Extracellular vesicles are conduits for E. coli heat-labile enterotoxin (LT) and the B-subunits of LT and cholera toxin in immune cell-to-cell communication.

Several pathogens excrete their toxins either directly into the host or through extracellular vesicles. Enterotoxigenic E. coli is capable of secreting heat-labile toxin LT in extracellular vesicles (EVs) which are delivered to mammalian cells. LT and its B-subunit, LTB, and their structurally and functionally related toxin from Vibrio cholerae, CT and CTB, are potent immunogens and adjuvants. However, despite their reported remarkable effects on immune cells, the mechanisms by which they mediate their immunological properties are still unclear. We show that B cells incubated with LT or LTB secreted EVs in the cell culture medium. However, compared to unstimulated cells, EVs and their internal protein content were significantly reduced in recipient B cells. Analysis of protein markers of the vesicles secreted by B cells were found to be enriched in exosomes of endosomal origin. B cells incubated with FITC-CTB secreted CTB in EVs which were taken up by recipient B and T cells. FITC-CTB transfected into exosomes from mouse dendritic cells were also taken up by recipient B cells. Moreover, B cells incubated with FITC-CTB secreted CTB in EVs which increased the number of recipient B cells expressing higher levels of CD25 and CD86. These results suggest that EVs from B cells are conduits for the enterotoxins, and play an important role in the enterotoxins immune cell-to-cell communication. This is the first report which looked at EVs as a mean to deliver these proteins from and to immune cells.

Role of fathers in overweight prevention: an analysis of a Caribbean cohort

OBJECTIVE: To investigate the role of parental characteristics and maternal perceptions of ways fathers might influence risk of overweight in Caribbean infants. DESIGN AND METHODS: Data from participants in a three island parenting intervention study were analyzed. Maternal and paternal characteristics were obtained by questionnaire at enrolment (infant age 6-10 weeks). At 18 months, 501 infants (82.9% of cohort) had weight and length measured using standardized methods and body mass index (BMI-Z scores) calculated. Participants with Z scores ≥1 were classified as at risk of overweight. Multi-level logistic regression analyses were utilized to assess the effect of parents’ characteristics on the risk of infant overweight. Additionally data from 4 focus group discussions among mothers with infants (6 - 24 months) in Jamaica were used to explore how any effects might be mediated. RESULTS: Overall 20.6% of the children were classified as at risk of overweight. The father was present in 52% of households. Fathers’ presence and higher paternal occupation level were associated with reduced risk of overweight after controlling for maternal age, education, occupation, receptive vocabulary and SES score. The presence of the father in the home (OR[95% CI] =0.78 (0.62 - 0.99)) decreased the odds of overweight in these infants. From focus group discussions mothers reported that the majority of fathers encouraged breastfeeding, healthier meal choices and discouraged use of unhealthy snacks. CONCLUSION: More information on paternal characteristics should be collected in future studies of childhood obesity. Interventions to address childhood overweight should include fathers as part of the strategy.

Turn off the TV?: attitudes towards TV-viewing and childhood obesity in Jamaican mothers

OBJECTIVE: TV-viewing has been associated with childhood obesity and reducing screen time might help address this epidemic in Caribbean children. We explored the attitudes and beliefs of Jamaican mothers on the impact of television viewing on childhood obesity. DESIGN AND METHODS: Community health aides recruited mothers, 18 years and older with children aged 6-24 months, from four primary care clinics in Jamaica. Four focus group discussions (2 rural and 2 urban) were conducted using a semi-structured interview guide. Audio recordings and field notes from discussions were collected by field investigators. Transcripts were reviewed by study investigators and immersion/crystallization techniques were used to identify emerging themes. RESULTS: the mothers had a mean age of 28.26 ñ 6.25 years and 63% were unemployed. Parenting decisions were made based on instinct developed through experience, example and external input (friends, family, community and media) and information not consistent with this instinct was not readily accepted. Among the risk factors for obesity identified by mothers, TV-viewing was not perceived as important. The causal link between TV-viewing and obesity in young children was unclear to mothers. The perceived benefits from TV-viewing on their child’s development outweighed any potential harm and strong evidence would be required to convince them otherwise. CONCLUSION: Jamaican mothers may not easily accept obesity interventions that discourage TV-viewing. Incorporating evidence from credible sources, and interventions focused on healthy growth and development using examples of children developing optimally without the aid of TV, may overcome this perception.

Mamas voices, mamas choices: understanding maternal beliefs that drive decision making around feeding practices which influence childhood obesity

OBJECTIVE: To explore the beliefs shaping maternal decision-making around feeding practices in early childhood in a subset of Jamaican mothers from rural and urban communities. DESIGN AND METHODS: Focus group discussions guided by semi-qualitative questionnaires were conducted with thirty mothers of infants 6-24 months recruited from health clinics in 2 urban and 2 rural Jamaican communities. Data from discussions transcribed from audio recordings and field notes were categorized and interpreted using pre-set themes through an iterative process to identify emergent themes. Analysis was guided by the Theory of Reasoned Action embedded in the Socio-Ecological Perspective. RESULTS: Rural and urban mothers’ beliefs, and by extension their actions, were influenced by (a) their instincts, (b) their accepted knowledge (from personal and observed experience, credible professional input, and personal experimentation), (c) cultural norms (i.e. views of body weight/health relationship and visual perceptions of ‘healthy’); (d) input of experienced family members; and (e) their accepted concept of infants’ innate ability to express needs. Additionally, rural mothers’ beliefs were influenced by non-family social networks. For all mothers, the use of growth charts in portable health records and reliance on specific local television programs with health segments for health information was salient. The latter presents a unique tool for potentially building maternal confidence for healthy feeding practices. CONCLUSION: Early childhood food choices are predominantly dictated by parental belief-driven actions. Effective interventions targeting the impact of maternal feeding practices on childhood obesity should incorporate supportive, credible professional input, address how and what knowledge influences individual beliefs, increase community-wide knowledge, and target cultural norms.

Adherence of academic geriatric practitioners to osteoporosis screening guidelines.

OBJECTIVES: To examine the bone mineral density (BMD) testing habits of geriatricians and geriatric fellows at the University of Connecticut fellowship training program to evaluate their adherence screening guidelines. DESIGN: Retrospective chart review. SETTING: University based academic geriatric practice in Farmington, CT. PARTICIPANTS: Chart review of two hundred female patients over age 65 under care of seven faculty geriatricians and eight geriatric fellows in training. MEASUREMENTS: Data collected included BMD testing status, patient's osteoporosis risk factors and functional status. RESULTS: Physicians ordered BMD tests in 151 (76%) patients; 128 (64%) had a bone mineral density test within three years. A personal history of fracture was the only osteoporosis risk factor that correlated to higher rates of osteoporosis testing. Physicians were more likely to order BMD screening in younger patients (92% in 65-74 vs. 74% in ages 85+, P=.031), patients independent in activities of daily living (72% vs. 32, P=.002), and patients without dementia (70% vs.37%, p=.007). BMD testing results found 82% with osteopenia or osteoporosis. CONCLUSIONS: A geriatric group that is highly attuned to bone health demonstrated more optimal adherence to OP testing guidelines for all "at-risk" older women and better than reported previously. Functional status more strongly predicted BMD testing than osteoporosis risk factors. This study suggests that with improved physician education and familiarity with the disease, high rates of BMD testing for earlier identification of geriatric patients at risk for osteoporosis are achievable.

Carcinoma in situ and tumor multifocality predict the risk of prostatic urethral involvement at radical cystectomy in men with transitional cell carcinoma of the bladder.

PURPOSE: Determining which patients are at risk for prostatic urethral involvement of urothelial carcinoma may alter assessment of the prostatic urethra before radical cystectomy and ultimately influence the choice of urinary diversion. We determined risk factors predictive of prostatic urethral involvement using preoperative bladder tumor characteristics in male patients who underwent radical cystoprostatectomy due to urothelial carcinoma of the bladder. MATERIALS AND METHODS: We reviewed 192 consecutive radical cystectomy specimens from men with transitional cell carcinoma from June 1995 to June 2000. The prostatic urethra in each specimen was analyzed and urethral involvement was characterized as carcinoma in situ, intraductal invasion or prostatic stromal invasion. We then examined which clinical bladder tumor characteristics correlated with the incidence and extent of prostatic urethral involvement by performing multiple variable analysis. RESULTS: Prostatic urethral involvement was evident in 30 of the 192 patients (15.6%). Of the 80 patients with carcinoma in situ in the bladder 25 (31.3%) had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.5%) of the 112 with no evidence of carcinoma in situ had prostatic urethral involvement. Likewise 25 of the 72 patients (34.7%) with multifocal tumors had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.2%) of the 120 with no evidence of multifocality had prostatic urethral involvement. In the multiple variable logistic regression model the odds of prostatic urethral involvement were 12 and 15-fold greater when carcinoma in situ and tumor multifocality were present, respectively. CONCLUSIONS: Carcinoma in situ and/or tumor multifocality are valuable prognostic indicators of prostatic urethral involvement. However, in their absence prostatic urethral involvement was rare. Ultimately the extent of prostatic urethral involvement may influence decisions, such as the choice of urinary diversion and need for urethrectomy, in men undergoing radical cystectomy.

Variability of results of cavernous nerve stimulation during radical prostatectomy.

PURPOSE: We assess the reliability of intraoperative cavernous nerve stimulation for producing an erectile response during radical prostatectomy. MATERIALS AND METHODS: In 61 patients cavernous nerve function was assessed during radical retropubic prostatectomy using a CaverMap nerve stimulator. Control stimulation was also performed before and after prostatic dissection by placing the nerve stimulator tip on the anterior bladder wall. An increase in penile circumference measured by the device was considered a tumescence response while any measurable detumescence was also categorized. RESULTS: Patient age ranged 43 to 72 years (mean 59.8). Before apical dissection 41% and 46% had tumescence, 31% and 21% had detumescence, and 28% and 33% had no response with stimulation of the neurovascular bundle and anterior bladder wall, respectively. After dissection 42% and 25% had tumescence, 16% and 18% had detumescence, and 42% and 57% had no response with stimulation of the neurovascular bundle and anterior bladder wall, respectively. CONCLUSIONS: A response to neurovascular bundle stimulation using this device does not necessarily correlate with the precise anatomical location of the cavernous nerves. There is considerable background variability related to anesthesia, surgical manipulation and other undefined factors that may cause minor but measurable changes in penile circumference.

The Missing Link: Early Methane ("T") Dwarfs in the Sloan Digital Sky Survey.

We report the discovery of three cool brown dwarfs that fall in the effective temperature gap between the latest L dwarfs currently known, with no methane absorption bands in the 1-2.5 µm range, and the previously known methane (T) dwarfs, whose spectra are dominated by methane and water. The newly discovered objects were detected as very red objects in the Sloan Digital Sky Survey imaging data and have JHK colors between the red L dwarfs and the blue Gl 229B-like T dwarfs. They show both CO and CH(4) absorption in their near-infrared spectra in addition to H(2)O, with weaker CH(4) absorption features in the H and K bands than those in all other methane dwarfs reported to date. Due to the presence of CH(4) in these bands, we propose that these objects are early T dwarfs. The three form part of the brown dwarf spectral sequence and fill in the large gap in the overall spectral sequence from the hottest main-sequence stars to the coolest methane dwarfs currently known.