Critical Micronutrients in Pregnancy, Lactation, and Infancy: Considerations on Vitamin D, Folic Acid, and Iron, and Priorities for Future Research

The Early Nutrition Academy and the European Commission-funded EURRECA Network of Excellence jointly sponsored a scientific workshop on critical micronutrients in pregnancy, lactation, and infancy. Current knowledge and unresolved questions on the supply of vitamin D, folic acid, and iron for pregnant women, lactating women, and infants, and their health effects were discussed. The question was addressed of whether, and under which circumstances, supplementation with these micronutrients in addition to usual dietary intakes is advisable. The workshop participants concluded that public health strategies for improving supplementation with these micronutrients in pregnancy, lactation, and infancy are required. Further research priorities should focus on adequately powered human intervention trials to obtain a stronger evidence base for the amounts of vitamin D, folic acid, and iron that have optimal effects on health. The conclusions of the workshop should help to inform the scientific community as well as public health policy strategies. Copyright (C) 2011 S. Karger AG, Base

Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay

<p>Abstract</p> <p>Background</p> <p>Hereditary hemochromatosis (HH) is a common genetic disease characterized by excessive iron overload that leads to multi-organ failure. Although the most prevalent genotype in HH is homozygosity for C282Y mutation of the <it>HFE </it>gene, two additional mutations, H63D and S65C, appear to be associated with a milder form of HH. The aim of this study was to develop a high-throughput assay for <it>HFE </it>mutations screening based on TaqMan technology and to determine the frequencies of <it>HFE </it>mutations in the Slovenian population.</p> <p>Methods</p> <p>Altogether, 1282 randomly selected blood donors from different Slovenian regions and 21 HH patients were analyzed for the presence of <it>HFE </it>mutations by an in-house developed real-time PCR assay based on TaqMan technology using shorter non-interfering fluorescent single nucleotide polymorphism (SNP)-specific MGB probes. The assay was validated by RFLP analysis and DNA sequencing.</p> <p>Results</p> <p>The genotyping assay of the H63D, S65C and C282Y mutations in the <it>HFE </it>gene, based on TaqMan technology proved to be fast, reliable, with a high-throughput capability and 100% concordant with genotypes obtained by RFLP and DNA sequencing. The observed frequency of C282Y homozygotes in the group of HH patients was only 48%, others were of the heterogeneous <it>HFE </it>genotype. Among 1282 blood donors tested, the observed H63D, S65C and C282Y allele frequency were 12.8% (95% confidence interval (CI) 11.5 – 14.2%), 1.8% (95% CI 1.4 – 2.5%) and 3.6% (95% CI 3.0 – 4.5%), respectively. Approximately 33% of the tested subjects had at least one of the three HH mutations, and 1% of them were C282Y homozygotes or compound heterozygotes C282Y/H63D or C282Y/S65C, presenting an increased risk for iron overload disease. A significant variation in H63D allele frequency was observed for one of the Slovenian regions.</p> <p>Conclusion</p> <p>The improved real-time PCR assay for H63D, S65C and C282Y mutations detection is accurate, fast, cost-efficient and ready for routine screening and diagnostic procedures. The genotype frequencies in the Slovenian population agree with those reported for the Central European populations although some deviations where observed in comparison with other populations of Slavic origin. Regional distribution of the mutations should be considered when planning population screening.</p

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice

The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25–20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

HFE Gene Variants Modify the Association between Maternal Lead Burden and Infant Birthweight: A Prospective Birth Cohort Study in Mexico City, Mexico

<p>Abstract</p> <p>Background</p> <p>Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (<it>HFE</it>) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight.</p> <p>Methods</p> <p>We investigated the role of <it>HFE C282Y</it>, <it>HFE H63 D</it>, and transferrin <it>(TF) P570 S </it>gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant <it>HFE </it>or <it>TF </it>genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates.</p> <p>Results</p> <p>3.1%, 16.8% and 17.5% of infants (N = 390) and 1.9%, 14.5% and 18.9% of mothers (N = 533) carried the <it>HFE C282Y</it>, <it>HFE H63D</it>, and <it>TF P570 S </it>variants, respectively. The presence of infant <it>HFE H63 D </it>variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal <it>HFE H63 D </it>variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant <it>HFE H63 D </it>genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal <it>HFE H63 D </it>variant carriers had a negative association between tibia lead and birthweight.</p> <p>Conclusions</p> <p>These results suggest that the <it>HFE H63 D </it>genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.</p

Selective phosphodiesterase inhibitors: a promising target for cognition enhancement

# The Author(s) 2008. This article is published with open access at Springerlink.com Rationale One of the major complaints most people face during aging is an impairment in cognitive functioning. This has a negative impact on the quality of daily life and is even more prominent in patients suffering from neurodegenerative and psychiatric disorders including Alzheimer’s disease, schizophrenia, and depression. So far, the majority of cognition enhancers are generally targeting one particular neurotransmitter system. However, recently phosphodiesterases (PDEs) have gained increased attention as a potential new target for cognition enhancement. Inhibition of PDEs increases the intracellular availability of the second messengers cGMP and/or cAMP. Objective The aim of this review was to provide an overvie

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules