The impact of glycaemic load on cognitive performance: A meta-analysis and guiding principles for future research.

The effect of breakfast glycaemic load (GL) on cognition was systematically examined. Randomised and non-randomised controlled trials were identified using PubMed, Scopus, and Cochrane Library (up to May 2022). 15 studies involving adults (aged 20 - 80 years) were included. Studies had a low risk, or some concerns, of bias. A random-effects meta-analysis model revealed no effect of GL on cognition up to 119 min post-consumption. However, after 120 min, immediate episodic memory scores were better following a low-GL compared to a high-GL (SMD = 0.16, 95% confidence interval [CI] = -0.00 to 0.32, p = 0.05, I2 = 5%). Subgroup analyses indicated that the benefit was greater in younger adults (<35 years) and those with better GT. A qualitative synthesis of 16 studies involving children and adolescents (aged 5 - 17 years) suggested that a low-GL breakfast may also benefit episodic memory and attention after 120 min. Methodological practises were identified which could explain a failure to detect benefits in some studies. Consequently, guiding principles were developed to optimise future study design.

A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?

Addiction to a wide range of substances of abuse has been suggested to reflect a 'Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D2 receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30-40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity.

Caffeine can decrease subjective energy depending on the vehicle with which it is consumed and when it is measured.

RATIONALE: Energy drinks contain glucose and caffeine, although in the longer term both adversely influence blood glucose homeostasis, with the unconsidered potential to have adverse consequences for cognition and mood. OBJECTIVE: The objective of this study was to consider the influence on interstitial glucose levels, mood and cognition of drinks differing in their caffeine content and glycaemic load. METHODS: Ninety minutes after a standard breakfast, a yoghurt-, glucose- or water-based drink, with or without 80 mg of caffeine, was consumed. RESULTS: The consumption of caffeine negatively influenced glucose homeostasis: that is, irrespective of the vehicle, caffeine consumption resulted in elevated levels of blood glucose throughout the study. Thirty minutes after consuming caffeine and water, rather than water alone, greater subjective energy was reported. However, after 90 and 150 min, caffeine administered in water increased tiredness, hostility and confusion. In contrast, combining caffeine with a yoghurt-based drink increased energy, agreeableness and clearheadedness later in the morning. There were no effects of caffeine on ratings of mood when it was taken with glucose. Caffeine, irrespective of vehicle, resulted in better memory, quicker reaction times in the choice reaction time test and the working memory task, and better and quicker responses with the vigilance task. CONCLUSION: Further research should consider how caffeine interacts with macronutrients and the timescale over which such effects occur.

The successful use of cardiopulmonary support for a transected bronchus.

A 20-year-old male was involved in a motor vehicle accident and computed tomography revealed a completely transected right mainstem bronchus. An Emergency Department (ED) right anterior thoracotomy was necessary soon after arrival at our institution secondary to acute desaturation that was unresponsive to ventilator and chest tube management. This allowed direct intubation and ventilation of the right middle and lower lobes directly through the thoracotomy incision, which stabilized the patient for transport to the operating room. Once there, percutaneous cardiopulmonary support (CPS) was initiated to allow primary surgical repair of the transected bronchus. Post surgery, the patient was transported to the surgical intensive care unit on CPS which he required for an additional two days. The patient eventually did well and was discharged home. To our knowledge this is the first successful reported case of using the Avalon Elite dual lumen veno-venous cannula for CPS in a patient with complete right main-stem bronchus transection and bilateral pulmonary contusions.

IFN-gamma: recent advances in understanding regulation of expression, biological functions, and clinical applications.

Interferon-gamma (IFN-gamma) is a key immunoregulatory protein that plays a major role in the host innate and adaptive immune response. Also known as type II interferon, IFN-gamma is a single-copy gene whose expression is regulated at multiple levels by the host. Transcription control is regulated through epigenetic mechanisms as well as the accessibility of chromatin and the binding of activating and inhibitory proteins to promoter and enhancer elements. Post-transcriptional control is mediated through mRNA localization and mRNA stability while post-translational control occurs through the activation of protein kinase R by the 5' portion of the mRNA, protein folding within the endoplasmic reticulum and the possible interaction of the mRNA with microRNAs. The biological effects of IFN-gamma are widespread, as almost every cell type is altered upon interaction with this protein. Thus it has become very apparent that IFN-gamma is a multipotent cytokine whose regulation and effects are complex and essential to host survival.

An IFNG SNP with an estrogen-like response element selectively enhances promoter expression in peripheral but not lamina propria T cells.

This study examines mucosa-specific regulatory pathways involved in modulation of interferon-gamma (IFN-gamma) in lamina propria T cells. Previous studies identified mucosa-specific CD2 cis-elements within the -204 to -108 bp IFNG promoter. Within this region, a single-site nucleotide polymorphism, -179G/T, imparts tumor necrosis factor-alpha stimulation of IFNG in peripheral blood lymphocytes, and is linked with accelerated AIDS progression. We discovered a putative estrogen response element (ERE) introduced by the -179T, which displays selective activation in peripheral blood mononuclear cells (PBMC) vs lamina propria mononuclear cells (LPMC). Transfection of PBMC with constructs containing the -179G or -179T site revealed CD2-mediated enhancement of the -179T compared to -179G allele, although, in LPMC, a similar level of expression was detected. Electrophoretic mobility shift assay (EMSA) analysis demonstrated CD2-mediated nucleoprotein binding to the -179T but not the -179G in PBMC. In LPMC, binding is constitutive to both -179G and -179T regions. Sequence and EMSA analysis suggests that the -179T allele creates an ERE-like binding site capable of binding recombinant estrogen receptor. Estrogen response element transactivation is enhanced by CD2 signaling, but inhibited by estrogen in PBMC but not in LPMC, although expression of estrogen receptor was similar. This is the first report to describe a potential molecular mechanism responsible for selectively controlling IFN-gamma production in LPMC.

Peroxisome proliferator activated receptor gamma in colonic epithelial cells protects against experimental inflammatory bowel disease.

INTRODUCTION: Peroxisome proliferator activated receptor gamma (PPARgamma) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPARgamma was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPARgamma. METHODS: Mice with targeted disruption of the PPARgamma gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPARgamma allele and designated PPARgamma(DeltaIEpC), were compared with littermate mice having only the PPARgamma floxed allele with no Cre transgene that expressed PPARgamma in the gut, designated PPARgamma(F/F). Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines. RESULTS: PPARgamma(DeltaIEpC) mice displayed reduced expression of the PPARgamma target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPARgamma(DeltaIEpC) mice in comparison with PPARgamma(F/F) mice. Interleukin (IL)-6, IL-1beta, and tumour necrosis factor alpha mRNA levels in colons of PPARgamma(DeltaIEpC) mice treated with DSS were higher than in similarly treated PPARgamma(F/F) mice. The PPARgamma ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPARgamma(F/F) and PPARgamma(DeltaIEpC) mice. CONCLUSIONS: These studies reveal that PPARgamma expressed in the colonic epithelium has an endogenous role in protection against DSS induced colitis and that rosiglitazone may act through a PPARgamma independent pathway to suppress inflammation.

Use of a crop and job specific exposure matrix for estimating cumulative exposure to triazine herbicides among females in a case-control study in the Central Valley of California.

AIMS: To determine if a job exposure matrix (JEM) could be developed using the California Department of Pesticide Regulation Pesticide Usage Database in conjunction with crop, time, and county specific self reported work history and to determine if this was a feasible method to obtain exposure estimates to triazine herbicides. METHODS: Agricultural work histories were gathered from women enrolled in a population based case-control study of ovarian cancer cases and random controls. The work histories were used in conjunction with the database to construct job exposure matrices which took into account weightings for job type, work location, and crop. RESULTS: Cumulative exposure estimates were determined for 98 study subjects. Mean exposure estimates were similar for cases and controls. The exposure estimates were robust and insensitive to varying job weight assumptions. The estimates from the original weights were highly correlated with those constructed using the conservative and maximum weights. Estimates from all three schemes produced similar multivariate age adjusted odds ratios comparing cases and controls. There was a high degree of agreement in categorised quartiles of exposure between the original and conservative, and original and maximum weights. CONCLUSIONS: The exposure estimate from the JEM provides a ranking of exposure within the study population that can be utilised as an "exposure score" with which to compare groups. Although it is not an absolute exposure measurement, it does offer a substantial advance over dichotomous categories based on self report of herbicide use, particularly when subjects are unlikely to recall specific names and dates of use of herbicides.

A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription.

Interferon-gamma (IFN-gamma) is an important cytokine that regulates cellular immune responses to intracellular pathogens and neoplasia. Regulation of IFN-gamma expression is stringently controlled at the transcriptional level. In this report we describe two novel single nucleotide polymorphisms (SNPs); one, at -179 in the promoter, occurs in 4% of African Americans. This SNP represents a guanidine to thymidine transition and creates a potential AP-1 binding element. Electrophoretic mobility shift analysis reveals a unique complex binding to an oligonucleotide containing the variant -179T but not to the -179G using nuclear extracts from human peripheral blood T cells. In reporter gene assays, T cell lines transfected with the variant -204(179T) IFN-gamma promoter show a six to 13-fold induction of luciferase activity in response to TNF-alpha over the common -204(179G) construct. The -179T allele identified in the proximal IFN-gamma promoter confers TNF-alpha inducibility and may prove important in human immune disorders and responsiveness to pathogens.

Disruption of leaves and initial extraction of wildtype CPMV virus as a basis for producing vaccines from plants.

Wildtype cowpea mosaic virus (CPMV) was extracted from fresh and frozen plant material by methods suitable for large-scale application. Deep freezing, crushing, and thawing in water or buffers gave 0.6+/-0.2 mg g(-1) of virus after up to 24 h. Release from sliced fresh leaves was lower at 0.14+/-0.03 mg g(-1). Homogenisation of frozen leaves for 1 min increased yield to a maximum, on average of 3.5 mg g(-1) but varying between batches from 2.2 to 4.8 mg g(-1) virus Long term storage at -80 degrees C increased subsequent yield by 2 mg g(-1) per year on average; the maximum was 10.4+/-1.9 mg g(-1) (665 days storage). Within a batch, similar yields were obtained between individual fresh plants, and from frozen versus fresh leaves. After homogenisation for 1 min, 90% of debris particles were smaller than 12 microm, half under 5 microm and 10% less than 1 microm. Homogenate (4% dry weight) was rheologically complex, exhibiting shear thinning with hysteresis at low shear rates which bears on subsequent processing. At shear rates above 200 s(-1), its apparent viscosity was 0.02 N s m(-2).

Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization.

Atopic diseases such as allergy and asthma are characterized by increases in Th2 cells and serum IgE antibodies. The binding of allergens to IgE on mast cells triggers the release of several mediators, of which histamine is the most prevalent. Here we show that histamine, together with a maturation signal, acts directly upon immature dendritic cells (iDCs), profoundly altering their T cell polarizing capacity. We demonstrate that iDCs express two active histamine receptors, H1 and H2. Histamine did not significantly affect the LPS-driven maturation of iDCs with regard to phenotypic changes or capacity to prime naive T cells, but it dramatically altered the repertoire of cytokines and chemokines secreted by mature DCs. In particular, histamine, acting upon the H2 receptor for a short period of time, increased IL-10 production and reduced IL-12 secretion. As a result, histamine-matured DCs polarized naive CD4(+) T cells toward a Th2 phenotype, as compared with DCs that had matured in the absence of histamine. We propose that the Th2 cells favor IgE production, leading to increased histamine secretion by mast cells, thus creating a positive feedback loop that could contribute to the severity of atopic diseases.

Hematopoietic switch from lymphoid to granulocytic development in 3LL tumor-bearing mice.

A significant splenomegaly and lymphadenopathy develops during the progressive growth of Lewis Lung (3LL) tumors in mice. Enlarged spleen and lymph nodes occur because of a pronounced increase in granulocytes in these organs. This granulocytosis in spleen and lymph node was not simply due to recruitment of granulocytes from peripheral blood to spleen and lymph nodes, but also a result of development and/or differentiation of granulocytes from the bone marrow. There was a marked increase in development of myeloid lineage cells, whereas lymphoid populations including T cells and B cells, were dramatically decreased in bone marrow and peripheral blood of 3LL tumor-bearing mice. These data demonstrate that host hematopoiesis shifts from lymphoid to granulocytic development in the 3LL tumor-bearing mice. Interestingly, a somatic mutation of N-Ras gene was found in 3LL tumor cells at codon 61, suggesting that mutated N-Ras may contribute to induction of granulocytosis in 3LL tumor-bearing mice.

Human B cell activation by autologous NK cells is regulated by CD40-CD40 ligand interaction: role of memory B cells and CD5+ B cells.

NK cells are a subpopulation of lymphocytes characterized primarily by their cytolytic activity. They are recognized as an important component of the immune response against virus infection and tumors. In addition to their cytolytic activity, NK cells also participate either directly or indirectly in the regulation of the ongoing Ab response. More recently, it has been suggested that NK cells have an important role in the outcome of autoimmune diseases. Here, we demonstrate that human NK cells can induce autologous resting B cells to synthesize Ig, including switching to IgG and IgA, reminiscent of a secondary Ab response. B cell activation by the NK cell is contact-dependent and rapid, suggesting an autocrine B cell-regulated process. This NK cell function is T cell-independent, requires an active cytoplasmic membrane, and is blocked by anti-CD40 ligand (anti-CD154) or CD40-mIg fusion protein, indicating a critical role for CD40-CD40 ligand interaction. Depletion studies also demonstrate that CD5+ B cells (autoreactive B-1 cells) and a heterogeneous population of CD27+ memory B cells play a critical role in the Ig response induced by NK cells. The existence of this novel mechanism of B cell activation has important implications in innate immunity, B cell-mediated autoimmunity, and B cell neoplasia.

HIV-positive patients with anal carcinoma have poorer treatment tolerance and outcome than HIV-negative patients.

PURPOSE: Anal carcinoma is being found in HIV-positive patients with increasing frequency. Most patients are treated with combined chemotherapy and radiation. It was our impression that HIV-positive patients do not fare as well as HIV-negative patients in terms of both response to and tolerance of therapy. METHODS: To test this hypothesis, we reviewed our experience with anal carcinoma and compared HIV-positive to HIV-negative patients by age, gender, sexual orientation, stage at diagnosis, treatment rendered, response to treatment, tolerance, and survival. From 1985 to 1998, 98 patients with anal neoplasms were treated. Seventy-three patients had invasive squamous-cell carcinoma (including cloacogenic carcinoma), and this cohort was analyzed. Thirteen patients were HIV positive and 60 were HIV negative. RESULTS: The HIV-positive and HIV-negative groups differed significantly by age (42 vs. 62 years, P < 0.001), male gender (92 vs. 42 percent, P < 0.001), and homosexuality (46 vs. 15 percent, P < 0.05). There were no differences by stage at diagnosis or radiation dose received. Acute treatment major toxicity differed significantly (HIV positive 80 percent vs. HIV negative 30 percent; P < 0.005). Only 62 percent of HIV-positive patients were rendered disease free after initial therapy vs. 85 percent of HIV-negative patients (P = 0.11). Median time to cancer-related death was 1.4 vs. 5.3 years (P < 0.05). A survival model did not show age, gender, stage, or treatment to be independent predictors. CONCLUSION: We found that HIV-positive patients with anal carcinoma seem to be a different population from HIV-negative patients by age, gender, and sexual orientation. They have a poorer tolerance for combined therapy and a shorter time to cancer-related death. A strong trend to poorer initial response rate was also seen. These results suggest that the treatment of HIV-positive patients with anal carcinoma needs to be reassessed.

Care of HIV-infected pregnant women in maternal-fetal medicine programs.

OBJECTIVE: To survey the evolution over the past decade of attitudes and practices of obstetricians in maternal-fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV)-infected pregnant women. METHODS: Directors of all 65 approved maternal-fetal medicine training programs were sent questionnaires, responses to which were to reflect the consensus among members of their faculties. Programs were stratified based upon the number of HIV-infected pregnant patients cared for in the previous year. RESULTS: Responses reflect experience with over 1000 infected pregnant women per year, nearly one-quarter with advanced disease. Combination antiretroviral therapy was prescribed by all respondents, universally in the 2nd and 3rd trimesters. A three-drug regimen (often containing a protease inhibitor) was used more often by those who treated at least 20 HIV-infected pregnant patients per year than by those programs seeing a lower number of patients (80 vs 59%). Despite the known and unknown risks of the use of antiretrovirals during pregnancy, only half of all responding programs report adverse events to the Antiretroviral Pregnancy Registry; reporting was more common among the institutions seeing a higher number of patients (61 vs 45%). Seventy-eight percent of higher volume programs enroll their patients in clinical studies, usually multicenter, versus 35% of lower volume programs. CONCLUSIONS: Care for HIV+ pregnant women has dramatically changed over the past decade. Antiretroviral therapy is now universally prescribed by physicians involved in maternal-fetal medicine training programs. Given limited experience with these agents in the setting of pregnancy, it is essential for maternal-fetal medicine practitioners to actively report on adverse events and participate in clinical trials.

Eosinophilic angiocentric fibrosis and Wegener's granulomatosis: a case report and literature review.

This report presents a case of eosinophilic angiocentric fibrosis in a man with Wegener's granulomatosis, the first report of a possible association between the two conditions. This association suggests a possible mechanism for its pathogenesis.

The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines.

Excessive release of proinflammatory cytokines mediates the toxic effect of superantigenic staphylococcal exotoxins (SE). Baicalin, a flavone isolated from the Chinese herb Scutellaria baicalensis Georgi and used in China to treat infectious diseases, inhibited SE-stimulated T-cell proliferation (by 98%) and production of interleukin 1beta, interleukin 6, tumor necrosis factor, interferon gamma, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta mRNA and protein by human peripheral blood mononuclear cells. These data suggest that baicalin may be therapeutically useful for mitigating the pathogenic effects of SE by inhibiting the signaling pathways activated by superantigens.

Alternative splicing of the proadrenomedullin gene results in differential expression of gene products.

The adrenomedullin (AM) gene codifies for two bioactive peptides, AM and proAM N-terminal 20 peptide (PAMP). We have found two forms of the AM mRNA. Form A is devoid of introns and results in a prohormone containing both peptides. Form B retains the third intron, which introduces a premature stop codon, producing a shorter prohormone with only PAMP. Tissues with a higher B/A ratio were more immunoreactive for PAMP than for AM. The form B message was found in the cytoplasmic compartment, thus excluding that the longer message was a result of contaminating nuclear mRNA. Form B was found in cells that express PAMP but not AM. mRNA expression in a variety of cell lines was investigated by ribonuclease protection assay and form B was found in significant amounts in two of them. Treatments that modify AM expression, such as exposure to hypoxia, were shown to change the B/A ratio and the relative secretion of AM and PAMP, indicating that the splicing mechanism for AM can be modulated and is physiologically relevant. Analysis of the sequence of the third intron and the fourth exon of the AM gene found motifs compatible with a highly regulated alternative splicing mechanism.

Cutting edge: IL-18-transgenic mice: in vivo evidence of a broad role for IL-18 in modulating immune function.

IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.