RESUMEN
BACKGROUND: Early-life exposure to famine has been hypothesized to influence long-term bone health, potentially increasing the risk of osteoporosis and fractures in later life. This systematic review and meta-analysis aimed to investigate the association between early-life famine exposure and the risk of osteoporosis, bone mineral density (BMD) loss, and fractures. METHODS: A comprehensive literature search was conducted across MEDLINE/PubMed, Scopus, Web of Science, and Embase, supplemented by manual searches on Google Scholar. Observational studies examining the impact of early-life famine exposure on osteoporosis, BMD, and fracture risk were included. Data were extracted and quality assessed independently by two reviewers, and meta-analyses were performed using the Mantel-Haenszel method for odds ratios (OR) and Hedges' g for standardized mean differences (SMD). Heterogeneity was assessed using the I2 statistic, and meta-regression analyses were conducted to explore potential sources of heterogeneity. RESULTS: From 6147 initial studies, 10 met the inclusion criteria, with 8 included in the meta-analysis. The early-life famine-exposed group showed a significantly higher incidence of osteoporosis (OR = 2.12, 95%CI [1.35, 3.34], I2 = 88%) and fractures (OR = 1.58, 95%CI [1.07, 2.33], I2 = 92%) compared to non-exposed individuals. Meta-regression indicated that higher female prevalence in studies made the association with osteoporosis stronger, while higher ages strengthened the association with fractures. Exposure during fetal and childhood stages was particularly associated with increased risks of osteoporosis and fractures. Additionally, famine exposure correlated with lower BMD, particularly in the heels, femoral neck, and total hip regions. CONCLUSION: Early-life famine exposure is significantly associated with an increased risk of osteoporosis, fractures, and lower BMD in later life. These results emphasize the lasting effects on bones from early lack of nutrition and stress the importance of specific interventions for bone health in groups with past famine experiences. Future studies should investigate the reasons behind these connections and assess preventative approaches to reduce the negative effects on bone health in those impacted.
RESUMEN
Highly active antiretroviral therapy (HAART) can suppress HIV replication to undetectable levels in plasma, but it is unlikely to eradicate cellular reservoirs of virus. Immunotherapies that are cytolytic may be useful adjuncts to drug therapies that target HIV replication. We have generated HIV-specific CD4(+) and CD8(+) T cells bearing a chimeric T-cell receptor (CD4zeta) composed of the extracellular and transmembrane domain of human CD4 (which binds HIVgp120) linked to the intracellular-zeta signaling chain of the CD3 T-cell receptor. CD4zeta-modified T cells can inhibit viral replication, kill HIV-infected cells in vitro, and survive for prolonged periods in vivo. We report the results of a phase II randomized trial of CD4zeta gene-modified versus unmodified T cells in 40 HIV-infected subjects on HAART with plasma viral loads <50 copies/ml. Serial analyses of residual blood and tissue HIV reservoirs were done for 6 months postinfusion. No significant between-group differences were noted in viral reservoirs following therapy. However, infusion of gene-modified, but not unmodified, T cells was associated with a decrease from baseline in HIV burden in two of four reservoir assays and a trend toward fewer patients with recurrent viremia. Both groups experienced a treatment-related increase in CD4(+) T-cell counts.