Suboptimal recognition of a T cell epitope of the major dog allergen Can f 1 by human T cells

We have previously proposed that mammalian lipocalin allergens are recognized suboptimally by the human immune system due to their homology with endogenous lipocalins. Here, we have characterized in detail the human T cell recognition of one of the previously identified T cell epitopes of the major dog allergen Can f 1, contained in peptide p105–120. A panel of peptide analogues (altered peptide ligands, APLs) of p105–120 was tested on two specific T cell clones restricted by different human leukocyte antigen (HLA) alleles. Interestingly, we identified for both of the clones several heteroclitic APLs that were capable of stimulating them at 10–30-fold lower concentrations than the natural peptide. Moreover, one of the heteroclitic APLs identified with the T cell clones, L115F, was observed to induce a stronger polyclonal T cell response than the natural allergen peptide from the peripheral blood mononuclear cells (PBMCs) of six Can f 1-allergic subjects studied. The heteroclitic APLs bound with the same affinity as p105–120 to common HLA-DR- and HLA-DP-alleles, suggesting that their improved stimulatory capacity is attributable to a more efficient T cell receptor (TCR) recognition rather than increased HLA binding. Collectively, our data suggest that p105–120 is recognized suboptimally by human T cells. This may contribute to the allergenicity of Can f 1.     

Fluid Balance and Blood Volume Measurement after Aneurysmal Subarachnoid Hemorrhage

Background  Patients with aneurysmal subarachnoid hemorrhage (SAH) are at risk for circulatory volume depletion, which is a risk factor for delayed cerebral ischemia (DCI). In a prospective observational study we assessed the effectiveness of fluid administration based on regular evaluation of the fluid balance in maintaining normovolemia. Methods  A total of 50 patients with aneurysmal SAH were included and were treated according to a standard protocol aimed at maintaining normovolemia. Fluid intake was adjusted on the basis of the fluid balance, which was calculated at 6-h intervals. Circulating blood volume (CBV) was measured by means of pulse dye densitometry (PDD) on alternating days during the first 2 weeks after SAH. Results  Of the 265 CBV measurements, 138 (52%) were in the normovolemic range of 60–80 ml/kg; 76 (29%) indicated hypovolemia with CBV < 60 ml/kg; and 51 (19%) indicated hypervolemia with CBV > 80 ml/kg. There was no association between CBV and daily fluid balance (regression coefficient β = −0.32; 95% CI: −1.81 to 1.17) or between CBV and a cumulative fluid balance, adjusted for insensible loss through perspiration and respiration (β = 0.20; 95% CI: −0.31 to 0.72). Conclusion  Calculations of fluid balance do not provide adequate information on actual CBV after SAH, as measured by PDD. This raises doubt whether fluid management guided by fluid balances is effective in maintaining normovolemia.     

Early childhood OCD: preliminary findings from a family-based cognitive-behavioral approach

ObjectiveTo examine the relative efficacy of family-based cognitive-behavioral therapy (CBT) versus family-based relaxation treatment (RT) for young children ages 5 to 8 years with obsessive-compulsive disorder (OCD).MethodForty-two young children with primary OCD were randomized to receive 12 sessions of family-based CBT or family-based RT. Assessments were conducted before and after treatment by independent raters blind to treatment assignment. Primary outcomes included scores on the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Improvement.ResultsFor the intent-to-treat sample, CBT was associated with a moderate treatment effect (d = 0.53), although there was not a significant difference between the groups at conventional levels. For the completer sample, CBT had a large effect (d = 0.85), and there was a significant group difference favoring CBT. In the intent-to-treat sample, 50% of children in the CBT group achieved remission as compared to 20% in the RT group. In the completer sample, 69% of children in the CBT group achieved a clinical remission compared to 20% in the RT group.ConclusionsResults indicate that children with early-onset OCD benefit from a treatment approach tailored to their developmental needs and family context. CBT was effective in reducing OCD symptoms and in helping a large number of children achieve a clinical remission.     

Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial

Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized to a protocol using FDC therapy as second and third steps compared with a protocol that used the same medications in free pill combination therapy for these steps. Eligible patients were adults (≥18 years) with hypertension. The primary outcome was the odds of a patient being controlled at their last visit between baseline to 6-month follow-up in the FDC group compared to the free pill group. 4427 patients (mean [SD] age: 49.0 [12.4] years, 70.5% female) were registered with mean (SD) baseline systolic/diastolic blood pressure 155 (20.6)/96 (13.1) mm Hg. Baseline characteristics of groups were similar. After 6-months, hypertension control rate improved in the two treatment protocols, but there were no differences between the groups after adjustment (FDC = 53.9% versus free pill combination = 47.9%, cluster-adjusted p = .29). Adverse events were similarly low (<1%) in both groups. Both protocols improved hypertension control rates at 6-months in comparison to baseline, though no differences were observed between groups. Further work is needed to determine if upfront FDC therapy is more effective and efficient to improve hypertension control rates.     

Prothrombotic gene variation in patients with large and small vessel disease

The classification of ischemic stroke into different subtypes is supported in genetic association studies. While several gene variants have been identified as being associated with ischemia subtypes, most studies have not been powered to study subtypes separately. We investigated 887 patients with nondisabling cerebral ischemia of arterial origin and classified ischemia as being caused by large or small vessel disease (LVD or SVD), primarily based on neuroimaging findings. In total, 621 patients had LVD and 266 SVD. The coagulation factor XIII subunit B gene (F13B) His95Arg variant was more common in patients with LVD (mean prevalence difference 9.9%; 95% CI 4.7-15). None of 21 other prothrombotic gene variants was associated with LVD or SVD. Many gene variants may not be specific for one subtype. We could not replicate the genetic associations identified in previous smaller previous studies. Thus claims about genetic associations with specific subtypes of ischemia should be interpreted with caution. The association between F13B His95Arg and LVD requires replication.