Differences in Gene Expression between First and Third Trimester Human Placenta: A Microarray Study

BACKGROUND: The human placenta is a rapidly developing organ that undergoes structural and functional changes throughout the pregnancy. Our objectives were to investigate the differences in global gene expression profile, the expression of imprinted genes and the effect of smoking in first and third trimester normal human placentas. MATERIALS AND METHODS: Placental samples were collected from 21 women with uncomplicated pregnancies delivered at term and 16 healthy women undergoing termination of pregnancy at 9-12 weeks gestation. Placental gene expression profile was evaluated by Human Genome Survey Microarray v.2.0 (Applied Biosystems) and real-time polymerase chain reaction. RESULTS: Almost 25% of the genes spotted on the array (n = 7519) were differentially expressed between first and third trimester placentas. Genes regulating biological processes involved in cell proliferation, cell differentiation and angiogenesis were up-regulated in the first trimester; whereas cell surface receptor mediated signal transduction, G-protein mediated signalling, ion transport, neuronal activities and chemosensory perception were up-regulated in the third trimester. Pathway analysis showed that brain and placenta might share common developmental routes. Principal component analysis based on the expression of 17 imprinted genes showed a clear separation of first and third trimester placentas, indicating that epigenetic modifications occur throughout pregnancy. In smokers, a set of genes encoding oxidoreductases were differentially expressed in both trimesters. CONCLUSIONS: Differences in global gene expression profile between first and third trimester human placenta reflect temporal changes in placental structure and function. Epigenetic rearrangements in the human placenta seem to occur across gestation, indicating the importance of environmental influence in the developing feto-placental unit

Treatment of osteochondral lesions of the talus: a systematic review

The aim of this study was to summarize all eligible studies to compare the effectiveness of treatment strategies for osteochondral defects (OCD) of the talus. Electronic databases from January 1966 to December 2006 were systematically screened. The proportion of the patient population treated successfully was noted, and percentages were calculated. For each treatment strategy, study size weighted success rates were calculated. Fifty-two studies described the results of 65 treatment groups of treatment strategies for OCD of the talus. One randomized clinical trial was identified. Seven studies described the results of non-operative treatment, 4 of excision, 13 of excision and curettage, 18 of excision, curettage and bone marrow stimulation (BMS), 4 of an autogenous bone graft, 2 of transmalleolar drilling (TMD), 9 of osteochondral transplantation (OATS), 4 of autologous chondrocyte implantation (ACI), 3 of retrograde drilling and 1 of fixation. OATS, BMS and ACI scored success rates of 87, 85 and 76%, respectively. Retrograde drilling and fixation scored 88 and 89%, respectively. Together with the newer techniques OATS and ACI, BMS was identified as an effective treatment strategy for OCD of the talus. Because of the relatively high cost of ACI and the knee morbidity seen in OATS, we conclude that BMS is the treatment of choice for primary osteochondral talar lesions. However, due to great diversity in the articles and variability in treatment results, no definitive conclusions can be drawn. Further sufficiently powered, randomized clinical trials with uniform methodology and validated outcome measures should be initiated to compare the outcome of surgical strategies for OCD of the talus

Systematic meta-review of supported self-management for asthma: a healthcare perspective

BACKGROUND: Supported self-management has been recommended by asthma guidelines for three decades; improving current suboptimal implementation will require commitment from professionals, patients and healthcare organisations. The Practical Systematic Review of Self-Management Support (PRISMS) meta-review and Reducing Care Utilisation through Self-management Interventions (RECURSIVE) health economic review were commissioned to provide a systematic overview of supported self-management to inform implementation. We sought to investigate if supported asthma self-management reduces use of healthcare resources and improves asthma control; for which target groups it works; and which components and contextual factors contribute to effectiveness. Finally, we investigated the costs to healthcare services of providing supported self-management. METHODS: We undertook a meta-review (systematic overview) of systematic reviews updated with randomised controlled trials (RCTs) published since the review search dates, and health economic meta-analysis of RCTs. Twelve electronic databases were searched in 2012 (updated in 2015; pre-publication update January 2017) for systematic reviews reporting RCTs (and update RCTs) evaluating supported asthma self-management. We assessed the quality of included studies and undertook a meta-analysis and narrative synthesis. RESULTS: A total of 27 systematic reviews (n = 244 RCTs) and 13 update RCTs revealed that supported self-management can reduce hospitalisations, accident and emergency attendances and unscheduled consultations, and improve markers of control and quality of life for people with asthma across a range of cultural, demographic and healthcare settings. Core components are patient education, provision of an action plan and regular professional review. Self-management is most effective when delivered in the context of proactive long-term condition management. The total cost (n = 24 RCTs) of providing self-management support is offset by a reduction in hospitalisations and accident and emergency visits (standard mean difference 0.13, 95% confidence interval -0.09 to 0.34). CONCLUSIONS: Evidence from a total of 270 RCTs confirms that supported self-management for asthma can reduce unscheduled care and improve asthma control, can be delivered effectively for diverse demographic and cultural groups, is applicable in a broad range of clinical settings, and does not significantly increase total healthcare costs. Informed by this comprehensive synthesis of the literature, clinicians, patient-interest groups, policy-makers and providers of healthcare services should prioritise provision of supported self-management for people with asthma as a core component of routine care. SYSTEMATIC REVIEW REGISTRATION: RECURSIVE: PROSPERO CRD42012002694 ; PRISMS: PROSPERO does not register meta-reviews

Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders:A Role for Serotonergic and Catecholamine Pathways

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal ‘programming’ of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11β-HSD2, an enzyme that inactivates glucocorticoids, increases anxiety‐ and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways

Spatio-temporal changes in chimpanzee density and abundance in the Greater Mahale Ecosystem, Tanzania

Species conservation and management require reliable information about animal distribution and population size. Better management actions within a species' range can be achieved by identifying the location and timing of population changes. In the Greater Mahale Ecosystem (GME), western Tanzania, deforestation due to the expansion of human settlements and agriculture, annual burning, and logging are known threats to wildlife. For one of the most charismatic species, the endangered eastern chimpanzee (Pan troglodytes schweinfurthii), approximately 75% of the individuals are distributed outside national park boundaries, requiring monitoring and protection efforts over a vast landscape of various protection statuses. These efforts are especially challenging when we lack data on trends in density and population size. To predict spatio-temporal chimpanzee density and abundance across the GME, we used density surface modeling, fitting a generalized additive model to a 10-year time-series data set of nest counts based on line-transect surveys. The chimpanzee population declined at an annual rate of 2.41%, including declines of 1.72% in riparian forests (from this point forward, forests), 2.05% in miombo woodlands (from this point forward, woodlands) and 3.45% in nonforests. These population declines were accompanied by ecosystem-wide declines in vegetation types of 1.36% and 0.32% per year for forests and woodlands, respectively; we estimated an annual increase of 1.35% for nonforests. Our model predicted the highest chimpanzee density in forests (0.86 chimpanzees/km2, 95% confidence intervals (CIs) 0.60–1.23; as of 2020), followed by woodlands (0.19, 95% CI 0.12–0.30) and nonforests (0.18, 95% CI 0.10–1.33). Although forests represent only 6% of the landscape, they support nearly one-quarter of the chimpanzee population (769 chimpanzees, 95% CI 536–1103). Woodlands dominate the landscape (71%) and therefore support more than a half of the chimpanzee population (2294; 95% CI 1420–3707). The remaining quarter of the landscape is represented by nonforests and supports another quarter of the chimpanzee population (750; 95% CI 408–1381). Given the pressures on the remaining suitable habitat in Tanzania, and the need of chimpanzees to access both forest and woodland vegetation to survive, we urge future management actions to increase resources and expand the efforts to protect critical forest and woodland habitat and promote strategies and policies that more effectively prevent irreversible losses. We suggest that regular monitoring programs implement a systematic random design to effectively inform and allocate conservation actions and facilitate interannual comparisons for trend monitoring, measuring conservation success, and guiding adaptive management

Revision after early aseptic failures in primary total knee arthroplasty

The purpose of this study was to evaluate cases of early aseptic failures presented during the first 5-year follow-up in a group of 981 primary total knee arthroplasty (primary TKA). Predisposing factors as well causes of failures and postoperative complications in different groups of aseptic failures were re-assessed and compared to a control group. A retrospective and cohort study compared one group of 944 primary TKA without surgical revision (890 patients) (Group A) with 22 primary TKA (22 patients) (Group B) that had revision TKA secondary to aseptic failure during the first five years follow-up. The cases of isolated patellar button replacement (n = 8) and infection (n = 7) were not considered in this study. All patients underwent a systematic assessment that included clinical and radiographic examinations, and IKS scores. Aseptic failure was more prevalent at the first 2-year follow-up (63%). TKA loosening (n = 11) and undiagnosed pain (n = 7) were considered the most frequent modes of failures, and laxity (n = 1) was a very rare early cause of failure. The aseptic failure group was characterized as average 5 years younger with a greater number of previous knee surgeries, lower IKS scores improvement, and more postoperative pain compared to control group, despite the fact that the aseptic failure group showed a prevalence of cases during the first 2-year follow-up. Inside this group, the undiagnosed pain group had lower improvement of IKS scores, a remarkable prevalence in prior surgical procedure (71%) and a minor mean interval between primary and revision TKA (11.6 months)