IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques.

Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4(+) T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.

Preparation and characterization of a magnetic and optical dual-modality molecular probe.

Multi-modality imaging probes combine the advantages of individual imaging techniques to yield highly detailed anatomic and molecular information in living organisms. Herein, we report the synthesis and characterization of a dual-modality nanoprobe that couples the magnetic properties of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) with the near infrared fluorescence of Cy5.5. The fluorophore is encapsulated in a biocompatible shell of silica surrounding the iron oxide core for a final diameter of approximately 17 nm. This silica-coated iron oxide nanoparticle (SCION) has been analyzed by transmission electron microscopy, dynamic light scattering, and superconducting quantum interference device (SQUID). The particle demonstrates a strong negative surface charge and maintains colloidal stability in the physiological pH range. Magnetic hysteresis analysis confirms superparamagnetic properties that could be manipulated for thermotherapy. The viability of primary human monocytes, T cells, and B cells incubated with the particle has been examined in vitro. In vivo analysis of agent leakage into subcutaneous A431 tumors in mice was also conducted. This particle has been designed for diagnostic application with magnetic resonance and fluorescence imaging, and has future potential to serve as a heat-sensitive targeted drug delivery platform.

The validity and reliability of EQ-5D health state valuations in a survey of Maori.

This note reports on a 2000 study of the content validity of the EQ-5D's representation of health for 66 Maori (New Zealand's indigenous people, comprising 14.5% of the population) accessed through cultural networks. Also examined was the construct validity of the health state valuation instrument and its test-retest reliability based on repeated valuations for the two extreme health states. The possibility that the EQ-SD fails to capture what Maori regard as 'health' derives from the so-called 'Maori health model' that augments biological health with mental, spiritual and family well-being. Seventy six percent of respondents considered the EQ-5D's representation of health to be adequate. This proportion is not statistically significantly different from the rates for non-Maori and Maori respectively in an earlier study and might suggest the EQ-5D has content validity for Maori. However, the high prevalence of missing valuations, particularly for dead, and logical inconsistencies suggests that the health state valuation instrument lacks construct validity, although there is evidence of test retest reliability.

Ecological validity in assessment of discourse in traumatic brain injury: ratings by clinicians and non-clinicians.

Researchers studying discourse after traumatic brain injury (TBI) increasingly recognize the need to take account of variation within the non-brain-damaged (NBD) population in order to validate their findings. This study investigated the use of ratings by professional clinicians trained in speech pathology (P raters) and by peers of TBI individuals (NP raters) as a method of placing TBI individuals' communication in context. Twenty TBI adults and 20 NBD controls matched for age, sex, education and social background retold a 1400 word story presented on audiotape, following which the narratives were transcribed and segmented. Raters used two 5-point scales, representing independent parameters of Content and Clarity, to rate the transcripts. Statistical analysis demonstrated that P raters tended to give higher ratings across the board than NP raters but that P and NP ratings were also highly correlated. In general, the ratings assigned to the two subject groups overlapped and exhibited an even spread across the range of mean ratings. On the evidence of this study clinicians appear to share perceptions regarding discourse performance with peers of the TBI subjects. In addition, many TBI subjects perform as well or better than NBD controls on high-level tasks.

Structural patterns in conversations with a woman who has autism.

The experience of conversing with a person who has autism is often described as unsatisfactory. This article offers some suggestions as to why that might be. Conversation between an adult diagnosed as autistic and a researcher was transcribed and analyzed using the methodology of Conversation Analysis. The analysis highlights differences in conversational style between the two participants based on features such as topic movement, topic maintenance, repairs, interference from earlier structures and common collocations, overlaps, latching, and pauses. It is suggested that many of the features of the subject's talk which result in an overly repetitive style may be cognitively motivated.

A high prevalence of obesity in a diabetic population: results of a survey of food patterns in 252 patients in a 2 year period.

Dietary patterns were reviewed and correlated with the patients' clinical details in 252 patients seen at the initial visit to a diabetic clinic of a major metropolitan teaching hospital. Except in the subgroup of male patients with insulin-dependent diabetes, there was an extremely high prevalence of obesity, especially in females (70% greater 120% of standard weight; 28% greater than 150%). Traditional 'low-carbohydrate' diets were commonly found irrespective of ethnic origin, particularly in those individuals who had received previous dietary education. This study highlights the urgent need for public health education programmes in order to try to prevent the development of obesity since therapy remains unsatisfactory once it is established.