The curvilinear relationship of early-life adversity and successful aging: the mediating role of mental health

Objectives: The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health.

Method: Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (M_age = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted.

Results: Significant inverse U-shaped associations were found between ELA and iQoL (β = ?.59, p = .005) and between ELA and mental health (β = ?.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = ?.84, BCa CI [?1.66, ?.27]).

Conclusion: Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.     

The thymus in seronegative myasthenia gravis patients

Summary In 5–10% of all patients with typical generalised myasthenia gravis (MG), serum antibody to the acetylcholine receptor (AChR) is undetectable. To determine whether these represent a distinct subgroup, we have compared the thymuses of 14 seronegatives, 70 seropositives and 12 non-myasthenic controls. By quantitative immunohistology on coded sections, the 7 seronegative samples were clearly distinguishable from the controls by the pronounced lymph node-type T-cell areas in the medulla. While these closely resembled those in the seropositive cases, germinal centres were significantly sparser, and total in vitro IgG production was disproportionately low (per B cell) in the 12 cases tested. Furthermore, specific anti-AChR production was never detected in any of these cultures. The data support the view that the medullary T-cell areas are the most consistent abnormalitiy in the MG thymus (though it may not be primary), and they strongly imply that seronegative and seropositive MG are distinct entities.     

Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100.

Bicyclams, in which the cyclam (1,4,8,11-tetraazacyclotetradecane) moieties are tethered via an aliphatic bridge (i.e., propylene, as in JM2763) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) (E. De Clercq, N. Yamamoto, R. Pauwels, M. Baba, D. Schols, H. Nakashima, J. Balzarini, Z. Debyser, B. A. Murrer, D. Schwartz, D. Thornton, G. Bridger, S. Fricker, G. Henson, M. Abrams, and D. Picker, Proc. Natl. Acad. Sci. USA 89:5286-5290, 1992). We have now found that the bicyclam JM3100, in which the cyclam moieties are tethered by an aromatic bridge [i.e., phenylenebis(methylene)], inhibits the replication of various HIV-1 and HIV-2 strains in various cell lines at a 50% effective concentration (EC50) of 1 to 10 ng/ml, which is about 100-fold lower than the concentration required for JM2763 to inhibit HIV replication and at least 100,000-fold lower than the cytotoxic concentration (> 500 micrograms/ml). In primary T4 lymphocytes or primary monocytes, JM3100 proved inhibitory to HIV-1(IIIB) and several clinical HIV-1 isolates at an EC50 of less than 1 ng/ml. On the basis of time-of-addition experiments, JM3100 appeared to interact with a viral uncoating event, and this was further corroborated by an uncoating assay in which RNase sensitivity of [5-3H]uridine-labeled virions was monitored. In addition, but possibly mechanistically related, JM3100 blocks formation of infectious particles. JM3100 was also found to interfere directly with virus-induced syncytium formation, albeit at a higher concentration (1 to 2 microgram/ml) than that required for inhibition of viral replication. Following subcutaneous injection of 10 mg of JM3100 per kg of body weight to rabbits, anti-HIV activity was detected in serum corresponding to serum drug levels exceeding for at least 6 h by >100-fold the EC(50) required to inhibit HIV replication in vitro. When combined with either 3'-azido-2',3' -dideoxythymidine or 2',3' -dideoxyinosine, JM3100 achieved a additive inhibition of HIV replication, and when repeatedly subcultivated in the presence of JM3100, the virus remained sensitive to the compound for at least 30 passages (120 days) in cell culture.     

Matrix Metalloproteinases in Breast Cancer

Abstract: Matrix metalloproteinases (MMPs) represent a class of enzymes able to degrade numerous extracellular matrix macromolecules facilitating tumor invasion and metastasis. The principal MMPs involved in breast pathology are analyzed with their various roles and functions: gelatinases A and B, stromelysin-3, collagenase-3, and MT-MMP1 (membrane type MMP). In vivo and in vitro studies clearly demonstrate an important cooperation between tumor and stromal cells for the expression of these MMPs in breast carcinomas. The large expression of MMPs plead in favor of a major role of these enzymes in breast carcinoma progression and their detection may be used in some cases as a prognostic indicator. Studies now are in progress, directed toward the modulation of these MMPs and their inhibitors with new therapeutic agents to block tumoral invasion and metastasis due to these enzymes.?     

Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion

The mammalian spinal cord contains a locomotor central pattern generator (CPG) that can produce alternating rhythmic activity of flexor and extensor motoneurones in the absence of rhythmic input and proprioceptive feedback. During such fictive locomotor activity in decerebrate cats, spontaneous omissions of activity occur simultaneously in multiple agonist motoneurone pools for a number of cycles. During these 'deletions', antagonist motoneurone pools usually become tonically active but may also continue to be rhythmic. The rhythmic activity that re-emerges following a deletion is often not phase shifted. This suggests that some neuronal mechanism can maintain the locomotor period when motoneurone activity fails. To account for these observations, a simplified computational model of the spinal circuitry has been developed in which the locomotor CPG consists of two levels: a half-centre rhythm generator (RG) and a pattern formation (PF) network, with reciprocal inhibitory interactions between antagonist neural populations at each level. The model represents a network of interacting neural populations with single interneurones and motoneurones described in the Hodgkin-Huxley style. The model reproduces the range of locomotor periods and phase durations observed during real locomotion in adult cats and permits independent control of the level of motoneurone activity and of step cycle timing. By altering the excitability of neural populations within the PF network, the model can reproduce deletions in which motoneurone activity fails but the phase of locomotor oscillations is maintained. The model also suggests criteria for the functional identification of spinal interneurones involved in the mammalian locomotor pattern generation.     

Association of fibroblastoid features with the invasivephenotype in human bronchial cancer cell lines

The acquisition of a metastatic phenotype by epithelial cells implicates a series of changes altering their differentiation, their overall behavior and morphology. In the present study, we have examined the relationships between the cellular morphology, E-cadherin expression, matrix metalloproteinases expression and in vitro invasive properties in two human bronchial immortalized cell lines. The (16HBE14o-) cell line which did not show any invasive abilities in the Boyden chamber assay displayed a typical epithelial morphology in monolayer, expressed high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin. In contrast, the BZR cell line which was highly invasive displayed a more elongated phenotype in monolayer, did not produce E-cadherin but expressed vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic progression of broncho-pulmonary cancer cells results in a cellular dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin and expression of vimentin) associated with enhanced degradative properties (expression of metalloproteinases).© Rapid Science 1998