Internally Displaced “Victims of Armed Conflict” in Colombia: The Trajectory and Trauma Signature of Forced Migration

While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement.     

Mother-to-Child Transmission of Chagas Disease in El Salvador

To estimate the incidence (any mother to child) and rate (from seropositive mother to child) of mother-to-child transmission of Trypanosoma cruzi, a serological census was conducted, targeting pregnant women and infants born to seropositive mothers, in four municipalities of El Salvador. Of 943 pregnant women, 36 (3.8%) were seropositive for T. cruzi. Of 36, 32 proceeded to serological tests of their infants when they became 6–8 months of age. Six infants seropositive at the age of 6–8 months further proceeded to second-stage serological test at the age of 9–16 months. As the result, one infant was congenitally infected. Thus, serological tests at the age of 6–8 months produced five false positives. To ensure earlier effective medication only for true positives, identification of seropositive infants at the age of 9–16 months is crucial. Incidence and rate of mother-to-child transmission were 0.14 (per 100 person-years) and 4.0%, respectively. Estimated number of children infected through mother-to-child transmission in El Salvador (170 per year) was much higher than that of human immunodeficiency virus (HIV; seven per year). It is recommended that serological testing for T. cruzi be integrated into those for HIV and syphilis as part of antenatal care package.     

CD8+-dependent CNS demyelination following ocular infection of mice with a recombinant HSV-1 expressing murine IL-2

Demyelinating diseases comprise a spectrum of immunopathologic syndromes in which myelin, the fatty covering of nerve cell fibers in the brain and spinal cord, is destroyed. In this study, we have shown for the first time that ocular infection of BALB/c mice with a recombinant herpes simplex virus type 1 (HSV-1) expressing IL-2 (HSV-IL-2) results in CNS demyelination as determined by light microscopy and EM. The demyelinated lesions involve periventricular white matter, brain stem, and spinal cord white matter. Demyelination was detected in the CNS of infected mice up to 75 days (the longest time point tested) post HSV-IL-2 infection. In contrast, mice infected with HSV-IFN-gamma or HSV-IL-4, which are identical to HSV-IL-2 but express IFN-gamma or IL-4 instead of IL-2, did not exhibit demyelination. Control mice infected with wild-type HSV-1 or parental virus also remained free of these symptoms. During early times (days 3-7), post-infection with HSV-IL-2 virus, a T(H)1 + T(H)2 pattern of cytokines was produced by lymphocytes of infected mice while mice infected with HSV-IFN-gamma or control viruses produced a T(H)1 pattern of cytokine. By day 21 post-infection, all infected groups exhibited a T(H)1 pattern of response. Immunohistochemistry and FACS analyses of infiltrates in the brains and spinal cords of HSV-IL-2-infected mice showed elevations in CD4+ and CD8+ T cells and macrophages. However, T cell depletion studies suggest that only central memory CD8+ T cells are directly involved in the demyelination process, with macrophages being involved through a bystander effect.     

Maternal activating mutation of the calcium-sensing receptor: implications for calcium metabolism in the neonate

Two infants were studied born of a mother with autosomal dominant hypocalcemia who is heterozygous for an activating mutation in the calcium-sensing receptor gene. Both infants had serum calcium levels in the low-normal range and parathyroid hormone levels in the high-normal range and were healthy. The mother's hypocalcemia had been treated with calcium carbonate and calcitriol and she has nephrocalcinosis and mild renal insufficiency. By genetic testing, both infants were shown to have normal calcium-sensing receptor gene alleles, i.e., they had not inherited the activating mutation from their mother. This provided reassurance to the family and ensured that treatment to correct apparent hypocalcemia would not be necessary. The fact that the infants had high normal parathyroid hormone levels with normal calcium may be due to the fact that with a normal calcium-sensing receptor their parathyroid glands responded in utero to the maternal hypocalcemia with an increase in parathyroid hormone.     

Improved protection from primary ocular HSV-1 infection and establishment of latency using multigenic DNA vaccines

PURPOSE: To compare the effectiveness of immunization with "naked" DNA corresponding to the genes encoding five HSV-1 glycoproteins, gB, gC, gD, gE, and gI (5gP DNA), with immunization with the five glycoproteins (5gP protein). Also, to compare immunization of 5gP protein in Montanide ISA 720 (SEPPIC, Paris, France), an adjuvant recently approved for use in humans, with immunization of 5gP protein in Freund's adjuvant. METHODS: BALB/c mice were vaccinated with 5gP DNA or 5gP protein emulsified in ISA 720 or Freund's adjuvant. Neutralizing antibody titers were determined by plaque-reduction assays. IL-2, -4, and -12 and IFN-gamma levels were determined by ELISA after in vitro stimulation of spleen cells. After ocular challenge with 2 x 10(5) plaque-forming units [pfu] per eye of HSV-1 strain McKrae, virus replication in the eye, survival, blepharitis, corneal scarring, and latency were determined. RESULTS: Neutralizing antibody titers (approximately 1:800-1:1200), corneal scarring (trace) and survival (100%) were similar for all vaccine groups, including 5gP DNA. Compared with the other vaccine groups, the 5gP DNA group had less ocular virus replication, as judged both by maximum virus titer and time of viral clearance. ISA 720 appeared more effective than Freund's against ocular virus replication and eye disease. The 5gP DNA-vaccinated mice had less blepharitis and latency than any other group and had the highest levels of IL-12 and IFN-gamma. All vaccine groups had similar levels of IL-2. CONCLUSIONS: The 5gP DNA vaccine appeared to be more effective than the corresponding protein subunit vaccine, regardless of adjuvant. Emulsification of the 5gP protein in ISA 720 appeared to be more effective than emulsification in Freund's adjuvant.     

Key apoptotic pathways for heat-induced programmed germ cell death in the testis

Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.