randomly assigned to one of five groups to receive: 1) one (1Norg, n = 5), 2) two (2Norg, n = 5), 3) four (4Norg, n = 5), or 4) eight (8Norg, n = 5) norgestomet implants or to serve as untreated control heifers (control, n = 5). On Day 7 (Day 0 = behavioral estrus), implants containing norgestomet were inserted, and they remained in place for 10 days. All heifers implanted with norgestomet were treated with 25 mg prostaglandin F2 alpha (PGF2 alpha) on Days 7 and 8 to lyse the CL. Controls were treated with 25 mg PGF2 alpha at the time norgestomet implants were removed from heifers of the other treatment groups. Blood samples were collected every 15 min for 24 h on Days 10 and 16 to determine the frequency of LH pulses. Beginning 24 h after removal of implants, samples of blood were collected at 4-h intervals for 96 h to determine the time of the preovulatory surge of LH. Daily blood samples were collected from Day 2 to Day 48 to determine concentrations of progesterone, and samples collected between Days 2 and 17 were used to determine concentrations of 17 beta-estradiol. Ultrasonography was performed daily from Day 2 until Day 23 to evaluate ovarian follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine basis for puberty in heifers and ewes.

Maturation processes that culminate in puberty and sexual maturity are initiated before birth, continue through prepuberty (> 50 days before puberty) and peripuberty (50 days before puberty) and are completed early after puberty. The hypothalamus is the primary site of change during transition to sexual maturity. Maturation of the hypothalamus results from decreased negative feedback of oestradiol that leads to increased frequency of release of LH pulses. Increased tonic release of LH pulses during sexual maturation is the primary endocrine factor that regulates the onset of puberty in ewe lambs and heifers. Increased frequency of release of LH pulses enhances development of ovarian follicles which produce enough oestradiol to induce behavioural oestrus and a preovulatory surge of gonadotrophins. In later stages of peripuberty, ovulation or luteinization of follicles results in transient increases in progesterone for shorter periods than is typical for luteal phases of the oestrous cycle of mature ewes and cows. Transient increases in progesterone are not generally preceded by behavioural oestrus. After the demise of the transient luteal structures, puberty is attained with occurrence of the first behavioural oestrus that is accompanied by ovulation and development of a corpus luteum with a typical lifespan. At puberty, all components of the hypothalamic-pituitary-ovarian axis are in place for oestrous cycles to be expressed. Factors that can influence the pubertal rise in release of LH pulses are genotype, gender, season of year when pubertal age is attained, growth or nutritional intake, social cues or treatment with exogenous progestins. Sexual maturation continues after puberty with an enhanced probability of pregnancy occurring from actions of ovarian steroids at the uterus.

Luteinizing hormone has a role in development of fully functional corpora lutea (CL) but is not required to maintain CL function in heifers.

We tested the hypothesis that endogenous pulses of LH have a role in development and maintenance of CL during the estrous cycle of the bovine female. Twenty heifers were synchronized to estrus by treating two times with prostaglandin F2 alpha 11 days apart (Day 0 = behavioral estrus). Heifers were then randomly assigned to one of four treatments (n = 5/group). Heifers were treated with an antagonist to LHRH (LHRH-Ant; N-Ac-D-Nal[2]1,4Cl-D-Phe2,D-Pal[3]3,D-Cit6,D-Ala10- LHR H; 10 micrograms/kg body weight) or vehicle (5% mannitol) once every 24 h: 1) LHRH-Ant Days 2-7, 2) LHRH-Ant Days 7-12, 3) LHRH-Ant Days 12-17, 4) no LHRH-Ant (control). Blood samples were collected from the jugular vein twice daily on Days 0-24, and area under the profile of progesterone in circulation during the luteal phase of the estrous cycle was characterized from the start of each treatment period until the demise of CL or Day 24, whichever came first. Luteolysis was considered to have occurred when three consecutive samples contained less than 1 ng progesterone/ml plasma. Areas under the profile of progesterone in circulation during the luteal phase of the estrous cycle were compared to those of heifers from the control group for the same period. LHRH-Ant treatment diminished LH pulses in all treatment groups compared to control (p < 0.05). Treatment with LHRH-Ant on Days 2-7 diminished function of CL (3.72 +/- 0.93 vs. 7.36 +/- 1.02 units, respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian follicular development in prepubertal heifers is influenced by level of dietary energy intake.

Objectives were twofold: 1) to determine the chronology of development of dominant ovarian follicles during the peripubertal period in heifers and 2) to determine whether feeding a diet with low energy content that delays onset of puberty alters chronology of dominant ovarian follicular development in peripubertal heifers. Ten heifers of composite breeding (1/4 Angus, 1/4 Hereford, 1/4 Red Poll, 1/4 Pinzgauer) were randomly assigned, at 8 mo of age, to receive a diet designed to produce 0.9 (n = 5) or 0.3 (n = 5) kg body weight gain per day for the duration of the experiment. To characterize changes in size of ovarian follicles, real-time linear ultrasonography of ovaries was conducted in all heifers every other day until puberty occurred. Blood samples were collected weekly to determine concentrations of progesterone and 17 beta-estradiol. Determination of time of puberty was based on increased concentrations of progesterone, ultrasound depiction of ovulation, and subsequent presence of a corpus luteum. Size of the dominant ovarian follicles differed prior to puberty (p < 0.03); diameter of the dominant ovarian follicle was greater in all heifers as the first ovulation approached as compared to earlier in prepuberty. Heifers fed the greater amount of energy exhibited larger dominant ovarian follicles at a younger age in comparison to heifers fed the lower amount of energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regulation of gonadotropin synthesis and release in ovariectomized ewes after treatment with a luteinizing hormone-releasing hormone antagonist.

Our working hypothesis was that synthesis and release of LH, but not FSH, were solely dependent on LHRH. Twenty ovariectomized (OVX) ewes were randomly assigned to one of five treatments (n = 4 per group). Ewes were administered a low (10 micrograms/kg) or high (100 micrograms/kg) dose of LHRH antagonist (LHRH-Ant) at 24-h intervals for 3 or 6 days. Control ewes received vehicle (5% mannitol) at 24-h intervals for 6 days. Blood samples were collected every 15 min for 4 h before LHRH-Ant or vehicle and every 2 h during the period of treatment to determine concentrations of LH and FSH. Twenty-four hours after the last treatment with LHRH-Ant or vehicle, anterior pituitaries were collected and divided in half along the midsagittal plane; the number of receptors for LHRH, pituitary content of LH and FSH, and relative amounts of mRNA for alpha, LH beta, and FSH beta subunits were determined. Concentrations of LH in serum decreased (p < 0.05) from 25.4 +/- 4.3 ng/ml before LHRH-Ant to less than 0.5 ng/ml within 4 h after the first treatment of LHRH-Ant and remained low (< 0.5 ng/ml) throughout the study. Serum concentrations of FSH declined gradually during the 3- or 6-day period of treatment with LHRH-Ant, from 37.3 +/- 2.4 and 26.5 +/- 4.8 ng/ml to 19.9 +/- 1.8 and 13.7 +/- 2.1 ng/ml, respectively. The magnitude of decline in serum concentrations of LH and FSH did not differ among ewes treated with low or high doses of LHRH-Ant.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival analysis and prognosis for dementia patients.

How long a dementia patient is cared for in the home before admission to a nursing home depends on the state of the patient and the state of the caregiver. Using 5-year follow-up data, the times until entry to nursing home and until death are modeled using a Cox survival model in which patient and caregiver variables at entry to study as well as changes in these variables over the following 12 months are the regression variables. Treatment variables quantify the effects of a caregiver training program. Statistical methods used in fitting the Cox survival model and consequent predictions of survival rates are discussed.

Pregnancy rate is greater when the corpus luteum is present during the period of progestin treatment to synchronize time of estrus in cows and heifers.

Our hypothesis was that conception in bovine females would be enhanced if the corpus luteum was present during the period of progestin treatment to synchronize estrus. In this study, 67 heifers (one replicate) and 124 cows (two replicates) were randomly assigned to one of two treatment groups. Seven days after estrus (Day 0), all animals were implanted with norgestomet and the implant remained in place for 10 days. All implants were removed on Day 17. Cows and heifers in one group received prostaglandin F2 alpha (PGF2 alpha) on Day 7 of the estrous cycle (PG 7; norgestomet without corpus luteum), and animals in the second group received PGF2 alpha on Day 17 (day of implant removal; PG 17; norgestomet with corpus luteum). All heifers and cows exhibiting behavioral estrus were artificially inseminated 12 h after estrus was detected during a 7-day period following removal of norgestomet. Blood samples were collected from cows of replicate 1 to determine serum concentrations of progesterone and 17 beta-estradiol. Percentage of females that had calves as a result of artificial insemination was greater (p < 0.01) in the PG 17 group (87% and 78% cows [two replicates] and 58% heifers) compared to the PG 7 group (31% and 44% cows [two replicates] and 41% heifers).(ABSTRACT TRUNCATED AT 250 WORDS)

Time until institutionalization and death in patients with dementia. Role of caregiver training and risk factors.

OBJECTIVE: To determine which variables best predict prognosis--time to nursing home admission (NHA) and death--in patients with dementia. DESIGN: Survival analysis employing the Cox proportional hazards model with the use of risk variables pertaining to dementia severity and its rate of progression and caregiver functioning. SETTING: Patients and their caregivers participating in a controlled intervention study of training for caregivers in home management of dementia. PARTICIPANTS: Patients with mild Diagnostic and Statistical Manual of Mental Disorders, Third Edition--defined dementia (N = 91; 68 patients with Alzheimer-type dementia, 20 with vascular dementia, and three with other types) and their caregivers. FOLLOW-UP: All subjects had repeated assessments in the first year to determine rates of change and thereafter annually to determine the date of NHA and/or death. RISK VARIABLES: (1) Caregiver training; (2) dementia severity at index assessment; (3) caregiver stress, neuroticism, and socialization; (4) changes in patients and caregivers during the first 12 months; and (5) patient characteristics. RESULTS: By 5 years' follow-up, 76% of patients had entered a nursing home and 42% had died. Dementia severity and rate of deterioration ("how far" and "how fast") and caregiver psychological morbidity significantly influenced rates of NHA and death. Training of caregivers was significantly associated with delayed NHA and reduced mortality. Greater patient age, non-Alzheimer's dementia, and, unexpectedly, greater caregiver psychological morbidity were associated with shorter survival to death. CONCLUSIONS: Both severity ("how far") and rate of deterioration ("how fast") influence time to NHA and death. Caregiver training may have important ameliorating effects on the prognosis of dementia.

Cost effectiveness of a training program for dementia carers.

An intensive 10-day residential training program for dementia carers has previously been shown to be associated with increased patient survival at home and decreased psychological morbidity in carers (Brodaty & Gresham, 1989). Results from a further follow-up, about 39 months after entry into the trial, were even more impressive. Patients whose carers had trained in the program had much higher adjusted rates of survival at home (53% versus 13%) and, unexpectedly, fewer deaths (20% versus 41%) than those whose carers did not have training. Patients whose carers had delayed training achieved intermediate results (31% surviving at home and 21% dying). These results were achieved with an average saving of $A7,967 ($U.S.5975) per patient over the first 39 months.

Nuclear protein, matrix and structural changes in rooster liver after estrogenic induction of vitellogenesis.

The estrogenic induction of vitellogenesis in avian and amphibian liver has been well characterized at the target gene level. Comparatively little however, is known about cognate nuclear events associated with the response, particularly those involving large-scale structural changes and the non-histone proteins (NHP). We have examined these aspects further in primary stimulated roosters. In the first 24 hr post induction with estradiol, hepatocyte nuclei enlarged by 50% and exhibited sharp rises in total protein and RNA content. In particular, the mass of residual NHP rose about 40%. Extensive internal reorganization was evident, including partial disaggregation of chromatin, proliferation of interchromatin components and de novo appearance of prominent "nuclear bodies". These changes were accompanied by quantitative fluctuations in nucleoplasmic and several matrix fraction proteins. A marked relative decrease was evident in all three lamins, as well as approximately 75 and approximately 175 kD proteins. Hn-RNP-associated polypeptides however, and various unidentified components became much more prominent. By 24 hr, cells were fully differentiated for bulk export of vitellogenin and low density lipoproteins. All changes persisted for several days before gradually regressing to normal over a 2-4 week period. Many key nuclear modifications, however, did not regress fully, including persistent enlargement, elevated NHP content and modified matrix fraction proteins. Collectively, these may reflect part of the "memory" effect, commonly observed in steroid target tissues, whereby a second, more pronounced response can be triggered long after primary induction has subsided.

Chinese hamster nuclear proteins. An electrophoretic analysis of interphase, metaphase and nuclear matrix preparations.

A comparison, by two-dimensional gel electrophoresis, of total interphase nuclear, metaphase chromosomal and nuclear matrix proteins from Chinese hamster V-79 cells was undertaken to examine the distribution of these proteins during mitosis. We have found a number of differences among these populations, although the two-dimensional gel patterns are generally similar. The most striking observation is that a loose cluster of six interphase nuclear polypeptides, with isoelectric points in urea between 5.7 and 6.7 and molecular masses ranging from 53 to 75 kDa, is greatly enriched in chromosome preparations. Each of these species is prominent also in the nuclear matrix. Preliminary evidence suggests that one of these polypeptides is the intermediate filament protein, vimentin. In addition, two major polypeptides of interphase nuclear preparations, a basic 94-kDa species and an approximately 65-kDa species, are absent from chromosomes. The latter polypeptide is the nuclear pore-lamina complex lamin B. Actin is present in all of these fractions, but tubulin has not been observed. hnRNP particle polypeptides are major components of the nuclear matrix, but are markedly reduced in metaphase chromosomes. The intermediate and basic 65-75-kDa nuclear matrix polypeptides we have previously demonstrated to be major components of rat liver nuclear matrix, are reduced in Chinese hamster matrix preparations and at least one of these species, a minor, basic, 68-kDa polypeptide, is missing entirely from metaphase chromosomes. These results are discussed in relation to nuclear and chromosome structure and the possibility of contamination of nuclear protein preparations from cultured cell lines with intermediate filaments.

Two-dimensinal gel electrophoresis of rat liver nuclear washes, nuclear matrix, and hnRNA proteins.

The proteins of rat liver cytoplasm, nuclear washes, matrix, membrane, heterogeneous nuclear (hn)RNA proteins and chromatin were examined by two-dimensional gel electrophoresis. The inclusion in the gels of six common protein standards of carefully selected molecular weight and isoelectric point allowed us to clearly follow the distribution of specific proteins during nuclear extraction. In the nuclear washes and chromatin, we observed five classes of proteins: (a) Exclusively cytoplasmic proteins, present in the first saline-EDTA wash but rapidly disappearing from subsequent washes; (b) ubiquitous proteins of 75,000, 68,000, 57,000, and 43,000 mol wt, the latter being actin, found in the cytoplasm, all nuclear washes and the final chromatin pellet; (c) proteins of 94,000, 25,000, and 20,500 mol wt specific to the nuclear washes; (d) proteins present in the nuclear washes and final chromatin, represented by species at 62,000, 55,000, 54,000, and 48,000 mol wt, primarily derived from the nuclear matrix; and (e) two proteins of 68,000 mol wt present only in the final chromatin. The major 65,000-75,000-mol wt proteins seen by one-dimensional gel electrophoresis of nuclear matrix were very heterogeneous and contained a major acidic, an intermediate, and a basic group. A single 68,000-mol wt polypeptide constituted the majority of the membrane-lamina fraction, consistent with immunological studies indicating that a distinct subset of matrix proteins occurs, associated with heterochromatin, at the periphery of the nucleus. Actin was the second major nuclear membrane-lamina protein. Two polypeptides at 36,000 and 34,000 mol wt constituted 60% of the hnRNP. Approximately 80% of the mass of the nonhistone chromosomal proteins (NHP) from unwashed nuclei is contributed by nuclear matrix and hnRNPs, and essentially the same patterns were seen with chromatin NHP. The concept of NHP being a distinct set of DNA-bound proteins is unnecessarily limiting. Many are derived from the nuclear matrix or hnRNp particles and vary in the degree to which they share different intracellular compartments.

Triple-spot proteins in two-dimensional gel electrophoresis.

A triple-spot pattern of polypeptides occurring in two-dimensional gel electrophoresis of proteins is described. The presence of a mutant protein, Pc 1 Duarte, which results in a splitting of all three polypeptides, is evidence that they are produced by the same gene. This pattern is seen in about 1% of the proteins from a variety of sources. Typically, about 50% of the protein occurs as a single major spot, the remainder occurring as two polypeptides with an additional negative charge and slightly different molecular weight. The reproducibility of this pattern implies a functional significance which is presently unknown. The implication of this configuration for patterns seen by one-dimensional gel electrophoresis is discussed.