Genetic control of anti-idiotypic vaccination against coronavirus infection

The idiotypic network can be experimentally altered to induce protective immune responses against microbial pathogens. Both internal image and noninternal image anti-idiotypic (anti-Id) antibodies have been shown to trigger antigen (Ag)-specific immune responses. Therefore, mechanisms of anti-Id vaccination appear to go beyond structural mimicry of Ag, but remain undefined. Using the neurotropic murine coronavirus animal model, we have previously shown that a polyclonal noninternal image anti-Id (Ab2) could vaccinate BALB/c mice. To characterize its mode of action, we have examined the immune modulating capability of this Ab2 in vivo in strains of mice with different H-2 haplotypes. Even though only internal image anti-Id are expected to induce non-genetically restricted immunity, this noninternal image Ab2 induced protective immunity in four of eight genetically different strains of mice susceptible to coronavirus infection. These were BALB/c (H-2^d), DBA/1 (H-2^d), DBA/1 (H-2^q), and SWR (H-2^q) mice. Protection was generally correlated with the induction of specific antiviral Ab (Ab3) that showed biological properties, such as virus neutralization in vitro, similar to the initial Ab1. To evaluate the genetic implication of the H-2 haplotypes in protection, congenic mice were also tested. Vaccination profiles suggest that cooperation between background gene(s) of the BALB/c mouse with H-2^d and H-2^q loci is necessary for an optimal protective immune response, although the main genetic element(s) regulating the antiviral response to Ab2 inoculation appeared to be located outside the major histocompatibility complex. These results are consistent with the ability of Ab2 to induce protective antiviral antibodies in genetically different animals by biological mimicry.     

Rare bioparticle detection via deep metric learning

Recent deep neural networks have shown superb performance in analyzing bioimages for disease diagnosis and bioparticle classification. Conventional deep neural networks use simple classifiers such as SoftMax to obtain highly accurate results. However, they have limitations in many practical applications that require both low false alarm rate and high recovery rate, e.g., rare bioparticle detection, in which the representative image data is hard to collect, the training data is imbalanced, and the input images in inference time could be different from the training images. Deep metric learning offers a better generatability by using distance information to model the similarity of the images and learning function maps from image pixels to a latent space, playing a vital role in rare object detection. In this paper, we propose a robust model based on a deep metric neural network for rare bioparticle (Cryptosporidium or Giardia) detection in drinking water. Experimental results showed that the deep metric neural network achieved a high accuracy of 99.86% in classification, 98.89% in precision rate, 99.16% in recall rate and zero false alarm rate. The reported model empowers imaging flow cytometry with capabilities of biomedical diagnosis, environmental monitoring, and other biosensing applications.

Conventional deep neural networks use simple classifiers to obtain highly accurate results. However, they have limitations in practical applications. This study demonstrates a robust deep metric neural network model for rare bioparticle detection.     

Evaluation of atypical human immunodeficiency virus immunoblot reactivity in blood donors

Blood donors reactive by enzyme-linked immunosorbent assay for antibody to the human immunodeficiency virus (HIV) who showed atypical patterns of viral core protein reactivity on Western blot were monitored for several months. Characterization of their antibodies was performed by 1) use of recombinant HIV proteins; 2) determination of cross-reactivity to HTLV-I, HTLV-II, and HTLV-IV: 3) assessment of immune status; and 4) identification of potentially interfering autoantibodies. Nineteen of 20 donors maintained the same HIV antibody reactivity throughout the follow-up period; the other donor became fully antibody-positive. Eighteen of 20 donors' sera showed clear reactivity with HIV recombinant core proteins. Ten of 19 donor samples demonstrated cross-reactivity to HTLV-IV; 3 of these 10 also cross-reacted with HTLV-I. The immune status of all donors was normal, although the medical histories and HLA antibody screens suggested possible autoimmune reactivity in 9 of 18 donors. During follow-up interviews, three donors reported possible risk factors for HIV infection that had not been acknowledged at the time of blood donation. We conclude that exclusion of donors with these atypical serologic test results is warranted while further studies to determine significance are being conducted.     

Use of a New High-Activity Arthroplasty Score to Assess Function of Young Patients With Total Hip or Knee Arthroplasty

The High-Activity Arthroplasty Score (HAAS) was specifically developed to assess subtle variations in functional ability after lower limb arthroplasty with particular regard to highly functioning individuals. The score was a 4-item self-assessment measure covering the 4 domains of walking, running, stair climbing, and general activities, with a possible score ranging from 0 to 18 points. The score was validated in 22 patients (total hip arthroplasty [THA], n = 11; total knee arthroplasty [TKA], n = 11) by comparison with the Oxford, Knee Society, Harris Hip, and Short WOMAC scores. The HAAS was then administered to 152 high-functioning arthroplasty patients (THA, n = 99; TKA, n = 53), all younger than 66 years. The HAAS produced a much wider range of scores, allowing greater differentiation of level of function between patients in assessing performance after TKA or THA.     

Audit of diabetes in a renal transplant population

AIMS: To determine the prevalence of diabetes and its glycemic control in the renal transplant population of northeast England (Newcastle, Sunderland, Middlesborough, and Carlisle). METHODS: All renal transplant notes in northeast England were reviewed. Data on patient details, type of diabetes, time of onset of diabetes, diabetes medications, time of insulin commencement, date of renal transplant, immunosuppressive medications, and HbA(1C) were recorded. RESULTS: Living renal transplant patients (n = 1073) transplanted between March 1982 and November 5, 2003 were identified. One hundred and nine (10.2%) patients had diabetes, of whom 39 were type 1 and 70 were type 2. Median HBA(1C) in patients with type 1 diabetes on tacrolimus was 10.1% +/- 1.94% (SD) versus 7.8% +/- 1.98% (SD) for patients not on tacrolimus. Among patients with type 2 diabetes, 25 had diabetes prior to transplant and 45 (4.5%) developed posttransplant diabetes (PTDM). Those who developed PTDM and were taking tacrolimus were more likely to require insulin for blood glucose control (0.39 U/kg/24 hours vs 0 U/kg/24 hours; P = .05) compared to those not on tacrolimus. Both type 1 and type 2 diabetics on tacrolimus showed better preservation of renal function as measured by mean serum creatinine (type 1: 145 +/- 53 vs 196 +/- 74, P = .02; type 2 pretransplant: 159 +/- 73 vs 172 +/- 59, P = .35; type 2 posttransplant: 123 +/- 35 vs 167 +/- 63, P = .01). CONCLUSIONS: Tacrolimus use in renal transplant patients with diabetes appeared to be associated with more problematic blood glucose control; however, it seemed to be better at preserving renal function. Intensive blood glucose monitoring is recommended for this group.     

Management of apparent life-threatening events

Apparent life-threatening events in infancy (ALTE) present a common yet complex management problem for the clinician. While an ALTE generally represents a benign event, in rarer instances it may indicate a serious underlying disorder. In most circumstances patients will require admission for a short period, thus providing the opportunity to perform a systematic, thorough examination, followed by the selective use of investigations. In all situations, however, even those with an unambiguous diagnosis, follow-up must be provided to detect recurrent episodes and to monitor long-term sequelae.