Alpha7-acetylcholine receptor antibodies in two patients with Rasmussen encephalitis

Rasmussen encephalitis (RE) sera were screened for antibodies to human alpha7 nicotinic acetylcholine receptors (nAChRs) using electrophysiology, calcium imaging, and ligand binding assays. Sera from two of nine patients with RE blocked ACh-induced currents through alpha7 nAChRs and the ACh-induced rise in intracellular free calcium ([Ca2+]i) and inhibited (125)I-alpha-bungarotoxin binding in cells expressing alpha7 nAChRs. Thus, the alpha7 nAChR is a potential target for pathogenic antibodies in patients with RE.     

The Effects on Health Behavior and Health Outcomes of Internet-Based Asynchronous Communication Between Health Providers and Patients With a Chronic Condition: A Systematic Review

Background

In support of professional practice, asynchronous communication between the patient and the provider is implemented separately or in combination with Internet-based self-management interventions. This interaction occurs primarily through electronic messaging or discussion boards. There is little evidence as to whether it is a useful tool for chronically ill patients to support their self-management and increase the effectiveness of interventions.

Objective

The aim of our study was to review the use and usability of patient-provider asynchronous communication for chronically ill patients and the effects of such communication on health behavior, health outcomes, and patient satisfaction.

Methods

A literature search was performed using PubMed and Embase. The quality of the articles was appraised according to the National Institute for Health and Clinical Excellence (NICE) criteria. The use and usability of the asynchronous communication was analyzed by examining the frequency of use and the number of users of the interventions with asynchronous communication, as well as of separate electronic messaging. The effectiveness of asynchronous communication was analyzed by examining effects on health behavior, health outcomes, and patient satisfaction.

Results

Patients’ knowledge concerning their chronic condition increased and they seemed to appreciate being able to communicate asynchronously with their providers. They not only had specific questions but also wanted to communicate about feeling ill. A decrease in visits to the physician was shown in two studies (P=.07, P=.07). Increases in self-management/self-efficacy for patients with back pain, dyspnea, and heart failure were found. Positive health outcomes were shown in 12 studies, where the clinical outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced expiratory volume [FEV]) improved. Physical symptoms improved in five studies. Five studies generated a variety of positive psychosocial outcomes.

Conclusions

The effect of asynchronous communication is not shown unequivocally in these studies. Patients seem to be interested in using email. Patients are willing to participate and are taking the initiative to discuss health issues with their providers. Additional testing of the effects of asynchronous communication on self-management in chronically ill patients is needed.     

Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein

The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the “Asp-Ala-Asp-Pro” (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy.     

Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.     

The association between fatal coronary heart disease and ambient particulate air pollution: Are females at greater risk?

The purpose of this study was to assess the effect of long-term ambient particulate matter (PM) on risk of fatal coronary heart disease (CHD). A cohort of 3,239 nonsmoking, non-Hispanic white adults was followed for 22 years. Monthly concentrations of ambient air pollutants were obtained from monitoring stations [PM < 10 microm in aerodynamic diameter (PM10), ozone, sulfur dioxide, nitrogen dioxide] or airport visibility data [PM < 2.5 microm in aerodynamic diameter (PM2.5)] and interpolated to ZIP code centroids of work and residence locations. All participants had completed a detailed lifestyle questionnaire at baseline (1976), and follow-up information on environmental tobacco smoke and other personal sources of air pollution were available from four subsequent questionnaires from 1977 through 2000. Persons with prevalent CHD, stroke, or diabetes at baseline (1976) were excluded, and analyses were controlled for a number of potential confounders, including lifestyle. In females, the relative risk (RR) for fatal CHD with each 10-microg/m3 increase in PM2.5 was 1.42 [95% confidence interval (CI), 1.06-1.90] in the single-pollutant model and 2.00 (95% CI, 1.51-2.64) in the two-pollutant model with O3. Corresponding RRs for a 10-microg/m3 increase in PM(10-2.5) and PM10 were 1.62 and 1.45, respectively, in all females and 1.85 and 1.52 in postmenopausal females. No associations were found in males. A positive association with fatal CHD was found with all three PM fractions in females but not in males. The risk estimates were strengthened when adjusting for gaseous pollutants, especially O3, and were highest for PM2.5. These findings could have great implications for policy regulations.     

Soy milk and dairy consumption is independently associated with ultrasound attenuation of the heel bone among postmenopausal women: the Adventist Health Study-2

Soy milk has become a popular substitute for dairy milk with important health claims. We hypothesized that soy milk, based on its nutrient composition, is comparable to dairy products and, therefore, beneficial for bone health. To test this hypothesis, we examined the benefit of soy milk and dairy products intake on bone health using broadband ultrasound attenuation of the calcaneus. Postmenopausal white women (n = 337) who had completed a lifestyle and dietary questionnaire at enrollment into the Adventist Health Study-2 had their calcaneal broadband ultrasound attenuation measured 2 years later. The association between osteoporosis (defined as a T-score <−1.8) and some dietary factors (soy milk, dairy) and selected lifestyle factors was assessed using logistic regression. In a multivariable model adjusted for demographics, hormone use, and other dietary factors, osteoporosis was positively associated with age (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.06-1.12) and inversely associated with body mass index (OR = 0.91; 95% CI, 0.86-0.97) and current estrogen use (OR = 0.27; 95% CI, 0.13-0.56). Compared with women who did not drink soy milk, women drinking soy milk once a day or more had 56% lower odds of osteoporosis (OR = 0.44; 95% CI, 0.20-0.98; P_trend = .04). Women whose dairy intake was once a day or more had a 62% reduction in the likelihood of having osteoporosis (OR = 0.38; 95% CI, 0.17-0.86; P_trend = .02) compared with women whose dairy intake was less than twice a week. Among individual dairy products, only cheese showed an independent and significant protection (OR = 0.28; 95% CI, 0.12-0.66; P_trend = .004) for women eating cheese more than once per week vs those who ate cheese less than once a week. We concluded that osteoporosis is inversely associated with soy milk intake to a similar degree as dairy intake after accounting for age, body mass index, and estrogen use.