In vivo detection and automatic analysis of GABA in the mouse brain with MEGA‐PRESS at 9.4 T

The goals of this study were to develop an acquisition protocol and the analysis tools for Meshcher–Garwood point‐resolved spectroscopy (MEGA‐PRESS) in mouse brain at 9.4 T, to allow the in vivo detection of γ‐aminobutyric acid (GABA) and to examine whether isoflurane alters GABA levels in the thalamus during anesthesia. We implemented the MEGA‐PRESS sequence on a Bruker 94/20 system with ParaVision 6.0.1, and magnetic resonance spectra were acquired from nine male wild‐type C57BL/6 J mice at the thalamus. Four individual scans were obtained for each mouse in a 2‐h time course whilst the mouse was anesthetized with isoflurane. We developed an automated analysis program with improved correction for frequency and phase drift compared with the standard creatine (Cr) fitting‐based method and provided automatic quantification. During MEGA‐PRESS acquisition, a single voxel with a size of 5 × 3 × 3 mm³ was placed at the thalamus to evaluate GABA to Cr (GABA/Cr) ratios during anesthesia. Detection and quantitative analysis of thalamic GABA levels were successfully achieved. We noticed a significant decrease in GABA/Cr during the 2‐h anesthesia (by linear regression analysis: slope < 0, p < 0.0001). In summary, our findings demonstrate that MEGA‐PRESS is a feasible technique to measure in vivo GABA levels in the mouse brain at 9.4 T.     

Intergenerational Sex as a Risk Factor for HIV Among Young Men Who Have Sex with Men: A Scoping Review

An emerging body of evidence suggests that intergenerational sexual partnerships may increase risk of HIV acquisition among young men who have sex with men (YMSM). However, no studies have comprehensively evaluated literature in this area. We applied a scoping review methodology to explore the relationships between age mixing, HIV risk behavior, and HIV seroconversion among YMSM. This study identified several individual, micro-, and meso-system factors influencing HIV risk among YMSM in the context of intergenerational relationships: childhood maltreatment, coming of age and sexual identity, and substance use (individual-level factors); family and social support, partner characteristics, intimate partner violence, connectedness to gay community (micro-system factors); and race/ethnicity, economic disparity, and use of the Internet (meso-system factors). These thematic groups can be used to frame future research on the role of age-discrepant relationships on HIV risk among YMSM, and to enhance public health HIV education and prevention strategies targeting this vulnerable population.     

Postnatal maternal cortisol levels predict temperament in healthy breastfed infants

BACKGROUND: The implications of the biologically active elements in breast milk for the breastfed infant are largely unknown. Animal models suggest that ingestion of glucocorticoids during the neonatal period influences fear behavior and modifies brain development. AIMS: To determine the association between postnatal maternal cortisol levels and temperament in breastfed infants. STUDY DESIGN: The relation between maternal cortisol and infant temperament was examined in breastfed and formula-fed infants. Plasma cortisol was used as a surrogate measure for breast milk cortisol levels (plasma and milk levels are correlated in the 0.6 to 0.7 range; [Patacchioli FR, Cigliana G, Cilumbriello A, Perrone G, Capri O, Alemà GS, et al. Maternal plasma and milk free cortisol during the first 3 days of breast-feeding following spontaneous delivery or elective cesarean section. Gynecologic and Obstetric Investigations 1992;34:159-163.]. If exposure to elevated cortisol levels during infancy influences temperament, then a relation between the two should be found among the breastfed infants, but not among the formula-fed infants. SUBJECTS: Two hundred fifty-three two-month-old infants and their mothers. OUTCOME MEASURES: Fearful temperament assessed with the Infant Behavior Questionnaire [Garstein MR, Rothbart MK. Studying infant temperament via the revised infant behavior questionnaire. Infant Behavior and Development 2003;26:64-86]. RESULTS: Among the breastfed infants, higher maternal cortisol levels were associated with reports of increased infant fear behavior (partial r=0.2; p<0.01). This relation did not exist among the formula-fed infants. Negative maternal affect at the time of assessment did not account for the positive association in the breastfed group. CONCLUSIONS: The findings are consistent with our proposal that exposure to cortisol in breast milk influences infant temperament. Biologically active components in breast milk may represent one avenue through which the mother shapes the development of the human infant during the postnatal period.     

In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes

Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were further identified as apoptotic in terms of active caspase-3 and DNA fragmentation assayed in situ. FACS analysis indicated that the apoptotic thymocytes are at an early double-positive stage and results with mice mutant for the Fas gene showed that the Fas-Fas ligand system is not involved. Comparison of BA/10 and BA/2 cells showed that the former, but not the latter, can be induced to express CDR-1 antigen which is characteristic of cortical epithelial thymic stroma and constitutively express DEC-205, a surface protein common to cortical thymic epithelium and dendritic cells. Antibody NLDC-145 that is specific for the DEC-205 protein strongly reduced the number of stromal cells with bound apoptotic thymocytes. Preincubation of thymocytes in dexamethasone dramatically increased the number of bound apoptotic cells, indicating that the thymic cortical epithelial cells can participate in clearance of apoptotic thymocytes through involvement of DEC-205.     

Jagged-1hi or Delta-1hi thymic stromal cell populations can trigger acquisition of Thy-1 and loss of B220

Effects of endogenous Notch ligands Jagged-1 and Delta-1 on maturation markers in adult mouse lymphocytes were checked in vitro on putative thymocyte precursors from bone marrow and on DN3 cells from the thymus. Both populations were cocultured with stromal cells (Small M, Histochem Cell Biol 2005;123:513) naturally expressing high levels of either Jagged-1 or Delta-1. Initially the bone marrow cells were Thy-1.2(neg) while the majority were B220(hi). These trends were reversed by culture on both the Jagged-1(hi) and Delta-1(hi) monolayers. Then DN3 thymocytes were cultured with stroma expressing these two ligands and the T cell receptor beta chain was expressed more clearly after coculture on Delta-1(hi) stroma. These findings indicate that stromal cells with endogenous Jagged-1 as well as Delta-1 could initiate early changes toward T cell commitment while Delta-1 favored later alphabeta-TCR development.     

Signatures of emotional face processing measured by event-related potentials in 7-month-old infants

The ability to distinguish facial emotions emerges in infancy. Although this ability has been shown to emerge between 5 and 7 months of age, the literature is less clear regarding the extent to which neural correlates of perception and attention play a role in processing of specific emotions. This study's main goal was to examine this question among infants. To this end, we presented angry, fearful, and happy faces to 7-month-old infants (N = 107, 51% female) while recording event-related brain potentials. The perceptual N290 component showed a heightened response for fearful and happy relative to angry faces. Attentional processing, indexed by the P400, showed some evidence of a heightened response for fearful relative to happy and angry faces. We did not observe robust differences by emotion in the negative central (Nc) component, although trends were consistent with previous work suggesting a heightened response to negatively valenced expressions. Results suggest that perceptual (N290) and attentional (P400) processing is sensitive to emotions in faces, but these processes do not provide evidence for a fear-specific bias across components.     

Cytotoxic and proliferative T-cell clones with antidonor reactivity from a patient transplanted for severe combined immunodeficiency disease

Patients who have become split lymphoid chimeras (T cells of donor origin, B cells and monocytes of host origin) following transplantation of HLA-haploidentical marrow for the treatment of severe combined immunodeficiency disease provide a unique model for the study of tolerance. One such patient, UPN 345, was transplanted with maternal marrow and was found to have antidonor proliferative reactivity without detectable donor-directed cytotoxicity when tested at 18, 23, and 66 mos following bone marrow transplantation. In bulk culture, the proliferation to donor cells could be blocked by monoclonal antibodies to HLA-DR and -DQ. Nine clones with antidonor reactivity were established by limiting dilution techniques from a mixed lymphocyte culture between engrafted T cells and irradiated donor E rosette-negative cells. All of the clones were of maternal donor origin, and all were CD3+CD4+CD8-. The clones were tested for proliferative and cytotoxic activity toward donor, host, and paternal B-lymphoblastoid cell lines (B-LCL). Six clones proliferated strongly to maternal B-LCL but not to host B-LCL. Six clones were found to exclusively lyse maternal B-LCL. Four of the clones had both antidonor cytotoxic and antidonor proliferative reactivity. Monoclonal antibody blocking studies were performed on five of the six clones with cytotoxic activity. The antidonor cytotoxicity was not inhibited by monoclonal antibodies to class I determinants; however, three clones were inhibited in the presence of monoclonal antibody to DR, one clone was inhibited by anti-DQ monoclonal antibody, and one clone was inhibited by anti-DP monoclonal antibody. The cytotoxicity of all five clones was inhibited by monoclonal antibody to CD4. These data indicate that antidonor reactivity may also include a cytotoxic component which is not apparent in bulk cultures and which, based on our limiting dilution studies, is probably controlled by regulatory cells. Both the antidonor cytotoxicity and the antidonor proliferation appear to be directed primarily toward donor HLA class II antigens that are not shared with the patient.     

Impact on treatment time of MRI-based brachytherapy in two implants (4 doses) compared with CT-based brachytherapy in five implants for cervical cancer

Purpose

Concurrent chemoradiotherapy and brachytherapy is the standard of care for locally advanced cervical cancer. Brachytherapy is an integral part of treatment and has improved overall survival. Research is needed to ascertain the planning modalities and schedules to best use resources and optimize treatment time course. We hypothesized that MRI-based brachytherapy when delivered with the described regimen would not prolong, and potentially shorten, overall treatment time as compared with CT-based brachytherapy.

History of Major Depressive Disorder Prospectively Predicts Worse Quality of Life in Women with Breast Cancer

Background

Data are scarce about whether past history of major depressive disorder in the absence of current depression places breast cancer patients at risk for worse quality of life.

Purpose

The current study prospectively examined quality of life during chemotherapy in breast cancer patients with a history of resolved major depressive disorder (n?=?29) and no history of depression (n?=?144).

Methods

Women with Stages 0?CII breast cancer were assessed prior to and at the completion of chemotherapy. Major depressive disorder was assessed via structured interview and quality of life with the SF-36.

Results

Patients with past major depressive disorder displayed greater declines in physical functioning relative to patients with no history of depression (p????0.01).

Conclusions

Findings suggest that breast cancer patients with a history of resolved major depressive disorder are at increased risk for declines in physical functioning during chemotherapy relative to patients with no history of depression.