Several formulas are available for the dietary treatment of cow's milk allergy (CMA). Clinical data suggest potentially different effect on immune tolerance elicited by these formulas. We aimed to comparatively evaluate the tolerogenic effect elicited by the protein fraction of different formulas available for the dietary treatment of CMA. Five formulas were compared: extensively hydrolyzed whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (HRF), soy formula (SF), and amino acid-based formula (AAF). The formulas were reconstituted in water according to the manufacturer's instructions and subjected to an in vitro infant gut simulated digestion using a sequential gastric and duodenal static model. Protein fraction was then purified and used for the experiments on non-immune and immune components of tolerance network in human enterocytes and in peripheral mononuclear blood cells (PBMCs). We assessed epithelial layer permeability and tight junction proteins (occludin and zonula occludens-1, ZO-1), mucin 5AC, IL-33, and thymic stromal lymphopoietin (TSLP) in human enterocytes. In addition, Th1/Th2 cytokine response and Tregs activation were investigated in PBMCs from IgE-mediated CMA infants. EHCF-derived protein fraction positively modulated the expression of gut barrier components (mucin 5AC, occludin and ZO-1) in human enterocytes, while SF was able to stimulate the expression of occludin only. EHWF and HRF protein fractions elicited a significant increase in TSLP production, while IL-33 release was significantly increased by HRF and SF protein fractions in human enterocytes. Only EHCF-derived protein fraction elicited an increase of the tolerogenic cytokines production (IL-10, IFN-γ) and of activated CD4+FoxP3+ Treg number, through NFAT, AP1, and Nf-Kb1 pathway. The effect paralleled with an up-regulation of FoxP3 demethylation rate. Protein fraction from all the study formulas was unable to induce Th2 cytokines production. The results suggest a different regulatory action on tolerogenic mechanisms elicited by protein fraction from different formulas commonly used for CMA management. EHCF-derived protein fraction was able to elicit tolerogenic effect through at least in part an epigenetic modulation of FoxP3 gene. These results could explain the different clinical effects observed on immune tolerance acquisition in CMA patients and on allergy prevention in children at risk for atopy observed using EHCF.

Keywords: amino acid formula; extensively hydrolyzed casein formula; extensively hydrolyzed whey formula; gut barrier; hypoallergenic formulas; immune tolerance; rice formula; soy formula.

The etiology of chronic urticaria (CU) remains elusive. Histamine-releasing factor (HRF) is reported to have a proinflammatory role in asthma and immediate hypersensitivity of the skin. The aim of this study was to examine the role of HRF in the pathogenesis of CU. Forty patients with CU were enrolled and their serum HRF concentrations were determined by ELISA. The results demonstrated that the concentrations of HRF and HRF-reactive IgE in the CU group were significantly higher than those in the control group, and there was a significant linear correlation between HRF and HRF-reactive IgE concentrations (r = 0.859, p < 0.001) in CU patients. Additionally, the HRF-reactive IgE concentration was significantly correlated with the disease activity (r = 0.693, p < 0.0001). HRF and HRF-reactive IgE alone failed to activate LAD2 cells. After being primed by the patient sera with the highest IgE concentrations and stimulated by HRF, β-hexosaminidase can be released from LAD2 cells. Our findings suggest that the synergistic actions of HRF and HRF-reactive IgE may play important roles in the pathogenesis of CU.

Histamine-releasing factor (HRF) is a cytokine produced by mononuclear leukocytes when stimulated with antigens or mitogens. HRF is capable of inducing degranulation of basophils and release of histamine. To determine if respiratory viruses can induce HRF production, mononuclear leukocytes from healthy adult donors were exposed to influenza or respiratory syncytial virus in vitro. HRF activity was tested by culturing the supernatants with fresh peripheral blood leukocytes and measuring the percentage of histamine released. Significant enhancement in histamine release was found in both virus groups compared with that of media controls. Thus, mononuclear leukocytes from normal individuals produce HRF in response to exposure to respiratory viruses, suggesting that this cytokine, which causes basophil degranulation, may play a role in the mechanism of virus-induced bronchospasm.

A cytokine, termed histamine-releasing factor (HRF) and produced by many cell types, has become the focus of research by many investigators due to its potential importance as a stimulus in chronic inflammation. We are producing and characterizing an HRF which causes IgE-mediated histamine release from human basophils. Following extensive purification procedures, the molecule will be sequenced and synthesized. A functional heterogeneity of IgE molecules was revealed by these studies. We are currently producing IgE antibody in vitro and testing the hypothesis that differential glycosylation is the basis for the heterogeneity. Knowledge of the structures and interactions of these molecules should advance our understanding of allergic and more chronic diseases.

Subsequent to an epidemiological study on eating behaviour in adolescents, a prospective study was carried out to examine the effect of health promotion lessons on disturbed eating behaviour. From the original sample (t1, n = 1944), a subgroup of 314 students of both sexes, 14-19 years of age, was selected. Participants came from a total of 20 classes in which a high percentage of students exhibited disturbed eating behaviour. Ten classes were then randomly selected to receive health promotion lessons (intervention group, high-risk; IGHR), while the other 10 classes served as controls (control group, high-risk; CGHR). The Eating Attitudes Test (EAT-26), the Giessen Physical Complaint List for Children and Adolescents (GSCL-C) and the Self-Report Symptom Check-List (SCL-90-R) were administered shortly before (t2) and 3 months after (t3) the interventions. The three health promotion lessons dealt with issues concerning beauty ideals, gender differences in psychosexual maturation and body awareness, healthy eating behaviour, physiology of nutrition, early symptoms of eating disorders and therapeutic approaches. The data analyses revealed an improvement on all three symptom scales for both groups between t2 and t3, but there were no significant differences between the IGHR and CGHR groups. When data from high-scoring female participants only were analysed (HRf-IGHR and HRf-CGHR), the multivariate analysis revealed a significant interaction between time and group (15.2% of variance explained). Our experiences in implementing health promotion lessons that conveyed knowledge about eating disorders and addressed physical and psychological issues in a more general way indicated that these interventions can be carried out in schools, and may contribute to increases in physical and psychological well-being in a high-risk population of adolescents.

OBJECTIVE

The objective of this study was to ascertain the effect of high-dose steroid therapy in traumatic optic neuropathy using the Heidelberg retina flowmeter (HRF) to detect changes in optic nerve head blood flow.

METHODS

We experimentally damaged the optic nerves of 10 white rabbits with a Hartman mosquito clamp. The first group (n = 5) was treated with intravenous dexamethasone (0.25 mg/kg) every 6 h for a 48-hour period. The second group (n = 5) served as controls. Both groups were tested prior to operation, 1 week, 1 month and 2 months after surgery.

RESULTS

Experimental optic nerve damage caused a significant decrease in optic nerve head blood flow of 50.51% (p = 0.001), with a volume decrease of 46.02% (p = 0.001) and a velocity reduction of 43.12% (p = 0.002) compared to the baseline. After 2 months, in the group treated with high-dose corticosteroid therapy, optic nerve head blood flow was increased by 76.90% (p = 0.012), volume by 77.53% (p = 0.012) and velocity by 47. 21% (p = 0.012) compared to the control group.

CONCLUSIONS

The high-dose corticosteroid therapy improved the optic nerve head blood flow as demonstrated in experimental traumatic optic neuropathy. The HRF may be used to assess the therapeutic responses in traumatic optic neuropathy under variable conditions.

Previous reports have suggested that a 65 kDa membrane protein, termed homologous restriction factor (HRF), in addition to protecting erythrocytes (E) against lysis by homologous complement (C), may also be involved in protecting cytolytic lymphocytes against lysis mediated by a pore-forming protein (PFP/perforin), one of their own lytic mediators. Here, we used HRF-deficient type III E of patients with paroxysmal nocturnal hemoglobinuria (PNH) to study their susceptibility to lysis mediated by homologous C and perforin, and compared it with lysis of HRF-bearing control or PNH type I E. We show that type III E of PNH patients are indeed more susceptible to lysis mediated by homologous C than control or type I E, but they are as susceptible to perforin-mediated lysis as type I E. In addition, all human E (type I or III) tested here are equally susceptible to lysis mediated by either human (homologous) or murine (heterologous) perforin. By immunoblot analysis, we confirm that type III E, in contrast to type I E, were deficient in the 65 kDa HRF. These results support the notion that homologous species restriction is seen in the C- but not in the lymphocyte perforin-system and argue against an active participation of HRF in protecting cells from perforin-mediated lysis.

OBJECTIVE

To determine the effect of photocoagulation on retinal blood flow (RBF) in eyes with ischaemic type central retinal vein occlusion (CRVO).

METHODS

Retinal blood flow was measured in 12 eyes with CRVO, 12 fellow eyes and 12 eyes of 12 age-matched healthy subjects using the Heidelberg retinal flowmeter (HRF). Microvascular blood flow values (volume, flow, velocity) were recorded from the upper temporal retina and macula. Eyes were re-examined 1 month after photocoagulation. We investigated whether there was a difference in RBF measurements before and after photocoagulation treatment.

RESULTS

In eyes with CRVO, mean RBF values (volume, flow and velocity) obtained from the upper temporal retina increased significantly after treatment (paired t-test, p < 0.05). In contrast, mean RBF values from the macula were unaffected by photocoagulation (paired t-test, p>> 0.05). Retinal blood flow values from the upper temporal retina obtained from control subjects were significantly higher than the values in eyes with CRVO before and after photocoagulation (unpaired t-test, p < 0.05), but there was no significant difference between control subjects and CRVO patients in RBF values from the macula (unpaired t-test, p>> 0.05). Mean RBF values were significantly higher in CRVO patients' fellow-eyes before photocoagulation in the eyes with CRVO (paired t-test, p < 0.05) but were lower than in age-matched healthy control eyes (unpaired t-test, p < 0.05). Macular blood flow did not differ between the eyes with CRVO and fellow eyes (paired t-test, p>> 0.05).

CONCLUSIONS

Laser photocoagulation increased retinal blood flow in eyes with CRVO, but RBF did not reach normal values. Photocoagulation was found to have no effect on RBF in the macular area.

An open clinical trial of thymopentin was conducted on 16 children with severe atopic dermatitis. The patients were treated with injections three times a week of 50 mg thymopentin for six weeks. They were then divided randomly into two groups: group A continued thymopentin for an additional six weeks, and group B were treated with normal saline. Clinical parameters and immunological function were evaluated serially. The total severity score started to decline from baseline significantly three weeks after treatment, and continued throughout the study period in group A but began to flare up in group B two weeks after stopping thymopentin. All the eight patients in group A completed the trial but three out of eight in group B dropped out because of flaring up of skin lesion. In vitro production of interleukin-4 tended to decrease and that of interferon gamma tended to increase, but total serum IgE, in vitro IgE synthesis, and abnormally low CD8+ CD11b+ suppressor T cells remained unchanged. Histamine releasing factor (HRF), plasma histamine, and respiratory burst activities of polymorphonuclear leucocytes were appreciably decreased after thymopentin treatment. It is concluded that the clinical efficacy of short term thymopentin treatment very possibly results from the decreased production of HRF and decreased release of polymorphonuclear leucocyte derived inflammatory mediators and may have no relation with antigen-IgE immune reaction.

In the present study, two Leishmania infantum hypothetical proteins present in the amastigote stage, LiHyp1 and LiHyp6, were combined with a promastigote protein, IgE-dependent histamine-releasing factor (HRF); to compose a polyproteins vaccine to be evaluated against L. infantum infection. Also, the antigenicity of the three proteins was analyzed, and their use for the serodiagnosis of canine visceral leishmaniasis (CVL) was evaluated. The LiHyp1, LiHyp6, and HRF DNA coding sequences were cloned in prokaryotic expression vectors and the recombinant proteins were purified. When employed in ELISA assays, all proteins were recognized by sera from visceral leishmaniasis (VL) dogs, and presented no cross-reactivity with either sera from dogs vaccinated with a Brazilian commercial vaccine, or sera of Trypanosoma cruzi-infected or Ehrlichia canis-infected animals. In addition, the antigens were not recognized by antibodies from non-infected animals living in endemic or non-endemic areas for leishmaniasis. The immunogenicity and protective efficacy of the three proteins administered in the presence of saponin, individually or in combination (composing a polyproteins vaccine), were evaluated in a VL murine model: BALB/c mice infected with L. infantum. Spleen cells from mice inoculated with the individual proteins or with the polyproteins vaccine plus saponin showed a protein-specific production of IFN-γ, IL-12, and GM-CSF after an in vitro stimulation, which was maintained after infection. These animals presented significant reductions in the parasite burden in different evaluated organs, when compared to mice inoculated with saline or saponin. The decrease in parasite burden was associated with an IL-12-dependent production of IFN-γ against parasite total extracts (produced mainly by CD4+ T cells), correlated to the induction of parasite proteins-driven NO production. Mice inoculated with the recombinant protein-based vaccines showed also high levels of parasite-specific IgG2a antibodies. The polyproteins vaccine administration induced a more pronounced Th1 response before and after challenge infection than individual vaccines, which was correlated to a higher control of parasite dissemination to internal organs.

OBJECTIVE

The present study attempted to test McCullough and Willoughby's hypothesis that self-control mediates the relationships between religiosity and psychosocial outcomes. Specifically, this study examined whether trait self-control (TSC) mediates the relationship of identified-introjected religiosity with positive and negative health-related-feelings (HRF) in healthy Muslims.

METHODS

Two hundred eleven French-speaking participants (116 females, 95 males; Mage = 28.15, SDage = 6.90) answered questionnaires. One hundred ninety participants were retained for the analyses because they reported to be healthy (105 females, 85 males; Mage = 27.72, SDage = 6.80). To examine the relationships between religiosity, TSC and HRF, two competing mediation models were tested using structural equation model analysis: While a starting model used TSC as mediator of the religiosity-HRF relationship, an alternative model used religiosity as mediator of the TSC-HRF relationship.

RESULTS

The findings revealed that TSC mediated the relationship between identified religiosity and positive HRF, and that identified religiosity mediated the relationship between TSC and positive and negative HRF, thereby validating both models. Moreover, the comparison of both models showed that the starting model explained 13.211% of the variance (goodness of fit = 1.000), whereas the alternative model explained 6.877% of the variance (goodness of fit = 0.987).

CONCLUSIONS

These results show that the starting model is the most effective model to account for the relationships between religiosity, TSC, and HRF. Therefore, this study provides initial insights into how religiosity influences psychological health through TSC. Important practical implications for the religious education are suggested.

The thresholded t-map produced by the General Linear Model (GLM) gives an effective summary of activation patterns in functional brain images and is widely used for feature selection in fMRI related classification tasks. As part of a project to build content-based retrieval systems for fMRI images, we have investigated ways to make GLM more adaptive and more robust in dealing with fMRI data from widely differing experiments. In this paper we report on exploration of the Finite Impulse Response model, combined with multiple linear regression, to identify the "locally best Hemodynamic Response Function (HRF) for each voxel" and to simultaneously estimate activation levels corresponding to several stimulus conditions. The goal is to develop a procedure for processing datasets of varying natures. Our experiments show that Finite Impulse Response (FIR) models with a smoothing factor produce better retrieval performance than does the canonical double gamma HRF in terms of retrieval accuracy.

The possible linear short-term coordination between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF) in conscious human beings has not yet been investigated because of the restricted time resolution of conventional time series analysis. At present, this short-term dynamics as an expression of relative coordination can be quantified by newly developed adaptive autoregressive modeling of time series using Kalman filtering. Thus, in 6 conscious healthy volunteers, RESP, HRF, and BPF were recorded during 10 min in the supine position, at rest and during paced breathing. A considerable part of calculated ordinary and partial coherence sequences of short-term resolution between RESP and HRF, RESP and BPF, and partially between HRF and BPF showed patterns varying in time that could be correlated to changes between gradual coordinations (coherence changing between 0.40 and 0.95). They were more seldom complete or absent. There were mostly opposite changes between partial coherence sequences RESP-HRF/BPF and RESP-BPF/HRF demonstrating competitive behavior between these coordinations. Paced breathing did not essentially affect any observed characteristics. Therefore, these coherence dynamics are not essentially dependent on voluntary breathing movements. We conclude that to a different extent these linear and changing couplings between RESP, HRF, and BPF in conscious human beings exhibit properties of short-term complete and more frequently gradual coordinations showing dynamics that can not be determined by conventional methods.

The 386 cases of invasive cervical carcinoma treated with radiotherapy alone were statistically analyzed to delineate the high risk factors (HRFs) associated with a significantly high treatment failure rate; they were (1) stages III-IV, (2) lesion greater than or equal to 4.0 cm, (3) small cell carcinoma or adenocarcinoma, (4) stages I-II with lesion greater than or equal to 4.0 cm, and (5) lymphographic evidence of nodal metastasis. Then, chemoradiotherapy (induction chemotherapy plus subsequent radiotherapy) was instituted to 113 invasive cervical carcinoma patients with at least one such HRF. Each patient received two to three cycles of induction chemotherapy at about 3-week intervals. For squamous cell carcinoma, cisplatin, 100 mg/m2 iv, was followed immediately by 5-fluorouracil, 1000 mg/m2, as a 24-hr iv infusion x 5 days. For adenocarcinoma, cisplatin, 70 mg/m2 iv, on Day 1 was followed by cytoxan, 250 mg/m2, on Day 2, and adriamycin, 45 mg/m2, on Day 3. Five-year survival of these patients according to each HRF, in the above order, was 69.1, 67.2, 68.1, 78.3, and 79.5% after chemoradiotherapy, all significantly higher than 57.4, 53.0, 54.5, 48.0, and 48.8% by radiotherapy alone. Drug toxicities such as leukopenia, hepatotoxicity, nephrotoxicity, and hypomagnesemia were seen in 46.5, 53.2, 47.1, and 55.4% of all cycles, respectively. The toxicities altered drug schedule in 191 (61.2%) ongoing induction chemotherapy cycles. Our cisplatin-based induction chemotherapy is considered an effective preradiotherapy adjunct that can reduce treatment failure in HRF-associated invasive cervical carcinoma.

Studies have demonstrated a declined incidence of allergic disorders in the population with helminthic infection. Though several hypotheses have been proposed to explain how helminthic infection protected people against allergies, the underlying mechanisms remain poorly understood. A human histamine-releasing factor (HRF) has been proved to be closely related to the development of allergic disorders and the homologues are ubiquitously expressed in all eukaryotic organisms including parasites. To study the role of this HRF in the relationship between parasitic infection and allergic diseases with experimental model of rats, the cDNA of the homologues of the human HRF from Wistar rat, Schistosoma japonicum, and Clonorchis sinensis containing a coding region of 519, 510, and 510 bp, respectively, were cloned. In addition, the cross-reactivity between recombinant rat HRF (rRHRF) and recombinant S. japonicum HRF (rSjHRF) as well as that between rRHRF and recombinant C. sinensis HRF (rCsHRF) was identified with ELISA and Western blotting. Based on their detected cross-reactivities, a hypothesis was put forward that the anti-parasitic HRFs antibodies could inhibit the effects of host HRF and those of parasitic HRFs and thus decreased the host sensitivities to allergens.

Respiratory sinus arrhythmia (RSA) has been traditionally defined as the high-frequency component of heart-rate fluctuations (HRF) synchronous with the respiratory movements (RM), i.e., the frequency of RSA corresponds to the respiration rate. It can be shown that at defined relations of mean heart and respiration rate some essential effects must be taken into consideration in studies using RSA parameters. The relevance of these effects is shown and a new strategy of RSA quantification demanded, at least in neonates. The diagnostic importance, physiological background and future application of the low-frequency components of the neonatal HRF are reviewed on the basis of our own results. Nonrespiratory cardiovascular HRF cannot always be detected in the neonate by power spectral analysis. Movement-related HRF have a potential diagnostic importance per se, but may also artefactually disturb the quantification of other HRF components. Long-term trends can be used to describe sleep-state related trends and their disturbances.

OBJECTIVE

The estimation of Glomerular Filtration Rate (GFR) by Cockroft-Gault or simplified MDRD functions is a powerful tool for the Chronic Kidney Disease (CKD) diagnosis. The aims of the present study are: 1)-To analyze the accuracy between Cockcroft-Gault and simplified MDRD equations in the Hidden Renal Failure (HRF) diagnosis; and 2)-To know the profile and coronary risk of patients diagnosed of HRF for each equation.

METHODS

Ten year follow-up of a cross sectional study. A total of 845 patients between 35 and 74 years old (average age 55 years, 56.7% female) without evidence of cardiovascular disease and taken care in a urban primary health center. HRF was defined as an estimated GFR <60 ml/min/1.73 m2 in patients with normal values of creatinine (<1.3 mg/dl in women and <1.4 mg/dl in men )

RESULTS

8.3% of studied population had HRF by Cockroft-Gault formula and 11.6% using MDRD. The HRF patients diagnosticated with Cockroft-Gault function were older (67.4 vs 64.4 years, p<0.001) and had a higher coronary risk using either the original Framingham equation and REGICOR function. Furthermore, those HRF patients diagnosticated using MDRD function had a higher body mass index (29.6 vs 26.3 kg/m2, p<0.001) and were women in a greater percentage. Kappa index of agreement of these two equations for diagnosis of HRF was 0,55. The HRF patients diagnosticated exclusively by the use of Cockroft-Gault function were mainly men (75%), older (69.1 vs 61.9 years, p<0.001) and they had a high coronary risk in the Framingham equation (32.7%) and REGICOR function (13.1%)

CONCLUSIONS

Cockroft-Gault and MDRD equations present a moderate agreement in HRF diagnosis (stage 3 of CKD) in patients between 35 and 74 years old. If we only use the MDRD function, a group of HRF patients would be excluded. This population was mainly male (75%), older (69 years old), with a high coronary risk estimated by original Framingham and REGICOR equations, and confirmed in the ten years follow-up of these patients.

BACKGROUND

Non-invasive ventilation (NIV) is used to treat acute hypercapnic respiratory failure (AHRF) in patients with chronic obstructive pulmonary disease (COPD); however, long-term outcomes following discharge are largely unknown. This study aimed to characterize long-term outcomes and identify associated markers in patients with COPD after surviving the first episode of HRF requiring NIV.

METHODS

This study retrospectively analyzed 122 patients, mean age 62 ± 8 years, 52% female and forced expiratory volume in 1 s (FEV1) predicted 30 ± 13%, admitted with an acute hypercapnic exacerbation of COPD and receiving a first-ever NIV treatment between 2000 and 2012.

RESULTS

A total of 40% of the patients required hospital readmission due to respiratory reasons within 1 year. Persistent hypercapnia leading to the prescription of domiciliary NIV, older age and lower body mass index (BMI) were risk factors for readmission due to respiratory reasons. Survival rates were 79% and 63% at 1 and 2 years after discharge, respectively. A shorter time to readmission and recurrent hypercapnic failure, lower BMI and acidemia on the first admission, as well as hypercapnia at hospital discharge were correlated with a decreased long-term survival.

CONCLUSIONS

Patients with COPD surviving their first episode of AHRF requiring NIV are at high risk for readmission and death. Severe respiratory acidosis, chronic respiratory failure and a lower BMI imply shorter long-term survival.

Little is known about oxalate transport in renal epithelia under basal conditions, let alone in hyperoxaluria when the capacity for renal oxalate excretion is increased. Sulfate anion transporter 1 (SAT1, Slc26a1) is considered to be a major basolateral anion-oxalate exchanger in the proximal tubule and we hypothesized its expression may correlate with urinary oxalate excretion. We quantified changes in the renal expression of SAT1 mRNA and protein in two rat models, one with hyperoxaluria (HYP) and one with renal insufficiency (HRF) induced by hyperoxaluria. The hyperoxaluria observed in the HYP group could not simply be ascribed to changes in SAT1 mRNA or protein abundance. However, when hyperoxaluria was accompanied by renal insufficiency, significant reductions in SAT1 mRNA and protein were detected in medullary and papillary tissue. Together, the results indicate that transcriptional modulation of the SAT1 gene is not a significant component of the hyperoxaluria observed in these rat models.

Posttraumatic stress disorder (PTSD) has been consistently reported as being highly comorbid with major depressive disorder (MDD) and as being associated with health related functional impairment (HRF). We used archival data from 283 previously war-zone deployed Canadian veterans. Latent profile analysis (LPA) was used to uncover patterns of PTSD and MDD comorbidity as measured via the PTSD Checklist-Military version (PCL-M) and the Patient Health Questionnaire-9 (PHQ-9). Individual membership of latent classes was used in a series of one-way ANOVAs to ascertain group differences related to HRF as measured via the Short-Form-36 Health Survey (SF-36). LPA resulted in three discrete patterns of PTSD and MDD comorbidity which were characterized by high symptoms of PTSD and MDD, moderate symptoms, and low symptoms. All ANOVAs comparing class membership on the SF-36 subscales were statistically significant demonstrating group differences across levels of HRF. The group with the highest symptoms reported the worst HRF followed by the medium and low symptom groups. These findings are clinically relevant as they demonstrate the need for continual assessment and targeted treatment of co-occurring PTSD and MDD.

Familial Mediterranean fever (FMF) has traditionally been considered as a monogenic autosomal recessive disorder caused by mutations in the MEFV gene with highest incidence among Mediterranean populations. In a considerable number of patients with typical FMF, only one MEFV mutation was identified and the possibility that more than one autoinflammatory gene may be responsible for their disease was investigated. In the present study, an extensive search for possible mutations in three hereditary recurrent fever (HRF) genes was performed in 128 MEFV heterozygous Greek-Cypriots clinically diagnosed based on their phenotype with FMF-like disease from a previous study. Sequence analysis was performed for MVK, TNFRSF1A and NLRP3 genes which is also known to cause HRFs. In total, three patients were identified with heterozygous mutations and a second mutation in an autoinflammatory gene. Two patients carried a MEFV mutation and a NLRP3 mutation, and an additional third carried a MEFV mutation and a TNFRSF1A mutation. Patient 1 carried MEFV p.[Val726Ala] (NM_000243.2:c.2177T>C) and NLRP3 p.[Val198Met] (NM_001243133.1:c.592G>A) variants and patient 2 carried MEFV p.[Glu148Gln] (NM_000243.2:c.442G>C) variant which is of uncertain significance and NLRP3 p.[Arg176Trp] (NM_001243133.1:c.526C>T). Lastly, patient 3 was identified to carry MEFV p.[Met694Val] (NM_000243.2:c.2080A>G) and TNFRSF1A p.[Arg121Gln] (NM_001065.3:c.362G>A) variants. The results from this study indicate that screening of genes known to cause HRFs in patients already identified with a single MEFV mutation, can reveal quite rare but potentially causative mutational combinations at different loci. Such interaction provide further evidence for possible locus-locus interactions and phenotypes resulting from digenic inheritance.

OBJECTIVE

A case series evaluating the acute effects of noninvasive positive pressure ventilation (NPPV) in patients with chronic hypercapnic respiratory failure (HRF) secondary to interstitial lung diseases (ILD).

METHODS

Ten patients with ILD were retrospectively evaluated. All had restrictive lung function (mean TLC, 47.6+/-12.6% predicted) and chronic hypercapnic respiratory failure (mean pH=7.39+/-0.02). Arterial blood gas analysis and lung function were compared before and after the application of controlled pressure-limited NPPV.

RESULTS

Daytime PaCO(2) during spontaneous breathing decreased by 5.4+/-1.3mmHg (95% confidence interval, 4.5-6.3), from 57.7+/-5.1mmHg to 52.3+/-5.9 (p<0.001); while daytime PaO(2) increased by 3.4+/-3.3mmHg (95% confidence interval, 1.0-5.8), from 63.7+/-3.5mmHg to 67.1+/-3.4 (p=0.01); and TLC increased by 3.9+/-4.5% (95% confidence interval, 0.7-7.1), from 47.6+/-12.6%mmHg to 51.5+/-10.0% (p=0.023).

CONCLUSIONS

In patients with ILD and chronic HRF controlled NPPV is tolerated and can acutely improve blood gas levels. Further studies examining the long-term benefits need to be explored.

To provide insight into the pathophysiology of idiopathic childhood occipital epilepsies (ICOEs), by mapping the contribution of retinotopic visual areas to the generation and sustainment of epileptic activity.

Thirteen patients affected by ICOEs (mean age = 10.9 years) underwent a video electroencephalography-functional magnetic resonance imaging (EEG-fMRI) study. A flexible-related fMRI analysis was applied to estimate the shape of the blood oxygen level-dependent (BOLD) response in each patient. Second-level analysis was performed using the interictal EEG discharge (IED)-specific response shape for the ICOE group. The resulting fMRI t-maps were warped to the Population-Average, Landmark- and Surface-based (PALS)-B12 atlas in Caret. For localization purposes, functional results were plotted and compared against 19 retinotopic areas for each hemisphere. A correlation analysis was performed between the hemodynamic maps and electroclinical variables.

The shape of the group-averaged hemodynamic response in ICOE patients showed an earlier time-to-peak and a more pronounced undershoot than the canonical hemodynamic response function (HRF). The random-effect analysis showed positive hemodynamic changes in the bilateral temporooccipital network. With regard to the retinotopic subdivision of the visual cortex, the primary visual area was consistently spared. Conversely, an extensive involvement of the occipitotemporal cortex, including the fusiform gyrus, and the occipitoparietal areas was observed. Moreover, a linear relationship was detected between the occipital spike-density and BOLD increases at the postcentral gyrus and temporooccipital cortex.

Our data indicate that both the ventral and dorsal visual pathways are involved in spike generation in ICOEs, to extents that vary between patients, and reinforce the concept of benign childhood seizure susceptibility syndrome as a substrate for ICOEs. Finally, these results underscore the need for appropriate neuropsychological testing in these children, aimed at revealing selective impairments in functions subserved by both visual pathways.

In many cnidarians, symbiotic algae live within host-derived symbiosomes. We determined whether a symbiosome membrane alters the response of isolated symbiotic algae to two signalling compounds that regulate algal carbon metabolism. Host release factor (HRF), which stimulates photosynthate release, and photosynthesis inhibiting factor (PIF), which inhibits photosynthetic carbon fixation, are found in homogenised tissue of the scleractinian coral Plesiastrea versipora. Compared with seawater controls, photosynthate release from isolated algae incubated in P. versipora homogenate for 2 h in the light was: 6 to 19-fold higher from its own algae (free of symbiosomes); 19 to 32-fold higher from Zoanthid robustus algae (within symbiosomes) and 3 to 24-fold higher from Z. robustus algae (free of symbiosomes); and from cultured algae (free of symbiosomes) was seven-fold higher from Montipora verrucosa and four-fold higher from Cassiopeia xamachana. Incubation of algae in P. versipora homogenate inhibited photosynthesis by: 33-49% in P. versipora algae; 29-47% in Z. robustus algae (regardless of whether or not the symbiosome was present); and 25% in M. verrucosa algae. In C. xamachana algae, photosynthesis increased. We conclude that the symbiosome is not essential for, yet does not block, the effects of HRF and PIF.