Outcome expectancy as a moderator of mental fatigue influence on cardiovascular response

Female undergraduates performed an easy (fatigue low) or difficult (fatigue high) scanning task and then were presented mental arithmetic problems with instructions that they would earn a high or low chance of winning a prize if they did as well as or better than 50% of those who had performed previously. As expected, blood pressure responses in the second work period rose or tended to rise with fatigue where the chance of winning was high. By contrast, the responses tended weakly to decline with fatigue where the chance of winning was low. The pressure findings support the suggestion of a recent fatigue analysis that success importance should moderate fatigue influence on CV responses to a challenge so long as fatigued performers view success as possible. They also conceptually replicate previous fatigue results and provide a special class of evidence that fatigue influence on CV response is mediated by effort.     

On chip cell separator using magnetic bead-based enrichment and depletion of various surface markers

This paper presents an on-chip magnetic cell sorting system for the sorting of cells based on a variety of surface markers. A polymer lab on a chip integrated with an electroplated array of Ni/Fe permalloy has been designed, fabricated, and characterized for the separation of cell substitutes at a variety of flow rates and incubation times. The system sequentially labels cell substitutes with magnetic beads and sorts them, repeating this process to sort for a variety of surface markers. Flow rates and incubation times were varied to characterize the system and produce the best combination of high specific capture and low nonspecific capture. The separation system developed on polymer is selective and efficient while being low cost, portable, and fabricated in a modular structure that can be integrated with other cell handling processes.     

Serotonin transporter gene polymorphisms and treatment-resistant depression

Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.     

Depletion of CD4+CD25+ T cells switches the whey‐allergic response from immunoglobulin E‐ to immunoglobulin free light chain‐dependent

Background Symptoms of allergy are largely attributed to an IgE‐mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig‐free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4⁺CD25⁺ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens. Objective To examine the contribution of CD4⁺CD25⁺ T cells and IgLC towards the whey‐allergic response. Methods Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25⁺ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey‐specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4⁺CD25⁺ T cells was confirmed in the spleen. Results Anti‐CD25 treatment strongly reduced whey‐specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3⁺ regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25‐depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti‐CD25‐treated mice, indicating that these responses were mainly IgLC dependent. Conclusions Depletion of CD4⁺CD25⁺ T cells resulted in a switch from an IgE‐ to an IgLC‐dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25⁺ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE‐independent responses and both mechanisms might play a role in allergic responses to the same allergen. Cite this as: B. C. A. M. van Esch, B. Schouten, B. R. J. Blokhuis, G. A. Hofman, L. Boon, J. Garssen L. M. J. Knippels, L. E. M. Willemsen and F. A. Redegeld, Clinical & Experimental Allergy, 2010 (40) 1414–1421.     

Epileptic phenotypes in children with respiratory chain disorders

Purpose: Epilepsy is a commonly reported but rarely described clinical hallmark of mitochondrial respiratory chain defects (RCDs) with encephalopathy. Methods: From 1990–2006 we collected data about 56 children with RCD (single, n = 24 or multiple, n = 20 mitochondrial complex deficiencies; mtDNA mutation, n = 11; mtDNA depletion n = 10 of 21; and nuclear gene mutation n = 11). Epileptic features were reviewed retrospectively. Results: First seizures were frequently (47 patients, 82.5%) preceded by failure to thrive, psychomotor delay, ataxia, or multisystemic dysfunction. Sixty percent of the patients had several seizure types. Six age‐related epilepsy phenotypes could be identified: status epilepticus complicating neonatal multivisceral deficiency (2 patients), neonatal myoclonic encephalopathy (3 patients), infantile spasms (8 patients), refractory or recurrent status epilepticus (21 patients), epilepsia partialis continua (4 patients), and myoclonic epilepsy (18 patients). Except for infantile spasms, epilepsy was difficult to control in most patients (95%). Valproate was administered to 25 patients, one of whom developed acute liver failure 6 days later. Twenty‐two patients (45%) died, half of them within 9 months from the onset of epilepsy. Discussion: In RCD, epilepsy is not only difficult to control but its occurrence often indicates a severe turn in the course of the disease. For one‐third of the patients, classical biochemical measures failed to reveal any abnormality and RCD could be detected in the liver only.     

Impact of allogeneic 2-RBC apheresis on iron stores of Brazilian blood donors

One limiting factor for automated two-red blood cells collections (2-RBC) is its potential iron depletion. We analyzed hematological parameters and iron balance before, two and four months after 2-RBC of 96 non-supplemented male donors. Four months after 2-RBC, ferritin level was significantly lower (P < 0.01) than baseline levels and the number of donors who presented ferritin <30 ng/ml increased from 18 to 47. We concluded that four months was not sufficient for iron recuperation in the population studied. In an attempt to avoid iron depletion after 2-RBC, we recommend augmentation in the interval between blood donations and pre-donation ferritin measurement.     

Selective CCR2‐targeted macrophage depletion ameliorates experimental mesangioproliferative glomerulonephritis

The CCL2/CCR2 chemokine/receptor axis directs the chemotaxis of infiltrating monocytes/macrophages and T cells and plays a pivotal role in tissue damage and fibrosis in kidney diseases. The eradication of the activated leucocytes should diminish the production of inflammatory mediators, limit tissue damage and ameliorate disease. A recombinant fusion protein (OPL‐CCL2‐LPM) comprised of the human CCL2 (monocyte chemoattractant protein‐1) chemokine fused to a truncated form of the enzymatically active A1 domain of Shigella dysenteriae holotoxin (SA1) has been developed. The CCL2 portion binds specifically to CCR2‐bearing leucocytes and the fusion protein enters the cells, where the SA1 moiety inhibits protein synthesis resulting in cell death. The compound was tested in a model of anti‐thymocyte serum (ATS)‐induced mesangioproliferative glomerulonephritis (ATS‐GN). Male rats were injected with ATS on day 0 and treated intravenously with vehicle, 50 or 100 µg/kg of OPL‐CCL2‐LPM Q2D from days 2, 4, 6 and 8. Urine and blood were collected on days 0, 5 and 9. Animals were sacrificed on day 9. No treatment‐related effects on body weight or signs of clinical toxicity were observed. Urine protein levels were decreased in treated animals. At the highest dose, histopathological analyses of kidney sections revealed maximum reductions of 36, 31, 30 and 24% for macrophage count, glomerular lesions, α‐smooth muscle actin and fibronectin respectively. These results indicate a significant protective effect of OPL‐CCL2‐LPM in this model of nephritis.     

Susceptibility of Riboflavin and Vitamin A in Breast Milk to Photodegradation and Its Implications for the Use of Banked Breast Milk in Infant Feeding

ABSTRACT. Up to 50 % of the riboflavin and up to 70 % of the vitamin A in human drip breast milk samples were destroyed during controlled exposure to daylight, either in translucent polythene bottles, or where the milk was pumped through naso-gastric tubing from a syringe to mimic the conditions of enteral feeding. Losses were also observed in milk which was exposed to standard phototherapy illumination under conditions similar to those encountered in the ward, and in this case riboflavin was destroyed to a greater extent than vitamin A. Photodegradation of riboflavin may contribute to the high incidence of biochemical riboflavin deficiency reported in preterm infants receiving breast milk without vitamin supplements. The implications of these findings for feeding high risk term and preterm infants on donor milk are discussed, and the use of low actinic vessels and tubing to minimise photodegradation is recommended.