Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis

A thorough understanding of the early natural history of cystic fibrosis (CF) lung disease is critical for the development of effective interventions in the youngest patients. We assessed the evolution of pulmonary infection, inflammation, and clinical course among 40 infants over a 2-year period through annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti-inflammatory cytokines, semiannual infant pulmonary function testing, and quarterly clinical evaluations. Both the prevalence of CF pathogens and their density in BAL fluid increased with age. Infants had neutrophilic lower airway inflammation and elevated IL-8 concentrations independent of whether CF pathogens were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations increased with density of CF pathogens in BAL fluid, whether the isolated organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar in CF subjects and non-CF historical controls. Infants generally had suboptimal growth (low weight and height percentiles) and obstructive lung disease (decreased expiratory flows and air trapping). Subjects from whom CF pathogens were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield chest X-ray scores. Our findings provide a foundation for future studies of early intervention in CF lung disease, including antimicrobial and anti-inflammatory therapy.     

Dendritic cell-activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8(+) T cell-dependent mouse model of human GVHD, we found that host dendritic cell (DC)-induced CD44(hi)CD8(+) effector/memory T cells were functionally defective in inducing GVHD, whereas CD44(lo)CD8(+) naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44(lo)CD8(+) T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44(lo)CD8(+) T cells, CD44(hi)CD8(+) T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8(+) T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.     

Decreased hematopoietic accessory cell function following bone marrow transplantation

Hematologic engraftment following bone marrow transplantation requires not only pluripotent stem cells but also functioning accessory cells whose trophic factors support the proliferation and differentiation of stem cells and progenitors to mature blood cells. To better understand the regulation of hematopoiesis following transplantation, we studied hemopoietic accessory cell function in bone marrow transplant recipients 3 weeks to 10 months following transplantation. In general, hematopoietic accessory cell function was decreased following bone marrow transplantation. Sequential fractionation of accessory cells demonstrated that adherent cells often produced near-normal functional burst-promoting activity (BPA) and granulocyte-macrophage colony-stimulating activity (GM-CSA), but Fc receptor-positive (Fc+) cells and T cells uniformly produced greatly reduced BPA and GM-CSA, as compared to transplant donor cells. This cellular deficiency was corrected by soluble burst-promoting activity and granulocyte-macrophage colony-stimulating activity and so appeared to be due to the failure of accessory cells to produce trophic hormones. Limiting-dilution analysis (LDA) for proliferating T-cell precursors demonstrated a greatly reduced frequency in phytohemagglutinin-responsive cells, supporting the role of deficient hematopoietic growth factor production by activated T cells in transplant recipients. This hemopoietic accessory cell defect may thus reflect more generalized lymphocyte dysfunction in these patients. Hematopoiesis following bone marrow transplantation appears to rely upon growth factors released by accessory cells in the adherent layer.     

Perigeniculate arachnoid cysts and CSF fistulae of the fallopian canal: Histopathologic correlates of a rare clinical entity

Cerebrospinal fluid (CSF) fistulae originating from the fallopian canal of the facial nerve is hypothesized to arise due to atypical patterns of subarachnoid space extension into the geniculate ganglion or more distal regions along the intratemporal course of the facial nerve, but its pathogenesis remains poorly understood. Although a rare etiology of CSF fistulae of the temporal bone, there are significant clinical ramifications due to the risk of recurrent meningitis, difficulty in identifying the anatomic location of the CSF leak, and technical challenges associated with surgical repair. We present three clinical cases of arachnoid cysts within the geniculate fossa with or without CSF fistulization and provide histopathologic correlates of this rare clinical phenomenon from a human temporal bone collection. The pediatric and adult patients presented suggest differential pathophysiologic mechanisms associated with CSF fistulae. Temporal bone histology reveals atypical patterns of subarachnoid space extension in the fallopian canal that may underlie arachnoid cyst formation and overt CSF leak from the geniculate region.     

Weight loss behaviors in Brazilian mixed martial arts athletes

Sport Sciences for Health - The aim of this study was to investigate the weight loss behaviors among Brazilian professional mixed martial arts (MMA) athletes. One hundred and seventy nine Brazilian...     

Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice

Parasitology Research - Toxoplasmosis is a zoonosis of worldwide distribution. Currently, two drugs, pyrimethamine and sulfadiazine, are used as a reference in the treatment of toxoplasmosis, but...     

CHALLENGING BEHAVIOUR AND COMMUNITY SERVICES: 5. Structuring staff and client activity

This paper describes important programmatic components of small, community based, residential services for people with severe mental handicaps and challenging behaviours. The approach described advocates the use of procedures to plan staff activity in considerable detail in order to achieve goals in the areas of supporting people's engagement in functional, age-appropriate activities and managing inappropriate behaviour.     

Assessment of the effects of skin microneedling as adjuvant therapy for facial melasma: a pilot study

Background

Melasma is a common chronic and relapsing acquired dyschromia. Skin microneedling was reported resulting sustained long-term improvement of recalcitrant melasma, however, the exact mechanism that promotes this skin lightening is not known. This study aimed to investigate clinical and histologic alterations promoted by skin microneedling in facial melasma.

Methods

Open pilot trial including six women with facial refractory melasma submitted to two sessions of microneedling (1.5 mm) each 30 days followed by daily triple combination and broad-spectrum sunscreen. Comparison of pretreatment (T0) and 15 days after last microneedling procedure (T45) was made by standardized pictures, skin colorimetry, MASI, MELASQoL and histological parameters (haematoxylin-eosin, picrosirius-red, periodic acid Schiff and Fontana-Masson staining).

Results

The age of the subjects varied from 34 to 46 years-old, the phototypes were III and IV (Fitzpatrick), and age of melasma onset was 20 to 38 years. Improvement of melasma was perceived in all subjects. There was a significant reduction of MASI score (?70%), MELASQoL (?55%) and increase in L* (+13%) colorimetric value (p <?0.03). All cases evidenced epithelium thickening, decrease in melanin pigmentation and densification of upper dermis collagen (p =?0.03). Patients were followed by 6 months under broad-spectrum sunscreen and triple combination without relapse.

Conclusion

In addition to classic treatment (broad-spectrum sunscreen and triple combination), skin microneedling promoted clinical and histological improvement of refractory facial melasma.