Gender inequality, women's empowerment, and adolescent birth rates in 363 Latin American cities.

BACKGROUND: Gender inequality is high in Latin America (LA). Empowering girls and young women and reducing gender gaps has been proposed as a pathway to reduce adolescent pregnancy. We investigated the associations of urban measures of women's empowerment and gender inequality with adolescent birth rates (ABR) in 366 Latin American cities in nine countries. METHODS: We created a gender inequality index (GII) and three Women Achievement scores reflecting domains of women's empowerment (employment, education, and health care access) using censuses, surveys, and political participation data at city and sub-city levels. We used 3-level negative binomial models (sub-city-city-countries) to assess the association between the GII and scores, with ABR while accounting for other city and sub-city characteristics. RESULTS: We found within country heterogeneity in gender inequality and women's empowerment measures. The ABR was 4% higher for each 1 standard deviation (1-SD) higher GII (RR 1.04; 95%CI 1.01,1.06), 8% lower for each SD higher autonomy score (RR 0.92; 95%CI 0.86, 0.99), and 12% lower for each SD health care access score (RR 0.88; 95%CI 0.82,0.95) after adjustment for city level population size, population growth, homicide rates, and sub-city population educational attainment and living conditions scores. CONCLUSION: Our findings show the key role cities have in reducing ABR through the implementation of strategies that foster women's socioeconomic progress such as education, employment, and health care access.

ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.

Spatial and temporal expression of S100B in cells of oligodendrocyte lineage.

The analysis of oligodendrocyte (OL) lineage development has been facilitated by the immunocytochemical characterization of OL-specific antigens and definition of the phenotypes sequentially acquired by differentiating OLs. The purpose of the present study was to address an enduring discrepancy between several reported cases of S100B immunodetection in CNS myelin and myelinating OLs on the one hand, and the systematic use of the S100B protein as an alleged astrocytic marker in studies of the mammalian CNS on the other. To resolve this discrepancy, we have compared the developmental distribution of EGFP+ cells in the CNS of s100b-enhanced green fluorescent protein (EGFP) (Vives et al., 2003) and cnp-EGFP (Yuan et al., 2002) mice, and examined the degree of overlap between EGFP expression and that of stage-specific markers of OL differentiation during the embryonic and postnatal phases of development. We demonstrate that the S100B protein is expressed in postnatal and adult populations of NG2+ progenitors of mouse brain, as well as in immature and mature myelinating OLs present in the brain and spinal cord of embryonic and adult mice, respectively. Comparison between EGFP and endogenous S100B expression in the s100b-EGFP and cnp-EGFP mice indicates that S100B protein expression is upregulated in immature and mature OLs. These results argue against the current view that S100B expression is restricted to the astrocytic lineage in the CNS, and indicate that the use of S100B in combination with other molecular markers will help discriminate oligodendrocytes from astrocytes.

Cambios recientes en la mortalidad por cáncer de próstata en Chile: estudio de tendencias en el período 1955-2001 / Recent changes in prostate cancer mortality in Chile: trends analysis from 1955 to 2001

Background: By the year 2000, prostate cancer became the second leading cause of cancer death in Chilean men of all ages and is the leading cause of cancer deaths in men of eighty years of age or older. Aim: To analyze the trends in mortality rates from prostate cancer in Chile in a fifty years series, estimating the rate of increase of such rates and their changes in time. Material and methods: A trend analysis for age standardized mortality rates was performed, using join point regression analysis, which allows estimation of the annual percent change of rates and to find significant changes in such trend. Results: Age standardized mortality rates in Chile reached their peak value in 1996, becoming apparently stable from then on. Crude rates have had a steady increase during the whole period. The trends analysis identified three different periods in the growth of the age standardized rates: a first one of slow increase in rates between 1955 and 1981 (0.9 percent annual increase), a second one of more aggressive growth starting in 1981 (2.6 percent annual increase), and a third period starting in 1996, in which rates slowly decline at an annual rate of 1 percent. Conclusions: The tendency of prostate cancer seen in Chile resembles that of industrialized countries, with an increase in its age standardized death rates that suffers a downturn by the end of the past decade. Besides early detection techniques, a substantial part of the reduction in mortality from prostate cancer could be explained by therapeutic improvements (Rev MÚd Chile 2004; 132: 579-87).

Clinical and molecular analysis of three Mexican families with Pendred's syndrome.

BACKGROUND: The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney. OBJECTIVE: To perform a detailed clinical and molecular analysis of patients with Pendred's syndrome from four patients from three unrelated Mexican families. METHODS: Thyroid function tests, perchlorate test, thyroid scintigraphy, audiometry, computer tomography and magnetic resonance imaging were performed in all affected individuals. Haplotype analyses were performed using microsatellite markers flanking the PDS locus, and the PDS gene was submitted to direct sequence analysis. RESULTS: All patients presented with sensorineural deafness, Mondini malformations of the cochlea, an enlarged vestibular aqueduct, goiter, and a positive perchlorate test. Two patients were hypothyroid, two individuals were euthyroid. Sequence analysis revealed a complex homozygous deletion/insertion mutation at the end of exon 4 in the index patient of family 1 resulting in a premature stop codon at position 138. In family 2, the affected individuals were compound heterozygous for a splice acceptor mutation (IVS2 -1G>A) and a 1231G>C transversion substituting alanine 411 by proline (A411P). In family 3, the index patient was found to be homozygous for a transversion 412G>T in exon 4 replacing valine 138 by phenylalanine (V138F). CONCLUSIONS: All patients included in this study presented with the classic Pendred syndrome triad and molecular analysis revealed pendrin mutations as the underlying cause. The identification of three novel mutations, one of them of complex structure, expands the spectrum of mutations in the PDS gene and emphasizes that they display marked allelic heterogeneity.

Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice.

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.

Control of tumor development by intratumoral cytokines.

The local immune reactions may influence the clinical outcome of human tumors. In carcinoma of the cervix, high gene expression of IL6 with tumor invasiveness whereas lack of gene expression of IFNbeta is correlated with poor prognosis. In colorectal cancer, lack of expression of IFNbeta is associated with the presence of distant metastasis and poor survival. The production of IL17 and IL18, inducers of IL6 and IFNbeta respectively is regulated in these tumors and may control the levels of the effector cytokines, i.e. IL6 and IFNbeta. The mechanisms by which these cytokines act are linked to the recruitment of effector cells such as macrophages.