The Effects of Recombinant Human Lactoferrin on Immune Activation and the Intestinal Microbiome Among Persons Living with Human Immunodeficiency Virus and Receiving Antiretroviral Therapy.

Lactoferrin modulates mucosal immunity and targets mechanisms contributing to inflammation during human immunodeficiency virus disease. A randomized placebo-controlled crossover clinical trial of recombinant human (rh) lactoferrin was conducted among 54 human immunodeficiency virus-infected participants with viral suppression. Outcomes were tolerability, inflammatory, and immunologic measures, and the intestinal microbiome. The median age was 51 years, and the median CD4+ cell count was 651/µL. Adherence and adverse events did not differ between rh-lactoferrin and placebo. There was no significant effect on plasma interleukin-6 or D-dimer levels, nor on monocyte/T-cell activation, mucosal integrity, or intestinal microbiota diversity. Oral administration of rh-lactoferrin was safe but did not reduce inflammation and immune activation. Clinical Trials Registration: NCT01830595.

Disclosing an autism diagnosis improves ratings of candidate performance in employment interviews.

LAY ABSTRACT: Employment interviews are challenging for many autistic people, for example, due to difficulties with interpreting questions. Autistic people also have differences in non-verbal communication, such as emotional expression, eye-contact, and gestures, with research showing that these factors negatively affect first impressions. Some studies have shown that perceptions of autistic people are more positive when the person observing them, such as an interviewer, is already aware of their diagnosis. However, previous research has not studied how disclosing one's autism diagnosis affects perceptions of a candidate undergoing a full employment interview. Participants in this study acted as raters, who watched a video of an autistic person undergoing a mock employment interview with a researcher, and then rated their overall impressions of them on factors important to real-world hiring decisions, such as confidence, motivation, and knowledgeability. Prior to watching the interview, raters were either (1) not aware of the interviewee's diagnosis, (2) made aware of their diagnosis, or (3) made aware of their diagnosis and provided with additional information about autism, such as differences in behaviours and communication. The results show that disclosing an autism diagnosis improved ratings compared to not disclosing the diagnosis. Providing additional information about autism alongside the diagnostic label did not improve ratings further. The findings are important for employers and autistic people; employers should consider improving procedures by which autistic people can disclose their diagnosis prior to interview should they wish, and autistic people may wish to consider the potential benefits of disclosing their diagnosis.

Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV).

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

Disruption of brain white matter microstructure in primary Sjögren's syndrome: evidence from diffusion tensor imaging.

OBJECTIVES: The relationship between cognitive symptoms and underlying neuropathology in primary SS (PSS) is poorly understood. We used high-resolution quantitative brain MRI to identify potential structural correlates of cognitive symptoms. METHODS: Subjects completed a comprehensive neuropsychometric evaluation. Imaging was performed on a 3 T MRI scanner with T(1) and proton density-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) sequences. We compared MRI group metrics (impaired PSS, not-impaired PSS and controls) and tested for correlations between DTI results and neuropsychological measurements (significance threshold P = 0.05). RESULTS: Nineteen PSS patients (who met American-European Consensus Group 2002 criteria) and 17 healthy controls completed the cognitive evaluation. MRI scans were performed in six impaired PSS, seven not-impaired PSS and seven controls. No differences were found in regional volumetrics, nor was there a difference in T(2) lesion load between groups. Fractional anisotropy (FA) in the inferior frontal white matter (WM) was lower (P = 0.021) and mean diffusivity higher (P = 0.003) in the impaired PSS relative to the control group. Inferior frontal FA was correlated with cognitive symptoms (P = 0.0064) and with verbal memory (P = 0.0125). CONCLUSIONS: In this exploratory study, frontal region WM microstructure alterations accompanied cognitive symptoms and were associated with mild cognitive impairment in PSS. While additional study is warranted to assess the specificity and stability of these results, DTI could provide novel insight into the pathological processes accompanying the subtle cognitive dysfunction commonly experienced by PSS patients.

A comparison of risk factors for atypical squamous cells and squamous intraepithelial lesions in a sample of US- and African-born HIV-positive women.

Previous research conducted in the USA and Africa has identified human immunodeficiency virus (HIV) infection as a risk factor for women developing squamous intraepithelial lesion (SIL) diagnosis. This study was conducted to compare the odds of a diagnosis of atypical squamous cells (ASCUS) or SIL in a sample of mostly African-born and US-born women (n=275). A greater proportion of US-born women had an ASCUS (68.9%) or SIL (81.3%) diagnosis than African-born women (29.5% ASCUS, 15.6% SIL). After adjusting for age, smoking status, absolute CD4, and a prescription for HIV-antiviral medications, the US-born women had a greater odds of a SIL diagnosis than the African-born women (OR=0.22, 95% CI: 0.06-0.79); no significant differences in ASCUS remained after adjustment. In this sample, proportionately more African-American (55.3%) and white American (51.1%) women smoke tobacco than African-born women (1.9%), explaining, perhaps, some of the difference. We found that an absolute CD4 less than 200, when compared to an absolute CD4 above 500, was highly predictive of a SIL diagnosis (OR=6.31, 95% CI: 2.10-18.93, p-trend <0.01). A prescription for HIV-antiviral medications was not a significant predictor of an ASCUS or SIL diagnosis.

Parents' views and experiences of talking about autism with their children.

The way an autism diagnosis is disclosed to parents has been found to play a crucial role in their acceptance of, and the way they cope with, their child's diagnosis. Yet, research into parents' subsequent experiences of disclosing a diagnosis to their children, and talking to their families about autism more generally, is limited. Using an online survey, the current study examined 558 parents' experiences of talking about autism with their autistic and non-autistic children. Results demonstrated that most parents (n = 379, 67.9%) had told their autistic children about their diagnosis. Despite few parents (n = 163, 20.4%) receiving advice or support regarding the disclosure of the diagnosis, those that had disclosed felt satisfied with the process (n = 319, 84.2%) and felt confident in talking about autism with their children (n = 339, 92.4%). Those who had not told their autistic children about the diagnosis largely planned to discuss this with their child in the future (n = 100, 73.5%), felt confident in doing so (n = 95, 70.9%) and were satisfied with their decision (n = 95, 70.4%). Analysis of open-ended data, using thematic analysis, highlighted the importance of openness and the need to tailor explanations to individual children's needs, while acknowledging that disclosure could often be challenging for parents.

Understanding psychiatrists' knowledge, attitudes and experiences in identifying and supporting their patients on the autism spectrum: online survey.

BACKGROUND: Psychiatrists play a critical role in identifying and supporting their patients on the autism spectrum in the UK, yet little is known about their knowledge, attitudes and experiences in this regard. AIMS: To understand psychiatrists' experiences of working with autistic individuals, their confidence in making diagnostic/management decisions and the factors that affect such decisions. METHOD: A total of 172 psychiatrists took part in an online self-report survey. RESULTS: Most psychiatrists reported receiving useful training on autism and were knowledgeable about the condition, particularly those with a personal connection to autism. Higher confidence in working with autistic patients was linked to greater levels of autism knowledge, experience and training. Several systemic and autism-specific factors were highlighted by psychiatrists, which were felt to challenge their ability to provide effective care and support for their patients on the autism spectrum. CONCLUSIONS: Psychiatrists' views corroborated previous research with the autism community, highlighting the need to co-design services that are accessible, respectful and person-centred. DECLARATION OF INTEREST: I.D. is the Royal College of Psychiatrists' Autism Champion.

Physical activity intervention in an academic setting: focus group results.

The purpose of this study was to elicit beliefs and attitudes about increasing physical activity in the workplace among staff and faculty in an academic setting as the first phase of a three-phase pilot study. Focus groups were conducted using the Theory of Planned Behavior as the basis for exploratory questions regarding workplace physical activity. The responses were tallied and themes emerged from the qualitative analysis. The primary themes indicated that physical activity at work would be beneficial because it could allow for more free time at home. However, it would not be advantageous if it took time away from work or conflicted with supervisors' needs. Differences in the likelihood of participation in a physical activity program were noted between staff and faculty. It was clear that successful design and implementation of the program needed the support of all employees in the school.

Circulating levels of tissue factor microparticle procoagulant activity are reduced with antiretroviral therapy and are associated with persistent inflammation and coagulation activation among HIV-positive patients.

Activation of coagulation pathways may contribute to risk for non-AIDS-related conditions among HIV-positive patients. Tissue factor (TF)-dependent procoagulant activity on circulating microparticles (MP-TF) in the plasma of 163 HIV-positive participants, both untreated and treated, with viral suppression was measured. MP-TF activity was 39% lower among treated versus untreated participants (P < 0.001), which persisted in adjusted models (-36%, P = 0.03). Among treated participants, MP-TF activity correlated modestly with D-dimer (r = 0.24, P = 0.01), von Willebrand factor (r = 0.36, P < 0.001), and interleukin-6 (r = 0.20, P = 0.04) levels. Future research should focus on mechanisms driving residual functional TF activity and whether these alterations have clinical consequences for non-AIDS-defining complications.

Addressing smoking during medical visits: patients with human immunodeficiency virus.

BACKGROUND: Tobacco use, especially cigarette smoking, is prevalent in patients with HIV and is associated with increased morbidity and mortality. The HIV patient-provider interaction about cigarette smoking is not well understood. PURPOSE: Assess HIV provider attitudes and practices regarding smoking-related services and interventions for patients with HIV and explore patient-provider interactions regarding cigarette smoking from the perspective of people with HIV. METHODS: A one-time survey about provider attitudes and practices regarding smoking among patients with HIV was completed by 92 HIV providers in 2010-2011. Additionally, a semi-structured interview was conducted in 2010 with 32 patients with HIV who smoke about their attitudes toward smoking and patient-provider interactions. The data were analyzed in 2010-2011. RESULTS: Providers and patients reported frequent assessment of smoking during clinic appointments. The most common smoking-related services that providers reported included delivering brief advice to quit or reduce smoking, suggesting the use of nicotine replacement products, and providing smoking-cessation print materials to patients. Greatest barriers to providing smoking interventions in the context of HIV medical care appear to be lack of time, providers feeling insufficiently confident to address smoking, and the perception by patients that providers who did not push them to quit are more understanding. Approximately half of physicians expressed interest in seeking additional education to address cigarette smoking among their patients. CONCLUSIONS: Numerous smoking-related services occur in the context of HIV medical encounters. However, patient-provider relationship factors and time restrictions represent major barriers to effective intervention for this complex health problem.

Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial.

BACKGROUND: Treatments that reduce inflammation and cardiovascular disease (CVD) risk among individuals with HIV infection receiving effective antiretroviral therapy (ART) are needed. DESIGN AND METHODS: We conducted a 2 × 2 factorial feasibility study of lisinopril (L) (10 mg daily) vs L-placebo in combination with pravastatin (P) (20 mg daily) vs P-placebo among participants receiving ART with undetectable HIV RNA levels, a Framingham 10 year risk score (FRS) ≥ 3%, and no indication for ACE-I or statin therapy. Tolerability and adherence were evaluated. Longitudinal mixed models assessed changes in blood pressure (BP), blood lipids, and inflammatory biomarkers from baseline through months 1 and 4. RESULTS: Thirty-seven participants were randomized and 34 [lisinopril/pravastatin (n=9), lisinopril/P-placebo (n=8), L-placebo/pravastatin (n=9), L-placebo/P-placebo (n=8)] attended at least one follow-up visit. Participants were 97% male, 41% white, 67% were current smokers, and 65% were taking a protease inhibitor. Median age was 48 years, CD4 count 483 cells/mm(3), FRS 7.79%, total cholesterol 184 mg/dL, and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol, LDL-C, or any of the inflammatory biomarkers. Participants randomized to lisinopril vs. L-placebo had significant declines in diastolic BP (-3.3 mmHg, p=0.05), hsCRP (-0.61 µg/mL, p=0.02) and TNF-α (-0.17 pg/mL, p=0.04). Participants taking lisinopril vs L-placebo were more likely to report missed doses (88 vs 35%; p=0.001) and have adherence <90% by pill count (42 vs. 0%; p=0.02). Few participants from either group reported side effects (n=3 vs. n=1). CONCLUSIONS: The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin. Our results also indicate that ACE-I therapy may have anti-inflammatory benefits for ART-treated persons with HIV infection and this should be further evaluated. TRIAL REGISTRATION: ClinicalTrials.gov NCT00982189.

Association of depressive symptoms and social support on blood pressure among urban African American women and girls.

PURPOSE: The purpose of this study was to explore the associations between depressive symptoms and perceived social support on blood pressure in African American women. DATA SOURCES: This cross-sectional study was conducted among 159 African American women from multiple sites in the Detroit Metro area. CONCLUSIONS: Results from this study found that both higher systolic and diastolic blood pressure were positively associated with higher depressive symptom scores (r= .20 and .18, p < .05). Higher depressive symptoms scores were, in turn, significantly associated with lower social support scores (r=-.44, p < .001). However, total social support scores were not significantly correlated with blood pressure readings. Higher depressive symptom scores were associated with increased systolic blood pressure independent of social support. IMPLICATIONS FOR PRACTICE: Findings of the present study suggest the importance of appropriate social support to help alleviate depressive symptoms. However, to effectively control blood pressure in patients with depressive symptoms, other pathophysiologic mechanisms between depressive symptoms and elevated blood pressures independent of social support should be examined in future research. Future studies should consider a cohort design to examine the temporal relationship of depressive symptoms, social support, and blood pressure readings.