Possible interactions between gonadotrophs and somatotrophs in the pituitary of tilapia: apparent roles for insulin-like growth factor I and estradiol

The unique organization of the teleost pituitary, in which cells are grouped according to their characteristic hormone, makes this a suitable model for studying pituitary paracrine interactions. In a number of fish, including tilapia, there are variations in the circulating levels of the gonadotropins and GH, which are elevated during the reproductive season, suggesting interactions between the reproductive and growth axes. The aim of this study was to investigate paracrine interactions between the gonadotrophs and somatotrophs in the tilapia pituitary. Initially, dispersed pituitary cells were separated on a density gradient in which the gonadotrophs were found in the least dense fractions, and the somatotrophs were concentrated in the densest fraction. After 4 days in culture, cells in the least dense fractions showed characteristic cytoplasmic extensions not seen in the somatotrophs, which appeared small and failed to form aggregates; somatotrophs were found, however, attached to other non-GH cells. Staining of the nuclei with 4,6-diaminidino-2-phenyl-dihydrochloride revealed that the isolated somatotrophs had undergone nuclear condensation and fragmentation typical of apoptosis. Addition of either estradiol or human recombinant insulin-like growth factor I (IGF-I; 10 nM) to the somatotroph cultures increased the number of cell aggregates and reduced the number of condensed or fragmented nuclei. Immunocytochemical studies on pituitary sections revealed IGF-I immunoreactivity in regions of the proximal pars distalis that stain with gonadotropin IIbeta antisera and also in regions of the rostral pars distalis characteristic of corticotrophs; immunoreactive IGF-I was never seen in the region of the somatotrophs. Incubation of cells from the different fractions with testosterone (10 nM; 24 h) revealed that cells of the least dense fractions, which were rich in gonadotrophs, possessed aromatizing ability, which was absent in the somatotroph-enriched fraction. These results suggest that estradiol and IGF-I, both generated from cells other than the somatotrophs, may exert antiapoptotic effects and thus possibly control the size of this population of cells.     

The Effect of Community-Based Prevention and Care on Ebola Transmission in Sierra Leone

Objectives. To examine the acceptability, use, effects on early isolation, and contribution to Ebola virus disease (EVD) transmission of Community Care Centers (CCCs), which were rapidly deployed in Sierra Leone during an accelerated phase of the 2014–2015 EVD epidemic.Methods. Focus group discussions, triads, and key informant interviews assessed acceptability of the CCCs. Facility registers, structured questionnaires, and laboratory records documented use, admission, and case identification. We estimated transmission effects by comparing time between symptom onset and isolation at CCCs relative to other facilities with the national Viral Hemorrhagic Fever data set.Results. Between November 2014 and January 2015, 46 CCCs were operational. Over 13 epidemic weeks, 6129 patients were triaged identifying 719 (12%) EVD suspects. Community acceptance was high despite initial mistrust. Nearly all patients presented to CCCs outside the national alert system. Isolation of EVD suspects within 4 days of symptoms was higher in CCCs compared with other facilities (85% vs 49%; odds ratio = 6.0; 95% confidence interval = 4.0, 9.1), contributing to a 13% to 32% reduction in the EVD reproduction number (R_o).Conclusions. Community-based approaches to prevention and care can reduce Ebola transmission.West Africa’s Ebola virus disease (EVD) epidemic is unprecedented in scale and intensity and larger than all previous EVD epidemics combined.1 Sierra Leone is the worst-affected country. Cases were first observed in May 2014 in the remote eastern part of the country intersecting Guinea and Liberia.2 The outbreak quickly progressed from a localized to a generalized epidemic. By May 2015, there were more than 8500 confirmed cases and 3800 reported deaths,3 though actual caseloads were presumed to be substantially higher.4Limiting Ebola transmission requires reducing the basic reproduction number (R_o), which is the number of secondary infections resulting from each infected case.5 The common underlying exposure is contact with infected body fluids of the sick or deceased.6 From a public health perspective, reducing R_o requires strong community systems to support early case detection and isolation as well as conducting safe and dignified burials. In addition, social mobilization can improve awareness and shift norms around key risk behaviors.7Sierra Leone underwent a phase of accelerated EVD transmission during the last quarter of 2014.8 At the time, high levels of fear and stigma prevailed, with widespread mistrust in Ebola response systems.9,10 The mainstay of case identification was a national alert system, where toll-free calls triggered the investigation of potential EVD suspects. In September, a 3-day national campaign was launched to disseminate information on Ebola to every household in the country and refer potential cases, which resulted in a spike in EVD suspects.11 (Ebola suspects are persons fitting the World Health Organization case definition for mobile teams or health stations of fever with recent contact, or fever plus 3 or more cardinal symptoms, or inexplicable bleeding, or sudden unexplained death.12) The demand for safe isolation and treatment beds rapidly outpaced supply. By the end of October, there were just 287 high-quality Ebola Treatment Center beds in 4 urban centers despite widespread transmission across all 14 districts.13The World Health Organization and partners advocated the establishment of Ebola Community Care Centers (CCCs) as a strategy to increase access to care and decentralize the EVD response.14 Key components of the model are outlined in Figure A, available as a supplement to the online version of this article at http://www.ajph.org. The CCCs in Sierra Leone were purpose-built, infection-prevention– and infection-control–compliant, 8- to 24-bed temporary facilities. Their primary aims were to support early case detection and isolation, provide basic supportive care for EVD suspects, and facilitate diagnostic testing and referral within a community context. The CCCs were also intended to act as hubs for a range of prevention services including safe burials, contact tracing, case finding, and social mobilization. Although recent models suggest that CCCs could limit transmission by shortening the time between symptom onset and admission, this has yet to be operationally assessed.15As influencing community dynamics and behaviors was central to the CCC strategy, a number of measures were adopted to enhance community engagement in the Ebola response. (The term community engagement refers to the process of working collaboratively with and through groups of people to address priority concerns.16 Social mobilization refers to a process that engages and motivates a wide range of partners and allies at national and local levels to raise awareness of and demand for a particular development objective through dialogue.17) An initial consultation took place with traditional leaders and community members who selected site locations and participated in CCC construction. Communities toured facilities before opening and in some places conducted traditional rituals to prepare facilities for use. Care, support, and nutritional services were provided by community members themselves. Social mobilization activities were conducted by trained facilitators from local nongovernmental organizations (approximately 10 per CCC) and aimed to enhance Ebola awareness and foster appropriate facility use. These included household visits, meetings with village leaders and community groups including youth and women’s groups, and mass media campaigns through radio and megaphone-based messaging.We report on the implementation of CCCs in Sierra Leone across 5 districts, with a focus on activities undertaken by the United Nations International Children’s Emergency Fund (UNICEF) in partnership with the Ministry of Health and Sanitation that established three quarters of facilities in the country. The objectives were to examine (1) acceptability of CCCs to local communities, (2) patterns of use, (3) their contribution to early suspect isolation, and (4) effects on EVD transmission in districts where they were deployed. Finally, emerging lessons are discussed to inform Ebola elimination efforts and the wider health systems–strengthening agenda.     

Discovery of fairy circles in Australia supports self-organization theory

Vegetation gap patterns in arid grasslands, such as the “fairy circles” of Namibia, are one of nature’s greatest mysteries and subject to a lively debate on their origin. They are characterized by small-scale hexagonal ordering of circular bare-soil gaps that persists uniformly in the landscape scale to form a homogeneous distribution. Pattern-formation theory predicts that such highly ordered gap patterns should be found also in other water-limited systems across the globe, even if the mechanisms of their formation are different. Here we report that so far unknown fairy circles with the same spatial structure exist 10,000 km away from Namibia in the remote outback of Australia. Combining fieldwork, remote sensing, spatial pattern analysis, and process-based mathematical modeling, we demonstrate that these patterns emerge by self-organization, with no correlation with termite activity; the driving mechanism is a positive biomass–water feedback associated with water runoff and biomass-dependent infiltration rates. The remarkable match between the patterns of Australian and Namibian fairy circles and model results indicate that both patterns emerge from a nonuniform stationary instability, supporting a central universality principle of pattern-formation theory. Applied to the context of dryland vegetation, this principle predicts that different systems that go through the same instability type will show similar vegetation patterns even if the feedback mechanisms and resulting soil–water distributions are different, as we indeed found by comparing the Australian and the Namibian fairy-circle ecosystems. These results suggest that biomass–water feedbacks and resultant vegetation gap patterns are likely more common in remote drylands than is currently known.Pattern-formation theory (1) and the influence of Alan Turing’s work on understanding biological morphogenesis (2) are increasingly recognized in environmental sciences (3). Vegetation patterns resulting from self-organization occur frequently in water-limited ecosystems and, similar to Turing patterns, show pattern morphologies that change from gaps to stripes (labyrinths) to spots with decreasing plant-available moisture (4–6). The patterns may emerge on completely flat and homogeneous substrate and are induced by positive feedbacks between local vegetation growth and water transport toward the growth location. The depletion of water in the vicinity of the growing vegetation inhibits the growth there and promotes the development of large-scale patterns with a typical periodicity (5, 7–9). Spatial self-organization by scale-dependent pattern-forming feedbacks of this kind is a population-level response to water stress that complements phenotype changes at the organism level (10).Banded or striped vegetation patterns such as tiger bush or mulga are well known from remote sensing (4, 11, 12), but landscape-scale evidence for gap patterns with circular bare-soil patches is very rare. The archetype of such a gap pattern is that of the fairy circles (FCs) of Namibia, which cover vast areas in a narrow range of climatic conditions (13, 14). However, the origin of the Namibian FCs is still unknown. Several competing hypotheses exist ranging from vegetation self-organization (13–17), termite-induced activity (18), and Euphorbia poisoning (19) to abiotic gas leakage (20). Among these, vegetation self-organization stands out as the most solid mechanism that explains the emergence of large-scale order (15, 16) and the strong dependence of fairy-circle distribution on mean annual precipitation (13). Furthermore, only self-organized biomass–water feedbacks can explain the shrinking in size and disappearance of fairy circles after above-average rainfall years and the typical enlargement and increased appearance of FCs after below-average rainfall years (21).According to pattern-formation theory, the large-scale order that emerges from a uniform state obeys a universal pattern whose particular form is dictated by the instability that the uniform state undergoes (8, 22). The fairy-circle gap pattern observed in Namibia (15) is likely an example of a universal hexagonal pattern that, according to pattern-formation theory, is induced by a nonuniform stationary instability (3, 21–24). The mechanisms inducing the instability may differ among ecosystems, but the resulting hexagonal order of the pattern is the same. This suggests that gap patterns similar to the Namibian FCs should be observable in other water-limited landscapes, even if the mechanism of their formation is different. Also, the opponents of the self-organization hypothesis argue “if the model of self-organization were correct, it should be generic and circular bare patches should occur globally” (25).Here, we report on the discovery and analysis of such a hexagonal gap pattern, 10,000 km away from Namibia in the remote outback of Western Australia. Using a comprehensive approach consisting of fieldwork, remote sensing, spatial pattern analysis, and process-based mathematical modeling we reveal in the following that this gap pattern is the consequence of a pattern-forming biomass–water feedback that differs from the feedback that drives the formation of FCs in Namibia.     

Validation of an innovative instrument of Positive Oral Health and Well-Being (POHW)

Introduction

Most existing measures of oral health focus solely on negative oral health, illness, and deficiencies and ignore positive oral health. In an attempt to commence exploration of this challenging field, an innovative instrument was developed, the “Positive Oral Health and Well-Being” (POHW) index. This study aimed to validate this instrument and to explore an initial model of the pathway between oral health attributes and positive oral health.

Methods

A cross-sectional, multicenter study (Israel, USA, and Germany), was conducted. Our conceptual model suggests that positive oral health attributes, which integrate with positive unawareness or positive awareness on the one hand and with positive perception on the other hand, may result via appropriate oral health behavior on positive oral health. The 17-item self-administered index was built on a theoretical concept by four experts from Israel and Germany. Reliability, factor, and correlation analyses were performed. For external correlations and to measure construct validity of the instrument, we utilized the oral health impact profile-14, self-perceived oral impairment, life satisfaction, self-perceived well-being, sociodemographic and behavioral data, and oral health status indices.

Results

Four hundred and seventy participants took part in our three-center study. The combined data set reliability analyses detected two items which were not contributing to the index reliability. Thus, we tested a 15-item construct, and a Cronbach’s α value of 0.933 was revealed. Primary factor analysis of the whole sample indicated three subconstructs which could explain 60 % of variance. Correlation analyses demonstrated that the POHW and OHIP-14 were strongly and negatively associated. The POHW correlated strongly and positively with general well-being, moderately with life satisfaction, and weakly with the perceived importance of regular dental checkups. It correlated moderately and negatively with perceived oral impairment, and marginally and negatively with dental caries experience (DMFT) and periodontal health status (CPI) scores. When DMFT and CPI clinical measurements were categorized, a higher score of POHW was revealed for better oral health.

Discussion

Our study introduced a new instrument with good reliability and sound correlations with external measures. This instrument is the first to allow measurability of positive instead of impaired oral health. We utilized subjective–psychological and functional–social measures. The current results indicate that by further exploring our conceptual model, POHW may be of importance for identifying patients with good and poor oral health, and building an effective and inexpensive strategy for prevention, by being able to evaluate the effect of interventions in a standardized way.

     

Molecular amino acid signatures in the MHC class II peptide-binding pocket predispose to autoimmune thyroiditis in humans and in mice

Hashimoto's thyroiditis (HT) is associated with HLA, but the associated allele is still controversial. We hypothesized that specific HLA-DR pocket-sequence variants are associated with HT and that similar variants in the murine I-E locus (homologous to HLA-DR) predispose to experimental autoimmune thyroiditis (EAT), a classical mouse model of HT. Therefore, we sequenced the polymorphic exon 2 of the HLA-DR gene in 94 HT patients and 149 controls. In addition, we sequenced exon 2 of the I-E gene in 22 strains of mice, 12 susceptible to EAT and 10 resistant. Using logistic regression analysis, we identified a pocket amino acid signature, Tyr-26, Tyr-30, Gln-70, Lys-71, strongly associated with HT (P = 6.18 x 10(-5), OR = 3.73). Lys-71 showed the strongest association (P = 1.7 x 10(-8), OR = 2.98). This association was seen across HLA-DR types. The 5-aa haplotype Tyr-26, Tyr-30, Gln-70, Lys-71, Arg-74 also was associated with HT (P = 3.66 x 10(-4)). In mice, the I-E pocket amino acids Val-28, Phe-86, and Asn-88 were strongly associated with EAT. Structural modeling studies demonstrated that pocket P4 was critical for the development of HT, and pockets P1 and P4 influenced susceptibility to EAT. Surprisingly, the structures of the HT- and EAT-susceptible pockets were different. We conclude that specific MHC II pocket amino acid signatures determine susceptibility to HT and EAT by causing structural changes in peptide-binding pockets that may influence peptide binding, selectivity, and presentation. Because the HT- and EAT-associated pockets are structurally different, it is likely that distinct antigenic peptides are associated with HT and EAT.     

Elucidating the origin of chromosomal aberrations in IVF embryos by preimplantation genetic analysis

Preimplantation genetic screening (PGS) has been proposed as a method for improving success rates in patients with repeated IVF failures. This approach is based on the hypothesis that such failures are the result of aneuploid embryos. It has been suggested that FISH analysis of blastomeres removed from preimplantation embryos represent the chromosomal constitution of the entire embryo. However, it is not yet clear whether it also represents the chromosomal constitution of the implanted embryo. PGS reanalysis on day 5 of embryos designated as "aneuploid" on day 3 may demonstrate a high rate of mosaicism for chromosomal aberration. Some of these mosaic embryos are capable of developing into normal embryos by "self-correction". Others, however, may accumulate additional chromosomal anomalies. It is therefore concluded that the chromosomal constitution of a preimplantation embryo may evolve during early cleavages. Meiotic and post zygotic mitotic errors may account for these chromosomal aberrations. This review will focus on elucidating the origin of chromosomal changes during preimplantation embryo development by studying their chromosomal constitution at different stages.